RU2340328C1 - Agent possessing antimicrobic and antimicotic action - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: agent contains sodium humate obtained from woody-herbaceous peat of the Temnoe deposit of Tomsk area, polyethylene alcohol with molecular mass 400, polyethylene alcohol with molecular mass 1500, dimexide and the water cleared at a certain parity of components.

EFFECT: expansion of area of use of preparations from peat and an arsenal of antimicrobic and antimicotic agents at level of known preparations, such as Nystatin and Nitrofunginum.

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Description

The invention relates to medicine, in particular to pharmacology and dermatovenerology, can be used to treat fungal skin diseases, including foot mycoses.

Mycoses are characterized by a chronic course and a certain resistance to a wide variety of treatment methods. Pathogenic fungi easily adapt to various adverse conditions and develop tolerance to any means of exposure. Yeast fungi intervene, populating the habitat of the bacterial flora that is natural to the human body, weakened or destroyed as a result of antibiotic therapy. According to the WHO, at least 20% of the world's population suffers from fungal infections, and in some regions (including Russia) there is a tendency to increase fungal diseases. The percentage of morbidity among miners, metallurgists, military personnel (60-80%), agricultural workers (20-30%) is especially high (A. Antoniev, Expertise on working capacity for skin diseases / A.A. Antonyev.- M. - 1982. - 224 p.).

Practical mycology today has a large assortment of antifungal agents, however, many of them have side effects in the form of dyspepsia, hepato-, nephrotoxic and teratogenic effects. During treatment, monitoring of the biochemical composition of the blood, the functional state of the liver and kidneys is required. With local therapy, allergic reactions are possible (Ruslanov D.V. Comprehensive treatment of patients with mycoses of the feet and hands: Dis .... k.m.s. / D.V. Ruslanov. - 1983. - 156 p.).

In recent years, effective antifungal drugs (Mikoseptin, Lamisil, Terbizil, Fungoterbin, Amiklon, etc.) have been developed in our country and abroad, used in the form of ointments, creams, gels. These drugs are expensive. In complicated forms of foot mycoses (eczematization, pyoderma), a comprehensive treatment of the disease is necessary, which leads to the joint use of the antifungal and anti-inflammatory drugs currently used, such as 1% Lamisil ointment, Tsinkundan ointment.

Known ointment "Zincundan" containing undecinic acid 10%, zinc salt of undecylenic acid 10%, salicylic acid anilide 10% and ointment base. Ointment has a topical and fungicidal effect when applied topically. It is used to treat fungal skin diseases. The course of treatment is usually long and lasts about 30 days or more. During treatment with ointment and after its completion, it is necessary to additionally apply (powder) the affected areas with Dustundan powder (containing the main components of Zincundan ointment and talc).

The prototype is 1% Lamisil ointment, which is used externally for fungal skin lesions caused by dermatomycetes, for yeast infections of the skin (candidiasis), lichen (pityriasis or colorful), when using the ointment, hyperemia, itching, burning sensation are observed. The drug rapidly diffuses through the skin and accumulates in the sebaceous glands (Mashkovsky M.D. Medicines. M .: Medicine, 2001.- T.2, 363 p.).

The objective of the invention is to expand the arsenal of funds from natural sources of biologically active substances (BAS) with antifungal and antimicrobial activity.

The technical result is a new drug with antimicrobial and antifungal effects in the treatment of mycoses.

The specified technical result is achieved by the fact that the agent containing the active substance and the ointment base contains sodium humate from the lowland wood-grass peat of the Temnoye field in the Tomsk Region as the active substance, and polyethylene glycol with a molecular weight of 400, polyethylene glycol with a molecular weight as a base 1500, dimexide and purified water in the following ratio of components, wt.%:

peat humate 5,0 polyethylene glycol with a molecular weight of 400 63.0 polyethylene glycol with a molecular weight of 1500 25.0 dimexide 2.0 purified water 5,0

The proposed ointment for the treatment of mycoses contains sodium humate from lowland wood-grass peat of the Temnoe deposit in the Tomsk Region, polyethylene glycol (PEG) with a molecular weight of 400, polyethylene glycol with a molecular weight of 1500, dimexide and purified water in the following ratio, wt.%:

peat humate 5,0 polyethylene glycol with a molecular weight of 400 63.0 polyethylene glycol with a molecular weight of 1500 25.0 dimexide 2.0 purified water 5,0

The agent in these concentrations is easily applied to the surface of the skin and does not form a dense film that could interfere with the respiration processes and the release of cellular metabolism products.

Characteristics of incoming components:

polyethylene glycol (PEG400) - (FS 42-1242-79);

polyethylene glycol (PEG-1500) - (FS 42-811-79);

purified water GOST 2874-82.

Sodium humate from peat is a dry powder of dark brown color, with a characteristic odor, isolated from lowland wood-grass peat of the Temnoe deposit, located in the Tomsk region of the Tomsk region and belonging to the Ob-Chulym province (I.V. Fedko et al. “Pharmaceutical evaluation of the properties of humic substances of peat obtained by various methods.” - Minsk. - 2006, p.249-251). The results of a study of the group composition of peat with a degree of decomposition of 35% and an ash content of 8.1% are described. Previously, it was not used as an antimicrobial and antifungal agent.

A hydrophilic polyethylene glycol (PEG) base, which is a composition of liquid and solid PEG, having a viscoplastic consistency: PEG-400 is a viscous transparent colorless liquid and PEG-1500 is a wax. PEG is the basis for treating infected wounds. Any antimicrobial and other substances that provide a complex effect on the purulent wound can be introduced into this base. Compared with the hydrocarbon bases commonly used in medical practice, PEG-based ointments give significantly better active ingredients (GF USSR. - 11th ed. - M .: Medicine, 1987. - Issue 1, 2 - P.334; S.400).

Dimexide is a liquid substance with a non-specific anti-inflammatory effect when applied topically. The drug has the ability to penetrate through biological membranes, including through skin barriers and mucous membranes without damaging them. Used to treat bruises, sprains, inflammatory edema, burns, phlegmon, purulent wounds that are not cleaned or poorly cleaned by conventional methods of treatment (Mashkovsky MD Medicines. M .: Medicine, 2000. - T.1, 175 p. .)

The proposed ointment for the treatment of mycoses is obtained as follows: Preparation of the base (fusion and mixing of PEG-1500 and PEG-400). To do this, in a tank 1 in a water bath, polyethylene glycol (PEG-1500) is melted at a temperature of 70-80 ° C and mixed with polyethylene glycol (PEG-400) when it is completely liquid. Preparation of medicinal substances (dissolution of sodium humate in purified water). Sodium humate is placed in a container 2 (porcelain mortar) and purified water pre-heated to 20 ° C is added in portions, with thorough mixing until the sodium humate is completely dissolved. The introduction of drugs into the base and homogenization of the resulting product. A concentrated aqueous solution of sodium humate is introduced into the molten base and homogenized for three minutes.

I. Antimicrobial action of sodium humate (GN) from peat of the Dark deposit in the Tomsk Region.

1. To study the antimicrobial activity in vitro, a thioglycolic medium containing sodium humate in 1: 1, 1:10, 1:20, 1:40 dilutions was prepared, where the studied cultures were seeded (Proteus mirabilis N132, Citrobacter diversus N244, Klebsiella pneumoniae N251) deposited in GNIISK them. L.Yu. Tarasevich, as well as the plasmocoagulase strain Staphylococcus aureus and the virulent strain Pseudomonas aeruginosa. Petri dishes were placed in a thermostat at t = 37 ° C and every 24 hours, for 7 days, the result of the presence of growth of these cultures on media was taken into account (Table 1)

From table 1 it can be seen that GN in a 1: 1 dilution has antimicrobial activity against all of the microorganisms listed above; and at a 1:10 dilution, to Proteus mirabilis, Citrobacter diversus, Klebsiella pneumoniae, Staphyloccocus aureus. At a 1:20 dilution, an antimicrobial effect was manifested towards Citrobacter diversus, Klebsiella pneumoniae. At a 1:40 dilution, no antimicrobial activity was detected.

Thus, GN has a certain antimicrobial activity, which is also confirmed in experiments conducted on rats with experimental infected wounds.

2. In the second series of experiments, the healing rate of experimental infected wounds was studied. In the experiment used 50 white rats (5 groups of 10 rats). Freshly cut wounds 1.0 × 1.0 cm in size were applied to the pre-trimmed areas of the back skin. Next, 1 ml of 18-hour broth cultures grown in Hottinger medium (pH 7.2–7.4) with an optical density of 100 were applied to the wounds. million - 1 billion CFU. After 4 days, the festering wounds of the experimental groups of animals were treated with 5% GN ointment (group I) and synthomycin emulsion (group II). In 1; 3 and 7 days after treatment with sterile tampons, the contents of the wound were taken and sown on universal and differential diagnostic media, a pure culture was isolated and their identification was performed (Table 2).

It was found that the proposed 5% GN ointment, like a synthomycin emulsion, has an antimicrobial effect with respect to Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter diversus, Staphylococcus aureus. Wound surfaces cleared faster from pus compared with control animals and wound healing was accelerated in the experimental groups compared with intact control rats (P <0.01-0.05).

II. Antifungal properties were studied in vitro by the method of double serial dilutions of them in Saburo's liquid nutrient medium.

The main causative agents of the most common fungal diseases were used as test cultures: Aspergillus niger 163/3685, Candida albicans - 4337, Trychophyton rubrum - VKPG-248/700, Trichophyton mentagrophytes var interdigitale - VKPG-268, Microsporum canis-VKPG-326 / 316.

The tests performed were controlled by test tubes with a nutrient medium, as well as test tubes with a nutrient medium and 0.01 ml of solvent, 0.2 ml inoculated with a culture of pathogenic fungi.

Crops, both experimental and control, were incubated in a thermostat at t = 37 ° C. Visual counts of cultures were performed for A.niger. and C. albicans after 48 hours, for Tr. rubrum., Tr. mentagrophites and M.canis after 6-7 days.

A fungistatic titer, which was evaluated in weight units (micrograms in one ml of culture medium), was taken as a criterion for the antifungal activity of this substance. The data obtained are presented in table 3.

An analysis of the data presented shows that the studied sodium humate retarded the growth of Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum cams at the level of such well-known drugs as nystatin and nitrofungin.

Thus, the proposed 5% ointment with sodium humate has a therapeutic effect in case of mycoses, which is apparently due to its anti-inflammatory, antimicrobial effects.

Antimicrobial and antifungal agent

Table 1 Antimicrobial activity of in vitro sodium humate (CFU / ml) GN breeding Microorganism Proteus mirabilis Citrobacter diversus Klebsiella pneumoniae Staphylococ cus aureus Pseudomonas aeruginosa 1: 1 0 0 0 0 0 1:10 0 0 0 0 fifteen 1:20 53 0 0 31 more than 100 1:40 more than 100 54 46 more than 100 more than 100

table 2 In vivo antimicrobial activity (CFU / ml) n = 10 (wounds infected with microflora, nosocomial purulent infection) Group Proteus mirabilis Pseudomonas aeruginosa Kiebsiella pneumonia Citrobacter diversus Staphylococcus aureus Days of Complete Healing 1st day 3rd day 7th day 1st day 3rd day 7th day 1st day 3rd day 7th day 1st day 3rd day 7th day 1st day 3rd day 7th day Ointment GN 5% 77 ± 0.4 ^{+ *} 37 ± 0.7 ^{+ *} 16 ± 0.6 ^{+ *} 80 ± 0.6 ^{+ *} 59 ± 0.3 ^{+ *} 29 ± 1.2 ^{+ *} 58 ± 2.0 ^{+ *} 40 ± 1.2 ^{+ *} 10 ± 0.2 ^{+ *} 56 ± 2.0 ^{+ *} 38 ± 1.6 ^{+ *} 3 ± 2.0 ^{+ *} 81 ± 1.1 ^{+ *} 56 ± 0.6 ^{+ *} 45 ± 2.0 ^{+ *} 15.5 ± 1.0 ^{+ *} Syntomycin emulsion 92 ± 1.0 ^{+ *} 56 ± 0.4 ^{+ *} 12 ± 0.9 ^{+ *} 92 ± 2.0 51 ± 1.2 ^{+ *} 20 ± 1.5 ^{+ *} 87 ± 0.7 ^{+ *} 51 ± 1.4 ^{+ *} 7 ± 1,1 ^{+ *} 59 ± 1.2 " 44 ± 0.4 ^{+ *} 4.1 ± 0.3 ^{+ *} 91.4 ± 2.0 ^{+ *} 58.1 ± 1.2 ^{+ *} 30.1 ± 1.7 ^{+ *} 16.6 ± 1.5 ^{+ *} Control (PEG) 97 ± 0.6 86 ± 1.6 55 ± 0.3 97 ± 2.0 85 ± 0.9 66 ± 1.9 95 ± 0.6 86 ± 3.1 59 ± 1.0 89 ± 0.7 87 ± 1,0 66 ± 0.5 97 ± 2.0 91 ± 1.4 85 ± 1.8 19.1 ± 1.7 Control (intact) 98 ± 0.7 92 ± 1.2 80 ± 0.3 96 ± 2.0 92 ± 3.1 67 ± 2.7 98 ± 0.6 86 ± 1,1 55 ± 1,2 88 ± 1.3 72 ± 0.4 60 ± 0.2 97 ± 0.2 88 ± 0.2 88 ± 2.0 22 ± 1.5 Note: the sign "+" indicates statistically significant results compared with the control group of animals. "*" - compared to the intact group

Table 3 Antifungal properties of total complexes isolated from lowland wood-grass peat The studied complexes Test mushrooms Triohophyton rubrum Triohophyton mentagrophytes Microsporum canis Aspergillus niger Candida albica Humate sodium 1 / 15.6 15.6-31.2 1 / 15.6-31.2 1/1000 1/1000 Nystatin 1 / 15.6-31.2 1 / 15.6-31.2 1 / 7.8-15.6 1/250 1/250 Nitrofungin 1 / 15.6-31.2 1 / 15.6 1 / 15.6 on on Note: n / a - at a substance concentration of 2000 μg / ml, an inhibitory effect was not observed.

Claims (1)

An antimicrobial and antifungal agent containing an active substance and an ointment base, characterized in that it contains sodium humate from lowland wood-grass peat of the Temnoye deposit in the Tomsk Region, and polyethylene glycol with a molecular weight of 400 polyethylene glycol with a molecular weight of 1500, dimexide and water, purified in the following ratio, wt.%: sodium humate lowland woody grass peat deposits "Dark" of the Tomsk region 5,0 polyethylene glycol with a molecular weight of 400 63.0 polyethylene glycol with a molecular weight of 1,500 25.0 dimexide 2.0 purified water 5.0.