WO2007061434B1 - A pharmaceutical formulation of glp-1 and its use for treating a metabolic syndrome - Google Patents

A pharmaceutical formulation of glp-1 and its use for treating a metabolic syndrome

Info

Publication number
WO2007061434B1
WO2007061434B1 PCT/US2006/008928 US2006008928W WO2007061434B1 WO 2007061434 B1 WO2007061434 B1 WO 2007061434B1 US 2006008928 W US2006008928 W US 2006008928W WO 2007061434 B1 WO2007061434 B1 WO 2007061434B1
Authority
WO
WIPO (PCT)
Prior art keywords
glp
administration
syndrome
formulation
metabolic syndrome
Prior art date
Application number
PCT/US2006/008928
Other languages
French (fr)
Other versions
WO2007061434A3 (en
WO2007061434A2 (en
Inventor
Mary S Kleppe
Michael V Templin
Steven C Quay
Original Assignee
Nastech Pharm Co
Mary S Kleppe
Michael V Templin
Steven C Quay
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nastech Pharm Co, Mary S Kleppe, Michael V Templin, Steven C Quay filed Critical Nastech Pharm Co
Priority to PCT/US2006/061503 priority Critical patent/WO2007065156A2/en
Priority to BRPI0620586-0A priority patent/BRPI0620586A2/en
Priority to MX2008007075A priority patent/MX2008007075A/en
Priority to JP2008543590A priority patent/JP2009518315A/en
Priority to EP06846441A priority patent/EP1965828A2/en
Publication of WO2007061434A2 publication Critical patent/WO2007061434A2/en
Publication of WO2007061434A3 publication Critical patent/WO2007061434A3/en
Publication of WO2007061434B1 publication Critical patent/WO2007061434B1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/26—Glucagons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

What is described is a pharmaceutical formulation for intranasal delivery of glucagon-like protein- 1 (GLP-1), comprising an aqueous mixture of GLP-1 and a dipeptidyl aminopeptidase (DPP) IV inhibitor, and a method of treating a metabolic syndrome in a mammal, comprising intranasally administering a pharmaceutical formulation comprising a pharmaceutically effective amount of GLP-1.

Claims

AMENDED CLAIMS received by the International Bureau on 22 August 2007 (22.08.07)
1. A pharmaceutical formulation for intranasal delivery of glucagon-like protein- 1 (GLP-I), consisting of an aqueous mixture of a GLP-I, a buffer, a permeation enhancer selected from methyl-β-cyclodextrin, didecanoyl phosphatidylcholine or ethylenediamine tetraacetic acid (EDTA), and a dipeptidyl aminopeptidase (DPP) IV inhibitor.
2. The formulation of claim 1, wherein the DPP IV inhibitor is lys(4-nitro-Z)- pyrrolidide.
3. The formulation of claim 2, wherein lys(4-nitro-Z)-pyrrolidide is at a concentration of at least about 5 mM.
4. The formulation of claim 2, wherein lys(4-nitro-Z)-pyrrolidide is at a concentration of at least about 30 mM.
5. The formulation of claim 2, wherein lys(4-nitro-Z)-pyrrolidide is at a concentration of at least about 50 mM.
6. The formulation of claim 1 , wherein the permeation enhancer is EDTA.
7. The formulation of claim 6, wherein EDTA is present at a concentration of 10 mg/ml.
8. The formulation of claim 1, wherein the buffer is 10 mM citrate.
9. The formulation of claim 1, wherein the formulation has a pH of about 2 to about 8.
10. The formulation of claim 9, wherein the formulation has a pH of 3.5 ± 0.50.
1 1. A pharmaceutical formulation for intranasal delivery of glucagon-like protein- 1 (GLP-I), consisting of an aqueous mixture of a GLP-I, and a permeation enhancer selected from 45 mg/ml methyl-β-cyclodextrin, 1 mg/ml didecanoyl phosphatidylcholine or 10 mg/ml ethylenediamine tetraacetic acid (EDTA).
12. The formulation of claim 1 or 1 1 wherein the GLP-I is present at a concentration of about 0.1 to about 50 mg/mL, preferably wherein the GLP-I is present at a concentration of about 0.25 to about 10 mg/mL. 113
13. A method of treating a metabolic syndrome in a mammal comprising intranasal administration of an amount of a formulation of any of claims 1-12 effective to alleviate one or more symptom or detectable condition of the metabolic condition.
14. The method of claim 13, wherein said administration causes a serum level of the GLP-I with a Tmax less than 40 minutes.
15. The method of claim 13, wherein said administration causes the GLP-I serum level above natural physiological levels for less than four hours.
16. The method of claim 13, wherein said intranasal administration comprises delivering an aerosol comprising about 0.3 to about 30 μg GLP-I per kg weight of the mammal.
17. The method of claim 13, wherein said intranasal administration comprises delivering an aerosol comprising 0.5 to 1.0 mg GLP-I per 0.1 ml of solution.
18. The method of claim 13, wherein said intranasal administration is given at a dosage frequency of between 0.1 to 24 hours.
19. The method of claim 13, wherein said administration causes a bioavailability of GLP-I ofat least 5%.
20. The method of claim 13, wherein said administration causes a bioavailability of GLP-I of at least 10%.
21. The method of claim 13, wherein the metabolic syndrome is selected from Type 2 diabetes, Type 1 diabetes, impaired glucose tolerance, hyperglycemia, metabolic syndrome (syndrome X and/or insulin resistance syndrome), glucosuria, metabolic acidosis, arthritis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, short stature due to growth hormone deficiency, infertility due to polycystic ovary syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome, short bowel syndrome, or the prevention of disease progression in Type 2 diabetes.
22. The method of claim 21, wherein the metabolic syndrome is Type 2 diabetes. 114
23. The method of claim 21, wherein the metabolic syndrome is obesity.
24. The method of claim 21, wherein the metabolic syndrome is hyperlipidemia.
25. The method of claim 13, wherein said administration reduces blood glucose levels by at least 10%.
26. The method of claim 13, wherein said administration increases plasma insulin levels by at least 10%.
27. The method of claim 25 or 26, wherein said administration is post-prandial.
28. The method of claim 13, wherein said administration delays gastric emptying.
29. Use of a formulation of any of claims 1-12, for the manufacture of a medicament for treating a metabolic syndrome in a mammal.
30. Use of claim 29, wherein intranasal administration of said medicament causes a serum level of the GLP-I with a Tmax less than 40 minutes.
31. Use of claim 29, wherein said administration causes the GLP-I serum level above natural physiological levels for less than four hours.
32. Use of claim 29, wherein said administration comprises delivering an aerosol of said medicament comprising about 0.3 to about 30 μg GLP-I per kg weight of the mammal.
33. Use of claim 29, wherein said intranasal administration comprises delivering an aerosol of said medicament comprising 0.5 to 1.0 mg GLP-I per 0.1 ml of solution.
34. Use of claim 29, wherein said intranasal administration is given at a dosage frequency of between 0.1 to 24 hours.
35. Use of claim 29, wherein said administration causes a bioavailability of GLP-I of at least 5%.
36. Use of claim 29, wherein said administration causes a bioavailability of GLP-I of at least 10%.
37. Use of claim 29, wherein the metabolic syndrome is selected from Type 2 diabetes, Type 1 diabetes, impaired glucose tolerance, hyperglycemia, metabolic syndrome (syndrome X and/or insulin resistance syndrome), glucosuria, metabolic acidosis, arthritis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, obesity, conditions exacerbated by 115
obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, short stature due to growth hormone deficiency, infertility due to polycystic ovary syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome, short bowel syndrome, or the prevention of disease progression in Type 2 diabetes.
38. Use of claim 37, wherein the metabolic syndrome is Type II diabetes.
39. Use of claim 37, wherein the metabolic syndrome is obesity.
40. Use of claim 37, wherein the metabolic syndrome is hyperlipidemia.
41. Use of claim 29, wherein said administration reduces blood glucose levels by at least 10%.
42. Use of claim 29, wherein said administration increases plasma insulin levels by at least 10%.
43. Use of claim 41 or 42, wherein said administration is post-prandial.
44. Use of claim 29, wherein said administration delays gastric emptying.
PCT/US2006/008928 2005-11-10 2006-03-10 A pharmaceutical formulation of glp-1 and its use for treating a metabolic syndrome WO2007061434A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
PCT/US2006/061503 WO2007065156A2 (en) 2005-12-02 2006-12-01 Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide
BRPI0620586-0A BRPI0620586A2 (en) 2005-12-02 2006-12-01 aqueous pharmaceutical formulation for intranasal administration and use of an aqueous pharmaceutical formulation to make a medicament
MX2008007075A MX2008007075A (en) 2005-12-02 2006-12-01 Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide.
JP2008543590A JP2009518315A (en) 2005-12-02 2006-12-01 Pharmaceutical formulations for increasing epithelial permeability of glucose-regulating peptides
EP06846441A EP1965828A2 (en) 2005-12-02 2006-12-01 Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US73552405P 2005-11-10 2005-11-10
US60/735,524 2005-11-10
US77646406P 2006-02-24 2006-02-24
US60/776,464 2006-02-24

Publications (3)

Publication Number Publication Date
WO2007061434A2 WO2007061434A2 (en) 2007-05-31
WO2007061434A3 WO2007061434A3 (en) 2007-08-30
WO2007061434B1 true WO2007061434B1 (en) 2007-10-11

Family

ID=36636466

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/008928 WO2007061434A2 (en) 2005-11-10 2006-03-10 A pharmaceutical formulation of glp-1 and its use for treating a metabolic syndrome

Country Status (1)

Country Link
WO (1) WO2007061434A2 (en)

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Publication number Priority date Publication date Assignee Title
EP2344519B1 (en) * 2008-11-07 2016-09-28 The General Hospital Corporation C-terminal fragments of glucagon-like peptide-1 (glp-1)
US20120021979A1 (en) * 2010-06-24 2012-01-26 Vanderbilt University GLP-1 receptor modulation of addiction, neuropsychiatric disorders and erectile dysfunction
DK3326620T3 (en) 2010-12-16 2020-05-25 Novo Nordisk As SOLID COMPOSITIONS CONTAINING A GLP-1 AGONIST AND SALT OF N- (8- (2- HYDROXYBENZOYL) AMINO) CAPRYLIC ACID
CN102614514B (en) * 2011-01-26 2014-12-10 王永祥 GLP-1 acceptor agonists used for treating pains
MX355361B (en) 2011-04-12 2018-04-17 Novo Nordisk As Double-acylated glp-1 derivatives.
EP2729157B1 (en) 2011-07-06 2019-01-16 The General Hospital Corporation A pentapeptide derived from the c-terminus of glucagon-like peptide 1 (glp-1) for use in treatment
US20150038417A1 (en) * 2011-12-09 2015-02-05 Novo Nordisk A/S GLP-1 Agonists
AU2013234496B2 (en) 2012-03-22 2017-07-27 Novo Nordisk A/S Compositions of GLP-1 peptides and preparation thereof
HUE042757T2 (en) 2012-03-22 2019-07-29 Novo Nordisk As Compositions comprising a delivery agent and preparation thereof
ES2871328T3 (en) 2012-06-20 2021-10-28 Novo Nordisk As Tablet formulation comprising a peptide and a delivery agent
RU2671406C2 (en) 2013-05-02 2018-10-31 Ново Нордиск А/С Oral dosing of glucagon-like peptide-1 compounds
IL275778B2 (en) 2018-02-02 2023-12-01 Novo Nordisk As Solid compositions comprising a glp-1 agonist, a salt of n-(8-(2-hydroxybenzoyl)amino)caprylic acid and a lubricant

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DK36492D0 (en) * 1992-03-19 1992-03-19 Novo Nordisk As PREPARATION
ATE316100T1 (en) * 1996-06-05 2006-02-15 Roche Diagnostics Gmbh EXENDIN ANALOGAS, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING SAME
US20030087820A1 (en) * 1999-01-14 2003-05-08 Young Andrew A. Novel exendin agonist formulations and methods of administration thereof
US20050222036A1 (en) * 2000-08-24 2005-10-06 Thomas Jefferson University Peptide compositions with effects on blood glucose
CA2466870A1 (en) * 2001-11-26 2003-06-05 Trustees Of Tufts College Methods for treating autoimmune disorders, and reagents related thereto
JP4124734B2 (en) * 2001-11-26 2008-07-23 アスビオファーマ株式会社 Nasal absorption pharmaceutical composition
DE60332856D1 (en) * 2002-10-23 2010-07-15 Bristol Myers Squibb Co GLYCINNITRIL BASED DIPEPTIDYLPEPTIDASE IV INHIBITORS
US7674913B2 (en) * 2003-11-12 2010-03-09 Phenomix Corporation Heterocyclic boronic acid compounds
US20050143303A1 (en) * 2003-12-26 2005-06-30 Nastech Pharmaceutical Company Inc. Intranasal administration of glucose-regulating peptides

Also Published As

Publication number Publication date
WO2007061434A3 (en) 2007-08-30
WO2007061434A2 (en) 2007-05-31

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