CN1076967C - 使用屈洛昔芬治疗心血管疾病 - Google Patents

使用屈洛昔芬治疗心血管疾病 Download PDF

Info

Publication number
CN1076967C
CN1076967C CN95194200A CN95194200A CN1076967C CN 1076967 C CN1076967 C CN 1076967C CN 95194200 A CN95194200 A CN 95194200A CN 95194200 A CN95194200 A CN 95194200A CN 1076967 C CN1076967 C CN 1076967C
Authority
CN
China
Prior art keywords
droloxifene
citrate
treatment
acid
disease
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN95194200A
Other languages
English (en)
Other versions
CN1153473A (zh
Inventor
罗兰·洛瑟
迈克尔·施里埃克
戴维·D·汤普森
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Inc
Original Assignee
Pfizer Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pfizer Inc filed Critical Pfizer Inc
Publication of CN1153473A publication Critical patent/CN1153473A/zh
Application granted granted Critical
Publication of CN1076967C publication Critical patent/CN1076967C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • 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
    • 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
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Vascular Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

使用屈洛昔芬治疗心血管疾病。

Description

使用屈洛昔芬治疗心血管疾病
这是1994年7月19日递交的美国专利申请流水号08/276,969的部分继续申请。
本发明涉及治疗心血管疾病的药物，其包含作为活性成分的具有如下化学式的屈洛昔芬：或其药学上可接受的盐。
屈洛昔芬是美国专利5,047,431公开的一种已知化合物，在该专利中，屈洛昔芬是一种抗肿瘤药物，尤其是用于乳腺癌的治疗和防治。屈洛昔芬对由于雌激素或类似物缺乏引起的骨骼疾病的缓解也很有用，该病在妇女绝经或子宫切除后比较常见。美国专利5,254,594。
在Gill-Sharma等人，J.Reproduction and Fertility(1993)99，395中公开了使用200和400毫克/千克/天的它莫西芬减少了雄性鼠的睾丸和第二性器官的重量。
Neubauer等人，The Prostate 23：245(1993)报道了雷洛昔芬治疗雄性鼠可导致腹侧的前列腺的退化。
本发明提供了治疗哺乳动物的选自心血管疾病或血胆固醇过高的症状或疾病的方法，包括给药于所述哺乳动物一定量的有效治疗所述症状或疾病的屈洛昔芬或其药学上可接受的盐。
制备屈洛昔芬(1-[4′-(2-二甲基氨基乙氧基)苯基]-1-(3′-羟苯基)-2-苯基丁-1-烯)及其药学上可接受的盐的方法记载于美国专利5,047,431，在此引入本文作为参考。
在本说明书中，“前列腺疾病”表示良性前列腺增生或前列腺癌。“心血管疾病”表示血胆固醇过高或动脉粥样硬化。“治疗”表示对疾病或病症的症状的治愈、减轻或防止疾病的发生。
本发明用于心血管疾病、血胆固醇过高或动脉粥样硬化的药物包括作为活性成分的屈洛昔芬及其盐。屈洛昔芬的药学上可接受的盐是那些常用的无毒类型的盐，例如有机酸(如甲酸、乙酸、柠檬酸、马来酸、酒石酸、甲磺酸、苯磺酸和甲苯磺酸)的盐，无机酸(如盐酸、氢溴酸、硫酸或磷酸)的盐，以及氨基酸(如天冬氨酸或谷氨酸)的盐。这些盐可以由本领域熟练化学师用公知的方法来制备。
本发明的用于疾病和病症的药物可以口服或非肠道给药于包括人的动物，制剂可以采用常规剂型，例如胶囊剂、微胶囊剂、片剂、颗粒剂、粉剂、锭剂、丸剂、栓剂、注射液、悬浮液和糖浆。
本发明用于疾病或病症的药物可以由常用方法来制备，使用常规的有机或无机添加剂，例如赋形剂(如蔗糖、淀粉、甘露糖醇、山梨醇、乳糖、葡萄糖、纤维素、滑石粉、磷酸钙或碳酸钙)，粘合剂(如纤维素、甲基纤维素、羟甲基纤维素、聚丙基吡咯烷酮、聚乙烯基吡咯烷酮、明胶、阿拉伯胶、聚乙二醇、蔗糖或淀粉)，分解剂(如淀粉、羧甲基纤维素、羟丙基淀粉、低级取代的羟丙基纤维素、碳酸氢钠、磷酸钙或柠檬酸钙)，润滑剂(如硬脂酸镁、轻质无水硅酸、滑石粉或月桂基硫酸钠)，矫味剂(如柠檬酸、甲醇、甘氨酸或橘子粉)，防腐剂(如苯甲酸钠、亚硫酸氢钠、对羟基苯甲酸甲酯或对羟基苯甲酸丙酯)，稳定剂(如柠檬酸、柠檬酸钠或乙酸)，悬浮剂(如甲基纤维素、聚乙烯基吡咯烷酮或硬脂酸铝)，分散剂(如羟丙基甲基纤维素)，稀释剂(如水)和基质蜡(如可可油、白凡士林或聚乙二醇)。在医药组合物中，活性成分可以为达到所需治疗效果的量，例如，口服和非肠道给药的单剂含量为1～100毫克。
活性成分每单剂含0.25-100毫克，通常每天对病人给药一到四次，但是上述剂量可以根据病人年龄、体重、病情和给药方式适当有所变化。优选每天一剂。
以下实施例用于说明本发明，而非限定本发明的权利要求书的保护范围。
实施例1
对前列腺重量的影响
三月龄雄性Sprague-Dawley鼠，14天内每天皮下注射给药赋形剂(水中10％乙醇)、雌二醇(30微克/公斤)、睾酮(1毫克/公斤)或屈洛昔芬的柠檬酸盐(10毫克/公斤)(n＝6/组)。14天后处死动物，取出前列腺并称量其湿重。测定平均重量并且用Student试验法确定相对于赋形剂治疗组的统计学显著性(p＜0.05)。
与赋形剂组比较，10毫克/公斤/天的屈洛昔芬的柠檬酸盐显著降低了前列腺的重量(p＜0.05)。睾酮组没有效果，而30微克/公斤的雌激素显著地降低了前列腺的重量。
这些数据表明屈洛昔芬的柠檬酸盐在治疗良性前列腺肥大和前列腺癌方面是有用的。
实施例2
对总胆固醇水平的影响
本发明的化合物对血浆中总胆固醇水平的影响采用以下方法测定。麻醉的4-6月龄的雌性Sprague-Dawley鼠被双侧卵巢切除，用屈洛昔芬的柠檬酸盐(5毫克/公斤/天，口服)或赋形剂处理28天，或做假性手术，血样即从这些鼠心脏刺孔获取。血样置于含30微升5％EDTA中(10微升EDTA/1毫升血)。在20℃2500rpm转速下离心后，移出血浆并在-20℃下保存至分析。总胆固醇的分析采用标准酶测定药盒，该药盒来自Sigma Diagnostic，P.O.Box 14508，St.Louis MO 61378(Procedure No.352)。下表表明了屈洛昔芬的柠檬酸盐对总胆固醇的影响。当服用屈洛昔芬的柠檬酸盐后(5mg/kg/天，28天，口服)，血浆总胆固醇显著下降(相对于赋形剂处理的卵巢切除鼠降低30％)。
        屈洛昔芬的柠檬酸盐对雌性鼠血浆总胆固醇水平的影响
血浆胆固醇(mg/dl) 变化％，相对于假性手术＋赋形剂组 变化％，相对于卵巢切除＋赋形剂组
假性手术＋赋形剂组     57       -       -
卵巢切除＋赋形剂组    112    96     -
屈洛昔芬的柠檬酸盐(5mg/kg/天，28天，口服)    78    +36    -30
对雄性Sprague-Dawley鼠(3月龄)进行同样的试验，用赋形剂和屈洛昔芬的柠檬酸盐(10毫克/公斤/天，14天，口服)治疗处理假性手术和睾丸切除的鼠。如下表所示，屈洛昔芬的柠檬酸盐显著降低了血浆总胆固醇，相对于假性手术组降低48％，相对于睾丸切除的赋形剂处理的动物降低59％。
        屈洛昔芬的柠檬酸盐对雄性鼠血浆总胆固醇水平的影响
血浆胆固醇(mg/dl) 变化％，假性手术＋赋形剂组 变化％，睾丸切除＋赋形剂组
假性手术＋赋形剂组     72     -     -
睾丸切除＋赋形剂组     91     -     -
屈洛昔芬的柠檬酸盐(10mg/kg/天，14天，口服)     37     -48     -59
这些数据表明屈洛昔芬的柠檬酸盐在治疗例如血胆固醇过高和动脉粥样硬化的心血管疾病方面是有效的。
实施例3
                    屈洛昔芬的柠檬酸盐片剂
屈洛昔芬的柠檬酸盐        100克
乳糖                      1190克
低级取代的羟丙基纤维素    250克
聚乙烯基吡咯烷酮          50克
硬脂酸镁                  10克
上述所列成分采取常用方法混合，如此所得混合物压成10,000片，每片含活性成分屈洛昔芬柠檬酸盐10毫克。

Claims (2)

1、屈洛昔芬或其药学可接受盐在制备治疗或预防哺乳动物所患的动脉粥样硬化或血胆固醇过高的药物中的应用。
2、权利要求1的应用，其中，所述药学可接受盐为柠檬酸盐。
CN95194200A 1994-07-19 1995-05-26 使用屈洛昔芬治疗心血管疾病 Expired - Fee Related CN1076967C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/276,969 1994-07-19
US08/276,969 US5441986A (en) 1994-07-19 1994-07-19 Estrogen agonists as remedies for prostate and cardiovascular diseases

Publications (2)

Publication Number Publication Date
CN1153473A CN1153473A (zh) 1997-07-02
CN1076967C true CN1076967C (zh) 2002-01-02

Family

ID=23058874

Family Applications (2)

Application Number Title Priority Date Filing Date
CN95194196A Pending CN1152868A (zh) 1994-07-19 1995-05-26 使用屈洛昔芬治疗前列腺疾病、子宫内膜异位和肥胖症
CN95194200A Expired - Fee Related CN1076967C (zh) 1994-07-19 1995-05-26 使用屈洛昔芬治疗心血管疾病

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN95194196A Pending CN1152868A (zh) 1994-07-19 1995-05-26 使用屈洛昔芬治疗前列腺疾病、子宫内膜异位和肥胖症

Country Status (17)

Country Link
US (4) US5441986A (zh)
EP (3) EP0771194A1 (zh)
JP (2) JP2930424B2 (zh)
KR (2) KR100221854B1 (zh)
CN (2) CN1152868A (zh)
AU (2) AU689257B2 (zh)
CA (2) CA2195093C (zh)
FI (2) FI970215A0 (zh)
HK (1) HK1000697A1 (zh)
HU (2) HUT77392A (zh)
IL (2) IL114585A (zh)
MX (2) MX9700534A (zh)
MY (1) MY113079A (zh)
NZ (2) NZ285159A (zh)
TW (1) TW403649B (zh)
WO (2) WO1996002243A1 (zh)
ZA (2) ZA955964B (zh)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6515009B1 (en) 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5811447A (en) 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6395494B1 (en) * 1993-05-13 2002-05-28 Neorx Corporation Method to determine TGF-β
US5770609A (en) 1993-01-28 1998-06-23 Neorx Corporation Prevention and treatment of cardiovascular pathologies
US6251920B1 (en) 1993-05-13 2001-06-26 Neorx Corporation Prevention and treatment of cardiovascular pathologies
US6491938B2 (en) 1993-05-13 2002-12-10 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5595722A (en) 1993-01-28 1997-01-21 Neorx Corporation Method for identifying an agent which increases TGF-beta levels
WO1996040098A2 (en) 1995-06-07 1996-12-19 Neorx Corporation Prevention and treatment of cardiovascular pathologies with tamoxifen analogues
US5441986A (en) * 1994-07-19 1995-08-15 Pfizer Inc. Estrogen agonists as remedies for prostate and cardiovascular diseases
US5733937A (en) * 1996-02-28 1998-03-31 Pfizer Inc. Methods for alleviating symptoms of premenstrual syndrome and late luteal phase dysphoric disorder
US5985932A (en) * 1996-02-28 1999-11-16 Pfizer Inc Inhibition of autoimmune diseases
IL120269A0 (en) * 1996-02-28 1997-06-10 Pfizer 1,1,2-triphenylbut-1-ene derivatives for treating Alzheimer's disease
US5719190A (en) * 1996-02-28 1998-02-17 Pfizer Inc. Inhibition of myeloperoxidase activity
IL120268A0 (en) * 1996-02-28 1997-06-10 Pfizer Use of (E)-1-[4'-(2-alkylaminoethioxy)phenyl]1-(3'-hydroxyphenyl)-2-phenylbut-1-enes in inhibiting pathological conditions
IL120262A (en) * 1996-02-28 2001-01-28 Pfizer Droloxifene and derivatives thereof for use in increasing serum testosterone levels
US5726207A (en) * 1996-02-28 1998-03-10 Pfizer Inc. Protection of ischemic myocardium against reperfusion damage
IL120263A0 (en) * 1996-02-28 1997-06-10 Pfizer Combination therapy to prevent bone loss-progesterone and estrogen agonists
IL120266A (en) 1996-02-28 2005-05-17 Pfizer Use of estrogen antagonists and estrogen agonists in the preparation of medicaments for inhibiting pathological conditions
TW442286B (en) * 1996-02-28 2001-06-23 Pfizer New therapeutic uses of estrogen agonists
IL120270A0 (en) * 1996-02-28 1997-06-10 Pfizer Combination therapy to treat osteoporosis
US6069175A (en) * 1996-11-15 2000-05-30 Pfizer Inc. Estrogen agonist/antagonists treatment of atherosclerosis
US6114395A (en) * 1996-11-15 2000-09-05 Pfizer Inc. Method of treating atherosclerosis
US6034102A (en) * 1996-11-15 2000-03-07 Pfizer Inc Atherosclerosis treatment
WO1998046588A2 (en) * 1997-04-11 1998-10-22 Neorx Corporation Compounds and therapies for the prevention of vascular and non-vascular pathologies
US20040092602A1 (en) * 1998-05-07 2004-05-13 Steiner Mitchell S. Method for treatment and chemoprevention of prostate cancer
US6413533B1 (en) * 1998-05-07 2002-07-02 The University Of Tennessee Research Corporation Method for chemoprevention of prostate cancer
US20040186185A1 (en) * 1998-05-07 2004-09-23 Steiner Mitchell S. Method for treatment and chemoprevention of prostate cancer
FI982733A (fi) * 1998-12-17 2000-06-18 Orion Yhtymae Oyj Trifenyylietyleeniantiestrogeenien liukoisia koostumuksia
CZ20013912A3 (cs) 1999-05-04 2002-05-15 Strakan Limited Androgen glykosid, sloučenina, testosteron-ß-D-glukosid, 5 alfa-Dihydrotestosteron- 17ß-D-glukosid, farmaceutický prostředek a pouľití sloučeniny
TWI359015B (en) * 1999-07-06 2012-03-01 Endorech Inc Pharmaceutical composition for treatment or preve
TW593256B (en) 1999-11-16 2004-06-21 Hormos Medical Oy Ltd Triphenylalkene derivatives and their use as selective estrogen receptor modulators
CO5271709A1 (es) 2000-01-12 2003-04-30 Pfizer Prod Inc Composiciones y procedimientos para el y tratamiento de afecciones que responden a estrogenos
US20080249183A1 (en) * 2001-11-29 2008-10-09 Steiner Mitchell S Treatment of androgen-deprivation induced osteoporosis
US20040248989A1 (en) 2003-06-05 2004-12-09 Risto Santti Method for the treatment or prevention of lower urinary tract symptoms
US20060270641A1 (en) * 2005-05-31 2006-11-30 Steiner Mitchell S Method for chemoprevention of prostate cancer
MX2008014825A (es) * 2006-05-22 2008-12-01 Hormos Medical Ltd Moduladores selectivos del receptor de estrogeno o inhibidores de aromatasa para tratar prostatitis cronica no bacteriana.
KR101510646B1 (ko) * 2007-02-14 2015-04-10 호르모스 메디칼 리미티드 치료적으로 유용한 트리페닐부텐 유도체의 제조 방법
US7504530B2 (en) * 2007-02-14 2009-03-17 Hormos Medical Ltd. Methods for the preparation of fispemifene from ospemifene
US9321712B2 (en) 2012-10-19 2016-04-26 Fermion Oy Process for the preparation of ospemifene

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5047431A (en) * 1980-12-11 1991-09-10 Klinge Pharma Gmbh & Co. 1,1,2-triphenylbut-1-ene derivatives

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3323321A1 (de) * 1983-06-24 1985-01-03 Schering AG, 1000 Berlin und 4709 Bergkamen Prophylaxe und therapie von koronaren herzkrankheiten durch senkung des oestrogenspiegels
US5262319A (en) * 1985-04-19 1993-11-16 Oncogene Science, Inc. Method for obtaining bone marrow free of tumor cells using transforming growth factor β3
FR2619383B1 (fr) * 1987-08-12 1989-12-08 Inst Vaisseaux Sang Proteine a activite vasculaire, derivee des monocytes et ses analogues, procede pour son extraction et leurs utilisations en therapeutique et pour la preparation d'anticorps
JPH04312526A (ja) * 1991-04-09 1992-11-04 Fujisawa Pharmaceut Co Ltd 骨疾患治療剤
DE4401554A1 (de) * 1993-02-16 1994-08-18 Freund Andreas Präparat zur Therapie und Prophylaxe von Erkrankungen, die bei Imbalancen von Plasmalipiden auftreten
US5455275A (en) * 1994-05-11 1995-10-03 Eli Lilly And Company Methods for inhibiting endometriosis and uterine fibroid disease with 1,1,2-triphenylbut-1-ene derivatives
US5426123A (en) * 1994-05-11 1995-06-20 Eli Lilly And Company Method for lowering serum cholesterol with 1,1,2-triphenylbut-1-ene derivatives
US5384332A (en) * 1994-05-11 1995-01-24 Eli Lilly And Company Methods for inhibiting aortal smooth muscle cell proliferation and restenosis with 1,1,2-triphenylbut-1-ene derivatives
US5441986A (en) * 1994-07-19 1995-08-15 Pfizer Inc. Estrogen agonists as remedies for prostate and cardiovascular diseases

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5047431A (en) * 1980-12-11 1991-09-10 Klinge Pharma Gmbh & Co. 1,1,2-triphenylbut-1-ene derivatives

Also Published As

Publication number Publication date
AU2417095A (en) 1996-02-16
NZ285158A (en) 2000-07-28
CA2195213C (en) 2000-03-14
EP1029540A2 (en) 2000-08-23
US5827892A (en) 1998-10-27
HUT77392A (hu) 1998-04-28
FI970214A (fi) 1997-01-17
EP0769941A1 (en) 1997-05-02
AU689257B2 (en) 1998-03-26
CA2195093C (en) 2000-03-07
IL114586A0 (en) 1995-11-27
US5852059A (en) 1998-12-22
MY113079A (en) 2001-11-30
JP2930424B2 (ja) 1999-08-03
HU9700162D0 (en) 1997-03-28
AU2416995A (en) 1996-02-16
JPH09507859A (ja) 1997-08-12
EP1029540A3 (en) 2001-05-16
CA2195213A1 (en) 1996-02-01
WO1996002242A1 (en) 1996-02-01
US5902830A (en) 1999-05-11
CA2195093A1 (en) 1996-02-01
MX9700538A (es) 1997-04-30
JPH09507860A (ja) 1997-08-12
HUT77391A (hu) 1998-04-28
KR100212352B1 (ko) 1999-08-02
KR100221854B1 (ko) 1999-09-15
TW403649B (en) 2000-09-01
KR970704429A (ko) 1997-09-06
NZ285159A (en) 2000-10-27
MX9700534A (es) 1997-04-30
KR970704430A (ko) 1997-09-06
CN1152868A (zh) 1997-06-25
WO1996002243A1 (en) 1996-02-01
EP0771194A1 (en) 1997-05-07
IL114586A (en) 2000-06-29
AU694220B2 (en) 1998-07-16
IL114585A (en) 2000-01-31
CN1153473A (zh) 1997-07-02
FI970215A (fi) 1997-01-17
FI970215A0 (fi) 1997-01-17
IL114585A0 (en) 1995-11-27
FI970214A0 (fi) 1997-01-17
HU9700163D0 (en) 1997-03-28
HK1000697A1 (en) 2002-05-10
US5441986A (en) 1995-08-15
ZA955963B (en) 1997-01-20
ZA955964B (en) 1997-01-20

Similar Documents

Publication Publication Date Title
CN1076967C (zh) 使用屈洛昔芬治疗心血管疾病
AU2001225413B2 (en) Drospirenone for hormone replacement therapy
US8236848B2 (en) Diindolylmethane for the treatment of HPV infection
US9084796B2 (en) Hormonal composition and its use
AU2001225413A1 (en) Drospirenone for hormone replacement therapy
US6906049B1 (en) Contraceptive medicine based on a progestational agent and an oestrogen and preparation method
AU782552B2 (en) Product for treating gynecomastia
US5039699A (en) Anti-peptic ulcer agent
AU784478B2 (en) Contraceptive medicament based on a progesterone and an oestrogen and method for producing the same
US20030165580A1 (en) Safe pharmaceutical composition for treatment and prevention of gynecological disease
EP0597415B1 (en) Iron therapy using Saccharose octasulfate ferric complex
CN1620298A (zh) 替勃龙用于治疗与施用阻止内源性雌激素合成的药物有关的疾病

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee