CN1126564C - 葡萄提取物的膦脂复合物作为抗动脉粥样硬化剂的应用 - Google Patents
葡萄提取物的膦脂复合物作为抗动脉粥样硬化剂的应用 Download PDFInfo
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- CN1126564C CN1126564C CN98811768A CN98811768A CN1126564C CN 1126564 C CN1126564 C CN 1126564C CN 98811768 A CN98811768 A CN 98811768A CN 98811768 A CN98811768 A CN 98811768A CN 1126564 C CN1126564 C CN 1126564C
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- extracts
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- vitis viniferae
- fructus vitis
- vitis vinifera
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- A—HUMAN NECESSITIES
- 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)
- A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
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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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E50/00—Technologies for the production of fuel of non-fossil origin
- Y02E50/30—Fuel from waste, e.g. synthetic alcohol or diesel
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- Urology & Nephrology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Medicines Containing Plant Substances (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Solid Fuels And Fuel-Associated Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
葡萄提取物的磷脂复合物适用于预防和治动脉粥样硬化的病理状态。
Description
本发明涉及从葡萄提取的、含2~7个儿茶素单元的寡聚原花色素的磷脂复合物在制备用于治疗和预防动脉粥样硬化以及心肌梗死和脑梗塞的药剂方面的应用。
已知葡萄提取物可用于治疗与静脉功能不全相关的心血管病,用于治疗毛细渗透性和抗性降低的疾病以及结瘢。如GB-A-1,541,469或FR-A-2,092,743中所述,这些提取物(它们可得自该植物的籽)是多酚(例如表儿茶素)及其聚合产物(该单体的C-3羟基部分地用棓酸酯化了)的混合物。葡萄提取物的磷脂复合物被描述于US-4,963,527中,现在可以以商标Leucoselect商购。
现已意外地发现了,当***施药(优选通过经口途径)时,按US-4,963,527制备的复合物在动物和人中都产生显著的抗动脉粥样硬化的活性。
更具体地说,发现了从葡萄提取的、含2~7个儿茶素单元的寡聚原花色素的磷脂复合物能以剂量依存关系预防或减少动脉粥样斑块的形成。
这种活性在喂食高胆固醇血的食物(为的是在血管水平,尤其在弓动脉、腹主动脉、颈动脉和脑血管中引起类似于人那样的动脉粥样病斑)的兔中得到了证实。在所述模型中,上述磷脂复合物改变了宏观和微观血管状态,与未处理的动物相比,既减少了动脉粥样斑块的数量又降低了它们的严重程度,获得意外的血管组织效益。在另一动脉粥样硬化模型(为了保护脑)中(其中,通过手术减小了兔颈动脉内的血管腔),随着喂食富含饱和脂肪的高胆固醇血的食物,表现出颈动脉梗阻的减轻、血管壁厚度的减小和动物存活率的增大。此外,在动脉粥样硬化患者中,通过多普勒超声波扫描术鉴定,观测到因动脉粥样化斑引起的颈动脉梗阻的减轻和颈动脉流的改善。
从葡萄提取的原花色素的磷脂复合物可以合适的口服制剂(例如片剂、软或硬明胶胶囊)在50~500mg(每天二至三次)的剂量范围(取决于受治疗的疾病的严重程度)应用。药物制剂的制备可按常规技术和赋形剂进行。
如下实施例更详细地阐述了本发明。
实施例1
3组(每组8只)新西兰兔接受下列处理:1)组:对比组,正常食物2)组:高胆固醇血的食物(0.2%胆固醇)3)组:高胆固醇血的食物+葡萄提取物的磷脂复合物(0.2%胆固醇+2%
Leucoselect(R))。
8周(在此期间测定胆固醇、LDL/VLDL、HDL和甘油三酯含量)后,杀死这些动物。
估测胸主动脉和腹主动脉上动脉粥样硬化损害的数量、尺寸和分布。
固定主动脉条并用苏丹IV染色(以便观察损害),通过气相色谱法估测血管胆固醇和氧化的胆固醇含量。
下表中报导的结果证明了,用葡萄提取物的磷脂复合物处理以统计上显著的方式减少了由高胆固醇血的食物引起的动脉粥样硬化损害。
表处理
损害的面积百分数1组 1%2组 27%3组 5%* *p<0.01,与2组相比
实施例2含500mg葡萄提取物的磷脂复合物的胶囊组成:
葡萄提取物的复合物
(含大豆磷脂酰胆碱) 200mg
乳糖 57mg
改性淀粉 40mg
硬脂酸镁 3,0mg
实施例3
耐胃的(gastro-resistant)片剂
葡萄提取物的复合物
(含大豆磷脂酰胆碱) 250mg
微晶纤维素 118mg
沉淀二氧化硅 3mg
硬脂酸镁 4mg
甲基丙烯酸阴离子聚合物及其酯 12mg
滑石粉 8mg
碳酸镁 8mg
玉米淀粉 5mg
***树胶 159mg
实施例4
软明胶胶囊
葡萄提取物的复合物
(含大豆磷脂酰胆碱) 266mg
花生油 209mg
部分氢化的植物油 100mg
大豆卵磷脂 5mg
Claims (4)
1.从葡萄提取的、含2~7个儿茶素单元的寡聚原花色素的磷脂复合物在制备用于治疗和预防动脉粥样硬化以及心肌梗死和脑梗塞的药剂方面的应用。
2.如权利要求1的应用,其中,所述药剂的单元剂量在50~500mg活性成分的范围内。
3.权利要求1或2的应用,其中,所述药剂被经口给药。
4.权利要求3的应用,其中,所述药剂呈软或硬明胶胶囊或者片剂的形式。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI97A002690 | 1997-12-04 | ||
IT97MI002690A IT1296920B1 (it) | 1997-12-04 | 1997-12-04 | Uso di complessi di estratti vitis vinifera con fosfolipidi come agenti anti-aterosclerotici |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1280498A CN1280498A (zh) | 2001-01-17 |
CN1126564C true CN1126564C (zh) | 2003-11-05 |
Family
ID=11378312
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN98811768A Expired - Fee Related CN1126564C (zh) | 1997-12-04 | 1998-11-30 | 葡萄提取物的膦脂复合物作为抗动脉粥样硬化剂的应用 |
Country Status (23)
Country | Link |
---|---|
US (1) | US6297218B1 (zh) |
EP (1) | EP1035859B1 (zh) |
JP (1) | JP4456267B2 (zh) |
KR (1) | KR100567867B1 (zh) |
CN (1) | CN1126564C (zh) |
AT (1) | ATE258802T1 (zh) |
AU (1) | AU743031B2 (zh) |
BR (1) | BR9805813B1 (zh) |
CA (1) | CA2312795C (zh) |
CZ (1) | CZ299555B6 (zh) |
DE (1) | DE69821524T2 (zh) |
DK (1) | DK1035859T3 (zh) |
ES (1) | ES2214755T3 (zh) |
HK (1) | HK1033267A1 (zh) |
HU (1) | HU228109B1 (zh) |
IT (1) | IT1296920B1 (zh) |
NO (1) | NO324796B1 (zh) |
PL (1) | PL191023B1 (zh) |
PT (1) | PT1035859E (zh) |
RU (1) | RU2207866C2 (zh) |
SI (1) | SI1035859T1 (zh) |
SK (1) | SK284865B6 (zh) |
WO (1) | WO1999029331A1 (zh) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1304183B1 (it) | 1998-12-18 | 2001-03-08 | Indena Spa | Complessi di proantocianidina a2 con fosfolipidi come agentiantiaterosclerotici. |
JP2001122791A (ja) * | 1999-10-20 | 2001-05-08 | Boehringer Ingelheim Internatl Gmbh | 下肢の慢性静脈不全の軽減および予防のための赤色ブドウ樹葉の水性抽出物よりなる食事補強剤 |
JP4574788B2 (ja) | 2000-03-24 | 2010-11-04 | 協和発酵バイオ株式会社 | プロアントシアニジン含有組成物 |
IT1320080B1 (it) * | 2000-10-25 | 2003-11-18 | Giuliani Spa | Composizione per uso farmaceutico o dietetico. |
FR2836337B1 (fr) * | 2002-02-28 | 2004-11-19 | Bio Serae Laboratoires | Utilisation des polymeres procyanidoliques a titre d'agents inhibuteurs des alpha-amylases et application dans des compositions a visees dietetiques |
ATE468847T1 (de) * | 2002-12-31 | 2010-06-15 | Boehringer Ingelheim Int | Filmtablette mit extrakt aus roten weinblättern |
US20040151769A1 (en) * | 2002-12-31 | 2004-08-05 | Boehringer Ingelheim International Gmbh | Film coated tablet containing an extract of red vine leaves |
ITMI20031313A1 (it) * | 2003-06-27 | 2004-12-28 | Indena Spa | Associazioni di agenti vasoprotettori e formulazioni che li contengono. |
EP1550450A1 (en) * | 2003-12-29 | 2005-07-06 | Boehringer Ingelheim International GmbH | Composition comprising an aqueous extract of red vine leaves and a blood circulating-improving agent for the treatment of chronic venous insufficiencies |
RU2367464C2 (ru) | 2004-02-19 | 2009-09-20 | Берингер Ингельхайм Интернациональ Гмбх | Состав для лечения хронических венозных недостаточностей, содержащий водный экстракт листьев красного винограда и противовоспалительное средство |
US20060088617A1 (en) * | 2004-10-23 | 2006-04-27 | Mccurry James M | Chocolate composition and method for benefiting the cardiovascular system |
AT501682A1 (de) | 2005-01-14 | 2006-10-15 | Hermine Dr Engl | Verfahren zur herstellung einer wirkstoffmischung |
EP1837030A1 (en) | 2006-03-09 | 2007-09-26 | INDENA S.p.A. | Phospholipid complexes of curcumin having improved bioavailability |
EP2829277A1 (en) | 2013-07-26 | 2015-01-28 | Natac Biotech, S.L. | Use of a-type proanthocyanidins in treating a mineralocorticoid receptor related disease |
WO2019087084A1 (en) | 2017-11-02 | 2019-05-09 | Eman Biodiscoveries Sd. Bhd. | Extract of orthosiphon stamineus, formulations, and uses thereof |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2092743A1 (en) * | 1970-06-15 | 1972-01-28 | Aquitaine Invest Pharma | Complete extraction of total flavanol gomers from plats -peripheral - venous activity |
GB1541469A (en) * | 1976-12-01 | 1979-02-28 | Inverni Della Beffa Spa | Method of obtaining flavonolic oligomers |
IT1201151B (it) * | 1987-01-14 | 1989-01-27 | Indena Spa | Complessi fosfolipidici con estratti da vitis vinifera,procedimento per la loro preparazione e composizioni che li cntengono |
US5484594A (en) * | 1988-06-28 | 1996-01-16 | Tecnofarmaci S.P.A. | Process for preparing grapeseed extracts enriched in procyanidol oligomers |
FI955691A (fi) * | 1994-11-28 | 1996-05-29 | Suntory Ltd | Lipoproteiini(a):ta alentava aine, kolesterolia alentava aine ja näitä aineita sisältävät lääkkeet |
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1997
- 1997-12-04 IT IT97MI002690A patent/IT1296920B1/it active IP Right Grant
-
1998
- 1998-11-30 PT PT98959890T patent/PT1035859E/pt unknown
- 1998-11-30 RU RU2000114174/14A patent/RU2207866C2/ru not_active IP Right Cessation
- 1998-11-30 KR KR1020007005420A patent/KR100567867B1/ko not_active IP Right Cessation
- 1998-11-30 EP EP98959890A patent/EP1035859B1/en not_active Expired - Lifetime
- 1998-11-30 SI SI9830609T patent/SI1035859T1/xx unknown
- 1998-11-30 HU HU0100522A patent/HU228109B1/hu not_active IP Right Cessation
- 1998-11-30 PL PL340884A patent/PL191023B1/pl not_active IP Right Cessation
- 1998-11-30 CN CN98811768A patent/CN1126564C/zh not_active Expired - Fee Related
- 1998-11-30 AT AT98959890T patent/ATE258802T1/de active
- 1998-11-30 WO PCT/EP1998/007662 patent/WO1999029331A1/en active IP Right Grant
- 1998-11-30 DK DK98959890T patent/DK1035859T3/da active
- 1998-11-30 ES ES98959890T patent/ES2214755T3/es not_active Expired - Lifetime
- 1998-11-30 CA CA002312795A patent/CA2312795C/en not_active Expired - Fee Related
- 1998-11-30 AU AU15627/99A patent/AU743031B2/en not_active Ceased
- 1998-11-30 JP JP2000524000A patent/JP4456267B2/ja not_active Expired - Fee Related
- 1998-11-30 SK SK827-2000A patent/SK284865B6/sk not_active IP Right Cessation
- 1998-11-30 CZ CZ20002038A patent/CZ299555B6/cs not_active IP Right Cessation
- 1998-11-30 DE DE69821524T patent/DE69821524T2/de not_active Expired - Lifetime
- 1998-12-29 BR BRPI9805813-4A patent/BR9805813B1/pt not_active IP Right Cessation
-
2000
- 2000-05-31 US US09/580,906 patent/US6297218B1/en not_active Expired - Lifetime
- 2000-06-02 NO NO20002827A patent/NO324796B1/no not_active IP Right Cessation
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2001
- 2001-06-08 HK HK01103945A patent/HK1033267A1/xx not_active IP Right Cessation
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