RU2372943C1 - Disinfectant compound - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: compound possesses improved bactericidal and viricidal activity. A disinfectant compound contains polyguanidine compound, quaternary ammonium compound and water, as quaternary ammonium compound, synergetic mixture of any two or three quaternary ammonium compounds of: alkyl benzyl ammonium chloride, or dialkyl dimethyl ammonium chloride, or alkyl trimethyl alkyl chloride, or trialkyl methyl alkyl chloride, or N-heterocyclic quaternary ammonium compound: N-lauryl pyridinium chloride, N-cetyl pyridinium chloride, polyethylene pyrrolidinium chloride, N-alkyl-N-ethyl piperidinium ethyl sulphate is used. The mass ratio for any two quaternary ammonium compounds is 1:(1÷3.5); for any three quaternary ammonium compounds (1:1:1) - (1:2:3), and the mass ratio for polyguanidine compound and mixed quaternary ammonium compounds 1: (0.25-4.0). As polyguanidine compound use poly-(4,9- guanidine dioxadodecane) (PGDD) phosphate, or poly-(4,9- guanidine dioxadodecane) chloride, or poly-(4,9- guanidine dioxadodecane) gluconate, or poly-(4,9- guanidine dioxadodecane) citrate, or poly-(4,9- guanidine dioxadodecane) benzoate, or polyhexamethylene guanidine (PHMG) citrate, or polyhexamethylene guanidine gluconate, or polyhexamethylene guanidine formate, or polyhexamethylene guanidine benzoate, or polyhexamethylene guanidine phosphate, or polyhexamethylene guanidine chloride, or polytrimethylene diguanidine, or poly-(3,6-dioxaoctaguanidine) chloride, or poly-(3,6-dioxaoctaguanidine) phosphate, or poly-(3,6-dioxaoctaguanidine) gluconate, or poly-(3,6-dioxaoctaguanidine) benzoate, or poly-(4,7,10-trioxatridecane guanidine) chloride, or poly-(4,7,10-trioxatridecane guanidine) phosphate, or poly-(4,7,10-trioxatridecane guanidine) gluconate, or poly-(4,7,10-trioxatridecane guanidine) benzoate, or 1,6-biguanidinohexane dihydrochloride.

EFFECT: enhancement of the disinfectant, spectrum of antimicrobic activity and intensification of biocide properties.

2 cl, 3 tbl

Description

The invention relates to the field of sanitation and hygiene. The tool has increased bactericidal and virucidal activity. When nonionic surfactants are added, the product acquires good washing properties. It has no harmful effect on the environment, it is safe when used in the presence of people, does not change the structure of the processed material. The invention can be used for disinfection of premises, washing of furniture, dishes, linen, for disinfection and pre-sterilization cleaning of medical devices, washing and disinfection of food industry equipment, washing and disinfection of buildings and equipment of livestock and poultry farms, as well as for disinfection of various types of water, in particular drinking water, urban and industrial wastewater, swimming pool water and equipment cooling systems, etc.

A disinfectant is known, including a mixture of a polyguanidine (PG) compound and a quaternary ammonium compound (HOUR), (US Pat. No. 2057796, class C11D 1/835, 1996). However, the known tool can be used mainly only for disinfection of toilets.

The closest solution to the proposed is a disinfectant, including the connection of PG and HOUR, as well as fir oil (US Pat. RF No. 2263708 class. C11D 3/48, B.I. No. 31, 2005).

The disinfectant has the following content of components, wt.%:

Disinfecting agent 2.2-3.0 Nonionic Surfactant 5.0-20.0 Fir oil 2.75-3.0 Water soluble dye 0.001-0.2 Water up to 100

The disadvantages of the known funds include insufficient biocidal activity, because the use of fir oil does not lead to a significant increase in bactericidal activity.

The technical problem solved by this invention is to expand the functionality of the disinfectant and enhance its biocidal properties. In addition, the spectrum of antimicrobial activity is expanding.

The technical problem is solved due to the fact that in a disinfection composition containing polyguanidine, a quaternary ammonium compound and water, as a quaternary ammonium compound, a synergistic mixture of any two or three quaternary ammonium compounds from the series: alkylbenzylammonium halide, or dialkyldimethylammonium halide halide, or or trialkylmethylammonium halide, or N-heterocyclic quaternary ammonium compound, the mass ratio being in the limit For any two of quaternary ammonium compounds - 1: (1-3.5); for any three quaternary ammonium compounds - in the range (1: 1: 1) - (1: 2: 3), and the mass ratio for the connection of polyguanidine and a mixture of quaternary ammonium compounds is in the range 1: (0.25-4.0) in the following ratio of components, wt.%:

polyguanidine compound 0.1-8.0 synergistic mixture of quaternary ammonium compounds 0.25 - 24.0 water rest

Poly- (4,9-dioxadodecane guanidine) phosphate (PDDG), or poly- (4,9-dioxadodecanguanidine) chloride, or poly- (4,9-dioxadodecane guanidine) gluconate, or poly- ( 4,9-dioxadodecanguanidine), or poly- (4,9-dioxadodecanguanidine) benzoate, or polyhexamethylene guanidine citrate (PHMG), or polyhexamethylene guanidine gluconate, or polyhexamethylene guanidine or guanidine, polyhexamethylene guanidinide or guanidine benzoate anidine, or poly- (3,6-dioxaoctaguanidine) chloride, or poly- (3,6-dioxaoctaguanidine) phosphate, or poly- (3,6-dioxaoctaguanidin) gluconate, or poly- (3,6-dioxoctoaguanidine) benzoate, or poly- (4,7,10-trioxo tridecane guanidine) chloride, or poly- (4,7,10-trioxo tridecane guanidine) phosphate, or poly- (4,7,10-trioxo tridecane guanidine) gluconate, or poly- benzoate (4.7 , 10-trioxo tridecanguanidine), or 1,6-biguanidinohexane dihydrochloride.

These compounds of polyguanidine are made by the International Institute of Ecological and Technological Problems.

The quaternary ammonium compounds used are illustrated by structural formulas.

Alkylbenzylammonium halide with an alkyl chain length of 8-22.

This group includes the quaternary ammonium compounds such as benzalkonium chloride and its derivative leaded alkildimetiletilbenzilammony chloride, lauryldimethylbenzylammonium chloride, tetradetsildimetilbenzilammony chloride, stearyl chloride, iso-oktilfenoksietoksi-2-etildimetilbenzilammony chloride (alkyl radical substituted at residue oktilfenoksietoksi iso-ethyl).

Dialkyldimethylammonium halide with an alkyl chain length of 8-22.

This group includes quaternary ammonium compounds such as dioctyl dimethyl ammonium chloride, didecyldimethyl ammonium chloride, dimethyl (octyl decyl) dimethyl ammonium chloride, dimethyl dimethyl ammonium chloride, distearyl dimethyl ammonium chloride, and their unsaturated methyl di-methyl di-methyl di-methyl di -).

Alkyltrimethylammonium halide with an alkyl chain length of 8-22.

This group includes the quaternary ammonium compounds such as lauryl trimethylammonium chloride, cocotrimethylammonium chloride, cetyltrimethylammonium chloride, dodecyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyl / beheniltrimetilammony chloride beheniltrimetilammony chloride, cocoamidopropyl trimethylammonium chloride, alkildi- (2-hydroxyethyl) -metilammony chlorides (two methyl residues are replaced by two residues of 2-hydroxyethyl), in particular: coco-bis- (2-hydroxyethyl) methylammonium chloride, stearyl bis- (2-hydroxyethyl) methylammo rd chloride.

Trialkylmetalammonium chloride with an alkyl chain length of 8-22.

This group includes quaternary ammonium compounds such as trioctyl methyl ammonium chloride, tri (octyl decyl) methyl ammonium chloride, tridecyl methyl ammonium chloride, trilauryl methyl ammonium chloride, and tricyl methyl ammonium chloride.

N-heterocyclic quaternary ammonium compounds.

Quaternary ammonium compounds such as N-laurylpyridinium chloride, N-cetylpyridinium chloride, polyethylene pyrrolidinium chloride, N-alkyl-N-ethylpiperidinium ethyl sulfate belong to this group.

Supplier - SBK Company 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.

Quaternary ammonium compounds (QAS) exhibit a relatively narrow spectrum of antimicrobial activity - they are effective against pathogens of intestinal and drip infections of bacterial etiology, fungi, some extracellular viruses, but are not active enough against cultures of Proteus vulgaris, Proteus morganii, Pseudomonas aeruginosa, which significantly limits the possibilities their use for the prevention of nosocomial infections.

There is evidence that about 89.5% of hospital strains of the microorganisms of the genus Proteus are resistant to HR. There are cases of nosocomial infections (sepsis with a high mortality rate), which are associated with the use in the clinic of HOUR solutions contaminated with Pseudomonas aeruginosa cultures. Most drugs in this group are not active against intracellular localized viruses, spore forms of bacteria, and mycobacterium tuberculosis.

The main structural elements that determine the antimicrobial properties of QAS include hydrophilic polar quaternary ammonium groups and hydrophobic hydrocarbon radicals. Antimicrobial activity in the homologous series of mono- and bis-quaternary ammonium salts depends on the type of substituents on the nitrogen atom, the length of the radical’s carbon chain, and its degree saturation and branching, the presence of hydroxyl, ether groups, etc. Compounds containing short-chain hydrocarbon radicals (C <8) at the Quaternary nitrogen atom lack or exhibit moderate antimicrobial properties. An increase in the number of carbon atoms in the radical leads to the appearance of surface activity and, together with it, antimicrobial properties. The activity increases with the introduction of unsaturated hydrocarbon radicals, an asymmetric nitrogen atom, and ether bonds into the QAS structure. Among mono-quaternary ammonium salts, the maximum activity, as a rule, is shown by compounds that contain 12-16 carbon atoms in the radical; among bis-quaternary salts of ethylene, propylene, hexamethylene, heptamethylene diammonium, compounds that contain 9-12 carbon atoms in the radical. Further lengthening of the carbon chain leads to a decrease in activity. The toxicity of HOURs, on the contrary, is inversely proportional to the length of the carbon chain - decreases as the number of carbon atoms in the radical increases. Aliphatic HRs are less toxic than cyclic ones.

These data indicate that an increase in antimicrobial activity can be achieved by selection of a mixture of HOURs that have distinctive chemical features and, due to this, exhibit the most pronounced synergism. Synergism is explained by the fact that the molecules of different quaternary ammonium compounds differ in electronic structure, and therefore interact with each other (chemically or electrostatically), forming the so-called “zwitterionic” double-tail surfactants. They give such efficiency.

Nevertheless, analysis and generalization of numerous literature data and research results suggest that the existing assortment of disinfectants from the HOUR group does not fully meet modern requirements for the consumer properties of preparations of this group according to criteria such as universality (used to disinfect a relatively narrow range of objects) , a narrow spectrum of antimicrobial activity, the relatively rapid formation and spread of HRV-resistant variants of microorganisms.

The noted shortcomings make it possible to recommend the use of preparations that contain HOUR mixed with active substances of other classes of chemical compounds, in particular with guanidine derivatives.

The mechanism of action of guanidine polycations is adsorption on a negatively charged surface of a bacterial cell, causing respiratory blockade and transport of metabolites through the bacterial cell wall. Guanidine polycations bind to phospholipids and proteins of the cytoplasmic membrane, which leads to its rupture. Penetrating into the cytoplasm, they cause irreversible damage to intracellular structures.

Thus, the combined action of QAS and guanidine polycations has a stronger bactericidal effect than each of these disinfectants separately. In addition, the spectrum of antimicrobial activity is expanding significantly, and due to the formation of a molecular polymer film of polyguanidines on the treated surface, the antimicrobial preservation period increases several times.

The composition is prepared as follows. Quaternary ammonium compounds are added to the flask with a stirrer containing water, mixing until a homogeneous mixture is formed.

An aqueous solution of polyguanidine is prepared in a separate flask with a stirrer.

A polyguanidine solution is added to the resulting solution of a mixture of a quaternary ammonium compound to a predetermined concentration.

The following examples illustrate the invention.

Example 1

In two flasks with mixers, 48 ml of water is poured into each. 3 g of polyhexamethylene guanidine (PHMG) hydrochloride is charged into the first, 0.5 g of alkyldimethylbenzylammonium chloride and 0.5 g of alkyldimethylethylbenzylammonium chloride are added to the second flask and stirred. After complete dissolution, the solution of the second flask is added to the solution of the first flask, obtaining 100 ml of the following disinfectant: 3% PHMG hydrochloride, 1% quaternary ammonium salt (in the form of a mixture with a 1: 1 ratio of alkyl dimethylbenzylammonium chloride and alkyl dimethylethylbenzylammonium chloride).

This composition can be used to disinfect rooms, furniture, etc., as well as to disinfect various types of water, for example, when bringing its indicators to the quality of drinking water, taking into account the established MPC for the constituent components of the disinfectant.

Example 2

For the case of obtaining funds with a detergent effect, the composition contains a nonionic surfactant in an amount of 3-12 wt.%. Syntanol ALM-10 (produced in accordance with TU 6-63-14-864-88) or neonol: AF 9-12, (produced in accordance with TU 38.507-63-300-93) was used as a non-ionic surfactant.

37 ml of water are poured into two flasks with stirrers. The first is loaded with constant stirring, PHMG hydrochloride in an amount of 4 g. In the second - 6 g of alkyldimethylbenzylammonium chloride, 4 g of cetyltrimethylammonium chloride, 2 g of laurylpyridinium chloride. After complete dissolution, the solution from the first flask is added to the second. To the homogeneous mixture obtained by mixing, 10 g of neonol AF 9-12 are added. After final mixing, 100 ml of the following disinfectant is obtained: 4% PHMG hydrochloride, 12% quaternary ammonium salt (in the form of a mixture with a ratio of 3: 2: 1 alkyl dimethylbenzylammonium chloride, cetyltrimethylammonium chloride, laurylpyridinium chloride), 10% neonol AF 9-12.

The introduction into the composition for the disinfection of neonol AF 9-12 or syntanol ALM-10 enhances the synergy of QAS and polyguanidines by improving penetration through cell membranes. Giving the composition a washing effect, neonol AF 9-12 and syntanol ALM-10 thereby increase its versatility, significantly expanding the scope of the proposed composition for disinfection.

This composition can be used for general disinfection of various rooms, for the disinfection of medical instruments, for washing food processing equipment, etc.

Other examples are summarized in table No. 1. The ratio of the components in the composition is the optimal value and is revealed as a result of numerous experiments. The data in table No. 1 confirm the optimality of the declared limits.

Alternative features of claim 1 and claim 2 of the claims provide the same technical result as shown in table No. 1.

Samples of the drugs were tested for antimicrobial activity. Minimum inhibitory concentrations (MICs) were determined for bacteria of the species Pseudomonas aeruginosa and molds of the species Aspergillus niger using serial dilution in liquid media.

As a liquid nutrient medium for the cultivation of bacteria of the species Pseudomonas Aeruginosa, trypcase-soy broth (TSB) from bioMerieux, France, was used to grow Aspergillus Niger, a moldy liquid medium, екаapek liquid.

Seventeen sterile tubes were poured into 2 ml of a liquid nutrient medium. 2 ml of stock solution was added to the first tube. The contents were mixed and 2 ml was transferred to a second tube and so on to the 15th tube, from which 2 mm was removed. The contents of the 16th test tube served as a control of the growth of microorganisms, and the 17th - the control of the sterility of the nutrient medium. In all tubes except the 17th, 0.2 ml of culture of the test microorganism was added.

Crops with bacterial cultures were incubated in an incubator at 37 ° C for 18-24 hours, and with mold cultures at 29 ° C for 10-14 days. The results were taken into account in the presence of the growth of microorganisms in the control culture and the absence in the control environment. Then the last tube was noted with a complete visible growth retardation of microorganisms. This dilution was the minimum inhibitory concentration for the test strain and determined the degree of its bacteriostatic activity for this drug.

To establish the bactericidal activity of all “not grown” (that is, which did not show visible growth of test microorganisms) tubes with liquid nutrient media and two “germinated” (as a control) using a bacteriological loop, seeding was performed on solid nutrient media. Crops with bacterial cultures were incubated at 37 ° C for 24-72 hours, and with cultures of fungi at 29 ° C for 10-14 days.

The last dilution of the drug in a nutrient medium, from which it was not possible to obtain viable cells of the tested microorganisms, was considered bactericidal. The results for determining the minimum inhibitory concentrations of disinfectants are presented in tables 2 and 3.

Data are presented for the following disinfectant formulations:

1. The prototype;

2. Solution A. HOUR + PHMG chloride in a ratio of 3: 1.

HOUR - a mixture of alkyldimethylbenzylammonium chloride and alkyldimethylethylbenzylammonium chloride in a ratio of 1: 1;

3. Solution B. HOUR + PHMG chloride in a ratio of 3: 1.

HOUR - a mixture of alkyldimethylbenzylammonium chloride, cetyltrimethylammonium chloride, laurylpyridinium chloride in a ratio of 3: 2: 1;

4. Solution C. HOUR + PHMG chloride in a ratio of 3: 1.

HOUR - a mixture of alkyldimethylbenzylammonium chloride, cetyltrimethylammonium chloride, laurylpyridinium chloride in a ratio of 3: 2: 1.

The composition of the solution includes 10% neonol AF 9-12.

Table 1 Examples illustrating the invention. No. / No. Polyguanidine Compound Mixture HOUR (wt.%) Water Technical result two ** three *** (wt.%) Connection Name 3 0.3 PHMG chloride 1,2 - rest the composition has a wide range of biocidal activity four 1,2 poly- (4,7,10-trioxatridecanguanidine) phosphate 4,5 rest 5 2.0 PGMG benzoate 0.5 - rest 6 6.5 PHMG phosphate 20,0 - rest 7 7.0 PHMG chloride - 24.0 rest 8 8.0 PGMG gluconate - 24.0 rest 9 0.05 PHMG chloride 5,0 rest decrease in bactericidal activity 10 8.1 * PHMG chloride 5,0 rest unreasonably high component consumption eleven 1,5 PHMG chloride 0.2 * rest decrease in bactericidal activity 12 1,5 PHMG chloride 24.5 * - rest increased toxicity * - examples beyond the stated limits. ** - in the mixture: alkyldimethylbenzylammonium chloride and lauryltrimethylammonium chloride. *** - in the mixture: polyethylene pyrrolidinium chloride, trioctylmethylammonium chloride, lauryl dimethylbenzylammonium chloride.

Continuation of table 1 Option 1 ** - in the mixture: alkyldimethylbenzylammonium chloride and lauryltrimethylammonium chloride. *** - in the mixture: polyethylene pyrrolidinium chloride, trioctylmethylammonium chloride, lauryl dimethylbenzylammonium chloride. Option 2 ** - Alkyldimethylethylbenzylammonium chloride and cocotrimethylammonium chloride *** - tetradecyldimethylbenzylammonium chloride, dioctyldimethylammonium chloride and behenyltrimethylammonium chloride Option 3 ** - stearyldimethylbenzylammonium chloride and distearyldimethylammonium chloride *** - dodecyl trimethylammonium chloride, didecyldimethylammonium chloride and iso-octylphenoxyethoxy-2-ethyldimethylbenzylammonium chloride Option 4 ** - di- (octyl-decyl) dimethylammonium chloride and cetyltrimethylammonium chloride *** - dicetyl dimethylammonium chloride, stearyltrimethylammonium chloride and N-alkyl-N-ethylpiperidinium ethyl sulfate Option 5 ** - stearyl / behenyltrimethylammonium and trioctylmethylammonium chloride *** - dialkyl dimethyl ammonium chloride, trilauryl methyl ammonium chloride and N-lauryl pyridinium chloride Option 6 ** - dialkylenebenzylmethylammonium chloride and cocoamidopropyl trimethylammonium chloride *** - Alkyldi- (2-hydroxyethyl) methylammonium chloride, N-cetylpyridinium chloride and three (octyl-decyl) methylammonium chloride Option 7 ** - coco-bis- (2-hydroxyethyl) -methylammonium chloride and tricylmethylammonium chloride *** - stearyl bis- (2-hydroxyethyl) methylammonium chloride, trilaurylmethylammonium chloride and dodecyltrimethylammonium chloride

table 2 Comparative data on the minimum inhibitory concentrations of disinfectants for bacteria of the species Pseudomonas aeruginosa. The composition of the disinfectant. The total concentration in water of all substances that make up the disinfectant (μg / ml). 1.28 ± 0.134 0.77 ± 0.069 0.32 ± 0.027 0.26 ± 0.018 Prototype + - - - Solution A + + - - Solution B + + + - Solution C + + + + The sign “+” marks the concentration that has a bactericidal effect, the “-" sign indicates a concentration that does not have a bactericidal effect. Table 3 Comparative data on the minimum inhibitory concentrations of disinfectants for molds of the species Aspergillus niger. The composition of the disinfectant. The total concentration in water of all substances that make up the disinfectant (mg / ml) 0.181 ± 0.021 0.101 ± 0.013 0.071 ± 0.0067 0,057 ± 0,0048 Prototype + - - - Solution A + + - - Solution B + + + - Solution C + + + + The “+" sign indicates the concentration that has a mycocidal effect, the “-" sign indicates a concentration that does not have a mycocidal effect.

Claims (2)

1. A disinfection composition containing a polyguanidine compound, a quaternary ammonium compound and water, characterized in that a quaternary ammonium compound is a synergistic mixture of any two or three quaternary ammonium compounds from the series: alkylbenzylammonium chloride or dialkyldimethylammonium chloride or alkyltrimethylammonium trialkylmethylammonium chloride, or N-heterocyclic quaternary ammonium compound: N-laurylpyridinium chloride, N-cetylpyridinium chloride, polyethylenepyrrolidinium x horide, N-alkyl-N-ethylpiperidinium ethyl sulfate, while the mass ratio for any two quaternary ammonium compounds is in the range 1: (1-3.5), the mass ratio for any three quaternary ammonium compounds is in the range (1: 1: 1) - (1: 2: 3), and the mass ratio for the connection of polyguanidine and a mixture of Quaternary ammonium compounds is in the range 1: (0.25-4.0) in the following ratio of components, wt.%:
polyguanidine compound 0.1-8.0 synergistic mixture of quaternary ammonium compounds 0.25-24.0 water rest 2. The disinfection composition according to claim 1, characterized in that poly- (4,9-dioxadodecanguanidine) phosphate, or poly- (4,9-dioxadodecanguanidine) chloride, or poly- gluconate (4,9 -dioxadodecanguanidine), or poly- (4,9-dioxadodecanguanidin) citrate, or poly- (4,9-dioxadodecanguanidine) benzoate, or polyhexamethylene guanidine citrate, or polyhexamethylene guanidinidinuidanidinidinidinidinidinidinidinidinidinidinidinidinidinidinidinidinidinidinuidinidin, or formate of polyhexamethylene guaniduanidine, or formate polyhexamethylene guaniduanidinidinuidinuidinidina, or polyhexamethylene guaniduinidin or formate of polyhexamethylene guaniduanide or ylidene, polyhexame tylenguanidine, or polytrimethyleneendiguanidine, or poly- (3,6-dioxaoctaguanidine) chloride, or poly- (3,6-dioxaoctaguanidine) phosphate, or poly- (3,6-dioxaoctaguanidine) gluconate, or poly- (3,6- dioxa octaguanidine), or poly- (4,7,10-trioxo tridecane guanidine) chloride, or poly- (4,7,10-trioxo tridecane guanidine) phosphate, or poly- (4,7,10-trioxo tridecane guanidine) gluconate, or poly- (benzoate 4.7,10-trioxo tridecane guanidine), or 1,6-biguanidinohexane dihydrochloride.