WO2024134493A1 - Système d'administration de médicament pour tirzépatide - Google Patents

Système d'administration de médicament pour tirzépatide Download PDF

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Publication number
WO2024134493A1
WO2024134493A1 PCT/IB2023/062939 IB2023062939W WO2024134493A1 WO 2024134493 A1 WO2024134493 A1 WO 2024134493A1 IB 2023062939 W IB2023062939 W IB 2023062939W WO 2024134493 A1 WO2024134493 A1 WO 2024134493A1
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WIPO (PCT)
Prior art keywords
delivery system
drug delivery
biocompatible polymeric
polymeric drug
tirzepatide
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PCT/IB2023/062939
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English (en)
Inventor
Megha Shyam MATLAPUDI
Vignesh Mohan
Lakshmi Rao Thakkalapally THAKKALAPALLY
Chandra Mohan SAMETHANAHALLI BASAPPA
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Quisitive Therapeutics
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Publication of WO2024134493A1 publication Critical patent/WO2024134493A1/fr

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    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction

Definitions

  • the present invention relates to the long-acting or controlled release delivery system of therapeutic peptide, Tirzepatide or pharmaceutically acceptable salts, or derivatives thereof which can be administered into patient to release for prolonged period.
  • Diabetes mellitus is a chronic disorder characterized by hyperglycemia that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces.
  • type 2 diabetes mellitus non-insulin- dependent, or adult-onset
  • impaired insulin secretion and insulin resistance are associated with elevated blood glucose levels.
  • Tirzepatide is commercially available as once weekly subcutaneous injection for adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • Tirzepatide is a dual glucagon-like peptide- 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonist, that can significantly reduce glycemic levels and improve insulin sensitivity, as well as reducing body weight by and improving lipid metabolism.
  • GLP-1 glucagon-like peptide- 1
  • GIP glucose-dependent insulinotropic peptide
  • GLP-1 glucagon-like peptide- 1
  • therapies of glucagon-like peptide- 1 (GLP-1) agonist for treatment of diabetes such as semaglutide (OZEMPIC (once weekly), exenatide (BYDUREON BCISE® (once weekly)), exenatide synthetic (BYDUREON (once weekly), BYDUREON PEN (once weekly) & BYETTA (twice daily)), liraglutide recombinant (VICTOZA (once daily)).
  • the currently approved therapies for treatment of type-2 diabetes are available or should be administered daily or as once weekly doses. It could be replaced by once- a-month dose to improve patient compliance. So, it is essential that Tirzepatide (MOUNJARO) require frequent administration on weekly basis when administered as subcutaneous injection which is difficult or cumbersome for patients. Other patients with impaired cognitive functions (Alzheimer’s disease or other similar disorders) who may not be able to self-administer drugs reliably, require help of caregiver. It requires trained personnel for administration and hence it is impractical for prolonged outpatient treatment.
  • MOUNJARO Tirzepatide
  • US patent no. 9474780 related to compound Tirzepatide and composition and method of treatment of type 2 diabetes mellitus.
  • US patent no. 11357820 related to pharmaceutical composition comprising Tirzepatide, or a pharmaceutically acceptable salt thereof for treatment of diabetes, obesity by once weekly administration.
  • US patent publication 2021/0338781 related to method for improving glycemic control by administering Tirzepatide in once weekly doses to the patients.
  • US patent no. 8642544 related to GUP-1 receptor agonist compounds and it generically discloses effective doses may be administered once per day, twice per day, thrice per day, once per week, biweekly, or once per month, depending on the formulation.
  • PCT publication WO2022/178366A1 claims modified peptide comprising a peptide selected from the group, UY3298176 (Tirzepatide) is one of the agents and further teaches administered about once per week or once every two weeks, optionally for at least one month.
  • PCT publication W02021/143810A1 related to polypeptide compound used as a GUP-1 receptor agonist, GIP receptor agonist or GCG receptor agonist one, two or three kinds of and composition is administered at a frequency of at least once a day, once a week, or once a month.
  • the ‘810 patent publication doesn’t specifically teach dual agonist of GUP-1 receptor agonist, GIP receptor agonist.
  • the present invention provides biodegradable polymeric drug delivery system for long -acting or controlled release of Tirzepatide once in a month or more to improve patient compliance.
  • the present invention relates to a biocompatible polymeric drug delivery system for long-acting or controlled release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) dual agonist, or pharmaceutically acceptable salts thereof comprising: a polymeric material to form a polymer matrix; wherein GIP/GLP- 1 dual agonist is homogeneously dispersed within the polymer matrix; wherein the polymer matrix comprises a biodegradable polymer and one or more pharmaceutically acceptable excipient(s).
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide-1
  • the present invention relates to a biocompatible polymeric drug delivery system for long -acting or controlled release of Tirzepatide, or pharmaceutically acceptable salts, or derivatives thereof comprising a polymeric material to form a polymer matrix; and Tirzepatide is homogeneously dispersed within the polymer matrix, wherein the polymer matrix comprises a biodegradable polymer and pharmaceutically acceptable excipient(s).
  • the present invention relates to a biocompatible polymeric drug delivery system for long -acting or controlled release of Tirzepatide or pharmaceutically acceptable salts, derivatives thereof can be administered by parenteral administration such as intramuscular, intraperitoneal, intra-abdominal, subcutaneous, intravenous, intra- arterial, subdermal, intradermal, intravitreal, intracerebral, intrathecal, epidural administration and the like.
  • parenteral administration such as intramuscular, intraperitoneal, intra-abdominal, subcutaneous, intravenous, intra- arterial, subdermal, intradermal, intravitreal, intracerebral, intrathecal, epidural administration and the like.
  • the present invention relates to a biocompatible polymeric drug delivery system for long -acting or controlled release of Tirzepatide or pharmaceutically acceptable salts, derivatives thereof, wherein the dose may be administered about once month and/ or more.
  • the present invention relates to a biocompatible polymeric drug delivery system in the form of microsphere, nanoparticles, implant, insert, lyophilized powder, injection, depot injection, in-situ gel, hydrogel and the like.
  • the present invention relates to a biocompatible polymeric drug delivery system used for the treatment of Tirzepatide sensitive diseases or disorders.
  • the present invention relates to a biocompatible polymeric drug delivery system for long-acting or controlled release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1) dual agonist or pharmaceutically acceptable salts thereof comprising a polymeric material to form a polymer matrix; and GIP and GLP-1 dual agonist or pharmaceutically acceptable salts thereof is homogeneously dispersed within the polymer matrix, wherein the polymer matrix comprises a biodegradable polymer and pharmaceutically acceptable excipients, wherein said glucose -dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1) dual agonist is Tirzepatide.
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide- 1
  • drug delivery system refers to a formulation/composition or a device that enables the introduction of therapeutic active agent in the body and improves its efficacy and safety by controlling the rate, time and place of release of drugs in the body.
  • the present invention may be in the form of microsphere, nanoparticles, implant, insert, lyophilized powder, injection, depot injection, in-situ gel, hydrogel and the like.
  • drug or “active agent”, “active pharmaceutical ingredient (API)” as used here includes glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide- 1 (GLP-1) dual agonist, tirzepatide or salts, derivatives, polymorphs, isoforms, metabolites, analogues thereof.
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide- 1
  • the active agent(s) can be small molecule, biologic agent, peptide or its derivatives, polymorphs, isoforms, metabolites, analogues thereof.
  • composition is intended to encompass a combination including active ingredients and pharmaceutically acceptable excipients, as well as any product which results, directly or indirectly, from combination, complexation, or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions involving one or more of the ingredient(s).
  • controlled release refers to long-acting or sustained or controlled or delayed or prolonged release of an active pharmaceutical ingredient in a specified amount over a specified period of time and/ or controlled-release refers to slowly release a drug in the body in a prolonged controlled fashion.
  • microspheres or “microparticles” as used herein is small spherical or spherical-like particles comprise of drug dissolved and (or) dispersed homogeneously throughout a polymer material, with a particle size ranging from 0. 1-1000 pm, and generally made up of biodegradable and biocompatible polymers.
  • nanoparticle or “nanoparticles” as used herein is small spherical or spherical-like particles comprise of drug dissolved and (or) dispersed homogeneously throughout a polymer material, with a particle size ranging from 1- 1000 nm, and generally made up of biodegradable and biocompatible polymers.
  • in-situ gel refers to the process of gel formation at the site of application after the composition or formulation has been applied to the site.
  • In-situ gelling systems are polymeric composition or formulation that are in solution or suspension forms, when it comes in contact with the body or physiological fluids or under physiological conditions it change to gel forms.
  • In-situ gel formation of drug delivery systems can be defined as liquid formulation generating a solid or semisolid depot after administration. These are generally liquid formulations that form semi-solid or solid depots after injection at the injection site.
  • In-situ gel formation of drug delivery systems can be defined as in-situ gels transformed in situ into solid implants after administration. This class of implant is classified by compositions that transform from a drug-containing liquid phase to a drug-infused gel phase upon exposure to a physiological environment.
  • polymer matrix refers to a polymer composition which contains one or more active ingredient(s), peptides, biodegradable polymers and one or more pharmaceutical acceptable excipient(s).
  • biodegradable polymer includes those polymers that degrades within the body as a result of natural biological processes, eliminating the need to remove a drug-delivery system after release of the active agent has been completed or biodegradable polymers are polymers that degrade when they are left in the environment.
  • biocompatible is used to describe a material or system which causes tolerable or no adverse reaction when applied to humans.
  • acceptable salts refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts, solvate, hydrate and the like thereof. Acceptable salt forms of compounds provided herein are synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods.
  • excipient or “pharmaceutically acceptable excipient(s)” or “adjuvant” or “carriers” means a component of a pharmaceutical product that is not a pharmacologically active ingredient, such as carrier, preservatives, buffers, polymers, cellulose and its derivatives, pH modifiers, antioxidants, surfactants, humectants, emollients, solvents, co-solvents, vehicles, non-volatile solvents, nonsolvents, organic solvents, hardening agents, lubricants, chelating agents, plasticizers, film forming agents, penetration enhancers, stabilizers, emulsifiers added to a drug to increase or aid its effect.
  • excipient or “pharmaceutically acceptable excipient(s)” or “adjuvant” or “carriers” means a component of a pharmaceutical product that is not a pharmacologically active ingredient, such as carrier, preservatives, buffers, polymers, cellulose and its derivatives,
  • excipients or adjuvants that are useful in preparing pharmaceutical compositions are generally safe, non- toxic, and neither biologically nor otherwise undesirable, and are acceptable for veterinary use as well as human pharmaceutical use and/or cosmetic use.
  • the term includes one or more excipient(s) or adjuvant(s).
  • caregiver or ‘caretaker’ as used herein includes healthcare professionals or trained professionals include but not limited to doctors, nurses or non-healthcare professionals such as family members, friends, relatives, who assists in administration of delivery system to the patient.
  • Tirzepatide sensitive diseases or disorders includes but not limited to adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD) and the like or related diseases.
  • NAFLD non-alcoholic fatty liver disease
  • the present invention provides biocompatible polymeric drug delivery system for long-acting or controlled release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1) dual agonist, or pharmaceutically acceptable salts thereof comprising: a polymeric material to form a polymer matrix; wherein GIP/GLP- 1 dual agonist is homogeneously dispersed within the polymer matrix; wherein the polymer matrix comprises a biodegradable polymer and one or more pharmaceutically acceptable excipient(s).
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide- 1
  • the present invention provides biocompatible polymeric drug delivery system for long-acting or controlled release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1) dual agonist is Tirzepatide or pharmaceutical acceptable salts, derivatives thereof.
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide- 1
  • the present invention provides biocompatible polymeric drug delivery system for long-acting or controlled release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1) dual agonist in combination with one or more other active agent(s).
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide- 1
  • the present invention provides biocompatible polymeric drug delivery system co-administration of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1) dual agonist with one or more other active agent(s).
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide- 1
  • the present invention provides biocompatible polymeric drug delivery system for long-acting or controlled release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide- 1 (GLP-1) dual agonist in combination or co-administration with one or more other active agent(s) include but not limited to use in treatment of cardiovascular related disease or disorder, diabetic related disease or disorder, kidney related disease or disorder, lipid or cholesterol related disease or disorder and chronic weight management related disease or disorder.
  • GIP glucose-dependent insulinotropic polypeptide
  • GLP-1 glucagon-like peptide- 1
  • the present invention provides biocompatible polymeric drug delivery system in the form of microsphere, nanoparticles, implant, insert, lyophilized powder, injection, depot injection, in-situ gel, hydrogel and the like.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system comprising; a polymeric material to form a polymer matrix; wherein Tirzepatide or pharmaceutically acceptable salts thereof is homogeneously dispersed within the polymer matrix; wherein the polymer matrix comprises a biodegradable polymer and one or more pharmaceutically acceptable excipient(s); wherein said biocompatible polymeric drug delivery system is in the form of microsphere.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system is in the form of microsphere, wherein said microsphere composition comprises drug and biodegradable polymer, wherein said microsphere composition may be suspended in suitable vehicle before administration.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system is in the form of microsphere, wherein said microsphere composition comprises drug and biodegradable polymer, wherein said microsphere composition may be administered by using self-administration devices and the like.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system comprising; a polymeric material to form a polymer matrix; wherein Tirzepatide or pharmaceutically acceptable salts thereof is homogeneously dispersed within the polymer matrix; wherein the polymer matrix comprises a biodegradable polymer and one or more pharmaceutically acceptable excipient(s); wherein said biocompatible polymeric drug delivery system is in the form of nanoparticles.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system is in the form of nanoparticles, wherein said nanoparticles composition comprises drug and biodegradable polymer, wherein said nanoparticles composition may be suspended in suitable vehicle before administration.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system is in the form of nanoparticles, wherein said nanoparticles composition comprises drug and biodegradable polymer, wherein said nanoparticles composition may be administered by using self-administration devices and the like.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system comprising; a polymeric material to form a polymer matrix; wherein Tirzepatide or pharmaceutically acceptable salts thereof is homogeneously dispersed within the polymer matrix; wherein the polymer matrix comprises a biodegradable polymer and one or more pharmaceutically acceptable excipient(s); wherein said biocompatible polymeric drug delivery system is in the form of implant or insert.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system comprising; a polymeric material to form a polymer matrix; wherein Tirzepatide or pharmaceutically acceptable salts thereof is homogeneously dispersed within the polymer matrix; wherein the polymer matrix comprises a biodegradable polymer and one or more pharmaceutically acceptable excipient(s); wherein said biocompatible polymeric drug delivery system is in the form of in-situ gel.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system comprising; a polymeric material to form a polymer matrix; wherein Tirzepatide or pharmaceutically acceptable salts thereof is homogeneously dispersed within the polymer matrix; wherein the polymer matrix comprises a biodegradable polymer and one or more pharmaceutically acceptable excipient(s); wherein said biocompatible polymeric drug delivery system is in the form of hydrogel.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting comprises of Tirzepatide with biodegradable polymer and one or more pharmaceutical acceptable excipient(s).
  • the present invention provides biocompatible polymeric drug delivery system for long-acting comprising; polymeric material to form a polymer matrix; wherein the polymer matrix comprises of biodegradable polymer include but not limited to polyglycolic acid (PGA), polylactic acid (PLA), poly-P- hydroxybutyrate (PHB), poly (lactic acid-co-glycolic acid) (PLGA), poly-8- caprolactone (PCL), polyethylene glycol (PEG); multi-armed polyethylene glycol (PEG) with functional groups such as PEG amine, PEG carboxyl, PEG succinimidyl carboxymethyl ester, PEG succinimidyl glutaramide, PEG nitrophenyl carbonate, PEG succinimidyl carbonate, PEG maleimide, PEG acrylate, PEG thiol, PEG vinylsulfone, PEG succinimidyl succinate, PEG succinimidyl glutarate, PEG isocianate, PEG azide, PEG-OH,
  • Multi-arm includes, but not limited to two or more arms and the like thereof; polycyanoacrylates, polyanhydrides, poly(amino acids), poly(ortho ester), polyphosphazenes, polypropylene fumarate), polyhydroxyvalerate (PHV), polydioxanone, polyglycolide (PG), poly(trimethylene carbonate), polyvalerolactone, poly(alpha-hydroxy acids), poly (lactones), polyketals poly(arylates), polyurethanes, polythioesters, poly(orthocarbonates), poly(phosphoesters), poly(ester-co-amide), poly(lactide-co- urethane, polyvinyl alcohol (PVA), PVA-g-PLGA, PEGT-PBT copolymer (polyactive), methacrylates, poly(N-isopropylacrylamide), PEO-PPO-PEO (pluronics), PEO-PPO-PAA copolymers, PLGA-PEO-PL
  • the present invention provides biocompatible polymeric drug delivery system for long-acting comprising; a polymeric material to form a polymer matrix; wherein the polymer matrix comprises pharmaceutically acceptable excipients such as organic solvent, non-solvent, hardening agent, stabilizer, polymers and the like or mixtures thereof.
  • pharmaceutically acceptable excipients such as organic solvent, non-solvent, hardening agent, stabilizer, polymers and the like or mixtures thereof.
  • excipients depends on the desired characteristics of the compositions and on the nature of other pharmacologically active compounds in the formulation.
  • organic solvent examples include but not limited to aliphatic alcohol, aromatic alcohol, chloroform, dimethyl chloride, polyvalent sugar alcohol, aromatic hydrocarbon, aldehyde, ketone, ester, ether, dioxane, alkanes, alkenes, conjugated dienes, methylene chloride (di chloromethane), 1,1,2-trichloroethane or other Cl - C4 halogenated alkanes, acetonitrile, ethyl acetate, polyols, polyimides, polyesters, polyaldehydes and mixtures thereof.
  • the solvent is composed of polar aprotic solvent include but not limited to N-methyl-2-pyrrolidone, 2-pyrrolidone, N, N-dimethylformamide, dimethyl sulfoxide, propylene carbonate, caprolactam, diacetin, triacetin, or any combinations thereof.
  • the biocompatible polar aprotic solvent is N- methyl-2 -pyrrolidone, diacetin, triacetin.
  • non-solvent examples include but not limited to alkanes, oils, glycerins, glycols, ethyl ether, petroleum ether, n-hexane, cyclohexane, acetone, siloxanes, silicone oils (polydidemethylsiloxane), vegetable oils, polyisobutylene, mineral oils, cyclic polydimethylsiloxanes and related oils and the like or mixtures thereof.
  • hardening agent examples include but not limited to hexane, heptane, cyclohexane, volatile silicone fluids such as siloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, polydimethylsiloxanes such as hexamethyldisiloxane and the like mixtures thereof.
  • stabilizer examples include but not limited to nitric acid, hydrochloric acid, sulfuric acid, perchloric acid, glacial acetic acid, methane sulfonic acid, trifluoromethanesulfonic acid, polysulfonic acid, polyacrylic acid, polymethacrylic acid, polymaleic acid, polytetraflourosulfonic acid, poly (ethylene -maleic) acid or polystyrene carboxylic acid, ammonium chloride, ammonium laureth sulfate, diethylene glycol mono [ (1,1,3, 3 -tetramethylbutyl) phenyl] ether and 4-benzoyl- 3-methyl-l-phenyl-2-pyrazol-5-one and the like or mixtures thereof.
  • emulsifying agent examples include but not limited to an anionic surfactant and a nonionic surfactant, sodium oleate, sodium stearate, sodium laurylsulfate, polyoxyethylene sorbitan fatty acid esters like polysorbate 80, polyethylene castor oil derivatives, polyvinylpyrrolidone, polyvinyl alcohol, carboxymethyl cellulose, methyl cellulose, lecithin, and gelatin and the like).
  • polymer examples include but not limited to polyethylene glycol) ether derivatives such as polyethylene glycol) mono- or di-alkyl ethers, poly(ethylene glycol)monomethyl ether or poly(ethylene glycol)dimethyl ether; poly(ethylene glycol)copolymers such as poly(ethylene glycol -co-polypropylene glycol); propylene glycol mono- or di-esters of a C2-19 aliphatic carboxylic acid or a mixture of such acids, such as propylene glycol dicaprylate or dicaprate; mono-, di- or tri-glycerides of a C2-19 aliphatic carboxylic acid or a mixture of such acids, such as glyceryl caprylate, glyceryl caprate, glyceryl caprylate/caprate, glyceryl caprylate/caprate/laurate, glycofurol and similar ethoxylated tetrahydrofurfuryl alcohols, Cl -4 alkyl ethers
  • excipient(s) used for the preparation of nanoparticles include but not limited to human serum albumin (HSA), ethyl acetate, Polyvinyl alcohol, Lecithin, Phosphotidyl choline, distearoylphosphatidylcholine, Mono-di-triglycerides, Glyceryl monooleate, Cholesterol, distearoyl phosphatidylglycerol, Tocopherol, Dioleoylphosphatidylcholine, Dioleoylphosphatidylcholine, N-(carbonyl- methoxypolyethylene glycol 2000)-l,2-distearoyl-sn-glycero3- phosphoethanolamine sodium salt, Hydrogenated soy phosphatidylcholine (HSPC), Sphingomyelin, Dimyristoyl-phosphatidylcholine, Cholesteryl sulfate, 1- Pahnitoyl -2 -o
  • excipient(s) used for the preparation of hydrogel include but not limited to Sodium CMC, Carboxymethyl Cellulose (CMC), Methyl cellulose, Guar gum, Xanthan gum, hyaluronic acid, alginate, cellulose, starch, chitosan, HPMC, HPC, HEC, modified cellulose polymer and the like or mixtures thereof.
  • CMC Carboxymethyl Cellulose
  • Methyl cellulose Methyl cellulose
  • Guar gum Xanthan gum
  • hyaluronic acid alginate
  • cellulose starch
  • chitosan HPMC
  • HPC HPC
  • HEC modified cellulose polymer and the like or mixtures thereof.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting in the form of microsphere composition.
  • Microsphere composition comprises of Tirzepatide with biodegradable polymer such as PLGA and the like with other excipients include but not limited to methylene chloride, polydimethylsiloxane, octamethylcyclotetrasiloxane and the like.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting in the form of nanoparticles composition.
  • Nanoparticles composition comprises of Tirzepatide with biodegradable polymer such as human serum albumin (HSA) and the like with other one or more excipient(s).
  • HSA human serum albumin
  • the present invention provides biocompatible polymeric drug delivery system for long-acting in the form of implant composition.
  • Implant composition comprises of Tirzepatide with biodegradable polymer such as PLGA or mixtures thereof and the like.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting in the form of In-situ gel composition.
  • In-situ gel composition comprises of Tirzepatide with biodegradable polymer such as PLGA or mixtures thereof with one or more suitable solvent(s) and other excipient(s).
  • the present invention provides biocompatible polymeric drug delivery system for long-acting in the form of In-situ gel composition.
  • In-situ gel composition comprises of Tirzepatide with biodegradable polymer such as polyorthoester or mixtures thereof with one or more suitable solvent(s), other excipient(s).
  • the present invention provides biocompatible polymeric drug delivery system for long-acting in the form of implant composition.
  • Implant composition comprises of Tirzepatide with biodegradable polymer such as PLGA and the like with other excipient include but not limited to glacial acetic acid and the like.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting in the form of hydrogel composition.
  • Hydrogel composition comprises of Tirzepatide with biodegradable polymer such as modified cellulose polymer and the like with other one or more excipient(s).
  • the present invention provides process for preparing biocompatible polymeric drug delivery system for long-acting of microsphere composition
  • process for preparing biocompatible polymeric drug delivery system for long-acting of microsphere composition comprising of following steps: i) add biodegradable polymer to organic solvent to form solution and then filter through 0.2 p Millipore or suitable membrane, ii) add API (active pharmaceutical ingredient) to above phase and homogenize to disperse the drug, iii) infuse non solvent under stirring, iv) transfer the above phase to hardening agent under stirring, v) collect the microsphere by filtration, vi) rinse the microsphere with hardening agent, viii) dry the microsphere.
  • the present invention provides process for preparing biocompatible polymeric drug delivery system for long-acting of implant composition
  • process for preparing biocompatible polymeric drug delivery system for long-acting of implant composition comprising of following steps: i) milling of biodegradable polymer by using jet mill, ii) blend the API (active pharmaceutical ingredient) and biodegradable polymer together, iii) add the above blended mixture to the hopper of the tween screw extruder to form the filaments, iv) pelletize the above filaments, v) add all the above pellets to the hopper of the tween screw extruder to form final filament, vi) cut the filaments to suitable dimensions.
  • the present invention provides process for preparing biocompatible polymeric drug delivery system for long-acting of implant composition comprising of following steps: i) flux the 1% water to stabilizer, ii) solubilize biodegradable polymer and stabilizer together and then freeze drying, iii) add freeze dried biodegradable polymer and API (active pharmaceutical ingredient) to stabilizer, iv) freeze drying above step for 24 hr, v) add all the above freeze-dried product to the hopper of the tween screw extruder to form the fdaments, vi) cut the filaments to suitable dimensions.
  • the present invention provides process of preparation of in-situ implant, wherein present invention in-situ implant is prepared by homogenization process or suitable procedure.
  • the present invention provides process for preparation of in-situ implant involving the following steps: i) polymer is solubilized in aprotic solvent, ii) further the polymer solution is taken in pre-filled syringe system. iii) then drug is solubilized in water and filled in the syringe and lyophilized to form a powder, iv) further mixing the component of polymer syringe with drug powder syringe to form a drug polymer mixture, which when injected forms in-situ implant.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system in the form of implant.
  • the present invention provides administration of implant by health care professionals or trained professionals.
  • the present invention provides the implant comprises: a core comprising a biodegradable polymer that forms the polymer matrix and a therapeutic peptide, Tirzepatide that is dispersed homogenously in the core polymer matrix and the core is having an outer surface that is coated by a non-medicated membrane layer.
  • the present invention provides the implant comprises a core comprising Tirzepatide and one or more excipient(s) dispersed homogenously within the core polymer matrix and a membrane layer on the outer surface of the core.
  • the process of preparation of implants includes but not limited to extrusion, coaxial extrusion, hot melt extrusion and the like or combination of processes thereof.
  • 1 cm to about 10 cm length for example about 0.5 cm to about 8 cm; about 1 cm to about 6 cm in length, about 1.2 cm to about 6.5 cm, about 1.4 cm to about 6 cm, 1.5 cm to about 5.5 cm, 1.75 cm to about 5 cm, 2 cm to about 4.5 cm, 2.2 cm to about 4 cm, 2.4 cm to about 3.5 cm, 2.5 cm to about 3 cm; about 0.5mm to about 8 mm in diameter, for example between about 0.6mm to about 7.5 mm, about 0.7mm to about 7 mm, about 0.8 mm to about 6.5 mm, about 0.9 mm to about 6 mm, about 1 mm to about 5.5 mm, about 1.1mm to about 5 mm, about 1.2 mm to about 4.5 mm, about 1.3 mm to about 4 mm, 1.4 mm to about 3.5 mm, about 1.5 mm to about 3 mm, about 1.6 mm to about 2.5 mm, about 1.7 mm to about 2 mm.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting is suitable for administration using selfadministration injection device.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting is suitable for administration using selfadministration injection device, wherein biocompatible polymeric drug delivery system is in the form of microsphere.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting is suitable for administration using selfadministration injection device, wherein biocompatible polymeric drug delivery system is in the form of nanoparticles.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting is suitable for administration using selfadministration injection device, wherein biocompatible polymeric drug delivery system is in the form of in-situ gel.
  • the present invention provides long-acting or controlled release biocompatible polymeric drug delivery system in the form of in-situ implant.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting is suitable for administration using selfadministration injection device, wherein biocompatible polymeric drug delivery system is in the form of lyophilized powder.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting is suitable for administration using selfadministration injection device, wherein biocompatible polymeric drug delivery system is in the form of hydrogel.
  • the present invention provides self- administration injection devices such as auto injector, electronic auto injector devices, prefdled syringe, dual chamber prefdled syringe, single dose or multiple dose pen injector, dual chamber cartridge with pen injector, dual chamber cartridge with auto-injector, cartridge with pen injector and the like or combinations thereof.
  • self- administration injection devices such as auto injector, electronic auto injector devices, prefdled syringe, dual chamber prefdled syringe, single dose or multiple dose pen injector, dual chamber cartridge with pen injector, dual chamber cartridge with auto-injector, cartridge with pen injector and the like or combinations thereof.
  • present invention provides self- administration injection devices in various dimensions and components of device assembly.
  • self-admini station injectable device suitable for parenteral administration such as intramuscular, intraperitoneal, intra-abdominal, subcutaneous, intravenous, intraarterial, subdermal, intradermal, intravitreal, intracerebral, intrathecal, epidural administration and similar route of administration.
  • the present invention relates to a biocompatible polymeric drug delivery system for long -acting or controlled release of Tirzepatide or pharmaceutically acceptable salts thereof can be administered by parenteral administration such as intramuscular, intraperitoneal, intra-abdominal, subcutaneous, intravenous, intraarterial, subdermal, intradermal, intravitreal, intracerebral, intrathecal, epidural administration and similar routes.
  • parenteral administration such as intramuscular, intraperitoneal, intra-abdominal, subcutaneous, intravenous, intraarterial, subdermal, intradermal, intravitreal, intracerebral, intrathecal, epidural administration and similar routes.
  • the present invention provides the dose of biocompatible polymeric drug delivery system for long -acting or controlled release of Tirzepatide or pharmaceutically acceptable salts thereof is administered about once in a month and/or more.
  • the present invention provides the dose of biocompatible polymeric drug delivery system for long-acting can be administered, for example, once every month, once every 2 months, once every 3 months, once every 4 months, once every 5 months, once every 6 months, once every 9 months, once every 12 months and the like or intermediate dosages, for example, once 1.5 month, once every 2.5 months, once every 3.5 months, once every 4.5 months, once every 5.5 months, once every 6.5 months, once every 9.5 months, once every 12.5 months and the like or any combinations thereof.
  • the present invention provides administration of biocompatible polymeric drug delivery system for long-acting based on the health care professional instructions.
  • the present invention described drug delivery system were sterilized by suitable sterilization method.
  • the present invention optionally comprises radio-opaque element include but not limited to barium sulphate, titanium oxide, bismuth oxide, tantalum, tungsten, or platinum and the like.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting comprises appropriate dosage and dosage regimen of Tirzepatide for the treatment of disease or disorders. In another embodiment, the present invention provides biocompatible polymeric drug delivery system for long -acting with suitable packaging materials.
  • the present invention provides biocompatible polymeric drug delivery system for long-acting for the treatment of Tirzepatide sensitive diseases or disorders.
  • Manufacturing Process i) Polymer and Tirzepatide were milled by using mill, ii) Blended Tirzepatide and biodegradable polymer together, iii) Above blended mixture added to the hopper of the extruder to form the filaments, iv) Above filaments Pelletized in mixer, v) Above pellets added to the hopper of the extruder for 2 nd extrusion to form final filament vi) the filaments were cuts to suitable dimensions.
  • Example B In-Situ Gel Implant with Stabilizer
  • Manufacturing Process i) Polymer was solubilized in stabilizer, ii) the solution was lyophilised to form polymer powder, iii) Lyophilized polymer powder and Tirzepatide were added to the above solution with stabilizer and dissolved, iv) the solution was lyophilised to form powder, v) above powder collected and extrusion was performed to form implants vi) the fdaments were cuts to suitable dimensions.
  • Tirzepatide was dissolved by addition of solvent, ii) above solution was added to polymer solution, iii) above mixture was homogenised, iv) homogenised mixture was subjected to evaporation, v) remaining dispersion was subjected to lyophilization.

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Abstract

La présente invention concerne un système d'administration de médicament polymère biocompatible pour une libération à durée d'action longue ou contrôlée d'un agoniste double de polypeptide insulinotropique dépendant du glucose (GIP) et de peptide-1 de type glucagon (GLP-1), ou des sels pharmaceutiquement acceptables de celui-ci comprenant un matériau polymère pour former une matrice polymère; et un agoniste double de GIP et GLP-1 est dispersé de manière homogène à l'intérieur de la matrice polymère, la matrice polymère comprenant un polymère biodégradable et des excipients pharmaceutiquement acceptables. Le système d'administration de médicament polymère biocompatible peut être administré à un patient pour être libérer pendant une période d'action longue ou contrôlée ou prolongée.
PCT/IB2023/062939 2022-12-19 2023-12-19 Système d'administration de médicament pour tirzépatide WO2024134493A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022049310A1 (fr) * 2020-09-07 2022-03-10 Cyprumed Gmbh Formulations pharmaceutiques améliorées d'agonistes du récepteur glp-1

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022049310A1 (fr) * 2020-09-07 2022-03-10 Cyprumed Gmbh Formulations pharmaceutiques améliorées d'agonistes du récepteur glp-1

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