KR20120089951A - Surgical mesh composite with anti-adhesion property and method for producing the same - Google Patents

Abstract

PURPOSE: A mesh composite for operation and a manufacturing method thereof are provided to prevent recurrence of herniotomy. CONSTITUTION: A mesh composite for operation comprises a mesh layer(11) for operation and a temperature sensitive polymer-containing layer(12). The mesh layer for operation and temperature sensitive polymer-containing layer are adhered. A biodegradable adhesive polymer layer is included between the mesh layer for operation and temperature sensitive polymer-containing layer. The temperature sensitive polymer-containing layer is a mixture layer.

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.

Tension-free surgery using mesh in hernia surgery (Lichtenstein IL, The tension-free hernioplasty, Am J Surg 1989; 157; 188-193) has a low recurrence rate, short surgery time, and wound recovery time. It is fast and has the advantage of allowing the patient to return to daily life quickly. Therefore, in general, tension-free surgery using mesh has been accepted as a useful method of treating hernias.

Since the mesh used for hernia surgery must have the property of strengthening the peritoneum by maintaining chemical and physical properties for many years, many materials in which non-absorbable polymers such as polypropylene or PET are made in a fiberized form are used. have.

On the other hand, after surgical operations such as hernia surgery or during the healing of wounds caused by inflammation, wounds, friction, etc., excessive fibrous tissue is formed or blood is leaked to coagulate, whereby neighboring organs or tissues to be separated are joined together. Adhesion occurs. If the wound on the site after adhesion to other tissues may cause pain, intestinal obstruction, infertility, etc., and may cause organ or tissue dysfunction, and in some cases, reoperation for adhesion detachment is necessary. According to US statistics, postoperative adhesion results in 49% to 74% of small intestine occlusion, 15% to 20% of infertility, 20% to 50% of chronic pelvic symptoms, and 19% of intestinal perforations in subsequent surgery. It is known.

As one of methods for preventing such adhesion, a method of preparing an adhesion inhibitor and inserting it during surgery is used. Two types of anti-adhesion agents are used, largely in the form of a solution containing a gel form and a film form including a film, a nonwoven fabric and a sponge form. The material used in the anti-adhesion agent serves as a physical barrier without adversely affecting the healing during the wound healing period in vivo, and is then decomposed. In addition, the material itself is not toxic, and the substances released through decomposition metabolism should also be harmless to the human body.

As a material that can be used as the anti-adhesion agent, a non-absorbent material such as expanded poly tetrafluoroethylene (ePTFE), poly vinyl alcohol (polyvinyl alcohol, PVA) and the like may be used. In addition, absorbent materials may be used, such as biosaccharide-derived natural polymers of polysaccharides and proteins, non-liver-derived natural polymers, and water-soluble synthetic polymers. Specifically, polyethylene glycol (PEG), oxidized regenerated cellulose (ORC), sodium carboxyl methyl cellulose (CMC), dextran sulfate, sodium hyaluronate (HA) , Chondroitin sulfate (CS), poloxamer, polylactic acid (PLA), polyglycolic acid (PGA), poly lactic-co-glycolic acid (PLGA), collagen and fibrin It is known to be usable. The materials may be used alone, or may be used together in a specific structure. The above anti-adhesion material may be used to impart anti-adhesion function to the mesh composite.

Therefore, in order to prevent the occurrence of adhesion after tensionless hernia surgery, the mesh for hernia surgery has been developed a lot of products in the form of a mesh complex including the adhesion function as well as the original mesh function.

Such products have been described in which polypropylene monofilaments are made of knitted mesh and then composited with oxidized regenerated cellulose (ORC). In addition to ORC, non-absorbent materials such as silicone elastomer or ePTFE Composites bonded to propylene mesh have also been provided. In addition, a hernia mesh composite prepared by weaving polypropylene and ORC in the form of a knitted fabric, and then thermally compressing them with an adhesive of polydioxane, which is an absorbent polymer, has also been proposed. ORC used in such a composite is manufactured in the form of a fabric is known to have a good adhesion to the severe bending organs or tissues, but has a disadvantage of low biocompatibility because it is not a component of the living body. In addition, since the pore size is very large, permeation of various cells, blood proteins, and the like can easily occur, resulting in a problem of low efficiency as a separator. On the other hand, non-absorbent materials such as ePTFE may have a very good effect on the formation of anti-adhesion barriers, but they do not have biodegradability and may cause inflammation between surgical sites and tissues.

In addition, a mesh composite prepared with a non-absorbent material such as polypropylene or PET in the form of a knitted fabric, and then bonded with an adhesive with hyaluronic acid or CMC hydrogel formed by a water-soluble carbodiimide reaction is also provided. Also shown is a mesh composite formed by bonding a knitted polypropylene monofilament and a hyaluronic acid / CMC mixture to a polyglycolic acid multifilament followed by photopolymerization. The photopolymerized hyaluronic acid / CMC forms a hydrogel in the body to form an anti-adhesion barrier. However, CMC used as an anti-adhesion agent is not a bio-derived material, so its biocompatibility is lower than that of other bio-derived materials. In addition, hyaluronic acid is one of the biological components, but has excellent biocompatibility, but has a problem in that it is difficult to stay in the body for a time necessary for preventing adhesion because it is easily decomposed and has a relatively short half life of 1 to 3 days.

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.

In addition, a composite having a two-layered structure in which a heparin, collagen, or gelatin, which is a bio-derived polymer, is electrospun, to produce a web, and then electrospun a copolymer of polyglycolide and polylactide is also developed. Since it is manufactured by nano spinning, it has excellent advantages such as adhesion to tissues and organs, flexibility, and operability, but it is difficult to control the residual amount of strong organic solvents used during electrospinning, and it is difficult to achieve proper physical strength and productivity. Problems can also occur.

As can be seen from the prior art, the mesh complex expressing the anti-adhesion function during hernia surgery has a variety of conditions required, but it can be seen that the research results and commercialization of the present so far. Therefore, the development of an ideal and effective anti-adhesion mesh composite is required.

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

The present invention surgical mesh layer; And a temperature sensitive polymer-containing layer, wherein the surgical mesh layer and the temperature sensitive polymer-containing layer provide a surgical mesh composite having a function of preventing adhesion.

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 temperature sensitive polymer-containing layer.

The present invention also provides a surgical mesh composite having an anti-adhesion function, wherein the temperature sensitive polymer-containing layer is a mixture layer in which a biodegradable adhesive polymer is mixed with a temperature sensitive polymer.

The present invention also provides a method for producing each of the surgical mesh complexes 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".

In addition, in the present invention, "temperature sensitive polymer" refers to a polymer that is water-soluble, exhibits a sol-gel phase transition in the body temperature range, and decomposes into a surfactant and a bioabsorbable single substance in the body.

The present inventors have developed a method for adhering a temperature sensitive polymer layer to various kinds of meshes in manufacturing a surgical mesh composite having an anti-adhesion function, and excellent in flexibility and shape safety, and thus easy to operate during the procedure. It is possible to invent surgical mesh composites that have sufficient adhesion to tissues and organs after surgery, physical strength to withstand abdominal pressure, and biocompatibility, and exhibit excellent anti-adhesion efficiency during wound healing.

According to one embodiment of the invention, the surgical mesh layer; And a temperature sensitive polymer-containing layer, wherein the surgical mesh layer and the temperature sensitive polymer-containing layer are provided with a surgical mesh composite having an anti-adhesion function.

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 and the absorbent polymer form a segmented pie form 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 that, there is a problem in that the fibers of the nonabsorbable component remaining after decomposition are too small to maintain the minimum strength, and the nonabsorbable 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, mesh, etc. are preferable, and the density of the mesh is 8 to 20 gauges / inch based on the needle spacing 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 layer preferably has a thickness of 100 to 800 µm, specifically 500 to 700 µm, and preferably 20 to 99% of the total thickness of the surgical mesh composite.

In addition, the surgical mesh layer is preferably included in 10 to 90% by weight relative to the entire surgical mesh composite.

When the thickness or weight of the surgical mesh layer compared to the mesh composite is less than the above range, the flexibility of the mesh composite becomes low due to the high proportion of the temperature sensitive polymer-containing layer, making it difficult to place the mesh complex on the surgical site during surgery, and the temperature-sensitive polymer-containing layer After gelation in the body, foreign body sensation may occur. This foreign matter can last until the temperature sensitive polymer containing layer is absorbed. In addition, when the thickness or weight is larger than the above range, the ratio of the temperature sensitive polymer-containing layer may be too small to expect the anti-adhesion effect.

In the above-described embodiment, the temperature sensitive polymer-containing layer is to achieve an anti-adhesion function.

In general, the ideal anti-adhesion agent should be i) anti-adhesion of the tissues or organs around the wound, ii) water soluble, iii) harmless to the human body, iv) easily decomposed and easily absorbed and excreted in the body, v) have no foreign body reaction, and vi) remain attached to tissues or organs for a period of time during which the wound heals.

Therefore, a temperature-sensitive polymer that is water-soluble and not only has excellent biocompatibility but also is gelled by body temperature to maintain its shape and stably stays on the wound for a certain period of time may be an ideal material as an anti-adhesion agent. By using the same as a sponge or casting using a film or a film form using the casting, it is possible to obtain a temperature-sensitive polymer containing layer which is biocompatible, biodegradable and excellent in form stability.

These temperature-sensitive polymers are dissolved in an aqueous solution and have a temperature-sensitive polymer that exhibits a sol-gel phase transition by temperature. The aqueous polymer solution dissolved in the body becomes a gel by body temperature and remains stable in the tissue, thus acting as an anti-adhesion membrane. can do. In addition, as time passes, the product may be decomposed into a low molecular weight surfactant and a bioabsorbable monomolecular substance, and the product absorbed or decomposed in the body may secondaryly prevent adhesion.

In the above-described embodiment, the temperature sensitive polymer may be used without limitation as long as it is biocompatible and biodegradable temperature sensitive polymer, but is based on a PEO-PPO (or PBO) -PEO block copolymer as a basic unit and connected by a dicarboxyl linker. Block copolymers can preferably be used. Here, the block copolymer means a basic unit in which a hydrophilic block, a polyethylene oxide (PEO) block is connected to a hydrophobic block, a polypropylene oxide (PPO) or a polybutylene oxide (PBO) block, and then a polyethylene oxide (PEO) block. For example, it may be represented as a PEO-PPO-PEO block copolymer or PEO-PBO-PEO block copolymer. In addition, a multi-block copolymer is a block copolymer in which a polyethylene oxide (PEO) block, which is a hydrophilic block, is connected to a polypropylene oxide (PPO) or polybutylene oxide (PBO) block, which is a hydrophobic block, and then connected to a polyethylene oxide (PEO) block. As a basic unit, it means a polymer in which two or more block copolymers are connected by a dicarboxyl linker.

The same or different two or more block copolymers selected from the group consisting of such a PEO-PPO-PEO block copolymer and a PEO-PBO-PEO block copolymer are linked with a dicarboxyl linker, and the multiblocked multiblock copolymer is a temperature sensitive polymer. As the sol-gel phase transition temperature is lower than the body temperature, it exists in the gel state in the body temperature range. In addition, since the weight average molecular weight is relatively large, the retention period may be improved by several days or more in a low concentration aqueous polymer solution. In addition, it is water-soluble and is decomposed in linkages in vivo, it is characterized in that it can be easily degraded and absorbed and excreted in vivo.

The dicarboxyl linker used in the linkage is pharmacologically acceptable, and includes oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimeline acid, subberic acid, azelaic acid, sebacic acid, and dodecadiic acid. C1-C12 alkyl dicarboxylic acid; C1-C10 unsaturated dicarboxylic acids, such as fumaric acid and maleic acid; And it may be at least one dicarboxylic acid selected from the group consisting of C6 ~ C10 allyl dicarboxylic acid, such as phthalic acid, terephthalic acid, among these, C1 ~ C10 alkyl dicarboxylic acid is preferred.

Since such a dicarboxyl linker is linked by an ester bond to the hydroxy group at both ends of the block copolymer, the ester bond is easily dissolved by carboxylic acid and PEO-PPO (or PBO)-in aqueous solution and by the action of an enzyme in vivo. May be decomposed into PEO block copolymers. This property imparts water solubility to the multiblock copolymer. At this time, the decomposed PEO-PPO (or PBO) -PEO block copolymer has an advantage of acting as a surfactant to exhibit a secondary anti-adhesion effect. Therefore, the multi-block copolymer is hydrolyzed in the body and decomposed into a block copolymer having a low molecular weight and a dicarboxylic acid, so that even when a high molecular weight polymer is decomposed, the block copolymer is continuously released to obtain a continuous anti-adhesion effect. do.

The multiblock copolymer described above may have a structure represented by Formula 1:

[Formula 1]

M-X-O- [PEO-Y-PEO-C (= O) -R-C (= O) -O] n-PEO-Y'-PEO-O-X-M

Where

PEO is polyethylene oxide,

Y and Y 'are each independently polypropylene oxide (PPO), polybutylene oxide (PBO), or a composite of PPO and PBO,

X is -H, or-anion group,

n is an integer between 1 and 100,

R is-(CH ₂ ) m- or Cm 'aryl,

m is an integer between 0 and 20, m 'is an integer between 6 and 12,

When X is not H, M is H, a monovalent or divalent cation group, and

M is not present when X is H.

Wherein X is the anion resulting from -SO ₃ ^-, -PO ₃ ^{2 -} and -C (= O) -RC (= O) -O - may be an anion group selected from the group consisting of.

In addition, in the above formula, the cationic group M may be a monovalent or divalent cationic group selected from the group consisting of Li, Na, K, Ag, Au, Ca, Mg, Zn, Fe, Cu, Co, and Ni.

In the above-described embodiments, the block copolymer PEO-PPO (or PBO) -PEO, which is the basic unit of the multi-block copolymer, may be a commercially available poloxamer. Poloxamer is a triblock copolymer compound in which a hydrophilic block polyethylene oxide (PEO) and a hydrophobic block polypropylene oxide (PPO) are connected by ether bonds in the form of PEO-PPO-PEO. The weight average molecular weight of the poloxamer polymer is 1,000-20,000 Daltons, and it is a block copolymer in which both terminal groups are hydroxyl groups. The block copolymer may include poloxamer ^{188 (Pluronic ® F-68)} , poloxamer 407 (Pluronic ^® F-127) can be preferably used.

Meanwhile, in the above-described embodiment, the temperature sensitive polymer is a multiblock copolymer in which poloxamer 407 or poloxamer 188, which is a block copolymer, is connected to an ester bond by dicarboxylic acid, and poloxamer 407 may be more preferably used. At this time, the temperature-sensitive polymer has a weight average molecular weight of 50,000 to 500,000 daltons. It also has the property of gelling at 15 ° C. or higher in aqueous solution.

In the above-described embodiment, the poloxamer may be used without purification or purified, and when purified, it is easy to prepare a high molecular weight polymer. Purification of the poloxamer may be purified by dissolving in methylene chloride and precipitating in hexane or by layer separation in an n-propanol / H 2 O solvent.

According to one embodiment of the present invention, the multi-block copolymer may be prepared by the following method. First, dicarboxylic acid dichloride diluted in a block copolymer of PEO-PPO (or PBO) -PEO is added to an appropriate amount according to the type of terminal groups present at both ends of the polymer, and then a coupling reaction is performed for a predetermined time. A product with increased molecular weight is obtained. The obtained product can be further purified by adding to ether to precipitate the polymer and dissolving it in methanol, and then adding ether to precipitate the polymer. The sock terminal of the multiblock copolymer can be bonded to the precipitated polymer by any known method.

Since the multi-block copolymer has a sol-gel phase transition temperature in an aqueous solution of 0.1 to 40% by weight, the gel may be maintained in the body temperature range because the sol-gel phase transition temperature is in the range of 10 to 35% by weight. Therefore, the temperature-sensitive polymer-containing layer from which the solvent is removed is gelated by body temperature while being dissolved in the body. Therefore, when applied to the wound site, it can be attached to the target site for 7 days or more, and thus has the advantage of remaining in the body for a sufficient period of time. In general, considering that the period of adhesion between organs and / or tissues caused by various operations is within 7 days after surgery, the fact that the multi-block copolymer may stay in a desired position in the body for 7 days or more may prevent adhesion. Is a very important characteristic.

As a solvent capable of dissolving the multi-block copolymer, distilled water, water for injection, physiological saline, organic solvents such as methylene chloride, acetone, ethyl acetate, 0.1 to 50% by weight of an aqueous alcohol solution, natural celiac solution and natural celiac solution One selected from the group consisting of artificial peritoneal fluid and the like having a composition may be used. Examples of the alcohol include straight or branched chain alcohols having 1 to 4 carbon atoms, such as ethanol; Glycols such as 1,2-propylene glycol, glycerol, polyethylene glycol 300 or polyethylene glycol 400 can be used.

Such a multi-block copolymer may consist only of a single substance of PEO-PPO-PEO or PEO-PBO-PEO block copolymer and does not need to contain other active ingredients. In addition, it is decomposed into a monoclonal PEO-PPO-PEO or PEO-PBO-PEO block copolymer and a linker dicarboxylic acid by temperature, pH conditions or the action of an enzyme in vivo, and the degradation product is another anti-adhesion mechanism. It is an important feature that it works.

Such multiblock copolymers may further contain drugs with independent pharmacological effects. Such drugs may be one that modulates the gelling properties of the temperature sensitive polymer or acts as an active ingredient in wound healing. Such drugs may include antithrombotic agents such as heparin or tissue plasminogen activators, aspirin, ibuprofen, ketoprofen or other nonsteroidal anti-inflammatory drugs, hormone chemostatic agents, analgesics or anesthetics .

The polyethylene oxide block in the multiblock copolymer is composed of ethylene oxide units having a number of units from about 2 to 2000, preferably from about 5 to 500, more preferably from about 80 to 120. In Formula 1, the number of units of each ethylene oxide constituting two PEO blocks may be the same or different. The number of units of propylene oxide or butylene oxide in the polypropylene oxide or polybutylene oxide block is in the range of 2 to 2000, preferably about 20 to 500, and more preferably about 30 to 250.

In order to exhibit the optimum anti-adhesion effect of the multi-block copolymer, the unit ratio of PEO and PPO (or PBO) in the PEO-PPO (or PBO) -PEO block portion is 0.2: 1 to 40: 1, preferably 1: 1 to 7.5: 1, and more preferably 1: 1 to 5: 1, wherein the PEO block is 10 to 85% by weight of the PEO-PPO (or PEO) -PBO unit, preferably 40 to 85 Included in weight percent.

The multi-block copolymer is a 1: 1 to 1: 3, preferably 1: 1 to 1: PEO-PPO (or PBO) -PEO block copolymer and a dicarboxylic acid linker in order to exhibit an optimal anti-adhesion effect. It is preferable to include in molar ratio of 2. In order to obtain an optimal anti-adhesion effect, all molecules of the PEO-PPO (or PBO) -PEO block copolymer and the dicarboxylic acid linker should participate in the reaction to form a multi-block copolymer free of unreacted materials. To this end, in the reaction of the PEO-PPO (or PBO) -PEO block copolymer with the dicarboxylic acid linker, an excess of dicarboxylic acid linker must be introduced to react all the PEO-PPO (or PBO) -PEO block copolymers. The molar ratio of the PEO-PPO (or PBO) -PEO block copolymer and the dicarboxylic acid linker in the reaction should be 1: 1 to 1: 3, preferably 1: 1 to 1: 2 as described above. In addition, when an excessive amount of dicarboxylic acid linker is added at a time, a non-uniform multiblock copolymer is produced. Therefore, an excessive amount of dicarboxylic acid linker is divided into two or more steps or slowly added in small amounts throughout the reaction time. .

In addition, the temperature sensitive polymer-containing layer including the multi-block copolymer preferably has a thickness of 50 to 2000 µm, more preferably 100 to 1000 µm.

In addition, the temperature sensitive polymer-containing layer including the multi-block copolymer is preferably included in 10 to 90% by weight based on the entire surgical mesh composite.

When the thickness or weight of the temperature-sensitive polymer-containing layer is smaller than the above range compared to the entire surgical mesh composite, it may be difficult to expect a sufficient anti-adhesion effect because the temperature-sensitive polymer-containing layer is too thin or too small. On the other hand, if the thickness or weight of the temperature sensitive polymer-containing layer is larger than the above range, the flexibility of the surgical mesh composite becomes low, making it difficult to position the surgical mesh complex at the surgical site during surgery, or foreign body feelings may remain due to the temperature sensitive polymer-containing layer after surgery. have.

The temperature sensitive polymer-containing layer and the surgical mesh layer may be adhered without using an adhesive by the thermal bonding or freezing bonding method described below. The surgical mesh composite thus prepared is capable of acting as an anti-adhesion film by gelation by body temperature of the biocompatible and bioabsorbable temperature-sensitive polymer-containing layer together with the basic function as a mesh. In addition, the temperature-sensitive polymer-containing layer may be decomposed into a low molecular weight surfactant and a bioabsorbable monomolecular substance in the body as time passes, and the product absorbed or decomposed in the body may secondaryly prevent adhesion.

Further, according to another embodiment of the present invention, there is provided a surgical mesh composite having an anti-adhesion function further comprising a biodegradable adhesive polymer layer between the surgical mesh layer and the temperature sensitive polymer-containing layer according to the above-described embodiment. . Specifically, the surgical mesh layer; Biodegradable adhesive polymer layer; And it may be provided with a surgical mesh composite having a temperature-sensitive polymer-containing layer is sequentially laminated to adhere 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 preferably has a thickness of 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.

The temperature sensitive polymer containing layer is preferably 50 to 2000 ㎛ and 100 to 1000 ㎛ More preferably. In addition, the temperature-sensitive polymer-containing layer is preferably included in 10 to 90% by weight relative to the 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 temperature sensitive polymer layer and the surgical mesh layer can be more strongly bonded by the biodegradable adhesive polymer layer, the adhesion between the layers is maintained for a long time after the application in the body can further improve the anti-adhesion efficacy. Each layer may be bonded by a thermal bonding or freezing bonding method described below.

In addition, according to another embodiment of the present invention, the temperature sensitive polymer-containing layer according to the above-described embodiment may be a mixture layer in which the biodegradable adhesive polymer is mixed with the temperature sensitive polymer. Specifically, the surgical mesh layer; And a mixture layer in which a biodegradable adhesive polymer is mixed with a temperature sensitive polymer, and the surgical mesh layer and the mixture layer provide a surgical mesh composite having an adhesion preventing function that is adhered thereto.

The temperature sensitive polymer and the biodegradable adhesive polymer is preferably mixed in a weight ratio of 1: 0.1 to 1: 2. When the weight ratio is not 1: 0.1, the effect of improving the adhesion with the surgical mesh layer is not obtained, and when the weight ratio is larger than 1: 2, the flexibility of the surgical mesh composite is very low, and thus ease of use during surgery.

The surgical mesh layer preferably has a thickness of 500 to 700 μm, and preferably 20 to 99% of the total thickness of the surgical mesh composite. In addition, the surgical mesh layer is preferably included in 10 to 90% by weight relative to the entire surgical mesh composite.

The mixture layer in which the biodegradable adhesive polymer is mixed with the temperature sensitive polymer has a thickness of 50 μm to 2000 μm. Is preferably from 100 to 1000 μm More preferably. The mixture layer is preferably included in 10 to 90% by weight relative to the total surgical mesh composite.

The mixture layer and surgical mesh layer in which the biodegradable adhesive polymer is mixed with the temperature sensitive polymer may be more strongly bonded by the biodegradable adhesive polymer, and thus the adhesion between the layers is maintained for a long time after application in the body, thereby further improving the anti-adhesion effect. Can be. Each layer may be bonded by a thermal bonding or freezing bonding method described below.

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 liquid phase temperature sensitive polymer containing layer; And c) there is provided a method for producing a surgical mesh composite having an anti-adhesion function comprising the step of laminating and bonding the surgical mesh layer and the polymer-containing layer.

Hereinafter, each step will be described in detail.

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

Next, b) providing a liquid phase temperature sensitive polymer containing layer. The temperature sensitive polymer-containing layer may be prepared by dissolving the polymer in an organic solvent such as methylene chloride, acetone, ethyl acetate, etc. at 0.1 to 40% by weight, and then applying the film to a shallow rectangular or circular container to prepare a film type temperature sensitive polymer layer. have.

Alternatively, the temperature-sensitive polymer may be dissolved in an aqueous solution to prepare a polymer layer in the form of a film by preparing an aqueous solution containing 1 to 20 wt%. At this time, if the temperature-sensitive polymer is contained below the concentration, the film is too thin and lacks strength to have morphological stability. If the concentration is exceeded, the film is too thick and lacks flexibility, which makes it difficult to handle during surgery.

Next, in step c), the liquid temperature-sensitive polymer-containing layer may be dried, the dried polymer-containing layer and the surgical mesh layer may be laminated, and thermally bonded to prepare a surgical mesh composite.

The polymer solution may be dried by lyophilization or solvent casting, and the dried polymer-containing layer may be in the form of a sheet, a film, a sponge, or the like.

The thermal bonding method, the surgical mesh and the temperature-sensitive polymer layer is bonded in a hot plate heated to 50 ℃ or more and 200 ℃ or less at a pressure of 1 to 200 psi for 1 second to 60 seconds to operate the two-layer structure having an anti-adhesion function A dragon mesh composite can be obtained.

Alternatively, in step c), the surgical mesh may be laminated on the liquid temperature sensitive polymer-containing layer and then adhered through a lyophilization method. Specifically, the temperature sensitive polymer solution is applied to a shallow rectangular or circular container and carefully placed on the surface of the aqueous solution so as not to sink the surgical mesh prepared as described above. Thereafter, frozen at -70 ° C for about 24 hours and freeze-dried for 3 days in a vacuum state to obtain a two-layered mesh composite having a polymer-containing layer and a surgical mesh layer bonded thereto.

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 A manufacturing method is provided, which comprises laminating a layer between a surgical mesh layer and a temperature sensitive polymer containing layer and then adhering. That is, specifically, a) providing a surgical mesh layer; b-1) providing a liquid phase temperature sensitive polymer containing layer; b-2) providing a biodegradable adhesive polymer layer; And c) drying the liquid temperature sensitive polymer-containing layer, and laminating and bonding the surgical mesh, the biodegradable adhesive polymer layer, and the dried temperature sensitive polymer layer in order. It is provided a method of manufacturing. Bonding in the above step can be carried out by a method of thermal bonding.

The biodegradable adhesive polymer layer may be in the form of a biodegradable adhesive film, the polymer is dissolved in an organic solvent such as methylene chloride, acetone, ethyl acetate in 1 to 20% by weight and dried at room temperature in a shallow rectangular or circular container You can get it.

Thereafter, the surgical mesh layer, the biodegradable adhesive polymer in the form of a film, and the temperature sensitive polymer-containing layer were heat-bonded for 1 to 60 seconds at a pressure of 1 to 200 psi on a hotplate heated to 50 ° C to 200 ° C. A surgical mesh composite of a layer structure can be obtained.

In addition, according to another embodiment of the present invention, the temperature-sensitive polymer-containing layer in step c) according to the above-described embodiment is a surgery having an anti-adhesion function which is a layer containing a mixture of biodegradable adhesive polymer mixed with the temperature sensitive polymer A method for producing a mesh composite for use is provided. Specifically, a) providing a surgical mesh layer; b-1) providing a liquid phase temperature sensitive polymer containing layer; b-2) mixing the liquid temperature sensitive polymer-containing layer and a biodegradable adhesive polymer to provide a polymer mixture layer; And c) there is provided a method for producing a surgical mesh composite having an anti-adhesion function comprising the step of laminating and bonding the surgical mesh layer and the polymer mixture layer. Bonding in the above step may be carried out by a method of freeze bonding.

According to another embodiment of the present invention, a) providing a surgical mesh; b-1) providing a liquid phase temperature sensitive polymer containing layer; b-2) mixing the liquid temperature sensitive polymer-containing layer and a biodegradable adhesive polymer to provide a polymer mixture layer; And c) drying the polymer mixture layer, and laminating and bonding the surgical mesh and the dried polymer mixture layer to provide a surgical mesh composite having an anti-adhesion function. Bonding in the above step can be carried out by a method of thermal bonding.

The step of providing the mixed layer will be described. After dissolving the biodegradable adhesive polymer described above in an organic solvent such as methylene chloride, acetone or ethyl acetate at 1 to 20% by weight, the temperature sensitive polymer is added to the solution at a concentration of 1 to 20% by weight and dissolved. To prepare a mixture. The mixture may then be dried in a shallow rectangular or circular container to obtain a mixture layer consisting of a mixture of temperature sensitive polymer 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 surgery, the polymer layer to prevent adhesion is quickly absorbed and excreted in the body, The mesh can be maintained to prevent recurrence of hernia surgery.

The mesh composite of the present invention has excellent flexibility and shape safety and is easy to operate during surgery, and has sufficient physical strength to withstand the pressure in the abdominal cavity after the surgery. In addition, the temperature-sensitive polymer layer used is water-soluble but gelled by body temperature to remain safely in the body for a certain period of time, as well as biocompatibility that the product is easily absorbed and excreted upon decomposition in the body. In addition, the material generated during the decomposition process acts as a surfactant to give a synergistic effect on the prevention of adhesion and to exhibit the effect of preventing the adhesion for a long time.

1 illustrates a mesh composite having a two-layer structure including a surgical mesh layer and a temperature sensitive polymer layer according to an embodiment of the present invention.
Figure 2 shows a three-layer mesh composite bonded to the surgical mesh layer and the temperature-sensitive polymer layer in the form of a film via 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 3

Heat-bonded two-layered surgical mesh composites were prepared and their anti-adhesion efficacy was evaluated. The two-layered surgical mesh composite includes a surgical mesh layer 11 and a temperature sensitive and biocompatible polymer-containing layer 12, as shown in FIG.

10 g of Poloxamer 407 (Pluronic ^® F-127, BASF, Molecular Weight: 12500 Daltons, PEO: PPO = 101: 56) was placed in a 100 ml 1-neck round bottom flask, heated in an oil bath at 120˚C, Water contained in the polymer was removed for 2 hours. The pressure was released and the reaction temperature was set to 100 ° C. while flowing nitrogen, and 100 ml of acetonitrile was added to the flask. After the dean stark and the cooler were installed in the reaction flask, 20 ml of the distilled acetonitrile was removed through the dean stark to completely remove the water in the reactants, and then 1 equivalent of succinyl dichloride was added to the reservoir of the dean stark apparatus. The reaction was time. After 24 hours, 96 ul of succinyl chloride was added to the reservoir of the dean stark apparatus in order to replace the terminal group of the synthesized poloxamer oligomer with a carboxyl group and reacted for 24 hours. The synthesized poloxamer oligomer was precipitated in 1 L of diethyl ether and filtered to give the product. The product thus obtained was again dissolved in 16 ml of methanol, precipitated and filtered through diethyl ether, and purified twice. The resultant was vacuum dried to obtain a poloxamer oligomer having a narrow molecular weight distribution. The average molecular weight of the obtained temperature sensitive polymer was 130,000 Daltons.

A temperature sensitive polymer having a molecular weight of 130,000 Daltons was dissolved in ultrapure water at concentrations of 5, 10, and 15% by weight, respectively, to prepare 100 g of temperature sensitive polymer aqueous solution, which was then prepared in a 150 mm × 400 mm × 30 mm rectangular container. Lyophilized under the same conditions as in Table 1 to prepare a sponge-like layer.

Freeze Drying Conditions Temperature [℃] Temperature rising rate
[° C / min.] Retention time
[hr.] -40 10 ↓ 0.1 3.3 -20 10 ↓ 0.1 3.3 0 10 ↓ 0.1 4.2 25 20

The temperature sensitive polymer-containing layer was laminated with a 100 mm × 150 mm PROFLEX ^® surgical mesh (Samyang Corp., Korea) on a hotplate heated to 80 ° C., and then the mesh and layer were heated by applying a pressure of 10 psi for 1 second. It adhere | attached (Mini Test Press 10 / MP-WCL from Toyo Seiki, Japan). After 1 second, the applied pressure was removed immediately and cooled at room temperature for 30 minutes to obtain a surgical mesh composite having a two-layer structure of a mesh layer and a temperature sensitive polymer-containing layer and having a thickness of about 600 μm and a size of 100 mm × 150 mm. At this time, the thickness of the mesh layer was 500 µm and the temperature sensitive polymer-containing layer was 100 µm.

Example  4 to 7

The same temperature sensitive polymers as Examples 1 to 3 were dissolved in methylene chloride solvent at concentrations of 5, 10, 15 and 20% by weight, respectively, to prepare 100 g of temperature sensitive polymer solution, which was then applied to a rectangular container as 1000 μm. And dried at room temperature for 6 hours to prepare a layer in the form of a film.

The same procedure as in the thermal bonding method of Examples 1 to 3 was performed to obtain a surgical mesh composite having a two-layer structure of a mesh and a temperature sensitive polymer layer having a thickness of about 600 μm and a size of 100 mm × 150 mm. In this case, the thickness of the mesh layer was 500 μm, and the temperature sensitive and biocompatible polymer-containing layer was 100 μm.

Experimental Example 1 Anti-adhesion Effect Experiment

In order to determine the anti-adhesion effect of the thermally bonded two-layered surgical mesh composite prepared in Examples 1 to 7 above, the degree of adhesion was confirmed through animal experiments using SD rats (Orient, Korea). Rats used were 6 weeks of age or older, and were reared separately in an environment in which a temperature of 16 to 22% and a relative humidity of 50 to 70% were maintained. The abdomen of the anesthetized rat is incised to create an artificial hernia situation, and the intestine in contact with the hernia site is cut to the extent that the epidermis is slightly peeled off, and the sutured abdominal wall is covered with the surgical mesh complex prepared above. It was. Seven days after the procedure, the state of treatment of hernia was maintained and the degree of adhesion of the tissue was measured. In this case, the degree of adhesion prevention effect was compared using the suture with a mesh without the temperature sensitive polymer-containing layer for adhesion prevention as a control, and the results are shown in Table 2.

Evaluation of Anti-adhesion Efficacy of Heat-bonded Two-layer Surgical Mesh Complexes number Type of adhesion prevention layer density
[weight%] Adhesion Prevention [%] Population [mari] Procedure population Cohesion Population Example 1 Sponge form layer 5 40 10 6 Example 2 10 100 0 Example 3 15 100 0 Example 4 Film form layer 5 10 9 Example 5 10 60 4 Example 6 15 100 0 Example 7 20 100 0 Control group 0 10

In all embodiments, the healing state of the hernia was maintained, and in the case of the mesh composite in which the sponge-type layer was heat-bonded, adhesion of 100% was prevented at a concentration of 10% or more, In case of 15% or more concentration 100% was prevented. In addition, no residual temperature sensitive polymer layer was observed, indicating that all of the applied multiblock copolymers were absorbed. In the control group using the mesh without the temperature sensitive polymer-containing layer to prevent adhesion, adhesion occurred.

Example  8 to 10

Cryobonded bilayer structured surgical mesh composites were prepared and their anti-adhesion efficacy was evaluated. This two-layered surgical mesh composite includes a surgical mesh layer 11 and a temperature sensitive polymer layer 12 as shown in FIG.

A temperature sensitive polymer having a molecular weight of 130,000 Daltons was dissolved in ultrapure water at concentrations of 5, 10 and 15% by weight, respectively, to prepare a 100g temperature sensitive polymer aqueous solution, and then applied to a rectangular container made of fluororesin having a size of 150 mm × 400 mm × 30 mm. . Place the 100 mm × 150 mm PROFLEX ^® surgical mesh (Samyang Corp., Korea) on the surface of the aqueous solution and lyophilize as it is under the conditions shown in Table 1 above. A layered surgical mesh composite was obtained. In this case, the total thickness of the composite was 650 μm, the mesh layer was 500 μm, and the temperature sensitive polymer containing layer was 150 μm.

Animal experiments were performed on the prepared surgical mesh composite in the same manner as in Experimental Example 1 to compare the degree of healing of the hernia and the degree of anti-adhesion effect, and the results are shown in Table 3.

Evaluation of anti-adhesion efficacy of cryobonded two-layered surgical mesh composite number Type of adhesion prevention layer density
[weight%] Adhesion prevention
[%] Population [mari] Procedure population Cohesion Population Example 8 Sponge form layer 5 30 10 7 Example 9 10 100 0 Example 10 15 100 0 Control group 0 10

In all examples, the healing state of the hernia was maintained, and the anti-adhesion efficacy evaluation resulted in 100% prevention of adhesion when the concentration of the temperature sensitive polymer-containing layer was 10% or more in the case of the freeze-bonded mesh composite. In addition, no residual temperature sensitive polymer-containing layer was observed, indicating that all of the applied multiblock copolymers were absorbed.

Example  11 to 18

A thermal bonded three-layer surgical mesh composite was prepared and its anti-adhesion efficacy was evaluated. The three-layered surgical mesh composite includes a surgical mesh layer 21, a biodegradable adhesive polymer layer 22, and a temperature sensitive polymer-containing layer 23 as shown in FIG. 2.

The sponge-like layer (Examples 11-14) and the film-like layer (Examples 15-18) of the temperature sensitive polymer were prepared under the same conditions as in Examples 1 to 7 but with the polymer concentration as shown in Table 4.

The biodegradable adhesive film dissolves a copolymer of polyglycolide-lactide in a weight average molecular weight of about 100,000 Daltons copolymerized at 3: 7 to 5% by weight in a methylene chloride solvent, and the solution is 150 mm × 400 mm × 30. The polyglycolide-lactide film was prepared by applying a mm-size fluororesin rectangular container and drying at room temperature for 6 hours.

The biodegradable adhesive film thus prepared was placed between the sponge-like film or the film-like layer of the temperature sensitive polymer and the surgical mesh layer, and then applied by applying a pressure of 20 psi for 1 second on a hotplate heated to 100 ° C. The pressure was removed and cooled at room temperature for 30 minutes to obtain a three-layer surgical mesh composite wherein the mesh layer and the temperature sensitive polymer-containing layer were thermally bonded by a polyglycolide-lactide copolymer film. At this time, the total thickness of the composite was 700 μm, the mesh layer was 500 μm, the polymer layer of the biodegradable adhesive film was 50 μm, and the temperature sensitive polymer containing layer was 150 μm.

Animal experiments were performed on the prepared surgical mesh composite in the same manner as in Experimental Example 1 to check the healing state of the hernia and compare the degree of anti-adhesion effect. The results are shown in Table 4.

Evaluation of Anti-adhesion Efficacy of Heat-bonded 3-layer Surgical Mesh Complexes number Type of adhesion prevention layer density
[weight%] Adhesion prevention
[%] Population [mari] Procedure population Cohesion Population Example 11 Sponge form layer One 50 10 5 Example 12 5 70 3 Example 13 10 100 0 Example 14 15 100 0 Example 15 Film form layer 5 80 2 Example 16 10 90 One Example 17 15 100 0 Example 18 20 100 0 Control group 0 10

In all examples, the healing state of hernias was maintained, and as a result of evaluation of anti-adhesion efficacy, in the mesh composite bonded with a sponge-type layer, adhesion of 100% at a temperature-sensitive polymer layer concentration of 10% or more was prevented. In the case of the mesh composite to which the adhesion was prevented 100% adhesion at a concentration of 15% or more. Meanwhile, no residual temperature sensitive polymer-containing layer was observed, indicating that all of the applied multiblock copolymers were absorbed.

Example  19 to 22

A surgical mesh composite was prepared using a mixture of temperature sensitive polymer and biodegradable adhesive polymer and its anti-adhesion efficacy was evaluated.

The biodegradable adhesive polymer (molecular weight: 100,000 Daltons) in which polyglycolic acid and polylactide were copolymerized at a ratio of 3: 7 was dissolved in 1, 5, 10, 15% by weight in an methylene chloride organic solvent.

The same temperature sensitive polymer as in Examples 1 to 3 was added to the biodegradable adhesive polymer solution at a concentration of 1, 5, 10, 15% by weight and dissolved to prepare a mixture. The mixture was filtered and then applied to a rectangular container made of fluororesin having a size of 150 mm × 400 mm × 30 mm and dried at room temperature for 12 hours to obtain a film-form mixture layer in which a temperature sensitive polymer and a biodegradable adhesive were mixed. After laminating the mixture layer and the mesh layer, a pressure of 10 psi was applied to the hot plate heated at 80 ° C. for 2 seconds to bond the same. The pressure was removed and cooled at room temperature for 30 minutes to prepare a surgical mesh composite having a two-layer structure in which the surgical mesh layer and the mixture layer were thermally bonded. In this case, the total thickness of the composite was 670 μm, the mesh layer was 500 μm, and the mixture layer of the temperature sensitive polymer and the biodegradable polymer was 170 μm.

Animal experiments were performed on the prepared surgical mesh composite in the same manner as in Experimental Example 1 to check the healing state of the hernia, and to compare the degree of anti-adhesion effect.

Evaluation of anti-adhesion efficacy of surgical mesh complexes number Type of adhesion prevention layer Concentration [% by weight] Adhesion Prevention [%] Population [mari] Procedure population Cohesion Population Example 19 Mixed film form layer One 40 10 6 Example 20 5 60 4 Example 21 10 100 0 Example 22 15 100 0 Control group 0 10

In all examples, the healing state of hernia was maintained, and the anti-adhesion efficacy evaluation resulted in 100% prevention of adhesion at a concentration of 10% or more in the case of the heat-bonded two-layered surgical mesh complex. No residual temperature sensitive polymer layer was observed, indicating that all applied multiblock copolymers were absorbed.

Experimental Example 2 Comparison of Adhesion Between Mesh and Polymer Layer

Heat-bonded two-layered surgical mesh composite prepared in Examples 1 to 7 above, freeze-bonded two-layered surgical mesh composite prepared in Examples 8 to 10, heat-bonded prepared in Examples 11 to 18 In order to investigate the adhesion between the mesh and the polymer layer of the surgical mesh composite using a mixture of the three-layered surgical mesh composite, the temperature sensitive polymer and the biodegradable adhesive polymer prepared in Examples 19 to 22, the following experiment was conducted. .

The surgical mesh composites, PROCEED ™ surgical mesh (Ethicon, USA), and PARIETENE ™ composite (Tyco Healthcare, USA) were cut into 1 cm x 15 cm and the mesh and anti-adhesion layers were cut to about 5 cm at one end of the sample. Separate it into Y shape. Tensile strength generated by pulling the separated mesh layer and anti-adhesion layer of this sample into the grip of tensile strength device (Hounsfield, H5KT, UK), respectively, and pulling it until the moving distance is 100mm at the speed of 10mm / min. The peaks of the peaks were averaged and measured by the adhesion between the mesh layer and the polymer layer. Table 6 shows a comparison of the measured values for each surgical mesh complex.

Comparative Evaluation of Adhesion Between Mesh and Polymer Layer in Surgical Mesh Composites number Concentration [% by weight] Adhesion [kgf] PROCEED ™
Surgical Mesh - 0.215 PARIETENE ™
Composite Not measurable Example 2 10 0.293 Example 6 0.27 Example 9 0.265 Example 13 0.337 Example 17 0.328 Example 21 0.304

In the case of PARIETENE ™ Composite, the strength of the thin film-like polymer layer was so weak that it could not be broken when it was bitten by the grip of the tensile strength device. All embodiments of the present invention exhibited adhesive strength over existing products. Therefore, when such a surgical mesh complex is inserted into the body it can exert an anti-adhesion effect in the correct position for a longer time.

Claims (24)

Surgical mesh layers; And
A temperature sensitive polymer containing layer,
The surgical mesh layer and the temperature-sensitive polymer-containing layer is a surgical mesh composite having a adhesion prevention function is bonded. 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 the temperature sensitive polymer-containing layer. The method of claim 1,
The temperature sensitive polymer-containing layer is a surgical mesh composite having an anti-adhesion function that is a mixture layer in which a biodegradable adhesive polymer is mixed with a temperature sensitive polymer. The method of claim 1,
The temperature-sensitive polymer is a surgical mesh composite having an anti-adhesion function in which the sol-gel phase transition temperature is in the range of 10 to 35 ℃ in an aqueous solution of 0.1 to 40% by weight. The method of claim 1,
The temperature sensitive polymer is a polyethylene oxide (PEO) -polypropylene oxide (PPO) -polyethylene oxide (PEO) block copolymer and polyethylene oxide (PEO) -polybutylene oxide (PBO) -polyethylene oxide (PEO) block copolymer Surgical mesh composite having an anti-adhesion function, wherein the at least one block copolymer selected from the group consisting of is a multiblock copolymer linked by a dicarboxyl linker. 6. The method of claim 5,
The block copolymer is a surgical mesh composite having a weight average molecular weight of 1,000 to 20,000 Daltons anti-adhesion function. 6. The method of claim 5,
The multi-block copolymer is a surgical mesh composite having a weight average molecular weight of 50,000 to 500,000 Daltons anti-adhesion function. 6. The method of claim 5,
Surgical mesh composite having an anti-adhesion function wherein the block copolymer is poloxamer. 6. The method of claim 5,
The dicarboxyl linker is selected from the group consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimeline acid, subberic acid, azelaic acid, sebacic acid, dodecanedioic acid, fumaric acid, maleic acid, phthalic acid and terephthalic acid Surgical mesh composite having at least one anti-adhesion function. The method of claim 1,
The temperature-sensitive polymer-containing layer is a surgical mesh composite having an anti-adhesion function, which comprises 10 to 90% by weight relative to the entire surgical mesh composite. The method of claim 1,
The temperature sensitive polymer-containing layer is a surgical mesh composite having an anti-adhesion function in the form of a sponge or a film. The method of claim 2,
The biodegradable adhesive polymer is glycolide (glycolide), glycolic acid (glycolic acid), lactide (lactide), lactic acid (lactic acid), caprolactone (ε-caprolactone), dioxanone (ρ-dioxanone), trimethylene 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 carbonate (trimethylene carbonate), polyanhydride and polyhydroxyalkanoate. The method of claim 2,
The temperature-sensitive polymer and the biodegradable adhesive polymer is a surgical mesh composite having an anti-adhesion function that is mixed in a weight ratio of 1: 0.1 to 1: 2. The method of claim 3, wherein
The mixture 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 liquid phase temperature sensitive polymer containing 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 temperature sensitive polymer-containing layer. 16. The method of claim 15,
The step c) is a method of producing a surgical mesh composite having a function of preventing adhesion after drying the liquid temperature-sensitive polymer-containing layer, the dried polymer-containing layer and the surgical mesh layer laminated. 16. The method of claim 15,
In the step c), the method of manufacturing a surgical mesh composite having a function of preventing adhesion by laminating a liquid-temperature-sensitive polymer-containing layer on the surgical mesh layer and lyophilized. 16. The method of claim 15,
Providing a biodegradable adhesive polymer layer after step b),
C) drying the liquid temperature sensitive polymer-containing layer in the step of adhering, and laminating the biodegradable adhesive polymer layer between the surgical mesh layer and the dried temperature-sensitive polymer-containing layer and thermally adhering; Method for producing a surgical mesh composite having a function. 19. The method of claim 18,
The step of providing the biodegradable adhesive polymer layer is that the copolymerization of polyglycolic acid and polylactide in a weight ratio of 1: 9 to 9: 1 is dissolved in an organic solvent in 1 to 20% by weight and then dried to prevent adhesion Method for producing a surgical mesh composite having a. 16. The method of claim 15,
The method of manufacturing a surgical mesh composite having an anti-adhesion function, wherein the temperature sensitive polymer-containing layer is a mixture layer of a temperature sensitive polymer and a biodegradable adhesive polymer in step c). 16. The method of claim 15,
The concentration of the liquid temperature-sensitive polymer-containing layer is 0.1 to 40% by weight of the method for producing a surgical mesh composite having an anti-adhesion function. The method of claim 16 or 18,
The thermal bonding is to prepare a surgical mesh composite having an anti-adhesion function that is thermally bonded to the surgical mesh layer and the temperature-sensitive polymer-containing layer continuously for 1 to 60 seconds on a heating plate of temperature 50 ~ 200 ℃, pressure 1 ~ 200 psi Way. The method of claim 20,
Method for producing a surgical mesh composite having an anti-adhesion function to freeze adhesion by laminating the mixture layer and the surgical mesh of step c). 21. The method of claim 20,
After drying the mixture layer of step c), the method for producing a surgical mesh composite having a function of preventing adhesion by laminating a surgical mesh and the dried mixture layer by heat bonding.

Images