JP4156038B2 - ニガウリの経口活性画分、その活性ペプチドおよび糖尿病治療におけるその使用 - Google Patents
ニガウリの経口活性画分、その活性ペプチドおよび糖尿病治療におけるその使用 Download PDFInfo
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/42—Cucurbitaceae (Cucumber family)
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/011—Hydrolysed proteins; Derivatives thereof from plants
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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
- A61P3/08—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
Landscapes
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- Diabetes (AREA)
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- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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| US08/850,855 | 1997-05-02 | ||
| PCT/US1998/006450 WO1998043484A1 (en) | 1997-04-01 | 1998-04-01 | Orally active fraction of momordica charantia, active peptides thereof, and their use in the treatment of diabetes |
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| WO2005063156A1 (en) * | 2003-12-22 | 2005-07-14 | Shear/Kershman Laboratories, Inc. | Oral peptide delivery system with improved bioavailability |
| EP1563842A1 (en) * | 2004-02-03 | 2005-08-17 | Novartis AG | Simarouba amara and/or Momordica charantia extracts for the treatment of coccidiosis in poultry |
| US20070269898A1 (en) * | 2004-09-15 | 2007-11-22 | Yokohama City University | Amino Acid Sequences Essential to Neuron Specific Gene Expression |
| WO2008120240A1 (en) * | 2007-03-30 | 2008-10-09 | Aparna Dixit | Anti diabetic protein |
| US20100081860A1 (en) * | 2008-04-24 | 2010-04-01 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational System and Method for Memory Modification |
| TWI342781B (en) * | 2008-12-01 | 2011-06-01 | Univ China Medical | Blood sugar-modulating polypeptides |
| WO2011032360A1 (zh) * | 2009-09-17 | 2011-03-24 | 中国药科大学 | 苦瓜mc-jj2多肽及其应用与微波促进固相合成方法 |
| WO2011032359A1 (zh) * | 2009-09-17 | 2011-03-24 | 中国药科大学 | 苦瓜mc-jj6多肽及其应用与微波促进固相合成方法 |
| CN101691394B (zh) * | 2009-09-17 | 2012-05-09 | 中国药科大学 | 微波促进固相合成苦瓜mc-jj6多肽类似物及其应用 |
| CN101824075A (zh) * | 2010-05-20 | 2010-09-08 | 中国药科大学 | 微波促进固相合成苦瓜mc-jj0101多肽类似物及其应用 |
| CN101824076A (zh) * | 2010-05-20 | 2010-09-08 | 中国药科大学 | 微波促进固相合成苦瓜mc-jj0105多肽类似物及其应用 |
| CN101942010A (zh) * | 2010-05-20 | 2011-01-12 | 中国药科大学 | 微波促进固相合成苦瓜mc-jj0106多肽类似物及其应用 |
| CN101824074A (zh) * | 2010-05-20 | 2010-09-08 | 中国药科大学 | 微波促进固相合成苦瓜mc-jj0107多肽类似物及其应用 |
| CN101838309A (zh) * | 2010-05-20 | 2010-09-22 | 中国药科大学 | 微波促进固相合成苦瓜mc-jj0102多肽类似物及其应用 |
| CN101824073A (zh) * | 2010-05-20 | 2010-09-08 | 中国药科大学 | 微波促进固相合成苦瓜mc-jj0103多肽类似物及其应用 |
| CN101830969A (zh) * | 2010-05-20 | 2010-09-15 | 中国药科大学 | 微波促进固相合成苦瓜降血糖mc-jj0104多肽类似物及其应用 |
| CN101985644B (zh) * | 2010-10-25 | 2013-06-12 | 邹远东 | 一种苦瓜多肽及其制备方法与应用 |
| ES2621355T3 (es) | 2011-01-28 | 2017-07-03 | Piramal Enterprises Limited | Procedimiento para la preparación de un extracto de Momordica Charantia |
| TWI588153B (zh) | 2012-05-18 | 2017-06-21 | 中國醫藥大學 | 多胜肽、編碼該多胜肽之核酸分子、以及該多胜肽之應用 |
| CN104650198B (zh) * | 2015-02-09 | 2018-05-08 | 武汉华康臣生物科技有限公司 | 三叉黑顶藻中分离的能治疗糖尿病的活性肽及其用途 |
| CN106729606A (zh) * | 2017-01-03 | 2017-05-31 | 河北省农林科学院经济作物研究所 | 苦瓜降糖提取物复合剂及其制备方法 |
| CN107412721B (zh) * | 2017-09-15 | 2020-11-24 | 李玉保 | 一种降血糖苦瓜多肽复方胶囊及其制备方法 |
| CN107412720A (zh) * | 2017-09-15 | 2017-12-01 | 李玉保 | 一种治疗糖尿病的苦瓜多肽复方植物药及其制备方法 |
| CN108707181B (zh) * | 2018-06-14 | 2021-03-12 | 苏秀兰 | 一种抑制肿瘤细胞增殖的苦瓜多肽及其制备方法和应用 |
| CN110755598A (zh) * | 2019-10-25 | 2020-02-07 | 李玉保 | 活化胰岛素及治疗糖尿病的复合苦瓜肽口服药及制备方法 |
| CN112675292B (zh) * | 2021-01-11 | 2021-11-02 | 中食安泓(广东)健康产业有限公司 | 含有益生菌的制剂在治疗疾病中的应用 |
| CN116813700B (zh) * | 2022-11-08 | 2025-01-24 | 苏秀兰 | 一种苦瓜生物活性肽、制备方法及其应用 |
| CN117700489B (zh) * | 2023-12-19 | 2024-08-20 | 深圳泰华赛尔生物科技有限公司 | 脂肪干细胞在治疗糖尿病的药物中的应用 |
| CN119320429B (zh) * | 2024-10-15 | 2025-07-29 | 天津桂芝堂科技有限公司 | 包含乳铁蛋白的药物组合物及在降血脂中的应用 |
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| US3817837A (en) * | 1971-05-14 | 1974-06-18 | Syva Corp | Enzyme amplification assay |
| US3905654A (en) * | 1973-11-14 | 1975-09-16 | Kelsey Hayes Co | Skid control system for dual brake |
| US3945988A (en) * | 1974-07-16 | 1976-03-23 | Pushpa Khann | Process for isolation of insulin from plant source |
| US4043989A (en) * | 1975-09-11 | 1977-08-23 | Syva Company | Oxazepam derivatives for immunoassay reagents |
| US4069105A (en) * | 1977-03-03 | 1978-01-17 | Syva Company | Lidocaine antigens and antibodies |
| US4156081A (en) * | 1977-04-15 | 1979-05-22 | Syva Company | Theophylline antigens and antibodies |
| JPS57106626A (en) * | 1980-12-22 | 1982-07-02 | Teijin Ltd | Cytotoxic protein complex and its preparation |
| US5098710A (en) * | 1987-06-18 | 1992-03-24 | Yaguang Liu | Production of kuguasu |
| US5086043A (en) * | 1987-06-18 | 1992-02-04 | Yaguang Liu | Production of Saponins of Lichi |
| US4985248A (en) * | 1987-06-18 | 1991-01-15 | Yaguang Liu | Pharmaceutical composition containing a safe extracts of fruits and vegetables for the treating and preventing of diabetes |
| ES2128362T3 (es) * | 1991-12-03 | 1999-05-16 | Proteus Molecular Design | Fragmentos de proteinas de prion. |
| US5750361A (en) * | 1995-11-02 | 1998-05-12 | The Regents Of The University Of California | Formation and use of prion protein (PRP) complexes |
-
1998
- 1998-04-01 KR KR10-1999-7008994A patent/KR100509438B1/ko not_active Expired - Fee Related
- 1998-04-01 JP JP54197198A patent/JP4156038B2/ja not_active Expired - Fee Related
- 1998-04-01 CN CN98805001A patent/CN1255044A/zh active Pending
- 1998-04-01 CA CA002285452A patent/CA2285452A1/en not_active Abandoned
- 1998-04-01 WO PCT/US1998/006450 patent/WO1998043484A1/en not_active Ceased
- 1998-04-01 EP EP98914405A patent/EP1005274B1/en not_active Expired - Lifetime
- 1998-04-01 AU AU68765/98A patent/AU749792B2/en not_active Ceased
- 1998-04-01 DE DE69839842T patent/DE69839842D1/de not_active Expired - Fee Related
- 1998-04-01 AT AT98914405T patent/ATE403672T1/de not_active IP Right Cessation
- 1998-04-01 ES ES98914405T patent/ES2310006T3/es not_active Expired - Lifetime
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1005274B1 (en) | 2008-08-06 |
| US6852695B2 (en) | 2005-02-08 |
| DE69839842D1 (de) | 2008-09-18 |
| ES2310006T3 (es) | 2008-12-16 |
| CA2285452A1 (en) | 1998-10-08 |
| AU749792B2 (en) | 2002-07-04 |
| US6127338A (en) | 2000-10-03 |
| CN1255044A (zh) | 2000-05-31 |
| US6391854B1 (en) | 2002-05-21 |
| EP1005274A4 (en) | 2004-09-08 |
| WO1998043484A1 (en) | 1998-10-08 |
| JP2002516608A (ja) | 2002-06-04 |
| AU6876598A (en) | 1998-10-22 |
| EP1005274A1 (en) | 2000-06-07 |
| US20020193310A1 (en) | 2002-12-19 |
| KR20010005917A (ko) | 2001-01-15 |
| KR100509438B1 (ko) | 2005-08-23 |
| ATE403672T1 (de) | 2008-08-15 |
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