WO2025222120A1

WO2025222120A1 - Method and apparatus for the treatment of migraine and other conditions

Info

Publication number: WO2025222120A1
Application number: PCT/US2025/025368
Authority: WO
Inventors: Megan BETTILYON; Charles Arthur HIXSON; John Roy Kane; Taylor Morgan MCAVOY; Howard Elliot SHERMAN; Maurizio Vecchione
Original assignee: Avacore Technologies Inc
Current assignee: Avacore Technologies Inc
Priority date: 2024-04-19
Filing date: 2025-04-18
Publication date: 2025-10-23
Anticipated expiration: 2026-10-19

Abstract

Embodiments described herein generally relate to methods and apparatus for adjusting and/or controlling body temperature and/or the flow of blood within blood vessels within a mammal. Embodiments of the present disclosure may further provide a therapeutic method for acute and preventive treatment of a migraine headache or other recurrent acute or chronic pain of a user, comprising: applying a vacuum to a portion of a body of a user and circulating warmed water over a surface of the portion of the body of the user, wherein applying the vacuum and circulating the warmed water is configured to overcome a vasoconstricted state of the portion of the body and manipulate blood flow to a head and/or distal appendages of the user.

Description

METHOD AND APPARATUS FOR THE TREATMENT OF MIGRAINE AND OTHER CONDITIONS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to United States Provisional Application Serial No. 63/636,672 filed April 19, 2024, which is herein incorporated by reference in its entirety.

BACKGROUND

Field

[0002] Embodiments described herein generally relate to methods and apparatus for adjusting and/or controlling body temperature and/or the flow of blood within blood vessels within a mammal.

Description of the Related Art

[0003] All mammals thermoregulate by using glabrous skin structures (such as palms, soles, and forehead). These structures act as the body’s natural heat radiators. The hypothalamus controls core body temperature by opening and closing valves (e.g., arteriovenous anastomoses (AVAs), vascular communications between small arteries and the venous plexuses) diverting arterial blood flow to the skin surface to radiate heat. When the body is at thermal homeostasis these valves are closed and vasoconstricted. Using DALY (disability-adjusted life years)/YLD (years lived with disability)/GBD (global burden of disease) measures, migraine has been found to be the number three for neurological conditions overall. Neurological conditions are the highest rated global health care category estimated to affect over 40% of the global population. While headaches disorders ranked 14^th in overall DALYs according in 2019, headaches disorders ranked 2^nd among women ages 15-49 at 4.9%. The potential to apply device-based therapeutics for at home use could have a significant impact on both the reduction of DALYs YLDs, and could additionally have measurable success in the reduction of adverse outcomes associated with migraine drugs. Access to safe, effective, at-home treatment would have a profound positive impact on migraines sufferers globally leading to increased productivity. [0004] Therefore, there is a need for an apparatus and a method to treat migraines as both a stand-alone device to reduce vasoconstriction, and adjuvant therapy with certain existing migraine drugs increasing their effectiveness at reducing the effects of a migraine on a patient.

SUMMARY

[0005] Embodiment of the disclosure include a therapeutic method, comprising: generating, by use of a device, a vacuum pressure within an internal region of a body element of the device while a portion of an extremity of a user that is disposed within the internal region; circulating a heated fluid through a thermal exchange unit of the device, wherein the thermal exchange unit is disposed over a surface of the portion of the extremity of the user and a temperature of the heated fluid is controlled by use of a heater that is in thermal communication with the heated fluid; receiving, by a controller, a pressure measurement signal that comprises pressure measurement information from a pressure sensor that is configured to sense a pressure level in the internal region; receiving, by the controller, a fluid temperature measurement signal that comprises fluid temperature information from a first temperature sensor that is configured to sense a temperature of the heated fluid; receiving, by the controller, user information, wherein the user information comprises information relating to one or more drug therapies used by the user to treat a migraines or other acute pain; and adjusting, by use of the controller, an amount of vacuum applied to the extremity or the temperature of the heated fluid based on a comparison of the user information and at least one of the fluid temperature information, the user temperature information, and the pressure measurement information with information stored in memory of the controller.

[0006] Embodiment of the disclosure include a therapeutic method, comprising: generating, by use of a device, a vacuum pressure within an internal region of a body element of the device while a portion of an extremity of a user that is disposed within the internal region; circulating a heated fluid through a thermal exchange unit of the device, wherein the thermal exchange unit is disposed over a surface of the portion of the extremity of the user and a temperature of the heated fluid is controlled by use of a heater that is in thermal communication with the heated fluid; receiving, by a controller, a pressure measurement signal that comprises pressure measurement information from a pressure sensor that is configured to sense a pressure level in the internal region; receiving, by the controller, a fluid temperature measurement signal that comprises fluid temperature information from a first temperature sensor that is configured to sense a temperature of the heated fluid; receiving, by the controller, a user temperature measurement signal that comprises user temperature information from a second temperature sensor that is configured to sense a temperature of the user; receiving, by the controller, user information, wherein the user information comprises information relating to one or more drug therapies used by the user to treat a migraines or other acute pain; and adjusting, by use of the controller, an amount of vacuum applied to the extremity or the temperature of the heated fluid based on a comparison of the user information and at least one of the fluid temperature information, the user temperature information, and the pressure measurement information with information stored in memory of the controller.

[0007] Embodiments of the present disclosure provide a device for performing a therapeutic method, comprising: a device comprising a pressure port and one or more body elements that at least partially define an internal region of the device; a thermal exchange unit that is in thermal communication with a heater, wherein the thermal exchange unit is configured to transfer heat between the thermal exchange unit and a portion of an extremity of a user disposed within the internal region of the device; a pump fluidly coupled to the internal region through the pressure port and configured to create a sub-atmospheric pressure within the internal region, causing atmospheric pressure external to the internal region to urge at least a portion of the thermal exchange unit against the portion of the extremity of the user; and a controller configured to control the pump and the heater, wherein the controller comprises a processor and non-volatile memory that, has program instructions stored therein The program instructions when executed by one or more processors causes the device to perform operations comprising: generating a sub-atmospheric pressure within the internal region while a portion of an extremity of the user is disposed within the internal region; circulating a heated fluid through the thermal exchange unit of the device, wherein the thermal exchange unit is disposed over a surface of the portion of the extremity of the user; receiving, by a controller, a pressure measurement signal that comprises pressure measurement information from a pressure sensor that is configured to sense a pressure level in the internal region; receiving a fluid temperature measurement signal that comprises fluid temperature information from a first temperature sensor that is configured to sense a temperature of the heated fluid; receiving, by the controller, user information, wherein the user information comprises information relating to one or more drug therapies used by the user to treat a migraines or other acute pain; and adjusting, by use of the controller, an amount of vacuum applied to the extremity or the temperature of the heated fluid based on a comparison of the user information and at least one of the fluid temperature information, and the pressure measurement information with information stored in memory of the controller.

[0008] Embodiments of the present disclosure may further provide a therapeutic device having an extremity of a user disposed therein and comprising non-volatile memory having a number of instructions stored therein which, when executed by one or more processors, causes the therapeutic device to perform operations comprising: receiving a pressure measurement signal that comprises pressure measurement information from a pressure sensor that is configured to sense a pressure level in an internal region of a body element of the therapeutic device; receiving a fluid temperature measurement signal that comprises fluid temperature information from a first temperature sensor that is configured to sense a temperature of a heated fluid circulated through a thermal exchange unit of the therapeutic device; receiving a user temperature measurement signal that comprises user temperature information from a second temperature sensor that is configured to sense a temperature of the user; receiving user information, wherein the user information comprises information relating to one or more drug therapies used by the user to treat a migraines or other acute pain; and adjusting an amount of vacuum applied to the extremity or the temperature of the heated fluid based on a comparison of the user information and at least one of the fluid temperature information, the user temperature information, and the pressure measurement information with information stored in the non-volatile memory.

[0009] Embodiments of the present disclosure may further provide a therapeutic method for acute and preventive treatment of a migraine headache or other recurrent acute or chronic pain of a user, comprising: applying a vacuum to a portion of a body of a user and circulating warmed water over a surface of the portion of the body of the user, wherein applying the vacuum and circulating the warmed water is configured to overcome a vasoconstricted state of the portion of the body and manipulate blood flow to a head and/or distal appendages of the user; and providing one or more drug therapies, while applying the vacuum and circulating the warmed water to the user, wherein the one or more drug therapies are configured to constrict certain extracranial and/or certain vascular structures in the head to improve an efficacy of said drugs.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] So that the manner in which the above recited features of the present disclosure can be understood in detail, a more particular description of the disclosure, briefly summarized above, may be had by reference to embodiments, some of which are illustrated in the appended drawings. It is to be noted, however, that the appended drawings illustrate only exemplary embodiments and are therefore not to be considered limiting of the scope of the disclosure, as the disclosure may admit to other equally effective embodiments.

[0011] Figure 1A is a perspective view of an exemplary device according to one or more embodiments of the present disclosure.

[0012] Figure 1 B is a partially exploded cross-sectional view of a portion of a thermal exchange unit according to one or more embodiments of the present disclosure.

[0013] Figure 2A is a side view of an exemplary device according to one or more embodiments of the present disclosure.

[0014] Figure 2B is a side view of another exemplary device according to one or more embodiments of the present disclosure. [0015] Figures 3A and 3B are a side cross-sectional view and a plan view of an exemplary device according to one or more embodiments of the present disclosure.

[0016] Figure 3C is a side cross-sectional view of another exemplary device according to one or more embodiments of the present disclosure.

[0017] Figure 3D is a perspective view of yet another exemplary device according to one or more embodiments of the present disclosure.

[0018] Figure 3E is a side cross-sectional view of another exemplary device according to one or more embodiments of the present disclosure.

[0019] Figure 3F is a side cross-sectional view of another exemplary device according to one or more embodiments of the present disclosure.

[0020] Figure 3G is a side cross-sectional view of another exemplary device according to one or more embodiments of the present disclosure.

[0021] Figure 4A illustrates one example of a thermal exchange unit according to one or more embodiments of the present disclosure.

[0022] Figure 4B illustrates one example of a thermal exchange unit according to one or more embodiments of the present disclosure.

[0023] Figure 5A is an isometric view of another exemplary device according to one or more embodiments of the present disclosure.

[0024] Figure 5B is a schematic view of an example of a control system of the device illustrated in Figure 5A according to one or more embodiments of the present disclosure.

[0025] Figure 6A illustrates a control system connected to a device according to one or more embodiments of the present disclosure.

[0026] Figure 6B is a schematic view of the control system connected to a device according to one or more embodiments of the present disclosure.

[0027] Figure 6C is a schematic view of interconnected components with the control system, which includes an artificial intelligence (Al) control system, according to one or more embodiments of the present disclosure. [0028] Figure 7 illustrates a process flow diagram of a therapeutic method for acute and preventive treatment of migraine headache or other recurrent acute or chronic pain, according to one or more embodiments of the present disclosure.

[0029] To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. It is contemplated that elements and features of one embodiment may be beneficially incorporated in other embodiments without further recitation.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0030] Embodiments of the disclosure include a therapeutic method for treating migraines or other acute pain by manipulating blood flow to the head and/or distal appendages of a patient and manipulating central, peripheral blood pressure and vaso-motor tone. This can be done using a system that includes a device which applies controlled heat to a distal appendage, head, or forehead while drawing a mild vacuum in a region formed between a portion of the device and the skin on a patient.

[0031] In one embodiment, the apparatus described herein uses a fluid perfusion sleeve (thermal exchange unit) that is placed over the portion of a patient (e.g., foot, hand and/or forearm) that includes a circulating temperature-controlled fluid (e.g. water, hydrogel at about 104°F) while simultaneously drawing a mild vacuum (e.g., 5mm Hg) within an internal region of the fluid perfusion sleeve in which the portion of the patient is positioned. The vacuum overcomes the vasoconstricted state within minutes and the AVA containing region of the patient (e.g. , palm) begins to heat blood that returns to the core body. Without the vacuum, the temperature-controlled fluid would only heat the skin surface, not the core body. Within minutes, the hypothalamus detects an elevated temperature and causes the arteriovenous anastomoses (A As) to vasodilate in the other heat exchange structures, thus greatly increasing peripheral blood flow to these structures. A side effect of adding heat to the body is the increase of peripheral circulation, particularly to the head (e.g., forehead), the hands, and the feet. This affects central blood pressure as increased blood flow is selectively shunted to the head and distal appendages. In this way blood flow is greatly increased to the forehead area. Testing this physiologic effect on non-surgical patients has produced preliminary evidence that it can lessen or even eliminate migraine pain depending upon which phase of migraine progression the patient is experiencing. This may be effective because the vasodilation affects the same pain receptors involved in the pain cascade of migraine progression and that this is similar to the mechanism of action used by leading migraine treatment drugs, such as triptan medications which can include Almotriptan (Axert), Eletriptan (Relpax), Frovatriptan (Frova), Naratriptan (Amerge), Rizatriptan (Maxalt), Sumatriptan (Imitrex), and Zolmitriptan (Zomig). In some embodiments, migraine treatment drugs can include beta blockers. In one example, beta blockers can include selective beta blockers, non-selective beta blockers, and beta blockers that include additional cardiac effects. Examples of typical beta blockers include, but are not limited to Atenolol (Tenormin), Bisoprolol (Zebeta, Monocor), Metoprolol (Lopressor, Toprol XL, Betaloe), Nebivolol (Bystolic), Betaxolol (Kerlone), Esmolol (Brevibloc), Propranolol (Inderal, Inderal LA, InnoPran XL), Timolol (Blocadren), Nadolol (Corgard), Pindolol (X/isken, X/iskazide), Carvedilol (Coreg, Coreg CR), Labetalol (Trandate), Sotalol, Penbutolol (Levatol), Carvedilol (Coreg, Coreg CR), and Labetalol (Trandate). In some embodiments, migraine treatment drugs can include over-the-counter drugs, such as acetaminophen (Tylenol), nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin, and caffeine-containing migraine products. In one example, the migraine treatment drug includes a combination of acetaminophen, aspirin, and caffeine (Excedrin Migraine).

[0032] The apparatus described herein includes a device that generally includes one or more collapsible and pliant body elements, capable of expanding from a first volume into an expanded second volume so the device can receive a portion of an extremity of the mammal therein and then be reduced from the expanded second volume into a pressurized third volume to conformably enclose the portion of the extremity. One or more thermal exchange units can be positioned in the collapsible and pliant body elements. Accordingly, the temperature of the extremity of a mammal can be regulated by providing a heated or cooled fluid or electric thermal energy to thermal exchange units within the device. Next, by evacuating the region in which the extremity is enclosed the contact surface area between the extremity of a mammal and the thermal exchange units is increased, due to the external atmospheric pressure acting on the pliant body elements against the skin of the extremity of the mammal. The application of pressure assures that sufficient contact and thermal heat transfer (heating or cooling) is provided to the extremity of the mammal. By controlling the application of pressure to the mammal’s extremity that is positioned within the enclosed region of the collapsible and pliant body elements skin perfusion can be improved. The pressure that is applied to the region surrounding the extremity can be adjusted to increase the blood perfusion at the skin surface of the extremity, and also improve heat transfer to the blood and rest of the body. It is believed that regulating a sub-atmospheric pressure in a region over a portion of the mammal’s extremity to allow an eternal pressure (e.g., atmospheric pressure) or force to create a contact pressure between the device components (e.g., thermal exchange units) and the extremity of, for example, a range of 3 to 10 mmHg will provide a desirable increase of blood perfusion. It is also believed that the exposure of the skin of the extremity to a sub-atmospheric pressure environment can also help the vasodilatation of the vasculature in the mammal’s extremity. The vasodilatation of the vasculature may also help to increase the thermal exchange between the thermal exchange units and the mammal’s extremity. In an effort to simplify the discussion provided herein the terms mammal, patient, and human being are used synonymously.

[0033] In some embodiments, the extremity can be any kinds of a distal appendage of a patient, such as an arm, a hand, a forearm, a forearm with an elbow, a hand with a wrist, a foot, a leg, a calf, an ankle, toes, a forehead, a limb, etc., where arteriovenous anastomoses (AVAs) are located and/or when increased blood flow is desired. Arteriovenous anastomoses (AVAs), which are connected to arteries and veins, are specialized blood vessels located primarily in the palms and fingers of the hands, the soles and toes of the feet, the cheeks, and the ears, etc. It is recognized that the device described herein may be adapted for use with other extremities that have vasculature structures suitable for the increasing blood flow methods described herein. Regulating the temperature of the patient’s extremity may include elevating, cooling, and/or maintaining the patient’s temperature. The patient may be a human or other mammal. [0034] In particular, the embodiments disclosed herein will provide a non-invasive, convenient apparatus for efficiently adjusting the temperature, applying a sub- atmospheric pressure, and/or applying compression pressure or forces, to the patient’s extremity to increase blood flow, promote venous blood return, that is useful for treating the effects of an undesirable condition in a patient that is caused by vasoconstriction, such as during one or more phases of a migraine e.g., prodrome, aura, headache, and postdrome). The devices and methods as described herein are configured to increase blood flow in the extremity of the patient, which may include an appendage. Experiments performed on humans indicate that optimal pressure to increase blood flow could be about 13-14 mmHg, but pressures between 1 and 80 mmHg, and more preferably 3 and 40 mmHg and more preferably 5 and 20 mmHg can increase blood perfusion. Pressures of between approximately 3 to 10 mmHg combined with the application of an appropriate amount of heat can increase blood flow as a percent per minute of the volume of the appendage (in this case, an arm) from a base level to about 400% per minute . The pressure applied to the skin by the device can be used to increase blood flow, which can be accomplished by a variety of methods including, but not limited to using atmospheric pressure to collapse a baglike structure that has been evacuated or by pressurizing or inflating, a cuff that encompasses a significant portion of appendage.

Apparatus Examples

[0035] Figure 1 A is a perspective view of another example of a device 100 according to one or more embodiments of the invention. The device 100 may be used to circulate fluid (e.g. water, hydrogel, or gas at about 104°F) while simultaneously drawing at least a mild vacuum (e.g. 5mm Hg) to a distal appendage (e.g., a hand, an arm, a forearm, a forearm with an elbow, a hand with a wrist, a foot, a leg, a calf, an ankle, toes, a forehead, a limb) of a user.

[0036] The device 100 may include a body element 102 having an opening 104 for a portion of an extremity E of a patient to be enclosed in an internal region 106 of the device 100, and a sealing element 108. In general, the body element 102 can be formed of a disposable low-cost material, a biocompatible material, a material that can be sterilized, and/or a hypo allergic material.

[0037] The size of the opening 104 may be sealed and reduced by the sealing element 108. The sealing element 108 may be formed of a biocompatible material (and therefore safe for contact with the skin of a patient) and capable of producing an airtight seal. In one embodiment, the sealing element 108 is detachably attached to the opening 104. In another embodiment, the sealing element 108 is formed of a disposable material, such as a disposable liner or an insert material. For example, the material of the sealing element 108 may be hydrogel, a sticky seal material, polyurethane, urethane, among others. One example of the material is hydrogel. Another example is a PS series thermoplastic polyurethane from Deerfield Urethane, Inc. Disposable sealing materials may be manufactured and packaged such that they are sterile before use and/or hypoallergenic to meet health and safety requirements. The sealing element 108 may include an air-permeable portion and/or formed of a permeable membrane material or a breathable material to permit the flow of air, etc. Examples of breathable materials are available from Securon Manufacturing Ltd. or 3M Company. The permeable portion may be positioned near any portion of the body portion to provide permeable outlets, allowing the vacuum to have the proper effect on the extremity E and providing a barrier keeping the device 100 from contamination for the comfort of the user.

[0038] In addition, the device 100 includes a thermal exchange unit 110 capable of containing a fluid therein. The fluid may be water. In some embodiment, the fluid is a closed loop high efficiency thermal transfer material other than water, such as hydrogel, which can be continuously flowing while in use and can be stored as a solid when not use, through shear thinning or thermal triggers.

[0039] In one embodiment, the thermal exchange unit 110 that is permanently attached to the device 100 and formed of a collapsible and pliant material, including but not limited to, urethane, polyurethane, elastomers, polypropylenes, polystyrenes, high density polyethylene’s (HDPE), low density polyethylene’s (LDPE), polyvinyl chloride), rubbers, polymeric materials, composite materials, among others. The thermal exchange unit 110 is generally designed to allow a fluid to be delivered therethrough to exchange heat with the extremity E. As a result, the thermal exchange unit 110 can be used to enclose the extremity E by forming the internal region 106, which can be evacuated. In addition, the body of the thermal exchange unit 110 is capable of forming into a minimized volume for folding, storage, and/or shipping. The space enclosed by the thermal exchange unit 110, or the internal region 106, can also be expanded so that the extremity E can be disposed therein. The internal region 106 of the thermal exchange unit 110 can be reduced under a pressurized condition to conformably apply even and equal pressure on the portion of the extremity E disposed inside the device 100.

[0040] The thickness of the material for the thermal exchange unit 110 is not limited as long as it is compliant enough to substantially conform to a shape of a portion the extremity E that the thermal exchange unit 110 is disposed on, it can sustain the pressurized conditions when the device 100 is used, and the fluid can be delivered therein. For example, a urethane material having a thickness of from about 1.5 mils to about 12 mils can be used to pliantly conform to the shape and size of the portion of the extremity E contained therein. Another possible material may include NTT- 6000, which is a polyether polyurethane manufactured using USP Class V1 compliant materials. The NTT-6000 material can be a 2-mil gage material that is a natural color and is available from American Polyfilm, Inc. Branford, CT NTT-6000. Optionally, the thermal exchange unit 110 may be connected to the opening 104 through the body element 102. Alternatively, the body of the thermal exchange unit 110 can form the opening 104 without using an additional body element 102. Additionally, the device 100 may include temperature sensors to measure the temperature of the fluid flowing in and out of the thermal exchange unit 110 and to measure the surface temperature of the extremity E, such as a user’s body surface temperature.

[0041] Further, a manifold 112 can be used to bundle the various fluid ports and pressure ports together. The manifold 112 can be used to fluidly or electrically connect a control system 114 including a controller 116, a fluid source 118, a pressure sensor 120, and/or a pump 122 to the various components found in the internal region 106 of the device 100. For example, the manifold 112 may include a pressure port 124, a pressure sensing line 126, a fluid supply line 128, and a fluid return line 130 therein. The manifold 112 may also be used to connect to one or more compression air plenums for applying compression pressure on the portion of the extremity E.

[0042] Pump 122 can include a vacuum-generating device or a positive pressuregenerating device. In one example, the pump 122 includes a vacuum ejector type of device or a positive displacement pump configured to generate a vacuum within the internal region 106 of the device 100. In another example, the pump 122 includes a manually operated bulb or a positive displacement pump configured to generate a positive pressure within the internal region 106 of the device 100.

[0043] The controller 116, which is described in more detail below, may be adapted to regulate the functions and process performed by the device 100, including adjusting the fluid flow in and out of the thermal exchange unit 1 10 from the fluid source 118 via the fluid supply line 128 and the fluid return line 130, regulating the temperature of the thermal exchange unit 110, monitoring the pressure level inside the device 100 via one or more pressure sensors 120, adjusting the pump 122 speed and the vacuum level inside the device 100, and monitoring the temperature of the extremity E received therein, among others.

[0044] Figure 1 B is a partially exploded cross-sectional view of a portion of the thermal exchange unit 110 according to one embodiment. The thermal exchange unit 110 is formed by bonding or sealing two layers (e.g., layers 132A and 132B) of a collapsible and pliant material together to form a composite element 132 having a fluid plenum 134 formed between the bonded and sealed layers to allow a fluid to be delivered from the fluid source 118 therethrough. The layers 132A and 132B can be sealed (e.g., seal 136) by use of a heat sealing, gluing, or other conventional compliant layer bonding technique. Then two or more composite elements 132 can then be bonded together (see “A” in Figure 1 B) at a sealing region 138, using a heat sealing, gluing, or other conventional technique, to form the internal region 106 in which the patient’s extremity E can be placed. The layers 132A and 132B may formed of a collapsible and pliant material, including but not limited to, urethane, polyurethane, polypropylenes, polystyrenes, high density polyethylene (HDPE), low density polyethylene’s (LDPE), polyvinyl chloride), rubbers, elastomers, polymeric materials, composite materials, Cflex, among others.

[0045] In one embodiment, a plurality of dimples 140 are formed between the layers 132A and 132B to form a stronger composite element 132 that will not dramatically expand when a fluid is delivered from the fluid source 118 to fluid plenum 134 region of the thermal exchange unit 110. In one embodiment, a separating feature 142 is formed through a region of the composite element 132 to allow fluid delivered from the fluid supply line 128 to flow through the fluid plenum 134 and around the separating feature 142 before the fluid exits the thermal exchanging unit 110 and enters the fluid return line 130. The separating feature 142 may be formed by RF welding, thermal sealing, gluing, or bonding the layers 132A and 132B together. In one embodiment, a composite element 132 is formed on either side, or wraps around, the extremity E in the device 100 to provide improved thermal contact and heat exchanging properties.

[0046] Figure 2A is a side view of another exemplary device 200, which may be used to circulate fluid while simultaneously drawing a mild vacuum to a distal appendage (e.g., foot) of a user, according to one embodiment of the invention.

[0047] The device 200 includes a body element 202 for forming a pressurized volume, and an opening 204 for enclosing an extremity E of a patient inside an internal region 206 of the device 200. The device 200 further includes a sealing element 208 formed on a portion of the opening 204 and adapted to seal the portion of the extremity E when placed inside the pressurized volume of the body element 202 so that a pressurized condition can be applied to the extremity E.

[0048] The body element 202 when not in use is generally configured to be flat or occupying a minimized space or volume such that the device 200 can easily and conveniently be folded, stored or shipped. The body element 202 is capable of expanding from the minimized volume into an expanded space or volume for containing a portion of an extremity of a patient therein. Under a pressurized condition, the volume or space of the body element 202 is reduced from the expanded volume into a pressurized volume, such as a volume to conformably enclose the portion of the extremity E. As a result, the pressure applied to the extremity E enclosed inside the internal region 206 of the device 200 is distributed evenly and equally. The minimized volume and the expanded volume can be maintained under atmospheric pressure.

[0049] The body element 202 may be formed of a transparent or semi-transparent material that allows viewing of the extremity E positioned therein. The thickness of the collapsible and pliant material is not limited as long as it can sustain the pressurized conditions when the device 200 is used; for example, a thickness of from about 0.5 mils to about 20 mils, such as about 1 .5 mils to about 12 mils, can be used to pliantly conform to the shape and size of the portion of the extremity E contained therein. Accordingly, the materials of the body element 202 are generally formed of a collapsible and pliant material. The materials used in the thermal exchange units 210 and/or the body element 202 are generally selected to allow good contact between the surfaces of the extremity E and the thermal exchange units 210 and/or the body element 202 when a sub-atmospheric pressure or a vacuum pressure level is achieved within the internal region 206 of the device 200. In some embodiments, the body element 202 can be similarly configured as the device 100. In such a case, the body element 202 can include a thermal exchange unit 210 that is formed by bonding or sealing two layers of a collapsible and pliant material together to form a composite element that has a fluid plenum formed between the bonded and sealed layers to allow a fluid to be delivered from the fluid source 118 through a fluid plenum region that is separated from an internal region 206 of the body element 202 by one of the two layers.

[0050] The sealing element 208 may be formed of the same material as the sealing element 108 and can be attached or detachably attached to the opening 204. In addition, the sealing element 208 can be used for contracting with the portion of the extremity E and capable of producing an airtight seal. The pressurized volume defined by the body element 202 and the sealing element 208 of the device 200 is created by applying vacuum or negative pressure (relative to the pressure external to the internal region 206) to the pressure port 124. One or more pressure ports may be adapted to be connected to the pump 122 on one end and the body element 202 on the other end. In addition, the pressure level inside the internal region 206 or the pressurized, reduced volume enclosed by the body element 202 can be monitored by a pressure sensor 120 placed inside the pressurized volume or space attached to the pressure sensing line 126. One or more pressure ports may be adapted to be connected to the pump 122 on one end and the body element 202 on the other end.

[0051] Further a manifold 212 can be used to bundle up various fluid ports and pressure port together. The manifold 212 can be used to fluidly or electrically connect to a control system 114 including a controller 1 16, a fluid source 1 18, a pressure sensor 120, and/or a pump 122 to the various components found in the internal region 206 of the device 200. For example, the manifold 212 may include a pressure port 124, a pressure sensing line 126, fluid supply line 128, and the fluid return line 130 therein. Accordingly, the fluid supply lines 128 and the fluid return lines 130 can be connected to one or more thermal sources through the apertures on the body element 202. In one embodiment, the manifold 212 incorporates quick-connecting and quickdisconnecting fittings, similar to CPC Colder Products Company in S.t Paul, Minn. In addition, the manifold 212 may be formed on a portion of the body element 202 for connecting the various fluid ports or pressure ports to pass through the apertures of the body element 202 to other vacuum manifold, fluid sources outside of the device 200 through various kinds of tubing’s and/or manifold connectors. The manifold 212 may be connected to the apertures of the body element 202, the pressure ports and the thermal exchange units of the device 200. The position of the apertures for the fluid ports or pressure ports can be located near any convenient portions of the body element 202 and can be close to the manifold 212 or grouped together for passing through the body element 202 via a single aperture.

[0052] Figure 2B illustrates another configuration of the device 200 in which the manifold 212 is attached to a desired region of the body element 202 to provide a central place where connections can be made to the internal and external components in the device 200.

[0053] According to an embodiment described herein, the device 200 can be used in combination with a mechanical compression device or a pressurized compression device. Alternatively, the device can itself be modified to include one or more pressure-applying gas plenums in order to apply pressurized compression forces, or a positive gas pressure to an extremity E of a patient (e.g., in the internal region 206), while also applying a fluid to a thermal exchange unit 210 contacting the extremity E and/or applying vacuum or negative pressure (relative to the pressure external to the internal region 206) to a portion of the extremity E. The fluid may be water. In some embodiment, the fluid is a closed loop high efficiency thermal transfer material other than water, such as hydrogel, which can be continuously flowing while in use and can be stored as a solid when not use, through shear thinning or thermal triggers.

[0054] Figures 3A and 3B are a cross-sectional view and a plan view of a device 300A can be positioned over a desired portion of a patient, such as a forehead or portion of the patient’s skin to regulate the body temperature of a patient and/or blood flow within a portion of the patient by circulating a temperature controlled fluid (e.g. water, hydrogel at about 104°F). In some embodiments of device 300A, the temperature of a portion of a patient is regulated by circulating a temperature controlled fluid while also simultaneously applying at least a mild vacuum (e.g. 5mm Hg) to the extremity E. The device 300A generally contains a body element 302 having an internal region 306 that is positioned between a compliant element 308C and a sealing element 308S, and one or more thermal exchange units 310. The compliant element 308C covers or encloses the one or more thermal exchange units 310. The sealing element 308S is attached to the outer edges of the body element 302.

[0055] In general, the body element 302 can be formed of a disposable low-cost material, a biocompatible material, a material that can be sterilized, and/or a hypo allergic material. The compliant element 308C is generally formed from a collapsible and pliant material, including but not limited to, urethane, polyurethane, polypropylenes, polystyrenes, high density polyethylene’s (HDPE), low density polyethylene’s (LDPE), polyvinyl chloride), rubbers, elastomers, polymeric materials, composite materials, among others.

[0056] The compliant element 308C can be formed of a transparent or semitransparent material that allows viewing of the extremity E. The thickness of the compliant element 308C is not limited as long as it can sustain the pressurized conditions when the device 300A is in use. In one example, a thickness from about 1.5 mils to about 12 mils can be used to pliantly conform to the shape and size of the portion of the extremity E contained therein.

[0057] The sealing element 308S is generally used to form a seal to the extremity E of the patient so as to enclose the thermal exchange units 310 in the internal region 306. The sealing element 308S is generally designed to form a seal between the body element 302 and the extremity E to allow a pressurized condition to be applied within the internal region 306. The sealing element 308S can be formed of a sticky seal material, such as hydrogel, polyurethane, urethane, among others. Another example is a PS series thermoplastic polyurethane from Deerfield Urethane, Inc. Disposable sealing materials may be manufactured and packaged such that they are sterile before use and/or hypoallergenic to meet health and safety requirements. The sealing element 308S may include an air permeable portion and/or formed of a permeable membrane material or a breathable material to permit the flow of air.

[0058] In one embodiment, the thermal exchange units 310 have an insulating layer 3101 disposed on one or more sides of the device 300A to reduce heat loss to environment away from the extremity E and/or improve the heat transfer process to the extremity E.

[0059] Referring to Figure 3B, during operation the control system 1 14, a pressurized condition is created in the internal region 306 by use of the various fluid ports or pressure ports, such as a pressure port 124, a pressure sensing line 126, the fluid supply line 128, and the fluid return line 130 that pass through a manifold 312 formed in the body element 302. In one embodiment, the internal region 306 is evacuated by use of a pump 122 that is connected to the pressure port 124 to create a vacuum condition in the internal region 306. The sub-atmospheric pressure created in the internal region 306 will cause the atmospheric pressure external to the device 300A to urge the compliant element 308C against the one or more thermal exchange units 310 and/or the extremity E to increase the blood flow and control the temperature of the patient. In this way the device 300A can be positioned on any open area of the subject, such as positions on a patient’s forehead, back, chest, thigh, or neck to increase the blood flow and control the temperature of the patient.

[0060] Figure 3C is a cross-sectional view of a device 300C that can be positioned over a desired portion of a patient, such as a forehead or portion of the patient’s skin to regulate the body temperature of a patient and/or blood flow within a portion of a patient by a circulating temperature controlled fluid (e.g. water, hydrogel at about 104°F) within a thermal exchange unit 310 that is formed in a region 334 that is defined between a first body element 332A and a second body element 332B. The thermal exchange unit 310 is capable of containing a fluid, such as water or hydrogel therein.

[0061] In one embodiment, the first body element 332A and the second body element 332B of the thermal exchange unit 310 are each formed of a collapsible and pliant material, including but not limited to, urethane, polyurethane, elastomers, polypropylenes, polystyrenes, high density polyethylene’s (HDPE), low density polyethylene’s (LDPE), polyvinyl chloride), rubbers, polymeric materials, composite materials, among others. In such a case, the thermal exchange unit 310 can be formed by bonding or sealing the two layers of a collapsible and pliant material together to form a composite element that has a fluid plenum formed between the bonded and sealed layers to allow a fluid to be delivered from the fluid source 118 through a fluid plenum region that is separated from an internal region 206 of the body element 202 by one of the two layers. As similarly discussed above in relation to Figures 1A-1 B and 2A-2B, the thermal exchange unit 310 is generally designed to allow a fluid to be delivered therethrough to exchange heat with the extremity E.

[0062] The thermal exchange unit 310 is configured to enclose the extremity E by forming the internal region 306, which can be evacuated by a pump 122. Further, the device 300C is fluidly and/or electrically connected to a control system 114, which, as discussed further below, will generally include a controller 116, a fluid source 118, a pressure sensor 120, and/or a pump 122. When applied and affixed to a portion of an extremity E of a patient by the sealing element 308S, the device 300C forms the internal region 306 that is positioned between the second body element 332B, the sealing element 308S, and the extremity E of a patient. The internal region 306 is in fluid communication with pump 122 so that a mild vacuum (e.g., 5mm Hg) can be applied to the extremity E. During operation, the internal region 306 of the thermal exchange unit 310 will collapse under a vacuum pressure condition created by the pump 122 to allow the inner surface of the second body element 332B to apply even and equal pressure on the portion of the extremity E disposed inside the device 300C.

[0063] Figure 3D is a cross-sectional view of a device 300D that can be positioned over a desired portion of an extremity E of a patient, such as a forehead, to regulate the temperature of a portion of a patient by use a heat exchanging unit 310 that utilizes a temperature controlled circulating fluid while a positive pressure is applied to the extremity E by use of pressure applying element 305, according to another embodiment. The pressure applying element 305 of the device 300D is formed by use of a first body element 302A and a second body element 302B that define an internal region 306P that is positioned between the first body element 302A, the second body element 302B, and a sealing element 308S. The sealing element 308S is attached to at least the outer edges of the first body element 302A and the second body element 302B. In general, the first body element 302A and the second body element 302B can be formed of a disposable low-cost material, a biocompatible material, a material that can be sterilized, and/or a hypo allergic material.

[0064] In one embodiment, the first body element 302A comprises the rigid or semi-compliant element material such as the exterior surface of the device 300D, maintains its shape during use. In another embodiment, first body element 302A comprises the compliant element 308C, which includes a collapsible and pliant material. The first body element 302A can be formed of a transparent or semitransparent material that allows viewing of the extremity E. The thickness of the first body element 302A comprises is not limited as long as it can sustain the pressurized conditions when the device 300D is used. In one example, a thickness from about 1 .5 mils to about 12 mils can be used to pliantly conform to the shape and size of the portion of the extremity E contained therein.

[0065] The sealing element 308S is generally used to form a seal to the extremity E of the patient so as to enclose the thermal exchange unit 310 in the internal region 306. The sealing element 308S is generally designed to form a seal between the second body element 302B and the extremity E to form a region that encloses the thermal exchange unit 310. The sealing element 308S can be formed of a sticky seal material, such as hydrogel, polyurethane, urethane, among others. Another example is a PS series thermoplastic polyurethane from Deerfield Urethane, Inc. Disposable sealing materials may be manufactured and packaged such that they are sterile before use and/or hypoallergenic to meet health and safety requirements. The sealing element 308S may include an air permeable portion and/or formed of a permeable membrane material or a breathable material to permit the flow of air.

[0066] During operation of the control system 114, a gas is delivered to achieve a positive pressure in the internal region 306P, to cause the second body element 302B to be urged against the thermal exchange units 310 and the extremity E. The pressure delivered in the internal region 306P can be any desirable pressure, such as between about 1 mmHg to about 80 mmHg above atmospheric pressure. In this way the device 300D can be positioned on any open area of the subject, such as positions on a human’s back, chest, thigh, or neck to the blood flow and control the temperature of the subject by application of pressure to the internal region 306P and thermal control of the thermal exchange units 310. During operation, by use of the pump 322 (e.g., manually operated bulb, positive displacement pump, etc.) the internal region 306P of the pressure applying element 305 will cause the inner surface of the second body 332B to apply even and equal pressure on the portion of the extremity E disposed inside the device 300D.

[0067] In one embodiment, the thermal exchange units 310 have an insulating layer 3101 disposed on one or more sides of the device 300D to reduce heat loss to environment away from the extremity E and/or improve the heat transfer process to the extremity E.

[0068] Figure 3E is a cross-sectional view of a version of a device 300E that can be positioned over a desired portion of an extremity E of a patient to regulate the temperature of a portion of a patient by use a thermal exchanging unit 310 that utilizes a temperature controlled circulating fluid while a positive pressure is applied to the extremity E by use of pressure applying element 305, according to another embodiment. Further, the device 300E is fluidly and/or electrically connected to a control system 114 including a controller 116, a fluid source 118, a pressure sensor 120 (not shown), and/or a pump 322 to regulate the body temperature of a patient and/or blood flow within a portion of the patient.

[0069] The pressure applying element 305 of the device 300E is formed by use of a first body element 302A and a second body element 302B that define an internal region 306P that is positioned between the first body element 302A, the second body element 302B, and a sealing element 308S. The sealing element 308S is attached to at least the outer edges of the first body element 302A and the second body element 302B. The internal region 306P of the pressure applying element 305 is in fluid communication with the pump 322 so that a positive pressure (e.g., 1 mmHg to about 80 mmHg) can be applied to the extremity E. During operation, the internal region 306P of the pressure applying element 305 will cause the inner surface of the second body 332B to apply even and equal pressure on the portion of the extremity E disposed inside the device 300E.

[0070] The thermal exchange unit 310 is positioned over the extremity E and between the pressure applying element 305 and the patient’s extremity E. In some embodiments, the thermal exchange unit 310 is similar to the thermal exchange units 110 and 310 described above, and includes an internal region 306E (e.g. , fluid plenum 134) that is formed between the second body 332B and the lower wall 309. In one embodiment, the first body element 302A, the second body element 302B, and the wall 309 each include a collapsible and pliant material. When applied and affixed to a portion of an extremity E of a patient by the sealing element 308S, the device 300E the thermal exchange unit 310 is positioned against the surface of the extremity E of a patient.

[0071] During operation, by use of the pump 322 (e.g., manually operated bulb, positive displacement pump, etc.) the internal region 306P of the pressure applying element 305 will cause the inner surface of the second body 332B to apply pressure to the thermal exchange unit 310 which in turn is configured to apply even and equal pressure to the portion of the extremity E that is disposed adjacent to the lower wall 309 of the device 300E.

[0072] Figure 3F is a perspective view of a device 300F that can be positioned over a desired portion of an extremity E of a patient, such as a head, forehead, or portion of the patient’s skin to regulate the body temperature of a patient and/or blood flow within a portion of the patient by circulating a temperature controlled fluid. In some embodiments of device 300F, the temperature of a portion of a patient is regulated by circulating a temperature controlled fluid while also drawing at least a mild vacuum (e.g. 5mm Hg) to the patient’s extremity E. The device 300F includes a body element 302 that includes a compliant element 308C, a sealing element 308S, and a plurality of thermal exchange units 310 that are positioned between the compliant element 308C and the extremity E of the patient. The compliant element 308C covers the sealing element 308S which can be affixed to a surface of an extremity E of a patient or positioned over the head of a patient (Figure 3G). In some embodiments, the sealing element 308S is attached to the lower outer edges of the compliant element 308C.

[0073] In general, as discussed above, the compliant element 308C can be formed of a disposable low-cost material, a biocompatible material, a material that can be sterilized, and/or a hypo allergic material. The compliant element 308C is generally formed from a collapsible and pliant material, including but not limited to, urethane, polyurethane, polypropylenes, polystyrenes, high density polyethylene’s (HDPE), low density polyethylene’s (LDPE), polyvinyl chloride), rubbers, elastomers, polymeric materials, composite materials, among others. The thickness of the compliant element 308C is not limited as long as it can sustain the pressurized conditions when the device 300F is in use. In one example, a thickness from about 1.5 mils to about 12 mils can be used to pliantly conform to the shape and size of the portion of the extremity E contained therein.

[0074] In some embodiments, the device 300F includes a plurality of thermal exchange units 310 positioned in a circular array about a central axis 313. Each of the plurality of thermal exchange units 310 are coupled to a fluid source 118 through a manifold 312 so that a temperature-controlled fluid can, in one configuration of the device 300F, flow in series through each of the thermal exchange units 310 or in another configuration of the device 300F flow in a parallel path through each of the thermal exchange units 310. As shown in Figure 3F, the thermal exchange units 310 include a separating feature 342 that is formed to cause the fluid delivered from an input line of a fluid supply line 348 to flow through a plenum region 341 and around the separating feature 342 before the fluid exits a thermal exchanging unit of the plurality of thermal exchange units 310 and enters an output line of the fluid supply line 348. The separating feature 342 may be formed by RF welding, thermal sealing, gluing, or bonding the two or more layers of material used to form the thermal exchanging unit 310 together. In one embodiment, the input lines within the plenum region 341 of each thermal exchange units 310 are fluidly coupled together within the manifold 312 and output lines within the plenum region 341 of each thermal exchange units 310 are fluidly coupled together within the manifold 312 to form the parallel flow path configuration within the device 300F. In another embodiment, the input lines within the plenum region 341 of each thermal exchange unit 310 are fluidly coupled to the output lines within an adjacently positioned plenum region 341 of an adjacently positioned thermal exchange unit of the plurality of thermal exchange units 310 to form the serial flow path configuration within the device 300F.

[0075] The sealing element 308S is generally used to form a seal to the extremity E of the patient so as to enclose the thermal exchange units 310 in an internal region 306 formed between the compliant element 308C and the extremity E of the patient. The sealing element 308S can be formed of a material, such as hydrogel, polyurethane, urethane, thermoplastic polyurethane, or other useful material. The sealing element 308S may include an air permeable portion and/or formed of a permeable membrane material or a breathable material to permit the flow of air.

[0076] During operation the device 300F that can be positioned over a desired portion of an extremity E of a patient, such as a head, forehead, or portion of the patient’s skin and the control system 114, which is connected through a manifold 312 that delivers temperature-controlled fluid to the thermal exchange units 310 to control the temperature of the patient. In some embodiments, the control system 114 is used to draw a vacuum pressure to an internal region 306 that is formed between the compliant element 308C and the extremity E of the patient to cause the thermal exchange unit 310 to be urged against the patient’s extremity E.

[0077] Figure 3G is a side view of a device 300G that can be positioned over a portion of the head of a patient to regulate the body temperature of a patient and/or blood flow within a portion of the patient. The device 300G can comprise one of the devices 300 described above, such as device 300F which has been sized to fit over the upper portion of a patient’s head. Alternately, in one example, the device 300G can include a device 300F that is sized to be positioned on and/or affixed, by the sealing element 308S, to a forehead region 361 of the patient’s head.

Thermal Exchange Unit Examples

[0078] Figures 4A and 4B each illustrate an example of a thermal exchange unit 400 that can be used to form at part of one of the thermal exchange units 210 and 310 described above. The thermal exchange unit 400 includes a thermal exchange body 402 having sides 402A and 402B. One side (e.g., side 402B) of the thermal exchange body 402 includes thermal contact domes 404 that have a thermal contact surface 406 that can be applied to a portion of the extremity E. The diameter of the thermal contact surfaces 406 and the shapes or sizes thereof can vary such that the sum of the total area of the thermal contact surfaces 406 can be maximized. The thermal exchange unit 400 may further include the fluid supply line 128 and the fluid return line 130 connected to a fluid source (e.g., the fluid source 118) for circulating a fluid through the thermal exchange body 402 of the thermal exchange unit 400.

[0079] The material of the thermal exchange body 402 may be any flexible, conductive and/or durable material. In one embodiment, the thermal exchange body 402 is formed of a flexible material which can easily conform to the shape of the extremity E. In another embodiment, the thermal contact domes 404 are formed of a rigid material to provide rigid contacts to the extremity E.

[0080] In addition, the material of the thermal contact domes 404 may be a material which provides high thermal conductivity, preferably much higher thermal conductivity than the material of the thermal exchange body 402. For example, the thermal contact domes 404 may be formed of aluminum, which provides at least 400 times higher thermal conductivity than plastics or rubber materials. In one embodiment, the thermal exchange unit 400 can be formed and assembled through RF welding. In another embodiment, the thermal exchange unit 400 may be formed and assembled through injection molding. There are many possible ways to design and manufacture the thermal exchange body 402 to provide a flexible thermal exchange unit that does not leak. In one embodiment, the thermal exchange body 402 is formed by bonding a compliant material that is sealed using conventional techniques at a joint 408.

[0081] In one embodiment, as discussed above, the thermal exchange unit 400 is formed from layers of several materials bonded together to form internal fluid flow paths for fluid to be delivered therein. The multiple layer configuration may result in uneven surfaces, due to the presence of the internal fluid flow paths. The resulting bumpy surfaces may provide less contact, thereby reducing surface area needed for maximum thermal transfer. The thermal exchange body 402 may also be formed using a low thermal conductivity material, such as polyurethane. To prevent these problems from affecting the results, the thermal exchange body 402 may be covered by one or more backing sheets such that a flat and even contact is made to the extremity. In addition, the backing sheet can be formed of high thermal conductive material to provide high thermal conductivity between the thermal exchange unit 400 and the extremity. For example, the backing sheets may be formed of a thin metal sheet, such as aluminum (like a foil) or other metal sheets. In general, aluminum or other metal materials may provide higher thermal conductivity than plastics or rubber, e.g., at least 400 times higher.

[0082] Figure 4B illustrates another example of the thermal exchange unit 400 that is formed using two layers of a compliant material 410 that are sealed at an edge region 412 by use of an RF welding, thermal sealing, gluing or other bonding process to form a sealed main body 414. The sealed main body 414 may have an inlet port 416 and an outlet port 418 that are in fluid communication with the fluid source 118, and the fluid supply line 128 and the fluid return line 130, respectively. The region formed between the two layers of the compliant material 410 is thus used as a fluid plenum that can receive (see arrow Ai ) and then exhaust (see arrow As) the fluid from the fluid source 118. In one embodiment, a separating feature 420 is formed in the thermal exchange unit to separate the fluid delivered into the inlet port 416 and the outlet port 418, and thus allow the thermal exchanging fluid to follow a desirable path through fluid plenum to optimize and/or improve efficiency of the heat transfer process. In one example, the fluid flow path sequentially follows the arrows Ai , A2 and A3. The separating feature 420 can be formed in the sealed main body 414 by RF welding, thermal sealing, gluing or other bonding process to bond the two layers of the compliant material 410 together. In one embodiment, a plurality of dimples 422 are formed between the layers of the compliant material 410 in the sealed main body 414 by RF welding, thermal sealing, gluing, or other bonding process to form a structure that will not expand when a heat exchanging fluid is delivered to the internal region of the sealed main body 414. In one embodiment, the thermal exchange unit 400 is formed and assembled through RF welding or thermal sealing techniques. In another embodiment, the thermal exchange unit 400 may be formed and assembled through injection molding. In one embodiment, the thermal exchange unit 400 illustrated in Figure 4B is formed from a pliant material, including but not limited to, urethane, polyurethane, polypropylenes, polystyrenes, high density polyethylene’s (HDPE), low density polyethylene’s (LDPE), polyvinyl chloride), rubbers, elastomers, polymeric materials, composite materials, among others.

[0083] Alternatively, the thermal exchange units 400 may be an electric pad having one or more electric wires connected to a power source. For example, the power source may be a low voltage DC current power source. In addition, the thermal exchange units may include a thermocouple to monitor the temperature and a thermo switch to automatically shut off the electric power when the temperature of the electric pad passes a safety level.

[0084] In another alternate configuration, the thermal exchange unit 400 may include an exothermic chemical reaction heat-generating device that releases heat as a byproduct of an initiated chemical reaction. The heat-generating device can be a flameless type chemical reaction heater, for example, that utilizes a reaction between iron powder, water, and salt to generate the required amount of heat to perform the therapeutic process. For example, the heat-generating device is a self-contained plastic material-encased device. The thermal exchange units may include a thermocouple to monitor the temperature to warn the patient that the temperature has reach an unsafe level.

[0085] The thermal exchange units 400 generally provide thermal exchange surfaces, with increased surface area, to heat, cool, and/or regulate the temperature of an extremity of a patient. The thermal exchange units 400 can be used to regulate the blood flow in an appendage by a variety of means. For instance, applying a temperature to a hand of about 0°C to 10°C can cause an increase in the average blood flow due to a phenomenon called the “hunting response” which keeps hunters and fisherman from getting frostbite while working in the extreme cold with their bare hands. Different individuals respond differently to cold applied to the hands, and in a some well-known laboratory tests, application of cold to the hands of a person from the Indian sub-continent improved average blood flow, but not as much as the same treatment improved the average blood flow in the typical Eskimo.

[0086] In some cases, the perception of warmth is enough to improve blood flow. For instance, a 23°C (room temperature) water pad feels cool in intimate contact with the leg of a normothermic subject who otherwise feels warm, and the “COOLNESS” of the pad can measurably reduce blood flow in the leg. However, if the same person’s leg has been exposed to 5°C cold for prolonged periods, this same 23°C (room temperature) water pad feels warm in comparison, so that it can actually increase blood flow in the same leg. Therefore the temperature blood flow relationship is determined by both perceived warmth and applied temperature. The application of the heat above the core body temperature is also able to increase blood flow.

Therapeutic System Example

[0087] Figure 5A is an isometric view of an example of a therapeutic system 501 that is a self-contained unit, according to one or more embodiments of the disclosure. Figure 5B is a schematic view of the control system 114 connected to device 500 of the therapeutic system 501 according to one or more embodiments of the present disclosure. The therapeutic system 501 includes an enclosure 590 that includes the device 500 that is fluidly and/or electrically connected to the control system 114. The device 500 and components of the control system 114 are both disposed within an internal region 593 of the therapeutic system 501. The internal region 593 is at least partially defined by a plurality of walls 594, which can include a rigid or flexible sheet of material, such as a metal or plastic material sheet. The internal region 593 of the enclosure 590 is isolated from the external environment by the walls 594 and an external surface of a body element 502 of the device 500 that is sealed to an opening 504 formed in one of the walls 594. In some embodiments, the body element 502 can be disposed in a first region 591 of the enclosure 590 and the components of the control system 114 can be disposed within a second region 592 of the body element 502.

[0088] The device 500 of the therapeutic system 501 includes components that are configured to circulate a fluid (e.g. water, hydrogel, or gas at about 104°F) while simultaneously drawing at least a mild vacuum (e.g. 5mm Hg) to a distal appendage (e.g., a hand, an arm, a forearm, a forearm with an elbow, a hand with a wrist, a foot, a leg, a calf, an ankle, toes, etc.) of a user. The device 500 will typically comprise a the device 100, the device 200, or one of the devices 300, which are discussed above in conjunction with Figures 1-3G.

[0089] In some embodiments, the device 500 includes a body element 502 that has an opening that is coupled to the opening 504 formed in a wall 594 so that a portion of an extremity E of a patient can be enclosed in the internal region 506 of the body element 502. In one embodiment, one end of a sealing element 508 is attached to the opening 504 formed in a wall 594. In general, the body element 502 can be formed of a disposable low-cost material, a biocompatible material, a material that can be sterilized, and/or a hypo allergic material. In one embodiment, the sealing element 508 is detachably attached to the opening 504. In another embodiment, the sealing element 508 is formed of a disposable material, such as a disposable liner or an insert material. For example, the material of the sealing element 508 may be hydrogel, a sticky seal material, polyurethane, urethane, among others. One example of the material is hydrogel. Another example is a PS series thermoplastic polyurethane from Deerfield Urethane, Inc. Disposable sealing materials may be manufactured and packaged such that they are sterile before use and/or hypoallergenic to meet health and safety requirements. The sealing element 508 may include an air-permeable portion and/or formed of a permeable membrane material or a breathable material to permit the flow of air, etc. The permeable portion may be positioned near any portion of the body portion to provide permeable outlets, allowing the vacuum to have the proper effect on the extremity E and providing a barrier keeping the device 500 from contamination for the comfort of the user.

[0090] The second region 592 of the enclosure 590 includes the components used to form the control system 114. In one example, as shown in Figures 5A and 5B, the second region 592 includes a fluid source 118, the pump 122 (e.g., vacuum pump), the fluid reservoir 556, the vacuum sensor 120A, the fluid temperature sensor 610, microcontroller 601 (described below) of the controller 116, and a power supply 551 , which is coupled to an external AC source 552 (e.g., 110V wall plug). The power supply 551 , which can be a rechargeable 12 VDC source, is used to power all of the components within the therapeutic system 501 .

[0091] In some embodiments, the fluid reservoir 556 is a sealed reservoir that includes an amount of a heat-exchanging fluid, such as deionized water, that is recirculated through the heat-exchanging portion of the thermal exchanging unit 510 by use of a pump within the fluid source 118 and interconnecting tubing 518. In one example, the amount of a heat-exchanging fluid can include between 0.5 and 2 liters of liquid.

[0092] During operation a desired portion of an extremity E of a patient is disposed within the internal region 506 of the body element 502 of the device 500 of the self- contained therapeutic system 501. The components within the device 500 are configured to recirculate the temperature-controlled fluid to the thermal exchange units 510 to control the temperature of the patient by use of the components within the fluid source 118 and heater 555, and power supply 551 , and use of one or more commands provided from the microcontroller 601. In some embodiments of the disclosure, the heater 555 can include a resistive heater element(s) coupled to the fluid reservoir 556. In some other embodiments, the heater 555 can include an exothermic chemical reaction heat-generating device that releases heat as a byproduct of an initiated chemical reaction. The heat-generating device can be a flameless type chemical reaction heater, for example, that utilizes a reaction between iron powder, water, and salt to generate the required amount of heat to perform the therapeutic process.

[0093] In some embodiments, the control system 114 is used to draw a vacuum pressure to an internal region 506 that is formed within an inner surface of the body element 502 and the extremity E of the patient to cause the thermal exchange unit 51 O to be urged against the patient’s extremity E. The controller 116, Al controller 624, and various sensors (e.g., the vacuum sensor 120A, a flow rate sensor (not shown), and the fluid temperature sensor 610) are provided for closed-loop control of one or more of the process variables (e.g., vacuum pressure, fluid temperature, process duration, thermal exchange fluid flow rate, etc.) of the therapeutic processes performed by the therapeutic system 501 .

Control System Example

[0094] Figure 6A illustrates the control system 114 that is connected to various parts of a device 600 according to an embodiment of the disclosure. Figure 6B is a schematic view of the control system of the device 600, according to one or more embodiments of the present disclosure. Figure 6C is a schematic view of the control system, which includes an artificial intelligence (Al) control system of the device 600, according to one or more embodiments of the present disclosure. The device 600 may include the device 100, the device 200, one of the devices 300, or device 500, which are discussed above in conjunction with Figures 1-3G and Figures 5A-5B.

[0095] The control system 114 generally contains a controller module 602 that houses all of the electronics and mechanical parts which are required to regulate the temperature, pressure, and compression pressurized force provided to the pressurized volume of the device 600. In this configuration, the control system 114 typically includes, for example, a fluid source 118, one or more pressure sensors (e.g., vacuum sensors 120A and 120B Figure 6B), a pump 122, conventional tubing 604, a fluid flow sensor 606, a fluid sensing assembly 608, a fluid temperature sensor 610, a body temperature sensor 612, communication interface 605 (Figure 6B), and Al controller 624 (Figure 6B), which are controlled by a microcontroller 601 (Figure 6B) of the controller 1 16. The body temperature sensor 612 is generally a device used to measure the patient’s temperature while the process of increasing the blood flow and controlling the patient's temperature is being performed. Temperature of the patient can be measured in the ear, mouth, on the skin, or rectally using an appropriate conventional temperature sensing device.

[0096] The control system 114 may also contain a fluid pump 118A of a fluid source 118, a heater 119, a cooler (not shown), thermocouples, a fluid pump, the microcontroller 601 , one or more power supplies, display panels, actuators, connectors, internal and external device communication, Al microcontroller, among others, that are controlled by the controller 116. The settings and current readings of the various elements of the control system 114 may be conveniently positioned onto a display panel 603 (e.g., lighted display, CRT) which provides an operator interface. The controller 116 may contain additional electronics used to enable communication between devices, such as wireless connection (WiFi or Bluetooth®) hardware or a wired connection hardware within the communication interface 605, for optimal operation of the device 600.

[0097] In one or more embodiments, the control system 114 includes the microcontroller 601 (Figure 6B) that includes a central processing unit (CPU) 601 A, a memory 601C, and support circuits 601 B. The microcontroller 601 is used to control one or more aspects of the processes and methods described herein. The CPU is a general-purpose computer processor configured for use in an industrial setting for controlling one or more components of a device, such as devices 100, 200, or one of the device 300s. The support circuits 601 B are conventionally coupled to the CPU and comprise cache, clock circuits, input/output subsystems, power supplies, and the like, and combinations thereof. Figure 6B illustrates an example of a control system 114 that includes various external components that are able to communicate with the microcontroller 601 by use of the support circuits 601 B.

[0098] The memory 601 C described herein, which is generally non-volatile memory, may include random access memory, read-only memory, floppy or hard disk drive, or other suitable forms of digital storage, local or remote. Software instructions (e.g., program 627) and data can be coded and stored within memory to instruct a processor within CPU. A program (or software instructions) readable by CPU determines which tasks are performable by the components in the device. Typically, the program includes code, which, when executed by the processor (CPU), performs tasks relating to the processes described herein. The program may include instructions that are used to control the various hardware and electrical components within the device to perform the various process tasks and various process sequences used to implement one or more of the methods described herein. In some embodiments, the program includes instructions used to perform one or more of the operations of one or more of the methods described below in relation to Figure 6. In one example, the program includes instructions that are configured to cause the performance of one or more of the blocks 710-760 described in relation to method 700.

[0099] The control system 114 may provide safety features including a device shutdown feature that is activated if the device sensors, such as the temperature and pressure sensors, fail or become disconnected. The control system 114 may also include an alarm circuit or an alert signal if the temperature of the apparatus is not regulated correctly. A relief valve (not shown) may be provided within the vacuum or pressure generating loop that contains the pump 122 of the device 600 such that the internal region of a device may be vented if the vacuum or pressure within the internal region exceeds a certain level.

[0100] In one embodiment, the body temperature sensor 612 can be provided to measure the temperature of a portion of a patient other than a foot, leg, or other extremity where the device is attached to. In another embodiment, a tympanic membrane can be attached to the ear canal as the body temperature sensor 612 to provide core temperature reading. As such, a reference temperature for the human, such as a user, can be obtained. Other sensors may include the patient’s blood flow, blood pressure, and heart rate. A patient’s blood flow can be measured by a blood flow measurement device that utilizes an ultrasonic doppler flow technique and is configured to provide a blood flow measurement signal to the components within the communication interface 605 of the controller 116. A patient’s blood pressure and heart rate can be measured by a blood pressure measurement device that utilizes a blood pressure cuff and is configured to provide a signal that includes the blood pressure and heart rate measurement information to the components within the communication interface 605 of the controller 116. These types of data are important to proper health care for the user keeping the user at normal temperature range and from various thermal maladies. The temperature of the skin in the device could be measured to indicate if the body portion is in a state of vasoconstriction or vasodilatation or what temperature the skin is compared to the device fluid temperature. Temperature of the skin can be measured by different means and different devices like Thermocouples, Thermistor, Heat flux and other measuring devices.

[0101] In one embodiment, a wearable sensor 614 can be provided to gather physiologic data concerning markers related to an onset or likelihood of developing a migraine or other acute pain. The wearable sensor 614 may be a non-invasive monitoring device. The wearable sensor 614 may gather physiologic data concerning homeostasis and other measurements of thermal stability of the user. The wearable sensor 614 may gather physiologic data concerning markers related to vasoconstriction and blood flow in the forehead and other body peripheral appendices. Data gathered by the wearable sensor 614 may be sent to the controller 116. In some embodiments, the wearable sensor 614 includes an electronic skin (E-skin) sensor that is adapted to unobtrusively monitor one or more physical/physiological parameters of a patient, including the patient’s biopotentials (e.g., a patient’s electrocardiogram (ECG), electroencephalogram (EEG), or electromyography (EMG)), body temperature, human motion, skin hydration as well as a library of metabolic markers (e.g., glucose, insulin, lactate, and cortisol). In some embodiments, the wearable sensor 614 can also include the use of an interstitial fluid (ISF) device that includes a microneedle (MN) array patch that can deliver drugs, vaccines, biomolecules, or other useful fluids or materials or extract various interstitial fluids (ISFs).

[0102] As shown in Figure 6A, the device 600 can be connected to the pump 122 (e.g., mechanical vacuum pump, mechanical pump and vacuum ejector) via a vacuum port 616 and a vacuum sensor return line 618 to provide a vacuum pressure or a negative pressure inside the device 600. It is important to maintain the vacuum and/or negative pressure levels and correctly sense and read out the vacuum/pressure levels inside the device where the extremity is exposed to and send the data to a vacuum transducer mounted in the controller 1 16. The signal controlling the pump 122 would come through wires from the vacuum transducer to control circuits in the controller 116. Additional set of data, such as pressure data applied to the extremity E by the vacuum, could be measured through a series of pressure sensors placed through the device 600 to record pressure levels and send data to the controller 116 for evaluation. The controller 116 can then adjust the levels of vacuum (or positive pressure) and the temperature within the device to control blood flow and the body’s core temperature as needed.

[0103] In addition, the device 600 with the thermal exchange unit 110, 210, 310, or 400 therein may be connected to the fluid source 118 via a fluid supply line 620 and a fluid return line 622. Further, the flow of a fluid provide inside the fluid supply line 620 can be monitored and regulated by controller 116 by use of a signal provided by the fluid flow sensor 606. In addition, a low fluid LED may be used and displayed on the front panel of the controller 116 to warn an operator of the fluid level in the reservoir of a fluid source. Additional sensor will be added to the fluid reservoir to send a signal when the fluid level is low and more fluid is needed. Further, there may be controlling signal that allow a conventional fluid pump to operate in a mode of returning fluid back from the fluid pads when the procedure or a single operation of the device is complete. Additionally, the device 600 may include a temperature sensor for the heated or cooled fluid circulating through various tubing’s and fluid lines. In addition, the thermal exchange units (e.g., 210, 310, 400 or 510) of the disclosure may include one or more temperature sensors and thermocouples to monitor the temperature of a patient’s extremity and provide temperature control feedback.

[0104] These lines and ports of the disclosure may be bundled, contained, and strain-relieved in the same or different protective sheaths connected to the controller 116. The lines may also be contained in the same or different tubing set with different enclosures for each medium used, such as fluid, vacuum, electric heat, and air lines. [0105] In one embodiment, the thermal exchange units of the device 600 are coupled in a closed loop configuration with the fluid source 118 which provides a fluid, such as water or hydrogel. For example, the thermal exchange unit may be coupled in a closed liquid loop configuration with a liquid tank housed within the controller module 602. In one embodiment, one or more resistive heating elements and/or thermoelectric devices are used to heat or cool the fluid contained in the liquid tank. The closed loop configuration reduces the maintenance requirements for the operator because it minimizes the loss of fluid that typically occurs if the thermal exchange unit is detached from the fluid source. Contamination of the fluid source 118 is also minimized by the closed loop configuration. Contamination of the fluid such as water can also be reduced by adding an antimicrobial agent to the fluid source. In different embodiments, the fluid may be either a liquid or a gas. In practice, the fluid flow rate should be as high as possible. It was found through testing that the inflow temperature and the outflow temperature through the pad should be within about <1.0°C. It has also been found that, in certain cases, blood flow did not increase at all if the pad fluid temperature was below 40°C. A high flow rate allows better temperature consistency, results in less thermal loss, and creates better thermal exchange. In a closed loop configuration including the thermal exchange unit and the fluid source, with a total system volume (e.g., 0.75 liters), a flow rate (e.g., 2 liters per minute) transfers as much fluid through the thermal exchange unit (e.g., twice than a flow rate of 0.35 liters per minute).

[0106] In an alternative embodiment, the thermal exchange unit and vacuum lines may be connected to the controller 116 using actuated fittings such as quick connect fittings with an automatic shut off mechanism. The automatic shut off mechanism halts the vacuum application and the heating medium flow as soon as the vacuum lines are disconnected. Actuated fittings may also allow the operator to change the thermal exchange unit. In addition, various quick disconnect connectors may be added to the controller 116 to allow various disposable parts of the device to be disconnected after each use.

[0107] In one embodiment, the controller 116 manages the temperature and flow of the temperature controlled fluid and negative or positive pressure applied to the patient for the duration of the treatment, which may be about 30 minutes, for example. The duration may be longer or shorter depending on the size of the extremity treated and the temperature of the extremity. As discussed further below, the general treatment process may be repeated one or more times as needed. In some cases, the duration of the treatment may be cycled “on” for a period of time and then “off” for a time period. In one example, the duration of the treatment is about 1 minute or longer and then off for a period of about 1 minute or longer, which is repeated for 5 cycles or more. The controller 116 is configured to halt the treatment after each treatment period. A “stop” button on the control system 114 may be used to turn off the fluid supply and the vacuum. In one aspect, the controller 116 is designed to monitor the expansion of the lower limb to determine venous refilling so that the refill time can be adjusted as desired. In general, only small amounts of pressure are needed to be supplied to the extremity to cause movement of blood within the extremity, such as between -3 mmHg and about -20 mmHg. The pressure applied to the extremity E can then be cyclically varied between a lower pressure and a higher pressure level for a desired number of times. When the cycled pressure drops to a low pressure (e.g., -3 mmHg) level, this provides time for venous refilling.

[0108] The control system 1 14 further includes an artificial intelligence (Al) controller 624, which is also controlled by the controller 116. In some embodiments, the Al controller 624 includes a separate central processing unit (CPU), memory, and support circuits from similar components found in the microcontroller 601 . In this case, one or more Al-related tasks are performed by use of an Al algorithm (i.e., software program), and Al model data is collected and stored in the memory of the Al controller 624. In an alternate embodiment, the Al controller 624 and/or functions thereof are performed using an Al algorithm 628 (i.e., software program) and Al model data collected and stored in the memory of the microcontroller 601 . As is discussed further below, the Al controller 624 receives user information, such as the temperature measured by the fluid temperature sensor 610, pulse, blood flow, e-skin, and blood pressure, data gathered by the wearable sensor 614, and user profile, and simulates Al algorithms to control in real time application of one or more drug therapies using the gathered data. The Al algorithms may create predictive procedures for prognostic purposes on the user’s risk of acute migraine. The Al controller 624 may further control the device 600 to simultaneously perioperatively heat the portion of the patient’s extremity E to provide a migraine therapy or other useful therapy by applying heat and in some cases a mild pressure to the extremity E (e.g., lower legs).

[0109] In general, an Al algorithm includes processes that require combining large sets of data with intelligent, iterative processing algorithms to learn from patterns and features in the data that it has analyzed and/or is analyzing. Each time an Al algorithm (and Al model) runs a round of data processing, it will test and measure its own performance so as to develop additional expertise based on the performance of these activities.

Therapeutic Method Examples

[0110] Figure 7 illustrates a process flow diagram of a therapeutic method 700 for acute and preventive treatment of a migraine headache or other recurrent acute or chronic pain by manipulating blood flow to the head and distal appendages and manipulating central, peripheral blood pressure and vaso-motor tone, according to one or more embodiments of the present disclosure. The one or more therapeutic devices described herein, include a novel mechanism of action in the pain cascade affecting migraines, that could be self-administered by the patient at home or in a clinical setting. The devices and methods provided herein can be used for treatment as a stand-alone therapeutic, or in combination with migraine drugs to improve the therapeutic results seen by the patient.

[0111] In block 710, a device such as the device 100, the device 200, or one of the devices 300 is positioned on an extremity E (such as a distal appendage or a forehead) of a user. In one non-limiting example, the method 700, which is described below, is performed by use of a device 300A.

[0112] In block 720, a vacuum is applied to a portion of the extremity E. Negative pressure is applied to the pressure port 124 thereby lowering the pressure within the internal region 306 relative to the pressure external to the internal region 306 and exposing the extremity E to a negative pressure in the range, for example, of between about 0 and about -20 mmHg, such as between about -10 mmHg and about -14 mmHg.

[0113] In block 730, simultaneously or sequentially, a heated fluid (e.g., water) is circulated through the thermal exchange units 310 disposed over a surface of the portion of the extremity E. In one example, the portion of the extremity include at least one of a wrist, hand, foot, leg, calf, ankle, toes, arm, head, forehead, or other region of a patient where arteriovenous anastomoses (AVAs) are located. The heated medium may be at a temperature of between about 95°F and about 104°F, for example, about 104°F. The flow rate of the pump 122 may be constant, and the flow rate of the fluid needs only to be maintained so that a constant pressure can be achieved in the internal region 306. If there is a slight leak in the device 300A, the required flow rate may be greater than about 1 liters per minute and is preferably about 0.5 liters per minute or lower. In one aspect, the flow rate of the pump 122 may be between about 0.5 liters and about 1 liters per minute, but is preferably less than about 1 liters per minute.

[0114] In some embodiments, the operations performed during blocks 720 and 730 are performed for a first period of time to allow the application of heat by use of the thermal exchanging units 310 and the application of a vacuum or pressure by the pump 122 to the pressure port 124 to promote vasodilation in the AVAs and overcome a vasoconstricted state caused by the onset of a migraine. In one example, the operations performed during blocks 720 and 730 are performed for between 1 minutes and about 2 minutes. In another example, the operations performed during blocks 720 and 730 are performed for an initial preparatory period of time that is between about 1 minute and about 10 minutes, such as between 4 and 9 minutes, and then used for a therapeutic period of time, such as greater than an additional 10 minutes, or greater than an additional about 20 minutes, such as between an additional 20 and 60 minutes. Applying the vacuum and circulating the heated fluid is configured to overcome a vasoconstricted state of the portion of the extremity E and manipulate blood flow to the portion of the extremity E of the user. [0115] During the operations performed during one or more of the blocks 710, 720, or 730 the control system 114 is configured to collect therapeutic information about the patient which is used by the controller 116 to control the temperature and pressure applied to the extremity E, and also the administration of one or more drug therapies to the patient as performed and described in subsequent blocks 740-760.

[0116] Referring to Figures 6B and 6C, in some embodiments, the control system 114 is configured to collect therapeutic information about the patient from various sources that are internal and external to a device, such as device 300A, for example. As shown in Figure 6C, for example, the microcontroller 601 and/or the Al controller 624 are configured to receive therapeutic information provided from sensors, devices, and external systems by use of various analog or digital communication signals.

[0117] As illustrated in Figure 6C, the control system 114 is configured to receive information from external devices that are configured to extract data from the patient during one or more therapeutic procedures. While not required for the treatment of a migraine headache, in one example, the control system 1 14 is configured to receive information from a machine or device that is aiding in the performance of anesthesia on a patient. In this example, the anesthesia device is collecting information relating to the core body temperature, heart rate, blood pressure, and EtCO2 levels for example of the patient and communicating the collected information to the Al controller 624 and/or controller 116 of the control system 114.

[0118] In another example, the control system 114 is configured to receive information from a pulse oximetry device. The pulse oximetry device is configured to provide oxygen saturation within the patient’s blood and pulse rate information to the Al controller 624 and/or controller 116 of the control system 114. The oxygen saturation level within a patient’s blood can indicate how well a drug, which is provided during the therapeutic process, will be metabolized by the patient. Thus, the oxygen saturation level information can be used by the Al controller 624 and/or controller 116 to improve the effectiveness of treating a migraine headache or other recurrent acute or chronic pain by adjusting one or more of the process variables of the therapeutic process. In general, the one or more of the process variables of the therapeutic process disclosed herein can include, for example, vacuum level applied to the extremity E, amount of applied pressure to the extremity, temperature of the thermal exchange unit(s), therapeutic procedure length (e.g., time), drug dosage level, and/or pulsing interval and duty cycle of the applied vacuum or an applied pressure to the extremity.

[0119] In another example, as described above, the control system 114 is configured to receive information from a blood flow measurement device, such as a device that utilizes an ultrasonic doppler flow technique. The blood flow measurement device is configured to provide periodic or real-time blood flow rate information within an extremity E of the patient to the Al controller 624 and/or controller 116. The blood flow measurement can indicate whether the patient is in a vasoconstricted state. If it is determined that the patient is in a vasoconstricted state, the Al controller 624 and controller 116 can be used to adjust one or more of the process variables of the therapeutic process to overcome the vasoconstricted state. In one example, the Al controller 624 and controller 116 provide a first command that causes a vacuum level applied to the patient’s extremity E to be increased from a starting level or its current level to a new higher vacuum level. The Al controller 624 and controller 116 can then monitor vasoconstricted state to determine if the vasoconstricted state has been overcome, and once it has been overcome, then deliver a second command to adjust the applied vacuum level to new vacuum level (e.g., a lower vacuum level).

[0120] In another example, as described above, the control system 114 is configured to receive information from an electronic skin (E-skin) sensor that is adapted to unobtrusively monitor one or more physical/physiological parameters of a patient, including the patient’s biopotentials (e.g., a patient’s electrocardiogram (ECG), electroencephalogram (EEG), or electromyography (EMG)), body temperature, human motion, skin hydration as well as a library of metabolic markers (e.g., glucose, insulin, lactate, adrenaline (or other a stress hormone), and cortisol). The E-skin device is configured to provide periodic or real-time data regarding the patient's physical/physiological parameters to the Al controller 624 and/or controller 116. In one example, a level of adrenaline is measured within a patient’s blood, which can indicate a trigger to the onset of a migraine or the status of a migraine headache. Thus, the adrenaline level information can be used by the Al controller 624 and/or controller 116 to improve the effectiveness of the treatment of a migraine or other recurrent acute or chronic pain by adjusting one or more of the process variables of the therapeutic process. In another example, the measurements provided by the e-skin sensor can be used to indicate the state of one or more cardiovascular conditions that can be treated as part of the therapeutic processes described herein.

[0121] In another example, as described above, the control system 114 is configured to receive information from a blood pressure measurement device. The blood pressure measurement device is configured to at least provide periodic blood pressure measurement information to the Al controller 624 and/or controller 116. The received blood pressure measurement information can indicate whether the patient has become overheated during the therapeutic process. Thus, the blood pressure information can be used by the Al controller 624 and/or controller 116 to improve the effectiveness of the treatment of a migraine headache or other recurrent acute or chronic pain by adjusting one or more of the process variables of the therapeutic process (e.g., reduce the thermal exchange fluid temperature).

[0122] In another example, the Al controller 624 and/or controller 116 of the control system 114 are configured to receive patient profile information 642. The patient profile information can include information relating to the patient’s medical history relating migraines, neurological information, drug interaction information, information relating to prior successful times the method 700 had been performed (e.g., prior used temperature or pressure parameters, etc.), or other useful information. The patient profile information 642 can be received as input into an algorithm running on the controller 116 or from a separate software application that utilized on an external device (e.g., personal computer, tablet, smart phone, etc.) that is in communication with the control system 114. In one example, the patient profile information 642 can include physical attribute information that can include the patient’s sex, weight, height, body-mass-index (BMI), and age. The patient profile information 642 can also include medical condition information, such as information relating to high blood pressure, diabetes, menstrual cycle, cancer related information, blood disorders, heart disease, migraine history, and other cancers. The patient profile information 642 can be used by the Al controller 624 and/or controller 116 to tailor one or more of the processes or process variables used in the performance of the activities performed during blocks 710-760.

[0123] In yet another example, the Al controller 624 and/or controller 1 16 of the control system 114 are configured to receive system-related sensor data from the body temperature sensor 612, the fluid temperature sensor 610, the fluid flow sensor 606, and/or the pressure sensor 120. Based on the received system-related sensor data and input from the Al controller 624, the controller 116 is configured to adjust one or more of the control system’s process parameters to improve the performance of the processes performed during blocks 710-730.

[0124] In block 740, one or more drug therapies are provided to the user, while applying the vacuum and circulating the heated fluid to the user. The drug therapies may be used to constrict certain extracranial and/or certain vascular structures in the when a head that were vasodilated during the performance of at least blocks 720 and 730. The process of vasodilating the vascular structures is thus used to improve the speed and efficacy of the delivery of the various drugs provided during the performance of the drug therapies. In some embodiments, the drug therapies can include the use of triptan containing medications, beta blockers, over the counter drugs, and/or combinations of one or more these medications.

[0125] In block 750, selectively increasing blood flow to the extremity E to increase the speed of a drug being provided to a region of the patient that is the target of the one or more drug therapies. Increasing blood flow within an extremity and to other extremities can be performed by increasing the vacuum applied to the extremity E of the patient by use of commands sent by the Al controller 624 and/or controller 116 to the components within the controller 116. If it is determined from one or more the measurements received by the Al controller 624 and/or controller 116 that the patient is in a vasoconstricted state, the Al controller 624 and controller 116 can be used to adjust one or more of the process variables of the therapeutic process to (e.g., vacuum level applied to the extremity E) overcome the vasoconstricted state. [0126] In block 760, selectively shunting blood flow to the extremities of the user to increase blood flow to the extremities. It is believed that a side effect of adding heat to the body is the increase of peripheral circulation, particularly to the forehead, the hands and the feet. This affects central blood pressure as increased blood flow is selectively shunted to the forehead and distal appendages. In this way blood flow is greatly increased to the forehead area. It is believed that this process will be effective at treating migraines since vasodilation, which creates the increase of peripheral circulation, affects the same pain receptors involved in the pain cascade of migraine progression, since this is similar to the mechanism of action used by migraine drugs (e.g., triptan). Therefore, it is believed that a therapeutic process that includes the vasodilation of the vascular structure can be effective in altering the state of the same pain receptors involved in the pain cascade of migraine progression to improve the results seen by the patient.

[0127] The therapeutic method 700 described herein can be performed in an episodic use scenario in which the method can be performed by the patient, or even a doctor, as needed from time to time. While not intending to limit the scope of the disclosure provided herein, it is believed that the therapeutic method 700 can be performed in discrete treatment intervals that can last for 20 to 30 minutes to treat the onset or effects of a migraine headache. While the therapeutic method 700 can also be performed for 30 minutes to 4 hours for other useful treatments such as treatments for cardiovascular conditions, hypothermia, pain management, or other useful treatments.

[0128] As discussed above, the Al algorithm(s) running in the Al controller 624 or within the controller 116 is used to adjust various operating parameters performed during the execution of the method steps found in blocks 710-760 to improve the performance of the method 700, and improve the migraine therapy process. The Al algorithm is configured to perform processes that require combining the data received from the various sensors and then by use of intelligent, iterative processing learn from the patterns and features in the data that it has analyzed to determine desired corrective actions that are then provided to the controller 116 to implement. Each time an Al algorithm (and Al model) runs a round of data processing, it will test and measure its own performance so as to develop additional expertise based on the performance of these activities that are then used to create the desired corrective action(s) that are then used by the controller 116 to adjust one or more operating parameters.

[0129] In some embodiments, the Al algorithm is configured to perform processes that require the combination of at least two different data sets received from the various sensors to provide an intelligent, iterative process to learn from the patterns and features in the collected and/or stored data to determine a desired corrective action that is then provided to the controller 116 to implement.

[0130] In some embodiments, the Al algorithm is configured to perform processes such as adjusting an amount of a negative pressure (i.e., vacuum) or positive pressure applied to an extremity of a patient or the temperature of a heated fluid that is recirculated through a thermal exchange unit based on a comparison of at least one of the patient profile information 642, heated fluid temperature information, patient temperature information, and pressure measurement information with information stored in memory of the controller 116. In one example, the Al algorithm is configured to perform processes such as adjusting an amount of a negative pressure (i.e., vacuum) or positive pressure applied to an extremity of a patient or the temperature of a heated fluid that is recirculated through a thermal exchange unit based on a comparison of the patient profile information 642 and at least one of the heated fluid temperature information, patient temperature information, and pressure measurement information with information stored in memory of the controller 116. In some embodiments, the information stored in memory of the controller 116 will include desired process variable control ranges for each of the process variables that have been determined by patient input, prior testing and/or modified by use of one or more iterations performed by the Al algorithm. The desired process variable control ranges for each of the process variables stored in memory can include a multifactorial set of information that can vary based on the current state of one or more of the process variables. [0131] The Al algorithm can be configured to help actively control in real time the adjustment, or suggested adjustment (e.g., information provided to the display screen), of a drug dose and/or type of drug for use in one or more drug therapies using the information provided by the comparison of information received by the controller 116 and/or information stored in memory. The Al algorithm can be further configured to, based on the comparison, adjust the amount of vacuum applied to the extremity or the temperature of the heated fluid based on a determination of a user’s risk of acute migraine based on information determined from prior iterations performed by the Al algorithm.

Therapeutic Process Examples

[0132] In one example, the Al algorithm receives patient profile information 642 relating to a blood pressure medication that the patient has taken or will take during the completion of the therapeutic method 700. In this example, the Al algorithm also receives information relating to the vasoconstricted state of the patient, such as blood flow rate information received from a blood flow measurement device 636 and/or blood pressure measurement information from a blood pressure measurement device to determine the state of vasoconstriction within a patient. The Al algorithm can then use the blood pressure medication information, any measured medication concentration levels in the patient’s blood information received from one of the sensors (e.g., e-skin sensor) and the vasoconstricted state of the patient information to adjust the vacuum level, and/or recirculating fluid temperature level to generate commands that are used by the controller 116 to compensate for an undesirable vasconstricted state of the patient and thus help resolve the effects of or onset of a migraine.

[0133] In another example, the Al algorithm receives blood oxygen level information from the pulse oximeter device and information relating to the vasoconstricted state of the patient, such as blood flow rate information received from a blood flow measurement device 636 and/or blood pressure measurement information from a blood pressure measurement device to determine the state of vasoconstriction within a patient. The Al algorithm can then use the blood oxygen level information and the vasoconstricted state of the patient information to generate commands that are used by the controller 116 to adjust the vacuum level, and/or recirculating fluid temperature level to adjust blood flow within the patient to compensate for any effects that blood oxygen level has on the ability of the patient to metabolize a migraine drug and thus help improve therapeutic process.

[0134] In another example, the Al algorithm receives blood pressure level information from a blood pressure measurement device and information relating to the temperature of the patient. The Al algorithm can then use the blood pressure level information and the patient’s temperature information to generate commands that are used by the controller 116 to adjust the vacuum level, recirculating fluid temperature, pulsing interval and duty cycle of the applied vacuum to the extremity, and/or therapeutic procedure duration to adjust the patient’s temperature and/or blood flow within the patient to control the results of the migraine therapy and/or the ability of the patient to metabolize a migraine drug.

[00135] The embodiments described above include a therapeutic method for treating migraines or other acute pain by manipulating blood flow to the head and distal appendages of a patient and manipulating central, peripheral blood pressure and vaso-motor tone. This can be done using a device which applies controlled heat to a distal appendage or forehead while drawing a mild vacuum on the device.

[00136] The embodiments described above also include devices that a water perfusion sleeve (thermal exchange unit) placed over the hand and forearm to circulate fluid (e.g. water, hydrogel at about 104°F) while simultaneously drawing a mild vacuum (e.g., 5mm Hg).

[0137] While the foregoing is directed to embodiments of the present invention, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.

Claims

What is claimed is:

1 . A therapeutic method, comprising: generating, by use of a device, a vacuum pressure within an internal region of a body element of the device while a portion of an extremity of a user is disposed within the internal region; circulating a heated fluid through a thermal exchange unit of the device, wherein the thermal exchange unit is disposed over a surface of the portion of the extremity of the user and a temperature of the heated fluid is controlled by use of a heater that is in thermal communication with the heated fluid; receiving, by a controller, a pressure measurement signal that comprises pressure measurement information from a pressure sensorthat is configured to sense a pressure level in the internal region; receiving, by the controller, a fluid temperature measurement signal that comprises fluid temperature information from a first temperature sensor that is configured to sense a temperature of the heated fluid; receiving, by the controller, a user temperature measurement signal that comprises user temperature information from a second temperature sensor that is configured to sense a temperature of the user; receiving, by the controller, user information, wherein the user information comprises information relating to one or more drug therapies used by the user to treat a migraine or other acute pain; and adjusting, by use of the controller, an amount of vacuum applied to the extremity or the temperature of the heated fluid based on a comparison of the user information and at least one of the fluid temperature information, the user temperature information, and the pressure measurement information with information stored in memory of the controller.

2. The method of claim 1 , wherein applying the vacuum comprises applying a negative pressure to the internal region of the device to lower pressure within an internal region of the device.

3. The method of claim 2, wherein the lowered pressure is between 0 and -20 mmHg.

4. The method of claim 1 , wherein the heated fluid is at a temperature of between 95°F and 104°F.

5. The method of claim 4, wherein the heated fluid causes a selective shunting of blood flow to the extremities of the user so as to increase blood flow within the head or forehead of the user.

6. The method of claim 1 , further comprising selectively increasing blood flow to the extremity to speed of a drug provided within the one or more drug therapies.

7. The method of claim 6, further comprises selectively shunting blood flow to the extremities of the user to increase blood flow within one or more of the extremities.

8. A device for performing a therapeutic method, comprising: a device comprising a pressure port and one or more body elements that at least partially define an internal region of the device; a thermal exchange unit that is in thermal communication with a heater, wherein the thermal exchange unit is configured to transfer heat between the thermal exchange unit and a portion of an extremity of a user disposed within the internal region of the device; a pump fluidly coupled to the internal region through the pressure port and configured to create a sub-atmospheric pressure within the internal region, causing atmospheric pressure external to the internal region to urge at least a portion of the thermal exchange unit against the portion of the extremity of the user; and a controller configured to control the pump and the heater, wherein the controller comprises a processor and non-volatile memory having program instructions stored therein which, when executed by one or more processors causes the device to perform operations comprising: generating a sub-atmospheric pressure within the internal region while a portion of an extremity of the user is disposed within the internal region; circulating a heated fluid through the thermal exchange unit of the device, wherein the thermal exchange unit is disposed over a surface of the portion of the extremity of the user; receiving, by a controller, a pressure measurement signal that comprises pressure measurement information from a pressure sensor that is configured to sense a pressure level in the internal region; receiving a fluid temperature measurement signal that comprises fluid temperature information from a first temperature sensor that is configured to sense a temperature of the heated fluid; receiving, by the controller, user information, wherein the user information comprises information relating to one or more drug therapies used by the user to treat a migraines or other acute pain; and adjusting, by use of the controller, an amount of vacuum applied to the extremity or the temperature of the heated fluid based on a comparison of the user information and at least one of the fluid temperature information, and the pressure measurement information with information stored in memory of the controller.

9. The device of claim 8, wherein the one or more body elements are configured to conform to a shape of the portion of the extremity when the pump creates sub-atmospheric pressure within the internal region.

10. The device of claim 8, wherein the pump is configured to create a negative pressure in the internal region relative to pressure external to the internal region of between 0 and -20 mmHg.

11. The device of claim 8, wherein the fluid is at a temperature of between 95°F and 104°F.

12. The device of claim 8, wherein the fluid comprises water.

13. The device of claim 8, further comprising: a wearable sensor controlled by the controller and configured to gather: physiologic data concerning markers related to an onset or likelihood of developing a migraine or other acute pain; physiologic data concerning homeostasis and other measurements of thermal stability of the extremity; or physiologic data concerning markers related to vasoconstriction and blood flow in the extremity.

14. The device of claim 8, wherein the program instructions further comprise: an artificial intelligence (Al) algorithm which when executed by the processor is configured to cause an adjustment of a drug dose and/or provide a suggested type of drug of the one or more drug therapies by use the information provided by the comparison.

15. The device of claim 14, wherein the Al algorithm is further configured to control the device to simultaneously perioperatively heat the portion of the extremity (the foot) to provide deep vein thrombosis (DVT) therapy, by selectively applying mild pressure via vacuum to the portion of the extremity.

16. The device of claim 8, wherein the program instructions further comprise: an artificial intelligence (Al) algorithm that is further configured to, based on the comparison, adjust the amount of vacuum applied to the extremity or the temperature of the heated fluid based on a determination of a user’s risk of acute migraine.

17. A therapeutic device having an extremity of a user disposed therein and comprising non-volatile memory having a number of instructions stored therein which, when executed by one or more processors, causes the therapeutic device to perform operations comprising: receiving a pressure measurement signal that comprises pressure measurement information from a pressure sensor that is configured to sense a pressure level in an internal region of a body element of the therapeutic device; receiving a fluid temperature measurement signal that comprises fluid temperature information from a first temperature sensor that is configured to sense a temperature of a heated fluid circulated through a thermal exchange unit of the therapeutic device; receiving a user temperature measurement signal that comprises user temperature information from a second temperature sensorthat is configured to sense a temperature of the user; receiving user information, wherein the user information comprises information relating to one or more drug therapies used by the user to treat a migraines or other acute pain; and adjusting an amount of vacuum applied to the extremity or the temperature of the heated fluid based on a comparison of the user information and at least one of the fluid temperature information, the user temperature information, and the pressure measurement information with information stored in the non-volatile memory.

18. The therapeutic device of claim 17, wherein the heated fluid is at a temperature of between 95°F and 104°F.

19. The therapeutic device of claim 17, wherein the operations further comprise selectively increasing blood flow to the extremity to speed of a drug provided within the one or more drug therapies.

20. The therapeutic device of claim 19, wherein the operations further comprise shunting blood flow to the extremity of the user to increase blood flow to the extremity.