CN1099286C - 福斯高林在制备治疗酒精成瘾的药物中的应用 - Google Patents
福斯高林在制备治疗酒精成瘾的药物中的应用 Download PDFInfo
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- CN1099286C CN1099286C CN96194036A CN96194036A CN1099286C CN 1099286 C CN1099286 C CN 1099286C CN 96194036 A CN96194036 A CN 96194036A CN 96194036 A CN96194036 A CN 96194036A CN 1099286 C CN1099286 C CN 1099286C
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- 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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
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Abstract
本发明涉及福斯高林和含有福斯高林的提取物在治疗酒精成瘾中的应用。
Description
本发明涉及治疗酒精成瘾的药物组合物,其特征在于它们含有作为有效成分的福斯高林或含它的提取物。
酒精滥用和酒精成瘾是可以统称为酒精中毒的现象,它代表整个现代社会一种严重的难题(Gessa G.L.,
Bisogno compulsivo di bere e “principio del piacere”[对饮酒的强迫需要和快乐原则],Medicinadelle tossicodipendenze[药物成瘾医学]II,5(1994))。例如,在意大利重度酗酒者超过人口的9%(大约为5百万人),并且酒精成瘾者超过1百万(Calamo-Specchia F.P.,
Epidemiologia dell alcolismo in Italia[意大利酒精中毒的流行病学],Atti del VII Congresso Nazionaledella S.I.A.[第7届S.I.A.全国大会记录]Mediserve,罗马,295-301,(1991))。如果考虑到诸如美国等国家,这些数字更高,在美国酒精成瘾者超过1千3百万。酒精滥用和酒精成瘾可导致社会资金的巨大浪费(最近报道,自1991年以来在美国每年花费大约200,000,000,000美元),并且还可引起所卷入的个体巨大的社会和心理损害。
除了那些心理本性疗法(群体疗法等),现存治疗酒精中毒的方法在于使用诸如戒酒硫和氨基甲酸钙的药物,它们在每次饮酒出现各种不需要的现象的时候对酒精的代谢起作用,抑制肝脏醛脱氢酶,由此升高血的乙醛水平。
按照本领域目前的状况,衍生物已经用于治疗酒精中毒的唯一植物是葛根(葛根),它在中医中广泛应用,并构成专利申请WO 93/00896的主题。
现在已经惊喜的发现福斯高林可成功地用于减少酒精和其他可引起成瘾的药物的自主消耗。
福斯高林,即17-β-乙酰氧基-8,13-环氧-1α,6β,9α-三羟基化-14-环-11-酮,其式为:它是从产于印度的植物Coleus forskohlii中分离的一种双萜,它可激活腺苷酸环化酶。
De Souza和Shah在《经济和药用植物研究》第2卷,H.Wagner,H.Hihiho和N.Farusuworth等,学术出版社,1988中描述了它的药理学活性。
已知福斯高林可用于治疗心血管和呼吸系疾病以及青光眼;例如在一篇综述中可见到上面的引证;如Seamon和Daly在Adv.Cycli Nucleotide Res.20,1中所述。
应用称为“撒丁岛酒精偏爱”(Sp)系的消耗酒精鼠对酒精消耗的抑制作用进行测定(Fadda F.,Mosca E.,Colombo G.,Gessa G.L.,酒精偏爱鼠:乙醇诱导的多巴胺代谢的刺激作用的遗传敏感性,Physiol.Behav.47,727(1990))。
在最近这些年中,已经成功地应用这些动物对不同物质对酒精自主消耗的作用进行了测定,使它们在酒精和水消耗之间进行自由选择,每天每公斤体重给6至7g酒精(水对酒精的比例大于2∶1);例如,见:BalakleevskyA.,Colombo G.,Fadda F.,Gessa G.L.在
《Ro19-4603,一种苯并二氮 杂卓受体反兴奋剂可减小选择性喂养的对高酒精偏爱的鼠自主酒精消 耗》,Alcohol Alcohol.25,449-452(1990)中以及Fadda F.,GarauB.,Colombo G.,Gessa G.L.在
《伊拉地平和其他钙通道拮抗剂减小酒精 偏爱鼠的酒精消耗》,酒精中毒:临床和实验研究16(3),449-452(1992)中所述。
将这些动物保持在正常的喂养条件下,在水(总是存在)和酒精(一种10%v/v的溶液)之间对它们进行自由选择,其中酒精一天供给4小时(即:在白天/夜晚循环中,黑暗的头4小时)。在每天的同一时间记录所消耗的水和酒精的量。任意供给食物。一旦酒精和水的消耗稳定下来,则口服给予溶解在二甲亚砜中剂量为50mg/kg的福斯高林,其给药的容积量为2ml/kg,一天一次,连续7天。相同量的载体作为对照。在治疗末记录酒精和水的消耗,直到重建治疗前所记录的值。
附图1A显示50mg/kg福斯高林重复口服给药对酒精消耗的影响;附图1B显示对水的影响。
从附图1的实验中可以得到这样的结论,福斯高林可明显地减小酒精消耗。此酒精消耗的减小保持不变,这样直到第7天,然后随着治疗的中止,此减小出现倒退。而且还惊奇地注意到,这种趋势伴随着水消耗逐渐升高的趋势,好象此动物用水代替了酒精。此后者的观察特别重要,这是因为它表明用所实验的产物进行的治疗被极好的耐受,并且动物在没有任何困难的情况下,通过用水代替酒精返回到一种更加生理化的生活周期。
因此本发明所提供的药物组合物可进行口服给药,并且含有作为有效成分的福斯高林。除了常用的赋形剂或载体,本发明的组合物可含有大约10至500mg的这种有效成分。实施例1 香粉制剂每2,300mg香粉含有:福斯高林 100mg蔗糖 2,000mg麦芽糊精 110mg柠檬酸 30mg桔橙香料 40mg氢化植物油 20mg实施例2 药片制剂每100mg片剂含有:福斯高林 25mg微晶纤维素 25mg乳糖 37mg胶体硅 1mg交联羧基甲基纤维素钠 6mg聚乙烯吡咯烷酮 5mg硬脂酸镁 1mg
Claims (1)
1.福斯高林在制备治疗酒精成瘾的药物中的应用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI951023A IT1275436B (it) | 1995-05-19 | 1995-05-19 | Uso della forskolina e di estratti che la contengono per il trattamento della alcol-dipendenza |
ITMI95A001023 | 1995-05-19 |
Publications (2)
Publication Number | Publication Date |
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CN1184422A CN1184422A (zh) | 1998-06-10 |
CN1099286C true CN1099286C (zh) | 2003-01-22 |
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Application Number | Title | Priority Date | Filing Date |
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CN96194036A Expired - Fee Related CN1099286C (zh) | 1995-05-19 | 1996-05-09 | 福斯高林在制备治疗酒精成瘾的药物中的应用 |
Country Status (18)
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US (1) | US5902823A (zh) |
EP (1) | EP0825859B1 (zh) |
JP (1) | JP3001641B2 (zh) |
KR (1) | KR100423486B1 (zh) |
CN (1) | CN1099286C (zh) |
AT (1) | ATE215368T1 (zh) |
AU (1) | AU697449B2 (zh) |
CA (1) | CA2221592C (zh) |
DE (1) | DE69620394T2 (zh) |
DK (1) | DK0825859T3 (zh) |
ES (1) | ES2175099T3 (zh) |
HK (1) | HK1005651A1 (zh) |
HU (1) | HU223474B1 (zh) |
IT (1) | IT1275436B (zh) |
NO (1) | NO316054B1 (zh) |
PT (1) | PT825859E (zh) |
RU (1) | RU2183455C2 (zh) |
WO (1) | WO1996036332A1 (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CA2298142C (en) | 1997-07-30 | 2005-07-12 | Indena S.P.A. | Soya extract, process for its preparation and pharmaceutical composition |
EP1645272A3 (en) * | 1998-05-12 | 2008-11-05 | The Endowment For Research In Human Biology, Inc. | Daidzin derivatives for the treatment of alcohol dependence or alcohol abuse |
US20060122261A1 (en) * | 2003-11-20 | 2006-06-08 | Muhammed Majeed | [method of preparing labdane diterpene composition, preferably isoforskolin and deacetylforskolin from forskolin extract and their use for promoting lean body mass and other applications] |
US20100144885A1 (en) * | 2006-09-29 | 2010-06-10 | The Board Of Trustees Of The University Of Illinois | Histone acetyl transferase activators and histone deacetylase inhibitors in the treatment of alcoholism |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5366990A (en) * | 1991-11-14 | 1994-11-22 | Reid Larry D | Method for treating alcohol abuse and alcoholism |
US5371104A (en) * | 1989-03-08 | 1994-12-06 | Feigenbaum; Jeffery J. | Compositions containing forskolin |
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Publication number | Priority date | Publication date | Assignee | Title |
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US4120975A (en) * | 1976-08-26 | 1978-10-17 | Fisons Limited | Method of psychiatric conditions |
US4782082A (en) * | 1982-12-27 | 1988-11-01 | Schering Corporation | Method for treating allergic reactions with Forskolin |
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1995
- 1995-05-19 IT ITMI951023A patent/IT1275436B/it active IP Right Grant
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1996
- 1996-05-09 AT AT96919731T patent/ATE215368T1/de not_active IP Right Cessation
- 1996-05-09 WO PCT/EP1996/001952 patent/WO1996036332A1/en active Search and Examination
- 1996-05-09 RU RU97120756/14A patent/RU2183455C2/ru active
- 1996-05-09 DK DK96919731T patent/DK0825859T3/da active
- 1996-05-09 US US08/952,472 patent/US5902823A/en not_active Expired - Fee Related
- 1996-05-09 KR KR1019970708221A patent/KR100423486B1/ko not_active IP Right Cessation
- 1996-05-09 AU AU58163/96A patent/AU697449B2/en not_active Ceased
- 1996-05-09 CA CA002221592A patent/CA2221592C/en not_active Expired - Fee Related
- 1996-05-09 HU HU9801236A patent/HU223474B1/hu not_active IP Right Cessation
- 1996-05-09 ES ES96919731T patent/ES2175099T3/es not_active Expired - Lifetime
- 1996-05-09 EP EP96919731A patent/EP0825859B1/en not_active Expired - Lifetime
- 1996-05-09 JP JP8534525A patent/JP3001641B2/ja not_active Expired - Fee Related
- 1996-05-09 PT PT96919731T patent/PT825859E/pt unknown
- 1996-05-09 DE DE69620394T patent/DE69620394T2/de not_active Expired - Fee Related
- 1996-05-09 CN CN96194036A patent/CN1099286C/zh not_active Expired - Fee Related
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1997
- 1997-11-10 NO NO19975155A patent/NO316054B1/no not_active IP Right Cessation
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1998
- 1998-06-03 HK HK98104794A patent/HK1005651A1/xx not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5371104A (en) * | 1989-03-08 | 1994-12-06 | Feigenbaum; Jeffery J. | Compositions containing forskolin |
US5366990A (en) * | 1991-11-14 | 1994-11-22 | Reid Larry D | Method for treating alcohol abuse and alcoholism |
Non-Patent Citations (1)
Title |
---|
LIFE SCIENCE,VOL.42,NO.6,1988 1988-01-01 SZABO"Forkolin promotes the development of ethanol tolerance in 6-hydroxydopam-ine-treated mice" * |
Also Published As
Publication number | Publication date |
---|---|
CA2221592C (en) | 2002-07-09 |
CN1184422A (zh) | 1998-06-10 |
ES2175099T3 (es) | 2002-11-16 |
JP3001641B2 (ja) | 2000-01-24 |
KR19990014876A (ko) | 1999-02-25 |
NO316054B1 (no) | 2003-12-08 |
IT1275436B (it) | 1997-08-07 |
JPH11500738A (ja) | 1999-01-19 |
ITMI951023A0 (it) | 1995-05-19 |
EP0825859A1 (en) | 1998-03-04 |
DE69620394T2 (de) | 2002-10-02 |
ITMI951023A1 (it) | 1996-11-19 |
NO975155D0 (no) | 1997-11-10 |
WO1996036332A1 (en) | 1996-11-21 |
HK1005651A1 (en) | 1999-01-22 |
US5902823A (en) | 1999-05-11 |
AU5816396A (en) | 1996-11-29 |
HUP9801236A3 (en) | 2001-09-28 |
HUP9801236A2 (hu) | 2000-06-28 |
NO975155L (no) | 1997-11-10 |
HU223474B1 (hu) | 2004-07-28 |
DK0825859T3 (da) | 2002-07-29 |
PT825859E (pt) | 2002-08-30 |
RU2183455C2 (ru) | 2002-06-20 |
DE69620394D1 (de) | 2002-05-08 |
AU697449B2 (en) | 1998-10-08 |
CA2221592A1 (en) | 1996-11-21 |
ATE215368T1 (de) | 2002-04-15 |
KR100423486B1 (ko) | 2004-06-05 |
EP0825859B1 (en) | 2002-04-03 |
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