Injection preparation for higher sperm production in farm breeders and cocks, and method for using it

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, more specifically, to using a chimeric somatostatin-containing protein for improving the reproductive properties of male farm animals and cocks, and may be used in veterinary science. The injection preparation is used in the form of a chimeric protein suspension with water-insoluble enzyme-inactive chloramphenicol acetyltransferase with no 10 C-terminal amino acids, amino acid spacer (Sp)n, wherein n=1, 2, 4, 8 and somatostatin-14 with AGCFWKTFTSC amino acid sequence in the refined vegetable oil with bee wax added at 250-1000 mg of the above chimeric protein per 100 ml of the refined vegetable oil containing 0.9-1.1 wt % of bee wax. The injection preparation is used in cocks and farm animals after achieving the physiological maturity at 50-200 mcg of the protein per 1 kg of a live body weight.

EFFECT: invention enables increasing sperm production: increasing the ejaculate volume and reducing the biologically damaged sperm in farm animals and cocks by using the preparation for injections with a low-reactogenicity adjuvant.

2 cl, 13 tbl

 

Scope

The invention relates to veterinary medicine, and specifically to inject the drug to increase spermophobia producers of farm animals and chickens and method of its application. The invention is intended to enhance the reproductive ability of producers of farm animals and chickens for their more effective use by increasing ejaculate volume with a significant reduction of the marriage of sperm on biological parameters (sperm motility, live sperm and their morphological completeness), which ultimately increase the profitability of artificial insemination of animals.

Known level

Modern veterinary science solves the problem of improving the reproductive abilities of producers of agricultural animals and poultry, using biologically active products - vitamins, macro-minerals, herbal preparations, as well as using physiological methods dosed direct contact of male-producers with sexually Mature females of animals in hunting.

Chemicals are expensive and do not always guarantee positive effect. Data from the literature known to the stimulating and adaptogenic effect of extracts of Rhodiola rosea. When fed to the boars, the manufacturer shall within 60 days of the preparation from the dried roots of Rhodiola rosea authors (Aginary, Accumultion. Veterinary medicine, No. 10, 2003) found an increase in the volume of ejaculate by 7.9-13.8 per cent with preservation to control the level of sperm concentration. After fertilization the biological characteristics of sperm returned to the initial level.

Stimulating effect on sperm production of bulls has a drug based on inactivated biomass halobacteria Halobacterium halobium, which contains amino acids, lipids, water - and fat-soluble vitamins (Gwitchin, Nagabharana, Raharison. Problems of productive animal biology, No. 4, 2011). When feeding the bulls-manufacturers of the drug on the basis of halobacteria ("Baxin-vet"), the authors noted a reduction in the number of rejected ejaculates, improving the quality of native seed enhancement of the survival of cryopreserved sperm after thawing for 5 hours outside the body at a temperature of 37°C. the Effect was maintained for 30 days after completion of the feeding of the drug in subsequent figures spermophobia returned to the level prior period.

In studies Sokolica, Carpov, Compiling shows the stimulating effect of the drug, "Baxin-vet" on the productive characteristics of boars manufacturers. Daily application of boar-manufacturers of the drug, "Baxin-vet" for three weeks at a dose of 5 and 10 mg / kg body weight when the content of the grunts even on the commercial diet has led to an increase in ejaculate volume and sperm count in the semen. (Sokolichin, Carpov, Compilin. "The influence of the drug, "Baxin-vet" on the sperm production of boars and the prolificacy of sows in intensive pork production". "Pig" No. 2, 2009).

In the work Spoonboy "Improving the reproductive function of boars with the use of biologically active substances" (the dissertation on competition of a scientific degree of candidate of biological Sciences, VNIIG, dubrovitsy, 2001) have shown that feeding boars-producers of biologically active drugs "SGOL and Stimulen" has a positive influence on the manifestation of reflexes intercourse and erection producers, increases the amount of ejaculate and the contents of sperm in the ejaculate.

In studies Sahalia the positive influence of selenium drug "Dipole" for the correction of the reproductive functions of bulls ("Application of selenium drug "Dipole" for the correction of the reproductive functions of bulls", Voronezh, 2000).

The studies described in the international application WO 03/064619 (WO 03/064619 A2, IPC AC 38/00, 20036), improvement of spermatogenesis is provided by activation of VEGF, which induces an increase in the vascularization of tissue gonads.

Another method of increasing spermophobia producers of agricultural animals and poultry based high concentrations in the body endogenous growth hormone induction of the synthesis automatisation antibodies. This leads to a decrease in the concentration of endogenous somatostatin and enhance the content of the hormone that, in turn, has a stimulating effect on the growth and proliferation of cells in the gonads of animals.

Somatostatin is a biologically active tetradecapeptide produced in the hypothalamus and the gastrointestinal tract of animals. For the first time the biological activity of a substance, later defined as somatostatinoma, was discovered in 1968 by Crusecom. Subsequently, from the hypothalamus of animals was selected substance representing low-molecular peptide having the ability to regulate the concentration of growth hormone in animals.

Somatostatin-14 has a strong inhibiting effect on the number of hormones (growth hormone, thyroid-stimulating hormone (TSH), insulin, glucagon, gastrin, pepsin), triggers the inhibition of the secretion of digestive enzymes, the pancreas, small intestine, slow motility of the gastrointestinal tract and the evacuation of its contents.

The study of amino acid composition of somatostatin various members of the animal Kingdom showed a sufficient degree of homology peptides, synthesized by living organisms at different stages of evolutionary development. Amino acid sequence of somatostatin-14 identification is on living organisms - from fishes to mammals.

A wide range of physiological actions of somatostatin-14 and no, unlike growth hormone, species specificity in mammals has been the basis for exploring the possibility of its use to optimize breeding and fattening, increase milk productivity of animals.

In the United States, Canada, great Britain for more than thirty years ago were made as a separate work by active immunization of animals (cattle, sheep, pigs) against somatostatin-14 (Spenser et al.). The authors of the research say that the dynamics of weight gain in the same conditions immunized animals exceeded the control group by 20-30%, while in the blood was found to have an increased content of endogenous growth hormone. In the research process was found to reduce the time of feeding, the increase in milk yield and, as a consequence, the reduction of non-productive costs per unit produced livestock products. Further experiments were carried out with different species of animals. Studied the effect of passive and active immunization in hormone levels, dynamics of the increase in body weight of animals and other parameters. Introduction antisomatostatin serum of rats resulted in increased concentrations of endogenous growth hormone, passive and is timetostring immunization of sheep was led to the increase in the residence time of food in the gastrointestinal tract, increased activity of digestive enzymes. Active immunization of animal proteins, the resulting chemical binding of the synthetic somatostatin protein-carriers, has led to increased levels of growth hormone, insulin growth factor, gastrin and other functionally related to somatostatin biologically active compounds. The result of the active antisomatostatin immunization has been an increase in the body weight of the animals at 8-17%.

Method somatostatinomas immune deprived of many of the disadvantages arising from the use of anabolic hormones or recombinant somatotropin. The mechanism of action is based on the temporary binding of endogenous somatostatin-14 specific antibodies and increasing concentrations of endogenous growth hormone in physiological limits. However, wide application of the method of active immunization of animals against endogenous somatostatin-14 a long time it was impossible due to its high cost as the main way of obtaining peptide was chemically synthesized, which is economically not allowed to implement this approach in practice. Because of the small size of the somatostatin-14 does not allow its direct microbial synthesis using recombinant DNA technology described several ways it is the synthesis in the form of chimeric proteins with subsequent isolation of the target product, not given satisfactory results. The main disadvantage of the above methods is extremely low immunogenicity obtained drugs against somatostatin, due to its masking of the molecule in the chimeric protein, therefore, these methods of producing chimeric proteins did not find wide practical use (R. Itakura et al., 1977 Expression in E. Coli of a chemically synthesized unit gene of hormone somatostatin, Science, 1986, 1056-1063; A.A. Shishkin and other Synthesis fragment somatostatin genes. Chemistry of natural compounds, 1988, No. 6, s-615).

The known method of constructing chimeric somatostatinergic proteins using amino acid spacer containing arginine and Proline, causing localization of somatostatin on the surface of carrier protein and, thereby, the high immunogenicity of the drug (RU 2031121 C1 IPC C12N 15/12, 1995). The design consists of a water-insoluble protein carrier (fragment of bacterial chloramphenicolchloramphenicol without the 10 C-terminal amino acids), tetramer spacer and C-terminal somatostatin-14. The molecular weight of the chimeric protein is 28 kDa. This chimeric protein is expressed by Escherichia coli In-6519 transformed by the plasmid pC(Sp)4 S. Strain deposited in Russian national collection of industrial microorganisms (VKPM) under number B-6519. Chimeric protein with the exposed somatostatin the om is a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acid residues, to which through spacer elements sequence attached to the amino acid sequence of somatostatin-14. Method antisomatostatin immunization of animals with the use of this chimeric somatostatinergic protein is suggested for use in the cattle industry to increase the productivity of farm animals (EN 2034457 C1 IPC AC 67/02, 1995). To the productivity of farm animals include: dairy, meat production, wool production (Large Soviet encyclopedia, editor Amerkhanov. M.: Publishing house "Soviet encyclopedia", 1975, volume 21, page 36, the category "Productivity of agricultural animals").

Know when to prepare the finished dosage form of the drug to increase meat and milk productivity of farm animals, containing an effective amount of a chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and sequence of somatostatin-14 amino acid sequence AGCFWKTFTSC used as adjuvant incomplete adjuvant's adjuvant (EN 2034457 C1 IPC AC 67/02, 1995). However, the high reactogenicity adjuvant, the presence of pain in animals when it is introduced and has resulted in the need to find other adjuvant systems.

It is known that the use of the drug to increase meat efficiency of broilers containing an effective amount of a chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and sequence of somatostatin-14 amino acid sequence AGCFWKTFTSC in liposomal form (RU 2337708 C1 IPC AC 39/385, 2006), which in this case is unacceptable due to low concentrations of active ingredient per unit volume (<1·10-3g/ml). For an animal weighing more than 500 kg would require the introduction of some twenty milliliters of the drug, which is in practice problematic circumstance.

The invention

The objective of the invention is the use of chimeric somatostatinergic protein to increase the reproductive characteristics of male farm animals and chickens, namely increasing spermophobia (increase ejaculate volume reduction marriage sperm on biological indicators) from the producers of farm animals and chickens in the form of a preparation for injection with low reactogenicity adjuvant that allows injection without pain manufacturers of farm animals and chickens.

Re is giving this task provides the drug to increase spermophobia producers of farm animals and chickens in suspension chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC refined vegetable oil with the addition of beeswax.

The drug contains a chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC based 250-1000 mg of the indicated chimeric protein per 100 ml of refined vegetable oils, including a 0.9-1.1 wt.% beeswax.

Use as an adjuvant for such preparation of vegetable oil, fully metabolized in the animal body, greatly reduce the level of reactogenicity adjuvant and creates the necessary conditions for the gradual admission of the active substance in the body of the animal (depot preparation). Can be used sunflower, cotton and peanut butter. The mechanism of drug action based on the temporary blocking activity of endogenous somatostatin farm animals and chickens, increased concentrations of somatotropic hormone, and increased activity of spermatogenesis. The presence of beeswax in the final recipe of the drug is justified by the need the firm achieve an equal distribution of the chimeric protein in a volume of vegetable oil, reducing the speed of sedimentation of the chimeric protein, maintaining sterile properties of the dosage form of the drug, which is especially important when the injection of the animals with the help of needle machines.

The way to increase spermophobia producers of farm animals and chickens provides two subcutaneous injections with an interval of 14 days of drug in suspension chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC refined vegetable oil with added beeswax males or agricultural animals after reaching physiological maturity based 50-200 µg of protein per 1 kg of body weight. Drug use in suspension chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC in the amount of calculation 250-1000 mg of the indicated chimeric protein per 100 ml of refined vegetable oils, including a 0.9-1.1 wt.% beeswax.

The implementation of the invention and efficacy

Forex is the efficiency of the implementation of the invention is illustrated by the example of getting a drug to increase sperm production in farm animals and chickens.

Obtained and purified from the impurities of the drug is protein dissolved in buffer 0.2 M Tris-HCL pH 8.0, containing 6M guanidinium and 2M of META. Add 50-fold molar excess of β-mercaptoethanol in the calculation of the number of S-S groups chimeric protein and the solution is quickly diluted 10-fold volume of buffer without handinhand. The resulting hybrid protein precipitate is separated by centrifugation for 15 minutes at 12000g and a temperature of 4°C and freeze-dried for storage or cooking oil suspension.

For the preparation of ready-made forms of drug use refined vegetable oil and beeswax. In vegetable oil, add the beeswax from the calculation of 0.9%. The oil is heated to a temperature of 45-50°C, stirring, achieve complete dissolution of the wax. Then oil with wax cooled to a temperature of 35-37°C and add a portion of the dry protein at the rate of 250 mg per 100 ml of adjuvant. The suspension is homogenized for 1-2 minutes and transfer to the filling equipment. The finished emulsion of the drug Packed in packagings (glass vials and disposable syringes). When different concentrations of the components of the drug is prepared similarly. Preferred are the following components per 100 ml refined oil: 250 mg of chimeric protein to 0.9 wt.% beeswax; 500 mg of chimeras the CSOs protein 1.0 wt.% beeswax; 1000 mg of chimeric protein - 1.1 wt.% beeswax.

The efficacy of the drug to increase sperm production in farm animals and chickens under physiological maturity, is illustrated by the following examples.

In industrial pig-breeding complex of boar-manufacturers of large white breed and Duroc breed was introduced to the drug twice with an interval of 14 days from the calculation of 50-200 µg of recombinant protein per 1 kg of body weight.

The grunts producers before and after use of the drug in the established order was carried out by taking sperm and determined ejaculate volume, sperm concentration in the ejaculate and the number of supermodes. Indicators of spermophobia boars using the drug in a dose of 50 μg per 1 kg of body weight are shown in table 1.

The drug had a positive effect on sperm production of boars.

After the first injection the animals of large white breed volume of ejaculate boars increased by 5.8 13.8%, and in 30-60 days after the second injection volume of ejaculate increased by 23.6-25.4 per cent, also increased the concentration of sperm in the ejaculate 12.1 to 14.1%, which influenced the increase in the number of received spermatos 38.3-42,6%. Close pok the performance spermophobia were detected using the drug and boars of Duroc breed.

Indicators of spermophobia boars using the drug in a dose of 100 μg per 1 kg of body weight are shown in table 2.

The drug at a dose of 100 μg per 1 kg of body weight also had a positive effect on sperm production of boars. 30-60 days after the second injection volume of ejaculate boars increased by 18.9 16.6%were also increased concentration of spermatozoa in the ejaculate 12.2 13.8%, and that influenced the increase in the number of received spermatos by 34.8-38,6%. Similar figures of spermophobia using the drug were found and boars of Duroc breed.

Indicators of spermophobia boars using the drug at a dose of 200 μg per 1 kg of body weight are shown in table 3.

The drug at a dose of 200 μg per 1 kg of body weight also had a positive effect on sperm production of boars. 30-60 days after the second injection volume of ejaculate boars increased by 16.5-15,9%, also increased the concentration of sperm in the ejaculate 11.1-12.9 percent, which influenced the increase in the number of received spermatos 29.1-37,1%. Similar figures of spermophobia using the drug were found and boars of Duroc breed.

Study of the effect of the drug on sperm production sires conducted by artificial insemination of selskokhozyaistv is the R animals.

An oil suspension of the drug, the animals were injected subcutaneously at a dose of 50-200 µg of protein per 1 kg of body weight twice with an interval of 14 days between injections.

The bulls before and after use of the drug in the established order was carried out by taking sperm and determined ejaculate volume, sperm concentration in the ejaculate, the number of received spermatos and the percentage of defective sperm on biological indicators of semen quality (sperm count with straight-forward movement, survival).

Indicators of spermophobia bulls when the drug is administered in doses of 50, 100 and 200 μg per 1 kg of body weight are shown in tables 4-6.

The results of the experiments indicate that the stimulation of spermophobia the bulls in the use of the drug.

So the volume of semen collected from bulls of Holstein breed through 90 days after the first injection of the drug at a dose of 50 μg per 1 kg of body weight (table 4), increased by 28.7%, from manufacturers Ayrshire breeds this index has increased by 22.2%.

During the reporting period improved quality indicators taken sperm (activity of spermatozoa, their survival rate after 5 hours). The result of the drug on the bulls-producing dose of 50 μg per 1 kg of body weight is to increase the number recip is the R spermatos - 23.4-34,7% and reduced scrap rate of sperm on biological parameters.

Table 4
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
Holstein breed
The average volume of ejaculation ml3,90±0,15to 4.23±0,104,37±0,125,02±0,11
Sperm motility with primopiano translational movement points7,02±0,027,0±0,027,0±0,027,0±0,02
The concentration of spermatozoa billion/mlof 1.23±0.091,20±0.061,18±0.051,18±0.05
The activity of spermatozoa, points3,31±0,25 3,82±0,183,90±0,163,95±0,16
Sperm motility, 5 hours after incubation at 37°C, the points1,46±0,231,52±0,221,59±0,201,59±0,20
Marriage sperm on biological indicators %51,2±5,639,7±4,935,7±2,235,8±2,1
Qty received spermatos from one animal726±35959±26978±15978±15
Ayrshire breed
The average ejaculate volume, ml4,19±0,17br4.61±0,144,88±0,125,12±0,13
Sperm motility with straight-forward movement, points7,01±0.037,0±0,027.0±0,027.05±0,04
The concentration of spermatozoa billion/ml 1,40±0,101,36±0,071,32±0,091,29±0,06
The activity of spermatozoa, pointsof 3.77±0,323,47±0,283,89±0,214,19±0,23
Sperm motility after 5 hours incubation at 37°C, the points0,80±0,181,12±0,191,12±0,221,11±0,17
Marriage sperm on biological indicators %28,6±8,531,0±6,226,5±5,324,5±5,0
Qty received spermatos from one animal1416±421520±371675±281747±28

Table 5
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
Holstein breed
The average volume of ejaculation ml3,85±0,124,18±0,134,22±0,15to 4.92±0,10
Sperm motility with primopiano translational movement points7,02±0,027,0±0,027,0±0,027,0±0,02
The concentration of spermatozoa billion/ml1,22±0,081,18±0,04of 1.16±0.051,17±0,03
The activity of spermatozoa, points3,36±0,253,82±0,183,88±0,143,93±0,18
Sperm motility, 5 hours after incubation at 37°C, the points1,42±0,231,48±0,241,54±0,211,56±0,18
Marriage sperm on biological indicators % 49,3±4,938,7±4,634,7±2,134,8±2,5
Qty received spermatos from one animal722±32941±28968±15971±15
Ayrshire breed
The average ejaculate volume, ml4,16±0,154,55±0,144,78±0,115,02±0,15
Sperm motility with straight-forward movement, points7,02±0,027,0±0,027,0±0,027,06±0,05
The concentration of spermatozoa billion/ml1,38±0,111,33±0,081,30±0,101,30±0,07
The activity of spermatozoa, points3,76±0,313,44±0,253,82±0,204,11±0,25
Sperm motility after 5 hours after incubation, n and 37°C. points0,81±0,171,10±0,151,11±0,231,10±0,15
Marriage sperm on biological indicators %29,8±6,531,5±5,227,5±4,225,5±5,2
Qty received spermatos from one animal1408±381505±321637±241719±21

Table 6
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
Holstein breed
The average volume of ejaculation mlto 3.92±0,114,19±0,124,20±0,154,88±0,11
Sperm motility with p is Molinaro translational movement, points7,02±0,027,0±0,027,0±0,027,0±0,02
The concentration of spermatozoa billion/ml1,21±0,071,16±0,031,14±0,041,16±0,03
The activity of spermatozoa, points3,34±0,233,81±0,193,885±0,143,90±0,18
Sperm motility, 5 hours after incubation at 37°C, the points1,43±0,221,49±0,221,53±0,201,52±0,16
Marriage sperm on biological indicators %45,3±4,236,7±4,433,7±2,135,8±2,5
Qty received spermatos from one animal719±31938±26962±14968±15
Ayrshire breed
The average volume of the ejaculate, ml4,17±0,154,58±0,124,77±0,114,99±0,14
Sperm motility with straight-forward movement, points7,01±0,027,0±0,027,0±0,02? 7.04 baby mortality±0,03
The concentration of spermatozoa billion/ml1,34±0,101,31±0,071,30±0,121,32±0,06
The activity of spermatozoa, points3,66±0,283,54±0,233,80±0,174,08±0,22
Sperm motility after 5 hours incubation at 37°C, the points0,84±0,161,09±0,131,12±0,191,12±0,15
Marriage sperm on biological indicators %28,7±6,530,5±4,626,9±4,325,8±4,2
Qty received spermatos from one animal/td> 1395±331487±281617±181682±20

The analysis of indicators of spermophobia bulls after application of the drug at a dose of 100 μg per 1 kg of body weight (table 5) indicates a positive effect of the drug on the controlled parameters. So the volume of semen collected from bulls of Holstein breed through 90 days after the first injection of the drug at a dose of 100 μg per 1 kg of body weight, increased by 27.8%, from manufacturers Ayrshire breeds this index has increased by 20.7%.

During the reporting period improved quality indicators taken sperm (activity of spermatozoa, their survival rate after 5 hours).

The result of applying the bulls-the manufacturers of the drug at a dose of 100 μg per 1 kg of body weight is to increase the number obtained spermatos - 22.1-34.5% and reduced scrap rate of sperm on biological parameters.

The analysis of indicators of spermophobia bulls after application of the drug at a dose of 200 μg per 1 kg of body weight (table 6) indicates a positive effect of the drug on the controlled parameters. So the volume of semen collected from bulls of Holstein breed through 90 days after the first injection of the drug at a dose of 200 μg per 1 kg of body weight, increase is registered by 24.5%, manufacturers Ayrshire breeds this index has increased by 19.6%.

During the reporting period improved quality indicators taken sperm (activity of spermatozoa, their survival rate after 5 hours).

The result of applying the bulls-the manufacturers of the drug at a dose of 200 μg per 1 kg of body weight is to increase the number obtained spermatos - 20.5-34.6% and reduced scrap rate of sperm on biological parameters.

Similar experiments were carried out on sheep Vyatka (nolinskoe) rocks.

An oil suspension of the drug, the animals were injected subcutaneously at a dose of 50-200 µg of protein per 1 kg of body weight twice with an interval of 14 days between injections (tables 7, 8, 9).

The sheep producers before and after use of the drug in the established order was carried out by taking sperm and determined ejaculate volume, sperm concentration in the ejaculate and the number of received spermatos.

Indicators of spermophobia sheep producers using the drug in a dose of 50 mg per 1 kg body weight are shown in table 7.

The results are presented in table 7 of the experiments indicate that the stimulation of spermophobia the sheep producers in the use of the drug. So the volume of ejaculate, taken from rams through 90 days after the first injection, increased by 18.0%. For the controls the period has been created improved quality indicators taken sperm (motility, survival of spermatozoa). The result of the drug on sheep producers is to increase the number obtained spermatos from one animal 28.1% and reduced scrap rate of sperm on biological parameters.

Table 7
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
The average volume of ejaculation ml2,05±0,032,22±0,022,31±0,032,42±0,04
The average sperm motility, points8,0±0,018,0±0,018,0±0,018,0±0,01
The concentration of spermatozoa billion/ml2,2±0,052,17±0,042,15±0,022,16±0,06
Survival spermatozoa is s, watch259±6,0282±10,0293±8,0305±6,0
Marriage sperm on biological indicators %28,6±8,524,5±6,822,6±5,520,9±5,2
Qty received spermatos from one animal32±3,036±2,838±3,241±2,1

In Table 8 indicators of spasmodically sheep producers using the drug in a dose of 100 μg per 1 kg of body weight.

Table 8
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
The average volume of ejaculation ml2,10±0,042,24±0,05to 2.29±0,022,38±0,0
The average sperm motility, points8,0±0,018,0±0,018,0±0,018,0±0,01
The concentration of spermatozoa billion/ml2,2±0,062,15±0,052,13±0,062,15±0,04
Survival of spermatozoa, hours256±5,0278±10,0289±6,0292±4,0
Marriage sperm on biological indicators %27,7±6,527,8±5,222,4±4,820,4±6,2
Qty received spermatos from one animal30±2,034±2,236±2,838±3,1

The results are presented in table 8 of the experiments indicate that the stimulation of spermophobia the sheep producers in the use of the drug in a dose of 100 μg per 1 kg of body weight. So the volume of ejaculate, taken from rams through 90 days after the first injection, elicense 13.3%. During the reporting period improved quality indicators taken sperm (motility, survival of spermatozoa). The result of the drug on sheep producers is to increase 90 days after the first injection quantity obtained spermatos from one animal by 26.6% and reduced scrap rate of sperm on biological parameters.

Table 9 indicators of spermophobia sheep producers using the drug at a dose of 200 μg per 1 kg of body weight.

Table 9
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
The average volume of ejaculation ml2,07±0,022,18±0,062,23±0,042,32±0,03
The average sperm motility, points8,0±0,018,0±0,018,0±0,01 8,0±0,01
The concentration of spermatozoa billion/ml2,20±0,042,12±0,032,17±0,052,17±0,03
Survival of spermatozoa, hours260±5,0274±9,0285±8,0289±7,0
Marriage sperm on biological indicators %28,8±6,525,1±5,223,2±4,822,4±3,2
Qty received spermatos from one animal31±2,034±2,237±3,239±4,1

The results are presented in table 9 of the experiments indicate that the stimulation of spermophobia the sheep producers in the use of the drug in a dose of 100 μg per 1 kg of body weight. So the volume of ejaculate, taken from rams through 90 days after the first injection, increased by 12.1%. During the reporting period improved quality indicators taken sperm (motility, survival of spermatozoa). The result of the drug on the sheep-producer the x is the increase of 90 days after the first injection quantity obtained spermatos from one animal by 25.8% and reduced scrap rate of sperm on biological parameters.

Study of the effect of the drug on productive qualities of roosters manufacturers (two-line hybrid plymouthrock and Cornish) was carried out on poultry farms.

The suspension of the preparation of the bird was administered subcutaneously at a dose of 50-200 µg of protein per 1 kg of body weight twice with an interval of 14 days between injections.

The roosters-producers before and after use of the drug in the established order was carried out by taking samples of sperm and determined ejaculate volume, sperm concentration in the ejaculate and the number of received spermatos.

Indicators of spermophobia in males when the drug is administered in a dose of 50 μg per 1 kg of body weight are given in table 10.

Table 10
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
The average volume of ejaculation ml0,52±0,020,57±0,030,68±0,050,74±0,02
Average podvizhnos the ü, points7,03±0,027,02±0,027,03±0,037,02±0,04
The concentration of spermatozoa billion/ml2,1±0,051,98±0,032,01±0,031,99±0,04
Survival of spermatozoa, hours132±8,5142±6,3148±3,2144±3,2
Marriage sperm on biological indicators %the 15.6±3,513,4±2,712,5±2.311,7±3,2
Qty received spermatos12,0±2,313,0±2,715,0±2,517,0±2,8
Fertilizing ability of sperm, %92929392

The results of the experiments indicate that the stimulation of spermophobia the roosters-producers in the use of the drug. So the volume of ejaculate, taken from males through 90 with the current after the first injection, increased by 42.3%. During the reporting period improved quality indicators taken sperm (survival of spermatozoa). The result of the drug on the cocks-producers is to increase the number obtained spermatos by 41.6% and reduced scrap rate of sperm on biological parameters.

Indicators of spermophobia in males when the drug is administered in a dose of 100 μg per 1 kg of body weight are shown in table 11.

Table 11
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
The average volume of ejaculation ml0,49±0,030,54±0,020,65±0,060,71±0,03
Average mobility, points7,03±0,027,01±0,017,02±0,047,02±0,06
The sperm concentration, m is rd/ml 2,11±0,041,95±0,042,01±0,061,98±0,03
Survival of spermatozoa, hours135±6,5140±7,3144±2,2143±4,2
Marriage sperm on biological indicators %16,7±3,014,2±1,713,5±1,912,2±3,3
Qty received spermatos12,0±3,212,0±2,714,0±3,216,0±2,9
Fertilizing ability of sperm, %92939293

The results of the experiments indicate that the stimulation of spermophobia the roosters-producers in the use of the drug. So the volume of ejaculate, taken from males within 90 days after the first injection, increased by 44.9%. During the reporting period improved quality indicators taken sperm (survival of spermatozoa). The result of the drug on Pete the Ah-producers is to increase the number obtained spermatos 33.3% and reduced scrap rate of sperm on biological parameters.

Indicators of spermophobia in males when the drug is administered in a dose of 200 μg per 1 kg of body weight are shown in table 12.

The results of the experiments indicate that the stimulation of spermophobia the roosters-producers in the use of the drug. So the volume of ejaculate, taken from males within 90 days after the first injection, increased by 35.3%. During the reporting period improved quality indicators taken sperm (survival of spermatozoa). The result of the drug on the cocks-producers is to increase the number obtained spermatos by 25.0% and reduced scrap rate of sperm on biological parameters.

Table 12
Indicator of the quality of spermBefore and after the injection (source)After the introduction of the drug through...
30 days60 days90 days
The average volume of ejaculation ml0,52±0,020,55±0,030,64±0,050,69±0,04
The average concentration in the guard points7,03±0,027,01±0,017,01±0,037,01±0,05
The concentration of spermatozoa billion/ml2,12±0,031,96±0,052,02±0,032,01±0,04
Survival of spermatozoa, hours137±5,5141±7,1145±3,2144±5,2
Marriage sperm on biological indicators %18,3±4,215,7±2,914,1±2,713,9±4,2
Qty received spermatos12,0±3,211,0±2,713,0±3,215,0±2,7
Fertilizing ability of sperm, %92939293

Due to the fact that in accordance with known drug to increase the productivity of farm animals (EN 2034457 C1 IPC AC 67/02, 1995) active substance (reko pinentry protein) suspended in incomplete Freund's adjuvant, it seems necessary to show low reactogenicity and lack of pain in animals with the introduction of somatostatinergic protein, suspended in vegetable oil with added beeswax.

For this purpose we have formed three groups of pigs (gilts rocks of the canadian breeding (Yorkshire, Landrace) of 10 animals each, located on the rearing weighing 20 kg Animals of one group was introduced subcutaneously with recombinant protein, suspended in incomplete Freund's adjuvant in a volume of 2 ml per head (concentration of active ingredient was 0.5 mg/ml), animals of the other group was subcutaneously introduced recombinant protein, suspended in vegetable oil with the addition of beeswax in a volume of 2 ml per head (concentration of active ingredient was 0.5 mg/ml).

Animals of the control group were intact preparations were not implemented.

The analysis of the results of the recombinant protein, suspended in incomplete Freund's adjuvant, 7 animals were spotted at the injection site infiltration, causing pain in animals (piglets were aggressive, the injection of the drug to palpate was impossible due to pain). From 7 animals, the reaction of the organism on which the drug has expressed the formation of infiltration, in 4 animals at 6-8 days after the drug showed signs of abscess. These complications have led to changes in physiological indicators of animal and caused the opening of abscesses with the appointment of animals with antibiotics.

Table 13 shows clinical and physiological parameters of laboratory animals.

Table 13
Rate (average for the experience)Group
control1 experienced (partial beta-blockers)2 experienced (vegetable oil with added beeswax
Prior to the introduction of drugs
Body temperature,°C38,8±0,1338,7±0,1538,8±0,15
Respiratory rate per minute, time12,7±0,1910,2±0,2212,0±0,33
Pulse rate per minute, time73,2±4.26 deaths66,9±4,8968,2±5,57
After the introduction of drugs for 6-8 days
Body temperature, °C39,0±0,1940,1±0,1639,1±0,17
Respiratory rate per minute, time13,2±0,2923,4±0,1913,8±0,45
Pulse rate per minute, time77,9±4.26 deathsof 92.6±4,9071,7±5,72

Analysis of the data given in table 13, allows to conclude that the introduction of the recombinant protein, suspended in incomplete Freund's adjuvant, causing a significant number of animals adverse reactions in the form of infiltrates with subsequent abscess formation. This fact is a significant obstacle for widespread use of recombinant protein on the specified Freund.

Corresponding to the invention the dosage form of the drug on the basis of recombinant protein and refined vegetable oils with added beeswax is a suspension in which a recombinant protein is a dispersion phase, and refined vegetable oil is a dispersive medium.

In accordance with the law of Stokes sedimentation rate of the dispersion phase content which becomes inversely proportional to the viscosity of the dispersion medium. To enhance the performance of the sedimentation stability of the oil suspension (specifically for increasing the viscosity of the dispersion medium) is added to part of the preparation of 0.9-1.1 wt.% beeswax (in this case, beeswax may not possess the properties of the emulsifier). In addition, beeswax has antibacterial properties and its presence in the composition of the dosage form increases the microbiological purity of the drug, which is an important factor when conducting subcutaneous injection animals.

The introduction of the drug on the basis of recombinant protein, suspended in refined vegetable oil with the addition of beeswax, in a mammalian organism initiates the formation of multiple distinct from other physiological processes. Formed antisomatostatin antibodies reduce the concentration of somatostatin and increase content in the body of somatotropic hormone. On the one hand, leads to the activation of the enzymes of the gastrointestinal tract of animals, slow evacuation of chyme from the lumen of the intestine, increase nutrient absorption and, consequently, to the increase of dairy and meat animal productivity (EN 2034457 C1 IPC AC 67/02,1995).

At the same time increasing the concentration of somatotropic hormone leads to activation of follicle-stimulating hormone animals, responsible the th for the functional state of the interstitial cells (Leydig cells), producing testosterone, the hormone that regulates the level of sperm production and quality of semen from animals-producers.

In the studies performed for the first time detected a higher concentration of testosterone in animals that received injections corresponding to the invention of the drug recombinant protein based on 25-27% (13.2 ng/ml and 16.5 ng/ml, respectively). This mechanism of action of the drug on the basis of recombinant protein is new and has not been previously described.

1. Injecting the drug to increase spermophobia producers of farm animals and chickens in suspension chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC refined vegetable oil with the addition of beeswax,
and injecting the drug contains a chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC based 250-1000 mg of the indicated chimeric protein per 100 ml of refined vegetable oils, including a 0.9-1.1 wt.% calinog the wax.

2. The way to increase spermophobia producers of farm animals and chickens, including two subcutaneous injections with an interval of 14 days of injection of the drug in suspension chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC refined vegetable oil with added beeswax males or agricultural animals after reaching physiological maturity based 50-200 µg of protein per 1 kg of body weight,
moreover, the use of injectable drug in suspension chimeric protein with a water-insoluble enzyme inactive chloramphenicolchloramphenicol without the 10 C-terminal amino acids, amino acid spacer (Sp)n, where n=1, 2, 4, 8, and somatostatin-14 amino acid sequence AGCFWKTFTSC in the amount of calculation 250-1000 mg of the indicated chimeric protein per 100 ml of refined vegetable oils, including a 0.9-1.1 wt.% beeswax.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, pharmacology, to methods and PTEN phosphatase inhibitor compositions for ovarian follicle and oocyte development in vitro. Using the PTEN phosphatase inhibitors, such as complexes of oxovanadate and peroxovanadate: bisperoxo (bipyridine) oxovanadate, bisperoxo (1,10-phenanthroline) oxovanadate, bisperoxo (picolinato) oxovanadate, bisperoxo (5-hydroxypyridine-2-carboxyl) oxovanadate, di- (picolinat) oxovanadate, di-(3-hydroxypicolinat) oxovanadate, bisperoxo (phenylbiguanide) oxovanadate, di-(phenylbiguanide) oxovanadate and bisperoxo (isoquinoline carboxylic acid) oxovanadate, provide the development and activation in vitro of oocytes and follicles, such as primordial, intermediate and primary ovarian follicles.

EFFECT: invention provides the development and activation in vitro of oocytes and follicles, such as primordial, intermediate and primary ovarian follicles.

14 cl, 3 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely andrology, as well as may be used in veterinary science for treating mammals suffering disturbed fertility. An agent for improving the reproductive function represents a clathrate complex of γ-cyclodextrin and arabinogalactan, or glycyrrhetinic acid with 9-phenyl-symmetrical octahydroselenoxantene in the α-crystalline form and is described by structural with Cu-K emitted X-ray powder pattern having characteristic reflections expressed in degrees of diffraction angle 2θ: 6.0 12.0 15.0 17.0 19.0 20.0 21.5, 21.7, 20.9 25.0 27.0 28.0 29.0 37.0 and a melting point of 96.8°C.

EFFECT: improved pregnancy and fertility rates.

18 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely andrology, as well as may be used in veterinary science for treating mammals suffering disturbed fertility. An agent for improving the reproductive function represents a clathrate complex of β-cyclodextrin and 9-phenyl-symmetrical octahydroselenoxantene in the α-crystalline form and is described by structural formula with Cu-K emitted X-ray powder pattern having characteristic reflections expressed in degrees of diffraction angle 2θ: 6.0 12.0 15.0 17.0 19.0 20.0 21.5, 21.7, 20.9 25.0 27.0 28.0 29.0 37.0 and a melting point of 96.8°C.

EFFECT: invention provides higher pregnancy and fertility rates.

6 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely oncology, and may be used for the drug-free correction of the drug-free correction of idiopathic asthenozoospermia. For this purpose, every second day medicinal leeches are used 4 times for each point of alternating zones: 4 point in the pubes: in the midline above the pubic bone at the base of the penis and 2 parallel points at the intersection of a lateral line of the abdomen and the pubic bone from both sides; in the perianal area - 4 points corresponding to III, VI, IX and XII o'clock of the perianal area at 1-2 cm from the pigmentation area; in the sacral area - 4 points located on a projection angle of the sacrum, and in the coccygeal area - 4 points corresponding to a projection of the coccyx; the therapeutic course is 2-3 weeks.

EFFECT: method enables increasing the fertility ensured by the significant improvement of sperm kinesiogram.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to urology and endocrinology, and may be used in the integrated treatment of male normogonadotropic infertility. For this purpose, the conventional therapeutic regimens are added with administration of follitropin alpha (gopal-f) subcutaneously three times a week, 150 IU for 6 weeks. In addition, blood is exposed to UV irradiation for 20 minutes, 2 times a week; the therapeutic course is 12 procedures.

EFFECT: method provides anti-inflammatory and immune stimulating action, as well as ensures the effective treatment ensured by the high stimulating capacity of spermatogenesis, improves endocrine organs promoting their recovery by improving microcirculation that causes the therapeutic effect and extends the range of therapeutic activities with reduced the length of treatment and requires no staying in hospital.

2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to molecular physiology and biochemistry, and may be used for normalizing spermatogenesis in animals in chronic natural gas poisoning. The method for spermatogenesis correction in animals suffered chronic natural gas poisoning, consisting in the use of selenium-containing preparations, and a correcting preparation is Selexen used in a combination with ascorbic acid administered orally to male albino rats in doses of 1.5 mg/kg and 500 mg/kg of animal's body weight, respectively once a day for 50 days, and at the same time from the third week of the administration of Selexen and ascorbic acid, the animals are exposed to sulphurous natural gas in the concentrations of 10 mg/m3 for 30 days, 240 minutes a day, and upon the completion of the experimental exposure, the morphological and kinetic parameters of spermatogenesis are to be examined.

EFFECT: implemented reduction of the toxic effects of natural gas on the reproductive function of male gonads.

1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and is intended for treatment of menstrual cycle irregularities in teenage girls with obesity. Method includes administration of siophor 5-10 minutes after meal for 10 days in the morning, in the afternoon and in the evening in dose 250.0 mg, from the 11-th day in the morning and afternoon in dose 250.0 mg, in the evening 500.0 mg for 10 days, from the 21-st day in the morning, afternoon and evening in dose 500.0 mg, in case of good tolerance from the 31-st day in the morning and afternoon - 500.0 mg, in the evening - 750.0 mg, for 6 months. Microacupuncture is performed in acupuncture points (AT): AP(X)55, AP(II)17, AP(II)18, AP(IV)22, AP(VI)28, AP(XIV)87, AP(XVI)100, influence is performed in time interval 10-13 hours, in the first two days influence id performed on AT AP(II)17, AP(II)18 on the right and left, on the 3-5-th days influence is performed on AT AP(X)55 on the left, and AT AP(II)17, AP(II)18, AT AP(IV)22 on the right, on the 6-10-th days AP(XVI)100 on the left, AT AP(II)17, AP(II)18, AP(VI)28, AP(XIV)87 on the right. Introduced microneedles are adhered with adhesive plaster. Patient periodically presses on them for 1 min when they feel sense of hunger. Course treatment with microacupuncture consists of 10 procedures. Microacupuncture treatment course is carried out 2 times per year.

EFFECT: invention increases treatment efficiency, makes it possible to prolong clinical remission.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology and may be used for treating chronic abacterial prostatitis. The treatment involves rectal phonophoresis daily within the therapeutic course of 10 procedures. Before phonophoresis, 60% aqueous Tisol 14 ml containing dissolved diclofenac 100 mg is introduced as a drug preparation into the patient in a knee-elbow position. It is added with 2-minute prostate massage, 3-minute rectal phonophoresis followed by one-hour pronation.

EFFECT: method provides the effective treatment ensured by reduced obstruction and irritation symptoms, pain syndrome management, prolonged remission, improved urofluometry, total score of the prostatic disease, quality of life index, as well as patients' libido.

2 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine, namely to urology and may be used for treating chronic abacterial prostatitis. The treatment involves administration of a drug preparation and rectal phonophoresis daily within the therapeutic course of 10 procedures. Before phonophoresis, aqueous solution of Tisol 14 ml 60 % is introduced into the patient in a knee-elbow position. It is added with 2-minute prostate massage, 3-minute rectal phonophoresis followed by one-hour pronation.

EFFECT: method provides the effective treatment ensured by reduced obstruction and irritation symptoms, pain management relief, prolonged remission, improved urofluometry, quality of life index, as well as patients' libido.

2 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely obstetrics and gynaecology, and may be used for relieving blood loss in managing non-developing pregnancy. That is ensured by intravenous drop-by-drop introduction of tranexamic acid 0.75 g dissolved in 0.9% sodium chloride 200 ml for 20-30 minutes in the first trimester of a gestation perion 30-60 minutes before instrumental extraction of a dead embryo from an uterine cavity.

EFFECT: method provides relieving blood loss and prevented developing coagulopathic bleeding.

3 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine, namely to compositions of ingredients, which have therapeutic purpose by external application on person's body. Ointment for treatment in case of frostbites includes wax, amaranth and glycerol with the following component ratio, wt %: wax 13-15; glycerol 15-20; amaranth oil - the remaining part.

EFFECT: ointment increases efficiency of healing action with absence of side complications, fast elimination of edema, absence of intoxication.

1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to a stable composition in the form of oral emulsion containing at least 50% of water, 0.2 to 3 wt % of oil containing at least 12 wt % of docosahexaenoic acid and eicosapentaenoic acid, an antioxidant, an aromatiser and at least 0.01 wt % of edible phospholipid emulsifier.

EFFECT: oral stable emulsion visible skin if used on a regular basis.

8 cl, 1 ex

FIELD: medicine.

SUBSTANCE: claimed invention relates to field of medications, in particular to tablet, manufactured by method of building-up coating, in composition of which included are core, containing medication, and core-surrounding coat from non-soluble or badly water-soluble material, core being located inside said coat in such way that coat on axis (X-Y) has greater thickness and lower density than on axis (A-B), orthogonal to axis (X-Y), coat porosity on axis (X-Y) being sufficient for ensuring penetration of water medium, so that when immersed into water medium after period from 2 to 6 hours destruction of coat and release of medication takes place. Invention also relates to method of said tablet manufacturing, pharmaceutical package containing it and treatment method. Said tablet form ensures fast release and delivery of active component after period of delay, which can be set with great accuracy.

EFFECT: system will ensure directed delivery of active component to place of absorption or action.

19 cl, 2 dwg, 3 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition of fast release includes granules obtained by granulation from melt. Granules contain DPP-IV inhibitor and meltable hydrophobic component with ratio from 1:1 to 1:10 (per dry weight). At least 90% of granule surface are covered with meltable hydrophobic component. Granules release approximately 50% of DPP-IV inhibitor during 30 minutes after peroral introduction of medication. DPP-IV inhibitor is N-(substituted glicyl)-2-cyanopyrrolodin or its pharmaceutically acceptable salt. Preferably DPP-IV is (S)-1-[(3-hydroxy-1-adamantyl)amino]acetyl-2-cyanopyrrolidin.

EFFECT: composition for fast release according to invention possesses improved stability in presence of moisture in comparison with known compositions for controlled or prolonged release.

20 cl, 9 tbl, 10 ex

FIELD: food products.

SUBSTANCE: edible composition that contains at least one facility for conditioning with covering layer, which consists of agent that imparts hydrophobic properties and inorganic particles and at least one material that has been selected from the group that consists of pharmaceutically active agent, powdered food components and their combinations. At that agent that imparts hydrophobic properties directly covers mentioned inorganic particles and is available in mentioned facility for conditioning in amount of approximately from 1 weight % to 10 weight %, in conversion to total mass of facility for conditioning. Facility for conditioning with covering layer is used in pharmaceutical products, such as acetaminophen.

EFFECT: prepared composition expresses better fluidity properties.

25 cl, 11 tbl, 29 ex

FIELD: chemical-and-pharmaceutical industry, in particular solid pharmaceutical formulation coated with enterosoluble coating.

SUBSTANCE: claimed coating has four layers wherein the first and the third layers comprise of hydroxypropyl cellulose, and the second and the fourth ones comprise of acetatephthalate cellulose, bee wax and twin 0-20 in specific component ratio in coating.

EFFECT: enhanced assortment of drug active ingredients coatable with claimed coating, including thermolabile immunobiological medicines.

4 cl, 7 ex

FIELD: chemical-pharmaceutical industry.

SUBSTANCE: it has been suggested to apply a solid composition for manufacturing a pharmaceutical tablet or a suppository, its melting point being 25°C or higher and it contains an uninterrupted lipid component that contains either one or more than one galactolipids, one or more glyceride ether of fatty acids, possibly one or several out of the following: water and mono-triatomic alcohol at the quantity being up to 15 weight% against the weight of composition, and one or more agent chosen among pharmacologically active agent. The method for manufacturing the composition mentioned includes mixing galactolipids and glyceride ethers of fatty acids followed by dissolving pharmacologically active agents in a liquid phase, cooling up to a solid state and forming a tablet or a filled capsule. Pharmaceutical tablet or suppository are depicted that include uninterrupted lipid phase possibly containing an inert nucleus and, also, food tablets or suppositories of similar composition that include food agents instead of pharmacologically active agent and, possibly, having got one or more submembranes consisting of food excipients. The innovation provides economy and increased comfort in usage.

EFFECT: higher efficiency.

42 cl, 13 ex, 10 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is a composition for nicotinic immunonanotherapy containing synthetic nanocarriers having a polymeric surface conjugated with a variety of nicotine residues with the variety of the nicotinic residues on the nanocarrier form an immunogenic surface providing a low affinity, a high-avidity binding of the nicotinic residues to the surfaces of an antigen presenting cell (APC) compared with an antibody binding, and a pharmaceutically acceptable excipient. The invention provides the nanocarriers capable to stimulate an immune response in T-cells and/or B cells and to produce the antinicotin antibodies with the humoral and cellular response to be achieved in the absence of an exogenous adjuvant.

EFFECT: invention provides the absence of the non-specific response on an inflammation caused by an adjuvant.

17 cl, 37 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely biopharmaceutics and may be used for preparing an immunogenic conjugate. That is ensured by: (a) a reaction of serotype 1 purified polysaccharide with an alkaline buffer to prepare serotype 1 partially des-O-acetylated polysaccharide; (b) a reaction of serotype 1 partially des-O-acetylated polysaccharide and a weak acid to produce serotype 1 neutralised partially des-O-acetylated polysaccharide; (c) a reaction of serotype 1 neutralised partially des-O-acetylated polysaccharide and an oxidising agent to prepare serotype 1 activated polysaccharide; (d) mixing of serotype 1 activated polysaccharide and a carrier protein; (d') combined lyophilisation of mixed serotype 1 activated polysaccharide and the carrier protein before a reaction with a reducing agent; (e) reaction of mixed serotype 1 activated polysaccharide and the carrier protein with the reducing agent to prepare a serotype 1 activated polysaccharide/carrier protein conjugate; and (f) capping of unreacted aldehydes in the serotype 1 activated polysaccharide/carrier protein conjugate. What is also presented is a method for preparing a multivalent immunogenic composition.

EFFECT: group of inventions enables preparing the composition presented in the form of vaccines that decreases a number of severe pneumococcal diseases.

27 cl, 17 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is presented is a lyophilised preparation containing at least one nicotine - virus-like particle conjugate, and a stabiliser composition containing at least one nonreducing disaccharide and at least one non-ionic surfactant wherein the pre-lyophilisation pH value of the stabiliser composition makes 5.8 to 6.6, preferentially 6.0 to 6.4.

EFFECT: invention provides producing the effective lyophilised vaccinal preparation able to keep stability for a long period of time.

14 cl, 3 dwg, 4 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention discloses compositions for inducing an immune response in a patient, containing a combination of two or more monovalent conjugates wherein each of the monovalent conjugates contains a carrier protein N19 conjugated with a saccharide antigen of the serogroups A, C, W135 or Y Neissera meningitides. A molecule of the carrier protein in the monovalent conjugate is preferred to be conjugated with more than one molecule of the saccharide antigen. Besides, the invention discloses a multivalent conjugate for inducing an immune response in a patient, containing two or more antigen-different saccharide antigens of the serogroups A, C, W135 or Y Neissera meningitides conjugated with the carrier protein N19. The compositions may contain one or more said monovalent conjugates and one or more said multivalent conjugates. The invention shows applicability of the multivalent conjugate and compositions in preparing a medicine for enhancing the immune response in a patient.

EFFECT: compositions used under the invention elicit much stronger and fast immune response and exhibit lower reactogenicity for a patient.

16 cl, 33 dwg, 2 tbl

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