DE3323321A1 - PROPHYLAXIS AND THERAPY OF CORONARY HEART DISEASES BY LOWERING THE OESTROGEN LEVEL - Google Patents

PROPHYLAXIS AND THERAPY OF CORONARY HEART DISEASES BY LOWERING THE OESTROGEN LEVEL

Info

Publication number
DE3323321A1
DE3323321A1 DE19833323321 DE3323321A DE3323321A1 DE 3323321 A1 DE3323321 A1 DE 3323321A1 DE 19833323321 DE19833323321 DE 19833323321 DE 3323321 A DE3323321 A DE 3323321A DE 3323321 A1 DE3323321 A1 DE 3323321A1
Authority
DE
Germany
Prior art keywords
estrogen
prophylaxis
therapy
coronary heart
heart diseases
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.)
Withdrawn
Application number
DE19833323321
Other languages
German (de)
Inventor
Ulrich Dr. 1000 Berlin Kerb
Paul-Eberhard Dr. Schulze
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.)
Bayer Pharma AG
Original Assignee
Schering AG
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 Schering AG filed Critical Schering AG
Priority to DE19833323321 priority Critical patent/DE3323321A1/en
Priority to EP19840902507 priority patent/EP0179062A1/en
Priority to JP50253684A priority patent/JPS60501656A/en
Priority to PCT/DE1984/000137 priority patent/WO1985000107A1/en
Publication of DE3323321A1 publication Critical patent/DE3323321A1/en
Withdrawn legal-status Critical Current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
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Utilisation of antiestrogen and aromatase inhibitors, optionally in combination with beta -receptor blockers for the prophylaxis and therapy of coronary heart diseases. Substances such as tamoxifen are considered to be used as antiestrogen, and such as testolactone to be used as aromatase inhibitors.

Description

Die Erfindung betrifft die Prophylaxe und Therapie vonThe invention relates to the prophylaxis and therapy of

koronaren Herzkrankheiten durch Senkung des Östrogenspiegels. Koronare Herzkrankheiten gehören zu den häufigsten lebensbedrohenden Gefäßerkrankungen. Zur Behandlung dieser Krankheiten verwendet man mehrere Präparate, die einmal auf das Gefäßsystem erweiternd wirken, die die gestörte Sauerstoffversorgung des Herzmuskelgewebes (Myocard) verbessern und die dazu noch die Bildung von Blutgerinseln (Thrombozytenaggregation) verhindern sollen.coronary artery disease by lowering estrogen levels. Coronary Heart disease is one of the most common life-threatening vascular diseases. To the Treatment of these diseases uses several preparations that are specific to the The vascular system dilates the disturbed oxygen supply to the heart muscle tissue (Myocardium) and also the formation of blood clots (platelet aggregation) should prevent.

Darüber hinaus wird auch der Blutdruck medikamentös gesenkt.In addition, the blood pressure is lowered with medication.

Obwohl seit vielen Jahren bekannt ist, daß Männer mit koronaren Herzkrankheiten wie Angina pectoris, Koronarinsuffizienz, drohendem oder eingetretenem Herzinfarkt im Serum erhöhte Östrogenspiegel aufweisen, hat man noch niemals versucht, eine Behandlung vorzunehmen, bei der der Östrogenspiegel gesenkt wird.Although it has been known for many years that men have coronary artery disease such as angina pectoris, coronary insufficiency, impending or current heart attack have elevated levels of estrogen in the serum, one has never attempted a Carry out treatment that lowers estrogen levels.

Eine Behandlung durch Senkung des Ostrogenspiegeis wurde bisher nur bei Erkrankungen endokriner Driisen vorgesclllagen, zum Beispiel bei Mammakarzinom (US-Patent L235.',93, Endocrinology 100 (1977) 1634 - 1695), Prostatahyperplasie (DE-OS 2 817 157 und DE-OS 3 121 153) oder Oligospermie (J. Clin. End. and Met. 52 (19 97 - 902).Treatment by lowering the estrogen level has only been available so far in diseases of the endocrine gland, for example breast cancer (U.S. Patent L235. ', 93, Endocrinology 100 (1977) 1634-1695), prostatic hyperplasia (DE-OS 2 817 157 and DE-OS 3 121 153) or oligospermia (J. Clin. End. And Met. 52 (19 97-902).

Zur Senkung des Ustrogenspiegels kornmen Antifistrogene wie Tamoxifen und insbesondere Aromatasehemmer wie Testolacton infrage.Antifistrogens such as tamoxifen are used to lower the level of estrogen and especially aromatase inhibitors such as testolactone.

Es wurde nun gefunden, das bei Männern, die unter koronaren Herzkrankheiten leiden, durch Senkung des Serum-Ostrogenspiegels eine therapeutische Wirkung eintritt.It has now been found to do this in men who suffer from coronary artery disease a therapeutic effect occurs by lowering the serum estrogen level.

So beobachtet man beispielsweise bei Patienten mit frischem Herzinfarkt nach oraler Applikation von Tamoxifen oder Testolacton täglich einmal oder mehrmals eine deutliche Verbesserung des Allgemeinbefindens und eine deutliche Steigerung der Herzleistung im Infarktbereich. Die gesteigerte Ilerzleistung kann zum Beispiel durch Radioiso-201 topentechnik ( Thallium-Myocardszintigraphie) und/oder durch Aufnahme eines EKGs nachgewiesen werden.For example, one observes in patients with a recent heart attack after oral administration of tamoxifen or testolactone once or several times a day a significant improvement in general well-being and a significant increase the cardiac output in the infarct area. The increased output can for example by Radioiso-201 topentechnik (thallium myocardial scintigraphy) and / or by Recording of an EKG can be detected.

Die Dosierung des Antiöstrogens bzw. des Aromatasehemmers richtet sich nach der Art und Schwere der Herzkrankheit.The dosage of the anti-estrogen or the aromatase inhibitor is directed depending on the type and severity of the heart disease.

Im allgemeinen wird man mit einer täglichen Dosis eines Antiöstrogens, die der von 10 bis 200 mg Tamoxifen entspricht, oder eines Aromatasehemmers, die der von 50 bis 1000 mg Testolacton entspricht, auskommen.Generally, a daily dose of an anti-estrogen will be used which corresponds to that of 10 to 200 mg of tamoxifen, or an aromatase inhibitor which which corresponds to 50 to 1000 mg testolactone get along.

Bei männlichen Patienten mit Angina pectoris wurden zum Beispiel täglich zweimal 100 mg Testolacton per os verabreicht. Schon nach kurzer Behandlungszeit waren die Schmerzen geringer und nach 4 Wochen waren die Patienten völlig beschwerdefrei. Die erfindungsgemäßen Ostrogenspiegelsenker sind damit auch zur Prophylaxe der koronaren erzkrankheiten geeignet.In male patients with angina pectoris, for example, were daily 100 mg testolactone administered orally twice. Already after a short treatment time the pain was less and after 4 weeks the patients were completely symptom-free. The estrogen level reducers according to the invention are therefore also used for prophylaxis of the coronary arteries suitable for ore diseases.

Zur Prophylaxe und Therapie von koronaren Herzkrankheiten sind erfindungsgemäß alle Stoffe geeignet, die eine Senkung des Ostrogenspiegels bewirken. Zu diesen Stoffen zählen alle Antiöstrogene, die sowohl steroidal als auch nichtsteroidal sein können. Zu den am besten untersuchten nicht-steroidalen Antiöstrogenen zahlen: Tamoxifen ((Z)-2-/p-(1 ,2-Diphenyl-1-butenyl)-phenoxy7-N,N-dimethylethylamin) und dessen Salze, Clomifen (1-/p-(ß-diethylaminoethoxy)phenyl7-1 2-diphenylchlorethylen, Cyclofenil (Bis(p-acetoxyphenyl)cyclohexylidenmethan, Nafoxidin (1-(2-/6-(6-Methoxy-2-phenyl-3,1i-dihydro-1-naphthyl)phenoxz7-ethyl)-pyrrolidin, hydrochlorid u.a.For the prophylaxis and therapy of coronary heart diseases are according to the invention all substances are suitable that cause a lowering of the estrogen level. To this Substances include all antiestrogens that are both steroidal and nonsteroidal could be. Among the best-studied non-steroidal anti-estrogens: Tamoxifen ((Z) -2- / p- (1, 2-Diphenyl-1-butenyl) -phenoxy7-N, N-dimethylethylamine) and its salts, Clomiphene (1- / p- (ß-diethylaminoethoxy) phenyl7-1 2-diphenylchlorethylene, cyclofenil (Bis (p-acetoxyphenyl) cyclohexylidenemethane, nafoxidine (1- (2- / 6- (6-methoxy-2-phenyl-3,1i-dihydro-1-naphthyl) phenoxz7-ethyl) pyrrolidine, hydrochloride, etc.

Als Beispiele für steroidale Antiöstrogene seien 11a-Methoxy-17a-ethinyl-östradiol und 16ß-Ethylöstradiol genannt.Examples of steroidal antiestrogens are 11a-methoxy-17a-ethynyl-estradiol and 16ß-ethyl estradiol called.

Ein Übersichtsreferat über die "Pharmalogie der Antiöstrogene", in dem noch weitere Antiöstrogene abgehandelt werden, ist publiziert in "Gynäkologe" 12 (1979) 199 - 211, Springer-Verlag.A review lecture on the "Pharmalogy of Antiestrogens", in to which other antiestrogens are dealt with, is published in "Gynäkologe" 12 (1979) 199-211, Springer-Verlag.

Da die beim Manne vorhandenen Ostrogene vorwiegend aus der peripheren Aromatisierung von androgenen Hormonen stammen (Excerpta Medica 1979, 42 - 50 und J. Clin. Endocrinol.Since the estrogens present in men mainly come from the peripheral Aromatization originate from androgenic hormones (Excerpta Medica 1979, 42-50 and J. Clin. Endocrinol.

Metab. 27 (1967) 1103 - 1111), sind Aromatasehemmer zur Senkung des Ostrogenspiegels beim Manne besonders gut geeignet Durch Verabreichung von Aromatasehemmern wird die Bildung von biologisch wirksamen Ostrogenen (Östrogenbiosynthese) verhindert bzw. gehemmt. Erfindungsgemäß sind alle Aromatasehemmer geeignet, die die Ustrogenbiosynthese hemmen und selbst nur geringe oder keine östrogene oder andere hormonelle Wirkung entfalten. Aromatasehemmer gemäß vorliegender Erfindung sind zum Beispiel Testolacton (17a-Oxa-D-homo-androsta-1 ,4-dien-3,17-dion, Androst-4-en-4-ol-3,17-dion (Endocrinology 1UO (1977) 1684 - 1695), ester des Androst-4-en-4-ol-3,17-dions (US-Patent i 235 393).Metab. 27 (1967) 1103 - 1111), are aromatase inhibitors to lower the Especially suitable for men’s estrogen level. By administering aromatase inhibitors the formation of biologically active estrogens (estrogen biosynthesis) is prevented or inhibited. According to the invention, all aromatase inhibitors are suitable which promote estrogen biosynthesis inhibit themselves and have little or no estrogenic or other hormonal effects unfold. Examples of aromatase inhibitors according to the present invention are testolactone (17a-Oxa-D-homo-androsta-1, 4-diene-3,17-dione, androst-4-en-4-ol-3,17-dione (Endocrinology 1UO (1977) 1684 - 1695), ester of androst-4-en-4-ol-3,17-dione (US patent i 235 393).

Weitere geeignete Aromatasehemmer werden beschrieben beispielsweise in Endocrinology 92 (1973) 866 - 880, DE-OS 3 124 719 und US-Patent 4 289 762.Other suitable aromatase inhibitors are described, for example in Endocrinology 92 (1973) 866-880, DE-OS 3,124,719 and U.S. Patent 4,289,762.

Die Erfindung betrifft auch Mittel zur Senkung des Östrogenspiegels für die Prophylaxe und Therapie von koronaren erzkrankheiten bei Männern, wobei Antiöstrogene und insbesondere Aromatasehemmer zur Senkung des Ostrogenspiegels geeignet sind.The invention also relates to agents for lowering the level of estrogen for the prophylaxis and therapy of coronary ore diseases in men, whereby Anti-estrogens and especially aromatase inhibitors to lower estrogen levels are suitable.

Die Wirkstoffe (Östrogenspiegelsenker) können mit den in der galenischen Pharmazie üblichen Zusätzen, Trägersubstanzen und/oder Geschmackskorrigentien nach an sich bekannten Methoden zu den üblichen Applikationsformen verarbeitet werden, beispielsweise für die orale, perkutane oder parenterale Applikation.The active ingredients (estrogen level reducers) can be combined with those in the galenic Pharmaceutical usual additives, carrier substances and / or taste corrections methods known per se are processed into the usual application forms, for example for oral, percutaneous or parenteral administration.

Für die bevorzugte orale Applikation kommen insbesondere Tabletten, Dragees, Kapseln, Pillen, Suspensionen oder Lösungen infrage.For the preferred oral administration, tablets are particularly suitable, Dragees, capsules, pills, suspensions or solutions in question.

Die wie oben angegeben formulierten Arzneimittel enthalten vorzugsweise 10 - 100 mg Tamoxifen oder biologisch äquivalente Mengen eines anderen Antiöstrogens oder 50 - 200 mg Testolacton oder biologisch äquivalente engen eines anderen Aromatasehemmers.The medicaments formulated as indicated above preferably contain 10-100 mg of tamoxifen or biologically equivalent amounts of another anti-estrogen or 50-200 mg testolactone or biologically equivalent compounds of another aromatase inhibitor.

Beispiel 1 100,0 mg 17a-Oxa-D-homoandrosta-1,4-dien-3,17-dion (Testolacton) 80,5 mg Lactose 39,5 mg Maisstärke 2,5 mg Poly-N-Vinylpyrrolidon 25 2,0 mg Aerosil 0r m& Magnesiumstearat 225,0 mg Gesamtgewicht der Tablette, die in üblicher Weise auf einer Tablettenpresse hergestellt wird.Example 1 100.0 mg of 17a-Oxa-D-homoandrosta-1,4-diene-3,17-dione (testolactone) 80.5 mg lactose 39.5 mg corn starch 2.5 mg poly-N-vinylpyrrolidone 25 2.0 mg Aerosil 0r m & magnesium stearate 225.0 mg total weight of the tablet used in usual Way is made on a tablet press.

Beispiel 2 50,0 mg 17a-Oxa-D-homoandrosta-1 ,4-dien-3, 17-dion (Testolacton) 115,5 mg Lactose 54,5 mg Maisstärke 2,5 mg Poly-N-Vinylpyrrolidon 25 2,0 mg Aerosil 0,5 mg Magnesiumstearat 225,0 mg Gesamtgewicht der Tablette, die in üblicher Weise auf einer Tablettenpresse hergestellt wird.Example 2 50.0 mg of 17a-Oxa-D-homoandrosta-1, 4-diene-3, 17-dione (testolactone) 115.5 mg lactose 54.5 mg corn starch 2.5 mg poly-N-vinylpyrrolidone 25 2.0 mg Aerosil 0.5 mg magnesium stearate 225.0 mg total weight of the tablet, in the usual way is made on a tablet press.

Beispiel 3 Zusammensetzung einer öligen Lösung: 50,0 mg 17a-Oxa-D-homoandrosta-1,4-dien-3,17-dion (Testolacton) 378,4 mg Rizinusöl 643,6 mg Benzylbenzoat 1072,0 mg - 1 ml Lösung Die Lösung wird in eine Ampulle gefüllt und sterilisiert.Example 3 Composition of an oily solution: 50.0 mg of 17a-oxa-D-homoandrosta-1,4-diene-3,17-dione (Testolactone) 378.4 mg castor oil 643.6 mg benzyl benzoate 1072.0 mg - 1 ml of solution The solution is filled into an ampoule and sterilized.

Beispiel 4 Zusammensetzung einer Tablette: 20,0 mg (Z)-2-/p-(1,2-Diphenyl-1-butenyl)-phenoxy7-N,N-dimethyläthylamin (Tamoxifen) 120,5 mg Lactose 59,5 mg Maisstärke 2,5 mg Poly-N-Vinylpyrrolidon 25 2,0 mg Aerosil 0,5 mg Magnesiumstearat 205,0 mg Gesamtgewicht der Tablette, die in iiblicher Weise auf einer Tablettenpresse hergestellt wird.Example 4 Composition of a tablet: 20.0 mg (Z) -2- / p- (1,2-diphenyl-1-butenyl) -phenoxy7-N, N-dimethylethylamine (Tamoxifen) 120.5 mg lactose 59.5 mg corn starch 2.5 mg poly-N-vinylpyrrolidone 25 2.0 mg Aerosil 0.5 mg Magnesium Stearate 205.0 mg total weight of the tablet, the is produced in the usual way on a tablet press.

Claims (14)

Patentansprüche 1.) Mittel zur Senkung des Ostrogenspiegels für die Prophylaxe und Therapie von koronaren Herzkrankheiten bei Männern.Claims 1.) Means to lower the estrogen level for the Coronary artery disease prophylaxis and therapy in men. 2.) Mittel nach Anspruch 1 auf Basis eines Antiöstrogens.2.) Agent according to claim 1 based on an anti-estrogen. 3.) Mittel nach Anspruch 1 auf Basis eines Aromatasehemmers. 3.) Agent according to claim 1 based on an aromatase inhibitor. 4.) Mittel nach Anspruch 1 in einer oralen Applikationsform.4.) Agent according to claim 1 in an oral application form. 5.) Mittel nach Anspruch 1 für die perkutane oder parenterale Applikation.5.) Agent according to claim 1 for percutaneous or parenteral application. 6.) Mittel nach Anspruch 1, enthaltend 10 - 100 mg Tamoxifen oder biologisch äquivalente Mengen eines anderen Antiöstrogens.6.) Means according to claim 1, containing 10-100 mg of tamoxifen or biologically equivalent amounts of another anti-estrogen. 7.) Mittel nach Anspruch 1, enthaltend 50 - 200 mg Testolacton oder biologisch äquivalente Mengen eines anderen Aromatasehemmers.7.) Means according to claim 1, containing 50-200 mg of testolactone or biologically equivalent amounts of another aromatase inhibitor. 8.) Prophylaxe und Therapie von koronaren Herzkrankheiten bei Männern durch Senkung des Östrogenspiegels.8.) Prophylaxis and therapy of coronary heart diseases in men by lowering the level of estrogen. 9.) Verwendung von Antiöstrogenen zur Prophylaxe und Therapie von koronaren Herzkrankheiten nach Anspruch 8. 9.) Use of antiestrogens for the prophylaxis and therapy of coronary heart diseases according to claim 8. 10.) Verwendung von Zamoxifen Sem;in Anspruch 9.10.) Use of Zamoxifen Sem; in claim 9. 11.) Verwendung von täglich 10 - 200 mg Tamoxifen bzw.11.) Use of 10 - 200 mg tamoxifen or biologisch äquivalente Mengen eines anderen Antiöstrogens nach Anspruch 9. biologically equivalent amounts of another anti-estrogen according to claim 9. 12.) Verwendung von Aromatasehemmern zur Prophylaxe und Therapie von koronaren Herzkrankheiten nach Anspruch 8.12.) Use of aromatase inhibitors for the prophylaxis and therapy of coronary heart diseases according to claim 8. 13.) Verwendung von Testolacton gemäß Anspruch 12.13.) Use of testolactone according to claim 12. 14.) Verwendung von täglich 50 - 1000 mg Testolacton bzw. biologisch äquivalente Mengen eines anderen Aromatasehemmers nach Anspruch 12.14.) Use of 50 - 1000 mg testolactone daily or biological equivalent amounts of another aromatase inhibitor according to claim 12.
DE19833323321 1983-06-24 1983-06-24 PROPHYLAXIS AND THERAPY OF CORONARY HEART DISEASES BY LOWERING THE OESTROGEN LEVEL Withdrawn DE3323321A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE19833323321 DE3323321A1 (en) 1983-06-24 1983-06-24 PROPHYLAXIS AND THERAPY OF CORONARY HEART DISEASES BY LOWERING THE OESTROGEN LEVEL
EP19840902507 EP0179062A1 (en) 1983-06-24 1984-06-19 Prophylaxis and therapy of coronary heart diseases by lowering the estrogen concentration
JP50253684A JPS60501656A (en) 1983-06-24 1984-06-19 Prevention and treatment of coronary heart disease due to decreased estrogen levels
PCT/DE1984/000137 WO1985000107A1 (en) 1983-06-24 1984-06-19 Prophylaxis and therapy of coronary heart diseases by lowering the estrogen concentration

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19833323321 DE3323321A1 (en) 1983-06-24 1983-06-24 PROPHYLAXIS AND THERAPY OF CORONARY HEART DISEASES BY LOWERING THE OESTROGEN LEVEL

Publications (1)

Publication Number Publication Date
DE3323321A1 true DE3323321A1 (en) 1985-01-03

Family

ID=6202619

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19833323321 Withdrawn DE3323321A1 (en) 1983-06-24 1983-06-24 PROPHYLAXIS AND THERAPY OF CORONARY HEART DISEASES BY LOWERING THE OESTROGEN LEVEL

Country Status (4)

Country Link
EP (1) EP0179062A1 (en)
JP (1) JPS60501656A (en)
DE (1) DE3323321A1 (en)
WO (1) WO1985000107A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310541A1 (en) * 1987-10-01 1989-04-05 Schering Aktiengesellschaft Antigestagenic and antioestrogenic compounds for the introduction of labour and interruption of pregnancy, as well as for the treatment of gynecologic disorders
EP0943328A2 (en) * 1989-07-07 1999-09-22 Endorecherche Inc. Combination therapy for prophylaxis and/or treatment of benign prostatic hyperplasia
WO2000045806A1 (en) * 1999-02-03 2000-08-10 Eli Lilly And Company α1-ADRENERGIC RECEPTOR ANTAGONISTS
EP1029540A2 (en) * 1994-07-19 2000-08-23 Pfizer Inc. Use of droloxifene for the treatment of cardiovascular diseases
US6423698B1 (en) 1989-03-10 2002-07-23 Endorecherche, Inc. Combination therapy for the prophylaxis and/or treatment of benign prostatic hyperplasia

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5811447A (en) * 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
CA2162586C (en) * 1993-05-13 2006-01-03 David J. Grainger Prevention and treatment of pathologies associated with abnormally proliferative smooth muscle cells

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4289762A (en) * 1980-06-27 1981-09-15 Merrell Dow Pharmaceuticals Inc. 10-(1,2-Propadienyl) steroids as irreversible aromatase inhibitors
US4322416A (en) * 1980-06-27 1982-03-30 Merrell Dow Pharmaceuticals Inc. 10-Alkynyl steroids
DE3121153A1 (en) * 1981-05-22 1982-12-09 Schering Ag, 1000 Berlin Und 4619 Bergkamen "USE OF AROMATASE INHIBITORS FOR PROPHYLAXIS AND THERAPY OF PROSTATE HYPERPLASIA"

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0310541A1 (en) * 1987-10-01 1989-04-05 Schering Aktiengesellschaft Antigestagenic and antioestrogenic compounds for the introduction of labour and interruption of pregnancy, as well as for the treatment of gynecologic disorders
US6423698B1 (en) 1989-03-10 2002-07-23 Endorecherche, Inc. Combination therapy for the prophylaxis and/or treatment of benign prostatic hyperplasia
EP0943328A2 (en) * 1989-07-07 1999-09-22 Endorecherche Inc. Combination therapy for prophylaxis and/or treatment of benign prostatic hyperplasia
EP0943328A3 (en) * 1989-07-07 1999-12-08 Endorecherche Inc. Combination therapy for prophylaxis and/or treatment of benign prostatic hyperplasia
EP1029540A2 (en) * 1994-07-19 2000-08-23 Pfizer Inc. Use of droloxifene for the treatment of cardiovascular diseases
EP1029540A3 (en) * 1994-07-19 2001-05-16 Pfizer Inc. Use of droloxifene for the treatment of cardiovascular diseases
WO2000045806A1 (en) * 1999-02-03 2000-08-10 Eli Lilly And Company α1-ADRENERGIC RECEPTOR ANTAGONISTS
US6410565B1 (en) 1999-02-03 2002-06-25 Eli Lilly And Company α1-adrenergic receptor antagonists

Also Published As

Publication number Publication date
JPS60501656A (en) 1985-10-03
EP0179062A1 (en) 1986-04-30
WO1985000107A1 (en) 1985-01-17

Similar Documents

Publication Publication Date Title
DE69328771T2 (en) METHOD FOR INHIBITING CARCINOGENESIS BY TREATMENT WITH DEHYDROEPIANDROSTERONE AND ITS ANALOGS
Benedek History of the development of corticosteroid therapy
DE69125714T2 (en) COMPOSITION FOR THE TREATMENT OF HUMAN PROSTATE ADENOCARCINOMA
Strauss et al. Effect of cyclic progestin-estrogen therapy on sebum and acne in women
DE60117046T2 (en) COMBINATION OF FENOFIBRATE AND COENZYME Q10 FOR THE TREATMENT OF ENDOTHELIAL MISSING FUNCTION
DE3733478A1 (en) ANTIGESTAGEN AND ANTIOOTROGENIC COMPOUNDS FOR THE INTRODUCTION OF BIRTH AND PREGNANCY, AND THE TREATMENT OF GYNAECOLOGICAL DISORDER AND HORMONE-RELATED TUMORS
DE69329381T2 (en) ANTI-ISCHEMICAL MEDICINAL PRODUCT
DE69829763T2 (en) USE OF TETRAHYDOLIPSTATIN IN THE TREATMENT OF DIABETES TYPE II
DE69710326T2 (en) USE OF A TOREMIFENEMETABOLITE TO REDUCE THE SERUM CHOLESTERIN LEVEL
DE29717252U1 (en) Drug kit consisting of a budesonide-containing and an ursodeoxycholic acid-containing drug for the treatment of cholestatic liver diseases
DE69420776T2 (en) Compositions containing idebenone for the treatment of M. Alzheimer's
DE3323585A1 (en) COMPOSITION TO REDUCE SEBUM SECRETION
DE3323321A1 (en) PROPHYLAXIS AND THERAPY OF CORONARY HEART DISEASES BY LOWERING THE OESTROGEN LEVEL
DE69131398T2 (en) USE OF 5-HT4 RECEPTOR ANTAGONISTS FOR TREATING Atrial FIBRILLATION AND PREVENTING STROKE
DE60204694T2 (en) COMBINATION THERAPY FOR THE TREATMENT OF HEART FAILURE
DE602004009288T2 (en) USE OF A COMBINATION OF AN AROMATASE HEATHER, A PROGESTINE AND AN ESTROGEN FOR THE TREATMENT OF ENDOMETRIOSIS
DE60206169T2 (en) COMBINATION CONTAINING A P-GP INHIBITOR AND AN ANTI-PILEPTIC ACTIVE
EP0198172A1 (en) Pharmaceutical preparation
DE3339295C2 (en)
DE60207442T2 (en) USE OF A COMBINATION COMPOSITION COMPRISING PROPIONYL L-CARNITINE AND OTHER ACTIVE SUBSTANCES FOR TREATING THE EFFECTIVE DYSFUNCTION
DE3607651A1 (en) COMBINATION OF AROMATASE INHIBITORS AND TESTOSTERONE-5 (ALPHA) REDUCTASE INHIBITORS
EP0005732B1 (en) Use of 2-amino-oxazolo- or 2-amino-thiazolo-[5,4-d]azepines and acid-addition salts thereof for the manufacture of a medicament for the treatment of Angina Pectoris
DE2161588C3 (en) Agents for the treatment of hyperlipoproteinemia
DE3809625C2 (en)
DE69018022T2 (en) Magnesium citrate as a dietary supplement.

Legal Events

Date Code Title Description
8139 Disposal/non-payment of the annual fee