RU2198654C2 - Method for treating onychomycosis - Google Patents

Abstract

FIELD: medicine, mycology, dermatology. SUBSTANCE: one should use a solution as antimicrobial product. To prepare this solution it is necessary to grind 14 tablets of lamysil to obtain powder-like state, then they are poured with 100 ml 1%-dimexide solution, the mixture obtained should be kept for 1 d in sealed dark glass-made vial, then 100 ml 70%-acetic acid should be added together with 100 ml 5%-iodine solution. Then the solution obtained should be applied upon nail laminae and nail-walls once daily, and upon feet's skin -twice weekly for 6 mo. The present method leads to higher efficiency of therapy due to increased percentage of clinicolaboratory healing of onychomycosis and prevents the development of disease relapses. EFFECT: improved results of therapy.

Description

 The invention relates to medicine, in particular to dermatology, and relates to one of its most urgent problems - the treatment of fungal lesions of the nail plates.

 Onychomycosis is a very common disease that occurs in 40% of the population [1]. Onychomycosis almost never affects children [4]. The incidence increases with age and is highest in older people [4]. As you know, older people not only more often than other age groups suffer from severe somatic pathology, which is a contraindication for the appointment of highly effective systemic antimycotic drugs, but often do not have the ability to use these drugs because of their high cost. Therefore, this category of patients is forced to receive only local therapy, which is less effective than systemic and cannot provide cure for common and long-existing fungal infections of the nails [4].

 Local antifungal drugs (bifonazole - cream, solution; isoconazole - cream; ketoconazole - cream; clotrimazole - ointment, cream, solution; miconazole - cream; econazole - cream, solution; naphthyne - cream, solution; terbinafine - cream; natamycin - cream; chloronitrophenol - solution) contain very high concentrations of active substances active against fungi - pathogens of onychomycosis. However, these high concentrations are created only on the surface of the nail plate, and in depth, to the nail bed, where the most viable mushrooms are located, antimycotics do not always penetrate in effective concentrations [4]. Traditionally, this problem was solved as follows: before the appointment of local antimycotics, surgical removal of the affected nail plates was performed. However, firstly, this operation is very painful, and secondly, along with the plate, the matrix is removed — the sprout zone of the nail, the nail bed is injured, which sometimes leads to the growth of deformed nails [4]. It should be noted that surgical removal of nails is acceptable for young patients who do not have common diseases and vascular diseases of the limbs [4]. In this regard, nail polishes were proposed for the treatment of onychomycosis, the main advantage of which is that they can be applied to the nail plate without removing it. Other drugs cannot penetrate the nail plate, which requires its preliminary removal [4].

 Closest to the proposed method is a method for the treatment of onychomycosis with local antimycotics in the form of nail polish (lotseril, batrafen).

 Batrafen varnish (8% cyclopirox) is applied every other day during the first month of treatment, twice a week for the second month, and then once a week. Lacquer laceril (5% amorolfin) is applied once a week.

 Before starting treatment with any varnish, as much as possible of the affected nail plate should be removed (mechanically or using keratolytic patches). The remaining nail plate, on which the varnish will be applied, must be filed with the included file to create an uneven surface. Varnish is applied with a brush or spatula. Before each application of varnish, the previous layer is removed with a solvent or alcohol swab and a nail plate is treated with a file. The varnish layer can also be removed by placing the nail in warm water, scraping the varnish of the branches of the scissors. The duration of treatment depends on the growth rate of a healthy nail plate. For the treatment of onychomycosis in the hands, 6 months is enough, on the legs - 9-12 months [4].

Significant disadvantages of this method are:
1) lack of effectiveness of the method: clinical and laboratory cure is achieved in 46% of patients [5];
2) a high percentage of relapses of the disease;
3) the high cost of treatment.

 The aim of this invention is to increase the effectiveness of treatment by increasing the percentage of clinical and laboratory cure of onychomycosis and preventing the development of relapse of the disease, a significant increase in the availability of the method (reducing the cost of treatment).

 This goal is achieved using the original penetrating solution with a preliminary cleaning of the affected parts of the nail (mechanically or using keratolytic patches).

Penetrating solution consists of:
1) 250 mg lamisil tablets, a broad-spectrum fungicidal antifungal drug from the class of allylamines, effective against dermatophytes, yeasts and molds [4]. Lamisil acts at the level of squalene epoxidase cycle, suppressing the enzyme - squalene epoxidase of fungi [5]. It has the highest activity among dermatophytes among systemic antimycotics, causing most (up to 94%) cases of dermatomycosis [4];
2) solutions of 5% iodine and 70% acetic acid with fungistatic properties;
3) 1% solution of dimexide - an anti-inflammatory drug with an antiseptic effect, which has the ability to enhance the penetration through the skin of a number of drugs [2], in particular lamisil, iodine and acetic acid.

 The ingredients used in the proposed antimycotic solution, in this combination enhance the effect of each other and give the method a new property that provides an extraordinary therapeutic effect.

 The penetrating solution is prepared as follows. 14 tablets of lamisil are ground to a powdery mass and filled with 100 ml of a 1% solution of dimexide. This mixture is insisted in a sealed container of dark glass for a day. Then, 100 ml of 70% acetic acid and 100 ml of 5% iodine solution are added to it. This solution is applied to the nail plates and nail rollers for 6 months (1 time per day). The same solution is applied to the skin of the feet 2 times a week for 6 months.

 The proposed method was tested at the clinical base of the Scientific Research Institute of Medical Mycology of St. Petersburg MAPO together with the Department of Dermatovenerolygia of St. Petersburg MAPO.

 Examples of the application of the method.

 Example 1. Patient C. 42 years old suffers from onychomycosis of the hands and feet for 15 years. Prior to going to the clinic of the Scientific Research Institute of Medical Mycology, St. Petersburg MAPO, she applied laceryl varnish to the affected nail plates for 6 months without a significant effect. On examination: all the nail plates of the toes and the first, third fingers of the right hand are normal, dull, with a yellow tinge from the free edge to the middle of the nail plate, with a thickening in the corners of the nail plate due to the accumulation of horny masses, on the skin of the hands and feet - lamellar peeling. In a laboratory study: microscopically in the scrapings of skin and nail scales, mycelium of the fungus was found, culturally - the growth of Trichophyton rubrum.

 Diagnosis: rubrophytia of the hands and feet of the squamous dry type with onychomycosis of the distal-lateral subungual form (normotrophic type of lesion of all nail plates of the toes, first and third fingers of the right hand).

 After preliminary cleaning of the affected parts of the nail plates, the patient applied the nail penetrating solution to the nail plates twice a week for 6 months, prepared as follows: 14 tablets of lamisil were ground to a powdery mass, 100 ml of a 1% solution of dimexide were poured , this mixture was infused for a day in a sealed container made of dark glass, then 100 ml of 70% acetic acid and 100 ml of 5% iodine solution were added to it.

 After treatment, the nail plates had a clinically healthy appearance. A month after completion of treatment, microscopic examination of the mycelium of the fungus was not detected, culture - Trichophyton rubrum was not detected.

 Example 2. Patient M., 84 years old, suffers from onychomycosis of the feet for 20 years. Prior to going to the clinic of the Scientific Research Institute of Medical Mycology, St. Petersburg MAPO used various external antifungal agents without effect. On examination: all the nail plates of the toes of the yellow color are thickened all over due to horny masses (moderate subungual hyperkeratosis), the nail plates on the free edge are dirty gray, loosened, and the skin on the feet is lamellar peeling. In a laboratory study, fungal mycelium was detected microscopically in scrapings of skin and nail scales, and culture - growth of Trichophyton rubrum.

 Diagnosis: rubrophytia of the feet of a squamous dry type with ophiomycosis of total dystrophic form (hypertrophic type of lesion of all nail plates of the toes of the feet).

 After preliminary cleaning of the affected parts of the nail plates, the patient applied the penetrating solution to the nail plates twice a week for 6 months on the skin of the feet, which was prepared as follows: 14 tablets of lamisil were ground to a powdery mass, 100 ml of a 1% solution of dimexide were poured , this mixture was infused for a day in a sealed container made of dark glass, then 100 ml of 70% acetic acid and 100 ml of 5% iodine solution were added to it.

 After the end of treatment, apparently unchanged nail plates have grown to half of the nail bed. A month after completion of treatment, microscopic examination of the mycelium of the fungus was not detected, culture - Trichophyton rubrum was not detected.

 In this way, 95 patients with onychomycosis aged 18 to 84 years were treated, 4 of them suffered onychomycosis of the hands, 91 onychomycosis of the feet. T. rubrum was sown in 82 people, C. albicans in 8 people, mold fungi in 5 human.

 Relapse of the disease was not observed within two years after the end of treatment. Side effects and complications were not observed.

Comparison of the treatment results of the proposed method with the prototype showed:
1) the percentage of clinical and laboratory cure of onychomycosis in patients treated with the original penetrating solution was 86.4, which significantly exceeds the same indicator (46%) in the treatment of varnishes (lotseril, bathrafen);
2) the absence of relapse of the disease;
3) the average cost of treatment with an original penetrating solution is 3.5 times cheaper than with varnishes (loteril, bathrafen).

Literature
1. Lamisil in the treatment of patients with onychomycosis. A manual for doctors. M., 1999 .-- 3 p.

 2. Mashkovsky M. D. Drugs. M .: Medicine, 1993, - 1 t. 222 s.

 3. Rukavishnikova M.V. Modern methods of treating patients with foot mycoses. The Journal of the attending physician 10.

 4. Sergeev Yu.V., Sergeev A.Yu. Onychomycosis. Fungal infections of the nails. M.: Geotar medicine, 1998 .-- 33 p., 100-108 p.

 5. Stepanova Zh.V. Fungal diseases. M .: Kron-press, 1996 .-- 48 p.

 6. Stepanova Zh.V. Onychomycosis. Russian Medical Journal 14, 1999.

Claims (1)

 A method of treating onychomycosis by local exposure to antimycotic agents, characterized in that a solution is used as an antimycotic agent, for the preparation of which 14 tablets of lamisil are ground to a powdery mass, they are poured with 100 ml of a 1% solution of dimexide, this mixture is infused for a day in a sealed container of dark glass, then 100 ml of 70% acetic acid and 100 ml of 5% iodine solution are added to it, after which the solution is applied once a day for 6 months to the nail plates and nail rollers, to the skin of the feet apply 2 times a week for 6 months.