JPH0568265B2 - - Google Patents

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention relates to a wound covering and protecting material made of a sheet-like material made of chitosan. The present invention relates to a wound covering protective material that has good adhesion to the skin, is difficult to dissolve in exudate, and is suitably used as a protective material for skin defects.

(Prior Art) In the past, many materials have been proposed and commercialized as protective materials for covering and protecting skin defects such as burns, skin harvesting sites for skin grafting, and skin grafts. These wound dressings are mainly classified into those made of synthetic materials and those made of natural materials. Examples of synthetic materials include velor made of nylon fibers and polyester fibers, porous polyurethane sheets, cross-linked polyvinyl alcohol porous sheets, etc.
Examples of natural materials include collagen nonwoven fabric (trade name: Meipatsuku, Meiji Seika Co., Ltd.), frozen pig skin (product name: Metaskin, Mitsui Pharmaceutical Co., Ltd.), fibrin membrane, and the like.

Recently, biological dressings derived from natural products have attracted attention because of their good affinity for living organisms, and are used as protective materials for skin defects and injuries.

On the other hand, chitin is an aminopolysaccharide contained in the exoskeleton of crustaceans, and it is important to make chitosan, which is obtained by deacetylating chitin, into fibers to make a nonwoven fabric. the lst Int.Conference on
Chitin/Chitosan), page 64,
Furthermore, on page 299, it is shown that chitosan is effective as a wound healing promoter.

(Problems to be Solved by the Invention) However, conventionally commercially available biological dressings such as collagen nonwoven fabrics and frozen pig skin are not necessarily sufficient as wound covering protection materials. One of its drawbacks is that its adhesion to the wound surface is insufficient. In general, covering protective materials are required to function like artificial skin to some extent, even if it is impossible to achieve full functionality.
That is, during treatment, it is preferable that the protective material work together with the wound surface to promote healing. If the adhesiveness of the protective material to the wound surface is poor, a large amount of exudate will accumulate at the interface of the affected area, delaying drying and, as a result, delaying epidermis formation. Second, there is a drawback that the protective material is easily decomposed early by exudate. This not only loses its function as a protective material, but also causes external infection, and of course prevents sufficient epidermis formation. Thirdly, the ability to move the exudate generated on the wound surface to the outside is small, and the exudate tends to accumulate in the affected area, causing a delay in healing of the wound surface. Therefore, there has been a long-awaited development of a protective material made of biological materials that has improved the above-mentioned drawbacks.

On the other hand, since chitosan fiber is a biological material and has excellent compatibility with living organisms, nonwoven fabrics, woven fabrics, knitted fabrics, etc. made of chitosan fiber are expected to be preferable as materials for protecting wound surfaces. however,
These sheets made of chitosan could not necessarily be said to be superior wound covering protection materials compared to conventional biological dressings. For example, when a nonwoven fabric made of chitosan fibers is brought into contact with a wound, it has the disadvantage that it is easily dissolved by body fluids exuding from the wound. Therefore, holes are formed in the surface of the protective material during treatment, and the protective material no longer functions as a protective material, which is not preferable.

Therefore, an object of the present invention is to use improved chitosan fibers as a protective material against various skin defects, which has the disadvantage of being easily dissolved by body fluids, and which facilitates rapid epidermal formation. Another object of the present invention is to provide a wound covering and protecting material that has the effect of smoothing the epidermis after healing.

(Means for Solving the Problems) As a result of extensive research to achieve the above objectives, the present inventors have found that a sheet-like material made of chitosan that has been subjected to a specific treatment is effective as a wound covering protection material. The present invention was developed based on the discovery that the method can be used effectively.

That is, the present invention is a wound covering and protective material comprising a sheet-like material made of chitosan treated with any one of acetic anhydride, propionic anhydride, and butyric anhydride.

Chitosan as used in the present invention is obtained by treating the exoskeleton of crustaceans, insects, etc. with hydrochloric acid and caustic soda.
Chitin obtained by separating and purifying protein and calcium components is deacetylated with, for example, a 20% or more caustic soda aqueous solution, and is dissolved in dilute acetic acid, for example, a 2% acetic acid aqueous solution. say.

The wound dressing protection material of the present invention is made of a sheet-like material made of chitosan treated with acetic anhydride, propionic anhydride, or butyric anhydride, and non-woven fabrics, woven fabrics, and knitted fabrics are suitable as such sheet-like materials. be. The sheet-like product in the present invention may be formed directly from chitosan powder treated with, for example, acetic anhydride, propionic anhydride, or butyric anhydride, or may be formed directly from chitosan powder. The obtained sheet-like material may be treated with any one of acetic anhydride, propionic anhydride, or butyric anhydride.
A sheet-like product may be prepared using the obtained fibers and then treated with either acetic anhydride, propionic anhydride, or butyric anhydride. Preferably, the fibers are prepared using fibers treated with either acetic acid, propionic anhydride, or butyric anhydride. To make chitosan fibers, for example, chitosan powder is dissolved in an aqueous solution of dilute acetic acid to obtain a dope, and the dope obtained is stored in a pressurized tank, transported by a metering pump, and passed through a nozzle into an alkaline aqueous solution. Known methods such as spinning and solidifying can be employed.

The fibers preferably have a single yarn denier of 0.3 to 20 d, more preferably 0.5 to 5 d, particularly 0.5 to 2 d, and have a strength of 1 g/d or more, especially 2 g/d or more.

To prepare sheets from chitosan fibers,
Known methods and devices can be selected and employed as appropriate. For example, to create a nonwoven fabric from chitosan fibers, a known continuous paper machine or batch paper machine can be used. In this case, as the binder, a fibrous binder made of polyvinyl alcohol is preferably used. For example, when manufacturing nonwoven fabrics using a batch-type paper machine, chitosan fibers and binder are uniformly dispersed in an excess amount of water at room temperature, water is removed from the bottom through a 20 to 200 mesh filter, and then dispersed on the filter. After laminating the chitosan fibers and compressing the thin pieces under pressure to squeeze out the water, they are dried in a roller-type heated compression dryer, preferably at 100 to 180°C, while being pressed between a rotating heating roller and a thick cloth. , preferably 3
Allow to dry for ~20 minutes.

The woven fabric is preferably plain weave, twill weave, or mock-shape weave, and the knitted fabric is preferably stockinette knit or lace knit. In this case, the fibers used may be spun yarn or long fibers.

The treatment of chitosan with acetic anhydride, propionic anhydride, or butyric anhydride involves treating chitosan with acetic anhydride, propionic anhydride, or butyric anhydride, alcohols such as methyl alcohol, ethyl alcohol, propyl alcohol, butyl alcohol, acetone, methyl ethyl ketone, etc. Ketones, dimethylformamide, dimethylacetamide, N-
It is preferable to conduct the reaction in a mixed solution with a non-aqueous solvent such as an amide such as methylpyrrolidone. The amount of acetic anhydride, propionic anhydride or butyric anhydride used is preferably 0.2 to 20 mol per 1 mol of chitosan, and the amount of the non-aqueous solvent used is preferably 5 to 20 mol per 1 part by weight of chitin. Parts by weight. The processing temperature is
Preferably, the temperature is 20 to 80°C and the treatment time is 30 minutes or more. In addition, if an alkali such as caustic soda is dissolved in the non-aqueous solvent in advance, it will neutralize the acetic acid, propionic acid, or butyric acid produced during the treatment, and the degree of polymerization of chitosan will decrease during the treatment. This is preferable because it becomes difficult. The treated chitosan may be transferred to a solution such as water, neutralized with an alkali, thoroughly washed, and then dried.

The sheet-like material in the present invention has a thickness of 0.05 to
It is preferably 0.5 mm, and preferably has a basis weight of 1 to 10 mg/cm ² expressed as weight per 1 cm ² .

The sheet-like product thus prepared can be preferably used as a wound dressing after sterilization.

(Examples) Hereinafter, the present invention will be explained in more detail by giving examples.

Example 1, Comparative Example 1 Chitin powder (manufactured by Chitsukarin Katakura) was ground into 100 meshes, treated in a 40% by weight NaOH solution at 121°C for 2 hours, neutralized with hydrochloric acid, and then washed repeatedly with water. After that, it was dried to obtain chitosan. The obtained chitosan was dissolved in a 2v/v% acetic acid aqueous solution.
The viscosity of 0.2wt% was 650 cp at 25°C. This chitosan was dissolved in a 5v/v% acetic acid solution at 20°C,
A transparent and viscous chitosan dope with a concentration of 5% by weight was obtained. This dope was filtered through a 1480 mesh wire mesh, depressurized and left to defoam, then placed in a tank at 20°C, transported under pressure using a gear pump, and transported with a diameter of 0.07.
It was extruded into a 5% NaOH aqueous solution through a 500-hole nozzle and solidified, and then taken off with a roller at a speed of 10 m/min. The obtained yarn is again 5%
Thoroughly coagulate in NaOH aqueous solution, wash thoroughly with water, and dry to create a single yarn denier of 1.2 denier.
500 filaments with a strength of 2.7 g/d were obtained.

The filament obtained as above is 8 mm
After cutting it into pieces, it was immersed in a methanol solution containing 2v/v% acetic anhydride for 1 hour, and then a nonwoven fabric was prepared in the following manner. First, the equipment is the sheet machine TAPPI-205OS-71 manufactured by Toyo Seiki Seisakusho.
0.5 g of chitosan fiber and 0.05 g of 1 d, 1 mm vinylon fiber (trade name: Unitika Euron, manufactured by Unitika Kasei) were dispersed in 1 part water. Next, water was added to the dispersion to make the total amount 6,
After being placed in the sheet machine, water was removed from below through an 80-mesh stainless steel net. After the laminate on the net was sandwiched between qualitative filter papers, it was compressed using a press at a pressure of 3 kg/mm ² to remove water. Furthermore, the nonwoven fabric was dried for 6 minutes while being pressed against a thick cloth on a rotating roll heated at 150° C. to obtain a nonwoven fabric. The thickness of the obtained nonwoven fabric was 0.16 mm, and the basis weight was 3 mg/cm ² . (Example 1).

For comparison, a nonwoven fabric was prepared in the same manner as in Example 1, except that chitosan fibers cut to 8 mm were not treated in a methanol solution containing acetic anhydride. The thickness of the obtained nonwoven fabric was 0.15 mm, and the basis weight was 3 mg/cm ² (Comparative Example 1).

When the nonwoven fabrics of Example 1 and Comparative Example 1 were used as protective materials for skin harvest wounds (thickness 15/1000 inch),
In the case of Comparative Example 1, it was no longer able to function as a protective material due to melting due to exudate on the first day, whereas in the case of Example 1, no melting occurred during treatment, and it disappeared on the 12th day. Healing is complete.

Example 2, Comparative Example 2 The same chitosan dope used in Example 1 was used.
It was filtered through a 1480 mesh wire mesh, depressurized and left to degas, then placed in a tank at 20°C, transported under pressure using a gear pump, and extruded into a 5% by weight NaOH aqueous solution through a nozzle with a diameter of 0.06 mm and 120 holes. After solidifying and washing with warm water (50℃), 15m/min
It was picked up by a winder at a speed of The obtained yarn was dissolved in methanol containing 20% by weight of acetic anhydride.
After soaking at ℃ for 3 hours, it was washed.

The obtained yarn has a denier of 210 and a strength of 3.1 g/d.
Two long fibers were twisted together 20 times/inch. Then, a patterned woven fabric was created using this material as warp and weft threads. The gap between the warp and weft of the created fabric was 1 mm, and the pore volume of the fabric was
It was 86% (Example 2).

For comparison, Example 2 except that the yarn was not treated in methanol containing 20% by weight acetic anhydride.
A patterned woven fabric with gaps between warps and wefts of 1 mm was prepared in the same manner as (Comparative Example 2).

The woven fabrics of Example 2 and Comparative Example 2 were applied to the right and left parts of the dorsal skin of domestic rabbits as protective materials, respectively, on the skin of the rabbit's back. Skin sampling was performed with a dermatome to a depth of 20/1000 inches.
The wound was protected with cotton gauze and observed over time. As a result, in the case of Comparative Example 2, it dissolved after one day and could no longer function as a protective material, whereas in the case of Example 2, it adhered well to the wound and did not dissolve. The affected area became moist and then dried, and epithelialization was completed on the 10th day, resulting in healing.

Example 3 The single filament with a denier of 1.2 denier and a strength of 2.7 g/d obtained by wet spinning in Example 1 was cut into 8 mm, and then placed in an ethanol solution containing 3 v/v% propionic anhydride. It was immersed at 40°C for 1.5 hours. Next, after washing it thoroughly with water,
Paper was made using the sheet machine used in Example 1 under exactly the same conditions as in Example 1, with a thickness of 0.15 mm.
A nonwoven fabric with a basis weight of 3 mg/cm ² was obtained. After steam sterilizing this nonwoven fabric, it was used as a protective material for the affected area of a superficial degree burn, and it served as a protective material without melting due to exudate, and the epidermis showed good healing on the 12th day.

Example 4 After cutting the single filament with a denier of 1.2 denier and a strength of 2.7 g/d obtained by the wet spinning of Example 1, it was placed in a dimethylacetamide solution containing 4 v/v% butyric anhydride. It was immersed for 2 hours at ℃. Next, after thoroughly washing this with water, paper was made under the same conditions as in Example 1, except that the amount of chitosan fibers processed in the sheet machine used in Example 1 was changed from 0.5 g to 0.4 g. conduct, thickness
A nonwoven fabric having a diameter of 0.11 mm and a basis weight of 2.4 mg/cm ² was obtained. After steam sterilizing this nonwoven fabric, we used it as a protective material for a skin harvest wound (18/1000 inch thick), and the healing was completed on the 12th day without any melting caused by the immersion solution during treatment, and the regenerated epidermis was smooth. It was hot.

(Effects of the Invention) When the wound dressing protection material of the present invention is used as a wound dressing protection material for skin defects such as burns, skin harvested areas, skin grafted areas, etc., it has excellent adhesion to the affected area, resistance to exudate,
Because it has an excellent effect of eliminating the liquid, the epidermis forms quickly and the healing condition can be maintained in good condition.

Claims (1)

[Claims] 1. A wound covering and protective material comprising a sheet-like material made of chitosan treated with any one of acetic anhydride, propionic anhydride, and butyric anhydride.