KR20120077489A - Surgical mesh composite with anti-adhesion property and method for producing the same - Google Patents

Abstract

PURPOSE: A mesh composite for an operation and a manufacturing method thereof are provided to maintain the flexibility, intensity, and lightness of mesh. CONSTITUTION: A mesh composite for an operation comprises a mesh layer(11) for an operation and a polyglutamic acid cross-linked body layer(12). The mesh layer for an operation and polyglutamic acid cross-linked body layer are bonded to each other. A biodegradable adhesive polymer layer is formed between the mesh layer for operation and polyglutamic acid cross-linked body layer. The polyglutamic acid cross-linked body layer is mixture layer in which polyglutamic acid cross-linked body and biodegradable adhesive polymer are mixed.

Description

Surgical mesh composite with anti-adhesion property and method for producing the same}

The present invention relates to a surgical mesh composite having a superior biocompatibility as well as having an anti-adhesion function after surgery and a manufacturing method thereof.

In general, hernia-free surgery, which is performed using a mesh during surgical operations such as hernia surgery, has the advantage of low recurrence rate, short operation time, and quick recovery of wounds. It is known as a useful method for surgery. Since the mesh used in hernia surgery must have the property of strengthening the peritoneum by maintaining its chemical and physical properties for many years, its material is a fiberized form of non-absorbable polymers such as polypropylene or polyethylene terephthalate. I use a lot of things.

After such a surgical operation or during the healing of wounds caused by inflammation, wounds, friction, etc., excessively generated fibrous tissues or blood spills and coagulates, whereby adhesions are formed in which peripheral organs or tissues to be separated are joined to each other. Postoperative adhesions may cause pain, intestinal obstruction, infertility, etc., due to the adhesion of wounds to other tissues, and may cause organ or tissue dysfunction, and in some cases, reoperation for adhesion detachment may be required. As a method of preventing such adhesion, a method of preparing an adhesion inhibitor and inserting it during surgery is used, and various types of adhesion inhibitors such as solutions, gels, and films are used. Materials that can be used as anti-adhesions should act as a barrier only during the healing of the wound in vivo, and then decompose, and not only the toxicity of the material itself, but also its metabolized substance should be harmless to the human body. . As a material which can be used as the anti-adhesion agent, expanded poly tetrafluoroethylene (ePTFE), poly vinyl alcohol (PVA), etc. may be used as a non-degradable material. Examples of the absorbent substance include biosaccharide-derived natural polymers of polysaccharides and proteins, non-living-derived natural polymers, and water-soluble synthetic polymers. These materials may be used alone or used together in a covalently bonded form between polymers or in the form of a film or sheet.

Hernia surgical mesh has been developed a lot of products in the form of a mesh composite that includes not only the original mesh function but also anti-adhesion function. These products have been provided with composites in which polypropylene monofilaments are made of knitted meshes and then bonded to polypropylene meshes with materials such as oxidized regenerated cellulose (ORC), non-absorbent silicone elastomers or ePTFE. . ORCs used in these complexes are known to be manufactured in the form of fabrics and thus have good adherence to organs or tissues that are severely curved, but because they are not constituents of living bodies, they have low biocompatibility and very large pore sizes. Since permeation of blood proteins and the like can easily occur, there is a problem of low efficiency as a separation membrane. On the other hand, non-absorbent materials such as ePTFE are not biodegradable, which may cause inflammation between the surgical site and the tissue.

In addition, a mesh composite prepared with a non-absorbent material such as polypropylene in the form of a knitted fabric, and then bonded with hyaluronic acid or CMC hydrogel and an adhesive is also presented. In addition, there is also proposed an anti-adhesion mesh composite formed by bonding a knitted polypropylene monofilament and a hyaluronic acid / CMC mixture to a polyglycolic acid multifilament, followed by photopolymerization. However, since CMC is not a bio-derived material, biocompatibility is not good, and hyaluronic acid is easily decomposed and has a short half-life of 1 to 3 days, which makes it difficult to stay in the body for a time necessary to prevent adhesion.

In addition, although a double-mesh mesh composite of a polyester / collagen film is also shown, collagen is an animal-derived material that may cause an immunorejection reaction or be exposed to animal pathogens or viruses.

Then, a composite having a two-layered structure in which a web is prepared by electrospinning heparin and the like and then electrospun PLGA copolymer is developed. However, such a composite is not easy to control the strong organic solvent residual amount used during electrospinning, there is a problem of low physical strength and productivity.

Mesh complexes used to prevent adhesion during hernia surgery require high convenience of surgery, relief of foreign body and biocompatibility of patients. In addition, the mesh composite is mainly a multi-structure, it should be good flexibility. In addition, the non-adsorbent polymer for preventing adhesion may be a source of adhesion again over time, and in the case of the absorbent polymer, inflammation may occur during absorption. Therefore, it is necessary to develop a mesh composite suitable for solving the problems of the prior art while satisfying such conditions.

Accordingly, an object of the present invention is to prepare a mesh composite using a polymer hydrogel containing polyamino acid as a component.

In addition, an object of the present invention is to provide a surgical mesh composite having an anti-adhesion function and excellent biocompatibility while maintaining the flexibility, strength and lightness of the mesh.

In addition, an object of the present invention is to provide a surgical mesh composite of a multi-layered multilayer structure having improved biocompatibility, anti-adhesion efficiency, biodegradability and morphological stability and the like and a method of manufacturing the same.

The present invention surgical mesh layer; And a γ-polyglutamic acid crosslinked layer, wherein the surgical mesh layer and the γ-polyglutamic acid crosslinked layer are bonded to provide a surgical mesh composite having an anti-adhesion function.

The present invention also provides a surgical mesh composite having an anti-adhesion function further comprising a biodegradable adhesive polymer layer between the surgical mesh layer and the γ-polyglutamic acid crosslinked layer.

The present invention also provides a surgical mesh composite having an anti-adhesion function, wherein the γ-polyglutamic acid crosslinked layer is a mixture layer in which a γ-polyglutamic acid crosslinked body and a biodegradable adhesive polymer are mixed.

In addition, the present invention provides a method for producing a surgical mesh composite described above.

Hereinafter, each of the surgical mesh composite according to a specific embodiment of the present invention and a manufacturing method thereof will be described in detail.

In the present invention, "surgical mesh composite" means "multi-layered structure in which the surgical mesh layer and the adhesion preventing polymer-containing layer are bonded".

According to one embodiment of the invention, the surgical mesh layer; And a γ-polyglutamic acid crosslinked layer, the surgical mesh composite having an anti-adhesion function to which the surgical mesh layer and the γ-polyglutamic acid crosslinked layer are attached is provided.

The inventors have developed a method for bonding a layer containing a material having excellent anti-adhesion performance to various kinds of meshes in manufacturing a surgical mesh composite having an anti-adhesion function, thereby providing excellent flexibility and shape safety. It is possible to invent surgical mesh complexes that are easily manipulated during surgery, adhere to tissues and organs after surgery, have sufficient physical strength to withstand abdominal pressure, and biocompatibility, and exhibit excellent anti-adhesion efficiency during wound healing. It became.

Hereinafter, each component of the surgical mesh composite according to the above-described embodiment will be described in detail.

The surgical mesh used in the surgical mesh layer of the present invention is not particularly limited and may be any kind of mesh commonly used in surgery.

In general, the surgical mesh has a porous mesh structure in the form of a knitted fabric, such as a circular knitting or a warp knitting, and is provided with sufficient flexibility and physical strength to withstand pressure in the body, which is easy to use in a surgical operation. Due to its easy cell proliferation, it has excellent adhesion to tissues and organs.

In the above-described embodiment, the surgical mesh is i) a mesh comprising a mono or multifilament of the non-absorbent polymer ii) a mesh comprising a monofilament in which the non-absorbent polymer and the absorbent polymer is conjugated, iii) the non-absorbent polymer And mono or multifilament of the absorbent polymer may be one or more selected from the group consisting of simple blended meshes. Examples of the non-absorbent polymer include polyolefins such as polypropylene, polyethylene, and copolymers of propylene and ethylene; Thermoplastic saturated polyesters; Polyamides such as nylon 6, nylon 66, and the like; Polyurethane; Polyvinylidene; And at least one polymer selected from the group consisting of fluoropolymers. Preferably polyolefins, thermoplastic saturated polyesters or mixtures thereof can be used.

Meanwhile, as the absorbent polymer, glycolide (glycolide), glycolic acid (glycolic acid), lactide (lactide), lactic acid (lactic acid), caprolactone (ε-caprolactone), dioxanone (ρ-dioxanone), trimethylene One homopolymer or a copolymer including two or more selected from the group consisting of trimethylene carbonate, polyanhydride and polyhydroxyalkanoate may be used. Preferably, a homopolymer or a copolymer including two or more selected from glycolide, glycolic acid lactide, lactic acid, and caprolactone (ε-caprolactone) may be used. have.

In the above-described embodiment, the mesh may be a mesh including a monofilament in the form of a composite spinning non-absorbent polymer and the absorbent polymer. Monofilaments by composite spinning are structurally sea / islands type, segmented pie type, side-by-side type, sheath / core type / core type) and the like, and a preferred shape is one having a segmented pie cross section.

In the segmented pie form, an appropriate combination of absorbent and nonabsorbent material is evenly placed on the surface of the fiber and formed around the absorbent material and connective tissue around the non-absorbent material. This can improve the adhesion between the mesh and tissue while ensuring fluidity of the peritoneum. In addition, the segmented pie monofilament, unlike the form of the composite yarn (sea / islands type, sheath / core type) in which the non-absorbent material is wrapped in the absorbent material, is combined with the tissue from the beginning, and the mesh and tissue from the beginning of the procedure. There is an advantage that can induce a firm attachment.

In the above embodiment of the present invention, the segmented pie monofilament used in the mesh is a non-absorbent polymer and the absorbent polymer complex spinning in the longitudinal direction, the non-absorbent polymer is a segmented pie form in which the absorbent polymer is alternately located It is preferred that the non-absorbent polymer is separated from each other by the absorbent polymer, and the absorbent polymer has a connected form, and preferably 3 to 10 segments, preferably 3 to 6 segments. Have The segmented pi monofilament has a monofilament form before the initial decomposition, but when the absorbent polymer decomposes after a certain time, the non-absorbent polymers are separated into strands like multifilaments, respectively, and exhibit flexibility. Therefore, compared to other partially absorbable mesh products such as a mesh product using only a conventional non-absorbent component or sea water, a mesh having improved biocompatibility and flexibility while reducing the amount of initial and residual materials can be provided.

The content of the absorbent polymer is 30 to 70% by volume, the content of the non-absorbent polymer is preferably 30 to 70% by volume. When the content of the absorbent polymer is less than 30% by volume, the volume of the absorbent polymer is too low when it is spun to separate the nonabsorbable polymer, but rather can be prepared in a form in which the nonabsorbable polymer is connected. If less than, there is a problem that the fibers of the non-absorbent component remaining after decomposition are too small to maintain the minimum strength, and the non-absorbent polymer is manufactured in an island-in-the-sea form in which the absorbent polymer is wrapped. More preferably, the content of the absorbent polymer is 40 to 60% by volume and the non-absorbent content is 40 to 60% by volume.

On the other hand, it is possible to use a dyed mesh at regular intervals made of the dyed fibers, which makes it easy to distinguish the mesh during surgery and easily measure the size of the mesh. At this time, it is preferable that only the absorbent polymer part is dyed so that dye remains in the body as much as possible. As the dye, D & C violet No. 2, D & C Green No. 6, FD & C Blue No. 2, etc. which are usually used for the production of sutures can be used.

The mesh described above may be basically manufactured in various types of tissues, but a net, square, hexagonal, and mesh shapes are preferable, and the density of the mesh is 8 to 20 gauges / inch based on the needle interval of the warp knitting machine. Is preferably. The pore size of the mesh of the present invention is 0.1 to 4.0 mm, preferably 0.2 to 3.0 mm.

The surgical mesh has a thickness of 100 to 800um, specifically 500 to 700㎛, preferably 20 to 99% of the total thickness of the surgical mesh composite.

In addition, the surgical mesh is preferably included in 10 to 90% by weight based on the entire surgical mesh complex.

When the thickness of the surgical mesh is less than 20% or the weight is less than 10% compared to the mesh complex, it is difficult to place the mesh complex at the surgical site during surgery due to the low flexibility of the mesh complex due to the high proportion of the polyglutamic acid crosslinked layer. The layer may swell in the body and cause a foreign body sensation after surgery, which may persist until the crosslinked layer is absorbed. When the thickness of the surgical mesh is 99% or more or the weight is 90% or more, the ratio of the polyglutamic acid crosslinked layer may be too small to expect anti-adhesion effect.

In the above-described embodiment, the γ-polyglutamic acid crosslinked layer is for achieving an anti-adhesion function, and includes a crosslinked product containing γ-polyglutamic acid (γ-polyglutamate). The crosslinked product is a crosslinked product in which γ-polyglutamic acid and an ε-polylysine or polyethyleneglycol polymer having a plurality of nucleophilic functional groups are crosslinked or a crosslinked product of γ-polyglutamic acid only.

Such γ-polyglutamic acid crosslinked product can be self-crosslinked by gamma ray or electron beam irradiation to form a gel. Alternatively, the γ-polyglutamic acid crosslinked body may be formed on a gel by a crosslinking reaction with a substance having a plurality of nucleophilic functional groups under water-soluble carbodiimide.

γ-polyglutamic acid is a biodegradable polymer that contains a carboxyl functional group and is capable of forming a covalent bond through reaction with an amine functional group, and salts thereof such as poly-γ-glutamic acid or sodium salt, and mixtures thereof Included. γ-polyglutamic acid is compared to other polymers containing a carboxyl functional group, for example, polysaccharide-based polymers such as alginic acid, xanthine gum, hyaluronic acid, carboxylate dextran, or multicarboxylate polyethylene glycol which is a synthetic polymer. It is easy to form a hydrogel due to its excellent solubility, and has the advantage of enhancing immune activity and anticancer effect.

The γ-polyglutamic acid can be obtained by natural or synthetic, specifically, microorganism, Bacillus Can be obtained by fermentation of subtilis .

In the above embodiment of the present invention, the weight average molecular weight of γ-polyglutamic acid is preferably 10,000 to 2,000,000 Daltons, more preferably 100,000 to 1,000,000 Daltons, particularly preferably 500,000 to 1,000,000 Daltons. When the weight average molecular weight exceeds 2,000,000 Daltons, the viscosity of the crosslinking reaction may be too high, so that the resulting crosslinked product may be nonuniform or too rigid. If the molecular weight is less than 10,000 Daltons, the crosslinking reaction may not be performed, and thus crosslinking is difficult to form.

In the above embodiment of the present invention, the nucleophile is an ε-polylysine or polyethylene glycol-based polymer having a plurality of nucleophilic functional groups, specifically ε-polylysine, a polyethylene glycol derivative of Formula 1, more specifically Formula 2 or Formula The polyethylene glycol derivative of 3 is mentioned, but it is not limited to this. The amine functional group has a high solubility in water and excellent safety for the human body.

[Formula 1]

I-[(CH ₂ CH ₂ O) n-CH ₂ CH ₂ X] m

Where

I is a radical derived from a polyhydric alcohol having 2 to 12 valents, and in each of the hydroxyl groups of the polyhydric alcohol, hydrogen is substituted with-(CH ₂ CH ₂ O) n-CH ₂ CH ₂ X to form a radical which is ether-bonded thereto. Indicates,

X represents an amine group or a thiol group,

n is 19 to 170, and

m is an integer from 2 to 12, combined with the radical I - indicates the number of _{(CH 2 CH 2 O) n} -CH 2 CH 2 X.

 [Formula 2]

In the above formula, X represents an amine group or a thiol group, and n is 19 to 170.

(3)

In the above formula, X represents an amine group or a thiol group, and n is 19 to 170.

The γ-polyglutamic acid crosslinked product may be prepared by a crosslinking reaction in the presence of a coupling agent with a carboxyl group present in γ-polyglutamic acid and an amine or thiol group present in a polylysine or a polyethylene glycol polymer. Such a coupling agent is not particularly limited in kind, but may be a water-soluble carbodiimide. Specifically, the water-soluble carbodiimide is 3- (3-dimethylaminopropyl) -1-ethyl carbodiimide hydrochloride (3- (3-dimethylaminopropyl) -1-ethyl carbodiimide? HCl, EDC? HCl), 1- [3- (dimethylamino) propyl] -3-ethyl carbodiimide methoxide (1- [3- (dimethylamino) propyl] -3-ethyl carbodiimide methiodide), N-cyclohex-3- (2-morphino Ethyl) carbodiimide meto-p-toluenesulfonate (N-cyclohexyl-3- (2-morphinoethyl) carbodiimide metho-p-toluenesulfonate), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide methidada (1-ethyl-3- (3-dimethylaminopropyl) carbodiimide methiodide (ETC)), diisopropyl carbodiimide (DIC), etc. are mentioned.

A crosslinked biodegradable polymer layer containing the poly-glutamic acid γ- is having a network of three-dimensional, cross-linking this layer can be in the form of a sheet, a film, a sponge or the like.

The weight ratio of γ-polyglutamic acid of the crosslinked product to ε-polylysine or polyethylene glycol polymer having a plurality of nucleophilic functional groups is 1: 0.05 to 1: 1. If less than 1: 0.05, the amount of nucleophilic functional groups is too small to form a crosslink. If the amount is greater than 1: 1, unreacted nucleophilic functional groups remain in the crosslinking body, thereby causing an inflammatory reaction in the body.

In the above-described embodiment, the surgical mesh composite is a composite bonded to the surgical mesh layer and the γ-polyglutamic acid crosslinked layer, it may be rectangular, elliptical or circular. The thickness may be 200 to 2500 μm, preferably 700 to 1700 μm.

In the surgical mesh composite, the γ-polyglutamic acid crosslinked layer preferably has a thickness of 100 to 1700 μm, more preferably 200 to 1000 μm.

In addition, the γ-polyglutamic acid crosslinked layer is preferably included in 10 to 90% by weight based on the entire surgical mesh composite.

In the above-described embodiment, the surgical mesh layer and the γ-polyglutamic acid crosslinked layer may be adhered without using an adhesive by a thermal bonding or cryoadhesive method described below.

Further, according to another embodiment of the present invention, there is provided a surgical mesh composite having an anti-adhesion function in which a biodegradable adhesive polymer layer is further formed between the surgical mesh layer and the γ-polyglutamic acid crosslinked layer according to the above-described embodiment. do. That is, the surgical mesh layer; Biodegradable adhesive polymer layer; And a γ-polyglutamic acid crosslinked layer may be sequentially laminated to provide a surgical mesh composite having an anti-adhesion function.

The biodegradable adhesive polymer layer may be in the form of a sheet, a film, a sponge, a foam, or the like, and may be manufactured by a method such as solvent casting. The polymer of the adhesive polymer layer is glycolide, glycolic acid, lactide, lactic acid, lactic acid, caprolactone (ε-caprolactone), dioxanone (ρ-dioxanone), trimethylene It may be a homopolymer or a copolymer including two or more selected from the group consisting of carbonate (trimethylene carbonate), polyanhydride and polyhydroxyalkanoate, the weight average molecular weight of 10,000 ~ 200,000 Daltons, preferably 50,000 to 150,000 daltons. Among them, a copolymer of glycolic acid and lactide may be preferably used, and the weight ratio of glycolic acid and lactide in the copolymer is 1: 9 to 9: 1, preferably 2: 8 to 8: 2.

At this time, the surgical mesh layer is preferably included in 10 to 90% by weight based on the entire surgical mesh composite.

In addition, the γ-polyglutamic acid crosslinked layer is preferably included in 10 to 90% by weight based on the entire surgical mesh composite.

In addition, the biodegradable adhesive polymer layer is preferably 0.1 to 20% of the total surgical mesh composite thickness. And the biodegradable adhesive polymer layer is preferably further included in 1 to 60% by weight based on the entire surgical mesh composite.

The surgical mesh layer, the biodegradable adhesive polymer layer and the γ-polyglutamic acid crosslinked layer may be adhered by a heat bonding or a freeze bonding method described below, and are preferably heat bonding.

The γ-polyglutamic acid crosslinked layer and the surgical mesh layer may be more strongly bonded by the biodegradable adhesive polymer layer, so that adhesion between the layers is maintained for a long time after application in the body, and thus the adhesion preventing effect may be further improved.

In addition, according to another embodiment of the present invention, the γ-polyglutamic acid crosslinked layer according to the above embodiment may be a mixture layer in which the γ-polyglutamic acid crosslinked body and the biodegradable adhesive polymer are mixed. That is, the surgical mesh layer; And a mixture layer in which a γ-polyglutamic acid crosslinked body and a biodegradable adhesive polymer are mixed, and the surgical mesh layer and the mixture layer may be provided with a surgical mesh composite having an anti-adhesion function.

The γ-polyglutamic acid crosslinked body and the biodegradable adhesive polymer are preferably mixed in a weight ratio of 1: 0.1 to 1: 2. If the ratio of the adhesive polymer is less than 1: 0.1, the adhesion with the mesh may not be maintained for a long time in the body, and thus the adhesion effect may not be expressed for a long time. If the ratio is higher than 1: 2, the flexibility of the mesh composite becomes very low, Ease of use

The mixture layer in which the γ-polyglutamic acid crosslinked body and the biodegradable adhesive polymer are mixed may be a biodegradable adhesive polymer embedded in the γ-polyglutamic acid crosslinked layer.

At this time, the surgical mesh layer is preferably included in 10 to 90% by weight relative to the entire surgical mesh composite.

The mixture layer of the γ-polyglutamic acid crosslinked body and the biodegradable adhesive polymer preferably has a thickness of 100 to 1700 μm. The mixture layer is preferably included in 10 to 90% by weight relative to the total surgical mesh composite.

The mixture layer of the γ-polyglutamic acid crosslinked body and the biodegradable adhesive polymer and the surgical mesh layer may be adhered by a heat bonding or a freeze bonding method described below, and are preferably heat bonding.

On the other hand, according to another embodiment of the present invention, there is provided a method for producing each of the surgical mesh complexes described above.

According to one embodiment of the invention, a) providing a surgical mesh layer; b) providing a γ-polyglutamic acid crosslinked layer; And c) laminating and attaching the surgical mesh layer and the γ-polyglutamic acid crosslinked layer to provide a method of manufacturing a surgical mesh composite having an anti-adhesion function. Specifically, a) providing a surgical mesh layer; b) crosslinking in an aqueous solution of? -polyglutamic acid to provide a? -polyglutamic acid crosslinked layer in a hydrogel state; And c) laminating and attaching the surgical mesh layer and the γ-polyglutamic acid crosslinked layer to provide a method of manufacturing a surgical mesh composite having an anti-adhesion function.

Hereinafter, the above-described embodiment will be described for each step.

First, a) providing a surgical mesh layer. Surgical mesh is a method of knitting mono or multifilament of the non-absorbent polymer as described above, a method of knitting into a monofilament in the form of a complex spinning non-absorbent polymer and absorbent polymer, or mono to The thing manufactured by the method of simple mixing and knitting a multifilament can be used.

Next, b) providing a γ-polyglutamic acid crosslinked layer, by irradiating gamma-ray or electron beam to the γ-polyglutamic acid aqueous solution Crosslinked A γ-polyglutamic acid crosslinked layer is provided.

The concentration of γ-polyglutamic acid contained in the aqueous solution is 1 to 20% by weight, preferably 2 to 10% by weight. If the concentration of γ-polyglutamic acid is less than 1% by weight, the number of functional groups is small so that the crosslinking reaction is not performed. If the concentration of γ-polyglutamic acid is less than 20% by weight, the degree of crosslinking does not increase, and the viscosity increases, resulting in uneven crosslinking reaction. The sieve is too rigid or brittle.

The crosslinking may crosslink the high energy light ray by a conventionally known method such as irradiation. The high energy rays include gamma rays or electron beams, and when irradiated with high energy rays, the polymer chain is cleaved and free radicals are generated to cause crosslinking reactions. When gamma rays are used, the irradiation dose is 10 to 200 kGy, preferably 30 to 150 kGy. If the radiation dose is too low, the amount of free radicals is small and the number of crosslinking points is small, making crosslinking difficult.At a dose exceeding 200kGy, the crosslinking point may be saturated or the polymer may decompose too much to be dissolved in an aqueous solution without forming a gel. have.

In addition, the step b) to provide a γ-polyglutamic acid crosslinked layer is a cross-linking reaction of γ-polyglutamic acid, ε-polylysine having a plurality of nucleophilic functional groups or polyethylene glycol-based polymer of formula (1) and water-soluble carbodiimide in an aqueous solution Γ-polyglutamic acid crosslinked layer in the hydrogel state can be prepared.

The concentration of γ-polyglutamic acid contained in the aqueous solution is 1 to 20% by weight, preferably 2 to 10% by weight. If the concentration of γ-polyglutamic acid is less than 1% by weight, the number of functional groups is small so that the crosslinking reaction is not performed. If the concentration of γ-polyglutamic acid is less than 20% by weight, the degree of crosslinking does not increase, and the viscosity increases, resulting in uneven crosslinking reaction. The sieve is too rigid or brittle.

In addition, the concentration of the ε-polylysine or polyethylene glycol polymer contained in the aqueous solution is 0.8 to 10% by weight, preferably 1 to 4% by weight.

In addition, the concentration of the water-soluble carbodiimide contained in the aqueous solution is 0.04 to 5% by weight, preferably 0.5 to 2% by weight.

The water-soluble carbodiimide is very well soluble in water and after the reaction is converted to urea, which is less toxic. However, after the preparation of the hydrogel for the removal of unreacted carbodiimide and urea may further comprise the step of washing the hydrogel with an aqueous solution.

Such γ-polyglutamic acid crosslinked product has excellent biocompatibility, gels at a pH near neutral, and has high safety since all toxic factors generated during the gelation process can be removed.

The hydrogel of the γ-polyglutamic acid crosslinked layer has a swelling degree of 2 to 1000, preferably 10 to 800, for bonding to the mesh. If the swelling degree is too high, the density of the crosslinked product is low, so it is difficult to maintain the shape of the gel after drying, and if it is too low, the crosslinked product is too rigid or brittle to adhere to the mesh.

In the present invention, the degree of swelling indicates the degree to which the crosslinked material contains water, and means the degree to which the crosslinked material absorbs water for 24 hours in an aqueous solution of pH 7.4 and 37 ° C. Specifically, equation (1) is followed.

[Equation 1]

Swelling degree = Wg1 (weight of gel absorbed water after immersion) / Wg0 (weight of hydrogel)

In step c), the prepared hydrogel crosslinked layer may be dried, the dried γ-polyglutamic acid crosslinked layer and the surgical mesh layer may be laminated, and thermally bonded to prepare a surgical mesh composite.

The hydrogel may be lyophilized or dried by solvent casting, and the dried γ-polyglutamic acid crosslinked layer may be in the form of a sheet, a film, a sponge, or the like.

The thermal bonding method may be bonded at a pressure of 2 to 150 psi, preferably 10 to 100 psi on a hot plate heated to 50 to 200 ° C., preferably 60 to 160 ° C. If the temperature of the heating plate is less than 50 ℃, the flexibility of the crosslinked body is not adhered to the mesh, and if the temperature exceeds 200 ℃, the crosslinked body may be too rigid or the basic structure of the mesh may be damaged by heat.

Alternatively, in step c), the prepared hydrogel crosslinked layer may be laminated on a surgical mesh layer and then adhered through a lyophilization method. Specifically, the hydrogel is applied to a shallow rectangular or circular container. Then carefully place the surgical mesh on the surface of the aqueous solution to prevent it from sinking. Thereafter, frozen at -70 ° C. for about 24 hours and then lyophilized for 3 days in a vacuum state to obtain a two-layer mesh composite having a γ-polyglutamic acid crosslinked layer and a surgical mesh layer adhered thereto.

On the other hand, before crosslinking the γ-polyglutamic acid in step b), it is also possible to laminate the surgical mesh layer on the aqueous solution and then crosslink. In this case, the method includes a-1) providing a surgical mesh layer; b-1) providing an aqueous solution containing γ-polyglutamic acid, ε-polylysine or a polyethyleneglycol-based polymer of Formula 1 and a water-soluble carbodiimide; b-2) stacking the surgical mesh layer on the aqueous solution before the aqueous solution forms a bridge; b-3) crosslinking the aqueous solution to obtain a laminate comprising a crosslinked γ-polyglutamic acid hydrogel and a surgical mesh layer; And c) adhering the surgical mesh layer and the γ-polyglutamic acid layer after drying the laminate.

The drying of step c) may be performed by oven drying or lyophilization.

And in the step c) is preferably carried out by the above-described thermal bonding method.

Further, according to another embodiment of the present invention, further comprising the step of providing a biodegradable adhesive polymer layer after the step b) according to the above embodiment, c) the biodegradable adhesive polymer in the bonding step Provided is a method for preparing a surgical mesh composite having an anti-adhesion function comprising laminating a layer between a surgical mesh layer and a γ-polyglutamic acid crosslinked layer and then adhering. That is, specifically, a-1) providing a surgical mesh layer; b-1) providing a γ-polyglutamic acid crosslinked layer in a hydrogel state; b-2) providing a biodegradable adhesive polymer layer; And c-1) drying the crosslinked layer in the hydrogel state, and laminating the dried γ-polyglutamic acid crosslinked layer, the biodegradable adhesive polymer layer, and the surgical mesh layer in order, and then adhering the adhesive layer. Methods of making a surgical mesh composite are provided. Bonding in this step can be carried out by the above-described thermal bonding method.

The step of providing the biodegradable adhesive polymer layer is i) dissolving the biodegradable adhesive polymer in an organic solvent such as methylene chloride, acetone, ethyl acetate in 1 to 20% by weight to prepare a polymer solution; ii) applying the polymer solution to a glass petri dish and solvent casting to form a polymer film.

In addition, according to another embodiment of the present invention, the γ-polyglutamic acid crosslinked layer in the step c) according to the above embodiment is the anti-adhesion function which is a mixture layer of the γ-polyglutamic acid crosslinked body and the biodegradable adhesive polymer There is provided a method of manufacturing a surgical mesh composite having a. That is, specifically, a) providing a surgical mesh layer; b-1) hydrogel state providing a γ-polyglutamic acid crosslinked layer; b-2) drying the prepared hydrogel crosslinked layer and mixing the biodegradable adhesive polymer to provide a mixture layer; And c) a surgical mesh layer, there is provided a method for producing a surgical mesh composite having an anti-adhesion function comprising the step of laminating the mixture layer. Bonding in this step can be carried out by the above-described thermal bonding method.

The step of providing the mixture layer will be described. The biodegradable adhesive polymer, already described above, is dissolved at 1 to 20% by weight in an organic solvent such as methylene chloride, acetone or ethyl acetate. The biodegradable adhesive polymer is introduced into a γ-polyglutamic acid crosslinked layer dried under reduced pressure. The pressure is then removed and the mixture layer is evaporated and dried in a shallow rectangular or circular vessel to obtain a mixture layer of γ-polyglutamic acid crosslinked and biodegradable adhesive polymer.

Surgical mesh complex of the present invention is used during surgical operations such as hernia surgery to perform the function of preventing adhesions that may occur immediately after the operation, the polymer to prevent adhesion is quickly absorbed and excreted in the body, The mesh layer can be maintained to prevent recurrence of hernia surgery.

In addition, the mesh composite of the present invention is excellent in flexibility and shape safety and easy to operate during surgery and has a physical strength sufficient to withstand the pressure in the abdominal cavity after the operation.

Figure 1 shows a mesh composite of a two-layer structure comprising a surgical mesh layer and an anti-adhesion crosslinked layer according to an embodiment of the present invention.
Figure 2 shows a three-layer mesh composite bonded to the surgical mesh and the anti-adhesion crosslinked layer through a biodegradable adhesive polymer layer according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are only intended to illustrate the present invention, and the scope of the present invention is not limited by these examples.

Example  1 to 12. γ- by Gamma Irradiation Polyglutamic acid Crosslinked  formation

The γ-polyglutamic acid Na salt (Bioleaders, Bacillus subtilis ) dried to the same content as in Table 1 was taken in a 20 ml vial, 20 ml of distilled water was added and then stirred at 200 rpm in a stirrer for about 2 hours to dissolve. After the aqueous solution was packaged with an aluminum packaging material, gamma irradiation with a ⁶⁰ Co light source was performed to obtain crosslinked γ-polyglutamic acid. The crosslinked product thus obtained was dried in an oven heated to 60 ° C. to obtain a γ-polyglutamic acid crosslinked product. After immersion for 24 hours at 37 ℃ in water of pH 7.4 to determine the degree of swelling. Swelling degree was calculated by the following equation and the results are shown in Table 1.

[Equation 1]

Swelling degree = Wg1 (weight of gel absorbed water after immersion) / Wg0 (weight of hydrogel)

Gelation of γ-polyglutamic acid by gamma irradiation number Poly γ-Glutamic Acid Na Salt ⁶⁰ Co gamma-irradiation dose (kGy) Swelling degree condition MW (kDa) weight(%) Example 1 50 10 30 950 Example 2 500 10 30 800 Example 3 500 10 50 300 Example 4 500 10 100 220 Example 5 500 10 150 200 Example 6 500 20 30 650 Example 7 500 30 30 570 Example 8 1000 10 30 600 Example 9 1000 20 30 560 Example 10 1000 30 30 510 Example 11 2000 10 30 500 Example 12 2000 20 30 480 Comparative Example 1 500 2 30 1200 Comparative Example 2 500 5 30 1350 Comparative Example 3 500 10 10 1950 Comparative Example 4 500 10 200 1400 Comparative Example 5 2000 30 30 - Insoluble

As shown in Table 1 above, it can be seen that the swelling degree increases as the gamma-irradiation dose is small. In other words, the increase in the degree of swelling means that the hydrogel contains more water, which means that the number of free radicals generated by gamma-irradiation is less, resulting in fewer covalent bonds, that is, fewer crosslinking points.

In addition, it can be seen that as the molecular weight of the γ-polyglutamic acid increases, the degree of swelling decreases. In addition, it can be seen that as the concentration of the γ-polyglutamic acid aqueous solution increases, the degree of swelling decreases. When the concentration of the γ-polyglutamic acid aqueous solution is too low as in Comparative Examples 1 to 4, or when the gamma-irradiation dose is too low or high, crosslinking is formed, but it is easy to adhere to the mesh because it shows high swelling degree. You will not.

Example  13 to 23. With polylysine  Γ- by reaction Polyglutamic acid Crosslinked  formation

To the content as shown in Table 2, dried γ-polyglutamic acid Na salt (Bioleaders, Bacillus subtilis ) was taken in a 10ml vial, 10ml of distilled water was added and dissolved by stirring at 200rpm for about 2 hours in a stirrer.

Dried ε-polylysine bromate (Handary, Streptomyces , MW 4,000 Daltons) And EDC-HCl was stored in a frozen 10ml vial in the content of Table 2, 10ml of distilled water was added and dissolved by stirring for 10 minutes at 200rpm in a stirrer to prepare a solution containing ε-polylysine bromate, EDC-HCl.

10 ml of the first reaction solution and the second reaction solution were respectively prepared by using a 10 ml pipette using an aqueous solution of γ-polyglutamic acid Na salt as the first reaction solution and an aqueous solution containing ε-polylysine bromate and an EDC-HCl solution as the second reaction solution. Drunk. Thereafter, the two reaction solutions were simultaneously added to a 50 ml glass beaker, followed by stirring for 10 seconds using a magnetic stirrer at room temperature, followed by gelation after pouring the solution into a glass petri dish.

The prepared gel was washed again in an aqueous 2% NaCl solution for 1 hour to remove unreacted EDC and urea, and then dried in an oven heated to 60 ° C. for 8 hours to prepare a γ-polyglutamic acid crosslinked film. The dried gel was immersed in water at pH 7.4 for 24 hours to measure the degree of swelling. Swelling degree was calculated by the above equation 1 and the results are shown in Table 2.

Gelation of γ-polyglutamic acid by water soluble carbodiimide reaction number Poly γ-Glutamic Acid Na Salt ε-polylysine weight (%) EDC? HCl Swelling degree condition MW (kDa) weight(%) weight(%) Example 13 50 6 1.2 0.6 23.2 Example 14 50 10 2 One 11.3 Example 15 500 3 0.6 0.3 17 Example 16 500 6 1.2 0.6 7.8 Example 17 500 10 2 One 4.2 Example 18 500 15 3 1.5 2.3 Example 19 1000 3 0.6 0.3 13.4 Example 20 1000 6 1.2 0.6 4.1 Example 21 1000 10 2 One 2.9 Example 22 2000 3 0.6 0.3 11 Example 23 2000 6 1.2 0.6 2.7 Comparative Example 6 50 3 0.6 0.3 Not gelated Comparative Example 7 500 2 0.5 0.25 - Not gelated Comparative Example 8 1000 15 3 1.5 1.8 Comparative Example 9 2000 10 2 One 1.9

As can be seen in Table 2, it can be seen that the swelling degree of the crosslinked body has a value of approximately 2 to 25. In addition, gelation was difficult when the molecular weight of the γ-polyglutamic acid was less than 50 kDa or when the concentration of the γ-polyglutamic acid aqueous solution was low. On the other hand, when the molecular weight of γ-polyglutamic acid was high or its concentration was high, the degree of crosslinking of the crosslinked product was increased, and the degree of swelling was 2 or less.

Example  24. Crosslinked product Mesh  Direct adhesive

A mesh made of warp knitted monofilament in the form of a segmented pie in which polypropylene and polycaprolactone were multispun at a ratio of 4: 6 was prepared. This was laminated to the γ-polyglutamic acid crosslinked film prepared in Example 17. Thereafter, pressure was applied for 2 seconds at a pressure of 20 psi on a heating plate heated to 90 ° C. to bond the mesh and the crosslinked body, and the applied pressure was immediately removed after 2 seconds. Thereafter, quenching to prepare a mesh composite having a two-layer structure including a mesh and a crosslinked product. At this time, the total thickness of the composite was 800 µm, the mesh layer was 500 µm, and the crosslinked layer was 300 µm.

Example  25. Sponge type γ- Polyglutamic acid Crosslinked product Mesh  adhesion

The γ-polyglutamic acid hydrogel prepared in Example 17 was cooled at −70 ° C. for 24 hours and then freeze-dried under reduced pressure at a rate of −40 ° C. to 0.1 ° C. per minute for 30 hours. The lyophilized γ-polyglutamic acid crosslinked product was ground for 3 minutes using a freeze mill manufactured by Specs to prepare a fine powder. The powder was added to distilled water to a concentration of 1 to 30% by weight and then strongly dispersed at a stirring speed of 3000 rpm. The suspension of the dispersed γ-polyglutamic acid crosslinked product was again lyophilized to prepare a γ-polyglutamic acid crosslinked sponge in the form of a foam.

Thereafter, the mesh and the crosslinked sponge used in Example 25 were sequentially stacked on a hot plate heated to 90 ° C., and a pressure of 20 psi was applied for 2 seconds to bond the mesh with the γ-polyglutamic acid crosslinked product. Thereafter, the pressure was removed and quenched to obtain a mesh composite having a two-layer structure including a mesh and a γ-polyglutamic acid crosslinked product. This two-layered surgical mesh composite includes a surgical mesh layer 11 and a γ-polyglutamic acid crosslinked layer 12, as shown in FIG. In this case, the total thickness of the composite was 900 μm, the mesh layer was 500 μm, and the crosslinked layer was 400 μm.

Example  26. Biodegradable Adhesive Polymer layer  Containing Mesh  Composite manufacturing

A copolymer having a weight average molecular weight of 70,000 Daltons in which polyglycolide-lactide was copolymerized at a weight ratio of 3: 7 was dissolved in methylene chloride at a concentration of 5% by weight. The solution was cast in a glass petri dish to prepare a polyglycolide-lactide film having a diameter of 120 mm and a thickness of 0.35 mm.

The prepared film was placed between the γ-polyglutamic acid crosslinked film prepared in Example 17 and the mesh described in Example 24, and then the mesh and γ-poly were applied by applying a pressure of 10 psi for 2 seconds on a hotplate heated to 110 ° C. Adhesion with glutamic acid crosslinked product. Pressure was removed and quenched to prepare a mesh composite having a three-layer structure in which the mesh and the γ-polyglutamic acid crosslinked body were adhered by a polyglycolide-lactide copolymer film. The three-layered surgical mesh composite includes a surgical mesh layer 21, a biodegradable adhesive polymer layer 22, and a γ-polyglutamic acid crosslinked layer 23, as shown in FIG. In this case, the total thickness of the composite was 850 μm, the mesh layer was 500 μm, the adhesive layer was 50 μm, and the crosslinked layer was 300 μm.

Example  27.γ- Polyglutamic acid Crosslinked product Mesh  Adhesion Using Biodegradable Polymers

A weight average molecular weight of 70,000 Daltons copolymerized with polyglycolide-lactide 3: 3 was dissolved in methylene chloride to a concentration of 5% by weight.

After cooling the γ-polyglutamic acid crosslinked gel solution of Example 16 for 24 hours at -70 ° C, the freezing body temperature was raised under reduced pressure for 30 hours at a rate of -40 ° C to 0.1 ° C per minute, and lyophilized to form a sponge. γ-polyglutamic acid crosslinked product was prepared. The dried γ-polyglutamic acid crosslinked product was placed on a glass-shaped Petri dish having a diameter of 120 mm, and then decompressed using a distillation head. Thereafter, 35 ml of the PLGA copolymer 5% solution was added using a syringe so that the PLGA polymer solution was uniformly infiltrated into the sponge-formed? -Polyglutamic acid crosslinked product for 1 hour. The pressure was released and the MC solvent was evaporated in a 40 ° C. drying oven to form a complex of PGLA with a γ-polyglutamic acid crosslinked product.

The γ-polyglutamic acid crosslinked sponge in which the PLGA polymer is embedded and the mesh are sequentially laminated on a hot plate heated to 90 ° C., and a pressure of 20 psi is applied for 2 seconds to bond the mesh and the γ-polyglutamic acid crosslinked sponge. The pressure was removed and quenched to 24 ° C. to prepare a two-layered mesh composite including a γ-polyglutamic acid crosslinked product containing a mesh and a PLGA copolymer. At this time, the total thickness of the composite was 900 μm, the mesh layer was 500 μm, and the mixture layer was 400 μm.

Example  28. Efficacy Assessment

In order to investigate the anti-adhesion effect of the surgical mesh complexes prepared in Examples 24 to 27, the degree of adhesion was confirmed through animal experiments using SD rats (Orient, Korea) as an animal model. Ten rats of 6 weeks or older were used, respectively, and they were bred separately in an environment in which a temperature of 16 to 22 ° C. and a relative humidity of 50 to 70% were maintained. The abdomen of the anesthetized rat was incised to create an artificial hernia situation, and the intestinal contact with the hernia site was cut to the extent that the epidermis was slightly peeled off, and then the surgical mesh complex prepared above was applied to the cut abdominal wall. . Two weeks after this procedure, the state of treatment of the hernia was maintained and the degree of adhesion of the tissue was measured. At this time, the suture without the mesh composite was compared with the degree of anti-adhesion effect as a control group and it is shown in Table 3. Control means that the animal was not treated with the surgical mesh complex.

Evaluation of anti-adhesion efficacy of mesh complex Mesh composite Adhesion Prevention [%] Population [mari] Example Procedure population Cohesion Population 24 80 10 2 25 70 3 26 100 0 27 100 0 Control group 0 10

In all examples, the healing state of hernia was maintained, and when the γ-polyglutamic acid layer crosslinked with the mesh was adhered to the PGLA film, adhesion was prevented 100%, and the sponge-type γ-polyglutamic acid layer was thermally bonded. 70% of the mesh composite and 80% of the film composite were prevented.

Claims (28)

Surgical mesh layers; And
a γ-polyglutamic acid crosslinked layer,
Surgical mesh composite having a function of preventing adhesion to the layer comprising the surgical mesh layer and γ-polyglutamic acid cross-linked. The method of claim 1,
Surgical mesh composite having an anti-adhesion function further comprises a biodegradable adhesive polymer layer between the surgical mesh layer and γ-polyglutamic acid crosslinked layer. The method of claim 1,
The γ-polyglutamic acid crosslinked layer is a surgical mesh composite having an anti-adhesion function, which is a mixture layer of γ-polyglutamic acid crosslinked and a biodegradable adhesive polymer. The method of claim 1,
The γ-polyglutamic acid crosslinked layer is a surgical mesh composite having an anti-adhesion function, wherein the γ-polyglutamic acid includes a crosslinked crosslinked with each other by gamma ray or electron beam irradiation. The method of claim 1,
The γ-polyglutamic acid crosslinked layer is γ-polyglutamic acid Ε-polylysine or polyethyleneglycol polymer having a plurality of nucleophilic functional groups comprises a crosslinked crosslinked Surgical mesh composite with anti-adhesion function. The method of claim 1,
The γ-polyglutamic acid is Surgical mesh composite having an anti-adhesion function with a weight average molecular weight of 10,000 to 2,000,000 Daltons. 6. The method of claim 5,
Surgical mesh composite having an anti-adhesion function that the polyethylene glycol-based polymer is represented by Formula 1:
[Formula 1]
I-[(CH ₂ CH ₂ O) n-CH ₂ CH ₂ X] m
In the above formula, I is a radical derived from a 2 to 12 valent polyhydric alcohol, wherein hydrogen is substituted with-(CH ₂ CH ₂ O) n-CH ₂ CH ₂ X in each of the hydroxyl groups of the polyhydric alcohol to form an ether bond thereto. Represents a radical of
X represents an amine group or a thiol group,
n is 19 to 170, and
m is an integer from 2 to 12, combined with the radical I - indicates the number of _{(CH 2 CH 2 O) n} -CH 2 CH 2 X. 6. The method of claim 5,
Surgical mesh composite having an anti-adhesion function in which the weight ratio of γ-polyglutamic acid and ε-polylysine or polyethylene glycol polymer having a plurality of nucleophilic functional groups is 1: 0.05 to 1: 1. The method of claim 1,
The surgical mesh complex has a thickness of 100 ~ 1200μm surgical mesh composite having an anti-adhesion function. The method of claim 1,
The γ-polyglutamic acid crosslinked layer is a surgical mesh composite having an anti-adhesion function that is contained in 10 to 90% by weight relative to the entire surgical mesh complex. The method of claim 2,
The biodegradable adhesive polymer layer is glycolide (glycolide), glycolic acid (glycolic acid), lactide (lactide), lactic acid (lactic acid), caprolactone (ε-caprolactone), dioxanone (ρ-dioxanone), tree Surgical mesh composite having an anti-adhesion function, which is a homopolymer or a copolymer including two or more selected from the group consisting of methylene carbonate, polyanhydride, and polyhydroxyalkanoate. 12. The method of claim 11,
The weight average molecular weight of the biodegradable adhesive polymer layer is 10,000 ~ 200,000 Dalton surgical mesh composite having an anti-adhesion function. The method of claim 10,
The biodegradable adhesive polymer layer is a surgical mesh composite having an anti-adhesion function further comprises 0.1 to 60% by weight relative to the entire surgical mesh composite. The method of claim 3, wherein
The γ-polyglutamic acid crosslinked body and the biodegradable adhesive polymer is a surgical mesh composite having an anti-adhesion function mixed in a 1: 0.1 to 1: 2 weight ratio. The method of claim 3,
Biodegradable adhesive polymer is embedded in the γ-polyglutamic acid crosslinked layer Surgical mesh composite with anti-adhesion function. The method of claim 3,
The mixed layer is a surgical mesh composite having an anti-adhesion function, which comprises 10 to 90% by weight relative to the total surgical mesh composite. a) providing a surgical mesh layer;
b) providing a γ-polyglutamic acid crosslinked layer; And
c) a method of manufacturing a surgical mesh composite having an anti-adhesion function comprising laminating and bonding the surgical mesh layer and the γ-polyglutamic acid crosslinked layer. The method of claim 17,
Step b) is a cross-linking reaction in γ-polyglutamic acid aqueous solution Hydrogel A method for producing a surgical mesh composite having an anti-adhesion function, to provide a γ-polyglutamic acid crosslinked layer. The method of claim 17,
The step c) is a surgical gel having a function of preventing adhesion after drying the crosslinked layer of the hydrogel state prepared in step b), laminating the dried γ-polyglutamic acid crosslinked layer and the surgical mesh layer Method of making mesh composites. The method of claim 17,
The step c) is a method for producing a surgical mesh composite having a function of preventing adhesion by laminating a cross-linked layer of the hydrogel state prepared in step b) on a surgical mesh and then lyophilized. The method of claim 17,
Providing a biodegradable adhesive polymer layer after step b),
C) drying the γ-polyglutamic acid crosslinked layer in a hydrogel state in the step of adhering, laminating the biodegradable adhesive polymer layer between the surgical mesh layer and the dried γ-polyglutamic acid crosslinked layer, and then performing thermal bonding. Method for producing a surgical mesh composite having an anti-adhesion function comprising. The method of claim 17,
In the step c) the γ-polyglutamic acid cross-linking layer is a method of producing a surgical mesh composite having an anti-adhesion function is provided as a mixture layer of γ-polyglutamic acid and biodegradable adhesive polymer. The method of claim 17,
Method for producing a surgical mesh composite having an anti-adhesion function further comprising the step of incorporating a biodegradable adhesive polymer into the γ-polyglutamic acid crosslinked layer provided in step b). The method of claim 17,
B) providing a γ-polyglutamic acid crosslinked layer gamma rays or electron beams were irradiated onto γ-polyglutamic acid aqueous solution Crosslinked Method for producing a surgical mesh composite having an anti-adhesion function comprising providing a γ-polyglutamic acid crosslinked layer. The method of claim 17,
B) γ-polyglutamic acid Providing the crosslinked layer γ-polyglutamic acid, γ-polyglutamic acid An epsilon polylysine having a plurality of nucleophilic functional groups or a polyethylene glycol polymer of Formula 1 and a water-soluble carbodiimide are cross-linked in an aqueous solution to obtain a hydrogel. 26. The method of claim 25,
The concentration of γ-polyglutamic acid contained in the aqueous solution is 1 to 20% by weight of the method for producing a surgical mesh composite having an anti-adhesion function. 26. The method of claim 25,
Γ-polyglutamic acid contained in the aqueous solution Method for producing a surgical mesh composite having an anti-adhesion function of the ε-polylysine having a plurality of nucleophilic functional groups or the polyethylene glycol-based polymer of formula 1 is 0.5 to 10% by weight:
[Formula 1]
I-[(CH ₂ CH ₂ O) n-CH ₂ CH ₂ X] m
Where
I is a radical derived from a polyhydric alcohol having 2 to 12 valents, and in each of the hydroxyl groups of the polyhydric alcohol, hydrogen is substituted with-(CH ₂ CH ₂ O) n-CH ₂ CH ₂ X to form a radical which is ether-bonded thereto. Indicates,
X represents an amine group or a thiol group,
n is 19 to 170, and
m is an integer from 2 to 12, combined with the radical I - indicates the number of _{(CH 2 CH 2 O) n} -CH 2 CH 2 X. 20. The method of claim 19,
Wherein c) in the step of adhering is a method for producing a surgical mesh composite having an anti-adhesion function that is carried out at a pressure of 2 ~ 150psi on a hot plate heated to 50 ~ 200 ℃.

Images