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WO2025147462A1 - Dispositifs implantables, formulations et méthodes de gestion du poids corporel - Google Patents

Dispositifs implantables, formulations et méthodes de gestion du poids corporel Download PDF

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Publication number
WO2025147462A1
WO2025147462A1 PCT/US2024/062393 US2024062393W WO2025147462A1 WO 2025147462 A1 WO2025147462 A1 WO 2025147462A1 US 2024062393 W US2024062393 W US 2024062393W WO 2025147462 A1 WO2025147462 A1 WO 2025147462A1
Authority
WO
WIPO (PCT)
Prior art keywords
once
weight management
management agent
reservoir
months
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/US2024/062393
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English (en)
Inventor
Adam Mendelsohn
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.)
Nano Precision Medical Inc
Original Assignee
Nano Precision Medical Inc
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 Nano Precision Medical Inc filed Critical Nano Precision Medical Inc
Publication of WO2025147462A1 publication Critical patent/WO2025147462A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/26—Glucagons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents

Definitions

  • the present disclosure provides a device for managing body weight in a subject, the device comprising: a capsule configured for implantation and having a reservoir; a weight management agent disposed within the reservoir; and a nanoporous membrane with a plurality of pores providing a diffusion path for the weight management agent out of the reservoir, wherein the weight management agent is an incretin mimetic.
  • the present disclosure provides a formulation for managing body weight in a subject, the formulation contained in a device, the device comprising: a capsule configured for implantation and having a reservoir; a weight management agent disposed within the reservoir; and a nanoporous membrane with a plurality of pores providing a diffusion path for the weight management agent out of the reservoir, wherein the weight management agent is an incretin mimetic.
  • the present disclosure provides a method of managing body weight in a subject, comprising: providing a device, the device comprising: a capsule configured for implantation and having a reservoir; a weight management agent disposed within the reservoir; and a nanoporous membrane with a plurality of pores providing a diffusion path for the weight management agent out of the reservoir, wherein the weight management agent is an incretin mimetic, and implanting the device in the subject.
  • FIG. 1 A represents a diagram of a device according to the disclosure with one reservoir.
  • FIG. IB represents a diagram of a device according to the disclosure with two reservoirs and two nanoporous membranes.
  • FIG. 2 represents the in vitro release rate of exenatide from an embodiment of devices of the invention.
  • FIG. 3 represents the effect on body mass of DIO mice after implantation of the devices of the invention from FIG. 2.
  • FIG. 4 represents the in vitro release rate of exenatide from an alternative embodiment of devices of the disclosure.
  • FIG. 5 represents the effect on body mass of Sprague Dawley rats after implantation of the devices of the disclosure from FIG. 4.
  • the disclosure pertains to the field of long-term treatment (e.g., more than 1 month) of a subject with an implantable device providing a sustained delivery of a therapeutic agent.
  • Embodiments of the disclosure include devices and formulations including one or more therapeutic agents and, optionally, one or more stabilizing, release rate modifying, or otherwise beneficial agents for the therapeutic agent. Additionally, embodiments of the disclosure include methods of treatment of a subject with devices and formulations of the disclosure.
  • Polypeptides refer to molecules with a backbone chain of 2 or more amino acid residues. Some polypeptides may have additional associated groups, such as metal ions in metalloproteins, small organic molecules such as in heme proteins, or carbohydrate groups such as in glycoproteins.
  • Proteins and “Proteins” refer to subgroups of polypeptides. In this disclosure the definition of peptides and proteins follows the practice of the United States Food and Drug Administration, the FDA, which defines peptides as polypeptides with up to 40 amino acid residues, and proteins as polypeptides with more than 40 amino acid residues.
  • Incretin mimetics refers to agents that act like incretin hormones such as glucagon- like peptide- 1 (GLP-1). They bind to GLP-1 receptors and stimulate glucose dependent insulin release, therefore acting as antihyperglycemics. Some incretin mimetics include inhibitors of dipeptyl peptidase - (DPP-4), which effectively increase the circulating levels of GLP-1 type peptides. Some incretin mimetics bind to one or more of the human GLP-1 receptor, the human glucose-dependent insulinotropic polypeptide (GIP) receptor and/or the human glucagon receptor. Some incretin mimetics bind to the human amylin receptor. Some incretin mimetics are single receptor agonists. Some incretin mimetics are dual receptor agonists. Some incretin mimetics are triple receptor agonists.
  • DPP-4 dipeptyl peptidase -
  • GIP human glucose-dependent insulinotropic polypeptide
  • Formulation of a therapeutic agent refers to the actual state in which a therapeutic agent is present in a product or in a product fabrication intermediate, and includes the therapeutic agent, plus, optionally, any used additional therapeutic agents, any used formulation excipients and any used formulation solvents.
  • Membrane refers to a permeable structure allowing mass transport of molecules from one side of the structure to the other through the structure.
  • “Dense” or “non-porous membranes” refers to membranes without fluid filled pores. In such membranes mass transport may take place by a dissolution-diffusion mechanism, in which therapeutic agents permeate the membrane by dissolving in the membrane material itself, and diffusing through it.
  • Nanoporous membrane and “nanopore membrane” are used interchangeably, and refer to porous membranes in which the pores have a smallest diameter of less than 1000 nanometer.
  • Nanotube membrane refers to a nanoporous membrane, wherein pores are formed by an array of nanotubes.
  • Titania nanotube membrane refers to an array of titania nanotubes on a titanium substrate where at least a portion of the titania nanotubes are open at both ends and capable of allowing diffusion from one side of the membrane to the other through the titania nanotubes.
  • Molecular diameter of a polymer refers to the diameter of the sphere of gyration of the polymer, which is a physical measure of the size of a molecule, and is defined as two times the mass weighted average distance from the core of a molecule to each mass element in the molecule.
  • Stokes diameter or “hydrodynamic diameter” refers to the dimension of a molecule plus its associated water molecules as it moves through an aqueous solution, and is defined as the radius of an equivalent hard sphere diffusing at the same rate as the molecule under observation.
  • Ion exchange resin or IER refers to a polymer comprising acidic or basic groups, or a combination thereof, made insoluble, for instance by cross-linking, and capable of exchanging anions or cations, or a combination thereof, with a medium surrounding it.
  • Fluid and “fluid form” as used in this disclosure refers to flowable states of matter and includes, but is not limited to gases, solutions, suspensions, emulsions, colloids, dispersions and the like.
  • Administration refers to the act of percutaneously accessing the body of a subject and injecting or implanting, or otherwise depositing, the therapeutic agent.
  • the therapeutic agent may be contained within a drug delivery device such as the device of FIG. 1A or IB.
  • the therapeutic agent may be delivered by an implantable device, once the implantable device is administered.
  • devices of the disclosure include a capsule 101 suitable for implantation, wherein the capsule has a reservoir 102 suitable for holding a therapeutic agent and a stabilizing, release rate modifying, or otherwise beneficial agent. In some embodiments more than one reservoir is present.
  • the capsule may be made of any suitable biocompatible material.
  • the capsule is made of a medical grade metal, such as titanium or stainless steel, or of a medical grade polymeric material, such as silicone, polyurethane, polyacrylate, polyolefin, polyester, polyamide and the like.
  • the capsule is made of multiple materials.
  • the capsule is made of titanium.
  • the capsule is made of a single piece of material.
  • the capsule is made of multiple pieces of materials, for instance a capsule having a reservoir for holding a therapeutic agent and a stabilizing, release rate modifying, or otherwise beneficial agent and having a cap holding a membrane as a pathway for release of the therapeutic agent, wherein the cap can be attached to the reservoir by any suitable means, such as welding, gluing, press fitting or using threaded means, or any combination of these.
  • the capsule may have any suitable size or shape.
  • the capsule is cylindrical, facilitating implantation or administration into the body by means of a tubular implantation device, such as a needle or trocar.
  • Devices of the disclosure have at least one membrane, as described in this disclosure, attached to the capsule and in fluid contact with the reservoir, wherein the membrane provides a pathway for mass transport of a therapeutic agent included within the reservoir out of that reservoir and into the body of a subject into which the capsule has been implanted.
  • attachment to the capsule refers to a component being fixed in place with respect to the capsule, and connected to the capsule directly or indirectly, by using any suitable means, including by welding, gluing, press-fitting and by using threaded means, or by any combination of these.
  • the nanotube membranes are part of an array of nanotubes 103, some of which are still attached to the titanium substrate 104 from which they were grown, and the substrate may be attached to the capsule. At least some of the nanotubes are open on both sides, 105 in FIG. 1 A, to allow for mass transport of a therapeutic agent out of the reservoir.
  • the membranes may be attached to the capsule with the substrate side facing into the reservoir or facing away from the reservoir.
  • the dimensions of the device may be determined based on total amount of formulation to be included in the reservoir, and on medically acceptable dimension limits. In certain aspects, the size of the device may be about 0.2 cm in diameter to about 2 cm in length, or about 0.25 cm in diameter to about 2.5 cm in length. In other aspects, the size is about 4 mm in diameter to about 40 mm in length. Other dimensions may be determined on a case-by-case basis.
  • the device has a reservoir capacity with a volume of about 10 microliters to about 10 milliliters.
  • the reservoir has a volume of about 10 pL to about 100 pL such as 10, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, or 100 pL.
  • the reservoir is about 25-60 pL or about 30-50 pL, or even about 30-45 pL.
  • the reservoir is about 100-500 microliters, 150-450 microliters, or about 150- 350 microliters, such as about 250 microliters.
  • FIG IB is a diagram of a device according to the disclosure with two reservoirs separated by an enclosure.
  • the various identifying numbers in FIG. IB corresponding to the same features in FIG. 1 A but appended with the letter b.
  • Embodiments of the disclosure include at least one membrane providing a pathway for mass transport of a therapeutic agent out of a reservoir of a device of the disclosure.
  • the membrane pores have a diameter of the same order of magnitude as the hydrodynamic diameter of dissolved substances, such as a therapeutic agent in a formulation. In some embodiments, the pores have a diameter smaller than hydrodynamic diameter of dissolved substances in a formulation. Because of the finite size of the pores, such membranes may act as a size cut-off filter for dissolved substances in the formulations of the drug delivery systems. [0049] In some embodiments, the membrane pores have diameters in a range of 1-5 times or 1, 2, 3, 4, or 5 times the molecular diameter of the drug molecules diffusing through their aqueous phase. In some embodiments the membrane pores have diameters, as described in US Patent No. 11, 129,791.
  • the implantation can be performed by any means known to one of skill in the art, for instance through subcutaneous insertion of the device using a hollow needle or trocar.
  • the incretin mimetic is used to manage body weight.
  • the incretin mimetic is exenatide or semaglutide or a combination.
  • an incretin mimetic is released at rate between 10 microgram per day and 500 microgram per day, or between 20 microgram per day and 400 microgram per day, or between 30 microgram per day and 300 microgram per day.
  • the implantation of devices of the disclosure is repeated one or more times.
  • the frequency of implantation or administration is less frequent than once a week, such as once every 2 weeks, or once every 3 weeks, or once every month.
  • the interval between repeat administrations can be longer than 1 month.
  • the therapeutic agent is contained within an implantable device when administration occurs.
  • the devices that were used for the exenatide examples included titanium capsules of approximately 25 mm length and 2.25 mm diameter.
  • a titanium substrate with a titanium oxide nanoporous membrane was welded to one end of the device.
  • the nanoporous membrane had a diameter of 0.3 mm and was composed of about 6,000,000 nanopores.
  • the membranes were manufactured as described in US patent Nos. 9814867 and 9770412. Using Atomic Layer Deposition (ALD) 20 or 80 (See below) layers of titanium oxide were added to the membranes, as described in US patent No. 9770412. A silicone septum was inserted at the other end of the device.
  • ALD Atomic Layer Deposition
  • the devices were implanted in 7 mice in a diet-induced obesity (DIO) mouse model, and the body weight was followed over 28 days. 7 mice with placebo devices were included as controls.
  • DIO diet-induced obesity
  • FIG. 5 shows the body mass profile of treated rats (lower trace) vs the placebo control (upper trace).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Child & Adolescent Psychology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)

Abstract

La divulgation a trait au domaine du traitement de patients avec des dispositifs d'administration implantables pour une libération à long terme d'agents thérapeutiques En particulier, la divulgation concerne des dispositifs, des formulations et des méthodes de gestion du poids corporel.
PCT/US2024/062393 2024-01-04 2024-12-31 Dispositifs implantables, formulations et méthodes de gestion du poids corporel Pending WO2025147462A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202463617522P 2024-01-04 2024-01-04
US63/617,522 2024-01-04
US202463663298P 2024-06-24 2024-06-24
US63/663,298 2024-06-24

Publications (1)

Publication Number Publication Date
WO2025147462A1 true WO2025147462A1 (fr) 2025-07-10

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Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9770412B2 (en) 2014-01-23 2017-09-26 Nano Precision Medical, Inc. Implant device for drug delivery
US9814867B2 (en) 2011-12-05 2017-11-14 Nano Precision Medical, Inc. Device having titania nanotube membrane for drug delivery
US10045943B2 (en) 2014-11-02 2018-08-14 Nano Precision Medical, Inc. Implantable medical devices for extended release of therapeutic agents
US10479868B2 (en) 2014-09-04 2019-11-19 Nano Precision Medical, Inc. Polymeric stabilizing formulations
US20210246271A1 (en) 2014-09-04 2021-08-12 Nano Precision Medical, Inc. Polymeric stabilizing formulations
WO2021173770A1 (fr) 2020-02-28 2021-09-02 Nano Precision Medical, Inc. Agents de stabilisation polymériques pour dispositifs implantables d'administration de médicaments
US11129791B2 (en) 2016-06-13 2021-09-28 Nano Precision Medical, Inc. Drug delivery device
US20220008345A1 (en) 2020-07-08 2022-01-13 Nano Precision Medical, Inc. Methods to control the rate of release of therapeutic agents from implantable devices
US20230022463A1 (en) * 2014-11-02 2023-01-26 Nano Precision Medical, Inc. Implantable medical devices for extended release of therapeutic agents
WO2023235302A1 (fr) 2022-06-01 2023-12-07 Nano Precision Medical, Inc. Dispositifs, méthodes et formulations pour commander la libération d'agents thérapeutiques à partir de dispositifs implantables

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9814867B2 (en) 2011-12-05 2017-11-14 Nano Precision Medical, Inc. Device having titania nanotube membrane for drug delivery
US9770412B2 (en) 2014-01-23 2017-09-26 Nano Precision Medical, Inc. Implant device for drug delivery
US10479868B2 (en) 2014-09-04 2019-11-19 Nano Precision Medical, Inc. Polymeric stabilizing formulations
US20210246271A1 (en) 2014-09-04 2021-08-12 Nano Precision Medical, Inc. Polymeric stabilizing formulations
US10045943B2 (en) 2014-11-02 2018-08-14 Nano Precision Medical, Inc. Implantable medical devices for extended release of therapeutic agents
US20230022463A1 (en) * 2014-11-02 2023-01-26 Nano Precision Medical, Inc. Implantable medical devices for extended release of therapeutic agents
US11129791B2 (en) 2016-06-13 2021-09-28 Nano Precision Medical, Inc. Drug delivery device
WO2021173770A1 (fr) 2020-02-28 2021-09-02 Nano Precision Medical, Inc. Agents de stabilisation polymériques pour dispositifs implantables d'administration de médicaments
US20220008345A1 (en) 2020-07-08 2022-01-13 Nano Precision Medical, Inc. Methods to control the rate of release of therapeutic agents from implantable devices
WO2023235302A1 (fr) 2022-06-01 2023-12-07 Nano Precision Medical, Inc. Dispositifs, méthodes et formulations pour commander la libération d'agents thérapeutiques à partir de dispositifs implantables

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GABERY, S ET AL.: "Semaglutide lowers body weight in rodents via distributed neural pathways", JCI INSIGHT., vol. 5, no. 1415456-99-3, 26 March 2020 (2020-03-26), pages e133429
SU NA ET AL: "Exenatide in obese or overweight patients without diabetes: A systematic review and meta-analyses of randomized controlled trials", INTERNATIONAL JOURNAL OF CARDIOLOGY, ELSEVIER, AMSTERDAM, NL, vol. 219, 15 June 2016 (2016-06-15), pages 293 - 300, XP029655613, ISSN: 0167-5273, DOI: 10.1016/J.IJCARD.2016.06.028 *

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