NO330026B1 - Anvendelse av metformin og glyburid for fremstilling av et farmasoytisk preparat - Google Patents

Anvendelse av metformin og glyburid for fremstilling av et farmasoytisk preparat Download PDF

Info

Publication number: NO330026B1
Authority: NO; Norway
Prior art keywords: metformin; glyburide; dose; treatment; therapy
Prior art date: 1999-11-03

Application number

NO20022087A

Other languages

English (en)

Norwegian (no)

Other versions

NO20022087D0 (no

NO20022087L (no

Inventor

Beth Anne Piper

Original Assignee

Bristol Myers Squibb Co

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.)

1999-11-03

Filing date

2002-05-02

Publication date

2011-02-07

1999-11-03 Priority claimed from US09/432,465 external-priority patent/US6586438B2/en

2002-05-02 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

2002-05-02 Publication of NO20022087D0 publication Critical patent/NO20022087D0/no

2002-06-24 Publication of NO20022087L publication Critical patent/NO20022087L/no

2011-02-07 Publication of NO330026B1 publication Critical patent/NO330026B1/no

Links

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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- 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

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Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Obesity (AREA)
Hematology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Hospice & Palliative Care (AREA)
Otolaryngology (AREA)
Emergency Medicine (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

NO20022087A 1999-11-03 2002-05-02 Anvendelse av metformin og glyburid for fremstilling av et farmasoytisk preparat NO330026B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US09/432,465 US6586438B2 (en)	1999-11-03	1999-11-03	Antidiabetic formulation and method
US09/460,920 US7598262B2 (en)	1999-11-03	1999-12-14	Method for treating diabetes
PCT/US2000/028311 WO2001032157A2 (en)	1999-11-03	2000-10-13	Pharmaceutical composition comprising a combination of metformin and glibenclamide

Publications (3)

Publication Number	Publication Date
NO20022087D0 NO20022087D0 (no)	2002-05-02
NO20022087L NO20022087L (no)	2002-06-24
NO330026B1 true NO330026B1 (no)	2011-02-07

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NO20022087A NO330026B1 (no)	1999-11-03	2002-05-02	Anvendelse av metformin og glyburid for fremstilling av et farmasoytisk preparat

Country Status (23)

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EP (1)	EP1229918B1 (es)
JP (1)	JP5183844B2 (es)
KR (1)	KR20070089259A (es)
CN (1)	CN1450902A (es)
AR (1)	AR026356A1 (es)
AT (1)	ATE390140T1 (es)
AU (1)	AU780106B2 (es)
BR (1)	BR0015294A (es)
CA (1)	CA2389928C (es)
EE (1)	EE05260B1 (es)
HU (1)	HU229352B1 (es)
IL (1)	IL149139A0 (es)
LT (1)	LT5058B (es)
LV (1)	LV12910B (es)
MX (1)	MXPA02004282A (es)
NO (1)	NO330026B1 (es)
NZ (1)	NZ518278A (es)
PL (1)	PL199278B1 (es)
RU (1)	RU2275915C2 (es)
SK (1)	SK287810B6 (es)
TW (1)	TWI280125B (es)
UY (1)	UY26424A1 (es)
WO (1)	WO2001032157A2 (es)

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US7563774B2 (en)	2000-06-29	2009-07-21	Metabasis Therapeutics, Inc.	Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes
FR2816840B1 (fr)	2000-11-17	2004-04-09	Flamel Tech Sa	Medicament a base de microcapsules d'anti-hyperclycemiant a liberation prolongee et son procede de preparation
FR2825023B1 (fr) *	2001-05-23	2005-04-15	Flamel Tech Sa	Forme pharmaceutique orale antidiabetique "une prise par jour"comprenant une biguanide et au moins un autre principe actif
WO2003011273A1 (en) *	2001-07-31	2003-02-13	The Governement Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services	Metformin in the treatment of hyperglycemic conditions
JP4732696B2 (ja)	2002-04-09	2011-07-27	フラメル・テクノロジー	活性成分の改変された放出のための、マイクロカプセルの水性懸濁液形態での経口医薬品製剤
EP1515701B1 (en)	2002-06-17	2014-09-17	Inventia Healthcare Private Limited	Process for the manufacture of multilayer tablet compositions comprising thiazolidinedione and biguanide
JP2007509865A (ja) *	2003-10-30	2007-04-19	ティオガファーマシュウティカルズ，インコーポレイテッド	神経障害の治療における選択的オピエート受容体調節物質の使用
SG149814A1 (en) *	2003-12-19	2009-02-27	Omega Bio Pharma Ip3 Ltd	Compositions and methods for treating diabetes
BRPI0510613A (pt) *	2004-05-03	2007-10-30	Omega Bio Pharma Ip3 Ltd	cisteaminas para tratar complicações de hipercolesterolemia e diabete
CN101801351B (zh)	2007-07-19	2012-12-12	武田药品工业株式会社	包含阿格列汀和盐酸二甲双胍的固体制剂
CN101801371B (zh)	2007-09-10	2012-11-28	詹森药业有限公司	可用作sglt抑制剂的化合物的制备方法
RU2372911C1 (ru) *	2008-03-12	2009-11-20	Николай Евгеньевич Староверов	Полиморфная аналоговая терапия
US9056850B2 (en)	2008-10-17	2015-06-16	Janssen Pharmaceutica N.V.	Process for the preparation of compounds useful as inhibitors of SGLT
PT2349324T (pt)	2008-10-17	2017-12-06	Sanofi Aventis Deutschland	Combinação de uma insulina e de um agonista do glp-1
US20110009347A1 (en)	2009-07-08	2011-01-13	Yin Liang	Combination therapy for the treatment of diabetes
WO2011058083A1 (de)	2009-11-13	2011-05-19	Sanofi-Aventis Deutschland Gmbh	Pharmazeutische zusammensetzung umfassend einen glp-1-agonisten, ein insulin und methionin
SG10201500871TA (en)	2009-11-13	2015-04-29	Sanofi Aventis Deutschland	Pharmaceutical composition comprising a glp-1 agonist and methionine
NZ703128A (en)	2010-05-11	2016-04-29	Janssen Pharmaceutica Nv	Pharmaceutical formulations comprising 1 - (beta-d-glucopyranosyl) - 2 -thienylmethylbenzene derivatives as inhibitors of sglt
RS55378B1 (sr)	2010-08-30	2017-03-31	Sanofi Aventis Deutschland	Upotreba ave0010 za proizvodnju leka za tretman diabetes mellitus tipa 2
AU2012213435B2 (en) *	2011-02-02	2017-03-30	Sanofi-Aventis Deutschland Gmbh	Prevention of hypoglycaemia in diabetes mellitus type 2 patients
US20120277147A1 (en) *	2011-03-29	2012-11-01	Sanofi-Aventis Deutschland Gmbh	Prevention of hypoglycaemia in diabetes mellitus type 2 patients
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
AR087744A1 (es)	2011-09-01	2014-04-16	Sanofi Aventis Deutschland	Composicion farmaceutica para uso en el tratamiento de una enfermedad neurodegenerativa
TWI758239B (zh)	2014-12-12	2022-03-21	德商賽諾菲阿凡提斯德意志有限公司	甘精胰島素/利司那肽固定比率配製劑
TWI748945B (zh)	2015-03-13	2021-12-11	德商賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患治療
TW201705975A (zh)	2015-03-18	2017-02-16	賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患之治療
US20170071970A1 (en)	2015-09-15	2017-03-16	Janssen Pharmaceutica Nv	Co-therapy comprising canagliflozin and phentermine for the treatment of obesity and obesity related disorders
CN110804017A (zh) *	2019-10-31	2020-02-18	天津大学	磺酰脲化合物与二甲双胍成盐、制备方法和应用
CN113143940A (zh) *	2020-12-30	2021-07-23	成都恒瑞制药有限公司	一种抗糖尿病药物组合物的制备方法

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3174901A (en)	1963-01-31	1965-03-23	Jan Marcel Didier Aron Samuel	Process for the oral treatment of diabetes
DE3833439A1 (de) *	1988-10-01	1991-09-12	Hoechst Ag	Verfahren zur mikronisierung von glibenclamid
DK36392D0 (da)	1992-03-19	1992-03-19	Novo Nordisk As	Anvendelse af kemisk forbindelse
TWI238064B (en)	1995-06-20	2005-08-21	Takeda Chemical Industries Ltd	A pharmaceutical composition for prophylaxis and treatment of diabetes
IT1276130B1 (it) *	1995-11-14	1997-10-27	Gentili Ist Spa	Associazione glibenclamide-metformina, composizioni farmaceutiche che la contengono e loro uso nel trattamento del diabete mellito di tipo
CZ298469B6 (cs)	1997-06-18	2007-10-10	Smithkline Beecham Plc	Farmaceutický prostredek obsahující 5-[4-/2-(N-methyl-N-(2-pyridyl)amino)ethoxy/benzyl]thiazolidin-2,4-dion a metformin, a lécivo pro lécení diabetesmellitus
DE69822505T2 (de) *	1997-12-08	2005-01-20	Bristol-Myers Squibb Co.	Neue metformin-salze und verfahren
EP0974356B1 (en) *	1998-07-15	2003-09-24	Merck Sante	Tablets comprising a combination of metformin and glibenclamide
EP2620443A1 (en)	2012-01-25	2013-07-31	Galecto Biotech AB	Novel galactoside inhibitors of galectins

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Publication number	Publication date
PL364885A1 (en)	2004-12-27
NO20022087D0 (no)	2002-05-02
LT5058B (lt)	2003-09-25
EE200200242A (et)	2003-12-15
TWI280125B (en)	2007-05-01
BR0015294A (pt)	2003-07-15
AU1082601A (en)	2001-05-14
LT2002063A (en)	2003-06-25
EE05260B1 (et)	2010-02-15
PL199278B1 (pl)	2008-09-30
CN1450902A (zh)	2003-10-22
EP1229918A2 (en)	2002-08-14
CA2389928A1 (en)	2001-05-10
RU2002114820A (ru)	2004-03-10
AU780106B2 (en)	2005-03-03
UY26424A1 (es)	2001-05-31
LV12910B (en)	2003-05-20
RU2275915C2 (ru)	2006-05-10
SK5002002A3 (en)	2004-05-04
JP5183844B2 (ja)	2013-04-17
WO2001032157A3 (en)	2002-01-24
HU229352B1 (en)	2013-11-28
HUP0300218A3 (en)	2006-02-28
EP1229918B1 (en)	2008-03-26
MXPA02004282A (es)	2003-02-17
NZ518278A (en)	2004-10-29
WO2001032157A2 (en)	2001-05-10
IL149139A0 (en)	2002-11-10
NO20022087L (no)	2002-06-24
KR20070089259A (ko)	2007-08-30
AR026356A1 (es)	2003-02-05
SK287810B6 (sk)	2011-10-04
ATE390140T1 (de)	2008-04-15
JP2003519621A (ja)	2003-06-24
HUP0300218A2 (hu)	2003-06-28
CA2389928C (en)	2010-03-23

Publication	Publication Date	Title
NO330026B1 (no)	2011-02-07	Anvendelse av metformin og glyburid for fremstilling av et farmasoytisk preparat
US7598262B2 (en)	2009-10-06	Method for treating diabetes
US7507768B2 (en)	2009-03-24	Antidiabetic formulation and method
JP2003519621A5 (es)	2007-11-29
AU8022900B2 (es)	2005-06-16
AU2002357095B2 (en)	2007-09-27	Antidiabetic formulation and method

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