WO2007065156B1 - Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide - Google Patents

Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide

Info

Publication number
WO2007065156B1
WO2007065156B1 PCT/US2006/061503 US2006061503W WO2007065156B1 WO 2007065156 B1 WO2007065156 B1 WO 2007065156B1 US 2006061503 W US2006061503 W US 2006061503W WO 2007065156 B1 WO2007065156 B1 WO 2007065156B1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
grp
concentration
medicament
cyclodextrin
Prior art date
Application number
PCT/US2006/061503
Other languages
French (fr)
Other versions
WO2007065156A3 (en
WO2007065156A2 (en
Inventor
Steven C Quay
Henry R Costantino
Michael V Templin
Alexis Kays Leonard
Mary S Kleppe
Joshua O Sestak
Original Assignee
Nastech Pharm Co
Steven C Quay
Henry R Costantino
Michael V Templin
Alexis Kays Leonard
Mary S Kleppe
Joshua O Sestak
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
Priority claimed from US11/293,676 external-priority patent/US20060074025A1/en
Priority claimed from PCT/US2006/008928 external-priority patent/WO2007061434A2/en
Application filed by Nastech Pharm Co, Steven C Quay, Henry R Costantino, Michael V Templin, Alexis Kays Leonard, Mary S Kleppe, Joshua O Sestak filed Critical Nastech Pharm Co
Priority to US12/095,801 priority Critical patent/US20080318837A1/en
Priority to JP2008543590A priority patent/JP2009518315A/en
Priority to BRPI0620586-0A priority patent/BRPI0620586A2/en
Priority to EP06846441A priority patent/EP1965828A2/en
Priority to MX2008007075A priority patent/MX2008007075A/en
Publication of WO2007065156A2 publication Critical patent/WO2007065156A2/en
Publication of WO2007065156A3 publication Critical patent/WO2007065156A3/en
Publication of WO2007065156B1 publication Critical patent/WO2007065156B1/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
    • A61K38/16—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
    • 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
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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

What is described is a pharmaceutical formulation comprising a mixture of a pharmaceutically effective amount of glucose-regulating peptide (GRP) and enhancers, wherein the pharmaceutical formulation is used in the treatment of a metabolic syndrome.

Claims

AMENDED CLAIMS received by the International Bureau on 30 July 2007 (30.07.07)
1. A pharmaceutical formulation for epithelial delivery of glucose- regulating peptide (GRP), comprising a GRP and enhancers of permeability, wherein the enhancers comprise a solubilizing agent, a surface active agent, a monoionogenic buffer, and a viscosity enhancing agent.
2. The formulation of claim 1 , wherein the enhancers increase permeability of the GRP by at least 10%.
3. The formulation of claim 1 , wherein the enhancers increase permeability of the GRP by at least 15-fold.
4. The formulation of claim 1 , wherein the enhancers increase bioavailability of GRP by at least about 25-fold.
5. The formulation of claim 1 , wherein the enhancers increase bioavailability of GRP by at least about 50-fold.
6. The formulation of claim 1 , wherein the bioavailability of GRP is at least about 1% relative to a delivery by subcutaneous injection.
7. The formulation of claim 1 , wherein the bioavailability of GRP is at least about 5% relative to a delivery by subcutaneous injection.
8. The formulation of claim 1 , wherein the bioavailability of GRP is at least about 10% relative to a delivery by subcutaneous injection.
9. The formulation of claim 1 , wherein a time to maximal concentration in circulation of the animal, Tmaχ, is less than about 45 minutes.
10. The formulation of claim 1 , wherein a time to maximal concentration in circulation of the animal, T1713x, is greater than about 60 minutes.
i
11. The formulation of claim 1 , wherein a time to maximal concentration in circulation of the animal, "U8x, is less than about 30 minutes.
12. The formulation of claim 1 , further comprising a chelating agent.
13. The formulation of claim 12, wherein the chelating agent is selected from the group consisting of ethylene diamine tetraacetic acid and ethylene glycol tetraacetic acid.
14. The formulation of claim 1 , wherein the solubiliziπg agent is selected from the group consisting of a cyclodextrin, hydroxypropyl-β- cyclodextrin, sulfobutylether-β-cyclodextm and methyl-β-cyclodextrin.
15. The formulation of claim 14, wherein the solubilizing agent is methyl-β-cyclodextriπ .
16. The formulation of claim 1 , wherein the surface-active agent is selected from the group consisting of nonionic polyoxyethylene ether, fusidic acid and its derivatives, sodium taurodihydrofusidate, L-α-phosphatidylcholine didecanoyl, polysorbate 80, polysorbate 20, polyethylene glycol, cetyl alcohol, polyvlnylpyrofidone, polyvinyl alcohol, lanolin alcohol and sorbitan monooleate.
17. The formulation of claim 16, wherein the surface-active agent is L- α-phosphatidylcholine didecanoyl.
18. The formulation of claim 1, comprising a GRP, methyl-β- cyclodextrin, and L-α-phosphatidylcholine didecanoyl.
19. The formulation of claim 1 , wherein the GRP is present at a concentration greater than about 50 mg/mL.
20. The formulation of claim 1 , wherein the GRP is present at a concentration of about 0.1 to about 50 mg/mL.
21. The formulation of claim 1 , wherein the GRP is present at a concentration of about 0.25 to about 10 mg/mL.
22. The formulation of claim 1 , wherein the GRP consists of GLP-1.
23. The formulation of claim 1 , wherein the GRP consists of exendin-4.
24. The formulation of claim 22 or 23, wherein the GRP derivative comprises the GRP covalently linked to a hydrophobic moiety.
25. The formulation of claim 24, wherein the hydrophobic moiety comprises an alky! chain.
26. The formulation of claim 24, wherein the hydrophobic moiety comprises a fatty acid chain.
27. The formulation of claim 1 , wherein the formulation is a non-sterile formulation.
28. The formulation of claim 27, further comprising a preservative selected from the group consisting of chlorobutaπol, methyl paraben, propyl parabeπ, butyl paraben, benzalkonium chloride, benzethonium chloride, sodium benzoate, sorbic acid, phenol, and ortho-, meta- or para-cresol.
29. The formulation of claim 1 , wherein the formulation is a sterile formulation.
30. The formulation of claim 22, further comprising a dipeptidyl aminopeptidase (DPP) IV inhibitor.
31. The formulation of claim 30, wherein the DPP IV inhibitor is lys(4- nitro-Z)-pyrrolidide,
32. The formulation of claim 31 , wherein lys(4-nitro-Z)-pyrrolidide is at a concentration of at least about 5 mM.
33. The formulation of claim 31 , wherein lys(4-nitro-Z)-pyrrolidide is at a concentration of at least about 30 mM.
34. The formulation of claim 31 , wherein lys{4-nitro-Z)-pyrrolidide is at a concentration of at least about 50 mM.
35. The formulation of claim 1 , wherein the formulation is suitable for intranasal delivery of GLP-1.
36. The formulation of claim 1. wherein the formulation has a pH of about of about 3 to about 6.
37. The formulation of claim 1 , wherein the formulation has a pH of 3.5 ± 0.50.
38. The formulation of claim 1 , comprising a GLP-1 , 45 mg/ml methyl- β-cyclodextrin, 1 mg/ml L-α-phosphatidylcholine didecanoyl, and 1 mg/ml EDTA.
39. A use of a GRP for the manufacture of a medicament for treating a metabolic syndrome in a mammal, wherein the medicament comprises a formulation of any of claims 1-38, and wherein such medicament comprises a pharmaceutically effective amount of the GRP.
40. The use of claim 39, wherein epithelial administration of the medicament to a mammal increases plasma insulin levels,
41. The use of claim 39, wherein epithelial administration of the medicament to a mammal reduces blood glucose levels.
42. The use of claim 39, wherein epithelial administration of the medicament to a mammal delays gastric emptying.
PCT/US2006/061503 2003-12-26 2006-12-01 Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide WO2007065156A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US12/095,801 US20080318837A1 (en) 2003-12-26 2006-12-01 Pharmaceutical Formation 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
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
EP06846441A EP1965828A2 (en) 2005-12-02 2006-12-01 Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide
MX2008007075A MX2008007075A (en) 2005-12-02 2006-12-01 Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide.

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
US11/293,676 2005-12-02
US11/293,676 US20060074025A1 (en) 2003-12-26 2005-12-02 Therapeutic formulations for transmucosal administration that increase glucagon-like peptide-1 bioavailability
US77646406P 2006-02-24 2006-02-24
US60/776,464 2006-02-24
USPCT/US2006/008928 2006-03-03
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
US80440606P 2006-06-09 2006-06-09
US60/804,406 2006-06-09
US80454306P 2006-06-12 2006-06-12
US60/804,543 2006-06-12
US80519106P 2006-06-19 2006-06-19
US60/805,191 2006-06-19

Publications (3)

Publication Number Publication Date
WO2007065156A2 WO2007065156A2 (en) 2007-06-07
WO2007065156A3 WO2007065156A3 (en) 2007-07-19
WO2007065156B1 true WO2007065156B1 (en) 2007-09-13

Family

ID=38005475

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/061503 WO2007065156A2 (en) 2003-12-26 2006-12-01 Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide

Country Status (5)

Country Link
EP (1) EP1965828A2 (en)
JP (1) JP2009518315A (en)
BR (1) BRPI0620586A2 (en)
MX (1) MX2008007075A (en)
WO (1) WO2007065156A2 (en)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8410085B2 (en) 2007-11-16 2013-04-02 Baylor College Of Medicine Phospholipid compositions and uses thereof
EP2344519B1 (en) 2008-11-07 2016-09-28 The General Hospital Corporation C-terminal fragments of glucagon-like peptide-1 (glp-1)
JP5892940B2 (en) 2009-11-25 2016-03-23 アリスジェン ソシエテ アノニム Mucosal delivery composition comprising a peptide complexed with a crown compound and / or counterion
WO2012061466A2 (en) 2010-11-02 2012-05-10 The General Hospital Corporation Methods for treating steatotic disease
EP2526971A1 (en) 2011-05-25 2012-11-28 ArisGen SA Mucosal delivery of drugs
WO2013006692A2 (en) 2011-07-06 2013-01-10 The General Hospital Corporation Methods of treatment using a pentapeptide derived from the c-terminus of glucagon-like peptide 1 (glp-1)
UA116217C2 (en) 2012-10-09 2018-02-26 Санофі Exendin-4 derivatives as dual glp1/glucagon agonists
WO2014096150A1 (en) 2012-12-21 2014-06-26 Sanofi Dual glp1/gip or trigonal glp1/gip/glucagon agonists
CN103405753B (en) * 2013-08-13 2016-05-11 上海仁会生物制药股份有限公司 Stable insulin secretion accelerating peptide liquid drugs injection pharmaceutical composition
TW201609795A (en) 2013-12-13 2016-03-16 賽諾菲公司 EXENDIN-4 peptide analogues as dual GLP-1/GIP receptor agonists
EP3080154B1 (en) 2013-12-13 2018-02-07 Sanofi Dual glp-1/gip receptor agonists
WO2015086733A1 (en) 2013-12-13 2015-06-18 Sanofi Dual glp-1/glucagon receptor agonists
WO2015086730A1 (en) 2013-12-13 2015-06-18 Sanofi Non-acylated exendin-4 peptide analogues
TW201625670A (en) 2014-04-07 2016-07-16 賽諾菲公司 Dual GLP-1/glucagon receptor agonists derived from EXENDIN-4
TW201625669A (en) 2014-04-07 2016-07-16 賽諾菲公司 Peptidic dual GLP-1/glucagon receptor agonists derived from Exendin-4
TW201625668A (en) 2014-04-07 2016-07-16 賽諾菲公司 Exendin-4 derivatives as peptidic dual GLP-1/glucagon receptor agonists
US9932381B2 (en) 2014-06-18 2018-04-03 Sanofi Exendin-4 derivatives as selective glucagon receptor agonists
MY175669A (en) * 2015-02-17 2020-07-03 Lilly Co Eli Nasal powder formulation for treatment of hypoglycemia
AR105319A1 (en) 2015-06-05 2017-09-27 Sanofi Sa PROPHARMS THAT INCLUDE A DUAL AGONIST GLU-1 / GLUCAGON CONJUGATE HIALURONIC ACID CONNECTOR
TW201706291A (en) 2015-07-10 2017-02-16 賽諾菲公司 New EXENDIN-4 derivatives as selective peptidic dual GLP-1/glucagon receptor agonists
CN117323410A (en) * 2022-06-30 2024-01-02 深圳翰宇药业股份有限公司 Polypeptide pharmaceutical solution preparation and preparation method thereof

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DK36492D0 (en) * 1992-03-19 1992-03-19 Novo Nordisk As PREPARATION
US7312196B2 (en) * 1997-01-08 2007-12-25 Amylin Pharmaceuticals, Inc. Formulations for amylin agonist peptides
US20050014681A1 (en) * 2001-11-26 2005-01-20 Yoshiharu Minamitake Medicinal compositions for nasal absorption
BR0314996A (en) * 2002-10-02 2005-08-09 Zealand Pharma As Composition, pharmaceutically acceptable composition, method for producing the composition, methods for stabilizing exendin-4 (1-39) or a variant, derivative or analogue thereof against degradation, before, during or after intended use, to treat diseases, to treat disease states associated with elevated blood glucose levels, to regulate blood glucose levels, to regulate gastric emptying, to stimulate the release of insulin in a mammal to reduce blood glucose level in a mammal, to reduce the level of plasma lipids in a mammal, to reduce mortality and morbidity after myocardial infarction in a mammal, to stimulate insulin release in a mammal, and to produce a stabilized exendin (1-39), and stabilized exendin (1-39)
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
EP1965828A2 (en) 2008-09-10
WO2007065156A3 (en) 2007-07-19
BRPI0620586A2 (en) 2011-11-16
MX2008007075A (en) 2008-11-12
JP2009518315A (en) 2009-05-07
WO2007065156A2 (en) 2007-06-07

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