CA2448218A1 - Sustained release formulation - Google Patents

Sustained release formulation Download PDF

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Publication number
CA2448218A1
CA2448218A1 CA002448218A CA2448218A CA2448218A1 CA 2448218 A1 CA2448218 A1 CA 2448218A1 CA 002448218 A CA002448218 A CA 002448218A CA 2448218 A CA2448218 A CA 2448218A CA 2448218 A1 CA2448218 A1 CA 2448218A1
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CA
Canada
Prior art keywords
composition
protein
zinc
kit
solvent
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.)
Granted
Application number
CA002448218A
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French (fr)
Other versions
CA2448218C (en
Inventor
Franklin Okumu
Jeffrey L. Cleland
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Genentech Inc
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Individual
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Publication of CA2448218A1 publication Critical patent/CA2448218A1/en
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Publication of CA2448218C publication Critical patent/CA2448218C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • 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
    • A61K38/27—Growth hormone [GH] (Somatotropin)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin

Abstract

A composition comprises a protein, a polyiol, and a metal. The protein is stabilized by the polyol and the metal, and is protected from denaturing when in contact with an organic solvent. The polyol may be a hydrocarbon containing two or more hydroxyl groups (-OH) bonded to carbon. The metal may be divalent.

Claims (83)

1. A composition, comprising:
a protein;
a polyol; and a metal cation.
2. The composition of claim 1, wherein said polyol is selected from the group consisting of a monosaccharide, a polysaccharide, glycerol, mannitol, sorbitol, inositol, and polyethylene glycol.
3. The composition of claim 1, wherein said polyol is selected from the group consisting of mannitol, threhalose, and polyethylene glycol.
4. The composition of any one of claims 1-3, wherein the mass ratio of polyol to protein is from 100:1 to 1:100.
5. The composition of any one of claims 1-3, wherein the mass ratio of polyol to protein is from 1:1 to 1:10.
6. The composition of any one of claims 1-5, wherein the metal cation is divalent.
7. The composition of any one of claims 1-6, wherein the metal cation is zinc.
8. The composition of claim 7, wherein the molar ratio of zinc to protein is from 1:1 to 100:1.
9. The composition of claim 7, wherein the molar ratio of zinc to protein is from 1:1 to 20:1.
10. The composition of claim 7, wherein the molar ratio of zinc to protein is from 1:1 to 10:1.
11. The composition of any one of claims 1-10, wherein the protein is selected from the group consisting of a growth hormone, insulin, and a growth factor.
12. The composition of any one of claims 1-11, further comprising a carrier material;
wherein the carrier material comprises a non-polymeric, non-water soluble liquid material having a viscosity of at least 5,000 cP at 37 °C
that does not crystallize neat under ambient physiological conditions.
13. The composition of claim 12, wherein the liquid material is a stearate ester, a stearate amide, a long-chain fatty acid amide, a long-chain fatty alcohol, a long-chain ester, or a disaccharide ester.
14. The composition of claim 12, wherein the liquid material is acetylated sucrose distearate.
15. The composition of claim 12, wherein the liquid material is disaccharide acetate butyrate.
16. The composition of claim 12, wherein the liquid material is sucrose acetate isobutyrate.
17. The composition of any one of claims 1-16, wherein the composition has a viscosity less than 1000 cP at room temperature.
18. The composition of any one of claims 1-16, wherein the composition has a viscosity less than 200 cP at room temperature.
19. A method of administering a protein, comprising:
injecting the composition of any of claims 1-18 into a patient in need of said protein.
20. The method of claim 19, wherein less than 10% of the protein is released within 24 hours of administration.
21. The method of claim 19, wherein less than 0.2% of the protein is released within 24 hours of administration.
22. The method of any one of claims 19-21, wherein the percentage of the protein released within a 24 hour period is from 0.05% to 3%.
23. The method of any one of claims 19-21, wherein the percentage of the protein released within a 24 hour period is from 1 % to 3%.
24. A method of making a sustained release composition, comprising:
mixing a complex and a liquid carrier to form said sustained release composition;
wherein said liquid carrier comprises sucrose acetate isobutyrate; and wherein said complex comprises a protein, a polyol, and zinc.
25. The method of claim 23, wherein said sustained release composition has a viscosity less than 1000 cP at room temperature.
26. The method of claim 23, wherein said sustained release composition has a viscosity less than 200 cP at room temperature.
27. The method of any one of claims 24-26, wherein the molar ratio of zinc to protein is from 100:1 to 1:1.
28. The method of any one of claims 24-26, wherein the molar ratio of zinc to protein is from 10:1 to 1:1.
29. The method of any one of claims 24-28, wherein said liquid carrier further comprises a solvent.
30. The method of claim 29, wherein said solvent is ethanol, benzyl benzoate, miglyol, propylene carbonate, or benzyl alcohol.
31. The method of any one of claims 29-30, wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 85:15 w/w.
32. The method of any one of claims 29-30, wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
33. The method of claim 29, wherein said sustained release composition comprises:
a sucrose acetate isobutyrate to solvent ratio from 50:50 w/w to 85:15 w/w, wherein the sucrose acetate isobutyrate and solvent together form said liquid carrier;
a zinc to protein molar ratio from 100:1 to 1:1, wherein the zinc and protein together form said complex; and a liquid carrier to complex ratio from 95:5 w/v to 85:15 w/v.
34. The method of claim 33, wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
35. The method of claim any one of claims 33-34, wherein the molar ratio of zinc to protein is from 10:1 to 1:1.
36. A kit, comprising:
a container;
a protein;
a polyol;
a metal cation; and a liquid carrier;
wherein the liquid carrier comprises sucrose acetate isobutyrate.
37. The kit of claim 36, comprising a unit dosage of the protein.
38. The kit of any one of claims 36-37, wherein the polyol, the metal cation, and the liquid carrier are sterile.
39. The kit of any one of claims 36-38, further comprising a syringe.
40. The kit of any one of claims 36-39, wherein the container comprises a septum.
41. The kit of any one of claims 36-40, wherein the metal cation is divalent.
42. The kit of any one of claims 36-41, wherein the metal cation is zinc.
43. A composition, comprising:
a protein;
an alcohol; and a metal cation;
wherein said alcohol is selected from the group consisting of a monosaccharide, a polysaccharide, glycerol, mannitol, sorbitol, inositol, and polyethylene glycol.
44. The composition of claim 43, wherein said alcohol is selected from the group consisting of mannitol, threhalose, and polyethylene glycol.
45. The composition of any one of claims 43-44, wherein the mass ratio of alcohol to protein is from 100:1 to 1:100.
46. The composition of any one of claims 43-44, wherein the mass ratio of alcohol to protein is from 1:1 to 1:10.
47. The composition of any one of claims 43-46, wherein the metal cation is divalent.
48. The composition of any one of claims 43-47, wherein the metal cation is zinc.
49. The composition of claim 48, wherein the molar ratio of zinc to protein is from 1:1 to 100:1.
50. The composition of claim 48, wherein the molar ratio of zinc to protein is from 1:1 to 20:1.
51. The composition of claim 48, wherein the molar ratio of zinc to protein is from 1:1 to 10:1.
52. The composition of any one of claims 43-51, wherein the protein is selected from the group consisting of a growth hormone, insulin, and a growth factor.
53. The composition of any one of claims 43-52, further comprising a carrier material;
wherein the carrier material comprises a non-polymeric, non-water soluble liquid material having a viscosity of at least 5,000 cP at 37 °C
that does not crystallize neat under ambient physiological conditions.
54. The composition of claim 53, wherein the liquid material is a stearate ester, a stearate amide, a long-chain fatty acid amide, a long-chain fatty alcohol, a long-chain ester, or a disaccharide ester.
55. The composition of claim 53, wherein the liquid material is acetylated sucrose distearate.
56. The composition of claim 53, wherein the liquid material is disaccharide acetate butyrate.
57. The composition of claim 53, wherein the liquid material is sucrose acetate isobutyrate.
58. The composition of any one of claims 43-57, wherein the composition has a viscosity less than 1000 cP at room temperature.
59. The composition of any one of claims 43-57, wherein the composition has a viscosity less than 200 cP at room temperature.
60. A method of administering a protein, comprising:

injecting the composition of any of claims 43-59 into a patient in need of said protein.
61. The method of claim 60, wherein less than 10% of the protein is released within 24 hours of administration.
62. The method of claim 60, wherein less than 0.2% of the protein is released within 24 hours of administration.
63. The method of any one of claims 60-62, wherein the percentage of the protein released within a 24 hour period is from 0.05% to 3%.
64. The method of any one of claims 60-62, wherein the percentage of the protein released within a 24 hour period is from 1% to 3%.
65. A method of making a sustained release composition, comprising:
mixing a complex and a liquid carrier to form said sustained release composition;
wherein said liquid carrier comprises sucrose acetate isobutyrate; and wherein said complex comprises a protein, an alcohol, and zinc;
wherein said alcohol is selected from the group consisting of a monosaccharide, a polysaccharide, glycerol, mannitol, sorbitol, inositol, and polyethylene glycol.
66. The method of claim 65, wherein said sustained release composition has a viscosity less than 1000 cP at room temperature.
67. The method of claim 65, wherein said sustained release composition has a viscosity less than 200 cP at room temperature.
68. The method of any one of claims 65-67, wherein the molar ratio of zinc to protein is from 100:1 to 1:1.
69. The method of any one of claims 65-67, wherein the molar ratio of zinc to protein is from 10:1 to 1:1.
70. The method of any one of claims 65-69, wherein said liquid carrier further comprises a solvent.
71. The method of claim 70, wherein said solvent is ethanol, benzyl benzoate, miglyol, propylene carbonate, or benzyl alcohol.
72. The method of any one of claims 70-71, wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 85:15 w/w.
73. The method of any one of claims 70-71, wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
74. The method of claim 70, wherein said sustained release composition comprises:
a sucrose acetate isobutyrate to solvent ratio from 50:50 w/w to 85:15 w/w, wherein the sucrose acetate isobutyrate and solvent together form said liquid carrier;
a zinc to protein molar ratio from 100:1 to 1:1, wherein the zinc and protein together form said complex; and a liquid carrier to complex ratio from 95:5 w/v to 85:15 w/v.
75. The method of claim 74, wherein the ratio of sucrose acetate isobutyrate to solvent is from 50:50 w/w to 70:30 w/w.
76. The method of claim any one of claims 74-75, wherein the molar ratio of zinc to protein is from 10:1 to 1:1.
77. A kit, comprising:
a container;
a protein;
an alcohol;
a metal cation; and a liquid carrier;
wherein the liquid carrier comprises sucrose acetate isobutyrate;
and wherein said alcohol is selected from the group consisting of a monosaccharide, a polysaccharide, glycerol, mannitol, sorbitol, inositol, and polyethylene glycol.
78. The kit of claim 77, comprising a unit dosage of the protein.
79. The kit of any one of claims 77-78, wherein the alcohol, the metal cation, and the liquid carrier are sterile.
80. The kit of any one of claims 77-79, further comprising a syringe.
81. The kit of any one of claims 77-80, wherein the container comprises a septum.
82. The kit of any one of claims 77-81, wherein the metal cation is divalent.
83. The kit of any one of claims 77-82, wherein the metal cation is zinc.
CA2448218A 2001-06-21 2002-06-21 Sustained release formulation Expired - Lifetime CA2448218C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US30027501P 2001-06-21 2001-06-21
US60/300,275 2001-06-21
US10/176,961 US7318931B2 (en) 2001-06-21 2002-06-21 Sustained release formulation
PCT/US2002/019597 WO2003000282A1 (en) 2001-06-21 2002-06-21 Sustained release formulation
US10/176,961 2002-06-21

Publications (2)

Publication Number Publication Date
CA2448218A1 true CA2448218A1 (en) 2003-01-03
CA2448218C CA2448218C (en) 2012-05-29

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Application Number Title Priority Date Filing Date
CA2448218A Expired - Lifetime CA2448218C (en) 2001-06-21 2002-06-21 Sustained release formulation

Country Status (10)

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US (2) US7318931B2 (en)
EP (1) EP1397155B1 (en)
JP (2) JP4460892B2 (en)
AU (1) AU2002320122B2 (en)
CA (1) CA2448218C (en)
DK (1) DK1397155T3 (en)
ES (1) ES2554106T3 (en)
IL (1) IL159048A0 (en)
PT (1) PT1397155E (en)
WO (1) WO2003000282A1 (en)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7318931B2 (en) * 2001-06-21 2008-01-15 Genentech, Inc. Sustained release formulation
US20040001889A1 (en) 2002-06-25 2004-01-01 Guohua Chen Short duration depot formulations
US7160551B2 (en) * 2002-07-09 2007-01-09 The Board Of Trustees Of The University Of Illinois Injectable system for controlled drug delivery
US20040033228A1 (en) 2002-08-16 2004-02-19 Hans-Juergen Krause Formulation of human antibodies for treating TNF-alpha associated disorders
RU2005111253A (en) * 2002-09-18 2005-11-20 Сантр Оспиталье Де Л` Юниверсите Де Монреаль (Схюм) (Ca) GHRH ANALOGUES
MY150740A (en) * 2002-10-24 2014-02-28 Abbvie Biotechnology Ltd Low dose methods for treating disorders in which tnf? activity is detrimental
CA2507522C (en) 2002-12-13 2015-02-24 Durect Corporation Oral drug delivery system
US7731947B2 (en) 2003-11-17 2010-06-08 Intarcia Therapeutics, Inc. Composition and dosage form comprising an interferon particle formulation and suspending vehicle
DE10312346A1 (en) * 2003-03-20 2004-09-30 Bayer Healthcare Ag Controlled release system
KR20060002922A (en) * 2003-03-31 2006-01-09 알자 코포레이션 Non-aqueous single phase vehicles and formulations utilizing such vehicles
ES2300758T3 (en) * 2003-05-01 2008-06-16 Ltt Bio-Pharma Co., Ltd. COMPOSITION OF SUSTAINED RELEASE CONTAINING CINC, ITS PREPARATION AND PROCEDURE TO PRODUCE THE SAME.
EP1708734A4 (en) * 2004-01-07 2009-06-17 Trimeris Inc HIV gp41 HR2-DERIVED SYNTHETIC PEPTIDES, AND THEIR USE IN THERAPY TO INHIBIT TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS
US20050266087A1 (en) * 2004-05-25 2005-12-01 Gunjan Junnarkar Formulations having increased stability during transition from hydrophobic vehicle to hydrophilic medium
LT2767292T (en) * 2004-09-17 2016-12-12 Durect Corporation Sustained Local Anesthetic Composition Containing SAIB
WO2006083761A2 (en) 2005-02-03 2006-08-10 Alza Corporation Solvent/polymer solutions as suspension vehicles
US11246913B2 (en) 2005-02-03 2022-02-15 Intarcia Therapeutics, Inc. Suspension formulation comprising an insulinotropic peptide
US20070027105A1 (en) 2005-07-26 2007-02-01 Alza Corporation Peroxide removal from drug delivery vehicle
EP1912676A2 (en) * 2005-07-28 2008-04-23 (Osi) Eyetech, Inc. Cyclitol linker polymer conjugate
US7456251B2 (en) 2006-02-02 2008-11-25 Trimeris, Inc. HIV fusion inhibitor peptides with improved biological properties
CN101453982B (en) 2006-05-30 2011-05-04 精达制药公司 Two-piece, internal-channel osmotic delivery system flow modulator
ES2422864T3 (en) 2006-08-09 2013-09-16 Intarcia Therapeutics, Inc Osmotic release systems and piston units
US8337883B2 (en) 2006-11-03 2012-12-25 Durect Corporation Transdermal delivery systems
AU2007234612B2 (en) 2006-12-14 2013-06-27 Johnson & Johnson Regenerative Therapeutics, Llc Protein stabilization formulations
KR20100016142A (en) * 2007-04-03 2010-02-12 트라이머리스, 인코퍼레이티드 Novel formulations for delivery of antiviral peptide therapeutics
RU2440097C2 (en) 2007-04-23 2012-01-20 Интарсия Терапьютикс, Инк. Method of treating insulin-independent diabetes and obesity, osmotic delivery system and method for making it
US7678764B2 (en) 2007-06-29 2010-03-16 Johnson & Johnson Regenerative Therapeutics, Llc Protein formulations for use at elevated temperatures
CA2695697A1 (en) 2007-08-07 2009-02-12 Advanced Technologies And Regenerative Medicine, Llc Protein formulations comprising gdf-5 in aqueous acidic solution
MX2010003179A (en) * 2007-09-25 2010-04-30 Trimeris Inc Methods of synthesis for therapeuthic anti-hiv peptides.
US8883146B2 (en) 2007-11-30 2014-11-11 Abbvie Inc. Protein formulations and methods of making same
CA2706658A1 (en) 2007-12-06 2009-06-18 Durect Corporation Methods useful for the treatment of pain, arthritic conditions or inflammation associated with a chronic condition
CA2714506C (en) * 2008-02-08 2016-06-07 Qps Llc Composition for sustained release delivery of proteins or peptides
EP2240155B1 (en) 2008-02-13 2012-06-06 Intarcia Therapeutics, Inc Devices, formulations, and methods for delivery of multiple beneficial agents
AU2009236459B2 (en) 2008-04-14 2013-07-25 Advanced Technologies And Regenerative Medicine, Llc Liquid buffered GDF-5 formulations
US20100260844A1 (en) 2008-11-03 2010-10-14 Scicinski Jan J Oral pharmaceutical dosage forms
NZ592644A (en) * 2008-11-28 2013-09-27 Abbott Lab Stable antibody compositions and methods for stabilizing same
SG175188A1 (en) * 2009-05-04 2011-11-28 Abbott Biotech Ltd Stable high protein concentration formulations of human anti-tnf-alpha-antibodies
EP3323423B1 (en) 2009-09-28 2020-06-17 Intarcia Therapeutics, Inc Rapid establishment and/or termination of substantial steady-state drug delivery
US20110229457A1 (en) * 2010-03-12 2011-09-22 Surmodics, Inc. Injectable drug delivery system
MX2013001858A (en) 2010-08-18 2013-09-13 Del Mar Pharmaceuticals Compositions and methods to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted hexitols such as dianhydrogalactitol and diacetyldianhydrogalactitol.
RU2015154965A (en) 2010-11-11 2019-01-16 Эббви Байотекнолоджи Лтд. IMPROVED HIGH-CONCENTRATED LIQUID PRODUCTS ANTIBODIES AGAINST TNF ALPHA
US20120208755A1 (en) 2011-02-16 2012-08-16 Intarcia Therapeutics, Inc. Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers
EP2758043A4 (en) 2011-08-17 2016-02-24 Dennis M Brown Compositions and methods to improve the therapeutic benefit of suboptimally administered chemical compounds including substituted hexitols such as dibromodulcitol
KR102276161B1 (en) 2011-10-25 2021-07-14 프로테나 바이오사이언시즈 리미티드 Antibody formulations and methods
EP2804602A4 (en) 2012-01-20 2016-08-10 Dennis Brown Use of substituted hexitols including dianhydrogalactitol and analogs to treat neoplastic disease and cancer stem cells including glioblastoma multforme and medulloblastoma
WO2013142817A2 (en) 2012-03-23 2013-09-26 Dennis Brown Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo
WO2013169600A1 (en) 2012-05-09 2013-11-14 Delmar Pharmaceuticals Veterinary use of dianhydrogalactitol, diacetyldianhydrogalactitol, and dibromodulcitol to treat malignancies
AU2013280644B2 (en) 2012-06-26 2018-08-02 Jeffrey A. BACHA Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or AHI1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof
CN105120659A (en) 2013-03-15 2015-12-02 度瑞公司 Compositions with a rheological modifier to reduce dissolution variability
AU2014251038A1 (en) 2013-04-08 2015-11-26 Dennis M. Brown Therapeutic benefit of suboptimally administered chemical compounds
CA2928568A1 (en) 2013-07-26 2015-01-29 Update Pharma Inc. Combinatorial methods to improve the therapeutic benefit of bisantrene
WO2015058868A1 (en) 2013-10-25 2015-04-30 Pangaea Biotech, S.L. Compositions and methods for the treatment of cancer
US20160303242A1 (en) 2013-12-09 2016-10-20 Durect Corporation Pharmaceutically Active Agent Complexes, Polymer Complexes, and Compositions and Methods Involving the Same
WO2016020901A1 (en) 2014-08-07 2016-02-11 Acerta Pharma B.V. Methods of treating cancers, immune and autoimmune diseases, and inflammatory diseases based on btk occupancy and btk resynthesis rate
US9889085B1 (en) 2014-09-30 2018-02-13 Intarcia Therapeutics, Inc. Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c
EP3302354B1 (en) 2015-06-03 2023-10-04 i2o Therapeutics, Inc. Implant placement systems
WO2017200943A1 (en) 2016-05-16 2017-11-23 Intarcia Therapeutics, Inc. Glucagon-receptor selective polypeptides and methods of use thereof
USD840030S1 (en) 2016-06-02 2019-02-05 Intarcia Therapeutics, Inc. Implant placement guide
USD860451S1 (en) 2016-06-02 2019-09-17 Intarcia Therapeutics, Inc. Implant removal tool
KR20190104039A (en) 2017-01-03 2019-09-05 인타르시아 세라퓨틱스 인코포레이티드 Methods Including Continuous Administration of GLP-1 Receptor Agonists and Co-administration of Drugs
CA3167217A1 (en) 2020-01-13 2021-07-22 Durect Corporation Sustained release drug delivery systems with reduced impurities and related methods

Family Cites Families (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1456433A (en) * 1973-06-25 1976-11-24 Quaker Oats Co Semi-moist cat food
US4016273A (en) 1975-07-16 1977-04-05 American Cyanamid Company Sustained release forms of certain oxazepines for parenteral administration
DE2916711A1 (en) 1979-04-25 1980-11-06 Behringwerke Ag Blood coagulation factors and process for their manufacture
US5411951A (en) 1984-10-04 1995-05-02 Monsanto Company Prolonged release of biologically active somatotropin
IL79681A (en) * 1985-08-12 1991-06-10 Int Minerals & Chem Corp Transition metal complexes of growth hormones and their prolonged release compositions
JPS62257990A (en) 1986-05-02 1987-11-10 花王株式会社 Production of enzyme granule for detergent
WO1989003671A1 (en) 1987-10-29 1989-05-05 Dainippon Pharmaceutical Co., Ltd. Sustained-release preparation
US5096885A (en) 1988-04-15 1992-03-17 Genentech, Inc. Human growth hormone formulation
JPH0223866A (en) 1988-07-11 1990-01-26 Kikkoman Corp Stabilization of sucrose phosphorylase
FR2634121B1 (en) 1988-07-13 1992-05-07 Imedex PROCESS FOR THE PREPARATION OF COLLAGEN MICROPARTICLES AND PRODUCTS OBTAINED
US4938763B1 (en) 1988-10-03 1995-07-04 Atrix Lab Inc Biodegradable in-situ forming implants and method of producing the same
US5324520A (en) 1988-12-19 1994-06-28 Vipont Pharmaceutical, Inc. Intragingival delivery systems for treatment of periodontal disease
US4975271A (en) 1988-12-19 1990-12-04 Vipont Pharmaceutical, Inc. Muscosal delivery systems for treatment of periodontal disease
US5114929A (en) 1989-03-21 1992-05-19 Beecham Group P.L.C. Pharmaceutical formulation
US5776963A (en) 1989-05-19 1998-07-07 Hoechst Marion Roussel, Inc. 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility
US5487897A (en) 1989-07-24 1996-01-30 Atrix Laboratories, Inc. Biodegradable implant precursor
US5324519A (en) 1989-07-24 1994-06-28 Atrix Laboratories, Inc. Biodegradable polymer composition
US5077049A (en) 1989-07-24 1991-12-31 Vipont Pharmaceutical, Inc. Biodegradable system for regenerating the periodontium
SE465950B (en) 1989-10-23 1991-11-25 Medinvent Sa Combination of an aggregate particle size, crystalline or freeze-dried drug with a pseudoplastic gel for preparation of an injectable preparation as well as a process for its preparation
US5133981A (en) 1989-11-17 1992-07-28 Atrix Laboratories, Inc. Purification of benzophenanthridine alkaloids extracts from alkaloid extracts
PT99345A (en) 1990-10-30 1992-09-30 Alza Corp PROCESS FOR THE PREPARATION OF APPROPRIATE SYSTEMS FOR THE LIBERATION OF THERAPEUTIC AGENTS
JPH04271785A (en) 1991-02-28 1992-09-28 Kao Corp Enzymic solid pharmaceutical and its production
US5416071A (en) 1991-03-12 1995-05-16 Takeda Chemical Industries, Ltd. Water-soluble composition for sustained-release containing epo and hyaluronic acid
AU1757092A (en) 1991-03-28 1992-11-02 Genentech Inc. Stable growth hormone metal ion formulations
US5252338A (en) 1991-06-27 1993-10-12 Alza Corporation Therapy delayed
AU2605592A (en) 1991-10-15 1993-04-22 Atrix Laboratories, Inc. Polymeric compositions useful as controlled release implants
US5912015A (en) 1992-03-12 1999-06-15 Alkermes Controlled Therapeutics, Inc. Modulated release from biocompatible polymers
US5711968A (en) 1994-07-25 1998-01-27 Alkermes Controlled Therapeutics, Inc. Composition and method for the controlled release of metal cation-stabilized interferon
US5716644A (en) 1992-06-11 1998-02-10 Alkermes, Inc. Composition for sustained release of non-aggregated erythropoietin
US5242910A (en) 1992-10-13 1993-09-07 The Procter & Gamble Company Sustained release compositions for treating periodontal disease
EP0674506B1 (en) 1992-12-02 2000-08-23 Alkermes Controlled Therapeutics, Inc. Controlled release growth hormone containing microspheres
PT686045E (en) * 1993-02-23 2001-04-30 Genentech Inc STABILIZATION BY EXPIPIENTS OF POLYPEPTIDES TREATED WITH ORGANIC SOLVENTS
US6087324A (en) 1993-06-24 2000-07-11 Takeda Chemical Industries, Ltd. Sustained-release preparation
NZ260909A (en) 1993-07-05 1995-04-27 Takeda Chemical Industries Ltd Production of sustained release preparation by allowing a water-soluble polypeptide to permeate into a biodegradable matrix in an aqueous solution
US6080429A (en) 1993-10-25 2000-06-27 Genentech, Inc. Method for drying microspheres
JP3125610B2 (en) 1993-12-24 2001-01-22 和光純薬工業株式会社 Method for stabilizing L-methionine γ-lyase
ATE178789T1 (en) 1994-02-21 1999-04-15 Takeda Chemical Industries Ltd POLYESTER MATRIX FOR A DELAYED RELEASE PHARMACEUTICAL COMPOSITION
US5556905A (en) 1994-03-30 1996-09-17 Reilly Industries, Inc. Physically-modified degradable thermoplastic compositions
JP4259610B2 (en) 1994-04-08 2009-04-30 キューエルティー・ユーエスエイ・インコーポレーテッド Liquid delivery composition
US5626862A (en) 1994-08-02 1997-05-06 Massachusetts Institute Of Technology Controlled local delivery of chemotherapeutic agents for treating solid tumors
US6004549A (en) 1994-12-14 1999-12-21 Schering Corporation Crystalline protein controlled release compositions
JP2001515457A (en) 1995-06-07 2001-09-18 アルカームズ コントロールド セラピューティックス，インコーポレイテッド Aggregation-stabilized bioactive substance release device
US5904935A (en) 1995-06-07 1999-05-18 Alza Corporation Peptide/protein suspending formulations
SK281571B6 (en) 1995-06-07 2001-05-10 Alkermes Controlled Therapeutics, Inc. Composition for sustained release of human growth hormone
US5968542A (en) 1995-06-07 1999-10-19 Southern Biosystems, Inc. High viscosity liquid controlled delivery system as a device
US5747058A (en) * 1995-06-07 1998-05-05 Southern Biosystems, Inc. High viscosity liquid controlled delivery system
US6413536B1 (en) 1995-06-07 2002-07-02 Southern Biosystems, Inc. High viscosity liquid controlled delivery system and medical or surgical device
BRPI9609033B8 (en) 1995-06-07 2017-04-04 Durect Corp composition and emulsion for the controlled release of a substance.
US6267958B1 (en) * 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
US5736152A (en) 1995-10-27 1998-04-07 Atrix Laboratories, Inc. Non-polymeric sustained release delivery system
CA2192773C (en) 1995-12-15 2008-09-23 Hiroaki Okada Production of sustained-release preparation for injection
US5792477A (en) 1996-05-07 1998-08-11 Alkermes Controlled Therapeutics, Inc. Ii Preparation of extended shelf-life biodegradable, biocompatible microparticles containing a biologically active agent
US5932547A (en) 1996-07-03 1999-08-03 Alza Corporation Non-aqueous polar aprotic peptide formulations
US5981489A (en) 1996-07-18 1999-11-09 Alza Corporation Non-aqueous protic peptide formulations
US5851229A (en) 1996-09-13 1998-12-22 Meadox Medicals, Inc. Bioresorbable sealants for porous vascular grafts
ATE272394T1 (en) 1996-10-31 2004-08-15 Takeda Chemical Industries Ltd DELAYED RELEASE PREPARATION
ES2158611T3 (en) 1996-12-20 2001-09-01 Alza Corp COMPOSITION IN INJECTABLE GEL WITH RETARD EFFECT AND PROCEDURE FOR THE PREPARATION OF SUCH COMPOSITION.
ZA9711385B (en) 1996-12-20 1999-06-18 Takeda Chemical Industries Ltd Method of producing a sustained-release preparation
US6051558A (en) 1997-05-28 2000-04-18 Southern Biosystems, Inc. Compositions suitable for controlled release of the hormone GnRH and its analogs
US6113947A (en) 1997-06-13 2000-09-05 Genentech, Inc. Controlled release microencapsulated NGF formulation
US6191107B1 (en) 1997-09-26 2001-02-20 Takeda Chemical Industries, Ltd. Complex of human growth hormone and zinc
JPH11158200A (en) 1997-09-26 1999-06-15 Takeda Chem Ind Ltd Human growth hormone/zinc complex and its use
US6039977A (en) 1997-12-09 2000-03-21 Alza Corporation Pharmaceutical hydrogel formulations, and associated drug delivery devices and methods
CN1173742C (en) 1997-12-26 2004-11-03 山之内制药株式会社 Sustained release medicinal compositions
DE19813010A1 (en) 1998-03-25 1999-10-14 Aventis Res & Tech Gmbh & Co Delayed release microcapsules
US6174547B1 (en) 1999-07-14 2001-01-16 Alza Corporation Dosage form comprising liquid formulation
US6143314A (en) 1998-10-28 2000-11-07 Atrix Laboratories, Inc. Controlled release liquid delivery compositions with low initial drug burst
CN1158068C (en) * 1998-12-23 2004-07-21 安姆根有限公司 Polyol/oil suspensions for the sustained release of proteins
ES2207123T3 (en) 1999-06-14 2004-05-16 Baxter International Inc. MICROSPHERAS OF SUSTAINED LIBERATION.
WO2000078335A1 (en) * 1999-06-18 2000-12-28 Southern Biosystems, Inc. COMPOSITIONS FOR CONTROLLED RELEASE OF THE HORMONE GnRH AND ITS ANALOGS
US6245806B1 (en) * 1999-08-03 2001-06-12 Merck & Co., Inc. HIV integrase inhibitors
US6458387B1 (en) 1999-10-18 2002-10-01 Epic Therapeutics, Inc. Sustained release microspheres
EP1274459B1 (en) 2000-04-19 2005-11-16 Genentech, Inc. Sustained release formulations comprising growth hormone
AU2001271491A1 (en) 2000-06-26 2002-01-08 Monsanto Technology Llc Non-aqueous surfactant-containing formulations for extended release of somatotropin
US7318931B2 (en) 2001-06-21 2008-01-15 Genentech, Inc. Sustained release formulation
GB2403086B (en) 2003-06-17 2005-07-20 Motorola Inc Cartesian loop transmitter and method of adjusting an output level of such transmitter
CN105709221B (en) * 2011-04-06 2020-11-17 拜欧瓦克西姆有限公司 Pharmaceutical composition for the prevention and/or treatment of HIV diseases in humans

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