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
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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
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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

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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
ES2329220T3 (en) 1999-01-06 2009-11-24 Genentech, Inc. MUTANT VARIANTS OF THE INSULIN SIMILAR GROWTH FACTOR (IGF)
WO2000040613A1 (en) 1999-01-06 2000-07-13 Genentech, Inc. Insulin-like growth factor (igf) i mutant variants
DE60005806T2 (en) 1999-04-08 2004-08-05 Genentech, Inc., South San Francisco 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
US6734162B2 (en) 2000-01-24 2004-05-11 Minimed Inc. Mixed buffer system for stabilizing polypeptide formulations
EP1292324A2 (en) * 2000-05-05 2003-03-19 Novo Nordisk A/S Critical illness neuropathy
EP1282437B1 (en) 2000-05-16 2008-03-19 Genentech, Inc. Treatment of 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
AU2002248464A1 (en) 2001-02-21 2002-09-12 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
US6835802B2 (en) 2001-06-04 2004-12-28 Nobex Corporation Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties
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
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
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
US6737401B2 (en) 2001-06-28 2004-05-18 Metronic Minimed, Inc. Methods of evaluating protein formulation stability and surfactant-stabilized insulin formulations derived therefrom
ES2298378T3 (en) 2001-06-28 2008-05-16 Novo Nordisk A/S STABLE FORMULATION OF MODIFIED GLP-1.
US7030082B2 (en) * 2001-09-07 2006-04-18 Nobex Corporation Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith
US7196059B2 (en) * 2001-09-07 2007-03-27 Biocon Limited Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith
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
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
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
ES2360182T3 (en) * 2002-05-07 2011-06-01 Novo Nordisk A/S SOLUBLE FORMULATIONS THAT INCLUDE MONOMERIC INSULIN AND ACILATED INSULIN.
DE10227232A1 (en) * 2002-06-18 2004-01-15 Aventis Pharma Deutschland Gmbh Sour insulin preparations with improved stability
KR101123113B1 (en) * 2002-07-29 2012-03-15 쎄라피콘 에스.알.엘. Nasal peptide pharmaceutical formulation
ITMI20021684A1 (en) * 2002-07-29 2004-01-29 Therapicon Srl PHARMACEUTICAL COMPOSITION OF NASAL PEPTIDE
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
PL3300721T3 (en) 2003-11-20 2019-08-30 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
ES2618028T3 (en) 2004-07-19 2017-06-20 Biocon Limited Insulin-oligomer conjugates, formulations and uses thereof.
AU2005273968A1 (en) * 2004-08-09 2006-02-23 Alios Biopharma Inc. 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
EP2494983B1 (en) 2004-11-12 2019-04-24 Novo Nordisk A/S Stable formulations of glp-1
US8263551B2 (en) 2004-11-22 2012-09-11 Novo Nordisk A/S Soluble, stable insulin-containing formulations with a protamine salt
BRPI0519468A2 (en) 2004-12-27 2009-01-27 Silence Therapeutics Ag coated lipid complexes and their use
EP1862174A1 (en) * 2005-03-02 2007-12-05 Ajinomoto Co., Inc. Inhibitor for insulin polymer formation
JP2008542235A (en) * 2005-05-25 2008-11-27 ノボ・ノルデイスク・エー／エス Stabilized polypeptide preparation
US8097584B2 (en) * 2005-05-25 2012-01-17 Novo Nordisk A/S Stabilized formulations of insulin that comprise ethylenediamine
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
US20100210506A1 (en) * 2005-10-20 2010-08-19 Mdrna, Inc. Intranasal administration of rapid acting insulin
EP1969004B1 (en) 2005-12-28 2011-08-10 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
CA2649630C (en) * 2006-04-20 2016-04-05 Silence Therapeutics Ag Lipoplex formulations for specific delivery to vascular endothelium
EP1852108A1 (en) 2006-05-04 2007-11-07 Boehringer Ingelheim Pharma GmbH & Co.KG DPP IV inhibitor formulations
BRPI0711558A2 (en) 2006-05-04 2011-11-08 Boeringer Ingelheim Internat Gmbh polymorphs
PE20080251A1 (en) 2006-05-04 2008-04-25 Boehringer Ingelheim Int USES OF DPP IV INHIBITORS
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
AU2008313248B2 (en) * 2007-10-16 2012-04-26 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
PL2910570T3 (en) 2008-03-18 2017-06-30 Novo Nordisk A/S Protease stabilized, acylated insulin analogues
AR071175A1 (en) 2008-04-03 2010-06-02 Boehringer Ingelheim Int PHARMACEUTICAL COMPOSITION THAT INCLUDES AN INHIBITOR OF DIPEPTIDIL-PEPTIDASA-4 (DPP4) AND A COMPARING PHARMACO
TWI394580B (en) 2008-04-28 2013-05-01 Halozyme Inc Super fast-acting insulin compositions
ES2531657T3 (en) 2008-05-01 2015-03-18 Arecor Limited Formulation of a protein
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"
KR20190016601A (en) 2008-08-06 2019-02-18 베링거 인겔하임 인터내셔날 게엠베하 Treatment for diabetes in patients inappropriate for metformin therapy
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
EP2344195A2 (en) 2008-09-10 2011-07-20 Boehringer Ingelheim International GmbH 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
NZ592283A (en) 2008-10-17 2012-09-28 Sanofi Aventis Deutschland Combination of an insulin and the GLP-1 agonist AVE0010
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
JP4959005B2 (en) 2008-10-30 2012-06-20 ノボ・ノルデイスク・エー／エス Treatment of diabetes mellitus with insulin injections less than daily injection frequency
JP2012512848A (en) 2008-12-23 2012-06-07 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 Salt forms of organic compounds
TW201036975A (en) 2009-01-07 2010-10-16 Boehringer Ingelheim Int Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy
AU2010208305A1 (en) 2009-01-28 2011-09-08 Smartcells, Inc. Synthetic conjugates and uses thereof
PE20120583A1 (en) 2009-01-28 2012-05-19 Smartcells Inc CONJUGATE-BASED SYSTEMS FOR CONTROLLED PHARMACOLOGICAL DELIVERY
EP2391216A4 (en) 2009-01-28 2013-06-19 Smartcells Inc Exogenously triggered controlled release materials and uses thereof
CA2750269A1 (en) 2009-01-28 2010-08-05 Smartcells, Inc. Crystalline insulin-conjugates
MX2011008562A (en) 2009-02-12 2011-09-09 Proyecto Biomedicina Cima Sl Use of cardiotrophin- 1 for the treatment of metabolic diseases.
AU2010217760B2 (en) 2009-02-27 2015-04-09 Tandem Diabetes Care, Inc. Methods and devices for determination of flow reservoir volume
US9250106B2 (en) 2009-02-27 2016-02-02 Tandem Diabetes Care, Inc. Methods and devices for determination of flow reservoir volume
WO2010107520A1 (en) 2009-03-20 2010-09-23 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
HUE027239T2 (en) * 2009-06-26 2016-10-28 Novo Nordisk As Preparation comprising insulin, nicotinamide and arginine
WO2011014704A2 (en) 2009-07-30 2011-02-03 Tandem Diabetes Care, Inc. Infusion pump system with disposable cartridge having pressure venting and pressure feedback
MX2012005184A (en) 2009-11-13 2012-06-08 Sanofi Aventis Deutschland Pharmaceutical composition comprising a glp-1 agonist and methionine.
MX2012005186A (en) 2009-11-13 2012-06-08 Sanofi Aventis Deutschland Pharmaceutical composition comprising a glp-1 agonist, an insulin, and methionine.
KR20210033559A (en) 2009-11-27 2021-03-26 베링거 인겔하임 인터내셔날 게엠베하 Treatment of genotyped diabetic patients with dpp-iv inhibitors such as linagliptin
CN101912600B (en) * 2010-01-11 2014-01-29 杨国汉 Method for improving stability of insulin in solution
US9186392B2 (en) 2010-05-05 2015-11-17 Boehringer Ingelheim International Gmbh Combination therapy
AU2011202239C1 (en) 2010-05-19 2017-03-16 Sanofi Long-acting formulations of insulins
CA2803504C (en) 2010-06-24 2022-08-30 Boehringer Ingelheim International Gmbh A combination for diabetes therapy comprising linagliptin and a long-acting insulin
WO2012015692A2 (en) 2010-07-28 2012-02-02 Smartcells, Inc. Recombinantly expressed insulin polypeptides and uses thereof
EP2598522A4 (en) 2010-07-28 2014-11-12 Smartcells Inc Recombinant lectins, binding-site modified lectins and uses thereof
WO2012015681A2 (en) 2010-07-28 2012-02-02 Smartcells, Inc. Drug-ligand conjugates, synthesis thereof, and intermediates thereto
JP6199186B2 (en) 2010-08-30 2017-09-20 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Use of AVE0010 for the manufacture of a medicament for the treatment of type 2 diabetes
DK2632478T3 (en) 2010-10-27 2019-10-07 Novo Nordisk As TREATMENT OF DIABETES MELITUS USING INSULIN INJECTIONS SUBMITTED AT VARIOUS INJECTION INTERVALS
AR083878A1 (en) 2010-11-15 2013-03-27 Boehringer Ingelheim Int VASOPROTECTORA AND CARDIOPROTECTORA ANTIDIABETIC THERAPY, LINAGLIPTINA, TREATMENT METHOD
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
US10457659B2 (en) 2011-04-29 2019-10-29 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
US20130011378A1 (en) 2011-06-17 2013-01-10 Tzung-Horng Yang 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
CA2841552C (en) 2011-07-15 2020-06-23 Boehringer Ingelheim International Gmbh Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
SI2750699T1 (en) 2011-08-29 2015-11-30 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for use in glycemic control in diabetes type 2 patients
TWI559929B (en) 2011-09-01 2016-12-01 Sanofi Aventis Deutschland Pharmaceutical composition for use in the treatment of a neurodegenerative disease
EP2773331B1 (en) * 2011-10-31 2016-02-10 Xeris Pharmaceuticals, Inc. Formulations for the treatment of diabetes
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
EP2849755A1 (en) 2012-05-14 2015-03-25 Boehringer Ingelheim International GmbH A xanthine derivative as dpp -4 inhibitor for use in the treatment of podocytes 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
BR112015011179A8 (en) 2012-12-19 2019-10-01 Wockhardt Ltd stable aqueous pharmaceutical compositions comprising human insulin or an analogue or derivative thereof, their use and processes for their preparation
CA2889162A1 (en) 2012-12-26 2014-07-03 Wockhardt Limited 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
EP2970124B1 (en) 2013-03-14 2019-05-22 The Board of Trustees of the Leland Stanford Junior University 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
AU2014247167B2 (en) 2013-04-03 2018-11-22 Sanofi Treatment of diabetes mellitus by long–acting formulations of insulins
US10137172B2 (en) 2013-04-30 2018-11-27 Novo Nordisk A/S Administration regime
WO2015008169A2 (en) * 2013-07-04 2015-01-22 Insuline Medical Ltd. Device, system and method for delivery of a long-acting drug
EP3052134B1 (en) 2013-10-04 2021-05-05 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
AR098168A1 (en) 2013-10-25 2016-05-04 Sanofi Sa STABLE FORMULATION OF GLULISINE INSULIN
EP3091995B1 (en) 2014-01-09 2024-03-20 Sanofi Stabilized pharmaceutical formulations of insulin aspart
US9895424B2 (en) 2014-01-09 2018-02-20 Sanofi Stabilized pharmaceutical formulations of insulin analogues and/or insulin derivatives
CN114939156A (en) 2014-01-09 2022-08-26 赛诺菲 Stabilized pharmaceutical formulations of insulin aspart
JP6944780B2 (en) * 2014-01-13 2021-10-06 サーマリン インコーポレイテッド Fast-acting insulin preparation and drug delivery system
ES2950384T3 (en) 2014-02-28 2023-10-09 Boehringer Ingelheim Int Medical use of a DPP-4 inhibitor
JP6970615B2 (en) 2014-12-12 2021-11-24 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Insulin glargine / lixisenatide fixed ratio prescription
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
EP3419649A1 (en) * 2016-02-25 2019-01-02 Wockhardt Limited Pharmaceutical composition of insulin glargine and amino acids
CA3022202A1 (en) 2016-06-10 2017-12-14 Boehringer Ingelheim International Gmbh Combinations of linagliptin and metformin
CN110087674B (en) 2016-12-16 2023-01-03 诺和诺德股份有限公司 Pharmaceutical composition containing insulin
SG11202003754YA (en) 2017-05-16 2020-05-28 Bhamis Research Laboratory Pvt Ltd High concentration protein formulations with reduced viscosity
PE20211202A1 (en) 2017-08-24 2021-07-05 Novo Nordisk As COMPOSITIONS OF GLP-1 AND ITS USES
US11413352B2 (en) 2017-12-18 2022-08-16 Merck, Sharp & Dohme LLC Conjugate based systems for controlled insulin delivery
EP3727424A4 (en) 2017-12-18 2021-10-27 Merck Sharp & Dohme Corp. 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
CR20220555A (en) 2020-03-31 2023-01-23 Protomer Tech Inc Conjugates for selective responsiveness to vicinal diols
AU2021382599A1 (en) 2020-11-19 2023-06-22 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
US20230374045A1 (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
US5474978A (en) * 1994-06-16 1995-12-12 Eli Lilly And Company Insulin analog formulations
US5461031A (en) * 1994-06-16 1995-10-24 Eli Lilly And Company Monomeric 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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