CA2295140A1 - Stable insulin formulations - Google Patents

Stable insulin formulations Download PDF

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Publication number
CA2295140A1
CA2295140A1 CA002295140A CA2295140A CA2295140A1 CA 2295140 A1 CA2295140 A1 CA 2295140A1 CA 002295140 A CA002295140 A CA 002295140A CA 2295140 A CA2295140 A CA 2295140A CA 2295140 A1 CA2295140 A1 CA 2295140A1
Authority
CA
Canada
Prior art keywords
formulation
insulin analog
monomeric insulin
tris
buffer
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
CA002295140A
Other languages
French (fr)
Other versions
CA2295140C (en
Inventor
Michael Rosario Defelippis
Michael Allen Dobbins
Bruce Hill Frank
Shun Li
Dawn Marie Rebhun
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Eli Lilly and Co
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Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2295140A1 publication Critical patent/CA2295140A1/en
Application granted granted Critical
Publication of CA2295140C publication Critical patent/CA2295140C/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
    • 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
    • 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
    • A61K38/28—Insulins
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • 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

Abstract

The present invention provides a monomeric insulin analog formulation stabilized against aggregation in which the buffering agent is either TRIS or arginine. The stable formulations of the present invention are useful for treating diabetes, and are particularly advantageous in treatment regimes requiring lengthy chemical and physical stability, such as, in continuous infusion systems.

Claims (28)

1. A solution formulation comprising:
a physiologically tolerated buffer selected from the group consisting of TRIS and arginine; a monomeric insulin analog;
zinc; and a phenolic preservative.
2. The formulation of Claim 1, wherein the monomeric insulin analog is LysB28ProB29-human insulin and the buffer is TRIS.
3. The formulation of Claim 1, wherein the monomeric insulin analog is AspB28-human insulin and the buffer is TRIS.
4. The formulation of Claim 2 further comprising an isotonicity agent and wherein the pH of the formulation is between pH 7.0 and pH 8.0 when measured at a temperature of 22°C.
5. The formulation of Claim 4, wherein the concentration of LysB28ProB29_human insulin is between about 100 and about 400 units per milliliter.
6. The formulation of Claim 5, wherein TRIS is present at a concentration of about 2 mg/mL; glycerol is the isotonicity agent and is present at a concentration of about 16 mg/mL; and m-cresol is present at a concentration of about 1.76 mg/mL and phenol is present at a concentration of about 0.715 mg/mL.
7. A stable, soluble formulation of a monomeric insulin analog for use in a continuous infusion system, consisting essentially of: an isotonicity agent; a buffer selected from the group consisting of TRIS and arginine; a monomeric insulin analog; zinc; and a phenolic preservative.
8. The insulin analog formulation of Claim 1 which further comprises protamine.
9. The formulation of Claim 8, wherein the insulin analog is LysB28ProB29,
10. The formulation of Claim 8, wherein the insulin analog is AspB28.
11. The formulation of any one of Claims 8 through 10 wherein the buffer is arginine.
12. The formulation of any one of Claims 1 through 7 for use in a continuous infusion system.
13. A method for treating diabetes comprising administering an effective dose of the formulation of any one of Claims 1 through 11 to a patient in need thereof.
14. A method for treating diabetes comprising administering an effective dose of the formulation of any, one of Claims 1 through 7, wherein the formulation is administered using a continuous infusion system.
15. A method for treating hyperglycemia comprising administering an effective dose of the formulation of any one of Claims 1 through 11 to a patient in need thereof.
16. A method for treating hyperglycemia comprising administering an effective dose of the formulation of any one of Claims 1 through 7, wherein the formulation is administered using a continuous infusion system.
17. The formulation of monomeric insulin analog as described in any one of Claims 1 through 11 for use as a medicament for the treatment of diabetes.
18. The formulation of monomeric insulin analog as described in any one of Claims 1 through 11 for use as a medicament for the treatment of hyperglycemia.
19. A formulation of monomeric insulin analog as hereinbefore described with reference to any one of the examples.
20. A process for preparing the monomeric insulin analog formulation of Claim 1 comprising the steps of mixing a physiologically-tolerated buffer selected from the group consisting of TRIS and arginine with a monomeric insulin analog; zinc; and a phenolic preservative.
21. The process of Claim 20, wherein the monomeric insulin analog is LysB28ProB29-human insulin and the buffer is TRIS.
22. The process of Claim 20, wherein the monomeric insulin analog is AspB28-human insulin and the buffer is TRIS.
23. A process for preparing a monomeric insulin analog formulation comprising the steps of mixing a buffer selected from the group consisting of TRIS and arginine with a monomeric insulin analog; zinc; protamine; and a phenolic preservative.
24. The process of Claim 23, wherein the monomeric insulin analog is LysB28ProB29.
25. The process of Claim 23, wherein the monomeric insulin analog is AspB28.
26. The process of any one of Claims 23 through 25, wherein the buffer is arginine.
27. The formulation of any one of Claims 1 through 7 when made by the process of Claim 20.
28. The formulation of any one of Claims 8 through 11 when made by the process of Claim 23.
CA2295140A 1997-06-13 1998-06-11 Stable insulin formulations Expired - Lifetime CA2295140C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US5308997P 1997-06-13 1997-06-13
US60/053,089 1997-06-13
PCT/US1998/012218 WO1998056406A1 (en) 1997-06-13 1998-06-11 Stable insulin formulations

Publications (2)

Publication Number Publication Date
CA2295140A1 true CA2295140A1 (en) 1998-12-17
CA2295140C CA2295140C (en) 2010-09-14

Family

ID=21981869

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2295140A Expired - Lifetime CA2295140C (en) 1997-06-13 1998-06-11 Stable insulin formulations

Country Status (31)

Country Link
US (3) US6034054A (en)
EP (1) EP0884053B1 (en)
JP (1) JP2002504908A (en)
KR (1) KR100597500B1 (en)
CN (1) CN1293916C (en)
AR (1) AR012894A1 (en)
AT (2) ATE226088T1 (en)
AU (1) AU734781B2 (en)
BR (1) BR9810116B1 (en)
CA (1) CA2295140C (en)
CO (1) CO4750643A1 (en)
CZ (1) CZ299637B6 (en)
DE (2) DE69808695T2 (en)
DK (1) DK0884053T3 (en)
EA (1) EA002880B1 (en)
ES (2) ES2185113T3 (en)
HK (1) HK1030747A1 (en)
HU (1) HUP0002877A3 (en)
ID (1) ID24310A (en)
IL (1) IL133348A0 (en)
NO (1) NO996131L (en)
NZ (1) NZ501382A (en)
PE (1) PE79099A1 (en)
PL (1) PL194244B1 (en)
PT (2) PT1283051E (en)
SV (1) SV1998000065A (en)
TR (1) TR199903036T2 (en)
TW (1) TW577753B (en)
UA (1) UA61109C2 (en)
WO (1) WO1998056406A1 (en)
ZA (1) ZA984697B (en)

Families Citing this family (157)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PE79099A1 (en) * 1997-06-13 1999-08-24 Lilly Co Eli STABLE INSULIN FORMULATIONS
US6211144B1 (en) * 1998-10-16 2001-04-03 Novo Nordisk A/S Stable concentrated insulin preparations for pulmonary delivery
IL143834A0 (en) 1999-01-06 2002-04-21 Genentech Inc Insulin-like growth factor (igf) i mutant variants
IL143866A0 (en) 1999-01-06 2002-04-21 Genentech Inc Insulin-like growth factor (igf) i mutant variants
CA2369451C (en) * 1999-04-08 2009-09-22 Genentech, Inc. Composition based on oppositely-charged polypeptides
US20040220103A1 (en) * 1999-04-19 2004-11-04 Immunex Corporation Soluble tumor necrosis factor receptor treatment of medical disorders
US6746853B1 (en) 1999-05-19 2004-06-08 Xencor, Inc. Proteins with insulin-like activity useful in the treatment of diabetes
US7169889B1 (en) * 1999-06-19 2007-01-30 Biocon Limited Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin
US7022674B2 (en) * 1999-12-16 2006-04-04 Eli Lilly And Company Polypeptide compositions with improved stability
WO2001052937A1 (en) * 2000-01-24 2001-07-26 Medtronic Minimed, Inc. Mixed buffer system for stabilizing polypeptide formulations
WO2001085256A2 (en) * 2000-05-05 2001-11-15 Novo Nordisk A/S Critical illness neuropathy
AU2001263215A1 (en) 2000-05-16 2001-11-26 Genentech Inc. Method for treating cartilage disorders
US7060675B2 (en) * 2001-02-15 2006-06-13 Nobex Corporation Methods of treating diabetes mellitus
US6867183B2 (en) * 2001-02-15 2005-03-15 Nobex Corporation Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
US6852694B2 (en) 2001-02-21 2005-02-08 Medtronic Minimed, Inc. Stabilized insulin formulations
DE10114178A1 (en) 2001-03-23 2002-10-10 Aventis Pharma Gmbh Zinc-free and low-zinc insulin preparations with improved stability
US6828305B2 (en) * 2001-06-04 2004-12-07 Nobex Corporation Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6835802B2 (en) 2001-06-04 2004-12-28 Nobex Corporation Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties
US6713452B2 (en) 2001-06-04 2004-03-30 Nobex Corporation Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US6828297B2 (en) 2001-06-04 2004-12-07 Nobex Corporation Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
US7713932B2 (en) 2001-06-04 2010-05-11 Biocon Limited Calcitonin drug-oligomer conjugates, and uses thereof
ATE382057T1 (en) 2001-06-28 2008-01-15 Novo Nordisk As STABLE FORMULATION OF MODIFIED GLP-1
US6737401B2 (en) * 2001-06-28 2004-05-18 Metronic Minimed, Inc. Methods of evaluating protein formulation stability and surfactant-stabilized insulin formulations derived therefrom
US7196059B2 (en) * 2001-09-07 2007-03-27 Biocon Limited Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
US6913903B2 (en) * 2001-09-07 2005-07-05 Nobex Corporation Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US7312192B2 (en) * 2001-09-07 2007-12-25 Biocon Limited Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US7166571B2 (en) * 2001-09-07 2007-01-23 Biocon Limited Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same
US6770625B2 (en) 2001-09-07 2004-08-03 Nobex Corporation Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith
US7030082B2 (en) * 2001-09-07 2006-04-18 Nobex Corporation Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith
US20030068361A1 (en) * 2001-10-09 2003-04-10 Rimona Margalit Liposome-encapsulated insulin formulations
US20030199445A1 (en) * 2002-02-07 2003-10-23 Knudsen Lotte Bjerre Use of GLP-1 compound for treatment of critically ill patients
WO2003094956A1 (en) * 2002-05-07 2003-11-20 Novo Nordisk A/S Soluble formulations comprising monomeric insulin and acylated insulin
DE10227232A1 (en) 2002-06-18 2004-01-15 Aventis Pharma Deutschland Gmbh Sour insulin preparations with improved stability
ITMI20021684A1 (en) * 2002-07-29 2004-01-29 Therapicon Srl PHARMACEUTICAL COMPOSITION OF NASAL PEPTIDE
KR101123113B1 (en) * 2002-07-29 2012-03-15 쎄라피콘 에스.알.엘. Nasal peptide pharmaceutical formulation
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
PL1633391T3 (en) 2003-06-03 2012-03-30 Novo Nordisk As Stabilized pharmaceutical peptide compositions
SI1687019T1 (en) 2003-11-20 2018-04-30 Novo Nordisk A/S Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
US7501426B2 (en) 2004-02-18 2009-03-10 Boehringer Ingelheim International Gmbh 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
EP1773878B1 (en) 2004-07-19 2015-03-04 Biocon Limited Insulin-oligomer conjugates, formulations and uses thereof
KR20070085227A (en) * 2004-08-09 2007-08-27 앨리오스 바이오파마 인크. Synthetic hyperglycosylated, protease-resistant polypeptide variants, oral formulations and methods of using the same
US7597884B2 (en) * 2004-08-09 2009-10-06 Alios Biopharma, Inc. Hyperglycosylated polypeptide variants and methods of use
DE102004054054A1 (en) 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for preparing chiral 8- (3-amino-piperidin-1-yl) -xanthines
BRPI0517341A (en) 2004-11-12 2008-10-07 Novo Nordisk As shelf stable pharmaceutical composition, methods for the preparation of a pharmaceutical composition, for the treatment of hyperglycemia, for the treatment of obesity, beta cell deficiency, igt or dyslipidemia, for the preparation of a stable solution of a glp-1 compound, for the preparation of a stable glp-1 compound and for the preparation of a shelf stable pharmaceutical composition of a glp-1 compound, stable solution of a glp-1 compound, and use of a stable solution of a glp-1 compound
CN101060856B (en) * 2004-11-22 2011-01-19 诺和诺德公司 Soluble, stable insulin-containing formulations with a protamine salt
EP1830888B1 (en) 2004-12-27 2015-08-05 Silence Therapeutics GmbH Lipid complexes coated with peg and their use
EP1862174A1 (en) * 2005-03-02 2007-12-05 Ajinomoto Co., Inc. Inhibitor for insulin polymer formation
WO2006125763A1 (en) * 2005-05-25 2006-11-30 Novo Nordisk A/S Stabilized polypeptide formulations
WO2006125762A1 (en) * 2005-05-25 2006-11-30 Novo Nordisk A/S Stabilized polypeptide formulations
DE102005035891A1 (en) 2005-07-30 2007-02-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg 8- (3-amino-piperidin-1-yl) -xanthines, their preparation and their use as pharmaceuticals
WO2007047948A2 (en) * 2005-10-20 2007-04-26 Nastech Pharmaceutical Company Inc. Intranasal administration of rapid acting insulin
WO2007074133A2 (en) 2005-12-28 2007-07-05 Novo Nordisk A/S Compositions comprising an acylated insulin and zinc and method of making the said compositions
US8927015B2 (en) * 2006-04-12 2015-01-06 Emisphere Technologies, Inc. Formulations for delivering insulin
US20090074852A1 (en) * 2006-04-20 2009-03-19 Silence Therapeutics Ag Lipoplex formulations for specific delivery to vascular endothelium
CN101437823B (en) 2006-05-04 2014-12-10 勃林格殷格翰国际有限公司 Polymorphs
PE20110235A1 (en) 2006-05-04 2011-04-14 Boehringer Ingelheim Int PHARMACEUTICAL COMBINATIONS INCLUDING LINAGLIPTIN AND METMORPHINE
EP1852108A1 (en) 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
WO2007135117A2 (en) * 2006-05-24 2007-11-29 Novo Nordisk A/S Soluble, stable insulin-containing formulations
US9023793B2 (en) * 2006-09-29 2015-05-05 Retrophin, Inc. Intranasal carbetocin formulations and methods for the treatment of autism
GB0700523D0 (en) * 2007-01-11 2007-02-21 Insense Ltd The Stabilisation Of Proteins
US8114428B2 (en) * 2007-03-08 2012-02-14 Sbf Synthetic Bone Factory Gmbh Methods for manufacturing a composition for treating bone and/or cartilage defects
WO2008118387A2 (en) * 2007-03-23 2008-10-02 Wayne State University Erythrocyte atp-release modulators
US20080260820A1 (en) * 2007-04-19 2008-10-23 Gilles Borrelly Oral dosage formulations of protease-resistant polypeptides
WO2009050738A2 (en) * 2007-10-16 2009-04-23 Biocon Limited An orally administerable solid pharmaceutical composition and a process thereof
US8986253B2 (en) 2008-01-25 2015-03-24 Tandem Diabetes Care, Inc. Two chamber pumps and related methods
US8691759B2 (en) 2008-03-18 2014-04-08 Novo Nordisk A/S Protease stabilized, acylated insulin analogues
PE20091730A1 (en) 2008-04-03 2009-12-10 Boehringer Ingelheim Int FORMULATIONS INVOLVING A DPP4 INHIBITOR
TWI394580B (en) * 2008-04-28 2013-05-01 Halozyme Inc Super fast-acting insulin compositions
CA2726824A1 (en) 2008-05-01 2009-11-05 Arecor Limited Protein formulation
TWI451876B (en) * 2008-06-13 2014-09-11 Lilly Co Eli Pegylated insulin lispro compounds
EP2328607A1 (en) 2008-07-16 2011-06-08 Arecor Limited Stable formulation of a therapeutic protein
UY32030A (en) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "TREATMENT FOR DIABETES IN INAPPROPRIATE PATIENTS FOR THERAPY WITH METFORMIN"
BRPI0916997A2 (en) 2008-08-06 2020-12-15 Boehringer Ingelheim International Gmbh DPP-4 INHIBITOR AND ITS USE
ES2477552T3 (en) 2008-09-08 2014-07-17 The Board Of Trustees Of The Leland Stanford Junior University Modulators of aldehyde dehydrogenase activity and methods of use thereof
KR20110067096A (en) 2008-09-10 2011-06-21 베링거 인겔하임 인터내셔날 게엠베하 Combination therapy for the treatment of diabetes and related conditions
US8408421B2 (en) 2008-09-16 2013-04-02 Tandem Diabetes Care, Inc. Flow regulating stopcocks and related methods
EP2334234A4 (en) 2008-09-19 2013-03-20 Tandem Diabetes Care Inc Solute concentration measurement device and related methods
US20200155558A1 (en) 2018-11-20 2020-05-21 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
BR122013025625B1 (en) 2008-10-17 2021-08-03 Sanofi-Aventis Deutschland Gmbh PHARMACEUTICAL COMPOSITION, ITS USE AND METHOD OF PREPARATION OF THE SAME, KIT AND DEVICE
WO2010062308A1 (en) 2008-10-28 2010-06-03 The Board Of Trustees Of The Leland Stanford Junior University Modulators of aldehyde dehydrogenase and methods of use thereof
RU2540922C2 (en) 2008-10-30 2015-02-10 Ново Нордиск А/С Treating diabetes mellitus by insulin injections as little as once day
KR20110103968A (en) 2008-12-23 2011-09-21 베링거 인겔하임 인터내셔날 게엠베하 Salt forms of organic compound
AR074990A1 (en) 2009-01-07 2011-03-02 Boehringer Ingelheim Int TREATMENT OF DIABETES IN PATIENTS WITH AN INAPPROPRIATE GLUCEMIC CONTROL THROUGH METFORMIN THERAPY
EP2391646B1 (en) 2009-01-28 2016-08-10 Smartcells, Inc. Crystalline insulin-conjugates
CA2750223A1 (en) 2009-01-28 2010-08-05 Smartcells, Inc. Exogenously triggered controlled release materials and uses thereof
JP2012516340A (en) 2009-01-28 2012-07-19 スマートセルズ・インコーポレイテツド Synthetic conjugates and uses thereof
EA027757B1 (en) 2009-01-28 2017-08-31 Смартселлз, Инк. Conjugate for controlled insulin delivery
US20110293562A1 (en) 2009-02-12 2011-12-01 Proyecto De Biomedicina Cima, S.L. Use of cardiotrophin-1 for the treatment of metabolic diseases
US9250106B2 (en) 2009-02-27 2016-02-02 Tandem Diabetes Care, Inc. Methods and devices for determination of flow reservoir volume
US8573027B2 (en) 2009-02-27 2013-11-05 Tandem Diabetes Care, Inc. Methods and devices for determination of flow reservoir volume
US8569231B2 (en) 2009-03-20 2013-10-29 Smartcells, Inc. Soluble non-depot insulin conjugates and uses thereof
WO2010107519A1 (en) 2009-03-20 2010-09-23 Smartcells, Inc. Terminally-functionalized conjugates and uses thereof
CA2764423A1 (en) * 2009-06-26 2010-12-29 Novo Nordisk A/S Preparation comprising insulin, nicotinamide and an amino acid
CA2921304C (en) 2009-07-30 2018-06-05 Tandem Diabetes Care, Inc. Infusion pump system with disposable cartridge having pressure venting and pressure feedback
DK2498802T3 (en) 2009-11-13 2015-04-13 Sanofi Aventis Deutschland Pharmaceutical composition comprising a GLP-1 agonist, insulin and a methionine
MY159565A (en) 2009-11-13 2017-01-13 Sanofi Aventis Deutschland Pharmaceutical composition comprising a glp-1 agonist and methionine
EA034869B1 (en) 2009-11-27 2020-03-31 Бёрингер Ингельхайм Интернациональ Гмбх Treatment of genotyped diabetic patients with dpp-4 inhibitors such as linagliptin
CN101912600B (en) * 2010-01-11 2014-01-29 杨国汉 Method for improving stability of insulin in solution
BR112012028136A2 (en) 2010-05-05 2016-08-09 Boehringer Ingelheim Int combination therapy
AU2011202239C1 (en) 2010-05-19 2017-03-16 Sanofi Long-acting formulations of insulins
KR20130093012A (en) 2010-06-24 2013-08-21 베링거 인겔하임 인터내셔날 게엠베하 Diabetes therapy
CA2805739A1 (en) 2010-07-28 2012-02-02 Smartcells, Inc. Drug-ligand conjugates, synthesis thereof, and intermediates thereto
JP2013541500A (en) 2010-07-28 2013-11-14 スマートセルズ・インコーポレイテツド Recombinant lectins, binding site modified lectins and their uses
JP2013535467A (en) 2010-07-28 2013-09-12 スマートセルズ・インコーポレイテツド Recombinantly expressed insulin polypeptide and uses thereof
HUE031181T2 (en) 2010-08-30 2017-06-28 Sanofi Aventis Deutschland Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2
JP6049625B2 (en) 2010-10-27 2016-12-21 ノヴォ ノルディスク アー／エス Treatment of diabetes mellitus using insulin injections given at various injection intervals
US9034883B2 (en) 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
CN102188367B (en) * 2011-01-05 2012-11-07 山东新时代药业有限公司 Insulin glargine injecta and preparation method thereof
WO2012149106A1 (en) 2011-04-29 2012-11-01 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for increasing proliferation of adult salivary stem cells
US9821032B2 (en) 2011-05-13 2017-11-21 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
US9993529B2 (en) 2011-06-17 2018-06-12 Halozyme, Inc. Stable formulations of a hyaluronan-degrading enzyme
US20130345113A1 (en) * 2011-07-13 2013-12-26 Ronald E. Strohbehn Method of Use of Activated Functional Proteins to Improve Animal Health
EP2731947B1 (en) 2011-07-15 2019-01-16 Boehringer Ingelheim International GmbH Substituted dimeric quinazoline derivative, its preparation and its use in pharmaceutical compositions for the treatment of type i and ii diabetes
KR101983982B1 (en) 2011-08-29 2019-05-30 사노피-아벤티스 도이칠란트 게엠베하 Pharmaceutical combination for use in glycemic control in diabetes type 2 patients
AR087744A1 (en) 2011-09-01 2014-04-16 Sanofi Aventis Deutschland PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OF A NEURODEGENERATIVE DISEASE
EA027744B1 (en) * 2011-10-31 2017-08-31 Ксерис Фармасьютикалс, Инк. Formulations for the treatment of diabetes mellitus
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
JP6224084B2 (en) 2012-05-14 2017-11-01 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Xanthine derivatives as DPP-4 inhibitors for the treatment of glomerular epithelial cell related disorders and / or nephrotic syndrome
US9180242B2 (en) 2012-05-17 2015-11-10 Tandem Diabetes Care, Inc. Methods and devices for multiple fluid transfer
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
US9555186B2 (en) 2012-06-05 2017-01-31 Tandem Diabetes Care, Inc. Infusion pump system with disposable cartridge having pressure venting and pressure feedback
JP6735561B2 (en) 2012-12-03 2020-08-05 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． O-glycosylated carboxy-terminal portion (CTP) peptide-based insulin and insulin analogs
CA2889165A1 (en) * 2012-12-19 2014-06-26 Wockhardt Limited A stable aqueous composition comprising human insulin or an analogue or derivative thereof
CN104870469A (en) * 2012-12-26 2015-08-26 沃克哈特有限公司 Pharmaceutical composition
TWI780236B (en) * 2013-02-04 2022-10-11 法商賽諾菲公司 Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives
US10201656B2 (en) 2013-03-13 2019-02-12 Tandem Diabetes Care, Inc. Simplified insulin pump for type II diabetics
KR20150135332A (en) 2013-03-14 2015-12-02 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof
US9173998B2 (en) 2013-03-14 2015-11-03 Tandem Diabetes Care, Inc. System and method for detecting occlusions in an infusion pump
US9492608B2 (en) 2013-03-15 2016-11-15 Tandem Diabetes Care, Inc. Method and device utilizing insulin delivery protocols
EP3517122A1 (en) 2013-04-03 2019-07-31 Sanofi Treatment of diabetes mellitus by long-acting formulations of insulins
WO2014177623A1 (en) 2013-04-30 2014-11-06 Novo Nordisk A/S Novel administration regime
EP3016704A4 (en) * 2013-07-04 2017-03-08 Insuline Medical Ltd. Device, system and method for delivery of a long-acting drug
BR112016007176A2 (en) 2013-10-04 2018-01-23 Merck Sharp & Dohme conjugate, composition, uses of a conjugate and composition, and method for treating an individual having diabetes
TW201605489A (en) 2013-10-25 2016-02-16 賽諾菲公司 Stable formulation of INSULIN GLULISINE
CN105960249B (en) 2014-01-09 2021-03-16 赛诺菲 Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives
BR112016013832A2 (en) 2014-01-09 2017-08-08 Sanofi Sa USE OF INSULIN ANALOG AND/OR DERIVATIVE, PHARMACEUTICAL FORMULATION AND PROCESS FOR THE PREPARATION OF THE SAME, KIT AND MEDICAL DEVICE
WO2015104310A1 (en) * 2014-01-09 2015-07-16 Sanofi Stabilized pharmaceutical formulations of insulin aspart
WO2015106269A2 (en) * 2014-01-13 2015-07-16 Thermalin Diabetes, Llc Rapid action insulin formulations and pharmaceutical delivery systems
ES2950384T3 (en) 2014-02-28 2023-10-09 Boehringer Ingelheim Int Medical use of a DPP-4 inhibitor
CN107206058A (en) 2014-12-12 2017-09-26 赛诺菲-安万特德国有限公司 Insulin glargine/lixisenatide fixed ratio preparaton
TWI748945B (en) 2015-03-13 2021-12-11 德商賽諾菲阿凡提斯德意志有限公司 Treatment type 2 diabetes mellitus patients
TW201705975A (en) 2015-03-18 2017-02-16 賽諾菲阿凡提斯德意志有限公司 Treatment of type 2 diabetes mellitus patients
CN105535942B (en) * 2016-01-28 2017-07-28 通化东宝药业股份有限公司 A kind of preparation method of insulin lispro protamine sulfate preparation and its insulin lispro protamine sulfate preparation of preparation
WO2017145104A1 (en) * 2016-02-25 2017-08-31 Wockhardt Limited Pharmaceutical composition of insulin glargine and amino acids
US10155000B2 (en) 2016-06-10 2018-12-18 Boehringer Ingelheim International Gmbh Medical use of pharmaceutical combination or composition
CN110087674B (en) 2016-12-16 2023-01-03 诺和诺德股份有限公司 Pharmaceutical composition containing insulin
WO2018211517A1 (en) 2017-05-16 2018-11-22 Bhami's Research Laboratory, Pvt. Ltd. High concentration protein formulations with reduced viscosity
EP4360651A2 (en) 2017-08-24 2024-05-01 Novo Nordisk A/S Glp-1 compositions and uses thereof
US11820805B2 (en) 2017-12-18 2023-11-21 Merck Sharp & Dohme Llc Conjugate based systems for controlled insulin delivery
US11413352B2 (en) 2017-12-18 2022-08-16 Merck, Sharp & Dohme LLC Conjugate based systems for controlled insulin delivery
US10335464B1 (en) 2018-06-26 2019-07-02 Novo Nordisk A/S Device for titrating basal insulin
CN110063932A (en) * 2019-04-12 2019-07-30 浙江大学 A kind of slow releasing composition preparation of polypeptide protein class drug and preparation method thereof
EP4106724A1 (en) 2020-02-18 2022-12-28 Novo Nordisk A/S Glp-1 compositions and uses thereof
GB2610490A (en) 2020-03-31 2023-03-08 Protomer Tech Inc Conjugates for selective responsiveness to vicinal diols
EP4247429A1 (en) 2020-11-19 2023-09-27 Protomer Technologies Inc. Aromatic boron-containing compounds and insulin analogs
WO2023017537A1 (en) 2021-08-12 2023-02-16 Celagenex Research (India) Pvt. Ltd. Oral algal oil based gastro-intestinal tract permeable peptide composition
WO2023225534A1 (en) 2022-05-18 2023-11-23 Protomer Technologies Inc. Aromatic boron-containing compounds and related insulin analogs

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1285023A (en) 1968-08-09 1972-08-09 Novo Terapeutisk Labor As Improvements in or relating to injectable insulin preparations
US4783441A (en) * 1979-04-30 1988-11-08 Hoechst Aktiengesellschaft Aqueous protein solutions stable to denaturation
JPS5767548A (en) * 1980-10-14 1982-04-24 Shionogi & Co Ltd Insulin analog and its preparation
AU550068B2 (en) * 1981-03-10 1986-02-27 Novo Nordisk A/S Zinc insulin stabilized with calcium or magnesium salts
FI78616C (en) * 1982-02-05 1989-09-11 Novo Industri As Process for preparing an infused stabilized insulin solution having an elevated zinc content
US4839341A (en) * 1984-05-29 1989-06-13 Eli Lilly And Company Stabilized insulin formulations
PH25772A (en) * 1985-08-30 1991-10-18 Novo Industri As Insulin analogues, process for their preparation
DK179286D0 (en) * 1986-04-18 1986-04-18 Nordisk Gentofte INSULIN PREPARATION
US5514646A (en) * 1989-02-09 1996-05-07 Chance; Ronald E. Insulin analogs modified at position 29 of the B chain
TW402506B (en) * 1993-06-24 2000-08-21 Astra Ab Therapeutic preparation for inhalation
US5461031A (en) * 1994-06-16 1995-10-24 Eli Lilly And Company Monomeric insulin analog formulations
US5474978A (en) * 1994-06-16 1995-12-12 Eli Lilly And Company Insulin analog formulations
US5547929A (en) * 1994-09-12 1996-08-20 Eli Lilly And Company Insulin analog formulations
AR002976A1 (en) * 1995-03-31 1998-05-27 Lilly Co Eli PARENTERAL PHARMACEUTICAL FORMULATIONS OF LONG-TERM EFFECT OF INSULIN; CRYSTALS OF SUCH ANALOGUES APPLICABLE IN SUCH FORMULATIONS AND PROCEDURE OF THE FORMULATIONS MENTIONED
PE79099A1 (en) 1997-06-13 1999-08-24 Lilly Co Eli STABLE INSULIN FORMULATIONS
WO1999034821A1 (en) * 1998-01-09 1999-07-15 Novo Nordisk A/S Stabilised insulin compositions

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