RU2364390C1 - Pharmaceutical injection tilorone-based composition for treatment of diseases with immunodeficiency signs - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine and pharmacology, namely pharmaceutical injection compositions for treatment of diseases with immunodeficiency signs, described as containing Tilorone and hydrophilic solvent in certain ratio.

EFFECT: invention provides extended application of common active substance Tilorone, reconstitution of local immunity and biocoenosis of skin and mucous membranes in treatment of pyodestructive processes of skin and mucous membranes, especially in deep lesion focus, reduction of secondary necrosis of affected tissues, relief of inflammatory reactions, maintenance of local anaesthetic effect, acceleration of healing.

4 cl, 5 ex, 5 tbl

Description

The invention relates to the chemical and pharmaceutical industry, as well as medicine and veterinary medicine, namely to pharmaceutical preparations used in the treatment of purulent-destructive processes of the skin, mucous membranes, etc., especially with deep subcutaneous location of lesions with clinical and laboratory signs of immune deficiency for example, such as chronic recurrent furunculosis, herpetic lesions of the skin and mucous membranes, atopic dermatitis complicated by bacterial-fungal infections, trophic ulcers s, postoperative suppuration of wounds to promote healing.

The intensity of the infectious process depends on the number and virulence of the pathogen, the state of natural barriers and the resistance of the microorganism. Susceptibility for most infections is individual and usually due to a lack of immunity. The infectious factor takes a leading place in the pathogenesis of such common inflammatory diseases of the skin and soft tissues as acne, boils, carbuncles, impetigo, abscess, phlegmon, etc.

Infections caused by opportunistic microorganisms occur in people with deficits in the immune system, when a small dose of microorganisms that do not infect people with a normal immune system is enough. The balance between macro- and microorganisms can be disturbed by both exogenous and endogenous factors (impaired neuroendocrine system, immunodeficiency, depletion of the body's adaptation mechanisms, concomitant chronic pathology, etc.). Failure of the body's immune response to an infectious factor entails a chronicization of the infectious process.

The degree of pathogenicity of microorganisms is individual and determines the different activity of the body's immune response to them. It is associated with the ability to attach to sensitive cells (adhesion), multiply on their surface, penetrate into these cells or underlying tissues, overcome non-specific and specific factors of immunity, have an immunosuppressive effect (Kutasevich Y.F., Ogurtsova A.N. containing fusidic acid in the treatment of infectious inflammatory diseases of the skin and soft tissues. www.consilium.com.ua/stuff/doctor/dermatovenerologiya/Infekcii-koji-i-podkojnoi-kletchatki/Mesto-narujnyh-preparatov/).

Inflammatory skin diseases are one of the most common pathologies in dermatovenereology. This is due to the borderline location of the skin, which leads to contact and interaction with various exogenous factors. The effect of a biological factor (microorganisms) on the skin is almost constant. Microorganisms located on the surface of the skin, under appropriate conditions, can penetrate the dermis, deposited in the structural units of the lymphatic system and take an active part in the formation of the toxic-allergic component in the complex system of development of various pathological conditions of the dermatological profile.

Activated saprophytic microflora of the skin during the development of dermatopathological processes has a significant effect on the development and course of the underlying skin disease. Many topical and systemic medications used in the treatment of dermatoses inhibit the reactivity and immune defense of the body, increasing the virulence and activity of saprophytic microorganisms. Resident microflora begins to take an active part as a background or pathogenic factor that has a significant impact on the development and course of many diseases ("Evaluation of the effectiveness of the drug Fusiderm in pustular skin infections and acne" www.consilium.com.ua/stuff/doctor/dermatovenerologiya / Infekcii-koji-i-podkojnoi-kletchatki / fuziderm-preparat /).

In the dermis of the skin and in the mucous membranes there is a network of lymphatic and blood vessels, cells of the immune system (T- and B-lymphocytes, dendrides cells, natural killers, etc.) are concentrated, which ensures the participation of the skin and mucous membranes in the immune response. With inflammation, especially with purulent-destructive processes, severe edema develops, the affected area is infiltrated by neutrophils, lymphocytes, eosinophils, free radicals and other toxic metabolic products accumulate in them, which further increase the destruction. Under these conditions, access to medications for inflammatory foci is extremely difficult with their oral administration, and with a deep location of the lesion foci - with external and local application.

Interferons (alpha, beta and gamma) protect the body from infection with viruses, bacteria and protozoa, inhibit the growth of malignant cells, and potentiate lymphotoxins. The action of interferons is carried out through a system of cellular synthesis of nucleic acids using a number of enzymes and inhibitors, leading to the degradation of foreign genetic information. Interferons stimulate phagocytosis, the activity of natural killer cells, and the expression of antigens. On the other hand, they can inhibit the formation of antibodies, the development of anaphylactic shock, inflammation, delayed-type hypersensitivity, which makes Interferons true immunomodulators, and the interferon system is the most important in the regulation of cell homeostasis (//med.rehaexpo.ru/2005/participants/direct/ production_4073.stm).

Exogenous interferons have disadvantages - allergenicity, toxicity, high price.

An alternative way, devoid of the disadvantages inherent in exogenous interferon, is to stimulate the synthesis in the body of its own (endogenous) interferons. It is carried out using interferonogen preparations (www.provisor.com.ua/arhive/2000/N20/cyclopheron.htm).

Immunomodulating injection preparations based on low molecular weight synthetic peptides having immuno-regulatory properties, for example, such as thymogen, immunofan, glutoxim, thymalin, tactivin, etc., are known. These drugs have low efficiency due to the rapid destruction of low molecular weight peptides in the body. Their life time in the body is several minutes (www.mtu-net.ru/doctor99/5nklassifiklpolioxidoniy2905.htm).

Known immunomodulatory drug polyoxidonium, introduced in the form of a lyophilized mass, which for the preparation of an injection solution is dissolved immediately before injection in an isotonic solution of sodium chloride or water for injection. For intravenous (drip) administration, a mass of polyoxidonium is dissolved in 2-3 ml of an isotonic solution of sodium chloride, hemodesis, reopoliglyukin or glucose, sterilely transferred to bottles with the indicated solutions with a volume of 100-400 ml. This injection solution cannot be stored (www.mtu-net.ru/doctor99/5nklassifik1polioxidoniy2905.htin). The process of preparing an injection form before medical procedures requires careful observance of sterility and dosage, as well as their control, which complicates the medical process and can lead to medical errors. In addition, this drug does not have a local anesthetic effect.

Known drug meglumine acridone acetate (trade name - cycloferon), which is a low molecular weight inducer of interferon, which has an antiviral, immunomodulating and anti-inflammatory effect. The main target cells of the drug are T and B lymphocytes. It stimulates the production of alpha, beta, and gamma interferons (up to 60-80 PIECES / ml and higher) by leukocytes, macrophages, epithelial cells, as well as tissues of the spleen, liver, lungs, brain, penetrates the cytoplasm and nuclear structures, activates synthesis of "early" interferons. The immunomodulatory effect is expressed in the correction of the immune status of the body in immunodeficiency states of various origins. The drug has a low toxicity. It has no mutagenic, teratogenic, embryotoxic and carcinogenic effects.

As a 12.5% (0.125 g / ml) aqueous solution for intramuscular and intravenous administration, cycloferon is used in the treatment of HIV infection, neuroviral infection (tick-borne meningitis, multiple sclerosis, arachnoiditis), viral hepatitis (A, B, C, D), CMV and herpes infections, influenza, acute respiratory viral infections, immunodeficiency conditions (postoperative period, burns, bronchitis, pneumonia, etc.), gastric ulcer and duodenal ulcer, cancer, rheumatoid arthritis, deforming osteoarthritis, spondylosis, skin diseases ( atonic dermatitis, eczema, dermatosis, viral papillomas) (Description of the drug, www.regmed.ru/InstrShow2.asp?InstrLinkNx=a86ba80ba84ba86b). The composition of a 12.5% solution includes 125 mg of methylglucamine acridone acetate (1 ampoule - 250 mg), water for injection up to 1 ml. Available in the form of 2 ml ampoules (www.znaharka.ru/index.php?productID=59289).

The drug is compatible with all drugs, including antibiotics, vitamins, chemotherapy, immunomodulators, interferons (Description of the drug www.regmed.ru/InstrShow2.asp?InstrLinkNx=a72ba78ba75ba74b). It is known that the immune response to the action of cycloferon is observed in no more than 40% of patients (www.mtu-net.ru/doctor99/5nklassifiklpolioxidoniy2905.htm).

One of the most powerful inducers of endogenous interferon is known - tilorone (www.amixin.ru), which is available in the form of a preoral drug (trade name "Amiksin", instruction for the drug http://www.regmed.ru/InstrShow2.asp?InstrLinkNx= 41ba48ba44ba43b, and Lavomax, Preparation Instructions, http://www.regmed.ru/InstrShow2.asp?InstrLinkNx=a41ba48ba44ba43b). It is used in the treatment of viral hepatitis A, B, C; herpetic and CMV infections, complex therapy of infectious-allergic and viral encephalomyelitis (multiple sclerosis, leukoencephalitis, uveoencephalitis), chlamydial infections of the urogenital and respiratory tract, influenza prevention, and other acute respiratory viral infections (Instructions for the drug, http://www.regmed.ru /InstrShow2.asp?lnstrLinkNx=а41ba48ba44ba43b).

Tiloron is a synthetic low molecular weight interferon inducer that stimulates the formation of alpha, beta and gamma interferons in the body. The main producers of interferon in response to oral administration of tilorone are intestinal epithelial cells, hepatocytes, T-lymphocytes, neutrophils and granulocytes. After oral administration, the maximum production of interferons is determined in the sequence intestine - liver - blood after 4-24 hours. Tiloron in human leukocytes induces the synthesis of interferon, stimulates bone marrow stem cells, depending on the dose, enhances antibody formation, reduces the degree of immunosuppression, and restores the ratio of T-suppressors and T-helpers. The mechanism of its antiviral action is associated with inhibition of the translation of virus-specific proteins in infected cells, as a result of which reproduction of viruses is suppressed. It is effective against pathogens of viral hepatitis, herpes viruses, including cytomegaloviruses. (Instruction for the drug, http://www.regmed.ru/InstrShow2.asp?InstrLinkNx=a41ba48ba44ba43b).

After oral administration, tilorone is rapidly absorbed from the gastrointestinal tract (GIT). When taken orally, its bioavailability is 60%. Tiloron quickly penetrates into the blood and is distributed in organs, tissues and body fluids. About 80% of tilorone binds to plasma proteins. The drug is excreted almost unchanged with feces (70%) and urine (9%) with a half-life of 48 hours. Tiloron in the body is not metabolized and does not cumulate (Information about the drug "Amiksin", http://www.vidal.ru/vidal_main/doc_5533.htm).

Tiloron, being a modulator of cytokine reactions and an antioxidant, is orally used in the secondary prevention of multiple sclerosis (V.I. Golovkin et al. Secondary prevention of multiple sclerosis with the domestic drug amixin - a modulator of cytokine reactions and antioxidant, //home.peterstar.ru/nwams /amixin2.html).

Tiloron is orally used in the treatment of tick-borne encephalitis (V. Tarasov. Tick-borne encephalitis. Medical newspaper No. 34, 2003, www.neuronet.ru/bibliot/b001/mg34_03.html).

Tiloron is not only an effective antiviral agent, but also a drug that increases the body's resistance to infections caused by bacteria, fungi and protozoa. It has an activating effect on macrophages. At the same time, not only the absorptive capacity of phagocytes increases, but also the production of reactive oxygen species by these cells that have a bactericidal effect. Tiloron has a stimulating effect on the phagocytic and bactericidal functions of macrophages, while reducing the intensity of lipid peroxidation.

It activates natural killers, which play a leading role in the antitumor defense of the body. Tiloron has an antitumor effect against virus-induced tumors. In combination with antitumor drugs, it contributes to a more significant inhibition of the growth of neoplasms, reduces the frequency and degree of metastasis, sometimes completely preventing it. In large doses, tilorone directly inhibits tumor growth. Tiloron in combination with cytostatics can reduce their dosage by half without changing the quantitative characteristics of the antitumor effect. It also reduces the severity of side effects of radiation therapy, and when administered to patients before surgery, it provides faster healing of wounds, prevents metastasis and the development of infection.

Tiloron has anti-inflammatory activity, which allows its effective use in the treatment of diseases such as multiple sclerosis, rheumatoid arthritis, silicosis. It inhibits platelet aggregation, while the magnitude of the effect is not inferior to aspirin, and in duration it exceeds it. When applied locally to skin and eyes damaged by herpes, it provides direct inactivation of the herpes virus (T.O. Filippova, N.Ya. Golovenko “TILORON: PROFILE OF BIOLOGICAL ACTIVITY I. PHARMACOLOGICAL PROPERTIES http://magazine.odmu.od.ua/antropo /2006/1/18.pdf).

Tiloron is well compatible with antibiotics and traditional viral diseases (www.amixin.com.ua).

Tilorone is readily soluble in water (about 10% at 20 ° C) and 95% ethanol (about 3.3% at 20 ° C) (Pharmacopoeia article of the enterprise FSP 42-0416-4243-03), which makes it promising for use in injectable preparations.

However, pharmaceutical preparations in the form of injectable dosage forms for subcutaneous, intramuscular and intravenous use containing the active substance Tiloron are not currently known.

The objective of the invention is the creation of an injectable pharmaceutical preparation for subcutaneous, intramuscular and intravenous use based on a low molecular weight interferon inducer.

Technical results that can be obtained using the present invention: expanding the field of application of the known active substance - tiloron, restoring local immunity and biocenosis of the skin and mucous membranes in the treatment of purulent-destructive processes of the skin and mucous membranes, especially with a deep location of the lesion foci, reducing secondary tissue necrosis in the affected areas, relief of inflammatory reactions, providing a local anesthetic effect, accelerating healing.

To solve this problem, the present invention proposes a pharmaceutical injection preparation containing, as an active substance, a low molecular weight interferon inducer and a solvent, which contains tilorone as a low molecular weight interferon inducer, for example, in the following ratio of components (wt.%):

tiloron 0.001-10,000 solvent rest

Moreover, as a solvent, for example, water for injection, or an isotonic solution of sodium chloride, or reamberin, or a blood-replacing liquid, for example, "Hemodez-N", or a physiologically acceptable mixture thereof, are proposed.

An injection drug based on tilorone is proposed, which additionally contains stabilizing components, while the ratio of components in the solution is established, for example, the following (wt.%):

tiloron 0.001-10,000 stabilizing components 0,050-7,000 solvent rest

As stabilizing components are used, for example, citric acid and sodium phosphate disubstituted 12-water, or citric acid and sodium citrate in the following components in a mixture (wt.%):

disodium 12-aqueous sodium phosphate 0.05-3.00 sodium citrate 0.05-3.00 citric acid 0.1-1.0

To ensure local anesthesia, an anesthetic, for example, lencaine, or lidocaine, or trimecaine, or novocaine, was introduced into the composition with a content of 0.25 to 5.00% by weight in the preparation.

During the destruction of living cells (for example, during purulent-destructive processes), substances that stimulate primarily the local immune system (T-lymphocytes) are released from the cells, activating the macrophages located next to the damage, which, in turn, synthesize and release into the surrounding space various stimulators of cell division, contributing to the elimination of disorders of the cellular system (A. N. Decina. Theory of soft cosmetic effects. Modern cosmetology, Novosibirsk, Nauka, 2000, www.golkom.ru/book/48_1.htm).

To restore the immune function of the skin and mucous membrane, a low molecular weight interferon inducer, tilorone, can be used for subcutaneous or intramuscular administration. In the form of an injectable preparation for subcutaneous or intramuscular administration, it can be used for local therapy in dermatology in the treatment of purulent-destructive processes of the skin and soft tissues, such as recurring furunculosis, acne vulgar, burns, long-healing soft tissue wounds, etc., especially with deep subcutaneous location of lesions. In addition, its use in the form of topical preparations in allergology and immunology for the complex treatment of allergic dermatoses, especially associated with fungal and herpetic infections, is promising.

With local exposure, tilorone increases the expression on the cell membranes of antigens of the major histocompatibility complex (HLA) of class 1 and class 2 (HLA-DR), increases the number and activity of NK cells, causes a targeted polarization Th0-> Th1, modulates the inflammatory response, depending from the phase of inflammation, positively affects the state of local immunity, has a direct and indirect effect on viruses, intracellular bacteria, fungi.

To ensure local anesthesia of the lesion, a local anesthetic is introduced into the tissue surrounding the lesion and containing nerve conductors that innervate the area of the purulent-destructive process (conduction method of local anesthesia). Local infiltration anesthesia in the case of purulent-destructive lesions is contraindicated, as the anesthetic infiltration of inflamed tissues is very painful and contributes to the spread of infection (www.destreferat.ru/referat-65155.html).

An injectable preparation for subcutaneous and intramuscular administration containing tilorone and anesthetic is administered subcutaneously or intramuscularly around the inflamed tissues of the lesion to ensure fast and efficient transport of the active substance to the cells responsible for stimulating local immunity and restoring the immune properties of tissues in the area of the lesion, including including with a deep subcutaneous location, as well as providing local anesthesia.

Tiloron, being a stable low molecular weight substance (molecular weight 483.5), dissolved in a hydrophilic solvent, easily penetrates deep into tissues with subcutaneous and intramuscular administration.

Tiloron, which has antioxidant properties, penetrates into the affected tissue from a hydrophilic solution, reducing secondary tissue necrosis around the lesion.

With intravenous administration, tilorone quickly spreads through the bloodstream throughout the body and easily penetrates into organs and tissues, stimulating cells that induce interferon.

The hydrophilic solvent of the proposed injection drug effectively transports the active substance - tilorone into the area of purulent-destructive lesions.

An isotonic solution of sodium chloride in a concentration of 0.9% is commercially available and is used as a detoxification agent for dissolving drugs and others (www.recipe.ru). It can be used as a tilorone solvent in injectable formulations.

Polyvinylpyrrolidone, a synthetic polymer inert to the body and not degraded by enzyme systems, is the basis of detoxifying blood-replacing fluids, for example, Gemodez-N (www.yugrafarm.ru/predel_vkl_formular) or Neogemodez (www.kurgansintez.ru/news/ /), binding toxic substances of various structures and removing them from the body. (Blood-replacing fluids, www.nedug.ru/libraru/doc.aspx?item=38053).

The composition of "Hemodez-N" includes medical povidone 8000 ± 2000 - 6%; sodium chloride - 0.55%; potassium chloride - 0.042%; calcium chloride 6-water (in terms of anhydrous) - 0.05%; magnesium chloride 6-water (in terms of anhydrous) - 0,0005%; sodium bicarbonate - 0.023%, water for injection - the rest. These fluids can be used as a tilorone solvent in injectable formulations.

Succinic acid (or its salts, for example, succinate) is a hypooxidant, normalizes the content of histamine and serotonin in the body, increases microcirculation in organs and tissues (A.I. Fedin “Oxidative stress and the use of antioxidants in neurology. Www.medmoskva.ru/news /Out.aspx? Item = 19107). With an increase in the load on any of the body systems, the maintenance of its work is ensured mainly due to the oxidation of succinic acid. The power of an energy production system using succinic acid is hundreds of times greater than all other energy systems in the body. This provides a wide range of non-specific therapeutic effects of succinic acid and its salts. In addition, succinic acid also has such effects as actoprotective and antiviral (S.V. Obolensky “Reamberin - a new tool for infusion therapy in the practice of critical state medicine”, www.critical.ru/consult/pages/reamberin.htm).

Reamberin is a balanced isotonic detoxifying solution containing meglumine sodium succinate 1.5%, sodium chloride 0.6%, potassium chloride 0.03%, magnesium chloride 0.012%, water for injection up to 100 ml. This liquid can be used as a tilorone solvent in injectable formulations.

Lnecain (marcain, bupivacaine) is one of the most powerful and long-acting modern anesthetics. It is used for conductive methods of anesthesia in the form of a 0.5% solution (www.destreferat.ru/reterat-65155.html).

Lidocaine (xylocaine, xicaine) - is considered the best drug for conduction anesthesia in 1% -2% solutions. It acts much stronger and longer than novocaine, slightly exceeding it in toxicity (wvvw.destreferat.ru/referat-65155.html).

Trimecaine (mesocaine) is used for conduction anesthesia in 1% -1.5% solutions. The anesthetic effect is stronger and longer than that of novocaine, the toxicity is slightly higher (www.destreferat.ru/referat-65155.html).

Novocaine (neocaine, pancaine, procaine) is the least toxic drug with a wide range of therapeutic effects. It is used for various types of local anesthesia in the form of a 0.25% -5% solution (www.destreferat.ru/referat-65155.html).

For the manufacture of an injectable solution, tilorone is dissolved in a predetermined amount in a solvent, for example, in water for injection. After which the solution is filtered through a filter system, cleaning from mechanical impurities. Then the solution is poured into ampoules. The ampoules are sealed, checked for leaks and sterilized in an autoclave for 30 minutes at a temperature of + 100 ° C.

To increase the reliability of sterilization, the tilorone solution after cleaning on filters from mechanical impurities is sterilized on filters with a pore diameter on the final filters of 0.2 μm or less. This pore diameter allows you to clean the solution from all microorganisms, ensuring its sterilization even without heating, or significantly reduce the time of thermal sterilization.

With prolonged heat sterilization, as well as with prolonged exposure to an alkaline solution, glass ampoules are leached. Leaching is the transition from an aluminosilicate matrix of glass to an aqueous solution of metal ions, mainly alkaline and alkaline earth (Na ⁺ , K ⁺ , Ca ²⁺ , Mg ²⁺ , etc.) due to their high mobility. The result of the release of alkali metals is an increase in the pH of the solution. In addition, the silicate matrix of the glass itself also changes during heat treatment, sometimes releasing pure silica in the form of crystals and flakes (spangles).

In the proposed pharmaceutical composition in the form of a hydrophilic aqueous solution as a pH-stabilizing component, a buffer system may be introduced, consisting in particular of sodium phosphate, disubstituted 12-aqueous and citric acid, or sodium citrate and citric acid. The buffer system reduces the pH of the solution within the acceptable pH range from 6.0 to 7.5 and ensures stabilization of the pH of the solution in ampoules in this pH range, which leads to a significant reduction in the leaching of glass and eliminates the appearance of sparkles in the solution during manufacture and storage.

The selected hydrophilic solvents that make up the components of the buffer system and anesthetics are approved for use in the medical industry in the Russian Federation.

The synthetic immunomodulator Tiloron in the proposed pharmaceutical injection composition for subcutaneous and intramuscular administration restores the local immunity of the skin and mucous membranes, which contributes to faster healing of purulent-destructive lesions, especially when they are deep subcutaneous, increases the body's resistance to skin diseases and diseases of the mucous membrane due to suppression viral, bacterial and fungal infections. The antioxidant properties of tilorone contribute to faster healing by reducing tissue necrosis. Anesthetic provides local anesthesia.

With intravenous use, tilorone restores the general immunity of the body.

The implementation of the proposed pharmaceutical injection composition is confirmed by the following examples, but is not limited to them.

Example 1

Obtaining a pharmaceutical injection composition based on tilorone and water for injection is carried out according to the following scheme:

1. Weigh the components (powders) in the required amount.

2. Measure the required volume of injectable water.

3. The components are poured into a solvent - injection water and dissolve them, maintaining the temperature during dissolution of not more than + 30 ° C.

4. The prepared solution is cleaned of mechanical impurities by filtering through a filter system with a final filter having a pore diameter of 0.45 μm.

5. The resulting solution is sterilized by filtering it at room temperature sequentially through a filter with a pore diameter of 0.2 μm, and then through a filter with a pore diameter of 0.1 μm.

6. After sterilizing filtration, the solution is poured into sterile 2 ml ampoules, the ampoules are sealed and checked for leaks.

7. The ampoules are placed in an autoclave and additionally sterilized for 5-10 minutes at a temperature of + 100 ° C.

The composition in one ampoule, volume 2 ml Components amount g % Tiloron (mass, g) 0.002 0.1 Injection water (volume, ml) the rest is up to 2.0 the rest is up to 100

All operations for the preparation of the solution, its filtration and ampulling are carried out under aseptic conditions in accordance with the requirements for the production of injection solutions.

The sterility of the solution of tilorone in ampoules is checked according to the method described in the State Pharmacopoeia (GF) XI, issue 2, p. 187.

The solution of tilorone in ampoules is characterized as transparent according to GF XI, issue 1, p .98. The pH of the tilorone solution is measured potentiometrically according to GF XI, issue 1, p. 113.

According to this technology, 1000 pieces of ampoules with 0.1% aqueous solution of tilorone of reduced composition were made.

In the manufacture and control storage for 12 months, 1000 pieces of defective ampoules were not detected in terms of pH, transparency and sterility.

Example 2

Obtaining a composition based on tilorone, injection water, stabilizing components is implemented according to the scheme specified in Example 1.

Using this technology, 1000 units of ampoules with a 1% solution of tilorone of reduced composition were manufactured.

The composition of the composition of one ampoule, volume 2 ml Components amount g % Tiloron (mass, g) 0.02 1,0 Sodium phosphate disubstituted 12-water (mass, g) 0,024 1,2 Citric acid (mass, g) 0.0053 0.265 Injection water (volume, ml) the rest is up to 2.0 the rest is up to 100

In the manufacture and control storage for 12 months, 1000 pieces of defective ampoules were not detected in terms of pH, transparency and sterility.

Example 3

Obtaining a composition based on tilorone, anesthetic and 0.9% isotonic sodium chloride solution is implemented as described in Example 1.

According to this technology, 1000 units of ampoules with a 0.1% solution of tilorone of reduced composition were manufactured.

The composition of the composition of one ampoule, volume 2 ml Components amount g % Tiloron (mass, g) 0.002 0.1 Lnecain (mass, g) 0.010 0.5 0.9% isotonic sodium chloride solution (volume, ml) the rest is up to 2 the rest is up to 100

In the manufacture and control storage for 12 months, 1000 pieces of defective ampoules were not detected in terms of pH, transparency and sterility.

Example 4. Obtaining a composition based on tilorone, anesthetic and blood substitute fluid "Hemodez-N" is implemented according to the scheme specified in Example 1.

According to this technology, 1000 units of ampoules with a 0.1% solution of tilorone of reduced composition were manufactured.

The composition of the composition of one ampoule, volume 2 ml Components amount g % Tiloron (mass, g) 0.002 0.1 Lidocaine (mass, g) 0.02 1,0 "Hemodez-N" (volume, ml) the rest is up to 2.0 the rest is up to 100

In the manufacture and control storage for 12 months, 1000 pieces of defective ampoules were not detected in terms of pH, transparency and sterility.

Example 5

Obtaining a composition based on tilorone, anesthetic and reamberin is carried out according to the scheme described in Example 1.

According to this technology, 1000 units of ampoules with a 0.1% solution of tilorone of reduced composition were manufactured.

The composition of the composition of one ampoule, volume 2 ml Components amount g % Tiloron (mass, g) 0.002 0.1 Novocaine (mass, g) 0,020 1,0 Reamberin (volume, ml) the rest is up to 2.0 the rest is up to 100

In the manufacture and control storage for 12 months, 1000 pieces of ampoules were not detected in terms of pH, transparency and sterility.

Conducted experiments on animals (rats, mice) with artificially created models of diseases with signs of immune deficiency showed significant efficacy of Tiloronum in the injectable form in the treatment of these diseases.

The therapeutic activity of tilorone in hydrophilic solvents with the presence of an anesthetic has not yet been known and does not follow from the prior art.

The proposed injection drug based on tilorone, hydrophilic solvents and anesthetics significantly expands the field of application of the known active substance - tiloron, provides restoration of local immunity and biocenosis of the skin, as well as mucous membranes in the treatment of purulent-destructive processes of the skin and mucous membranes, especially with deep subcutaneous location of foci lesions, has a high therapeutic activity, reduces secondary tissue necrosis in the affected areas associated with excess free by oxidative oxidation, relieves inflammatory reactions, provides local anesthesia, accelerates healing.

The search for information did not reveal identical and similar technical solutions.

So far, no similar solution has been proposed, although the drug Tiloron has been known since 1970 (T.O. Filippova, N.Ya. Golovenko. “TILORON: PROFILE OF BIOLOGICAL ACTIVITY I. PHARMACOLOGICAL PROPERTIES http://magazine.odmu.od.ua ./antropo/2006/1/18.pdf).

The inventive pharmaceutical preparation can be recommended in the treatment of purulent-destructive lesions of the skin and mucous membranes, especially with deep subcutaneous location of the lesion.

The proposed pharmaceutical injection preparation for subcutaneous, intramuscular and intravenous use on the basis of tilorone can be used for industrial serial production.

Claims (4)

1. Pharmacological injection composition for the treatment of diseases with signs of immune deficiency, characterized in that it contains tilorone and a hydrophilic solvent, in the following ratio, wt.%:
tiloron 0.005-10,000 hydrophilic solvent rest 2. The composition according to claim 1, characterized in that it contains as a hydrophilic solvent a substance selected from the series: water for injection, isotonic sodium chloride solution, reamberin, hemodez-H blood substitute fluid, or a physiologically acceptable mixture thereof. 3. The composition according to claim 1, characterized in that it further comprises, as an anesthetic, a substance selected from the range: lencaine, lidocaine, trimecaine, novocaine. 4. The composition according to claim 1, characterized in that it further comprises, as a stabilizing component, a substance selected from the range: citric acid, sodium phosphate disubstituted 12-aqueous, sodium citrate, or a physiologically acceptable mixture thereof.