RU2470671C1 - Method for textile treatment for cardiovascular surgery - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to textile treatment for cardiovascular surgery. A method involves textile treatment with a composition containing gelatin and intermolecular cross-linking of gelatin by an aqueous solution of glutaric dialdehyde, an antibiotic and 0.9% sodium chloride in certain proportions.

EFFECT: method enables make textiles hermetic and antimicrobial, reduced postoperative chemotherapeutic load on the patient.

5 cl, 11 tbl, 11 ex

Description

The invention relates to medicine, namely to the processing of textiles for cardiovascular surgery in order to give them tightness and antimicrobial properties.

A known method for the manufacture of vascular prostheses, comprising impregnating a tube of flexible porous material with a gelatin composition containing pre-modified gelatin with a certain amount of amino groups less than in the starting material, treating the impregnated tube with the aim of forming cross-links between amino groups. Modification of gelatin is proposed to be carried out by interaction with anhydride or polycarboxylic acid chloride (US No. 4747848, Vascular grafts). In the composition of the coatings obtained by this method, there are no active substances that can give the surface of the product a stable thromboresistant effect. The processing technology is multi-stage and difficult to implement.

A known method of closing pores in vascular prostheses with gelatin crosslinked with diisocyanate (US No. 4784659, Vessel and prosthesis impregnated with diisocyanate crosslinked gelatin). The method includes preparing a composition based on polycarboxylic acid modified gelatin, applying the composition to the textile base of the prosthesis, and stabilizing the coating by treatment with diisocyanates. The compounds of the class of diisocyanates used in the method are highly toxic substances. At the stage of coating stabilization, in addition to the main reaction — the formation of intermolecular bonds in the gelatin matrix — an uncontrolled process of formation of products of side reactions of diisocyanates with other components of the composition proceeds. The resulting substances are difficult to completely remove from the coating volume, and their entry into the bloodstream is undesirable due to unpredictable behavior in the body.

Known prosthesis made of polytetrafluoroethylene (PTFE = fluorone) (US No. 5716395, 1998, Prosthetic vascular graft), which provides for the possibility of impregnation of the prosthesis material with antibiotics.

A known method for coating antibiotics of vascular prostheses and other implants (US No. 4442133, 1984, Antibiotic bonding of vascular prostheses and other implants), based on the preliminary processing of the material of the prosthesis tridecylmethylammonium chloride in order to give it cationic properties and subsequent sorption on the obtained material of antibiotics with anionic properties . This treatment method improves the binding of substances with anionic properties, including some antibiotics, through ionic bonds. However, the mechanical properties of the prosthesis material (its waterproofness) remain unchanged.

There is a method of treating implants from textile materials with a composition containing acetylsalicylic acid, heparin and gelatin, and performing intermolecular crosslinking of gelatin with an aqueous solution of glutaraldehyde, followed by treatment with a solution of glycerol in a mixture of water and ethanol (RU No. 2135214). The method adopted for the prototype.

Analysis of the known methods of processing products from textile materials showed that there are no methods that provide products with both waterproof and antimicrobial properties.

The technical result achieved by the invention is to give products for cardiovascular surgery from textile materials waterproof and antimicrobial properties.

The claimed technical result is achieved in a method for processing textile products for cardiovascular surgery, including treating the product with a composition containing gelatin and intermolecular crosslinking of gelatin with an aqueous solution of glutaraldehyde, in which the composition for processing the product further comprises glycerin, at least one antibiotic and 0 , 9% sodium chloride solution in the following ratio of components (wt.%):

gelatin 5.0-7.5 glycerol 20.0-30.0 antibiotic effective amount 0.9% sodium chloride solution rest.

It is advisable that the composition contains at least one antibiotic from the series of cefotaxime, ciprofloxacin, doxycycline, oxacillin. This list is not exhaustive and may contain other antibiotics.

It is also advisable that the composition additionally contains metronidazole in an amount of 4.0-10.0 wt.%.

It is effective that the composition contains cefotaxime and metronidazole in amounts (wt.%):

cefotaxime 4.0-10.0; metronidazole 4.0-10.0.

It is also advisable to pre-treat the textile base with an aqueous solution of glutaraldehyde in a concentration of 0.5-0.75% until uniform impregnation of the base material is achieved, and then treat with the composition.

Glycerin introduced into the composition, binding to gelatin, gives the vascular prosthesis plasticity, i.e. performs the role of a plasticizer, due to the fact that it is able to retain moisture, and also gives the final product waterproof properties, resistance to acids and insolubility in acetone and organic solvents.

The inclusion of antibiotics with antibacterial activity against aerobic and anaerobic gram-positive and gram-negative microorganisms in the composition for impregnating the textile base of the product provides an increase in the efficiency of binding of antibiotics in the gel and preservation of their antibacterial properties for a long time.

This is due to more effective binding of antibiotics and an increase in the capacity of the gelatin matrix, i.e. her ability to retain antibiotics in her composition. Antibiotic binding is non-covalent and is mainly due to the formation of hydrogen and ionic bonds with functional groups in the gelatin matrix.

The formation of hydrogen bonds in this case occurs directly during the formation of the matrix simultaneously with the crosslinking of the gelatin polypeptides due to covalent binding of the aldehyde groups of glutaraldehyde and the available amino groups in the structure of the polypeptides. In addition, the presence of free amino groups in the antibiotic molecule (cefotaxime), part of the antibiotic molecule can bind to the matrix (and with each other) by covalent bonds due to interaction with glutaraldehyde molecules.

The content in the composition of cefotaxime and additionally metronidazole in quantities (wt.%):

cefotaxime 4.0-10.0 metronidazole 4.0-10.0

provides a high antibacterial effect to the product, since with the proposed method of introducing antibiotics into the coating, metronidazole potentiates the action of cefotaxime.

All components of the composition are in optimal concentrations.

A gelatin content below 5.0 wt.% Does not provide effective closure of pores of textile material, above 7.5 wt.% - makes the composition non-technological due to its high viscosity.

The use of a glycerol solution with a concentration below 20.0 wt.% Does not provide the required elasticity of the coating, above 30.0 wt.% - leads to a deterioration in its mechanical strength.

The amount and type of antibiotic is selected depending on the effect of the antibacterial effect required in a particular situation.

0.9% sodium chloride solution - the rest.

Pretreatment of the textile base with an aqueous solution of glutaraldehyde in a concentration of 0.5-0.75% until uniform impregnation of the material is achieved minimizes the number of free aldehyde groups that are not bound to gelatin.

A concentration of glutaraldehyde below 0.5% does not provide the necessary degree of crosslinking of gelatin; above 0.75% - degrades the mechanical strength of the coating.

The method is carried out, for example, as follows.

The composition is prepared from gelatin, glycerin, an antibiotic and a 0.9% sodium chloride solution in predetermined concentrations with constant stirring using an electric mixer for 5-7 minutes (this is the minimum time that is necessary to obtain homogeneity) until a homogeneous mass is obtained, then stand in the refrigerator for one day (this is the minimum time for which maximum gelatin swells) at a temperature of +40 - + 50 ° C (this is the minimum temperature at which gelatin swells) before gel swelling a.

Processing of the product, as well as its drying, is carried out in a stretched state to ensure uniform application of chemical solutions.

A textile product, such as a vascular prosthesis, is immersed and soaked in a 0.5-0.75% solution of glutaraldehyde for 2-3 minutes until uniform impregnation of the base material is achieved.

The solution with swollen gelatin is heated in a water bath at a temperature of +40 - + 55 ° C (this temperature is optimal, since gelatin does not dissolve at a temperature below 40 ° C, it is prone to hydrolysis above 55 ° C) and is constantly stirred using an electric stirrer .

A vascular prosthesis soaked in glutaraldehyde is immersed for 2-5 minutes (this time is optimal, since if the exposure is less than 2 minutes, the coating will be very thin and not all pores will close, after exposure more than 5 minutes the coating layer will be very thick and uneven ) An impregnated prosthesis is dried for one day at room temperature.

A prosthesis with such an impregnation on the stand can withstand pressure up to 300 mmHg, which indicates its tightness.

Evaluation of the antimicrobial properties of the studied samples was carried out in order to demonstrate the presence of the drug in the prosthesis material or in the fluid in which this material was up to 3 days.

Example 1. The textile basis of a vascular prosthesis made of fluorone-lavsan and consisting of a tube with a diameter of 10 mm was kept for 2-3 minutes in a 0.5% solution of glutaraldehyde with the aim of wetting, as evidenced by the absence of visible air bubbles on the surface of the porous textile material. Then they were placed in a stretched state in a pre-prepared (24 hours before use) and heated to a temperature of +45 - + 50 ° С composition of the following composition:

Gelatin - 5%

Glycerin - 25%

Cefotaxime - 10%

Metronidazole - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 50%.

The residence time of the textile base moistened with glutaraldehyde in the composition was 300 seconds (5 minutes).

The textile material impregnated with the composition was dried for 24 hours at room temperature, and then hydraulic tests were carried out on a bench, which allows measuring the pressure that can be applied to the test material and does not lead to the leakage of liquid from a vessel pretreated with the described method. The maximum hydrostatic pressure at which the treated material retains waterproof properties during hydraulic tests was 300 mm Hg.

The mechanical properties (elasticity and tensile strength) of the obtained material comply with the requirements for vascular prosthesis materials.

The antimicrobial properties of the obtained material (prosthesis) were evaluated after sterilization by the method of ozonation according to the size of the zones of inhibition of growth of microorganisms (distance from the edge of the object to the border of the growth zone of the microorganism), measured after 24 h of growth for the following objects:

- product fragments before incubation in physiological saline, as well as after 1-2- and 3-day incubation;

- filter paper disks saturated with physiological saline containing antibiotics that diffuse during incubation of the prosthesis material (0-3 days).

The results of the study of the antibacterial properties of fragments of the treated material and filter paper disks saturated with physiological saline in which the prosthesis material was incubated from 0 to 3 days (with a change of medium every 24 hours) are presented in Table 1.

Table 1 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 25 fifteen 8 0 0 12 four 0 S. epidermidis 23 13 6 0 0 10 3 0 E. coli 439 10 5 2 0 0 5 2 0 P. aeruginosa 25923 6 3 one 0 0 3 one 0 Bacteroides spp. 10 5 2 0 0 3 one 0 Fusobacterium spp. 9 four 2 0 0 3 one 0 Peptostreptococcus spp. 9 5 3 0 0 2 one 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 2. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 7%

Glycerin - 25%

Cefotaxime - 10%

Metronidazole - 4%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 54%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 2.

table 2 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 25 16 8 0 0 fourteen 5 0 S. epidermidis 23 13 6 0 0 9 four 0 E. coli 439 eleven 6 2 0 0 6 3 0 P. aeruginosa 25923 7 four one 0 0 3 2 0 Bacteroides spp. 8 four one 0 0 2 one 0 Fusobacterium spp. 6 3 2 0 0 2 one 0 Peptostreptococcus spp. 7 3 2 0 0 one 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 3. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 5%

Glycerin - 25%

Cefotaxime - 5%

Metronidazole - 5%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 60%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 3.

Table 3 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 13 ± 0.3 7 ± 0.2 4 ± 0.1 0 0 9 ± 0.2 4 ± 0.2 0 S. epidermidis 12 ± 0.5 6 ± 0.2 3 ± 0.1 0 0 7 ± 0.5 4 ± 0.3 0 E. coli 439 5 ± 0.1 3 ± 0.1 1 ± 0.1 0 0 4 ± 0.2 2 ± 0.1 0 R. aeruginosa 25923 3 ± 0.1 2 ± 0.2 1 ± 0.2 0 0 2 ± 0.1 2 ± 0.2 0 Bacteroides spp. 5 ± 0.1 3 ± 0.1 1 ± 0.1 0 0 1 ± 0.1 1 ± 0.2 0 Fusobacterium spp. 5 ± 0.2 2 ± 0.1 1 ± 0.2 0 0 2 ± 0.2 1 ± 0.3 0 Peptostreptococcus spp. 4 ± 0.1 3 ± 0.1 1 ± 0.1 0 0 1 ± 0.1 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 4. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 7.5%

Glycerin - 20%

Cefotaxime - 5%

Metronidazole - 5%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 62.5%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 4.

Table 4 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 14 ± 0.1 8 ± 0.3 5 ± 0.1 0 0 10 ± 0.3 4 ± 0.2 0 S. epidermidis 13 ± 0.3 6 ± 0.2 4 ± 0.2 0 0 8 ± 0.3 3 ± 0.2 0 E. coli 439 6 ± 0.1 4 ± 0.1 2 ± 0.1 0 0 3 ± 0.1 1 ± 0.1 0 P. aeruginosa 25923 3 ± 0.2 2 ± 0.1 1 ± 0.1 0 0 2 ± 0.1 2 ± 0.1 0 Bacteroides spp. 6 ± 0.1 4 ± 0.1 1 ± 0.2 0 0 1 ± 0.2 1 ± 0.1 0 Fusobacterium spp. 4 ± 0.2 2 ± 0.1 1 ± 0.1 0 0 3 ± 0.1 1 ± 0.2 0 Peptostreptococcus spp. 4 ± 0.2 2 ± 0.2 1 ± 0.1 0 0 1 ± 0.1 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 5. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 6%

Glycerin - 25%

Cefotaxime - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 59%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 5.

Table 5 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S.aureus 210 23 12 5 0 0 10 5 0 S. epidermidis 22 eleven four 0 0 9 four 0 E. coli 439 9 5 2 0 0 four 3 0 R. aeruginosa 25923 four 2 one 0 0 2 one 0 Bacteroides spp. 0 0 0 0 0 0 0 0 Fusobacterium spp. 0 0 0 0 0 0 0 0 Peptostreptococcus spp. 0 0 0 0 0 0 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 6. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 5.5%

Glycerin - 20.5%

Ciprofloxacin - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 64%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 6.

Table 6 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 21 eleven 5 0 0 10 5 0 S. epidermidis 16 8 3 0 0 6 3 0 E. coli 439 10 5 3 0 0 5 2 0 R. aeruginosa 25923 9 four 2 0 0 3 one 0 Bacteroides spp. 0 0 0 0 0 0 0 0 Fusobacterium spp. 0 0 0 0 0 0 0 0 Peptostreptococcus spp. 0 0 0 0 0 0 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 7. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 7.5%

Glycerin - 25%

Ciprofloxacin - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 57.5%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 7.

Table 7 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 twenty 10 four 0 0 9 four 0 S. epidermidis 17 9 5 0 0 7 four 0 E. coli 439 10 four 2 0 0 four one 0 R. aeruginosa 25923 10 5 2 0 0 four 2 0 Bacteroides spp. 0 0 0 0 0 0 0 0 Fusobacterium spp. 0 0 0 0 0 0 0 0 Peptostreptococcus spp. 0 0 0 0 0 0 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 8. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 5.5%

Glycerin - 25.5%

Doxycycline - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 59%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 8.

Table 8 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 eighteen 9 four 0 0 7 2 0 S. epidermidis 21 eleven 5 0 0 8 3 0 E. coli 439 3 one 0 0 0 one 0 0 R. aeruginosa 25923 2 one 0 0 0 one 0 0 Bacteroides spp. 3 one 0 0 0 one 0 0 Fusobacterium spp. 2 one 0 0 0 one 0 0 Peptostreptococcus spp. 3 one 0 0 0 one 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 9. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 7.5%

Glycerin - 20%

Doxycycline - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 62.5%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 9.

Table 9 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 17 10 5 0 0 8 2 0 S. epidermidis twenty 12 6 one 0 7 2 0 E. coli 439 four 2 one 0 0 2 one 0 R. aeruginosa 25923 2 one one 0 0 one one 0 Bacteroides spp. 3 2 one 0 0 2 0 0 Fusobacterium spp. 3 2 one 0 0 one 0 0 Peptostreptococcus spp. 2 2 0 0 0 one 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 10. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 5%

Glycerin - 25%

Oxacillin - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 60%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 10.

Table 10 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 twenty 9 four 0 0 8 3 0 S. epidermidis eighteen 7 3 0 0 5 2 0 E. coli 439 3 one 0 0 0 one 0 0 R. aeruginosa 25923 four 2 one 0 0 2 one 0 Bacteroides spp. 0 0 0 0 0 0 0 0 Fusobacterium spp. 0 0 0 0 0 0 0 0 Peptostreptococcus spp. 0 0 0 0 0 0 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Example 11. Processing and analysis of material properties was carried out analogously to example 1.

When processing used a composition of the following composition:

Gelatin - 7.5%

Glycerin - 20.5%

Oxacillin - 10%

0.9% isotonic (physiological) solution of sodium chloride NaCl - 62%.

The antimicrobial properties of the obtained material were investigated and evaluated by the same method as in example 1. The results of the study are presented in table 11.

Table 11 Sample Solution (disk) microorganism growth inhibition zone after 24 hours of incubation (mm) Duration of incubation (days) 0 one 2 3 0 one 2 3 S. aureus 210 21 eleven 3 0 0 8 four 0 S. epidermidis 17 7 3 0 0 6 3 0 E. coli 439 3 2 one 0 0 2 one 0 R. aeruginosa 25923 5 3 one 0 0 2 2 0 Bacteroides spp. 0 0 0 0 0 0 0 0 Fusobacterium spp. 0 0 0 0 0 0 0 0 Peptostreptococcus spp. 0 0 0 0 0 0 0 0

Thus, the preservation of the antimicrobial properties of the material and the transition of the components into the environment surrounding the material occurs for at least 48 hours.

Thus, the gelatin matrix obtained by the claimed method can be considered not only as a “sealing impregnation” of the textile base of the product, but also as a means of delivering the antibiotic directly to the site of surgery. This will reduce the chemotherapeutic load on the patient in the postoperative period, since antibiotic delivery is carried out not only by parenteral administration, but also directly as part of the material used for surgical intervention.

Claims (5)

1. A method of processing textile products for cardiovascular surgery, comprising treating the product with a composition containing gelatin and intermolecular crosslinking of gelatin with an aqueous solution of glutaraldehyde, characterized in that the composition for processing the product further comprises glycerin, at least one antibiotic and 0, 9% sodium chloride solution in the following ratio of components, wt.%:
gelatin 5.0-7.5 glycerol 20.0-30.0 antibiotic effective amount 0.9% sodium chloride solution rest 2. The method according to claim 1, characterized in that the composition contains at least one antibiotic from the series cefotaxime, ciprofloxacin, doxycycline, oxacillin as an antibiotic. 3. The method according to claim 1, characterized in that the composition further comprises metronidazole in an amount of 4.0-10.0 wt.%. 4. The method according to claim 2 and 3, characterized in that the composition contains cefotaxime and metronidazole in amounts, wt.%:
cefotaxime 4.0-10.0 metronidazole 4.0-10.0 5. The method according to claim 1, characterized in that the textile base is pre-treated with an aqueous solution of glutaraldehyde in a concentration of 0.5-0.75% until a uniform impregnation of the base material is achieved, and then treated with the composition.