RU2233586C1 - Preparation for regulating reproductive function and sexual activity in vertebrates and method for regulating reproductive function and sexual activity in vertebrates - Google Patents

Abstract

FIELD: veterinary science, animal science.

SUBSTANCE: the suggested preparation as progestogen contains the following compound of total formula in efficient amount:

where R - a substitute containing either aryl or heteryl radical. The above-mentioned compound should be introduced for vertebrates in efficient quantity. The present innovation enables to stimulate estrus in animals and increase synchronism of its manifestation, regulate both hyper- and hypofunction of ovaries and, also, decrease sexual activity in female and male vertebrates, moreover, suppression of sexual cyclic recurrence is of reversible nature.

EFFECT: higher efficiency of regulation.

10 cl, 6 ex, 4 tbl

Description

The invention relates to the field of veterinary medicine and animal husbandry, and in particular to a means and method of regulating the reproductive function and sexual activity of vertebrates.

Known means for regulating the sexual activity of vertebrates, containing a combination of progestogen and estrogen in effective amounts, where 3,17-dihydroxy-6-methylpregn-4,6-diene-20-one or its esters are used as a progestogen - “sex barrier” " The tool is used to inhibit the reproduction of vertebrates (see patent RU 2101013 C1, 01/10/98).

A known method of regulating the reproductive function and sexual activity of vertebrates, including sequential parenteral administration of progestogen and chorionic gonadotropin with estradiol benzoate (see, for example, SU 974981, 11.23.82).

The method is used to synchronize hunting in farm animals.

The objective of the present invention is to increase the efficiency of regulation of reproductive function and sexual activity of vertebrates.

The problem in terms of means and method of regulating the reproductive function and sexual activity of vertebrates is solved due to the fact that according to the invention as a progestogen, the agent contains in an effective amount a compound of the general formula I:

where R is a substituent containing an aryl (aromatic) or heteryl (aromatic with a heteroatom) radical, which is administered to the animal in an effective amount.

It is advisable to add a natural or synthetic estrogen to an effective amount of a compound of general formula I.

It is advisable to use an effective amount of a compound of formula I as a progestogen, where R = - (CH ₃ ) ₂ C ₆ H ₅ is amol phenylpropionate.

It is also advisable as a progestogen to use an effective amount of a compound of formula I, where R = —C ₅ H ₄ N is amonic isonicotinate.

It is also recommended that vitamins in an effective amount and / or flavorings and perfumes be added to the composition of the product.

It is also advisable to introduce neurotropic agents (central anticholinergics or adrenergic blockers) into the composition of the drug in an effective amount.

It is advisable to administer to the animals an effective amount of a compound of general formula I in the form of tablets.

It is also recommended that animals administer an effective amount of a compound of general formula I in the form of powders.

It is also recommended that animals administer an effective amount of a compound of general formula I in capsule form.

It is also advisable to administer to animals an effective amount of a compound of general formula I in the form of vaginal suppositories.

It is also recommended that animals administer an effective amount of a compound of general formula I in the form of uterine spirals.

It is also advisable to administer to animals the compounds of general formula I in the form of drops (using polyethylene glycol or natural vegetable oils as a solvent).

It is also recommended that the animals be given injections of the compounds of general formula I.

It is also advisable to administer to animals compounds of the general formula I in the form of subcutaneous implants.

It is recommended that when the animals are administered an effective amount of the compounds of general formula I, an additional FFA in an effective amount is additionally administered.

It is also advisable, when the animals are administered an effective amount of the compounds of the general formula I, to additionally administer prostaglandin in an effective amount.

The technical result provided by the invention, both in terms of means and in part of the method, is that they can stimulate hunting in animals and increase the synchronism of its manifestation, regulate hyper- and hypofunction of the ovaries of animals, and also reduce the sexual activity of individuals of both sexes while the suppression of sexual cyclicality is reversible.

The tool and method for regulating the reproductive function and sexual activity of vertebrates according to the invention are illustrated by the following examples, which, however, do not cover, and even more so do not limit the entire scope of the claims of this invention.

Scheme for obtaining steroid esters

R see table 1 physico-chemical data

Example 1. Obtaining compounds of General formula I by the example of obtaining phenylpropionate amol.

To a solution of 10 g of 17α-acetoxy-3β-hydroxy-6-methylpregn-4,6-dien-20-one (amole) in 30 ml of pyridine, 6.8 ml of phenylpropionic acid chloride are added with stirring. The reaction mass is stirred and add 10 ml of concentrated ammonia solution, re-mix and then add 60 ml of water. After 30 minutes at room temperature, it was cooled to 10 ° C and held for 2 hours at room temperature. The precipitate is filtered off, washed with water, dried to constant weight. 13.21 (98.6% of theory) of amol phenylpropionate are obtained. The yield of purified amol phenylpropionate 12.1 g (90.3% of theory), mp 140-142 ° C, the amount of impurities less than 1% (TLC).

According to the classification accepted in toxicology, the above compounds with gestagenic activity belong to low-toxic compounds (LD50 with a per os administration of more than 10 g). When applying to the skin and mucous membranes, they do not have a local irritant effect, but they are able to penetrate intact skin, which makes them dangerous in the production environment, since a single exposure to the drug’s skin will have an effect for a long time (depending on compliance with personal protective measures and personal hygiene).

Example 2. The effect of neurotropic drugs on the contraceptive effect of the claimed group of compounds.

The effect of neurotropic drugs (central cholinolytics - amisil and antispasmodic and adrenergic blocking agents on the example of pyroxan) was studied in rats with the combined use of neurotropic drugs with amol phenylpropionate and ethinyl estradiol. The results of the experiments are shown in table 2.

The combined use of neurotropic drugs with gestagens of the claimed series and ethinyl estradiol leads to increased contraceptive action, which may allow the use of the studied compounds for the purpose of contraception in lower concentrations.

Example 3. Suppression of sexual arousal in vertebrates.

Cats and dogs were used as experimental animals. The results of the experiments are shown in table 3.

The data shown in table 3 show that the drug is an effective tool for inhibiting sexual arousal in all experimental animals.

Example 4. Regulation of reproductive function.

The experiments were performed on 30 sexually mature female rats weighing 180-200 g with a normal estrous cycle. Animals were kept in standard cages. For feeding used compound feeds, vegetables and cottage cheese. Vivarium lighting is modal. The vivarium room temperature is 20 ° C. The drug (phenylpropionate) was administered orally in oil form for 14 days at a dose of 0.6 mg / kg weight in combination with ethinyl estradiol (0.03 mg / kg).

Male rats were implanted into females 3 days after the administration of the test preparations. Fertilization day was determined by the presence of sperm in vaginal smears. Contraceptive activity was assessed by the number of non-pregnant rats out of the number of fertilized.

It was found that the introduction of the drug causes a contraceptive effect in 87.5% of rats.

Thus, the results obtained make it possible to judge the achievement of the goal - a highly effective drug was obtained, the use of which leads to a persistent contraceptive effect in animals.

Example 5. The study of the effect of compounds of General formula I on the synchronism of hunting in cows.

The experiments were carried out on 3 groups of cows with a total number of 45 goals. The cows of the 1st group were treated with one of the compounds of the general formula I - amol isonicotinate in combination with prostaglandin analogues F ₂ α and FFA; for the treatment of cows of the 2nd and 3rd groups, progesterone and acetomepregenol were used.

The results of the processing of animals are shown in table 4.

The data shown in table 4 show that the use of the claimed compounds allows to obtain a high synchronizing effect.

Example 6

200 cows were examined. The experimental and control groups of 19 and 5 animals, respectively, were selected from among the examined livestock.

The cows of the experimental group were injected intramuscularly with 10.0 ml of Surfagon, 10.0 ml of a 1.0% solution of phenolpropionate amol in a mixture of tetravite and benzyl benzoate (7 parts of tetravite and 3 parts of benzyl benzoate) and with an interval of 7 days 1000.00 IE of foligon and 500 mcg of estrumate. In the control group, the same treatment regimen was used, but instead of amol phenylpropionate, 10.0 ml of 1.25% progesterone was mixed with tetravit.

All cows of the experimental and control group 48 hours after the injection of estrumate showed signs of hunting and were inseminated; Before insemination, animals were injected intramuscularly with 5.0 ml of surfagon.

In 10 cows of the experimental group and in all control animals 04.12; 12/07; 12/9; 12.12 blood samples were taken for subsequent determination of the profile dynamics of sex steroids (progesterone and 17β-estradiol).

A preliminary analysis of the results showed that the test drug phenolpropionate amol in a dose of 0.1 g per head blocks the functional activity of the ovaries of cows for at least 7 days. Side effects of the drug were not found.

Claims (10)

1. A tool for regulating the reproductive function and sexual activity of vertebrates based on a progestogen, characterized in that, as a progestogen, the agent contains in an effective amount a compound of the general formula I

where R is a substituent containing an aryl (aromatic) or heteryl (aromatic with heteroatom) radical. 2. The tool according to claim 1, characterized in that it further comprises an effective amount of natural or synthetic estrogen. 3. The tool according to any one of paragraphs.1 and 2, characterized in that as a progestogen contains in an effective amount of a compound of formula I, where R = - (CH ₂ ) ₂ C ₆ H ₅ - amyl phenylpropionate. 4. The tool according to any one of claims 1 and 2, characterized in that as a progestogen contains in an effective amount a compound of formula I, where R = —C ₅ H ₄ N is amonic isonicotinate. 5. The tool according to any one of claims 1 to 4, characterized in that it further contains vitamins in an effective amount and / or flavorings and perfumes. 6. The tool according to any one of claims 1 to 5, characterized in that it further comprises neurotropic agents in an effective amount. 7. A method of regulating the reproductive function and sexual activity of vertebrate animals, comprising administering a progestogen, characterized in that, as a progestogen, animals are administered in an effective amount an agent according to any one of claims 1 to 6. 8. The method according to claim 7, characterized in that the tool according to any one of claims 1 to 6 is administered either in the form of tablets, or in the form of powders, or in the form of capsules, or in the form of uterine spirals, or in the form of drops, or as injections, or as subcutaneous implants. 9. The method according to claim 7, characterized in that the animals are additionally injected with FFA in an effective amount. 10. The method according to claim 7, characterized in that the animals are additionally injected with prostaglandin.