RU2228936C2 - Antibacterial polymeric compositions - Google Patents

Abstract

FIELD: polymers, chemical technology. SUBSTANCE: invention relates to antibacterial polymeric compositions and method for improving activity of polymer based on acrolein monomer. Method involves oxidation of polymer in air medium to form oxidized acrolein polymer comprising monomer links of 2-propenal and monomer links of 2-acrylic acid. Method involves the following stages: preparing the solution of oxidized acrolein polymer comprising carboxyl groups in mixture containing water and one or more alcohols taken among group consisting of polyols, polyethylene glycols and alcanols; heating solution at temperature in the range from 40 to 150 C for time providing the improvement of antibacterial effect of acrolein polymer. Invention describes also an antibacterial compound, antibacterial composition, disinfecting or antiseptic composition, preserving, disinfecting or antiseptic compound prepared by the above indicated method. Method provides preparing antibacterial, preserving, disinfecting or antiseptic compound comprising derivative of poly-(2-propenal, 2-acrylic acid) of new configuration that elicits the improved antibacterial activity and comprise less free acrolein. Also, method provides preparing compositions containing derivative of poly-(2-propenal, 2-acrylic acid) of new configuration that are effective disinfecting agents or antiseptics. EFFECT: improved preparing method, valuable properties of compositions. 28 cl, 13 tbl, 8 ex

Description

FIELD OF THE INVENTION

The present invention relates to antimicrobial polymer compositions. In particular, the antimicrobial polymer compositions of the present invention contain compounds having polyacrolein subunits with their aldehyde group in a free, hydrated, hemiacetal or acetal form, and have biostatic and / or biocidal properties. The invention is directed to compositions containing these polymeric compounds, and to the use of these compositions as biostatic and / or biocidal.

Background of the invention

Antimicrobial properties of polymers with a wide spectrum of action (hereinafter referred to as "the polymers of the invention") containing a repeating polymer unit:

or the specified link in its hydrated, hemiacetal or acetal form, represented by the formula:

,

,

,

,

,

,

,

,

или

or

where R is hydrogen or alkyl and n is an integer of one or more,

have been demonstrated previously (Melrose et al., International Patent Publication WO 88/04671). The polymers described in this source include poly (2-propenal, 2-acrylic acid).

It was also previously noted (Melrose, International Patent Publication WO 96/38186) that poly (2-propenal, 2-acrylic acid) is formed when the aldehyde groups of poly (2-propenal) -sin-polyacrolein undergo partial autooxidation with the formation of carboxyl groups by heating the dry polymer in air at 100 ° C, preferably at a temperature between 80 and 100 ° C. It was further noted that the resulting polymer is soluble in dilute aqueous bases, for example, an aqueous solution of sodium carbonate.

An earlier technical solution (Werle et al., Australian Patent Application 11686/95, now patent expired) claims the solubility of these polymers in polyols, but not solubility in an aqueous medium, when heated to 75 ° C. It was further stated that after heating to 75 ° C, a short-term treatment with sodium hydroxide provides solubility in water and, obviously, as a result of this, increased antimicrobial activity.

To increase the stability of compositions containing the polymers of the subject invention, Melrose & Huxham (International Patent Application PCT / AU99 / 00578) formulated compositions with anionic surfactants. In addition, the aforementioned technical solution revealed that in the main compositions, in contrast to acidic compositions, the polymers of the subject invention have faster antimicrobial activity, but are less stable.

It is especially desirable that the polymers of the subject invention are not unstable, releasing acrolein, since this monomer is very irritating to the eyes, lungs, tissues and skin.

One of the objectives of the present invention is to develop methods for producing compositions, these methods allow to obtain polymers of the object of the invention of a new configuration, in particular poly (2-propenal, 2-acrylic acid), which have improved antimicrobial activity.

Another objective of the present invention is to develop methods for producing compositions, these methods allow to obtain polymers of the object of the invention of a new configuration, in particular poly (2-propenal, 2-acrylic acid), which better retain antimicrobial activity.

Another objective of the present invention is the development of methods for producing compositions, these methods allow to obtain polymers of the invention of a new configuration, in particular poly (2-propenal, 2-acrylic acid), which contain less free acrolein.

Another objective of the present invention is the development of compositions containing new polymer configurations of the object of the invention, in particular poly (2-propenal, 2-acrylic acid), which are effective disinfectants or antiseptics.

In the text of the description, unless the context otherwise requires, the word “include” or options such as “include” or “including” should be understood as covering the indicated integer or groups of integers, but not the exclusion of any other integer or groups of integers.

SUMMARY OF THE INVENTION

In accordance with the present invention, a method for improving the antimicrobial activity of a polymer based on acrolein monomer is developed, in which the polymer is oxidized in air to form an oxidized acrolein polymer containing 2-propenal monomer units and 2-acrylic acid monomer units, comprising the following steps:

preparing a solution of an oxidized acrolein polymer containing carboxyl groups in a mixture containing water and one or more alcohols selected from the group consisting of polyols, polyethylene glycols and alkanols;

heating the solution at a temperature in the range of 40 to 150 ° C. for a period of time sufficient to improve the antimicrobial effect of the acrolein polymer.

Also preferably, the polymers are heated in the range of 40 to 115 ° C.

Still more preferably, the polymers are heated in the range of 70-90 ° C.

Preferably, the polymers are heated between 1 and 1400 hours, thereby increasing the antimicrobial activity of the polymers.

It is also preferred that the polymers are heated between 10 and 60 hours.

In one embodiment, the polymers are heated in the presence of one or more polyethylene glycol, polyol, or alkanol, thereby providing (one or both) improved stability or improved antimicrobial activity. Water is invariably present in these alcohols.

Preferably, polyethylene glycol is present in the process for producing polymers in an amount of between 50 and 99% by weight.

Also preferably, polyethylene glycol is present in the process for producing polymers in an amount between 64 and 95% by weight.

In another embodiment of the invention, a compound having basic properties is added to the polymers prior to and / or during heating, thereby enhancing the antimicrobial activity of the polymers.

It is preferable to add a compound having basic properties selected from alkali metal hydroxides, alkali metal carbonates and mixtures thereof, which creates a pH of polymers between 7 and 9.

Also preferably, the pH is about 8.

Also in another embodiment of the invention, the release of free acrolein monomer is inhibited, resulting in a lesser likelihood that the polymers are a source of tissue or skin irritation.

Preferably, the polymer is initially heated, mainly in a dry state, to a temperature between 80 and 100 ° C.

Also preferably, the polymer is initially heated to about 85 ° C.

An antimicrobial compound or composition prepared by one or more of the methods described above is also provided in accordance with the present invention.

In accordance with the present invention also developed a preservative or composition obtained by one or more of the above methods.

In accordance with the present invention, a disinfectant or antiseptic compound or composition obtained in whole or in part by the methods described above has also been developed.

Preferably, the disinfectant or antiseptic compound or composition has a pH of greater than 6, thereby enhancing antimicrobial activity.

In accordance with the present invention, methods have been developed for producing polymers of a new configuration, including poly (2-propenal, 2-acrylic acid) and compositions based on them, when the compositions exhibit increased atimicrobial activity and / or increased stability and / or contain less free acrolein, making polymers and / or compositions based on them more suitable as preservatives and / or active ingredients in disinfectant and / or antiseptic formulations in acidic or Christmas environments.

BEST MODES FOR CARRYING OUT THE INVENTION

Since the known solutions recorded some instability of poly (2-propenal, 2-acrylic acid), as evidenced by the loss of antimicrobial activity of its compositions, the applicant’s laboratories used a routine industrial method to quantify the mentioned instability by standard “accelerated aging” at elevated temperature, for example, at 40 ° C. However, to the greatest surprise of the applicants, the increased “aging” temperature of poly (2-propenal, 2-acrylic acid) in aqueous solutions or aqueous solutions of polyethylene glycol at 40 ° C not only showed a decrease in antimicrobial activity, but in reality a real increase in the antimicrobial activity of poly (2-propenal, 2-acrylic acid), see examples 2 (a) and (b). This fact is completely contradictory and unexpected from the point of view of the known solutions, which suggest that an increase in temperature should lead to "accelerated aging", i.e. accelerated loss of antimicrobial activity.

Therefore, the method of providing increased antimicrobial activity by obtaining a new configuration of the polymers of the invention, including poly (2-propenal, 2-acrylic acid), is called "superactivation", and the polymers are called "superactivated polymers".

The authors of the present invention found that superactivation in an aqueous solution of polyethylene glycol is accelerated in an alkaline environment, see example 2 (c), which is even more surprising in terms of known solutions.

In addition, superactivation is accelerated by heat and moisture, separately, see example 4.

In addition, it was found that dry heating of the polymers of the object of the invention at a temperature between 80-85 ° C gives polymers, see example 1, which are soluble in an aqueous medium and suitable for subsequent superactive.

Superactivation is accelerated in the presence of polyethylene glycols, or polyols, or alkanols, see example 3, according to the authors, since the presence of polyethylene glycol, or polyol, or alkanol protects and stabilizes the carbonyl groups of the polymers, probably due to the formation of acetals, from alkaline decomposition by the Cannizaro reaction.

An additional advantage of superactivation is that it provides the formation of less polluting acrolein, which is a source of tissue and skin irritation, see example 6.

It is emphasized that superactivation is completely different and complements any increase in antimicrobial activity that may result from the fact that simply more polymer is available in any aqueous test medium as a result of the increased hydrophilicity of the polymer, as was shown in Australia's patent application AU-A- terminated 11686/95 (hereinafter referred to as "11686/95"). The inventors exactly repeated the method described in 11686/95, and then subsequently found that subsequent superactivation of a partially soluble polymer clearly provides additional significant antimicrobial activity, see example 5. It should be noted that even superactivation does not make the polymer from 11686/95 completely soluble unlike superactivation, starting with polymers initially heated in the temperature range between 80-85 ° C.

The optimal time to achieve superactivation of solutions of poly (2-propenal, 2-acrylic acid) depends inversely on temperature, see example 7. It will be seen that even aging at room temperature can be used for superactivation, especially when it is accelerated in the presence of hydroxyl solvent and / or base, but it is obvious that in practice this may be impractical due to the required longer periods of time.

The inventors of the present invention have found superactivated polymers, as described herein, suitable for use as preservatives in water-based products or methods, and also as active ingredients in disinfectants or antiseptics that have the advantage of increased antimicrobial activity, see Example 8. In addition to Moreover, the authors of the present invention have found that the antimicrobial activity of said disinfectants or antiseptics increases with increasing pH, eg above pH 6, see also Example 8.

The invention will now be described with reference to several examples, which should not be construed as limiting the scope of its claims.

Biocidal test

Dilute the sample with a 1% aqueous sodium bicarbonate solution to obtain the desired concentration (unless otherwise indicated, 0.125% in the polymer). 19.9 g of the diluted sample is weighed into a sterile cylinder and 0.1 ml of a suspension of 10 ⁷ -10 ⁸ Ps.aeruginosa is inoculated and mixed. At predetermined time intervals, 1 ml of the inoculated sample is transferred into 9 ml of letino broth and mixed. Series 1 is plated in 10 dilutions plates. Pour with tryptone-soy agar. Incubated for 3 days at 37 ° C.

Example 1

This example describes a method for producing poly (2-propenal, 2-acrylic acid) by oxidation of a solid acroleion polymer in air. This poly (2-propenal, 2-acrylic acid) is a preferred method for preparing the starting material for use in the method of the present invention. Water (720 ml at room temperature, approximately 20 ° C) and acrolein (60 g; freshly distilled, plus hydroquinone up to 0.25% m / m) are placed in an open glass in a fume hood and very quickly mixed mechanically. Then add 0.2 M aqueous sodium hydroxide solution (21.4 ml) to bring the pH to 10.5-11.0. The solution immediately turns yellow, which is typical of the hydroquinone anion, and within a minute the color disappears and the clear solution becomes milky. About 1 minute later, the precipitation of a white crystalline flocculated polymer begins, and within 15-30 minutes the process ends. The precipitate formed is filtered off and washed with water (250 ml), dried at room temperature on paper filters for 2 days (yield 25 g), then distributed in a thin layer in glass Petri dishes and heated at 40 ° C for 8 hours. This heating process is continued according to the following scheme: 50 ° C for 15 hours; 65 ° C / 4 hours; 75 ° C / 18 hours; 84 ° C / 24 hours.

It is assumed that this method can be expanded by including, for example, the stepwise addition of acrolein in a closed container and subsequent faster drying.

Typically, a solution of the resulting poly (2-propenal, 2-acrylic acid) is prepared by adding 2 g of the polymer of the invention with stirring for 15-30 minutes to a 1% m / m aqueous solution of sodium carbonate (100 ml), and then diluted as required. These solutions are completely transparent, in contrast to dilute solutions, for the preparation of which the polymer obtained in accordance with Example 5 11686/95 was used; compare with example 5 below.

Example 2

(a) 5 g of poly (2-propenal, 2-acrylic acid) is dissolved in 64 g of polyethylene glycol ("PEG") 200 and combined with 31 g of a 0.71% sodium carbonate solution. Part of the solution (at pH 5.8) is left at room temperature, while the rest is heated at 60 ° C for 12 or 25 days. Samples are diluted with 1% sodium bicarbonate solution and a biocidal test is carried out at polymer concentrations of 0.125% m / m. Unexpectedly, samples that undergo "accelerated aging" show improved antimicrobial activity, as can be seen from the data in table 1.

(b) 1 g of poly (2-propenal, 2-acrylic acid) is dissolved in 200 ml of 0.1% Na ₂ CO ₃ and left to stand overnight. Sodium lauryl sulfate was added in an amount of 0.05% and the solution was acidified with HCl to pH 5.9. Portions of the solution are stored at room temperature and at 60 ° C. Biocidal tests are carried out on 0.125% polymer solutions using 1% NaHCO ₃ as diluent. The "aged" sample shows an unexpected improvement in performance, which can be seen from the data in table 2.

(c) A 5% solution of a superactivated polymer is prepared as in Example (2a), but PEG 200 is replaced by PEG 1000. Part of this solution is treated with conc. NaOH to pH 8.1. Samples are heated at 60 ° C and subjected to biocidal testing. A sample exposed to more alkaline environmental conditions unexpectedly shows excellent biocidal activity, which can be seen from the data in table 3.

Example 3

(a) 5% polymer solutions in the range of degrees of superactivation, an apparent pH of 5.7, are prepared in the same way as in example 2 (a), but changing the percentage of PEG 200.

Samples are heated at 60 ° C and the change in stability over time is recorded. Physical stability is believed to disappear with the onset of precipitation or gelation. UV measurements are carried out at a polymer concentration of 0.01% in a 1% sodium carbonate solution. A decrease in the absorption ratio at 268 nm: 230 nm is considered synonymous with a decrease in chemical stability. The results are presented in table 4.

The results of physical and UV spectral measurements show a positive effect of PEG on stability; at a higher PEG content, higher levels of physical and chemical stability are achieved.

(b) The following solutions A and B are prepared by dissolving 4 g of poly (2-propenal, 2-acrylic acid) in 196 g of 1% sodium bicarbonate and adjust the pH to 7 (A) and 5.5 (B) with dilute Hcl. Solution C is prepared by dissolving 50 g of poly (2-propenal, 2-acrylic acid) in PEG 200 (640 g) at 65-70 ° C. Then add a solution of 4 g of sodium carbonate in water (306 g), the apparent pH is 7, and then 5.5 at the end of the treatment period of 31 days.

All samples are stored at 40 ° C. At various time intervals, samples containing an equivalent 0.125% amount of polymer are subjected to a biocidal test. The results are presented in table 5.

Example 4

1 g of poly (2-propenal, 2-acrylic acid) is heated either in a dry or wet closed chamber, in both cases at 60 ° C for 3 days. Solutions of dry polymer or wet polymer are prepared at 0.125% m / v (adjusted for moisture content), respectively, and are evaluated for biocidal activity. The results are shown in table 6.

The polymers are characterized by absorption in the region of carbonyl or carboxyl groups in the IR spectrum in the range between 1700-1730 cm ^-1 , the presence of carbonyl groups (for example, with Schiff's reagent) and have Mw = ca.10000 and Мn = ка.5000; titration shows the concentration of carboxyl groups ca.5% mol.%. These parameters are similar (but not the same) to those of poly (2-propenal, 2-acrylic acid).

Example 5

In duplicate experiments, a polymer sample was prepared and then dissolved in ethanediol, exactly as described in Example 5 11686/95. Half of this material is heated at 80 ° C for 24 hours (after which the solubility in the aqueous medium remains incomplete). Samples are compared for antimicrobial activity using a standard biocidal activity test. Both samples treated by heating, i.e. superactivated, show a clear increase in antimicrobial activity, as shown in table 7.

Example 6

50 g of poly (2-propenal, 2-acrylic acid) are dissolved in PEG 200 (640 g) at 65-70 ° C. An aqueous solution of sodium carbonate (4 g) in water (306 g) is then added. The sample is separated and either left at room temperature or heated at 80 ° C for 24 hours. The change in the acrolein content in the solution is determined over time by phase reversal HPLC; the results are presented in table 8.

Example 7

Solutions of poly (2-propenal, 2-acrylic acid) are prepared, as in Example 6, and treated at temperatures of 40, 60, 80, 100 and 115 ° C for various periods of time. Samples are subjected to a standard biocidal activity test to confirm an increase in the rate of destruction of microorganisms, the results are presented in table 9.

It can be seen that the length of time required for superactivation is inversely proportional to temperature. All polymer solutions obtained by superactivation are fully compatible, in all proportions, with aqueous solvents.

Example 8

(a) 540 g of poly (2-propenal, 2-acrylic acid) is dissolved in 2304 g of PEG 200 at 65 ° C. before mixing with 43.2 g of sodium carbonate in 712 g of water. The solution is then heated to 100 ° C. for 4 hours and 36 g of sodium lauryl sulfate, 7 g of ECOTERIC T20 (non-ionic detergent) and 2 g of lemon flavor are added. The composition, pH 6, was diluted 1:30 with hard water and infected with Staphylococcus aureus (a gram-positive bacterium of particular importance in terms of infections in hospitals) and Salmonella choleraesuis (a gram-negative bacterium of particular importance in terms of contamination of food preparation areas), respectively, using Association of Agricultural Chemists Official Methods of Analysis (1955) 991.47, 991.48 (Hard Surface Carrier Test Method). The results are presented in table 10.

Bringing the pH of this composition to higher values increases the antimicrobial activity, as evidenced by the biocidal test. The results are presented with tables 11 (a) and 11 (b).

(b) 1200 g of poly (2-propenal, 2-acrylic acid) is dissolved in 7680 g of PEG 200 at 60 ° C, and then 96 g of Na ₂ CO ₃ are added in 3024 g of water. The solution was heated at 100 ° C for 6 hours.

The composition is added to the reservoir of the cooling tower with forced draft in a concentration of 300 million hours (30 million parts of polymer) 3 times a week. Dosing is carried out in the evening to provide a contact time of 8-12 hours before the operation; it is assumed that the residual concentration is halved every 3-6 hours of operation. Recirculation water has an average temperature of 27 ° C, pH 8.5, conductivity 3000 ec. The number of bacteria is determined and compared with a neighboring, identical tower, to which a bio-dispersant is added daily. The results are presented in table 12.

The data presented indicate that the processing program supports the number of microbes within the framework of AS / NZ Standard 3666/3 (Int): 1998 and lower than the number of microbes in the adjacent tower containing the biodispersant (which, as it was found, acts unusually inadequately in severe conditions hot summer during testing).

It is believed that modifications and changes that would be obvious to experts in this field are covered by the scope of the claims of the present invention.

Claims (28)

1. A method of improving the antimicrobial activity of a polymer based on acrolein monomer, in which the polymer is oxidized in air to form an oxidized acrolein polymer containing 2-propenal monomer units and 2-acrylic acid monomer units, the process comprising the steps of: preparing a solution of an oxidized acrolein polymer containing carboxyl groups in a mixture containing water and one or more alcohols selected from the group consisting of polyols, polyethylene glycols and alkanols; and heating the solution at a temperature in the range of 40 to 150 ° C. for a period of time sufficient to improve the antimicrobial effect of the acrolein polymer. 2. The method according to p. 1, characterized in that said oxidized polymer containing carboxyl groups is formed by heating a solid acrolein polymer in air at an elevated temperature so that carboxyl groups are formed. 3. The method according to p. 2, characterized in that the specified acrolein polymer comprising carboxyl groups formed by heating in air at a temperature in the range between 80 and 100 ° C. 4. The method according to p. 2, characterized in that the acrolein polymer comprising carboxyl groups formed by heating in air at a temperature of about 85 ° C. 5. The method according to p. 1, characterized in that the pH of the solvent is a value in the range from 7 to 9. 6. The method according to p. 1, characterized in that the pH of the solvent is approximately 8. 7. The method according to p. 2 or 3, characterized in that the mixture further comprises compounds having basic properties selected from alkali metal hydroxides, alkali metal carbonates and mixtures thereof. 8. The method according to p. 7, wherein the alkali metal hydroxide is sodium hydroxide, and the alkali metal carbonate is sodium carbonate. 9. The method according to p. 1, characterized in that the solution is heated in the range from 40 to 115 ° C. 10. The method according to p. 1, characterized in that the solution is heated in the range of 70-115 ° C. 11. The method according to p. 9, characterized in that the solution is heated to about 100 ° C. 12. The method according to any one of paragraphs. 1 to 3, characterized in that the solution is heated for a period of time from 1 to 1400 hours, thereby increasing the antimicrobial activity of the polymers. 13. The method according to any one of the preceding paragraphs, characterized in that the solution is heated for a period of time from 4 to 60 hours 14. The method according to p. 11, characterized in that one or more alcohols contains polyethylene glycol present in the solution in an amount between 50 and 99 wt.% By weight of the solution. 15. The method according to p. 14, characterized in that the polyethylene glycol is present in the solution in an amount between 64 and 95 wt.% By weight of the solution. 16. The method according to PP. 7-15, characterized in that the compounds having the basic properties are added to the polymers before and / or during heating, thereby improving the antimicrobial activity of the polymers. 17. The method according to any one of the preceding paragraphs, characterized in that the release of free acrolein monomer from acrolein polymer is reduced. 18. The antimicrobial compound obtained by the method according to any one of the preceding paragraphs. 19. The antimicrobial compound according to claim 18, containing a derivative of poly (2-propenal, 2-acrylic acid), formed by the interaction between one or more alcohols selected from the group consisting of polyethylene glycol and polyols, and poly (2-propenal, 2 -acrylic acid) with the formation of protected carbonyl groups. 20. The antimicrobial compound of claim 19, wherein the protected carbonyl groups are acetals. 21. The antimicrobial compound of claim 19 or 20, wherein the alcohol is polyethylene glycol. 22. The antimicrobial compound according to claim 21, where the alcohol is polyethylene glycol with mol.v. from 200 to 1000. 23. Antimicrobial composition obtained by the method according to any one of paragraphs. 1-17. 24. The antimicrobial composition according to p. 23, where the antimicrobial compound according to PP. 18-22 is present in a composition containing from 64 to 95 wt.% Polyethylene glycol. 25. The antimicrobial composition according to p. 24, where the pH of the composition is between 7 and 9. 26. A disinfectant or antiseptic composition obtained by the method according to any one of paragraphs. 1 - 16. 27. A disinfectant or antiseptic composition according to claim 26, containing the antimicrobial compound according to claim 19. 28. Preservative, disinfectant or antiseptic compound obtained by the method according to any one of paragraphs. 1-16.