RU2844022C2 - Device for subcutaneous delivery of fluid medicament - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medical equipment and generally refers to a fluid drug delivery device and methods for using it. Device for fluid drug delivery through the skin of a user comprises a reusable portion and a disposable portion. Reusable part comprises drive component and control unit for control over drive component. Disposable portion is configured to interact with the non-reusable portion and comprises a first reservoir for containing the fluid medicament, a first plunger head movable by the first lead screw in the first container, and a first nut. First container comprises a first sleeve. First bushing is fixed in the first reservoir. First nut is concentrically fixed by the first bushing and made with possibility of rotation in it. First nut by means of thread interacts with the thread of the above first lead screw. First nut is configured for connection in a releasable manner to the drive component and is configured for rotation by the drive component when the reusable part interacts with the disposable part, and while the reusable part interacts with the disposable part. During the first nut rotation in the first bushing, the first lead screw is linearly displaced in the direction dependent on the direction of rotation of the first nut. Fluid medicament reservoir for delivery through the skin of a user by the fluid medicament delivery device, containing reusable part, is made with possibility to interact with reuse part and comprises a plunger head movable by a lead screw in said reservoir; bushing fixedly mounted in reservoir; and a nut concentrically fixed by the bushing and made with possibility of rotation in it. Nut thread interacts with lead screw. Nut is made with possibility of functional connection with reusable part drive component and is rotatable by the reusable part drive component during the interaction of the receptacle and the reusable part, and while the reusable part interacts with the reservoir. Nut is made with possibility of linear displacement of lead screw in reservoir in direction dependent on direction of nut rotation in sleeve.

EFFECT: drug delivery device is suitable for use by individuals with Parkinson's disease or other CNS disorders.

26 cl, 40 dwg, 2 tbl

Description

AREA OF TECHNOLOGY

[1] The invention generally relates to systems and methods for delivering a drug and, in particular, to a device for delivering a flowable drug and methods for using it.

LEVEL OF TECHNOLOGY

[2] Delivery of drugs, nutrients, or other fluids into the subcutaneous tissue of a patient is known to be an effective treatment method for a variety of medical conditions. Subcutaneous administration of fluids may result in more efficient delivery of the substance into the bloodstream than other routes of administration (e.g., via the digestive tract, respiratory tract, etc.).

[3] Subcutaneous delivery is often accomplished with an infusion pump. An infusion pump is typically a portable device worn by the patient that contains a drug reservoir and drive components for delivering the drug into the patient's body. Infusion pumps can deliver the drug in a more precise and controlled manner than can be achieved by manual delivery by the patient or health care personnel. Infusion pumps can generally be of one of two types. The first type involves a self-contained pump unit worn by the patient at a location remote from the delivery site (e.g., on a belt). The self-contained pump unit pumps the drug from a reservoir through tubing into an infusion set attached to the patient's skin and having access to the subcutaneous tissue (e.g., via a flexible cannula). The second type is generally referred to as a "patch pump" and includes a drug reservoir, drive components, and a cannula, all contained in a single unit that is adhered to the patient's skin. In some situations, infusion pumps deliver a continuous flow of medication into the patient's body (sometimes called a basal dose). Infusion pumps can also deliver intermittent doses that are controlled by the patient in some cases (sometimes called a bolus dose).

[4] Given that subcutaneous drug administration is typically performed with liquid substances, most infusion pump developments have been made to treat medical conditions for which a liquid formulation of the drug is therapeutically feasible. The most obvious example is the use of infusion pumps for subcutaneous delivery of insulin to patients with diabetes.

[5] The most common drug used to treat Parkinson's disease is the drug levodopa, which is often administered to the patient in combination with the drug carbidopa. To date, therapeutic formulations of levodopa/carbidopa are only available in solid or powder form and are usually administered to the patient as an oral pill or inhalation product.

[6] Recently, applicant has developed for the first time a liquid formulation of levodopa/carbidopa having a therapeutic concentration suitable for delivery to subcutaneous tissue (described in more detail in U.S. Patent Application Publication Nos. 2013/0253056 and 2014/0051755, which are incorporated herein by reference in their entireties). This discovery has demonstrated for the first time the practical feasibility of creating an infusion pump device for use in patients with Parkinson's disease and other central nervous system (CNS) disorders.

[7] People with Parkinson's disease and other CNS disorders have different symptoms than people with diabetes. In addition, drug dosage volumes vary for different conditions. Thus, currently available infusion pumps intended for the treatment of diabetes or other diseases are often inappropriate and ineffective for the treatment of Parkinson's disease. Accordingly, there is a need for a new drug delivery device suitable for use in people with Parkinson's disease or other CNS disorders.

DISCLOSURE OF THE ESSENCE OF THE INVENTION

[8] Accordingly, the present invention describes improved drug delivery devices suitable for delivering liquid drugs to patients with Parkinson's disease and other CNS disorders, and methods of using the same. Although these devices are sometimes referred to herein as devices for delivering liquid formulations of levodopa/carbidopa to patients with Parkinson's disease, it is understood that these devices can also be used to deliver other fluids (liquids and gases). In general, these devices can be used to deliver any fluid drug for the treatment of any medical condition, as well as to deliver non-therapeutic fluid drugs, such as nutrients, vitamins, imaging agents, and the like. Furthermore, although the present application often describes delivery devices that deliver subcutaneous injections, in some embodiments, these devices can deliver other types of injections, such as intravenous, intra-arterial, intra-articular, intramuscular, and the like injections.

[9] Worldwide, more than 10 million people suffer from Parkinson's disease. Common symptoms of Parkinson's disease include tremors, slow movements, muscle rigidity, balance problems, dizziness, and sleep problems (fatigue). In some embodiments, the drug delivery devices described herein are easier to use than known devices for patients with some or all of these symptoms. As one example, many known devices require a patient to direct a syringe needle into a relatively small opening in a sealing septum and manually expel drug from the syringe to fill the pump. In some embodiments, the device described herein uses a filling station and a vial adapter configured to receive a vial to fill the device, which requires less effort and/or fine motor coordination than known approaches.

[10] As another example, a known method for inserting a cannula into tissue (e.g., subcutaneous tissue) requires a patient to manually apply an insertion force. According to some embodiments, the delivery device described herein uses at least one cannula insertion mechanism that inserts one or more cannulas into the tissue with a force applied in this manner. Such a cannula insertion mechanism may comprise, for example, a mechanical movement mechanism (e.g., a mechanism such as an energy storage device, such as a torsion spring), an electromechanical mechanism, a pneumatic mechanism, and/or an electromagnetic mechanism.

[11] The cannula insertion mechanism may be adapted or configured to allow the patient to apply significantly less force to pierce the skin to provide, for example, subcutaneous delivery of a drug. The amount of force required for the patient may, for example, be in the range of about 3 N to about 50 N. Although subcutaneous delivery of a fluid drug is discussed herein, it should be understood that this should in no way be considered limiting. In some cases, the fluid drug may, for example, be delivered to other layers of the user's subcutaneous tissue and/or directly to the user's blood vessels.

[12] According to some embodiments, the device may comprise a plurality of cannulas (e.g., two cannulas, three cannulas, or more) for delivering a fluid drug into tissue. If necessary, the plurality of cannulas in the extended position may interact with the tissue simultaneously. The tips of the cannulas may be spaced apart from each other by a predetermined minimum distance to reduce the likelihood of occurrence or development of skin disorders such as nodules, abscesses, hematomas, and/or the like.

[13] According to some embodiments, the device may be configured to selectively deliver a fluid drug to a patient via a plurality of cannulas. For example, the cannulas may be used alternately to deliver a desired amount of fluid drug via a selected cannula over a specific period of time. In cases where the device contains only two cannulas, they may be used alternately.

[14] According to another embodiment, the plurality of cannulas may be grouped into two or more sets of selectable cannulas, which allows two or more sets of cannulas to be used alternately or simultaneously to deliver a desired amount of a flowable medication to a patient over a given period of time. If the plurality of cannulas form only two sets, the two sets may be used alternately. In the event that the plurality of cannulas are operatively grouped into three or more sets of cannulas, the sets may be used sequentially or in parallel, with each set being used for a period of a given time. The period of time of use of one set of cannulas may be the same as or different from the period of use of another set of cannulas.

[15] According to some embodiments, the device may be configured to deliver bolus and basal doses of a fluid drug. The device may be configured to provide manual, semi-automated, and fully automated control of the delivery of bolus and basal doses of a fluid drug, such as, for example, carbidopa and/or levodopa, and/or a prodrug of levodopa (e.g., levodopa amide, levodopa phosphate, carbidopa phosphate) and/or apomorphine.

[16] As another example, in some embodiments, a delivery device comprises a reusable portion comprising a motor and an electronic control unit, and a disposable portion comprising a reservoir for a drug. Although the general concept of using a reusable portion and a disposable portion is known, in known devices, the connection between the two portions may involve complex mechanical circuits that may require significant strength and/or physical dexterity to connect and disconnect. In some embodiments, the reusable portion and the disposable portion of the device described herein are attached to each other using fastening circuits that are relatively simple to connect and disconnect, such as in a one-step procedure using, for example, magnetic and/or snap-on connectors. In addition, in some embodiments, the disposable portion comprises a linear actuator, such as, for example, a mechanism that converts rotation into linear motion. The linear actuator may comprise, for example, a nut for rotating a lead screw causing the plunger to move through the drug reservoir. In some cases, the nut may interact directly with a structure in the disposable part (e.g., a gear) to enable the two parts to be fastened together. These exemplary features and other features of improved drug delivery devices are described in detail below.

[17] It should be noted that, for the sake of simplicity only, the following description may be described in embodiments and examples that relate to the movement of a "plunger". However, this should in no way be considered limiting. Accordingly, the device according to some embodiments may be configured to move a sealing element through the drug reservoir. According to some embodiments, the sealing element may be operatively connected to the plunger. If necessary, the sealing element may be formed integrally with the plunger. If necessary, the distal end of the plunger may be terminated by a sealing element.

[18] According to some embodiments, the device is configured to selectively move the plunger in a first direction to expel fluid from the reservoir, such as for subcutaneous delivery of a fluid medication, and in the opposite direction to generate a suction force that draws the fluid medication into the reservoir.

[19] According to some embodiments, a reservoir configured to contain a fluid may be configured to selectively compress (e.g., push in) and expand. The compression of such a reservoir may force the fluid out of the reservoir for delivery to a user, and the expansion of such a reservoir may generate a suction force that draws the fluid into the reservoir. Accordingly, the device may be adapted or implemented in a plungerless form. In other words, the device may not have a movable plunger and/or a sealing element.

[20] According to some embodiments, control of the device for selectively displacing fluid from the reservoir or generating a suction force to draw fluid back into the reservoir may depend, for example, on the results of measuring values of physiological or other parameters. For example, the device may displace fluid from the reservoir for delivery to the user as long as one or more physiological parameter values meet a certain "delivery criterion." On the other hand, if one or more physiological parameter values do not meet a certain "suction criterion," the device may stop displacing fluid from the reservoir and instead generate a suction force.

[21] According to one aspect, the invention relates to a device for delivering a flowable medication to the subcutaneous tissue of a user. The device may comprise: (i) a reusable part that comprises a drive component and a control unit for controlling the drive component; and (ii) a disposable part configured to be attached to the reusable part, wherein the disposable part has a reservoir for containing a flowable medication, a plunger for displacing the liquid medication from the reservoir, a lead screw attached to the plunger, and a nut configured to move the lead screw such that when the reusable part and the disposable part are fastened to each other, the nut operatively interacts with the drive component, for example, by means of a drive mechanism that is associated with the drive component.

[22] According to some embodiments of the above aspect, the reservoir may contain a fluid drug comprising a liquid formulation of levodopa and/or carbidopa. The reusable portion may also include a battery for supplying energy to the drive component (e.g., a motor assembly that may include a motor and a planetary gear, a chain gear, a belt gear, a pneumatic gear, a magnetic gear, and/or the like). In some cases, the drive mechanism includes at least one gear wheel (e.g., a pinion gear, an intermediate gear, and a load-bearing gear connected in series). The nut may have a profile configured to interact with a mating profile of the load-bearing gear.

[23] According to some embodiments, the disposable portion may also comprise an outer surface configured to adhere to the surface of the user's skin. Microdermal anchors may be connected to the outer surface to adhere the device to the skin surface. In some cases, the outer surface is attached to the skin surface by means of a negative pressure generated therebetween. The device may also comprise an adhesive layer adhered to the outer surface, wherein the side facing the skin surface of the adhesive layer comprises a continuous adhesive, and the opposite side facing the device of the adhesive layer comprises a non-continuous adhesive.

[24] According to some embodiments, the disposable portion also comprises a cannula in fluid communication with the reservoir, such that the cannula, when operatively interacting with the tissue of the patient, delivers the fluid drug into the subcutaneous tissue of the user. The reusable portion and the disposable portion may be secured to each other using a magnetic force and/or a snap-fit connection. In some cases, when the reusable portion and the disposable portion are secured to each other, the actuating component and the reservoir are coplanar. In some cases, when the reusable portion and the disposable portion are secured to each other, the longitudinal axis of the actuating component is substantially parallel to the longitudinal axis of the reservoir. In some cases, when the reusable portion and the disposable portion are secured to each other, the actuating component and the reservoir overlap in the longitudinal direction by at least 50%.

[25] According to some embodiments, the disposable part may also have a second reservoir for containing additional fluid medicament, a second plunger for displacing additional fluid medicament from the second reservoir, a second lead screw attached to the second plunger, and a second nut configured to move the second lead screw, so that when the reusable part and the disposable part are secured to each other, the second nut is associated with the drive component. In some cases, the drive component is configured to simultaneously drive both of the first and second plungers. According to still other embodiments, the drive component is configured to separately drive each of the first and second plungers. The plunger may include a fluid-contacting surface formed from an elastic material. In certain configurations, the reusable part defines a cavity for receiving the lead screw when the lead screw is retracted from the reservoir.

[26] According to some embodiments, the reusable portion may also comprise a computing unit that monitors the operation of the device. The reusable portion may also comprise a control button to allow the user to select an operating mode of the device (e.g., a filling mode, a delivery mode, and/or a pause mode). According to some embodiments, the device may comprise a fluid sensor to sense a fluid drug (e.g., to detect the fluid and/or to measure its amount and/or volume) in the reservoir and/or a contact sensor to sense contact between the outer surface of the disposable portion and the surface of the user's skin. In some cases, the fluid sensor and/or the contact sensor may comprise, for example, a capacitive sensor. The contact sensor may measure the electrical resistivity between at least two locations on the device. In some configurations, the fluid sensor is located along the reservoir and is substantially parallel to the surface of the user's skin. The fluid sensor and the contact sensor may be the same component.

[27] According to some embodiments, the device also comprises a connection sensor (e.g., a Hall sensor) for detecting a connection between the reusable portion and the disposable portion. In some cases, the device also comprises a physiological sensor for detecting at least one physiological characteristic of the user. Examples of a physiological sensor include: (i) a temperature sensor for measuring the user's skin temperature; (ii) a conductivity sensor for measuring the user's sweat level; (iii) a displacement sensor for measuring the user's body movement; (iv) a nerve activity sensor; (v) an oxygen saturation level sensor; (vi) a blood analytical sensor (e.g., hemoglobin, cholesterol, glucose, etc.); (vii) an acoustic sensor for measuring bowel function; (viii) an ECG sensor for detecting the user's heart rate and/or (ix) an EMG sensor for detecting a muscle spasm in the user. In some cases, the device also comprises a functionality sensor for detecting at least one functional parameter of the device. Examples of a functionality sensor include a flow sensor, a pressure sensor, a DC electric current sensor, and/or a temperature sensor. In some embodiments, the flowable formulation may comprise levodopa.

[28] According to another aspect, the invention relates to a method of delivering a flowable medication to subcutaneous tissue of a user. The method may comprise: (a) providing a device comprising: (i) a reusable portion comprising an actuating component and a control unit for controlling the actuating component; and (ii) a disposable portion configured to be attached to the reusable portion, comprising: a reservoir for containing the flowable medication, a plunger for displacing the flowable medication from the reservoir, a lead screw attached to the plunger, and a nut configured to move the lead screw so that when the reusable portion and the disposable portion are secured to each other, the nut is operatively associated with the actuating component, such as by means of a drive mechanism; (b) providing fluid communication of the device with the subcutaneous tissue of the user; and (c) controlling the device to provide the ability to deliver the flowable medication from the device to the subcutaneous tissue of the user.

[29] According to some embodiments of this aspect, the reservoir comprises a fluid drug comprising a liquid formulation of levodopa and/or carbidopa. The reusable portion may comprise a battery, and the method may also include supplying the reusable portion with energy from the battery. The drive component may comprise a motor assembly (e.g., a motor and a planetary gear). The drive mechanism may comprise at least one gear wheel (e.g., a pinion gear, an intermediate gear, and a load gear connected in series). In some cases, the nut has a profile configured to interact with a mating profile of the load gear.

[30] According to some embodiments, the step of providing fluid communication includes adhering the outer surface of the disposable portion to the surface of the user's skin. The adhering step may also include adhering microdermal anchors attached to the outer surface to the surface of the skin. The adhering step may also include generating a negative pressure between the outer surface and the surface of the skin. In some cases, the adhering step may include adhering a layer of adhesive adhered to the outer surface to the surface of the skin, wherein the side of the adhesive layer facing the skin surface comprises a continuous adhesive, and the opposite side of the adhesive layer comprises a non-continuous adhesive.

[31] According to some embodiments, the step of communicating via a fluid includes inserting a cannula in fluid communication with a reservoir into the subcutaneous tissue. In some cases, before providing fluid communication of the device with the subcutaneous tissue, the method may include fastening together a reusable part and a disposable part using, for example, a magnetic connection and/or a snap connection. The step of fastening together may include fastening together the reusable part and the disposable part such that the drive component and the reservoir are coplanar. In some cases, the reusable part and the disposable part may be fastened together such that the longitudinal axis of the drive component is substantially parallel to the longitudinal axis of the reservoir, and/or such that the drive component and the reservoir overlap in the longitudinal direction by at least 50% percent.

[32] According to some embodiments, the disposable part may also comprise: a second reservoir for containing additional fluid medicament; a second plunger for displacing additional fluid medicament from the second reservoir; a second lead screw attached to the second plunger; and a second nut configured to move the second lead screw, wherein when the reusable part and the disposable part are secured to each other, the second nut is associated with the drive component. In some cases, the step of controlling the device to enable delivery of the fluid medicament includes simultaneously actuating both of the first and second plungers. According to still other embodiments, the step of controlling the device to enable delivery of the fluid medicament includes separately actuating both of the first and second plungers. In some cases, the plunger comprises a fluid-contacting surface formed of an elastic material. In some cases, the reusable part defines a cavity for receiving the lead screw when the lead screw is retracted from the reservoir.

[33] According to some embodiments, the reusable portion also comprises a computing unit configured to monitor the operation of the device. The reusable portion may comprise a control button that allows the user to select an operating mode of the device (e.g., a filling mode, a delivery mode, and a pause mode). In some cases, the method may also include recognizing a fluid drug in the reservoir using a fluid sensor and recognizing contact between the outer surface of the disposable portion and the surface of the user's skin using a contact sensor. The fluid sensor and the contact sensor may include a capacitive sensor. The method may include measuring an electrical resistivity between at least two locations on the device using the contact sensor. The fluid sensor may be located along the reservoir and is substantially parallel to the surface of the user's skin. In some cases, the fluid sensor and the contact sensor are the same component.

[34] According to some embodiments, the method may also include recognizing a connection between a reusable part and a disposable part using a connection sensor (e.g., a Hall sensor). In some cases, the method may also include recognizing at least one physiological characteristic of a user using a physiological sensor. Examples of a physiological sensor include: (i) a temperature sensor for measuring the skin temperature of a user; (ii) a conductivity sensor for measuring the sweat level of a user; (iii) a displacement sensor for measuring the displacement of a user's body; (iv) a nerve activity sensor; (v) an oxygen saturation level sensor; (vi) a blood analytical sensor (e.g., hemoglobin, cholesterol, glucose, etc.); (vii) an acoustic sensor for measuring bowel function; (viii) an ECG sensor for determining the heart rate of a user and/or (ix) an EMG sensor for detecting a muscle spasm in a user. In some cases, the method may also include recognizing at least one functional parameter of the device using a functionality sensor. Examples of a functionality sensor include a flow sensor, a pressure sensor, a DC current sensor, and/or a temperature sensor. According to some embodiments, the fluid drug may contain levodopa.

[35] According to another aspect, the invention relates to another device for delivering a flowable medication to the subcutaneous tissue of a user. The device may comprise: a pump module comprising at least one reservoir for containing a flowable medication; and a cannula insertion mechanism adapted to be attached to the pump module, comprising an insertion needle, a cannula assembly comprising a flexible cannula connected to a rigid fluid connection and releasably connected to the insertion needle, so that when the flexible cannula is located in the subcutaneous tissue, the cannula assembly fluidly communicates the reservoir with the subcutaneous tissue via the rigid fluid connection.

[36] According to some embodiments of this aspect, the cannula insertion mechanism also comprises a delivery mechanism comprising, for example, a spring (for example, a torsion spring) associated with the insertion needle, wherein releasing the spring causes: (i) delivering the insertion needle and the cannula into the subcutaneous tissue and (ii) removing the insertion needle from the subcutaneous tissue while leaving the cannula in the subcutaneous tissue. In some cases, the pump module also comprises a plunger for displacing the liquid medication from the reservoir, an actuation component configured to actuate the plunger in the reservoir, and a control unit for controlling the actuation component. In some cases, the delivery mechanism and the insertion needle are removed from the pump module after the cannula is placed in the subcutaneous tissue. The device may also comprise at least one additional cannula insertion mechanism configured to insert at least one additional cannula into the subcutaneous tissue to enable fluid communication between the reservoir and the subcutaneous tissue. In some cases, the at least one reservoir may include more than one reservoir. The cannula insertion mechanism may also be configured to deliver more than one cannula into the subcutaneous tissue, such that at least one cannula connects each reservoir to the subcutaneous tissue. In some cases, the cannula insertion mechanism may comprise more than one cannula insertion mechanism, such that each reservoir has a corresponding cannula insertion mechanism configured to deliver at least one cannula into the subcutaneous tissue, such that at least one cannula connects each reservoir to the subcutaneous tissue. In some cases, each reservoir delivers the fluid drug to different injection sites on the user's body. In some cases, all of the reservoirs deliver the fluid drug simultaneously. In some such cases, at least two of the reservoirs contain a different fluid drug. In other cases, the at least two reservoirs deliver the fluid drug at different times relative to each other. In some such cases, at least two of the reservoirs contain a different drug.

[37] According to some embodiments, the device also comprises a temperature control unit configured to control the temperature of the fluid medication. For example, the temperature of the fluid medication can be controlled to be maintained in a temperature range of about 8-15 °C, about 22-37 °C, and/or about 32-42 °C (among many other examples). The temperature control unit can be configured to heat and/or cool the fluid medication contained in the reservoir. The temperature control unit can also be configured to heat and/or cool the fluid medication when it is located in the cannula. The temperature control unit can comprise at least one of a heating element and a cooling element. The temperature control unit can comprise a device for thermally isolating or thermally separating the fluid medication from at least one of the body heat of the user and the heat of the environment. In some cases, the temperature control unit comprises a temperature sensor for sensing the temperature of the fluid medication (e.g., at the tip of the cannula). In some cases, the temperature control unit uses thermoelectric technologies. According to some embodiments, the device may be configured to adaptively deliver a fluid based on a measured physiological characteristic of the user, such as, for example, the patient's body temperature. According to some embodiments, the device may comprise an active heat pump assembly for removing heat, for example, from the patient's skin, reservoir(s), disposable part, reusable part, fluid medicine, etc.

[38] According to some embodiments, the device also includes a skin property control unit. In some cases, the skin property control unit may apply ultrasonic vibration to the injection site. In some cases, the cannula may form a delivery opening in its sidewall. According to some embodiments, the cannula may form a plurality of delivery openings, each of which is formed at a different height along the sidewall of the cannula. The cannula may be made of stainless steel, silicone, carbon fiber, polytetrafluoroethylene (PTFE), and/or combinations thereof. The cannula may comprise a surface coating (e.g., an oil backing, an analgesic drug, etc.) that reduces the trauma of insertion of the cannula. According to some embodiments, the device also includes a penetration depth control unit that controls the depth of insertion of the cannula into the subcutaneous tissue. In some embodiments, the device also comprises a tissue detection unit that detects the type of subcutaneous tissue near the cannula (e.g., dermis, muscle, fat, blood vessel, air, water, and/or combinations thereof, etc.). In some embodiments, the fluid drug may comprise levodopa.

[39] According to another aspect, the invention relates to another method of delivering a flowable medicament to the subcutaneous tissue of a user. The method may comprise: (a) providing a pump module comprising at least one reservoir for containing a flowable medicament; (b) attaching a cannula insertion mechanism to the pump module, wherein the cannula insertion mechanism comprises an insertion needle, a cannula assembly comprising a flexible cannula connected to a rigid fluid connection and releasably connected to the insertion needle; and (c) providing fluid communication between the pump module and the subcutaneous tissue of the user such that the cannula assembly provides fluid communication between the reservoir and the subcutaneous tissue via the rigid fluid connection.

[40] According to some embodiments of this aspect, the cannula insertion mechanism may also comprise a delivery mechanism comprising, for example, a spring (for example, a torsion spring) associated with the insertion needle, and the method may also include releasing the spring, causing (i) delivery of the insertion needle and the cannula into the subcutaneous tissue and (ii) removal of the insertion needle from the subcutaneous tissue while leaving the cannula in the subcutaneous tissue. In some cases, the pump module may also comprise a plunger for displacing the liquid drug from the reservoir, a drive component configured to actuate the plunger in the reservoir, and a control unit for controlling the drive component. The method may also include removing the delivery mechanism and the insertion needle from the pump module after placing the cannula in the subcutaneous tissue. In some cases, the method may also include attaching at least one additional cannula insertion mechanism to the pump module, wherein the additional cannula insertion mechanism is configured to insert at least one additional cannula into the subcutaneous tissue to provide fluid communication between the reservoir and the subcutaneous tissue. In some cases, the at least one reservoir may comprise more than one reservoir. In some cases, releasing the torsion spring causes delivery of more than one cannula into the subcutaneous tissue, such that at least one cannula fluidly communicates each reservoir with the subcutaneous tissue. The method may also include attaching at least one additional cannula insertion mechanism to the pump module in such a way that each reservoir has a corresponding cannula insertion mechanism configured to deliver at least one cannula into the subcutaneous tissue, such that at least one cannula fluidly communicates each reservoir with the subcutaneous tissue. In some cases, each reservoir may deliver the fluid medication to a different injection site on the user's body. In some cases, all reservoirs deliver the fluid medication simultaneously. In some such cases, at least two of the reservoirs contain different drug. In some cases, at least two of the reservoirs deliver the fluid drug at different times relative to each other. In some such cases, at least two of the reservoirs contain different fluid drug.

[41] According to some embodiments, the method may also include controlling the temperature of the fluid medication using a control unit (e.g., a heating element and/or a cooling element). For example, the temperature of the fluid medication may be controlled to maintain the temperature in a temperature range including: from about 8°C to about 15°C, from about 22°C to about 37°C, or from about 32°C to about 42°C (among many other examples). The temperature controlling step may include heating and/or cooling the fluid medication contained in the reservoir. The temperature controlling step may also include heating and/or cooling the fluid medication when the fluid medication is in the cannula. The temperature controlling step may also include thermal insulation of the fluid medication from at least one of the body heat of the user and the heat of the environment. In some cases, the method includes sensing the temperature of the fluid medication (e.g., at the tip of the cannula) using the temperature control unit. In some cases, the temperature control step involves the use of thermoelectric methods.

[42] According to some embodiments, the method also includes controlling a property of the user's skin using a skin property control unit. The step of controlling the skin property may include applying ultrasonic vibration to the injection site. In some cases, the cannula may form a delivery opening in its sidewall. In some cases, the cannula forms a plurality of delivery openings, wherein each delivery opening is formed at a different height along the sidewall of the cannula. The cannula may be made of stainless steel, silicone, carbon fiber, polytetrafluoroethylene (PTFE), and/or combinations thereof. The cannula may comprise a surface coating (e.g., an oil base, an analgesic drug, etc.) that reduces the trauma of insertion of the cannula. In some cases, the method may also include controlling the depth to which the cannula is inserted into the subcutaneous tissue using a penetration depth control unit. In some cases, the method may also include detecting the type of subcutaneous tissue near the cannula using a tissue detection unit (e.g., dermis, muscle, fat, blood vessel, air, water, and/or combinations thereof, etc.). According to some embodiments, the fluid drug may comprise levodopa.

[43] According to another aspect, the invention relates to a control unit for a device delivering a fluid medicament to the subcutaneous tissue of a user. The device may comprise a drive component for displacing the fluid medicament, at least one patient sensor for determining the state of the user's medical indications, and a timer. The control unit may comprise a drive component module configured to control the drive component and deliver the fluid medicament based on signals received from the patient sensor(s) and/or the timer.

[44] According to some embodiments of this aspect, the drive component comprises a motor. The signals received from the patient sensor may comprise a user's sleep state, a user's food intake indicator, and/or a user's physical activity indicator. In some cases, the user's sleep state includes a user's sleep stage, and the drive component module is configured to control the drive component and deliver the fluidic medication based on the sleep stage. The patient sensor for determining the user's physical activity indicator may comprise an ECG sensor and/or an accelerometer. The patient sensor for determining the user's food intake indicator may comprise an acoustic sensor. The signals received from the timer may include the time of day. In some cases, the drive component module is also configured to control the volume of the fluidic medication delivered to the injection site during a specific period of time. In some cases, the drive component module is also configured to deliver the fluidic medication in periods including at least one working period and at least one non-working period. The device may also comprise a pressure sensor configured to detect the pressure of the fluid drug, wherein the drive component module is also configured to control the drive component based on the signal received from the pressure sensor. According to some embodiments, the fluid drug may comprise levodopa.

[45] According to another aspect, the invention relates to a method of controlling a device that delivers a fluid medicament to the subcutaneous tissue of a user. The device may comprise a drive component for displacing the fluid medicament, at least one patient sensor for determining the state of the user's medical indications, and a timer. The method may include the steps of receiving a signal from the patient sensor(s), receiving a signal from the timer, and controlling the drive component for delivering the fluid medicament based on the signals received from both the patient sensor(s) and the timer.

[46] According to some embodiments of this aspect, the drive component may comprise a motor. The signal received from the patient sensor may comprise data on the user's sleep state, the user's food intake indicator, the user's physical activity indicator, and/or the user's weight. In some cases, the user's sleep state includes the user's sleep stage, and the drive component module is configured to control the drive component and deliver the fluid medication based on the sleep stage. The patient sensor for determining the user's physical activity indicator may comprise an ECG sensor and/or an accelerometer. The patient sensor for determining the user's food intake indicator may comprise an acoustic sensor. The signal received from the timer may comprise the time of day. In some cases, the method also includes controlling the volume of the fluid medication delivered to the injection site during a specific period of time. The method may also include controlling the drive component to deliver the fluid medication in periods including at least one working period and at least one non-working period. The method may also include recognizing the pressure of the fluid drug using a pressure sensor, wherein the control step may also include controlling the drive component based on a signal received from the pressure sensor. According to some embodiments, the fluid drug may contain levodopa.

[47] According to another aspect, the invention relates to a charging/filling station for a device configured to deliver a flowable medicament to the subcutaneous tissue of a user. The charging/filling station may comprise a cradle for receiving the device, a charging unit configured to charge a rechargeable battery of the device, a display device, and a communication module configured to instruct at least one of a control unit and a drive component of the device to initiate a filling operation of the device.

[48] According to some embodiments of this aspect, the device comprises a reservoir for a drug, and the cradle is configured to hold the device with the reservoir, for example, in a substantially vertical orientation. If necessary, the cradle may comprise a connection or proximity sensor configured to detect an operably positioned device in the cradle. In response to detecting the presence of the device in the cradle, the filling station may provide an output prompt prompting the user to authorize the start of a battery charging sequence. According to another embodiment, in response to detecting the presence of the device in the cradle, the filling station may automatically initiate the battery charging sequence.

[49] According to some embodiments, the adapters for the vial (described below) may comprise a connection or proximity sensor configured to detect a usable connection of the vial to the vial adapter. In response to detecting a usable connection of the vial to the vial holder and provided that the device is operatively positioned in the cradle, the filling station may provide an output signal prompting the user to initiate a charging sequence using the vial. According to another embodiment, in response to detecting a usable connection of the vial to the vial adapter, the filling station may automatically initiate a charging/filling sequence using the vial provided that the device is operatively positioned in the cradle.

[50] The term "the device is operatively positioned in the cradle" may, for example, refer to the orientation of the device in the cradle as well as the orientation of the device relative to the world coordinate system. For example, a device is said to be in an "operative position" when it is in a certain orientation relative to the earth's gravitational field, such as such that a flowable drug can flow by simple gravity from a vial into the reservoir(s) of the device.

[51] In some cases, the charging unit charges the battery wirelessly. The display device may comprise an LED display device. The display device may comprise a graphical user interface that may provide the ability for a user to input an instruction to initiate a filling operation. In some cases, the display device also comprises a touch screen. In some cases, the communication module may communicate with the computing device via a wired and/or wireless communication network (not shown).

[52] The computing device used in this application may include, for example, a multi-functional mobile communication device, also known as a "smartphone," a personal computer, a laptop, a tablet computer, a server (which may refer to one or more servers or storage and/or service systems associated with a commercial or corporate entity, including, for example, a file sharing resource, a cloud computing data storage service, an online file storage service, a peer-to-peer LAN file storage or hosting service, and/or a file sharing service), a personal digital assistant, a workstation, a wearable device, a portable computer, a notebook computer, an in-vehicle device, a fixed device, and/or a home appliance control system.

[53] The communication module may, for example, contain input/output device drivers (not shown) and network interface drivers (not shown) to provide for the transmission and/or reception of data over a communication network to provide external communication with a communication device. A device driver may, for example, provide communication with a keyboard or a universal serial bus (USB) port. The network interface driver may, for example, execute protocols for using the Internet or Intranet, a wide area network (WAN), a local area network (LAN), such as a wireless local area network (WLAN), a metropolitan area network (MAN), a personal area network (PAN), an extended intranet, 2G, 3G, 3.5G, 4G, including, for example, the WIMAX mobile broadband system or the 5G long term evolution (LTE) system, a Bluetooth® system (for example, a Bluetooth intelligent system), a ZigBee™ system, a near field communication (NFC) system, and/or any other current or future communication networks, standards and/or systems.

[54] The communication module may receive a state of the user's medical indications, such as from the device and/or cloud storage. In some cases, the display device may display the state of the medical indications. The filling operation may include moving the plunger through the drug reservoir to generate a suction force to draw the fluid drug from the vial into the drug reservoir through the vial adapter. The communication module may be configured to instruct the device to initiate the filling operation when the device is in the cradle of the charging station/filling station. According to some embodiments, the fluid drug may comprise levodopa.

[55] According to some embodiments, the device may be configured to allow a user to initiate the withdrawal of fluid from the vial(s) into the drug reservoir in the disposable portion without necessarily using a filling station. For example, the device may include a user interface located in the reusable and/or disposable portion that allows the user to input commands that cause the pump to rotate the drive component, which in turn may cause the plunger to move and thereby fill the drug reservoir.

[56] According to another aspect, the invention relates to a method of charging/filling a device configured to deliver a flowable drug to the subcutaneous tissue of a user. The method includes the steps of receiving the device in a cradle, charging a rechargeable battery of the device with a charging unit and sending a command to at least one of the control unit and the drive component of the device to initiate a filling operation of the device. The rechargeable battery of the device and the charging coil can be located within the housing of the reusable part at a necessary distance. For example, at a practically permissible distance from each other, for example, to prevent damage to the battery by electromagnetic radiation that may be present near the coil.

[57] According to some embodiments of this aspect, the method may also include holding the device in a cradle such that the fluid contained in the drug reservoir of the device is subject to the gravitational field of the earth and flows toward the outlet of the reservoir. In some cases, the charging step may include charging a rechargeable battery wirelessly. The device may comprise a display device that may comprise a graphical user interface and/or a touch screen. In some cases, the method may also include receiving an instruction to initiate a filling operation received from a user interacting with the graphical user interface. The method may also include exchanging information with a computing device via a wired and/or wireless communication network. In some cases, the method may include receiving a state of medical indications of the user, for example, from the device and/or cloud storage. In some cases, the method may include displaying the state of medical indications. The filling operation may include moving the plunger through the drug reservoir to generate a suction force to draw the fluid drug from the vial into the drug reservoir through the vial adapter. In some cases, the step of instructing the device to initiate the filling operation is performed when the device is in the cradle. According to some embodiments, the fluid drug may contain levodopa.

[58] According to another aspect, the invention relates to an adapter for a vial of medicine for use with a device for delivering a flowable medicine to subcutaneous tissue of a user. The device may comprise a reservoir for containing the flowable medicine. The adapter for the vial of medicine may comprise a first port configured to connect to the reservoir, a second port configured to connect to a vial of medicine containing the flowable medicine, and a needle located in the first and second ports, so that when the adapter for the vial is connected to the reservoir and the vial of medicine, the needle enables fluid communication between the vial of medicine and the reservoir.

[59] According to some embodiments of this aspect, the needle is configured to pierce (i) a closure septum located in the device to gain access to the reservoir and (ii) a vial stopper to gain access to the contents of the vial with the drug. In some cases, the needle may comprise a metallic material and may be configured to pierce the vial stopper with an insertion force of no more than about 10 N. The needle may be protected from accidental contact with the user. According to some embodiments, the flowable drug may comprise levodopa.

[60] According to another aspect, the invention relates to a method for filling a device for delivering a flowable drug into subcutaneous tissue of a user. The device may comprise a reservoir for containing the flowable drug. The method may include the steps of connecting a first port of an adapter for a vial containing the drug to the reservoir by connecting a second port of an adapter for a vial of the drug to the vial of the drug containing the flowable drug, and placing a needle in the first and second ports for fluid communication between the vial of the drug and the reservoir.

[61] According to some embodiments of this aspect, the needle is configured to ignite (i) a sealing septum located in the device to gain access to the reservoir and (ii) a vial stopper to gain access to the contents of the vial with the drug. The needle may comprise a metallic material and may be configured to ignite the vial stopper with an insertion force of no more than about 10 N. In some cases, the method may also include protecting the needle from accidental contact with the user. According to some embodiments, the flowable drug may comprise levodopa.

[62] According to another aspect, the invention relates to a filling system that may comprise (i) a device for delivering a flowable medicament to a subcutaneous tissue of a user, comprising a reservoir for receiving and containing the flowable medicament, and (ii) a vial adapter comprising: a first port configured to connect to the reservoir, a second port configured to connect to a medicament vial containing the flowable medicament, and a needle positioned in the first and second ports, wherein when the vial adapter is connected to the reservoir and the medicament vial, the needle provides fluid communication between the medicament vial and the reservoir.

[63] According to another aspect, the invention relates to a holder for attaching a pumping device to a user. The holder may comprise: a receiving portion configured to receive the pumping device and to releasably hold the pumping device; a fastening component for attaching the holder to the user and/or an item of equipment (e.g. clothing) worn by the user; and a position-changing component located between the receiving portion and the fastening component for changing the position and/or orientation of the pump relative to the fastening component.

[64] According to some embodiments of this aspect, the position-changing component is configured to change the orientation of the pumping device to different angular positions and/or the position of the pumping device. In some cases, the pumping device comprises an outer tube, and the position-changing component is configured to rotate the pumping device to a position preferred for the tube. In some cases, the fastening component may comprise a clip configured to clamp on a belt worn by the user. The receiving portion may comprise a quick-release connector.

[65] According to another aspect, the invention relates to a method of attaching a pumping device to a user. The method may include the steps of receiving and detachably holding the pumping device on a holder, attaching the holder to at least one of the user and an article of clothing worn by the user, and changing the relative position of the pumping device using a position-changing component on the holder.

[66] According to some embodiments of this aspect, the step of changing the relative position includes rotating the pumping device to different angular positions. In some cases, the pumping device comprises an outer tube, and the step of rotating the pumping device includes rotating the pumping device to a position preferred for the tube. In some cases, the step of attaching the holder includes attaching a clip of the holder to a belt worn by the user. In some cases, the step of receiving and holding in a releasable manner includes using a quick-release connector.

[67] According to some aspects, the device may comprise a cannula portion, a reservoir portion, and a control and drive portion, all, some, or none of which may be the same as the disposable portion and/or the reusable portion described above or may have common features with the said portions. The cannula portion comprises a cannula that is configured to interact with the skin of a patient for subcutaneous delivery of a fluid medication. The reservoir portion comprises a medication reservoir configured to receive a fluid medication from a vial. The control and drive portion comprises a motor and control electronics for controlling the delivery of the fluid medication from the reservoir through the cannula to the subcutaneous tissue site.

[68] The cannula portion may be releasably connected and operatively coupled to the reservoir portion such that the cannula located in the cannula portion is in fluid communication with the reservoir located in the reservoir portion. The control and drive portion may be releasably connected and operatively coupled to the reservoir portion such that the control electronics and the drive may control the operation of delivering fluid from the drug reservoir.

[69] The cannula portion, the reservoir portion, and/or the control and drive portion may be reusable or disposable, or may be both reusable and disposable.

[70] This Disclosure introduces a selection of concepts in a simplified form, which are also described below in the sections "BRIEF DESCRIPTION OF THE DRAWINGS" and "IMPLEMENTATION OF THE INVENTION." This Disclosure is not intended to identify the main features or essential attributes of the claimed subject matter of the present invention, nor is it intended to be used as a limitation on the scope of protection of the claimed subject matter of the present invention.

BRIEF DESCRIPTION OF DRAWINGS

[71] In the drawings, like reference numerals generally refer to the same parts throughout the various views. Furthermore, the drawings are not necessarily to scale, but instead are generally intended to illustrate the principles of the present invention. In some instances, references to preceding elements are implied without necessarily further citing the drawing or description in which they appear. The number of elements shown in the drawings are in no way to be considered limiting and are intended for illustrative purposes only. In the following description, various embodiments of the present invention are described with reference to the accompanying drawings, in which:

[72] FIG. 1 schematically shows a transparent perspective view of a drug delivery device according to some embodiments;

[73] FIG. 2 schematically shows a transparent perspective view of a disposable portion according to some embodiments;

[74] FIG. 3 schematically shows a transparent perspective view of a reusable portion according to some embodiments;

[75] FIG. 4A is a schematic side view of a disposable portion and a reusable portion secured together, according to some embodiments;

[76] FIG. 4B is a schematic side view of a sealing configuration of a disposable portion and a reusable portion according to some embodiments;

[77] FIG. 5 schematically shows a perspective cross-sectional view of a plunger assembly in a drug reservoir according to some embodiments;

[78] FIG. 6 schematically shows a perspective view of a plunger head with a cover according to some embodiments;

[79] FIGS. 7A-7C are schematic perspective views illustrating a magnetic connection between a disposable portion and a reusable portion according to some embodiments;

[80] FIGS. 8A-8B are schematic perspective views illustrating a snap-fit connection between a disposable portion and a reusable portion according to some embodiments;

[81] FIGS. 9A-9F are schematic perspective views illustrating a hinge latch connection between a disposable portion and a reusable portion, according to some embodiments;

[82] FIGS. 10A-10C are schematic views showing perspective views of a drug delivery device with multiple reservoirs according to some embodiments;

[83] FIG. 10D is a schematic side view of a plunger head and a lead screw attached to the plunger head of a delivery device according to some embodiments;

[84] FIG. 10E is a schematic cross-sectional side view of the plunger head and lead screw shown in FIG. 10D, according to some embodiments;

[85] FIG. 11 is a schematic perspective view of vial adapters attached to a disposable portion in a blister pack according to some embodiments;

[86] FIGS. 12A-12C show various views of a filling station comprising a delivery device, according to some embodiments;

[87] FIG. 13A is a schematic perspective view of a drug delivery device at a filling station according to some embodiments;

[88] FIG. 13B shows an enlarged view of the vial adapter shown in FIG. 13A, according to some embodiments;

[89] FIG. 14 is a schematic perspective view of a delivery device comprising an access opening and a control button, according to some embodiments;

[90] FIGS. 15A-15G are schematic illustrations of various configurations and methods of charging a delivery device according to some embodiments;

[91] FIG. 16 is a schematic perspective view of a self-contained pump and infusion set assembly according to some embodiments;

[92] FIGS. 17A-17G are schematic perspective views of a pump holder according to some embodiments;

[93] FIGS. 18A-18D show adhesive patterns for an adhesive portion according to some embodiments;

[94] FIG. 19 schematically shows an adhesive on the skin surface facing side of the adhesive portion according to some embodiments;

[95] FIG. 20 schematically shows an adhesive on the device surface facing side of a portion with an adhesive according to some embodiments;

[96] FIGS. 21A-21C schematically illustrate a cannula insertion mechanism according to some embodiments;

[97] FIGS. 22A-22B schematically show a cannula having openings in a side wall, according to some embodiments;

[98] FIGS. 23A-23D schematically illustrate fluid communication methods of a reservoir with a cannula according to some embodiments;

[99] FIGS. 24A-24E schematically show another cannula insertion mechanism according to some embodiments;

[100] FIGS. 25A-25E schematically show various configurations of a delivery device having multiple reservoirs and/or multiple cannulas, according to some embodiments;

[101] FIG. 26 is a schematic perspective view of a drug delivery device antenna sensor according to some embodiments;

[102] FIGS. 27A-27F are schematic diagrams showing various sensors that may be included in a delivery device, according to some embodiments;

[103] FIG. 28 is a schematic perspective view of a temperature control unit of a delivery device according to some embodiments;

[104] FIGS. 29A-29C are schematic perspective views of a skin/tissue property control unit and a skin/tissue detection unit of a delivery device according to some embodiments;

[105] FIG. 30 is a schematic perspective view of a cannula opening assembly of a delivery device according to some embodiments;

[106] FIG. 31 is a schematic perspective view of a depth control unit of a delivery device according to some embodiments;

[107] FIG. 32 is a flow chart of exemplary steps performed by a patient using a drug delivery device, according to some embodiments;

[108] FIG. 33 is a table listing exemplary parameter values associated with the configuration and operation of a drug delivery device, according to some embodiments;

[109] FIG. 34A is a schematic block diagram of a device for determining a quantity of liquid according to some embodiments;

[110] FIGS. 34B-34J schematically show various embodiments of liquid quantity sensing devices operatively associated with reservoirs;

[111] FIG. 35 schematically shows a block diagram of a device for determining the amount of liquid according to alternative embodiments;

[112] FIG. 36 is a schematic side view of a disposable/reusable portion operatively coupled to a position sensor, according to some embodiments;

[113] FIG. 37A schematically shows a liquid quantity sensing device operatively associated with a reservoir, according to some embodiments;

[114] FIG. 37B is a schematic side view of a portion of a reusable device comprising a liquid quantity sensing device, according to some embodiments;

[115] FIG. 37C is a schematic view of a partially cross-sectional top view of a reusable portion according to some embodiments;

[116] FIG. 37D schematically shows an enlarged partial sectional view of the top view shown in FIG. 37C with a liquid quantity sensing device;

[117] FIG. 37E is a schematic perspective view of the relative position of a reservoir and a capacitive liquid quantity sensor configured to measure the amount of liquid in the reservoir, according to some embodiments;

[118] FIG. 37F schematically shows a disposable portion operatively coupled to a reusable portion and the resulting relative positioning of a capacitive liquid amount sensor in the reusable portion and a reservoir in the disposable portion;

[119] FIG. 37G schematically shows a front view and a rear view of a capacitive liquid amount sensor according to some embodiments;

[120] FIG. 37H is a schematic block diagram of a capacitive liquid quantity sensing system according to some embodiments;

[121] FIG. 38 schematically shows sensors located at or near the outlet of the cannula to measure a characteristic of a fluid contained in the cannula, according to some embodiments;

[122] FIG. 39 schematically shows various mixing elements associated with a reservoir, according to some embodiments; and

[123] FIG. 40 shows a block diagram of an example of a method for setting operating parameter values of a pumping device.

IMPLEMENTATION OF THE INVENTION

[124] Embodiments of the present invention relate to an improved device for subcutaneous delivery of a drug to a patient. In some embodiments, the device may be in the form of either a patch pump or a stand-alone pump used with an infusion set. FIG. 1 shows an exemplary patch pump 100 that includes a disposable portion 102 and a reusable portion 104. FIG. 2 shows a transparent view of the disposable portion 102 according to one embodiment. As shown in the drawing, the disposable portion 102 includes a reservoir 106 for the drug, a plunger assembly 108, and a portion 110 with an adhesive for securing to the skin of a patient. FIG. 3 shows a transparent view of the exemplary reusable portion 104. As shown in the drawing, the reusable part 104 may comprise a drive component 112 (e.g., a motor (DC or AC)), a drive mechanism 114 (e.g., a gear transmission), a memory unit 115, a control unit 116, and a power source 118 (e.g., a battery). According to some embodiments, the disposable part 102 may comprise a power source 119.

[125] In some cases, the memory unit 115 and the control unit 116 may be part of a single computing unit 117.

[126] It should be understood that separate electronic control devices and/or memory units may be allocated to each processing function and/or element (such as device 100 and/or filling station 154 (described below)). For simplicity, the following description refers to the computing unit 117 as a general-purpose controller and the memory unit, which perform all necessary control and/or processing functions. In some cases, device 100 includes only the computing unit 117.

[127] Each disposable portion 102 and reusable portion 104, as well as their relationship and interaction with each other, are described in detail below.

[128] FIG. 4A shows a diagram of the interaction of the disposable portion 102 and the reusable portion 104. As shown in the drawing, according to some embodiments, the plunger assembly 108 of the disposable part 102 includes a plunger head 120, a lead screw 122 attached to the plunger head 120 without the actual possibility of rotation relative to the head, and a nut 124 having an internal threaded profile that cooperates with the threads on the lead screw 122. Rotation of the nut 124 can cause a linear movement of the lead screw 122 such that the plunger head 120 is displaced in any direction within the reservoir 106 depending on the direction of rotation of the nut 124. In some cases, the nut 124 has an opening 125 (see FIG. 5) to allow the lead screw 122 to be displaced in a proximal direction 172 toward the reusable part 104.

[129] According to some embodiments, the proximal side of the reusable portion 104 has a tubular cavity 127 for receiving a screw formed with a sealing relative to the reusable portion 104. When the disposable portion 102 and the reusable portion 104 are operatively connected to each other, the tubular cavity 127 for receiving a screw can be located opposite the opening 125 and oriented relative to this opening in such a way that their axes substantially coincide, and also in such a way that a portion of the moving lead screw 122 protruding from the opening 125 is received in the tubular cavity 127. In addition, the tubular cavity 127 for receiving a screw can be an axis of rotation for the load-bearing gear 136, the functions of which are described in detail in this document. Such a configuration allows for the possibility of arranging at least some or all of the electronic elements of the reusable part 104 in a sealed manner, thus protecting them from the environment outside the reusable part 104, while simultaneously ensuring the possibility of implementing the appropriate functional means of this device during operation and control of the moving components of the disposable part 102 by means of the electronic components of the reusable part 104. As shown in FIG. 4B, the sealing structure can be obtained by using one or more sealing rings. For example, the first sealing ring 129A can be connected (for example, located over) with the proximal end of the tubular cavity 127 for receiving a screw, and the second sealing ring 129B can be connected (for example, located over) with the distal end of the tubular cavity 127.

[130] According to some embodiments, the tubular cavity 127 for receiving the screw may be open to the reservoir at both ends and, thus, provide drainage of liquids during disassembly. According to other embodiments, the tubular cavity 127 for receiving the screw may also be closed at one or both ends to prevent the ingress of materials, for example, when the disposable part 102 and the reusable part 104 are in the assembled position. According to some embodiments, the components of the device may be made or may consist of an inert material or materials having a relatively high elasticity, so that after the force causing the deformation of the component is removed, the component returns to its original shape. For example, the component may have a relatively low ductility and, for example, low rigidity. In addition, the plunger head 120 may be made in the form of a single part, which is placed with a fit in the reservoir to create liquid-insulating properties. Therefore, according to some embodiments, the plunger head 120 can create a liquid seal without an O-ring. Additional or alternative components of this device may also not include an O-ring.

[131] The nut 124 may rotate within the sleeve 126 (see FIG. 5). The displacement of the plunger head 120 in one direction may expel the drug contained in the reservoir from the reservoir into the patient's body (as described below). The displacement of the plunger head 120 in the other direction may create space in the reservoir (and in some cases generate a vacuum) to allow the reservoir 106 to be filled (as described below). According to some embodiments, the linear movement for generating forces in the reservoir 106 (e.g., compressive forces for delivering fluid or suction forces for filling) is performed only by components located in the disposable portion 102 (e.g., the lead screw 122 and the plunger head 120). According to such embodiments, the drive components located in the reusable portion 104 do not perform linear movement in the reservoir 106.

[132] As shown in FIG. 6, according to some embodiments, the fluid-contacting surface 139 of the plunger head 120 may be formed from a flexible material that is not hazardous to contact with the fluids contained in the reservoir 106. The fluid-contacting surface 139 may be defined as a surface that comes into fluid contact with the fluid contained in the reservoir 106 during delivery or filling operations. The fluid-contacting surface 139 may reduce or eliminate contact with the drug by using other materials (e.g., other components of the device 100). In some cases, the fluid-contacting surface 139 is formed by a cap 141 placed over the plunger head. In such cases, the cover 141 may serve as a seal that prevents the fluid contained in the reservoir 106 from flowing past the plunger head 120. In some cases, in addition to the seal of the cover 141 or as an alternative to the seal of the cover 141, a sealing ring 143 (see FIG. 4A) (or a sealing gasket or other sealing mechanism) may be included in the plunger head 120.

[133] As shown in FIG. 4A, according to some embodiments, the nut 124 can rotate when interacting with the structure in the reusable portion 104. As noted above, the reusable portion 104 can include a drive component 112 for generating a force for driving the plunger assembly 108 (for example, by rotating the nut 124). In general, the drive component 112 can be any component configured to generate such a force, such as a motor. The reusable portion 104 can also include a drive mechanism 114 for transmitting a driving force from the drive component 112 to the plunger assembly 108. For example, the drive mechanism 114 can be a gear transmission. As shown in the drawing, the gear train may comprise a planetary gear 130 (for example, to reduce the speed and increase the torque of the engine), a pinion gear 132 associated with the planetary gear 130, an intermediate gear 134 associated with the pinion gear 132, and a load gear 136 associated with the intermediate gear 134. Many different gearbox configurations are possible. Alternative drive train systems may also be used, such as belt and pulley systems, rack and pinion systems, etc.

[134] In the configuration shown in FIG. 4A, the nut 124 may be releasably connected to the load gear 136 to provide transmission of driving force from the drive component 112 to the nut 124. According to some embodiments, the nut 124 may have an outer profile that interacts with a mating profile of the load gear 136. As shown in FIG. 4A, the mating profile may be formed in a projection 128 extending from the load gear 136. As indicated above, the load-bearing gear can transmit force to the nut 124, which can cause a linear movement of the lead screw 122 inside the reservoir 106. In some cases, only the components located in the disposable part 102 move linearly in the reservoir 106. Thus, according to the present embodiment, the load-bearing gear does not move linearly in the reservoir 106. Also, other methods can be used to connect the nut 124 to the load-bearing gear 136 in a detachable manner.

[135] According to some embodiments, when the disposable portion 102 and the reusable portion 104 interact with each other, the drive component 112 and the reservoir 106 are coplanar. For example, as shown in FIG. 4A, the longitudinal axis 135 of the drive component 112 and the longitudinal axis 137 of the reservoir 106 lie in the same plane. In some cases, when the disposable portion 102 and the reusable portion 104 interact with each other, the longitudinal axis 135 of the drive component 112 and the longitudinal axis 137 of the reservoir 106 are substantially parallel. In some cases, when the disposable portion 102 and the reusable portion 104 interact with each other, the drive component 112 and the reservoir 106 can overlap in the longitudinal direction. The overlap amount can be at least 30%, at least 40%, at least 50%, at least 60% and/or at least 70% of the length of the drive component 112, or in some cases at least 30%, at least 40%, at least 50%, at least 60% and/or at least 70% of the length of the reservoir 106. Each of the configurations described above in this paragraph can reduce the profile of the device 100, which can make the device 100 more suitable for wearing and less burdensome for the user. As an example, if the drive component 112 and the reservoir 106 are not coplanar, and, for example, the longitudinal axis 135 runs along the Z axis, the device is much thicker and more bulky.

[136] In addition to or as an alternative to the interaction between the nut 124 and the load-bearing gear 136, various technologies may be used to fasten the disposable portion 102 and the reusable portion 104 together. According to some embodiments, the portions are fastened together using a magnetic force. As shown in FIGS. 7A-7C (depicting an embodiment comprising two drug reservoirs described below), the first magnet 138 of the disposable portion 102 and the second magnet 140 of the reusable portion 104 may be arranged to attract each other when the two portions are arranged together (e.g., such that the nut 124 interacts with the load-bearing gear 136). According to some embodiments, the parts may be fastened together using a snap-fit connection that uses a locking means 142 to fasten the parts together, as shown, for example, in FIGS. 8A-8B. According to some embodiments, the parts may be fastened together using a hinged latch. As shown in FIG. 9A, the hinged latch may comprise a lever 144 located in the disposable part 102 that cooperates with a corresponding groove 146 on the reusable part 104 to fasten the parts together. The lever 144 may have a flexible hinge 148 that, when pressed, releases the lever 144 of the groove 146. In some cases, the lever 144 is on the reusable part 104 and the groove 146 is on the disposable part 102. Various additional configurations and arrangements of the hinged latch are shown in FIG. 9B-9F.

[137] Regardless of the method of connection used, in general, the disposable portion 102 and the reusable portion 104 can be connected and disconnected at any time, regardless of the position of the plunger head 120 in the reservoir 106 or the amount of fluid in the reservoir 106. In some cases, said parts can be disconnected when the reservoir 106 becomes empty and the disposable portion 102 needs to be replaced, but said parts do not necessarily have to be disconnected only at that time.

[138] In general, the reusable portion 104 may be operatively connected to the disposable portion 102 in any orientation relative to each other. As shown in FIGS. 10A-10C, in some embodiments, the reusable portion 104 and the disposable portion 102 may be fastened to each other in such a way that the nut 124a cooperates with the load gear 136a, and the nut 124b cooperates with the load gear 136b, and the reusable portion 104 and the disposable portion 102 may also be fastened to each other at a 180° rotation relative to this orientation, for example, in such a way that the nut 124a cooperates with the load gear 136b, and the nut 124b cooperates with the load gear 136a. In some cases, such an approach may improve the convenience and ease of use of the device 100, since in this case the patient does not bother to ensure the correct relative orientation of the reusable part 104 and the disposable part 102 before they are fastened to each other. According to other embodiments, the reusable part 104 and the disposable part 102 must be in a specific orientation to be fastened to each other (for example, only the nut 124a interacts with the load-bearing gear 136a, and only the nut 124b interacts with the load-bearing gear 136b). This can be achieved using various methods, for example, by using specific mating profiles for the nut 124a/load-bearing gear 136a and the nut 124b/load-bearing gear 136b.

[139] According to some embodiments, the device 100 may comprise multiple reservoirs. FIGS. 10A-10C illustrate an exemplary embodiment in which the disposable portion 102 comprises two reservoirs 106a, 106b that comprise separate plunger assemblies 108a, 108b, each of which is driven by separate actuators 114a, 114b. As shown in FIG. 10C, in some cases, both plunger assemblies 108a, 108b may be driven by a single actuator component 112. As shown in FIG. 10C, the drive component 112 can cause the rotation of the single drive gear 132 (for example, via the planetary gear 130), which can cause the rotation of both gears 136a, 136b of the load operation (via the intermediate gears 134a, 134b), which can cause the movement of both plungers 120a, 120b and the displacement of fluid from both reservoirs 106a, 106b (or the generation of a suction force to fill the reservoirs, as described below). According to some embodiments, the gears, nuts and/or lead screws can be modified such that the plunger assemblies 108a, 108b move in the same direction or in opposite directions relative to each other. According to other embodiments, the device 100 can be modified such that the drive component 112 controls the plunger devices completely separately. According to other embodiments, the device 100 can be modified such that a separate drive component 112 controls each of the plunger assemblies 108a, 108b. According to some embodiments using multiple reservoirs, all of the reservoirs (or a subset of two or more reservoirs) can deliver fluid through a common outlet. According to other embodiments, each reservoir can deliver fluid through its own separate outlet.

[140] In some embodiments using multiple reservoirs, each of the reservoirs may contain the same fluid or different fluids. In cases where the reservoirs are filled with the same fluid, the use of multiple reservoirs may help improve the performance of the device or increase the time the device can be used without replacing the disposable portion 102. In some cases where the reservoirs are filled with different fluids, each reservoir may contain different medications (e.g., medications that are prescribed to be taken at the same time). For example, one reservoir may contain levodopa and another reservoir may contain carbidopa. In some cases, one of the reservoirs may be empty (in such cases, the device may be configured or adapted such that the plunger assembly moves or does not move through the empty reservoir). In some embodiments, the device 100 may further be configured with more than two reservoirs (e.g., 3, 4, 6, 8, etc.). The same concepts described above relating to control of plunger assemblies by either a single drive component or multiple drive components apply to embodiments in which more than two reservoirs are used.

[141] As shown in FIG. 10D and 10E, the lead screw 122 may have a threaded portion 121 that extends along the lead screw 122 and a non-threaded portion 123, for example, at the connecting end of the lead screw 122. The non-threaded portion 123 may extend from the distal end of the lead screw 122 in its proximal direction toward the plunger head 120. In other words, the end portion of the distal end of the lead screw 122 may be non-threaded. The diameter of the non-threaded portion 123 may be less than, greater than, or equal to the outer diameter of the threaded portion 121. In addition, the other end portion at the proximal end of the lead screw 122 immediately below the plunger head 120 may also be non-threaded.

[142] By designing the lead screw 122 having a non-threaded distal end portion 123, a limited mechanical positional tolerance can be provided. For example, in cases where a plurality of lead screws are used to simultaneously expel a fluid medicament from a corresponding plurality of reservoirs. For example, rotation of the corresponding nuts 124a and 124b by the drive gear 132 can cause the simultaneous movement of the first and second lead screws 122a and 122b (along with their corresponding plunger heads 120a and 120b) in the reservoirs 106a and 106b, such as, for example, in the embodiments with a two-piston design, schematically shown in FIG. 10C.

[143] The first and second lead screws 122a and 122b cannot, for example, move with precise temporal and/or spatial synchronization. As a result, the first plunger head 120a, for example, can reach the distal end of the reservoir 106a earlier than the second plunger head 120b. Thus, the first plunger head 120a can approach the distal end of the reservoir 106a and stop, despite the fact that the first nut 124a is still forced to rotate, and also despite the fact that the nut 124b transmits a rotational force to the second plunger head 120b, causing it to move in the distal direction. Due to the presence of an unthreaded section on the end portion of any of these two lead screws, the locked lead screw 122a is disconnected from the internal thread of the nut 124a. As a result, both nuts 124a and 124b can continue to rotate, and only nut 124b continues to transmit translational force to the corresponding lead screw. In such embodiments, the drive gear 132 can continuously impart rotational force to the nuts 124a and 124b without causing damage to the mechanical components of the device motor or plunger assemblies in the event of approaching the plunger heads 120a and 120b to the distal ends of the reservoirs.

[144] In some embodiments, the disposable portion 102 is delivered to the patient with the reservoir 106 still filled with the drug. To facilitate filling, in some cases, the disposable portion 102 is delivered to the patient with a vial adapter 150 attached (e.g., pre-packaged in a sterilized package). In another embodiment, the vial adapter may be pre-installed in the disposable portion 102 in the package. After unpackaging, the vial adapter is removed from the disposable portion 102 to allow it to be in fluid communication with an infusion (e.g., standard) set or patch pump tubing to deliver fluidic drug that has been transferred from the vials to the reservoir(s) of the disposable portion.

[145] FIG. 11 shows an exemplary blister package 152 that includes a disposable portion 102 attached to vial adapters 150 (this embodiment includes two adapters 150 for two drug reservoirs 106a, 106b). In other embodiments, the device 100 can be provided to a patient with the disposable portion 102 and the vial adapter 150 separated from each other (e.g., in separate sterilized packaging kits). As shown in FIG. 11, for a multiple reservoir embodiment, a separate vial adapter 150 can be used for each reservoir. In other embodiments, a single vial adapter 150 (or in some cases a subset of two or more vial adapters) can be used to fill all of the reservoirs 106. According to further embodiments, the disposable portion 102 may be delivered pre-filled with the drug and the vial adapter 150 is not used.

[146] According to some embodiments, the device 100 is configured to use a filling station to fill the reservoir 106 with a drug. FIG. 12A shows an exemplary filling station 154.

[147] The filling station 154 may comprise a cradle 155 that receives the device 100 such that the filling station 154 and the device 100 are communicatively connected. Any type of connection may be used, such as a wired connection and/or a wireless connection (e.g., via a Wi-Fi network, Bluetooth, etc.). In some cases, the cradle 155 holds the device 100 such that the reservoir 106 is held substantially vertically (e.g., as shown in FIG. 4A, the longitudinal axis 137 substantially extends along the Y-axis) to reduce air leakage into the reservoir 106 during the filling process.

[148] As shown in FIG. 12A, according to some embodiments, filling station 154 may be controlled by a computing device (e.g., a smartphone) 156 that is communicatively coupled to filling station 154 (either wired or wirelessly). In such embodiments, computing device 156 may provide a display device that has a graphical user interface ("GUI") for interacting with a user to enter control commands. The graphical user interface may be used when computing device 156 executes a mobile application stored therein and/or obtained by accessing cloud storage. Computing device 156 may transmit (wired or wirelessly) instructions to filling station controller 157 of filling station 154 that may instruct control unit 116 in device 100 to control components of device 100 in accordance with user instructions. According to other embodiments, the filling station controller 157 can control the components of the device 100 directly (for example, using a wired or wireless connection). According to other embodiments, the computing device 156 can directly control the components of the device 100. In cases in which the computing device 156 directly controls the device 100, the filling station 154 cannot be used. According to other embodiments, the computing device 156 may not be used, and the filling station 154 may contain its own user interface. In general, the user interface of the filling station can be any interface configured to receive instructions from the user, such as a display device presenting a graphical user interface, buttons, etc. In operation, after the user removes the disposable part 102 and the vial adapter 150 from the blister pack 152, these components can be connected to the reusable part 104 (which the user may already have from a previous dose administration), and these connected parts can be inserted into the filling station 154. Then, the vial 158 can be inserted into the vial adapter 150. The vial 158 can contain a fluid to be delivered by the device 100, for example, a drug to be delivered to a patient. FIG. 13A shows a transparent side view of an example of this configuration.

[149] FIG. 13B is an enlarged view of an exemplary vial adapter 150 shown in FIG. 13A. As shown in the drawing, the vial adapter 150 may be attached to the disposable portion 102 via a first port 160. The first port 160 may be attached using known connection methods, such as a threaded connection (as shown in the drawing), an interference fit, a tongue and groove connection, and the like. The vial adapter 150 may comprise a hollow aspiration needle 162 that pierces the disposable closure septum 164 on the disposable portion 102 for fluid access to the reservoir 106. In order to prevent potential lateral/shearing forces applied by the vial adapter 150 from causing the closure septum to slip (e.g., during transport and/or storage), in some cases the aspiration needle 162 is not rigidly connected to the vial adapter 150 and is instead held in place by a loose portion 166 that is configured to move relative to each other between the aspiration needle 162 and the vial adapter 150. The relative movement may be in any direction, such as in the upward and downward directions (along the axis of the needle 162), in the lateral direction (perpendicular to the axis of the needle 162), etc. The end of the needle 162 for collecting, opposite the end that pierces the packaging seal 164, passes into the second port 168 of the adapter 150 for the vial. The user can insert the vial 158 into the second port 168 in such a way that the needle 162 for collecting has fluid access to the contents of the vial 158 (for example, by piercing the seal 170 (or other stopper) located on the vial 158). The adapter 150 can protect the needle 162 for collecting from inadvertent contact with the user.

[150] The needle 162 for aspirating the agent may be adapted or constructed such that the insertion force required to pierce the vial closure is relatively low, such as about 4 N or less, about 5 N, about 6 N, about 7 N, about 8 N, about 9 N, about 10 N, etc., compared to the higher insertion forces typically required to pierce the vial closure, which is often accomplished with a plastic piercing needle. A reduced insertion force may be advantageous for patients with decreased physical tone, such as those suffering from Parkinson's disease or other CNS disorders. For example, the needle 162 may be formed from a rigid metal material to provide a reduced insertion force. When both the packaging closure 164 and the vial closure 170 are pierced, the hollow interior of the aspiration needle 162 forms a fluid path for the drug between the vial 158 and the reservoir 106. In other cases, the aspiration needle 162 may be made of plastic, in which case the insertion force may be, for example, in the range of from about 30 N to about 40 N.

[151] According to some embodiments, after vial 158 and reservoir 106 are fluidly connected, the contents of vial 158 may be transferred to reservoir 106 for filling. According to some embodiments, the filling process requires movement of the plunger head 120, for example, because the plunger head 120 blocks the reservoir and/or because a suction force must be generated to draw fluid from the vial 158 through the needle 162 to draw the agent into the reservoir 106. In such embodiments, the plunger head 120 may be moved in response to control signals transmitted by the control unit 116 (or in some cases the controller 157 of the filling station 154) or the computing device 156. For example, the control signals may cause the drive component 112 to actuate the drive mechanism 114 such that the nut 124 rotates and causes the lead screw 122 and the plunger head 120 attached thereto to move in a direction away from the vial 158, for example, in a direction toward the reusable portion 104 (shown schematically in arrow 172) to generate a suction force (e.g., a vacuum) within the reservoir 106, as a result of which the fluid from the vial 158 is drawn into the reservoir 106. The plunger head 120 can move in the direction of the arrow 172 until it approaches the sleeve 126, and/or until a predetermined amount of fluid is contained in the reservoir 106 for the drug.

[152] In some cases, the reusable portion 104 defines a space or cavity 176 for receiving the lead screw 122 when the plunger moves in the direction of the arrow 172, for example, from the proximal end to the distal end of the reusable portion 104. The presence of the cavity 176 in the reusable portion 104 of the device 100 allows the lead screw 122 to always remain closed and protected, which helps reduce obstacles that may otherwise block or interfere with the movement of the lead screw 122. In addition, protecting the lead screw 122 can increase the safety and comfort of wearing the device by the patient by shielding the patient from the moving component(s). According to some embodiments, the device 100 can include an access hole 184 (see FIG. 14), so that access to the lead screw 122 can be provided, for example, for lubrication, repair, and/or removal of an obstacle or obstruction.

[153] According to some embodiments, the reusable portion 104 comprises one or more openings located at the distal end thereof. Examples of uses for such opening(s) may include preventing dirt or other debris from accumulating within the cavity 176, removing debris from the cavity through said opening(s), and/or accessing the cavity through said opening(s). The opening is shown, for example, in FIG. 4A (opening 177) and in FIG. 12B (openings 177A and 177B).

[154] In general, the drug reservoir 106 may be filled at any appropriate filling rate. For example, the filling rate may be in the range of about 0.1 ml/min to about 5 ml/min. As further examples, the filling rate may be in the range of about 0.5 ml/min to about 2 ml/min, from 0.7 ml/min to about 1.5 ml/min, and/or from 1 ml/min to about 1.2 ml/min.

[155] The vial adapter 150 may be vented or non-vented. The vial adapter 150 may be non-vented to prevent fluid from escaping from the vent holes when the vial adapter 150 is disconnected from the device 100. In embodiments with a non-vented vial adapter, the pressure in the vial 158 may decrease as fluid is drawn out of the vial 158 during the filling process. In some cases, the pressure inside the vial 158 at the end of the filling process is from about 0.3 bar to about 0.5 bar.

[156] In some cases, the control signals may cause more complex movements of the plunger head 120. For example, in some cases, upon receiving a fill instruction, the control unit 116 may cause the drive component to move the plunger head 120 until it contacts the delivery end 174 of the drug reservoir 106 (e.g., in cases where the plunger head 120 has not yet contacted the delivery end 174, i.e., when the disposable portion 102 has been transferred to the patient). This action may facilitate the implementation of a variety of functions. For example, it can remove air from the reservoir 106 to allow a vacuum to be created when the plunger head 120 is retracted. As another example, this action can provide the control unit 116 with a known position of the plunger head 120 before filling (retraction) begins to ensure repeatability of the amount of fluid drawn into the reservoir for the drug. This action can be advantageous in cases where the position of the plunger head 120 in the reservoir 106 for the drug can change when delivering the disposable part 102 to the patient.

[157] In some cases, the control unit 116 may receive information from a sensor that informs it about the initial location of the plunger head 120 in order to determine how far the plunger head 120 should be moved to contact the delivery end 174 of the reservoir 106 for the drug. According to other embodiments, the control unit 116 may cause the plunger head 120 to move until the sensor reports that the plunger head 120 is in the delivery end 174 of the reservoir 106 for the drug. Below, the sensors of the device are described in more detail. According to other embodiments, the control unit 116 can control in an open loop mode (without feedback) and cause the plunger head 120 to move a predetermined distance, in relation to which it is known that it is sufficient to bring the plunger head 120 into contact with the delivery end 174. After the plunger head 120 is placed in the delivery end 174, it can be retracted in the direction of the arrow 172 to cause filling of the reservoir 106 with a drug, as described above. Many other methods and control algorithms can be used for filling the reservoir 106 for the drug. According to some embodiments, the control unit 116 can control in a closed loop mode (with feedback), for example, based on a force feedback signal provided by a sensor (not shown).

[158] In some cases, the control unit 116 (or in some cases the controller 157 of the filling station 154 or the computing device 156) may initiate the filling operation upon receiving instructions from the user to initiate the filling. For example, the user may select the graphical symbol "Initiate Filling" on a graphical user interface, such as on the computing device 156 or the filling station 154. According to other embodiments, the control unit 116 (or in some cases the controller 157 of the filling station 154 or the computing device 156) may automatically initiate the filling operation upon receiving the device 100 in the cradle 155 without receiving an input command from the user to fill. According to other embodiments, the filling operation may be initiated based on the time of day (for example, determined by a signal received from the clock generator of the processing unit 182 of the filling station 154).

[159] According to some embodiments, the filling station 154 may perform other functions in addition to the filling function or as an alternative to the filling function described above. For example, the filling station 154 may include a charging module 178 (see FIG. 12A) for charging the power source 118 (see FIG. 3). The charging module 178 may use any known charging methods, such as electrical contact wires, inductive coils for wireless charging, and the like. The charging module 178 may charge the power source 118 so that it has at least enough electrical energy to perform a full delivery cycle (e.g., 12 hours, 18 hours, 24 hours, 36 hours, 48 hours, 72 hours, etc.).

[160] Some example configurations and methods of charging are described with reference to FIGS. 15A-15G. FIG. 15A shows an example of a wireless charging method that uses inductive power transfer from a charging module 178 to a device 100 (e.g., a power source 118). The charging module 178 shown in FIG. 15A is described schematically. As noted above, in some embodiments, it may be located in a filling station 154 (see FIG. 12A). FIG. 15B shows an example charging method that uses a charging wire 175. The wire may be connected to any power source (e.g., a loading station, a power outlet, a computing device, etc.). In some cases, the charging wire 175 may also be configured to transmit data. In some embodiments, as shown, for example, in FIG. 15C, the device 100 can be charged when it is attached to the patient's body. For example, as shown in the drawing, the charging module 178 can irradiate a wireless charging area in which the device 100 worn by the patient is wirelessly charged. In some cases, the device 100 can actively deliver a drug during charging. According to some embodiments, as shown, for example, in FIG. 15D, the charging module 178 can be a mat (or can have another design) that can be placed on, under and / or within any surface on which the user can lie, sit and / or stand. For example, as shown in the drawing, the charging module 178 can be placed on a mattress and / or a charging mat and wirelessly charges the device 100 during the patient's sleep. According to some embodiments, as shown, for example, in FIG. 15E, the charging module can be worn by the user (e.g., attached to the patient's clothing (e.g., belt), bracelet, necklace, etc.). The wearable charging module 178 can charge the device 100 wirelessly (as shown in the drawing) and/or using a wire. According to some embodiments, the device 100 can be charged by an adhesive paper battery glued to the device (see FIG. 15F). According to some embodiments, the drug contained in the device 100 can serve as an electrolyte for the battery that supplies energy to the device 100 (see FIG. 15G). In general, the device 100 can receive energy from any suitable power source 118. According to some embodiments, power source 118 is a specific battery having parameters (electrical voltage and/or current) that meet the functional requirements of device 100 (e.g., 3.7 V).

[161] According to some embodiments, the filling station 154 may have a function of detecting the presence of the device 100 in the cradle 155, which in some cases may cause the filling station 154 to initiate a filling process, a charging process (e.g., wireless charging), and/or another process. For example, the filling station may comprise a magnetic relay 171 (e.g., a reed relay) that can detect a magnet 173 (e.g., a reusable portion 104) near the device 100. FIG. 12B is a perspective view from below of the filling station 154 (in dashed lines) containing the device 100, showing an exemplary magnetic relay 171. FIG. 12C is a cross-sectional view of the filling station 154 containing the device 100, showing an exemplary arrangement of the magnetic relay 171 and the magnet 173.

[162] As another example, the filling station 154 may comprise a communication module 180. In some cases, the communication module 180 and the filling station controller 157 are part of a single processing unit 182. The communication module 180 may receive and transmit information between the device 100 and the filling station 154, the computing device 156, and/or the cloud storage. For example, the transmitted information may comprise information about a user's condition and/or medical indication that may affect the configuration and operation of the device 100. As one example, a user may enter his or her medical indications (e.g., stage 2 Parkinson's disease) into the filling station 154 and/or the computing device 156, which may be transmitted to the device 100 via the communication module 180. In such cases, the electronics in the device 100 (e.g., the computing unit 117) may configure the device and control the device accordingly for a patient having such indications. Medical indications are one of many examples of information that can be transmitted to the device 100 for configuring it and controlling its operation. Some other examples include specific dosing schedules, a user's sleep schedule, a user's meal schedule, a user's weight/height, a user's age, a user's medical indications, a time of day, and the like. In some cases, a user's medication schedule is set on a time basis, such that the amount of medication to be delivered is set on an hourly basis. In such cases, the timer of the processing unit 182 of the filling station 154 (or, in some cases, the computing device 156) can be synchronized with the timer of the computing unit 117 of the device 100 to ensure that the correct dosage of medication is delivered according to the correct schedule.

[163] The communication module 180 may also transmit information from the device 100 back to the filling station 154 and/or the computing device 156. For example, as described in more detail below, the device 100 may track data collected by its sensors while the device 100 is worn by a patient. The collected data may include medical data, such as the amount of medication delivered, the period of time during which the medication was delivered, the delivery schedule, and the like. The collected data may also contain information about the user, such as the number of steps taken, hours of sleep/wake, and the like. The collected data may also contain operational data for the device 100, such as the occurrence of any malfunctions, the amount of energy in the power source 118, the next time the service or replacement of the reusable part 104 is due, and the like. The information transmitted from the device 100 to the filling station 154, the computing device 156 and/or the cloud storage via the communication module 180 can be presented to the user on the display device of the filling station 154 and/or the computing device 156.

[164] According to some embodiments, the communication module 180 is not used and/or absent, and the communication is performed directly between the device 100 and the computing device 156 and/or the cloud storage, and vice versa. In such embodiments, the exchange of information transmitted to and from the device 100 may occur between devices remote from the device 100 (e.g., computers, laptops, smartphones, tablets, smart watches and/or any device that can communicate via wireless networks with the cloud storage and/or access the cloud storage). In such cases, the information transmitted from the device 100 may be accessed by a remote user, a caregiver, medical personnel or other people. In some cases, the user (or other people) may also transmit information to the device 100 from remote locations.

[165] According to some embodiments, after the filling process is completed, the vial 158 and the vial adapter 150 may be removed from the device 100. In particular, the first port 160 of the adapter 150 may be removed (e.g., unscrewed) from the device. The device 100 may then be removed from the filling station 154, and in some cases this may be done after any data exchange or charging processes have taken place. In some cases, the user may be warned that the power source 118 has not received a sufficient charge to perform a full cycle of drug delivery. In some of these cases, the user may not be able to activate the delivery mode (e.g., by pressing the button 230, as described below) if the power source 118 does not have a sufficient charge (e.g., to perform a full cycle of drug delivery). The device 100 may then be connected to the patient.

[166] As shown in FIG. 16, in embodiments in which the device 100 is a self-contained pump unit, the tube 186 may be connected to the outlet(s) 188 of the reservoir(s) 106 for the drug of the device 100. In some cases, the tube 186 may be connected to the outlet(s) 188 via a luer connector 190. The other end of the tube may comprise an infusion set 192, which may comprise an infusion set needle 194, through which access is provided to the subcutaneous tissue. The infusion set 192 (or in some cases a plurality of infusion sets) may be adhered to the desired site(s) of administration on the patient's body, such as the abdomen, thigh, upper arm, etc. The device 100 may be wearable by the patient, such as being attached to an item of clothing worn by the patient (e.g., a belt), adhered to the patient's skin, carried in the patient's pocket or in a belt pouch, etc.

[167] According to some embodiments, the device 100 may be supported by a pump holder 196 that provides the ability to support the pump in a variety of different orientations. An exemplary pump holder 196 is shown in FIGS. 17A-17B. As shown in the drawing, the pump holder 196 may include a clip portion 197 for attaching to a user or an article of clothing worn by the user (e.g., a belt) and a snap portion 198 for attaching to the device 100. FIG. 17C shows the pump holder 196 with the snap portion 198 attached to the reusable portion 104 of the device 100 (although in other embodiments the snap portion 198 may be attached to the disposable portion 102). In FIG. 17D-17E show an example of a fastening scheme between the snap portion 198 and the reusable portion 104, for which, in general, any quick connection/disconnection scheme can be used that allows for quick and easy connection of the device 100 to the holder 196 and disconnection of the device 100 from the holder 196. FIG. 17D shows a side view of the holder 196 attached to the reusable portion 104, and FIG. 17E shows an enlarged sectional view of the portion surrounded by the dotted line in FIG. 17D. As shown in the drawing, the reusable portion 104 can comprise a groove 193 and a recess 195 that are configured to cooperate with corresponding clips 193a, 195a on the snap portion 198. According to some embodiments, the groove 193 and/or the recess 195 can be omitted. Many other fastening schemes may be used (e.g., alternative groove/notch configurations, magnets, etc.). In some cases, the device 100 may be configured to be connected or disconnected with one hand.

[168] In some situations, it may be preferable to have the tube 186 coupled to the device 100 positioned in a particular orientation that is preferred to achieve a particular insertion site, such as to prevent tugging/discomfort or to keep the tube away from the patient. The holder 196 may provide a solution by using a rotating mechanism 199 that rotates the device 100 (and, as a result, the tube 186) to the desired orientation. In general, the holder 196 may comprise any structure that is capable of rotating and holding the tube in various orientations (e.g., angular positions). An exemplary rotating mechanism 199 is shown in FIGS. 17F-17G (with reference to FIG. 17A). As shown in the drawing, the rotating mechanism 199 may comprise a disk 189. In some cases, the disk 189 is rotatably attached to the clamp portion 197, and the opening 191 in the latch portion 198 may rotate around the disk 189 to achieve different angular positions of the device 100. According to other embodiments, the disk 189 is rotatably attached to the latch portion of the disk 189 and may rotate relative to the clamp portion 197 to rotate the device 100 into different angular positions. In general, the device 100 may be located in any desired angular position. In some cases, the rotating mechanism 199 may comprise a structure configured to bring the device 100 to some predetermined positions. As one example, the rotating mechanism 199 may comprise stoppers 187 configured to hold the disk 189 in 4 predetermined positions (as shown in FIGS. 17F-17G).

[169] In operation, the fluid may be delivered from the reservoir(s) 106 through the tube 186, the infusion set 192 into the subcutaneous tissue. In some cases, each reservoir 106 for a drug may deliver the fluid to separate infusion sets 192. According to other embodiments, two or more reservoirs 106 may deliver the fluid to the same infusion set 192.

[170] In embodiments in which the device 100 is a patch pump, it can be adhered to a surface of the patient's skin (e.g., abdomen, thigh, upper arm, etc.). In general, any method of adhesive fastening that provides a strong fastening of the device 100 to the surface of the skin can be used. For example, the outer surface of the disposable part 102 can be adapted or configured to adhere to the surface of the skin. In some cases, microdermal anchors can be used to attach the outer surface to the surface of the skin. According to other embodiments, a negative pressure can be generated between the surface of the skin and the outer surface (e.g., using a suction cup). According to other embodiments, a part 110 with an adhesive (see FIG. 2) can be used. The portion 110 with an adhesive may comprise an adhesive layer located both on the side facing the device, which is attached to the device 100, and on the side facing the skin surface, which is attached to the skin surface. The portion 110 with an adhesive and/or the adhesive layer may have elastic properties that allow the portion 110 with an adhesive and/or the adhesive layer to be stretched to conform to a specific surface. Each of the surface of the side facing the skin surface 110a and the surface of the side facing the device 110b may comprise a continuous or non-continuous adhesive. In some cases, one side comprises a continuous adhesive (for example, the side 110a facing the skin surface), and the other side comprises a non-continuous adhesive (for example, the side 110b facing the device surface).

[171] In general, the adhesive may be applied to the adhesive portion 110 in any pattern that promotes secure adhesion to the device 100. Several examples are shown in FIGS. 18A-18D. FIG. 18A depicts a pattern of three adhesive regions 183, which in some cases constitute the minimum number of regions that secure the device in a given plane and prevent unwanted rotations. FIG. 18B depicts a pattern comprising a larger number of adhesive regions 183 that form a linear matrix. FIG. 18C depicts a pattern comprising a concentric ring of adhesive 183 located around an opening 185 in the adhesive portion 110 through which a cannula is inserted (as described below). In some cases, the concentric ring of adhesive 183 is discontinuous and/or offset radially from the opening 185. In FIG. 18D shows a template having adhesive stripes 183 diagonally oriented relative to the longitudinal axis of the device (according to other embodiments, the stripes can be straight, curved, etc.). Many other examples of adhesive templates can be used.

[172] The adhesive patterns described above may be applied to both the skin-facing side 110a and the device-facing side 110b of the adhesive portion 110. For example, FIG. 19 shows a pattern of adhesive regions forming a linear matrix as shown in FIG. 18B on the skin-facing side 110a of the adhesive portion 110. As another example, FIG. 20 shows a pattern of three adhesive regions as shown in FIG. 18A on the device-facing side 110b of the adhesive portion 110.

[173] In embodiments in which the device 100 is a patch pump, after the device 100 is adhered to the surface of the patient's skin, a fluid communication can be established between the drug reservoir(s) 106 of the device 100 and the subcutaneous tissue. In general, any known method of fluid communication between the above-mentioned device 100 and the subcutaneous tissue can be used to insert the cannula into the subcutaneous tissue. In addition, a new method for establishing a fluid communication according to the present invention is described herein.

[174] Various embodiments of the present invention relate to a cannula insertion mechanism 200. In some cases, the cannula insertion mechanism 200 may be a stand-alone component that is attached to the pump 100 when the pump 100 is adhered to the surface of the patient's skin. In some cases, like the disposable portion 102 and the vial adapter 150, the cannula insertion mechanism 200 may be delivered to the patient in a sterilized package. FIGS. 21A-21C illustrate an exemplary configuration and operation of the mechanism 200 according to some embodiments. The mechanism 200 may include, for example, a torsion spring 202 that rotates a cam 204. The cam 204 has an eccentric rod 206 attached to a cannula plunger 208. The plunger 208 of the cannula comprises an upper portion 210 firmly attached to the needle 214 and a lower portion 212 that holds the cannula 216 (e.g., a flexible cannula) so that the cannula 216 is mounted on the needle 214. Before the cannula 216 is delivered, the rotation of the torsion spring 202 is limited by the pin 218. In operation, when the user presses the button 220, the pin 218 is displaced, allowing the torsion spring 202 to rotate the cam 204. As shown in FIG. 21B, in an exemplary embodiment, during the first stage of delivery, the rotation of the torsion spring 202 initially forces the plunger 208 of the cannula to move downward, causing the needle 214 and the cannula 216 to be inserted into the subcutaneous tissue of the patient. At the end of the working stroke, the lower part 212 of the cannula plunger 208 is held in place (for example, by means of the notch and groove assembly 222 and 224, respectively). As shown in FIG. 21C, in the exemplary embodiment, during the second stage of delivery, since the torsion spring 202 continues to rotate the cam 204, the upper part 210 of the cannula plunger 208 is displaced upward, removing the needle 214 from the subcutaneous tissue, while leaving the cannula 216 in place. Once the cannula 216 is in place, the cannula insertion mechanism 200 (e.g., comprising the torsion spring 202, the cam 204, the eccentric rod 206, the upper portion 210, and the needle 214) may be removed from the device 100 while leaving the lower portion 212 and the cannula 216 in place to deliver fluid from the reservoir 106 into the subcutaneous tissue.

[175] In some cases, the cannula 216 is hollow and the fluid flows through the central cavity from the tip 215 of the cannula 216. According to still other embodiments, the cannula 216 has at least one delivery opening 217 in the side wall 219 of the cannula 216, as shown, for example, in FIGS. 22A and 22B. In some cases, the cannula 216 may have a plurality of delivery openings 217 formed at different heights along the side wall 219 of the cannula 216. The delivery openings 217 may be formed at the same or different peripheral positions along the circumference in the side wall of the cannula 219. In some cases, the openings 217 are formed equidistant from each other and/or the upper part or the lower part of the cannula 216. In other cases, the openings 217 are formed non-equidistant from each other and/or the upper part or the lower part of the cannula 216. The cannula 216 may be formed from any suitable material, such as stainless steel, silicone, carbon fiber, polytetrafluoroethylene (PTFE), and/or combinations thereof. In some cases, a single cannula 216 may be divided into a plurality of injection tubes. According to some embodiments, the cannula comprises a plurality of openings, and at least two of said plurality of openings are formed at different heights or the same height along the side wall of the cannula.

[176] According to some embodiments, many modifications of the mechanism 200 shown in FIGS. 21A-21C can be used. For example, the torsion spring 202 can be released using various mechanisms other than the button assembly 220 and the pin 218. In general, any structure that securely holds the torsion spring, for example, in a compressed position until the user moves the said structure and releases the torsion spring. One example can include a hinged latch. Many other structures can be used. As another example, the insertion force can be provided by structures other than a torsion spring, such as a linear spring, a force applied by the user, etc. As another example, the lower portion 212 of the cannula plunger 208 can be held in place using a structure other than the recess and groove assembly 222 and 224, respectively. In general, any design that securely holds the lower portion 212 in place after the needle 214 is delivered into the subcutaneous tissue may be used. For example, in some embodiments, the holding design may include a press fit, flexible fingers, etc.

[177] According to some embodiments, the cannula insertion mechanism 200 also performs a function of fluid communication between the reservoir 106 and the cannula 216 such that fluid withdrawn from the reservoir 106 is delivered through the cannula 216 to the subcutaneous tissue of the patient. FIGS. 23A-23C illustrate the functional means for fluid communication according to exemplary embodiments with reference to the same delivery steps as the cannula placement shown in FIGS. 21A-21C. In FIGS. 23A-23C, the torsion spring 202 and cam 204 assembly of the cannula insertion mechanism 200 are not shown in order not to obscure the view of some structures illustrating the fluid communication function. However, in operation, the torsion spring 202 and cam 204 assembly of the cannula insertion mechanism 200 may be connected to the cannula plunger 208 shown in FIGS. 23A-23C to move the upper portion 210 and the lower portion 212 to the various positions shown. Like reference numerals refer generally to like elements in FIGS. 21A-21C and in FIGS. 23A-23C, despite the fact that the configurations of these structures have somewhat different geometric characteristics between the two sets of drawings according to some embodiments.

[178] As described above, in some embodiments, prior to insertion of cannula 216 into the subcutaneous tissue, drug reservoir 106 and cannula 216 are not in fluid communication. The fluid reservoir 106 may be sealed with a shipping closure 226. The shipping closure 226 may be different from the packaging closure 164 (see FIGS. 23A-23C) or may be the same as the packaging closure 164. In addition to the cannula holder 216, the lower portion 212 of the cannula plunger 208 may also include a rigid fluid nozzle 228 (e.g., a hollow needle) in fluid communication with the cannula 216. In such embodiments, during the first stage of delivery (see FIG. 23B), when the cannula 216 is positioned in the subcutaneous tissue, the nozzle 228 may pierce the shipping closure 226, allowing the reservoir 106 to be in fluid communication with the cannula 216. (i.e., fluid from fluid reservoir 106 moves through nozzle 228 into cannula 216, from which it is delivered to the subcutaneous tissue of the patient). As described above, in some cases, during the second stage of delivery (see FIG. 23C), the upper portion 210 of cannula plunger 208 is removed along with needle 214, while the lower portion 212, cannula 216, and nozzle 228 remain in place. FIG. 23D is an enlarged view of the lower portion 212, cannula 216, and nozzle 228 in place after cannula insertion mechanism 200 (including torsion spring 202, cam 204, eccentric rod 206, upper portion 210, and needle 214) has been removed from device 100.

[179] FIGS. 24A-24E illustrate another cannula insertion mechanism 400 that, in some embodiments, may be used to insert the cannula 216 into the subcutaneous tissue and/or fluidically communicate the reservoir 106 with the cannula 216. Similar to the cannula insertion mechanism 200 shown in FIGS. 21A-21C, the cannula insertion mechanism 400 may be used to deliver a cannula plunger 208 that has an upper portion 210 and a lower portion 212. Parts that are interchangeable (or nearly interchangeable with minor design changes) between the two cannula insertion mechanisms 200, 400 are marked with the same reference numerals in FIGS. 21A-21C and 24A-25E, although these designs may be shown with minor geometric differences in the various drawings.

[180] According to some embodiments, the cannula insertion mechanism 400 also uses the rotational force of the torsion spring 202. However, instead of being connected via the eccentric rod 206, the torsion spring 202 may be connected to the sleeve 404. The torsion spring 202 may be attached to the sleeve 404 in any known manner, for example, a portion of the torsion spring 202 may be inserted into an elongated opening 405 in the sleeve 404 (see FIG. 24B). The sleeve 404 can be connected to the internal gear 406 in such a way that rotation of the sleeve 404 causes rotation of the internal gear 406 inside the external gear 407. In general, the sleeve 404 and the internal gear 406 can be connected in any way, for example, using a connection by means of an elongated hole and a pin, a tongue and groove type connection, a connection using an intermediate shaft, etc. The internal gear 406 can also be connected to the upper part 210 of the plunger 208 of the cannula. In general, the internal gear 406 and the upper part 210 can be connected, for example, using any known technology. The internal gear 406 can comprise a pin 409, which is inserted into a corresponding elongated hole 411 in the upper part 210.

[181] FIGS. 24C-24E illustrate an exemplary operation of the cannula insertion mechanism 400 according to some embodiments. FIG. 24C illustrates the mechanism 400 prior to inserting the cannula into the tissue. The torsion spring 202 may be constrained (e.g., held from being released) in any manner. For example, the sleeve 404 may be held by a pin that may be released by pressing a button, similar to the configuration shown in FIGS. 21A-21B, using a pin 218 and a button 220. In this approach, the torsion spring 202 may be the only component subject to tension, allowing the remaining elements of the insertion mechanism 400 to be unstressed. As another example, the internal gear 406 may be held by a pin that may be released by pressing a button, similar to the configuration shown in FIG. 21A-21B, in which a pin 218 and a button 220 are used. As another example, the upper part 210 of the plunger 208 of the cannula can be held by a pin that can be released by pressing a button, similar to the configuration shown in FIG. 21A-21B, in which a pin 218 and a button 220 are used. With this approach, the freedom of movement between the components of the insertion mechanism 400 can be minimized.

[182] When released, the torsion spring 202 rotates the sleeve 404, which forces the internal gear 406 to rotate counterclockwise, which causes the upper portion 210, the lower portion 212, the cannula 216 and the needle 214 to move in a direction toward the skin/tissue of the patient's body. The mechanism 400 can be designed or configured such that when the internal gear 406 reaches a position inside the outer gear 407 that is closest to the patient's skin, the cannula 216 and the needle 214 are delivered to the desired depth into the patient's body (see FIG. 24D). After the cannula 216 and the needle 214 have been delivered to the desired depth, the inner gear 406 continues to rotate within the outer gear 407. As in the embodiment described above, the upper portion 210 may be firmly connected to the needle 214 and releasably connected to the lower portion 212, so that as the inner gear 406 continues to rotate, the upper portion 210 separates from the lower portion 212 and the needle 214 is removed from the patient's body and the cannula 216, while the lower portion 212 and the cannula 216 remain in their delivered positions (see FIG. 24E). In some cases, the cannula insertion mechanism 400 may be adapted or configured such that the insertion force (e.g., the force applied to the cannula 216/needle 214 for insertion into the tissue) remains constant during various parts of the delivery process (e.g., during insertion of the cannula 216 and needle 214 into the tissue and/or during retraction of the needle 214).

[183] The cannula insertion mechanism 400 may also communicate fluidically with the reservoir 106 and the cannula 216, such as by piercing the sealing septum with the rigid fluid tube 228, similar to the method described above with respect to the cannula insertion mechanism 200. After delivering the cannula 216, the insertion mechanism 400, the torsion spring 202, the sleeve 404, the internal gear 406, the external gear 407, the top 210, and the needle 414 may be removed from the device.

[184] Various modifications may be made to the cannula insertion mechanism 400 shown in FIGS. 24C-24E. As one example, although FIGS. 24C-24E show the inner gear 406 rotating counterclockwise within the outer gear 407, according to other embodiments, the inner gear 406 may rotate clockwise within the outer gear 407. As another example, according to some embodiments, the sleeve 404 may be connected to the outer gear 407, which may be connected to the cannula plunger 208 and may rotate (e.g., relative to the stationary inner gear) to deliver the cannula 216 into the tissue. As another example, according to some embodiments, the internal gear 406 and the external gear 407 may be replaced by structures that interact without threads, such as using a cam-and-roller connection that operates on the cam, a tongue-and-groove connection, etc.

[185] According to some embodiments, a variety of other methods may be used to fluidly communicate the reservoir 106 and the cannula 216. As one example, the torsion spring 202 may be replaced with a linear spring that expands and contracts in a linear manner to extend and retract the insertion needle 214. As another example, the lower portion 212 may have an opening (as opposed to the rigid fluid conduit 228) that fluidly communicates the reservoir 106 and the cannula 216 after the lower portion 212 is deployed. According to still other embodiments, a flexible tube may fluidly communicate the drug reservoir 106 with the cannula 216. In some cases, the tube connects to the lower portion 212 and/or the cannula 216 after the lower portion 212 is deployed.

[186] In some embodiments, multiple cannula insertion mechanisms 200 may be used to deliver a plurality of cannulas 216 into the subcutaneous tissue. FIG. 25A shows an example embodiment of a device 100 having a plurality of cannulas 216. In some embodiments, the plurality of cannulas 216 may be connected to a single drug reservoir 106 (e.g., see FIG. 25B). In some embodiments, when more than one drug reservoir 106 is used, a separate cannula insertion mechanism 200 may be used to deliver a cannula 216 into the subcutaneous tissue corresponding to each drug reservoir 106 (e.g., see FIG. 25C). According to other embodiments, when more than one reservoir 106 for a drug is used (for example, in the case where more than one reservoir 106 delivers a fluid through a single outlet), a single cannula insertion mechanism 200 (for example, see FIG. 25D) can be used to deliver a single cannula 216 associated with more than one reservoir 106. In such embodiments, various schemes can be used to control which fluid from which reservoir is delivered through the single cannula 216 at any given time. FIG. 25E shows an example scheme that includes a pumping valve 221a for the first reservoir 106a and a pumping valve 221b for the second reservoir 106b. The valves may be independently controlled such that the discharge valve 221a may be open while the discharge valve 221b is closed, and vice versa, which may provide for the delivery of either the contents of the tank 106a or the contents of the tank 106b at a given time. In some cases, both discharge valves 221a and 221b are open, so that a combination of the contents of the tanks 106a and 106b are delivered at a given time. In some cases, both discharge valves 221a and 221b are closed and neither of the contents of the tanks is delivered. The pressure valves 221a and 221b can be opened and closed using any means, such as electronically (for example, via the control unit 116), pressure and/or hydrodynamic force generated in the device 100, or can be controlled as one-way check valves, etc. Although the above embodiments have generally been described and shown using two cannulas and/or two reservoirs 106 for a drug, according to other embodiments, any number of cannulas 216 and/or reservoirs 106 can be used. For example, 2, 3, 4, 5, 6, 10 or more cannulas and 2, 3, 4, 5, 6, 10 or more reservoirs 106 for a drug can be used.

[187] The use of multiple cannulas 216 and/or multiple drug reservoirs 106 may have various beneficial effects. For example, the dispensing rate may be increased. As another example, the device 100 may remain operational if one of the cannulas 216 becomes clogged or otherwise fails. As another example, delivery using multiple cannulas 216 and/or reservoirs 106 may be performed in a variable manner, which may provide various benefits (e.g., intermittent use of different components may extend and/or improve their functionality). Embodiments that include multiple drug reservoirs 106 may provide for the delivery of different drugs either intermittently or simultaneously. For example, as described above, one drug reservoir may contain levodopa and another drug reservoir may contain carbidopa. In some cases, different drugs may be delivered through separate cannulas (e.g., see FIG. 25C). In other cases, different drugs may be delivered using the same cannula (see FIGS. 25D-25E).

[188] According to some embodiments, the device 100, after establishing communication with the subcutaneous tissue (e.g., via the tube 186 and the infusion set 192 or via the cannula 216), can deliver the contents of the reservoir 106 into the subcutaneous tissue in some cases at a specific predetermined rate. In some cases, the drive component 112 can be controlled to move the plunger head 120 a predetermined distance for a predetermined time to deliver a predetermined amount of fluid for a predetermined time. For example, the drive component 112 (e.g., a DC motor) can be configured to perform a certain amount of rotation (e.g., a number of revolutions), which can cause the load gear 136 to rotate the nut 124 a certain number of revolutions (e.g., via the planetary gear 130, the pinion gear 132, and the idler gear 134), which, in turn, can cause the lead screw 122 and the plunger head 120 to move a predetermined distance in the reservoir 106 to displace a predetermined amount of fluid into the subcutaneous tissue. In some cases, the fluid is delivered to the patient in discrete microstep volumes (e.g., one microstep volume can be delivered based on a certain number of revolutions or a fraction of a revolution of the lead screw 122). The microstep volume and the flow rate can be combined to determine how often the microstep volume is delivered to the patient. For example, if the microstep volume is 5 μL and the flow rate is 40 μL/hour, then one microstep volume can be delivered to the patient every 7.5 minutes. In other cases, the drive component 112 operates such that the fluid is continuously delivered to the subcutaneous tissue. In other cases, the drive component 112 operates such that the fluid is delivered in intermittent cycles (e.g., during working portions of the cycle (when the fluid is delivered) and during non-working portions of the cycle (when the fluid is not delivered)). In embodiments in which the drive component 112 is a motor, the motor shaft can comprise an optical encoder (e.g., an encoding disk) for tracking the rotation of the motor. As noted above, the drive component 112 can be controlled by the control unit 116, which in some cases can receive instructions from the filling station 154 and/or the computing device 156.

[189] According to some embodiments, the device 100 may comprise a user interface with which the user interacts before the device 100 begins delivery. For example, the user interface may be a mechanical control button 230 (see FIG. 14). In some cases, the user interface may allow the user to switch the device into different modes, such as a prime mode, a delivery mode, and a pause mode. The prime mode may be used at the beginning of a dosing cycle with a new disposable portion 102 and may include priming the system such that the fluid fills the fluid channel extending from the reservoir 106 to the subcutaneous tissue (e.g., the rigid fluid tube 228, the lower portion 212, and the cannula 216). The delivery mode may include delivering the fluid to the subcutaneous tissue at a desired rate according to a desired schedule. The pause mode may include, for example, stopping the delivery of the fluid (temporarily or permanently) if the device 100 needs to be reconfigured or removed, or for any other reason. According to further embodiments, the device 100 may automatically begin delivering the fluid after the cannula 216 is inserted into the subcutaneous tissue.

[190] According to some embodiments, the device 100 may comprise sensors for detecting various conditions of the device 100, the patient, and/or the environment. For example, as shown in FIG. 26, the device 100 may comprise an antenna 232 that detects a nearby material. The antenna 232 may have a surface 234 located near the reservoir 106 that senses the level of the fluid in the drug reservoir 106 and/or the position of the plunger head 120 in the reservoir 106, which can be used to determine the amount of fluid in the device 100 (e.g., by the computing unit 117). The antenna 232 may also have a surface 236 that is substantially parallel to the surface of the patient's skin, so that the antenna 232 can sense the degree of contact between the device 100 and the skin surface. In some cases, the degree of contact may be determined by measuring the electrical resistivity between at least two locations on the device 100. According to some embodiments, the antenna 232 may be a capacitive sensor (for example, a CapSense® brand sensor). In some cases, if the degree of contact between the device 100 and the skin surface is insufficient, the indicator unit may notify the patient of a warning (the indicator and warning unit are described in more detail below) or, in some cases, stop the operation of the device 100 at least temporarily. On the other hand, the patient may also be warned of a sufficient degree of contact.

[191] The device 100 may comprise other various types of sensors. For example, the device may comprise a connection sensor for detecting a connection between the disposable portion 102 and the reusable portion 104. The connection sensor may comprise a Hall sensor, which may comprise a hollow magnet. The sensor may measure the asymmetric shape of a metal plate in the disposable portion 102 and/or the reusable portion 104. In some cases, the connection sensor may measure the level of proximity of the disposable portion 102 and the reusable portion 104 (e.g., the portions are located far from each other, are close to each other, are connected together, etc.). The device 100 may also comprise physiological sensors for detecting at least one physiological characteristic of the user. The physiological sensors may include, for example: (i) a temperature sensor for measuring the skin temperature of the user; (ii) a conductivity sensor for measuring the level of sweating of the user; (iii) a displacement sensor for measuring the movement of the user's body; (iv) a nerve activity sensor; (v) an oxygen saturation level sensor; (vi) an acoustic sensor for measuring digestion or bowel function; (vii) an ECG sensor for determining the heart rate of the user and/or (viii) an EMG sensor for detecting muscle spasm in the user, among many other examples. According to some embodiments, some of the above-described sensors may be located remotely relative to the device 100 and communicated with the device 100 via a wired and/or wireless connection. As another non-limiting example, a movement sensor may be placed around the patient's neck or on his wrist and communicated with the device 100 wirelessly.

[192] The device 100 may also comprise functionality sensors for sensing at least one functional parameter of the device 100. The functionality sensors may include, for example: (i) a flow rate sensor for measuring the flow rate of a fluid flowing through the device 100; (ii) a pressure sensor for measuring the pressure of the fluid in the device 100 (or the pressure at other locations/components in the device 100); (iii) a DC electric current sensor for measuring the current consumption of the drive component 112; and/or (iv) a temperature sensor for measuring the temperature of the fluid in the device 100 (or the temperature of other locations/components in the device 100).

[193] FIG. 27A shows an example of a flow sensor 229. The flow sensor 229 may use any flow sensing method, such as an echo Doppler measurement to measure the velocity of the drug flowing through the rigid tube 228 and/or the cannula 216. In some cases, measurements obtained from the flow sensor 229 or another sensor may be used to determine the actual amount of drug delivered to the patient. In some cases, the actual delivery amount and/or rate may be compared to a programmed amount and/or flow rate to assess a characteristic of the device 100 and/or physiological parameters of the patient that may affect delivery (e.g., high and/or low injection resistance). The comparison may be performed by the computing unit 117 of the device 100, the processing unit 182 of the filling station 154, and/or another device (e.g., a smartphone). Then, if necessary, the delivery parameters can be changed based on the comparison. For example, if the actual quantity and/or delivery speed is lower than the programmed quantity and/or speed, the control unit 116 can increase the quantity and/or delivery speed. Conversely, if the actual quantity and/or delivery speed is higher than the programmed quantity and/or speed, the control unit 116 can decrease the quantity and/or delivery speed.

[194] FIG. 27B shows an example of a pressure sensor 231. The pressure sensor 231 may use any pressure measuring technology, such as a piezoelectric sensor. As shown in FIG. 27B, in some cases, the pressure sensor 231 may be located in the drug reservoir 106 (e.g., on the plunger head 120). In some cases, the pressure measurements may indicate a problem with the functionality of the device 100. For example, a low pressure measurement may indicate a leak. As another example, a high pressure measurement may indicate a clogged cannula 216. In some cases, the pressure sensor 231 may provide an indication of the resistance to injection at a particular injection site. For example, if the fluid pressure in the cannula 216 (or anywhere in the device 100) is high, this may indicate that the injection site to which the fluid is delivered is resistant to injection. In some cases, if a specific pressure threshold is exceeded, a warning may be generated to change the injection site (or in some cases, the operation of the device 100 may be stopped).

[195] According to an alternative or additional method for determining injection resistance, skin impedance may be measured to determine how well a drug is absorbed by body tissue (e.g., when measuring the body's hydration level). For example, if a drug is poorly absorbed, the skin and/or underlying tissue may have different properties than when the drug is well absorbed. FIGS. 27C-27D illustrate exemplary electrodes 223a, 223b that may be used to measure skin impedance (in other embodiments, more or fewer electrodes may be used).

[196] As shown in FIG. 27C, in some cases, the electrodes 223a, 223b are located directly below the device 100. For example, the electrodes 223a, 223b can extend through the openings 225a, 225b in the adhesive portion 110. In such cases, the electrodes 223a, 223b can have a spring base to maintain contact with the patient's skin. As shown in FIG. 27D, in other cases, the electrodes 223a, 223b can be located outside the area directly below the device 100. For example, the electrodes 223a, 223b can extend from the device 100 in the form of tongue portions 227a, 227b. According to some embodiments, the electrodes 223a, 223b may be located on the reusable portion 104 and/or the disposable portion 102. In some cases, the electrodes 223a, 223b may be communicatively coupled to the control unit 116 to form a closed feedback system for improving (or optimizing) the flow rate of the fluid. For example, if the drug is poorly absorbed, the control unit 116 may decrease (or in some cases increase) the flow rate, and vice versa.

[197] FIG. 27E shows exemplary temperature sensors 233a, 233b. In general, a temperature sensor may be located anywhere on the device. For example, as shown in FIG. 27E, one temperature sensor 233a may be located near the reservoir 106 to measure the temperature of the contents of the reservoir, and another temperature sensor 233b may be located near the skin surface to measure the temperature of the patient. The temperature sensors 233a, 233b may use any temperature detection technology, such as thermocouples, resistance temperature sensors, thermistors, infrared ray measuring devices, silicon-based measuring devices, and the like.

[198] FIG. 27F shows an example of a DC current sensor 235. The DC current sensor 235 may be located anywhere on the device 100, such as embedded near the drive component 112. The DC current sensor 235 may operate using any method of sensing an electric current, such as an ammeter.

[199] The device 100 may also comprise drug level sensors and/or may be in communication with these sensors. The drug level sensors may determine the amount and/or concentration of a particular drug or other analyte in the blood, tissue, muscle, fat, and/or other biological structures of a patient. In general, a drug level sensor may recognize the amount and/or concentration of any detectable drug, such as levodopa, carbidopa, levodopa/carbidopa combinations, insulin, and the like. In some cases, the drug level sensor is a component located in the device 100. According to other embodiments, the drug level sensor is remote from the device 100, such as an external wearable device, a device implanted in the patient's body, and the like. Remote drug level sensors may communicate with the device via wired and/or wireless connections.

[200] According to some embodiments, the control unit 116 may receive signals from various sensors of the device (for example, those mentioned above, among many other examples) and may control the drive component 112 in response to the received signals. In some cases, the control unit 116 may also receive an input signal from a timer of the computing unit 117 (for example, the time of day) and may control the drive component 112 in delivering a fluid based on the indicated input signal from the timer and/or signals received from the sensors. Examples of information that may be communicated to the control unit 116 in the signals from the sensors include, for example, the sleep state of the user, an estimate of the user's food consumption, an estimate of the user's physical activity, a quantitative estimate of the user's movements, the level of the user's medication, the temperature of the user, other physical parameters of the user (for example, age, height, weight), and the like.

[201] As one of many examples, for the sole purpose of illustrating the functionality of the control unit 116, the control unit 116 may receive a signal from a motion sensor (e.g., an accelerometer, a gyroscope, etc.) on the device 100 indicating that the physical activity that the user has performed during the day is higher than average. In addition, the control unit 116 may receive an input signal from a timer indicating that the current time is 2 o'clock in the afternoon (2PM), and based on information stored in the memory unit 115, the control unit 116 may have knowledge that, according to the usual meal schedule, the patient will not eat another meal until 5 o'clock in the afternoon. Under such conditions, the control unit 116 may be programmed that the user should take an increased dose of a medicine before 5 o'clock in the afternoon to maintain a stable health condition. Then, the control unit 116 can control the drive component 112 based on these determinations, for example, the control unit 116 can cause the motor to make an additional number of revolutions in order to cause the load gear 136 to rotate the nut 124 an additional number of revolutions (for example, via the planetary gear 130, the pinion gear 132 and the idler gear 134), which will cause the lead screw 122 and the plunger head 120 to move an additional distance through the reservoir 106 for the drug to introduce an additional amount of fluid into the subcutaneous tissue. In some cases, the drive component module of the control unit 116 is used to control the drive component 112. According to some embodiments, the control of the drive component 112 can be performed in an adaptive or dynamic manner. In this context, the term "adaptive" refers to control in response to changes in the detected or measured characteristics (for example, one or more physiological characteristics of the patient). In this context, the term "dynamic" refers to control by forcibly changing the operating parameters of the drive component 112.

[202] As another example, the control unit 116 may receive a signal from a motion sensor (e.g., an accelerometer, a gyroscope, etc.) located on the device 100 (or sometimes remote from the device 100) that provides an indication of the state of the patient's medical conditions. For example, patients with Parkinson's disease or other CNS disorders (e.g., essential tremor) sometimes exhibit more pronounced tremors when they do not take medication properly. Based on the signal from the motion sensor, the control unit 116 may determine whether to change the amount of medication delivered to the patient (e.g., increase or decrease). For example, if the signal from the motion sensor indicates that the patient exhibits excessive tremors, the control unit 116 may control the drive component 112 in such a way as to deliver a greater amount of medication to the patient. According to another embodiment, as another example, if the signal from the movement sensor indicates that the patient is moving slowly or sluggishly (as a result of a possible side effect caused by taking the indicated drug), the control unit 116 can control the drive component 112 in such a way as to deliver a smaller amount of the drug. According to some embodiments, the movement sensor and the control unit 116 can operate in a feedback system in a closed loop mode to influence the desired characteristics of the patient's movement (for example, to reduce tremor).

[203] As another example, the control unit 116 may receive a signal from an ECG sensor measuring the heart rate of a patient and/or another motion sensor (e.g., an accelerometer) indicating that the patient is exercising or performing other physically intense activity. Based on this signal, the control unit 116 may change the dosage of the drug delivered to the patient (e.g., increase or decrease the dose). In some cases, the dosage may be changed to different degrees corresponding to the difference between the measured heart rate and the resting heart rate.

[204] As another example, the control unit 116 may receive a signal from an acoustic sensor or other sensor indicating that the patient is digesting food (e.g., the acoustic sensor may detect sounds of the digestive system (e.g., stomach, intestinal tract, small intestine) characteristic of digestion of food).

[205] In some cases, the sensors may detect the relative amount of food consumed. Based on the signal, the control unit 116 may change the dosage of the drug delivered to the patient (e.g., increase or decrease the dose).

[206] As another example, the control unit 116 may receive a signal from the drug level sensor and control the drive component 112 to deliver the drug in response to this signal. For example, if the signal from the drug level sensor indicates that the drug level is low, the control unit 116 may control the drive component 112 in such a way as to deliver a greater amount of the drug. Conversely, if the signal from the drug level sensor indicates that the drug level is high, the control unit 116 may control the drive component 112 in such a way as to deliver a lesser amount of the drug (or in some cases, at least temporarily stop the delivery of the drug). In this way, the drug level sensor and the control unit 116 may form a closed-loop feedback system to maintain the desired drug level.

[207] As another example, the control unit 116 may receive a signal from a sensor indicating a sleep state and/or sleep stage of the user. The sensor may be any type of sensor configured to determine a sleep state and/or sleep stage, such as an accelerometer, a timer, a polysomnography device (e.g., electroencephalogram (EEG) sensors, electrocochleogram (EOG) sensors, electrocardiogram (ECG) sensors, electromyogram (EMG) sensors, oxygen level sensors, respiratory/air flow sensors, a microphone), etc. Based on the signal, the control unit 116 may change the dosage of the drug delivered to the patient (e.g., increase or decrease the dose). In some cases, the drug is delivered only when the patient is in a specific sleep state or stage. For example, the drug is delivered only when the patient is in a rapid eye movement (REM) sleep or deep sleep. In other cases, the drug is not delivered when the patient is in specific sleep states or sleep stages. In other cases, the drug is delivered continuously but at different dosages depending on the state and/or sleep stage.

[208] In some embodiments, the dose may be delivered to manage the patient's medical condition/indication in accordance with the patient's sleep schedule. As one example of many, the dose for a patient with Parkinson's disease may be managed such that the patient awakens in an "ON state" (the terms "ON state" and "OFF state" refer to stages in which a patient with Parkinson's disease is located, wherein the patient generally feels better during the "ON state" when the drug is managing symptoms, and generally feels worse during the "OFF state" when the drug is not managing symptoms; these terms are well known to those skilled in the art and should not be confused with the terms "on period" and "off period" of drug delivery, as described elsewhere herein). In some cases, the user may instruct the control unit 116 regarding the patient's sleep schedule, such as by entering a wake-up time and a sleep time via a graphical user interface provided by the filling station 154, the computing device 156, and/or the device 100 itself. The sleep schedule may be stored in the memory unit 115. For example, if the user enters a wake-up time of 6 a.m., the control unit 116 may change the dose delivery schedule such that the patient will be in the enhanced state of well-being "ON state" at 6 a.m. The exact delivery schedule will depend on the particular patient, for example, the device 100 may switch to delivering a larger amount of the drug at 2 a.m., 4 a.m., etc. As another example, if the user enters a sleep time of 10 p.m., the control unit 116 may change the dose delivery schedule such that the patient will not enter the degraded state of well-being "OFF state" until he or she is already asleep (e.g., only at 11 p.m.). Many additional examples can be given of altering dosing intensity based on the patient's sleep schedule.

[209] In general, the device 100 may be adapted or configured to vary the dose amount from an amount corresponding to an improved "ON state" (e.g., according to a daytime schedule) to an amount corresponding to a worsened "OFF state" (e.g., according to an evening schedule) at any time of the day or night.

[210] Similarly, the device 100 may be adapted or configured to vary the dosage from an amount corresponding to a state of worsened well-being "OFF state" (e.g., according to an evening schedule) to an amount corresponding to a state of improved well-being "ON state" (e.g., according to a daytime schedule) at any time of the day or night. Thus, the device may provide users with any sleep schedule.

[211] Delivering a medication to a patient based on the patient's sleep schedule is one example of a delivery profile. As used herein, the term "delivery profile" means a schedule according to which a medication is delivered to a patient, which in some cases may be based on the patient's activity and/or environment. In general, device 100 is configured to deliver a medication according to any schedule within the physical limitations of the device. Several examples include: (i) a delivery profile for a leisurely day at home, which may include delivering a lower amount of medication than during a high-activity day; (ii) a delivery profile for a high-activity day, which may include delivering a higher amount of medication than for a leisurely day at home; (iii) an evening delivery profile, which may include delivering a higher amount of medication in the evening (e.g., to maintain a patient in an enhanced "ON state" for a longer period of time than usual). Many other delivery profiles may be used. In some cases, the user may select pre-programmed delivery profiles from a graphical user interface provided by the filling station 154, the computing device 156, and/or another device. In some cases, the user may program the device 100 to deliver according to a customized delivery profile.

[212] According to some embodiments, the computing unit 117 may include a module designed to monitor the control unit 116 (or any other unit) and mitigate incorrect processing (e.g., "hang" states, "slow" states, etc.). In some cases, the monitoring module may be a watchdog circuit. The monitoring module may be implemented as a separate circuit or even a separate panel that is separated from the control unit 116. In some cases, the monitoring module may be programmed to receive an acknowledgement signal from the control unit 116 during a repeating period of time. If the monitoring module does not receive an update during a specific period of time, it may generate a reset signal for the control unit 116. The computing unit 117 may also check the connection of the device to the cloud storage (or in some cases, the processing unit 182 may check the connection of the filling station to the cloud storage).

[213] According to some embodiments, device 100 may provide information and/or warnings to the patient before delivery, during delivery, and/or after delivery, such as based on data collected by the sensors described above (in addition to a plurality of other sensors). Device 100 may include any type of indicator unit configured to communicate with the patient, such as visual, audio, and/or tactile feedback. The indicator unit may transmit any amount of information collected by the sensors. As one example, the indicator unit may include a single indicator light that communicates the amount of fluid remaining in the drug reservoir 106. For example, the indicator light may be green, yellow, or red depending on the amount of fluid remaining. In some cases, the intensity of the signal transmitted to the patient may increase as the drug reservoir 106 is emptied. For example, a warning signal (e.g., a yellow indicator light, a single beep, a single vibration) can be generated when the drug reservoir 106 contains a first predetermined amount of the remaining drug (e.g., 20%); a replacement signal (e.g., a red indicator light, a plurality of beeps, a plurality of vibrations) can be generated when the drug reservoir 106 contains a second predetermined amount of the remaining drug (e.g., 10%); and an urgent replacement signal (e.g., a flashing red indicator light, repeated beeps, repeated vibrations) can be generated when the drug reservoir is empty (e.g., 5% or less). As another example, the indicator unit can provide a signal when the drug level for the patient is too high and/or too low (e.g., according to readings from a drug level sensor). As another example, the display unit may provide an alarm if the device is faulty and needs to be reconfigured or replaced (e.g., if the control unit 116 is "stuck," if the pressure in the device is abnormal, if the contact with the skin is insufficient, among many other examples). As another example, the display unit may comprise a display device with a screen on which the data collected by the sensors (or a subset thereof) is digitally displayed to the patient. In some cases, the patient's condition may be taken into account when determining the intensity of the warning. For example, if the patient is sleeping, the warning may be more intense (e.g., louder, longer, brighter, etc.) to ensure that the patient is warned. According to another embodiment, if the warning is not critical, it may be less intense if the patient is sleeping so as not to startle the patient. According to some embodiments, the display unit may provide a plurality of additional feedback signals.

[214] The indicator unit may also provide feedback when the disposable portion 102 and the reusable portion 104 are connected and/or disconnected. In some cases, if the disposable portion 102 and the reusable portion 104 are not properly secured to each other properly, the pump may not operate (e.g., the control unit 116 will not initiate filling and/or delivery operations). In some cases, if the disposable portion 102 and the reusable portion 104 are disconnected during operation of the pump, operation may be stopped (e.g., the control unit 116 may stop filling and/or delivery operations). Operations may be initiated (or resumed) after the disposable portion 102 and the reusable portion 104 are connected (or the connection is restored).

[215] According to some embodiments, all of the data collected by the sensors described above (among many other examples) may be transmitted to the filling station 154, the computing device 156, and/or the cloud storage, as described above. In some cases, the data (or a subset thereof) is transmitted, processed, and/or displayed in real time as it is collected (e.g., to alert a caregiver, a medical professional, and/or a patient of an emergency). In other cases, the data (or a subset thereof) is downloaded, processed, and/or displayed only after the device 100 is placed in the filling station 154.

[216] According to some embodiments, the device 100 may comprise units for further controlling the process of delivering the fluid. For example, the device 100 may comprise a temperature control unit 237 that may control the temperature of the fluid and/or other components of the device 100, as shown, for example, in FIG. 28. In general, the temperature of the fluid may be controlled to maintain any preferred temperature. For example, the temperature of the fluid may be controlled to maintain it in a range from about 4°C to about 40°C. Many other temperature ranges may be used. For example, according to some embodiments, each integer value in the range from about 4°C to about 40°C (e.g., 5°C, 6°C, 7°C, etc.) may be a minimum or a maximum within a subrange with any other integer value within the specified range. Some example temperature ranges include ranges from about 8°C to about 15°C, from about 22°C to about 37°C, and from about 32°C to about 42°C. In some cases, the temperature control unit 237 may control the temperature of the drug to maintain it within an effective range for the particular drug. In embodiments in which the device 100 contains multiple drugs, each drug may be maintained at different temperatures (or within different temperature ranges). In other embodiments, all drugs may be maintained at the same temperature (or within the same temperature range).

[217] The temperature control unit 237 may comprise components that heat, cool, and/or provide thermal insulation for the fluid. In general, the temperature control unit 237 may comprise any components configured to perform these actions, such as a heating element, a cooling element, a thermoelectric module, a thermal insulation shell, and the like. In some cases, the temperature control unit 237 may heat and/or cool the fluid when it is in the reservoir 106. In some cases, the temperature control unit 237 may heat and/or cool the fluid when it is in the cannula 216. According to some embodiments, the temperature control unit 237 may comprise a temperature sensor (see FIG. 27E) for sensing the temperature of the fluid at various locations in the device 100, which can be used as an input for the control unit 116 and/or other components. In some cases, the temperature control unit 237 comprises a temperature sensor located at the delivery site in the cannula 216 (for example, the tip 215 and/or the opening 217 in the side wall), or as shown, for example, as a sensor 233c. Based on the measurement data obtained from the temperature sensor, the unit can heat and/or cool the fluid using various technologies (for example, thermoelectric technologies based on the Peltier effect).

[218] According to some embodiments, the device 100 may comprise a skin/tissue property control unit 239 used to control the properties of the skin surface at the delivery site, as shown, for example, in FIG. 29A. In general, any property of the skin may be controlled. For example, the skin/tissue property control unit 239 may comprise a vibration unit that causes ultrasonic vibration of the skin/tissue, which may facilitate the introduction and/or distribution of a drug into the tissue. As another example, the skin/tissue property control unit 239 may prepare the skin for the insertion of a cannula and/or the delivery of a drug. For example, the control unit 239 may comprise a reagent delivery unit that may deliver lubricating reagents, therapeutic reagents, etc., which may improve the receptivity of the skin/tissue to the cannula 216 and/or the fluid. Many other examples may be given.

[219] According to some embodiments, the device 100 may comprise a skin/tissue determination unit 241 for determining properties of tissue that surrounds the cannula 216, such as after the cannula 216 has been delivered into the tissue. An exemplary skin/tissue determination unit 241 is shown in FIGS. 29B-29C. In some cases, the determination unit 241 may determine the type of biological material (e.g., tissue) surrounding the cannula 216 (e.g., dermis, skin, fat, blood vessel, bone, muscle, etc.). For example, the type of biological material may be identified by measuring the impedance between two electrodes 243a, 243b located on the cannula 216. The measured impedance may be mapped to a correspondence diagram with known values for various biological materials.

[220] According to some embodiments, the device 100 may comprise a cannula opening unit 245 for opening an occluded or partially occluded cannula 216, as shown, for example, in FIG. 30. For example, the cannula 216 may be occluded by a drug, skin, tissue, and/or another substance. In general, any method for opening the cannula 216 may be used. For example, the opening unit 245 may be a vibrating unit that applies ultrasonic vibrations to the cannula 216. As another example, a suction force may be applied to the cannula 216. As another example, the cannula 216 may be heated (e.g., using a q tip heating method) and/or cooled.

[221] According to some embodiments, the device 100 may comprise a penetration depth control unit 247 for controlling the depth (or height) to which the cannula 216 and/or the needle 214 are inserted into the skin/tissue, as shown, for example, in FIG. 31. For example, the unit 247 may be used to penetrate the skin/tissue to a depth d1, for example, to prevent unwanted contact with the patient's muscle, bone, organs, etc., which may be located at an additional depth d2. In some cases, the unit may comprise a sensor that performs a subcutaneous inspection, for example, by means of an optical system that emits infrared waves (or other wavelengths) into the patient's body at an identified treatment site and receives reflected waves. If the optical system identifies an unwanted structure located at the delivery depth of the cannula 216 and/or the needle 214, the delivery system may be deactivated. This can be achieved in various ways, for example, by blocking the opening through which the cannula 216 and/or the needle 214 are delivered. According to other embodiments, the depth of penetration control unit 247 can deliver the needle 214 and/or the cannula 216 further into the tissue to the desired position and/or retract the needle 214 and/or the cannula 216 back to the desired position. According to some embodiments, the adjustment of the position of the needle 214 and/or the cannula 216 can be controlled automatically (for example, by the control unit 116 or the controller of the cannula insertion mechanism 200). According to other embodiments, manual adjustment can be used, in which the user can manually adjust the position of the needle 214 and/or the cannula 216 (for example, by controlling the cannula insertion mechanism 200 and/or the delivery of needles 214 and/or cannulas 216 having different lengths).

[222] As noted above, the patient may receive a signal (e.g., a visual, acoustic, and/or tactile feedback signal) when the drug reservoir 106 is empty or close to empty. At this point, the patient may remove the device 100 (e.g., disconnect the self-contained pump from the belt and infusion sets 192, remove the patch pump from the skin surface, etc.), separate the disposable portion 102 from the reusable portion 104, dispose of the disposable portion 102, attach the reusable portion 104 to a new disposable portion 102, and repeat the filling and delivery process described above.

[223] FIG. 32 is a flow chart showing exemplary daily steps 300 that may be performed by patients using the device 100. At step 302, the patient may prepare new parts to be used (e.g., a disposable part (including an attached vial adapter) and a vial). At step 304, the patient may remove the device used on the previous day from the skin (e.g., remove an adhesive layer from the skin). At step 306, the patient may separate the reusable part from the previous disposable part and dispose of the previous disposable part. At step 308, the patient may attach the reusable part to the new disposable part (including the attached vial adapter) and place the assembled device in the filling station. At step 310, the patient may insert a new vial into the vial adapter. At step 312, the patient may initiate the filling process by entering instructions to the filling station and/or the computing device. In step 314, after the filling process is complete, the patient may remove the device from the filling station and separate the vial adapter and vial from the device and dispose of the vial adapter and vial. In step 316, the patient may locate a new insertion site and clean it (e.g., wipe with alcohol). In step 318, the patient may remove the insert from the adhesive part and place the device on the cleaned insertion site. In step 320, the patient may attach the cannula insertion mechanism to the device and activate the cannula insertion mechanism (e.g., by pressing a button). In step 322, the patient may remove the cannula insertion mechanism from the device and dispose of it. In step 324, the patient may initiate the delivery process (e.g., by pressing a button on the device). After the drug reservoir is emptied, steps 300 may be repeated. According to some embodiments, some or all of the above steps 300 may be performed by a person other than the patient (e.g., a caregiver, a physician, etc.). It should be noted that the above steps 300 are given only as an example; in other embodiments, some of the above steps are not performed, but other steps are performed.

[224] FIG. 33 is a table showing minimum, maximum, and nominal values of certain parameters related to the configuration and operation of device 100, according to some embodiments. Each value between the minimum value and the maximum value for each parameter shown in FIG. 33 (not just the nominal value) is considered as provided and is expressly supported herein up to the number of significant digits indicated in each particular range.

FLOWING DRUGS

[225] Contemplated flowable medicaments, i.e., pharmaceutically acceptable formulations that can be contained in device 100 and/or delivered by device 100, can include compositions that comprise carbidopa, levodopa, carbidopa esters, and/or levodopa esters (e.g., levodopa or a carbidopa phosphoester or alkyl ester). In some embodiments, the formulation is carbidopa, levodopa, or a carbidopa/levodopa formulation that also includes two or more antioxidants, such as: (a) ascorbic acid or a salt thereof (e.g., sodium ascorbate); and (b) another antioxidant, such as cysteine or a cysteine derivative (e.g., L-cysteine or N-acetylcysteine (NAC), glutathione, or diacetylcysteine), or a sulfite (e.g., sodium sulfite). Such pharmaceutically acceptable formulations may comprise: levodopa; carbidopa from about 0.1% to about 6% by weight; arginine or meglumine, or a combination thereof from about 1% to about 25% by weight; and/or at least one o-quinone antioxidant. According to still other embodiments, the formulation comprises: levodopa from about 8% to about 16% (e.g., from about 11% to about 15% or from about 12% to about 14%) by weight; carbidopa from about 1% to about 4% by weight; arginine, meglumine, an o-quinone antioxidant, or any suitable combination thereof from 0.1% to about 40% by weight. In these embodiments, the pharmaceutically acceptable formulation can comprise less than about 10.0 μg/mL, less than about 5.0 μg/mL, less than about 2.50 μg/mL, less than about 1.0 μg/mL, less than about 0.75 μg/mL, less than about 0.5 μg/mL, less than about 0.25 μg/mL, less than about 0.1 μg/mL, less than about 0.05 μg/mL, or less than about 0.025 μg/mL of hydrazine, for example, as determined by gas chromatography mass spectrometry (GCMS). In particular embodiments, the composition contains less than about 0.1 μg/mL hydrazine, or less than about 0.05 μg/mL hydrazine, or from about 0.1 μg/mL to about 0.5 μg/mL hydrazine, for example, as determined by a GCMS method.

[226] The disclosed liquid medicaments may include an o-quinone antioxidant selected from the group consisting of: ascorbic acid and/or its salt, L-cysteine, N-acetylcysteine (NAC), glutathione, diacetylcystine and/or its salt, and a combination thereof. The composition may also include ascorbic acid or its salt from about 0.1% to about 10% by weight and a component selected from the group consisting of about N-acetylcysteine (NAC) from 0.01% to about 1% by weight, L-cysteine from about 0.01% to about 1% by weight, glutathione from about 0.001% to about 1% by weight, diacetylcystine or its salt from about 0.001% to about 1% by weight, or any combination thereof.

[227] According to still other embodiments, the pharmaceutically acceptable liquid formulation comprises: (a) carbidopa (e.g., from about 0.1% to about 10% carbidopa); (b) ascorbic acid or a salt thereof; and (c) one of L-cysteine, N-acetylcysteine (NAC), glutathione, and diacetylcysteine, or salts thereof. The formulation, for example, can include less than about 10.0 μg/mL, less than about 5.0 μg/mL, less than about 2.50 μg/mL, 1.0 μg/mL, less than 0.75 μg/mL, less than 0.5 μg/mL, less than 0.25 μg/mL, less than 0.1 μg/mL, less than 0.05 μg/mL, or less than 0.025 μg/mL of hydrazine, for example, as determined by a GCMS method. In particular embodiments, the formulation comprises less than about 0.1 μg/mL hydrazine, less than about 0.05 μg/mL hydrazine, or from about 0.1 μg/mL to about 0.5 μg/mL hydrazine, for example, as determined by a GCMS method. The composition may include from about 0.1% to 10% (e.g., from about 0.3% to about 2%, about 0.5%, from about 1.0% to about 1.3%, about 1.2%, or about 1.3%) by weight of ascorbic acid. The composition may include from about 0.01% to about 1% (e.g., from about 0.1% to about 0.6%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, or about 0.8%) by weight of L-cysteine or a salt thereof. The composition may comprise from about 0.1% to about 10% (e.g., from about 0.1% to about 6%, from about 0.1% to about 4%, from about 0.6% to about 1.4%, from about 1.2% to about 4%, about 0.75%, about 1.4%, about 3%, or about 3.3%) by weight of carbidopa. The composition may comprise from about 0.1% to about 10% (e.g., from about 0.4% to about 0.6%, from about 0.4% to about 1%, about 0.5%, or about 1.2%) by weight of ascorbic acid or a salt thereof. The composition may include from about 0.01% to about 1% (e.g., from about 0.1% to about 1%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, or about 0.8%) by weight of L-cysteine or N-acetylcysteine (NAC). The composition may include, for example, less than about 4% (e.g., less than about 2%, less than about 1%, less than about 0.5%, less than about 0.1%, less than about 0.05%, or less than about 0.01%) by weight of levodopa, or may not include levodopa. In some embodiments, the formulation comprises levodopa (e.g., from about 2% to about 16%, from about 2% to about 8%, from about 8% to about 16%, about 6%, from about 12% to about 15%, from about 2% to about 16%, about 12%, or about 13% by weight levodopa). The formulation may also comprise arginine, meglumine, or a combination thereof, such as from about 0.1% to about 40%, from about 1% to about 25%, from about 10% to about 25%, from about 12% to about 40%, from about 32% to about 42%, or from about 15% to about 16% by weight arginine, meglumine, or any suitable combination thereof.

Components Quantity according to examples Quantity according to examples Levodopa 0-16% 5-7% Carbidopa 0.1-6% 0.6-1.5% Arginine 0.1-40% 14-16% Ascorbic acid or sodium ascorbate 0.1-10% 0.3-0.7% L-cysteine or N-acetylcysteine (NAC), or glutathione 0.01-1% 0.3-0.5%

[228] In particular embodiments, the formulation comprises from about 2% to about 8% by weight levodopa, from about 0.1% to about 3% by weight carbidopa, from about 10% to about 25% by weight arginine, from about 0.1% to about 10% (e.g., from about 0.3% to about 2%) by weight ascorbic acid or a salt thereof, and from about 0.001% to about 5% by weight L-cysteine or a salt thereof. In yet other embodiments, the formulation comprises: from about 8% to about 16% by weight levodopa; from about 1% to about 4% by weight carbidopa; from about 12% to about 40% by weight of a component selected from the group consisting of arginine or meglumine, or a combination thereof; from about 0.1% to about 10% by weight of ascorbic acid or a salt thereof; from about 0.001% to about 1% by weight of L-cysteine or a salt thereof, or any combination thereof. According to these embodiments, the composition has less than about 0.5 or 0.1 μg/mL hydrazine (e.g., less than about 0.05 μg/mL or less than about 0.01 μg/mL hydrazine), as determined by GCMS.

[229] The composition may include the components listed in the following tables:

Components Quantity according to examples Quantity according to examples Levodopa 4-8% 5-7% Carbidopa 0.5-2% 0.6-1.5% Arginine 13-18% 14-16% Ascorbic acid 0.1-2% 0.3-0.7% L-cysteine, HCl-cysteine and/or N-acetyl cysteine 0.1-2% 0.3-0.5%

Components Quantity according to examples Quantity according to examples Levodopa 10-15% 12-15% Carbidopa 1.2-4% 2-4% Arginine/meglumine or combination of the above 25-40% 30-38% Ascorbic acid or sodium ascorbate 0.1-2% 0.3-0.7% L-cysteine or HCl-cysteine 0.1-1% 0.2-0.5%

[230] In yet other specific embodiments, the formulation comprises from about 2% to about 8% by weight levodopa, from about 0.1% to about 3% by weight carbidopa, from about 10% to about 25% by weight arginine, from about 0.1% to about 10% by weight ascorbic acid or a salt thereof, and from about 0.001% to about 5% by weight N-acetylcysteine (NAC). In yet other embodiments, the formulation comprises: from about 8% to about 16% by weight levodopa; from about 1% to about 4% by weight carbidopa; from about 12% to about 40% by weight of a component selected from the group consisting of arginine or meglumine, or a combination thereof; from about 0.1% to about 10% by weight ascorbic acid or a salt thereof; from about 0.001% to about 1% by weight of N-acetylcysteine (NAC), or any combination thereof. In these embodiments, the formulation comprises less than about 0.5 μg/mL or less than about 0.1 μg/mL of hydrazine (e.g., less than 0.05 μg/mL or less than about 0.01 μg/mL of hydrazine), as determined by a GCMS method. The formulation may include components as shown in the following tables:

Components Quantity according to examples Quantity according to examples Levodopa 4-8% 5-7% Carbidopa 0.5-2% 0.6-1.5% Arginine 13-18% 14-16% Ascorbic acid 0.1-2% 0.3-0.7% N-acetylcysteine (NAC) 0.1-2% 0.3-0.5%

Components quantity according to examples quantity according to examples Levodopa 10-15% 12-15% Carbidopa 1.2-4% 2-4% Arginine/meglumine or combination of the above 25-40% 30-38% Ascorbic acid or sodium ascorbate 0.1-2% 0.3-0.7% N-acetylcysteine (NAC) 0.1-1% 0.2-0.5%

[231] In particular embodiments, the formulation comprises from about 2% to about 8% by weight levodopa, from about 0.1% to about 3% by weight carbidopa, from about 10% to about 25% by weight arginine, from about 0.1% to about 10% by weight ascorbic acid or a salt thereof, and from about 0.001% to about 5% by weight glutathione. In yet other embodiments, the formulation comprises: from about 8% to about 16% by weight levodopa; from about 1% to about 4% by weight carbidopa; from about 12% to about 40% by weight of a component selected from the group consisting of arginine or meglumine, or a combination thereof; from about 0.1% to about 10% by weight ascorbic acid or a salt thereof; from about 0.001% to about 1% by weight glutathione, or any combination thereof. In these embodiments, the composition comprises, for example, less than about 0.5 μg/mL or less than about 0.1 μg/mL hydrazine (e.g., less than about 0.05 μg/mL or less than about 0.01 μg/mL hydrazine), as determined by a GCMS method. The composition may include the components shown in the following tables:

Components Quantity according to examples Quantity according to examples Levodopa 4-8% 5-7% Carbidopa 0.5-2% 0.6-1.5% Arginine 13-18% 14-16% Ascorbic acid 0.1-2% 0.3-0.7% Glutathione 0.1-2% 0.3-0.5%

Components Quantity according to examples Quantity according to examples Levodopa 10-15% 12-15% Carbidopa 1.2-4% 2-4% Arginine/meglumine or combination of the above 25-40% 30-38% Ascorbic acid or sodium ascorbate 0.1-2% 0.3-0.7% Glutathione 0.1-1% 0.2-0.5%

[232] In particular embodiments, the formulation comprises from about 2% to about 8% by weight levodopa, from about 0.1% to about 3% by weight carbidopa, from about 10% to about 25% by weight arginine, from about 0.1% to about 10% by weight ascorbic acid or a salt thereof, and from about 0.001% to about 5% by weight diacetylcystine or a salt thereof. In yet other embodiments, the formulation comprises: from about 8% to about 16% by weight levodopa; from about 1% to about 4% by weight carbidopa; from about 12% to about 40% by weight of a component selected from the group consisting of arginine or meglumine, or a combination thereof; from about 0.1% to about 10% by weight ascorbic acid and/or a salt thereof; from about 0.001% to about 1% by weight of diacetylcystine or a salt thereof, or any combination thereof. In these embodiments, the formulation comprises, for example, less than about 0.5 μg/mL or less than about 0.1 μg/mL hydrazine (e.g., less than 0.05 μg/mL or less than 0.01 μg/mL hydrazine), as determined by a GCMS method. The formulation may include the components presented in the following tables:

Components Quantity according to examples Quantity according to examples Levodopa 4-8% 5-7% Carbidopa 0.5-2% 0.6-1.5% Arginine 13-18% 14-16% Ascorbic acid 0.1-2% 0.3-0.7% Diacetylcystine 0.1-2% 0.3-0.5%

Components Quantity according to examples Quantity according to examples Levodopa 10-15% 12-15% Carbidopa 1.2-4% 2-4% Arginine/meglumine or combination of the above 25-40% 30-38% Ascorbic acid or sodium ascorbate 0.1-2% 0.3-0.7% Diacetylcystine 0.1-1% 0.2-0.5%

[233] The composition of any of the above embodiments may include a surfactant. The surfactant may be any one of polysorbate 20, 40, 60, or 80, or any combination thereof. In particular embodiments, the composition includes from about 0.01% to about 5% of the surfactant (e.g., polysorbate 80) or from about 0.1% to 0.5% of the surfactant (e.g., polysorbate 80). In yet other particular embodiments, the composition includes about 0.3% of the surfactant (e.g., polysorbate 80).

[234] The composition of any of the above embodiments may comprise from about 11% to about 15% by weight levodopa. For example, the composition may comprise from about 12% to about 14% by weight levodopa (e.g., about 12% or about 13.2% levodopa).

[235] The composition of any of the above embodiments may comprise from about 0.6% to about 4%, from about 0.8% to about 3%, or from about 1.2% to about 4% by weight of carbidopa. For example, the composition may comprise from about 2.5% to about 3.5% (e.g., about 3.0% or about 3.3%) by weight of carbidopa.

[236] The composition of any of the above embodiments may include from about 25% to about 40% (e.g., from about 32% to about 40%, about 32%, or about 36%) by weight of a component selected from the group consisting of arginine or meglumine, or a combination thereof. For example, the composition may include about 32% arginine, about 32% meglumine, about 36% arginine, or about 36% meglumine.

[237] The composition of any of the above embodiments, after storage for: 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 20, or 24 hours; 1, 2, 3, 5, 7, 10, 14, 21, 28, or 30 days; 1, 2, 3, 4, 6, 9, or 12 months; or 1, 1.5, 2, 2, 5, or 3 years at 25°C, 2-8°C, or -20°C, contains less than about 0.1 μg/mL hydrazine, as determined by GCMS. The composition of any of the above embodiments may contain less than about 5% (e.g., less than about 4%, 3%, 2%, 1%, 0.5%, 0.3%, 0.2%, 0.1%, or 0.05%) by weight of 3,4-dihydroxyphenyl-2-methylpropionic acid (a degradant of RRT 1,4) relative to the amount of carbidopa, as determined by high performance liquid chromatography (HPLC).

[238] The composition of any of the above embodiments may have a dosage form selected from the group consisting of a liquid, gel, cream, solid, film, emulsion, suspension, solution, aerosol (e.g., liquid dosage form), or any combination thereof.

[239] According to some embodiments, the subject liquid medicament has a pharmaceutically acceptable liquid formulation comprising: from about 4% to about 8% (e.g., about 6%) by weight levodopa, from about 0.1% to about 1.5% (e.g., from about 0.6% to about 1.4%, about 0.75%, or about 1.4%) by weight carbidopa, from about 10% to about 20% (e.g., from about 15% to about 16%, about 15.2%, or about 15.6%) by weight arginine, and from about 0.1% to about 1.5% (e.g., from about 0.4% to about 1%, from about 0.4% to about 0.6%, or about 0.5%) by weight ascorbic acid or a salt thereof. In such embodiments, the formulation, after 1 day at 25°C, after 30 days at 25°C, or after 180 days at 25°C, comprises less than about 1.0 μg/mL, less than about 0.75 μg/mL, less than about 0.5 μg/mL, less than about 0.2 μg/mL, less than about 0.1 μg/mL, or less than about 0.05 μg/mL hydrazine, as determined by GCMS. The formulation may further comprise from about 0.1% to about 0.7% (e.g., about 0.4% or about 0.5%) by weight of L-cysteine or N-acetylcysteine (NAC). According to a specific embodiment, the composition comprises: (a) from about 0.4% to about 0.6% or from about 0.4% to about 1% by weight of ascorbic acid or a salt thereof; and (b) from about 0.1% to about 0.7% by weight of L-cysteine or N-acetylcysteine (NAC). In this aspect, the composition may also comprise from about 0.1% to about 0.5% (e.g., about 0.3%) by weight of Tween-80 polysorbate.

[240] In some embodiments, the liquid medicament has a pharmaceutically acceptable liquid formulation comprising: from about 8% to about 16% (such as from about 12% to about 15%, about 12%, or about 13.2%) by weight of levodopa; from about 1% to about 4% (such as about 3.0% or about 3.3%) by weight of carbidopa; from about 20% to about 42% (such as from about 32% to about 42%, about 32%, or about 36%) by weight of a component selected from the group consisting of arginine or meglumine, or a combination thereof; from about 0.1% to about 1.5% (e.g., from about 1.0% to about 1.4%, about 1.2%, or about 1.3%) by weight of ascorbic acid or a salt thereof (e.g., sodium ascorbate), wherein, for example, the specified composition after: 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 20, or 24 hours; 1, 2, 3, 5, 7, 10, 14, 21, 28, or 30 days; 1, 2, 3, 4, 6, 9, or 12 months; or 1; 1.5; 2; 2.5 or 3 years at 25°C contains less than about 1.0 μg/mL, less than about 0.75 μg/mL, less than about 0.5 μg/mL, less than about 0.2 μg/mL, less than about 0.1 μg/mL, or less than about 0.05 μg/mL hydrazine, as determined by GCMS. The formulation may also include from about 0.1% to about 1% (e.g., from about 0.1% to about 0.5%, about 0.3%, or about 0.5%) L-cysteine or a salt thereof (e.g., HCl-cysteine) or N-acetylcysteine (NAC). According to a specific embodiment, the composition comprises from about 0.1% to about 0.5% L-cysteine or N-acetylcysteine (NAC) and from about 1.0 to about 1.4% by weight of ascorbic acid or a salt thereof, or any combination thereof.

[241] In some embodiments, the liquid formulation may comprise from about 0.1% to about 10% carbidopa, such as from about 0.5% to about 8%, from about 0.6% to about 5%, from about 0.1% to about 1%, from about 1% to about 2%, such as about 0.75%, about 1.4%, or about 4% carbidopa. For example, the disclosed formulation may comprise from about 1% to about 3% by weight, from about 2.5% to about 3.5% by weight, from about 0.6% to about 4% by weight, or from about 1.2% to about 4% by weight carbidopa. In some embodiments, the disclosed compositions comprise from about 0.01% to about 6% by weight of carbidopa, from about 0.1% to about 6% by weight of carbidopa, or from about 1% to about 4% by weight of carbidopa, such as from about 0.6% to about 4% or from about 1.2% to about 3% or about 4% by weight of carbidopa. In some embodiments, the composition may include arginine and/or meglumine or salts thereof, or any combination thereof. For example, the above-described formulation may comprise from about 0.1% to about 42%, such as from about 1% to about 10%, from about 12% to about 18%, from about 0.1% to about 40%, from about 2% to about 7%, about 3.2%, about 3.4%, about 3.6%, about 3.7%, or about 4.6% arginine and/or meglumine or a salt thereof, or any combination thereof. According to still other embodiments, the disclosed formulations comprise from about 10% to about 20%, from about 10% to about 25%, from about 12% to about 18%, about 12.8%, about 14.8%, about 15.2%, about 15.5%, or about 18.5% arginine and/or meglumine or a salt thereof, or any combination thereof. In some embodiments, arginine, meglumine, salts thereof, or any combination thereof are present in an amount of from about 25% to about 40%, from about 30% to about 38%, about 32%, or about 36%.

[242] The formulations may include levodopa. For example, in some embodiments, the formulation includes from about 1% to about 20% levodopa, such as from about 2% to about 8%, from about 4% to about 7%, about 5%, or about 6% levodopa. In yet other embodiments, the formulations include from about 8% to about 20%, from about 8% to about 16%, from about 10% to about 14%, from about 11% to about 14%, about 12%, or about 13.2% levodopa. The disclosed formulation may have a molar ratio of carbidopa to arginine (or meglumine) of from about 1:1 to about 1:25, or from about 1:1 to about 1:35.

[243] The compositions may include one, two or more antioxidants or o-quinone antioxidants. For example, the disclosed composition may include one, two or more agents each independently selected from the group consisting of ascorbic acid, its salts (e.g., sodium ascorbate, calcium ascorbate, potassium ascorbate, ascorbyl palmitate or ascorbyl stearate, in particular sodium ascorbate), cysteine or cysteine derivatives (e.g., L-cysteine, N-acetylcysteine (NAC), glutathione, diacetylcystine, S-methyl-N-acetylcysteine amide, acetyl derivative of S-methyl-N-acetylcysteine methylhydrazide, S-methylcysteine morpholinamide, S-methyl-N-acetylcysteine morpholinamide or salts thereof), or any suitable combination thereof. For example, the composition described may include ascorbic acid or a salt thereof and a cysteine derivative such as N-acetylcysteine (NAC).

[244] Formulations may include other antioxidants such as di-tert-butyl methyl phenols, tert-butyl methoxyphenols, polyphenols, tocopherols, and ubiquinones (eg, caffeic acid).

[245] The formulations may also include a tyrosinase inhibitor. Exemplary tyrosinase inhibitors include captopril, methimazole, quercetin, arbutin, aloesin, N-acetylglucosamine, retinoic acid, α-tocopheryl ferulate, magnesium ascorbyl phosphate (MAP), substrate analogs (e.g., sodium benzoate, L-phenylalanine), and C ⁺⁺ chelators (e.g., _Na2- EDTA, Na2 _- EDTA-Ca, dimercaptosuccinic acid (DMSA) (succimer), DPA (D-penicillamine), trientine HCl, dimercaprol, clioquinol, sodium thiosulfate, triethylenetetramine (TETA), tetraethylenepentamine (TEPA), curcumin, neocuprein, tannin, and cuprizone).

[246] The compositions may include ascorbic acid or a salt thereof (e.g., sodium ascorbate). For example, the disclosed compositions may include from 0.1% to about 10% or more ascorbic acid (or a salt thereof), or from about 0.1% to about 2%, such as from about 0.2% to about 1.5%, from about 0.2% to about 2.0%, from about 0.2% to about 2.5%, from about 0.3% to about 1.2%, such as about 0.4%, about 0.5%, about 0.75%, about 0.85%, or about 1.0% by weight of ascorbic acid. For example, the disclosed composition may include from about 0.8% to about 1.3% or from about 1% to about 2.5% by weight of ascorbic acid or a salt thereof. According to a specific embodiment, the described composition may include from about 0.5% to about 0.85%, or, for example, about 0.5%, about 0.75%, about 0.85%, about 1.0%, about 1.2%, or about 1.3% by weight of sodium ascorbate or ascorbic acid.

[247] In particular embodiments, the formulations may include a bisulfite, such as sodium bisulfite or one or more other sulfite salts, such as sodium hydrogen sulfite or sodium metabisulfite. In some embodiments, the formulations may include, for example, N-acetylcysteine (NAC), L-cysteine, diacetylcystine, and/or glutathione. In particular embodiments, the formulations include from about 0.001% to about 5%, from about 0.01% to about 5%, from about 0.1% to about 5%, from about 0.001% to about 1%, from about 0.01% to about 1%, or from about 0.1% to about 1% by weight of each of N-acetylcysteine (NAC), L-cysteine, diacetylcystine, and/or glutathione. For example, the disclosed composition may comprise from about 0.01% to about 5%, such as from about 0.05% to about 1%, from about 0.1% to about 0.6%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, or about 0.5% N-acetylcysteine (NAC) and/or L-cysteine. In a particular embodiment, the disclosed composition comprises about 0.4% or about 0.5% N-acetylcysteine (NAC). In another particular embodiment, the disclosed composition comprises about 0.3%, about 0.4%, or about 0.5% L-cysteine.

[248] For example, the composition may include ascorbic acid (or a salt thereof) and a cysteine derivative, such as L-cysteine and/or N-acetylcysteine (NAC). In an exemplary embodiment, the disclosed composition includes from about 0.1% to about 10% ascorbic acid (or a salt thereof) and from about 0.001% to about 5% or from about 0.001% to about 1% by weight of each of L-cysteine and/or N-acetylcysteine (NAC) and/or diacetylcystine and/or glutathione. According to specific embodiments, the composition comprises ascorbic acid and L-cysteine, sodium ascorbate and N-acetylcysteine (NAC), ascorbic acid and N-acetylcysteine (NAC), sodium ascorbate and L-cysteine, ascorbic acid and diacetylcystine, sodium ascorbate and diacetylcystine, ascorbic acid and glutathione, or sodium ascorbate and glutathione.

[249] The compositions disclosed are liquids and may include a surfactant. For example, the composition disclosed may comprise Polysorbate-20, -40, -60, or -80 in an amount of, for example, from about 0.01% to about 5%, from about 0.1% to about 0.5%, for example, about 0.3% Polysorbate-20, -40, -60, and/or -80. In particular embodiments, Polysorbate-80 is present in an amount of about 0.3%.

[250] Such compositions or solutions may have a pH that is pharmaceutically acceptable for subcutaneous administration, such as a pH of from about 8 to about 10, such as from about 9.1 to about 9.8, such as from 9.2 to 9.6 at a temperature of 25°C.

[251] According to specific embodiments, the liquid medicinal product is one of those presented in Tables 1 and 2.

Table 1 DS (%) Levodopa Carbidopa Arginine Ascorbic acid L-cysteine NAC Tween-80 pH 1 6 1.4 15.5 0.5 0.4 - 0.3 9.4-9.6 2 6 1.4 15.5 0.5 - 0.5 0.3 9.4-9.6 3 6 0.75 15.2 0.5 0.4 - 0.3 9.4-9.6 4 6 0.75 15.2 0.5 - 0.5 0.3 9.4-9.6 Limits 6 0.6-1.4 15-16 0.5 0.4 0.5 0.3 9.4-9.6

Table 2 DS (%) Levodopa Carbidopa Arginine Meglumine Sodium ascorbate L-Cysteine NAC HCl-Cysteine Tween-
80 pH 1 12 3 32 - 1,2 0.3 - - - 9.6-9.8 2 13.2 3.3 36 - 1.3 0.3 - - - 9.6-9.8 3 13.2 3.3 - 36 1.3 0.3 - - - 9.6-9.8 4 12 3 - 32 1,2 - 0.3 - - 9.6-9.8 5 12 3 32 - 1,2 - 0.3 - - 9.6-9.8 12-15 1,2-4 32-42 32-42 1.0-1.3 0.1-0.5 ≤2 9.6-9.8 * **

* Can replace L-cysteine.

** If necessary, add to stabilize the composition.

[252] In other embodiments, the flowable drug may comprise apomorphine and an organic acid or amino acid. As used herein, the term "organic acid" refers to an organic compound with acidic properties, such as carboxylic acids, dicarboxylic acids, sulfonic acids, alcohols, hydroxy acids, thiols, and thio acids. For example, organic acids for use in the formulation may contain at least two, at least three, or at least four carbon atoms, such as tartaric acid. Examples of organic acids include, but are not limited to, amino acids such as aspartic acid, glutamic acid, and arginine, and dicarboxylic acids such as fumaric acid, oxalic acid, malonic acid, succinic acid, glutaric acid, maleic acid, and the like. Additional examples of organic acids include lactic acid, malic acid, aconitic acid, citric acid, alicolic acid, ascorbic acid, formic acid, acetic acid, tartaric acid, and glucuronic acid. Examples of organic acids include, but are not limited to, amino acids, carboxylic acids, and dicarboxylic acids. For example, carboxylic acids and/or dicarboxylic acids proposed for use in the composition may contain at least two, at least three, or at least four carbon atoms, such as tartaric acid. Dicarboxylic acids proposed for use in the claimed compositions may be hydrophilic or substituted with hydrophilic groups, such as hydroxyl groups. The amino acids proposed for use in the claimed compositions may be, without limitation, acidic natural amino acids such as aspartic acid or glutamic acid, or acidic non-naturally occurring amino acids such as cysteine acid. The term "naturally occurring amino acid" refers to any of the amino acids found in proteins. Examples of natural amino acids include, but are not limited to, alanine, arginine, aspartic acid, glutamic acid, histidine, lysine, etc. The term "non-naturally occurring amino acid" refers to non-proteinogenic amino acids that are either naturally occurring or chemically synthesized. Examples of non-naturally occurring amino acids include, but are not limited to, ornithine, β-alanine, 2-aminoadipic acid, 3-aminoadipic acid, y-carboxyglutamic acid, hydroxylysine, 4-guanidinobutyric acid, 3-guanidinopropionic acid, 4-azidobutyric acid, 5-azidopentanoic acid, and the like. Both D-amino acids and L-amino acids are contemplated as being suitable for use herein.

[253] In some embodiments, the liquid medicament also comprises a local anesthetic, i.e., a medicament that causes reversible loss of sensation in a localized area of the body while maintaining consciousness, and/or an anti-inflammatory agent. Examples of local anesthetics include, but are not limited to, amide-based local anesthetics such as lidocaine, prilocaine, bupivacaine, levobupivacaine, ropivacaine, mepivacaine, dibucaine, and etidocaine, and ester-based local anesthetics such as novocaine, ametocaine, cocaine, benzocaine, and tetracaine. Examples of anti-inflammatory agents include, but are not limited to, non-steroidal anti-inflammatory agents such as diclofenac, ketorolac, salicylate esters, ibuprofen, piroxicam, and benzydamine, and steroidal anti-inflammatory agents such as prednisone, dexamethasone, betamethasone, hydrocortisone, prednisone, and their salts.

[254] The pharmaceutical composition may be a liquid solution, i.e. a substantially homogeneous liquid mixture at room temperature, for example 25°C, or a semi-solid solution in the form of, for example, a gel, chewing gum or lozenge. Such liquid or semi-solid mixtures may contain water and/or other pharmaceutically acceptable carriers and/or excipients. According to a particular embodiment, the composition described is substantially aqueous.

[255] Each numerical value recited herein is considered to represent a minimum value or a maximum value within a range of values of the corresponding parameter. Accordingly, when used in the appended claims, a numerical value provides express support for the stated range, which may lie above or below the stated numerical value, in accordance with the descriptions provided herein. Each value between the minimum value and the maximum value within each numerical range presented herein (including the table shown in FIG. 33) is considered and expressly supported herein by taking into account the number of significant digits stated in each specific range.

[256] As briefly indicated herein, the device may comprise a first fluid sensor for detecting one or more characteristics of the fluid drug. The one or more characteristics may be monitored continuously. Such characteristics may include, for example, a chemical characteristic, an optical characteristic, a biological characteristic, and/or a physical characteristic.

[257] Non-limiting examples of chemical characteristics may include the concentration of an analyte (e.g., the concentration of an active pharmaceutical ingredient (API) such as carbidopa, levodopa, and/or apomorphine), the distribution of the active pharmaceutical ingredient in the drug flow, the state of aggregation of the active pharmaceutical ingredient and/or the drug flow, a state map of the API and/or the drug flow, and/or a pH value.

[258] Non-limiting examples of physical characteristics may include mass, volume, electrical conductivity, temperature, density, color, reflectivity, transparency, viscosity, fluid type, and/or thermal conductivity. Physical characteristics may also be measured to determine whether a fluid drug received in a drug reservoir contains gas bubbles.

[259] According to some embodiments, the fluid sensor may comprise an optical sensor configured to measure a characteristic of the fluid and/or associated with the fluid. The characteristics associated with the fluid contained in the drug reservoir may be measured using methods that are based on continuous, discrete, transmissive and/or reflective measurement technologies.

[260] The optical sensor may measure or determine a characteristic of the fluid based on one or more characteristics of light detected by one or more photodetectors of the fluid sensor. Such a characteristic of light may be, for example, the wavelength of the light, the amplitude, the polarization, the phase difference, or any combination thereof. The detection of light may include methods based on transmission and/or reflection.

[261] If necessary, the amount of fluid in the drug reservoir 106 can be determined based on the level and/or volume of fluid in the drug reservoir 106. The fluid sensor can be configured to continuously or intermittently measure the amount of fluid in the drug reservoir.

[262] As shown in FIG. 34A, the fluid sensor may include, for example, a device 3100 for determining the amount of liquid. The device 3100 for determining the amount of liquid may comprise a radiation source 3102 (e.g., an emitter) configured to emit light, a detector 3104 configured to recognize light, a memory device 3106, a processor 3108, and a power supply 3110 (e.g., a power source such as a battery) for supplying energy to various components of the device 3100 for determining the amount of liquid.

[263] According to some embodiments, the device 3100 for determining the amount of fluid may be configured to continuously or intermittently measure the amount of fluid in the drug reservoir. If necessary, the measurement of the amount of fluid may be based on transmission, reflection, or both. If necessary, the amount of fluid in the drug reservoir may be determined based on the level and/or volume of fluid in the drug reservoir. According to some embodiments, the measurement of the volume of the agent in the drug reservoir may be measured by determining the time of flight (TOF) of emitted light in the drug reservoir and/or measuring the attenuation of light propagating through the drug reservoir 106.

[264] The configurations described below herein with reference to FIGS. 34B-34G may be considered to provide a method for continuously measuring the amount of liquid in the drug reservoir 106 based on one or more characteristics of light detected by one or more detectors of the arrangement(s).

[265] As shown in FIG. 34B, the radiation source 3102 according to one embodiment may be located on the underside of the plunger head 120 or integrated into it, and the detector 3104 may be located opposite the radiation source 3102 such that the light 500A emitted by the radiation source 3102 propagates from the plunger head 120 in a direction toward the distal end of the reservoir 106 containing the detector 3104 positioned to detect the light 500A. According to one embodiment, FIG. 34B schematically illustrates a method for measuring the amount of liquid that is based on the transmission of light. The direction of displacement of the plunger 120 from the proximal end to the distal end of the reservoir 106 (or vice versa) is schematically indicated in the drawing by a double-headed arrow P.

[266] As shown in FIG. 34C, the radiation source 3102, according to some embodiments, may be located at the distal end of the reservoir 106 for the drug, and the detector 3104 may be located on the underside of the plunger head 120 or integrated therein in such a way that the light 500A emitted by the radiation source 3102 propagates from the distal end of the reservoir 106 in a direction toward the plunger head 120 containing the detector 3104 positioned to detect the reflected light 500B. The example shown in FIG. 34C schematically illustrates, in analogy with FIG. 34B, a method for measuring the amount of liquid that is based on the transmission of light.

[267] As shown in FIG. 34D, both the radiation source 3102 and the detector 3104, according to some embodiments, may be located on the underside of the plunger head 120 or embedded therein such that the reflected light 500B, which is generated in response to the radially transmitted light 500A from the plunger head 120 into the distal end of the reservoir 106, is detected by the detector 3104. The arrangement in FIG. 34D shows an exemplary method for measuring the amount of liquid based on the reflection of light.

[268] Also, as shown in FIG. 34E, the drug reservoir 106 may further comprise a second detector 3105 located at the distal end of the reservoir 106 and configured to detect light 500A emitted by the radiation source 3102 in a direction toward the distal end of the reservoir 106. The arrangement shown in FIG. 34E shows an exemplary method for measuring the amount of liquid contained in the reservoir 106 based on the transmission and reflection of light.

[269] As shown in FIG. 34F and 34G, the arrangement shown in FIG. 34D and 34E can be reversed. FIG. 34F schematically shows that the radiation source 3102 and the first detector 3104, according to some embodiments, can be located at the distal end of the drug reservoir 106 such that the reflected light 500B generated in response to the emitted light 500A and passing from the distal end in the direction of the plunger head 120 is detected by the detector 3104. Thus, the arrangement shown in FIG. 34F shows a reflection-based method for measuring the amount of liquid contained in the drug reservoir 106.

[270] The arrangement shown in FIG. 34G may further include a second detector 3105 located on the underside of the plunger head 120 or embedded therein such that light 500A emitted from the distal end of the reservoir 106 toward the plunger head 120 is detected by the second detector 3105.

[271] Thus, the arrangement shown in FIG. 34G represents examples of a method for measuring the amount of liquid contained in the drug reservoir 106, both based on reflection and based on transmission.

[272] In some embodiments, the radiation source and detector shown in FIGS. 34D-34F are located in identical positions. In some embodiments, a plurality of radiation sources may be located around the detector, or vice versa.

[273] As described above herein, the configurations schematically shown in FIGS. 34B-34G are considered to provide a method for continuously measuring the amount of liquid in the drug reservoir 106 based on one or more characteristics of light detected by one or more detectors in the described arrangement(s).

[274] The configurations described below in this document with reference to FIGS. 34H-34I are considered to implement methods for intermittently measuring the amount of liquid contained in the reservoir 106. For example, a plurality of radiation sources 3112 can be arranged on a cylindrical shell or curved body of the reservoir 106 for a drug in a row extending from the bottom of the reservoir to the top, at different heights h _i of the reservoir 106. The reservoir 106 can also contain a plurality of detectors 3114 that are arranged on the cylindrical body of the shell of the reservoir 106 in such a way that they can detect light emitted by each of the plurality of radiation sources 3112. For example, the plurality of detectors 3114 can be arranged opposite the plurality of radiation sources 3112 in a row extending from the bottom of the reservoir to the top, facing the light sources 3112.

[275] Each of the light sources 3112 may emit a plurality of light beams 500C from different positions h _i along the drug reservoir 106. The light beam 500Ci propagates through the drug reservoir 106 in a direction that may be substantially perpendicular to the longitudinal axis 137 of the plunger head 120 and impinges on a corresponding detector 3114i. In response to detecting the light 500C impinging on the detectors 3114, the detectors 3114 may generate an output signal that comprises a characteristic of the detected light beam. Such a characteristic may be a change in the intensity of the light beam 500Ci propagating through the reservoir 106 and/or a transit time. The arrangement shown in FIG. 34H, can, for example, provide the ability to generate a function of a height-dependent characteristic of a fluid contained in a reservoir 106. For example, density, color, transmittance and/or the like can be measured as a function of the height of the level of a fluid contained in a reservoir 106 for a drug. According to some embodiments, a plurality of light sources 3112 and/or a plurality of detectors 3114 can be used at a corresponding height h1 above the bottom side of the reservoir 106.

[276] As shown in FIG. 34H, the arrangement shown in FIG. 34I may further include a light source 3102 and a second detector 3105 located, for example, on the lower side of the plunger 120, as well as a first detector 3104 located at the distal end of the drug reservoir 106. Thus, the light sources and detectors shown in FIG. 34I may provide the ability to emit light in the longitudinal and/or radial directions in the drug reservoir 106. Additional or alternative configurations of emitted light in the longitudinal and/or radial directions in the reservoir 106 may be used. If necessary, light can be selectively (e.g., alternatingly) emitted in the longitudinal and radial directions into the drug reservoir 106. For example, during period t1, light 500A may be emitted in the longitudinal direction into reservoir 106, and during a subsequent period t2, light 500C may be emitted in the transverse direction into reservoir 106, etc.

[277] Reference is now made to FIG. 34J. According to some embodiments, an array of light sources 3102 may be located on one side of the drug reservoir 106, and an array of detectors 3104 may be located opposite the array of light sources 3102. In this manner, the characteristics of the light and, accordingly, the characteristics of the fluid may be mapped in a correspondence pattern in a radial direction across the reservoir 106, as schematically shown by arrow R, for example, to determine a value related to the homogeneity and/or heterogeneity of the fluid contained in the drug reservoir 106.

[278] According to some embodiments, the device 4100 for determining the amount of liquid may be configured to determine the amount of liquid in the reservoir 106 based on a measurement of the characteristics of pressure waves propagating in the liquid. FIG. 35 shows a block diagram of the device for determining the amount of liquid. The device 4100 for determining the amount of liquid, for example, may include a mechanical wave generator 4102 (e.g., a transducer) and a mechanical wave receiver 4104, which is configured to measure the characteristics of the mechanical waves generated by the transducer 4102. For example, the transducer 4102 may include an ultrasonic transducer, and the mechanical wave receiver 4104 may include an ultrasonic sensor. According to some embodiments, the transducer 4102 and the mechanical wave receiver 4104 may use the same sensing element. If necessary, microelectromechanical and/or piezoelectric transducers can be used to generate pressure waves in the liquid contained in the reservoir 106 for the drug, for example, to determine values related to the characteristics of the liquid, such as temperature, transparency, turbidity, viscosity and/or the like. For example, a less transparent liquid can indicate an increased level of crystallization. In the case where the measured characteristic indicates that the transparency level of the fluid is below the lower threshold value, the delivery of the fluid drug can be stopped. If necessary, the fluid can be stirred for a predetermined period of time. If necessary, the fluid can be stirred until the transparency level of the fluid exceeds the upper threshold value of transparency.

[279] In some embodiments, the drug reservoir may comprise an automatic control element that operates according to a pre-programmed timing and/or in accordance with the level of clarity of the liquid.

[280] According to some embodiments, the device 100 may comprise a position tracking device (e.g., a position sensor 600), for example, to determine the position (e.g., the penetration length) of the plunger 120 relative to the distal and/or proximal end of the reservoir 106 to obtain, for example, the amount of fluid contained in the reservoir 106 for the drug. The position sensor 600 can count the number of revolutions in either direction of rotation. The most proximal or distal position of the plunger 120 in the reservoir 106 may be the starting point or the end point of the counting of the number of revolutions, for example, of the gear 136 of the load operation for determining the distance of movement of the plunger head 120.

[281] According to some embodiments, the plunger head 120 may include a contact sensor (not shown) located on the lower and/or upper surfaces thereof to enable the determination of when the plunger head 120 interacts or contacts the lower or upper surfaces of the drug reservoir 106.

[282] As shown in FIG. 36, the position tracking device is schematically designated by the position number "600" and is schematically shown as operatively coupled, for example, to the load gear 136, for example, to provide an output signal of the position of the load gear that is indicative of the angular position of the load gear 136. The load gear can be operatively interacting with the nut 124. The angular position of the nut 124 can be determined based on the angular position of the load gear 136. The angular position of the nut 124 can be related to the position of the plunger head 120 in the longitudinal direction in the reservoir 106 for the drug. As a result, the position signal of the load gear provided by the position tracking device 600 can be used to determine the position of the plunger head 120 in the longitudinal direction. Based on the position of the plunger head 120 in the longitudinal direction, the amount of fluid contained in the reservoir 106 for the drug can be determined, for example, by the computing unit 117.

[283] According to some embodiments, the device 100 may use a sensor (not shown) to sense the angular orientation of the plunger head 120 relative to the drug reservoir 106.

[284] As shown in FIG. 37A, the sensor 3700 can be used to determine the amount of fluid in the tank 106 by measuring a change in the electrical characteristic of the sensor 3700. The sensor 3700 can be located inside the tank 106 and extend longitudinally along it parallel to its longitudinal axis, so that the sensor 3700 can make direct contact with the fluid contained in the tank 106. The measurable electrical characteristic of the sensor 3700 can change depending on the amount of overlap between the sensor and the fluid and, if necessary, on the characteristic of the fluid. Such an electrical characteristic can be, for example, capacitance and/or electrical impedance. For example, the measured capacitance of the sensor 3700 may increase with an increase in the level of the fluid in the reservoir 106. According to another embodiment, the capacitance of the sensor 3700 may decrease with a decrease in the level of the fluid in the reservoir 106. According to some embodiments, a portion of the sensor 3700 may extend or extend beyond the reservoir 106 for the drug or may be otherwise located such that said portion does not enter into an operational interaction of recognition with the fluid. Accordingly, the output signal of the recognition of a portion of said fluid may not depend on the amount of fluid contained in the reservoir for the drug. The output signal provided by the extended portion of the sensor may thus serve as an initial value for determining the amount of fluid contained in the reservoir 106 with the fluid.

[285] As shown in FIGS. 37B-37F, the capacitive sensor 3800 may be coupled (e.g., glued and/or otherwise attached) to the support portion 145 of the reusable portion 104 such that when the disposable portion 102 and the reusable portion 104 are operatively coupled to each other, the sensors 3800a and 3800b are positioned opposite the reservoirs 106a and 106b and/or face the said reservoirs such that they provide an output signal indicating the amount of fluid in the reservoirs of the means 106a and 106b. Although the method for capacitively measuring the amount of fluid is described using an example of a device that uses a two-piston arrangement, this should in no way be considered limiting.

[286] In a two-piston arrangement, the reusable portion may have a generally T-shaped configuration, the support portion 145 of which may contain the magnet 140 (see FIGS. 7B-7C) and the sensors 3800a and 3800b, as schematically shown in FIG. 37C. In a single-piston arrangement, the reusable portion 104 may be considered to have a generally L-shaped configuration, the support portion 145 of which may contain the sensor 3800.

[287] As shown in FIGS. 37C and 37D, the sensor 3800 may be configured to bend. A sensor, such as the sensor 3800 shown in the drawing, may be implemented as a flexible printed circuit board (FPCB). If necessary, the support portion 145 may be bent inward or have a concave shape to appropriately approach the rounded surface of the reservoir 106 for a drug. Accordingly, the sensor 3800 may acquire a curved shape when mounted on the support portion 145, for example, the reusable portion 104 in a single- or dual-piston arrangement.

[288] Reference is now made to FIG. 37E, which schematically shows a perspective view of the relative positioning between the drug reservoir 106 and the capacitive fluid amount sensor 3800 configured to measure the amount of fluid in the drug reservoir 106 according to some embodiments; and further to FIG. 37F schematically shows the disposable portion 102 of the device 100 operatively connected to the reusable portion 104, as well as the resulting relative positioning between the capacitive fluid amount sensor 3800 located on the reusable portion 104 and the drug reservoir located in the disposable portion. As shown in FIG. 37F, the capacitive fluid amount sensor 3800 is located outside of both the drug reservoir 106 and the reusable portion 104.

[289] Reference is now made to FIG. 37G, which schematically illustrates a view of the front and back of a capacitive fluid quantity sensor 3800 according to some embodiments. The capacitive fluid quantity sensor 3800 may be configured to provide output sensing signals without requiring the sensor to directly interact with the fluid. In other words, the sensor 3800 may be a non-contact fluid quantity sensor.

[290] The sensor 3800 may comprise a substrate 3802 on which a front input electrode 3812, a front output electrode 3814, and a front reference electrode 3816 are disposed. The front output electrode 3814 may be located between the front input electrode 3812 and the front reference electrode 3816. Similarly, the sensor 3800 may also comprise a rear input electrode 3822, a rear output electrode 3824, and a rear reference electrode 3826. The rear output electrode 3824 is located between the rear input electrode 3812 and the rear reference electrode 3816. The front and rear input electrodes 3812 and 3822 may be disposed opposite each other to form a reference capacitor 3832 with a liquid dielectric (C _RL ); the front and rear output electrodes 3814 and 3824 (for level measurement) can be arranged to form a capacitor 3834 for level measurement (C _level ). In addition, the front and rear reference electrodes 3816 and 3826 can be arranged to form a capacitive ambient sensor that can generate a reference output signal (C _RE ) of the ambient sensor 3836 that characterizes the capacitance of the ambient medium.

[291] According to some other embodiments, as schematically shown in FIG. 37H, two electrodes forming a capacitor may be located next to each other or adjacent on the same surface of the substrate material 3802 and separated from each other by a shielding material 3830. The positional terms "front" and "back" referring to different electrodes may in some cases be replaced by the terms "left" and "right", respectively. The electrodes may be electrically connected to each other to form a plurality of configurations.

[292] Position-related terms such as "upper," "lower," "right," "left," "down," "below," "low," "upper," "above," "raised," "high," "vertical," and "horizontal," and grammatical variations thereof, as may be used herein, do not necessarily indicate that, for example, a "lower" component is located below an "upper" component, or that a component that is "lower" is actually located "below" another component, or that a component that is "upper" is actually located "above" another component, since such directions, components, or both may be inverted, rotated, moved in space, placed in a diagonal orientation or position, placed horizontally or vertically, or modified in similar ways. Accordingly, it should be understood that the terms "lower," "below," "upper," and "above" may be used herein for exemplary purposes only, to illustrate the relative position or placement of certain components, and to indicate a first and second component, or both.

[293] As already shown in FIG. 37F, for example, the device can be configured such that when the disposable portion 102 and the reusable portion 104 are operatively connected to each other, the input and output capacitors 3832 and 3834 face the reservoir(s) 106, while the reference capacitor 3836 never faces any fluid that may be contained in the drug reservoir 106. Accordingly, the output signal of the reference capacitor 3836 can be substantially constant, regardless of the type and/or amount of fluid contained in the reservoir 106. Accordingly, the sensor 3800 can be calibrated to measure a large number of different fluids, without necessarily knowing the characteristics of said fluids. The relationships between the values of the output signals of the input and output capacitors 3832 and 3834, along with the readings obtained from the reference capacitor 3836, provide the ability to determine the amount of fluid in the reservoir 106 for the drug. The processor 3108 of the device 100 can be configured to independently process the signals provided by the plurality of sensors 3800 to provide separate output signals indicating the amount of fluid in each of the plurality of reservoirs for the drug that can be used in the same device.

[294] As shown in FIG. 37H, the output signal of the capacitive liquid amount sensor 3800 may be transmitted to the capacitive-to-digital converter 148, the output signal of which may be transmitted to the control unit 116, for example, for further processing.

[295] The liquid level, for example, can be determined from the following equation:

,

Where:

h _RL - height of the reference liquid sensor block (often equal to 1, but not always);

C _level - the capacitance of the level capacitor;

C _level (0) - the capacity of the level capacitor in the absence of liquid (empty tank);

C _RL - the capacity of the reference liquid sensor; and

C _RE = capacitance of the reference environment sensor.

[296] According to some embodiments, the electrical property of the sensor 3700 may be changed as a result of changing the position of the plunger head 120.

[297] According to some embodiments, the output signals of the fluid sensor(s) and/or the functional means related to the pump may be used to determine the functional state of the pumping device 100. For example, the output power required to displace the fluid from the drug reservoir 106; the number, for example, of turns of the nut, required to push a certain amount of fluid from the cannula 216 (for example, indicated by the output signal of the encoder angle of rotation); the flow rate (for example, measured by the fluid sensor); the pressure (for example, measured by the fluid sensor); and/or the like may be input, for example, to the processor 3108 to monitor the functional state of the pumping device 100 and to detect, for example, a blockage of the fluid passage in the pumping device 100 and/or to detect a leak of fluid from the pumping device 100.

[298] For example, if the processor 3108 determines that the output signal of the sensor and/or the functionality related to the pump meets the conditions of the "clogging criterion," the processor can generate a corresponding output signal. If necessary, such a clogging criterion can relate to a measured flow rate that has decreased for a certain period of time below a lower flow rate threshold. If necessary, such a clogging criterion can be associated with a pressure output signal that has increased for a certain period of time above a certain high pressure threshold. For example, if the output signal corresponds to a pressure of 4 bar or more for a certain period of time, the conditions of the clogging criterion can occur. The output signal that is generated in the event of an occurrence of a condition corresponding to a clogging condition can include, for example: a warning (e.g., visual, audible and/or tactile); a command to stop the operation of the drive component 112; and/or the like.

[299] According to some embodiments, the sensor output signal and/or the functional output signal associated with the pump may be analyzed to determine the viscosity of the fluid contained in the pump cylinder and/or the pump channels. For example, the pressure required to displace the fluid from the reservoir 106 for delivery to the patient may be an indicator of the viscosity of the fluid.

[300] According to some embodiments, the plunger assembly 108 may comprise a rotatable element (not shown) to implement a rotational viscometer. Alternative methods for measuring the viscosity of the fluid in the pump device 100 include, for example, vibration methods for measuring the damping of oscillations of an electromechanical resonator immersed in the fluid. The temperature of the fluid and/or other characteristics of the fluid may also be taken into account when determining its viscosity.

[301] According to another embodiment, the processor 3108 may determine that the output signal of the sensor and/or the pump-associated functionality meets the conditions of the "leak criterion" so that the processor may generate a corresponding output signal.

[302] If necessary, such a leakage criterion may be associated with a measured flow rate that has increased for a certain period of time above an upper flow rate threshold. If necessary, such a leakage criterion may be associated with a pressure drop for a certain period of time below a lower pressure threshold. For example, if the output signal corresponds to a pressure of 1 bar or less for a certain period of time, a leakage criterion condition may occur. The output signal that is provided in the event that a leakage condition occurs may include, for example: a warning (e.g., visual, audible, and/or tactile); a command to stop the operation of the drive component 112; and/or the like.

[303] According to some embodiments, the measurement results of the plurality of fluid sensors may be compared with each other, for example, to determine whether and to what extent a characteristic of the fluid drug undergoes a change from the time the fluid drug exits the reservoir 106 until it reaches the cannula 216 for delivery to the patient's body. The measurement results may be used, for example, to determine a change in the concentration of an analyte in the fluid drug, a flow rate and/or pressure in the cannula 216, and/or the like.

[304] The measured and/or determined characteristic of the fluid medicament may be input to the control unit 116 to control the operation of the pump. For example, the operation of the drive component 112 may be based on such input data.

[305] As shown in FIG. 38, the device 100 may comprise one or more additional fluid sensors (e.g., fluid sensors 3810A and 3910B) that are located at or near the outlet of the cannula 216 to measure a characteristic of the fluid contained in the cannula 216. The additional fluid sensors 3810A and 3810B may be used, for example, to determine the flow rate at which a fluid medication is delivered to a patient.

[306] Although the sensors 3810A and 3810B are shown arranged in a sequential order with respect to the direction of flow, which is schematically indicated by the positional numeral in the form of an arrow F, this should in no way be construed as limiting. For example, the sensors 3810A and 3810B may be arranged in the cannula 216 such that they face each other. Additional or alternative configurations may also be used.

[307] According to some embodiments, the data provided by the fluid sensor(s) may indicate the volume of agent delivered to the patient over a specified period of time, the expected remaining time to deliver a specified amount of fluid medication to the patient (e.g., the required amount and/or the amount of medication remaining in the reservoir), and/or the like.

[308] According to some embodiments, the device 100 may comprise mixing elements arranged and configured to actively and/or passively mix a fluid medicament stored in a reservoir and/or expelled through a fluid channel of the device 100. The mixing elements, for example, may comprise ribs (not shown) that extend into the cavity of the fluid channel and change the local flow direction of the fluid medicament. Optionally, the ribs are arranged in an alternating pattern opposite one another along a longitudinal axis of the cavity of the fluid channel. Optionally, the ribs are arranged like a series of screws along the flow path of the fluid. As described above, the mixing elements may be activated if the measured characteristic indicates that the transparency level of the fluid has reached or fallen below a lower threshold value. The stirring element may be a physical element located in the reservoir for the drug, or according to another embodiment, may comprise a mechanism that acts on the reservoir 106 for the drug from its outside, for example, using vibration and/or acoustic waves. As shown, for example, in FIG. 39, the stirring element may comprise a vibration-inducing element 133 that is connected to the reservoir 106 for the drug.

[309] According to some embodiments, the plunger assembly 108 and the drive components may be configured such that the plunger head 120 rotates during its axial movement in the reservoir 106 for the drug. The rotation of the plunger head 120 may be used to mix the fluid contained in the reservoir 106. For example, the mixing element may be implemented as ribs 4200 located on a superficial distal portion of the plunger head 120 with the ability to extend into a portion of the reservoir 106 that may contain a fluid for delivery to a patient, and the ribs 4200 may be positioned so as to mix the fluid during axial movement of the plunger head 120. As shown in FIG. 39, the plunger head 120 and the ribs 4200 located on it can rotate in the direction R1 during the axial displacement of the plunger head 120 in the distal direction P1 and rotate in the direction R2 during the axial movement of the plunger head 120 in the proximal direction P2. The ribs 4200 can, if necessary, be made integral with the plunger head 120. If necessary, the ribs 4200 can be connected to the plunger head 120.

[310] According to some embodiments, one or more physiological sensors may be operatively connected to and/or used in the device 100 to measure one or more physiological characteristics of a patient using the pumping device 100, before delivery, during delivery, and/or after delivery of a flowable medication. As shown in FIG. 38, the pumping device 100 may comprise one or more physiological sensors 3910A and 3910B. The first physiological sensor 3910A may be, for example, connected to the cannula 216 for transcutaneous sensing of the subcutaneous environment of the patient, and the second physiological sensor 3910B may be, for example, connected to the underside of the adhesive portion 110. The first physiological sensor 3910A can be configured to subcutaneously measure a physiological characteristic of a patient, and the second physiological sensor 3910B can be configured to noninvasively interact with a part of the surface of the patient's skin to measure a physiological characteristic related to the patient. According to some embodiments, the physiological sensor can be implemented as a non-inertial sensor and/or an inertial sensor (not shown). Inertial sensors can include accelerometers and/or gyroscopes for measuring relevant parameters, such as tremor, stiffness of the patient's gait and/or the like. Thus, such non-inertial sensors can be connected to a limb and/or a lower back of the patient to measure the patient's tremor, stiffness and/or gait. The output signal of the non-inertial and/or inertial sensors can be used to control the operation of the pump.

[311] According to some embodiments, image sensors may be used in connection with the pump device 100 to capture the patient's facial expression and/or other movements. The output signals of the image sensor may be used to control the operation of the pump.

[312] According to some embodiments, the pumping device 100 may use sensors (not shown) that are configured to determine the type of fluid contained in the reservoir 106 and/or delivered through the fluid channel of the pumping device. For example, based on one or more markers contained in the fluid medication, the output signal of such sensors may be used to determine whether the fluid medication contains carbidopa, levodopa, and/or dopamine.

[313] As shown in FIG. 40, the method of setting the values of operating parameters of a pumping device may include, as indicated in step 3902, receiving, for example, at a filling station, user-defined values of operating parameters of a pump. According to some embodiments, the user-defined values of operating parameters of a pump may be more preferable than the default values of operating parameters of a pump.

[314] The user-defined values of the operating parameters of the pump may be specified, for example, by the user via a touch screen of the filling station 154. As indicated in step 3904, the method may also include determining whether the received user-defined value of the operating parameter of the pump is within the acceptable thresholds of the operating parameter. If the received user-defined values of the operating parameters of the pump are within the acceptable thresholds of the operating parameter, in step 3906 the method may include controlling the operation of the pumping device 100 according to the received user-defined values of the operating parameters of the pump. For example, the user-defined values of the operating parameters of the pump may be transmitted (e.g., wirelessly) from the filling station 154 to the pumping device 100.

[315] If it is determined at step 3904 that the received user-defined values of the pump operating parameters are not within the acceptable thresholds, at step 3908 the method may include operating the pumping device 100 according to the default values of the pump operating parameters. In this case, the method may include, for example, transmitting the default values of the pump operating parameters (e.g., from the filling station 154) to the pumping device 100 and controlling the pumping device 100 accordingly.

[316] If necessary, the default values of the pump operating parameters and/or the thresholds of the pump operating parameter can be stored in the pump device 100 and/or the filling station 154. If necessary, the default values of the pump operating parameters can be transmitted from the pump device 100 together with the thresholds of the pump operating parameters of the filling station 154. If necessary, the default values of the pump operating parameters can be stored (or pre-stored) in the filling station 154 along with the thresholds of the pump operating parameter.

[317] If necessary (for example, received or, for example, previously saved) default values of the operating parameters of the pump can be transmitted (for example, displayed) by the filling station 154 to the user. If necessary, if the provided user-defined values of the operating parameters of the pump are not within the permissible operating thresholds, the default values of the operating parameters of the pump can be transmitted to the pumping device 100 to control the pump accordingly. If necessary, if the provided user-defined values of the operating parameters of the pump are not within the permissible operating thresholds, the pumping device 100 can be commanded to initiate the operation of the pumping device 100 according to the default values of the operating parameters of the pump stored in the pumping device 100.

[318] The term "controller" as used herein may also refer to a processor. For example, a controller may comprise circuitry programmed to cause a device to perform the methods, processes, and/or operations described herein. For example, a controller may be implemented as a hardware circuit, including, for example, customized very large scale integrated circuits (VLSI) or gate arrays, an application specific integrated circuit (ASIC), off-the-shelf semiconductor devices such as logic chips, transistors, and/or other discrete components. A controller may also be implemented as programmable hardware devices such as field programmable gate arrays, programmable logic arrays, programmable logic devices, and/or the like.

[319] The software instructions for implementing the methods and/or processes described in this document may be implemented as a computer program product that may be tangibly embodied in a storage medium, including, for example, a non-transitory tangible computer-readable and/or non-transitory tangible machine-readable storage device. The computer program product may be directly loaded into an internal memory device of a digital computer containing portions of the program code for enabling the implementation of the methods and/or processes described in this document.

[320] In addition to this or in another embodiment, the methods and/or processes described herein may be implemented as a computer program that may be intangibly embodied as a computer-readable signal medium. The computer-readable signal medium may include a propagated data signal (e.g., a communication signal) with computer-readable program code embodied therein, such as in baseband or as part of a carrier. Such a propagated signal may have any of a variety of forms, including but not limited to, electromagnetic form, optical form, or any suitable combination thereof. The computer-readable signal medium may be any computer-readable medium that is not a non-transitory computer or machine-readable storage device and that can transmit, carry, or transport a program for use by or in conjunction with the devices, systems, platforms, methods, operations, and/or processes described herein.

[321] The terms "non-transitory computer-readable storage device" and "non-transitory computer-readable storage device" include media for distribution, media for intermediate storage, random access memory of a computer, and any other medium or device capable of being stored for subsequent reading by a computer program implementing embodiments of the method described herein, and these terms do not include a propagating data signal.

[322] Computer-readable and executable instructions may also be loaded into a computer, other programmable data processing device, or other device to enable the calling of a sequence of operational steps performed by the computer, other programmable apparatus, or other device to perform a computer-implemented process, such that the instructions executable by the computer, other programmable apparatus, or other device perform the functions/actions specified in the process chart and/or block or blocks of the flow chart.

[323] In the description, unless otherwise indicated, adverbs such as "substantially" and "about" that modify the state or characteristic of a relationship of a feature or features of an embodiment of the invention are to be understood to mean that the state or characteristic is defined within tolerances that are acceptable for the operation of the embodiment in the application for which it is intended. For example, the terms "about," "substantially," and/or "close" to a quantity or numerical value may be understood to be within an inclusive range of -10% to +10% of the corresponding quantity or value.

[324] The expression "related to" means indirectly or directly "connected with".

[325] It should be noted that the terms "adapted to" and "operating to" may encompass the meaning of the term "adapted or configured to." In other words, a machine "configured to" solve a problem may, in some embodiments, include simple features and, in some other embodiments, a machine that is substantially constructed to perform the function.

[326] As used herein, the expression "A, B, C, or any suitable combination of the foregoing" shall be interpreted to mean all of the following: (i) A or B or C, or any combination of A, B, and C; (ii) at least one of A, B, and C; and (iii) A and/or B and/or C. This concept is illustrated for three elements (i.e., A, B, C), but extends to smaller and larger numbers of elements (e.g., A, B, C, D, etc.).

[327] The terms and expressions used herein are used as terms and expressions of description and not of limitation, and there is no intention in the use of such terms and expressions to exclude any equivalents of the features or portions thereof shown and described. Furthermore, in light of the specific embodiments of the present invention described, it will be apparent to those skilled in the art that other embodiments incorporating the concepts described herein may be used without departing from the spirit and scope of the present invention. The structural features and functions of some embodiments may be arranged in various combinations and permutations, all of which are considered to be within the scope of the present invention. Unless otherwise required, the described steps of the various methods may be performed in any order, and certain steps may be performed substantially simultaneously. Accordingly, the described embodiments are to be considered in all respects only illustrative and not limiting. Furthermore, the configurations described herein are intended to be illustrative and not limiting in any way. Similarly, although physical explanations are provided for explanatory purposes, they are not intended to be tied to any particular theory or mechanism or to restrict the applied formula to them.

Claims (57)

1. A device for delivering a fluid drug through the skin of a user, comprising: a reusable part containing: drive component and a control unit for controlling the drive component; and a disposable part designed to interact with a reusable part and containing: a first reservoir for containing a flowable medicinal product, wherein said first reservoir comprises a first sleeve, wherein the first sleeve is fixedly mounted in the first reservoir; a first plunger head configured to be moved by a first lead screw in a first reservoir, and a first nut, concentrically secured by the first sleeve and configured to rotate therein, wherein the first nut interacts with the thread of said first lead screw by means of a thread, wherein the first nut is configured to be connected in a detachable manner to the drive component and is configured to rotate by the drive component when the reusable part interacts with the disposable part, and while the reusable part interacts with the disposable part, wherein the first nut, when rotating in the first sleeve, is configured to linearly shift the first lead screw in a direction dependent on the direction of rotation of the first nut. 2. The device according to claim 1, wherein the first nut includes a first part inserted into the first sleeve and fixed in the axial direction by the first sleeve, and a second part having an outer profile designed with the possibility of interaction in a detachable manner with the mating profile of the gear working under load, driven by the drive component. 3. The device according to claim 1, wherein the disposable part also comprises an outer surface designed to be adhered to the user's skin. 4. The device of claim 1, wherein the disposable portion also comprises a cannula in fluid communication with the first reservoir, wherein the cannula is configured to deliver a fluid medicament from the first reservoir to the subcutaneous tissue of the user. 5. The device of claim 1, wherein the reusable portion and the disposable portion are configured to be secured to each other using a magnetic force or a snap-fit connection, or a combination thereof. 6. The device of claim 1, wherein the reusable portion and the disposable portion are coplanar during fastening to each other and when they are fastened to each other. 7. The device of claim 1, wherein the reusable portion also comprises a first cavity for receiving the first lead screw when the first lead screw is retracted into or withdrawn from the first reservoir. 8. The device according to claim 1, wherein the disposable part also comprises: a second reservoir for containing additional flowable medicinal product, wherein said second reservoir comprises a second sleeve, wherein the second sleeve is fixedly mounted in the second reservoir; a second plunger head for displacing additional flowable medicinal product from the second reservoir, configured to move in the second reservoir by a second lead screw; and a second nut, concentrically secured by the second sleeve and configured to rotate in it, wherein the second nut interacts with the thread of the second lead screw by means of a thread, wherein when the reusable part and the disposable part are fastened to each other, the second nut is detachably connected to the drive component and is configured to rotate by the drive component in a direction controlled by the control unit, wherein the second nut, when rotating in the second sleeve, is configured to linearly shift the second lead screw in a direction dependent on the direction of rotation of the second nut. 9. The device according to claim 8, wherein the drive component is configured to selectively actuate the first plunger head and the second plunger head simultaneously or separately. 10. The device according to claim 8, wherein the reusable portion comprises a first cavity for receiving the first lead screw when the first lead screw is withdrawn from the first reservoir, and a second cavity for receiving the second lead screw when the second lead screw is withdrawn from the second reservoir. 11. The device according to claim 8, wherein the reusable part also comprises a control button for selecting the operating mode of the device, wherein the operating mode is selected from a group of modes consisting of: a filling mode in which the control unit controls the drive component to fill the infusion set with a medicinal product; a drug delivery mode in which the control unit controls the drive component to deliver the drug to the user at a desired rate or according to a desired schedule; a filling mode in which the control unit controls the drive component to perform at least one of the following actions: (i) retracting the first plunger head to fill the first reservoir; (ii) retracting the second plunger head to fill the second reservoir, and (iii) retracting both the first plunger head and the second plunger head to fill both the first reservoir and the second reservoir; and pause mode. 12. The device according to claim 8, wherein a fluid sensor is located along at least one of the first reservoir and the second reservoir. 13. The device according to item 8, also comprising: a cannula in fluid communication with at least one of the first reservoir and the second reservoir, wherein the cannula is configured to deliver a fluid medicament into the subcutaneous tissue of the user from at least one of the first reservoir and the second reservoir; and a sensor for detecting at least one functional parameter of the device or fluid, wherein the sensor comprises at least one of a flow sensor, a pressure sensor, a DC sensor and a temperature sensor for measuring the temperature of the fluid drug in the cannula or the first reservoir or the second reservoir, or combinations thereof. 14. The device of claim 8, wherein the fluid medicament in the first reservoir and/or in the second reservoir contains levodopa or carbidopa, or a combination of levodopa and carbidopa. 15. The device of claim 8, wherein the reusable portion is configured to interact with the disposable portion in a first orientation and in a second orientation rotated 180° relative to the first orientation, wherein in each orientation each of the first nut and the second nut interacts with a load-bearing gear of the drive component. 16. The device of claim 8, wherein the reusable portion and the disposable portion are configured to interact with each other only in a specific orientation of the reusable portion relative to the disposable portion, wherein each of the first nut and the second nut is configured to interact only with a specific load-bearing gear of the drive component. 17. The device of claim 8, wherein the reusable portion and the disposable portion are configured to be secured to each other using magnetic force, a snap-fit connection, or a combination thereof. 18. The device of claim 1, wherein the flowable drug contained in the first reservoir comprises levodopa or carbidopa, or a combination of levodopa and carbidopa. 19. The device according to claim 1, wherein the reusable part also comprises a control button for selecting the operating mode of the device, wherein the operating mode is selected from a group of operating modes consisting of: a filling mode in which the control unit controls the drive component to fill the infusion set with a medicinal product; a drug delivery mode in which the control unit controls the drive component to deliver the drug from the first reservoir to the user at a desired rate or according to a desired schedule; a filling mode in which the control unit controls the drive component to retract the first plunger head to fill the first reservoir; and pause mode. 20. A disposable portion for containing a flowable medicinal product for delivery through the skin of a user by a device for delivering a flowable medicinal product containing a reusable portion, wherein the disposable portion comprises: a first reservoir for containing a flowable medicinal product, wherein the first reservoir is configured to interact with the reusable portion; a first plunger head configured to move with a first lead screw in a first reservoir; a first sleeve fixedly mounted in the first reservoir; and a first nut, concentrically secured by the first sleeve and configured to rotate therein, wherein the first nut interacts with the first lead screw by means of a thread, wherein the first nut is configured to be operatively connected to the drive component of the reusable part and is configured to rotate by the drive component of the reusable part during interaction of the reusable part and the disposable part, and while the reusable part interacts with the disposable part, wherein the first nut is configured to linearly shift the first lead screw in the first reservoir in a direction dependent on the direction of rotation of the first nut in the first sleeve. 21. A disposable part according to claim 20, in which the first nut includes a part inserted into the first sleeve and fixed in the axial direction by the first sleeve in said sleeve, and a part having an outer profile configured to interact in a detachable manner with a mating profile of a load-operating gear driven by a drive component. 22. The disposable part according to claim 20, wherein the flowable drug comprises levodopa or carbidopa, or a combination of levodopa and carbidopa. 23. The disposable part according to item 20, also containing: a second reservoir for containing additional flowable medicinal product; a second plunger head, configured to be moved by a second lead screw in a second reservoir; a second sleeve fixedly mounted in the second reservoir; and a second nut, concentrically secured by the second sleeve and configured to rotate in it, wherein the second nut interacts by means of a thread with the second lead screw for linear displacement of the second lead screw in the second reservoir in a direction dependent on the direction of rotation of the second nut in the second sleeve. 24. A disposable part according to claim 23, in which each of the first nut and the second nut includes a first part inserted into a corresponding one of the first sleeve and the second sleeve and fixed in the axial direction in said sleeve of a corresponding one of the first sleeve and the second sleeve, and a second part having an outer profile configured to interact in a detachable manner with a mating profile of a gear working under load, driven by a drive component. 25. A reservoir for containing a flowable drug for delivery through the skin of a user by a device for delivering a flowable drug, comprising a reusable portion, wherein the reservoir is configured to interact with the reusable portion and comprises: a plunger head designed to be moved by a lead screw in the said reservoir; a sleeve fixedly installed in the tank; and a nut concentrically secured by the sleeve and configured to rotate in it, wherein the nut interacts with the lead screw by means of a thread, wherein the nut is configured to be functionally connected to the drive component of the reusable part and is configured to rotate by the drive component of the reusable part during interaction between the reservoir and the reusable part, and while the reusable part interacts with the reservoir, wherein the nut is configured to linearly shift the lead screw in the reservoir in a direction dependent on the direction of rotation of the nut in the sleeve. 26. The reservoir according to claim 25, in which the nut includes a first part inserted into the sleeve and fixed in the axial direction by the sleeve in said sleeve, and a second part having an outer profile configured to interact in a detachable manner with the mating profile of the gear working under load, driven by the drive component.