KR0148546B1 - Process for preparing interpenetrating polymer network film of chitin for an artificial skin - Google Patents

Abstract

The present invention relates to a method for producing a chitin-based interpenetrating structure film for artificial skin, and more specifically, 10 to 90% by weight of chitin and 10 to 90% by weight of polyethylene glycol macromer having a molecular weight of 100 to 20,000 in the presence of an organic solvent. After the reaction, the method relates to a method for producing a chitin-based interpenetrating structure film for artificial skin which is cured by adding an ultraviolet curing accelerator to the reactant for 10 to 120 minutes. The film can be used as decomposed absorbent artificial skin or surgical sutures by reinforcing strength when wet with chitin.

Description

Method of manufacturing chitin-based interpenetrating structure film for artificial skin

The present invention relates to a method for manufacturing an interpenetrating polymer network (IPN) film for artificial skin, and more particularly, to a chitin-based interpenetrating structure that can be used as a decomposed absorbent artificial skin by reinforcing strength when the chitin is wet. It relates to a method for producing a film.

Chitin can be separated into chitin, such as α, β, and γ, depending on the raw material extracted from the crystal structure. α-chitin can be obtained from crustaceans such as shrimp and crab, and the crystal structure is tetragonal and molecular chains are alternately arranged. β-chitin is monoclinic and molecular chains are arranged in parallel. It can be extracted from the pod bones. And γ-chitin is composed of chitin mixture of α and β structure.

α-chitin is resistant to solvents due to the formation of strong micelle structures by intramolecular and molecular hydrogen bonding, which makes it difficult to swell in general organic solvents. In addition, there is a lot of difficulties in the production of chitin derivatives due to low chemical reactivity. Moreover, because chitin is extracted from calcareous crustaceans, some of the calcium is still present after separation into crustaceans.

On the other hand, β-chitin extracted from podaceous bone can be dissolved in strong acid or some weak acid due to the difference in binding structure, and swelling of organic solvent is easy, resulting in better chemical reactivity compared to α-chitin. It can be low, resulting in a purer chitin. Treatment of chitin with acids and alkalis results in chitosan, which can swell in water and destroy the crystallinity of chitin, but it can be a much larger water-soluble substance.

Chitin and chitosan deacetylated chitin and its derivatives are prepared and dissolved in an organic solvent or mixed solvent using strong acid, weak acid, or DMAc-LiCl, and combined with functional groups to form fibers, paper, medicine, food, cosmetics, It can be applied to various fields such as wastewater treatment.

There is no conventional report on the preparation of IPN using chitin. A paper on the preparation of IPN using chitosan and the swelling behavior and drug release has been published by Yao et al. (Journal of Polymer Science: Part A. Polymer Chemistry, Vol. 32, p. 1213-1223 (1994)). In general, chitin has a stronger micelle structure than chitosan, and thus, even when crosslinked, the chitin has a strong mechanical strength when wet. There are numerous reports about the formation of IPNs. However, there are no reports on their application to medical polymers.

The skin is at the forefront of protecting the body from the outside, and if the skin is damaged, it is likely to be exposed to dangerous situations. The function of the skin is complex and artificially manufactured skin substitutes cannot perform all the functions of the skin, but can protect the wound. Artificial skin can be categorized as used for the purpose of protecting the temporary wound from the clinical point of view and for permanent attachment. The former has the function of actually acting on the skin as wound skin, allogeneic skin, and other cultured skin. On the other hand, the latter is also known as self-cultivated skin by culturing fibroblasts or keratinocytes from their healthy skin in vitro and constructing a part of the skin structure.

The need for artificial skin is the treatment of burns. In patients with extensive severe lacerations, the skin defect can be autografted by surgery. Therefore, artificial skin is required for the purpose of temporary skin protection until autologous skin transplantation is possible. As such wound coating or artificial skin, collagen, calcium alginate salt, chitosan nonwoven fabric, hyaluronic acid nonwoven fabric, polyurethane film, silicone film and the like are used. However, the absorber has a disadvantage in that the strength is significantly reduced when absorbing the ooze coming from the skin has been improved and low effort is in progress.

The present inventors earnestly studied to improve the shortcomings of the conventional artificial skin, and when the chitin is formed into a crosslinked structure, the present inventors have realized that the mechanical strength is high even when wet.

Accordingly, it is an object of the present invention to provide a method for producing a chitin-based interpenetrating structure film which can be used for disintegrating absorbent artificial skin, surgical suture, and the like.

The method of the present invention for achieving the above object is a mixture of 10 to 90% by weight of chitin and 10 to 90% by weight of polyethylene glycol macromer (PEG macromer) having a molecular weight of 100 to 20,000 in the presence of an organic solvent, and then ultraviolet light to the mixture A curing accelerator is added to cure ultraviolet light for 10 to 120 minutes.

Hereinafter, the manufacturing method of the present invention will be described in more detail.

According to the present invention, the chitin-based interpenetrating film blends 10 to 90% by weight of chitin and 10 to 90% by weight of polyethylene glycol macromer having a molecular weight of 100 to 20,000 in the presence of an organic solvent to mix well. At this time, the amount of the mixture of chitin and polyethylene glycol macromer is preferably dissolved in the range of 2 to 10% by weight with respect to the organic solvent in terms of efficiency. The UV curing accelerator is then added to the mixture in an amount of 10 to 35 parts by weight based on 100 parts by weight of the solids of the mixture and cast on a glass plate. At this time, it is dissolved in an appropriate solvent and added. Thereafter, the mixture is cured with ultraviolet lamps for 10 to 120 minutes with an ultraviolet lamp to form an interpenetrating crosslinked structure, whereby a transition occurs from a solution phase into a semisolid gel form having an interpenetrating structure, and then the excess solvent remaining in the substrate is removed. Drying in a reduced pressure oven to prepare a chitin-based interpenetrating structure film for artificial skin having a dense surface. Thus prepared chitin interpenetrating structure film for artificial skin of the present invention is crosslinked by polyethylene glycol macromers, chitin is achieved through a chemical structure that is linearly bonded on the crosslinked polyethylene glycol macromer chain.

On the other hand, chitin usable in the present invention includes α-chitin, β-chitin or γ-chitin, but extracts bones of squids, including squid, cuttlefish, squid, or cuttlefish, and treated with acid and alkali to treat calcium and Β-chitin without protein is preferred.

The polyethylene glycol macromer is preferably polyethylene glycol dimethacrylate, polyether dimethacrylate, polypropylene glycol dimethacrylate or polyester dimethacrylate, but is not limited thereto.

The organic solvent that can be used in the present invention is formic acid, acetic acid or trifluoroacetic acid is preferred, the UV curing accelerator is benzophenone, acetophenone, anthraquinone, xanthone, campoquinone, fluorenone or derivatives thereof Although it can use it, it is not limited to this.

Solvents used in the addition of the UV curing accelerator include N-vinylpyrrolidone, N-methylpyrrolidone, dimethylformamide, dimethylacetamide or dimethyl sulfoxide.

On the other hand, the film produced by the above method can be used as a surgical suture, artificial skin, but is not limited thereto. In order for a material to be used as an artificial skin, the wetted swelling mechanical strength should be 1 MPa or more, preferably 2 MPa or more, since the mechanical strength should not be lowered even if the exudates from the wound are absorbed by the artificial skin material. The dry strength should be 20 MPa or more, but the chitin-based IPN of the present invention satisfies the above conditions.

Hereinafter, the method and effect of the present invention will be described in more detail with reference to Examples and Comparative Examples, but the scope of the present invention is not limited to the following Examples.

Production example (production of PEG macromer)

2 x 10 ^-3 mol of reagents of PEG molecular weight 4000, 6000, 10,000, and 20,000 are dissolved in 150 ml of benzene and stored in a glass vessel cooled to 0 ° C. 0.7 ml of triethylamine and 0.7 ml of acryloyl chloride are added to the glass vessel and reacted at about 80 ° C. with stirring for 3 hours. The reactant in the glass vessel is poured into n-hexane, an aliphatic hydrocarbon, to prepare polyethylene glycol methacrylate, and dried under reduced pressure in an oven of 10 mmHg or less at 40 ° C. for 1 day.

[Examples 1 to 12]

After mixing polyethylene glycol dimethacrylate and β-chitin of each molecular weight prepared in Preparation Example in the composition ratio shown in Table 1 below, 2.4 wt% of the mixture was dissolved in formic acid solution and left for 30 minutes in a nitrogen atmosphere, followed by 0.3 A solution of 2 g of 2,2-dimethoxy-2-phenylacetphenol in 1 ml of N-vinylpyrrolidone was cast on a glass plate and cured for about 60 minutes in a 450 W ultraviolet lamp. Drying in a reduced pressure oven to obtain a chitin-based interpenetrating structure film according to the present invention having a dense surface.

[Comparative Examples 1 to 5]

As shown in Table 1, it was carried out in the same manner as in the above example except that chitin or polyethylene glycol dimethacrylate was not used.

On the other hand, the thermal properties (glass transition temperature), crystallinity, etc. of the polyethylene glycol dimethacrylate, which will remain uncrosslinked in the IPN film of the above example and the comparative example, were measured by a thermal analyzer, and the degree of parallel swelling (EWC) in the ionized water was measured. In addition, Instron was used to measure tensile strength at break in a dry state and in a parallel swelling state.

It can be seen that the IPN film of the present invention is crosslinked from the glass transition temperature and the degree of crystallization of Table 1 while maintaining a constant strength, so that the degree of crystallinity is low and the processing is easy. In addition, the degree of parallel swelling (water content) of the IPN film according to the present invention is 50% or more, and the tensile strength when wet is mostly 1 MPa or more, which maintains its mechanical strength, making it very suitable for artificial skin and surgical sutures. have.

Claims (7)

10 to 90% by weight of chitin and 10 to 90% by weight of polyethylene glycol macromer having a molecular weight of 100 to 20,000 are mixed in the presence of an organic solvent, and then the UV curing accelerator is added to the mixture to be flexible on the glass plate, followed by 10 to 20 minutes of UV curing. And, the method of producing a chitin-based interpenetrating structure film for artificial skin, characterized in that the surface is dense by drying the excess solvent under reduced pressure. The method of manufacturing a chitin-based interpenetrating structure film for artificial skin, according to claim 1, wherein the chitin is α-chitin, β-chitin or γ-chitin. The chitin-based interpenetrating structure for artificial skin according to claim 1, wherein the polyethylene glycol macromer is polyethylene glycol dimethacrylate, polyether dimethacrylate, polypropylene glycol dimethacrylate or polyester dimethacrylate. Method for producing a film. The method of claim 1, wherein the organic solvent is formic acid, acetic acid, or trifluoroacetic acid. The method of claim 1, wherein the UV curing accelerator is benzophenone, acetophenone, anthraquinone, xanthone, camphorquinone, fluorenone, or derivatives thereof. The method of manufacturing a chitin-based interpenetrating structure film for artificial skin according to claim 1, wherein the ultraviolet curing accelerator is dissolved in an organic solvent in an amount of 10 to 35 parts by weight based on 100 parts by weight of the solids of the mixture. The method of claim 6, wherein the organic solvent is N-vinylpyrrolidone, N-methylpyrrolidone, dimethylformamide, dimethylacetamide or dimethyl sulfoxide. .