CN104968341A - Glp1r激动剂和二甲双胍的组合及其在治疗2型糖尿病和其他障碍中的用途 - Google Patents
Glp1r激动剂和二甲双胍的组合及其在治疗2型糖尿病和其他障碍中的用途 Download PDFInfo
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- CN104968341A CN104968341A CN201480004613.0A CN201480004613A CN104968341A CN 104968341 A CN104968341 A CN 104968341A CN 201480004613 A CN201480004613 A CN 201480004613A CN 104968341 A CN104968341 A CN 104968341A
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- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
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- ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical class [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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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)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
- C07C279/26—X and Y being nitrogen atoms, i.e. biguanides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (23)
Applications Claiming Priority (3)
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US201361753567P | 2013-01-17 | 2013-01-17 | |
US61/753,567 | 2013-01-17 | ||
PCT/US2014/011394 WO2014113357A1 (en) | 2013-01-17 | 2014-01-14 | Combinations of a glp1r agonist and metformin and use thereof for the treatment of type 2 diabetes and other disorders |
Publications (2)
Publication Number | Publication Date |
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CN104968341A true CN104968341A (zh) | 2015-10-07 |
CN104968341B CN104968341B (zh) | 2020-06-09 |
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CN201480004613.0A Active CN104968341B (zh) | 2013-01-17 | 2014-01-14 | Glp1r激动剂和二甲双胍的组合及其在制备治疗2型糖尿病和其他障碍的药物中的用途 |
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US (1) | US20150313908A1 (zh) |
EP (1) | EP2945618B1 (zh) |
JP (1) | JP6445459B2 (zh) |
KR (1) | KR102165434B1 (zh) |
CN (1) | CN104968341B (zh) |
AU (1) | AU2014207748B2 (zh) |
CA (1) | CA2896308C (zh) |
EA (1) | EA201591123A1 (zh) |
ES (1) | ES2687083T3 (zh) |
HK (1) | HK1210424A1 (zh) |
IL (1) | IL239714A0 (zh) |
MX (1) | MX366685B (zh) |
SG (2) | SG10201704716XA (zh) |
WO (1) | WO2014113357A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021196951A1 (zh) * | 2020-04-01 | 2021-10-07 | 杭州中美华东制药有限公司 | Glp-1受体激动剂游离碱的药学上可接受的酸式盐及其制备方法 |
WO2021196949A1 (zh) * | 2020-04-01 | 2021-10-07 | 杭州中美华东制药有限公司 | 一种glp-1受体激动剂的晶型a及其制备方法 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019060653A1 (en) | 2017-09-22 | 2019-03-28 | Regeneron Pharmaceuticals, Inc. | GLP-1 RECEPTOR AGONISTS (GLUCAGON-LIKE PEPTIDE 1) AND USES THEREOF |
KR20210005843A (ko) * | 2018-05-08 | 2021-01-15 | 브이티브이 테라퓨틱스 엘엘씨 | Glp1r 작용제의 치료적 용도 |
WO2024064842A1 (en) | 2022-09-21 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Methods of treating obesity, diabetes, and liver dysfunction |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101959405A (zh) * | 2008-03-07 | 2011-01-26 | 转化技术制药公司 | 治疗糖尿病的氧杂二氮杂蒽化合物 |
US20110118180A1 (en) * | 2009-11-13 | 2011-05-19 | Sanofi-Aventis Deutschland Gmbh | Method of treatment of diabetes type 2 comprising add-on therapy to metformin |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4080472A (en) | 1974-03-22 | 1978-03-21 | Societe D'etudes Et D'exploitation De Marques Et Brevets S.E.M.S. | Metformin 2-(p-chlorophenoxy)-2-methylpropionate |
US20090221652A1 (en) * | 2005-11-07 | 2009-09-03 | Geesaman Bard J | Combinations of metformin and meglitinide |
EA023430B1 (ru) * | 2009-03-30 | 2016-06-30 | виТиви ТЕРАПЬЮТИКС ЭлЭлСи | Замещенные производные азоантрацена, фармацевтические композиции и способы их применения |
WO2011031620A1 (en) | 2009-09-11 | 2011-03-17 | Transtech Pharma, Inc. | Solid compositions comprising an oxadiazoanthracene compound and methods of making and using the same |
TR201809460T4 (tr) * | 2009-11-13 | 2018-07-23 | Sanofi Aventis Deutschland | Bir GLP- 1-agonisti, bir insülin ve metiyonin içeren farmasötik bileşim. |
US20130040878A1 (en) * | 2011-05-13 | 2013-02-14 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for use in the treatment of diabetes type 2 patients |
-
2014
- 2014-01-14 CN CN201480004613.0A patent/CN104968341B/zh active Active
- 2014-01-14 ES ES14702159.6T patent/ES2687083T3/es active Active
- 2014-01-14 SG SG10201704716XA patent/SG10201704716XA/en unknown
- 2014-01-14 WO PCT/US2014/011394 patent/WO2014113357A1/en active Application Filing
- 2014-01-14 EP EP14702159.6A patent/EP2945618B1/en active Active
- 2014-01-14 AU AU2014207748A patent/AU2014207748B2/en active Active
- 2014-01-14 EA EA201591123A patent/EA201591123A1/ru unknown
- 2014-01-14 SG SG11201504778UA patent/SG11201504778UA/en unknown
- 2014-01-14 MX MX2015008555A patent/MX366685B/es active IP Right Grant
- 2014-01-14 CA CA2896308A patent/CA2896308C/en active Active
- 2014-01-14 JP JP2015553775A patent/JP6445459B2/ja active Active
- 2014-01-14 KR KR1020157018661A patent/KR102165434B1/ko active IP Right Grant
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2015
- 2015-06-30 IL IL239714A patent/IL239714A0/en unknown
- 2015-07-14 US US14/799,222 patent/US20150313908A1/en not_active Abandoned
- 2015-11-13 HK HK15111246.2A patent/HK1210424A1/zh unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101959405A (zh) * | 2008-03-07 | 2011-01-26 | 转化技术制药公司 | 治疗糖尿病的氧杂二氮杂蒽化合物 |
US20110118180A1 (en) * | 2009-11-13 | 2011-05-19 | Sanofi-Aventis Deutschland Gmbh | Method of treatment of diabetes type 2 comprising add-on therapy to metformin |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021196951A1 (zh) * | 2020-04-01 | 2021-10-07 | 杭州中美华东制药有限公司 | Glp-1受体激动剂游离碱的药学上可接受的酸式盐及其制备方法 |
WO2021196949A1 (zh) * | 2020-04-01 | 2021-10-07 | 杭州中美华东制药有限公司 | 一种glp-1受体激动剂的晶型a及其制备方法 |
CN115315426A (zh) * | 2020-04-01 | 2022-11-08 | 杭州中美华东制药有限公司 | Glp-1受体激动剂游离碱的药学上可接受的酸式盐及其制备方法 |
CN115461344A (zh) * | 2020-04-01 | 2022-12-09 | 杭州中美华东制药有限公司 | 一种glp-1受体激动剂的晶型a及其制备方法 |
CN115315426B (zh) * | 2020-04-01 | 2023-12-12 | 杭州中美华东制药有限公司 | Glp-1受体激动剂游离碱的药学上可接受的酸式盐及其制备方法 |
CN115461344B (zh) * | 2020-04-01 | 2024-01-12 | 杭州中美华东制药有限公司 | 一种glp-1受体激动剂的晶型a及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
JP2016505039A (ja) | 2016-02-18 |
CN104968341B (zh) | 2020-06-09 |
WO2014113357A1 (en) | 2014-07-24 |
EA201591123A1 (ru) | 2015-11-30 |
KR20150104572A (ko) | 2015-09-15 |
KR102165434B1 (ko) | 2020-10-14 |
SG10201704716XA (en) | 2017-07-28 |
JP6445459B2 (ja) | 2018-12-26 |
EP2945618A1 (en) | 2015-11-25 |
AU2014207748A1 (en) | 2015-07-09 |
CA2896308A1 (en) | 2014-07-24 |
MX366685B (es) | 2019-07-19 |
MX2015008555A (es) | 2016-01-22 |
EP2945618B1 (en) | 2018-06-13 |
SG11201504778UA (en) | 2015-07-30 |
AU2014207748B2 (en) | 2018-10-11 |
US20150313908A1 (en) | 2015-11-05 |
CA2896308C (en) | 2021-11-09 |
ES2687083T3 (es) | 2018-10-23 |
IL239714A0 (en) | 2015-08-31 |
HK1210424A1 (zh) | 2016-04-22 |
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