KR20100078883A - Antimicrobial suture - Google Patents

Abstract

PURPOSE: An antimicrobial suture and a method of manufacturing the same are provided, which allow an excellent infection inhibition effect to a desired level. CONSTITUTION: A method of manufacturing an antimicrobial suture includes: a process of manufacturing a biguanide solution in which a biguanide antimicrobial agent is melted in a solvent; a process of manufacturing a macromolecular solution in which the film formation polymer and fatty acid and its salt or its ester salt are melted in the other solvent; a process of manufacturing a coating solution by mixing the biguanide solution and macromolecular solution; a process of applying the coating solution on the suture surface; and a process of drying the coated suture.

Description

Antimicrobial Suture

The present invention relates to sutures, specifically sutures exhibiting antimicrobial properties and a method of making the same.

There is always a risk of infection when contacting patients with medical devices or medical devices. In particular, medical devices that are used inside the body are in direct contact with tissues and body fluids in the body, thereby increasing the risk of infection even more. Efforts have been made to introduce infection inhibitors into medical devices to reduce the risk of such infections.

However, the problem is whether the medical equipment containing the infection inhibitor is maintained at a desired level during the period of use in the body. Sufficient anti-infective agents should be introduced into the medical device to maintain the inhibitory effect for sufficient time of use of the medical device, which may adversely affect the surface properties of the medical device and, together with the antimicrobial properties, There is also the possibility of simultaneous toxicity, so it is important to keep the concentration of the antimicrobial at an appropriate level.

An object according to one embodiment of the present invention is to provide a suture exhibiting an excellent inhibitory effect to the desired degree.

An object according to another embodiment of the present invention is to provide a method for producing a suture exhibiting excellent infection inhibitory 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 salt thereof.

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

If the surface of the suture is coated with a biguanide antimicrobial agent to prevent infection by bacteria or bacteria during surgery, it can suppress and sterilize the growth of bacteria and exert an excellent infection suppression effect, as well as wound recovery (hemostasis and suture site). Splicing).

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

The suture according to the present invention is coated with a coating material comprising a biguanide antimicrobial agent, a biodegradable film-forming polymer and a fatty acid, a salt thereof or an ester salt thereof (hereinafter 'fatty acid component'), a biguanide antimicrobial agent Is released by simple diffusion or released through pores generated in the structure of the film-forming polymer, thereby maintaining the concentration at an appropriate concentration to exert the desired antimicrobial properties.

Conventional US Patent No. 5616338 discloses a catheter in which silver and chlorhexidine are applied using a non-degradable polyurethane as a coating material, and WO97 / 25085 discloses chlorhexidine and triclosan together. An example of application to a medical device such as a catheter is disclosed, but sutures coated with a coating material mixed with a biodegradable film-forming polymer and a fatty acid component have not been reported.

The biguanide antimicrobial agent is not particularly limited, but may include, for example, chlorhexidine and salts thereof. The salt of chlorhexidine dichloranidine (chlorhexidine diphosphanilate), chlorhexidine digluconate (chlorhexidine digluconate), chlorhexidine diacetate, chlorhexidine dihydrochloride (chlorhexidine dihydrochloride), chlorhexidine dichloride chloride Chlorhexidine dihydroiodide, chlorhexidine diperchlorate, chlorhexidine dinitrate, chlorhexidine sulfate, chlorhexidine sulfide chlorhexidine sulfitechlor, Chlorhexidine di-acid phosphate, chlorhexidine difluorophosphate, chlorhexidine diformate, Chlorhexidine dipropionate, chlorhexidine di-iodobutyrate, chlorhexidine di-n-valerate, chlorhexidine dicaproate, chlorhexidine dicaproate Chlorhexidine malonate, chlorhexidine succinate, chlorhexidine malate, chlorhexidine tartrate, chlorhexidine dimonoglycolate, chlorhexidine monocolate Chlorhexidine dilactate, chlorhexidine di-.alpha.-hydroxyisobutyrate, chlorhexidine diglucoheptonate, chlorhexidine di-isothionate i-isothionate, chlorhexidine dibenzoate, chlorhexidine dicinnamate, chlorhexidine dimandelate, chlorhexidine di-isophthalate, chlorhexidine di-2- It may be one or more selected from the group consisting of chlorhexidine di-2-hydroxynapthoate, and chlorhexidine embonate. Specifically, the salt of chlorhexidine may be chlorhexidine digluconate, chlorhexidine diacetate or chlorhexidine dihydroclyde.

In one embodiment, the biguanide may be used in sufficient amount to provide antimicrobial properties to the suture, the structure of the suture, the number of filaments, the rigidity of the braid or twist, the suture Depending on size and composition, coating material. Specifically, the biguanide antimicrobial agent may be included 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. The silver salt is specifically, silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodate, silver iodide, silver lactate, low Silver laurate, silver nitrate, silver oxide, silver palmitate and silver sulfadiazine.

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

The antimicrobial agent included in the suture may adversely affect the surface properties of the medical device, and may also have cytotoxicity simultaneously with antimicrobial properties, so it is important to maintain the concentration of the antimicrobial agent at the level of the present invention. The antimicrobial agent may be dissolved in a solvent to prepare a coating solution and then applied to a suture. Although not limited to this, methods such as dipping, spraying, wiping, brushing, and the like are possible. More specifically, the suture may be passed through a polymer solution, or the coating solution may be spray sprayed to wet the suture and then dried at a time and temperature such that the solvent is removed.

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

The copolymer of glycolide and lactide is biodegradable and has a mechanism in which the antimicrobial agent coated by erosion is released to the environment as the polymer is hydrolyzed in the body. That is, since the biodegradable polymer includes an antimicrobial agent to form a polymer matrix, the release rate of the antimicrobial agent may be affected by the decomposition rate of the biodegradable polymer. Specifically, PGLA is a biodegradable polymer licensed by the KFDA and is suitable for use as a film-forming polymer for sutures having an antibacterial function because of a low risk of contamination, which may cause bacterial infection.

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 included in the copolymer is 1 to 3: 7 to 9, specifically, 3: 7.

The biodegradable film forming polymer may be included in 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, may be included in 0.5 to 2% by weight based on the weight of the suture, the coating It is desirable to apply uniformly to the suture surface. Therefore, due to the antimicrobial agent that is initially incorporated into the film-forming polymer and then released to the surroundings along with the degradation of the biodegradable film-forming polymer, the infection can be continuously suppressed without causing toxicity while the suture is maintained in the body. In the case of sutures that need to be maintained longer in the body than catheters, antimicrobials such as biguanides are applied to the sutures together with biodegradable film-forming polymers to release the antimicrobial agents for a sufficient time to maintain the effect of the antimicrobial activity. You can do that.

The fatty acid may include saturated, unsaturated, fatty acids having 12 or more carbon atoms, specifically, stearic acid, palmitic acid, myristic acid, loriic acid, and the like. Saturated fatty acids or unsaturated fatty acids such as oleic acid, linoleic acid, linolenic acid and the like.

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

The salts of the fatty acid salts or fatty acid esters may include polyvalent metal ion salts of fatty acids or fatty acid esters having 6 or more carbon atoms, specifically 12 to 22 carbon atoms, or mixtures thereof. Specifically, the salt of the fatty acid salt or fatty acid ester may include stearic acid, palmitic acid, calcium of oleic acid, magnesium, barium, aluminum, zinc, 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. If the content of the fatty acid component exceeds the above range, the tied knot is easily loosened, so it is difficult to maintain the knot after surgery, and there is a problem that the suture appears cloudy. On the other hand, if the content of the fatty acid component is less than the above range there is a problem that the knot process is not smooth.

The suture can be divided into a monofilament made of one strand and a multifilament made of a plurality of strands according to its shape, and in general, the multifilament suture is easily infected by bacteria or bacteria due to the microcavity between the strands. May cause a reaction. Thus, the suture to which the biguanide antimicrobial agent is coated may be a multifilament comprising several strands of long fibers.

The suture can also be divided into absorbent, biodegradable and non-degradable, non-absorbable sutures, wherein the biodegradable sutures made of absorbent material (natural / synthetic) are absorbed and disappeared in vivo over several months, but the non-absorbable sutures It remains permanent in the organization. Most of these non-absorbable sutures are likely to cause bacterial infection, so it is preferable to use an absorbent suture for wound areas inside the body that are at 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 that can be decomposed / exhausted through metabolism due to low molecular weight of a high molecular weight polymer by water or an enzyme present in a living body.

The bio-absorbable polymer is specifically glycolide (glycolide), glycolic acid (glycolic acid), lactide (lactide), lactic acid (lactic acid), caprolactone (e-caprolactone), dioxanone (p-dioxanone), tree It may be a homopolymer of a polymer selected from methylene carbonate (trimethylene carbonate) and polyethylene glycolide (polyethylene glycolide), polyanhydride, polyhydroxyalkanoate and the like or a copolymer containing them. Specifically, a single polymer of polydioxanone or a copolymer comprising the same, a copolymer of polyglycolic acid and polylactide, a single polymer such as polycaprolactone, polytrimethylenecarbonate, polyethylene glycolide, DL-polylactide, or the like It may be a copolymer comprising them, preferably a copolymer of polyglycolic acid and polylactide.

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

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

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

In the step a), biguanide antimicrobial agent is not particularly limited,

For example, chlorhexidine and salts thereof may be used, and the biguanide antimicrobial agent may be used in an amount sufficient to provide antimicrobial properties to the suture, specifically 0.02 to 0.5 based on the weight of the coating solution. Wt%, specifically, 0.05 to 0.2 wt%.

In step a), the film forming polymer may be a biodegradable polymer, specifically a homopolymer or copolymer of glycolide, lactide, caprolactone, trimethylene carbonate, dioxanone, dioxepanone, more specifically glycol Copolymers of lead and lactide (PGLA).

In step a), the biodegradable film forming polymer may be included 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, and uniformly coated on the suture surface to be coated. It is preferable to apply.

In step a), the fatty acid may comprise saturated, unsaturated, fatty acids having 12 or more carbon atoms, specifically stearic acid, palmitic acid, myristic acid, loriic 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 salts of fatty acid salts or fatty acid esters are fatty acids 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 of oleic acid, magnesium, barium, aluminum, zinc, and more specifically, calcium stearate.

In step a), the fatty acid, salts thereof or ester salts thereof 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), the biguanide antimicrobial agent may be dissolved in one or more solvents selected from the group consisting of ethanol, methanol, methylene chloride and hexane, and the biguanide antimicrobial agent is well dissolved in alcohols such as methanol or ethanol. The solvent may be specifically methanol or ethanol. At this time, the solvent may be used in 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 fatty acid, salts thereof or ester salts thereof can be dissolved in ethyl acetate or methylene chloride solvent. At this time, the solvent may be used in 75 to 98% by weight, specifically 85 to 96% by weight based on the total weight of the coating solution.

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

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

Step c) is a step of applying the coating solution to the suture, in particular by adjusting the speed of the roller placed before and after the bath (bath) containing the coating solution, it may be to immerse the suture in the bath containing the coating solution have.

Step d) is a process of removing the solvent, the solvent may be removed by drying at 70 to 90 ℃.

The suture coated with the antimicrobial agent as described above may be packaged in a package through EO sterilization after vacuum drying. Sutures prepared according to the method of the present invention are attached to the surgical needle in a conventional manner.

The present invention also relates to a mesh including the suture, specifically, a medical mesh, which may be, 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 may be manufactured by weaving or knitting a filament-shaped suture, or may be manufactured through a general nonwoven fabric manufacturing method.

Hereinafter, the present invention will be described in detail with reference to examples, but these are only for explaining the present invention, and the scope of the present invention is not limited in any way by the following examples.

Examples 1 and 2

Glycolide and lactide copolymer (PGLA) and calcium stearate (Calcium Stearate) in a weight ratio of 30:70 were dissolved in ethyl acetate and dispersed. Chlorhexidine diacetate and / or sulfadiazine silver were dissolved in methanol and added to the polymer solution as described in Table 1 to prepare a coating solution containing an antimicrobial agent.

NeoSorb sutures were immersed in a bath containing a coating solution and then dried at 70-90 ° C.

TABLE 1

Example 3

Coating by the method of Example 1, but varying the concentration of PGLA in a weight ratio of 30:70, based on the weight of the coating solution of 0.5, 1, 2, 3% by weight of 30:70 PGLA copolymer and a fixed ratio Calcium stearate was dissolved in ethyl acetate and dispersed, 0.2 wt% of chlorhexidine diacetate was dissolved in methanol based on the weight of the coating solution, and the two solutions were mixed with each other to prepare an antimicrobial coating solution and coated on a NeoSorb suture. .

Test Example 1

Sutures coated with Examples 1 and 2 and Comparative Example 1 were placed on a medium inoculated with Staphylococcus aureus and Staphylococcus epidermis at a concentration of 1.5 X 10 ⁵ . Placement and incubation for 24 hours at 37 ℃ was measured the activation zone (Inhibition zone).

Comparative Example 1 was tested in the same manner for a suture coated with a coating material without the antimicrobial component.

Table 2 Inhibition zone (mm)

Test Example 2

The antimicrobial agent release behavior of the antimicrobial suture prepared in Example 3 was analyzed, and the results are shown in FIG. 1.

Referring to FIG. 1, the higher the concentration of the film-forming polymer PGLA370, the higher the delayed release rate. In addition, the antimicrobial agent near the surface of the film-forming polymer matrix is rapidly released, causing burst release, and the antimicrobial agent contained in the film-forming polymer matrix is delayed by the slower diffusion. have.

Those skilled in the art to which the present invention pertains will be able to perform various applications and modifications within the scope of the present invention based on the above contents.

1 is a graph analyzing the antimicrobial agent release behavior according to the concentration of the film-forming polymer.

Claims (26)

Biguanide antibacterial agents; Biodegradable film forming polymers; And A suture comprising a coating layer consisting of a coating material comprising a fatty acid, a salt thereof or an ester salt thereof. The suture of claim 1, wherein the biguanide antimicrobial comprises chlorhexidine or a salt thereof. The suture of claim 1, wherein the biguanide antimicrobial agent is contained in an amount of 0.001 to 0.1 wt% based on the total weight of the suture. The suture of claim 1, wherein the coating material further comprises silver or silver salt. The suture of claim 4, wherein the silver or silver salt and biguanide have a molar ratio of 1: 0.2 to 1: 5. The suture of claim 1, wherein the biodegradable film-forming polymer is a copolymer of glycolide and lactide (Poly (glycolic acid-co-lactic acid): PGLA). The suture of claim 1, wherein the biodegradable film forming polymer is included in an amount of 0.5 to 10 wt% based on the total weight of the coating solution in which the coating material is dissolved. The suture of Claim 1, wherein the fatty acid, salt thereof, or ester salt thereof comprises calcium stearate. The suture according to claim 1, wherein the fatty acid, salt thereof, or ester salt thereof is included in an amount of 2 to 15 wt% based on the total weight of the coating solution in which the coating material is dissolved. The suture of claim 1, wherein the suture is an absorbent antimicrobial suture. a) preparing a biguanide solution in which a biguanide antimicrobial agent is dissolved in a solvent, and preparing a film forming polymer and a polymer solution in which a fatty acid, a salt thereof, or an ester salt thereof is dissolved in a solvent; b) preparing a coating solution by mixing the biguanide solution and the polymer solution of step a); c) applying the coating solution of step b) to the suture surface; And d) a method of manufacturing a suture comprising the step of drying the suture of step c). The method of claim 11, wherein the biguanide antimicrobial agent is chlorhexidine or a salt thereof. 12. The method of claim 11, wherein the step a) uses 0.001 to 0.1% by weight of biguanide antibacterial agent based on the total weight of the suture. 12. The method of claim 11, wherein the step a) uses a copolymer of biodegradable glycolide and lactide (PGLA) as the film forming polymer. 12. The method of claim 11, wherein the step a) uses 0.5 to 10% by weight of the film-forming polymer based on the total weight of the coating solution. 12. The method of claim 11, wherein said fatty acid, salt thereof, or ester salt thereof is calcium stearate. 12. The method of claim 11, wherein step a) uses from 2 to 15% by weight of fatty acids, salts thereof or ester salts thereof, based on the total weight of the coating solution. 12. The method of claim 11, wherein the step a) dissolves the biguanide antimicrobial in at least one solvent selected from the group consisting of ethanol, methanol, methylene chloride and hexane. The method of claim 11, wherein the solvent included in the biguanide solution is 2 to 15% by weight based on the total weight of the coating solution. 12. The method of claim 11, wherein step a) dissolves the film-forming polymer and fatty acid, salts thereof or ester salts thereof in ethyl acetate or methylene chloride solvents. 12. The method of claim 11, wherein the solvent included in the polymer solution is 75 to 98% by weight based on the total weight of the coating solution. 12. The method of claim 11, wherein step b) further comprises adding silver or silver salt to the coating solution. The method of claim 22, wherein the step b) is added to the silver or silver salt so that the molar ratio of silver or silver salt and biguanide is 1: 0.2 to 1: 5. The method of claim 11, wherein the step b) is a method for producing a suture, characterized in that mixing the biguanide solution and the polymer solution in a ratio of 1:10 to 1:30 based on the weight ratio. A mesh comprising the suture of claim 1. The mesh of claim 25 wherein the mesh is an anti-adhesion mesh, a hernia surgical mesh or a surgical mesh.

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