[go: up one dir, main page]

WO2025141544A1 - Appareil de mesure de la concentration de microbulles en temps réel - Google Patents

Appareil de mesure de la concentration de microbulles en temps réel Download PDF

Info

Publication number
WO2025141544A1
WO2025141544A1 PCT/IB2024/063347 IB2024063347W WO2025141544A1 WO 2025141544 A1 WO2025141544 A1 WO 2025141544A1 IB 2024063347 W IB2024063347 W IB 2024063347W WO 2025141544 A1 WO2025141544 A1 WO 2025141544A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
constituent
concentration
controller
flow rate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/IB2024/063347
Other languages
English (en)
Inventor
Tiran BERCOVICI
Michael Plaksin
Yonatan Shachaf
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Insightec Ltd
Original Assignee
Insightec Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Insightec Ltd filed Critical Insightec Ltd
Publication of WO2025141544A1 publication Critical patent/WO2025141544A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/48—Diagnostic techniques
    • A61B8/481—Diagnostic techniques involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/16877—Adjusting flow; Devices for setting a flow rate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3306—Optical measuring means
    • A61M2205/3313—Optical measuring means used specific wavelengths
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3331—Pressure; Flow
    • A61M2205/3334—Measuring or controlling the flow rate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3375—Acoustical, e.g. ultrasonic, measuring means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/50—General characteristics of the apparatus with microprocessors or computers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0039—Ultrasound therapy using microbubbles

Definitions

  • Microbubbles are gas-filled lipid vesicles used as contrast agents in ultrasound applications.
  • FUS Focused Ultrasound
  • microbubbles are provided to patients through intravenous infusion.
  • the concentration of microbubbles in a patient's blood greatly influences the efficiency and safety of the FUS procedure since microbubbles respond to ultrasound stimulation by producing cavitation.
  • Microbubble concentration in the infusion liquid is currently calculated based on the volume of microbubbles added to the total infusion volume using the concentrated microbubble concentration provided by its manufacturer. Microbubble concentration is typically measured by the manufacturer or by the user immediately after microbubble activation, prior to its dilution in the infusion bag. However, the microbubble concentration in the infusion liquid may change during treatment due to microbubble instability, infusion handling, or other factors. Therefore, the determination of the exact dosage of microparticles that is delivered is challenging. Infusion delivery rate in patients was previously suggested to be adjusted based on the acoustic feedback acquired by the FUS system or based on infusion flow rate, but not in response to the actual microbubble concentration present in the infusion liquid.
  • the present disclosure relates to, inter alia, systems and methods for determining concentration of composition in real time at the time of infusion and for providing an updated rate of administration of drugs based, inter alia, on the determined concentration of composition.
  • the present disclosure provides a system for measuring concentration of a composition in real time at the time of a parenteral administration.
  • the system comprises (a) an apparatus capable of measuring a physical property of the composition, the apparatus comprising a detector; (b) a controller, operably coupled to the detector, and (c) an outlet being connected to a port of administration of the composition to a subject.
  • the controller is configured to store a desired concentration of the composition selected by an operator, optionally a human operator.
  • the system further comprises an inlet from a reservoir of the pharmaceutical composition into an apparatus.
  • the controller is configured to measure the physical property of the composition.
  • the condition of the treated organ/body region is provided to the controller by an operator, optionally a human operator. In some embodiments, the condition of the treated organ/body region provided to the controller by an additional piece of medical equipment connected to the controller. In some embodiments, the condition of the treated organ ⁇ body region provided to the controller by an additional piece of medical equipment connected to the controller. In some embodiments, the physical property is selected from light absorbance, fluorescence and phosphorescence. In some embodiments, the apparatus comprises a light source and a detector of light. In some embodiments, the composition is or comprises a microbubble composition. In some embodiments, the composition is or comprises a pharmaceutical composition.
  • the controller is configured to adjust a flow rate of the composition in the outlet, based on an algorithm that analyzes the condition of the treated organ ⁇ body region and adjust the concentration of the composition accordingly.
  • the condition of the treated organ/body region is provided to the controller by an operator, optionally a human operator.
  • the condition of the treated organ/body region provided to the controller by an additional piece of medical equipment connected to the controller.
  • the light source is or comprises a light emitting diode (LED).
  • the detector of light is or comprises a light emitting diode (LED).
  • the light is infrared (IR) light.
  • the light source is an IR LED.
  • the detector of light is an IR LED.
  • the composition is or comprises a microbubble composition. In some embodiments, the composition is or comprises a pharmaceutical composition. In some embodiments, the reservoir of the composition is an infusion bag. In some embodiments, the reservoir of the composition is a drip chamber.
  • the parenteral administration is infusion.
  • the detector provides an output of concentration of the composition.
  • the output is or comprises a print out and/or an on-screen display.
  • the apparatus and/or the controller comprise a manual control unit configured to manually adjust the flow rate.
  • the flow rate is manually adjusted by a human operator.
  • the flow rate is manually adjusted by a human operator based on the output of concentration of the composition.
  • the apparatus and/or the controller comprise an automated control unit configured to automatically adjust the flow rate. In some embodiments, the apparatus and/or the controller automatically adjust the flow rate based on the output of concentration of the composition and/or human input. In some embodiments, the apparatus and/or the controller automatically increase the flow rate compared to initial flow rate when the concentration of the composition is lesser compared to the desired concentration. In some embodiments, the apparatus and/or the controller automatically decrease the flow rate compared to initial flow rate when the concentration of the composition is greater compared to the desired concentration. In some embodiments, the apparatus and/or the controller automatically maintain the flow rate substantially equal to initial flow rate when the concentration of the composition is substantially equal compared to the desired concentration.
  • the apparatus or the controller automatically adjust the flow rate of the composition, based on an algorithm that analyzes the condition of the treated organ/body area and adjust the pharmaceutical concentration accordingly.
  • the composition comprises a sedimentable ingredient.
  • the sedimentable ingredient is selected from a microbubble, a lipid nanoparticle (LNP) or a liposome.
  • the composition is or comprises a microbubble composition.
  • the microbubble composition comprises one or more lipid-based microspheres.
  • the microbubble composition is perflutren lipid microspheres.
  • the microbubble composition comprises (R)-hexadecanoic acid, l-[(phosphonoxy)methyl]-l,2-ethanediyl ester, monosodium salt (DPPA); (R)-4-hydroxy- N,N,Ntrimethyl-10-oxo-7-[(l-oxohexadecyl)oxy]-3,4,9-trioxa-4-phosphapentacosan-l-aminium, 4-oxide, inner salt (DPPC); (R)-a-[6-hydroxy-6-oxido-9-[(l-oxohexadecyl)oxy]-5,7,l l-trioxa-2- aza-6-phosphahexacos-l-yl]-co-methoxypoly(ox-l,2-ethanediyl), monosodium salt; and (N- (methoxypolyethylene glycol 5000 carbamoyl)-l,2-dipalmit
  • the microbubble compositions are lipid-coated echogenic microbubbles filled with octafluoropropane gas.
  • the microbubble compositions comprise octafluoropropane encapsulated in an outer lipid shell comprising (R)-hexadecanoic acid, l-[(phosphonoxy)methyl]- 1,2-ethanediyl ester, monosodium salt (DPPA); (R)-4-hydroxy-N,N,Ntrimethyl-10-oxo-7-[(l- oxohexadecyl)oxy]-3,4,9-trioxa-4-phosphapentacosan-l-aminium, 4-oxide, inner salt (DPPC); (R)-a-[6-hydroxy-6-oxido-9-[(l-oxohexadecyl)oxy]-5,7,l l-trioxa-2-aza-6-phosphahexacos-l
  • the composition comprises or further comprises a biologic drug selected from an antibody, a virus, a vaccine composition, a protein therapeutic, and a nucleic acid therapeutic selected from RNA, mRNA, chemically modified mRNA, a small interfering RNA (siRNA), a microRNA (miRNA), and an antisense RNA.
  • the composition comprises or further comprises a small molecule drug.
  • the apparatus and/or the controller communicate with one or more additional piece of medical equipment. In some embodiments, the apparatus and/or the controller adjusts the desired concentration based on an input from the additional piece of medical equipment. In some embodiments, the apparatus and/or the controller provide an input to the additional piece of medical equipment to control its function.
  • the additional piece of medical equipment is an ultrasound transducer.
  • the input from the apparatus and/or the controller controls the kind of an ultrasound beam, a shape of an ultrasound beam, a pulse pattern of an ultrasound beam, a pulse duration of an ultrasound beam, a pulse repetition frequency (PRF) of an ultrasound beam, the center frequency of ultrasound beam, a spatial peak temporal average acoustic intensity (Ispta), a spatial peak pulse average acoustic intensity (Isppa), a power of the ultrasound beam, and/or the duration of sonication.
  • PRF pulse repetition frequency
  • the determining is performed using a standard curve of test measurements of the physical property and test concentrations of the composition.
  • the standard curve is saved in the controller.
  • the present disclosure provides a system for measuring microbubble concentration in the infusion liquid in real time based on infrared (IR) spectrophotometry.
  • the system comprises an apparatus capable of measuring absorbance of infrared (IR) light by the microbubbles in the infusion liquid.
  • the apparatus comprises two light emitting diodes (LEDs).
  • the two LEDs are positioned on the same horizontal line placed around a reservoir or below the reservoir.
  • the two LEDs are positioned at an angle that is between 0° and 360° with respect to each other around the center of the apparatus and/or around the reservoir.
  • temporarily altering a tissue characteristic comprises or consists of disrupting one or a plurality of regions.
  • the one or a plurality of regions are the BBB and the disruption may alter its permeability.
  • the controller is configured to control a parameter (such as power, frequency, pulse duration and/or pulse repetition frequency) of the transmitted acoustic energy based at least in part on spectral components of the cumulative harmonic response.
  • the controller is configured to control a parameter of the transmitted acoustic energy based at least in part on cumulative harmonic response data from within a defined interval.
  • the interval is within a current sonication.
  • the interval includes data from at least one previous sonication.
  • Another aspect of the present disclosure provides (i) a system for measuring concentration, constituent size, and/or constituent shape of a composition (without limitation, e.g., a microbubble composition) in real time at the time of a parenteral administration to a subject, (ii) an ultrasound transducer for sonicating a target volume to cause disruption of a target tissue therein system, and (iii) comprising one or more computer processors and computer memory coupled thereto.
  • the composition is or comprises a microbubble composition.
  • the one or more computer processors and computer memory coupled thereto comprise the controller of any of the embodiments disclosed herein.
  • the ultrasound transducer is capable of delivering a focused ultrasound (FUS).
  • the focused ultrasound (FUS) is selected from magnetic resonance imaging (MRI)-guided FUS, computerized tomography (CT)-guided FUS, electroencephalogram (EEG)-guided FUS, and positron emission tomography (PET)-guided FUS.
  • the FUS is MRI-guided FUS.
  • the computer memory comprises machine executable code that, upon execution by the one or more computer processors and/or controller, measures the concentration, constituent size, and/or constituent shape of the composition (without limitation, e.g., a microbubble composition) in real time at the time of a parenteral administration, adjusts the flow rate of the composition that is administered to the subject and/or provides input to the ultrasound transducer.
  • the input from the apparatus and/or the controller controls the kind of an ultrasound beam (e.g., a low intensity focused ultrasound (LIFU) or a high intensity ultrasound (HIFU)), the center frequency of ultrasound beam (e.g., a specific value in the range of about 30 kHz to about 3 MHz, such as about 220 kHz), a shape of an ultrasound beam, a pulse pattern of an ultrasound beam, a spatial peak temporal average acoustic intensity (Ispta) (e.g., a specific value in the range of about 5 and about 1000 W/cm 2 ), a spatial peak pulse average acoustic intensity (Isppa), a power of the ultrasound beam (e.g., a specific value in the range of about 0.5 W to about 100 W, e.g., about 5 W), and/or the duration of sonication (e.g., a specific value in the range of about 10 seconds and about 160 minutes such as about 60 seconds).
  • an ultrasound beam e.g.,
  • the determining is performed using an equation.
  • the equation provides a correlation between test measurements and test concentrations, constituent sizes, and/or constituent shapes to determine the concentration, constituent size, and/or constituent shape.
  • the equation is saved in the controller.
  • the physical property is selected from light absorbance, fluorescence and phosphorescence.
  • the present disclosure provides a method of administering a composition to a subject.
  • the method comprises (a) providing a composition in a reservoir, (b) connecting the reservoir to the system of any of the embodiments disclosed herein, and (c) connecting the system to a port of administration of the composition to the subject.
  • the composition is or comprises a microbubble composition.
  • the composition is or comprises a pharmaceutical composition.
  • the present disclosure provides a method of treating a subject in need thereof suffering from a disease or disorder.
  • the method comprises a step of administering a composition to the subject.
  • the step of administering comprises (a) providing the composition in a reservoir, (b) connecting the reservoir to the system of any of the embodiments disclosed herein, and (c) connecting the system to a port of administration of the composition to the subject.
  • the method further comprises administering an ultrasound beam to the subject a second composition that is capable of preventing or treating the disease or disorder.
  • the composition is or comprises one or more microbubble compositions.
  • the one or more microbubble compositions are administered immediately before and/or during the application of the ultrasound beam. In some embodiments, the one or more microbubble compositions are administered contemporaneously with the application of the ultrasound beam. In some embodiments, the composition is or comprises a microbubble compositions. In some embodiments, the composition is or comprises a pharmaceutical composition.
  • the present disclosure provides a method of treating a subject in need thereof suffering from a disease or disorder that is capable of being treated with ultrasound.
  • the method comprises a step of administering a composition.
  • the step of administering comprises (a) providing a composition in a reservoir, (b) connecting the reservoir to the system of any of the embodiments disclosed herein, and (c) connecting the system to a port of administration of the composition to the subject.
  • the method further comprises administering an ultrasound beam to the subject.
  • the method further comprises administering an ultrasound beam to the subject and a second composition that is capable of preventing or treating the disease or disorder.
  • the composition is or comprises one or more microbubble compositions.
  • the present disclosure provides a method of diagnosing a disease or disorder in a subject.
  • the method comprises a step of administering a composition to the subject.
  • the step of administering comprises (a) providing the composition in a reservoir, (b) connecting the reservoir to the system of any of the embodiments disclosed herein, and (c) connecting the system to a port of administration of the composition to the subject.
  • the method further comprises administering an ultrasound beam to the subject and a second composition that is capable of preventing or treating the disease or disorder.
  • the composition is or comprises a pharmaceutical composition.
  • the composition is or comprises one or more microbubble compositions.
  • the one or more microbubble compositions are administered immediately before and/or during the application of the ultrasound beam. In some embodiments, the one or more microbubble compositions are administered contemporaneously with the application of the ultrasound beam. In some embodiments, the method further comprises obtaining a biological sample from the subject. In some embodiments, the biological sample is blood. In some embodiments, the method further comprises measuring the amount in the biological sample of a molecule (without limitation, a nucleic acid, a protein or a metabolite). In some embodiments, the molecule is predominantly present in an affected tissue but substantially not present in the biological sample under normal conditions. Such methods are disclosed in WO 2023/275617, the contents of which are incorporated by reference in their entirety.
  • the composition comprising microbubbles is administered immediately before and/or during the application of the ultrasound beam. In some embodiments, the composition comprising microbubbles is administered contemporaneously with the application of the ultrasound beam.
  • the disease or disorder is selected from a neurological condition.
  • the neurological condition is selected from Alzheimer’s Disease, Parkinson's Disease, essential tremor, neuropathic pain, epilepsy, addiction, post-traumatic stress disorder, depression and obsessive-compulsive disorder.
  • the disease or disorder is selected from a musculoskeletal pathology.
  • the musculoskeletal pathology is selected from osteoarthritis, soft tissue shoulder pathology, and myofascial pain.
  • the disease or disorder is selected from a cancer.
  • the cancer is a brain tumor or a metastatic brain tumor.
  • the disease or disorder is selected from a cardiovascular condition.
  • the cardiovascular condition is selected from varicose veins, blood clots, calcified arteries, and calcified veins.
  • the disease or disorder is selected from a kidney condition.
  • the kidney condition is a kidney stone.
  • the disease or disorder is selected from an eye condition.
  • the eye condition is selected from dry eye disease, glaucoma, presbyopia, macular degeneration, retinal impairment, and retinal injury.
  • the second composition to the subject wherein the second composition comprises a pharmaceutical agent that is used for treating the neurological condition, the musculoskeletal condition, the cancer, the cardiovascular condition, the kidney condition, or the eye condition. Kits
  • kits that can simplify the undertaking any method described herein.
  • An illustrative kit of the disclosure comprises any composition described herein in a reservoir and/or a system described herein, e.g., a system for measuring the concentration, constituent size, and/or constituent shape of the composition.
  • the kit further comprises a device for applying an ultrasound beam across the cranium of the human patient (e.g., ultrasound transducers), and/or one or more microbubbles described herein in unit dosage form, and/or a positron emission tomography (PET) device, a single photon emission computed tomography (SPECT) device, an ultrasonography device, a diffusion-tensor imaging (DTI) device, a functional MRI (fMRI) device, a functional MRI (fMRI) device, an X-ray fluoroscopy device, an angiography device (including a magnetic resonance angiography (MRA) device), a magnetoencephalography (MEG) device, an electroencephalography (EEG) device, a near-infrared spectroscopy (NIRS) device, an optical imaging device, a bone densitometry device and a combination of two or more thereof.
  • a device for applying an ultrasound beam across the cranium of the human patient e.g., ultrasound
  • the unit dosage form is a container, such as a pre- filled syringe, or an infusion bag with gravitation-based flow controller, which can be sterile, containing any composition described herein and a pharmaceutically acceptable carrier, diluent, excipient, or vehicle.
  • the kit can further comprise a label or printed instructions instructing the use of any composition described herein.
  • microbubble includes lipid based microbubbles (e.g., perflutren lipid microspheres), and microbubble alternatives, such as phase-shift droplets, nanobubbles, nanodroplets or nanoparticles, e.g., gold nanoparticles.
  • lipid based microbubbles e.g., perflutren lipid microspheres
  • microbubble alternatives such as phase-shift droplets, nanobubbles, nanodroplets or nanoparticles, e.g., gold nanoparticles.
  • the examples herein are provided to illustrate advantages and benefits of the present technology and to further assist a person of ordinary skill in the art with preparing or using the systems and apparatus for measuring drug concentration in real time according to the present technology.
  • the examples herein are also presented in order to more fully illustrate the preferred aspects of the present technology.
  • the examples should in no way be construed as limiting the scope of the present disclosure, as exemplified by the appended claims.
  • the examples can include or incorporate any of the variations, aspects or embodiments of the present technology described above.
  • the variations, aspects or embodiments described above may also further each include or incorporate the variations of any or all other variations, aspects or embodiments of the present technology.
  • Example 1 Determination of Microbubble Concentration using an Infrared (IR) Device
  • Microbubble (MB) samples having different concentrations were prepared.
  • the concentrations prepared were within the range of concentration of MBs that are clinically used in the infusion bags.
  • MB concentrations were measured using a Counter coulter.
  • MB concentrations were also assessed using an infrared device of the present disclosure.
  • the infrared (IR) radiation generated by a light emitting diode (LED) was passed through the MB samples and the generated voltage was measured using an IR sensor LED.
  • the generated voltage was plotted as a function of MB concentration, as measured using the Counter coulter. As shown in FIG. 3, there was a good correlation between the generated voltage with the MB concentration, as measured using the Counter coulter. Therefore, FIG. 3 serves a calibration curve for MB based on generated voltage.
  • Example 2 Analysis Microbubble Stability Over Typical Clinical Treatment Time Frame
  • Microbubble (MB) samples having different concentrations which were within the range of concentration of MBs that are clinically used in the infusion bags, were prepared by diluting a stock solution. MB concentrations in the dilutions were also assessed using an infrared device of the present disclosure at 0 min, 10 min, 20 min, 30 min, 40 min, 60 min, 80 min, 150 min, 180 min, 210 min, 240 min, and 270 min from preparation of the dilutions.
  • the infrared (IR) radiation generated by a light emitting diode (LED) was passed through the MB samples and the generated voltage was measured using an IR sensor LED. The generated voltage was plotted as a function of time since the preparation of dilutions.
  • Example 3 Analysis Microbubble Stability as a Function of Time and Concentrations

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Vascular Medicine (AREA)
  • Anesthesiology (AREA)
  • Physics & Mathematics (AREA)
  • Radiology & Medical Imaging (AREA)
  • Fluid Mechanics (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente divulgation concerne des systèmes et des procédés pour mesurer la concentration, la taille ou la forme des constituants d'une composition en temps réel au moment d'une administration parentérale sur la base de la mesure d'une propriété physique de la composition.
PCT/IB2024/063347 2023-12-31 2024-12-31 Appareil de mesure de la concentration de microbulles en temps réel Pending WO2025141544A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363616747P 2023-12-31 2023-12-31
US63/616,747 2023-12-31

Publications (1)

Publication Number Publication Date
WO2025141544A1 true WO2025141544A1 (fr) 2025-07-03

Family

ID=94284081

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2024/063347 Pending WO2025141544A1 (fr) 2023-12-31 2024-12-31 Appareil de mesure de la concentration de microbulles en temps réel

Country Status (1)

Country Link
WO (1) WO2025141544A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060042632A1 (en) * 2004-08-31 2006-03-02 Bishop Gregory D Apparatus for monitoring a patient during drug delivery
WO2009001243A1 (fr) * 2007-06-22 2008-12-31 Koninklijke Philips Electronics N.V. Appareil pour l'administration contrôlée de molécules à l'aide d'un système d'injection contrôlée
US20210170084A1 (en) * 2019-12-10 2021-06-10 Baxter International Inc. Combined extracorporeal and drug delivery system and method
EP4085943A1 (fr) * 2011-12-21 2022-11-09 DEKA Products Limited Partnership Pompe peristaltique avec porte pivotante et levier pivotant
WO2023275617A2 (fr) 2021-07-01 2023-01-05 Insightec, Ltd. Surveillance de diagnostic et de traitement basée sur une rupture de la barrière hémato-encéphalique

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060042632A1 (en) * 2004-08-31 2006-03-02 Bishop Gregory D Apparatus for monitoring a patient during drug delivery
WO2009001243A1 (fr) * 2007-06-22 2008-12-31 Koninklijke Philips Electronics N.V. Appareil pour l'administration contrôlée de molécules à l'aide d'un système d'injection contrôlée
EP4085943A1 (fr) * 2011-12-21 2022-11-09 DEKA Products Limited Partnership Pompe peristaltique avec porte pivotante et levier pivotant
US20210170084A1 (en) * 2019-12-10 2021-06-10 Baxter International Inc. Combined extracorporeal and drug delivery system and method
WO2023275617A2 (fr) 2021-07-01 2023-01-05 Insightec, Ltd. Surveillance de diagnostic et de traitement basée sur une rupture de la barrière hémato-encéphalique

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
H. MULVANA ET AL.: "Characterization of Contrast Agent Microbubbles for Ultrasound Imaging and Therapy Research", IEEE TRANSACTIONS ON ULTRASONICS, FERROELECTRICS, AND FREQUENCY CONTROL, vol. 64, no. 1, 2017, pages 232 - 251, XP011638836, DOI: 10.1109/TUFFC.2016.2613991
KOO ET AL.: "Characterizing how size distribution and concentration affect echogenicity of ultrasound contrast agents", ULTRASONICS, vol. 127, 2023, pages 106827
LAKSHMANAN ET AL.: "Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and J\1RJ", NATURE PROTOCOLS, vol. 12, no. 10, 2017, pages 2050 - 2080, XP055757758, DOI: 10.1038/nprot.2017.081
LUYPAERT ET AL.: "Near-infrared spectroscopy applications in pharmaceutical analysis", TT.ZIΕANTCR, vol. 72, no. 3, 2007, pages 865 - 883, XP022049233, DOI: 10.1016/j.talanta.2006.12.023
SENNOGA ET AL.: "Evaluation of methods for sizing and counting of ultrasound contrast agents", ULTRASOUND IN MEDICINE & BIOLOGY, vol. 38, no. 5, 2012, pages 834 - 845

Similar Documents

Publication Publication Date Title
Chen et al. Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets
Chen et al. Lipid/PLGA hybrid microbubbles as a versatile platform for noninvasive image-guided targeted drug delivery
US9302124B2 (en) Systems and methods for opening a tissue
Lammertink et al. Sonochemotherapy: from bench to bedside
Cheng et al. Influence of nanobubble concentration on blood–brain barrier opening using focused ultrasound under real-time acoustic feedback control
Fan et al. Submicron-bubble-enhanced focused ultrasound for blood–brain barrier disruption and improved CNS drug delivery
CN105658243B (zh) 超声介导的药物递送
Radhakrishnan et al. Scavenging dissolved oxygen via acoustic droplet vaporization
WO2012143739A1 (fr) Thérapie sonodynamique
US20100178305A1 (en) Ultrasonic nanotherapy of solid tumors with block copolymers stabilized perfluorocarbon nanodroplets
CN108430579B (zh) 通过使用超声系统治疗脑肿瘤的系统
Rojas et al. In vivo molecular imaging using low-boiling-point phase-change contrast agents: a proof of concept study
US20240358984A1 (en) Ultrasound delivery
Gong et al. Comparison of sonication patterns and microbubble administration strategies for focused ultrasound-mediated large-volume drug delivery
US20200306178A1 (en) Scavenging Dissolved Oxygen Via Acoustic Droplet Vaporization
KR20190134084A (ko) 과불화탄소 나노입자, 이를 포함하는 약물 전달용 초음파 조영제 및 그의 제조방법
WO2025141544A1 (fr) Appareil de mesure de la concentration de microbulles en temps réel
Ador et al. Ultrasound-Assisted Blood–Brain Barrier Opening Monitoring by Photoacoustic and Fluorescence Imaging Using Indocyanine Green
Margolis et al. Image-guided focused ultrasound-mediated molecular delivery to breast cancer in an animal model
US20250186343A1 (en) Emulsion for non-invasive blood-brain barrier transient opening and controlled drug release into the brain
Yang et al. Evaluation of dose distribution of molecular delivery after blood-brain barrier disruption by focused ultrasound with treatment planning
Margolis et al. THREE-DIMENSIONAL (3-D) FOCUSED ULTRASOUND FOR IMPROVED DRUG DELIVERY
Chattenton Drug delivery across the blood-brain barrier using short-pulse focused ultrasound and microbubbles for the treatment of diffuse intrinsic pontine glioma
US20230226184A1 (en) Improvements in ultrasound-mediated therapy
Chien et al. Blood-brain barrier opening in a large animal model using individualized closed-loop microbubble cavitation-based feedback control of focused ultrasound sonication

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24838036

Country of ref document: EP

Kind code of ref document: A1