CN1158567A - 治疗皮肤病的组合物 - Google Patents
治疗皮肤病的组合物 Download PDFInfo
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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
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/006—Antidandruff preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
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Abstract
本发明涉及一种胆固醇合成抑制剂,可以用于治疗、缓和或预防皮肤病。
Description
发明领域
本发明涉及应用于皮肤表面以改善皮肤状况的组合物领域。本发明提供了用于改善各种皮肤状况特别是痤疮的方法和组合物。发明背景
痤疮是一种毛囊皮脂腺滤泡的慢性炎症,尤其是在面部和颈部,并且绝大多数发生在约14-19岁的青春期。痤疮与皮脂分泌物增加,滤泡管下动脉圆锥角化过度,微生物移生的增加和炎症有关(Strauss,J.S.,J.Dermatol.Treat.(皮肤病治疗杂志),1:3-6(1989))。人们已经提出了多种治疗痤疮和其它皮脂腺炎症的方法,从具体饮食,防止皮肤与已知导致痤疮(acneignic)的制剂(如低级化妆品)接触,到含有孕酮或雌激素及其它激素制剂的使用,但它们中的大多数还未被证明是有效的。此外,人们还建议在表面和全身使用防腐剂,抗菌剂和广谱抗菌化合物。
迄今为止,所有使用的抗痤疮制剂在抑制皮脂腺中微生物种群的发展,角化和粉刺的形成方面都是有效的。然而,迄今为止所用的抗痤疮制剂中仅有少数几个对降低皮脂分泌率有效(Gollnick,H.,J.Dermatol.Treat.(皮肤病治疗杂志),1:S23-S28(1990)),还没有任何制剂被用于控制毛囊皮脂腺单元中脂质的生物合成。
通过甲羟戊酸酯途径可以合成类异戊二烯基团如胆固醇,角鲨烯和胆固醇酯(Goldstein,J.L.,Brown,M.S.,Nature(自然),34B,425(1990)),其中终产物是胆固醇。调节甲羟戊酸酯制备的关键酶,即上述类异戊二烯基团的前体是3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶。这种酶抑制剂抑制了胆固醇的合成,并因此被用作治疗动脉硬化,高血脂以及相关疾病的抗高胆固醇血药物。这种抑制剂的实例有洛伐他汀(MerckIndex 5460,U.S.4,231,938)。含有HMG-CoA还原酶抑制剂的药物组合物可通过口服或非肠道给药的方式用于患有动脉硬化或高血脂病人。
发明概述
我们惊喜地发现,根据本发明通过表面使用胆固醇合成抑制剂可以治疗痤疮。因此,本发明的用途是用胆固醇合成抑制剂治疗多种皮肤病。
本发明提供了用于皮肤表面并含有载体和作为活性成份的有效量的胆固醇合成抑制剂的组合物。
本发明组合物可以是药物组合物或化妆品组合物。
本发明药物组合物可用于多种适应症,包括普通痤疮,牛皮癣,头皮的溢脂性皮炎和saborea。
本发明进一步涉及胆固醇合成抑制剂如HMG-CoA还原酶抑制剂在治疗,缓和或预防皮肤病的表面药物组合物的制备方面的应用。
本发明还提供了改善皮肤状况的方法,包括在皮肤表面使用含有载体和作为活性成份的有效量的胆固醇合成抑制剂的组合物。本方法的具体应用是治疗,缓和或预防痤疮。
术语“有效量”应该被理解为达到所需治疗或预防效果所需的活性成份的平均量。例如,在本发明药物组合物中胆固醇合成抑制剂的有效量是指在治疗方案下该药物组合物的使用范围足以达到改善皮肤状况的用量。
用于本发明的胆固醇合成抑制剂是抑制终产物如胆固醇或甲羟戊酸酯方法之各步中任何中间体产生的各种制剂,其中胆固醇由前体乙酰CoA和乙酰乙酰CoA产生的。该抑制剂可以是各步中抑制酶的抑制剂,或作为隔离中间体的的制剂,这两种制剂都减少该方法所产生的胆固醇的量。
本发明优选的胆固醇合成抑制剂是HMG-CoA还原酶抑制剂如洛伐他汀。
洛伐他汀的浓度优选约0.2-10%,最优选约2%。
该胆固醇合成抑制剂可以与多种其它制剂如抗微生物剂,例如抗菌素,以治疗或预防二次感染,去皮剂,单独或含间苯二酚的全反维生素-A等一起用于皮肤。
本发明组合物的载体可以是任何药物或化妆品可用的载体,例如,乙醇,明胶,脂质体剂型,软膏,油膏等。
实施例:I.组合物的制备
研磨洛伐他汀胶囊(MevacorTM,Merck,U.S.A.),通过用95%乙醇萃取将活性成份从赋形剂中分离并过滤,得到2%洛伐他汀的乙醇溶液。II.临床试验
分别在两个临床试验中测试上述制剂的效率。A.试验1
将如上所述制备药物组合物每天两次表面用于患有普通痤疮的两个人的面部,共12周。试验开始前30天患者需要中断所有其它表面和全身抗痤疮治疗,进行治疗前7天中断一切面部化妆。
在治疗开始之前和开始治疗后4,8和12周通过记录全部痤疮损伤部位,包括红肿的痤疮部位(丘疹和脓疱)和未红肿的痤疮部位(白和黑粉刺)来测定痤疮状况。
两个患者的所有上述痤疮都得到明显改善,而且,在12周的治疗期结束时损伤的数量减少了一半多。可能是由于乙醇的原因,试验对轻度干燥的皮肤没有明显副作用。B.试验2
两男两女4名患者,年龄在16-25岁,患有轻微到中度痤疮,用上述制剂治疗。所有药物和化妆品停用14天,然后要求每名患者使用上述制剂,每天两次,使用8星期。治疗期间禁止采用任何其它形式的治疗和化妆。在治疗前和治疗后4和8周记录痤疮部位(丘疹,脓疱,白和黑粉刺)的数量,结果示于下列表1。表1的结果说明,所有类型的损伤部位数量的减少证明4名患者的情况全部得到改善。
表1治疗前和治疗期间痤疮损伤部位的数量
患者 | 损伤 | 治疗前 | 治疗后1个月 | 治疗后2个月 |
1 | 丘疹脓疱白和黑粉刺 | 101118 | 7310 | 327 |
2 | 丘疹脓疱白和黑粉刺 | 171718 | 151515 | 2106 |
3 | 丘疹脓疱白和黑粉刺 | 71222 | 2714 | -47 |
4 | 丘疹脓疱白和黑粉刺 | 201615 | 18910 | 555 |
平均 | 丘疹脓疱白和黑粉刺 | 131418 | 10812 | 256 |
Claims (14)
1.一种用于皮肤表面的组合物,含有载体和作为活性成份的有效量的胆固醇合成抑制剂。
2.根据权利要求1的组合物,为药物组合物。
3.根据权利要求2的药物组合物,其中胆固醇合成抑制剂是3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂。
4.根据权利要求3的药物组合物,其中抑制剂是洛伐他汀。
5.根据权利要求4的药物组合物,其中洛伐他汀的浓度约为0.2-10%。
6.根据权利要求5的药物组合物,其中洛伐他汀的浓度约为2%。
7.根据上述任一个权利要求中的药物组合物,用于治疗普通痤疮,牛皮癣,头皮的溢脂性皮炎和saborea等皮肤病。
8.根据权利要求7的用于治疗痤疮的药物组合物,包括下列抗痤疮制剂:抗微生物剂,去皮剂或各种retinoeide。
9.胆固醇合成抑制剂用于制备治疗,缓和或预防皮肤病的表面药物组合物的用途。
10.根据权利要求9的用途,其中胆固醇合成抑制剂是3-羟基-3-甲基戊二酰辅酶A还原酶(HMG-CoA还原酶)抑制剂。
11.根据权利要求10的用途,其中抑制剂是洛伐他汀。
12.一种治疗,缓和或预防皮肤病的方法,包括在皮肤表面使用有效药量的胆固醇合成抑制剂。
13.根据权利要求12的方法,其中胆固醇合成抑制剂是3-羟基-3-甲基戊二酰辅酶A还原酶(HMG-CoA还原酶)抑制剂。
14.根据权利要求13的方法,其中抑制剂是洛伐他汀。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL11094394A IL110943A (en) | 1994-09-13 | 1994-09-13 | Compositions comprising an inhibitor of cholesterol synthesis for the treatment of skin disorders |
IL110943 | 1994-09-13 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1158567A true CN1158567A (zh) | 1997-09-03 |
CN1106841C CN1106841C (zh) | 2003-04-30 |
Family
ID=11066547
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN95195041A Expired - Fee Related CN1106841C (zh) | 1994-09-13 | 1995-09-13 | 治疗皮肤病的组合物 |
Country Status (14)
Country | Link |
---|---|
US (1) | US6126947A (zh) |
EP (1) | EP0793489B9 (zh) |
JP (1) | JP4128616B2 (zh) |
KR (1) | KR970705990A (zh) |
CN (1) | CN1106841C (zh) |
AT (1) | ATE321548T1 (zh) |
AU (1) | AU694274B2 (zh) |
BR (1) | BR9509006A (zh) |
CA (1) | CA2199844C (zh) |
DE (1) | DE69534908T2 (zh) |
IL (1) | IL110943A (zh) |
MX (1) | MXPA97001884A (zh) |
RU (1) | RU2159611C2 (zh) |
WO (1) | WO1996008248A1 (zh) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
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EP0738510A3 (fr) * | 1995-04-20 | 2005-12-21 | L'oreal | Utilisation d'un inhibiteur d'HMG-coenzyme A-reductase pour lutter contre le vieillissement de la peau et pour traiter l'acné. Composition comprenant au moins un inhibiteur HMG-coenzyme A reductase et au moins un actif possédant des propriétes desquamantes |
US5840752A (en) * | 1996-11-21 | 1998-11-24 | Henry; James P. | Reduction of hair growth |
FI972040A (fi) * | 1997-05-13 | 1998-11-14 | Nokia Telecommunications Oy | Menetelmä pakettivälitteiseen tiedonsiirtoon |
WO1999056545A1 (en) * | 1998-05-05 | 1999-11-11 | Anwel Saqib R | Hair and skin treatment method and composition |
FR2801508B1 (fr) * | 1999-11-29 | 2003-11-14 | Oreal | Utilisation d'inhibiteurs d'hmg coa-reductase pour le traitement de la seborrhee |
US20020010128A1 (en) * | 2000-04-13 | 2002-01-24 | Parks Thomas P. | Treatment of hyperproliferative, inflammatory and related mucocutaneous disorders using inhibitors of mevalonate synthesis and metabolism |
DE10036798A1 (de) * | 2000-07-28 | 2002-02-07 | Beiersdorf Ag | Mittel zur Behandlung der Haare und der Kopfhaut |
US6699886B2 (en) * | 2001-05-31 | 2004-03-02 | Cellegy Pharmaceuticals, Inc. | Store operated calcium influx inhibitors and methods of use |
US7060729B2 (en) * | 2002-09-05 | 2006-06-13 | Reza Babapour | Composition and method for treating skin |
JP4630065B2 (ja) * | 2002-09-20 | 2011-02-09 | 興和株式会社 | 外用剤 |
ES2481167T3 (es) | 2003-08-22 | 2014-07-29 | Dupont Nutrition Biosciences Aps | Composición que comprende una bacteriocina y un extracto de una planta de la familia Labiatae |
GB2388581A (en) | 2003-08-22 | 2003-11-19 | Danisco | Coated aqueous beads |
EP1731147A4 (en) * | 2004-03-31 | 2010-06-30 | Kowa Co | EXTERNAL PREPARATION |
US7183285B2 (en) * | 2004-04-29 | 2007-02-27 | Pharmix Corp. | Compositions and treatments for inhibiting kinase and/or HMG-CoA reductase |
US20050272770A1 (en) * | 2004-04-29 | 2005-12-08 | John Griffin | Compositions and treatments for inhibiting kinase and/or HMG-CoA reductase |
US20060111436A1 (en) * | 2004-11-23 | 2006-05-25 | John Griffin | Compositions and treatments for modulating kinase and/or HMG-CoA reductase |
US20070015779A1 (en) * | 2005-04-29 | 2007-01-18 | John Griffin | Compositions and treatments for inhibiting kinase and/or hmg-coa reductase |
GB2459922A (en) * | 2008-05-13 | 2009-11-18 | Univ Dundee | Treatment for keratinizing dermatological disorders by reduction in keratin expression |
FR2954124B1 (fr) * | 2009-12-18 | 2012-04-06 | Fabre Pierre Dermo Cosmetique | Utilisation du 2,3-dihydroxypropyl dodecanoate pour le traitement de la seborrhee |
US20120149775A1 (en) * | 2010-11-29 | 2012-06-14 | Shiseido Company, Ltd. | Methods for preventing and improving skin elastic property loss |
US9273192B1 (en) * | 2014-11-06 | 2016-03-01 | George Reck | Method of preventing microbial growth on water treatment dispersant |
EP3355882A1 (en) * | 2015-10-01 | 2018-08-08 | Kythera Biopharmaceuticals, Inc. | Compositions comprising a statin for use in methods of adipolysis |
RU2718904C1 (ru) | 2016-10-24 | 2020-04-15 | Колгейт-Палмолив Компани | Композиции для ухода за полостью рта и способы их применения |
JP2022036341A (ja) * | 2018-10-12 | 2022-03-08 | 学校法人慶應義塾 | 慢性皮膚炎の治療のための医薬組成物 |
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Publication number | Priority date | Publication date | Assignee | Title |
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GB1047235A (zh) * | 1963-09-09 | |||
GB1026927A (en) * | 1964-01-20 | 1966-04-20 | Richardson Merrell Inc | Triphenylhaloethylenes |
US4231938A (en) * | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
GB2081580A (en) * | 1980-08-07 | 1982-02-24 | Anand Chaman Lal | Sapindus trifoliatus extracts |
US4743597A (en) * | 1986-01-27 | 1988-05-10 | Javitt Norman B | Composition comprising an oxygenated cholesterol and use thereof for topical treatment of diseases |
US5075327A (en) * | 1988-08-10 | 1991-12-24 | Hoffmann-La Roche Inc. | Antipsoriatic agents |
CA2040996A1 (en) * | 1990-05-02 | 1991-11-03 | Robert L. Albright | Composition and method for controlling cholesterol |
FR2663850B1 (fr) * | 1990-07-02 | 1994-01-14 | Gird Galderma | Composition pharmaceutique ou cosmetique contenant en association un retinouide et un sterol. |
US5466687A (en) * | 1992-10-22 | 1995-11-14 | Dr. Karl Thomae Gmbh | Arylidene-1-azacycloalkanes and arylalkyl-1-azacyclo-alkanes, their salts, medicaments containing these compounds and their use, and processes for their preparation |
DE4303840A1 (de) * | 1992-10-22 | 1994-08-11 | Thomae Gmbh Dr K | Aryliden-1-azacycloalkane und Arylalkyl-1-azacycloalkane, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
DE4239151A1 (de) * | 1992-11-20 | 1994-05-26 | Thomae Gmbh Dr K | N,N-Disubstituierte Arylcycloalkylamine, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
IL109037A (en) * | 1993-03-19 | 1999-01-26 | Cellegy Pharma Inc | Preparations for causing phase separation of lipid layers and preparation of the above preparations |
US5730992A (en) * | 1994-09-13 | 1998-03-24 | Ramot University Authority For Applied Research And Industrial Development, Ltd. | Compositions for the treatment of skin disorders |
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1994
- 1994-09-13 IL IL11094394A patent/IL110943A/xx not_active IP Right Cessation
-
1995
- 1995-09-13 CN CN95195041A patent/CN1106841C/zh not_active Expired - Fee Related
- 1995-09-13 WO PCT/US1995/011678 patent/WO1996008248A1/en active IP Right Grant
- 1995-09-13 MX MXPA97001884A patent/MXPA97001884A/es active IP Right Grant
- 1995-09-13 AT AT95934980T patent/ATE321548T1/de not_active IP Right Cessation
- 1995-09-13 KR KR1019970701625A patent/KR970705990A/ko not_active Application Discontinuation
- 1995-09-13 DE DE69534908T patent/DE69534908T2/de not_active Expired - Lifetime
- 1995-09-13 BR BR9509006A patent/BR9509006A/pt not_active Application Discontinuation
- 1995-09-13 AU AU37173/95A patent/AU694274B2/en not_active Ceased
- 1995-09-13 CA CA002199844A patent/CA2199844C/en not_active Expired - Fee Related
- 1995-09-13 EP EP95934980A patent/EP0793489B9/en not_active Expired - Lifetime
- 1995-09-13 JP JP51033996A patent/JP4128616B2/ja not_active Expired - Fee Related
- 1995-09-13 RU RU97106064/14A patent/RU2159611C2/ru not_active IP Right Cessation
-
1997
- 1997-10-15 US US08/950,764 patent/US6126947A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CA2199844A1 (en) | 1996-03-21 |
RU2159611C2 (ru) | 2000-11-27 |
JPH10505838A (ja) | 1998-06-09 |
MXPA97001884A (es) | 2004-04-16 |
WO1996008248A1 (en) | 1996-03-21 |
EP0793489A1 (en) | 1997-09-10 |
BR9509006A (pt) | 1998-06-23 |
KR970705990A (ko) | 1997-11-03 |
CN1106841C (zh) | 2003-04-30 |
JP4128616B2 (ja) | 2008-07-30 |
IL110943A (en) | 1997-02-18 |
DE69534908D1 (de) | 2006-05-18 |
DE69534908T2 (de) | 2007-01-25 |
AU694274B2 (en) | 1998-07-16 |
EP0793489A4 (en) | 2001-12-19 |
AU3717395A (en) | 1996-03-29 |
EP0793489B9 (en) | 2006-08-30 |
ATE321548T1 (de) | 2006-04-15 |
CA2199844C (en) | 2007-04-10 |
EP0793489B1 (en) | 2006-03-29 |
US6126947A (en) | 2000-10-03 |
IL110943A0 (en) | 1994-11-28 |
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