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 LEVELInfo
- 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
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- 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.)
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- 208000029078 coronary artery disease Diseases 0.000 title claims abstract description 11
- 238000011321 prophylaxis Methods 0.000 title claims abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 9
- 239000000262 estrogen Substances 0.000 title claims description 19
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims abstract description 18
- 239000003886 aromatase inhibitor Substances 0.000 claims abstract description 16
- 229940046836 anti-estrogen Drugs 0.000 claims abstract description 15
- 230000001833 anti-estrogenic effect Effects 0.000 claims abstract description 15
- 239000000328 estrogen antagonist Substances 0.000 claims abstract description 15
- 229960005353 testolactone Drugs 0.000 claims abstract description 13
- BPEWUONYVDABNZ-DZBHQSCQSA-N testolactone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(OC(=O)CC4)[C@@H]4[C@@H]3CCC2=C1 BPEWUONYVDABNZ-DZBHQSCQSA-N 0.000 claims abstract description 13
- 229940046844 aromatase inhibitors Drugs 0.000 claims abstract description 10
- 229960001603 tamoxifen Drugs 0.000 claims abstract description 9
- 229940011871 estrogen Drugs 0.000 claims description 18
- 229940122815 Aromatase inhibitor Drugs 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 abstract description 4
- 239000002876 beta blocker Substances 0.000 abstract 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- BPEWUONYVDABNZ-UHFFFAOYSA-N testolactone Chemical compound O=C1C=CC2(C)C3CCC(C)(OC(=O)CC4)C4C3CCC2=C1 BPEWUONYVDABNZ-UHFFFAOYSA-N 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 229910002012 Aerosil® Inorganic materials 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 3
- 230000003637 steroidlike Effects 0.000 description 3
- -1 1, 2-Diphenyl-1-butenyl Chemical group 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- GVOUFPWUYJWQSK-UHFFFAOYSA-N Cyclofenil Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1C=CC(OC(C)=O)=CC=1)=C1CCCCC1 GVOUFPWUYJWQSK-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- RSPINGMAWKOXBT-BZGHQHJYSA-N (8r,9s,13s,14s,16s,17s)-16-ethyl-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1C[C@H](CC)[C@H](O)[C@@]1(C)CC2 RSPINGMAWKOXBT-BZGHQHJYSA-N 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010052895 Coronary artery insufficiency Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- JEYWNNAZDLFBFF-UHFFFAOYSA-N Nafoxidine Chemical compound C1CC2=CC(OC)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)=C1C1=CC=CC=C1 JEYWNNAZDLFBFF-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 206010003883 azoospermia Diseases 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 229960003608 clomifene Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 229960002944 cyclofenil Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 231100000508 hormonal effect Toxicity 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 229950002366 nafoxidine Drugs 0.000 description 1
- 208000008634 oligospermia Diseases 0.000 description 1
- 230000036616 oligospermia Effects 0.000 description 1
- 231100000528 oligospermia Toxicity 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
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)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrane Compounds (AREA)
- Pyrrole Compounds (AREA)
Abstract
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)
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 |
| JP59502536A 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)
| 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 |
| EP0943328A3 (en) * | 1989-07-07 | 1999-12-08 | 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 |
| EP1029540A3 (en) * | 1994-07-19 | 2001-05-16 | 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 (4)
| 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 |
| US6395494B1 (en) | 1993-05-13 | 2002-05-28 | Neorx Corporation | Method to determine TGF-β |
| CA2162586C (en) * | 1993-05-13 | 2006-01-03 | David J. Grainger | Prevention and treatment of pathologies associated with abnormally proliferative smooth muscle cells |
| US6613083B2 (en) | 2001-05-02 | 2003-09-02 | Eckhard Alt | Stent device and method |
Family Cites Families (3)
| 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" |
-
1983
- 1983-06-24 DE DE19833323321 patent/DE3323321A1/en not_active Withdrawn
-
1984
- 1984-06-19 JP JP59502536A patent/JPS60501656A/en active Pending
- 1984-06-19 EP EP19840902507 patent/EP0179062A1/en not_active Withdrawn
- 1984-06-19 WO PCT/DE1984/000137 patent/WO1985000107A1/en not_active Ceased
Cited By (6)
| 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 |
| EP0943328A3 (en) * | 1989-07-07 | 1999-12-08 | Endorecherche Inc. | Combination therapy for prophylaxis and/or treatment of benign prostatic hyperplasia |
| 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 |
| WO1985000107A1 (en) | 1985-01-17 |
| EP0179062A1 (en) | 1986-04-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |