WO2012082009A1

WO2012082009A1 - Branched oligomers on the basis of a guanidine derivative and disinfecting agent containing said oligomers (alternatives)

Info

Publication number: WO2012082009A1
Application number: PCT/RU2011/000536
Authority: WO
Inventors: Станислав Анатольевич КЕДИК; Игорь Павлович СЕДИШЕВ; Алексей Валерьевич ПАНОВ
Original assignee: Kedik Stanislav Anatol Evich
Priority date: 2010-12-13
Filing date: 2011-07-20
Publication date: 2012-06-21

Abstract

The invention relates to branched oligomers of hexamethylenediamine and guanidine of formula (I). The above-mentioned compounds can be used as active components of disinfecting agents. The invention also relates to the use of the above-mentioned agents for sterilizing various items, drinking water or circulating water.

Description

Branched oligomers based on a guanidine derivative and a disinfectant containing them (options)

The invention relates to the field of organic chemistry, namely to the synthesis of branched oligomers based on derivatives of hexamethylene guanidines, which can be used as disinfectants in medicine, veterinary medicine, agriculture and housing and communal services, in transport, in the purification of water and air, etc. .

State of the art

Methods for producing condensation products of guanidine and some of its derivatives with hexamethylenediamine are described in US Pat. No. 2,325,586.

(published on 08/03/1943). The specified source discloses the basic conditions and methods for carrying out such condensations, in particular, the ratio

reacting substances close to equimolar, as well as temperature (60-250 ° C, preferably: 130-200 ° C), reaction time (2-20 hours) and methods for producing salts of the resulting condensation products. As the main field of application, textile auxiliary substances are indicated,

providing an increase in the tintability of various synthetic dyes, as well as giving the finished textile product

water repellent properties. The description and claims emphasizes that the products have an unbranched chain of carbon atoms.

In the patent RU 2039735 (publ. 20.07.1995) a method for producing a disinfectant is disclosed, comprising the steps of: (a) condensing guanidine carbonate (KG) with hexamethylenediamine (HMDA) and (b) producing

the corresponding salt of PHMG by treating the carbonate with organic and

inorganic acids.

In step (a), equimolar amounts of CG and HMDA are heated at 140 ° C for 10-15 hours, or at 130 ° C for more than 25 hours. In step (b), an equivalent amount of an organic or inorganic acid is added to a solid reaction product, a concentrated acid solution or triturated with an aqueous suspension of the corresponding sparingly soluble acid, and

the resulting product is dried in vacuo. The disadvantage of this method is the problems that accompany the receipt of the source of carbonate. In particular, the formation of amides at the amino groups of guanidine under the action of carbonic acid, as well as other oxygen-containing acids, at high temperature makes KG unpromising for this application {Patterson P. "Guanidine and Guanidine salts" in the monograph Kirk-

Othmer Encycl. Chem. Technol., 3-rd Ed., N.-Y., 1978, v. 10, p. 514-521). In addition, the resulting products often do not have sufficient disinfectant properties. For example, the minimum concentration inhibiting the growth of E. coli is unsatisfactorily high.

The patent RU 2052453 (publ. 20.01.1996) describes a method for producing a disinfectant containing hydrochloride

polyhexamethylene guanidine (PHMG). The method includes the following stages: (a) preliminary preparation of guanidine hydrochloride (GHC), (b) condensation with hexamethylenediamine (HMDA), (c) purification of the condensation product from toxic HMDA, which involves its conversion to the base form of PHMG

the action of a concentrated alkali solution and repeated washing with water, and (g) treatment with an equivalent amount of organic or

inorganic acid in the form of a concentrated solution or grinding it with an aqueous suspension of the corresponding sparingly soluble acid to obtain the corresponding salt of PHMG.

In step (a), cyanguanidine (dicyandiamide, DCDA) is heated with ammonium chloride (XA) at 180-200 ° C and a molar ratio of DCC: XA = 1: 2 for 2-3 hours. At stage (b), in the resulting reaction mass add HMDA in an amount of 1.0-1.5 mol / mol GHC and the resulting mixture was incubated for 10-15 hours at the same temperature. The disadvantages of the method are the decrease in the yield of GHC in the first stage due to the formation of significant amounts of hydroxy (amino) - s-triazines (ammeline and ammelide), as well as losses of up to 20% of the base when washing with water in stage (c). In addition, slight deviations

parameters of the technological regime (temperature, feed rate of reagents, concentration, mixing intensity) significantly affect the yield and properties of the resulting disinfectant. In the patent RU 2170743 (publ. 20.07.2001) a method for producing a disinfectant is provided, which is carried out by the condensation of HMDA with guanidine derivatives in a melt. In accordance with the first embodiment, the condensation process is carried out for 1 to 2 hours at 180-200 ° C and a molar ratio of HMDA to the guanidine derivative 1: (1, 2-2.0). One of the reagents is used in the form of its salt. Further purification of the product is first carried out by trituration or recrystallization in excess of that inorganic acid, the salt of HMDA or the guanidine derivative of which was used in the condensation reaction, and then the isolated product is washed with ethyl alcohol.

The second variant of this method involves the use of hexamethylene dihydrogenidine dihydrochloride obtained in accordance with the first embodiment as an intermediate for re-interaction with HMDA. Condensation is carried out for 1-2 hours at 180-200 ° C and a molar ratio of HMDA to the guanidine derivative of 1: 1.2. The resulting product is treated with a base or inorganic salt at 20-120 ° C and the ratio

product / base (salt) 1.0: (0.5-4.0), and further purification is carried out with water. Derivatives of hexamethylene guanidines of the formula:

where A ^~ and B- represent OH ^" , H ₂ P0 ₄ ^~ , NaHP0 ₄ ^~ Na ₂ P0 ₄ ^~ , (NH ₄ ) HP0 ₄ ^~ , SG;

m = 1-90, n = 0-90, m + n = 1-90.

The disadvantages of the obtained products are their insolubility in low-polar practically anhydrous environments, as well as a narrow circle of fungi and microorganisms, the growth of which they can have a slowing effect. In addition, the preparations have extremely unsatisfactory organoleptic characteristics, and therefore cannot be used, for example, as an additive to polyterephthalates in the manufacture of glassware for drinks.

As the closest analogue of the present invention, a method for producing disinfectants by melt condensation of hexamethylenediamine and a guanidine derivative, proposed in patent RU 2223791 (publ. 02.20.2004) is considered. The difference between the closest analogue and the first a variant of the method disclosed in patent RU 2170743, is the purification of the finished product in a liquid organic acid medium with the introduction of an equivalent amount of an alkali metal salt of an organic acid, further removal of the inorganic salt and isolation of the finished product, for example, by evaporation of the solution in vacuo. Preferably before

by isolating the finished product, an equivalent amount of acid is added to the reaction mixture, forming the desired salt of the hexamethylene guanidine derivative.

The second variant of the closest analogue of the method in accordance with the present invention is characterized by further purification of the finished product and its isolation in salt form. In this case, the finished product is converted into the base form by treatment with an inorganic base and it is purified by extraction with an organic solvent, after which the finished product is treated with an equivalent amount of organic or inorganic acid. In addition, this variant of the method allows the use of hexamethylenediguanidine dihydrochloride obtained in accordance with the first embodiment as an intermediate for re-interaction with HMDA.

In patent RU 2057796 (publ. 10.04.1996) a disinfectant is disclosed containing a disinfecting agent, a surfactant, a perfume, a dye and water, characterized in that the agent contains a disinfectant

Alkyldimethylbenzylammonium chloride or its mixture with Quaternary

with ammonium salts of dimethylamine and tertiary amine or a salt of a quaternary ammonium base modified with copolymers

polyvinylpyrrolidone, in combination with polyhexamethylene guanidine hydrochloride or polyhexamethylene guaniline phosphate in a mass ratio of 1: (1-4), and as a surfactant, the product contains a biodegradable nonionic surfactant with a surface tension of 30-40 mN / m with a disinfectant content of 0.02 up to 3.0 wt.%, nonionic surfactant from 0.3 to 25.0 wt.%, dye from 0.001 to 0.25 wt.%, perfumes from 0.1 to 15.0 wt.%, the balance is water. The specified tool is intended for the treatment of bathrooms and is unsuitable for disinfection of drinking water due to the presence of surfactants, perfumes and dye in it. In addition, the ratio of the components of the disinfecting agent is not effective when used in the disinfection of water.

The closest analogue of the present invention is

disinfectant in accordance with patent RU 2182889

(publ. May 27, 2002), containing a disinfecting agent and water, as a disinfecting agent, including the first component - polyhexamethylene guanidine hydrochloride or

polyhexamethylene guanidine hydrophosphate and the second component is alkyldimethylbenzylammonium chloride or its mixture with quaternary

ammonium salts of dimethylamine and / or tertiary amine, characterized in that the mass ratio m of the first and second components is in the range of 5: 1 <m <10: 1. The tool provides disinfection of drinking water while enhancing its bactericidal action.

Thus, prior art compounds have

certain disadvantages, namely limited solubility in

low-polar media, for example, in mixtures containing non-aqueous solvents, as well as a fairly narrow spectrum of antibacterial activity, which reduces the effectiveness of disinfectants obtained from them.

All similar products known to the authors of the present invention are characterized by the absence of hydrocarbon radicals at the amide nitrogen atom (> C = NH), i.e. unbranched oligomeric chain. In addition, descriptions of well-known inventions do not suggest that branched structures can be obtained under the conditions disclosed in the respective publications. Also, the prior art does not indicate that such branched compounds may have improved toxicological, corrosive and / or biological properties.

Disclosure of invention

The purpose of this invention are derivatives.

hexamethylene guanidines with improved and stably reproducible disinfecting properties, reduced toxicity and corrosiveness, with an expanded scope, not limited to aqueous solutions, for example, potentially applicable in the industry of coatings and polymeric materials, in the food industry, veterinary medicine and pharmacy. Another goal is to develop a method for producing the corresponding derivatives of hexamethylene guanidines.

Another objective of this invention is the creation of

disinfectants with improved efficacy and toxicity for various applications. In one embodiment,

the disinfectants in accordance with the invention can be used to remove bacterial, viral and fungal contaminants from hard surfaces, such as floors, walls, doors, medical equipment and instruments, dishes, patient care items, etc. In another embodiment, the disinfectants in accordance with the invention can be used in the field of water treatment, in particular for the disinfection of wastewater before it is discharged into water bodies and in the preparation of drinking water or recycled water.

Brief Description of the Drawings

The figure 1 presents the spectra of ¹³ C-NMR of oligomers

hexamethylenediamine and guanidine (OHMG) with a relatively small

molecular weight in the form of hydrochlorides (lower spectrum) and model compounds: hexamethylene diguanidine dihydrochloride (HMDH) and aniline tetraethalhexamethylene dihydrochloride (TEGMDG).

Embodiments of the invention

In a first embodiment, the invention relates to branched oligomers of hexamethylenediamine and guanidine of the formula (I)

a)

/ CH / NH where R represents CH, CH, s

CH. CH, or a ni, n ₂ and n ₃ are 1-3, az is 0.15-1.10 s molecular weight

a distribution of MJM _n from 5.4 to 9.3 with a weight average molecular weight M _w ranging from about 3800 to 6300 and a number average molecular weight M М in the range from about 600 to 1100.

In the first embodiment, branched oligomers are characterized by a z value from 0.54 to 0.68 and a molecular weight distribution of MJM _n from 5.87 to 6.37 with a weight average molecular weight M _w ranging from about 4600 to 6300 and a number average molecular weight M М in the range of from about 780 to 980.

In a further embodiment, the invention provides a disinfectant, characterized in that it contains 0.1-25% (w / v) of the branched oligomer of hexamethylenediamine and guanidine of the formula (I), where ni, p ₂ and p ₃ are equal 1-3, ζ is 0.15-1.10 with a molecular weight distribution MM от from 5.4 to 9.3 with a mass average molecular weight M _w ranging from about 3800 to 6300 and a number average molecular weight M в in the range from approximately 600 to 1,100 in the form of hydrochloride, and also water as a solvent.

In another embodiment, the invention relates to the use of the aforementioned disinfectant for removing bacterial, viral and fungal contaminants, as well as spore contaminants, from various objects when exposed to the specified agent for 2-90 minutes.

Another implementation of the present invention is

a disinfectant containing a disinfectant and

solvent, characterized in that the disinfecting agent consists of the first component - branched oligomers of hexamethylenediamine and guanidine of the formula (I), where n, n ₂ and n ₃ are 1-3, z is 0.15-1.10 with a molecular weight distribution MJM „from 5.4 to 9.3 with a weight average molecular weight M _w ranging from about 3800 to 6300 and a number average molecular weight M _p ranging from about 600 to 1100 in the form of their hydrochloride, phosphate or succinate salts, and the second component - alkyldimethylbenzylammonium chloride or alkyldimethyl (e yl) benzylammonium chloride, or mixtures of one of these compounds with quaternary ammonium salts of dimethylamine and / or (C2-C ₁₀ ) -tertiary amine, wherein

the disinfectant contains from about 1, 5 to about 50% (mass.) of the first component, the mass ratio of the first and second components is in the range from 3.5: 1 to 10: 1, and the solvent is water.

In a preferred embodiment, the disinfectant contains tap water or steam condensate as a solvent,

ogmg hydrochloride or phosphate as a first component and

alkyldimethylbenzylammonium chloride as a second component.

In a more preferred embodiment, the content of the first component in the disinfectant is from 3.0% (mass.) To 6.0% (mass).

In another more preferred embodiment, the content of the first

component in the disinfectant is from 9% (mass.) to 12% (mass).

In another preferred embodiment, the mass ratio of the first and second components of the disinfectant is in the range from 4: 1 to 6: 1.

In a further embodiment, the invention provides

the use of a disinfectant containing a disinfecting agent and a solvent, characterized in that the disinfecting agent consists of the first component - branched oligomers of hexamethylenediamine and guanidine of the formula (I), where ni, p ₂ and p ₃ are 1-3, ζ is 0.15- 1.10 with a molecular weight distribution of MM „from 5.4 to 9.3 with a weight average molecular weight M _w ranging from about 3800 to 6300 and a number average molecular weight M _p ranging from about 600 to 1100 in the form of their hydrochloride, phosphate or succinate salts, the second component - alkyldimethyl benzalkonium chloride or (ethyl) benzylammonium chloride, or mixtures of one of these compounds with quaternary ammonium salts of dimethylamine and / or (C ₂ -C ₁₀₎ -tretichnogo amine, wherein

the disinfectant contains from about 1.5% (mass.) to about 50% (mass.) of the first component, mass

the ratio of the first and second components is in the range from 3.5: 1 to 10: 1, and the solvent is water, for disinfecting wastewater before it is discharged into water bodies and / or in the preparation of drinking water or recycled water.

In a preferred embodiment, the disinfectant is used in the preparation of drinking water.

In a more preferred embodiment, the circulating water is swimming pool water.

As a result of extensive research, the authors of the present invention found that in the conditions for the synthesis of derivatives

hexamethylene guanidines presented in the present description and

illustrated by specific examples, it is possible to obtain

branched structures with unexpected properties. This allows you to overcome some of the disadvantages of the prior art. Accordingly, in a first embodiment, the present invention provides branched oligomers of hexamethylenediamine and guanidine, useful as active ingredients in disinfectants.

The authors unexpectedly found that during the oligomerization of guanidine hydrochloride (HG) and hexamethylenediamine (PUSCHA) taken in molar ratios of HMDALT from 1.00: 1.0 to 1.00: 1.20, in the reaction temperature range from 180 to 230 ° C flowing for 3 to 12 hours, sufficient quantities of products with characteristic physicochemical characteristics can be isolated from the reaction mass

properties.

In particular, it was found that in the ¹³ C-NMR spectrum of the compounds of the present invention (OHMG), which are products of oligomerization of guanidine hydrochloride (HG) and hexamethylenediamine (HMDA), at least one characteristic signal of carbon atom nuclei associated with a substituted an imide group nitrogen atom (> C = NR), where R is a branching of the main chain. Based on the results obtained, the structure of the OGMG compounds in the form of the corresponding bases can be characterized more specifically by the following structural formula (I):

and

II '-NH / NH, where R represents / CH ιιι> ΝΗ,

"CH, CH, or CH, CH,

I III IV '

NH

an _l5 n ₂ and n ₃ are 1-3, az is 0.15-1.10.

To assign signals in the ¹³ C-NMR spectrum and to prove the structure of the obtained compounds as branched oligomers, the authors synthesized, isolated, purified and characterized monomeric compounds of a related structure: hexamethylene diguanidine dihydrochloride (HMDH) and tetraethylhexamethylene hexane dihydrochloride of the following:

GMDG TEGMDG

In the spectrum of HMDH there is a singlet at 158.92 ppm, corresponding to the carbon atom of the terminal guanidine fragment, while in the spectrum

TEGMDG the chemical shift of a similar signal is at 156.34 ppm, which is associated with the replacement of the imide nitrogen atom by an ethyl group (Fig. 1)

It will be apparent to those skilled in the art that the structure of the compounds of the present invention includes terminal substituted and unsubstituted guanidine groups, however, the signal with the highest integral intensity

corresponds to the carbon atom of a trisubstituted (branched) guanidine fragment. AND

The full assignment of chemical shifts of carbon atoms relative to DSS, made on the basis of experimental data and adequate quantum-chemical calculations, is shown in Table 1.

Table 1

* atom designations are given in formula (I)

From the integrated intensities of the signals “unbranched” and

"Branched" links, end fragments of guanidine and

hexamethylenediamine, knowing their molecular weights (141, 182, 100 and 58,

respectively), the number average molecular weight (M „) of OGMG can be calculated as follows:

M „= (+ n ₂ + 2n ₃ ) -t + g-t + [guan} _kosh L00 + [HMDA] _K0 - 58, where the molar amounts of terminal fragments of guanidine

2 + z 2 + z

[guan] conc and hexamethylenediamine [HMDA \ _K a ·

+ la + l are expressed through the integrated intensities of the signals SJJ, Sm, S / y, S _/ g, Sm; Sjy- and Siv of the corresponding carbon atoms as follows:

Having studied the intrinsic viscosity and other rheological properties of solutions of the compounds of the present invention in 0.3 M NaCl at 298 K, the authors substantiated the possibility of describing sedimentation equilibrium by the Philpot-Svensson model, which allows us to calculate the mass-average molecular weights according to ultracentrifugation as follows: W

12

Where

Z is the height of the gradient curve, cm;

C _x is the concentration of the solution in the range of 0.8- ^ 2.0 g / dl;

V- 0.786 cm3 / g — specific partial volume of the oligomer in solution;

Po = 1.0096 g / cm3 is the density of the solvent;

ω = 2πη / 60 is the angular velocity of rotation of the rotor.

The application of the above formulas for specific embodiments of the present invention is illustrated by the examples given in the description.

Thus, the authors clearly argue that the OGMH hydrochlorides in accordance with the present invention are

branched structures with an average number of branches from 0.16 to 1.08 per molecule and are characterized by a fairly wide molecular weight distribution („„ = 5.4 ... 9.3) with a weight average molecular weight M _w ranging from about 3800 to 6300 and the number average molecular weight M „in the range from about 600 to 1,100.

Under synthesis conditions, the compounds in accordance with the present invention are formed in the form of their hydrochloride salts. Specialist in this field should be obvious methods of converting OGMG hydrochlorides into other salts, as well as the necessary conditions for this (ratio of reagents,

solvents, etc.).

In particular, by the action of OHMG hydrochlorides on the sodium salts of weaker organic acids, such as acetic, butyric, lactic, succinic, glutamic and the like, in the medium of acetic or propionic acid, the corresponding OHMG salts can be obtained in accordance with the present invention.

Alternatively, the OHMG hydrochlorides of the present invention can be converted to the free base form by the action of an excess of a concentrated aqueous alkali solution in the presence of

isopropyl alcohol. Salts of acids such as benzoic, p-toluenesulfonic, phosphoric and similar, by the action of an equivalent amount of the corresponding acid in an alcohol medium, such as ethyl or benzyl alcohol.

Intermediate preparation of ogmg bases may also be

used to purify oligomerization products from toxic and corrosive HMDA and HG contained in them. To this end, in accordance with the present invention, a 50% molar excess of a concentrated alkali solution, for example NaOH, is added to a solution of OHMG hydrochloride to a pH of about 12, and the upper layer of the reaction mixture is selected in the form of a viscous turbid white liquid. The resulting product contains a suspension of the base ogmg and up to 1% of the mass. HMDA.

Alternatively, the preparation of the base can be carried out in the presence of an alcohol, such as ethanol or isopropanol, taken in an amount of 0.5-1.0 volumes from the total volume of the reaction mass, consisting of equal volumes

approximately 50% aqueous solutions of oligomer and alkali. In this case, the residual content of HMDA can be reduced to 0.02-0.1% by mass, depending on the time and temperature of the process, as well as the ratio of reagents and alcohol.

By conducting toxicity and corrosion studies

of the proposed compounds, the authors found that the branching of the structure contributes to a statistically significant decrease in LD5 ₀ / LD ^c ₅ o by 10-15%, and corrosion activity - by 10-50% compared with the known compounds.

It was also found that OGMG in accordance with this

the invention exhibit higher bactericidal, antiviral and antifungal activity as active components

disinfectants compared with embodiments of the closest analogue disclosed in patent RU 2223791. Comparative studies were

conducted for 1% aqueous solutions. However, the authors found that the compounds of the present invention are sufficiently soluble in mixtures of water with alcohols (ethanol, butanol, propanols), in alcohols, esters (ethyl acetate), amides (formamide) and also have the claimed

disinfecting activity. In accordance with the present invention for the preparation

a disinfectant, you can use the salt form of OGMG directly or in the form of a pre-prepared concentrated solution. Depending on the salt form of OHMG, such a solution may contain water or organic solvents as a solvent, for example, including alcohols, glycols and other suitable compounds miscible with water, as an organic component.

If necessary, compatible additives can be introduced into the concentrated solution, providing additional benefits, for example, lowering the freezing point, viscosity and / or surface tension, solubilizing other contaminants (fats, oils, etc.), dyes and the like. The term “compatible additives” refers to stable chemical compounds that do not enter into undesirable reactions with the OGMG salts of the present invention or otherwise do not impair the beneficial properties of the disinfectant. For example, glycols can be introduced into a concentrated solution to reduce the freezing temperature in order to protect the solution from the effects of low temperatures during transportation and storage. Dyes in the molecules of which there are no negatively charged groups, for example methylene blue or safranin, can be used to color concentrated solutions with the aim of marking them.

For OHMG hydrochloride in accordance with the present invention, it is preferable to prepare concentrated aqueous solutions containing from 10 to 40% (w / v) of the active component. Most preferred are solutions containing about 25% (w / v) OHMG hydrochloride.

In the case of salts with low solubility in water, organic solvents such as ethyl acetate, chloroform, etc. can be used to prepare solutions. The choice of solvent depends on the purpose of the further

use of the solution and is in the competence of the average specialist in the relevant field of technology. Concentrated solutions have a sufficiently long shelf life when stored in sealed packaging, which is preferably 3 years. The disinfectant is preferably used in the form of essentially aqueous solutions containing from 0.1 to 5% (w / v) OHMG hydrochloride. The choice of application is determined by the type and size

contaminated facility, as well as suspected or established

contamination to be disposed of and is within the competence of the average specialist in the relevant field. For example, to treat large surfaces (walls, doors) with contaminants of moderately pathogenic bacteria, these surfaces are wiped with a 0.1-0.5% solution and left for 15-60 minutes. In case of contamination with highly pathogenic bacteria, viruses (for example, for treating floors in the infectious diseases departments of hospitals), as well as fungi, the concentration should be increased by 5-10 times, and the exposure time should be increased to 60-90 minutes. Small objects are treated by immersing in a 1–2% solution (utensils) or soaking (linen, tools, patient care items) in a 2–4% solution for 30–60 minutes. Preferably, the disinfectant retains beneficial activity for 3 months.

The invention also relates to the use of disinfectants with improved bactericidal properties and safety indicators compared with known analogues, for disinfecting water. The authors of the present invention found that the introduction to the composition

a disinfectant of the compounds of formula (I) in the form of

hydrochloride, phosphate or succinate salts with a lower content of the bactericidal component allows to achieve bactericidal activity at a level comparable to the activity of known agents. This allows to reduce the manufacturer’s costs and the cost of the finished product, as well as the technogenic load on the ecosystem during the disinfection of wastewater discharged into natural reservoirs. Alternatively, administering the same amounts of the compounds of formula (I) as are present in known and used agents,

provides higher bactericidal activity.

Within the framework of the most general theory, bactericidal action

the disinfectant is due to the sorption of the cation of the polyelectrolyte containing guanidine groups on the surface of the cell, which leads to a decrease in the intensity of electron transport and the efficiency of the system phosphorylation. As a result, the permeability of the extracellular membranes increases sharply, which leads to cell swelling to the size that causes its death. Such a mechanism is universal, therefore

disinfectants containing polyguanidine compounds are effective against both gram-positive and gram-negative microorganisms.

In addition, positively charged guanidine groups of the polymer of formula (I) are able to further impart to the disinfectant the properties of a cationic flocculant. Within the framework of the most general theory, the effect of polymer flocculants is explained by the adsorption of filamentous macromolecules simultaneously on different particles. The resulting aggregates form flakes that can be easily removed by settling or filtering (L. Kulsky. Theoretical foundations and water conditioning technology. Second ed., K., 1971, p. 138). The addition of polyelectrolyte to water in concentrations effective for flocculation can cause coarsening and coalescence of particles of contaminants, especially of the anionic type, which reduces their concentration in water.

To expand the spectrum of antimicrobial action in order to destroy mycobacterium tuberculosis, viruses (hepatitis, AIDS) and pathogenic fungi and molds, the disinfectant is included

alkyldimethylbenzylammonium chloride or alkyldimethyl (ethyl) benzylammonium chloride.

The disinfectant may be prepared as

concentrated solution, which reduces the cost of its storage and transportation. In this case, the content of the first component is from about 10% (mass.) To about 50% (mass).

The concentrated solution is dosed directly into the water to be purified. Alternatively, before dosing, the solution is diluted with water to obtain a more dilute solution, which is then dosed into the water to be purified. The choice between concentrated and dilute solution is obvious to a person skilled in the art and depends, in particular, on the type of water to be purified. For example, with a high bacterial load (wastewater before discharge into open water), dosing is preferred concentrated solution. When disinfecting water after

pre-treatment for the purpose of its further use as drinking water, preferably dosing a more dilute solution.

A disinfectant, regardless of the content of the first component, is prepared by dissolving OGMG in water in the form of its hydrochloride, phosphate or succinate, followed by the addition of the second component directly or in the form of a solution to the resulting solution. Preferably, tap water or steam condensate is used as the solvent, OGMG hydrochloride or phosphate is the first component, and alkyldimethylbenzylammonium chloride is the second component. The content of the first component is preferably from 3.0% (mass.) To 6.0% (mass). In another preferred embodiment, the content of the first component is from 9% (mass.) To 12% (mass). The mass ratio of the first and second components is preferably in the range from 4: 1 to 6: 1.

In a preferred embodiment, the invention relates to the use of a disinfectant for disinfection in the preparation of drinking or circulating water. Examples of recycled water are swimming pool water with a reverse water supply system, water in equipment cooling systems, hot water and condensate from open heat supply systems, etc. Preferably, the recycled water is swimming pool water. Also, the tool can be used for disinfection of municipal wastewater.

Further, the present invention will be illustrated by examples of synthesis and study of the specific compounds of the invention, as well as

receipt and use of disinfectants, confirming its industrial applicability.

Examples 1-6. Obtaining ogmg in accordance with the invention

To a weighed portion of guanidine hydrochloride (GG) weighing 9.55-11.46 g (0.1-0.12 mol), depending on the molar ratio of HMDA / GG, at 160 ° C and vigorously stirring for 30 minutes, add in small portions 11 62 g (0.1 mol) of hexamethylenediamine (HMDA). After the addition is complete, the temperature is quickly raised to the reaction temperature (TP) and continued stirring the mixture at a given temperature for the duration of the reaction (BP). The composition of the initial mixture of reagents and the reaction conditions are shown in table 2.

table 2

Example 7. Determination of physico-chemical characteristics of branched oligomers of hexamethylenediamine and guanidine

A) Determination of the number average molecular weight (М „) of ОГМГ from the integrated signal intensities in the ¹³ С NMR spectrum.

¹³ C NMR spectra were recorded on a Bruker AV-600 spectrometer with a frequency on carbon nuclei of 150 MHz at a temperature of 303 K in full mode

broadband suppression of proton signals and the absence of the nuclear Overhauser effect. The delay between pulses according to the 5Τ _Ϊ rule was 60 seconds to eliminate the effect of relaxation effects. The number of scans is 200. DSS was used as the internal standard.

200 μl were sequentially transferred to an ampoule for NMR with a diameter of 5 mm

D ₂ 0, 300 μl of a 50% solution of OHMG hydrochloride in H ₂ 0 and 100 μl of a 15% aqueous hydrochloric acid solution and mixed thoroughly. If a precipitate appeared, the solution was heated to 70 ° C until it was completely dissolved. The values of M „are calculated on the basis of the integrated signal intensities Sa SJJJ, Sjv, SJJ; Sm; S / y and S / y.

B) Determination of the mass-average molecular weight (M _w ) of OGMG according to ultracentrifugation.

The determination of the weight average molecular weights was carried out by

the results of measuring the specific and characteristic viscosities on

analytical ultracentrifuge company MOM (Hungary) in 0.3 M NaCl as solvent, at a temperature of 298 K and a rotor speed of 50,000 rpm (200,000 g) for oligomer solutions with different concentrations.

The obtained physico-chemical characteristics are shown in table 3.

Table 3

H / O - not determined with sufficient accuracy.

Example 8. The study of the toxicity and corrosivity of OGMG Toxicity was determined in mice according to GOST 12.1.007-76 at

intragastric (LD ₅₀ ) and cutaneous (LD ^C ₅₀ ) administration.

Corrosion activity was evaluated by the mass corrosion coefficient (ϋΓο ™) of 30KhGSA steel in 1% OGMG and NaCl solutions at 20 ° С for 2 hours (the mass corrosion coefficient in the presence of NaCl was assumed to be 1, 00).

The results are presented in table 4. Table 4

Examples 2 * and 8 * relate to the corresponding compounds of the closest analogue (RF Patent 2,223,791).

Example 9. The study of the disinfectant properties of OGMG

The disinfecting properties of OGMG against bacterial and viral contaminants were studied using a dish model (Petri dishes), for which a dish set of 4 Petri dishes was completely immersed in 1 liter of 1%

a disinfectant solution prepared from 40 ml of a 25% concentrated solution. After disinfection, the dishes were immediately immersed

sequentially in two containers with warm water for 5 minutes each.

The disinfecting properties of OHMG in relation to fungal and spore pollutants were studied on a model of the floor surface in a room (a piece of linoleum 20x20 cm), which was wiped with rags moistened with a solution of the agent at the rate of 100 ml / m ^{2 of the} treated surface. Efficiency was evaluated after 2 minutes by the number of surviving organisms.

Table 5 presents the test data of 1% aqueous solutions of OGMG in accordance with the present invention as disinfectants in objects with bacterial (E. coli), viral (colophagus MS-2) and fungal (Penicillum chrysogenum) contamination, as well as spore contamination (Bacillus cereus) with an exposure time of 2 minutes. Table 5

Examples 2 * and 8 * relate to the corresponding compounds of the closest analogue (Patent RU 2223791).

Example 10. Obtaining a means for disinfecting water

In tap water with stirring, dissolve the hydrochloride or phosphate OGMG in an amount corresponding to its content specified in table 6.

Table 6

ADMBAH - alkyldimethylbenzylammonium chloride

ADM (E) BAH - alkyldimethyl (ethyl) benzylammonium chloride

Then, the amount of the second component indicated in Table 6 is added to the resulting solution with stirring. The obtained disinfectants in the form of transparent solutions with a density close to 1 g / cm are stored in closed jars at room temperature until

studies described in the following examples. Example 11. The study of the toxicological properties of the disinfectant lethal effect in acute experience

For the study were taken preparations prepared in accordance with example 1. Doses were selected taking into account the parameters of acute toxicity.

polyhexamethylene guanidine hydrochloride (LD ₅₀ = 630 mg / kg) and Catamine AB (LD ₅₀ = 478-667 mg / kg).

The studies were performed on male outbred white rats with a body weight of 280-310 g, 6 animals in each of 4 experimental groups. 0.5-2.0 ml of each of agents 1a, 16 and 1c was injected through the gastric tube into the animals, which corresponded to doses of 5000, 10000, 15000 and 20,000 mg / kg. The observation period was 14 days. During the entire observation period, none of the animals showed signs of acute toxicity. No animal deaths have been reported. Thus, the disinfectant in accordance with the invention is classified as low-toxic drugs (class 3 for acute toxicity).

Example 12. The study of the toxicological properties of the disinfectant lethal effect in a subchronic experience

The studies were carried out on sexually mature males of outbred white rats with a body weight of 210-270 g, 5 animals in each of 8 experimental groups. The volume of each of the agents 1a, 16, and 1c, corresponding to the doses of 0.5, 0.1, 0.02, and 0.002 mg / kg, was daily administered to the animals through a gastric tube. The observation period was 30 days. Indicators of toxicity were the morphological and functional state of the gonads, the hemoglobin content and the number of red blood cells. The selection of material for the study was carried out on 1, 5, 10, 15, 20 and 30 days.

During the experiment, no animal died. The appearance, behavior and condition of the skin of animals in the experimental and control groups did not differ. No pathological changes in the size and relative mass of the testes were observed. The number of sperm, their motility and osmotic resistance did not significantly differ from the control values. Changes in the hemoglobin content and the number of red blood cells in the blood did not go beyond the physiological norm. So Thus, the disinfectant in accordance with the invention is classified as low-toxic drugs (4th grade cumulative ability).

Example 13. Studies of the organoleptic properties of water treated with a disinfectant

Studies of the organoleptic properties of treated water

disinfectant, conducted experienced certified tasters in accordance with the guidelines "Justification of hygienic standards of chemicals in the water of water bodies of drinking, cultural and domestic water use" N ° 2.1.5.720-98. As a control, dechlorinated tap water was used (Moscow, Central Administrative District)

A) Odor intensity rating

All 9 tasters rated the severity of the odor at a concentration of 1000 mg / l means 16 and 1B at the level of 3 points. The smell is characterized as slightly differentiable technical. Water odor ratings

tasters are shown in table 7.

Table 7

B) the study of foaming

The study of foaming when disinfectants 16 and 1c were introduced into the water was carried out in 1.0 L cylinders according to the Shtupel method in the Mozhaev modification in 4 series (table 8). Table 8

At a concentration of 1000 mg / l, a dense

fine bubble foam, at a concentration of 15.6 mg / l (dilution 64 times), a large bubble foam forms, and when diluted 128 times, the level of foaming does not differ from the control water, i.e. threshold

the concentration of foaming is equal to 15.6 mg / L.

C) Study of pH shift and assessment of the taste of water

When 1000 mg / l of disinfectants 1a, 16 and 1c were introduced, the pH shift beyond 6.0-9.0 established by SanPiN 2.1.4.1074-01 was not noted: the pH values of water are 7.74, 7.67 and 7, 63 for funds 1A, 16 and 1B, respectively.

The intensity of the taste of water at a concentration of 15.6 mg / l (threshold concentration of foaming) does not differ from the control water in the opinion of all tasters. Thus, an organoleptic indicator limiting the use of a disinfectant in accordance with the present invention is a threshold concentration of foaming equal to 1.6 mg / L.

Example 14. A comparative study of the effectiveness of various disinfectants in the preparation of drinking water

Study of the effectiveness of chlorine, sodium hypochlorite and two

disinfectants - funds disclosed in patent RU 2182889, and funds in accordance with the present invention, was carried out in the autumn-winter period as part of the guidelines “Drinking water. Hygienic requirements for water quality of centralized drinking water supply systems. Quality control "SanPiN 2.1.4.559-96. The method for determining the total number of bacteria in water is to determine the content in 1 cm ^{3 of} water

mesophilic, mesotrophic and facultative aerobes capable of growing on nutrient agar at 37 ° C for 24 hours, forming colonies visible with an increase of 2-5 times.

In the course of studies it was found that the required degree

water disinfection (river water, Moscow, CAO) is achieved with the following concentrations of disinfectants (table 9):

Table 9

The results of a comparative study show that bactericidal activity at the level of the agent disclosed in patent RU 2182889 is achieved by the proposed agent with a lower content of the bactericidal component. Means containing compounds of formula (I) in amounts comparable to those known from RU 2182889 exhibit a higher bactericidal

activity.

Example 15. A comparative study of the stability and long-term bactericidal action of various disinfectants in the preparation of drinking water

The study of the stability and long-term bactericidal action of two disinfectants - the funds disclosed in patent RU 2182889, and means 16 in accordance with the present invention, was carried out in samples taken in the autumn period.

A known tool can be found in water for 20 days in concentrations of not less than 90% of the initial, which are from 0.5 to 5.0 mg / L. The center of re-contamination in disinfected water (with a microbial load within the original) without disappearing additives disappears within 1 hour.

The tool 16 in accordance with the present invention in concentrations of not less than 90% of the initial, constituting from 0.5 to 5.0 mg / l, is stored in water for 24 days. The center of re-contamination in disinfected water (with a microbial load within the original) without adding additives means on the 20th day of the experiment disappears within 45 minutes.

Example 16. A comparative study of the effectiveness of disinfection of municipal wastewater with various disinfectants

A study of the effectiveness of disinfecting municipal wastewater with two disinfectants - the agent disclosed in patent RU 2 182 889, and means 16 in accordance with the present invention, was carried out in wastewater samples after mechanical treatment taken in the autumn period (Moscow, Central Administrative District) . The coli index (CI) and the calculated bactericidal efficacy (BE) are presented in table 10. The bactericidal effect of water treatment, which is at least 98%, is achieved earlier when using means 16 in accordance with the present invention.

Table 10

Key Figures

Contact Time, Known Remedy

Means 16 min (RU 2182889)

CI BE,% CI BE,%

0 2170000 2160000

5,829,000 61.79 569,000 73.66

10 44500 97.95 25300 98.83

15 24,500 98.87 4970 99.77

30 10,200 99.53 1950 99.91 Example 17. A comparative study of bactericidal and

bacteriostatic properties of water in pools with a recirculating water supply system

A study of the effectiveness of the bactericidal and bacteriostatic properties of the water of pools with a recirculating water supply system in the case of using two disinfectants - the agent disclosed in patent RU 2 182 889, and agent 16 in accordance with the present invention was carried out in samples of sewage from a swimming pool (Moscow, NEAD) at a concentration of each agent of 8 mg / l. The indicator coli index (CI) and the calculated bactericidal efficacy (BE) are presented in table 11.

Table 11

Industrial applicability

The data presented confirm that derivatives

hexamethylene guanidines in accordance with this invention have improved, stably reproducible disinfecting properties (in particular, persistent bactericidal and bacteriostatic effects), reduced toxicity and corrosion activity, and have a wider range of applications compared to known analogues.

Claims

012/082009 28 The claims

1. Branched oligomers of hexamethylenediamine and guanidine

formulas (I)

(I)

eleven

.SC ^ H _j where represents _/ CH, w MH ₂

CH, cn, or cn, cn,

I III IV '

NH

and p n ₂ and n ₃ are 1-3, az is 0.15-1.10 s molecular weight

the distribution of MM „from 5.4 to 9.3 with a weight average molecular weight M _w in the range from about 3800 to 6300 and a number average molecular weight M„ in the range from about 600 to 1100.

2. The branched oligomers according to claim 1, in which z is 0.54-0.68 with a molecular weight distribution MJM „from 5.87 to 6.37 when

a weight average molecular weight _w in the range of from about 4600 to 6300; and a number average molecular weight M в in the range of from about 780 to 980.

3. A disinfectant, characterized in that as the active component it contains 0.1-25% (mass / vol.) Branched

hexamethylenediamine and guanidine oligomer of the formula (I) where p ₂ and p ₃ are 1–3, z is 0.15–1.10 with a molecular mass distribution of MM „from 5.4 to 9.3 with a weight average molecular weight of M _w in the range of from about 3800 to 6300 and the number average molecular weight M в in the range of from about 600 to 1100 in the form of a hydrochloride, and also water as a solvent.

4. The use of a disinfectant according to claim 3 for the removal of bacterial, viral and fungal contaminants, as well as contamination with spores, from various objects when exposed to the specified agent for 2-90 minutes.

5. A disinfectant containing a disinfecting agent and a solvent, characterized in that the disinfecting agent consists of the first component is the branched oligomers of hexamethylenediamine and guanidine of the formula (I), where, p ₂ and p ₃ are 1-3, z is 0.15-1.10 with a molecular weight distribution of MM „from 5.4 to 9.3 with a weight average molecular weight of My, in the range of from about 3800 to 6300, and a number average molecular weight of M, in the range of from about 600 to 1100 in the form of their hydrochloride, phosphate or succinate salts, and a second component, alkyldimethylbenzylammonium chloride or alkyldimethyl (ethyl) benzylammonium chloride or mixtures of one of these compounds with four ary ammonium salts of dimethylamine and / or (C ₂ -C ₁₀₎ -tretichnogo amine, wherein

6. The disinfectant according to claim 5, characterized in that it contains tap water or steam condensate as a solvent, OHMG hydrochloride or phosphate as a first component, and

alkyldimethylbenzylammonium chloride as a second component.

7. A disinfectant according to claim 5 or 6, characterized in that the content of the first component is from 3.0% (mass.) To 6.0% (mass).

8. The disinfectant according to claim 5 or 6, characterized in that the content of the first component is from 9% (mass.) To 12% (mass).

9. A disinfectant according to claim 5 or 6, characterized in that the mass ratio of the first and second components is in the range from 4: 1 to 6: 1.

10. The use of a disinfectant containing

a disinfecting agent and a solvent, characterized in that

the disinfecting agent consists of the first component - branched oligomers of hexamethylenediamine and guanidine of the formula (I), where pi n ₂ and n ₃ are 1-3, z is 0.15-1.10 with a molecular weight distribution of MM _n from 5.4 to 9.3 with a weight average molecular weight M _w ranging from about 3800 to 6300 and a number average molecular weight M М in the range from

approximately 600 to 1100 in the form of their hydrochloride, phosphate or succinate salts, and the second component is alkyldimethylbenzylammonium chloride or alkyldimethyl (ethyl) benzylammonium chloride, or a mixture of one of these compounds with quaternary ammonium salts of dimethylamine and / or (C2-C ₁₀ ) -tertiary amine, while the disinfectant contains from about 1 , 5% (mass.) To about 50% (mass.) Of the first component, the mass ratio of the first and second components is in the range from 3.5: 1 to 10: 1, and the solvent is water, for disinfection of wastewater before discharge in in doomy and / or in the preparation of drinking water or recycled water.

11. The use according to claim 10, characterized in that the disinfectant is used in the preparation of drinking water.

12. The use of claim 10, wherein the circulating water is swimming pool water.