RU2353354C1 - Local and external pharmaceutical product based of low molecular interferon inducer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and pharmacology, namely to pharmaceutical composition applied for external and local treatment of pyodestructive processes in skin and mucous membranes and characterised by that it contains Tilorone and at least one end additive chosen from: agent with antibacterial activity to gram-positive and/or gram-negative bacteria, antimicotic, local anaesthetic agent, reparative stimulator, hypooxidant, biogenic elements, a base or their mixture in certain ratio.

EFFECT: invention ensures extended application of the known active agent Tilorone, restored local immunity and biocoenosis of skin and mucous membranes in treatment of pyodestructive processes, anaesthetic effect; additional reparative stimulation; improved microcirculation in lesion focus, reduced inflammatory reactions in skin and mucous membranes, decreased secondary tissue neurosis of the affected areas, improved microcirculation in lesion focus, reduced itching, maintained high therapeutic activity and usability, more rapid and improved healing.

10 cl, 19 ex

Description

The invention relates to the chemical and pharmaceutical industry, as well as medicine and veterinary medicine, namely, pharmaceutical preparations for external and local use in the treatment of purulent-destructive processes of the skin and mucous membranes 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, postoperative suppuration of the ra et al., to accelerate and improve 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 defects in the immune system, on the one hand, and as a result of the changed biological properties of opportunistic microorganisms and their multiple antibiotic resistance, on the other hand. 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 YF, Ogurtsova AN “The place of the outside preparations 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 treatment of purulent-destructive skin processes, antibacterial drugs and their combination with glucocorticosteroids are widely used for topical use, for example, Triderm ointment or cream - a combined steroid containing glucocorticoid (betamethasone), antimycotic (clotrimazole) and antibiotic (gentamicin). Contraindications for the appointment of topical corticosteroids are fungal, purulent, viral skin diseases, perioral dermatitis. With prolonged use of halogenated steroids, skin atrophy, telangiectasia, steroid acne, hypertrichosis, and secondary infection are observed. When used on large areas of the skin, it is possible to develop systemic side effects characteristic of glucocorticosteroids (A.G. Pashinyan “Preparations for the treatment of dermatitis”, www.remedium, ru / drugs / drugs / detail.php & ID = 10143 t).

Drugs containing glucocorticosteroids (ointments, drops) should not be used for viral diseases of the eyes and skin (including drugs with the addition of antibacterial agents), since the formation of common ulcers is possible due to inhibition of regeneration processes (Drug Reference. Bark Hormones adrenal glands and their synthetic analogues. "http // pharm.stirol.net / med_search.php? action = show & namenum = 751).

When using glucocorticosteroids, the T-cell system of immunity can be disrupted, which plays a big role in the development of pyoderma (T. A. Belousova, M. V. Goryachkina. “Bacterial skin infections: the problem of choosing the optimal antibiotic”, www.rmj, ru / articles_3825. htm).

Thus, local treatment with glucocortcosteroids in combination with antibacterial drugs does not always lead to the desired result, since the immune function of the skin is not restored and its microbiocenosis is further disturbed.

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, dendritic cells, natural killer cells, 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 skin or mucous membrane is infiltrated by neutrophils, lymphocytes, eosinophils, free radicals and other toxic metabolic products accumulate in them, which further increase the destruction. In these conditions, access to medications for inflammatory foci is extremely difficult with their oral and injection use.

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 - 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).

The well-known drug trekrezan, which is an adaptogen and immunomodulator, which, when used in the form of tablets in complex therapy, shortens the resuscitation period in the treatment of patients with purulent-necrotic wounds, inhibits the development of herpes, increasing the immune status of the body (M.G. Voronkov, M.M.Rasulov “Trekrezan - the founder of a new class of adaptogens and immunomodulators (review).” Chemical-Pharmaceutical Journal. Volume 41, No. 1, 2007, pp. 3-7).

Trekrezan has interferogenic activity. In the first hours after the administration of trekrezan, alpha-interferon is produced, which is replaced by gamma-interferon a day later (P. D. Shabanov et al. “Trekrezan immunomodulator: profile of general and immunotropic activity”, http: //www.nitek-group. com / en / innovations / trecrezane / profile.htm).

However, trekrezan does not modulate the production of interferon beta, which reduces its immunomodulatory effect, in comparison with other immunomodulators. The antioxidant properties of trekrezan are used in topical cosmetic compositions (Lifkrez cream Trekrezan, http://old.ros-expo.com/wares_full/7486.html).

Currently, topical preparations based on trekrezan that restore the immune properties of the skin and mucous membranes in the treatment of purulent-destructive processes are not known.

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 the synthesis "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.

In the form of tablets 0.15 g (Description of the drug, www.regmed.ru/InstrShow2.asp?InstrLinkNx=a83ba87ba88ba75b) and in the form of a 12.5% (0.125 g / ml) aqueous solution for intramuscular and intravenous administration of cycloferon is used in the treatment of HIV infections, neuroviral infections (tick-borne meningitis, multiple sclerosis, arachnoiditis), viral hepatitis (A, B, C, D), CMV and herpes infections, influenza, SARS, immunodeficiency states (postoperative period, burns, bronchitis, pneumonia etc.), gastric ulcer and 12 duodenal ulcer, cancer, rheumatoid Foot arthritis, osteoarthritis deformans, spondylosis, skin diseases - atopic dermatitis, eczema, dermatosis, papilloma virus (Description of the preparation, www.biomedservis.ru/preparat/pr_cycloferon_liniment.htm).

In the form of a liquid ointment - liniment containing 5% N-methylglucamine salt of acridonoacetic acid, 0.1% catapol antiseptic and 1,2-propylene glycol as a base up to 100% (Description of the drug www.znaharka.ru/ index.php? ProductID = 92430) cycloferon is used locally in the treatment of genital herpes, urethritis, balanoposthitis (nonspecific, candidal, gonorrhea and trichomonas etiology), vaginitis (bacterial and candidal), chlamydia, and skin diseases. The drug is compatible with all drugs, including antibiotics, vitamins, chemotherapy, immunomodulators, interferons (Description of the drug www.regmed.ru/InstrShow2.asp?InstrLinkNx=a72ba78ba75ba74b).

A high antibacterial and antichlamydial effect of the drug due to the activation of the immune system, as well as anti-inflammatory and antiproliferative effect of the drug have been established. The immunomodulatory effect of cycloferon in the form of liniment is expressed in the correction of local immunity in immunodeficiency states of various origins and autoimmune diseases (Description of the drug www.znaharka.ru/index.php?productID=92430).

The main producing cells of interferon after administration of the drug in the form of a liniment are the lymphoid elements of the mucous membrane: macrophages, T and B lymphocytes, as well as epithelial cells (http://www.biomedservice.ru/preparat/pr_cycloferon_liniment.htm). The main area of application of 5% of cycloferon liniment is the treatment of herpetic infections, as well as urogenital sexually transmitted infections.

It is known that an immune response to the action of cycloferon is observed in no more than 40% of patients (www.mtu-net.ru/doctor99/5nklassifik1polioxidoniy2905.htm).

The drug is available for local and external use in the form of liniment. This form is convenient for intraurethral administration, but inconvenient for external use, as it is not fixed on the surface of the affected area or wound and dries quickly.

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 = 41 ba48ba44ba43b and Lavomax, Instructions for the preparation, http://www.regmed.ru/InstrShow2. Asp? InstrLinkNx = a41 ba48ba44ba43b).

It is used in the treatment of viral hepatitis A, B, C; herpes and CMV infection; complex therapy: infectious-allergic and viral encephalomyelitis (multiple sclerosis, leukoencephalitis, uveoencephalitis), chlamydial infections of the urogenital and respiratory tract; prevention of influenza and other acute respiratory viral infections.

Tiloron is a low molecular weight synthetic inducer of interferon, stimulating 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 digestive tract. Moreover, 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 used orally 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 known to be used orally 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 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, as an immunomodulator, 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. Golovenka. “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).

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

However, pharmacological preparations in the form of ready-made dosage forms for local and external use containing the active substance Tiloron are not known.

The objective of the invention is the creation of pharmacological preparations for local and external use based on the active substance - a low molecular weight inducer of interferon.

Technical results that can be obtained by using the present invention: expanding the field of application of the known active substance - tilorone, restoring local immunity and biocenosis of the skin and mucous membranes in the treatment of purulent-destructive processes of the skin, obtaining an anesthetic effect; additional stimulation of reparative processes; improving microcirculation, stopping inflammatory reactions in the skin and mucous membranes, reducing secondary tissue necrosis in the affected areas, improving microcirculation in the lesion, reducing itching, providing high therapeutic activity and ease of use, accelerating and improving healing.

To solve the problem, the present invention proposes a pharmaceutical preparation for local and external use containing the active substance — a low molecular weight interferon inducer, a target additive and a base that contains tilorone as a low molecular weight interferon inductor, for example, in the following ratio of components (wt.%):

tiloron  0.001000-10.0 target additive  0.000001-30.5 the basis  rest

In this case, the target additive is a substance with antibacterial activity against gram-positive and / or gram-negative bacteria, or an antimycotic, or a local anesthetic, or a stimulant of reparative processes, or a hypoxidant, or biogenic elements in the form of physiologically acceptable compounds, or their physiologically acceptable mixture, for example , with the following amount in the composition of the drug (wt.%):

substance with antibacterial activity regarding gram-positive and / or gram negative bacteria  0.01-13.00 antimycotic  0.5-3.0 local anesthetic  0.5-4.0 reparative stimulant  0.5-4.0 hypooxidant  0.001-1,000 nutrients  0.000001-5.5

As a substance having antibacterial activity against gram-positive and / or gram-negative bacteria, there can be, for example, an antibiotic, or a complex of bacteriolytic and proteolytic enzymes, for example, lysoamidase, or Trilon B, or ethyldiaminetetraacetic acid, or a mixture thereof, for example, in the following their amount in the composition of the drug (wt.%):

Antibiotic  0.01-5.00 a complex of bacteriolytic and proteolytic enzymes  0.10-5.00 Trilon B  0.01-2.00 ethyldiaminetetraacetic acid  0.01-1.00

In this case, the antibiotic may be, for example, gentamicin sulfate, or the fusidic acid sodium salt, or a mixture thereof.

As an antimycotic, there may be, for example, clotrimazole, or cyclopiroxolamine.

In the preparation of the invention, the local anesthetic may be, for example, quinoxicaine, trimecaine, pyromecaine, lidocaine, anestezin, or a mixture thereof.

In the proposed preparation, a substance that is a stimulant of reparative processes is, for example, methyluracil, acetamin, etaden, calcium pantothenate, solcoseryl, catapol, or a mixture thereof.

In the proposed preparation, for example, succinic acid can be used as an antioxidant.

The composition of the proposed drug may include the following nutrients in the form of their physiologically acceptable compounds, for example, zinc, or manganese, or their physiologically acceptable mixture at the following content in the drug (wt.%):

zinc  0.00002-5.00 manganese  0.000001-0.50

In accordance with the invention, the dosage forms of the pharmaceutical preparation for topical and external use on the basis of tilorone are liquid dosage forms, for example, suspensions and emulsions in the form of liniments, ointment-like soft dosage forms, for example, ointments, gels, creams, as well as formulated soft dosage forms - suppositories and gelatin capsules for rectal or vaginal administration.

An emulsion of perfluororganic compounds or its mixture with hyperosmolar hydrophilic substances in the following ratio of components in the mixture (wt.%) Is proposed as a basis in a preparation for local and external use containing tilorone.

organofluorine emulsion  5.0-90.0 hydrophilic substances  rest

It is known that in the intact stratum corneum of the epidermis there are no channels through which particles with sizes above 10 nm could penetrate into the depth of the skin. Moreover, the larger the size of the substance’s molecule, the lower its permeability through the transepidermal barrier. It was found that substances with a molecular weight of 100 kilodaltons do not overcome the transepidermal barrier, that is, this value is the limit of skin permeability. Through microchannels that determine the permeability of the skin characterize the most likely intercellular pathway of the transport of substances through the upper scaly keratin layer of the epidermis.

The most important role in the implementation of barrier-protective functions in the permeability of the skin is played by the state of water molecules present in the microcapillary holes of the horny and shiny skin layers. The water inside the microchannels is largely in a structured state, which significantly slows down the processes of Brownian motion, which are responsible for equalizing the concentration gradient, i.e. permeability. The ordered structural organization of water in the microcapillary holes of the stratum corneum prevents the intensive evaporation of water from the skin surface, creating an additional barrier to the dehydration process. However, water, oxygen, nitrogen, and other low molecular weight substances sufficiently easily diffuse through the skin. In this case, substances capable of reacting (binding) with fragments of the epidermis, including cellular systems, first reach saturation in the epidermis, and then begin to interact with deeper layers of the skin.

The intercellular substance of the epidermis and dermis is a gel formed, for example, from hyaluronic acid or from a substance similar to it. Such gel-like structures with a reticular structure are convenient for binding various low- and high-molecular substances (salts, sugars, amino acids, vitamins, peptides, proteins, epidermal cell metabolism products, etc.). Living cells of the epidermis with greater or lesser efficiency retain some of the substances that pass through the horny and shiny layers.

With the regular use of the same type of medicinal and cosmetic products for external use, the fragments of the skin treated with these products are in a state of constant saturation, in which their concentration in the skin remains almost unchanged. Moreover, many low molecular weight components of the drug used can quite easily overcome the transepidermal barrier. 60% of plasma and 45% of plasma proteins daily penetrate from microcapillaries of the circulatory system into tissues, including the epidermis. Returning to the circulatory and lymphatic systems, they carry with them metabolites associated with proteins (cell waste products - toxins) and catabolites (biologically active substances - peptides, proteins, etc., synthesized inside the cell). Substances that have overcome the transepidermal barrier also appear in the blood and, in accordance with this, affect all body tissues.

During the destruction of living skin 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 near the damage (Langerhans cells), which, in turn, synthesize and thrown into the surrounding space a variety of stimulators of cell division, contributing to the elimination of disorders of the cellular system. Langerhans cells are located in the basal layer of the epidermis. They have from 2 to 5 processes, penetrating to the granular layer and invading the basement membrane. The role of these cells, in the first place, is to regulate the rate of division of the cells of the basal layer in various types of disturbances in its structure (monograph by A. N. Decina, “Theory of Soft Cosmetic Effects. Modern Cosmetology”, Novosibirsk, Nauka, 2000, www.golkom .ru / book / 48_1.htm).

Thus, the main requirement for drugs for local and external use with tilorone is the effective transport of the active substance to the cells responsible for stimulating local immunity and restoring the immune properties of the skin and mucous membranes.

In local therapy of purulent-destructive skin lesions, it is important to transport active substances to the lesion through the transepidermal barrier in the case of a subcutaneous location of the lesion or in the depth of the wound in case of its superficial location. In addition, an important factor in the successful treatment of purulent-destructive skin lesions is the effective transport of toxic metabolic products from the lesion to the skin surface. Most fully meet these requirements hydrophilic bases with hyperosmolar properties.

Osmolar hydrophilic solvents, for example, aqueous solutions of salts, alcohols and their aqueous solutions (for example, ethyl or isopropyl), glycerin, low molecular weight polyethylene oxides (for example PEO-400), propylene glycols (for example, 1,2-propylene glycol), etc., easily penetrate through the transepidermal barrier or deep into the wound, transporting the active substances dissolved in them to the lesion and displacing toxic metabolic products from the lesion zone. At the same time, due to their osmolar properties, they bind water located in the cellular systems of the spike and granular layers, which leads to a decrease in the size of cell systems and, consequently, to an increase in the intercellular space and cross section of microchannels, i.e., an increase in the permeability of the epidermis. In addition, they thin the gel of hyaluronic acid filling the intercellular space, which is an additional factor in increasing the permeability of the epidermis.

If hyperosmotic conditions are created by adding salt systems, the permeability of the epidermis will additionally increase due to a change in the structure of the microcapillary channels of the horn and shiny layers, since when the channel cavities are saturated with positively charged metal ions (Na ⁺ type), the channel structures are transformed into a structure (according to the " flip-flop ") with a tendency to expand the diameter of the channel due to the electrostatic repulsion of positive charges localized on metal atoms (A. N. Decina." Theory of FIR beauty effects. Modern cosmetology ", Novosibirsk," Nauka ", 2000, www.golkom.ru/book/48_1.htm).

To restore the immune function of the skin and mucous membrane in the present invention, a low molecular weight interferon inducer, tilorone, is used for local and external use. In the form of preparations for local and external use, 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 vulgaris, burns, long-term healing wounds of soft tissues, etc. In addition, it is promising its use in the form of preparations for local and external use in allergology and immunology in the complex treatment of allergic dermatoses, especially associated with fungal and herpes infections, as well as uroge therapy italnyh infections, sexually transmitted diseases.

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 on phases of inflammation, positively affects the state of local immunity, has a direct and indirect effect on viruses, intracellular bacteria, fungi.

Tiloron, being a low molecular weight substance (molecular weight 483.5), dissolved in a liquid hydrophilic and hyperosmolar base, with local and external use, it easily penetrates deep into the cells of the skin and mucous membrane responsible for local immunity in the area of the drug.

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

Using a liquid low molecular weight hydrophilic and hyperosmolar base and tilorone, liniments, emulsions and suspensions are produced having high penetrating power.

Adding hydrophilic solvents to hydrophilic thickeners with sorption properties, such as high molecular weight polyethylene oxides (for example, PEO-1500), proxanols (for example, procasanol-268), medical polyvinylpyrrolidones (for example, with a molecular weight of 12600 ± 2700 or 8000 ± 2000) or other substances with sorption properties (for example, calcium or magnesium alginate), enhances the transport of toxic metabolic products from the site of subcutaneous lesions or the depth of the wound to the surface of the skin.

For example, PEO-1500 molecules stably maintain primary localization due to a sufficiently high molecular weight: they remain in the microchannels of the stratum corneum of the epidermis or in the wound cavity and actively bind inflammatory exudate, transporting it to the surface of the skin with which the liquid evaporates. The released PEO-1500 molecules reattach water to themselves, and the process repeats itself (“Theory and practice of local treatment of purulent wounds.” / Ed. By prof. B.M.Dotsenko, Kiev, “Health”, 1995, p.234 -235).

On a soft hydrophilic and hyperosmolar basis, consisting of a low molecular weight hydrophilic solvent with hyperosmolar properties, a hydrophilic thickener-sorbent and tilorone, soft forms for topical and external use are made: ointments, creams, gels, suppositories with high penetrating and sorption ability.

Gelatin capsules for rectal and vaginal administration are also filled with liquid and soft hydrophilic compositions on a hyperosmolar basis.

For a complex effect on the foci of purulent-destructive lesions, a substance having antibacterial activity against gram-positive and / or gram-negative bacteria is introduced into the proposed preparation.

Such a substance is, for example, an antibiotic gentamicin sulfate, fusidic acid sodium salt, or a mixture thereof.

Gentamicin sulfate is a porous powder, readily soluble in water, but practically insoluble in alcohol. It belongs to the group of antibiotic aminoglycosides. It has a bacteriostatic effect against many gram-positive and gram-negative microorganisms, including Proteus, Escherichia coli, Salmonella, and others, and acts on penicillin-resistant staphylococci strains.

Gentamicin sulfate for topical use is used as a 1% paraffin-vaseline-based ointment for the treatment of pyoderma, paronchia, sycosis, infected seborrheic dermatitis, folliculitis, furunculosis, acne vulgaris, secondary bacterial infection in fungal and viral infections of the skin (www.nizhpharm.ru/user /products/p1127.html). Such a base, being hydrophobic, does not ensure the penetration of the antibiotic through the transepidermal barrier to the lesion.

Fusidic acid, for example, in the form of a sodium salt, is a crystalline powder soluble in water and alcohol. Affects staphylococci, meningococci, gonococci. In relation to pneumococci and streptococci is significantly less active. Staphylococci resistant to penicillins, streptomycin, chloramphenicol, erythromycin and other antibiotics are sensitive to fusidic acid. The drug is not active against Escherichia coli, Salmonella, Proteus and other gram-negative bacteria, as well as fungi and protozoa.

When fusidic acid is combined with other antibiotics, a significant increase in its effect on microorganisms sensitive to it is observed. It acts on the microbial cell bacteriostatically. The mechanism of its action is associated with the rapid suppression of protein synthesis. The advantage of fusidic acid in the treatment of chronic torpid infections of skin and soft tissue infections, as well as secondarily infected dermatoses, is its wide pharmaceutical profile, low resistance and lack of cross-resistance with other antibiotics, as well as high penetrating ability.

Fusidic acid is able to affect the local immune responses of the skin, inhibiting the release of interleukins, a tumor necrosis factor. It is also known that fusidic acid in clinical concentrations is an inhibitor of chemotakis neutrophils and inhibits the function of T-lymphocytes. Fusidic acid sodium salt has high permeability through intact skin (Kutasevich Y. F., Ogurtsova AN “The place of external preparations 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 /).

For local and external use, fusidic acid is used in the form of gels. For example, in the form of a 2% Fusidin gel containing fusidic acid 2 g, zinc oxide 3 g, glycerol 20 g, sodium carboxymethyl cellulose 3.5 g, nipagin 0.08 g, distilled water up to 100 g. This gel is prescribed in case of purulent-inflammatory diseases caused by microorganisms sensitive to fusidic acid (superficial folliculitis, furunculosis, pyoderma, impetigo, hydradenitis, superficial and limited burns, deep wounds, abrasions, etc.), or 2% Prefusin gel containing fusidium acid 2 prednisolone - 0.5 g, zinc oxide - 3 g, etc. substances, water distilled up to 100 g. This gel is used externally for purulent-inflammatory skin diseases and for the complex therapy of dermatoses (eczema, neurodermatitis, etc.) (www.prodenas.ru/go.php?name=bme&mtype=b&type=DRUG&sid = 1366 & file = pv).

Fusidic acid in the form of sodium salt is also used in ointments, for example, in Fuzimed ointment, containing 2% fusidic acid sodium salt, 1% methyluracil, as well as excipients: polyvinylpyrrolidone (PVP) low molecular weight medical 12600 ± 2700, anhydrous lanolin, medical vaseline, distilled water (www.biosintez.com/preparat.asp?id=183).

Another substance that affects the focus of purulent-destructive lesions and has antibacterial activity against gram-positive bacteria is a complex of bacteriological and proteolytic enzymes.

Bacteriolytic enzyme complexes are known that lyse gram-positive microorganisms resistant to antibiotics (patents RU 1549227, C12N 9/00, 1995.12.20; RU 2193063, C12N 9/00, 2002.11.20). The complex of bacteriolytic enzymes (patent RU 1549227) used in medicine under the name lysoamidase, and veterinary medicine - lysomast, consists of three bacteriolytic enzymes immobilized on the polysaccharide, which increases their stability. The polysaccharide provides long-term (for several years) preservation of the high activity of the enzymes included in it, as well as the immunostimulating properties of the drug lysoamidase.

Bacteriolytic enzymes included in the active complex of the drug destroy cells of a wide range of gram-positive pathogenic microorganisms, such as staphylococci and streptococci, including those with multiple antibiotic resistance, radio-resistant micrococci, meningococci, gonococci, gram-positive bacilli. Due to the presence of proteases and enzymes in the complex, which also have proteolytic activity, the drug cleans wounds from necrotic masses well. Fragments of destroyed cells have an immunostimulating effect. Clinical studies of the drug showed that lysoamidase in the treatment of purulent wounds of soft tissues accelerates the course of the wound process compared to other traditional and non-traditional means. The microflora content decreases faster, the cytogram normalizes faster, necrotic mass rejection is faster, granulation and even tissue epithelization are faster. The terms of treatment of patients with purulent wounds of soft tissues were reduced in many cases by 2 times.

Lizoamidase stimulates reparative processes, exerting, in addition to necrolytic and bacteriolytic effects, an effect on the course of the 2nd phase of inflammation, not only due to the reduction of the 1st phase, which is typical for all enzyme preparations used for treatment in such cases, but also for account of the directly stimulating effect on the cells of granulation tissue, acting directly on proliferate cells. Clinical studies have also shown that with topical treatment of deep burns with a 1% solution of lysoamidase, it helps cleanse wounds from necrotic tissue and purulent discharge, in addition, it is effective in treating oily seborrhea and mild acne.

On the basis of this complex, a pharmaceutical preparation was developed, produced in the form of lyophilized powder, packaged in 10 ml vials of 50 PE, 100 PE with hermetically sealed rubber stoppers. At the same time, the delivery package includes a base - a solvent in ampoules of 5 ml per 1 ampoule per 50 PE (pharmacopoeial articles FS 42-3329-96 and FS 42-3332-96). The drug is used in liquid form in a phosphate buffer solution with a concentration of 5 PE (50 LE) in 1 ml; 10 PE (100 LE) in 1 ml; 25 PE (250 LE) in 1 ml. The therapeutic range of lysoamidase concentrations in solution is from 0.5 to 5%.

As a substance that violates the structure of the membranes of gram-negative microorganisms, the proposed solution also used ethylenediaminetetraacetic acid (EDTA), its disodium salt (Trilon B), or a mixture thereof.

EDTA reduces the resistance of bacteria to antibiotics and other antibacterial substances, especially those for which calcium and magnesium ions are antagonists of their antimicrobial effects, for example, polymyxins and aminoglycosides. Therefore, EDTA can be used together with aminoglycosides in the proposed preparation, for example, gentamicin sulfate, to reduce the resistance of microorganisms to them. With prolonged contact of the EDTA solution with various types of microorganisms in the cells of the latter, the destruction of nucleic acids occurs, which leads to their lysis. In addition to affecting the cell membrane and bacterial metabolism, EDTA induces the loss of plasmids in staphylococcus transductant strains, and also inhibits the genetic transfer of R-plasmids in staphylococci, which inhibits transduction of resistance, for example, to erythromycin 200 times.

Trilon B has a pronounced damaging effect on the microbial cell, since it is a chelating substance that binds divalent metal ions, which causes the membrane to lose the lipopolysaccharide complex. As a result of this, the cell wall becomes fragile, its permeability to various substances, including antimicrobial action, increases.

Trilon B exhibits a bacteriostatic effect in relation to strains of gram-negative and gram-positive pyogenic bacteria: staphylococcus and bacillus of blue-green pus - at a concentration of 0.075%; Proteus and E. coli - 0.15%.

For the treatment of purulent-destructive skin lesions with polyvalent microflora, Trilon B should be used with targeted antimicrobial agents. In these cases, Trilon B, increasing the permeability of the microbial cell wall, increases the sensitivity of microorganisms to antibacterial drugs, for example, antibiotics. Trilon B has a preservative effect for drugs (“Theory and practice of local treatment of purulent wounds” / Ed. By Prof. B. M. Dotsenko, Kiev, “Health”, 1995, pp. 144-144).

Since the mechanisms of action of antibiotics, EDTA and Trilon B on gram-negative and gram-positive microorganisms are different, to enhance the lysis of gram-negative and gram-positive microorganisms, it is advisable to use these substances in a single drug, for example, in the form of complexes: gentamicin sulfate (0.5-1.0 %) and EDTA (0.01% -0.20%); EDTA (0.01-0.20%) and Trilon B (0.05-2.00%); gentamicin sulfate (0.5-1.0%), EDTA (0.01-0.20%) and Trilon B (0.05-2.00%).

For a complex effect with fungal skin lesions, an antimycotic, for example, clotrimazole, or cyclopiroxolamine is introduced into the proposed preparation.

Clotrimazole is an antifungal drug for topical and topical use, an imidazole derivative. The mechanism of action is to inhibit the synthesis of ergosterol, which is necessary for building the cell membrane of fungi, which leads to a violation of its permeability and subsequent cell lysis. The drug also causes an increase in the permeability of the phospholipid membrane of liposomes, vacuolization of the cytoplasm, and a decrease in the number of ribosomes. In addition, clotrimazole inhibits the activity of peroxidases, which facilitates the accumulation of hydrogen peroxide in the fungal cell, which takes part in its destruction. It has a wide spectrum of action: effective against dermatophytes, yeast fungi, has an antibacterial effect on staphylococci and streptococci. For external use, the concentration of the drug in the epidermis is higher than in the dermis and subcutaneous tissue.

Clotrimazole after application to the skin is absorbed in an amount not exceeding 1%, but penetrates the stratum corneum of the epidermis and accumulates there. To a small extent absorbed from the mucous membranes (3%). The absorbed drug is metabolized in the liver and excreted by the kidneys; The half-life is 3-5 hours (//medi.ru/doc/g2713.htm). The drug is used in the form of 1% ointment, 1% cream, 2% gel and 1% solution for external use.

Cyclopiroxolamine is a broad-spectrum antimycotic, highly active against dermatomycetes, as well as yeast, gram-positive and gram-negative bacteria, mycoplasmas and trichomonads. The fungicidal effect of the drug is associated with the suppression of transmembrane transport of amino acids, K + and phosphates in growing fungal cells. This drug has almost no toxic effect on the body, is well released from the base, selectively accumulates in the epidermis and its derivatives (www.medicreferat.com.ru/pageid-1053-4.html). The drug is available in the form of a 1% solution for external use, 1% cream (www.yarapteka.ru/modules.php?name=spr&inf=283).

Disruption of microcirculation is one of the main factors in the pathogenesis of the inflammatory process. It includes not only blood flow through arterioles, capillaries and venules, but also transcapillary exchange, which provides tissue homeostasis necessary for life. Microcirculatory disorders are divided into intravascular changes, disorders of the vessels themselves and extravascular changes. The therapeutic range of drugs used to improve microcirculation in wound tissues can be largely realized due to their antihistamine, anti-inflammatory and dehydrating effects.

The use of trilon B in the proposed drug provides improved microcirculation in the tissues of the wound, since trilon B reduces the activity of histamine.

In addition, since Trilon B is a water-soluble antioxidant, its use in the proposed drug also reduces secondary tissue necrosis around the wound or lesion ("Theory and practice of local treatment of purulent wounds" / Ed. By prof. B.M.Dotsenko, Kiev , "Health", 1995, pp. 179-185).

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).

One of the main tasks of local treatment of purulent-destructive lesions of the skin and mucous membrane is the problem of suppression of pain.

To solve this problem, the proposed preparation uses a local anesthetic substance as the target additive, which can be used quinoxicaine (a quinoline derivative), which has bacterial and antioxidant activity, lidocaine, trimecaine, which retains its activity in an acidic environment, which is characterized by a purulent wound, pyromecaine , anestezin, dibucaine.

Lidocaine, trimecaine and pyromecaine are the most promising in the composition of the proposed drug on a hydrophilic basis.

For the proposed fat-based preparation, for example, anestezin (benzocaine) and dibucaine should be used.

The proposed preparation based on tilorone contains a wound healing substance (methyluracil, acetamine, etaden, calcium pantothenate, solcoseryl, catapol or a mixture thereof) to provide additional stimulation of repair processes in the wound.

Methyluracil, being a pyrimidine derivative, has anabolic and anti-catabolic activity. The substance has no local irritant effect; accelerates the processes of cell regeneration, reducing the healing time of wounds; stimulates cellular and humoral defense factors; has an anti-inflammatory effect; stimulates erythro- and leukopoiesis.

Acemine accelerates tissue regeneration and epithelization processes. It is used to treat long-term non-healing wounds and burns.

Etaden stimulates reparative processes in the epithelial and hematopoietic tissues, activating the metabolism of nucleic acids. It is indicated for the treatment of thermal and radiation injuries of the skin, rectal mucosa, nonhealing granulating wounds, etc.

Solcoseryl is a cattle blood extract freed from proteins and lacking antigenic activity. The substance accelerates the growth of granulations and epithelization of wounds, improves metabolic processes in tissues ("Theory and practice of local treatment of purulent wounds." / Ed. By Prof. B. M. Dotsenko, Kiev, "Health", 1995, p. 179- 187, 191-196).

Catapol stimulates tissue regeneration. In addition, it has anti-inflammatory, anti-burn and antiseptic effects (http://www.recipe.ru/docs/ls/index.php?filter=bysearch&filter_param=Katapol&action=descr-drug-table&drugid=5777).

Pantothenic acid in the form of calcium pantothenate (vitamin B ₅ ) is a promising wound healing agent. It is used to treat burns and sluggishly healing wounds. Pantothenic acid, as a component of coenzyme A, plays a key role in the metabolism of carbohydrates, proteins and fats, and therefore is important for maintaining and restoring all tissue cells. She is involved in reactions that provide energy to cells, and also takes part in the synthesis of vital compounds such as sterols (e.g. cholesterol), hormones (e.g. growth hormones, stress and sex hormones), neurotransmitters (e.g. acetylcholine), phospholipids (components of cell membranes), porphyrin (a component of hemoglobin), antibodies, and also takes part in the metabolism of drugs (“Essentials about Vitamins”, DSV Nutritional Products, www.dsm.com/ru_RU/html/dnpru/hnh_maininfovit_index_basics_panto.htm).

Zinc is a component of more than 200 enzymes (www.osteoform.ru/products/calc.htm). It provides carbon dioxide transfer, stability of biological membranes, and promotes wound healing (http://vitamini.solvay-pharma.ru/elements/article.aspx?id=1816). Zinc takes part in the processes of cell division and differentiation, the formation of T-cell immunity, the functioning of many enzymes, the pancreas insulin, the antioxidant enzyme superoxide dismutase, the sex hormone dihydrocorticosterone, and plays an important role in the regeneration of skin, hair, nails, and secretion of the sebaceous glands. It helps to absorb vitamin E and maintain a normal concentration of this vitamin in the blood. Zinc strengthens the body's immune system, promotes wound healing, as it plays an important role in protein synthesis (www.microelements.ru/Zn). An insufficient concentration of zinc in the body leads to impaired function of the immune system. With zinc deficiency, toxic metals accumulate, wounds heal poorly, and skin diseases develop. Zinc supplements stimulate the production of white blood cells - one of the antitumor components of the immune system, and support the overall activity of T-lymphocytes and natural antitumor cells (natural killer cells), (//mirzdorovia.com.ua/spravka2.php).

Manganese is an essential element for protecting body cells. It is required for wound healing. The absorption of manganese is promoted by zinc and vitamin C (//mirzdorovia,com.ua/spravka2.php). Manganese prevents free radical oxidation, ensures the stability of the structure of cell membranes; provides the development of connective tissue; participates in the regulation of the exchange of vitamins C, E, group B. The skin manifestations of manganese deficiency are violations of skin pigmentation, the appearance of a small scaly rash, vitiligo; growth retardation of nails and hair. Its deficiency also leads to an immune disorder, allergic reactions (www.microelements.ru/Mn).

As a preservative in the proposed pharmaceutical preparation, for example, nipagin with antimicrobial activity is used. In addition, Trilon B and the hyperosmolar base also have a preservative effect.

From the microbiological point of view, due to the presence of external polysaccharide membranes and hydrophilic capsules in gram-negative and gram-positive bacteria, which impede the penetration of hydrophobic antibacterial substances into microbial cells, hydrophilic bases are preferable, since they serve as drug conductors into the microbial cell (“Theory and practice of local treatment purulent wounds ”/ Under the editorship of Professor B. M. Dotsenko, Kiev,“ Health ”, 1995, p. 229).

Hydrophilic bases that can be used with tilorone in the proposed drug are divided into two groups:

- water-soluble bases, which usually contain purified water, hydrophilic non-aqueous solvents: polyethylene oxide, for example, PEO-400, 1,2-propylene glycol, glycerin, ethyl cellosolve, dimexide, and water-soluble polymers: polyethylene oxide, for example PEO-1500, proxanol for example, proxanol-268, polyvinylpyrrolidone, for example, 8000 ± 200 or 12600 ± 2700;

- water-based base, which in addition to water-soluble polymers and hydrophilic non-aqueous solvents contain lipophilic substances:

higher fatty alcohols, petroleum jelly, liquid paraffin, lanolin, waxes (these bases are usually oil / water emulsions and require the presence of an oil / water emulsifier).

Basics with hyperosmolar properties play an important role in local therapy of purulent-destructive skin lesions. They provide an outflow of purulent exudate from a wound or lesion, have an anti-inflammatory effect due to the absorption of fluid and reduce tissue edema, and also protect tissues from overhydration. Often they contribute to enhancing the action of antibacterial substances.

In addition, the use of a hyperosmolar base also improves microcirculation in the tissues of the wound due to its dehydrating effect. In this case, the applied base, consisting of hyperosmolar substances, has an indirect anti-inflammatory effect due to the absorption of fluid and reduction of edema of the wound tissue or in the subcutaneous lesion.

Substances with high hyperosmolar properties include polyethylene oxides - water-soluble products of the polymerization of ethylene oxide, which are physiologically indifferent compounds. This class of substances includes hydrophilic non-aqueous solvents - PEO-400, 1,2-propylene glycol, glycerin, ethyl cellosolve, dimexide - and polymers (polyethylene oxide, for example PEO-1500, proxanol-268, polyvinylpyrrolidone). They are easily applied to the wound surface and evenly distributed on it, improving the contact of the ointment with the tissues and contents of the wound, mix well with wound exudate and maintain their uniformity, low toxicity and do not irritate tissues, do not violate their physiological functions.

The ability of polyethylene oxides to provide an antimicrobial drug with an interstitial effect fundamentally distinguishes this ointment base from fatty bases or solutions of antibiotics (antiseptics), the antimicrobial effect of which is limited only by the wound surface, although it is the deep microflora that determines the severity and direction of the purulent process.

The main property of PEO is that they have a pronounced dehydrogenating (moisture-absorbing) effect on the tissue. Due to the high ability to hydrate, these polymers actively absorb wound exudate, and with it microbial toxins, pro-inflammatory cytokines - tissue breakdown products, as well as various biologically active substances - lysosomal enzymes and other inflammatory mediators, thereby interrupting its progressive course. Of fundamental importance is the fact that in a purulent wound or subcutaneous lesion, the dehydrating effect of PEO extends not only to tissues, but also to microbial cells contained in the wound or lesion.

Dehydration of microbial cells leads to a significant decrease in their biological activity and, in particular, resistance to the action of certain drugs. Therefore, in the presence of PEO, the antimicrobial effect of antibiotics is increased tenfold. It is also important that the dissolution of antibiotics, sulfanilamides and other substances in PEO leads to an increase in their dispersion with an increase in therapeutic activity, which is also facilitated by a faster release of antimicrobial substances from the base.

PEO is an active conductor of drugs across the skin barrier. The important thing is that this penetrating without damage to the cells ability of PEO is enhanced in conditions of inflammation.

Hydrophilic bases on polyethylene oxides are able to dissolve in the secrets of the mucous membranes, completely release medicinal substances, not irritate the mucous membranes, have a long shelf life, high physiological indifference, which contributes to their use in liquid, ointment-like and formable soft dosage forms.

An important biomedical requirement for ointment soft dosage forms is the ability to wet the wound surface and spread over it, due to the surface-active properties of solvents, polymers, surfactants and the base as a whole. The most pronounced surface activity are alcohols and ethyl cellosolve, which are unsuitable for inclusion in the composition of the base in high concentrations.

Of the glycols, it is preferable to use 1,2-propylene glycol and PEO-400 compared to glycerol having weak surface-active properties.

When mixing the PEO-400 solvent with PEO-1500 polymer, the latter acts as a thickener, which, depending on the amount in the total mass, provides the required consistency of the created dosage form. In addition, PEO-1500 is an osmotically active substance that absorbs purulent exudate due to the binding of water molecules to hydroxyl and ether groups.

Proxanol-268 is a block copolymer of propylene and ethylene oxides. Proxanol-268 as an osmotically active substance provides a more uniform absorption pattern and has a longer period of osmotic action. The total mass of absorbed water with proxanol-268 solutions in 24 hours significantly exceeds that in the case of PEO-1500. This is due to the higher mass of proxanol-268 (8.7 times more than PEO-1500).

The kinetics of water absorption by solvents and polymers depends on their molecular weight, concentration and molecular structure. For example, PEO-400 absorbs more water than 1,2-polyethylene glycol, and has a longer period of osmotic action. Sorption activity of 1,2-propylene glycol is maintained for 4-6 hours. This is due to both its lower molecular weight in comparison with PEO-400 and the lower hydrophilic-lipophilic balance (HLB), which for propylene glycol is 9.38. The value of HLB is greater, the greater the hydrophilicity of a substance. Therefore, the higher the HLB and molecular weight, the stronger and longer the osmotic effect of a substance at a given concentration will manifest itself. 1,2-propylene glycol, PEO-400, PEO-1500, proxanol-268 can be preservatives in the developed dosage forms ("Theory and practice of local treatment of purulent wounds" / Edited by prof. B.M. Dotsenko, Kiev, "Health ", 1995, p. 174; 227-235).

On the basis of PEO-1500 polyethylene oxide, the Geko hydrogel is commercially available, which represents a colorless gel-like mass formed by the action of ionizing radiation on a solution of polyethylene oxide in water. The gel is biologically inert, non-toxic. It has a widely varying structural viscosity, liquefies with the addition of alcohol, glycerol, with vigorous stirring, the pH of a 20% aqueous suspension is 4.0-8.0. Chemical composition: PEO-1500 - 3.5%; distilled water - 96%; preservative (sodium benzoate) - 0.5%. It is used as a basis in the production of ointments, creams, gels, liniment in the pharmaceutical and cosmetic industries (www.medpeterburg. Ru / news / Out.aspx? Tem = 21284). The gel has a stabilizing effect on enzymes (patent RU No. 2089177, A61K 7/48, 1997.09.10).

Dimexide - a 30% solution of dimethyl sulfoxide (DMSO) is used as an anti-inflammatory drug for external use, inactivating hydroxyl radicals and improving the course of metabolic processes in the focus of inflammation. It also has a local anesthetic, analgesic and antimicrobial effect, has moderate fibrinolytic activity. Penetrates through the skin, mucous membranes, the membrane of microbial cells (increases their sensitivity to antibiotics) and other biological membranes without damaging them, and can carry out various drugs deep into the wound ("Theory and practice of local treatment of purulent wounds" / Ed. Prof. B. M. Dotsenko, Kiev, “Health”, 1995, pp. 172-174).

Polyvinylpyrrolidone, a synthetic polymer inert to the body and not degraded by enzyme systems, is the basis of a detoxifying blood substitute fluid that binds toxic substances of various structures and removes them from the body (blood substitute fluids, www.nedug.ru/libraru/doc.aspx?item=38053) .

Hyaluronic acid - a polysaccharide from the glucosaminoglycan family, has the ability to bind 1000 times more water than it weighs. Hyaluronic acid has the highest hygroscopicity compared to other moisturizing agents, such as glycerin and sorbitol. In this case, the absorbed water is retained inside the gel and does not evaporate even when the relative humidity of the surrounding air decreases. Due to its high hydrophilicity, hyaluronic acid forms highly viscous gels with water that moisturize the skin and mucous membranes. Hyaluronic acid is non-toxic. As part of the gels, hyaluronic acid has an antimicrobial, wound healing and anti-inflammatory effect, promotes the regeneration of the epithelium, prevents the formation of granulation tissues, adhesions, scars, normalizes blood circulation, and does not cause clinical complications.

Hyaluronic acid has a positive effect on the course of local inflammatory processes, binds the microflora, as well as the products of its decay and vital activity, has a pronounced anti-inflammatory effect and a local anesthetic effect. At the same time, hyaluronic acid also provides mechanical protection for wounds, as it forms a thin film that prevents the penetration of environmental factors, pathogenic agents, into the wound. Gels based on hyaluronic acid are used to treat local and general purulent-inflammatory processes, thermal and chemical burns, trophic ulcers in chronic venous insufficiency, radiation injuries of the skin, cracks, abrasions, as well as for the treatment of long-healing wounds of various etiologies (patent RU No. 2195262 , A61K 9/06, 2002.12.27).

Sodium hyaluronate - the sodium salt of hyaluronic acid, is readily soluble in water with the formation of a viscous colorless gel with a pH of 6.0-7.5 (0.1% solution). In its activity, sodium hyaluronate is a complete analogue of hyaluronic acid, promotes tissue regeneration without scarring, and has the ability to stimulate cell migration and proliferation. Used in concentrations ranging from 0.01 to 0.5%.

Organosilicon glycerohydrogel is a new ointment base for external cosmetic and medicinal products, because it combines the beneficial properties inherent in many other ointment bases. This gel conducts various medicines well, has anti-inflammatory, decongestant and antioxidant activity, is able to protect tissues from drying out, saturate them with oxygen, it is non-toxic, economical, and stable during storage. The presence of silicon has a beneficial effect on all types of tissues: epithelial, connective, skin, bone, promotes regenerative processes, enhances blood supply. Due to the fact that silicon glycerates and glycerohydrogels based on them penetrate well through the skin and conduct drugs, the dose of these substances in pharmaceutical compositions can be reduced (www.uran.ru/gazetanu/2007/04/nu11/wvmnu_p3_11_042007.htm). Given the high transcutaneous activity of organosilicon glycerohydrogel, it can be used to create drugs for local and external use, transdermal therapeutic systems. This gel can be used as a source of an essential trace element - silicon for the regulation of silicon metabolism in the body (Boyakovskaya TG “Development of organosilicon glycerohydrogels and a comparative assessment of their transcutaneous activity”, abstract of the dissertation, www.vita.chel.su/files/docs /diss/bojakovskii.doc).

It is known that organofluorocarbon emulsions with gas-transporting properties, such as perfluorane, were used in the complex treatment of wounds and wound infections (Krylov NL et al. “Hemosorption and infusion of perftoran in the complex treatment of wounds and wound infection.” Problems of intensive care in the clinic. Abstracts scientific conference. December 12-13, 1985 - M .: B.I., 1985 - p. 12-13). Experimental studies have shown that perfluorocarbon compounds have a membrane effect and have a stimulating effect on the metabolic processes of living cells (they activate redox, hydrolytic reactions, the synthesis of nucleic acids, proteins, lipids, etc.). The contact of perfluorocarbons with damaged cells leads to rapid detoxification, suppression of the inflammatory response and active proliferation of epidermal cells. A positive effect was obtained with the cutaneous use of perfluorocarbon compounds in the treatment of patients with atopic dermatitis, eczema, trophic ulcers, herpes, acne, and pyoderma. A characteristic property of perfluorocarbons is their antipruritic effect, not inferior to hormonal drugs (Umerov Zh.G., Filippov EA “Perfluorocarbon compounds are promising anti-inflammatory drugs for the treatment of skin diseases.” IX All-Union Congress of Dermatovenerologists. Almaty, September 23-27 1991 Abstracts of reports. - M., 1991, p. 354). Perfluorocarbons with gas transporting properties stimulate wound healing and / or improve metabolism in integumentary tissues, which is associated with their effect on gas exchange of adjacent tissues, since wound damage is accompanied by increasing tissue cell hypoxia and increasing acidosis (patent RU No. 2033163, АКК 33/16, 1995.04. twenty).

Organofluorine emulsions with gas-transporting properties are known (for example, patent RU No. 2088217, АКК 9/10, 1997.08.27), which can be stored at room temperature for at least 1 year.

The type of dosage form of the proposed pharmaceutical preparation depends on the molecular weight of the used hyperosmolar substances, their ratio in the composition of the mixture, the rheological properties of the mixture, as well as the quantitative ratio of the hyperosmolar base with other components of the pharmaceutical preparation. Based on these quantitative ratios and rheological properties of the mixture, the dosage form of the proposed pharmaceutical product for topical and external use may be a liquid, gel, cream, ointment or suppository.

The ointment form is most preferable for external use, since it is well fixed and held on the wound surface, has longer therapeutic activity, cheaper to manufacture, and is convenient to use, which enhances the patient's motivation for treatment.

Using tilorone - a substance that has antibacterial activity against gram-positive and / or gram-negative microorganisms, or an antimycotic, or a local anesthetic substance, or a stimulator of reparative processes, or a hypoxidant, or biogenic elements in the form of physiologically acceptable compounds, or their physiologically acceptable mixtures, as well as hydrophilic bases with hyperosmolar properties, compositions of hydrophilic liquids for external and local use, hydrophilic ointments, g idrophilic creams, hydrophilic gels, which can also be used for the manufacture of suppositories and gelatin or other capsules for rectal and vaginal use.

Hydrophilic liquids, being hyperosmolar (solutions, emulsions, suspensions in the form of liniments), increase the permeability of the skin, effectively transporting the active substance - tilorone, as well as targeted additives to the area of purulent-destructive lesions.

Hydrophilic ointments are hyperosmolar, as a result of which, in addition to the effective transportation of active substances and targeted additives to the area of purulent-destructive lesions, they can absorb a significant amount of exudate and bring it to the surface of the skin or mucous membrane.

Hydrophilic creams are prepared on the basis of a water / oil or water / oil / water emulsion stabilized with suitable emulsifiers. These also include colloidal dispersed systems consisting of water-dispersed or mixed water-glycol solvents of higher fatty alcohols or acids, stabilized by hydrophilic surfactants. Creams are biphasic or multiphase disperse systems, the dispersion medium of which at the set storage temperature, as a rule, has a Newtonian type of flow and low values of rheological parameters. The action of hydrophilic-based creams is similar to the action of hydrophilic-based ointments, but they have a lower viscosity than ointments, therefore they penetrate more easily through the transepidermal barrier and into the depth of the wound. According to the rheological properties, they occupy an intermediate position between the liquid and the ointment.

Hydrophilic gels (hydrogels) are prepared on the basis of water, a hydrophilic mixed or non-aqueous solvent (glycerin, 1,2-propylene glycol, PEO-400 polyethylene oxide) and a hydrophilic gelling agent (carbomers, cellulose derivatives, tragacanth, sodium hyaluronate, hyaluronic acid, etc. .). In addition, the new hydrophilic gels mentioned above are currently being developed. Gels are single, double, or multiphase disperse systems with a liquid disperse medium, the rheological properties of which are due to the presence of gelling agents in relatively low concentrations. In this dosage form, the gelling agents can additionally fulfill the role of stabilizers of disperse systems: suspensions or emulsions.

Hydrophilic gels containing bound water in their composition do not have such a dehydrating effect as liquids, creams or ointments on a hydrophilic basis with hyperosmolar properties. They moisturize the focus of inflammation, protecting the wound from drying out. In this case, the heat transfer of the gel-coated part of the surface is reduced, as a result of which it is heated. Under the gel layer, moisture does not evaporate, the upper layers of the skin or mucous membrane macerate (soak), which contributes to the absorption into the skin thickness of various medicinal substances that are present in the gel. In this case, the active substance and the target additives contained in the hydrophilic gel layer on the surface of the skin or mucous membrane diffuse through the transepidermal barrier to the lesion. Gels are advisable to apply at the healing stage, when there is no longer any need to remove toxic products of purulent-destructive lesions from the lesion site.

Hydrophilic suppositories, prepared on hydrophilic hyperosmolar bases, are easily dissolved by rectal or vaginal administration, evenly distributing medicinal substances throughout the mucosa, which have both local and resorptive effects on the body.

Gelatin capsules for rectal and vaginal administration are more promising in comparison with suppositories from a technological, biopharmaceutical and economic point of view. The gelatin shell protects the drug from environmental factors and has advantages over suppositories, since it can encapsulate substances in the form of ointment, liniment, cream, gel, emulsion, suspension, etc.

The release of the drug substance occurs faster and easier than in suppositories, since under the influence of a weakly alkaline medium (pH 7.3-7.6) of the mucous membranes, the gelatinous membranes swell, and in this state even a weak effect on them is enough to break it and releasing content. The amount of drug substance in the capsule, which has the necessary therapeutic effect, is a double dose of suppositories.

Thus, the production of rectal and vaginal products in a gelatin shell allows you to save expensive biologically active ingredients and reduce the cost of drugs. Rectal gelatin capsules with the proposed pharmaceutical product meet all the requirements for ideal suppositories and can be used in medicine for the treatment of proctologic diseases, and vaginal capsules for the treatment of diseases of the urogenital system in women.

A synthetic immunomodulator - a low molecular weight inducer of interferon tiloron in the proposed pharmaceutical preparation restores the local immunity of the skin and mucous membranes, which contributes to faster healing of purulent-destructive lesions, increases the body's resistance to skin diseases and diseases of the mucous membrane due to the suppression of viral, bacterial and fungal infections. The antioxidant properties of tilorone also contribute to faster healing by reducing tissue necrosis.

Substances with antibacterial activity against gram-positive and / or gram-negative bacteria enhance the effect of tilorone on the healing of purulent-destructive lesions of the skin and mucous membrane.

So antibiotics have a bacteriostatic effect against many gram-positive and gram-negative microorganisms.

A complex of bacteriolytic and proteolytic enzymes, such as lysoamidase, in the proposed pharmaceutical preparation lyses gram-positive microorganisms, including those resistant to antibiotics, and also, due to its proteolytic activity, cleans the lesions from necrotic masses, while providing an immunostimulating effect. In addition, lysoamidase stimulates reparative processes due to the stimulating effect on granulation tissue cells.

The use in the proposed preparation of a broad-spectrum substance of Trilon B that violates the structure of the membranes of gram-negative microorganisms ensures the lysis of gram-negative microorganisms. Moreover, as options, a substance was proposed, both in the form of a monocomponent and as a mixture of components, each of which has its own mechanism of lysis of gram-negative microorganisms, which significantly enhances the death of their cells.

The combined use of antibiotics, a complex of bacteriolytic and proteolytic enzymes with Trilon B or EDTA, or a mixture thereof, significantly enhances the antibacterial effect of the proposed drug. In addition, a broad-spectrum substance, Trilon B, provides improved microcirculation in the tissues of the lesion by reducing the activity of histamine, and, being a water-soluble antioxidant, reduces secondary tissue necrosis in the circumference of the wound.

The use of antimycotics in the proposed drug together with tilorone provides a complex effect of the drug for fungal skin lesions.

The use of a local anesthetic substance in the proposed preparation, either a monocomponent or as a mixture of components, significantly suppresses pain in the treatment of purulent-destructive lesions of the skin and mucous membrane. At the same time, the use of a local anesthetic substance with antibacterial and antioxidant activity, for example, quinoxicain, enhances the therapeutic effect of the proposed pharmaceutical agent.

To provide additional stimulation of the repair processes in the foci of purulent-destructive lesions, the proposed pharmaceutical agent used both a monocomponent and a mixture of components with a different mechanism and spectrum of action, a substance that stimulates reparative processes in the foci of lesion.

The use of a hypoxidant in the proposed preparation, for example, succinic acid or its salt, increases microcirculation in the lesion and suppresses the inflammatory process.

The use of a hydrophilic and hyperosmolar base in the proposed pharmaceutical preparation provides fast delivery of the active substance and targeted additives to both microbial cells and tissue cells, which increases the therapeutic activity of the proposed drug. In addition, the dehydrogenation with a hydrophilic base of cells of gram-positive and gram-negative microorganisms reduces their resistance to the destructive effect of substances with antibacterial activity against gram-positive and / or gram-negative bacteria. It also increases the therapeutic activity of the proposed drug.

The use of a hyperosmolar base additionally improves microcirculation in the lesion due to its dehydrating effect, and also has an additional anti-inflammatory effect due to fluid absorption and reduced swelling of the lesion tissue. The hyperosmolar base provides an outflow of purulent exudate from the lesion and protects the tissue from overhydration. It is easily applied to the surface of the lesion, it is well kept on it, evenly distributed on it, improving the contact of the ointment with the tissues and contents of the lesion, penetrates well under the scab, mixes well with wound exudate, while maintaining its uniformity, low toxicity and is not irritating action on the tissue does not violate their physiological functions.

The dissolution of the active substance and target additives in a polyethylene oxide base increases their dispersion and the ability to more quickly release from the base, which also increases the therapeutic activity of the proposed drug. This base is a conductor of active substances through the skin barrier, while such a penetrating without damage to cells is enhanced in conditions of inflammation. The hydrophilic base on polyethylene oxides is able to dissolve in the secrets of the mucous membranes, completely releasing medicinal substances without irritating the mucous membrane, has a long shelf life and high physiological indifference.

The emulsion of perfluorocarbon compounds has a membrane effect and has a stimulating effect on the metabolic processes of living cells (it activates redox, hydrolytic reactions, the synthesis of nucleic acids, proteins, lipids, etc.). The contact of the perfluorocarbon emulsion with damaged cells leads to rapid detoxification, suppression of the inflammatory response and active proliferation of epidermal cells. It has an antipruritic effect, not inferior to hormonal drugs.

The use of biogenic elements in the proposed preparation together with tilorone strengthens local immunity, promotes faster healing of purulent-destructive lesions.

The drug is obtained by mixing the components by known methods.

The implementation of the invention is illustrated by the following examples, but is not limited to.

Example 1. Liniment No. 1.

In 100 g, 5% of liniment is contained, g:

tiloron  5,0 fusidic acid sodium salt  2.0 cyclopiroxolamine  1,0 catapol  0.1 quinoxicaine  1,0 1,2-propylene glycol  40,0 organofluorine emulsion  20,0 purified water up to 100 g

Example No. 2. Liniment No. 2

100 g of 3% of liniment contains, g:

tiloron  3.0 gentamicin sulfate  0.5 clotrimazole  1,0 Trilon B  0.1 trimecaine  3.0 1,2-propylene glycol  20,0 organofluorine emulsion  30,0 proxanol-268  5,0 purified water up to 100 g

Example 3. Liniment No. 3 (emulsion).

100 g of a 2% emulsion contains, g:

tiloron  2.0 calcium pantothenate  5,0 pyromecain  1,0 zinc chloride  0.0052 manganese acetate  0.0017 succinic acid  0.5 organofluorine emulsion  20,0 purified water up to 100 g

Example 4. Cream No. 1.

100 g of 3% cream contains, g:

tiloron  3.0 lysoamidase  2.0 Trilon B  0.05 organofluorine emulsion  20,0 glycerol  17.0 1,2-propylene glycol  12.0 PEO-1500  10.0 phosphate buffer  14.0 purified water up to 100 g

Example 5. Cream No. 2.

100 g of 5% cream contains, g:

tiloron  3.0 gentamicin sulfate  0.1 clotrimazole  1,0 Trilon B  0.05 dimexide  2.0 organofluorine emulsion  20.00 glycerol  17.00 1,2-propylene glycol  12.00 proxanol-268  10.00 phosphate buffer  14.00 purified water up to 100 g

Example 6. Cream No. 3.

100 g of 2% cream contains, g:

tiloron  2.00 methyluracil  1,0 lidocaine  1,0 zinc chloride  0.0052 manganese acetate  0.0017 succinic acid  0.5 organofluorine emulsion  35.00 PEO-400  25.00 proxanol-268  18.00 purified water up to 100 g

Example 7. Ointment No. 1.

100 g of 3% ointment contains, g:

tiloron  3.0 lysoamidase  2.00 Trilon B  0.02 proxanol-268  18.0 1,2-propylene glycol  22; 0 organofluorine emulsion  20,0 PEO-400 polyethylene oxide  28.0 purified water up to 100 g

Example 8. Ointment No. 2.

100 g of 5% ointment contains, g:

tiloron  5,0 gentamicin sulfate  1,0 clotrimazole  1,0 Trilon B  0.1 EDTA  0.1 trimecaine  2.0 proxanol-268  24.0 organofluorine emulsion  24.0 purified water up to 100 g

Example 9. Ointment No. 3.

100 g of 2% ointment contains, g:

tiloron  2.00 quinoxicaine  1.00 methyluracil  3.00 atsemin  1.00 nipagin  0.08 glycerol  20,0 zinc chloride  0.0052 manganese acetate  0.0017 succinic acid  0.5 sodium carboxymethyl cellulose  3,5 organofluorine emulsion  20,0 PEO-400  25.0 PEO-1500  20,0 isotonic sodium chloride solution up to 100 g

Example 10. Gel No. 1.

100 g of 2% gel contains, g:

tiloron  2.0 lysoamidase  2.0 pyromecain  1,0 organofluorine emulsion  20,0 polyethylene oxide gel 1500  up to 100 g

Example 11. Gel No. 2.

100 g of 3% gel contains, g:

tiloron  3.0 Trilon B  0.04 gentamicin sulfate  0.1 clotrimazole  1,0 pyromecain  1,0 nipagin  0.1 PEO-400 polyethylene oxide  10.0 organofluorine emulsion  20,0 hyaluronic kilota  0.50 purified water up to 100 g

Example 12. Gel No. 3.

100 g of 3% gel contains, g:

tiloron  3.0 trimecaine  4.0 methyluracil  2.0 nipagin  0.1 zinc chloride  0.0052 manganese acetate  0.0017 succinic acid  0.5 organofluorine emulsion  20,0 glycerohydrogel based silicon glycerates  50,0 purified water  up to 100 g

Example 13. A mixture for the preparation of suppositories No. 1.

In 100 g of a 5% mixture for the preparation of suppositories contains, g:

tiloron  5,0 Trilon B  1,0 gentamicin sulfate  0.1 trimecaine  4.0 etaden  4.0 proxanol-268  50,0 polyethylene oxide-400  15.0 organofluorine emulsion  10.0 purified water up to 100 g

300 pieces were made from this mixture. rectal suppositories in the form of a "cigar" with a diameter of 10 mm, weighing 2.5 g with a tilorone content of 0.125 g in one suppository. The solubility of hydrophilic suppositories is no more than 1 hour at a temperature of (37 ± 1) ° С, which corresponds to the requirements of the Global Fund XI (Art. Suppositories, pp. 151-153).

Example No. 14. Mix for the preparation of suppositories No. 2.

In 100 g of a 5% mixture for the preparation of suppositories contains, g:

tiloron  5,0 lysoamidase  2.0 anestezin  4.0 etaden  4.0 proxanol-268  55.0 polyethylene oxide-400  15.0 organofluorine emulsion  10.0 purified water up to 100 g

300 pieces were made from this mixture. rectal suppositories in the form of a "cigar" with a diameter of 10 mm, weighing 2.0 g with a tilorone content of 0.1 g in one suppository. The solubility of hydrophilic suppositories is no more than 1 hour at a temperature of (37 ± 1) ° С, which corresponds to the requirements of the Global Fund XI (Art. Suppositories, pp. 151-153).

Example No. 15. Mix for the preparation of suppositories No. 3.

In 100 g of a 5% mixture for the preparation of suppositories contains, g:

tiloron  5,0 trimecaine  4.0 etaden  4.0 dimexide  3.0 succinic acid  0.5 zinc chloride  0.0052 manganese acetate  0.0017 proxanol-268  55.0 polyethylene oxide-400  8.0 organofluorine emulsion  10.0 purified water  up to 100 g

300 pieces were made from this mixture. rectal suppositories in the form of a "cigar" with a diameter of 10 mm, weighing 2.5 g with a tilorone content of 0.125 g in one suppository. The solubility of hydrophilic suppositories is no more than 1 hour at a temperature of (37 ± 1) ° С, which corresponds to the requirements of the Global Fund XI (Art. Suppositories, pp. 151-153).

Example 19. Gelatin capsules.

The ointment from example 10 is filled with 500 pieces. gelatin capsules No. 00, a volume of 0.95 ml. The disintegration of the obtained capsules is less than 20 min, which meets the requirements of the Global Fund XI (St. Capsules, p. 143).

On the basis of the proposed solution, a number of new drugs were created in the form of liquid and soft dosage forms containing the active substance Tiloron, target additives and an emulsion of perfluororganic compounds.

The proposed preparations based on tilorone, the above target additives and a base containing an emulsion of perfluororganic compounds significantly expand the scope of the known active substance - tilorone, provide restoration of local immunity and biocenosis of the skin and mucous membranes in the treatment of purulent-destructive processes of the skin, have high therapeutic activity, give anesthetic effect; stimulate reparative processes; improve microcirculation in the lesion, stop inflammatory reactions in the skin, reduce secondary tissue necrosis in the affected areas associated with excessive free radical oxidation, reduce itching, are easy to use, accelerate and improve healing.

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

The above set of features of the proposed pharmaceutical product (composition of the drug, its dosage form and quantitative ratio of components) was not previously known, which indicates the novelty of the proposed solution. The set of essential features of the claimed pharmaceutical product for external use on the basis of tilorone does not follow explicitly from the studied prior art, has significant differences from the considered analogues. Until now, a similar solution has not 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).

Therefore, the applicant believes that the claimed pharmaceutical preparation for topical and external use on the basis of tilorone has an inventive step.

The inventive pharmaceutical preparation can be recommended in the treatment of purulent-destructive lesions of the skin and mucous membranes.

The proposed pharmaceutical preparation for topical application on the basis of tilorone can be used for industrial serial production of liquid and soft dosage forms, such as emulsions, suspensions, liniments, ointments, creams, gels, as well as for industrial production of formed soft dosage forms: suppositories and gelatin capsules for rectal and vaginal use.

Claims (10)

1. The pharmaceutical composition for the treatment of purulent-destructive lesions of the skin and mucous membranes for external and local use, characterized in that it contains tilorone and at least one of the following target additives selected from the range:
a substance that has antibacterial activity against gram-positive and / or gram-negative bacteria, antimycotics, a local anesthetic, a stimulant of reparative processes, a hypooxidant, biogenic elements or their mixture, base, in the following ratio of components, wt.%:
tiloron 0.005-10.00 antibacterial substance activity against gram-positive and / or gram negative bacteria 0.01-13.00 antimycotic 0.50-3.00 local anesthetic 0.50-4.00 reparative stimulant 0.50-4.00 hypooxidant 0.001-1.00 nutrients 0.000001-5.50 the basis rest 2. The pharmaceutical composition according to claim 1, characterized in that as a substance having antibacterial activity against gram-positive and / or gram-negative bacteria, it contains substances selected from the group — antibiotic, lysoamidase, trilon B, ethyldiaminetetraacetic acid. 3. The pharmaceutical composition according to claim 1, characterized in that as an antibiotic it contains gentamicin sulfate, or the sodium salt of fusidic acid, or a mixture thereof. 4. The pharmaceutical composition according to claim 1, characterized in that it contains clotrimazole or cyclopiroxolamine as an antimycotic. 5. The pharmaceutical composition according to claim 1, characterized in that as a local anesthetic substance it contains substances selected from the group: quinoxicaine, trimecaine, pyromecaine, lidocaine, anestezin or a mixture thereof. 6. The pharmaceutical composition according to claim 1, characterized in that, as a stimulant of reparative processes, it contains substances selected from the group: methyluracil, acetamine, etaden, calcium pantothenate, solcoseryl, catapol or a mixture thereof. 7. The pharmaceutical composition according to claim 1, characterized in that as a hypooxidant it contains succinic acid or its salts. 8. The pharmaceutical composition according to claim 1, characterized in that as biogenic elements it contains zinc, or manganese, in the form of physiologically acceptable compounds, or their physiologically acceptable mixture. 9. The pharmaceutical composition according to claim 1, characterized in that it contains an emulsion of organofluorine compounds or its mixture with hydrophilic substances selected from the series: dimexide, glycerin, 1,2 propylene glycol, proxanol-268, polyethylene oxide-1500, polyvinylpyrrolidone , gel of polyethylene oxide 1500, glycerohydrogel based on silicon glycerates, calcium or magnesium alginate, sodium carboxymethyl cellulose, hyaluronic acid. 10. The pharmaceutical composition according to claim 1, characterized in that it is made in the form of a liquid dosage form solution for external use or topical application, a suspension or emulsion in the form of a liniment, or a soft dosage form - an ointment or gel or cream, or formed soft dosage form - suppositories or capsules for rectal or vaginal use.