CS229719B1

CS229719B1 - Agent to provoke belling with home animals

Info

Publication number: CS229719B1
Application number: CS832781A
Authority: CS
Inventors: Antonin Rndr Csc Cerny; Jiri Ing Csc Krepelka; Milos Rndr Csc Beran; Arnos Rndr Pospisil; Karel Rezabek; Miroslav Seda; Marie Auskova; Jana Chlebounova; Helena Raskova; Petr Krejci; Jaroslav Cerny; Jiri Spacil; Alois Krajicek; Josef Kral
Original assignee: Cerny Antonin; Krepelka Jiri; Beran Milos; Arnos Rndr Pospisil; Karel Rezabek; Miroslav Seda; Marie Auskova; Jana Chlebounova; Helena Raskova; Petr Krejci; Jaroslav Cerny; Jiri Spacil; Alois Krajicek; Josef Kral
Priority date: 1981-11-12
Filing date: 1981-11-12
Publication date: 1984-06-18

Abstract

Vynález se týká prostředku, pro vyvolávání říje u hospodářských zvířat, který obsahuje jako účinnou látku ergolinový derivát obecného vzorce I nebo II, inhibující sekreci prolaktinu a tím zvyšující sekreci gonadotropinů v adenogypofýze zvířat. Prostředek, který lze podávat peroráIně nebo panteralně, je určen pro regulaci říje a laktace u hospodářských zvířat, především u prasnic a krav.The invention relates to a composition for development rearing in livestock, which it contains ergolin as the active substance a derivative of formula (I) or (II) inhibiting prolactin secretion and thereby increasing secretion of gonadotropins in adenogypophysis of animals. A composition that can be administered orally or panterally, it is designed for regulation oestrus and lactation in farm animals, especially in sows and cows.

Description

1 229 719

FIELD OF THE INVENTION The present invention relates to a method for inducing oestrus in farms. animals containing an ergoline derivative of formula (1) as active ingredient

/ 1 /,

wherein X denotes hydrogen atoms, or together form a 9,10 double bond or ergoline derivative of formula II

Wherein H is a group -OOHB, or, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent and / or carrier and / or excipient.

As is well known, the regulation and appropriate timing of proliferation functions in the livestock chain brings great economic savings and gains. The basic task is to achieve this and to fertilize females in economically feasible terms, using methods that use, for example, hormones, prostaglandins or even original synthetic substances. Ergoline derivatives of formula (1) or (II) show significant activity in terms of inhibition of prolactin secretion and a corresponding increase in gonadotropin secretion in the hypophysis of farm animals.

The Ergoline Derivatives of Formula (I) or (II) and processes for their preparation are known in the art and have been approved by the Applicant's Certificate No. 127 998, 132 156, U3 170, 152 153, 156 178, 201 303 and 204 606, but their use for production the composition according to the invention is novel, and the composition according to the invention which contains the ergoline derivative of the formula I or II is also novel.

The method of inducing oestrus, found by the inventors in female mammals, is based on the finding that the pro-lactation of prolactin and the secretion of gonadotropins PSH and IH, leading to ovulation, is a negative / inverse proportionality and that prolactin secretion induced by ergoline derivatives of the general formula I or II, administered at appropriate dosages and appropriate dosing regimens, is accompanied by an increase in PSH and I> H ·

It is known that prostaglandins can also be used for these purposes. However, the advantage of the compositions of the invention is that they act by a different mechanism of action and that their active ingredients are made more easily and economically than the said prostaglandins.

The composition according to the invention can be used for breeding farm animals and other mammals both for direct development of the pest and its synchronization in large-scale farms, or for shortening the time between delivery and the following concept. Examples of use of the composition of the invention in cows and powder

A group of 124 cows aged 2.5 to 10 years, but mostly 3 years old, many of whom had no provable estrous for a long time, were injected with bis-hydrogen maleate D-6-methyl 1-8 / 3 - / 2-isopropanol. pylaminoethyl / ergoline (formula II, H 2 OB 3 KHCE / CE 3 / g), intramuscularly, at a dose of 0.1 mg / kg, i.e., an average of 50 mg / animal, regardless of the current stage of the estrile loop. In the case of 117 cows / 95, estrus occurring in the vast majority of animals was observed within 5 days. The composition containing the dihydrogenoate H- (D-6-methyl-8-ergolinyl) -fluoromethylurea which was administered at a concentration of 4 mg / ml at a dose of 10 mg / 100 kg / 0.1 mg / was tested. kg / intramuscular gilts with an average weight of 110 kg and an age of 7 to 5 months. In the control group there were 129 animals, 52 animals in the experimental group. Saline solution was administered to the control group. After insemination, the control group was followed by an average of 35 $ 6 cases in the control group after 25 days, in 71 cases in the experimental group.

Births in animals after administration of the composition according to the invention were normal, the number of all live-born piglets (6 to 10) was unaffected, their development was in line with standard. Neither sows nor piglets were affected by the application of the invention.

The composition of the invention may contain the active substance bull in the form of a base or in the form of a soluble addition salt with a pharmaceutically acceptable organic or inorganic acid. the dosage forms into which the composition is formulated are intended for oral or parenteral administration. For example, capsules, tablets, pellets, granules and the like, administered directly, optionally solutions, powders, premixyapods, administered in drinking water or admixed with the feed, serve for oral administration. Subcutaneous, intramuscular or intravenous injections can be administered parenterally. Formulations for oral administration can be prepared according to conventional pharmaceutical practice with the addition of customary solvents, diluents, carriers or excipients such as talc, starches, sugars, cellulose derivatives, or fabric stabilizers.

For parenteral administration, the active ingredient, preferably in the form of a salt, is dissolved in a suitable solvent, for example, in sterile water, saline, gluceyapod solution, optionally with the addition of suitable solubilizers and / or stabilizers.

A suitable dose of the composition according to the invention depends on the second active ingredient used, the route of administration and the animal species and is usually determined by the veterinarian *

The individual compositions of the invention and their compositions are exemplified by the following non-limiting examples. Example 1

10% D-6-methyl-8 - / 2-isopropylaminoethyl / - ergoline bishydrogen maleate 1.0 g saoharose 1.0 g water to 10.0 ml

The components were mixed in water until dissolved, and the solution was made up to a volume of 10.0 mL. It is administered in drinking water at a dose of 0.1 ml per 100 kg animal weight. Example 2

2.5% D- (D-6-methyl-8c -ergolenyl) -phenyl-N-di-ethylmono-hydrogen maleate powder 2.5 g saoharose to 100.0 g The active ingredient is perfectly homogenized with saoharose.

The powder is administered dissolved in drinking water or mixed into the feed at a dose of 1 g per 100 kg animal weight * Example 3

Solution for injection 229,719 K- / S-6-methyl-8o-ololinyl / SiO, ethyl diethylurea-hydrogen maleate 20.0 g ethanol med · 2.0 g glycerin 6.0 g water to 20.0 g The active substance is dissolved in a mixture of ethanol, glycerol and water and, after filling to a volume of 20 ml, the solution is sterile filtered. A solution for 1 injection is obtained, containing 1 mg of the active ingredient in 1 ml of solution. The injection is applied to the intestinal barrel at a dose of about 0.04 to 0.1 mg / kg animal weight. Example 4Granulate> - / D »6 ™ methyl-3c <-ergolenyl} - *, N * di-ethylmo- siona-hydrogen maleate 2.5 glactose 50.0 gsaoharoaa 18.0 gcuric starch 25.0 gpolyvinylpyrrolidone 4.5 g Effective the substance is mixed with lactose, saoharose acoustical starch, homogenized and granulated with 3 (a solution of polyvinylpyrrolidone in water). The granulate is dried at a temperature below 35 ° C. up to 1.0 g / 100 kg animal weight Example 5 Tablets / D-6-ethyl-8β -ergolinyl / acetamide 25.0 mg lactose 300.6 mg saoharoaa 44.0 mg maize Starch 192.0 mg polyvinylpyrrolidone 12.0 mg stearin 2.4 mg ultra amylopectia 24.0 mg 229 719 - 6 - the quenching substance is gradually mixed with the lactate, saoharose and corn starch, and the granulate is prepared as in Example 4 · Atearin and ultraamylopithium are added to the dry granulate and tablets with a diameter of 15 mm and a weight of 600 mg are punched on the tablets. orally 1 to 2 tb 1/500 kg animal weight ·

Claims

7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 7 The formulation, which is a derivative of general oestrus in farm animals, that it contains ergoline formula I as active substance

Wherein X is hydrogen, or taken together to form a double bond at position 9,10, or an ergoline derivative general formula IZ

wherein fi represents a group -OONB1 or a OBO SHOB / OH2 / g, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent and / or carrier and / or excipient # 4