RU2352330C1 - Pharmaceutical preparation for local and external application on basis of low-molecular inductor of interferon - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine and pharmacology, namely, pharmaceutical composition applied at treatment of purulent-destructive processes of a skin and mucosas at external and local application, characterised that it contains tylorone, an emulsion of perfluoroorganic bonds, and as, at necessity, a hydrophylic basis at a certain parity of components.

EFFECT: invention provides expansion of a scope of known active substance - tylorone, restoration of tissue immunity and biocenosis of a skin and mucosas at treatment of purulent-destructive processes of a skin, depression of a secondary necrosis of tissues on the amazed sites, microcirculation improvement in the lesion centre, cupping of inflammatory reactions, reduction of an itch maintenance of high therapeutic activity and convenience in use, acceleration and healing improvement.

19 ex, 4 cl

Description

The invention relates to the chemical-pharmaceutical industry, as well as medicine and veterinary medicine, namely to pharmaceutical preparations for external and local use in the treatment of purulent-destructive skin processes with clinical and laboratory signs of immune deficiency, for example, such as chronic recurrent furunculosis, herpetic lesions skin and mucous membranes, atopic dermatitis complicated by bacterial-fungal infections, trophic ulcers, postoperative suppuration of wounds, to accelerate and improve healing phenomena.

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. Adrenal cortex hormones 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 even more 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, 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 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 is 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 later replaced by gamma-interferon a day later (PD Shabanov et al. “Trekresan 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 in the treatment of purulent-destructive processes are unknown.

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 -infection, neuroviral infection (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 idnogo arthritis, osteoarthritis deformans, spondylosis, skin diseases (atopic dermatitis, eczema, dermatosis, papilloma virus) (Description of the preparation, www.biomedservis.ru/preparat/pr_cycloferon_liniment.htm).

Its use enhances the antibacterial effect of antibiotics used in the treatment of acute intestinal infections (http://www.biomedservice.ru/preparat/pr_cycloferon_tabl.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 topically in the treatment of genital herpes, urethritis, balanoposthitis (nonspecific, candidal, gonorrhea and trichomonas etiology), vaginitis (bacterial and candidal), chlamydia, 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 a 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 herpes, 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= 41ba48ba44ba43b, or Lavomax, Instruction for the drug produced in the form of tablets, http://www.regmed.ru/InstrShow2.asp?InstrLinkNx=a41ba48ba44ba43b).

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. 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 used orally for secondary prevention of sclerosis (V.I. Golovkin et al. “Secondary prevention of multiple sclerosis with the help of 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 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 inducer of interferon, 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, but exceeds its duration. 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).

Tiloron 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). This makes it promising for use in preparations for local and external use.

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

The objective of the invention is the creation of pharmaceuticals for local and external use based on a low molecular weight inducer of interferon as an active substance.

Technical results that can be obtained 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 and mucous membranes, reducing secondary tissue necrosis in affected areas, improving microcirculation in the lesion, relief of inflammatory reactions, reduction of itching, ensuring high therapeutic activity and convenience in use mations, accelerate and enhance healing.

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

tiloron 0.001-10.00 the basis rest

In accordance with the invention, topical dosage forms based on tilorone are liquid dosage forms, for example emulsions in the form of liniments, ointment-like soft dosage forms, for example ointments, gels, creams, and also formed soft dosage forms - suppositories and gelatin capsules for rectal or vaginal use.

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 (A.N. Decina, “Theory of Soft Cosmetic Effects. Modern Cosmetology”, Novosibirsk, Nauka, 2000, www.golkom. com / 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.

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 (in particular ethyl or isopropyl), glycerol, low molecular weight polyethylene oxides (in particular PEO-400), propylene glycols (in particular, 1,2-propylene glycol), etc. easily penetrate the tranepidermal barrier or into the depth of 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 styloid and granular layers, which leads to a decrease in the size of cellular 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 and external therapy in dermatology in the treatment of purulent-destructive processes of the skin and soft tissues, such as recurring furunculosis, acne vulgaris, burns, long-healing soft tissue wounds, etc. In addition, It is promising to use it in the form of preparations for local and external use in allergology and immunology in the complex treatment of allergic dermatoses, especially those associated with fungal and herpes infections, as well as those FIPA urogenital 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 having sorption properties, such as high molecular weight polyethylene oxides (e.g. PEO-1500), proxanols (e.g. procasanol-268), medical polyvinylpyrrolidones (e.g. 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 skin surface.

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 (“Theory and practice of local treatment of purulent wounds.” Edited 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.

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 bases, 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.

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 uniformly over they are distributed, improving the contact of the ointment with the tissues and contents of the wound, mix well with wound exudate and at the same time maintain their uniformity, low toxicity and do not irritate the tissues, do not violate their physiological functions.

The ability of polyethylene oxides (PEO) to provide an antimicrobial drug with an interstitial action 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, including 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, a block copolymer of propylene and ethylene oxides, as an osmotically active substance provides a more uniform absorption pattern and has a longer osmotic period. 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 the molecular weight, the stronger and longer the osmotic effect of the substance will appear at a given concentration. 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. It is liquefied by adding alcohol, glycerol, with vigorous stirring, the pH of a 20% aqueous suspension of 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, liniments in the pharmaceutical and cosmetic industries (www.medpeterburg.ru/news/Out.aspx?Item=21284). The gel has a stabilizing effect on enzymes (patent RU No. 2089177, A61K 7/48, 1997.09.10).

Dimexide - 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 a variety of drugs deep into the wound. (“Theory and practice of local treatment of purulent wounds” under the editorship of 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 highly 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 carry drugs, the dose of these substances in pharmaceutical compositions can be reduced (www.uran.ru/gazetanu/2007/04/null/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 organofluorine 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 .: BI, 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.

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

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 and hydrophilic bases with hyperosmolar properties, which include emulsions of perfluororganic compounds, compositions of hydrophilic liquids for external and local use, hydrophilic ointments, hydrophilic creams, hydrophilic gels, which can also be used for the manufacture of suppositories and gelatin or other capsules, are proposed. for rectal and vaginal use.

Hydrophilic liquids, being hyperosmolar (emulsions, suspensions in the form of liniments) increase the permeability of the skin, effectively transporting the active substance - tilorone 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 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 compared to 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 release the contents . 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 gelatin capsules for the treatment of diseases of the urogenital system in women.

The low molecular weight interferon inducer (synthetic immunomodulator) - tiloron in the proposed pharmaceutical preparation restores 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.

The use of a hydrophilic and hyperosmolar base in the proposed pharmaceutical preparation provides fast delivery of the active substance to both microbial cells and tissue cells, which increases the therapeutic activity of the proposed drug. In addition, 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, it 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 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 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 1,2-propylene glycol 20,0 organofluorine emulsion 40,0 purified water up to 100

Example 2. Liniment No. 2.

100 g of 3% of liniment contains, g:

tiloron 3.0 1,2-propylene glycol 20,0 organofluorine emulsion 40,0 proxanol-268 5,0 purified water up to 100

Example 3. Liniment No. 3 (emulsion).

100 g of a 2% emulsion contains:

tiloron 2.0 organofluorine emulsion 50,0 isotonic sodium chloride solution up to 100

Example 4. Cream No. 1.

100 g of 5% cream contains, g:

tiloron 5.00 organofluorine emulsion 22.00 glycerol 17.00 1,2-propylene glycol 12.00 phosphate buffer 14.00 purified water up to 100

Example 5. Cream No. 2.

100 g of 3% cream contains, g:

tiloron 3.0 organofluorine emulsion 40,0 PEO-400 30,0 PEO-1500 20,0 purified water up to 100

Example 6. Cream No. 3.

100 g of 2% cream contains, g:

tiloron 2.0 organofluorine emulsion 35.0 PEO-400 25.0 proxanol-268 18.0 purified water up to 100

Example 7. Ointment No. 1.

100 g of 5% ointment contains, g:

tiloron 5,0 proxanol-268 18.0 1,2-propylene glycol 42.0 organofluorine emulsion 28.0 purified water up to 100

Example 8. Ointment No. 2.

100 g of 3% ointment contains, g:

tiloron 3.0 PEO-400 polyethylene oxide 47.0 organofluorine emulsion 20,0 PEO-1500 polyethylene oxide 17.0 purified water up to 100

Example 9. Ointment No. 3.

100 g of 2% ointment contains, g:

tiloron 2.00 nipagin 0.08 glycerol 20,0 sodium carboxymethyl cellulose 3,5 zinc oxide 3.0 organofluorine emulsion up to 100

Example 10. Gel No. 1.

100 g of 5% gel contains, g:

tiloron 5,0 organofluorine emulsion 20,0 polyethylene oxide gel 1500 up to 100

Example 11. Gel No. 2.

100 g of 3% gel contains, g:

tiloron 3.0 nipagin 0.1 organofluorine emulsion 10.0 PEO-400 polyethylene oxide 30,0 sodium hyaluronate 0.50 purified water up to 100

Example 12. Gel No. 3.

100 g of 2% gel contains, g:

tiloron 2.0 organofluorine emulsion 20,0 glycerohydrogel based silicon glycerates 50,0 purified water up to 100

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 organofluorine emulsion 10.0 proxanol-268 65.0 polyethylene oxide-400 15.0 purified water up to 100

300 pieces of rectal suppositories in the form of a “cigar” with a diameter of 10 mm and a weight of 2.5 g with a tilorone content of 0.125 g in one suppository were made from this mixture. 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 organofluorine emulsion 8.0 polyethylene oxide-1500 68.0 polyethylene oxide-400 15.0 purified water up to 100

300 pieces of rectal suppositories in the form of a “cigar” with a diameter of 10 mm and a weight of 2.0 g with a tilorone content of 0.1 g in one suppository were made from this mixture. 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 dimexide 3.0 organofluorine emulsion 10.0 proxanol-268 64.0 polyethylene oxide-400 10.0 purified water up to 100

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 described in example 7 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 (Art. Capsules, p. 143).

Based on the proposed solution, a number of new drugs have been created in the form of liquid and soft dosage forms containing the active substance Tiloron and an emulsion of perfluororganic compounds.

The proposed preparations based on tilorone 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, and improve microcirculation in the lesion , stop inflammatory reactions in the skin, reduce secondary tissue necrosis in the affected areas, associated with excess free radical m oxidation, reduce itching, 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, the quantitative ratio of the components and its dosage form) 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 local and external use based on a low molecular weight interferon inducer - tilorone and organofluorine emulsions 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 release of formed soft dosage forms - suppositories and capsules for rectal and vaginal use.

Claims (3)

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, an emulsion of perfluororganic compounds, and also, if necessary, a hydrophilic base in the following ratio of components, wt.%:
tiloron 0.005-10.0 emulsion of perfluororganic compounds 5.0-90.0 the basis rest 2. The pharmaceutical composition according to claim 1, characterized in that it contains 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, or a mixture thereof. 3. The pharmaceutical composition according to claim 1, characterized in that it is made in the form of a liquid dosage form — a solution for external use and topical application, a suspension or emulsion in the form of a liniment, or a soft dosage form — an ointment, or a gel, or a cream, or a formed soft dosage form - suppositories or capsules for rectal or vaginal use.