RU2098109C1 - Antiallergic, antiinflammatory agent, method of its preparing, curative and cosmetic agent and its use - Google Patents

Abstract

FIELD: biotechnology, medicine. SUBSTANCE: agent is a substance obtained from the strain of microorganism Staphylococcus aureus C2 GISK N 222 passed thermophilic development stage. Agent has a protein at amount 100-1000 PNU at biological activity 19%, not less (by index of inflammatory response elimination). Method of preparing involves the culturing this microorganism on liquid or agar-containing nutrient medium at 30-50 C for time necessary for sufficient microorganism growth. Then microorganisms were isolated from nutrient medium and placed in 0.5% carbolic acid (phenol) solution and the obtained suspension is treated at 90-100 C for time providing microorganisms destruction. The obtained suspension is cooled and the destructurized microorganism residues were filtered off. The obtained solution is sterilized and poured in ampoules for injection or in vials for nasal drops or for external use. The prepared agent is used as a special addition for preparing ointments, suppositories, creams and lotions. EFFECT: enhanced effectiveness of agent. 11 cl, 3 tbl

Description

 The invention relates to medicine, in particular to the production of microbial preparations with anti-allergic and anti-inflammatory properties.

 Known drugs with anti-inflammatory properties, obtained by chemical, biological synthesis or a combination of these methods (herbal extracts, antibiotics, sulfamides). These substances are not anti-allergic drugs and often cause allergies themselves.

 An analogue of the proposed drug are hormones, glucocorticosteroids, obtained by chemical synthesis and have anti-allergic and anti-inflammatory effects. (D. Metzler, Biochemistry. M. Mir, 1980, v. 2, p. 586). However, the latter, in addition to the indicated medicinal properties, violate many types of human metabolism of water, salt, fat, etc. and lead the patient to hormonal dependence.

 The closest analogue prototype of the claimed drug is the non-hormonal drug "Paspat" Luitpold Werk Munchen (Germany), which is a multivalent mixture of autolysates from eight microorganisms, one of which is St. aureus, which has an antiallergic effect and contains 18.0 30.0 mg / 100 ml of protein nitrogen or 18000 30000 PNU (0.01 mg / ml of protein nitrogen corresponds to 1000 PNU), i.e. 1.1 1.87 mg / ml of protein. However, the drug has a weak anti-inflammatory effect and does not have high biological activity, since it contains a sufficiently large amount of protein. The method of obtaining the drug is complicated, as it involves the cultivation and processing of eight different microorganisms. For these reasons, the drug is not widely used in medical practice.

The closest analogue to the prototype of the method of obtaining the proposed tool is a method of obtaining a non-hormonal drug "Paspat" Luitpold Werk Munchen (Germanu), which consists of a separate process of cultivating each type of microorganism, their destruction and obtaining a polyvalent mixture of autolysates of microorganisms [2]
The prototype of a therapeutic agent used as an ointment is an agent containing lanolin (5.0) and petrolatum (15.0) as a base, and pilocarpine hydrochloride (0.2) as a target additive (Vinogradov V.M. et al. Pharmacology with a prescription (L. Medicine, 1974), as well as a therapeutic agent that contains cocoa butter (2.0) as a base and is used in the form of suppositories for pain, tenesmus, and hemorrhoids.

Known strain of Staphylococcus auren C2 GISK N 222 used for the manufacture of anti-inflammatory drug [1]
Known cosmetics containing a base and various targeted additives. The prototype of the claimed cosmetic product is a spermaceti cream based on natural fats and oils and the target additive spermaceti extract (GOST 29189-91).

 The aim of the invention is to obtain a highly effective non-hormonal agent with anti-allergic and anti-inflammatory effects with high protein activity and, accordingly, its low content in the drug.

This goal is achieved by the fact that a non-hormonal drug with anti-allergic and anti-inflammatory effects is obtained by processing the thermophilic stage of development of the microorganism Staphylococcus aureus strain C2 N 222, contains protein in an amount of 0.0063-0.063 mg / ml (protein nitrogen in an amount of 100 to 1000 PNU) , and has a biological activity according to the index of elimination of the inflammatory reaction of at least 19%
The biological activity of the proposed funds was determined as follows. Five white mongrel mice (19 21 g) are injected once intravenously with 0.5 ml of a 100-fold diluted 0.9% sodium chloride solution for injection, five control mice are injected with 0.5 ml of a 0.9% sodium solution chloride for injection. After 60 minutes, 0.02 ml of an aqueous solution of concanvaline A containing 5 mg / ml is subplanted into the paw pad of each animal. 0.02 ml of 0.9% sodium chloride solution for injection is injected into the contralateral limb. After 90 minutes, the animals are killed by decapitation, the limbs are separated by the knee joint and weighed on an analytical balance.

For each animal, the reaction index is calculated by the formula:
IR (PP _to ) • 100% / P _to ,
where P is the mass of the limb of the animals in mg administered with concanvaline A;
P _{to the} mass of the contralateral limb in mg with the injected solution of sodium chloride.

The described experiment is repeated 3 times, calculate the average value of the reaction index for the experimental and control groups of animals. To obtain the drug microorganism St. aureus strain C2 N222, which has passed the thermophilic stage of development, is cultivated on a nutrient medium, liquid or containing agar, at T 35 50 ^o C for a time that provides sufficient growth of the microorganism, usually 18 24 hours, the resulting microorganism is separated from the nutrient medium, placed in 0, 5% solution of carbolic acid and treated at T 90 100 ^o C, during the time providing the destruction of the microorganism, cool the resulting substance to 20 22 ^o C and filtered from the degraded microorganism. Cultivation of Staphylococcus aureus strain C2 N222 is carried out by the surface method in test tubes, mattresses on nutrient media containing agar, and in flasks and / or fermenters on nutrient media not containing agar. For an embodiment of the process on agar-free nutrient media, the cultivation of a microorganism, its destructuring, cooling of the culture fluid and filtering of the degraded microorganism are successively carried out in the same bioreactor equipped with devices for mixing aeration, thermoregulation and filtration. The resulting preparation is sterilely filled into ampoules for subcutaneous injection or into vials for drops in the nose or into vials for external use. The results of the study of the drug are given below.

 Other therapeutic forms containing an anti-allergic and anti-inflammatory agent obtained as a target additive by treating a thermophilic stage of development of St. aureus C2 N222 and containing protein in an amount of 0.0063 0.063 mg / ml (protein nitrogen in an amount of 100 to 1000 PNU) are therapeutic ointments and suppositories.

Ointments contain the target additive in an amount of 5 to 10% and as a basis, lanolin, petrolatum or a mixture thereof in an amount of 90 to 95%
Medicinal candles contain the target additive in an amount of 5 to 10% and as the base anesthetic in an amount of 5 to 10% cocoa butter in an amount of 80 to 90%
To improve the effectiveness of cosmetics, the proposed tool is introduced into them as a target additive.

 Cosmetic cream contains the target additive in an amount of 1 5% and as a base it contains emulsion waxes in an amount of 2 6% vegetable oils in an amount of 5 15% glycerin in an amount of 1 6% higher alcohols in an amount of 0.5 3% ethyl alcohol in the amount of 1 to 5% of the rest is water.

Cosmetic medicinal product lotion contains the target additive in an amount of 1 5% and as a basis it contains a water-alcohol mixture with aromatic substances in an amount of 95 99%
A method of obtaining an anti-allergic and anti-inflammatory agent is as follows. Staphylococcus aureus mesophilus culture aureus pcs C2 N222 (Deposited at the Museum of Standardization and Control of Medical and Biological Preparations named after N.A. Tarasevich), prepared by repeated passages at a cultivation temperature up to 60 70 ^o C, seeded on a sterile complex nutrient medium containing 20 22% of the broth, 0, 4 0.6% glycerol, 1.0 1.5% egg albumin and 0.5 1.0% agar, poured into test tubes, flasks or mattresses, cultivated in an incubator at a temperature of 35-50 ^o C for 18 24 hours, wash the culture off the surface of the agar
A toxicological study was conducted in a cardiocenter.

 Total. 1. Acute toxicity: once in / abdominal. in / muscle p / dermal mice and rats Wistar in doses of 1.5; 7.5 and 15.0 ml / kg does not cause signs of intoxication of animal death (doses 600, 3000 and 6000 times higher than the therapeutic).

Due to the absence of animal deaths, it was not possible to establish a lethal dose (LD ₅₀ ), which is practically non-toxic.

 II. Chronic toxicity (3 and 6 months). In Wistar rats, doses were 5, 25 and 100 times higher than therapeutic doses, the drug did not affect the general condition, behavior, body weight, blood, total protein, activity of liver enzymes, alkaline phosphatase, LDH, the pancreas, kidneys, CCC-N, histology of organo-N, there is no locally irritating effect. On dogs the same result.

 No contraindications were detected at a dose of 0.0025 ml / kg.

 The Research Institute of Pharmacological Genetics performed a study of the mutagenic properties of the drug.

 A comprehensive study of the mutagenic properties did not reveal the mutagenic activity of the drug when tested in doses that are therapeutic for humans. This observation allows us to draw a conclusion about the genetic safety of the use of the drug within the dosages recommended for clinical trials.

 Embryotoxicity and teratogenicity. Under the influence of the drug, a decrease in the number of born rat pups is observed in 40- and 100-fold therapeutic doses. However, the drug does not affect the indicators of postnatal mortality and body weight dynamics of rat pups during the first month of life.

 Thus, the embryotoxic effect of the drug cannot be ruled out, and therefore pregnancy should be considered a contraindication for its purpose.

 The immunotoxicity and allergenicity of the drug were studied at the VSC for the safety of biologically active substances.

 Conclusion It does not have immunotoxic and allergenic properties.

A 0.5% solution of carbolic acid is heated in a water bath at a temperature of 90-100 ^° C for 1 h, cooled to a temperature of 20-22 ^° C, filtered through bacterial filters and standardized with physiological saline based on determining the concentration of protein in the solution. Another embodiment of the method according to the invention is the cultivation of a mesophilic strain of Staphylococcus aureus, prepared by repeated passages at a cultivation temperature of up to 60 70 ^o C. The producer is seeded in flasks or in fermenters with a sterile complex medium of the same composition, but not containing agar, cultured at a temperature of 35 - 50 ^o C for 18 to 24 hours, the biomass was separated, the precipitate was suspended in a 0.5% solution of a carboxylic acid, the suspension is heated at a temperature of 90 95 ^o C for 1 h, cooled to tamper 20 rounds 22 ^o C, filtered through a bacterial filter and standardize saline based on the determination of protein concentration in solution. During the cultivation process in fermenters, the microorganism is degraded, the culture fluid is cooled and the target product is isolated sequentially in the same bioreactor equipped with a bubbler, an electric stirrer, a jacket for supplying coolants, a temperature control system and a filtering device. The substance sterile filtered from the degraded microorganism is standardized with physiological saline, the biological activity is determined by finding the index of elimination of the inflammatory reaction and sterilely poured into 0.5 ml ampoules used in medical practice for injection, or into 10 ml vials for drops in the nose or 50 ml vials for external use.

 The obtained substance is also used to obtain therapeutic and cosmetic products containing a base and a healing supplement anti-allergic and anti-inflammatory agent obtained by processing the thermophilic stage of development of St. aureus strain C2 N222 and containing protein in an amount of 0.0063 0.063 mg / ml (protein nitrogen in an amount of 100 to 1000 ZTG).

The target additive in the manufacture of therapeutic ointments is added in an amount of 5
10% in a pre-heated to 60 70 ^o C, a mixed base containing lanolin in an amount of 50 to 90% petrolatum in an amount of 50 to 90% or a mixture of these components. The resulting mixture is homogenized and packaged in specially prepared jars or tubes.

Therapeutic candles are made by adding the target additive in an amount of 5-10% to a pre-homogenized base containing anesthetic additive 5 10% cocoa butter 80 90% at a temperature of 50 - 70 ^o C. The resulting mixture is subjected to homogenization and poured into specially prepared forms.

To obtain a cosmetic cream, the base is preliminarily prepared: emulsion waxes in an amount of 2 6% are fused with vegetable oils in an amount of 5 to 15% and higher molecular alcohols in an amount of 0.5 to 3% at a temperature of 90 ^o C, filtered through a gauze filter and cooled to 60 ^o C; glycerin in an amount of 1 6% is mixed with ethyl alcohol in an amount of 1 - 5% and a pre-mixed target additive in an amount of 1 5% with water in an amount of 81% is added to this mixture, the resulting solution is added in small portions with vigorous stirring in the prepared viscous phase, maintaining the temperature of the mixture is 60 ^o C. The resulting cream is packaged in pre-prepared cans having a container liner.

 In the manufacture of cosmetic lotions, a target additive of 1–5% is added to the base, which is a water – alcohol mixture with aromatic substances in an amount of 95–99%, mixed and poured into bottles.

 The practical implementation of the method is illustrated by the following examples.

Example 1. Mesophilic culture of Staphylococcus aureus St. aureus strain C2 N222, prepared by repeated passages at a cultivation temperature up to 60 70 ^o C, seeded in test tubes with 10 ml of sterile beveled complex nutrient medium containing 20% open-hearth broth, 0.6% glycerol, 1.0% egg albumin and 0, 5% agar, cultured in an incubator at 37 ^° C for 24 hours, washed off the culture from the surface of the agar with a 0.5% solution of carbolic acid in saline, heated in a water bath at a temperature of 92 ^° C for 1.5 hours, filtered through bacterial filters of Millipor company with a pore diameter of 0.22 microns and after dstvii standardize saline based on the determination of protein concentration in solution. The amount of protein obtained by this method after filtration of 0.1 mg / ml The biological activity of the drug, determined by the index of elimination of the inflammatory reaction is 30%
The result is a process productivity of 5.8 mg / h per liter of nutrient medium.

A standardized anti-allergic and anti-inflammatory agent for the concentration of protein nitrogen 300 PNU is added as a target additive to the therapeutic cosmetic cream in an amount of 2%
To obtain a cosmetic cream, the base is preliminarily prepared: emulsion waxes in an amount of 6% are fused with stone oil in an amount of 8% and higher molecular alcohols in an amount of 1% at a temperature of 90 ^o C, filtered through a gauze filter and cooled to 60 ^o C; glycerol in an amount of 2% is mixed with ethyl alcohol in an amount of 2% and a pre-mixed target additive of 2% with water in an amount of 81% is added to this mixture, the resulting solution is added in small portions with vigorous stirring to the prepared viscous phase, maintaining the temperature of the mixture at 60 ^o C. The resulting cream is packaged in pre-prepared cans with a capacity of 75 ml, having a container liner.

Example 2. Mesophilic culture of Staphylococcus aureus St. aureus strain C2 N222 prepared by repeated passages at a cultivation temperature of up to 60 ^° -70 ^° C is seeded in 750 ml Erlenmeyer flasks onto agar-free medium containing 100 ml of sterile complex medium of the following composition, meat and peptone broth 22; glycerol 0.5; 0 egg albumin 1.0, cultivated in a thermostat at a temperature of 40 ± 1 ^o C for a period of time up to 24 hours on a circular shaker at a speed of 220 rpm, the biomass is centrifuged at 3000 rpm, the sediment is suspended in 10 ml 0.5% carbolic acid, suspensions are heated at 90 ^o C for 1 h, filtered through bacterial filters of the Millipor company with a pore diameter of 0.22 μm and standardized with physiological saline based on determining the concentration of protein in the solution. With this variant of the method, a protein concentration is obtained after filtration of 0.4 mg / ml, the biological activity of the drug according to the index of elimination of the inflammatory reaction is 37%. The productivity of the process with 1 liter of culture medium is 11.11 mg of protein per hour.

 The standardized anti-allergic and anti-inflammatory agent is standardized to a concentration of protein nitrogen of 500 PNU, used as anti-allergic and anti-inflammatory drops in the nose, sterilely spilled in 10 ml bottles or in 50 ml bottles for external use, and also as a target additive for cosmetic lotions . In the manufacture of a cosmetic lotion, in the base, which is a water-alcohol mixture with aromatic substances in the amount of 96%, the target additive in the amount of 4% is added, mixed and poured into bottles.

Example 3. Mesophilic culture of Staphylococcus aureus St. aureus strain C2 N222 prepared by repeated passages at a cultivation temperature of up to 60 ^° -70 ^° C is seeded on agar-free medium containing the following components, meat-peptone broth 20; glycerol 0.5; egg albumin 1.0. Cultivation is carried out in a laboratory fermenter manufactured by the Swiss company Hemap with a capacity of 15 l, equipped with a two-tier turbine type agitator with an electric drive based on a DC motor with rotation speed adjustment from 0 to 1000 rpm. The fermenter is also equipped with an automatic temperature control system. The volume of medium in the fermenter is 10 l, aeration is maintained at 4 l / min (0.4 rpm), and stirring is 220 rpm, the temperature is maintained at 40 ± 1 ^o C. After 18 hours of cultivation, the mixer is turned off, they block the air outlet and, under the influence of excessive pressure, microorganisms are filtered from the culture medium through a Millipor filter with a membrane having a pore diameter of 0.22 μm mounted in the lower part of the fermenter. After removal of the entire liquid phase from the fermenter, 1 l of sterile saline solution containing 0.5% carbolic acid is transferred to it. Turn on the stirrer and bring the temperature of the liquid in the fermenter to 90 95 ^o C. When the stirrer is switched on 25 50 rpm maintain the liquid containing the target product at a temperature of 90 ^o C for 50 min, then cool this liquid to a temperature of 20 ^o C. After cooling, isolating (sterilizing filtration) a solution containing the drug through a filter manufactured by Millipor with a membrane having a pore diameter of 0.22 μm. As a result of filtration, 0.8 l of a sterile solution of anti-allergic and anti-inflammatory drug with a protein concentration of 0.5 mg / ml is obtained (taking into account losses). The biological activity of the drug is determined by the index of elimination of the inflammatory reaction is 47%. At the same time, the productivity of the process is 14.7 mg of protein per hour. A standardized anti-allergic and anti-inflammatory agent up to a concentration of protein nitrogen of 300 PNU is used as an injection solution sterilely filled in 0.5 ml ampoules, and also as a sterile substance for the preparation of therapeutic ointments and suppositories.

The target additive in the manufacture of therapeutic ointment is added in an amount of 7% to a pre-heated to 60 70 ^o C mixed base containing lanolin in an amount of 50% petrolatum in an amount of 43%. The resulting mixture is homogenized and packaged in specially prepared tubes with a capacity of 50 ml.

Therapeutic candles are made by adding the target additive in an amount of 8% to a pre-homogenized base containing an anesthetic additive of 7% cocoa butter 85% at a temperature of 50 70 ^o C. The resulting mixture is homogenized and poured into specially prepared forms.

In special experiments, the necessity and sufficiency of the claimed range of cultivation temperatures is shown. It was found that at temperatures below 35 ^o C and above 50 ^o C there is a slowdown in the growth of the microorganism and a decrease in the biological activity of the target product. The need and sufficiency of the claimed temperature range for the stage of microorganism destructuring has also been confirmed. It was shown that for temperatures below 90 ^o C there is no complete extraction of the target product from the culture fluid. At temperatures above 100 ^o C, the rheological properties of the culture fluid deteriorate, which leads to additional losses at the filtration stage and, consequently, to a decrease in the productivity of the process.

 The advantages of the claimed funds in comparison with the prototype (drug Paspat) are confirmed in special biomedical experiments.

 In the first series of experiments, a comparative assessment of antiallergic properties in the treatment of the most common allergic diseases was carried out. Two groups of patients underwent a course of treatment, respectively, with the proposed tool and drug according to the prototype. Patients suffered from allergic rhinitis, urticaria, bronchial asthma. The course consisted of 6-10 injections subcutaneously in 0.2 ml once a week. The protein load according to the proposed method per injection is 0.00125 0.0125 mg, and according to the prototype 0.225 0.375 mg, that is 30 180 times higher.

 The results of a comparative analysis of the action of Paspat preparations and the preparation according to the proposed method for patients with allergic diseases are presented in table. one.

 Improving the condition for rhinitis, atonic dermatitis, urticaria and Quincke's edema means a transition to milder forms of the disease.

 The cure implies the absence of symptoms of allergic inflammation after a course of treatment according to the proposed method and the prototype. At the same time, in patients who underwent treatment with the proposed drug, there was a decrease in the level of dysbiosis, which was much more pronounced than when using the drug according to the prototype (Paspat drug). In the second series of experiments, a comparative assessment of the anti-inflammatory properties of the proposed tool and prototype in the treatment of the most common inflammatory diseases.

 Two groups of patients underwent a course of treatment, respectively, with the proposed tool and drug according to the prototype. Patients suffered from inflammatory diseases: chronic bronchitis, chronic rhinitis (non-allergic), hypersensitivity to infections, furunculosis. The course consisted of 6 10 injections subcutaneously in 0.2 ml once a week. The protein load according to the proposed method for one injection is 0.00125 0.0125 mg, and according to the prototype 0.225 0.375 mg, that is 30 180 times higher.

 The results of a comparative analysis of the effects of Paspat preparations and the drug according to the proposed method for patients with inflammatory diseases are presented in table. 2.

 The action in the forms of a drop in the nose and solution for external use, as well as ointments and suppositories containing the drug as the target additive, was tested. Due to the fact that the preparation of the prototype is available only in the form of a dosage form for injection, a comparative analysis of the medicinal properties of the above forms of the preparation of the prototype does not seem to be correct. Therefore, the anti-allergic and anti-inflammatory effects of these forms were evaluated only for the proposed drug. The results are shown in table. 3.

 The use of ointments with the target additive according to the proposed method in the treatment of patients with chronic non-allergic rhinitis, as well as for external use in places of lichenization of the skin with allergic dermatitis, led to a significant improvement in 80% of cases. Therapeutic candles with the addition of the target supplement according to the proposed method were used for patients in whom the mucous membrane of the gastrointestinal tract is involved in the allergic process and with irritation of the anus. Improvement was observed in 84% of treated patients. Thus, the proposed tool has a non-hormonal origin, has a high anti-allergic and anti-inflammatory effect, has a protein load on the patient 30,180 times less than the drug of the prototype, is a vital product of only one microorganism that underwent a thermophilic developmental stage, in contrast to the prototype, where the drug is a product of autolysis of eight microorganisms. It should be noted that although the cosmetic and therapeutic agents of the invention have been described in relation to creams, lotions, ointments and suppositories, the invention can also be applied to such cosmetics as shampoos, toothpastes, soaps, etc. Therefore, the claims are formulated quite broadly.

 A test of the cosmetic cream was carried out on white outbred mice, rats and rabbits.

 It was found that a cream with a 2% content of the main active substance does not have an irritating and allergenic effect on conjunctival and skin-responsive test models.

 Clinical testing of the cream was carried out in a laboratory for the study of reparative processes in the skin of MMA named after THEM. Sechenov on 25 women from 18 to 42 years old with allergic dermatitis, in some complicated by acne rash.

 The cream is well absorbed and tolerated by the subjects, does not cause sensitization and locally irritating effects.

 The cream removes the foci of allergic inflammation, acne, redness, swelling, peeling decreases. Shine and greasy skin are reduced.

Cream composition
Emulsion waxes 6
Glycerin 2
Ethyl alcohol 2
higher alcohols 1
Stone fruit oil 8
Ventol 0.05 0.1
Active Start 2
Odus 0.2 0.5
Drinking water Up to 100
The main active ingredient of the cream, which determines its anti-allergic and anti-inflammatory effect, is the agent from Staphylococcus aureus, which has undergone a thermophilic processing stage.

 The cream is used as a non-specific antiallergic agent, it is an emulsion of the oil / water type with a thick consistency. The cream has a strong anti-inflammatory effect.

Claims (10)

 1. An anti-allergic and anti-inflammatory agent, characterized in that it is a substance obtained from the Staphylococcus aureus C2 strain of GISK N 222, which has previously undergone the thermophilic stage of development and has a biological activity of at least 19% in the index of eliminating the inflammatory reaction, contains protein in an amount of 0, 0063 - 0.063 mg / ml, protein nitrogen in an amount of 100 to 1000 PNU. 2. A method of obtaining a means of antiallergic and anti-inflammatory action, characterized in that the strain Staphylococcus aureus C2 GISK N 222, which has passed the thermophilic stage of development, is cultured on a nutrient medium, liquid or containing agar, at 30 ^{° to} 50 ^° C for a time that ensures sufficient growth of the microorganism , resulting biomass was separated from the culture medium, placed in a 0.5% solution of carbolic acid and treated at 90 100 ^o C for a time ensuring the destruction of the biomass, the resulting substance was cooled and filter from degradative-extracting biomass residues, sterilized and filled into ampoules for injection in vials or as nasal drops, or for external use.  3. The method according to p. 2, characterized in that the cultivation of the strain of the microorganism is carried out for 18 to 24 hours 4. The method according to p. 2 or Z, characterized in that the cooling of the substance is carried out to 20 22 ^o C.  5. The method according to p. 2, or 3, or 4, characterized in that when using a liquid nutrient medium, the cultivation and destruction of the biomass of the microorganism, the cooling of the obtained substance and its filtration from the degraded biomass residues are sequentially carried out in the same bioreactor equipped with devices aeration-mixing, thermoregulation and filtration.  6. A therapeutic agent of anti-inflammatory and anti-allergic action, containing a base and a targeted additive, characterized in that as a target additive it contains an anti-inflammatory and anti-allergic effect, described in paragraph 1, in an amount of 5 to 10 wt.  7. The tool according to p. 6, characterized in that it is made in the form of an ointment containing, as a basis, lanolin, petrolatum or a mixture thereof in an amount of 90 to 95 wt.  8. The tool according to claim 6, characterized in that it is made in the form of candles containing 5 to 10 wt. anesthetic and 80 to 90 wt. cocoa butter.  9. A cosmetic product containing a base and a target additive, characterized in that as the target additive it contains 1 to 5 wt. anti-allergic and anti-inflammatory drugs, described in paragraph 1.  10. The tool according to p. 9, characterized in that it is made in the form of a cream containing, as a basis, wt. Emulsion waxes 2 6
Vegetable oils 5 15
Glycerin 1 6
Higher alcohols 0.5 3
Ethyl alcohol 1 5
Water Else
11. The tool according to p. 9, characterized in that as a basis it contains a water-alcohol mixture with flavoring substances.

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