Formulated with contraceptive activity

 

(57) Abstract:

The invention relates to medicine, in particular to hormonal tools, and comes with contraceptive activity gestagen-estrogenic composition. Features gestagen-estrogenic composition containing as progestogen 3-butyrate 6-methyl-17-acetoxyphenyl-4,6-Dien-3-ol-20-it, and as estrogen 3,17-diacetate 11 nitroxy-17-itinerante-1,3,5(10)-triene-3,9,17-Tirol. The inventive composition has a high contraceptive activity, inhibits pregnancy when using not only commonly used, but also reduced doses of progestogen and estrogen. 1 C.p. f-crystals, 2 tab.

The invention relates to hormonal tools and comes with contraceptive activity gestagen-estrogenic composition containing as progestogen 3-butyrate 6-methyl-17-acetoxyphenyl-4,6-Dien-3-ol-20-it, and as estrogen 3,17-diacetate 11 nitroxy-17-itinerante-1,3,5(10)-triene-3,9, 17-triol.

The scope of medicine, where the subject of the invention can find application for regulation of fertility, as well as for hormone replacement therapy in gynecology and endocrinology.

It is known the use of a progestogen-oestrogen pre is anpilova I. A.//Modern contraception Moscow, 1993, S. 52-123] and as a means of hormone replacement therapy in gynecology and endocrinology [Bogdan W., Szekeres L., Jambor E.//Modern hormonal oral contraceptives and their therapeutic applications, Budapest, 1996, S. 3-22]. At the same time as the progestogen used 17-ethinyl-19-nortestosterone (norethisterone) and its analogs with 5(10)-double bond (norethynodrel), and WITH13is an alkyl group (norgestrel) [Mashkovsky M. D. // Medicines, Moscow, New wave, 2000, H. 2, S. 49-54]. The range used estrogen is significantly narrower and includes levonorgestrel and its methyl analog (mestranol), effective only at high doses.

Oral contraceptives the last generation (prototype) are compounds containing ethinylestradiol and the progestogen three types of analog norgestrela. These include 3-oxime norgestrela (norgestimate), similar norgestrela with an additional 14(15)-double bond (gestodene) and (C3-detoxing with11-methylene group (desogestrel).

The disadvantage of contraceptive pills is the immutability of the estrogenic component, largely contributing to the side effects of contraceptives [Korchow Century. Century.//Estrogen-progestin is used only a derivative of norethisterone or similar norgestrela, significantly limits the ability to create new hormonal contraceptive products.

The aim of the invention is to increase safety gestagen-estrogenic compounds, as well as expanding their range. To achieve this objective, it is suggested gestagen-estrogenic composition containing as progestogen 3-butyrate 6-methyl-17-acetoxyphenyl-4,6-Dien-3-ol-20-it formula I, and as estrogen 3,17-diacetate 11 nitroxy-17-itinerante-1,3,5(10)-triene-3,9,17-triol of formula II

The inventive composition has a high contraceptive activity, inhibits pregnancy when using not only commonly used, but also reduced doses of progestogen and estrogen.

In table.1 presents a comparative study of the proposed structure and the progestogen-estrogen combinations, representing the compositions of all the most common oral contraceptive products created over the past 20 years. As follows from the presented data, when using the commonly used dose of the inventive composition shows 100% inhibition of pregnancy and superior effect of the combination of ethinyl estradiol (EE) with norethisterone 2.1, EE with norgestrel in 1,78, and EE with dezo the but) in commonly used doses are equal to the claimed composition contraceptive effect.

The inventive composition was prepared by dissolving 15 g of estrogen and 90 g gestagen in 1 ml of olive oil.

When using reduced doses of progestogen and estrogen, taken in amounts, respectively, 0,0375 and 0.015 mg/kg, which is half the contents of each steroid in the low-dose drug femoden, the claimed composition retains a high contraceptive activity, inhibiting pregnancy 100%. As follows from the table.2, the drug femoden in these doses has no contraceptive activity, and drug cilest in comparable doses equal to 1/3 of the commonly used, has a contraceptive effect in 2.8 times smaller effect of the claimed composition. Contraceptive activity was determined by the standard method [Alipov Century. And., Korchow Century. Century.//Contraceptives, Leningrad, Medicine, 1985] on rats in each group at least 14 animals.

The result of the experiment revealed a more active mating females with the introduction of the proposed structure on the background of the Comparators, shown inhibitory effect on sexual behavior. The absence of this inhibitory effect on the sexual behavior of the proposed structure suggests that in clinical trials the drug based on it will not take contraceptive activity, exceeds the effect of the progestogen-oestrogen compounds used in all oral contraceptives last generations. The composition can be used effectively reduced when compared to commonly used content progestogen and estrogen.

Based on the comparison of the proposed structure with the prototype and analogs can be stated that for the first time, the compositions of the gestagen and estrogen meets the criteria of the invention.

A study of toxicity as claimed composition and of its components in two species (rats, mice). The toxicity of the composition is not detected when using a cumulative dose of steroids 1 g/kg weight of the animal, exceeding therapeutic dose over five orders of magnitude, with a ratio of gestagen: estrogen 6:1. The study organotropic effects showed no significant changes from the internal organs of animals. Was not observed mortality with the introduction of estrogen II at doses up to 1.5 g/kg or progestogen I in doses up to 1 g/kg weight of the animal.

1. Formulated with contraceptive activity and characterized in that as the gestagen features 3-butyrate 6-methyl-17-7-acetoxyphenyl-4,6-Dien-3-ol-20-she Faure CLASS="ptx2">

2. Composition under item 1, characterized in that the ratio of the progestogen/oestrogen is 6:1.

3. The composition according to PP.1 and 2, characterized in that it is designed for oral administration.

 

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