Method of human blood coagulation viii factor concentrate production and related product
FIELD: medicine; pharmacology.
SUBSTANCE: invention refers to method of human blood coagulation VIII factor production and related product. Method includes blood serum as cryoprecipitate, heparine added, PEG-4000, centrifugation, supernatant is added with tributyl phosphate and Twin-80, repeated centrifugation, sediment washed with sodium chloride, then it is dissolved in tris-HCl buffer with additives, let through column filled with gel and attached antibodies to Willebrand's factor, factor VIII elution, dialysis. Produced concentrate does not contain Willebrand's factor and has activity not less than 300 ME/mg of protein with purity not less 98% and contains albumin of concentration of 0.1%. Product is lyophilized with further processing.
EFFECT: product does not display any toxicity and cause allergic reaction.
6 cl, 2 ex
The invention relates to the field of preparative biochemistry, pharmacy and medicine and relates to a method of obtaining a concentrate of factor VIII clotting of blood and the product it contains.
Factor VIII plays an important role in the blood clotting system and is a major component of pharmaceuticals for the treatment of hemophilia. In plasma its content is small at ten-thousandths of a percent relative to the total protein. This determines the main problem in creating preparations containing this factor - the need for high efficiency of technological processes of their production, taking into account the main component of cost is the cost of human blood plasma. All preparations containing this factor, divided by the way they are received on genetic engineering and the drugs derived from human blood plasma. The last group represents the concentrates of different purity. Maximum clearance is achieved using monoclonal antibodies attached to a particular carrier, and the minimum is two or three non-chromatographic purification stages of cryoprecipitate. Drugs intermediate degree of purification obtained using a combination of those or other chromatographic methods. Such a variety of preparations containing factor VIII, due to the lack of the receiving consensus about the necessary and sufficient treatment from other components of blood plasma.
The fundamental difference technology is based on a different approach to the spectrum of proteins that are in the final dosage form of factor VIII. First of all it concerns the question of the necessity of cleaning from von Willebrand factor. In fact, on the one hand, von Willebrand factor, while in complex with factor VIII, stabilizes the last, with another subunit of von Willebrand factor form a huge complexes among themselves. Therefore, even if be cleansed from all other proteins in blood plasma, the specific activity of factor VIII in this drug will be far from optimal (when von Willebrand factor in the product is not at all or molar ratio of factor VIII: von Willebrand factor 1:1) and is determined by the ratio of factors. It is known that such an attitude in vitro can reach 1:100. And, considering the high molecular weight von Willebrand factor in relation to factor VIII is a clear need for the destruction of such a supramolecular complex with von Willebrand factor. In this case, regardless of the use of other techniques you can expect a higher yield and high specific activity of factor VIII in the final preparation both high and low purity.
The question of how and at what stage of the determination of factor VIII needed to destroy the Assembly of von Willebrand factor, closely svazas problem of maintaining the stability of factor VIII in the process of isolation and purification. After removal of the factors that lower the stability of factor VIII, such as prothrombin and thrombin, the most inactivating effect on it may have procedures for viral inactivation. The fact that it's pretty hard procedures and their implementation in one way or another requires stabilizing factors. Partly the complex of factor VIII and von Willebrand factor performs the same function. Therefore, the destruction of supramolecular aggregates of von Willebrand factor should be carried out either after the procedure, viral inactivation, or to artificially introduce additional stabilizers.
Known methods of obtaining a concentrate of factor VIII, in particular described in patent RU 2025129, EN 2148411, EN 2055593.
The closest is the method described in patent RU 2253475.
The essence of the present invention is that a method was developed to obtain preparations containing factor VIII, wherein using thiol-disulfide exchange was destroyed supramolecular complexes of von Willebrand factor, the activity of factor VIII were not addressed. The proposed method allowed us to develop a method to obtain preparations containing factor VIII, which are more efficient and specific content in comparison with similar methods, but does not include this stage.
Another aspect of the claimed invention I have is the product for use in medicine, veterinary medicine and/or research purposes, containing a concentrate of active factor VIII clotting person with a specific activity of not less than 300 IU/mg and 0.1% albumin, and purity more than 98%, obtained as described in the description and claims.
The product may be a solution or a lyophilized powder (for which the above concentrate is transferred into vials and dried by freezing under vacuum). If necessary, it may further contain conventional pharmaceutical excipients, solvents and/or excipients that are acceptable for parenteral (e.g. intravenous bolus or infusion, intramuscular, intranasal) administration. Listed excipients are mixed with a dry concentrate or added to the solution according to conventional methods. Fillers are, for example, sugars (glucose, lactose, sucrose, maltose, or mixtures thereof), sugar recovery (aritra, mannitol and other) in a physiologically acceptable concentrations, if necessary, antioxidants, traditional injectable pharmaceutical compositions. Optionally, the product may contain inorganic and/or organic salts and their combinations to maintain an acceptable pH values.
The solvent for the lyophilized product can service shall be distilled pyrogen-free water, saline, buffered saline solution.
You can also liofilizirovanny the finished product containing a concentrate of factor VIII and any of the following, auxiliary substances, in particular albumin, or a combination thereof.
The product can have an appropriate package and, optionally, instructions for use.
The implementation of the method is illustrated by the following examples.
1 kg of cryoprecipitate blood plasma was dissolved for 1 hour in water containing heparin (3 units/ml) at a temperature of 25°C. was Added aluminum hydroxide, brought the pH to 7.0 and after 15 minutes of incubation was centrifuged. To the obtained supernatant was added heparin to a final concentration of 3 units/ml, was then added 2-mercaptoethanol to a final concentration of 2 mm and incubated for one hour, then add the polyethylene glycol - 4000 to a final concentration of 2%. After adjusting the pH to 6.6 incubated for 15 minutes and centrifuged. The precipitate was discarded and the supernatant were dialyzed against water containing heparin (3 units/ml)was added glycine to a final concentration of 13%, and incubated for one hour. Then centrifuged, the precipitate was discarded. To the supernatant was added tributyl phosphate to a final concentration of 0.3% tween 80 to a final concentration of 1%, brought the pH to 7.2, and incubated at on the th temperature for 6 hours. After this was added sodium chloride to a final concentration of 14%, incubated for one hour and centrifuged. The precipitate was washed with sodium chloride solution and were dialyzed against a solution containing 200 mm sodium chloride, 2.5 mm calcium chloride, 20 mm sodium citrate, 10 mm lysine and 100 mm glycine. The specific activity was about 60 IU/mg of total protein. Added albumin to a concentration of 0.1%, sterile filtered and subjected to freeze-drying in combination with a subsequent heat treatment. The output process of the activity of factor VIII was about 60%.
Example 2. A preferred variant of the method.
Precipitate factor VIII concentrate prepared as in example 1. After washing the precipitate with a solution of sodium chloride was dissolved in 10 mm Tris HCl buffer containing 100 mm sodium chloride, 2.5 mm calcium chloride, 10 mm lysine and 5 units/ml heparin. The solution was passed through the affinity column containing 1 l of gel with sewn antibody to von Willebrand factor (anti-vWF gel, Immunotech, France). The elution of factor VIII was performed after washing 8 column volumes of equilibrating buffer. The composition of the eluting buffer consisted of 10 mm Tris HCl, 250 mm sodium chloride, 100 mm glycine, 2.5 mm calcium chloride, 250 mm ammonium sulfate, 2,55% glycerol. The resulting solution were dialyzed against a solution containing 200 mm sodium chloride, 2.5 mm calcium chloride, 20 mm C the waste sodium, 10 mm lysine and 100 mm glycine. The specific activity was about 300 IU/mg) was Added albumin to a concentration of 0.1%, sterile filtered and subjected to freeze-drying in combination with a subsequent heat treatment. The output process of the activity of factor VIII was about 70%.
Product purity not less than 98%.
The resulting product is pyrogen-free, does not show toxicity in experiments on laboratory animals (rats, rabbits), does not cause allergic reactions and can be used in medicine, animal health, research purposes.
1. A method of obtaining a concentrate of factor VIII clotting of the blood, characterized by the fact that cryoprecipitate plasma is dissolved in water containing 3 units/ml heparin at a temperature of 25°add the aluminum hydroxide to bring the pH to 7.0, incubated, centrifuged, the resulting supernatant add heparin, then 2-mercaptoethanol to a final concentration of 3 units/ml and 2 mm, respectively, incubated for one hour, add the polyethylene glycol - 4000 to a final concentration of 2%, adjusted pH to 6.6, incubated for 15 min, centrifuged, supernatant cialiswhat against water containing 3 units heparin/ml, then add glycine to a final concentration of 13%, incubated for one hour, centrifuged, the supernatant add tributyl phosphate to the end the end of the ation 0.3% tween 80 to a final concentration of 1%, bring the pH to 7.2, incubated at room temperature for 6 h, then add sodium chloride to a final concentration of 14%, incubated for one hour, centrifuged, the precipitate washed with a solution of sodium chloride, dissolved in 10 mm Tris HCl buffer containing 100 mm sodium chloride, 2.5 mm calcium chloride, 10 mm lysine and 5 units/ml heparin solution passed through a column Packed with gel with sewn antibody to von Willebrand factor, elute buffer consisting of 10 mm Tris HCl, 250 mm sodium chloride, 100 mm glycine, 2.5 mm calcium chloride, 250 mm ammonium sulfate, 2,55% glycerol, and the resulting solution deleteroute against a solution containing 200 mm sodium chloride, 2.5 mm calcium chloride, 20 mm sodium citrate, 10 mm lysine and 100 mm glycine, to the obtained concentrate, having a specific activity of not less than 300 IU/mg protein, add albumin to a concentration of 0.1%, sterile filtered, lyophilizers and subjected to heat treatment.
2. The product represents a concentrate of factor VIII clotting of the blood, characterized by the fact that obtained by the method according to claim 1, has a specific activity of not less than 300 IU/mg protein with a purity not less than 98% and contains albumin to a concentration of 0.1%.
3. The product according to claim 2, characterized in that it is a solution or lyophilized powder.
4. The product according to claim 2, characterized in that before omnitele contains pharmaceutical excipients, carriers, solvents and/or excipients that are acceptable for parenteral administration.
5. Product according to any one of claim 2 through 4 for use in medicine, veterinary medicine and/or research purposes.
6. The product according to claim 5 for the treatment or prevention of conditions associated with a lack of factor VIII.
FIELD: technological processes.
SUBSTANCE: preparation of human blood coagulation factor VIII is made by producing cryoprecipitate out of blood plasma, virus inactivating treatment, purification of cryoprecipitate solution, concentration, sterilizing filtration, bottling and drying. At the same time cryoprecipitate is produced with the help of running water with the temperature of (4±2)°C during unfreezing of fresh frozen plasma, virus inactivating treatment is carried out by means of solvent-detergent method, chromatographic purification of virus inactivated cryoprecipitate solution is carried out with application of sorbent with fractionation interval up to 20,000 kilodaltons, at the flow rate of (20±15) cm/hr, with further concentration by means of ultrafiltration on hollow fibers. Stabilizers are added, such as albumin in final concentration of (5±3) g/l, sugars and amino acids up to final concentration of (10±3) g/l. During drying initial preparation temperature is (25±15)°C below zero, final temperature is (25±8)°C, total duration of preparation drying process is (45±7) hours.
EFFECT: coagulation factor yield stability is increased and technological production design is simplified.
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a novel stable ready formulation of pharmaceutical composition containing VIII factor and can be used in treatment of hemophilia. Invention relates to a solid pharmaceutical composition prepared by lyophilization of an amino acid-free solution and comprising the following components: (a) VIII factor in the concentration 50-10000 IU/ml for human VIII factor or human recombinant VIII factor, or 50-10000 U/ml for swine VIII factor or swine recombinant VIII factor; (b) surfactant in the concentration above critical micellar concentration up to 1% (vol./vol.); (c) calcium chloride; (d) sucrose; (e) sodium chloride; (f) trisodium citrate, and (g) amino acids-free buffer in the concentration 1-50 mM with pH 6-8 before lyophilization and after dissolving in water for injection. Also, invention relates to a liquid pharmaceutical composition prepared after dissolving indicated stable solid pharmaceutical composition in sterile water optionally containing sodium chloride. Invention provides preparing a stable ready formulation of pharmaceutical composition of VIII factor wherein albumin is replaced with other stabilizing agents.
EFFECT: improved and valuable properties of pharmaceutical composition.
25 cl, 3 tbl, 3 ex
FIELD: medicine, pharmaceuticals.
SUBSTANCE: invention relates to pharmaceutical agent containing factor VII or factor VII-related polypeptide and factor VIII or factor VIII-related polypeptide. Disclosed are application of factor VII or factor VII-related polypeptide and factor VIII or factor VIII-related polypeptide in production of drug, kit for episodic bleeding treatment, as well as methods for prophylaxis and treatment of episodic bleeding in subject.
EFFECT: accelerated coagulation of FVIII-deficit plasma.
43 cl, 1 tbl, 2 dwg, 6 ex
SUBSTANCE: invention relates to methods for preparing biologically active substances from donor blood. Method for enriching donor blood plasma cryoprecipitate with factor VIII involves defrosting freshly frozen donor blood plasma at +1-4°C to obtain cryofractions from plasma cryosupernatant and cryoprecipitate. After formation of the donor blood freshly frozen plasma dry calcium chloride is added in the amount from 0.001 to 0.004 mole/l followed by addition of sodium citrate in the amount from 0.05 to 0.10 mole/l and stirring at +1-4°C for 10-15 min. Then prepared cryoprecipitate deposit is separated by centrifugation. For preparing cryoprecipitate freshly frozen plasma is used prepared by usual method with using conventional preserving agents. Using the method provides significant increasing the content of factor VIII in cryoprecipitate being without appreciable co-precipitation of inert proteins.
EFFECT: improved enriching method.
2 tbl, 3 ex
FIELD: pharmaceutical industry and biotechnology.
SUBSTANCE: method consists in the following: kryoprecipitate of donor blood plasma is suspended in heparin solution, resulting suspension is consecutively treated with aluminum hydroxide and polyethylene glycol-400 to remove ballast proteins until content of aluminum hydroxide in solution achieves 0.3% and that of polyethylene glycol-400 2%. Thus treated material is subjected to viral inactivation by solvent-detergent technique in presence of Tween and microfiltration followed by chromatographic fractionation on DEAE-containing carrier using buffer solutions, pH 6.75-6.85, with different ionic forces. Resulting concentrate of factor VIII is stabilized with albumin solution to provide final albumin concentration in the preparation 0.1%, sterilized by microfiltration, and transferred into lyophilized form, in which viruses are additionally inactivated via heat treatment.
EFFECT: preserved specific activity of factor VIII with high degree of purification and increased storage stability.
5 cl, 1 tbl
FIELD: medicine, hematology, pharmacy.
SUBSTANCE: invention relates to the composition of factor VIII composed without addition of albumin and comprising the following excipients of composition in addition to factor VIII: from 4% to 10% of filling agent taken among group consisting of mannitol, glycine and alanine; from 1% to 4% of stabilizing agent taken among group consisting of sucrose, trehalose, raffinose, arginine; from 1 mM to 5 mM of calcium salt, from 100 mM to 300 mM of NaCl, and buffer agent for pH value maintenance about between 6 and 8. Alternatively, the composition can comprise from 2% to 6% of hydroxyethylstarch; from 1% to 4% of stabilizing agent taken among group consisting of sucrose, trehalose, raffinose, arginine; from 1 mM to 5 mM of calcium salt, from 100 mM to 300 mM of NaCl, and buffer agent for pH value maintenance between 6 and 8. In additional variant of realization of invention the composition can comprise: from 300 mM to 500 mM of NaCl, from 1% to 4% of stabilizing agent taken among group consisting of sucrose, trehalose, raffinose and arginine; from 1 mM to 5 mM of calcium salt, and buffer agent. The composition provides stability in the absence of albumin or other proteins.
EFFECT: valuable properties of compositions.
35 cl, 11 tbl, 7 ex
FIELD: medicine; immunology.
SUBSTANCE: sorbent is offered to remove immunoglobulin from human blood plasma. This sorbent contains agarous matrix covalently combined with ligand. As a ligand at that it contains F(ab)2 fragments of specific affinely-purified polyclonal antibodies blocking human immunoglobulin G. Sorbent is actually biologically inert, biocompatible agarous matrix. Sorbent is characterized with higher sorptive capacity and safety of immunosorbents used practical purposes, specifically for therapeutic aphaeresis in comparison to well-known polyclonal bodies based sorbents.
EFFECT: considerable reduction of prospective immunological response of human body for foreign protein.
1 ex, 1 tbl
FIELD: medicine; chemistry-pharmaceutical industry.
SUBSTANCE: trophoblastic beta-1-glycoprotein is released from serosity produced as a result of differential centrifugation of retroplacental human blood. Supernatant after first centrifugation is saturated with sodium chloride (0.1-1.0 mole/l) to prevent non-specific sorption and centrifuged once more with triton X-100 (0.01-0.05%) to virus inactivation. Then it is applied to affine sorbent that is sepharose with solid-phase monoclonal antibodies to trophoblastic beta-1-glycoprotein. Protein is eluated with 0.1 M glycine-HCI buffer solution, and after neutralization and in-depth analysis second affine chromatography is carried out on sepharose with modified protein G, released from streptococcus cell wall to prevent immunoglobulin contamination. Solution passed through column and trophoblastic beta-1-glycoprotein is been concentrating and dialyzing from saline and lyophilized.
EFFECT: increased output and purity of end product.
FIELD: medicine, purulent surgery.
SUBSTANCE: it is necessary to apply dressings with suspension consisting of thrombocytes-rich plasma, 10%-CaCl2 solution at equal volume and antibacterial preparation to which ulcerous microflora is sensitive. The volume of dressing for 1 dressing should be determined by the following formula: V=S×h×C, where S - the area of ulcerous defect, h - its depth, C - the coefficient. At the rate of ulcerous surface epithelization being under 25% weekly C=1.25, and at the rate being above 25% weekly C=1.0. The innovation provides the chance for individual dosing autogenous tissue growth factors and matched efficient antibacterial preparations and, thus, accelerated phase II of wound process and shortened terms of epithelization of ulcerous defects in the present category of patients.
EFFECT: higher efficiency of therapy.
FIELD: medicine, ophthalmology, pharmacy.
SUBSTANCE: invention proposes a pharmaceutical composition used in treatment of cornea injuries that comprises, mas.p.p.: sodium deoxyribonucleate, 14-15; sodium chloride, 0.8-0.9; lyophilized blood plasma, 74-75, and distilled water, the balance. Components are mixed in aseptic conditions and packaged. Invention provides anti-inflammatory, antiviral, antibacterial, reparative and regenerative effect, decreasing treatment period and declining post-operative complications.
EFFECT: improved, enhanced and valuable medicinal properties of pharmaceutical composition.
2 tbl, 5 ex
FIELD: medicine, pharmaceutical industry.
SUBSTANCE: invention proposes a method for making tablets of alpha-fetoprotein preparation. Method involves mixing alpha-fetoprotein with a stabilizing agent, addition of a filling agent consisting of microcrystalline cellulose and potato starch or lactose, coating the prepared mixture by envelope consisting of acetylphthalylcellulose in the following ratio of components, weight%: alpha-fetoprotein, 0.01-0.03; stabilizing agent, 8.57-14,28; microcrystalline cellulose, 40-45.7; potato starch or lactose, 40-45.7, and acetylphthalylcellulose, 1.14-2.85. Rheopolyglucin is used as a stabilizing agent, and alpha-fetoprotein is obtained from abortive, cord or placental blood by separation of inert proteins from blood by centrifugation, fractionation of supernatant with ammonium sulfate or sodium sulfate, or ethyl alcohol for 1 h, repeated centrifugation of solution, carrying out the first chromatography treatment of supernatant on an affinity sorbent using Sepharose CL-4B, elution of alpha-fetoprotein with 0.1 M glycine-HCl buffer solution at pH 2.5 up to obtaining zero values of optical density at wavelength 280 nm, and the following chromatography treatment on an affinity sorbent using Sepharose CL-4B containing immobilized antibodies against human IgG and dialysis of alpha-fetoprotein solution against 0.15 mole/l of sodium chloride solution. The end product is diluted with rheopolyglucin up to the concentration alpha-fetoprotein 0.9 mg/ml and that of dextran 10 mg/ml. Invention provides increasing yield of alpha-fetoprotein and maximal purity of the end product, increasing stability of alpha-fetoprotein in storage, expanding region of its using and design of preparation of prolonged effect.
EFFECT: improved preparing method.
FIELD: medicine, urology.
SUBSTANCE: it is necessary to introduce autofibronectin under ureteric mucosa at the distance of about 4-5 mm being below its foramen in avascular area, at 5-6-7 endoscopic hours at the dosage of 5-10 ml till complete closing the mouth at the top of the tubercle developed. The innovation provides efficient removal of cystoureteric reflux, accelerates activation of fibroblasts and mobilization of collagen in area of fibronectin injection and prevents the manifestation of local inflammatory and general allergic reactions.
EFFECT: higher efficiency.
FIELD: medicine, in particular balneology and physical therapy.
SUBSTANCE: claimed additive contains dihydroquercetin or mixture of dihydroquercetin and milky whey in ratio from 2:1 to 1:2 as biologically active additive for balneological bath agent. Dalneological bath agent includes base, osmolytically active components such as glycerol and inorganic salts, as well as biologically active additive of plant and/or animal origin, wherein osmolytic activity is 7700-11000 mOsm/l. As biologically active additive of plant and/or animal origin it contains dihydroquercetin or mixture of dihydroquercetin and milky whey in ratio from 2:1 to 1:2 and as the base it contains water and/or concentrated milk in the next component ratio (mass %): glycerol 25.0-30.0; inorganic salts 10.0-15.0; dihydroquercetin or mixture of dihydroquercetin and milky whey 0.2-1.0; and balance: water and/or concentrated milk up to 100 %.
EFFECT: new effective additive for balneological bath agent.
5 cl, 9 ex
FIELD: medicine, oncology.
SUBSTANCE: the present innovation deals with surgical therapy and chemotherapy. Moreover, in pre-surgical period it is necessary to sample 200 ml blood in such patients, due to centrifuging blood should be divided into plasma, leukomass and thromboerythromass. One should add leukovorin into the vial with leukomass at the dosage of 500 mg/sq. m to incubate in a CO2-incubator for 24 h and fluorouracil into the vial with thromboerythromass at the dosage of 1000 mg/sq. m to incubate for 30 min. Plasma should be frozen. In the course of the operation it is important to introduce intravenously by drops the content of the vial with thromboerythromass. On the next day the incubated leukomass with leukovorin should be injected for a patient intravenously by drops. Then, in post-surgical period on the 12th-14th d defrosted plasma should be incubated with fluorouracil at the dosage of 1000 mg/sq. m and metotrexate at the dosage of 25 mg/sq. m to be intravenously injected by drops. The innovation enables to decrease the frequency of relapses and metastases, decrease toxicity of anti-tumor preparations and prolong life period and improve quality of life in such patients.
EFFECT: higher efficiency of therapy.
SUBSTANCE: method involves taken patient blood in preoperative period in the amount of 200 ml. Plasma is separated from the blood by centrifuging. 40 ml of autoplasma and chemopreparation are introduced into the first flask. The remaining blood corpuscles, plasma and chemopreparation are enclosed in the second flask. The flasks are separately incubated for 40 min at 37°C. Then, operation is executed by subserously introducing autoplasma incubated with chemopreparation from the first flask along the tumor periphery before mobilizing large intestine. Intravenous drip-feed infusion of autoblood incubated with chemopreparation from the second
flask is concurrently carried out into peripheral vein.
EFFECT: enhanced effectiveness in preventing local relapses and metastases occurrence in remote period.
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to using blood plasma or serum as an agent for treatment of wounds and to a pharmaceutical composition used in treatment of wounds and comprising blood plasma or serum, and to a method for treatment of wounds by applying indicated composition on wound site for normalization of tissue medium around the wound site. Pharmaceutical composition for treatment of wounds comprises pharmaceutically effective amount of blood plasma and serum as an active agent with pH value in the range from 3.5 to 6.5. Invention allows using the composition for recovery, substitution, relieve, acceleration, assistance to healing and/or cure of any damaged or traumatized tissue. Also, invention relates to preparing the amount of such composition providing normalization of different activating cells of substance and pathological cells around the wound site and promotes to the wound healing.
EFFECT: improved and valuable medicinal properties of composition.
12 cl, 9 dwg, 15 ex
FIELD: medicine, ophthalmology.
SUBSTANCE: one should apply an autohemocomponent preparation being supernatant liquid of patient's autoblood at increased serotonin content obtained due to irreversible thrombocytic aggregation due to the impact of 0.5 mg ATP per 1.0 ml plasma followed by a 30-min-long centrifuging at the rate of 1000, 2000 and 3000 rot./min for 20, 7 and 3 min, correspondingly. In case of no exudative phenomena on patient's eye bottom the obtained preparation should introduced at the quantity of 7-10 ml once in 48 h for 1 mo (totally, 15 injections). In case of exudative-hemorrhagic phenomena it should be introduced parabulbarly at the volume of 0.5 ml and parenterally - 7.0-10.0 ml once in 48 h for 1 mo per 15 injections, correspondingly. The preparation enables to improve visual functions due to decreased tissue hypoxia and normalization of microcirculation in visual analyzer.
EFFECT: higher efficiency of therapy.
2 cl, 7 dwg, 2 ex