Composition as bactericidal and antifungal agent (versions) and macroporous bactericidal material based on it

FIELD: biotechnology.

SUBSTANCE: invention relates to compositions and polymeric materials for biomedical use, comprising silver nanoparticles (0.0005-0.02 wt %) stabilised by amphiphilic copolymers of maleic acid (0.0008-0.05 wt %), low molecular weight organic amines (0.0002-0.04 wt %) and water. In addition, the said composition may additionally comprise the polymeric structure-forming agent.

EFFECT: introduction to the composition of the polymer structure-forming agent enables to obtain the macroporous structured hydrogel materials having prolonged bactericidal and antifungal action.

3 cl, 2 tbl, 9 ex

 

The invention relates to biocompatible compositions and composite polymer materials for biomedical application containing nanoscale silver, stable amphiphilic copolymers of maleic acid and low molecular weight organic amines.

The invention can be used to produce macroporous structured materials with prolonged antibacterial and antifungal action.

The proposed composition and materials most effectively can be used for disinfection of water from various sources, containing one - and divalent cations, as well as to receive steam and water-permeable coatings on wounds, antibacterial properties which persist for several days in biological fluids, as well as in hard water.

In this application the following abbreviations are used:

LF nanoparticles;

SNP - silver nanoparticles;

ADSP nanosized silver, stable amphiphilic copolymers of maleic acid;

EM, CM and cm - copolymers of maleic acid with accordingly ethylene, styrene and vinyl pyrrolidone;

EM10SEE10and VM10- amphiphilic copolymers of maleic acid modified on 10% hydrophobic octadecylamine groups on one of the two carboxyl groups of Titkov maleic acid.

PVA - polyvinyl alcohol;

GlyOEt - ethyl ester of glycine;

IleOBzl - benzyl ether isoleucine;

It is known that nano-sized particles of silver have antibacterial and antifungal properties, and maximum efficiency is achieved when the particle diameter of 1-10 nm. Small concentrations of SNP safe for human cells, but is detrimental to most bacteria and viruses. It is believed that the microorganisms in the process of mutation is virtually unable to develop resistance to the drugs of silver in contrast to resistance to many antibiotics narrow steps [G.D. Wright /Adv. Drug Deliv. Rev. 2005, vol. 57, p.1451].

Some mechanisms indiscriminate antibacterial and antifungal action of nanoscale silver: (a) in General, nanoparticles with a diameter of 1-10 nm adhesively attached to the cell membrane of pathogens and break functions, such as permeability and respiration; (b) LF can penetrate into the cell by connecting with gray - and phosphorus-containing compounds such as DNA and some protein fragments, causing damage to them; (C) SNP slowly oxidized water-soluble oxygen, generating cations of silver, which provide additional bactericidal effect. Damaging the bacterial cells, the nanoparticles causes inhibition of the growth and respiration of pathogenic ICRI the organisms. Antibacterial and antifungal effect of SNP depends on the dose and the optimal concentrations leads to cell death [Wigginton N.S., de Titta A., Piccapietra F. et al. Binding of silver nanoparticles to bacterial proteins depends on surface modifications and inhibits enzymatic activity. / Environ. Sci. Technol. 2010, v.44, n.6, 2163-2168].

It is known that to obtain and stabilization of silver nanoparticles (SNP) in aqueous solutions using low-molecular organic amino compounds connection.

Known composition, which includes primary, secondary, or tertiary amines used in the preparation and stabilization of SNP [patent Canada No. 2741917]. Hydrazine or its derivatives (4-10 fold molar excess of amine per mole of silver) is injected into the system in two phases and is used as a reductant cationic silver. The process of obtaining SNP is carried out in an organic solvent, such as toluene, which limits the use of such compositions in aqueous solutions containing salts, such as saline solution, for biomedical purposes.

Known composition, which is used for biomedical purposes, containing primary aliphatic amine, dissolved in a linear hydrocarbon solvent in 65-155°C, for example, methyl alcohol (MeOH), to stabilize the SNP. Silver nanoparticles are formed when recovering formic acid dispersion of silver oxide, also dispergirovany the Noi in MeOH, when heated [patent Canada No. 2741917]. The resulting composition of nanosized silver requires thorough cleaning from non-aqueous solvent. In addition, in this patent there is no indication on the stability of the selected drug nanoscale silver in aqueous salt solutions.

Known composition, in which the use of L-histidine as a stabilizer of nanoscale silver (9-21 nm) in the aquatic environment. A connection is established SNP with the carboxylate group of L-histidine. However, in an aqueous medium containing salt, is the aggregation of nanosized silver, which affects its solubility and reduces the bactericidal properties [Liu, Zhiguo; Xing, Zhimin; Zu, Yuangang; Tan, Shengnan; Zhao, Lin; Zhou, Zhen; Sun,Tongze. / Materials Sci. and Engineering. C: Materials for Biol. Appl. (2012), 32(4), 811-816].

Known composition of organic-inorganic nanostructures in the form of a suspension containing stabilized nanoparticles (NP) of noble metals, in the form of polycomplex, in a two-phase reaction system, consisting of two large contacting immiscible liquids, with polycomplex includes organic molecules containing amino groups in number of 2 or more, and nanoparticles of noble metals [RF patent N 2364472]. In the mentioned patent describes compositions containing as organic molecules molecules of linear polyamines diamines, polyamine of spermine, polyall lamina, which stabilize LF precious metals, including silver, at the interface of two immiscible phases. The invention allows to obtain nanostructured metal-polymer complexes on the basis of polyamines containing noble metal nanoparticles with a size up to 10 nm. However, the use of such complexes in biomedical purposes is limited by the need for a thorough cleaning from organic solvents not miscible with water.

Known composition, which is used to produce macroporous polymeric hydrogels for biomedical application, filled with nanosized particles of silver (2-10 nm), stabilizirovannykh amphiphilic copolymers of maleic acid [RF patent N 2404781]. The composition contains, along with biocompatible polymers-builders (2-13 wt.%), fillers in the form of nanoscale silver (0,007-0.3 wt.%), stable amphiphilic copolymers of maleic acid (0.02 to 0.6 wt.%), as well as therapeutic substances (0.01 to 0.6 wt.%) and the water. From the composition obtained by way of ristrutturare macroporous polymeric hydrogels and films containing SNP and therapeutic agents with adjustable strength and diffusion characteristics. The specified composition and material based on it most effectively can be used for water disinfection and adnych solutions as well as to receive steam and water-permeable coating on the wound with wound healing properties and prolonged antibacterial and antifungal action. The song on the totality of symptoms is the closest to the claimed composition and selected as a prototype.

The disadvantage of the composition of the prototype is a low colloidal stability of stabilized nanoscale particles of silver in aqueous solutions containing salts, which limits its use in contact with biological fluids and tissues. Composition-the prototype can be used effectively as a bactericidal agent only in environments that do not contain salts, in particular in distilled or soft water, its use in hard water inefficiently, i.e., the scope of the prototype is limited. The material obtained from the composition of the prototype, also ineffective in environments containing salt.

The present invention is the creation of new compositions as antibacterial and antifungal drugs, and macroporous bactericidal material having a wider scope.

The solution of this problem is achieved

(i) the composition as a bactericidal and antifungal funds, including the restored stable nanosized Orebro (of 0.0005 to 0.02 wt.%), polymer stabilizer based on amphiphilic copolymers of maleic acid with comonomers selected from the group comprising ethylene, isobutylene, styrene, vinyl pyrrolidone, acrylamide, vinyl acetate, methyl methacrylate and stearylamine derivatives of these copolymers (0,0008 to 0.05 wt.%), water and optionally low molecular weight organic amines, or derivatives thereof, selected from the group comprising esters of amino acids, amino sugar, amino compounds oligosaccharides and peptides, histamine, methenamine (is 0.0002 to 0.04 wt.%); (ii) a composition comprising recovered stabilized nanoscale silver (of 0.0005 to 0.02 wt.%), polymer stabilizer based on amphiphilic copolymers of maleic acid with comonomers selected from the group comprising ethylene, isobutylene, styrene, vinyl pyrrolidone, acrylamide, vinyl acetate, methyl methacrylate and stearylamine derivatives of these copolymers (0,0008 to 0.05 wt.%), low molecular weight organic amines, or derivatives thereof, selected from the group comprising esters of amino acids, amino sugar, amino compounds oligosaccharides and peptides, histamine, methenamine (is 0.0002 to 0.04 wt.%), water and optionally polymer structure-former such as polyvinyl alcohol, gelatin, starch, pectin, agarose, collagen, and mixtures thereof (2,0-13,0 wt.%), and (iii) macroporous material with antibacterial and antifungal activity, recip is authorized on the basis of one song.

The technical result consists in increasing the coagulation stability of the compositions and materials containing stabilized silver nanoparticles in aqueous salt solutions, in particular in biological environments, which leads to increased antibacterial and antifungal activity of such compositions and materials in the above conditions.

Upon receipt of the claimed composition and macroporous bactericidal material were used the following substances:

- nano silver (2-10 nm), obtained by recovery of cationic silver sodium borohydride in the presence of equimolar number of amphiphilic copolymers of maleic acid as stabilizers [Samoilova N.A., Kurskaya E.A., Krayukhina M.A., Askadsky A.A., Yamskov I.A. / J. Phys. Chem. (2009) v.113, nil, p.3397-3403];

copolymers of maleic acid and 10% octadecylamine derivative obtained by the method described in [Conix, A.; Smets, G. / J. Polym. Sci. 1995, v.15, p.221] and [Krayukhina, M. A.; Kozibakova, S. A.; Samoilova, N. A.; Babak, V. G.; Karayeva, S. Z.; Yamskov, I. A. / Russ. J. Appl. Chem. 2007, v.80, p.1145];

the monomers for the synthesis and modification of co-stabilizers nanoscale silver: maleic anhydride, ethylene, styrene, N-vinyl pyrrolidone, acrylamide, methyl methacrylate, vinyl acetate from Aldrich";

- plastics-builders: polyvinyl alcohol (PVA) with molecular weight of 60,000 and a degree of dezetilirovanny is 98% of the production Sterlitamakskogo chem. mill, potato starch, agarose Sigma;

- silver nitrate (reagent-grade) and borgerende (CHP) of the company "Rahim";

- amines and their derivatives from "Aldrich".

Selection of specific co-stabilizers (SP) of the above (1), macromolecule which differ in the size and hydrophilic-hydrophobic balance, allows you to adjust the adsorption and diffusion properties of ADSP when sharing with porous materials (macroporous gels, filter, and dressings).

Increased antibacterial and antifungal activity of ADSP in aqueous salt solutions is achieved by introducing into the composition of low molecular weight organic amines. Competing with cations of sodium or calcium for binding to ionized carboxyl groups of residues of maleic acid (which provide colloidal stability and solubility of ADCP in the aquatic environment), amines shift coagulation threshold in the area of higher concentrations of inorganic salts. As a component that increases the colloidal stability of ADSP in aqueous salt solutions, for the claimed compositions choose only non-toxic and biocompatible organic amines, for example, esters of L-amino acids, amino sugar, amino compounds oligosaccharides and peptides that can be used for Biomed is medical purposes.

The claimed composition, the optimum composition of which is set by varying the types of hydrophobic co monomer of maleic acid, an amine, the molar ratio of amine : ADSP, as well as inorganic cation enables its effective use for disinfecting biological fluids and tissues containing inorganic salts, using traditional dressings impregnated with aqueous solutions of compositions, as well as for adsorption composition on a porous filters used for disinfection and purification of mediterranei, for example, hard water.

To obtain the claimed macroporous materials based on the composition in the composition include polymer amendment (2,0-13 wt.%). When the concentration of the amendment below 2% are obtained fragile greatly swelling the samples, the practical use of which is difficult. And at concentrations of builders above 13% are formed very dense samples with pore sizes that hinder the diffusion of stabilized nanoscale silver with amines of the cryogel in the aquatic environment.

Macroporous hydrogel materials get in the way ristrutturare. The materials obtained on the basis of the claimed composition, are macroporous hydrogels filled with Ag The Item together with low molecular weight amines. The gradual diffusion of ADSP of porous hydrogels in aqueous salt solutions allows the use of materials such as antibacterial and antifungal dressing devices of prolonged action. The materials can be adjusted diffusion of ADSP. The materials have high colloidal stability in aqueous solutions of salts.

Earlier example, pathogenic fungi F. Oxisporum it was found that the antifungal activity of nanosized silver with an average diameter of particles (1-10 nm)stabilized with a copolymer of maleic acid and ethylene (ADEM), already observed at a concentration of about 10 ppm (i.e., about 10 mg/l) [Samoilova N.A., Kurskaya E.A., Krayukhina M.A., Askadsky A.A., Yamskov I.A. / J. Phys. Chem. B. 2009, v.113, n 11, p.3395 - 3403]. Taking into account the molecular weight of the Monomeric component copolymer ADEM equal to 252, one antifungal drug dose is about 0.04 mmol per liter (or of 0.004 mmol in 100 g of solution).

Taking into account the possibility of prolonged action and composition of the material in aqueous salt solutions, when the variation of the composition, the authors decided that the minimum content of ADSP should correspond to the composition of such a composition, which after 7 days stay in the aqueous salt solution ensures the preservation of nanoscale silver in the solution in an amount of not lower than one antifungal dose.

When determining the maximum content of ADCP in the song came from the fact that the concentration of ADSP in saline solution should not exceed approximately 4,6 antifungal doses (20 mg/l or 0,0185 mmol per 100 g)that sootveststvuet greatest non-toxic therapeutic doses of Ag° in solution when applied externally). ["Biosafety nanoobjects" data laboratory of ecological genetics, Institute of General genetics him. N.I. Vavilov RAS, also Hussan S.. et al. / Toxicological Sci. 2006, v.92,n2, pp.456-463].

The number of ADSP and Amin, included in the macroporous gel material, depends on the level of diffusion of nanoscale silver in aqueous solution, as well as its colloidal stability, the value of the final concentration of ADCP in the salt solution should be in the range from 1 to 4.6 antifungal doses, i.e. from 0.004 to 0,0185 mmol per 100 g of the solution within 7 days of diffusion.

The colloidal stability of ADSP in aqueous solutions of salts depends on the quantitative and qualitative composition and including, on the molar ratio of amine : ADSP. Experimentally it was found that the most successful protective effect of amines on the colloidal stability in solutions of sodium chloride and calcium is observed when the molar ratio of amine : ADSP equal 03-2,0 : 1. Outside the specified interval molar ratios of observed processes of coagulation, the value is positive decreasing antibacterial and antifungal activity of ADSP.

The invention is illustrated in the following examples. The specific formulations of the inventive compositions and the resulting macroporous material and their antifungal action in environments containing salt shown in the following examples and tables 1 and 2.

When calculating the molecular weight of each of ADSP in solutions used molecular mass of one mole of each link of the co-stabilizers (SP) nanoscale silver, i.e. fundamental mole, equal to 144 for EM, 169 for EM, 227 for VM, 252 for WM, 220 CM and 245 for SM10; the number of SP in the composition was determined from the molar ratio SP : Ag=1 : 1.

In all the examples studied antifungal properties of the claimed compositions and materials of different composition in aqueous environments containing salts of sodium or calcium. The density of all solutions considered equal to one. The presence of antifungal activity was determined by the presence of silver nanoparticles in aqueous solutions of at least one antifungal dose of 0.004 mmol in 100 g of solution. Intensity yellow (λmax415-420 nm), characterizing the absorption of nanoscale silver (diameter up to 100 nm) in aqueous solution was determined concentration of ADSP (ratio of molar absorption equal to about 104). Effective believed that the composition of such a composition in which its antifungal activity (determined what may the presence of the SNP in the amount of not less than 1 antifungal dose) lasts for 7 nights stay in the aqueous salt solution.

Example 1. To obtain 100 g of a solution containing 1.5 mmol (378 mg) ADEM, mix 50 g of a solution containing 1.5 mmol AgNO3,and 50 g of a solution containing 1.5 mmol copolymer stabilizer, then under stirring was added 23 mg (approximately 7.5 mmol sodium borohydride. The resulting solution was purified from low molecular weight components by the method of exhaustive dialysis, subjected to freeze drying and get Adam in the form of powder.

The composition is prepared as follows: a weighed sample of 1.3 mg (0.005 mmol) Adam, (containing 0.5 mg of silver and 0.8 mg of copolymer EM), dissolved in 25 grams of distilled water. Then, to the obtained solution under stirring was added 25 grams of an aqueous solution containing 0.2 mg (0,0015 mmol) of histamine hydrochloric acid (111 MM) and add 50 g of water. In the finished composition (100 g) was injected 20 mmol NaCl to study antifungal properties of the composition in a medium containing salt. The resulting solution (100 g) contained 10 mmol NaCl. When the molar ratio of histamine : ADEM is 0.3 : 1. As can be seen from the data given in the table, the concentration of ADEM in combination with histamine after 7 days stored at one antifungal dose of 0.004 mmole per 100 g of solution.

Example 2. Stabilized nanoparticles AgBM get similarly as ADCP, according to the method described in example 1 for Adam.

The aqueous composition (100 g, containing 6.2 mg (0,0185 mmol) AgBM (2 mg Ag+4,2 mg of copolymer VM) and 3.3 mg (0,013 mmol) of hydrochloric acid glucosamine (252 MM) prepared according to the method described in example 1. In the finished composition (100 g) was injected 48 mmol NaCl to study antifungal properties of the composition in a medium containing salt. The resulting solution (100 g) contains 24 mmol NaCl (which is higher than the concentration of salt in the saline solution of 15.4 mmol/100 g). The molar ratio of glucosamine : AgBM is 0.7 : 1. It is shown that after 7 days the concentration of the AgBM in combination with glucosamine remains at the level of one antifungal dose.

In examples 1-10 was ADSP receive according to the method described in example 1. Composition and saline environment in examples 3-6 are prepared by methods similar to those described in examples 1 and 2. Example 6 relates to compositions in which no amine shown for comparison. For preparation of compositions you can use ADSP in the form of a solution, purified from low molecular weight components by the method of exhaustive dialysis, or in the form of a powder after freeze drying. The data of examples 1-6 and 7-10 are shown in tables 1 and 2, respectively.

Table 1
Antifungal effect of the inventive compositions in aqueous solutions containing NaCl and CaCl 2
Number exampleThe content of the component 100 g of the composition mg (mmol)The amount of salt introduced into 100 g of an aqueous solutionThe number of ADSP (mol/number of antifungal doses) in solution in 15 min, 1 day and 7 days after the injection of salt
AgSPAmine, the molar ratio of amine : ADSP15 min1 day7 days
1.0,5 (0,05;EM 0,8 (0,05;Histamine 0,2NaCl050,00480,0045
(0,0015), 0,3 : 110 mmol1,31,21,1
2.2,0 (0,0185)BM 4,2 (0,0185)The hydrochloric acid glucosamineNaCl0,0135 0,01130,0067
3,3 (0,013) of 0.7 : 124 mmol3,42,81,7
3.2,0 (0,0185)BM10 4,7 (0,0185)IleOBzlCaCl20,01120,00800,0057
14,5 (0,037) 2 : 12.6 mmol2,82,01,4
4.0,4 (0,004)EM 0,6 (0,004)HistamineNaCl0,00320,00240,0010
0,1 (0,0008), 0,2 : 18 mmol0,80,60,3
5.2,0 (0,0185)CM 4,2 (0,0185)IleOBzl 16(0,041), 2,2 : 1CaCl22.6 mmol opalescencea suspension of brown particlesprecipitate calcium salts with AgCM
6.2,0 (0,0185)BM 4,2 (0,0185)noNaCl, 24 mm0,0030,001colloidal precipitate of metallic silver

The data in table 1 show that the concentration of nano silver salt solution is markedly reduced due to the formation of colloidal precipitate (Example 5), which dramatically reduces and bactericidal properties of the composition.

The claimed composition mentioned above, from which the claimed macroporous material contains a polymer amendment (2-13 wt.%). The way to obtain macroporous materials based on the composition includes the preparation of an aqueous solution or dispersion of the amendment, the subsequent introduction of aqueous nano-silver, stabilized copolymers of maleic acid (ADSP) and low molecular weight organic amine, further once or twice ristrutturazione, which includes freezing, storage in a frozen state at a temperature of minus 10 to 30°C in those who tell 10-20 hours and manual defrosting within 2-4 hours consistently at 2-6°C 20-24°C [RF patent №2404781].

Example 7. AgCM receive, as described in example 1.

Prepare a solution of ADSP and amine, at a molar ratio of histamine : AgCM=0,5 : 1. A portion of 16.4 mg (0,050 mmol) (5,5 mg silver+10,9 mg CM) dissolved in 9 g of distilled water, then with stirring, add 9 g of an aqueous solution containing 2.8 mg (0,025 mmol) of histamine hydrochloric acid (111 MM).

As amendment use a 2.5% solution of agarose. Dry agarose (2.5 g) is subjected to swelling in 80 g of distilled water and dissolved under stirring and heated to 90-100°C. Then the resulting solution was added a solution containing AgCM and histamine, bring the weight up to 100 g with distilled water and frozen in a metal container of the desired thickness (for example, 2 cm) at minus 20°C for 18 hours. Next, produce a stepped thawing of the sample by its consistent curing for 2 hours at 4, then at 22-23°C. the Process of freezing and thawing produces twice.

Obtained after thawing the sample has a spongy structure. To determine the level of diffusion of SNP gel in aqueous saline wet sample of the gel was placed in 100 g of an aqueous solution containing 20 mmol NaCl. After 7 days of diffusion SNP concentration of nano-silver in the NaCl solution was 0,0055 mmol/100 g, i.e. about 1.4 antifungal dose nanoscale with the ribs (table 2, example 7).

Example 8. For preparation of a solution containing equimole number AgBM and amine in 9 g of distilled water dissolve a portion of 20.1 mg (to 0.060 mmol) AgBM (containing 6.5 mg of silver and 13.6 mg VM), then under stirring was added 9 g of an aqueous solution containing 14,8 mg (to 0.060 mmol) of ethyl ether hydrochloric acid lysine (MM 247).

As amendment use a 6% solution of PVA. The PVA sample (6 g) is subjected to swelling in 80 g of distilled water. Then the variance of the PVA is dissolved when heated to 80-90°C and the resulting solution was added with stirring a solution containing equimole number AgBM and Amin, adding distilled water to bring the weight of the solution to 100 g, was placed a solution in the metallic form and once frozen at a temperature of -16°C for 18 hours with subsequent speed thawing, as described in example 6.

The thawed sample macroporous gel is placed in 100 g of an aqueous solution of calcium chloride with a concentration of 2 mmol/100 g Shows that after 7 days in the salt solution contains 1,3 antifungal dose AgBM.

Example 9. For the preparation of an aqueous solution containing the amine and AgCM10 in a molar ratio of 1.5 : 1, mixing 9 g of an aqueous solution containing 65,3 mg (0.185 mmol AgCM10 (20 mg silver+45,3 mg SM10), and 9 g of a solution containing of 38.9 mg (0,278 mmol) of ethyl EPE is and glycine hydrochloric acid GlyOEt HCl.

As amendment use 13% dispersion of fine collagen, obtained by acid treatment of a dispersion of coarse-fibered collagen. This dispersion receive mechanical grinding of the dermis (solenoi skins of bovine (pH about 11.5). The dispersion was washed with water, 0.5 M solution of hydrochloric acid to bring the pH to 3, stand for several hours to obtain a fine-fibrous collagen, then alkalinized 0.5 M NaOH solution to a pH of about 3.5 to 4.5.

To the resulting dispersion was added with stirring the above solution of nanosized silver and amine, the mixture is placed in a metal mold, frozen at a temperature of -25°C for 18 hours and thawed, consistently soaking for 2 hours at temperatures of 4 and 22-23°C.

Formed after thawing wet macroporous collagen material obtained from 100 g of the composition, placed in 100 g of sodium chloride solution with a concentration of 24 mmol/100 g After 7 days, the concentration of nano-silver in the solution was 0,0080 mmol/100 g of the solution, i.e. the 2 antifungal dose (table 2, example 9).

Table 2.
Antifungal action of the inventive polymeric material in water the solution, containing NaCl and CaCl2
Number exampleThe content of components in 100 g of the composition mg (mmol)The amount of salt introduced into 100 g of an aqueous solutionThe number of ADSP (mmol/number of antifungal doses), with the diffusion of ADSP of material in an aqueous solution of salt (100 g) through
AgSPAmine, the molar ratio of amine : ADSPStructure-educational1 day3 days7 days
7.0,5 (0,05)CM 10,9 (0,050)Histamine 2,8 (0,025) of 0.5 : 1The agarose 2.5 gNaCl, 20 mmol0,0036 0,90,0048 1,20,0055 1,4
8.6,5 (to 0.060)VM 13,6 (to 0.060)LysOEt 14,8 (to 0.060) 1 : 1PVA 6 gCaCl22.0 mmol0,004 1,00,0048 1,2 0,0052 1,3
9.20 (0,185)SM10 of 45.3 g (0,1850)GlyOEt 38,9 (0,278) of 1.5 : 1Collagen dispersion 13 gNaCl, 24 mm0,0048 1,20,0060 1,50,0080 2,0
10*.0,5 (0,05)CM 10,9 (0,050)noThe agarose 2.5 gNaCl, 20 mmol0,0004 0, 10,0008 0,20,0015 0,4
*The composition of example 10, in which no amine shown for comparison.

The claimed composition and the materials exhibit antifungal activity in solutions containing salts, which allows their use in such environments as saline and biological fluids, and also in hard water.

The given examples show that the extension of the scope of nanosized silver, stable amphiphilic copolymers of maleic acid as antibacterial and antifungal funds in aqueous salt solutions is ensured by the introduction nizkomolekulyarnye the organic amines in a molar ratio of amine : ADSP=0,3-2,0 : 1. Amines proposed in the invention of a number of highly soluble in water over a wide temperature range and are not toxic substances.

The claimed composition, antibacterial and antifungal properties which persist for several days in salt water environments most effectively can be used for disinfection of water from various sources, containing one - and divalent cations. Composition not containing the amendment, which can be subjected to freeze drying, to produce powders that are applicable for the same purpose, either directly or after dilution in water and receiving the corresponding composition. Compositions in the form of a powder for easy storage and transport.

Declare macroporous material can be used as a dressing tool with prolonged antibacterial and antifungal activity in solutions containing salts (e.g., in plasma) within a few days. The claimed material retains its properties when stored in a moist condition.

1. The composition as a bactericidal and antifungal funds, including the restored stable nanosized silver, polymer stabilizer based on amphiphilic copolymers of maleic acid with comonomers selected from the group comprising ethylene, isobutylene, styrene, vinyl pyrrolidone, acrylamide, vinyl acetate, methyl methacrylate; stearylamine derivatives of these copolymers and water, characterized in that it further contains a low molecular weight organic amines, or derivatives thereof, selected from the group comprising esters of amino acids, amino sugar, amino compounds oligosaccharides and peptides, histamine, methenamine, in the following ratio, wt.%:

Nanoscale silver0,0005-0,02
The copolymer stabilizer nanoscale silver0,0008-0,05
Low molecular weight organic aminesis 0.0002 to 0.04
WaterThe rest is up to 100

2. The composition as a bactericidal and antifungal funds, including the restored stable nanosized silver, polymer stabilizer based on amphiphilic copolymers of maleic acid with comonomers selected from the group comprising ethylene, isobutylene, styrene, vinyl pyrrolidone, acrylamide, vinyl acetate, methyl methacrylate; stearylamine derivatives of these copolymers; polymer structure-former such as polyvinyl alcohol, gelatin, starch, pectin, agarose, collagen, and mixtures thereof; and water, characterized in that it further contains a low molecular weight organic amines, or derivatives thereof, selected from the group comprising esters of amino acids, amino sugar, amino compounds oligosaccharides and peptides, histamine, methenamine; in the following ratio, wt.%:

Nanoscale silver0,0005-0,02
The copolymer stabilizer nanoscale silver0,0008-0,05
Low molecular weight organic aminesis 0.0002 to 0.04
Polymer structure-former2,0-13,0
WaterThe rest is up to 100

3. Macroporous material with antibacterial and antifungal activity, obtained on the basis of the composition according to claim 2.



 

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2 cl, 6 dwg

FIELD: nanotechnology.

SUBSTANCE: invention relates to nanotechnology equipment and designed for closed cycle of production and measurement of new products of nanoelectronics. The nanotechnological complex comprises a robot-distributor with the ability of axial rotation, coupled with the chamber of loading samples and the module of local influence, as well as the measuring module comprising a scanning probe microscope, an analytical chamber, a monochromator and an x-ray source. The measuring module and the analytical chamber are coupled with the robot-dispenser, the monochromator is coupled with the analytical chamber, and the x-ray source - with the monochromator. The module of local influence comprises a module of focused ion beams and the first scanning electron microscope.

EFFECT: enhanced functional capabilities of the nanotechnological complex.

6 cl, 6 dwg

FIELD: chemistry.

SUBSTANCE: electric sensor for hydrazine vapours contains a dielectric substrate, on which placed are: electrodes and a sensitive layer, which changes photoconductivity as a result of hydrazine vapour adsorption; the sensitive layer consists of the following structure - graphene-semiconductor quantum dots, whose photoconductivity decreases when hydrazine molecules are adsorbed on the surface of quantum dots proportionally to the concentration of hydrazine vapour in a sample. If hydrazine vapours are present in the air sample, hydrazine molecules are adsorbed on the surface of quantum dots, decreasing intensity of quantum dot luminescence, which results in decrease of graphene conductivity proportionally to the concentration of hydrazine vapours in the analysed sample.

EFFECT: increase of sensitivity, decrease of determination sluggishness and simplification of the sensor manufacturing.

1 ex, 7 dwg

FIELD: metallurgy.

SUBSTANCE: gold cylindrical nanoparticles not over 100 nm in length are sprayed onto surface of tested object, depth of the ply of said particles allowing the filling of cavities of would-be fractures. Then, said surface is dried to remove sprayed ply therefrom. Then, object surface is subjected to non-interlaced scan by fs-laser beam. At a time, intensity of two-photon luminescence signal is registered in every area under analysis to fix the location of said area corresponding to object coordinate. 2D array of two-photon luminescence signal intensities is formed to produce the map of distribution of nanoparticle luminescence intensities excited by laser radiation.

EFFECT: possibility to reveal surface defects for their early detection.

3 cl, 7 dwg

FIELD: power industry.

SUBSTANCE: invention may be used when producing carbon nanotubes and hydrogen. Microwave plasma converter comprises flow reactor 1 of radiotransparent heat-resistant material, filled with gas permeable electrically conductive material - catalyst 2 placed into the ultrahigh frequency waveguide 3 connected to the microwave electromagnetic radiation source 5, provided with microwave electromagnetic field concentrator, designed in the form of waveguide-coax junction (WCJ) 8 with hollow outer and inner conductors 9, forming discharge chamber 11 and secondary discharge system. Auxiliary discharge system is designed from N discharge devices 12, where N is greater than 1, arranged in a cross-sectional plane of discharge chamber 11 uniformly in circumferential direction. Longitudinal axes of discharge devices 12 are oriented tangentially with respect to the side surface of discharge chamber 11 in one direction. Nozzle 10 is made at outlet end of inner hollow conductor 9 of WCJ 8 coaxial. Each of discharge devices 12 is provided with individual gas pipeline 13 to supply plasma-supporting gas to discharge zone.

EFFECT: invention permits to increase the reaction volume, production capacity and period of continuous operation, stabilise burning of microwave discharge.

3 cl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention can be used in the field of elaboration of diamond-based materials for magnetic therapy, quantum optics and medicine. A method of determining an angle of misorientation of diamond crystallites in a diamond composite includes placement of the diamond composite into a resonator of an electronic paramagnetic resonance (EPR) spectrometer, measurement of EPR spectrums of nitrogen-vacancy NV-defect in the diamond composite with different orientations of the diamond composite relative to the external magnetic field, comparison of the obtained dependences of EPR lines with the calculated positions of EPR lines of NV-defect in the diamond monocrystal in the magnetic field, determined by the calculation. After that, the angle of misorientation of the diamond crystallites is determined by an increase of width of EPR line in the diamond composite in comparison with the width of EPR line in the diamond monocrystal.

EFFECT: invention ensures higher accuracy of measurements.

3 cl, 6 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method of modifying envelopes of polyelectrolyte capsules with magnetite nanoparticles. The disclosed method involves producing a container matrix in form of porous calcium carbonate microparticles, forming envelopes of polyelectrolyte capsules by successive adsorption of polyallyl amine and polystyrene sulphonate and modifying with magnetite nanoparticles on the surface of the container matrix or after dissolving the matrix through synthesis of magnetite nanoparticles via chemical condensation.

EFFECT: invention enables to obtain modified polyelectrolyte capsules, designed to deliver medicinal substances which do not harm the human body.

3 cl, 4 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for the delivery of a pharmaceutical agent to a focus of a disease. The composition contains a water-insoluble pharmaceutical agent which is paclitaxel, a pharmaceutically acceptable carrier which is albumin, preferentially human serum albumin. The relation (wt/wt) of albumin to paclitaxel makes 9:1. The pharmaceutical composition contains nanoparticles containing paclitaxel and albumin wherein the nanoparticles have a size of less than 200 nm.

EFFECT: administering the pharmaceutical composition according to the invention provides enhanced characteristics of the delivery of paclitaxel to the site of the disease and reduced adverse side effects.

24 cl, 5 tbl, 51 ex

FIELD: medicine.

SUBSTANCE: what is described is an umbrella device (occluder) with a modified coating layer for the left atrial appendage occlusion. The umbrella device (occluder) with the modified coating layer is made from a titanium nickelide alloy. It has the coating modified layer having a thickness of 80-95 nm which consists of at least two sub-layers: an external sub-layer having a thickness of 20-25 nm contains oxygen, carbon, silicone and titanium in the following ratio, at %: oxygen 25-65, carbon 1-5, silicone 1-10, titanium - the rest; an intermediate sub-layer having a thickness of 60-70 nm contains oxygen, carbon, silicone, titanium and nickel in the following ratio, at %: oxygen 5-30, carbon 1-5, silicone 10-30, nickel 1-50, titanium - the rest, with silicone reaching its maximum concentration at a depth of 30-35 nm from the surface. The modified coating layer of the umbrella device (occluder) has no evident interface of the sub-layers specific for a deposited layer.

EFFECT: umbrella device with the modified coating layer possesses biocompatibility, corrosive resistance and no toxicity.

9 cl, 2 dwg

FIELD: metallurgy.

SUBSTANCE: initial components represent SiO2 or titaniferous magnetite and SiO2 to be mixed with carbonate Li(Li2CO3) at the ratio of 55-70 mol. % initial components, Li2CO3 and FeCO3 making the rest in equal amounts of cathode materials LixFeyMzSiO4/C. Then, powder is fused at 1180±5°C. After cooling, obtained alloy is ground to introduce therein, as high-molecular compound, polymethyl methacrylate or soot in amount of 2-5% of alloy. Then, thermal treatment is performed in cycling mode. For this it is heated to ≥600°C and held for 55-65 minutes. Now, it is cooled to room temperature in 5-10 cycles along with powder surface modification by carbon at heating.

EFFECT: storage battery higher discharge capacity.

5 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: membrane is made of a tetrafluoroethylene copolymer with functional perfluorinated comonomers of the general structural formula: where R: (D), (E), (K), M-H, Li, K, Na; a=24.75-18.38 mol.%; b=78.62-81.12 mol.%; c=5.0-0.5 mol.%; and is from 10 mcm and higher thick, density is 1.93-2.10 g/cm3, mechanical strength is 16-22 MPa and a coefficient of gas permeability by hydrogen (K) is 1-3.7×10-16 m3m m-2Pa-1s-1 at 20-90°C. A method of obtaining consists in combination of a porous polytetrafluoroethylene film with a perfluorosulphocationite polymer in a medium of an organic or a water-organic solvent in the presence of a modifier. The modifier is represented by hydrocarbon polymers, fluoropolymers, perfluoropolymers or their mixtures, inorganic compounds or their mixtures.

EFFECT: high drops of pressure, high current density and efficiency of an electrolysis cell exploitation.

13 cl, 3 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: asphalt-concrete mixture containing oil viscous bitumen, a filling agent, sand with fraction to 5 mm, crushed stone and an additive contains as crushed stone crushed granite with fraction 5-15 mm, as sand - sweepings of rock crushing, as the filling agent - sludge of HES water preparation and as the additive - a homogeneous short-fibre cellulose fibre and an organomineral modifier, containing sludge of HES water preparation, Portland cement, a polymer additive Butonal NS 198 and sodium pyrophosphate, with the following component ratio, wt %: oil viscous bitumen 6.3-6.9, crushed granite with fraction 5-15 mm 62.8-67.5, sweepings of rock crushing with fraction 0-5 mm 13.5-17.6, homogeneous short-fibre cellulose fibre 0.2, filling agent - sludge of HES water preparation 12.47-12.48, sludge of HES water preparation 0.0158-0.0238, Portland cement 0.0016-0.00235, polymer additive Butonal NS 198 0.0024-0.00357, sodium pyrophosphate 0.0002-0.00028.

EFFECT: increased water resistance of asphalt-concrete mixtures.

2 tbl

FIELD: medicine.

SUBSTANCE: material consists of several layers: an inner layer is made from chitosan nanofibres/superfine fibres, and an outside layer are used as an electrical forming substrate and exercise the protective function. The chitosan layer is made from herbal or mixed herbal and animal chitosan and can contain antibiotic. The multilayer material can contain at least one more layer of biopolymer nanofibres/superfine fibres electroformed of cellulose diacetate or gelatin. The three-layer material with the chitosan layer of the nanofibres/superfine fibres is applicable for local wound and burn healing.

EFFECT: material resistance to mechanical stress.

15 cl, 4 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of modifying envelopes of polyelectrolyte capsules with magnetite nanoparticles. The disclosed method involves producing a container matrix in form of porous calcium carbonate microparticles, forming envelopes of polyelectrolyte capsules by successive adsorption of polyallyl amine and polystyrene sulphonate and modifying with magnetite nanoparticles on the surface of the container matrix or after dissolving the matrix through synthesis of magnetite nanoparticles via chemical condensation.

EFFECT: invention enables to obtain modified polyelectrolyte capsules, designed to deliver medicinal substances which do not harm the human body.

3 cl, 4 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: bitumen-concrete mixture contains crushed rock, sand and oil bitumen BND 90/130, nano-modified with a mechanically activated mixture of rubber crumbs with an additive, where the bitumen is modified using rubber crumbs with size of 0.25 mm and the additive is natural zeolite, with the following ratio of ingredients, wt %: said bitumen 93.0 of the weight of the rubber-bitumen mixture, said crumbs 7.0 of the weight of the rubber-bitumen mixture, natural zeolite 2.0 of the weight of the rubber crumbs.

EFFECT: high plasticity at subzero temperatures.

1 ex, 6 tbl

FIELD: physics.

SUBSTANCE: magnetoresistive gradiometer head has a substrate with a dielectric layer on which there are four rows of thin-film magnetoresistive strips connected in series by nonmagnetic low-resistance jumpers in each arm of a bridge circuit, said rows being connected into a bridge circuit by said jumpers, each of said strips having top and bottom protective layers with a ferromagnetic film in between, where in all thin-film magnetoresistive strips, the easy magnetisation axis of the ferromagnetic film is directed at an angle of 45° relative to the longitudinal axis of the thin-film magnetoresistive strip, a first insulating layer on top of the thin-film magnetoresistive strips on which is formed a conductor with two contacts with working parts lying over the thin-film magnetoresistive strips with working parts of the conductor, lying over the thin-film magnetoresistive strips, a second insulating layer and a protective layer, wherein all thin-film magnetoresistive strips are arranged in one row, and the row of thin-film magnetoresistive strips closest to the edge of the substrate lies at a distance from the other three rows of thin-film magnetoresistive strips of not less than a tenth of repetition periods of said rows, the second insulating layer is provided with a calibration conductor placed over the working thin-film magnetoresistive strips of the bridge circuit.

EFFECT: design of a magnetoresistive gradiometer head with a planar calibration conductor which enables to determine operating capacity of the head without using an external source of a local magnetic field.

3 dwg

FIELD: medicine.

SUBSTANCE: group of inventions refers to a drug preparation used as a photosensitiser (PS), and to a method for photodynamic therapy with using it. The preparation represents a nanostructured water dispersion of methyl ether of O-propyl oxime-N-propoxybacteriopurpurinimide C40H50N6O6.

EFFECT: invention provides high photoinduced anti-tumour activity in the system in vitro and in vivo, complete tumour growth inhibition and recovery in animals ensured by the selective collection in the tumour and fast washout.

7 cl, 5 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to a composition containing encapsulated triterpenic acid: betulinic acid, ursolic acid or derivatives thereof in the form of salts and esters, or triterpene alcohol - betulin, which may be used in medicine for treating and preventing viral infections caused by DNA and RNA-containing viruses, such as influenza viruses, oncogenic viruses, herpes virus, herpes zoster virus, as well as infections caused by gram-positive and gram-negative bacteria: Staphylococcus spp., Streptococcus spp., Enterococcus spp., Shigella spp., Escherichia spp., Salmonella spp., Proteus spp., Acinetobacter spp., Citrobacter spp., Pseudomonas spp., Serratia spp., Klebsiella spp., Antracoides spp., Cryptococcus spp., pathogenic fungi of the genus Microsporum, Trichophyton, Nocardia, Aspergillus, yeast-like fungi of the genus Candida, including multiresistant strains, as well as Actinomycetes and some pathogenic protozoa: Entamoeba histolytica, Trichomonas vaginalis. The invention presents the composition containing an active ingredient presented by 0.5 wt % of betulin or 0.5 wt % of encapsulated triterpenic acid: betulinic acid, ursolic acid or derivatives thereof in the form of salts and esters and others, and carriers presented by: β-cyclodextrins, fullerene, lecithins and polymers binding to the ingredients to form ingredient-carrier complexes, and excipients.

EFFECT: higher efficacy of using the composition.

3 cl

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