How biostimulatory of an animal's body
(57) Abstract:Usage: biology, immunology, biotechnology, agriculture, farming, livestock farming for biostimulatory the body of the animal. The aim of the invention is the stimulation of overall survival, fecundity, growth and weight of animals. This goal is achieved through the use of as a stimulator of purified antibodies isolated from the serum of animals immunized with protein S 100 when they intraperitoneal or intramuscular injection the animals. The invention is suitable for mass productivity and increasing volumes of commodities in terms of fur farms. table 4. The invention relates to biology, immunology, biotechnology, agriculture, farming, animal husbandry. The feasibility of implementation in the agricultural practice of new, cost-effective ways of increasing the productivity of domesticated animals does not require special justification. The potential success here can be expected, in particular, on developments in the field of genetic engineering. Currently, however, such methods are at the very early stages of development, the road, the complex is x for quantitative use.At the same time, the development of molecular biology and immunology allows us, today, to offer and be subjected to experimental test of the much more simple and accessible and at the same time potentially effective ways of influencing the growth, development and fertility of animals. Some of them may be economically justified and suitable for practical use.The results of experimental verification of one of these theoretically informed hypotheses and were the basis of the present invention. Its essence consisted in the following.Data about the closest functional metabolic interactions between the nervous and immune systems, as well as the presence of common antigens specific for the nervous and immune cells (Abramov centuries interaction of the nervous and immune systems, Novosibirsk, Nauka, 1988), determine the potential simultaneous modulation ( in particular, stimulating) effects on the functional state of the two leading systems management homeostasis of the organism. A similar effect can be provided by using antibodies (antisera) a certain specificity. At a certain intensity of halogen with exceptiona is the General condition of the body, to contribute to its better adaptation to the environment and to increase resistance to adverse factors.The basis of the invention on the results of experimental verification of the assumption that the weak (stimulating) effects of antisera to proteins of the S100 group (these proteins are synthesized by astrocytes of the brain and a number of cells of the immune system Carbone et al. Human Pathol. 1985, v.16, No 11, 1157-1164), injected into the body of the holes, favorable impact on protective and homeostatic potential of the animals and hence to reduce their mortality and to increase fertility. Single intraperitoneal or intramuscular injection adult mink fraction of immunoglobulins isolated from the antisera to S100, prevented the mortality of adult animals in the autumn-winter period and contributed to the emergence of larger and more viable offspring.To date, antibodies or antisera (antibodies) to the S100 was used solely for research purposes. Including, to study the involvement of S100 proteins in the mechanisms of behavior (Yurkevich C. O. Poletayev A. B. J. the high.nerve.activities. 1982, 31, 1, 79-85); for immunohistochemical studies (K. Shefasson et al. Brain Res. 1982, 234, 2, 309-allows you to use them as prototypes or analogues.As the prototype of the present invention can be considered work, analyzed in the review Gelfand (Clin. Immunol. a. Immunopathol. 1989, 53, 2, pt. 2, S1-S6), which are considered essentially the adaptogenic properties of drugs and non-immune donor gamma-globulin, initially tested on animals, and improves the General condition of patients with different forms of pathology (tumor, infection, allergic diseases, abortion, and others) as a result of injections of large doses (up to 2 g/kg/day) donor gamma-globulin. The reasons for the positive effects and the overall normalization of homeostasis in mammals and man under the influence of drugs gamma-globulins are not clear. It is assumed that the basis of the observed adaptive homeostatic effects may lie in the presence polirovannyj preparations of immunoglobulins antibodies of the desired orientation (cannot exclude the presence in the preparations of antibodies to S100 proteins). The high cost of drugs polirovannyj gamma-globulin obtained from thousands of healthy donors, limiting the wide application of such effects even in the clinic and makes it almost impossible to use such preparations in animal husbandry and serovodorodnoi as bioadaptive common actions the main purpose of the application of which to animals is to increase the efficiency and cheaper way to achieve byadopting effect.Used the method of producing an antigen for immunization (S100 proteins) are well known (see for example, J. Neurochem. 1983, 40, 1, 145-152). Immunization of rabbits S100 proteins was performed as described previously (Belyaev, S. V. and others Biochemistry, 1982, T. 46, No. 12, 2193-2201).Used method use fractions of immunoglobulins from the serum of immunized S100 animals, the use of the passive anti-S100 immunization of animals recipient to stimulate their viability, fertility, growth and weight do not have analogues.The method is as follows. Getting drug BIOSTIMULANT-PS, i.e. the fraction of antibodies from antisera to S100 proteins, was performed according to conventional methods. 5 adult rabbits immunized with protein S100, from marginal ear vein were collected in 50-60 ml of blood, separating the serum from the formed elements, three perioadele (enriched) immunoglobulin fraction from it in polysystem solution of ammonium sulfate, were dialyzed fraction obtained against of 0.14 M solution of sodium chloride, spectrophotometric determination, aslevel on ampoules and sealed. The drug was stored until use at 4oC.The drug was tested on 2 groups of dark brown mink: young six animals (n= 50), introducing them to a single dose of 10 mg/kg of the drug intraperitoneally; Mature fifteen-year old pregnant female burrows (n= 15) after a single intraperitoneal injection im 10 mg/kg of the drug at the beginning of the last third of pregnancy.To confirm the lack of species specificity of the effects of the drug was tested on small groups (10 PCs) pregnant females of other animals foxes, Arctic foxes and raccoons with a single intraperitoneal injection of the drug at the rate of 7 mg/kg of body weight.The experiments were carried out in the breeding animal-breeding sovkhoz "Codesense" Olonets district Karelian ASSR.Evaluation of the effectiveness of the drug biostimulant-PS.The effect of the drug on the young mink was evaluated taking into account:
the level of mortality of animals during the autumn-winter period (November to March) in animals treated with bioadaptive receiving an injection of immune gamma-globulin or not treated with drugs (passive control);
the ratio of animal keeping or Phnom groups of animals (on the average daily balance of the diet).The effect of the drug administered to pregnant mink on the state of young mink was evaluated taking into account:
the average number of offspring in females of different groups;
the frequency of occurrence of weak litters;
frequency of occurrence of dyspeptic disorders requiring antibiotic therapy, puppies from the litter females of different groups;
the level of mortality of pups during the first 3 months of life out of a litter of females of different groups.Example 1. The drug biostimulant-PS on the state of young mink are given in table.1.Example 2. The drug biostimulant-PS, administered to pregnant mink on the state of young mink are given in table.2.Comparative efficacy of injections of the lowest (1 mg/kg) and high (10 mg/kg) doses of the drug biostimulant-PS to change the body weight of young Minks during the autumn-winter period (November-March) as an integral indicator of overall physiological state of the animals is shown in table.3.The drug biostimulant-PS, administered to pregnant females: the number of litter from different species are given in table.4.The drug biostimulant-PS (single intraperitoneal injection of the mink immunoglobulins, highlighted the Valo to improve the overall physical condition of the animals.A single injection of the drug biostimulant-PS pregnant females mink, and other animals made it possible to obtain a large number of puppies and more viable offspring.Getting drug biostimulant-PS does not require sophisticated equipment and expensive reagents.Species nespecificnomu S100 proteins allows the use of antisera, antibodies or immunoglobulins (biostimulant-PS) to improve the viability and productivity of different species of animals, which is why the drug biostimulant-PS will be able to find wide application in various sectors of the livestock and farming. How biostimulatory of the animal organism, comprising introducing into the body of the immunoglobulin, wherein the body enter the biostimulator PS containing immunoglobulin to protein S100, and the introduction is carried out once at a dose of 1 to 10 mg/kg weight of the animal.
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FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to applying compounds of the formula (I) for preparing an antibacterial composition and veterinary composition eliciting with the enhanced activity.
EFFECT: valuable properties of agents.
4 cl, 3 tbl, 78 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to macrocyclic peptides of the general formula (I): wherein W means nitrogen atom (N); R21 means hydrogen atom (H), (C1-C6)-alkoxy-, hydroxy-group or N-(C1-C6-alkyl)2; R22 means hydrogen atom (H), (C1-C6)-alkyl, CF3, (C1-C6)-alkoxy-group, (C2-C7)-alkoxyalkyl, C6-aryl or Het wherein het means five- or six-membered saturated or unsaturated heterocycle comprising two heteroatoms taken among nitrogen, oxygen or sulfur atom and wherein indicated Het is substituted with radical R24 wherein R23 means hydrogen atom (H), -NH-C(O)-R26, OR26, -NHC(O)-NH-R26, -NHC(O)-OR26 wherein R26 means hydrogen atom, (C1-C6)-alkyl; R3 means hydroxy-group or group of the formula -NH-R31 wherein R31 means -C(O)-R32, -C(O)-NHR32 or -C(O)-OR32 wherein R32 means (C1-C6)-alkyl or (C3-C6)-cycloalkyl; D means a saturated or unsaturated alkylene chain comprising of 5-10 carbon atoms and comprising optionally one-three heteroatoms taken independently of one another among oxygen (O), sulfur (S) atom, or N-R41 wherein R41 means hydrogen atom (H), -C(O)-R42 wherein R42 means (C1-C6)-alkyl, C6-aryl; R4 means hydrogen atom (H) or one-three substitutes at any carbon atom in chain D wherein substitutes are taken independently of one another from group comprising (C1-C6)-alkyl, hydroxyl; A means carboxylic acid or its alkyl esters or their derivatives. Invention relates to pharmaceutical compositions containing indicated compounds and eliciting activity with respect to hepatitis C virus and these peptides inhibit activity of NS3-protease specifically but don't elicit significant inhibitory activity with respect to other serine proteases.
EFFECT: valuable biochemical and medicinal properties of peptides.
106 cl, 9 tbl, 61 ex