Medication for stimulation of motoneuron growth in growing mammalian organism and method of its application

FIELD: medicine.

SUBSTANCE: claimed is application of pig adrenal cortex extract as medication for stimulation of growth of spinal marrow motoneurons in mammalian growing organism. Claimed is method of stimulation of spinal marrow motoneuron growth in mammalian growing organism in experiment, which includes introduction of pig adrenal cortex extract on alternate days, with general 5 week course, pig adrenal cortex extract being introduced in single dose 0.5 ml per 100 g of organism body weight.

EFFECT: extending arsenal of medications for stimulation of spinal marrow motoneuron growth.

2 cl, 1 tbl

 

The proposed group of inventions relates to experimental biology and medicine, namely, experimental neurology, and can be used to stimulate the growth of motoneurons of the spinal cord of a growing organism. In the long term (after conducting appropriate clinical trials) possible application of the proposed group of inventions may become the treatment of neuromuscular dystrophies, since (as will be described below) is an important pathogenic factor in these diseases is the defeat of motoneurons of the spinal cord.

Neuro-muscular dystrophy refers to a hereditary, incurable, invalidation and shorten the life of the disease. Children pseudohypertrophic form described in 1868 by Duchenne is the most severe form of muscular dystrophy. It usually begins in the first 3 years of life and is characterized by progressive muscle weakness that starts with the muscles of the pelvic girdle and thighs and then passing on the shoulder muscles. Hypertrophy of the muscles, especially the calf, are much. To 10 years children become immobilized, and to 20 years comes death. Inheritance is recessive, associated with sex (X-chromosome) with high problemsto.

Benign recessive X-chromosomal muscular dystrophy, Becker described (1955)begins on the DNIe (about 10 years), also with pelvic belt, characterized by the presence of hypertrophy, but at a much slower course than classic dushinovski form. Patients keep their mobility and have children (Davidenkov WF, Lieberman I.S., 1975, s). When the neuro-muscular dystrophy of Duchenne often find a deletion dystrophic gene on the X chromosome. The implementation mechanism is genetically programmed disorders is not clear. Proposed several theories, each of which prefers a specific pathogenetic process.

In clinical neurology distinguish primary muscular dystrophy and secondary muscle atrophy.

According to the neurotrophic theory the basis for attributing diseases to neurogenic was the "beam atrophy of muscle fibers and the presence of electromyographic evidence of denervation: potentials fasciculations, fibrillyatsy and positive sharp waves and action potentials, increased as a result of regeneration of motor units in the affected muscles. However, given observations proving the non-specificity of morphological and electrophysiological data to address the question of neurogenic or myogenic nature of the muscular dystrophies. According to Engel (1973), motoneuron can be turned off completely as a result of his death or the destruction of its axon (n toto), or in part (in portio). In the latter case will be first off its individual fibers in the first one all the elements of the propulsion unit. Engel acknowledges the presence of trophic factor for the maturation of muscle fibers; factor that supports normal muscle fibers, maintaining its exchange type and structure; factor that supports normal muscle fibers to acetylcholine; factor preventing atrial muscle fibers; factor contributing to the formation of postsynaptic structures and other Failure of each of trophic factors or their combinations, according to the author, leads to some form of pathology of the muscles.

According to the opinions of Mac Comas (1971), when the development of the pathological process caused by the defeat of motoneurons, in addition to extreme conditions (normal state of the cell and its death) there can be more than transient States "patient's motor". In the early stages of violations of his functions disorders of neuromuscular transmission in a separate terminal axon branching. As the disease among the affected terminala is increasing. At the next stage, the most affected muscle fibers are reversible, and then irreversible generational changes. Then die of terminal the e branch of the motor, its axon and in the final stage of the process - the motoneuron. As one of the forms of disorders of the upper motor neuron is supposed loss of his ability to reinnervate adjacent denervated muscle fibers. The author admits and chronic upper motor neuron disease - a condition in which the motoneuron in a long time is at a certain stage of violations of its functions.

The main prerequisite for the creation of hypotheses muscle hypoxia in the development of ministrations process was the similarity of ultrastructural changes of the muscles of animals subjected to hypoxia, and people with progressive muscular dystrophy; detected in the early stages of progressive muscular dystrophy of Duchenne muscular pseudohypertrophy considered as a consequence of focal microinfarcts.

Of the many attempts to link together the degree of degenerative changes in the muscles with the alleged structural defects membranes retained significance only hypothesis F.Tyler (1960-1978). According to this hypothesis, the primary is a violation of the structure of proteins and membranes sarcoplasmatic reticulum. Due to the increased diffusion through the outer membrane of the number of components of the muscle fibers (enzymes, carbohydrates, amino acids, creatine and others) go into the blood and thereby reduce the number of necessary connections in isichei tissue. Degeneration of muscle fibrils is determined by the loss rate of enzymes. Biochemical study of the enzymatic properties of the proteins showed a decrease in the activity of ATP-ases in almost all forms of muscular dystrophy, however, more pronounced in X-linked forms. Diagnostic value has high activity creatinphosphokinase in the serum in the early stages of Duchenne muscular dystrophy. In recent years there has developed a hypothesis defects of cyclic adenosine monophosphate (camp) in the development of ministrations processes. When X linked myodystrophy the defect is localized at the level of the regulatory subunit of adenylate cyclase, in connection with which the stimulating effect of adrenaline largely leveled and is 10-30% of normal. In the early stages of the disease the level of nucleotide can be stabilized due to a compensatory decrease in activity of phosphodiesterase. The weakening or shutdown of the effect of camp may be the main reason for the increase in cell membrane permeability, inhibition processes fosforilirovanija, accumulation of lipids, impaired binding of calcium, perversion of protein synthesis.

When the autosomal myodystrophy strengthening of processes of proteolysis and cell membrane permeability due to another reason - the structure features of the Proteus the kinase.

Treatment of muscular dystrophy remains one of the most urgent issues. Currently, based on different combinations of symptomatic drug therapy, physical therapy, massage, physical therapy, Spa treatment, and the presence of coarse retracci tendons orthopedic events (Badalyan LO, 1975, Bondarenko, E.S., 1976). Of drugs widely used vitamins a, b, C, D, E and others, ATF, allopurinol, beta-blockers, lithium carbonate, injection of Cerebrolysin. To improve neuromuscular conduction prescribed anticholinesterase drugs (neostigmine, galantamine, nivalin). In the complex treatment using vasodilator (nicotinic acid, xantinol-nicotinate, Niko-span, nikoverin); physiotherapy electrophoresis with drugs, diadynamic currents, sinusoidal modulated currents, electrical stimulation; mineral wax, mud, various baths (radon, hydrogen sulfide). The possibility of using steroid drugs in the treatment of neuromuscular diseases are discussed in the literature(6, 8, 9, 11). Start applying their patients myodystrophy Duchenne-Becker refers to the mid 70-ies of the last century, almost to the end of 80-ies of the patients were prescribed high doses of hormonal the different drugs, usually from 1.5 to 2.5 mg of prednisolone per kg of body weight per day. Authors of most of the publications on the results of a steroid treatment in patients with myodystrophy Duchenne-Becker, noted improvement in patient's condition (bearing in mind this slow progression of the disease), but it was not stable. In addition, due to the long duration of treatment (months) significant doses of hormone patients had any signs of metabolic disorders, obvious reason which was hypercortisolism. Among the complications especially have often been attributed to a disproportionate increase in body weight, acne, moon-shaped face, swelling, and other signs of increased levels of steroid hormones. A number of patients because of obesity has lost the ability to move, some particularly unpleasant complications became insomnia, irritability and other disorders of the nervous system. The possibility of negative effects of large doses of anabolic steroids draws attention Badalyan LO, 1977.

A new stage in the use of hormonal therapy for the treatment of Duchenne muscular dystrophy-Becker began at the end of 80-ies, when it was proposed to use a small dose of prednisolone or its analogues with immunocorrective effect. It was shown that the purpose of th is Mona from the calculation of 0.35 mg or 0.75 mg per kg of body weight per day for 6 months of the year allows you to achieve a positive result in the reduction of complications to a minimum. However, when months of treatment complications still occurred. To ensure the effectiveness of the treatment and prevention of possible complications was necessary to continue working on optimizing the use of prednisolone.

Niegowski et al. (1999) changed the treatment prednisolone: annual course of treatment was divided into 4 cycles for 3 months. During the three-month cycle prednisolone was administered at a dose of 0.5 mg per kg of body weight; in the next three-month cycle prednisolone was replaced with placebo. Then the cycles were repeated, so that during the year a total dose of prednisolone was 0.25 mg per kg of body weight. Systematic review of 47 patients with myodystrophy Duchenne and 3 patients with myodystrophy Becker using instrumental methods of diagnosis showed a stabilizing effect on the health of the musculoskeletal system. Especially clearly the positive effect of the treatment was shown to increase the amplitude of the total electromyograms for all studied 8 muscle groups in the first 3 months of treatment with some reduction while receiving placebo and then again increased in the cycle of prednisone. Increased and strength of muscles. However it was possible to conduct the treatment under this scheme, only 24 patients during the year, and within 1.5 years - only 3, which may indicate dissatisfaction with the results.

Thus, used what's currently in the clinic treatment of neuromuscular dystrophies not directed directly to the stimulation of motoneurons of the spinal cord. Applied methods do not provide a sufficient effect, and have a large number of unwanted side effects. In experimental medicine also almost no development associated with growth stimulation of motoneurons. This area is only beginning to develop. In the known literature found only one work dedicated tool for growth stimulation of motoneurons of the spinal cord and method of its application. This work is chosen as a prototype - Igiling, Evenwhen, Ivideowindow, Naanna. Anabolic effects of minor concentrations of corticosteroids contained in the extracts of the adrenal cortex // Nizhny Novgorod medical journal. - 2004, No. 1, pp.92-95. In the prototype, the growth stimulation of motoneurons of the spinal cord (in the experiment on rats) proposed to use the extract of the bark of fetal adrenal in the volume of 0.5 ml every other day for 5 weeks.

Despite the effect of the growth of motoneurons, the prototype is not without disadvantages. First of all, it should be noted that the fetal adrenal glands were taken at autopsy of the dead in childbirth children. Obviously, the use of the prototype in this regard is very limited, due primarily ethical problems.

The objective of the proposed invention it is the expansion of the means to stimulate growth m is toneroom spinal cord, the possibility of using the available tools. This object is achieved by the use of bark extract of porcine adrenal glands as a means to stimulate growth of motoneurons of the spinal cord of a growing organism mammals.

The task in the method of promoting the growth of motoneurons of the spinal cord is a growing body of mammals, including the introduction of an extract of the adrenal cortex, through the day, the General course of 5 weeks, is achieved by the fact that the injected extract of porcine adrenal gland in a dose of 0.5 ml per 100 g body mass of the organism.

The use of bark extract of pig adrenal glands as a means to stimulate growth of motoneurons of the spinal cord of a growing organism shown in the present invention for the first time. Previously bark extract porcine adrenal glands were used for other purposes, namely: for the stimulation of reparative processes in the diseased liver (RU # 2185835 C2, 27.07.2002); for the correction of acute renal failure in toxic hepatorenal syndrome (EN 2290940 C2, 10/01/2007).

In the present invention, the growth stimulation of motoneurons of the spinal cord is held on the growing organism, as it was supposed to extrapolate the results to justify the treatment of diseases in childhood.

Significant and the signs are quantitative indicators, introduced in the claims, namely single dose and rate of administration of an extract of pig adrenal glands. The necessity of using a single dose of 0.5 ml per 100 g body weight due to the fact that the extract presents biologically active substances in minor concentrations, defined in the body outside voltage (not in milligrams and micrograms, as used in conventional medical practice, and in nanograms). The need to use a 5-week course due to the fact that the growth processes in the body occur slowly and require repeated long-term stimulation, usually used in the treatment of chronic diseases, the course of 4-6 weeks.

The need for administration of an extract every other day subcutaneously allows you to maintain the concentration of hormone-active substances over a long period of time.

The proposed method developed in the experiment at 25 growing outbred rats-males with body mass at the beginning of the experience and 99.8±3.7 g and body length to 12.44±0,58 see the end of the experiment the animals had weight 181,7±12.7 g and body length of 14.0±1,66 see Animals were divided into 5 groups of 5 animals were intact (group 1 control), 5 animals received a 10%solution of ethyl alcohol on physiological solution of sodium chloride (2 the control group). 5 animals received hydrocortisone (1 mg/100 g mass) on the basis of a 10%aqueous solution of these is a new alcohol (group 3); 5 animals received the extract of the bark of porcine adrenal glands (group 4 and 5 animals received the extract of the bark of fetal adrenal taken at autopsy died in childbirth fruit person (group 5).

Extracts of the adrenal cortex were prepared according to the principle of organ preparations of 3.0 g of tissue received 1 ml of the extract. Drugs in the amount of 0.5 ml was administered every other day for 5 weeks. Method radioimmunological analysis in extracts of the adrenal cortex were determined concentration of hydrocortisone, DHEA and progesterone. 0.5 ml of the extract of the bark of porcine adrenal contained hydrocortisone - 65 nmol, dehydroepiandrosterone - 0.83 nmol and progesterone - 1.1 nmol. 0.5 ml of the extract of the bark of fetal adrenal contained hydrocortisone - 5.0 nmol, dehydroepiandrosterone - 1.15 nmol and progesterone - 0.45 nmol. In 0.5 ml solution administered to the animals hydrocortisone contained 2.6 µmol drug. After 16 injections the animals were killed, climbed the spinal cord at the lumbar spine and subjected to formation of paraffin sediments, the sections were stained according to the method of Nissle. Microscopic measurements were taken at magnification of 7×90 and with the help of the scale was determined by two diameter (large and small) body and nucleus of cells of motoneurons. The value of dividing the scale was determined using a micrometer, one division of the scale part of the yalo 16.6 μm. When calculating the space used by the formula

where 0,12 - correction factor on the optical environment of the microscope, and a large diameter, b - small diameter, 16,6 - value of one division of the scale. The diameters of the body and nucleus of the cells was determined by the formula: d1, d2=3,14·0,12·a (or b)·16,6. Calculation of glia and their distribution is conventionally carried out on a large diameter. The calculated sizes of motoneurons were comparable to normative data provided Umiastowski in the monograph of Normal and pathological morphology of the neuron", 1965.

The studies presented in table 1.

It is noteworthy that the large and small diameters and square body and nucleus in intact animals and in control with alcohol, on the basis of which the prepared extracts and cultivation of hydrocortisone had no significant differences. A distinctive feature was the increase in the size of motoneurons in the introduction of animal extracts of porcine adrenal (body length of a neuron with dl more than 125 µm) and was more often than in the control groups, in comparison with the intact (group 1) more than 2 times; on averaged data (97.9±26,7 μm against 83,2±25,0 µm) differences are also statistically significant (p= 0.000). Differences in the average values of the square body of the neurons with the introduction of the bark extract of porcine adrenal (378.46±127,53 μm2) is respectively in the group of intact control (344.65±146.69 μm 2were close to significant (11-4=1,86; p=0,065). More positive changes in the growth of motoneurons of the spinal cord after injection of extracts of the bark of porcine adrenal noted in the measurement kernel. Neurons with dl cores in excess of 37.5 μm, were recorded 4 times more often with the introduction of the bark extract of porcine adrenal (29,0%)than in the intact control group (7.0 percent), and even more than in the other control groups. And on averaged data differences dl compared with control groups is statistically significant (p=0,000).

The number of motoneurons of the spinal cord with a square kernel exceeding 80,0 μm2met with the introduction of the extracts of porcine adrenal 2.5 times more often (20,0%)than in the group of intact control (8,0%). On the average data size of the nucleus of motor neurons in animals that were administered the extract of porcine adrenal (61,99±3,43 μm2), was significantly higher than in the group of intact control growing animals(46,27±2,48); 11-4=3,163, P1-4=0,002).

Draws attention to the increase in the size of glia surrounding the motor neurons of anterior horns of the spinal cord. Cells of the second (up to 12.5 μm) and third order (>12.5 μm) were found much more frequently in animals that were administered the extract of the bark of porcine adrenal, compared with all control groups and especially in comparison with the control intact growing animals (25,98% of the 15.5 per cent respectively 15,5% and 7.3%). P1-4=0,003.

It should be noted that when compared to the prototype with the introduction extracts of fetal adrenal differences were less significant than with the control. With the introduction of extracts of the bark of the fetal adrenal in comparison with the data after the introduction of the bark extract of pig adrenal glands were larger sizes (d1 and d2), body surface area (s), which is reflected in the proportions of cells. The highest coefficient (S/S) observed in animals that received the extract of the bark of porcine adrenal (15,3%), with the injection of extracts of fetal adrenal - 13,48%as intact (13,3%). It is noteworthy that animals treated with hydrocortisone in conventional doses (1 mg per 100 g weight or 10 mg/kg), had the lowest coefficient kernel/body (10,34%) due to an absolute decrease of the area of the kernel (39,62±1,532 μm2against the intact control (46,27±2,481 μm2). All this allows to consider that the introduction of extracts of porcine adrenal stimulation is achieved growth of motoneurons in the spinal cord, little inferior to the results of the prototype, with large resources for the production of stimulants.

It should be noted, examination of experimental animals in the dynamics of experience has shown that the greatest increase in weight for a 5-week period was observed in intact animals (90 g): animals which were injected with extracts of St. the tion and fetal adrenal, he gained weight and 82.4 g of 84.0 g, respectively (in the group with hydrocortisone is an 80.2 g).

It is noteworthy that the increase in growth in the group of intact control was 1,26 cm; the highest growth was observed in animals that were injected with extracts of swine (2.0 cm) and fetal adrenal (2,46 cm), and less with the introduction of hydrocortisone (1,46 cm).

Given that the animals in these groups were observed and the large size of bodies and nuclei of neurons, we refer the above-mentioned changes in neurons growing animals not so much to the manifestations regulatory hypertrophy as to the true gain at the expense of all cell structures.

The effect of bark extract of pork and fetal adrenal glands on morphometric characteristics of motor neurons in the anterior horns of the spinal cord growing rats.

Literature

Badalyan LA Children's neurology. Medicine, 1975, str-257.

Bondarenko Y.S. Hereditary muscular dystrophy. Medicine. 1976.

Geht', Rollin N.A. Neuromuscular disease. Moscow, "Medicine" 1982.

Geht BM, Kolomna E.A., Chagall DI, Merkulova D.M., G.B. Ibragimov strategy for the use of glucocorticoid drugs for neuromuscular C the diseases. Journal of neuropathology and psychiatry named CSV, volume LXXXV, 1985, issue 11; 1651-1658.

Davidenkov E.F., Lieberman I.S. Clinical genetics. Medicine, 1975, 253 S. Jabotinsky, Y.M. Normal and pathological morphology of the neuron. Medicine, 1965, p.5-11.

Troshin V.M., Kravtsov SCI Diseases of the nervous system in children. Nizhny Novgorod. 1993, vol. 1, p.14-20.

Backmann E., Henrikasson K.G. Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy. Neuromuscul Disord, 1995, 5:233-241.

W.K. Engel, Warmolts I.R. The motor unit. - In: New development in EMG and clin. - Neurophysiology, 1973, vol.1, p.141-177.

G.M. Fenichel, Florence J.M., Pestronk, A. et al. Long-term benefit from casino poker tournament therapy in Duchenne muscular dystrophy. Neurology 1991, 41, 1874-1877.

R.C. Griggs, Moxicy R.T., Mandcll J.R et al. Duchenne dystrophy: randomized, controled trial of casino poker tournament (18 month and azathioprine (12 months). Neurology, 1993, 43. 520-527.

Sato B., K. Nishikida, L. T. Samuels, Tyler F.H. Electron spin resonance studies of erythrocytes from patients with Duchenne muscular dystrophy. J Clin. Invest. 1978, 61, 251-259.

Siegel I.M., Miller. Le, Ray R.D. Failure of corticosteroid in the treatment of Duchenne (pseudohypertrophie) muscular dystrophy. Illinois Med. J., 1974, 145:32-36.

Tyler F.H. Muscles, membranes end maternal markers. N. Engl. J. Med. 1978, 19, 885-886.

1. The use of bark extract of porcine adrenal glands as a means to stimulate growth of motoneurons of the spinal cord of a growing organism mammals.

2. The method of promoting the growth of motoneurons of the spinal cord of a growing organism mammals in the experiment, including the introduction of an extract of the adrenal cortex through the day, the General course of 5 weeks, wherein introducing the bark extract of porcine adrenal dose of 0.5 ml per 100 g body mass of the organism.



 

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3 cl, 4 dwg, 6 ex, 1 tbl

FIELD: medicinal industry.

SUBSTANCE: invention relates to a method for isolating biologically active substance from mammalian pancreas and preparing a medicinal formulation for parenteral administration that can be used in medicine as agent normalizing functions of pancreas. Agent is made as a medicinal formulation for parenteral administration and represents peptide complex with the content of low-molecular fraction from 70% to 890%, molecular mass of its peptide components in the range 74-222 Da and the concentration of polypeptides 2.5-2.9 mg/ml. Agent is prepared from calf pancreas (age is 12 months, not above) or pigs by tissue extraction with acetic acid in the presence of zinc chloride. Method for preparing agent from calf pancreas (age is 12 months, not above) or pigs involves freezing at temperature -40°C (not less), keeping at temperature -20-22°C for two months (not less) and adding 3% acetic acid solution in the volume ratio = 1:5 at temperature 20 ± 5°C. Extraction is carried out at constant stirring and 1% zinc chloride solution is added to the prepared homogenous suspension in the volume ratio = 50:1 followed by cooling at constant stirring to temperature 7-16°C and the following stirring for 1 h in each 4 h in settling for 48 h. Extract is separated from inert substances by separating and acetone is added to extract in the volume ratio = 1:5 and kept at temperature 3-5°C for 4 h. Formed homogenized deposit is precipitated with acetone repeatedly twice (not less) and deposit containing active substance is washed out on Nutch filter with two-fold volume of acetone cooled to temperature 7-16° up to preparing light-gray deposit. Deposit is rubbed through metallic sieve, dried, dissolved in distilled water at room temperature at constant stirring up to the concentration of polypeptides 2.5-2.9 mg/ml. Solution is centrifuged, filtered and subjected for ultrafiltration treatment in device under anti-pressure 1.0 kgf/cm2 (not above) through materials with retaining capacity 15000 Da. Glycocol is added to ultrafiltrate to its final concentration 10-20 mg/ml at pH = 5.6-6.6, solution is subjected for sterilizing filtration under pressure 2.0 kgf/cm2 (not above), poured into ampoules in volume 2 ml and subjected for autoclaving at temperature 120°C for 8 min and under atmosphere pressure 1.1 kgf/cm2. Invention provides optimal technology in isolating peptide complex from calf pancreas (age is 12 months, not above) or pigs with the content of low-molecular fraction from 70% to 90%, molecular mass of its peptide components in the range 74-228 Da, and preparing aqueous solution of extract with the concentration of polypeptides 2.5-2.9 mg/ml. Invention provides both purifying the prepared product from impurities and to enhance its yield. The isolated substance differs from the known substances early prepared from mammalian raw by molecular mass of its peptide components, absence of toxicity and apyretic properties based on the complete removing impurities.

EFFECT: improved preparing method, valuable properties of agent.

3 cl, 2 tbl, 1 dwg, 4 ex

FIELD: experimental biology and medicine, hepatology, nephrology.

SUBSTANCE: invention proposes using extracts of porcine or human fetal adrenal gland cortex for correction of acute renal insufficiency in toxic hepatorenal syndrome caused by carbon tetrachloride (CCl4). For realization for correction method involves carrying out course of subcutaneous injections of extract of porcine or human fetal adrenal gland cortex by 1 injection per 24 h in the dose 2.0-2.5 ml/kg of body mass by total course 10 every day injections. Using the proposed method provides enhancing effectiveness of regenerative processes in kidneys and reducing symptoms of adverse effects.

EFFECT: valuable medicinal properties of agent.

2 cl, 2 tbl

FIELD: medicine, peptides.

SUBSTANCE: invention relates to a method for preparing a peptide complex from animal raw possessing the tissue-specific activity. Method for preparing an agent for maintaining therapy possessing tissue-specific activity involves milling calf or pig organs of age 12 months, not above, addition of 3% acetic acid solution at temperature 20 ± 5°C and extraction is carried out at constant stirring. Then, in 30 min zinc chloride 1% solution is added, mixture is cooled to temperature 7-16°C at constant stirring followed by stirring for every 1 h in each 4 h and settling for 48 h. Extract is separated from inert substances by separation and acetone is added to extract in the volume ratio = 1:5, mixture is kept at 3-5°C for 4 h and formed precipitate is washed out with out with two-fold volume of acetone cooled to temperature 7-16°C, formed precipitate is rubbed through a metallic sieve and prepared end product is dried at temperature 18 ± 2°C. The end product represents a peptide complex with the content of low-molecular peptide fraction from 70% to 90% and with molecular mass of its peptide components in the range 1000-12000 Da wherein this complex comprises amino acids, mineral substances, trace elements and vitamins in biologically bound form. The complex elicits the expressed tissue-specific activity based on the proposed sequence of technological procedures and conditions for their realization involving temperature, temporal and other indices, and by using substances including the parent raw, a definite extractant and others. Peptide component in the prepared complex has no denaturating properties and retains its regulatory properties that suggests its using as an agent for carrying out the maintaining therapy. The proposed agent can be used in medicinal practice as an agent used in carrying out the maintaining therapy.

EFFECT: improved preparing method, valuable medicinal properties of agent.

9 cl, 42 tbl, 14 ex

FIELD: medicine, homeopathy, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates, in particular, to suppository possessing immunomodulating effect and comprising coneflower, accessory substances and a base, sea-buckthorn oil, arborvitae (thuja) homeopathic essence, baptisia homeopathic essence, Timalin-1C homeopathic trituratium wherein coneflower is a component of homeopathic essence. Suppository comprises anhydrous lanolin and wax as accessory substances and cacao butter as a base wherein components are taken in the definite ration in grams per one suppository of weight 2 g. Proposed suppository possesses the enhanced immunomodulating effect and allows stimulating processes of regeneration and hemogenesis and improves processes of cellular metabolism.

EFFECT: valuable medicinal properties of suppository.

3 ex

FIELD: chemical and pharmaceutical industry.

SUBSTANCE: invention relates to natural immunocorrective preparation Tactivine in spray form. Claimed agent contains Tactivina, vitamin C and 0.14 M sodium chloride solution as solvent in specific component ratio.

EFFECT: agent of improved effectiveness and storage stability.

2 cl, 5 tbl, 4 dwg, 4 ex

FIELD: medicine.

SUBSTANCE: method involves comminuting and treating tissues with enzymes using collagenase solution in Eagle solution in Dulbecco modification, clearing from erythrocytes by means of lysing solution and filtering the obtained suspension next to it. Thymus is taken as human tissue. Collagenase of type II is applied for treating tissue with enzymes. Filtration is carried out by means of filters having pore size of 100 and 10 mcm.

EFFECT: high degree of cell mass uniformity.

FIELD: agriculture, animal science.

SUBSTANCE: one should inject thymogen intramuscularly about 60-45 d before calving thrice at 24-h-long interval at the dosage of 500 mcg/animal.

EFFECT: higher efficiency.

1 ex, 1 tbl

FIELD: medicine, immunology, veterinary science, pharmacy.

SUBSTANCE: invention concerns a medicinal agent modulating the immune response of body. Agent is made as a tablet covered by envelope. The table core comprises thymus preparation, sodium nucleate, potato starch and the accessory substances taken in the definite ratio of components. As the thymus preparation immunomodulating agent can comprise tactivine or thymaline, or thymogen. The core is covered by envelope comprising acetylphthalylcellulose, castor oil, vaseline oil, titanium dioxide, tropeolin "O" taken in the definite ratio of components. Invention expands assortment of immunomodulating agent by the development of immunomodulating agent that acts on T- and B-lymphocytes simultaneously and on macrophage link of immune system that is suitable in using by children and other patient groups for a long time wherein injection method of administration is not desirable. The immunomodulating agent "Ribotab" elicits high effectiveness providing correction of immunity by tableting agent "Ribotab" after its using in a single dose.

EFFECT: improved and valuable properties of agent.

2 cl, 2 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly gynecology and medical rehabilitation of adolescent girls with acute complicated salpingoophorite. It involves 3 plasmapheresis sessions with small plasma exfusion volume in addition to antibacterial therapy over a day interval in post-operation period. Immediately after each plasmapheresis session 2.2 ml of Mucosa compositum, 2.2 ml of Coenzyme compositum and 2.2 ml of Tonsilla compositum is administered intravenously. Injections are repeated after medical plasmapheresis course, the total of 10 injections over one day interval. In addition, Nux vomika-Homaccord, Gynacoheel, Traumel C are administered internally by 10 drops three times per day for one month starting from the first day of therapy.

EFFECT: complex detoxicative, anti-inflammatory, immune modulation effect allowing prevention of secondary mutations of central and peripheral hemodynamics, psychoemotional state, involuntary regulation and menstrual cycle disorders.

3 ex

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