DE2218831A1 - Sequential oral contraceptives - contg low estrogen and varied gestagen doses - Google Patents
Sequential oral contraceptives - contg low estrogen and varied gestagen dosesInfo
- Publication number
- DE2218831A1 DE2218831A1 DE2218831A DE2218831A DE2218831A1 DE 2218831 A1 DE2218831 A1 DE 2218831A1 DE 2218831 A DE2218831 A DE 2218831A DE 2218831 A DE2218831 A DE 2218831A DE 2218831 A1 DE2218831 A1 DE 2218831A1
- Authority
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- Germany
- Prior art keywords
- estrogen
- gestagen
- ethynyl
- stage
- doses
- 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.)
- Granted
Links
- 239000000262 estrogen Substances 0.000 title claims abstract description 28
- 229940011871 estrogen Drugs 0.000 title claims abstract description 27
- 239000000583 progesterone congener Substances 0.000 title claims abstract description 24
- 239000000697 oral hormonal contraceptive Substances 0.000 title 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 10
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims description 9
- 229960004400 levonorgestrel Drugs 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000003433 contraceptive agent Substances 0.000 claims description 3
- IMONTRJLAWHYGT-ZCPXKWAGSA-N Norethindrone Acetate Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@](C#C)(OC(=O)C)[C@@]1(C)CC2 IMONTRJLAWHYGT-ZCPXKWAGSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 abstract description 4
- 229960003604 testosterone Drugs 0.000 abstract description 2
- 230000001548 androgenic effect Effects 0.000 abstract 1
- 230000002280 anti-androgenic effect Effects 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 4
- 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 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- JFRPGRWPRUCLQL-TWYXDQSVSA-N (8r,9s,13s,14s,17r)-3-ethyl-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-ol;(8r,9s,10r,13s,14s,17r)-17-ethynyl-13-methyl-2,3,6,7,8,9,10,11,12,14,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ol Chemical compound C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.C1C[C@]2(C)[C@@](C#C)(O)CC[C@H]2[C@@H]2CCC3=CC(CC)=CC=C3[C@H]21 JFRPGRWPRUCLQL-TWYXDQSVSA-N 0.000 description 2
- -1 17-hydroxy-progesterone ester Chemical class 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 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
- 238000012937 correction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000001076 estrogenic effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229960003387 progesterone Drugs 0.000 description 2
- 239000000186 progesterone Substances 0.000 description 2
- DBPWSSGDRRHUNT-UHFFFAOYSA-N 17alpha-hydroxy progesterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C(=O)C)(O)C1(C)CC2 DBPWSSGDRRHUNT-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- NIXVMBBZNVOBHS-ASRKUVFVSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-6,10,13-trimethyl-3-oxo-2,8,9,11,12,14,15,16-octahydro-1h-cyclopenta[a]phenanthren-17-yl] acetate;(8r,9s,13s,14s,17r)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 NIXVMBBZNVOBHS-ASRKUVFVSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000003152 gestagenic effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 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
- A61K31/56—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
-
- 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
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Methode zur Kontrazeption durch Verabfolgung von Stufenkombinationspräparaten Hormonelle Methoden zur Kontrazeption sind bereits bekannt, so unter anderem die orale Applikation von Kombinationspräparaten, wie wie z.B. Ovulen(R), Anoviar(R), Lyndiol und ähnliche Kombinationen östrogener und gestagener Wirkstoffe. Weiterhin bekannt ist die Applikation von reinen Sequentialpräparaten, wie -z.B.Method of contraception through the administration of multi-stage combination preparations Hormonal methods of contraception are already known, including the oral application of combination products such as Ovulen (R), Anoviar (R), Lyndiol and similar combinations of estrogenic and gestagenic agents. Farther known is the application of pure sequential preparations, such as -z.B.
Ovanon(R) etce mit der zunächst ein östrogen in hoher Dosierung ohne Gestagenzusatz über 7 Tage und dann anschliessend das Ostrogen in gleichbleibend hoher Dosierung unter Zusatz einer relativ hohen Gestagenmenge über 15 Tage verabfolgt wird und bei der die folgenden 6 Tage zur Anpassung an den normalen Zyklus der Frau einnahmefrei bleiben. Ferner ist bekannt die Applikation von modifi-(R) zierten Sequentialpräparaten, wie z.B. tombiquens(R), Tri-Ervonum(R) und Oraconal(R), etc., wobei zunächst ein östrogen in hoher Dosierung unter Zusatz einer geringen Gestagenmenge über 16 Tage und dann anschliessend das östrogen bei gleichbleibender Dosierung unter Zusatz einer auf das ca. 10-fache gesteigerten Gestagenmenge über 7 Tage verabfolgt wird-. Zur Anpassung an den normalen Zyklus der Frau schliesst sich bei der Applikation dieser Präparate eine fünftägige hormonfreie Phase an, in der Placebos oder beliebige andere Wirkstoffe, wie z.B. Stärkungsmittel, Eisenpräparate et. verabfolgt werden.Ovanon (R) etce with the first an estrogen in high dosage without Gestagen added for 7 days and then the estrogen in constant high dosage with the addition of a relatively high amount of progestogen administered over 15 days and during the following 6 days to adjust to the woman's normal cycle stay ingestion-free. The application of modified (R) is also known Sequential preparations such as tombiquens (R), Tri-Ervonum (R) and Oraconal (R), etc., initially an estrogen in high dosage with the addition of a small amount of progestin over 16 days and then the estrogen with the same dosage administered with the addition of an approximately 10-fold increased amount of gestagen over 7 days will-. The application closes to adapt to the normal cycle of women of these preparations a five-day hormone-free phase, in the placebos or any other active ingredients, such as tonics, iron supplements et. administered.
Nachteile der Applikation der angegebenen Sequentialpräparate sind insbesondere die Verabfolgung relativ hoher Östrogendosen, die neben den üblichen, durch Östrogenüberschuss bedingten Erscheinungen, wie z.B. gastrointestinalen Störungen, Ubelkeit, Gewichtszunahme unter Ödembildung etc.,zu einer Erhöhung des Risikos thromboembolischer Ereignisse führt. Die Einnahme der hohen Östrogendosen wurde andererseits jedoch für erforderlich gehalten, da nur so die kontrazeptive Sicherheit der Sequentialpräparate für gewährleistet angesehen wurde.Disadvantages of the application of the specified sequential preparations are especially the administration of relatively high doses of estrogen, which in addition to the usual, symptoms caused by excess estrogen, such as gastrointestinal disorders, Nausea, weight gain with edema formation, etc., to an increase in the risk of thromboembolic Events leads. The ingestion of high doses of estrogen was on the other hand, however considered necessary, as this is the only way to ensure the contraceptive safety of sequential preparations was considered guaranteed.
Uberraschenderweise lässt sich nun eine zuverlässige Kontrameption auch dadurch erzielen, dass zunächst eine Kombination aus einem Östrogen in geringer Dosierung und einem Gestagen in geringer Dosierung über 10 bis 12 Tage und anschliessend eine Kombination aus dem östrogen bei gleichbleibender Dosierung und dem Gestagen bei einer auf das 2- 3-fache gesteigerten Dosierung über 11 - 9 Tage appliziert wird. Zur-Anpassung an den normalen Zyklus der Frau von ca. 28 Tagen werden an den folgenden 5 bis 7 Tagen keine Östrogene und Gestagene verabfolgt. Diese Phase kann in an sich bekannter Weise einnahmefrei gehalten werden, ebensogut können auch Placebos oder andere Wirkstoffe verabfolgt werden, ohne dass die Sicherheit der Methode dadurch beeinflusst wird.Surprisingly, a reliable contrameption can now be found also achieve this by initially having a combination of an estrogen in lower levels Dosage and a progestin in low doses for 10 to 12 days and then a combination of the estrogen with the same dosage and the progestin applied at a 2–3 fold increased dosage over 11–9 days will. In order to adapt to the normal cycle of women of around 28 days, the No estrogens and progestins were administered for the following 5 to 7 days. This phase can can be kept intake-free in a manner known per se, placebos can just as well or other active ingredients are administered without affecting the safety of the method being affected.
Damit wird erstmalig die von der Ärzteschaft dringend empfohlene Applikation niedriger Östrogendosen im Sequentialprinzip ermöglicht. Zum anderen werden durch Steigerung der Gestagenmenge in der Mitte des Applikationszeitraums der Ablauf des normalen Zyklus, d.h. die normalen physiologischen Vorgänge imitiert. Durch diese quasi-Anpassung an den physiologischen Zyklus ergibt sich sowohl eine bessere Verträglichkeit der Präparate als auch eine optimale Zykluskontrolle.This is the first time that the application is urgently recommended by the medical profession low estrogen doses based on the sequential principle. For another, be through Increase in the amount of gestagen in the middle of the application period of the end of the normal cycle, i.e. mimicking normal physiological processes. Through this quasi-adaptation to the physiological cycle results in both better tolerability of the preparations as well as an optimal cycle control.
Die Erfindung betrifft somit eine Methode zur Kontrazeption, die dadurch gekennzeichnet ist, dass man eine Kombination aus einem östrogen in geringer Dosierung und einem Gestagen in geringer Dosierung über 10 - 12 Tage und anschliessend eine Kombination aus dem Östrogen bei gleichbleibender Dosierung und dem Gestagen bei auf das 2- 3-fache gesteigerten Dosierung über 11 - 9 Tage appliziert.The invention thus relates to a method of contraception that thereby characterized is that you can get a combination of an estrogen in low dosage and a low dose gestagen for 10-12 days and then one Combination of the estrogen with the same dosage and the progestin applied to the 2-3 fold increased dosage over 11 - 9 days.
Darüber hinaus betrifft die vorliegende Erfindung auch Zweistufenkombinationskontrazeptionsmittel, die in der ersten Stufe eine Kombination aus einem Östrogen in geringer Dosis sowie einem Gestagen in geringer Dosis und den in der galenischen Pharmazie üblichen Trägerstoffen, Geschmackskorrigentien und/oder Füllstoffen enthalten und die in der 2. Stufe eine Kombination aus einem Östrogen bei gleichbleibender Dosis sowie einem Gestagen bei auf das 2 - 3-fache gesteigerten Dosis und den in der galenischen Pharmazie üblichen Trägerstoffen, Geschmackskorrigentien und/oder Füllstoffe enthalten. In addition, the present invention also relates to two-stage combination contraception agents, which in the first stage is a combination of a low dose estrogen as well a low dose gestagen and the usual carrier substances used in galenic pharmacy, Contain flavor corrections and / or fillers and the one in the 2nd stage Combination of an estrogen at the same dose as a progestin at a dose increased 2 to 3 times and that in the galenic Contain carrier substances, flavor corrigents and / or fillers customary in pharmacy.
Als für die erfindungsgemässe Methode zur Kontrazeption geeignete Östrogenkomponente kommen die gebräuchlichen östrogene in Betracht. Dabei sollte das angewandte Östrogen vorzugsweise in solchen Dosen verabreicht werden, dass die erfindungsgemäss eingesetzte Östrogenmenge gleich der ist, die der Verabfolgung von 0,030 bis 0,050 mg 17a-thinyl-östradiol entspricht. Als Östrogenkomponente sind unter anderem auch die 17a-Äthinyl-östradiolester oder -äther geeignet. Bevorzugt ist 17a-Äthinyl-östradio1, Als Gestagenkomponente gemäss der vorliegenden Erfindung sind alle gestagenwirksamen Substanzen geeignet.Dabei sollte das angewendete Gestagen vorzugsweise in solchen Dosen verabreicht werden, dass die erfindungsgemäss in den ersten 10 bis 12 Tagen eingesetzte Gestagenmenge gleich der ist, die der Verabfolgung von täglich 0,050 bis 0,125 mg d-Norgestrel entspricht. Die erfindungsgemäss in den 11 - 9 Tagen der zweiten Phase eingesetzte Gestagenmenge soll gleich der sein, die der Verabfolgung von täglich ca. 0,100 - 0,350 mg d-Norgestrel entspricht.As suitable for the method according to the invention for contraception Estrogen components come into consideration the common estrogens. It should the estrogen used should preferably be administered in doses such that the The amount of estrogen used according to the invention is the same as that for administration corresponds to from 0.030 to 0.050 mg of 17a-thynyl-estradiol. As an estrogen component are Among other things, the 17a-ethynyl estradiol esters or ethers are also suitable. Preferred is 17a-ethynyl-estradio1, as a gestagen component according to the present invention all gestagen-active substances are suitable are preferably administered in doses such that the invention in the The amount of progestin used for the first 10 to 12 days is the same as that at the time of administration of 0.050 to 0.125 mg d-norgestrel per day. According to the invention in The amount of progestin used in the 11-9 days of the second phase should be the same as that which corresponds to the administration of approx. 0.100 - 0.350 mg d-norgestrel per day.
Als Gestagenkomponente sind unter anderem geeignet Progesteron und seine Derivate, wie z.B. 17-Hydroxy-progesteron-ester und l9-Nor-17-hydroxy-progesteron-esters 17a-thinyl-testosteron sowie 17a-Äthinyl-19-nor-testosteron und deren Derivate. -Unter Derivate werden Verbindungen verstanden, die unter Einführung von Doppelbindung(en), durch Substitution oder die Herstellung von funktionellen Derivaten, wie z.B. Estern, Äthern, Ketalen etc., gebildet werden.Progesterone and progesterone, among others, are suitable as a gestagen component its derivatives, such as 17-hydroxy-progesterone ester and l9-nor-17-hydroxy-progesterone-esters 17a-thinyl testosterone and 17a-ethinyl-19-nor-testosterone and their derivatives. -Under derivatives are understood to be compounds which are introduced with the introduction of double bond (s), by substitution or the production of functional derivatives such as esters, Ethers, ketals, etc., are formed.
Die Doppelbindungen können unter anderem in 1(2)-, 6(7)- und/ oder 16(17)-Stellung vorliegen. Als Substituenten kommen unter anderem in Betracht Halogen, insbesondere Fluor, Chlor und Bromatome, Niedrigalkyl, insbesondere die Methylgruppe, Alkenyl, Alkinyl, insbesondere die Äthinylgruppe, und/oder die Hydroxygruppe, die 4-, 6-, 7-, 16- und/oder 17-stndig sein können, sowie Methylengruppen, die 1(2)-, 6(7> und/oder 16(17)-ständig sein können.The double bonds can inter alia in 1 (2) -, 6 (7) - and / or 16 (17) position exist. Possible substituents include halogen, especially fluorine, chlorine and bromine atoms, lower alkyl, especially the methyl group, Alkenyl, alkynyl, especially the ethynyl group, and / or the hydroxyl group, the 4-, 6-, 7-, 16- and / or 17-position, as well as methylene groups, which 1 (2) -, 6 (7> and / or 16 (17) - can be.
Als Ester kommen die Ester der Säuren infrage, die üblicherweise in der Steroidchemie zur Veresterung der Steroidalkohole verwendet werden. Beispielsweise genannt seien Alkancarbonsäuren, insbesondere Alkancarbonsäuren mit 1 - 7 Kohlenstoffatomen. Als Äther seien beispielsweise Alkyl- und Tetrahydropyranyläther genannt. Als Ketale seien beispielsweise die des Äthandiol oder die der Propandiole genannt.The esters of the acids that are usually used in of steroid chemistry can be used to esterify steroid alcohols. For example Alkanecarboxylic acids, in particular alkanecarboxylic acids having 1 to 7 carbon atoms, may be mentioned. Examples of ethers are alkyl and tetrahydropyranyl ethers. As ketals for example, those of ethanediol or propanediols may be mentioned.
Bevorzugte Gestagen sind d-Norgestrel und 17a-thinyl-19-nortestosteron-acetat.- Die östrogenen und gestagenen Wirkstoffkomponenten werden vorzugsweise zusammen oral appliziert, sie können jedoch auch getrennt oder parenteral verabreicht werden. Dazu werden die Wirkstoffe mit den in der galenischen Pharmazie üblichen Zusatzen, Trägersubstanzen und/oder Geschmackskorrigentien nach an sich bekannten Methoden zu den üblichen Applikationsformen verarbeitet. Für die bevorzugte orale Applikation kommen insbesondere Tabletten, Dragees, Kapseln, Pillen, Suspensionen oder Lösungen infrage, uni für die parenterale Applikation insbesondere ölige Lösungen, wie z.B. Sesamöl oder Rizinuslösungen, die gegebenenfalls zusätzlich noch ein Verdünnungsmittel, wie z.B. Benzylbenzoat oder Benzylalkohol enthalten können.Preferred gestagens are d-norgestrel and 17a-thynyl-19-nortestosterone acetate. the Estrogenic and gestagenic drug components are preferably taken orally together applied, but they can also be administered separately or parenterally. For this purpose, the active ingredients are combined with the additives customary in galenic pharmacy, Carrier substances and / or taste corrections according to methods known per se processed into the usual forms of application. For the preferred oral application come in particular tablets, coated tablets, capsules, pills, suspensions or solutions in question, uni for parenteral application in particular oily solutions, e.g. Sesame oil or castor solutions, which may also contain a diluent, such as benzyl benzoate or benzyl alcohol.
Beispiel 1 (Zusammensetzung eines Dragees tSe Stufe) 1. Stufe 0,050 mg 17a-Äthinylöstradiol 0,050 mg d-Norgestrel 33,150 mg Lactose 18,000 mg Maisstärke 2;100 mg Polyvinylpyrrolidon 1*650 mg Talkum 55,000 mg Gesamtgewicht, das mit üblicher Zuckermischung auf etwa 90 mg ergänzt wird.Example 1 (composition of a coated tablet tSe level) 1st level 0.050 17a-ethinylestradiol 0.050 mg d-norgestrel 33.150 mg lactose 18,000 mg corn starch 2; 100 mg polyvinylpyrrolidone 1 * 650 mg talc 55,000 mg total weight, that with usual Sugar mixture is supplemented to about 90 mg.
2. Stufe 0,050 mg 17a-Äthinylöstradiol 0,125 mg d-Norgestrel 33,075 mg Lactose 18,000 mg Maisstärke 2,100 mg Polyvinylpyrrolidon -1,650 mg Talkum 55,000 mg Gesamtgewicht, das mit üblicher Zuckermischung auf etwa 90 mg ergänzt wird.2nd stage 0.050 mg 17a-ethinyl estradiol 0.125 mg d-norgestrel 33.075 mg lactose 18,000 mg corn starch 2,100 mg polyvinylpyrrolidone -1,650 mg talc 55,000 mg total weight, which is supplemented with a normal sugar mixture to about 90 mg.
Beispiel 2 (Zusammensetzung einer Tablette je Stufe) 1. Stufe 0,050 mg 17a-Äthinylöstradiol-1,000 mg 17a-Äthinyl-19-nor-testosteron-acetat 32,100 mg Lactose 18,000 mg Maisstärke 2,100 mg Polyvinylpyrrolidon 1,650 mg Talkum ~Ow100 mg Magnesiumstearat 55,000 mg Gesamtgewicht, das mit üblicher Zuckermischung auf ca. 90 mg ergänzt wird. Example 2 (Composition of a tablet per stage) 1st stage 0.050 17a-ethynyl estradiol-1,000 mg 17a-ethynyl-19-nor-testosterone acetate 32,100 mg Lactose 18,000 mg corn starch 2,100 mg polyvinylpyrrolidone 1,650 mg talc ~ Ow100 mg of magnesium stearate 55,000 mg total weight with the usual sugar mixture on about 90 mg is supplemented.
2. Stufe 0,050 mg 17a-Äthinylöstradiol 2,000 mg l7a-Äthinyl-19-nor-testosteron-acetät 31,100 mg Lactose 18,000 mg Maisstärke 2,100 mg Polyvinylpyrrolidon 1,650 mg Talkum 0,100 mg Magnesiumstearat 55,000 mg Gesamtgewicht, das mit üblicher Zuckermischung auf ca. 90 mg ergänzt wird.2nd stage 0.050 mg 17a-ethynylestradiol 2.000 mg l7a-ethynyl-19-nor-testosterone-acetate 31,100 mg lactose 18,000 mg corn starch 2,100 mg polyvinylpyrrolidone 1,650 mg talc 0.100 mg magnesium stearate 55,000 mg total weight with the usual sugar mixture is supplemented to about 90 mg.
Claims (1)
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2218831A DE2218831C3 (en) | 1972-04-14 | 1972-04-14 | Use of hormones for contraception |
| DE19732310963 DE2310963A1 (en) | 1972-04-14 | 1973-03-02 | METHOD OF CONTRACTION BY FOLLOWING STAGE COMBINATION PREPARATIONS |
| AU54228/73A AU479744B2 (en) | 1972-04-14 | 1973-04-06 | Method of contraception by the aministration of stage-combustion preparations |
| SE7304992A SE443508B (en) | 1972-04-14 | 1973-04-09 | TWO-STEP COMBINATION PREPARATION FOR ORAL CONTRACTION |
| NLAANVRAGE7305034,A NL174620C (en) | 1972-04-14 | 1973-04-11 | PACKAGING UNIT CONTAINING AN ANTI-CONCEPT. |
| GB1732873A GB1433032A (en) | 1972-04-14 | 1973-04-11 | Contraceptive method and preparations |
| US05/350,590 US3939264A (en) | 1972-04-14 | 1973-04-12 | Method for contraception by the administration of sequential contraceptive preparations |
| BE129984A BE798185A (en) | 1972-04-14 | 1973-04-13 | PHARMACEUTICAL COMPOSITIONS, IN PARTICULAR BASED ON OESROGENS AND THEIR USE |
| DK202973A DK141354C (en) | 1972-04-14 | 1973-04-13 | TWO STEP COMBINATION PREPARATIONS FOR ORAL PREGNANCY PREVENTION |
| CA168,714A CA1013674A (en) | 1972-04-14 | 1973-04-13 | Method of contraception by the administration of stage-combination preparations |
| ZA732580A ZA732580B (en) | 1972-04-14 | 1973-04-13 | Method of contraception by the administration of stage-combination preparation |
| US05/486,757 US3969502A (en) | 1972-04-14 | 1974-07-09 | Method for contraception by the administration of sequential contraceptive preparations |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2218831A DE2218831C3 (en) | 1972-04-14 | 1972-04-14 | Use of hormones for contraception |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2218831A1 true DE2218831A1 (en) | 1973-10-31 |
| DE2218831B2 DE2218831B2 (en) | 1979-01-04 |
| DE2218831C3 DE2218831C3 (en) | 1979-08-30 |
Family
ID=5842383
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2218831A Expired DE2218831C3 (en) | 1972-04-14 | 1972-04-14 | Use of hormones for contraception |
Country Status (3)
| Country | Link |
|---|---|
| CA (1) | CA1013674A (en) |
| DE (1) | DE2218831C3 (en) |
| ZA (1) | ZA732580B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3029726A1 (en) * | 1980-08-06 | 1982-02-25 | Werner Dr.med. 4400 Münster Steinschulte | Post coital contraceptive for enteral or parenteral admin. - contg. racemic norgestrel or levonorgestrel |
| DE3229612A1 (en) * | 1981-08-10 | 1983-02-24 | Syntex (U.S.A.) Inc., 94304 Palo Alto, Calif. | PHARMACEUTICAL PACK |
-
1972
- 1972-04-14 DE DE2218831A patent/DE2218831C3/en not_active Expired
-
1973
- 1973-04-13 CA CA168,714A patent/CA1013674A/en not_active Expired
- 1973-04-13 ZA ZA732580A patent/ZA732580B/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3029726A1 (en) * | 1980-08-06 | 1982-02-25 | Werner Dr.med. 4400 Münster Steinschulte | Post coital contraceptive for enteral or parenteral admin. - contg. racemic norgestrel or levonorgestrel |
| DE3229612A1 (en) * | 1981-08-10 | 1983-02-24 | Syntex (U.S.A.) Inc., 94304 Palo Alto, Calif. | PHARMACEUTICAL PACK |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA732580B (en) | 1974-03-27 |
| DE2218831C3 (en) | 1979-08-30 |
| CA1013674A (en) | 1977-07-12 |
| AU5422873A (en) | 1974-10-10 |
| DE2218831B2 (en) | 1979-01-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OI | Miscellaneous see part 1 | ||
| OI | Miscellaneous see part 1 | ||
| C3 | Grant after two publication steps (3rd publication) |