Combination of dexpanthenol, methyluracil and chloramphenicol for inhibiting inflammatory processes

Abstract

The present invention relates to medicine and the pharmaceutical industry, and more particularly to agents capable of inhibiting inflammatory processes, and even more particularly to agents that have an antimicrobial, sorptive, angioprotective and wound-healing effect on local inflammatory processes of the skin and soft tissues, for use in surgery, traumatology and dermatology. What is proposed in the present invention is a combination including dexpanthenol, methyluracil and chloramphenicol, and also a pharmaceutical composition based thereon.

Description

[0001] A COMBINATION OF DEXPANTHENOL, METHYLURACIL AND CHLORAMPHENICOL FOR INHIBITING INFLAMMATORY PROCESSES.

[0002] Description

[0003] The field of technology to which the invention relates

[0004] The present invention relates to medicine and the pharmaceutical industry, namely to agents having the ability to inhibit inflammatory processes, in particular having an antimicrobial, sorption, angioprotective and wound-healing effect on local inflammatory processes of the skin and soft tissues, used in surgery, traumatology and dermatology.

[0005] State of the art

[0006] Today, a pressing issue in modern medicine is the treatment of skin wounds, including contaminated ones, that occur in various patients, including those with complicated concomitant pathologies, such as diabetes mellitus, damage to the nervous system, allergic reactions, and other diseases that slow down the course of the wound healing process [Li S. et al. Imaging in chronic wound diagnostics / / Advances in wound care. - 2020. - V. 9. - No. 5. - P. 245-263].

[0007] The purulent-inflammatory process of soft tissue disease is a complex set of reactions that develop in the body in response to tissue damage. The course of the wound healing process is conventionally divided into three main phases.

[0008] Phase I is the inflammatory phase, consisting of two successive periods: vascular changes and wound cleansing through the suppression of microflora and the rejection (resorption) of non-viable tissue. During the vascular phase of the inflammatory phase, vessels in the tissues adjacent to the walls and base of the wound dilate; plasma exudation and the release of leukocytes from blood vessels begin and gradually increase. Exudate and cellular elements secreting proteolytic enzymes liquefy areas of dead tissue.

[0009] The vascular period gives way to a period of cleansing, liquefaction of necrotic tissue, and its rejection, along with small foreign bodies, which are removed from the wound by a flow of exudate, which takes on the character of pus. The presence of pus, a source of tissue decay, in the wound increases the concentration of para-aminobenzoic acid (PABA), which is essential for the vital activity of microorganisms.

[0010] In the first phase of the wound healing process, a characteristic feature of a purulent wound is the presence of purulent-necrotic detritus. Primary necrosis in the wound occurs as a result of direct mechanical trauma and microbial toxins in the damaged area. The mechanism of secondary necrosis is more complex. The development of purulent processes in the wound occurs through the destruction of the immunoleukocyte barrier by bacterial exotoxins and endotoxins, which have a necrotic effect on tissue, as well as by their proteolytic enzymes and hyaluronidase, which causes depolarization of the connective tissue matrix.

[0011] Thus, the infection penetrates deeper tissues, causing their necrosis and thereby creating favorable conditions for the continued growth of microorganisms. As cells are destroyed, proteolytic and other hydrolytic enzymes are released into the tissue, which have a damaging effect on the wound walls.

[0012] After wound cleansing, phase II of the wound healing process begins—the regeneration phase. This phase is characterized by the development of granulation tissue due to new capillary formation and the migration of a significant number of fibroblasts. The peak macrophage count is reached on the sixth day and remains high for two weeks. During this period, wound fibroblasts actively produce fibronectin and type III collagen, replacing the matrix they have lost. Gradually, this process is replaced by the production of type I collagen, the fibers of which are stabilized by mucopolysaccharides of the interstitial connective tissue. The synthesis of collagen and protein-polysaccharide complexes of the connective tissue matrix is ​​directly linked to the process of new capillary formation.

[0013] Forming tissues provide a unique biological basis from which collagen-producing fibroblasts migrate. In the early stages of wound healing, young microvessels deliver oxygen to the cells actively synthesizing proteins in the wound, as protein synthesis processes at the site of inflammation require significant energy. Wound epithelialization begins in the first hours after injury. Epithelial cells located at the wound margins shift toward the wound. During this period, they lose their differentiation. Granulation tissue becomes denser, and the number of microvessels, macrophages, mast cells, and fibroblasts decreases.

[0014] Within the first 24 hours, 2-4 layers of basal epithelial cells form. The epithelium may encroach on the fibrin covering the wound, leukocyte-necrotic masses, or granulation tissue. Wound epithelialization becomes strong only when the epithelium grows over the granulation tissue; otherwise, the epithelium dies. Epithelialization of small wounds occurs primarily through cell migration, beginning with the basal layer. Wounds larger than 0.1 cm undergo epithelialization not only through migration but also through mitotic division of epithelial cells. Differentiation of the migrating epidermis is already evident during the migration period. As the growing epithelium differentiates, granularity appears in the cells, the superficial layers undergo keratinization, and the basal layer of cells becomes structurally similar to transitional epithelium. The newly formed epithelial covering differs from the healthy one by the absence of sweat and sebaceous glands, as well as hair follicles.Currently, due to a decrease in the immune status and high allergy levels of patients, there is an increase in the number of wounds with a sluggish healing process.

[0015] Phase III—the scar organization and epithelialization phase—is characterized by a decrease in fibroblast numbers, a reduction in enzymatic activity, and the organization of collagen fibers under the influence of collagenase from the growing epidermis. Smooth muscle contraction causes the wound edges to converge. The initial, delicate collagen is replaced by stronger collagen, resulting in scar formation.

[0016] Normal wound healing, with the formation of a complete scar, is complete within 25-29 days of wound inception. However, signs of the transition from acute wound inflammation to chronicity are often detected. In such a wound, increased migration of mononuclear cells into the wound and decreased granulocyte cell numbers, as well as migration of T- and B-lymphocytes, are observed. A slower progression of the inflammatory process and a tendency toward chronicity may be due to the progression of an autoimmune mechanism.

[0017] The listed phases of the wound healing process are observed in all wounds, but they are expressed to varying degrees, depending on the type of healing: primary intention, secondary intention, or under a scab - the phase of regeneration, formation and maturation of granulation tissue.

[0018] There is no sharp boundary between the phases. Moreover, in extensive wounds with jagged, contused edges, all three phases can be observed simultaneously. While in one area the wound has already cleared and is filling with granulation tissue, in another, young granulation tissue is still growing at the wound base, and in a third, the protracted period of clearing, i.e., the first inflammatory phase, is still ongoing, with clearly visible areas of necrotic tissue, separated from adjacent tissue by growing granulation tissue. Fresh wounds, before they become covered with granulation tissue, are capable of absorbing toxins, bacteria, and tissue breakdown products. Wounds covered with granulation tissue have virtually no absorptive capacity.

[0019] The development of microorganism resistance to drugs widely used in clinics dictates the need to develop and implement new complex drugs with a broad spectrum of therapeutic activity not only in relation to the aerobic but also the anaerobic component and fungi, as well as for the corresponding phases of the wound process.

[0020] It should be noted that all traumatic wounds, most burn wounds and many surgical wounds are initially contaminated with microbes.

[0021] The objective of the present invention is to create a pharmaceutical combination in the form of a liquid, soft, solid and / or gaseous dosage form based on -2,4-dihydroxy-M-(3-hydroxypropyl)-3,3-dimethylbutaneamide (dexpatenol), dioxomethyltetrahydropyrimidine (methyluracil) and chloramphenicol, providing treatment of purulent wounds and burns, purulent-inflammatory diseases of the skin, etc. and improving the conditions for cleansing wounds from purulent necrotic tissue, suppressing the growth of microflora, reducing the duration of the acute purulent process.

[0022] When using the proposed invention, the following technical results can be obtained: increased therapeutic activity in comparison with known drugs, improved course of the wound process, rapid wound cleansing, reduced content of purulent discharge and signs of local inflammatory reactions, reduced wound healing time, relief of local inflammatory processes.

[0023] To solve the stated problem, the present invention proposes a pharmaceutical combination for external and topical use, containing K-2,4-dihydroxy-TH-(3-hydroxypropyl)-3,3-dimethylbutanamide (dexpatenol), dioxomethyltetrahydropyrimidine (methyluracil) and chloramphenicol. The essence of the invention

[0024] The present invention provides a combination of three compounds, in particular the combination according to the present invention includes dexpanthenol, dioxomethyltetrahydropyrimidine (methyluracil) and chloramphenicol.

[0025] The combinations of the present invention may contain the said three components in any ratio, wherein each of the said components is contained in the combination in an effective amount.

[0026] Within the framework of the present invention, the said effective amount is an amount sufficient to exhibit the effect inherent in each of the components individually, or to exhibit the effect of combined action. In particular, such effects may be, for example, the prevention and / or treatment of diseases and / or disorders selected from the group including disorders of the skin, integuments and mucous membranes, various skin lesions, dry skin when the integrity of its integuments is compromised, skin damage, burns, abrasions, skin irritations, chronic ulcers, bedsores, skin cracks, purulent wounds, including those infected with mixed microflora (including staphylococci, Pseudomonas aeruginosa and Escherichia coli), bacterial skin infections, incl.boils, wounds, including deep and long-term non-healing wounds, slowly healing wounds, infected burns, trophic ulcers, bone fractures, photodermatitis, cuts, diaper rash, inflamed splinters, ingrown nails, inflammatory processes and disorders of the mucous membranes, for example, with damage to the gums, cornea, cracks in the heels and soles, skin damage in chronic skin diseases, skin diseases of various origins, characterized by a violation of the integrity of the skin or the presence of an inflammatory process, treatment of the skin, herpes, including at the stage of crust formation, various abscesses, weeping wounds, complications of long-term inflammatory processes.

[0027] As used in the present invention, the term "combination" means a composition containing at least three components: dexpanthenol, dioxomethyltetrahydropyrimidine (methyluracil) and chloramphenicol, in any amount other than zero.

[0028] As used in the present invention, the term "composition" means a composition comprising the above-mentioned combination according to the invention and at least one additional component selected from active or excipient substances. The term "pharmaceutical composition," as used in the present invention, means a composition comprising the combination according to the invention and at least one pharmaceutically acceptable substance, including, without limitation, carriers, diluents, buffers, solubilizers, etc.

[0029] As noted above, the ratio of components in the claimed combination can be any ratio that achieves the composition's effectiveness. A qualified specialist can easily select the necessary ratios and quantities, based on the following recommended component contents in the final composition / preparation:

[0030] Dexpanthenol - from 1.0 to 20.0 wt.% of the final composition, preferably from 5.0 to 10.0 wt.%.

[0031] Chloramphenicol - from 0.250 to 20.000% by weight of the final composition, preferably from 0.250 to 10.000%

[0032] Methyluracil - from 0.05 to 20.00 wt.% of the final composition, preferably from 0.05 to 10%

[0033] Thus, the compositions of the invention contain from 1 to 20 wt. % dexpanthenol, including all intermediate values, i.e. 1%, 1.1%, 1.2%, 1.3% up to 19.8%, 19.9%, 20%, from 0.250 to 20.000 wt. % chloramphenicol, including all intermediate values, i.e. 0.250%, 0.255%, 0, 260% up to 19.990%, 19.995%, 20.000%, from 0.05 to 20.00 wt. % methyluracil, including all intermediate values, i.e. 0.05%, 0.1%, 0.15% up to 19.90%, 19.95%, 20.00%. In one embodiment of the present invention, the claimed combination contains dexpanthenol, methyluracil and chloramphenicol in the following ratios by weight: (1 -98):(1 -98):(0.01 - 10), including all intermediate values, for example 1:1:0.01, 1:1:0.1, 1:2:0.01, 2:1:0.01, 2:2:0.01, 1:2:0.1, 2:1:0.1, etc.The preferred ratios of the claimed substances are 1:8:1.5, 1:4:0.75, 5:4:0.75, 25:4:0.75, 50:4:0.75, the most preferred ratio is 5:4:0.75 by weight for dexpanthenol, methyluracil and chloramphenicol, respectively.

[0034] The combinations according to the invention and pharmaceutical compositions based on them may additionally contain at least one additional component selected from the following: an anesthetic, a stimulator of reparative processes, a bacteriolytic, proteolytic, collagenolytic enzyme or a complex thereof, an antibiotic, a synthetic antibacterial agent (except for an antibiotic), including a substance that reduces the resistance of microorganisms, an antimycotic, an immunomodulator, dioxidine.

[0035] The claimed combination additionally contains substances selected from the following series as a stimulator of reparative processes: xymedone, solcoseryl, pantothenic acid in the form of, for example, calcium pantothenate, etaden or a physiologically acceptable mixture thereof, without being limited to them.

[0036] The claimed combination additionally contains substances selected from the following group as an antibiotic: ofloxacin, ciprofloxacin, netilmicin, amikacin, but not limited to them.

[0037] The claimed combination additionally contains, but is not limited to, clotrimozole or ciclopiroxolamine as an antifungal agent.

[0038] The claimed combination additionally contains, but is not limited to, lysoamidase, ultralysin, imozymase, or lysozyme as a bacteriolytic, proteolytic, or collagenolytic enzyme or a complex thereof. The claimed combination additionally contains, but is not limited to, a substance selected from the following group as a synthetic antibacterial agent, including one that reduces microorganism resistance: quinofuryl, ethylenediaminetetraacetic acid, its disodium salt (Trilon B), the diaminopyrimidine derivative trimethoprim, dimethyl sulfoxide, a surface-active antiseptic, or a physiologically acceptable mixture thereof.

[0039] As a synthetic antibacterial agent in the form of a surface-active antiseptic that reduces the resistance of microorganisms, the composition contains a substance selected from the following series: miramistin, decamethoxin, catapol, polyhexanide, octenidine, sodium lauryl sulfate, but not limited to them.

[0040] The claimed combination additionally contains substances selected from the following range as an immunomodulator: polyoxidonium, cycloferon, tiloron, but not limited to them.

[0041] In addition, compositions based on the claimed combination contain, if necessary, at least one component from a number of auxiliary substances, without limitation: a preservative, a stabilizer, a non-ionic detergent, a solubilizer, or a mixture thereof.

[0042] The pharmaceutical compositions of the present invention additionally contain, as a base, hydrophilic substances selected from the series: proxanol (emuksol), polyethylene oxide, propylene glycol, polyvinylpyrrolidone, polyethylene oxide gel 1500, glycerohydrogel based on silicon glycerates, calcium or magnesium alginate, acrylic acid copolymer, sodium carboxymethylcellulose, oxidized cellulose, methylcellulose, glycerol, or a physiologically acceptable mixture in various combinations thereof that provide rheological requirements for the base depending on the dosage form of the pharmaceutical composition and, if necessary, in a mixture with at least one substance from the series: phosphate buffer solution, purified water, vaseline oil, emulsifier, alcohols of higher fatty synthetic fractions, cetyl alcohol, stearyl alcohol, vinylin, povidone or combinations thereof.

[0043] The claimed pharmaceutical composition is additionally made in the form of a liquid dosage form: solution, suspension, without limitation, or a soft dosage form: ointment, gel, liniment, suppositories, without limitation, or a solid dosage form: capsules for rectal or vaginal use, or in the form of a gaseous dosage form: aerosol or spray.

[0044] In one embodiment, the pharmaceutical composition additionally contains protegin X, cetyl alcohol, stearyl alcohol, white beeswax, lanolin, soft white paraffin, almond oil, liquid paraffin, macrogol 1500, macrogol 400, and purified water.

[0045] In another embodiment, the pharmaceutical composition according to the present invention contains (per 1 g) dexpanthenol - 25 mg, methyluracil - 20 mg, chloramphenicol - 3.75 mg, protegin X - 25 mg, cetyl alcohol - 9 mg, stearyl alcohol - 6 mg, white beeswax - 20 mg, lanolin - 125 mg, soft white paraffin - 65 mg, almond oil - 25 mg, liquid paraffin - 75 mg, macrogol 1500 - 95.25 mg, macrogol 400 - 381 mg, purified water - up to 1000 mg.

[0046] The combination of the present invention, as well as compositions containing it, can be used for a wide range of skin, integumentary, and mucous membrane disorders. Thus, the claimed combination is used, without limitation, to moisturize and treat various skin lesions, enhance skin and mucous membrane regeneration, normalize cellular metabolism, and increase the strength of collagen fibers. The claimed combination has a regenerative, metabolic, and anti-inflammatory effect. Furthermore, the combination of the present invention is used to prevent and treat dry skin due to damage to its integrity, to activate the healing process of skin injuries, burns, abrasions, skin irritations, chronic ulcers, bedsores, cracks, and skin grafts.The claimed combination has a complex anti-inflammatory, antimicrobial and regenerative effect, also has a broad spectrum of antimicrobial action against gram-positive and gram-negative microorganisms, including Staphylococcus spp., Pseudomonas aeruginosa and Escherichia coli, increases the level of local immunity, induces interferonogenesis, enhances cellular regeneration processes, accelerates wound healing, and has an anti-inflammatory effect.

[0047] The claimed combination is used to treat purulent wounds in animals infected with mixed microflora (including staphylococci, Pseudomonas aeruginosa and Escherichia coli).

[0048] The claimed combination is also used to treat bacterial skin infections, including boils, wounds, including deep and long-term non-healing wounds, slow-healing wounds, burns, including infected burns, bedsores, trophic ulcers, burns, bone fractures, photodermatitis, trophic ulcers, bedsores, deep wounds.

[0049] The claimed combination easily penetrates deep into tissue without damaging biological membranes. Its wound-healing, anti-inflammatory, and antibacterial effects are maintained in the presence of pus and necrotic tissue. This combination, with its healing and anti-inflammatory effects, penetrates deeper into the skin compared to other similar medications, providing a more effective solution.

[0050] The stated combination can be used in the treatment of the following disorders: abrasions, cuts, diaper rash, inflamed splinters, ingrown nails, inflammatory processes and disorders of the mucous membranes, for example, with damage to the gums, cornea, cracked heels and soles, skin damage in chronic skin diseases, can be used in the complex treatment of skin diseases, treatment of the skin, herpes, including at the stage of crust formation, various abscesses, purulent wounds, weeping wounds, complications in long-term inflammatory processes, for example, ingrown hairs, nails.

[0051] In one embodiment, the present invention relates to a combination for inhibiting inflammatory processes, comprising in an effective amount:

[0052] - pantothenic acid, panthenol or dexpanthenol

[0053] - methyluracil

[0054] - chloramphenicol.

[0055] In another embodiment, the present invention relates to a combination for the treatment of wounds comprising in an effective amount:

[0056] - pantothenic acid, panthenol or dexpanthenol,

[0057] - methyluracil,

[0058] - chloramphenicol.

[0059] In another embodiment, the wound being treated with the claimed combination or composition is infected.

[0060] In another embodiment, the present invention relates to the use of the combination of the present invention for the treatment of wounds. In one embodiment, the wound is infected.

[0061] In another embodiment, the present invention relates to the use of a combination according to the present invention for the prevention and / or treatment of diseases and / or disorders selected from the following group: disorders of the skin, integuments and mucous membranes, various skin lesions, dry skin when the integrity of its integuments is compromised, skin lesions, burns, abrasions, skin irritations, chronic ulcers, bedsores, cracks in the skin, purulent wounds, including those infected with mixed microflora (including staphylococci, Pseudomonas aeruginosa and Escherichia coli), bacterial skin infections, incl.boils, wounds, including deep and long-term non-healing wounds, slowly healing wounds, infected burns, trophic ulcers, bone fractures, photodermatitis, cuts, diaper rash, inflamed splinters, ingrown nails, inflammatory processes and disorders of the mucous membranes, for example, with damage to the gums, cornea, cracks in the heels and soles, skin damage in chronic skin diseases, skin diseases of various origins, characterized by a violation of the integrity of the skin or the presence of an inflammatory process, treatment of the skin, herpes, including at the stage of crust formation, various abscesses, weeping wounds, complications of long-term inflammatory processes.

[0062] In another embodiment, the present invention relates to a pharmaceutical composition for topical use comprising a combination of the present invention in an effective amount and at least one auxiliary pharmaceutically acceptable substance, including water.

[0063] In one embodiment, the present invention relates to a pharmaceutical composition as defined above, wherein the pharmaceutically acceptable substance is selected from the group consisting of: fillers, excipients, binders, disintegrants, diluents, surfactants, glidants, lubricants, or combinations thereof.

[0064] In another embodiment, the present invention relates to the use of a combination of the present invention or a pharmaceutical composition of the present invention for the treatment of inflammatory diseases of the skin and / or mucous membranes.

[0065] In another embodiment, the present invention relates to the use of a combination of the present invention or a pharmaceutical composition of the present invention for inhibiting an inflammatory process of the skin and / or mucous membranes.

[0066] Implementation of the invention

[0067] In one embodiment, the combination of the invention may be formulated as a sponge. In one embodiment, the sponge is biodegradable. In one embodiment, the sponge is, for example, a collagen sponge. In one embodiment, the sponge contains collagen, a 2% solution substance—45.125 g (0.9025 g dry collagen), dioxomethyltetrahydropyrimidine (methyluracil)—0.04 g, chloramphenicol—0.0075 g, and dexpanthenol—0.05 g.

[0068] If using a sponge, the wound must first be treated with an antiseptic solution and any remaining necrotic tissue removed. If necessary, the sponge can be cut into pieces of the desired size and shape. The sponge should fit snugly over the entire wound surface and extend 1-1.5 cm beyond its edges. If necessary, the sponge can be covered with a fixing bandage or two layers of gauze. The wound's condition is monitored 1-2 times daily. The sponge can be changed if necessary. Treatment continues until complete epithelialization or the wound is completely filled with granulation tissue.

[0069] The following are examples that confirm, without limitation, the implementation and effectiveness of the present invention.

[0070] Example 1

[0071] The studies conducted assessed the effect of the claimed combination according to the invention in comparison with individual dexpanthenol preparations and a combination of methyluracil with chloramphenicol.

[0072] Animals

[0073] Forty white Wistar rats weighing 200–250 g were used in this study. The animals were maintained for 12 hours in a light / dark cycle at a temperature of 21 ± 2°C and humidity from 45 to 55%. The rats were fed regular rat chow and given unlimited access to water.

[0074] Combination according to the invention

[0075] Dexpanthenol

[0076] A commercially available ointment, Dexpanthenol, containing 5% dexpanthenol, was used.

[0077] Methyluracil + chloramphenicol A commercially available ointment, Levomekol, containing 4 g of methyluracil and 0.75 g of chloramphenicol per 100 g of the drug was used.

[0078] Surgical procedure and its application

[0079] Rats were anesthetized intramuscularly with ketamine hydrochloride (25 mg / kg). The dorsal hair was shaved, and a 2-cm linear incision was made through the entire skin depth. Four groups of 10 rats were formed. The control group received no treatment. The second group received dexpanthenol ointment, the third group received Levomekol ointment, and the fourth group received a combination of the invention at a 1:1 ratio. The wounds were treated daily with saline. After cleaning, the entire wound area was covered with a sufficient amount of cream.

[0080] Assessment and measurement of wound healing rate

[0081] Wound areas in all three groups were measured on day 1, as well as on days 3, 5, 7, 10, 14, and 21 after excision. Measurements were made using transparencies and a permanent marker. Graph paper was used to record and measure wound area. The following formula was used to assess the degree of wound healing:

[0082] Wound healing rate (%) = 100 * (1 - wound area / original wound area)

[0083] The visual condition of the wounds was also assessed for the presence of infection / inflammation and the presence of purulent discharge.

[0084] Table 1. Degree of wound healing in groups

[0085] * Significant difference from the control group (P<0.05)

[0086] ** Significant difference from the Dexpanthenol group (P< 0.01) Table 2. Wound condition in groups. Number of animals with inflammation (purulent discharge).

[0087] * Significant difference from the control group (P<0.05)

[0088] ** Significant difference from the Dexpanthenol group (P< 0.01)

[0089] In addition to reduced inflammatory processes, the declared combination has reduced allergenicity compared to the combination of methyluracil + chloramphenicol.

[0090] Example 2

[0091] The studies were carried out similarly to Example 1, except that 3 animals were included in each group, and 5 experimental groups + 1 control were studied.

[0092] Combinations according to the invention (experimental groups)

[0093] Commercially available preparations of Dexpanthenol and Levomekol were mixed to a homogeneous mass in the following ratios: 1:10 (group 1), 1:5 (group 2), 1:1 (group 3), 5:1 (group 4), 10:1 (group 5), respectively, and used for processing.

[0094] Table 3. Degree of wound healing in experimental groups

[0095] * Significant difference from the control group (P<0.05) From the data presented, it can be concluded that the stated combinations remain effective at different ratios of components.

Claims

Invention formula 1. A combination for inhibiting inflammatory processes, containing in effective amounts: - pantothenic acid, panthenol or dexpanthenol - methyluracil - chloramphenicol.

2. A combination for the treatment of wounds containing in an effective amount: - pantothenic acid, panthenol or dexpanthenol, - methyluracil, - chloramphenicol.

3. The combination according to claim 2, wherein the wound is infected.

4. Use of a combination according to any one of paragraphs 1-3 for the treatment of wounds.

5. Use according to paragraph 4, where the wound is infected.

6. Use of a combination according to any one of paragraphs 1-3 for the prevention and / or treatment of diseases and / or disorders selected from the following group: disorders of the skin, integuments and mucous membranes, various skin lesions, dry skin when the integrity of its integuments is compromised, skin damage, burns, abrasions, skin irritations, chronic ulcers, bedsores, cracks in the skin, purulent wounds, including those infected with mixed microflora (including staphylococci, Pseudomonas aeruginosa and Escherichia coli), bacterial skin infections, incl.boils, wounds, including deep and long-term non-healing wounds, slowly healing wounds, infected burns, trophic ulcers, bone fractures, photodermatitis, cuts, diaper rash, inflamed splinters, ingrown nails, inflammatory processes and disorders of the mucous membranes, for example, with damage to the gums, cornea, cracked heels and soles, skin damage in chronic skin diseases, skin diseases of various origins, characterized by a violation of the integrity of the skin or the presence of an inflammatory process, treatment of the skin, herpes, including on. stages of crust formation, various abscesses, weeping wounds, complications of long-term inflammatory processes.

7. A pharmaceutical composition for topical use comprising a combination according to any one of claims 1-3 in an effective amount and at least one auxiliary pharmaceutically acceptable substance, including water.

8. The composition of claim 7, wherein the pharmaceutically acceptable substance is selected from the group consisting of: fillers, excipients, binders, disintegrants, diluents, surfactants, glidants, lubricants, or combinations thereof.

9. Use of a combination according to any of paragraphs 1-3 or a pharmaceutical composition according to paragraph 7 for the treatment of inflammatory diseases of the skin and / or mucous membranes.

10. Use of a combination according to any of paragraphs 1-3 for inhibiting the inflammatory process of the skin and / or mucous membranes.

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