Water-soluble bactericide composition and its preparation


(57) Abstract:

Usage: the invention relates to water-soluble bactericidal compositions containing fine metal silver, stable protective high-molecular compound. The invention relates also to a method for producing these compositions. The solution can be used in the manufacture of highly effective drugs for medicine and veterinary medicine. Goal - the creation of a highly effective bactericidal agent, characterized by low toxicity and allergenicity, as well as the reproducibility of the physico-chemical characteristics. The essence of the invention: composition containing the following ingredients, by weight. hours : poly-N-vinyl pyrrolidone-2 810 MM3-1,631061; fine metal silver 0,01-2,33. A method of making such compositions, which is implemented by the interaction of silver nitrate with an aqueous-alcoholic solution of poly-N-vinylpyrrolidone-2 with the following concentrations of ingredients, wt.%: poly-N-vinyl pyrrolidone-2 0,065-11,00; silver nitrate 0.25 to 29,73; ethyl alcohol 5,0-38,6; water the rest up to 100. The interaction of lead in the dark at 65-75oC in an atmosphere of inert gas. Positive e is effective the drug is 4-6 times lower compared to known commercial colloidal preparations of silver. The composition is stored at room temperature without changes. Adding water is dispersed. 2 S. p. f-crystals, 1 table.

The invention relates to water-soluble composition with bactericidal activity, containing fine metal silver, stable synthetic high-molecular compounds.

The invention relates also to a method for producing such compositions.

Announced a comprehensive solution can find the use for the manufacture of silver-containing microbicides, effective in the treatment of purulent-septic complications of wounds, ulcers, bedsores, burns, bacterial lesions of the mucosa of the eyes, the mouth, the top ways and genitourinary system.

Both of the proposed object composition and method of obtaining United by a common creative idea, directed to the improvement of the efficiency of obtaining and achieving reproducibility of properties of the composition.

Abbreviations and terms used in this bid description and transcript:

PVP poly-N-vinyl pyrrolidone-2 with the General formula of elementary link:

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MM srednekislye molecular mass.

Known commercial moderada colloidal composition, stable protective high-molecular compounds of protein nature of unknown chemical structure:

protargol contains 7,5-8,0% colloidal silver oxide,

colloid contains 70.0% of colloidal metallic silver.

A method of obtaining the protargol is implemented in the following technological operations:

1. Swollen gelatine washed with water until no reaction to chlorine ion and hydrolyzing in water at 1.5-2 ATM at 130oC to obtain a liquid solution Galatz.

2. The solution gelatos evaporated to a density of 1.06 g/cm3and process 16-20 wt.-NYM NaOH solution at 80-85oC to stop shedding ammonia.

3. Then the aqueous solution evaporated to a density of 1.12 g/cm3and filtered.

4. To the cooled filtrate is added with stirring an aqueous solution of silver nitrate and at 65-70oC get the colloidal silver oxide, stabilizirovannoi hydrolization Galatz.

5. The aqueous solution is dried.

The total duration of the synthesis is 140-160 hours Irretrievable loss of silver 1% return waste silver 4% of the Product is obtained as a brown-yellow or brown powder.

Known the% aqueous sodium hydroxide solution and heated to the formation of hydrolyzed casein.

2. To aqueous silver nitrate solution was added 20% aqueous sodium hydroxide solution to the quantitative precipitation of silver oxide.

3. The silver oxide was added a solution of hydrolyzed casein and heated under stirring.

4. Oxide of silver is precipitated by 7% aqueous sulfuric acid solution, washed with water, peptizer 20% aqueous sodium hydroxide solution, evaporated the solution to a density of 1.3 g/cm3and separating the precipitate of collargol.

The final product after drying and granulation has the appearance of a greenish or cinematically plates with a metallic sheen. The total duration of the process is 280 h, irretrievable loss of silver and 2.8%

The main disadvantage of the known method of producing a preparation of colloidal silver is low technology and the difficulty of obtaining the target product with reproducible properties due to the variability of the composition and heterogeneity of the protein source of raw materials and products of its hydrolysis.

In addition, the presence of traces of ionic silver and other compounds of silver gives the drugs toxicity, and the presence of protein stabilizer may trigger allergic reactions.

The aim of the invention is sozdaetsya reduced toxicity and allergenicity, and reproducible physico-chemical characteristics.

This problem was solved by a composition comprising the following ingredients in the following mass ratios:

Poly-N-vinyl pyrrolidone-2 810 MM3-16,31051

Fine metal silver 0,01-2,33

The problem was solved also by way of obtaining this composition, which was realized by the combination of the following essential features:

1. Water-alcohol solution of poly-N-vinylpyrrolidone-2 at 65-75oC add aqueous silver nitrate solution, the process is conducted at the same temperature until complete exhaustion of ionic silver with the following concentrations of reagents in water, wt.

Poly-N-vinylpyrrolidone-2 0,065-11,00

Silver nitrate 0.25 to 29,73

Ethyl alcohol 5,0-38,6

Water the Rest to 100

2. The interactions are in the dark.

3. The interaction of lead in the atmosphere of inert gas.

4. MM poly-N-vinylpyrrolidone-2 8103-16,3105.

The composition of the claimed composition is confirmed by standard telemetricheskie method. Monitoring the depletion of ionic silver in the course of interaction was performed by the method of sampling the reaction mixture using usaimi with the invention, was evaluated according to the small angle of the cut of x-rays.

Analysis of the known level of science and technology did not allow to detect any documents about bactericidal compositions containing fine metal silver, stable synthetic polymers, in particular poly-N-vinyl pyrrolidone-2.

Thus it can be argued that the claimed complex solution is new as in the first and second independent claims

Of fame drugs colloid and protargol, in which the stabilizers of colloidal silver particles are hydrolysates of natural proteins, gelatin and casein, does not follow completely the possibility of using poly-N-vinylpyrrolidone-2 as a stabilizer.

Moreover, among the investigated range of synthetic vodorastvorimyh polymers effective was the only poly-N-vinyl pyrrolidone-2, and such a polymer, such as polyvinyl alcohol, no effect was given.

In addition, as we have discovered, poly-N-vinylpyrrolidone-2 acts in the proposed method not only as a stabilizer of colloidal silver, but also as a reactant which takes part in the restoration of ustanavlivaetsya to the molecular actions of ethanol on silver ions, coordinated with poly-N-polyvinylpyrrolidone-2. In the absence of nitrate of silver does not react with ethanol. Thus, it can be argued that the claimed integrated solution meets both independent claims the requirement of "inventive step".

Used synthetic poly-N-polyvinylpyrrolidone-2 is used in medicine as a plasma substitute (drug Gemodez", Pharmacopeia FS 42-1194-78).

Antimicrobial activity of drugs known and declared it was estimated by the method of serial dilutions in meat-peptone agar at pH 7,2-7,4.

As the test cultures used 25 strains of pathogenic microorganisms.

Comparison of the antimicrobial properties of known drugs and claimed showed that these drugs have the same activity and spectrum of action. Meanwhile, it is found that the increase in the content of colloidal silver in the claimed drug does not lead to a proportional increase of bactericidal activity, and even reduces it. Optimum efficiency is observed in compositions with a content of colloidal silver 7-8% of the Acute toxicity was determined by intraperitoneal injection to animals.

For a better understanding of the essence of the claimed invention and confirm its industrial applicability examples of its specific implementation.

Example 1.

In the dark glass reaction apparatus equipped with a stirrer, addition funnel and a bubbler for blowing an inert gas load 200 g of poly-N-vinylpyrrolidone-2 M 12600, add with stirring a mixture of 1000 ml of water and 300 ml of ethanol (19% solution of ethanol). Received 14% solution of poly-N-vinylpyrrolidone-2 heated for 10 min to 75oC and at this temperature, add with stirring a solution of 27,39 g of silver nitrate (H. H.) in 500 ml of water (5.2 wt.). The reaction mixture containing 12% ethanol, 10% poly-N-vinyl-pyrrolidone-2 and 1.4% silver nitrate, stirred at the same temperature for 60 minutes Water-alcohol solution is dried in the spray dryer. The yield of the target product 217,2 g (99,9%), silver content 7,94%

Example 2. In the conditions of example 1 using poly-N-vinyl pyrrolidone-2 M 8000, in the reaction mixture entering the powdered product, containing 7,87% silver.

Example 3.

In the conditions of example 1 using poly-N-vinylpyrrolidone-2 M 35000 the reaction is performed for 4 h at 65oC. the Yield of dry product is 99.8% when the content of silver to 7.67%

Example 4. Under the conditions of example 1, 0.6 g of poly-N-vinylpyrrolidone-2 MM 16,3105dissolved in a mixture 545 ml of water and 455 ml of ethanol (40% ethanol). To the resulting 0,66% solution of poly-N-vinylpyrrolidone-2 at 65oC for 20 min add portions solution 0,236 g of silver nitrate in 25 ml of water (1% solution). The reaction mass containing 38.6% of ethanol, 0,0645% poly-N-vinylpyrrolidone and 0.025% silver nitrate, stirred at 65oC 15 h the Yield of dry product of 99.75% silver content 19,92%

Example 5.

In the conditions of example 1 to a solution of poly-N-vinylpyrrolidone-2 add solution 3,18 g of silver nitrate in 58 ml of water. The reaction mixture containing 13,35% poly-N-vinylpyrrolidone-2, 15.8% ethanol and 0.21% silver nitrate, heated at 75oC for 1 hour After drying, the yield of the target product of 99.9% when the silver content of 1.0%

Example 6

In the conditions of example 1 to 200 g of poly-N-vinylpyrrolidone-2 M 8000 add a mixture of 1000 ml of water and 300 ml of ethanol, and then add 734,9 g of silver nitrate, rastvoreno agreat at the 75oC with stirring for 3.5 hours After drying, the yield of the target product is 99.8% with a silver content of 70.0% of

Examples 7-9 are made in the conditions of example 1. All the data in examples 1-9 are presented in the table.

The stated interval parameters have the following justification:

1. Sequential change of attitude PVP:Ag 1 0,075-0,085 to 1 0,07 and further to 1 0,01 necessitates an increase in the minimum bactericidal concentration, respectively, with 0.62 to 1.2 and 5.0 g/ml.

Reduction of the concentration of PVP to 0.05% and the concentration of AgNO3to 0.02% is accompanied by a slowing of the recovery process by up to 25 h and the formation of large particles of silver.

3. Increasing the concentration of PVP to 14.5-15% increases the viscosity of the solution, which is accompanied by increased losses to 5% during drying of the product.

4. The increase in the concentration of silver nitrate to 32-35% leads to accelerated growth of embryos of metallic silver, the formation of a "silver mirror" and to increased losses of silver.

5. The decrease in the concentration of ethyl alcohol to 2-3% leads to a significant slowing of reaction recovery and to the presence in the final product of the traces of ionic silver.

6. Increase convertname loss of silver due to the reaction of a "silver mirror".

7. Reduction MM PVP to (4-5)103increases the toxicity of the final product.

8. The increase in MM PVP to 2,5106entails a sharp increase of viscosity and deterioration of the solubility of the dry target of the composition in water.

9. Lowering the reaction temperature to 50-55oC slows down the process and increase to 80-85oC leads to a significant loss of silver due to the reaction of a "silver mirror".

The reduction of the silver content in the target composition to 1% (example 5), i.e. 20 times in comparison with the composition in example 4, leads to a decrease in antimicrobial activity only 2 times, however, the toxicity of such compositions is reduced considerably.

The composition obtained in identical conditions (examples 1, 2, 3, 7), characterized by high reproducibility of physico-chemical properties, such as the silver content, is low (about 0.01%) loss of silver during synthesis, the absence of extraneous compounds of silver, narrow distribution of silver particles in size with a high proportion (60-70%) ultrafine particles with radii and stability of performance of antimicrobial activity and toxicity.

1. Water-soluble bactericidal composition containing vysokodispersnom the e protective polymer poly-N-vinyl pyrrolidone-2 mol.m. 8 1031,63 106when the ratio, by weight.h.

Poly-N-vinyl pyrrolidone-2 1

Fine metal silver 0,01 2,33

2. The method of obtaining water-soluble bactericidal composition containing fine metal silver, stabilized by a protective polymer, by restoring ionic silver in aqueous solutions when heated, followed by drying, characterized in that the recovery of ionic silver are in the atmosphere of inert gas in the interaction 0,025 29,73 wt. the silver nitrate solution with 5.0 and 38.6 wt. aqueous solution of ethyl alcohol containing 0,065 of 11.0 wt. poly-N-vinylpyrrolidone-2, the reaction is carried out in the dark with heating to 65 75oC.


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1 cl, 3 ex, 1 tbl

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(I), wherein, as polymer carrier, are used water-soluble copolymers of N-vinylpyrrolidone with α,β-(methyl)acrylic acid alkyl esters and quaternary ammonium salts thereof having general formula: (II), in which formulas A represents triterpenoid residue belonging to series of acids: betulinic {1}, betulonic {2}, glycyrrhetinic {3}, glycyrrhisic {4}, ursolic {5}, ursonic {6}, oleanolic {7}, oleanonic {8}, meristothropic {9}, diketomeristothropic {10}, macedonic {11}, diketomacedonic {12},equinocystic {13}, or mixture of above-indicated carboxyl-containing triterpenoids, where R1 and R2 are hydrogen or methyl; R3 methyl or ethyl; R4 is C6-C16-alkyl; Hal is iodine, bromine, or chlorine atom; k = 65-95 mol %; l = 0.1-34 mol %; n = 0.5-5.4 mol %; molecular weight is equal to (7-100)·103. Polymer derivatives of above-defined triterpenoids are prepared by reaction of terpolymer II, wherein k = 65-95 mol %; l = 0.1-34 mol %; x = 1.0-34.9 mol %; R1-R4, Hal and molecular weight as above. Reaction is carried out in organic solvent at concentration of terpolymer 1 to 30%, concentration of triterpenoid 0.05 to 3.4%, and molar ratio of motif containing quaternary nitrogen to triterpenoid between 1 and 10. Products are isolated by removing solvent.

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4 ex