KR20180015415A - A adhesion prevention film - Google Patents

Abstract

The present invention relates to an adhesion prevention film, and more particularly, to an adhesion prevention film, which is manufactured by mixing a composition including polyethylene oxide (PEO) and pectin, and then casting, melt-extruding or blow-molding the resulting mixed composition, thus enhancing adhesion to a mucous membrane. The present invention provides a composition for adhesion prevention, comprising PEO and pectin and being capable of enhancing adhesion to a mucous membrane. Also, the present invention is manufactured by mixing a composition including PEO and pectin, and then casting, melt-extruding or blow-molding the composition, thus providing an adhesion prevention film with excellent mechanical strength, flexibility, adhesion, cytotoxicity, biodegradability, biocompatibility, adhesion prevention characteristics and the like.

Description

A adhesion prevention film < RTI ID = 0.0 >

The present invention relates to an adhesion preventive film, and more particularly, to an adhesion preventive film which is prepared by mixing a composition comprising polyethylene oxide (PEO) and pectin, and then casting, melt extruding or blow molding the mixed composition, To an anti-adhesion film capable of improving adhesion.

In recent years, attempts have been made to apply biodegradable polymers to medical fields such as adhesion preventive films and window epithelium replication.

Adhesion refers to a phenomenon in which a fibrous tissue is excessively formed during the healing process of a wound formed in the abdominal cavity after surgical laparotomy, or the surrounding organs or tissues and the wound are bonded to each other by coagulating the blood by flowing out.

Adhesion causes various aftereffects and secondary illness to the patient, and the tissue in which adhesion occurs can not perform normal activities.

The anti-adhesion agent forms a physical barrier at the site where adhesion is expected and prevents adhesion between the surgical site and normal tissue.

The film form and the gel form are widely used as the antiadhesive agent, but the film form is difficult to apply to the complicated shape surgical site, and the gel form is decomposed or absorbed before the wound heals, resulting in low efficacy as an anti-adhesion agent.

In order to solve these problems, various anti-adhesion agents have been actively developed.

Korean Patent Laid-Open No. 10-2007-0010572 discloses a method for preparing a biodegradable polymer, comprising the steps of: a) dissolving a biocompatible polymer and a polyhydric alcohol in distilled water, and then freezing and thawing the biocompatible polymer aqueous solution to form a pre- b) coating and drying a polyvinyl alcohol aqueous solution on a polymer film, a nonwoven fabric or a fiber; c) attaching and pressing the pre-hydrated gel onto the polyvinyl alcohol-coated polymer film, nonwoven fabric or fiber; And d) packaging the compressed hydrogel by using a packaging material, and irradiating the compressed gel with radiation.

Also, Korean Patent No. 10-0552954 discloses a composition for preventing or treating inflammation, which comprises chondroitin sulfone, dermatan sulfide, keratan sulfide, heparan sulfate, hyaluronic acid, collagen and its degradation products such as gelatin, elastin and fibrin And a PEG-PPG-PEG block copolymer having a molecular weight of 5,000 Da or more and 100,000 Da or less and a PEG content of 50 to 90% by weight, wherein the PEG-PPG-PEG block copolymer is selected from the group consisting of graft copolymers, Wherein the polymer is chemically bonded by a chemical bond selected from the group consisting of a random copolymer, a cross-copolymer, a cross-linking, and a partially interpolated polymer, wherein the bio-derived polymer comprises 0.5 wt% to 50 wt% PPG-PEG block copolymer is contained in an amount of 50 to 99.5% by weight and is swollen when absorbed in the body and gelled by body temperature A film for preventing adhesion is disclosed.

On the other hand, Japanese Patent Laid-Open No. 09-263671 discloses a method for producing a hydrogel by forming and drying an aqueous solution of polyvinyl alcohol, heat-treating it, impregnating it with an aqueous solution to expand it, and irradiating it with radiation, wherein the polyvinyl alcohol aqueous solution and / Or an impregnated aqueous solution after the heat treatment, at least one polymer selected from polyvinyl alcohol, polyvinyl pyrrolidone, methyl vinyl ether anhydride copolymer and isobutylene maleic anhydride copolymer, Discloses a method for producing a gel.

However, since the film disclosed in the above document has low adhesion to the mucous membrane, the film does not remain on the wound for a long time, and therefore, the adhesion prevention property is poor.

Korean Patent Publication No. 10-2007-0010572A Korean Patent Registration No. 10-0552954B1 Japanese Patent Application Laid-Open No. 09-263671A

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made to solve the above problems occurring in the prior art, and it is an object of the present invention to provide a composition for preventing adhesion which comprises polyethylene oxide (PEO) and pectin and can improve stickiness to mucosa.

The present invention also relates to a process for preparing a composition comprising mixing a composition comprising polyethylene oxide (PEO) and pectin, and then casting, melt extruding or blow molding the mixture composition to obtain a composition having mechanical strength, flexibility, tackiness, An anti-adhesion property, and an anti-adhesion property.

In order to achieve the above object, the present invention provides a composition for preventing adhesion, which comprises polyethylene oxide (PEO) and pectin and can improve the stickiness to mucous membrane.

In one embodiment of the present invention, the weight ratio of the polyethylene oxide to the pectin is 80 to 98: 2 to 20.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide derivative, wherein the polyethylene oxide derivative is characterized in that the terminal hydroxyl group of the polyethylene oxide is converted to a carboxyl group.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide-polylactic acid copolymer.

The present invention also provides an adhesion preventive film which is prepared by mixing a composition comprising polyethylene oxide (PEO) and pectin, and then casting, melt extruding or blow molding the mixed composition, and improving the stickiness to the mucosa do.

In one embodiment of the present invention, the weight ratio of the polyethylene oxide to the pectin is 80 to 98: 2 to 20.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide derivative, wherein the polyethylene oxide derivative is characterized in that the terminal hydroxyl group of the polyethylene oxide is converted to a carboxyl group.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide-polylactic acid copolymer.

The present invention also relates to a method of making a composition comprising mixing a composition comprising polyethylene oxide (PEO) and pectin; And a process for producing a film by casting, melt extrusion or blow molding the mixed composition. The present invention also provides a method for producing an adhesion preventive film capable of improving adhesion to mucous membranes.

In one embodiment of the present invention, the weight ratio of the polyethylene oxide to the pectin is 80 to 98: 2 to 20.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide derivative, wherein the polyethylene oxide derivative is characterized in that the terminal hydroxyl group of the polyethylene oxide is converted to a carboxyl group.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer.

In one embodiment of the present invention, the composition further comprises a polyethylene oxide-polylactic acid copolymer.

In addition, the present invention is an article comprising the above-mentioned anti-adhesion film, wherein the product is an anti-adhesion film or window epithelium.

The present invention can provide a composition for preventing adhesion which comprises polyethylene oxide (PEO) and pectin and can improve the stickiness to the mucosa.

The present invention also relates to a process for preparing a composition comprising mixing a composition comprising polyethylene oxide (PEO) and pectin, and then casting, melt extruding or blow molding the mixture composition to obtain a composition having mechanical strength, flexibility, tackiness, It is possible to provide an anti-adhesion film excellent in compatibility, anti-adhesion property and the like.

Hereinafter, the present invention will be described in detail based on examples. It is to be understood that the terminology, examples and the like used in the present invention are merely illustrative of the present invention in order to more clearly explain the present invention and to facilitate understanding of the ordinary artisan, and should not be construed as being limited thereto.

Technical terms and scientific terms used in the present invention mean what the person skilled in the art would normally understand unless otherwise defined.

The present invention relates to a composition for preventing adhesion, which comprises polyethylene oxide (PEO) and pectin and which can improve stickiness to mucous membranes.

Although polyethylene oxide is widely used as a material for adhesion preventive membrane due to its excellent biodegradability, mechanical properties and flexibility, it has low adhesion to the mucous membrane and can not remain on the wound surface for a long time when used as a adhesion preventive membrane.

Pectin is a polymer of D-galacturonic acid and contains a large number of carboxyl groups in the molecule. Such carboxyl groups can improve stickiness to mucous membranes and improve anti-adhesion properties.

The weight ratio of polyethylene oxide and pectin is 80 to 98: 2 to 20, preferably 85 to 95: 5 to 15. When the weight ratio is more than 98: 2, the tackiness and adhesion prevention characteristics are deteriorated. When the weight ratio is less than 80:20, the mechanical strength is lowered and side effects such as inflammation reaction may occur.

The weight average molecular weight of the polyethylene oxide is preferably 10,000 to 1,000,000 g / mol. If the weight average molecular weight is out of the above range, the mechanical strength, flexibility, tackiness, and adhesion prevention characteristics of the adhesion preventive film are lowered.

The weight average molecular weight of the pectin is preferably 2,000 to 100,000 g / mol, more preferably 5,000 to 20,000 g / mol. When the molecular weight is less than 2,000 g / mol, the tackiness and adhesion prevention properties are deteriorated. When the molecular weight exceeds 100,000 g / mol, the dispersibility is poor and the workability is deteriorated.

The composition may further comprise a polyethylene oxide derivative, and the polyethylene oxide derivative may improve adhesion to the mucous membrane of the adhesion preventive film.

The polyethylene oxide derivative is characterized in that the terminal hydroxyl group of the polyethylene oxide is converted to a carboxyl group.

The carboxyl group-introduced polyethylene oxide derivative may be prepared by oxidizing polyethylene oxide with an oxidizing agent such as NaClO, KMnO ₄ , K ₂ Cr ₂ O ₇ , H ₂ Cr ₂ O ₇ , H ₂ CrO ₄ , or a mixture of polyethylene oxide and maleic anhydride, And an acid anhydride such as succinic anhydride, or a dicarboxylic acid such as succinic acid or adipic acid.

The polyethylene oxide derivative may be used in an amount of 1 to 10 parts by weight based on 100 parts by weight of the polyethylene oxide. When the content of the polyethylene oxide derivative is less than 1 part by weight, the effect of addition is insignificant. When the amount of the polyethylene oxide derivative is more than 10 parts by weight, do.

  The weight average molecular weight of the polyethylene oxide derivative is 10,000 to 1,000,000 g / mol, preferably 50,000 to 200,000 g / mol. If the molecular weight is less than 10,000 g / mol, the tackiness and adhesion prevention properties are deteriorated, and if it exceeds 1,000,000 g / mol, the mechanical strength is lowered.

The composition may further comprise a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer, and the copolymer may improve adhesion to the mucous membrane of the adhesion preventive film.

The copolymer may be used in an amount of 1 to 10 parts by weight based on 100 parts by weight of the polyethylene oxide. If the amount of the copolymer is less than 1 part by weight, the effect of addition is insignificant. If the amount is more than 10 parts by weight, mechanical strength is lowered.

  The weight average molecular weight of the copolymer is 10,000 to 500,000 g / mol, preferably 50,000 to 200,000 g / mol. When the molecular weight is less than 10,000 g / mol, the tackiness and adhesion prevention characteristics are deteriorated, and when it exceeds 500,000 g / mol, the mechanical strength is lowered.

The composition may further comprise a polyethylene oxide-polylactic acid copolymer, which can improve the biodegradability of the adhesion preventive film and improve the adhesion to the mucosa.

The copolymer may be used in an amount of 1 to 10 parts by weight based on 100 parts by weight of the polyethylene oxide. If the amount of the copolymer is less than 1 part by weight, the effect of addition is insignificant. If the amount is more than 10 parts by weight, mechanical strength is lowered.

  The weight average molecular weight of the copolymer is 10,000 to 200,000 g / mol, preferably 50,000 to 100,000 g / mol. If the molecular weight is less than 10,000 g / mol, the tackiness and adhesion prevention properties are deteriorated, and when it exceeds 200,000 g / mol, the mechanical strength is lowered.

The composition may further comprise a polyethylene oxide-polypropylene oxide copolymer, which can improve the mechanical strength and flexibility of the anti-adhesion film.

The copolymer may be used in an amount of 1 to 10 parts by weight based on 100 parts by weight of the polyethylene oxide. When the content of the copolymer is less than 1 part by weight, the effect of addition is insignificant. When the amount of the copolymer is more than 10 parts by weight, .

  The weight average molecular weight of the copolymer is 10,000 to 200,000 g / mol, preferably 50,000 to 100,000 g / mol. When the molecular weight is less than 10,000 g / mol, the mechanical strength is lowered, and when the molecular weight is more than 200,000 g / mol, the tackiness and the anti-adhesion property are deteriorated.

The composition may further comprise a derivative of a polyethylene oxide-polypropylene oxide copolymer, and the derivative may improve adhesion to the mucous membrane of the adhesion preventive film.

The derivative of the polyethylene oxide-polypropylene oxide copolymer is characterized in that the terminal hydroxyl group of the polyethylene oxide-polypropylene oxide copolymer is converted to a carboxyl group.

The carboxyl group-introduced polyethylene oxide-polypropylene oxide copolymer derivative is prepared by oxidizing the copolymer with an oxidizing agent such as NaClO, KMnO ₄ , K ₂ Cr ₂ O ₇ , H ₂ Cr ₂ O ₇ or H ₂ CrO ₄ Or by reacting the copolymer with an acid anhydride such as maleic anhydride or succinic anhydride or a dicarboxylic acid such as succinic acid or adipic acid.

The amount of the derivative of the copolymer may be 1 to 10 parts by weight based on 100 parts by weight of the polyethylene oxide. If the amount is less than 1 part by weight, the effect of addition is insignificant. If the amount is more than 10 parts by weight, the mechanical strength is lowered.

  The weight average molecular weight of the copolymer derivative is 10,000 to 200,000 g / mol, preferably 50,000 to 100,000 g / mol. If the molecular weight is less than 10,000 g / mol, the tackiness and adhesion prevention properties are deteriorated, and when it exceeds 200,000 g / mol, the mechanical strength is lowered.

In addition, the composition of the present invention may further comprise at least one selected from the group consisting of chitosan, chitin, carboxymethylcellulose, xanthan gum, acacia gum, alginate, pullulan, hyaluronic acid, carrageenan, polycaprolactone, polyurethane, polydioxane, polyalkyl methacrylate, , Polyvinyl pyrrolidone, and the like.

The present invention relates to an adhesion preventive film which is prepared by mixing a composition comprising polyethylene oxide (PEO) and pectin and then casting, melt extruding or blow molding the mixed composition, and improving the stickiness to the mucosa .

The weight ratio of polyethylene oxide and pectin is 80 to 98: 2 to 20, preferably 85 to 95: 5 to 15. When the weight ratio is more than 98: 2, the tackiness and adhesion prevention characteristics are deteriorated. When the weight ratio is less than 80:20, the mechanical strength is lowered and side effects such as inflammation reaction may occur.

The film may further include a polyethylene oxide derivative, and the polyethylene oxide derivative may improve adhesion to the mucous membrane of the anti-adhesion film.

The polyethylene oxide derivative is characterized in that the terminal hydroxyl group of the polyethylene oxide is converted to a carboxyl group.

The polyethylene oxide derivative may be used in an amount of 1 to 10 parts by weight based on 100 parts by weight of the polyethylene oxide. When the content of the polyethylene oxide derivative is less than 1 part by weight, the effect of addition is insignificant. When the amount of the polyethylene oxide derivative is more than 10 parts by weight, do.

  The weight average molecular weight of the polyethylene oxide derivative is 10,000 to 1,000,000 g / mol, preferably 50,000 to 200,000 g / mol. If the molecular weight is less than 10,000 g / mol, the tackiness and adhesion prevention properties are deteriorated, and if it exceeds 1,000,000 g / mol, the mechanical strength is lowered.

The film may further comprise a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer, and the copolymer may improve adhesion to the mucous membrane of the adhesion preventive film.

The film may further include a polyethylene oxide-polylactic acid copolymer, and the copolymer may improve the biodegradability of the anti-adhesion film and improve the adhesion to the mucosa.

The film may further include a polyethylene oxide-polypropylene oxide copolymer, and the copolymer may improve the mechanical strength and flexibility of the anti-adhesion film.

The film may further include a derivative of a polyethylene oxide-polypropylene oxide copolymer, and the derivative may improve adhesion to the mucous membrane of the adhesion preventive film.

The derivative of the polyethylene oxide-polypropylene oxide copolymer is characterized in that the terminal hydroxyl group of the polyethylene oxide-polypropylene oxide copolymer is converted to a carboxyl group.

The present invention relates to a method of making a composition comprising mixing a composition comprising polyethylene oxide (PEO) and pectin; And a process for producing a film by casting, melt extrusion or blow molding of the mixed composition. BACKGROUND OF THE INVENTION

The anti-adhesion film may be prepared by mixing a composition comprising polyethylene oxide and pectin and then casting or mixing a composition containing polyethylene oxide and pectin, followed by pressing or by a conventional method such as melt extrusion or blow molding .

Wherein the composition is selected from the group consisting of a polyethylene oxide derivative, a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer, a polyethylene oxide-polylactic acid copolymer, a polyethylene oxide-polypropylene oxide copolymer and / or a polyethylene oxide- And may further include derivatives of the copolymer.

The thickness of the adhesion preventive film of the present invention is not particularly limited, but is preferably 10 to 1,000 占 퐉.

In addition, the present invention is an article comprising the above-mentioned anti-adhesion film, wherein the product is an anti-adhesion film or window epithelium.

The anti-adhesion film has excellent mechanical strength, flexibility, tackiness, cytotoxicity, biodegradability, biocompatibility, and anti-adhesion characteristics and can be widely used for anti-adhesion film, window epithelium replication and the like.

Hereinafter, the present invention will be described in detail with reference to examples. The following examples are intended to illustrate the practice of the present invention and are not intended to limit the scope of the present invention.

(Example 1) Production of polyethylene oxide / pectin film

The composition was prepared by stirring a polyethylene oxide / pectin aqueous solution (5% w / w) at room temperature for 3 to 4 hours.

The content of polyethylene oxide / pectin was adjusted to 90/10 (w / w).

The above composition was fed into a petri dish to prepare a polyethylene oxide / pectin film having a thickness of 0.1 mm.

The polyethylene oxide / pectin film thus prepared was dried in an oven at 55 ° C. and then dried in a vacuum oven at 55 ° C. for 6 hours to remove residual moisture.

(Example 2) Production of polyethylene oxide / pectin film

A film was prepared in the same manner as in Example 1 except that the content of polyethylene oxide / pectin was adjusted to 99/1 (w / w).

(Example 3) Production of polyethylene oxide / pectin film

A film was prepared in the same manner as in Example 1 except that the content of polyethylene oxide / pectin was adjusted to 70/30 (w / w).

(Example 4) Production of polyethylene oxide / pectin / polyethylene oxide derivative film

5 parts by weight of a polyethylene oxide derivative (obtained by converting the terminal hydroxyl group of polyethylene oxide into a carboxyl group) was added to 100 parts by weight of polyethylene oxide, and the content of polyethylene oxide / pectin was adjusted to 90/10 (w / w) A film was prepared in the same manner as in Example 1.

(Example 5) Production of polyethylene oxide / pectin / polyethylene oxide derivative / polyethylene oxide-polyacrylic acid copolymer film

The content of polyethylene oxide / pectin was adjusted to 90/10 (w / w), and 5 parts by weight of a polyethylene oxide derivative (obtained by converting the terminal hydroxyl group of polyethylene oxide into a carboxyl group) was added to 100 parts by weight of polyethylene oxide, A film was prepared in the same manner as in Example 1, except that 5 parts by weight of a polyethylene oxide-polyacrylic acid copolymer was added to 100 parts by weight of polyethylene oxide.

(Comparative Example 1) Production of polyethylene oxide film

A film was prepared in the same manner as in Example 1 except that pectin was not used and only polyethylene oxide was used.

The mechanical properties and the adhesive strength of the films prepared in Examples and Comparative Examples were measured, and the results are shown in Table 1 below.

(Mechanical Properties)

The tensile strength, tensile elastic modulus and elongation at break of the film were measured at a constant elongation rate of 10 mm / min using a tensile tester (Instron 2710-105, USA).

(Adhesive strength)

Tissue adhesiveness testing using beef embryos was conducted using a tensile testing machine (Instron 4464, UK).

The prepared film was prepared with a width of 1 inch and a length of 7 inches, folded, and both ends were stuck to the upper grip using a 1/2 inch mast tape so as to have a shape like a droplet.

The small intestine (small intestine) was cut to 1 square inch, fixed to the grip below, and the crosshead moved down to contact the intestines of the film and the cattle for 5 minutes.

The maximum force required to separate the film from the small intestine was measured.

division Example Comparative Example One 2 3 4 5 One The tensile strength
(MPa) 0.24 0.23 0.24 0.26 0.25 0.26 Tensile modulus
(MPa) 1.3 1.4 1.3 1.6 1.3 1.5 Elongation at break
(%) 38 39 41 36 34 35 Adhesive strength
(cN) 6.9 6.3 6.4 7.8 8.2 5.8

From the results shown in Table 1, the films of Examples 1 to 5 are excellent in adhesion to mucous membranes and can be used stably for anti-adhesion film, window epithelium replication, and the like.

On the other hand, Comparative Example 1 is inferior in adhesiveness to mucosa as compared with Examples 1 to 5.

Claims (16)

A composition for preventing adhesion, which comprises polyethylene oxide (PEO) and pectin, and which can improve stickiness to mucosa.
The method according to claim 1,
Wherein the weight ratio of the polyethylene oxide to the pectin is 80 to 98: 2 to 20.
The method according to claim 1,
The composition further comprises a polyethylene oxide derivative,
Wherein the polyethylene oxide derivative is obtained by converting a terminal hydroxyl group of polyethylene oxide to a carboxyl group.
The method of claim 3,
Wherein the composition further comprises a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer.
5. The method of claim 4,
Wherein the composition further comprises a polyethylene oxide-polylactic acid copolymer.
(PEO) and pectin, and then casting, melt-extruding or blow-molding the mixed composition,
An adhesion preventive film capable of improving stickiness to mucosa.
The method according to claim 6,
Wherein the weight ratio of the polyethylene oxide to the pectin is 80 to 98: 2 to 20.
The method according to claim 6,
The composition further comprises a polyethylene oxide derivative,
Wherein the polyethylene oxide derivative is obtained by converting a terminal hydroxyl group of polyethylene oxide to a carboxyl group.
9. The method of claim 8,
Wherein the composition further comprises a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer.
10. The method of claim 9,
Wherein the composition further comprises a polyethylene oxide-polylactic acid copolymer.
Mixing a composition comprising polyethylene oxide (PEO) and pectin; And
And a step of preparing the mixed composition by casting, melt extrusion or blow molding, thereby improving the adhesion to the mucous membrane.
12. The method of claim 11,
Wherein the weight ratio of the polyethylene oxide to the pectin is 80 to 98: 2 to 20.
12. The method of claim 11,
The composition further comprises a polyethylene oxide derivative,
Wherein the polyethylene oxide derivative is obtained by converting a terminal hydroxyl group of polyethylene oxide to a carboxyl group.
14. The method of claim 13,
Wherein the composition further comprises a polyethylene oxide-polyacrylic acid copolymer or a polyethylene oxide-polymethacrylic acid copolymer.
15. The method of claim 14,
Wherein the composition further comprises a polyethylene oxide-polylactic acid copolymer.
An article comprising the anti-adhesion film of claim 6,
Characterized in that the product is an anti-adhesion film or window epithelium.