RU2359455C1 - Biocidal composition for skin processing - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: biocidal composition contains polyguanidine compound poly-(4,9-dioxadodecanguanidine) chloride or poly-(4,9-dioxadodecanguanidine) phosphate, or polyhexamethyleneguanidine succinate, as solvent, contains water, or ethanol, or ethanol and water mixture and additionally contains benzalkonium chloride, sorbitol, water extract of Sedum maximum and α-hydroxyacid - glycolic or malic, or citric with definite component ratio (wt %).

EFFECT: increase of level and spectrum of biocidal composition disinfecting effect.

3 tbl, 3 ex

Description

The invention relates to medicine and can be used in surgery, obstetrics, ambulance stations and other medical institutions.

In addition, the proposed biocidal composition can be used in enterprises of the food industry, utilities, public catering and in everyday life.

It is known that the compositions traditionally used for antiseptic treatment of the skin contain a disinfectant component and a solvent (alcohol or water-alcohol mixture). It is also known that chlorhexidine bigluconate (gibitan) is widely used as a disinfecting component, and a water-alcohol mixture (Plivacept drug, manufacturer - Pliva company, Croatia) is used as a solvent (A. Krasilnikov. Antiseptics Handbook. Minsk: Higher School, 1995, p. 83). Chlorhexidine bigluconate is currently used as the main active ingredient in most modern mucocutaneous antiseptic compounds. However, it is known that chlorhexidine bigluconate is weakly effective against mycobacteria (in particular Proteus), yeast and dermatophytes. Its activity against Pseudomonas aeruginosa and viruses is extremely low.

The closest technical solution to the proposed solution is a composition for treating the hands of medical personnel, purulent wounds, injection and surgical fields of 0.5-2.0% aqueous solution of polyhexamethylene guanidine phosphate or 0.5% alcohol-containing solution of polyhexamethylene guanidine phosphate (US Pat. RF No. 2122865, C. A61L 2/16, BI No. 34, 12/10/98).

However, the known composition is characterized by a relatively low antimicrobial activity against viruses, fungal infections and mycobacterium tuberculosis.

The technical problem solved by the invention is to increase the level and spectrum of disinfectant action while maintaining a prolonged effect.

To solve the technical problem in a biocidal composition for treating the skin, including a polyguanidine compound and a solvent, poly- (4,9-dioxadodecanguanidine) chloride, or poly- (4,9-dioxadodecanguanidine) phosphate, or poly- ( 4,9-dioxadodecanguanidine), or polyhexamethylene guanidine succinate, water or ethyl alcohol, or a mixture of ethyl alcohol and water are used as a solvent, and benzalkonium chloride, sorbitol, an aqueous extract of stonecrop, α-hydroxy acid are added - glycolic, or apple, or lemon in the following ratio of components, wt.%:

 polyguanidine compound 0.5-3.0  benzalkonium chloride 0.05-0.5  sorbitol 0.1-0.5  large stonecrop water extract 0.05-1.0  α-hydroxy acid 0.05-0.15  solvent rest

The invention is illustrated as follows.

The highly effective polyguanidine compounds used in the skin treatment composition have a wide range of biocidal activity.

Chloride is used as polyguanidine compounds.

poly- (4,9-dioxadodecanguanidine (PDDG) ECOSEPT, phosphate

ECOSEPT poly- (4,9-dioxadodecanguanidine (PDDH), polyhexamethylene guanidine succinate (PHMG) and PDCG succinate.

These compounds are produced by the Institute of Ecological and Technological Problems (IETP). ECOSEPT trademark belongs to ROO IETP.

Most preferred is the use of PGMG succinate and PDGS succinate.

PGMG succinate (disubstituted) has the following structural formula:

n-30-50.

The poly- (4,9-dioxadodecanguanidine) succinate (disubstituted) has the following structural formula:

n = 30-50.

It should be noted that succinic acid, which is part of the PGMG succinate and PDDG succinate, is a bioactive natural compound. It is present in the human body and therefore a salt of succinic acid is necessary for a person. PHMG succinate and PDDG succinate increase the prolonged biocidal effect of the composition after application to the skin.

Benzalkonium chloride is a quaternary ammonium compound (HOUR).

Among mono-quaternary ammonium salts, compounds that contain 12-16 carbon atoms in the radical show maximum activity.

Benzalkonium chloride with a chain length of C ₁₂ -C ₁₆ has the following structural formula:

where n = 12-16.

Supplier SBK was founded in 1997 on the basis of the Russian representative office of the raw materials division of the German chemical concern Henkel KgaA (currently Cognis Deutshland GmbH) and specializes in the supply of raw materials for various branches of the chemical industry.

During the interaction of the polyguanidine compound with QAS, a synergistic mixture is formed that has a wide spectrum of biocidal activity: bactericidal (effective against Pseudomonas aeruginosa, staphylococci, Salmonella, pathogens of dysentery, diphtheria, Legionella), virucidal (HIV infection, hepatitis, herpes, influenza), fungi (effective against dermatophytosis, candida albicans, aspergillus niger and other mold fungi).

Sorbitol - a polyhydric alcohol has the following structural formula:

Sorbitol is a white crystalline substance that has a softening effect on the skin and helps to make the skin feel velvety. Like weight - 182.2, t _PL - 97 ° C, soluble in water, alcohol. Use sorbitol brand "SORBITOL", manufacturer - concern RT SORINI CORPORATION Tbk (Indonesia)

The water extract of stonecrop great has a beneficial effect on the skin. It has a wound healing effect, enhances metabolic processes in tissues and their regeneration. In conjunction with disinfecting components - compounds of polyguanidine and QAS enhances the biocidal effect of the composition.

To prepare the extract, 150 g of leaves and roots of the plant are placed in a container (8-10 l), 6 l of boiling water is poured and insisted for 4 hours. After filtering, about 5.5 L of extract is obtained.

Glycolic acid (hydroxyacetic), mol. mass 76.05, (C ₂ H ₄ O ₃ ), is a colorless crystalline substance, readily soluble in water, alcohol, ether. It has antioxidant and anti-inflammatory properties. Contained in unripe grapes, beets, sugarcane. Use 99% glycolic acid of the brand GLYPURE 99, Manufacturer DuPont de Nemours International SA Belgium.

Malic acid (hydroxy succinic acid) (TU 6-09-5562-91), mol. weight 134.1, _mp = 98-99 ° C, (C ₄ H ₆ O ₅ ), is a colorless crystalline substance, readily soluble in water and alcohol. It is used in the production of wine, fruit water, and medicines. Malic acid has anti-inflammatory and moisturizing properties.

Citric acid - α-hydroxytricarboxylic acid (GOST-3652), (C ₆ H ₈ O ₇ ), mol. the mass of 192.2 is a colorless crystal, readily soluble in water and alcohol. It has antioxidant and anti-inflammatory properties. It is used as a complexing agent and acidity regulator.

Citric acid is used in the food and pharmaceutical industries.

Introduction to the biocidal composition of α-hydroxy acid allows, in addition to its antiseptic effect, to regulate the ionic strength of the solution, to beneficially affect the skin's water-holding ability.

Water is used as the basis of the composition according to GOST 609-84 (distilled).

Ethyl alcohol is used as the basis of the composition according to GOST 18300-87. It was found that the ratio of the amounts of alcohol and water in a mixture of alcohol with water does not significantly affect the disinfecting effect of the composition.

The quantitative content of the components of the biocidal composition is optimal and is selected on the basis of numerous experiments.

Table 1 presents data confirming the optimality of the declared limits.

Alternative features of claim 1 of the claims provide the same technical result as shown in table. one.

The biocidal composition is prepared as follows.

A polyguanidine compound and HOUR are dissolved in a solvent.

Then, an aqueous solution of stonecrop, sorbitol, α-hydroxy acid, is successively introduced, after which the volume of the solution is adjusted to the desired concentration by adding solvent.

Perfume can be added as needed. In examples of specific performance, the content of the components is presented, wt. %

Example 1

 PLLH chloride 1,5  benzalkonium chloride 0.2  sorbitol 0.3  large stonecrop water extract 0.5  lemon acid 0.1  distilled water rest

The resulting composition can be used in preschool institutions, schools to protect the skin from the penetration of pathogenic microbes and bacteria. It has a moisturizing effect, does not upset the pH balance.

Example 2

 PDH phosphate 0.5  benzalkonium chloride 0.5  sorbitol 0.1  large stonecrop water extract 0.05  glycolic acid 0.05  ethanol rest

The resulting composition can be used at blood transfusion stations for the treatment of elbow bends of donors and for the treatment of staff hands.

Example 3

 pdg succinate 3.0  benzalkonium chloride 0.05  sorbitol 0.5  large stonecrop water extract 1,0  Apple acid 0.15  a mixture of ethyl alcohol and distilled water rest

The resulting composition provides long-term skin protection against pathogenic microbes and fungal infections, has low toxicity, does not irritate the skin with prolonged use.

The remaining examples are summarized in table 1.

Tests to determine the antimicrobial activity of the drug were carried out in two ways. The first method was used to determine the zones of suppression of microorganisms during the diffusion of the test substance into a solid nutrient medium (Fedorov Yu.A., Koren V.N. “Microbiological methods for the study of dental hygiene products” in the book “Fundamentals of oral hygiene.” L .: “Medicine ", 1973, p. 3-215).

For this, 1 ml of a 24-hour microbial suspension of test microorganisms with a concentration of 5 × 10 ⁵ CFU / ml was applied to the surface of a solid nutrient medium in a Petri dish (20 ml). It was dried for 30 min, and then, in a nutrient medium, wells with a diameter of 6 mm were made into which samples of the developed biocidal agent were placed. The number of holes did not exceed 6 per Petri dish. For 30 minutes, Petri dishes were kept at room temperature (20 ° C), then they were placed in a thermostat for 24-48 hours at a temperature of 37 ° C, and after this period, zones of inhibition of microbial growth, including the diameter of the wells, were taken into account. The size of the zones of oppression was judged on the antimicrobial effect of the investigated composition. It should be borne in mind that the diffusion rate of polymer disinfectants is lower than the diffusion rate of low polymer disinfectants.

To obtain reliable results, all experiments were performed in triplicate, testing time - 48 hours. The experimental data were processed statistically.

Table 2 presents the results of antimicrobial activity tests. Tests (Table 2) showed that gram-positive microorganisms (S.aureus) are most sensitive to the tested biocidal formulations for treating the skin. All tested biocidal compositions formed growth retardation zones from 22 to 40 mm, which corresponds to a fairly high activity.

The second way to test antimicrobial activity is to determine the minimum time required to completely suppress the growth and development of test microorganisms.

A suspension of test microorganisms was added to the test substance in an amount of 10 ⁵ CFU / ml; for this, 1 ml of the test substance was poured into test tubes. The tubes were shaken and, at intervals of 2-5-10 and 30 minutes, were sown on solid nutrient media. Petri dishes were placed for 24-48 hours in a thermostat at 37 ° C. After this period, the number of colonies grown was counted and the bactericidal activity of the test substance was judged by this indicator. The test results of antimicrobial activity over time are presented in table 3.

Of the presented in table. 3 data it follows that after 2 minutes of contact in any case, no living microflora was detected after contamination of the nutrient medium with Escherichia coli.

Table 1
The components of the biocidal composition, wt.% No. p / p Polyuganidine compound Benzalkyl chloride (HOUR) Sorbitol Large stonecrop extract α-hydroxy acid Dissolve the tel Note one 2 3 four 5 6 7 8 one PDDG Chloride - 1.5 0.2 0.3 0.5 Lemon juice 0.1 Water - ost. The composition has high biocidal properties and prolonged action, therapeutic effect in relation to damaged skin, because accelerates the healing and regeneration of the skin, is convenient to use, and is easily washed off with water if necessary 2 PDDG Phosphate - 0.5 0.5 0.1 0.05 Glycolic acid 0.05 Alcohol - ost. 3 Succinate PDDG - 0.3 0.05 0.5 1,0 Apple to 0.15 A mixture of alcohol and water 50:50 - ost. four PGMG Succinate - 1.5 0.5 0.5 0.5 Lemon citric acid 0.1 Water - ost. 5 PDDG Phosphate - 1.5 0.2 0.3 1,0 Apple to 0.1 Water - ost 6 PDG Succinate - 3.1 * 0.2 0.3 0.5 Malic acid 0.1 Water - ost. Unjustified consumption of des. facilities 7 PDCG succinate - 0.3 * 0.2 0.3 0.5 Malic acid 0.1 Alcohol - ost. Low biocidal effect 8 PDDG Phosphate - 1.5 0.03 * 0.3 0.5 Malic acid 0.1 Water - ost. Low biocidal effect 9 PDDG Phosphate - 1.5 0.55 * 0.3 0.5 Malic acid 0.1 Alcohol - ost. Unjustified consumption of des. facilities 10 PDDG Phosphate - 1.5 0.2 0.08 * 0.5 Citric acid 0.1 Water - ost. Insufficient softening effect eleven PDDG Phosphate - 1.5 0.2 0.55 * 0.5 Citric acid 0.1 Water - ost. Turbidity of the composition 12 PDDG Phosphate - 1.5 0.2 0.3 0.03 * Citric acid 0.1 Water - ost. Reduced therapeutic effect 13 PDDG Phosphate - 1.5 0.2 0.3 1.1 * Citric acid 0.1 Water - ost. Change the color of the composition fourteen PDDG Phosphate - 1.5 0.2 0.3 0.5 Citric acid 0.03 * Water - ost. Raising the pH of the composition fifteen PDDG Phosphate - 1.5 0.2 0.3 0.5 Citric acid 0.17 * Water - ost. Change in pH of the composition Note: * - the content of the component is beyond the stated limits.

table 2 Samples of biocidal composition for skin treatment Microorganism growth inhibition zones, mm S.aureus E.coli Ps. aeruginosa Example 1 32 25 26 Example 2 28 22 24 Example 3 40 27 26 Example 4 33 25 22 Example 5 thirty 23 26

Table 3 Samples of biocidal composition for skin treatment Seeding * after a period of time (min) 2 5 10 thirty Example 1 not upd. not upd. not upd. not upd. Example 2 not upd. not upd. not upd. not upd. Example 3 not upd. not upd. not upd. not upd. Example 4 not upd. not upd. not upd. not upd. Example 5 not upd. not upd. not upd. not upd. * bacteria of the species E. coli, 10 ⁵ CFU / cm ³

Claims (1)

A biocidal composition for treating the skin, comprising a polyguanidine compound and a solvent, characterized in that poly- (4,9-dioxadodecanguanidine) chloride, or poly- (4,9-dioxadodecanguanidine) phosphate, or poly- succinate (4 , 9-dioxadodecanguanidine), or polyhexamethylene guanidine succinate, water or ethyl alcohol, or a mixture of ethyl alcohol and water are used as a solvent, and additionally contains benzalkonium chloride, sorbitol, an aqueous extract of stonecrop and α-hydroxy acid-glycol vuyuyu, or apple, or lemon in the following ratio of components, wt.%:
polyguanidine compound 0.5-3.0 benzalkonium chloride 0.05-0.5 sorbitol 0.1-0.5 large stonecrop water extract 0.05-1.0 α-hydroxy acid 0.05-0.15 solvent rest