RU2570753C2 - Method of external treatment of skin mycosis - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: loci of skin affection are successively processed first with eliminating solution, which represents 10-20% hypertonic solution of sodium chloride, then - 1% water solution of carbol fuchsin and after 10-15 minutes composition, which consists of 20-30 parts of tisolium and 80-70 parts of antimycotic, selected from the group: pimafucin, travogen, fungoterbine-neo, zalain, is applied, with processing being carried out twice per day for 14 and more days, daily alternating all 5 mentioned antimyotics in composition.

EFFECT: invention makes it possible to increase treatment efficiency, reduce number of recurrences, optimise therapy of patients with mycotic skin affection.

8 ex, 1 tbl

Description

The invention relates to dermatology and mycology and relates to a method for the external treatment of mycotic lesions of the skin, can be used to optimize the treatment of patients in this category.

In recent years, the number of patients with mycotic lesions of the skin has increased. Given that in 80% of cases, skin mycoses affect a limited area of the skin, in the treatment of patients it is most often inappropriate to use systemic antimycotics. It should be noted that when choosing a treatment option, systemic drugs for some patients are generally unacceptable for prescribing for a number of reasons, of which, first of all, the presence of concomitant comorbid conditions and contraindications to their prescription should be indicated. According to the WHO, only 5% of all mycoses are primary, in other cases these are processes that develop against the background of intercurrent diseases. In such a situation, the topical effects of antimycotic agents remain the priority treatment technologies for patients with mycotic lesions of the skin.

Currently, there is a wide range of antimycotics available for practical use, which are used externally. It is very important that they belong to different pharmacological groups of drugs and have different dosage forms in the form of solutions, creams, ointments, film-forming agents. The experience of their application is significant. At the same time, in order to increase the effectiveness of therapy and reduce the number of recurrences of the disease that are recorded quite often, the development of options and prescription algorithms, available antimycotics, combinations and stages of their use, ways to increase the concentration of antimycotics in the lesion, as well as the creation of medicinal compositions from finished dosage forms and pharmaceutical compositions.

There are many known methods for external treatment of skin mycoses, presented in a number of patents [Patent No. 1297286, IPC A61 No. 5/06; RF patent №2125872, IPC A61K 31/185; RF patent No. 2417073, IPC A 61K 9/06; RF patent No. 2120305 C1, IPC A61K 47/38].

There is a method of treating surface forms of skin mycoses by irradiating the affected areas with light, with preliminary application of preparations belonging to the class of photocoumarins to the skin surface [see RF patent No. 1297286 IPC A61 No. 5/06, published on November 28, 1999]. The disadvantage of this method is the use of drugs with low antimycotic activity and unproven preliminary exposure of patients to light.

There is a method of treating skin mycoses, in which lesions for at least 6 days are treated with a medicinal composition consisting of salicylic acid and benzoic acid, taken in 2.5 parts of each, and 95 parts of tisol [see RF patent No. 2125872, IPC A61K 31/185, published on 02.10.1999].

A known method of treating skin mycoses, in which an antifungal composition for topical application is used, containing terbinafine, deoxyproline cellulose and a mixture of octyl acrylamide and acrylate copolymer in an amount of from 1 to 10 wt.% And a solvent selected from the group consisting of ethanol. The disadvantage of this method is the complexity of preparing a multicomponent design in pharmacies and the short shelf life of this mixture, as well as terbinafine is not active enough against yeast-like fungi of the genus Candida, which are diagnosed independently or accompany mycotic processes caused by dermatophytes [see RF patent No. 2417073, IPC 61K 9/06, published on 04/27/2011].

A known method of treating mycosis of smooth skin using a pharmaceutical composition having antifungal activity, containing clotrimazole or ketoconazole, a lipophilic base and target additives, a stabilizer, emulsifier, characterized in that castor oil, sodium benzoate and succinic acid are used as a lipophilic base in various ratios . The disadvantages of the method include the low antimycotic activity of clotrimazole (ketoconazole) and their low concentration in the specified drug mixture [see RF patent No. 2120305 C1, IPC A61K 47/38, published on 10/20/1998].

The closest in technical essence to the method we offer is a method that uses combinations of thisol with benzoic and salicylic acids, in which it is recommended to treat the affected lesions with a medicinal composition consisting of salicylic acid and benzoic acid, taken in 2.5 parts of each, and 95 parts of insulation . The use of thysol as a conductor of drugs and a potentiator of reducing the inflammatory effect, as well as the inclusion of salicylic acid as a keratolytic, is understandable. However, one of the drawbacks of this method is the low antimycotic activity of benzoic and salicylic acids, which play a greater role as an antiseptic and keratolytic rather than antimycotics [see RF patent No. 2125872, IPC A61K 31/185, published on 02.10.1999].

The aim of the invention is to optimize the treatment of patients with mycotic lesions of the skin.

This goal is achieved by the method of external treatment of skin mycoses using compositions consisting of two components, one of which is 20-30 parts of thysol, the second - 80-70 parts of one of the antimycotics, which are applied alternating: either pimafucin, or travogen, or mifungar , or fungoterbin-neo, or zalin, with pre-treatment of the affected lesions 2 times a day with eliminating solutions, for example 10-20% hypertonic, followed by quenching with fucorcin for 14 or more days.

The method is as follows: the foci of skin lesions are sequentially treated first with a eliminating hypertonic solution of 10-20%, then they are quenched with fucorcin and applied after 10-15 minutes, alternating one of the compositions consisting of two components, one of which is 20-30 parts of the insulation, the second 80-70 parts - one of the antimycotics: or pimafucin, or travogen, or mifungar, or fungoterbin-neo, or zalin. Treatment of lesions is carried out twice a day. The duration of treatment is two weeks.

We monitored two groups of patients, each of which had skin lesions in limited areas.

In the first, there were 11 patients with candidal skin lesions caused by yeast-like fungi of the genus Candida albicans, and 23 with diagnosed dermatomycetes: 15 patients with rubrophytosis (Trichopyton rubrum fungi verified (T. rubrum) in the lesion) and 8 with epidermophytosis confirming verification of genus fungi Epidermophyton floccosum (E. floccosum). Therapy of patients was carried out in the regimen of prescribing antiseptics (fucorcin) and one of the antimycotic drugs used in the second group of patients prescribed in the monotherapy variant also lasting 14 days.

The second group consisted of 114 patients, which in turn were distributed depending on the etiological factor that determined the variant of fungal skin lesions. The results of prescribing one of the four treatment options are presented in table 1.

The first observation group received only one of the modern antimycotics used to treat patients of the second group.

The second used an alternation of 5 topical antimycotics, alternating them with daily drug changes and using tizol as a conductor in order to create longer-acting therapeutic concentrations.

The therapy of patients of the first and second groups basically differed in their third stage, during which, in the first case, one antimycotic was used, and in the second antimycotics for external use, belonging to different groups (antibiotics and chemotherapeutic drugs), alternated. In addition, various concentrations of antiseptics were used, which were used to treat the foci before applying antimycotic agents.

Effective therapy in the first group of patients who received treatment for candidiasis, rubrophytes and epidermophytosis was in 10 (90.91%), 11 (73.33%) and 6 (75.0%), respectively. In other cases, continued therapy was required.

The effectiveness of therapy in the second group, presented in table 1, was generally achieved in 107 (93.86%) patients. It should be noted that all 4 used therapeutic technologies were effective for patients with candidiasis. Out of 21 patients, no relapses were recorded in any case. High concentrations of antimycotics (80 parts in comparison with 70 parts) in the combination of antimycotics - conductor were more effective both in patients with epidermophytosis and in patients with rubromycosis. The effectiveness of therapy in the group of 38 patients treated for smooth skin lesions with E. floccosum fungi was achieved in 36 (94.74%). Moreover, when using technologies No. 1 and No. 2, regardless of the concentration of hypertonic solution in the presence of 80 parts of the proportion of antimycotics and 20 parts of the drug, which creates a concentration of which in 11 patients it was 100.0%.

In the group of patients with skin pathology due to rubrophytosis, out of 55 patients, 50 patients had effective therapy, which amounted to 90.91%. Compared with groups of patients with a different etiological factor of inflammation, this group of patients was the most problematic in terms of therapy. In this group, the minimum cure was in patients from group No. 3, whose therapy was characterized by a lower proportion of antimycotics, which amounted to 70 parts, and the percentage of hypertonic solution (10%) used to treat pathological foci. At the same time, all other technologies recommended by us (No. 1, No. 2 and No. 4), fully met expectations.

In conclusion, it should be emphasized that the results obtained were achieved using only topical therapy. Systemic treatment was not carried out.

Example 1. Patient A., 53 years old, was hospitalized at the Republican Clinical Dermatovenerologic Dispensary of the Republic of Tatarstan (Kazan) for 14 days. He received complaints about the appearance of rashes of an itchy nature on the arch of the foot and in the interdigital folds between the 4 and 5, 3 and 4 toes of both feet. On admission: skin folds and arches of both feet were characterized by intense redness, swelling, weeping and maceration with the addition of deep and painful erosions and cracks. The boundaries of the foci are sharp, the fringe is whitish in the form of a peeling epidermis on the periphery. Clinical diagnosis: intertriginous form of epidermophytosis of the feet. Microscopic examination revealed mycelium of the fungus. Cultural: growth of the fungus Trichophyton rubrum, sensitive to azole-type drugs and terbinafins. A three-stage therapy was carried out, consisting of the elimination of fungi with a 0.05% solution of chlorhexidine abigluconate (stage 1), quenching of foci with an aqueous 1% solution of methylene blue (stage 2) in order to enhance the sanitizing effect and, finally, the third stage with the use of an azole-type preparation (herbogen) and the combination drug fungoterbin-neo. The patient was discharged in satisfactory condition with clinical recovery. Mycelial filaments were not detected in smears. However, in control studies after 1 month, bacteriological fungi were again determined. Repeated course of antimycotics in the alternation of pimafucin, travogen, mifungar, fungoterbin-neo and zalina allowed to achieve mycological cure. During the control examination and laboratory tests after 21 days and after 3 months, clinical and etiological cure was recorded.

Example 2. Patient N., 32 years old, was on outpatient treatment of Center Dermatology LLC (Kazan). I turned to a dermatovenerologist with complaints of dry skin of the feet, the appearance of painful cracks in the calcaneal areas. The treatment prescribed in other medical institutions (lubrication with Baby Cream, fat) did not achieve the desired result. On examination: the skin pattern of both feet is strengthened, the surface is dry, covered, especially in the area of skin furrows, with flour-like scales. Similar peeling captures the interdigital folds, the lateral surfaces of the feet. Clinical diagnosis: clinical rubrophytia of the skin of the feet. Microscopically: detected mycelium of the fungus Trichophyton rubrum. Culturally, T. rubrum fungi were verified. A three-stage therapy was carried out, consisting of the elimination of mushrooms with a hypertonic solution of sodium chloride (stage 1), quenching of foci with an aqueous 1% solution of fucorcin (stage 2) in order to enhance the sanitizing effect and, finally, the third stage using a drug from the group of polyene antibiotics (pimafucin) and combined drug pimafucort. The patient received treatment for 10 days, after which she was invited for a follow-up examination after 14 days. Laboratory studies have re-verified the presence of fungi. After that, a repeated course of therapy was carried out, which repeated stages 1 and 2, and the third was changed and it included the use of alternating antimycotics in the form of pimafucin, travogen, mifungar, fungoterbin-neo and zalin. During the control examination and laboratory tests after 21 days and after 3 months, clinical and etiological cure was recorded.

Example 3. Patient V., 43 years old, turned for consultation at the Department of Dermatovenereology, GBOU VPO Kazan State Medical University. Clinical examination revealed a lesion on the skin, represented by hyperemic fine-plate peeling, small cracks in the first and forefinger, as well as the interdigital gap, with a transition to the back and palmar surfaces of the skin of the right hand and spreading it 3-5 cm into one and the other sides with a total diameter of up to 10 cm. This focus of inflammation was surrounded by a corolla of exfoliating epithelium. Subjectively bothered by itching. Recently, a patient with a diagnosis of candidiasis was observed by a dermatovenerologist at the place of residence. The use of mithungar cream for 14 days was recommended. After which, according to the patient, the process regressed, but after two weeks complaints about inflammation, peeling, dryness and itching in the above area began to again disturb the patient. In a second study of scraping material from the focus of inflammation, fungi of the genus Candida albicans were found. After that, the therapeutic measures were changed and they consisted of a phased treatment of skin lesions first with a 20% hypertonic solution, then they were quenched with an aqueous 1% fucorcin solution, and 15 minutes after drying, one of the antimycotic drugs was applied, namely: pimafucin, travogen, mifungar , fungoterbin-neo, zalan, which were changed daily and each of which was combined with 20 parts of the gel insulator, leaving the treatment before applying antimycotics the same. The course of therapy was 14 days. Visually and subjectively, the cure occurred on the 5th day of therapy. An etiological cure was recorded in the first control study conducted 14 days after completion of therapy. In control studies conducted twice with an interval of 1 month, yeast-like fungi of the genus Candida albicans were also not found.

Example 4. Patient N., 23 years old, was monitored at the Department of Dermatovenereology, GBOU VPO Kazan State Medical University from December 2012 to October 2013 with a diagnosis of Dyshidrotic rubrophytia of smooth skin of the feet. Against the background of erythematic-edematous foci of the rear of the feet, there were multiple vesicles and multichamber bubbles, upon opening of which hemorrhagic crusts formed. The foci are prone to peripheral growth and resolution in the center. Subjective: itching, burning. Foci were treated with an aqueous 1% solution of methylene blue, and then, after stopping wetting, baths were used for 15 minutes with a slightly pink solution of manganese. Then, after 15 minutes, the foci were quenched with the antiseptic fucorcin and, with an exposure of 15 minutes, they were treated first with a travertine, and upon completion of the weeping they switched to a travogen. The clinical picture was leveled during therapy on day 14. The treatment was completed, however, in the control study after treatment, T. rubrum fungi were again verified. The therapy was continued. For 14 days, the patient used antimycotics and, along with the travogen, pimafucin, mifungar, fungoterbin-neo, zalin alternated. 14 days after completion of therapy, no fungi were detected in control studies. The patient was under observation for quite a long time and in the repeated studies, fungi were not identified.

Example 5. Monitoring of group No. 1, consisting of 33 patients, 7 of whom had skin lesions caused by yeast-like fungi of the genus Candida albicans and 26 patients with dermatomycete skin lesions (22 patients with T. rubrum and 4 with E. floccosum). In this group of patients, lesions were treated 2 times a day with a 20% hypertonic solution, then they were quenched with a 1% solution of fucorcin, and after 15 minutes one of the compositions consisting of two parts was applied, the first of which is 20 parts of insulating agent, the second - 80 parts of from antimycotics: or pimafucin, or travogen, or mythungar, or fungoterbin-neo, or zalain, which were alternated with their daily replacement. The duration of treatment was at least two weeks.

Symptoms were evaluated, including erythema, peeling, pruritus, vesiculation, and inlay. The final criterion for effectiveness was the treatment effectiveness indicator, which was determined after 4-6 weeks on the basis of negative microscopic examination and culture analysis. Negative results of microscopic examination and culture analysis were considered as evidence of cure of mycosis, which was registered in 100.0%, 95.46% and 100.0%, respectively, and in the group as a whole 96.97%.

Example 6. Monitoring of group No. 2, consisting of 29 patients, 4 of whom had skin lesions caused by yeast-like fungi of the genus Candida albicans, and 25 patients with dermatomycete skin lesions (18 patients with T. rubrum and 7 with E. floccosum). In this group of patients, lesions were also treated 2 times a day with a 10% hypertonic solution, then they were quenched with a 1% solution of fucorcin and after 15 minutes one of the compositions consisting of two parts was applied, the first of which is 20 parts of insulating material, the second - 80 parts of one from antimycotics: or pimafucin, or travogen, or mythungar, or fungoterbin-neo, or zalain, which were alternated with their daily replacement. The duration of treatment was at least two weeks.

The disappearance of symptoms was assessed: erythema, peeling, itching, vesiculation and inlay. The effectiveness criterion was an indicator of the effectiveness of treatment, which was determined after 4-6 weeks on the basis of negative results of microscopic examination and culture analysis. Negative results of microscopic examination and culture analysis were considered as evidence of cure mycosis, which was registered in 100.0%, 94.44% and 100.0%, respectively, and in the group as a whole, 96.55%.

Example 7. Monitoring of group No. 3, consisting of 25 patients, 5 of which had skin lesions caused by yeast-like fungi of the genus Candida albicans, and 25 patients with dermatomycete skin lesions (9 patients with T. rubrum and 11 with E. floccosum). In this group of patients, lesions were also treated 2 times a day with a 10% hypertonic solution, then they were quenched with a 1% solution of fucorcin and after 15 minutes one of the compositions consisting of two parts was applied, the first of which is 30 parts of thysol, the second - 70 parts of one of antimycotics: or pimafucin, or travogen, or mythungar, or fungoterbin-neo, or zalain, which were alternated with their daily replacement. The duration of treatment was at least two weeks.

Similarly, the disappearance of symptoms was assessed: erythema, peeling, itching, vesiculation, and inlay. The effectiveness criterion was an indicator of the effectiveness of treatment, which was determined after 4-6 weeks on the basis of negative results of microscopic examination and culture analysis. The negative results of microscopic examination and culture analysis were considered as evidence of the cure of mycosis, which was registered in 100.0%, 77.78% and 90.91%, respectively, and in the group as a whole 88.0%.

Example 8. Monitoring of group No. 4, consisting of 27 patients, 5 of whom had skin lesions caused by yeast-like fungi of the genus Candida albicans, and 22 patients with dermatomycete skin lesions (6 patients with T. rubrum and 16 with E. floccosum). In this group of patients, lesions were also treated 2 times a day with a 20% hypertonic solution, then they were quenched with a 1% solution of fucorcin and after 15 minutes one of the compositions consisting of two parts was applied, the first of which is 30 parts of insulating material, the second - 70 parts of one of antimycotics: or pimafucin, or travogen, or mythungar, or fungoterbin-neo, or zalain, which were alternated with their daily replacement. The duration of treatment was at least two weeks.

The disappearance of symptoms was assessed: erythema, peeling, itching, vesiculation and inlay. The effectiveness criterion was an indicator of the effectiveness of treatment, which was determined after 4-6 weeks on the basis of negative results of microscopic examination and culture analysis. Negative results of microscopic examination and culture analysis were considered as evidence of cure of mycosis, which was registered in 100.0%, 83.33% and 93.75%, respectively, and in the group as a whole 92.59%.

The efficacy rates of treatment of mycosis after 6 weeks were very high in all four subgroups from the second group, and they significantly exceeded the indicator in the first group, which is clearly seen from the data presented in table 1.

Thus, the method of staged therapy of patients, which differs in the regimen of prescribing antimycotics, namely, their combined use, unlike monotherapy, can significantly increase its effectiveness, which indicates the advisability of this option for the use of antimycotic drugs.

The proposed method relates to the use of stable fixed-dose formulations for topical use in the staged treatment of skin mycoses, while external antimycotic drugs of various pharmacological groups are prescribed after preliminary mechanical removal of fungi from the skin surface, combined with a drug that allows delivering the antimycotic to the site of inflammation and create a concentration sufficient to cure it.

Claims (1)

A method for the external treatment of skin mycoses, characterized in that the foci of skin lesions are sequentially treated first with an elimination solution, which is a 10-20% hypertonic solution of sodium chloride, then with a 1% aqueous solution of fucorcin, and after 10-15 minutes a composition consisting of from 20-30 parts of thysol and 80-70 parts of an antimycotic, which is selected from the group: pimafucin, travogen, mithungar, fungoterbin-neo, zalain, and the treatment is carried out twice a day for 14 or more days, alternating all 5 of these antimikos daily Ikov in the composition.