KR101553250B1 - Antimicrobial Suture - Google Patents

Abstract

The present invention relates to a biguanide antimicrobial agent; Biodegradable film-forming polymers; And a coating layer composed of a coating material comprising a fatty acid, a salt thereof or an ester thereof, and a process for producing the same.
The suture according to the present invention comprises a biodegradable film-forming polymer and a fatty acid, a salt thereof or an ester thereof, so that the biaguanide antimicrobial agent is released at a proper concentration to exhibit excellent antimicrobial activity, , It is possible to sufficiently inhibit the proliferation of the virus to promote the junction of the suture site and to exhibit an excellent hemostatic effect.

Description

Antimicrobial Suture

The present invention relates to a suture, specifically a suture exhibiting antimicrobial activity, and a process for producing it.

There is always a risk of infection when contacting patients with medical equipment or medical devices. Particularly, the medical device used in the inside of the body is in direct contact with tissues or body fluids in the body, and the risk of infection is greatly increased. Efforts have been made to introduce infection control agents into medical devices to reduce the risk of such infections.

However, it is a question of whether the infectious agent-containing medical device maintains the desired level of infection-inhibiting activity during the period of use in the body. It is necessary to introduce a sufficient amount of anti-infective agents into the medical device to maintain the inhibitory effect for a sufficient time of use of the medical device, which may adversely affect the surface properties of the medical device, It is important to keep the concentration of the antimicrobial agent at an appropriate level.

An object according to an embodiment of the present invention is to provide a suture that exhibits an infection control effect of a desired degree.

Another object of the present invention is to provide a method for producing a suture exhibiting excellent infection control effect.

The suture according to the present invention comprises a coating layer composed of a biguanide antimicrobial agent, a biodegradable film-forming polymer, and a coating material comprising a fatty acid, a salt thereof or an ester thereof.

Also, a method for producing a suture according to the present invention comprises the steps of: a) preparing a bargain solution in which a biguanide is dissolved in a solvent, and preparing a polymer solution in which a film-forming polymer and a fatty acid or a fatty acid salt are dissolved in a solvent; b) preparing a coating solution by mixing the iguanide solution of step a) with a polymer solution; c) applying the coating solution of step b) to the surface of the suture; And d) drying the suture of step c).

When the surface of the suture is coated with a bioguardid antimicrobial agent to prevent bacterial or bacterial infection during surgery, it can inhibit bacterial proliferation and sterilize, thereby exhibiting excellent infection control effect. In addition, wound repair Junction).

The construction of the suture according to the present invention can be suitably applied to a surgical mesh, such as an anti-adhesion mesh and a hernia surgery, in addition to a surgical suture.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph illustrating the release behavior of antimicrobial agents according to the concentration of a film-forming polymer. FIG.

The suture according to the present invention is coated with a coating material comprising a biguanide antibacterial agent, a biodegradable film-forming polymer and a fatty acid, a salt thereof or an ester salt thereof (hereinafter referred to as a 'fatty acid component'), and a biaguanide antibacterial agent Can be released by simple diffusion or released through the pores formed in the structure of the film-forming polymer, and can be maintained at a concentration suitable for exhibiting the desired antimicrobial activity.

US Patent No. 5616338 discloses a catheter using silver and chlorhexidine using a non-degradable polyurethane as a coating material, and International Patent Application Publication No. WO 97/25085 discloses a catheter comprising chlorhexidine and triclosan together A catheter or the like. However, no suture coated with a coating material in which a biodegradable film-forming polymer and a fatty acid component are mixed has been reported.

The above-mentioned bioaguanide antibacterial agent is not particularly limited, but may include, for example, chlorhexidine and salts thereof. The salts of chlorhexidine include chlorhexidine diphosphanilate, chlorhexidine digluconate, chlorhexidine diacetate, chlorhexidine dihydrochloride, chlorhexidine dichloride, Chlorhexidine dihydroiodide, chlorhexidine diperchlorate, chlorhexidine dinitrate, chlorhexidine sulfate, chlorhexidine sulfite, chlorhexidine thiosulfate, chlorhexidine dinitrate, chlorhexidine sulfite, chlorhexidine thiosulfate, Chlorhexidine di-acid phosphate, chlorhexidine difluorophosphate, chlorhexidine diformate, Chlorhexidine di-n-valerate, chlorhexidine dipropionate, chlorhexidine di-iodobutyrate, chlorhexidine di-n-valerate, chlorhexidine dicaproate, chlorhexidine dipropionate, But are not limited to, chlorhexidine malonate, chlorhexidine succinate, chlorhexidine malate, chlorhexidine tartrate, chlorhexidine dimonoglycolate, chlorhexidine monodiglycolate, Chlorhexidine dilactate, chlorhexidine di-alpha-hydroxyisobutyrate, chlorhexidine diglucoheptonate, chlorhexidine di-isothionate, chlorhexidine di-isothionate, -isothionate, chlorhexidine dibenzoate, chlorhexidine dicinnamate, chlorhexidine dimandelate, chlorhexidine di-isophthalate, chlorhexidine di-2-hydroxy Chlorhexidine di-2-hydroxynaphthoate, chlorhexidine embonate, and the like. In particular, the salt of chlorhexidine may be chlorhexidine digluconate, chlorhexidine diacetate or chlorhexidine dihydrochloride.

In one embodiment, the biguanide may be used in an amount sufficient to provide an antibacterial property to the suture and may include the structure of the suture, the number of filaments, the rigidity of the braid or twist, Size and composition, and coating material. Specifically, the bioaganide antimicrobial agent may be contained in an amount of 0.001 to 0.1% by weight, specifically 0.005 to 0.05% by weight, based on the weight of the suture.

In one embodiment, the coating material may further comprise silver or silver salts. Specific examples of the silver salts include silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, It may be at least one selected from the group consisting of silver laurate, silver nitrate, silver oxide, silver palmitate and silver sulfadiazine.

The silver or silver salt and the biguanide may be mixed in a molar ratio of 1: 0.2 to 1: 5.

The antimicrobial agent contained in the suture may adversely affect the surface properties of the medical device and may have cytotoxicity together with antimicrobial activity so that it is important to maintain the concentration of the antimicrobial agent at the level of the present invention. The antibacterial agent may be dissolved in a solvent to prepare a coating solution and then applied to a suture. Methods such as dipping, spraying, wiping, brushing and the like are possible, although not limited thereto. More specifically, the suture may be passed through the polymer solution, or the coating solution may be sprayed and wetted to the suture, followed by drying at a time and temperature such that the solvent is removed.

The biodegradable film-forming polymer may specifically be a glycolide, a lactide, a caprolactone, a trimethylene carbonate, a dioxanone, a dioxepanone homopolymer or a copolymer thereof, and more specifically, a glycolide and a lactide (Poly (glycolic acid-co-lactic acid): PGLA).

In the case of the copolymer of glycolide and lactide, biodegradable polymer is hydrolyzed in the body and the antimicrobial agent coated by erosion is released to the surroundings. That is, since the biodegradable polymer forms a polymer matrix including an antimicrobial agent, the release rate of the antimicrobial agent may be affected by the decomposition rate of the biodegradable polymer. Specifically, PGLA is a biodegradable polymer approved by the KFDA, and it is suitable for use as a film-forming polymer of a suture having an antibacterial function because the possibility of causing bacterial infection is low.

In one embodiment, the copolymer of glycolide and lactide has an inherent viscosity of 0.8 to 1.2, and the weight ratio of glycolide and lactide contained in the copolymer is 1 to 3: 7 to 9, 3: 7.

The biodegradable film-forming polymer may be contained at a concentration of 0.5 to 10% by weight, based on the total weight of the coating solution in which the coating material is dissolved, and may be included at 0.5 to 2% by weight based on the weight of the suture, It is preferable that the suture is uniformly applied on the suture surface. Therefore, the antimicrobial agent released into the surroundings together with the decomposition of the biodegradable film-forming polymer after being incorporated into the film-forming polymer in the early stage can not inhibit the infection while maintaining the suture in the body and can continuously suppress the infection. In the case of sutures that are longer in the body than the catheter, biocompatible agents such as biogranide along with biodegradable film-forming polymers are applied to the suture to release the antimicrobial agent for a sufficient time to maintain the effectiveness of the antimicrobial activity. Can be done.

The fatty acid may include saturated, unsaturated, and fatty acids having 12 or more carbon atoms. Specific examples thereof include stearic acid, palmitic acid, myristic acid, lauric acid, The same saturated fatty acid or an unsaturated fatty acid such as oleic acid, linoleic acid, linolenic acid, and the like.

The fatty acid ester may be sorbitan tristearate or hydrogenated castor oil.

The salt of the fatty acid salt or the fatty acid ester may include a polyvalent metal ion salt of a fatty acid or a fatty acid ester having 6 or more carbon atoms, specifically 12 to 22 carbon atoms, or a mixture thereof. Specifically, the salt of the fatty acid salt or fatty acid ester may include stearic acid, palmitic acid, calcium, magnesium, barium, aluminum and zinc of oleic acid, and more specifically, calcium stearate.

The content of the fatty acid component may be 2 to 15% by weight, specifically 3 to 10% by weight, based on the total weight of the coating solution in which the coating material is dissolved. When the content of the fatty acid component exceeds the above range, the tied knot is easily loosened, which makes it difficult to maintain the knot after the operation, and there is a problem that the suture tends to be swollen. On the other hand, if the content of the fatty acid component is less than the above range, there is a problem that the knotting process is not smooth.

The suture may be divided into monofilaments composed of one strand and multifilament composed of several strands of long fibers depending on the type of the suture. Generally, the multifilament suture is easily infected with bacteria or bacteria due to the micro space between the strands, It can cause a reaction. Thus, the suture coated with the biaguanide antimicrobial agent may be a multifilament comprising multiple strands of long fibers.

The suture can also be divided into absorbable, biodegradable and non-degradable, non-absorbable sutures, biodegradable sutures made of absorbable material (natural / synthetic) are absorbed in vivo over several months, It remains permanently in the organization. Most of these nonabsorbable sutures are likely to cause bacterial infections, so it is desirable to use absorbable sutures for wound sites inside the body where there is a risk of contamination.

That is, the suture may be composed of a bioabsorbable polymer or a bioabsorbable polymer. The bioabsorbable polymer refers to a polymer capable of decomposing / releasing a high molecular weight polymer through low metabolism by metabolism or the like due to water or an enzyme present in the living body.

The bioabsorbable polymer may specifically be selected from the group consisting of glycolide, glycolic acid, lactide, lactic acid, e-caprolactone, p-dioxanone, A homopolymer of a polymer selected from the group consisting of methylene carbonate, polyethylene glycolide, polyanhydride, polyhydroxyalkanoate, and the like, or a copolymer containing the same. Specifically, a homopolymer of a polydioxanone homopolymer or a copolymer containing it, a copolymer of polyglycolic acid and polylactide, a homopolymer such as polycaprolactone, polytrimethylene carbonate, polyethylene glycolide, DL-polylactide, or the like And may be a copolymer comprising polyglycolic acid and polylactide.

The bioabsorbable polymer may be a homopolymer or a copolymer such as polyolefin, polyamide, polyurethane, polyvinylidene fluoride or the like, and specifically includes polypropylene, polyethylene, polyvinylidene fluoride or nylon 6, Polyamides such as nylon 66 and the like.

The suture may be produced by a known method such as braiding, weaving, knitting, etc. using the above-mentioned polymer, and for example, a filament may be prepared by stretching, orientation, twisting and the like.

The present invention also relates to a process for preparing a solution of a) a biguanide antimicrobial agent in a solvent, preparing a solution of a polymer in which a film-forming polymer and a fatty acid or a fatty acid salt are dissolved in a solvent; b) preparing a coating solution by mixing the iguanide solution of step a) with a polymer solution; c) applying the coating solution of step b) to the surface of the suture; And d) drying the suture of step c).

In the above step a), the biaguanide antibacterial agent is not particularly limited,

For example, chlorhexidine and its salts may be used, and the above-described bioaguanide antimicrobial agent may be used in an amount sufficient to provide antibacterial properties to the suture, and specifically, 0.02 to 0.5 By weight, specifically 0.05 to 0.2% by weight.

In the step a), the film-forming polymer may be a biodegradable polymer, and specifically, a glycolide, a lactide, a caprolactone, a trimethylene carbonate, a dioxanone, a dioxepanone homopolymer or a copolymer, Lead and lactide copolymers (PGLA).

In the step a), the biodegradable film-forming polymer may be contained in the antimicrobial coating solution at a concentration of 0.5 to 10% by weight, specifically 0.5 to 5% by weight, based on the total weight of the coating solution, .

In step a) above, the fatty acid may include saturated, unsaturated, and fatty acids having 12 or more carbon atoms, and specifically stearic acid, palmitic acid, myristic acid, saturated fatty acids such as lauric acid or unsaturated fatty acids such as oleic acid, linoleic acid, linolenic acid and the like.

In step a), the fatty acid ester may be sorbitan tristearate or hydrogenated castor oil, and the salt of the fatty acid salt or fatty acid ester may be a fatty acid having 6 or more carbon atoms, specifically 12 to 22 carbon atoms Or polyvalent metal ion salts of fatty acid esters or mixtures thereof. Specifically, the salt of the fatty acid salt or fatty acid ester may include stearic acid, palmitic acid, calcium, magnesium, barium, aluminum and zinc of oleic acid, and more specifically, calcium stearate.

In step a) above, the fatty acid, its salt or its ester salt may be used in an amount of from 2 to 15% by weight, in particular from 3 to 10% by weight, based on the total weight of the coating solution.

In step a), the biaguanide antimicrobial agent may be dissolved in at least one solvent selected from the group consisting of ethanol, methanol, methylene chloride and hexane, and the biaguanide antimicrobial agent is dissolved in an alcohol such as methanol or ethanol The solvent may be specifically methanol or ethanol. At this time, the solvent may be used in an amount of 2 to 15% by weight, specifically 3 to 10% by weight, based on the total weight of the coating solution.

In step a) above, the film-forming polymer, and the fatty acid, its salt or its ester salt, may be dissolved in ethyl acetate or methylene chloride solvent. At this time, the solvent may be used in an amount of 75 to 98% by weight, specifically 85 to 96% by weight, based on the total weight of the coating solution.

In the above step b), the coating solution may further include silver or silver salts, and a coating solution having a molar ratio of silver or silver salt and a biguanide of 1: 0.2 to 1: 5 may be used.

In step b) above, the preferred coating solution according to the present invention may be used in an amount of 20 to 35% by weight, more specifically 25 to 30% by weight, based on the total weight of the suture. In addition, the solution of the biaguanide antimicrobial agent and the solution of the polymer in the coating solution may be prepared in a ratio of 1: 5 to 1:40, specifically 1:10 to 1:30, based on the weight ratio.

The step c) is a step of applying the coating solution to the suture, specifically, by adjusting the speed of the roller disposed before and after the bath containing the coating solution to immerse the suture in the bath containing the coating solution have.

The step d) is a step of removing the solvent, and the solvent can be removed by drying at 70 to 90 ° C.

The suture coated with the antimicrobial agent can be vacuum dried and then packaged in an EO (Ethylene Oxide Gas) sterilization package. The suture manufactured according to the manufacturing method of the present invention is attached to a surgical needle according to a conventional method.

The present invention also relates to a mesh comprising said suture, in particular a surgical mesh, said mesh being, for example, an anti-adhesion mesh, a hernia surgical mesh or a surgical mesh.

The method of manufacturing the mesh through the suture is not particularly limited, but the mesh according to the present invention can be manufactured by weaving or knitting filament-type sutures, or by a general nonwoven fabric manufacturing method.

EXAMPLES The present invention will now be described more specifically with reference to the following examples. However, these examples are for illustrative purposes only and are not intended to limit the scope of the present invention in any way.

Example  1 and 2

A copolymer of glycolide and lactide (PGLA) and calcium stearate (Calcium Stearate) in a weight ratio of 30:70 was dissolved and dispersed in ethyl acetate. To the thus prepared solution, chlorhexidine diacetate and / or sulfadiazine silver was dissolved in methanol as shown in Table 1, and the solution was added to the polymer solution to prepare a coating solution containing the antimicrobial agent.

Neosorb (Samyang) suture was immersed in a bath containing the coating solution and then dried at 70-90 ° C.

Example  3

A PGLA copolymer having a weight ratio of 0.5: 1, 1: 2, 3: 3 by weight based on the weight of the coating solution and having a weight ratio of 30:70 and a fixed ratio Of calcium stearate was dissolved and dissolved in ethyl acetate, and 0.2% by weight of chlorhexidine diacetate was dissolved in methanol based on the weight of the coating solution. The two solutions were mixed together to prepare an antimicrobial coating solution and coated on a NeoSorb suture .

Test Example  One

The sutures coated with Examples 1 and 2 and Comparative Example 1 were placed on a medium inoculated with Staphylococcus aureus and S. epidermis at a bacterial concentration of 1.5 X 10 ⁵ The incubation zone was measured after incubation at 37 ° C for 24 hours.

Comparative Example 1 was similarly tested for a suture coated with a coating material except for the antimicrobial agent component.

Test Example  2

The antimicrobial release behavior of the antibacterial suture prepared in Example 3 was analyzed, and the results are shown in FIG.

Referring to FIG. 1, it can be seen that the higher the concentration of the film-forming polymer PGLA370, the greater the delayed release. In addition, it can be seen that the antimicrobial agent near the surface of the film-forming polymer matrix is rapidly released to cause burst release, and the antimicrobial agent contained in the film-forming polymer matrix is more slowly released by diffusion have.

It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (26)

Biguanide An antibacterial agent, such as chlorhexidine or its salt;
A copolymer of glycolide and lactide as a biodegradable film-forming polymer (glycolic acid-co-lactic acid: PGLA); And
A coating composition comprising a coating material comprising a fatty acid, a salt thereof or an ester salt thereof,
The bioaganide antibacterial agent is contained in an amount of 0.001 to 0.1% by weight based on the total weight of the suture,
The biodegradable film-forming polymer is contained in an amount of 0.5 to 10% by weight based on the total weight of the coating solution in which the coating material is dissolved,
The fatty acid, its salt or ester salt thereof is contained in an amount of 2 to 15% by weight based on the total weight of the coating solution in which the coating material is dissolved,
Characterized in that it exhibits antimicrobial activity against Staphylococcus aureus or S. epidermis. delete The suture according to claim 1, wherein the bioguarde antimicrobial agent is contained in an amount of 0.005 to 0.05% by weight based on the total weight of the suture. The suture of claim 1, wherein the coating material further comprises silver or silver salts. 5. The suture according to claim 4, wherein the silver or silver salt and the bioaganide antimicrobial agent have a molar ratio of 1: 0.2 to 1: 5. delete The suture of claim 1, wherein the biodegradable film-forming polymer comprises from 0.5 to 5% by weight based on the total weight of the coating solution in which the coating material is dissolved. The suture according to claim 1, wherein the fatty acid, its salt or its ester salt comprises calcium stearate. The suture according to claim 1, wherein the fatty acid, its salt or its ester salt is contained in an amount of 3 to 10% by weight based on the total weight of the coating solution in which the coating material is dissolved. The suture according to claim 1, wherein the suture is an absorbent antibacterial suture. delete delete delete delete delete delete delete delete delete delete delete delete delete delete A mesh comprising the suture of any one of claims 1, 3 to 5 and 7 to 10. 26. The mesh of claim 25, wherein the mesh is an anti-adhesion mesh, a hernia surgical mesh, or a surgical mesh.

Images