Antimicrobial agent

 

(57) Abstract:

The invention relates to the field of medicine and for the creation of structures with a wide spectrum of antimicrobial action. Antimicrobial agent in powder and tablet form, containing powdered complex one or a mixture of two or more Quaternary ammonium compounds or complex with powdered organic compounds, inorganic or polymeric origin, produce active oxygen when dissolved; or a mixture of H with metal salts or metal complexes with urea, and optionally excipients. The tool has a high bactericidal activity, stable during prolonged storage, does not irritate the respiratory tract, has prolonged activity against wide spectrum of gram-positive and gram-negative bacteria, viruses, fungi. 3 S. and 9 C. p. F.-ly, 3 tables.

The invention relates to the field of medicine and for the creation of structures with a wide spectrum of antimicrobial action.

It is known that Quaternary ammonium compounds (QAC) have a broad spectrum of antimicrobial action.

In particular, it is known that alkyldimethylbenzylammonium bacteria and fungi (E. A. Ruzic and other Antibiotics, 26, 11, S. 847-851, 1981).

Organic and inorganic peroxy compounds including hydrogen peroxide, in turn, also have a broad spectrum of antimicrobial activity (U.S. Patent 4320116; 2429971; 2266835; 2836533; 4404191; 4477438; 4518585 and others).

Patented funds combining peroxide compounds with Quaternary ammonium compounds; it is assumed that new members should have higher antimicrobial activity than the original components (U.S. Patent 2917428; 2436673; 4324784; French Patent 2663852).

The closest in technical essence and the achieved result is a tool available called STC (Russia THAT 2386-019-13164401-95 the patent of Russia 1587725, B 35, 1989), consisting of a mixture of hydrogen peroxide and Catamine AB (50% aqueous solution of alkyldimethylbenzylammonium, Russia, THE 9392-003-48-182528-99).

Despite the high bactericidal activity this tool has a number of disadvantages: security and inconvenience in the work - formulation composition based on the use of concentrated aqueous solutions of hydrogen peroxide and often causes burns personnel, regardless of use of protective equipment; estabished respiratory tract irritation staff During long-term storage and transport of oxygen is liberated, which leads to increased pressure in the tanks. Heavily corroded tools when handling.

The technical task of the present invention is to remedy these disadvantages and expansion applications.

Offered powder or preformed antimicrobial compounds, including powdered antimicrobial compositions consisting of a mixture of powdered complexes of Quaternary ammonium compounds and:

powdered compounds that produce active oxygen when dissolved in water or other media

water-soluble powder form of salts of the metals M2+M3+.

To solve this problem are obtained powdery complex one or a mixture of two or more Quaternary ammonium compounds (QAC) with urea, thiourea and other complexing compounds organic, inorganic, polymeric origin.

The solutions obtained complexes HOUR in water or other liquid environments exhibit high antibacterial activity. The activity of solutions of a mixture of two or more complexes of Quaternary ammonium compounds above Abduh and more than an HOUR with powdered compounds, produce active oxygen (when dissolved in water or other media) or with a water-soluble complexes or salts of metals obtained new powder formulations, solutions in which water or other environments exhibit high antimicrobial activity. The prepared formulations that combine powdered complexes of Quaternary ammonium compounds: (a) powdered sources of active oxygen, as, for example, a complex of hydrogen peroxide with urea (peroksigidrat urea or hydroponic) or polyvinylpyrrolidone, perborate sodium, peroxiderythromycin potassium, percarbonate sodium, monopersulfate potassium, peroxomonosulfate potassium, parperfeito sodium, monoperoxyphthalate uranyl magnesium, ammonium persulfate, benzoyl peroxide, peroxides of calcium, zinc and other compounds, inorganic and organic origin that produce active oxygen in water or other media; (b) salts and complexes of metals, such as, for example, complexes lCl3or Zn(OH)2with urea, etc.

In the study of antimicrobial activity of the obtained compounds was found that aqueous solutions of metal salts and HOUR by themselves exhibit high antibacterial SVK hemostatic means, RF patent 2142278) was highly active antibacterial drug (Methods of microbiological control of medicines /PF/, vol. 2. Art. 187, and amendments thereto from 28.12.95 year).

The method is one-step synthesis of a mixture of powdered sources of active oxygen, and Quaternary ammonium compounds from a liquid source mixtures. For example, from a mixture of liquid hydrogen peroxide and Catamine AB (aqueous 50% solution of dimethylammoniumchloride) in collaboration with urea obtained powder containing a mixture of peroxyhydrate urea and complex Catamine AB with urea. Or from aqueous solution ll36N2Oh, Catamine AB and urea obtained powder containing in the structure all the original components.

To regulate the operational, physical, chemical and disinfectant properties of powder mixtures described in this application, the composition was administered accessories. These include:

a) carbonates, bicarbonates, chlorides, sulphates, hydrosulfate and other water-soluble salts of alkali and alkaline earth metals;

b) a water-soluble polymer is PVA, PVP, starch, cellulose derivatives, alginic acid and other synthetic and natural is proizvodnye higher fatty alcohols, phenols, acids, sorbitan, lanolin, etc., metal salts, Surfactants (lauryl-M, lauralanthalasa-M, and others);

g) organic acids and their salts - tartaric, benzoic, oxalic, adipic, citric, malic, salicylic, and other

d) moist collectors, components for regulating the pH of the mixture, corrosion inhibitors, and others;

e) stabilizers (for example, for stabilizing hydrogen peroxide) salt - salt MD2+Sn2+, Zn2+Cd2+, Al3+and other

W) dyes, odorants, and other ingredients needed in the recipe.

The ratio of the powdered forms of oxygen or metal salts to powdered forms of the Quaternary ammonium compound is from 9:1 to 1:9. The number of auxiliary compounds ranges from 0 to 76% by weight of the basic component.

The proposed composition is stable during long storage, dissolve easily in water, no smell, does not irritate the respiratory tract. Solutions of the compounds in water or other environments are stable and have a prolonged effect against a wide spectrum of gram-positive and gram-negative bacteria, viruses, fungi, etc.

Based on the above mixtures created powdery and who their teeth. Powdered salt of Quaternary ammonium compounds were added in the composition of household bleach to render them antiseptic properties. They can be used for processing domestic and industrial premises, hotels, cafes, bars, beauty salons, aircraft, road and rail transport, sports facilities and equipment and other crowded places, honey. equipment, veterinary clinics, clothing, shoes, etc.

Below are examples of the preparation of the powder components of new antimicrobial drugs and examples of the preparation of various compositions based on them.

la) Examples of preparation of powdered complexes of Quaternary ammonium compounds with urea, thiourea and other complexing agents.

Example 1.

To 60 g of Catamine AB (50% solution dimethylammoniumchloride in water) is added 60 g of urea and stirred at a temperature of 55-60oWith 1 hour. Falls white mass, adherent to the wall of the vessel. Added 400 ml of isopropyl alcohol, cooled to 0oC and the precipitation is filtered. Dried powder in a vacuum of 100 mm stop RT. tbsp. at a temperature of 30-40oC.

The output of the powder of the complex is salmonellae, such as lauryl-, myricetin, cetil, stearyl, diisobutyldimethoxysilane-, N-alkanolamines, Diisobutyl, paroxetineandlorazepamiy, alkyldimethylbenzylammonium, alkyldimethylbenzylammonium, (tert-octylphenoxy)diethylbenzamide.

Example 2.

To 200 ml of isopropyl alcohol is poured 60 g of a 50% solution of didecyldimethylammoniumchloride in water and 60 g of urea was Stirred at 55-60oWith 1 hour. The resulting solution light yellow color was filtered through a nylon filter, the filtrate was cooled tooC and left to stand until the precipitate discarded. The precipitate was filtered and dried in vacuum at 100 mm RT. Art. at 30-40oC.

The output of the complex mixture of 60 g

Similarly prepared complex of urea with other Quaternary ammonium compounds, such as dialkyldimethyl, dioctyladipate, alkyltrimethyl, alkylmethacrylamide, octylacrylamide, and also complexes of urea with didecyldimethylammoniumchloride, alkyltrimethylammonium, satellitetelevision, tetradecyltrimethylammonium, cetylpyridinium, sterilisability(trimethylammonium) and other chetverti the ml of isopropyl alcohol added 60 g of a 50% solution of a mixture of (1.1) alkyldimethylbenzylammonium and alkyldimethylbenzylammonium chloride and 60 g of urea. Was stirred at 55-60oWith 1 hour. The resulting solution was filtered through a nylon filter, the filtrate was cooled and left to stand until the precipitate discarded. The precipitate was filtered off, washed with twice 200 ml of isopropyl alcohol.

The output of the complex mixture of 60 g

Example 4.

To 60 g of a 50% solution of alkyldimethylbenzylammonium (Ketamin AB) add 60 g of thiourea and stirred at 55-60oWith 1 hour. Falls white mass. Add 400 ml of isopropyl alcohol, cooled to 0oC, the precipitate is filtered off and dried in vacuum at 30-40oC. Exit 58,

Example 5.

In 200 ml of isopropyl alcohol was dissolved 30 g of dimethyldiallylammonium and 45 g of polyvinylpyrrolidone. The mixture was kept at 35-40oWith 6 hours. The precipitation is filtered off and dried in vacuum. The output of complex 48 g

IB) Preparation of complexes of metal salts with urea.

Example 6.

150 ml isopropylate alcohol dissolve 70 g of urea and 54 g ll36N2Oh and stirred for 2 hours at 60oC. is Cooled, the precipitated white precipitate is filtered off, washed with cold ethanol and dried in vacuum. Similarly prepare the complexes of urea with other salts metrogo ammonium compound.

Example 7.

A) To 100 ml of 30% hydrogen peroxide at 20oWith the addition of 6 g of Catamine AB (50% aqueous solution of apsiltintos.laminatas) and mixed, the resulting mixture is added to 90 g of urea and stirred for 1 hour at 20oC. During this time, the urea is completely dissolved. In the next hour, gradually begins with the loss of a crystalline precipitate. Mix for a further 1 hour at 30oC, cooled to 0oand added 600 ml of chilled isopropyl alcohol. The precipitate is filtered, washed with 300 ml of cold isopropyl alcohol. Dried the resulting complex mixture of hydrogen peroxide and Catamine AB with urea in a vacuum of 100 mm stop RT. senior Exit 32,

B) Preparing a mixture of 100 ml of 38% hydrogen peroxide, and 6 g of Catamine AB. To the mixture is added to 90 g of urea and stirred for 1 hour at 38-40oC. the Liquid mixture is filtered, transferred into molds, cooled to -5oC. is maintained at this temperature for 6 hours. The precipitation is allocate by centrifugation and dried in a vacuum drying oven to a moisture content of not more than 0.1%.

Similarly prepare a powder mixture of complexes of hydrogen peroxide and other Quaternary ammonium compounds of the mixture, contains both Katanin AB, ll3and urea.

Example 8.

In 70 ml of isopropyl alcohol was dissolved successively 36 g of urea, 1.5 g of Catamine AB and 27 g of AlCl36N2The acting is Stirred for 2 hours at 50oC. saliva covered by the suspension. Cool 2 hours at 0oTo add another 50 ml of isopropyl alcohol and filtered. White powder complex of urea with ll3and Catalina AB dried in vacuum at 30-40oC.

III) Examples of preparation of powdered antimicrobial compositions of complexes of Quaternary ammonium compounds.

Example 9. (wt.%)

Complex Catamine AB with urea - 50-100

Accessories - 0-50

Example 10. (wt.%)

Complex Catamine AB with urea - 25-50

Complex dimethyldiallylammonium with urea - 25-50

Accessories - 0-50

IV. Examples of the preparation of powdered antimicrobial compositions based powdered complexes of Quaternary ammonium compounds (QAC) and peroksigidrat urea.

Example 11.

In a mixer to prepare powder compositions are mixed, wt.%:

Peroksigidrat urea (hydroponic, stomegatonny substances - 0-50

Example 12.

Analogously to example 11 to prepare a mixture, wt.%):

Peroksigidrat urea (hydroponic) - 20-50

Complex dimethyldiallylammonium with urea - 3-10

Accessories - 0-50

Example 13.

Analogously to example 11 to prepare a mixture, wt.%:

Peroksigidrat urea (hydroponic) - 20-50

Complex alkyldimethylbenzylammonium - 10

Complex alkyldimethylbenzylammonium - 10

Accessories - 0-50

Example 14.

Analogously to example 11 to prepare a mixture, wt.%:

Peroksigidrat urea (hydroponic) - 10-30

Complex Catamine AB with urea - 1-10

Complex didecyldimethylammoniumchloride with urea - 1-10

Accessories - 0-50

Example 15.

Analogously to example 11 are mixed, wt.%:

The complex of hydrogen peroxide with polyvinylpyrrolidone - 20-50

Complex dimethylammoniumchloride with urea - 3-10

Accessories - 0-50

V. Examples of cooking powdered antimicrobial mixtures and blends for tableting based complexes HOUR and peroxisome.

VI. Example 16 (wt.%):

Perborate sodium - 40

Complex Catamine AB with MOC is 0,3

Oxalic acid - 20

Magnesium stearate - 1

The sodium sulfate - 10

Example 17 (wt.%):

Perborate sodium - 30

Complex Catamine AB with urea - 3

Sodium bicarbonate - 30

The sodium sulfate - 10

Tartaric acid - 20

Starch (maize) - 5

Sodium chloride - 1

Magnesium stearate - 1

Example 18(wt.%):

Percarbonate sodium (12% active oxygen) - 45

Complex Catamine AB with urea - 4

Sodium carbonate - 30

Sodium chloride - 10

Sodium dodecyl sulfate - 0,3

Tartaric acid - 10

Aerosil - 0,3

The sodium oleate - 0,4

Example 19. (wt.%):

The potassium persulfate (4.5% of active oxygen) - 20

Complex Catamine AB with urea - 4

Sodium chloride - 60

Sodium carbonate - 15

Inhibitor - 0,7

Aerosil - 0,3

Example 20. (wt.%):

Perperemeshat sodium (9% active oxygen) - 20

Complex dimethylammoniumchloride with urea - 5

The sodium sulfate - 50

Sodium bicarbonate - 20

Alkylarylsulfonate - 5

VI. Examples preparation of antimicrobial compounds on the basis of the HOUR and metal salts.

Example 21 (wt.%):

The complex of aluminium chloride with urea - 25-50

Complex Catamine AB with urea - 1-10 the blame - 25-50

Complex Catamine AB with urea - 1-10

Accessories - the Rest.

Example 23 (liquid composition) (wt.%):

lCl36N20 - 25g

Katamin AB - 1 g

Water Up to 100 ml

VII. Examples of the antiseptic compositions for hygienic treatment of hands of medical personnel, leather, surgical and injectable fields, etc. are given in table. 2.

VIII. Examples of the preparation of powder compositions based complexes HOUR and peroxides of metals.

Example 29. Therapeutic composition for external use, wt.%:

Peroxide zinc - 10

Peroxide calcium - 1

Complex Catamine AB with urea - 0,2

PEG - 59,8

Propylene glycol - 29

IX. Examples of the preparation of the compositions of the powders and tablets for mouth rinsing, cleaning and teeth whitening based complexes HOUR and peroxisome.

Example 30 (wt.%):

Monopersulfate potassium - 20

Complex Catamine AB with urea - 3

Ethylenediaminetetraacetic acid - 1

Sodium bicarbonate - 20

Sodium carbonate - 10

Citric acid - 10

Malic acid - 10

Sulfamic acid 3

Ulfat sodium o/ - 12

Sodium dodecyl sulphate - 0,5

PEG 4000 - 6

Example 31 (wt.%):

Monopersulfate potassium - 20

Sodium chloride - 60

Sodium carbonate - 15

Complex Catamine AB with urea - 5

Comparative evaluation of antibacterial activity of the obtained compounds (MIC - minimum inhibitory concentration) is shown in table. 3.

1. Antimicrobial agent containing powder of the complex of one or a mixture of two or more Quaternary ammonium compounds (QAC), and auxiliary substances selected from the group of water-soluble salts of alkali and alkaline earth metals, water-soluble synthetic and natural polymers and copolymers, anionic and/or nonionic surfactants, organic acids and their salts, moist collectors, mixture, regulating pH, corrosion inhibitor, stabilizer, colorant, odorant, the number of auxiliary components is from 0 to 76% by weight of the basic component.

2. Antimicrobial agent containing powder of the complex of one or a mixture of two or more HOURS with powdered organic compounds, inorganic or polymeric origin, produce active oxygen when dissolved, selected from the group of solid photoshopprivate potassium, peroxomonosulfate potassium, parperfeito sodium, monoperoxyphthalate uranyl magnesium, ammonium persulfate, benzoyl peroxide, calcium peroxide, peroxide zinc, as well as auxiliary substances selected from the group of water-soluble salts of alkali and alkaline earth metals; water-soluble synthetic and natural polymers and copolymers; anionic and/or nonionic surfactants; organic acids and their salts, moist collectors, mixture, regulating pH, corrosion inhibitor, stabilizer, colorant, odorant, the ratio of the compounds of the sources of active oxygen, and the HOUR is 9: 1-1: 9, and the number of auxiliary components from 0 to 76% by weight of the basic component.

3. Antimicrobial agent containing powder of the complex of one or a mixture of two or more HOURS with metal salts or complex metal with urea, and an excipient selected from the group of water-soluble salts of alkali and alkaline earth metals; water-soluble synthetic and natural polymers and copolymers, anionic and/or nonionic surfactants, organic acids and their salts, moist collectors; mixtures of regulating pH, ingot from 0 to 76% by weight of the basic component.

4. Antimicrobial agent under item 1, or 2, or 3, characterized in that as the water-soluble salts of alkali and alkaline earth metals it contains carbonates, bicarbonates, chlorides, sulphates, hydrosulfate.

5. Antimicrobial agent under item 1, or 2, or 3, characterized in that water-soluble polymers it contains polyvinyl alcohol, polyvinylpyrrolidone, starch, cellulose derivatives, alginic acid.

6. Antimicrobial agent under item 1, or 2, or 3, characterized in that anionic and nonionic substances it contains ampholytes, betaines, polyoxyethylene derivatives of higher fatty alcohols, phenols, acids, sorbitan, lanolin, metal salts, lauryl-M, lauralanthalasa-M

7. Antimicrobial agent under item 1, or 2, or 3, wherein as the organic acids, it contains tartaric, benzoic, oxalic, adipic, citric, malic, or salicylic.

8. Antimicrobial agent under item 1, or 2, or 3, characterized in that it is made in powder form.

9. Antimicrobial agent under item 1, or 2, or 3, characterized in that it is made in pill form.

10. Antimi and teeth whitening.

11. Antimicrobial agent under item 1, or 2, or 3, characterized in that it has a prolonged effect against a wide spectrum of gram-positive and gram-negative bacteria, viruses, fungi.

12. Antimicrobial agent under item 1, or 2, or 3, characterized in that it is intended for processing facilities, transport, sports equipment, clothes, shoes.

 

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