RU2180572C1 - Antibacterial agent and method of its preparing - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: invention relates to method of development of agent used for control of microorganisms. Invention proposes an agent containing hydrogen peroxide, quaternary ammonium compound, organic acid or a mixture of two and more organic acids and carbamide taken in the definite ratios. Invention proposes also method of preparing the agent with the above indicated components. EFFECT: high antibacterial activity and stability of preparation. 5 cl, 4 tbl, 7 ex

Description

 The invention relates to the field of medicine and, in particular, relates to the creation of funds for combating microorganisms.

 Liquid antimicrobial formulations based on a mixture of hydrogen peroxide and quaternary ammonium compounds are known.

 For example, a product called "PVC", manufactured according to TU-2386-019-13164401-95, contains 25-38% hydrogen peroxide and up to 2% quaternary ammonium compound (HOA) - alkyl dimethylbenzylammonium chloride as the active ingredient.

 The tool called "Grillen" is a liquid that contains 9-25 wt.% Hydrogen peroxide and 18-25 wt.% N-alkanoylaminopropyl dimethylbenzylammonium chloride. (The list of new des. Means authorized for use 0001-92 from 09/17/92.).

Both drugs have a wide range of antimicrobial effects. However, both of them have a number of significant drawbacks:
1. Unsafe and inconvenient in operation - both formulations are based on the use of concentrated solutions of hydrogen peroxide, which often causes burns, regardless of the use of protective equipment.

 2. Causes irritation of the upper respiratory tract of personnel.

 3. They have low stability - during long-term storage and transportation oxygen is released, which leads to an increase in pressure in the tanks.

 4. Strongly corrode tools.

The closest in technical essence and the achieved result is a powdered antimicrobial agent consisting of hydrogen peroxide, urea, dimethylbenzylammonium chloride and aerosil (US Pat. RF 2083228). Despite the obvious positive result achieved in this patent, the method for producing a disinfectant described therein has several disadvantages:
1. The process is multi-stage and non-technological.

 2. The result is a preparation of a heterogeneous composition.

 There is also a method of obtaining antiseptic and disinfectant preparations based on chlorides, iodides or bromides of alkyl dimethylbenzylammonium (HOUR) and hydrogen peroxide in powder form (US Pat. RF 20663852). To obtain a powder form, a number of salts are introduced into the composition.

 An object of the present invention is to expand the range of antimicrobial agents, increase their activity and stability.

 An antimicrobial agent based on hydrogen peroxide and QAS is devoid of these disadvantages. One way to solve this problem is to transfer antimicrobial agents from liquid to solid powder form.

 A method for producing powdered antimicrobial agents based on hydrogen peroxide and HOUR is also provided.

 To solve this problem, an antimicrobial agent is proposed that contains, in addition to hydrogen peroxide, HOUR, urea and one organic acid or a mixture of two or more organic acids.

 To improve the technology and obtain a homogeneous composition of the drug, the process of obtaining a new powdered antimicrobial agent is carried out in one stage.

 According to the proposed method, an aqueous solution of hydrogen peroxide, an aqueous solution or an HOUR powder, urea and an organic acid are mixed in the apparatus. Organic acid is introduced at the beginning of the process or at its completion before the separation of the powdery preparation from an aqueous solution.

 As organic acids, mainly low and medium molecular weight acids were used. Such as lactic, formic, acetic, tartaric, oxalic, adipic, citric, malic, salicylic, water-soluble acids.

The composition of the preparations obtained by this technology in%, weight ranges from:
Hydrogen Peroxide - 28 - 35
HOUR - 1.5 - 2.5
Organic Acid - 0.01 - 1
Urea - Else
The preparations obtained by the proposed method are crystalline powders that are easily pressed into tablets, readily soluble in water, stable during long-term storage, have a prolonged effect against a wide range of gram-positive and gram-negative bacteria, viruses. They can be used for processing domestic and industrial premises, hotels, cafes, bars, salons, airplanes, auto and railway transport, sports facilities and equipment, medical equipment, veterinary hospitals, clothes, shoes.

 Examples of the preparation of powder formulations and their antimicrobial properties.

 Example 1

800 g of hydrogen peroxide (H ₂ O ₂ content _of 37%, pH 3) were poured into a vessel with a working stirrer, followed by 125 g of a 50% aqueous solution of benzalkonium chloride and 715 g of urea in series. Urea quickly dissolves in the mixture and a homogeneous solution is obtained, while the pH of the mixture rises from 3 to 8. The contents of the reactor are heated to 40-42 ^o C and kept at this temperature for 1 hour. Then, 10.6 g of acetic acid are introduced into the reactor over 10 minutes. The resulting slightly yellowish, foaming solution is poured into a crystallizer and cooled to -3, -5 ^o With stirring. Withstand at this temperature for 30-35 hours.

Isolation of the complex from the suspension is carried out by vacuum filtration or centrifugation (preferably by centrifugation). Drying is carried out in a vacuum drying oven at a temperature of 25-35 ^o C in vacuum.

 Similarly prepared antimicrobials using other benzalkonium chlorides such as lauryl, cetyl, stearyl, diizobutilkrezoksietoksietil-, N-alkanoilaminopropil, diisobutyl, fenoksietoksietildimetilbenzilammony chlorides alkildietilbenzilammony chloride alkildimetilnaftilmetilammony chloride (tert-oktilfenoksietil) dietilbenzilammony chlorides and dialkildietil diaoctyldimethylammonium chlorides, alkyltrimethylammonium chloride.

 Example 2

Analogously to example 1, the tool is prepared from 850 g of hydrogen peroxide (contains H ₂ O ₂ 30%), 90 g of dimethyl didecylammonium bromide, 715 g of urea and 10.6 g of acetic acid. The selection of the powdered agent is similar to that described above. An antimicrobial agent with other quaternary ammonium compounds (didecyldimethylammonium bromide, alkyltrimethylammonium bromide, cetyldimethylbenzylammonium bromide, tetradecylpyridinium bromide, cetylmethyltrimethyltrimethylamidobetrylmethyltrimethylamidecarbyltrimethylamide carbide.

 Example 3

Analogously to example 1, a powdered antimicrobial agent is prepared from 340 g of hydrogen peroxide (H ₂ O ₂ content _of 35%), 120 g of a 50% aqueous solution of N-alkanoylaminopropyl dimethylbenzylammonium chloride, 240 g of carbamide and 4.6 g of acetic acid.

 Example 4

 Analogously to example 1, a powdered antimicrobial agent is prepared from 800 g of hydrogen peroxide, 125 g of catamine AB and 715 g of urea. Before isolation, 10 g of a previously prepared mixture of acetic and citric acid (1: 1) is introduced into the liquid reaction mixture.

 Example 5

 The process is carried out analogously to example 1. Before isolation of the crystalline antimicrobial agent, 10 g of salicylic acid are added to the liquid reaction mixture.

 Example 6

 Analogously to example 1, a powdered antimicrobial agent is prepared from 1000 ml of 38% hydrogen peroxide, 120 g of a 50% aqueous solution, a mixture of (1: 1) alkyl dimethylbenzylammonium chloride and alkyl diethylbenzylammonium chloride, 600 g of carbamide and 10 g of formic acid.

 Example 7

 The toxic and antimicrobial properties of the preparations obtained were studied using the example of the powder obtained in example 1. Its registered name is Okades.

 1. Okadez is a crystalline powder of white or light yellow color, contains 28-34% hydrogen peroxide, 2.0% alkyldimethylbenzylammonium chloride (catamine AB) as the active substance. The shelf life of the product in the unopened packaging of the manufacturer is 2 years; the shelf life of working solutions is 1 day.

According to the parameter of acute toxicity when introduced into the stomach, Okadez belongs to class 3 of moderately hazardous substances according to GOST 12.1.007-76 (LD ₅₀ is 1208 ± 157 mg / kg).

When applied to the skin (LD ₅₀ > 2500 mg / kg), the Okadez product belongs to the 4th class of low-hazard substances according to OST 12.1.007-76.

 When inhaled in saturating concentrations (vapors), the Okadez product in powder form belongs to class 4 of low-hazard substances in terms of volatility. The tool does not dust.

 "Okadez" has a pronounced local irritating effect in the form of a powder with a single exposure to the skin and mucous membranes of the eyes (possibly corneal damage), does not have a sensitizing effect. Working solutions in concentrations of 1.5-7.0% with single and multiple repeated applications do not exert a local irritating effect on the skin and eyes, 10-12% solutions cause dry skin when repeated applications and in contact with the eyes cause slight irritation of the mucous membranes.

 2. Okadez has antimicrobial activity against bacteria (including Mycobacterium tuberculosis), viruses (including parenteral hepatitis viruses and HIV), fungi of the genus Candida, Trichophyton, as well as detergent properties.

 The study of the antimicrobial properties of the funds was carried out in accordance with the methods set forth in the collection "Test methods for disinfectants to assess their safety and effectiveness", M., 1998, part 2.

Test surfaces (tiles, metlach tiles, linoleum, painted wood), dishes, fabric tests (calico), tests made of rubber, plastic, glass were tested as test objects. As test microorganisms, Escherichia coli (strain 1257), Staphylococcus aureus (strain 906), Mycobacterium B ₅ , Candida albicans (strain 15), gypsum trichophyton, type 1 polio virus (vaccine. Strain LSC 2ab) were used. Inactivated horse serum in the amount of 40 and 80%, 40% fecal emulsion, 10% semolina was used to simulate organic pollution. The neutralization of the agent was carried out with a solution containing 3% tween-80, 3% saponin, 0.1% histidine, 0.1% cysteine, sodium thiosulfate.

 The following are the modes of disinfection of various objects with Okasez solutions (Table 1-4).

 Powdered antimicrobial agents based on hydrogen peroxide and QAS can be used to treat indoor surfaces, hard furniture, sanitary equipment, linen, dishes, patient care items, cleaning materials, for bacterial infections (including tuberculosis), and viral (including parenteral hepatitis and HIV infection) etiology, candidiasis and dermatophytosis, in medical institutions, public catering establishments, at public facilities, for disinfection of medical devices appointment for viral infections (including parenteral hepatitis and HIV infection) etiology in health facilities.

Claims (4)

1. Antimicrobial agent containing hydrogen peroxide and a quaternary ammonium compound, characterized in that it further comprises urea and one or a mixture of two or more organic acids in the following ratio of ingredients, weight. %:
Hydrogen Peroxide - 25-35
Quaternary ammonium compound - 1.5-2.5
Organic acid or a mixture of two or more organic acids - 0.01-1
Urea - Else
2. The antimicrobial agent according to claim 1, characterized in that acids of low and medium molecular weight are used as the organic acid.  3. The antimicrobial agent according to claim 2, characterized in that they use an organic acid selected from the group: formic, acetic, lactic, tartaric, oxalic, adipic, citric, malic, and salicylic. 4. A method of producing an antimicrobial agent by mixing hydrogen peroxide and a quaternary ammonium compound followed by isolation of a powdery preparation, characterized in that urea is additionally introduced, then the mixture is heated to 40-42 ^o C and maintained at this temperature, then an organic acid or a mixture of two and more organic acids, the resulting solution is cooled to minus 3-5 ^o C, incubated for 30-35 hours, the target product is isolated and dried at 25-35 ^o C in vacuum.  5. The method according to p. 4, characterized in that the organic acid is selected from the group: formic, acetic, lactic, tartaric, oxalic, adipic, citric, malic, salicylic.

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