RU2292919C1 - Agent for skin integument disinfection - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention describes an agent used in disinfection of skin integument and comprising polyguanidine compound as a disinfecting component and a solvent. As a disinfecting component polyguanidine compound is used, namely, poly-(4,9-dioxadodecane guanidine) phosphate or poly-(4,9-dioxadodecane guanidine) chloride, or polyhexamethylene guanidine citrate, or polyhexamethylene guanidine gluconate, or polyhexamethylene guanidine benzoate, or polyhexamethylene guanidine sebacate, or polyhexamethylene guanidine chloride, or a synergetic mixture of a polyguanidine compound with polyethylene pyrrolidinium chloride with molecular mass 50000-100000 Da taken in the ratio = 1:(1-10). As a solvent water or ethyl alcohol, or mixture of ethyl alcohol and water are used, and agent proposes additionally propylene glycol, polyethylene glycol and nutritive acid salt chosen from the group comprising citric acid sodium or potassium salt, or lactic acid sodium or potassium salt in the following ratio of components, wt.-%: above indicated polyguanidine compound or its synergetic mixture with polyethylene pyrrolidinium chloride with molecular mass 50000-100000 Da in the ratio = 1:(1-10), 0.5-3.0; polyethylene glycol, 0.1-1.0; propylene glycol, 1.0-10.0; nutrient organic acid salt, 0.1-1.5, and solvent, the balance. Invention can be used in surgery, obstetrics, cardiology for hygienic treatment of hands of surgeons and medicinal staff. Invention provides enhancing level and spectrum of the disinfecting agent, reducing its toxicity and negative effect on skin integuments.

EFFECT: improved, enhanced and valuable medicinal properties of agent.

1 tbl, 9 ex

Description

The invention relates to medicine and can be used in surgery, obstetrics, cardiology, etc. for hygienic treatment of the hands of surgeons and medical staff, skin of injection and surgical fields, elbow bends of donors, in hospitals, ambulances and other medical institutions. It can also be used to treat the skin of the hands and feet of personnel at the enterprises of the food industry, utilities, catering and at home.

The invention can also be used as an effective skin antiseptic with emollients for treating children’s hands, including the school contingent, and can also be used to disinfect feet and shoes in order to prevent fungal diseases. It can be used in extreme situations.

Such a vast and diverse scope of the claimed funds is due to its properties and action, because it has disinfectant and antiseptic properties, bactericidal (including anti-tuberculosis), virucidal, fungicidal activity, including against fungi of the genus Candida and dermatophytes.

Disinfection of the skin is one of the main measures to combat the spread of intestinal and nosocomial infections, pulmonary tuberculosis in public institutions.

It is known that the compositions traditionally used for antiseptic treatment of the skin contain a disinfectant component and a solvent (alcohol or a water-alcohol mixture). It is also known that chlorhexidine bigluconate (gibitan) is widely used as a disinfecting component, and a water-alcohol mixture is used as a solvent (Plivacept drug, manufacturer - Pliva company, Croatia) (A. Krasilnikov, Antiseptic Handbook, Minsk .: Higher School, 1995, p. 83). Chlorhexidine bigluconate is currently used as the main active ingredient in most modern mucocutaneous antiseptics. 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. All this limits the range of applications for disinfecting the skin, in which it is included.

Since it is known that chlorhexidine bigluconate is currently used as the main active ingredient in most modern skin antiseptics, all of the above disadvantages of gibitan limit the scope of use of these funds.

It is also known that at present, skin antiseptics containing Quaternary ammonium compounds (HOURs) as a disinfecting component have been used to treat skin integuments. These are drugs of the Velt series, for example, Veltalex-M. The drugs are distinguished by a wide spectrum of action, have found application in medicine and everyday life. However, HOURs are not among the strong antimicrobial substances and do not have a long-term effect (prolonged effect), in addition, certain types of the most resistant microorganisms are not suppressed by HOURS (spore forms, mycobacterium tuberculosis).

The closest solution to the proposed one is to use 0.5-2.0% aqueous or 0.5% solution of a mixture of 70% ethyl alcohol and 30% water, polyhexamethylene guanidine phosphate for the treatment of hands of medical personnel, purulent wounds, injection and surgical fields (Pat. RF No. 2122865, class A 61 L 2/16 B.I. No. 34, 12/10/98)

The disadvantages of the known solution include the fact that the polyhexamethylene guanidine phosphate used in the known solution, synthesized based on guanidine carbonate, is characterized by a relatively low antimicrobial activity and is not active enough against viruses, mesenteric fungi and mycobacterium tuberculosis.

The technical problem solved by this invention is to increase the level and spectrum of the disinfecting effect of the composition, reducing its toxicity and the negative impact of the composition on the skin (dryness, cracks) with its frequent use due to the use of low toxicity with a balanced composition and with improved antimicrobial and dermatological effects as well as a prolonged effect.

To solve the technical problem in a means for disinfecting the skin, including a disinfecting component and a solvent, poly (4,9-dioxadodecanguanidine) phosphate, or poly (4,9-dioxadodecanguanidine) chloride, or polyhexamethylene guanidine citrate are used as a disinfecting component - a polyguanidine compound. or polyhexamethylene guanidine gluconate, or polyhexamethylene guanidine benzoate, or polyhexamethylene guanidine sebacinate, or polyhexamethylene guanidine chloride, or a synergistic mixture of polyguany compound dyne with polyethylene pyrrolidinium chloride in a ratio of 1: (1-10) with a molecular weight of 50,000 -100,000 in a ratio of 1: (1-10), water or ethyl alcohol, or a mixture of ethyl alcohol and water, and additionally contains propylene glycol, are used as a solvent, polyethylene glycol and a salt of a food acid selected from the group comprising the sodium or potassium salt of citric acid, or the sodium or potassium salt of lactic acid in the following ratio of components, wt.%:

The above polyguanidine compound or its synergistic mixture with polyethylene pyrrolidinium chloride molecular weight of 50,000-100,000 in 0.5-3.0 Polyethylene glycol 0.1-1.0 Propylene glycol 1.0-10.0 Food grade organic acid salt 0.1-1.5 Solvent Rest

It was found that the ratio of the amounts of alcohol and water does not affect the disinfectant effect of the product.

The invention is illustrated as follows.

Poly (4,9-dioxadodecanguanidine) phosphate (PPDG), or poly- (4,9-dioxadodecanguanidine) chloride (CPDG), or polyhexamethylene guanidine citrate (PGMG citrate), or polyhexamethine gluconate (gluconate) PHMG), or polyhexamethylene guanidine benzoate (PHMG benzoate), or polyhexamethylene guanidine sebacinate (PHMG sebacinate), or polyhexamethylene guanidine chloride (PHMG chloride).

The skin disinfection agents used in the composition - highly active polyguanidine compounds - have a wide range of biocidal activity: antibacterial, fungicidal, virucidal. They are low toxic, do not penetrate intact skin (hazard class IV), remain on it for a long time, protecting it from environmental influences.

The synergistic mixture of the highly active polyguanidine compound with the polymeric quaternary ammonium compound used in the composition with the ratio of polyguanidine to polyethylene pyrrolidinium chloride 1: (1-10) has a wide spectrum of biocidal activity: bactericidal (effective against Pseudomonas aeruginosa, staphylococci, salmonella, diarrhea, excuda legionella, mycobacterium tuberculosis, etc.), virucidal (HIV infection, hepatitis, herpes, flu), fungicidal (dermatophytosis, candida albicans, asperg illus niger and other mold fungi).

The synergistic mixture consists of two components: polyalkylene- (oxyalkylene) guanidine and a polymeric quaternary ammonium compound - polyethylene pyrrolidinium chloride. In this case, polyguanidines have the following structural formulas:

Polyalkylene guanidine
n = 30-50

polyoxyalkylene guanidine
n = 30-50

Polyethylenepyrrolidinium chloride is a polymeric quaternary ammonium compound (PCA) of the following structural formula:

polyethylene pyrrolidinium chloride (PCH) n = 300-400

The use of a relatively high molecular weight PCAS (50-100 thousand) allows to reduce the share of more expensive polyguanidine while maintaining high biocidal activity.

In the Russian Federation Polyethylene pyrrolidinium chloride is produced under the trademark VPK-402 and is usually sold in the form of 40% aqueous solutions (D. A. Topchiev et al. “Cationic Polyelectrolytes”, Moscow, Nauka, 2004).

A synergistic mixture of two biocides is obtained by mixing their solutions.

It turns out that although PCAS is a relatively inactive biocide, in a synergistic mixture with polyguanidine, it provides a high bactericidal effect.

If the ratio of the GHG compound to the HRP is less than 1:10, then there will be a decrease in biocidal properties, and if this ratio is more than 1: 1, this will lead to an unreasonably high consumption of GHGs.

The propylene glycol included in the product softens the skin, prevents peeling and cracking. In addition, it has a bactericidal effect.

Propylene glycol - propanediol-1,2; 1,2-dioxipropane is a colorless viscous liquid obtained by hydration of propylene oxide. The empirical formula is C ₃ H ₂ O ₂ . Structural formula

Propylene glycol was used in accordance with TU 6-09-2434-81 with a mass fraction of the main substance of 99.0%. (Manufacturer - Khimprom LLC, Kemerovo.) It is widely used in the pharmaceutical industry as an auxiliary substance for the preparation of medicines (registration certificate PN 000384 / 01-2001, FSP 42-0175-0541-00), in food as a moisture-retaining agent agent and as a component in the production of flavorings (hygienic conclusion No. 77.99.02.916 .. D.00 4766.07.02 from 07.17.2002). It has a preserving, bactericidal property.

Polyethylene glycol (PEG-9) (TU 6-14-714-79) is a viscous or waxy substance, soluble in organic solvents, limited in water; precipitates from aqueous solutions at a temperature close to 100 ° C. Polyethylene glycol is used as a thickener in pharmacopeia and cosmetics, as a binder for tablets, creams, and candles.

According to our experiments, the use of PEG guanidine antiseptics softens their effect on the skin and enhances the biocidal effect. PEG is able to penetrate the subcutaneous tissue and transport medications there, as well as improve the stability of the composition over time, increase the wetting and regenerating ability of the proposed tool.

In addition, the penetrating ability of the product is also improved, which favorably affects its healing properties.

The sodium salt of citric acid (sodium citrate) used in the composition, or the potassium salt of citric acid (potassium citrate), or the sodium / potassium salt of lactic acid (sodium / potassium lactate) enhance the antimicrobial properties of the skin, maintain the pH of the product at the level of optimal data for skin integument of man.

Sodium / potassium salt of lactic acid retains tissue moisture, protects them from drying out.

The water-soluble salt of food organic acid contained in the claimed product, in addition to its antiseptic effect, regulates the ionic strength of the disinfectant solution and favorably affects the skin's water-holding ability, which ensures the absence of cracks on the skin and the appearance of dry skin. At the same time, a thin polymer film forms on the surface of the skin, lasting for a long time and providing a prolonged antiseptic effect of the agent.

The quantitative content of the components of the tool is optimal and is selected on the basis of numerous experiments. The table presents data confirming the optimality of the declared limits.

Alternative features of claims 1, 2 and 3 of the claims provide the same technical result as shown in the table.

On the effectiveness of the claimed composition, a conclusion was made on the basis of the results of determining its antimicrobial activity, on the effectiveness of skin disinfection on the hands of volunteers in relation to their own microflora and during artificial infection with E. coli and Staphylococcus aureus culture.

Tests to determine the antimicrobial activity of the drug were carried out in two ways. According to the first method, zones of suppression of microorganisms were determined during the diffusion of the test substance into the solid nutrient medium of апapek. (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, 215 S.). 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). Dried for 30 minutes, and then in a nutrient medium made holes with a diameter of 6 mm, in which were placed samples of the developed disinfectant. 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, microbial growth inhibition zones, 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 test drug. It should be borne in mind that the diffusion rate of polymer disinfectants is significantly lower than the diffusion rate of low molecular weight disinfectants.

To obtain reliable results, all experiments were performed with triplicate, testing time 48 hours. The experimental data were processed statically.

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

A suspension of the test microorganism was added to the test agent in an amount of 10 ⁶ CFU / ml. To do this, 1 ml of the experimental agent was previously introduced into the test tube. The tubes were shaken and, at intervals of 2-5-10 minutes and 30 minutes, seeding was performed on solid nutrient media. Petri dishes were placed for 24-48 hours in a thermostat at 37 ° C. After the expiration of this period, the number of colonies grown was calculated and the bactericidal activity of the test agent was judged by this indicator.

From the obtained data it follows that gram-positive microorganisms (S.aureus) and gram-negative (E. Coli, Ps.Aeruginosa) were highly sensitive to the tested agents according to the examples. All tested formulations of the agent also have high biocidality to fungal microflora and other microorganisms, which is confirmed by data on growth retardation of these microorganisms in a zone with a diameter of 12 to 29 mm. This indicator complies with regulatory requirements for pronounced and high activity.

From the data obtained it follows that the antibacterial effect in all studied drugs develops rapidly. After 2 minutes of contact, no living microflora was found in any experimental case for all types of crops.

Tests for skin disinfection were carried out on 30 volunteers without a burdened allergic history for 30 days.

According to the application samples (hands with natural microflora), the dynamics of microflora accumulation showed that for experimental formulations, even 5 hours after treatment, the number of bacteria on the hands was about 100 times lower compared to naturally accumulated microflora on washed hands. After 30 seconds and 2 minutes (test for protective agents) and after 30 minutes, almost complete absence of bacteria was found on the treated hands (0.4 when infected with Staphylococcus aureus and 0.8 when infected with Escherichia coli).

According to patchwork data, it is shown that the product is harmless, does not have an irritating and allergenic effect.

The practical implementation of the invention is illustrated by the following examples.

Example 1. In 0.5 l (50.0 wt.%) Of water, 2.5 g (0.25 wt.%) Of poly (4,9-dioxadodecanguanidin chloride) is dissolved with stirring, and 56 are added to form a synergistic mixture. ml (0.25 wt.%) of a 40% aqueous solution of polyethylene pyrrolidinium chloride. Then, 1.0 g (0.1 wt.%) Of sodium disubstituted is sequentially introduced. 5 ml (0.5 wt.%) Of PEG-9 and 50 ml (5.0 wt.%) Of propylene glycol are poured into the resulting solution. Then, by adding rectified alcohol, the volume of the solution was adjusted to 1 liter (43.9 wt.%). The resulting solution can be used in the treatment of hands of medical personnel.

Example 2. 10 g (1.0 wt.%) Of polyethylene pyrrolidinium chloride and 5 g (0.5 wt.%) Of a 70% aqueous solution of poly- (4,9-dioxadodecanguanidine phosphate) are dissolved in 0.5 L of water, after which mix. To the resulting solution, add 15 g (1.5 wt.%) Sodium lactate, 10 ml (1.0 wt.%) PEG-9, 25 ml (2.5 wt.%) Propylene glycol and after obtaining a homogeneous solution by adding water, bring the volume of the solution is up to 1 l (93.5 wt.%). The resulting solution can be used to treat the hands of medical personnel and station personnel soon.

Example 3. In 0.5 l of rectified alcohol, 25 g (2.5 wt.%) Of poly- (4,9-dioxadodecanguanidin chloride), 6.25 g (0.25 wt.%) Of 40% aqueous polyethylene pyrrolidinium chloride are dissolved, then mix. Then add 5 g (0.5 wt.%) Of monosubstituted potassium citrate. 5 ml (0.5 wt.%) Of PEG-9 and 100 ml (10.0 wt.%) Of propylene glycol are poured into the resulting solution. The total volume of the solution was adjusted to 1 liter (86.25 wt.%) By adding alcohol. The resulting solution can be used at blood transfusion stations for processing the hands of staff and elbow bends of donors.

Example 4. 5.0 g (0.5 wt.%) Of PHMG chloride are dissolved in 0.5 L (50 wt.%) Of water, 1 g (0.1 wt.%), PEG-9.1 g ( 0.1 wt.%) Sodium citrate, 100 ml (10.0 wt.%) Of propylene glycol and the addition of ethyl alcohol bring the volume of the solution to 1 l (39.3 wt.%). The resulting composition dries quickly on the skin and does not even give a short-term stickiness. It can be used at ambulance stations, blood transfusion stations, in surgical practice.

Example 5. In accordance with the procedure of example 4, 7.5 g (0.75 wt.%) Of poly- (4,9-dioxadodecanguanidine) citrate, 2 g (0, 2 wt.%) PEG-9, 1 g (0.1 wt.%) Potassium lactate 50 ml (5.0 wt.%) Of propylene glycol and ethanol bring the volume of the solution to 1 l (43.95 wt.%). The resulting composition is quickly absorbed into the skin and is recommended for the disinfection of the surgeon's hands.

Example 6. By the method of example 4, 30 g (3.0 wt.%) Of polyhexamethylene guanidine gluconate, 5 g (0.5 wt.%) Of polyethylene glycol, 1 g (1%) are dissolved in 0.5 l (50.0 wt.%) Of water. 0.1 wt.%) Sodium citrate and 10.0 ml (1.0 wt.%) Propylene glycol. The volume of the solution was adjusted with ethyl alcohol to 1 liter (45.4 wt.%). The resulting composition has a very low toxicity and does not irritate the skin with repeated use.

Example 7. According to the method of example 4 in 0.5 l (50.0 wt.%) Water is dissolved 5 g (0.5 wt.%) Benzoate PHMG, 1 g (0.1 wt.%) Polyethylene glycol, 50 ml ( 5.0 wt.%) Propylene glycol, 2 g (0.2 wt.%) Sodium lactate, 50 ml (5.0 wt.%) And the volume of the solution was adjusted with alcohol to 1 l (44.2 wt.%). Recommended for use in the food industry for the processing of staff hands.

Example 8. According to example 7 receive a means for disinfection of the following composition, wt.%:

PGMG Sebacinate 0.5 Propylene glycol 5,0 Polyethylene glycol 1,0 Sodium citrate 0.1 Water fifty Ethanol Rest

Example 9. According to example 1 receive a means for disinfection of the following composition, wt.%:

PHMG Chloride 0.3 Polyethylene pyrrolidinium chloride 0.7 Propylene glycol 10.0 Polyethylene glycol 1,0 Sodium citrate 0.5 Water fifty Ethanol Rest

It should be noted that it is also possible to use the disco component only with a solvent. Such a tool has a high disinfecting effect and good absorbency in the skin, for example:

Poly-4,9-dioxadodecanguanidine chloride 1.0 wt.% Ethanol Rest

However, this composition dries the skin, and therefore it can be used only for quick, single disinfection.

Table 1 No. pr. The connection polyguanidine, wt.% Hour, wt.% Polyethylene glycol, wt.% Propylene glycol, wt.% Salt of food organic acid, wt.% Solvent, wt.% Tech. results FPDG HPDG PHMG Citrate Gluconad PGMG PGMG Benzonate PGMG Sebacinate PHMG Chloride Na citrate Citrate K Lactol Na Lactol K one 2 3 four 5 6 7 8 9 10 eleven 12 13 fourteen fifteen 16 17 one - 0.25 - - - - - 0.25 0.5 5,0 0.10 - - - rest The product has a high disinfecting effect, is convenient to use, can be easily removed with water if necessary, and has a therapeutic effect in relation to damaged skin. 2 0.5 - - - - - - 1,0 1,0 2,5 - - 1,5 - rest 3 - 2,5 - - - - - 0.25 0.5 10.0 - 0.5 - - rest four - - - - - - 0.5 - 0.1 10.0 0.1 - - - rest 5 - - 0.75 - - - - - 0.2 5,0 - - - 0.1 rest 6 - - - 3.0 - - - - 0.5 1,0 0.1 - - - rest 7 - - - - 0.5 - - - 0.1 1,0 - - 0.2 - rest 8 - - - - - 0.5 - - 1,0 5,0 0.1 - - - rest 9 - - - - - - 0.3 0.7 1,0 10.0 0.5 - - - rest 10 - - - - - - 0.2 * 0.1 * 1,0 10.0 0.5 - - 0.1 rest Insufficient disinfectants. act eleven - 3.0 * - - - - - 0.3 * 1,0 10.0 0.5 - - - rest Worse consumer tool properties 12 - 2,5 - - - - - - 0,07 * 10.0 0.5 - - - rest Lowered. prolong. effect

one 2 3 four 5 6 7 8 9 10 eleven 12 13 fourteen fifteen 16 17 13 - - - - 1,0 - - - 1.1 * 10.0 0.5 - - - rest The appearance of stickiness means fourteen - - - - 1,0 - - - 1,0 0.7 * 0.5 - - - rest Decrease in stability of the average, and also increase. dry skin fifteen - - - - 1,0 - - - 1,0 10.3 * 0.5 - - - rest Deterioration of tech. tool properties 16 - - - - 1,0 - - - 1,0 5,0 0,07 * - - - - Leads to a boost. composition pH 17 - - - - 1,0 - - - 1,0 5,0 1.6 * - - - - Leads to reduced. composition pH * - examples beyond the stated examples.

Claims (1)

An agent for disinfecting the skin, including a disinfecting component - a polyguanidine compound and a solvent, characterized in that poly phosphate (4,9-dioxadodecane guanidine) or poly chloride (4,9, -dioxadodecane guanidine) is used as a disinfecting component - polyguanidine compounds or polyhexamethylene guanidine citrate, or polyhexamethylene guanidine gluconate, or polyhexamethylene guanidine benzoate, or polyhexamethylene guanidine sebacinate, or polyhexamethylene guanidine chloride, or a synergistic mixture of compounds of polyguanidine with polyethylene pyrrolidinium chloride with a molecular weight of 50000-100000 in a ratio of 1: (1-10), water or ethyl alcohol, or a mixture of ethyl alcohol and water are used as a solvent, and additionally the agent contains propylene glycol, polyethylene glycol and a salt of a food acid selected from the group comprising sodium or potassium salt of citric acid, or sodium or potassium salt of lactic acid in the following ratio of components, wt.%: The above polyguanidine compound or its synergistic mixture with polyethylene pyrrolidinium chloride with molecular weight of 50,000-100,000 in ratio 1: (1-10) 0.5-3.0 Polyethylene glycol 0.1-1.0 Propylene glycol 1.0-10.0 Food grade organic acid salt 0.1-1.5 Solvent Rest