RU2726982C1 - Local application of dioxydine in infectious-inflammatory epithelial affection - Google Patents

Abstract

FIELD: medicine; pharmaceuticals.SUBSTANCE: group of inventions relates to pharmaceutics, specifically to use of dioxidine for treating and/or preventing infectious-inflammatory epithelial injuries and wound healing, to a medicinal agent, pharmaceutical composition, a ready dosage form and a kit for treating and/or preventing infectious-inflammatory epithelial injuries and wound healing. Use of dioxydine involves local application of 0.001–0.4 wt/vol. % aqueous solution of dioxidine with pH from 3 to 7.5. Drug, pharmaceutical composition and the finished dosage form are aqueous 0.001–0.4 wt/vol. % dioxidine solution having pH of 3 to 7.5. Kit contains a bottle with a drug, a pharmaceutical composition or a ready dosage form, a nozzle and instructions for use.EFFECT: group of inventions provides preserving the antimicrobial and anti-inflammatory activity of dioxidine in solutions, high photostability, high resistance to self-oxidation of dioxidine in solutions, high quality of dioxydine solutions and safety thereof due to the absence of microcrystals therein, accelerated healing of wounds and/or burns, recovery of damaged epithelium, reduced complications in treatment, provision of conditions for fast wound epithelisation, wider range of anti-infectious and anti-inflammatory topical agents for treating and/or preventing infectious-inflammatory epithelial injuries.109 cl, 1 dwg, 6 ex, 4 tbl

Description

The invention relates to pharmacology, medicine and the chemical-pharmaceutical industry, namely to a new local use of dioxidine (hydroxymethylquinoxalindioxide) in the form of a 0.001-0.4% solution for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium. The invention can be used for the treatment and / or prevention of genital lesions, including after diagnostic or surgical procedures, postpartum injuries, perineal and / or vaginal wounds, postpartum infections, for the treatment and / or prevention of diseases of the genital organs, such as vulvovaginitis, cervicitis , endometritis, uterine abscess, salpingo-oophoritis. The invention can also be used for the treatment and / or prevention of infectious and inflammatory lesions of the skin and mucous membranes, in particular, pyoderma and dermatomycosis, candidiasis of the skin and mucous membranes, mycoses of the feet, as well as for the treatment of superficial burns of II and IIIA degrees, and the preparation of burns wounds to dermatoplasty.

Epithelial damage, mainly of a mechanical nature, is one of the common causes of infectious and inflammatory lesions of the skin, mucous membranes and genitals. Damage can be both pronounced (trauma, deep wounds) and insignificant (microcracks, small superficial injuries, including chafing), which, against the background of a general weakening of immunity and a decrease in the regenerative abilities of the body, can lead to the development of infectious and inflammatory lesions of various etiology. Infectious and inflammatory lesions of the skin and mucous membranes include, in particular, pyoderma and dermatomycosis, candidiasis and mycoses. Infectious and inflammatory lesions of the genital organs include diseases of the genital organs and postpartum infections, including after diagnostic or surgical procedures, postpartum injuries, perineal and / or vaginal wounds. These infectious and inflammatory lesions are one of the common reasons for patients seeking medical attention. An important problem is the search for optimal means and methods of treatment for this category of patients. Therapeutic measures should be etiopathogenetically justified and safe; hypoallergenicity and low toxicity of the selected drug should also be taken into account.

With regard to wound microflora, high rates of evolution are especially noted with a change in its biological properties and the rapid development of resistance to antibacterial drugs. The use of general antibiotic therapy to suppress microflora in the wound is limited by the need to administer large doses of antibiotics, since, along with the effect on the bacterial cell, they also have a negative effect on the patient's body - they violate the immune system, cause dysbiosis, mycotic lesions [1]. The most common treatment for acute infectious and inflammatory lesions is a combination of antibiotics and topical antiseptics. However, it is known that a common problem with most antibacterial drugs, both antibiotics and antiseptics, for topical use is that they cause various side effects. At the same time, the treatment of chronic infectious and inflammatory lesions, requiring the use of long courses of various drugs, further aggravates these side effects, especially for the mucous membranes, and immunodeficiency, which contributes to the recurrence of the disease and is especially unacceptable in pediatric practice [4].

Thus, the search for new effective and safe drugs for the treatment of infectious and inflammatory lesions of the epithelium of a wide spectrum of action, preferably from the group of antiseptics, remains relevant today.

Dioxidine (hydroxymethylquinoxalindioxide, or 2,3-bis- (hydroxymethyl) quinoxaline 1,4-di-N-oxide) is a domestic synthetic broad-spectrum antimicrobial drug. Dioxidine is a derivative of quinoxaline di-N-oxide, has antibacterial and antiprotozoal activity, is characterized by high reactive properties, increased ability to polarize and redox reactions. Quinoxaline di-N-oxide derivatives have been intensively developed and studied since the 1960s. both in Russia and in other countries [7]. The drug was approved for medical use in 1976.

hydroxymethylquinoxaline dioxide

Dioxidine is an odorless greenish-yellow crystalline powder; slightly soluble in water, ethanol and chloroform. It has a wide spectrum of antibacterial action with a bactericidal type, is active against both gram-positive and gram-negative bacteria, aerobic and anaerobic, spore-forming and asporogenic bacteria in the form of macrocultures and microbial associations. An antiseptic has a detrimental effect on pathogens such as staphylococci, streptococci, gonococci, treponema pallidum, Trichomonas, chlamydia, Proteus vulgaris, dysentery bacillus, Friedlander's bacillus, Klebsiella, Pseudomonas aeruginosa, salmonella, pathogens, etc., pathogens, etc. others, as well as herpes viruses, human immunodeficiency viruses, etc. The broad spectrum of action of dioxidine against most pathogens of hospital infections, as well as those bacterial strains that are resistant to other chemotherapy drugs, including antibiotics, determines the importance of dioxidine for therapy.

Dioxidine also has antifungal activity, in particular against Candida albicans. C. albicans, as you know, is the causative agent of various opportunistic infections in humans, which are transmitted by contact, mainly direct (sexual, fecal-oral, transdermal), but also indirect (through furnishings, personal belongings, dishes, hygiene items, etc.) .p.) transmission mechanism. C. albicans is one of the most common hospital-borne infections.

When used to treat infected wounds, dioxidine promotes faster cleaning of the wound surface, enhances reparative regeneration, marginal epithelialization, and has a beneficial effect on the course of wound healing processes [8].

Dioxidine penetrates well into various organs and tissues, is excreted mainly by renal mechanisms and does not cumulate with repeated administrations. Despite the long period of use of dioxidine (since the 1970s) for the treatment of pyoinflammatory processes in clinical practice, the effectiveness of this drug has remained, which indicates that the resistance of microorganisms to it practically does not develop. This confirms the result of a multicenter study conducted in 2011. There is published evidence of good tolerability of the drug when applied topically. During therapy with dioxidine, no nephrotoxic and ototoxic effects, as well as a negative effect on liver function, were noted [7]. The activity of dioxidine is enhanced in an anaerobic environment due to the induction of the formation of reactive oxygen species [9].

Dioxidine is characterized by sensitivity to light (photolability) [10, 11] and at the same time is an oxidizing agent, which makes it difficult to obtain stable solutions with it and the selection of auxiliary substances, especially in connection with the ability of dioxidine to self-oxidize. Based on this, dioxidine must be stored out of the reach of light at a temperature of 15-25 ℃, however, non-compliance with storage conditions, as noted, makes it difficult to maintain the initial concentration of dioxidine and, accordingly, the proper quality of the drug.

According to the requirements for medicinal products, their quality must be checked both directly at the plant and in pharmacies and other medical institutions after the receipt of the batch. Medicines in liquid forms are checked for authenticity and proper quality in accordance with well-known methods (determination of the color of the solution, transparency, purity of the solution - the presence of crystalline precipitate and mechanical impurities, pH of the solution, etc.). One of the existing problems for a number of drugs, including dioxidine, is the rejection of some of the containers with the drug due to the presence of microcrystals in them. Basically, microcrystals are formed in connection with the ingress of impurities into the solution, which, even in small amounts, subsequently become crystallization centers. The crystals grow in size over time. The crystallization effect of a substance in a preparation can lead to a change in its concentration, the proper efficacy when using it.

The following dosage forms of dioxidine are known and introduced into clinical practice: 0.5% and 1% solutions for injections and 5% ointment. It is known to use these dosage forms of dioxidine as a topical agent for the treatment of a number of infectious and inflammatory lesions in the field of otolaryngology [7], as well as the use of a 1% solution of dioxidine and 5% dioxidine ointment in surgery, including for the treatment of wounds, and in terms cleansing wounds and the transition of the stage of inflammation to the stage of regeneration, the effectiveness of dioxidine is comparable to modern antiseptic drugs (polyhexanide, acerbine solution) and is almost 2 times higher than the results of treatment in traditional solutions of chlorhexidine, miramistin, levomekol and levosin ointments [1, 8, 21, 22] ...

An obvious disadvantage of existing dosage forms is the insufficient stability of dioxidine as a result of its photolability and the effect of self-oxidation, and the presence of microcrystals in dioxidine solutions.

Thus, the object of the present invention is to develop a storage-stable, economically feasible, commercially available, effective formulation of dioxidine for topical use in the treatment and / or prevention of infectious-inflammatory lesions of the epithelium, which has high efficiency, increased photostability, increased resistance to self-oxidation, increased safety due to the absence of microcrystals, accelerating wound healing, restoring damaged epithelium, reducing complications during treatment and providing conditions for rapid epithelialization of wounds.

The authors of the present invention unexpectedly found that aqueous 0.001-0.4% solutions of dioxidine have high antimicrobial and anti-inflammatory activity, similar to the activity of the known 0.5 and 1% solutions, in the treatment and / or prevention of infectious-inflammatory lesions of the epithelium with significantly increased stability and safety, promote accelerated healing of wounds and burns of various etiologies, areas and depths, restore damaged epithelium, reduce complications during treatment and provide conditions for rapid epithelialization of wounds, which made it possible to create an effective, safe and stable finished dosage form for the treatment of infectious and inflammatory lesions of the epithelium ...

The dioxidine solutions according to the present invention do not contain microcrystals due to the fact that the microcrystallization processes in them are more complicated and longer than in 1% and 0.5% dioxidine solutions, and the filtration process of dioxidine solutions according to the invention by means of membrane and tangential filtration systems is faster and more efficient than for 1% and 0.5% dioxidine solutions. The increased stability and safety of dioxidine solutions according to the present invention in comparison with 0.5 and 1% solutions is due to their increased resistance to self-oxidation, reduced photolability and the absence of microcrystals. Thus, the present inventors were able to improve the quality and safety of dioxidine solutions while maintaining their effectiveness.

The technical results of the claimed invention are:

- preservation of the antimicrobial and anti-inflammatory activity of dioxidine in solutions according to the present invention in comparison with the known 0.5% and 1% dioxidine solutions;

- increasing the photostability of dioxidine in solutions according to the present invention;

- increasing the resistance of dioxidine to self-oxidation in solutions according to the present invention;

- improving the quality of dioxidine solutions according to the present invention and their safety due to the absence of microcrystals in them;

- acceleration of healing of wounds and / or burns of various etiology, area and depth, restoration of damaged epithelium, reduction of complications during treatment, provision of conditions for rapid epithelialization of wounds when using dioxidine solutions according to the present invention;

- expanding the arsenal of anti-infectious and anti-inflammatory drugs for local use for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium.

The following are definitions of terms that are used in the description of the present invention.

"Medicinal principle" or "active principle" (drug substance, drug substance) means a physiologically active substance of synthetic or other (biotechnological, plant, animal, microbial and other) origin that has pharmacological activity and is an active principle of a pharmaceutical composition used for the production and manufacturing of a medicinal product (product).

"Drug (preparation)" - a substance (or a mixture of substances in the form of a pharmaceutical composition) in the form of a spray, liquid for rinsing or washing, capsules, injections, ointments and other ready-made forms, intended for local treatment and prevention of diseases, as well as restoration of damage epithelium and mucous membranes.

"Finished dosage form" - the state of a medicinal product in a convenient state for use, corresponding to the methods of its administration and use, and ensuring the achievement of the required therapeutic effect.

"Pharmaceutical composition" means a composition comprising 0.001-0.4% dioxidine solution and at least one of the components selected from the group consisting of pharmaceutically acceptable and pharmacologically compatible excipients, solvents, diluents, carriers, auxiliary, dispensing agents such as preservatives, stabilizers, fillers, disintegrants, humectants, emulsifiers, suspending agents, thickeners, sweeteners, flavoring additives, flavor neutralizers, fragrances, flavors, antibacterial agents, fungicides, lubricants, the choice and ratio of which depends on their nature, method administration of the composition and dosage. Examples of suspending agents are ethoxylated isostearyl alcohol, polyoxyethylene, sorbitol and sorbitol ether, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, as well as other pharmaceutically acceptable surfactants, and mixtures of these substances. The composition may also include isotonic agents such as sugars, sodium chloride and the like. Examples of suitable carriers, solvents, diluents and delivery vehicles are water (purified, distilled, bidistilled, injectable), ethanol, polyalcohols, buffers, and mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters (such as ethyl oleate). Examples of fillers are lactose, milk sugar, microcrystalline cellulose, sodium citrate, calcium carbonate, calcium phosphate, and the like. To adjust the pH, various organic and inorganic acids can be used, such as malic, ascorbic, citric, acetic, succinic, tartaric, fumaric, lactic, aspartic, glutaric, glutamic, sorbic acids, and their pharmaceutically acceptable salts, as well as pharmaceutically acceptable bases such as methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, propylamine, dipropylamine, tripropylamine, ethylenediamine, monoethanolamine, diethanolamine, triethanolamine, guanidine, morpholine, piperidine, pyrrolipine, 1-buperazyl-1-buperazyl-1 , N-methylpiperazine, 1,4-dimethylpiperazine, N-benzylphenylethylamine, tris- (hydroxymethyl) aminomethane, N-methylglucosamine, arginine, lysine, ammonia, sodium hydroxide, calcium hydroxide, potassium hydroxide, aluminum hydroxide, iron hydroxide, magnesium hydroxide and zinc hydroxide as well as other amino acids and pharmaceutically acceptable compounds. Examples of dispersing agents and distributing agents are starch, alginic acid and its salts, silicates. Examples of lubricants are magnesium stearate, sodium lauryl sulfate, talc, colloidal silicon dioxide, and high molecular weight polyethylene glycol. A pharmaceutical composition for topical administration of an active principle, alone or in combination with another active principle, can be administered to animals and humans in a standard administration form, as a mixture with conventional pharmaceutical carriers. Suitable unit forms of administration include rinses or rinses, or suspensions, sprays, aerosols, gels, ointments, and other topical administration forms.

Pharmaceutical compositions can include pharmaceutically acceptable excipients. By pharmaceutically acceptable excipients is meant diluents, auxiliary agents and / or carriers used in the pharmaceutical field. The pharmaceutical composition, along with 0.001-0.4% dioxidine solution according to the present invention, may include other active substances, including those with activity, provided that they do not cause undesirable effects.

If it is necessary to use the pharmaceutical composition of the present invention in clinical practice, it can be mixed with conventional pharmaceutical carriers.

The carriers used in the pharmaceutical compositions of the present invention are those that are used in the pharmaceutical field to obtain common forms, in particular binders, lubricants, disintegrants, solvents, diluents, stabilizers, suspending agents, flavors, bases, diluents, additional antiseptic agents.

The dioxidine solutions according to the present invention can be aqueous solutions, aqueous alcoholic and alcoholic solutions. The dioxidine solutions according to the present invention can be isotonic solutions, hypotonic or hypertonic solutions. The most preferred are isotonic solutions of dioxidine, since they provide the most favorable conditions for epithelial cells and cells of the mucous membranes of the body. However, local application of dioxidine does not exclude the possibility of using hypertonic and hypotonic solutions, which, when applied topically, do not have pronounced adverse effects on the cells of the body.

An isotonic agent is a compound that is physiologically tolerable and provides the composition with a suitable tonicity to prevent the free passage of water through the cell membranes in contact with the composition. Agents for adjusting tonicity can be any pharmaceutically acceptable compounds and nonionic agents, including pharmaceutically acceptable salts (in particular sodium chloride), polyols (including sugar alcohols such as C3-6 sugar alcohol, glycerin, erythritol, traitol, arabitol, xylitol, ribitol, sorbitol, mannitol, dulcitol and iditol), sugars (in particular sucrose, fructose, dextrose or glucose) or amino acids (in particular glycine). As a solvent The solvent in aqueous solutions of dioxidine according to the present invention can be purified water, distilled water, water for injection, bidistilled water (which can be brought to isotonic solution by adding suitable pharmaceutically acceptable agents, for example, weighed portion of sodium chloride), sodium chloride solution , glucose solution, preferably isotonic.

The dioxidine solutions according to the present invention have a pH (pH, acidity) of 3.0 to 7.5. However, the authors of the present invention have found that the highest activity of dioxidine solutions, including the ability to accelerate wound healing, restore damaged epithelium, reduce complications during treatment, provide conditions for rapid epithelialization of epithelial lesions of the mucous membranes, as well as the highest stability of dioxidine solutions (photostability, resistance to self-oxidation, absence of microcrystals) is achieved at a pH value of 5.0 to 7.5, while the optimum properties of dioxidine solutions are manifested at a pH value of 5.2 to 7.2. Thus, more preferably, the dioxidine solutions of the present invention have a pH of 5.0 to 7.5, even more preferably, the dioxidine solutions of the present invention have a pH of 5.2 to 7.2. The pH of the dioxidine solutions of the present invention can be adjusted by adding organic or inorganic pharmaceutically acceptable acids and bases.

The subject of the present invention is the use of dioxidine in the form of a 0.001-0.4% solution for the treatment and / or prevention of infectious-inflammatory lesions of the epithelium and wound healing, more preferably in the form of a 0.01-0.4% solution, more preferably in the form 0.05-0.40% solution, more preferably 0.095-0.40% solution, more preferably 0.10-0.40% solution, more preferably 0.10-0.35 % solution, more preferably in the form of 0.10-0.30% solution, more preferably in the form of 0.10-0.25% solution, more preferably in the form of 0.10-0.20% solution, more preferably , in the form of 0.10-0.15% solution, for example, 0.01% solution, 0.05% solution, 0.10% solution, 0.15% solution, 0.20% solution, 0.25% solution , 0.30% solution, 0.35% solution or 0.40% solution.

More preferred is the application, where at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes.

More preferable is the application, where at least one infectious-inflammatory lesion of the genital organs is selected from the group consisting of infectious-inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum injuries, wounds of the perineum and vagina, postpartum infections and inflammatory diseases of the genital organs, such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis.

More preferred is the use where at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after trauma, wounds, burns, skin and mucous membrane lesions as a result of pyoderma, candidiasis and / or mycoses of the feet.

More preferred is the application where the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees and the preparation of burn wounds for dermatoplasty.

More preferable is the application where the infectious-inflammatory lesion of the genital organs has arisen as a result of mechanical damage to the epithelium after diagnostic or surgical procedures.

More preferable is the use where the infectious and inflammatory lesion of the genital organs has arisen as a result of postpartum trauma.

More preferable is the application, where the infectious and inflammatory lesion of the genital organs has arisen after the wounds of the perineum and vagina.

More preferable is the application, where the infectious and inflammatory lesion of the genital epithelium has arisen as a result of postpartum infections.

More preferred is the use where the infectious-inflammatory lesion of the genital organs is vulvovaginitis.

More preferred is the use where the genital infection is cervicitis.

More preferred is the use where the genital inflammatory lesion is endometritis.

More preferred is the use where the infectious-inflammatory lesion of the genital organs is an abscess of the uterus.

More preferred is the use where the infectious-inflammatory lesion of the genital organs is salpingo-oophoritis.

More preferred is the use where the at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma.

More preferred is the application where the infectious-inflammatory lesion of the skin and mucous membranes is candidiasis.

More preferred is the application where the infectious-inflammatory lesion of the skin and mucous membranes is mycosis of the feet.

More preferred is the use where the dioxidine solution is a 0.1% solution.

More preferred is the application where the dioxidine solution is a 0.25% solution.

More preferred is the application where the dioxidine solution is used as a spray or liquid for topical application.

More preferred is the application where the dioxidine solution is used 1 to 6 times a day.

More preferred is the application where the dioxidine solution is used 2 to 4 times a day.

More preferred is the application where the dioxidine solution is applied 3 times a day.

More preferred is the application where the dioxidine solution is applied for 1-7 days.

More preferred is the application where the dioxidine solution is applied for 10 days.

More preferred is the application where the dioxidine solution is applied for 14 days.

More preferred is the application where the dioxidine solution is applied for 21 days.

More preferred is the application where the dioxidine solution is applied for 30 days.

More preferred is the application where the dioxidine solution is applied in the form of drops.

More preferred is the use where the solution is a solution of dioxidine in water for injection.

More preferred is the application where the dioxidine solution has a pH of 3.0 to 7.5.

More preferred is the application where the dioxidine solution has a pH of 5.0 to 7.5.

More preferred is the application where the dioxidine solution has a pH of 5.2 to 7.2.

More preferred is the use where the dioxidine solution is an isotonic solution.

More preferred is an application where sodium chloride solution is used as the isotonic solvent.

More preferred is the use where the dioxidine solution is a hypotonic solution.

More preferred is the use where the dioxidine solution is a hypertonic solution.

More preferred is the use wherein the tonicity of the dioxidine solution is adjusted with a tonicity agent selected from the group consisting of pharmaceutically acceptable compounds, acids and bases, and nonionic agents, including pharmaceutically acceptable salts such as sodium chloride, polyols, sugar alcohols such as SZ-6 sugar alcohol, glycerin, erythritol, traitol, arabitol, xylitol, ribitol, sorbitol, mannitol, dulcite and idit; sugars such as sucrose, fructose, dextrose or glucose; or amino acids.

More preferred is the use where the dioxidine solution is an alcoholic solution.

More preferred is the use where the dioxidine solution is an aqueous alcoholic solution.

More preferred is the use where the dioxidine solution is an aqueous solution.

More preferable is the use, where the solvent is a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution.

The subject of the present invention is a method of using dioxidine in the form of a 0.001-0.4% solution for the treatment and / or prevention of infectious-inflammatory lesions of the epithelium and wound healing, comprising treating epithelial and wound lesions with a 0.001-0.4% solution of dioxidine, more preferably 0 , 01-0.4% solution, more preferably 0.05-0.40% solution, more preferably 0.095-0.40% solution, more preferably 0.10-0.40% solution, more preferably 0 , 10-0.35% solution, more preferably 0.10-0.30% solution, more preferably 0.10-0.25% solution, more preferably 0.10-0.20% solution, more preferably , 0.10-0.15% solution, for example, 0.01% solution, 0.05% solution, 0.10% solution, 0.15% solution, 0.20% solution, 0.25% solution, 0 , 30% solution, 0.35% solution or 0.40% solution.

More preferred is a process wherein the dioxidine solution has a pH of 3.0 to 7.5.

More preferred is a process wherein the dioxidine solution has a pH of 5.0 to 7.5.

More preferred is a process wherein the dioxidine solution has a pH of 5.2 to 7.2.

More preferred is a method wherein the dioxidine solution is an isotonic solution.

More preferred is a method where sodium chloride solution is used as the isotonic solvent.

More preferred is a method wherein the dioxidine solution is a hypotonic solution.

More preferred is a method wherein the dioxidine solution is a hypertonic solution.

More preferred is a method where the regulation of the tonicity of the dioxidine solution is carried out using a tonicity agent selected from the group consisting of pharmaceutically acceptable compounds, acids and bases, and non-ionic agents, including pharmaceutically acceptable salts such as sodium chloride, polyols, sugar alcohols such as SZ-6 sugar alcohol, glycerin, erythritol, traitol, arabitol, xylitol, ribitol, sorbitol, mannitol, dulcite and idit; sugars such as sucrose, fructose, dextrose or glucose; or amino acids.

More preferred is a method wherein the dioxidine solution is an alcoholic solution.

More preferred is a method wherein the dioxidine solution is an aqueous alcoholic solution.

More preferred is a method wherein the dioxidine solution is an aqueous solution.

More preferable is a method where a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution is used as a solvent.

More preferred is a method where at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes.

More preferable is the method, where at least one infectious-inflammatory lesion of the genital organs is selected from the group consisting of infectious-inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum injuries, wounds of the perineum and vagina, postpartum infections and inflammatory diseases of the genital organs, such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis.

More preferred is a method where at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after trauma, wounds, burns, skin and mucous membrane lesions as a result of pyoderma, candidiasis and / or mycoses of the feet.

More preferred is a method where the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees, and the preparation of burn wounds for dermatoplasty.

More preferable is the method, where the infectious and inflammatory lesion of the genital organs has arisen as a result of mechanical damage to the epithelium after diagnostic or surgical procedures.

More preferable is the method, where the infectious and inflammatory lesion of the genital organs has arisen as a result of postpartum trauma.

More preferable is the method, where the infectious-inflammatory lesion of the genitals has arisen after the wounds of the perineum and vagina.

More preferred is a method where an infectious-inflammatory lesion of the genital epithelium has arisen as a result of postpartum infections.

More preferable is the method, where the infectious-inflammatory lesion of the genital organs is vulvovaginitis.

More preferred is a method wherein the genital infection is cervicitis.

More preferred is a method wherein the genital inflammatory lesion is endometritis.

More preferred is a method where the infectious and inflammatory lesion of the genital organs is an abscess of the uterus.

More preferred is a method where the infectious-inflammatory lesion of the genital organs is salpingo-oophoritis.

More preferred is a method wherein at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma.

More preferred is a method wherein the infectious-inflammatory lesion of the skin and mucous membranes is candidiasis.

More preferred is a method where the infectious and inflammatory lesion of the skin and mucous membranes is mycosis of the feet.

More preferred is a method wherein the dioxidine solution is a 0.1% solution.

More preferred is a method wherein the dioxidine solution is a 0.25% solution.

More preferred is a method where the dioxidine solution is applied as a spray or liquid for topical application.

More preferred is a method where the dioxidine solution is applied 1 to 6 times a day.

More preferred is a method where the dioxidine solution is applied 2 to 4 times a day.

More preferred is the method where the dioxidine solution is applied 3 times a day.

More preferred is a method where the dioxidine solution is used for 1-7 days.

More preferred is a method where the dioxidine solution is applied for 10 days.

More preferred is a method where the dioxidine solution is applied for 14 days.

More preferred is a method where the dioxidine solution is applied for 21 days.

More preferred is a method where the dioxidine solution is applied for 30 days.

More preferred is a method where the dioxidine solution is applied in the form of drops.

More preferred is a method wherein the solution is a solution of dioxidine in water for injection.

More preferred is a method wherein the solution is an isotonic dioxidine solution.

More preferred is the method where the isotonic solution is a solution of dioxidine in isotonic sodium chloride solution.

Also, the subject of the present invention is a medicament for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium, and wound healing, which is a 0.001-0.40% dioxidine solution, more preferably 0.01-0.40% solution, more preferably 0.05-0.40% solution, more preferably 0.10-0.40% solution, more preferably 0.10-0.35% solution, more preferably 0.10-0.30% solution, more preferably 0.10-0.25% solution, more preferably 0.10-0.20% solution, more preferably 0.10-0.15% solution, e.g. 0.01% solution, 0.05% solution, 0.10% solution, 0.15% solution, 0.20% solution, 0.25% solution, 0.30% solution, 0.35% solution, 0.40% solution.

More preferred is a drug wherein the dioxidine solution has a pH of 3.0 to 7.5.

More preferred is a drug wherein the dioxidine solution has a pH of 5.0 to 7.5.

More preferred is a drug wherein the dioxidine solution has a pH of 5.2 to 7.2.

More preferred is a drug wherein the dioxidine solution is an isotonic solution.

More preferable is a medicament where sodium chloride solution is used as an isotonic solvent.

More preferred is a drug wherein the dioxidine solution is a hypotonic solution.

More preferred is a drug wherein the dioxidine solution is a hypertonic solution.

More preferable is a drug, where a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution is used as a solvent.

More preferred is a medicament where the regulation of the tonicity of the dioxidine solution is carried out using an agent for adjusting the tonicity selected from the group consisting of pharmaceutically acceptable compounds, acids and bases, and non-ionic agents, including pharmaceutically acceptable salts such as sodium chloride, polyols , sugar alcohols such as SZ-6 sugar alcohol, glycerin, erythritol, traitol, arabitol, xylitol, ribitol, sorbitol, mannitol, dulcitol and iditol, sugars such as sucrose, fructose, dextrose or glucose, or amino acids.

More preferred is a drug wherein the dioxidine solution is an alcoholic solution.

More preferred is a drug wherein the dioxidine solution is a water-alcohol solution.

More preferred is a drug wherein the dioxidine solution is an aqueous solution.

More preferable is a drug, where at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes.

More preferable is a drug, where at least one infectious-inflammatory lesion of the genital organs is selected from the group consisting of infectious-inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum injuries, wounds of the perineum and vagina, postpartum infections, and inflammatory diseases of the genital organs such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis.

More preferred is a drug, where at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after trauma, wounds, burns, skin and mucous membrane lesions as a result of pyoderma, candidiasis and / or mycoses of the feet.

More preferred is a drug, where the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees, and the preparation of burn wounds for dermatoplasty.

More preferable is a drug, where the infectious and inflammatory lesion of the genital organs has arisen as a result of mechanical damage to the epithelium after diagnostic or surgical procedures.

More preferable is the drug, where the infectious and inflammatory lesion of the genitals has arisen as a result of postpartum trauma.

More preferable is a drug, where the infectious and inflammatory lesion of the genitals has arisen after the wounds of the perineum and vagina.

More preferable is a drug where an infectious and inflammatory lesion of the genital epithelium has arisen as a result of postpartum infections.

More preferable is a drug where the infectious and inflammatory lesion of the genitals has arisen as a result of postpartum infections.

More preferred is a drug where the infectious-inflammatory lesion of the genital organs is vulvovaginitis.

More preferred is a drug wherein the genital infection is cervicitis.

More preferred is a drug wherein the genital infection is endometritis.

More preferable is a drug where the infectious-inflammatory lesion of the genital organs is an abscess of the uterus.

More preferred is a drug where the infectious and inflammatory lesion of the genital organs is salpingo-oophoritis.

More preferred is a medicament where at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma.

More preferred is a drug wherein the infectious-inflammatory lesion of the skin and mucous membranes is candidiasis.

More preferred is a drug where the infectious and inflammatory lesion of the skin and mucous membranes is mycosis of the feet.

More preferred is a drug wherein the dioxidine solution is a 0.1% solution.

More preferred is a drug wherein the dioxidine solution is a 0.25% solution.

More preferred is a medicament wherein the dioxidine solution is administered as a topical spray or liquid.

More preferred is a medicament wherein said agent is intended to be administered 1 to 6 times a day.

More preferred is a medicament, wherein said agent is intended to be administered 2 to 4 times a day.

More preferred is a medicament wherein said agent is intended to be administered 3 times a day.

More preferred is a medicament, wherein said agent is intended to be administered for 1-7 days.

More preferred is a medicament wherein said agent is intended to be used for 10 days.

More preferred is a medicament wherein said agent is intended to be used for 14 days.

More preferred is a medicament wherein said agent is intended to be used for 21 days.

More preferred is a medicament, wherein said agent is intended to be administered within 30 days.

Also, the subject of the present invention is a pharmaceutical composition for the treatment and / or prevention of infectious-inflammatory lesions of the epithelium, and wound healing, which is a 0.001-0.40% solution of dioxidine, more preferably 0.01-0.40% solution, more preferably 0.05-0.40% solution, more preferably 0.10-0.40% solution, more preferably 0.10-0.35% solution, more preferably 0.10-0.30% solution, more preferably 0.10-0.25% solution, more preferably 0.10-0.20% solution, more preferably 0.10-0.15% solution, e.g. 0.01% solution, 0.05% solution, 0.10% solution, 0.15% solution, 0.20% solution, 0.25% solution, 0.30% solution, 0.35% solution, 0.40% solution.

More preferred is a pharmaceutical composition wherein the dioxidine solution has a pH of 3.0 to 7.5.

More preferred is a pharmaceutical composition wherein the dioxidine solution has a pH of 5.0 to 7.5.

More preferred is a pharmaceutical composition wherein the dioxidine solution has a pH of 5.2 to 7.2.

More preferred is a pharmaceutical composition wherein the dioxidine solution is an isotonic solution.

More preferable is a pharmaceutical composition where sodium chloride solution is used as an isotonic solvent.

More preferred is a pharmaceutical composition wherein the dioxidine solution is a hypotonic solution.

More preferred is a pharmaceutical composition wherein the dioxidine solution is a hypertonic solution.

More preferred is a pharmaceutical composition, where a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution is used as a solvent.

More preferred is a pharmaceutical composition wherein the regulation of the tonicity of the dioxidine solution is carried out with a tonicity agent selected from the group consisting of pharmaceutically acceptable compounds, acids and bases, and non-ionic agents, including pharmaceutically acceptable salts such as sodium chloride, polyols , sugar alcohols such as SZ-6 sugar alcohol, glycerin, erythritol, traitol, arabitol, xylitol, ribitol, sorbitol, mannitol, dulcitol and iditol, sugars such as sucrose, fructose, dextrose or glucose, or amino acids.

More preferred is a pharmaceutical composition wherein the dioxidine solution is an alcoholic solution.

More preferred is a pharmaceutical composition wherein the dioxidine solution is an aqueous alcoholic solution.

More preferred is a pharmaceutical composition wherein the dioxidine solution is an aqueous solution.

More preferred is a pharmaceutical composition where at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes.

More preferable is a pharmaceutical composition, where at least one infectious and inflammatory lesion of the genital organs is selected from the group consisting of infectious and inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum trauma, perineal and vaginal wounds, postpartum infections, and inflammatory genital diseases. organs such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis.

More preferred is a pharmaceutical composition where at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after trauma, wounds, burns, skin and mucous membrane lesions as a result of pyoderma, candidiasis and / or mycoses of the feet.

More preferred is a pharmaceutical composition, where the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees, and the preparation of burn wounds for dermatoplasty.

More preferable is a pharmaceutical composition, where the infectious and inflammatory lesion of the genital organs has arisen as a result of mechanical damage to the epithelium after diagnostic or surgical procedures.

More preferred is a pharmaceutical composition where the infectious-inflammatory lesion of the genital organs has arisen as a result of postpartum trauma.

More preferable is a pharmaceutical composition, where the infectious-inflammatory lesion of the genital organs has arisen after the wounds of the perineum and vagina.

More preferred is a pharmaceutical composition where the infectious-inflammatory lesion of the genital epithelium has arisen as a result of postpartum infections.

More preferred is a pharmaceutical composition wherein the infectious-inflammatory lesion of the genital organs is vulvovaginitis.

More preferred is a pharmaceutical composition wherein the genital infection is cervicitis.

More preferred is a pharmaceutical composition wherein the genital infection is endometritis.

More preferred is a pharmaceutical composition where the infectious-inflammatory lesion of the genital organs is an abscess of the uterus.

More preferred is a pharmaceutical composition where the infectious-inflammatory lesion of the genital organs is salpingo-oophoritis.

More preferred is a pharmaceutical composition, where at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma.

More preferred is a pharmaceutical composition wherein the infectious-inflammatory lesion of the skin and mucous membranes is candidiasis.

More preferred is a pharmaceutical composition where the infectious-inflammatory lesion of the skin and mucous membranes is mycosis of the feet.

More preferred is a pharmaceutical composition wherein the dioxidine solution is a 0.1% solution.

More preferred is a pharmaceutical composition wherein the dioxidine solution is a 0.25% solution.

More preferred is a pharmaceutical composition wherein the Dioxidine solution is administered as a topical spray or liquid.

Also, the subject of the present invention is a finished dosage form for the treatment and / or prevention of infectious-inflammatory lesions of the epithelium, and wound healing, which is a 0.001-0.40% dioxidine solution, more preferably 0.01-0.40% solution, more preferably , 0.05-0.40% solution, more preferably 0.10-0.40% solution, more preferably 0.10-0.35% solution, more preferably 0.10-0.30% solution, more preferably 0.10-0.25% solution, more preferably 0.10-0.20% solution, more preferably 0.10-0.15% solution, for example 0.01% solution, 0.05 % solution, 0.10% solution, 0.15% solution, 0.20% solution, 0.25% solution, 0.30% solution, 0.35% solution, 0.40% solution.

More preferred is the finished dosage form, where the dioxidine solution has a pH of 3.0 to 7.5.

More preferred is a finished dosage form where the dioxidine solution has a pH of 5.0 to 7.5.

More preferable is the finished dosage form, where the dioxidine solution has a pH value of 5.2 to 7.2.

More preferred is a finished dosage form where the dioxidine solution is an isotonic solution.

More preferable is a finished dosage form, where sodium chloride solution is used as an isotonic solvent.

More preferred is the finished dosage form, where the dioxidine solution is a hypotonic solution.

More preferred is the finished dosage form, where the dioxidine solution is a hypertonic solution.

More preferable is the finished dosage form, where a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution is used as a solvent.

More preferred is a finished dosage form, where the regulation of the tonicity of the dioxidine solution is carried out using an agent for adjusting the tonicity selected from the group consisting of pharmaceutically acceptable compounds, acids and bases, and nonionic agents, including pharmaceutically acceptable salts such as sodium chloride, polyols, sugar alcohols such as C3-6 sugar alcohol, glycerin, erythritol, traitol, arabitol, xylitol, ribitol, sorbitol, mannitol, dulcitol and iditol, sugars such as sucrose, fructose, dextrose or glucose, or amino acids.

More preferred is a finished dosage form where the dioxidine solution is an alcohol solution.

More preferable is the finished dosage form, where the dioxidine solution is a water-alcohol solution.

More preferred is a finished dosage form where the dioxidine solution is an aqueous solution.

More preferable is a finished dosage form, where at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes.

More preferable is the finished dosage form, where at least one infectious-inflammatory lesion of the genital organs is selected from the group consisting of infectious-inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum injuries, wounds of the perineum and vagina, postpartum infections, and inflammatory diseases of the genital organs such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis.

More preferable is the finished dosage form, where at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after trauma, wounds, burns, skin lesions and mucous membranes as a result of pyoderma, candidiasis and / or mycoses of the feet.

More preferable is the finished dosage form, where the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees, and the preparation of burn wounds for dermatoplasty.

More preferable is the finished dosage form, where the infectious-inflammatory lesion of the genitals arose as a result of mechanical damage to the epithelium after diagnostic or surgical procedures.

More preferable is the finished dosage form, where the infectious-inflammatory lesion of the genitals has arisen as a result of postpartum trauma.

More preferable is the finished dosage form, where the infectious-inflammatory lesion of the genitals arose after the wounds of the perineum and vagina.

More preferable is the finished dosage form, where the infectious and inflammatory lesion of the epithelium of the genital organs has arisen as a result of postpartum infections.

More preferable is the finished dosage form, where the infectious-inflammatory lesion of the genital organs is vulvovaginitis.

More preferable is the finished dosage form, where the infectious-inflammatory lesion of the genital organs is cervicitis.

More preferable is the finished dosage form, where the infectious and inflammatory lesion of the genital organs is endometritis.

More preferable is the finished dosage form, where the infectious-inflammatory lesion of the genital organs is an abscess of the uterus.

More preferable is the finished dosage form, where the infectious-inflammatory lesion of the genital organs is salpingo-oophoritis.

More preferred is a finished dosage form, where at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma.

More preferred is a finished dosage form, where the infectious-inflammatory lesion of the skin and mucous membranes is candidiasis.

More preferred is the finished dosage form, where the infectious and inflammatory lesion of the skin and mucous membranes is mycosis of the feet.

More preferred is a finished dosage form where the dioxidine solution is a 0.1% solution.

More preferred is a finished dosage form where the dioxidine solution is a 0.25% solution.

More preferred is a finished dosage form where the dioxidine solution is used as a spray or liquid for topical application.

More preferred is the finished dosage form, where the dioxidine solution is used 1 to 6 times a day.

More preferred is a finished dosage form where the dioxidine solution is used 2 to 4 times a day.

More preferable is the finished dosage form, where the dioxidine solution is applied 3 times a day.

More preferable is the finished dosage form, where the dioxidine solution is used within 1-7 days.

More preferred is a finished dosage form where the dioxidine solution is used for 14 days.

More preferred is the finished dosage form where the dioxidine solution is used for 21 days.

More preferable is the finished dosage form, where the dioxidine solution is used for 30 days.

Also, the subject of this invention is a kit for the treatment and / or prevention of infectious-inflammatory lesions of the epithelium, comprising a bottle with a drug according to the present invention, a pharmaceutical composition according to the present invention or a finished dosage form according to the present invention, at least one nozzle selected from the group, consisting of a spray nozzle, a dropper nozzle and a gynecological nozzle, and instructions for use.

The examples below illustrate, but do not cover all possible embodiments of the invention and do not limit the invention.

Example 1. Obtaining solutions of dioxidine.

Method for preparing dioxidine solutions 1.

10 g of dioxidine was mixed with 1000 ml of water for injection. Then the solution was filtered, diluted with water for injection, and the corresponding weighed portions of NaCl were added to obtain isotonic solutions with dioxidine concentrations of 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5, and 1%. The resulting solutions were filtered and placed in 10 ml ampoules, which were sealed. The pH of the solutions was in the range from 5.2 to 7.2.

Method for preparing dioxidine solutions 2.

10 g of dioxidine was mixed with 1000 ml of isotonic 0.9% NaCl solution. The resulting solution was filtered and diluted with isotonic 0.9% NaCl solution to dioxidine concentrations of 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5, and 1%. The obtained isotonic solutions of dioxidine were filtered and placed in 10 ml ampoules, which were sealed. The pH of the solutions was in the range from 5.2 to 7.2.

Method for preparing dioxidine solutions 3.

We purchased a ready-made solution of dioxidine 10 mg / ml (1%), manufactured by Valenta Pharm JSC, ampoules of 10 ml, diluted with water for injection and added the corresponding weighed portions of NaCl until isotonic solutions were obtained with dioxidine concentrations of 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1%. The pH of the solutions was in the range from 5.2 to 7.2.

Dioxidine solutions prepared according to Production Method 1, Production Method 2 and Production Method 3 did not show statistically significant (p <0.05) differences in the activity and stability of the dioxidine molecule. The following examples show data on dioxidine solutions prepared according to Production Method 2.

Example 2. Study of the photostability of dioxidine solutions.

Photostability was studied on a series of 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1.0% dioxidine solutions obtained in Example 1, which were placed in chemically inert transparent containers with a volume 10 ml.

The light source was an artificial daylight fluorescent lamp emitting in the visible and ultraviolet (UV) ranges, equivalent to the emission standard D65 / ID65. The samples were exposed to light providing illumination of at least 1.2 Mill. Lux / hr and the total energy of the ultraviolet spectrum near at least 200 W × h / m ² during the day [12].

Dioxidine concentration was determined by HPLC (Table 1). The initial concentration of dioxidine in the corresponding solutions 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1.0% was taken as 100%.

Sequentially chromatographed 0.02 ml of the test solution, obtaining at least five chromatograms for each of the solutions. Chromatogram registration time - not less than 6-fold retention time of the main peak of hydroxymethylquinoxylindoxide. The retention time of hydroxymethylquinoxylindoxide was about 4.4 min [13].

Table 1. The amount of dioxidine in% of the initial content according to HPLC.

Irradiation time, h Dioxidine solution concentration,% 0.001 0.01 0.1 0.25 0.3 0,4 0.5 1,0 0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 4 88.0 ± 0.2 90.1 ± 0.1 95.0 ± 0.1 93.2 ± 0.1 89.6 ± 0.1 86.0 ± 0.2 87.6 ± 0.2 81.2 ± 0.2 8 86.5 ± 0.2 87.1 ± 0.1 91.6 ± 0.1 88.0 ± 0.2 85.0 ± 0.2 82.4 ± 0.3 77.8 ± 0.2 73.6 ± 0.3 12 80.2 ± 0.3 84.2 ± 0.2 87.4 ± 0.2 86.2 ± 0.2 82.8 ± 0.2 79.2 ± 0.2 74.8 ± 0.2 68.4 ± 0.6 18 77.8 ± 0.3 81.9 ± 0.3 85.6 ± 0.2 83.4 ± 0.2 81.4 ± 0.2 77.2 ± 0.3 71.2 ± 0.2 66.0 ± 0.5 24 75.1 ± 0.5 80.6 ± 0.3 85.0 ± 0.3 82.0 ± 0.3 80.2 ± 0.2 75.0 ± 0.3 70.4 ± 0.4 65.0 ± 0.9

It was found that after one day of irradiation, the solutions of dioxidine 0.001, 0.01, 0.1, 0.25, 0.3, 0.4% according to the present invention had statistically significant better indicators of chemical purity compared to solutions with concentrations of 0.5 and 1.0%, which indicates that the aqueous solutions of dioxidine according to the present invention have better stability indicators than solutions with concentrations of 0.5 and 1% with a statistical significance level of p <0.05.

Example 3. Study of the resistance of dioxidine to self-oxidation in stress tests.

The resistance to self-oxidation of dioxidine in aqueous solutions was studied on a series of solutions of dioxidine 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1.0%, prepared according to example 1, and placed in ampoules of 10 ml, which were sealed. For better visualization of self-oxidation processes, ampoules with dioxidine solutions were placed in a thermostat at 70 ℃ (normal storage conditions for dioxidine solutions suggest storage in a place inaccessible to light at 15-25 ℃) [12]. The results of the study are presented in Table 2.

Dioxidine concentration was determined by HPLC (Table 2 and Table 3). The initial concentration of dioxidine in the corresponding solutions 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1.0% was taken as 100%.

Sequentially chromatographed 0.02 ml of the test solution, obtaining at least five chromatograms for each of the solutions. The chromatogram registration time is not less than 6 times the retention time of the main peak of hydroxymethylquinoxylindoxide [13].

Table 2. The amount of dioxidine in% of the initial content according to HPLC data in an aqueous solution when heated to 70 ℃.

Storage time, h Dioxidine concentration in solution,% 0.1 0.25 0.3 0,4 0.5 1,0 0 100.0 100.0 100.0 100.0 100.0 100.0 five 99.9 ± 0.1 99.8 ± 0.1 99.7 ± 0.1 99.7 ± 0.2 99.6 ± 0.2 99.1 ± 0.3 ten 99.8 ± 0.1 99.7 ± 0.2 99.7 ± 0.2 99.5 ± 0.2 99.2 ± 0.2 98.3 ± 0.2 15 99.8 ± 0.1 99.6 ± 0.2 99.5 ± 0.2 99.3 ± 0.3 98.9 ± 0.3 97.6 ± 0.4 20 99.7 ± 0.2 99.6 ± 0.2 99.4 ± 0.5 99.1 ± 0.2 98.5 ± 0.3 97.1 ± 0.4 thirty 99.6 ± 0.2 99.4 ± 0.3 99.3 ± 0.2 98.8 ± 0.3 97.9 ± 0.4 96.7 ± 0.5 45 99.5 ± 0.3 99.4 ± 0.3 99.1 ± 0.2 98.3 ± 0.4 96.8 ± 0.5 95.2 ± 0.6

It was found that by the end of the second day of heating, dioxidine solutions according to the present invention had better stability indicators (resistance to self-oxidation) compared to solutions with concentrations of 0.5 and 1.0% with a statistical significance level of p <0.05.

Thus, aqueous 0.001, 0.01, 0.1, 0.25, 0.3, 0.4% dioxidine solutions according to the present invention have better stability indicators than solutions with concentrations of 0.5 and 1%. In this connection, in the solutions of dioxidine according to the present invention, there will be no change in the concentration of dioxidine as a result of its self-oxidation, which determines their safety and proper effectiveness during the entire storage period.

Example 4. Study of the antimicrobial activity of dioxidine solutions against potential causative agents of various infections in the field of surgery, gynecology and dermatology.

The study is carried out on a panel of 39 strains of bacteria and fungi (Table 3) on a series of solutions of dioxidine 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1.0%.

Table 3. Tested strains of microorganisms

Bacterial species (gram - + / -) Strain code Bacterial species (gram - + / -) Strain code Facultative anaerobes Serratia marcescens (-) ATCC 29021 Staphylococcus aureus (+) ATCC 29213 Citrobacter werkmanii (-) ATCC 51114 Staphylococcus aureus (+) NRS384 * Aerobic bacteria Staphylococcus aureus (+) NRS123 * Haemophilus influenzae (-) ATCC 49247 Staphylococcus aureus (+) NRS100 * Pseudomonas aeruginosa (-) ATCC 27853 Staphylococcus aureus (+) NRS70 * Stenotrophomonas maltophilia (-) ATCC 700267 Staphylococcus aureus (+) NRS382 * Acinetobacter baumannii (-) ATCC 17978 Staphylococcus aureus (+) NRS483 * Moraxella catarrhalis (-) ATCC 43617 Staphylococcus aureus (+) NRS71 * Neisseria meningitidis (-) ATCC 13077 Staphylococcus aureus (+) NRS112 * Anaerobic bacteria Staphylococcus aureus (+) NRS1 * Peptostreptococcus anaerobius (+) ATCC 27337 Staphylococcus epidermidis (+) ATCC 35983 Bacterioides fragilis (-) ATCC 25285 Streptococcus pneumoniae (+) ATCC 49619 Treponema denticola (-) ATCC 35405 Streptococcus pyogenes (+) ATCC BAA-572 Porphyromonas gingivalis (-) ATCC 33277 Streptococcus oralis (+) ATCC 55229 Fusobacterium nuclеatum (-) ATCC 25586 Enterococcus faecalis (+) ATCC 29212 Prevotella intermedia (-) ATCC 25611 Enterococcus faeclum (+) ATCC 700221 Aggregatibacter actinomycetemcomitans (-) ATCC 33384 Escherichia coli (-) ATCC 25922 Actinomyces israelii (+) ATCC 23860 Klebsiella pneumoniae (-) ATCC 43816 Mushrooms Enterobacter cloacae (-) ATCC 222 Candida albicans ATCC 10231 Enterobacter aerogenes (-) ATCC 13048 Aspergillus niger ATCC 16404 Proteus mirabilis (-) ATCC 29906 Candida glabrata ATCC 60406

Notes: * MRSA (methicillin-resistant Staphylococcus aureus)

39 96-well plates were used to test the antimicrobial activity of dioxidine, each plate was used to determine the antimicrobial activity of dioxidine solutions against one of the bacterial or fungal strains (see Table 3). All operations were performed in compliance with sterility requirements. In 55 wells of the plate, 100 μl of a suitable medium for the cultivation of the strain were sequentially introduced, then 100 μl of the cell suspension of the corresponding strain were added and thoroughly mixed. Then, 100 μL of 0.001% dioxidine solution was sequentially introduced into five wells of the plate and the resulting mixture was thoroughly mixed again. A similar procedure was performed for all subsequent concentrations of dioxidine solutions up to 1% solution. Wells 51 to 55 of the plate did not add dioxidine solution, they only contained culture medium and cell suspension, and served as a control. The plate was then incubated under conditions optimal for the given strain [14]. After 24 hours, the results were checked by viewing the plates in transmitted light and determining the optical density (OD) of the cell culture in the wells using a microplate reader [15]. The growth of the culture in the presence of dioxidine was compared with the growth of the culture in five control wells.

All series of dioxidine solutions were highly active against all tested bacterial strains and Candida albicans fungi, inhibiting cell growth. The Aspergillus niger fungal strain showed resistance to dioxidine.

Thus, dioxidine solutions with concentrations of 0.001, 0.01, 0.1, 0.25, 0.3, 0.4% showed high antibacterial activity, comparable to currently used solutions with concentrations of 0.5 and 1.0 %.

Example 5. Study of dioxidine solutions according to the invention in the treatment of epithelial lesions in an open wound model in mice.

The study used 90 female Wistar rats, which were randomly divided into 9 groups, in each experimental group 10 animals: dioxidine 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1.0%, as well as the control group. Dioxidine solutions were prepared according to example 1. Rats were housed in five rats in temperature-controlled boxes (with an average temperature of 21 ° C) with a 12-hour day and night cycle and with sufficient water and food.

An in vivo wound healing experiment was carried out in mice. Two full-length wounds with a diameter of 6 mm were created on the back of each mouse. A silicone rubber ring with an inner diameter of 6 mm was adhered to the skin around the wound to prevent wound shrinkage and allow wound healing through granulation tissue formation and re-epithelialization, a process similar to that in humans [16]. Each group of animals, with the exception of the control one, was treated with a dioxidine solution with the corresponding concentration 3 times a day. The wounds in the control group were treated with isotonic NaCl solution. On days 3, 5 and 7 after the start of the experiment, the rats were examined to assess the degree of wound healing (by the area of wound epithelialization, which was calculated in% as the ratio of the total area of epithelialization sites in the wound to the total area of the wound). The data obtained are presented in table 5 with a statistical significance level of p <0.05.

Table 5. Area of epithelialization of wounds in rats of each control group in%.

Wound inspection day Wound epithelialization area in experimental groups of rats,% control 0.001 * 0.01 * 0.1 * 0.25 * 0.3 * 0.4 * 0.5 * 1.0 * 0 0 0 0 0 0 0 0 0 0 3 16.9 ± 0.7 22.4 ± 0.8 23.1 ± 0.7 25.7 ± 0.7 26.1 ± 0.6 26.3 ± 0.7 24.1 ± 0.8 22.6 ± 0.8 21.9 ± 0.7 five 34.3 ± 1.6 51.2 ± 1.6 52.4 ± 1.8 56.1 ± 1.6 53.3 ± 1.5 51.7 ± 1.7 49.5 ± 1.6 48.2 ± 1.7 44.6 ± 1.8 7 61.4 ± 2.2 86.9 ± 3.1 87.9 ± 3.3 88.6 ± 3.2 89.1 ± 3.4 88.4 ± 3.3 87.4 ± 3.4 86.1 ± 3.4 82.8 ± 3.6

* The numbers indicated as the designation of the experimental group correspond to the concentration of dioxidine in the solution with which the rat wounds were treated.

In all experimental groups of animals, with the exception of the control, there were marked signs of wound healing, however, the best results were shown by groups that were treated with wounds with 0.1, 0.25, 0.3% dioxidine solutions, respectively. Already on the third day, all experimental groups of animals showed a significant amount of granulation tissue. The presented data indicate that wound healing when using 0.001, 0.01, 0.1, 0.25, 0.3 and 0.4% dioxidine solutions occurs statistically significantly (p <0.05) more efficiently than when using 0.5% and 1% dioxidine solutions.

Example 6. Investigation of dioxidine solutions according to the present invention in the treatment of epithelial lesions in a human cell culture model.

The experiment was carried out on human skin culture. In total, 8 different concentrations of dioxidine solution were tested to assess its effect on the rate of wound healing - 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 or 1%, obtained according to example 1 ...

Circular skin membranes were prepared and cultured in an air-liquid culture system [17]. After removal of subcutaneous fat, circular skin membranes with a diameter of 16 mm were excised, followed by washing at 32 ° C in Hank's balanced salt solution supplemented with fungizone, L-glutamine and gentamicin to disinfect the skin. Skin membranes were cultured in an air-liquid system in 6-well plates in a humidified incubator at 32 ° C, 5% CO ₂ and 40% O ₂ , skin membranes in each plate constituted the experimental group 0.001, 0.01, 0.1, 0 , 25, 0.3, 0.4, 0.5 or 1%, corresponding to the studied concentration of dioxidine solution, and also one plate contained a control group. Culture medium containing a mixture of Dulbecco's Modified Eagle's Medium (DMEM) and Ham's F-12 + glutamax-I (3: 1) supplemented with 10% fetal calf serum (FCS), L-glutamine, human epidermal growth factor and hydrocortisone was renewed daily ... The experiment was carried out after three days of cultivation [18].

Using a pipette tip, a wound of the monolayer was applied, after which the medium was removed, the skin membranes were washed with Hanks solution, and fresh culture medium was added [19]. After that, the corresponding concentrations of dioxidine 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5, or 1% were added to each well of the plates with the experimental groups, and isotonic NaCl solution. The intensity of wound healing with the use of dioxidine solutions was assessed after 48 hours by means of the MTT test according to the degree of regeneration of the monolayer of the experimental group in relation to the control, expressed in% [20].

In FIG. 1 shows the effectiveness of wound healing when using 0.001, 0.01, 0.1, 0.25, 0.3, 0.4, 0.5 and 1% dioxidine solutions.

The presented data indicate that the use of dioxidine solutions improves the regeneration of the monolayer, epithelialization processes and, thus, accelerates wound healing. In this case, wound healing when using 0.001, 0.01, 0.1, 0.25, 0.3 and 0.4% dioxidine solutions is statistically significantly more efficient than when using 0.5% and 1% dioxidine solutions.

The invention can be used in medicine, chemistry, pharmaceutical industry.

List of references.

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Claims (109)

1. The use of dioxidine in the form of 0.001-0.4 w / v% aqueous solution for topical use for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium and wound healing, where the dioxidine solution has a pH value of 3 to 7.5. 2. Use according to claim 1, characterized in that at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genital organs, skin and mucous membranes. 3. Use according to claim 2, characterized in that at least one infectious and inflammatory lesion of the genital organs is selected from the group consisting of infectious and inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum trauma, perineal and vaginal wounds, postpartum infections and inflammatory diseases of the genital organs such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis. 4. The use according to claim 2, characterized in that at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after trauma, wounds, burns, skin lesions and mucous membranes as a result of the development of pyoderma, candidiasis and / or mycoses of the feet. 5. Use according to claim 4, characterized in that the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees and the preparation of burn wounds for dermatoplasty. 6. Application according to PP. 2, 3, characterized by the fact that the infectious and inflammatory lesion of the genitals arose as a result of mechanical damage to the epithelium after diagnostic or surgical procedures. 7. Application according to PP. 2, 3, characterized by the fact that the infectious and inflammatory lesion of the genitals arose as a result of postpartum trauma. 8. Application according to PP. 2, 3, characterized by the fact that an infectious-inflammatory lesion of the genital organs occurred after wounds of the perineum and vagina. 9. Application according to PP. 2, 3, characterized by the fact that the infectious-inflammatory lesion of the genitals arose as a result of postpartum infections. 10. Application according to PP. 2, 3, characterized by the fact that the infectious and inflammatory lesion of the genital organs is vulvovaginitis. 11. Application according to PP. 2, 3, characterized by the fact that the infectious-inflammatory lesion of the genital organs is cervicitis. 12. Application according to PP. 2, 3, characterized by the fact that the infectious and inflammatory lesion of the genital organs is endometritis. 13. Application according to PP. 2, 3, characterized by the fact that the infectious and inflammatory lesion of the genital organs is an abscess of the uterus. 14. Application according to PP. 2, 3, characterized by the fact that the infectious-inflammatory lesion of the genital organs is salpingo-oophoritis. 15. Application according to PP. 2, 4, characterized in that at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma. 16. Application according to PP. 2, 4, characterized in that the infectious and inflammatory lesion of the skin and mucous membranes is candidiasis. 17. Application according to PP. 2, 4, characterized in that the infectious-inflammatory lesion of the skin and mucous membranes is mycosis of the feet. 18. Use according to claim 1, characterized in that the dioxidine solution is a 0.1 w / v% solution. 19. Use according to claim 1, characterized in that the dioxidine solution is a 0.25 w / v% solution. 20. Use according to claim 1, 18, 19, characterized in that the dioxidine solution is used in the form of a spray or liquid for topical use. 21. Use according to claim 1, characterized in that the dioxidine solution is used from 1 to 6 times a day. 22. Use according to claim 1, characterized in that the dioxidine solution is used 2 to 4 times a day. 23. Use according to claim 1, characterized in that the dioxidine solution is used 3 times a day. 24. Application according to PP. 21-23, characterized in that the dioxidine solution is used for 1-7 days. 25. Application according to PP. 21-23, characterized in that the dioxidine solution is used for 10 days. 26. Application according to PP. 21-23, characterized in that the dioxidine solution is used for 14 days. 27. Application according to PP. 21-23, characterized in that the dioxidine solution is used for 21 days. 28. Application according to PP. 21-23, characterized in that the dioxidine solution is used within 30 days. 29. Use according to claim 1, characterized in that the solvent is a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution. 30. Use according to claim 1, characterized in that the solution is an isotonic solution of dioxidine. 31. Use according to claim 30, characterized in that the isotonic solution is a dioxidine solution in an isotonic sodium chloride solution. 32. Use according to claim 1, characterized in that the solution is a hypotonic dioxidine solution. 33. Use according to claim 1, characterized in that the solution is a hypertonic dioxidine solution. 34. A drug for local use for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium and wound healing, which is an aqueous 0.001-0.4 w / v% dioxidine solution, where the dioxidine solution has a pH value of 3 to 7, five. 35. A medication according to claim 34, characterized in that the dioxidine solution is an isotonic solution. 36. A medicinal product according to claim 35, wherein a sodium chloride solution is used as an isotonic solvent. 37. A drug according to claim 34, characterized in that the dioxidine solution is a hypotonic solution. 38. A drug according to claim 34, characterized in that the dioxidine solution is a hypertonic solution. 39. A medicinal product according to claim 34, characterized in that the solvent is a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution. 40. A medicament according to claim 34, characterized in that at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes. 41. A drug according to claim 40, characterized in that at least one infectious and inflammatory lesion of the genital organs is selected from the group consisting of infectious and inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum injuries, wounds of the perineum and vagina, postpartum infections, and inflammatory diseases of the genital organs, such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis. 42. A medicinal product according to claim 40, characterized in that at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after injuries, wounds, burns, skin lesions and mucous membranes as a result of the development of pyoderma, candidiasis and / or mycoses of the feet. 43. A drug according to claim 42, characterized in that the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees and the preparation of burn wounds for dermatoplasty. 44. The drug according to PP. 40, 41, characterized in that the infectious-inflammatory lesion of the genital organs resulted from mechanical damage to the epithelium after diagnostic or surgical procedures. 45. The drug according to PP. 40, 41, characterized by the fact that the infectious and inflammatory lesion of the genitals arose as a result of postpartum trauma. 46. The drug according to PP. 40, 41, characterized by the fact that an infectious-inflammatory lesion of the genitals occurred after wounds of the perineum and vagina. 47. The drug according to PP. 40, 41, characterized by the fact that infectious and inflammatory lesions of the genital epithelium arose as a result of postpartum infections. 48. The drug according to PP. 40, 41, characterized in that the infectious and inflammatory lesion of the genital organs is vulvovaginitis. 49. The drug according to PP. 40, 41, characterized in that the infectious and inflammatory lesion of the genital organs is cervicitis. 50. The drug according to PP. 40, 41, characterized in that the infectious and inflammatory lesion of the genital organs is endometritis. 51. The drug according to PP. 40, 41, characterized in that the infectious-inflammatory lesion of the genital organs is an abscess of the uterus. 52. The drug according to PP. 40, 41, characterized by the fact that the infectious-inflammatory lesion of the genital organs is salpingo-oophoritis. 53. The drug according to PP. 40, 42, characterized in that at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma. 54. The drug according to PP. 40, 42, characterized in that the infectious-inflammatory lesion of the skin and mucous membranes is candidiasis. 55. The drug according to PP. 40, 42, characterized in that the infectious and inflammatory lesion of the skin and mucous membranes is mycosis of the feet. 56. A medicament according to claim 34, characterized in that the dioxidine solution is a 0.1 w / v% solution. 57. A medicament according to claim 34, characterized in that the dioxidine solution is a 0.25 w / v% solution. 58. A drug according to claim 34, characterized in that the dioxidine solution is used in the form of a spray or liquid for topical application. 59. A pharmaceutical composition for topical use for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium and wound healing, which is an aqueous 0.001-0.4 w / v% dioxidine solution, where the dioxidine solution has a pH of 3 to 7, five. 60. A pharmaceutical composition according to claim 59, characterized in that the dioxidine solution is an isotonic solution. 61. A pharmaceutical composition according to claim 60, wherein a sodium chloride solution is used as an isotonic solvent. 62. A pharmaceutical composition according to claim 59, characterized in that the dioxidine solution is a hypotonic solution. 63. A pharmaceutical composition according to claim 59, characterized in that the dioxidine solution is a hypertonic solution. 64. A pharmaceutical composition according to claim 59, characterized in that the solvent is a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution. 65. The pharmaceutical composition according to claim 59, characterized in that at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes. 66. The pharmaceutical composition according to claim 65, characterized in that at least one infectious and inflammatory lesion of the genital organs is selected from the group consisting of infectious and inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum injuries, perineal and vaginal wounds, postpartum infections and inflammatory diseases of the genital organs, such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis. 67. A pharmaceutical composition according to claim 65, characterized in that at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after trauma, wounds, burns, skin lesions and mucous membranes as a result of the development of pyoderma, candidiasis and / or mycoses of the feet. 68. A pharmaceutical composition according to claim 67, characterized in that the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees and the preparation of burn wounds for dermatoplasty. 69. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that the infectious and inflammatory lesion of the genitals arose as a result of mechanical damage to the epithelium after diagnostic or surgical procedures. 70. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that the infectious-inflammatory lesion of the genitals arose as a result of postpartum trauma. 71. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that an infectious-inflammatory lesion of the genital organs occurred after wounds of the perineum and vagina. 72. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that infectious and inflammatory lesions of the genital epithelium arose as a result of postpartum infections. 73. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that the infectious and inflammatory lesion of the genital organs is vulvovaginitis. 74. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that the infectious and inflammatory lesion of the genital organs is cervicitis. 75. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that the infectious and inflammatory lesion of the genital organs is endometritis. 76. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that the infectious and inflammatory lesion of the genital organs is an abscess of the uterus. 77. The pharmaceutical composition according to PP. 65, 66, characterized by the fact that the infectious and inflammatory lesion of the genital organs is salpingo-oophoritis. 78. The pharmaceutical composition according to PP. 65, 67, characterized in that at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma. 79. The pharmaceutical composition according to PP. 65, 67, characterized in that the infectious-inflammatory lesion of the skin and mucous membranes is candidiasis. 80. The pharmaceutical composition according to PP. 65, 67, characterized in that the infectious and inflammatory lesion of the skin and mucous membranes is mycosis of the feet. 81. A pharmaceutical composition according to claim 59, characterized in that the dioxidine solution is a 0.1 w / v% solution. 82. A pharmaceutical composition according to claim 59, characterized in that the dioxidine solution is a 0.25 w / v% solution. 83. A pharmaceutical composition according to claim 59, characterized in that the dioxidine solution is used in the form of a spray or liquid for topical use. 84. A finished dosage form for topical use for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium and wound healing, which is an aqueous 0.001-0.4 w / v% dioxidine solution, where the dioxidine solution has a pH value of 3 to 7 ,five. 85. The finished dosage form according to claim 84, characterized in that the dioxidine solution is an isotonic solution. 86. The finished dosage form according to claim 85, where sodium chloride solution is used as an isotonic solvent. 87. The finished dosage form according to claim 84, characterized in that the dioxidine solution is a hypotonic solution. 88. A finished dosage form according to claim 84, characterized in that the dioxidine solution is a hypertonic solution. 89. The finished dosage form according to claim 84, characterized in that the solvent is a solvent selected from the group consisting of purified water, distilled water, bidistilled water, water for injection, sodium chloride solution, glucose solution. 90. A finished dosage form according to claim 84, characterized in that at least one infectious-inflammatory lesion of the epithelium is selected from the group consisting of infectious-inflammatory lesions of the genitals, skin and mucous membranes. 91. A finished dosage form according to claim 84, characterized in that at least one infectious-inflammatory lesion of the genital organs is selected from the group consisting of infectious-inflammatory lesions of the genital organs after diagnostic or surgical procedures, postpartum injuries, perineal and vaginal wounds, postpartum infections and inflammatory diseases of the genital organs, such as vulvovaginitis, cervicitis, endometritis, uterine abscess and salpingo-oophoritis. 92. A finished dosage form according to claim 84, characterized in that at least one infectious-inflammatory skin lesion is selected from the group consisting of skin lesions after injuries, wounds, burns, skin lesions and mucous membranes as a result of the development of pyoderma, candidiasis and / or mycoses of the feet. 93. A finished dosage form according to claim 92, characterized in that the treatment of an infectious-inflammatory skin lesion includes the treatment of superficial and deep burns of II and IIIA degrees and the preparation of burn wounds for dermatoplasty. 94. The finished dosage form according to PP. 90, 91, characterized by the fact that the infectious-inflammatory lesion of the genitals arose as a result of mechanical damage to the epithelium after diagnostic or surgical procedures. 95. The finished dosage form according to PP. 90, 91, characterized by the fact that the infectious and inflammatory lesion of the genitals arose as a result of postpartum trauma. 96. The finished dosage form according to PP. 90, 91, characterized by the fact that an infectious-inflammatory lesion of the genitals occurred after wounds of the perineum and vagina. 97. The finished dosage form according to PP. 90, 91, characterized by the fact that infectious and inflammatory lesions of the genital epithelium arose as a result of postpartum infections. 98. The finished dosage form according to PP. 90, 91, characterized by the fact that the infectious and inflammatory lesion of the genital organs is vulvovaginitis. 99. The finished dosage form according to PP. 90, 91, characterized by the fact that the infectious and inflammatory lesion of the genital organs is cervicitis. 100 The finished dosage form according to PP. 90, 91, characterized by the fact that the infectious and inflammatory lesion of the genital organs is endometritis. 101. The finished dosage form according to PP. 90, 91, characterized by the fact that the infectious and inflammatory lesion of the genital organs is an abscess of the uterus. 102. The finished dosage form according to PP. 90, 91, characterized by the fact that the infectious and inflammatory lesion of the genital organs is salpingo-oophoritis. 103. The finished dosage form according to PP. 90, 92, characterized in that at least one infectious-inflammatory lesion of the skin and mucous membranes is pyoderma. 104. The finished dosage form according to PP. 90, 92, characterized in that the infectious and inflammatory lesion of the skin and mucous membranes is candidiasis. 105. The finished dosage form according to PP. 90, 92, characterized in that the infectious and inflammatory lesion of the skin and mucous membranes is mycosis of the feet. 106. The finished dosage form according to claim 84, characterized in that the dioxidine solution is a 0.1 w / v% solution. 107. The finished dosage form according to claim 84, characterized in that the dioxidine solution is a 0.25 w / v% solution. 108. A finished dosage form according to claim 84, characterized in that the dioxidine solution is used in the form of a spray or liquid for topical use. 109. A kit for the treatment and / or prevention of infectious and inflammatory lesions of the epithelium and wound healing, comprising a bottle with a drug according to any one of paragraphs. 34-58, a pharmaceutical composition according to any one of claims. 59-83 or a finished dosage form according to any one of paragraphs. 84-108, at least one nozzle selected from the group consisting of a spray nozzle, a dropper nozzle, and a gynecological nozzle, and instructions for use.

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