KR960014022B1 - Biodegradable chitin filament and fiber for surgical sutures - Google Patents

Abstract

The biodegradable fiber, a complex of chitin & cellulose (which is called a chitulose), is prepared by melting chitin and plant cellulose in a soluble solvent; and spining under moisture condition. The chitulose is useful for the prodn. of a biodegradable surgical suture, and a chitulose resin which is applicable to an artificial skin, an edible packing material for food.

Description

Biodegradable Chitin Suture, Fiber and Chitin Resin Modified with Cellulose

The present invention relates to biodegradable chitin fibers and resins, and more particularly, to soluble fibers, bioabsorbable chitin sutures and resins which improve biodegradation rate and mechanical properties by depositing a small amount of plant-based cellulose on chitin.

Chitin is a polysaccharide composed of poly (N-acetyl-O-glucosamine) and is widely present in nature such as the exoskeleton of shellfish. Chitin has one aminoacetyl group in addition to the above repeating unit.

The use of fibrillated chitin as an absorbent suture is already disclosed in Japanese Patent Application No. 55-152558 and Japanese Patent Application No. 55-164268. However, conventional bioabsorbable chitin sutures have a problem that their strength decreases in a short time because the bioabsorbability is too fast. In general, the bioabsorbable sewing thread maintains sufficient strength for 10 to 15 days after sufficient healing progresses after use, but is then preferably absorbed in vivo as soon as possible. Thus, conventional bioabsorbable sutures are undesirable in this regard.

The present inventors maintain a close strength at the beginning of use, for example, until buried up to 10 to 15 days after being buried in a living body, but after that period of time, the living body is made of chitin to prepare a suture that is rapidly absorbed into the living body. As a result of repeated studies on absorbent sutures, it was found that sutures made of a composite prepared by liquefying chitin and cellulose followed by wet spinning have the effect of inhibiting the initial bioabsorption rate after surgery, thus completing the present invention.

Accordingly, it is an object of the present invention to provide a suture having an ideal bioabsorption rate as a bioabsorbable suture by adjusting the initial bioabsorption rate of a conventional chitin suture.

Another object of the present invention is to provide a biodegradable fiber suitable for the production of sutures having the ideal bioabsorption rate.

This object of the present invention is to wet spin a mixed solution of chitin and cellulose to produce a chitin-cellulose complex (hereinafter referred to as chitulose) fiber, from which the rate of bioabsorption is improved by a conventional method. This can be achieved by making a bioabsorbable chitin suture.

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

A first feature of the invention relates to chitulose fibers. The chitulose fibers according to the present invention are mixed with chitin and cellulose in a suitable solvent capable of dissolving this cationic component to obtain a chitulose solution, which is extruded through a nozzle into a coagulating solution by a wet spinning method, and wound up. It is prepared by making.

Chitin and cellulose constituting the chitulose fibers of the present invention may be used in addition to their derivatives, respectively. Chitin can be prepared by separating and purifying proteins and calcium carbonate by treating the exoskeleton such as crustaceans and insects with acid treatment and base treatment. Cellulose can also be prepared by separating and purifying cellulose from wood.

In addition, in order to manufacture the chitulose fibers of the present invention, it is important to select a solvent capable of dissolving chitin and cellulose at the same time. As such a solvent, for example, a mixture of trichloroacetic acid and chlorinated hydrocarbons, a mixture of dichloroacetic acid and combustion hydrocarbons, a mixture of dimethylacetamide and lithium chloride, or a mixture of N-methyl pyrrolidone and lithium chloride can be used. have.

Preferred chitulose fibers have a single yarn denier of 0.5 to 20 d, and a health level of 2 g / d or more, more preferably 3 g / d or more, and most preferably 4 g / d or more.

Another feature of the invention relates to a chitulose suture having an ideal bioabsorption rate made from chitulose fibers.

The method for producing the chitulose suture from the chitulose fibers according to the present invention is not limited, and various methods can be used. For example, it can be produced by agglomeration or twisting about 10 to 20 strands of chitulose fibers having a total denier of 20 ~ 200d.

Sutures may be preferably used USP size 12-0 to 12-5 of Table 1 of the Absorbable Surgical Suture described in USP XX 759, but is not limited thereto. no.

The flexibility and bioabsorption rate of the bioabsorbable suture made from the chitulose fibers of the present invention depend on the amount of cellulose added to the chitin. The mechanism by which the strength changes as the cellulose content of chitin is changed is due to the toughness of cellulose in the hydrogen bonds between the sugar chains and the chains and the hydrogen bonds in the chains. When hydrogen bonds come together to mix and liquefy the two materials, they become sutures with flexible and tough properties. Therefore, the bioabsorption rate of the bioabsorbable suture made of the chitulose fibers of the present invention can be easily controlled. That is, bioabsorbable sutures having various bioabsorption rates can be prepared by varying the amount of cellulose added to the chitin. In general, the cellulose is preferably added in an amount of 6 to 15%.

When used in vivo, the bioabsorbable suture of the present invention has a higher strength retention than the suture composed of chitin only for 10 to 15 days, which is the first time of use. However, since the bioabsorbable suture has a property of being rapidly absorbed into the body after this period, it is ideal as a bioabsorbable suture. will be.

In addition, the chitulose resin of the present invention can also be applied to biodegradable diapers, artificial skin, drug release control packaging material, fast-treatment bandages, and biodegradable food packaging materials for human consumption.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the present invention is not limited by these examples.

Comparative Example Chitin (supplied by Sigma Co.) extracted from shellfish was milled [Cutting Mill Willy, Model No. C-CMA (Cheil Science 11-06)] to powder to 100 mesh. 10 kg of this powder was treated with 200 liters of 2N aqueous chloride solution at room temperature for 4 hours, neutralized with 1N aqueous sodium hydroxide solution, washed with distilled water sufficiently, filtered and dried, followed by drying with solvent [dimethylacetamide (DMAc: lithium chloride). = 20: 1.5 (weight ratio)], the chitin was liquefied at room temperature to 1.5%, filtered and degassed to obtain a homogeneous solution with a transparent spinnable viscosity (about 350 poise). Was fed at a pressure of about 8.4 kg / cm 2 (120 psi), discharged into a methanol from a nozzle of 0.15 mm ψ and 300 holes to solidify, and then wound up at a speed of 10 m / min to obtain chitin fibers having a single yarn denier of 8 d. After sterilizing the fibers, they were immersed in the back muscles of rats weighing 400-500 g, and collected according to the curing time. The degree of degradation was observed under a scanning microscope (Table 1). After observation with the lapse of 3 l pots and then buried in the old time as a result, after 1 months to determine the degradation degree of 18% degradation it was 29% after 2 months, 6 months was completely decomposed.

The physical properties of these conventional chitin sutures are described as comparative examples in Table 2.

a: elongation (%), b: breaking force (g), c: denier, d: strength (g / d)

Example 1 Chitin extracted from crab shell (supplied by Sigma Co.) was milled [Cutting Mill Willy, Model No. C-CMA (Cheil Science 11-06)] to powder to 100 mesh. 10 kg of this powder was treated with 200 liter of 2N aqueous hydrochloric acid solution at room temperature for 4 hours, neutralized with 1N aqueous sodium hydroxide solution, washed with distilled water sufficiently, filtered and dried. This chitin was solubilized in a solvent [dimethylacetamide: lithium chloride = 20: 1.5 (weight ratio)] to 1.5% in the same manner as in the comparative example. 10 kg of α-cellulose from cellulose Sigma Co. was immersed in 200 liters of distilled water for 24 hours, filtered and immersed in methanol for 5 hours to swell. The swollen cellulose was mixed with the chitin solution in a weight ratio of 6.7%, 13.3%, and 26.7%, respectively, at room temperature, liquefied at room temperature, filtered, and degassed to obtain a uniform spinning viscosity (about 360 poise). A solution was obtained. The solution was placed in a spinning tube, and nitrogen gas was fed at a pressure of about 8.4 kg / cm 2 (120 psi), discharged into a methanol from a nozzle of 0.15 mm ψ, 300 holes, and coagulated, followed by winding at a speed of 10 m / min. Phosphorus chitulose fibers were obtained. The physical properties of the chitulose fibers varied with the content of cellulose, which was the highest when 13.3% cellulose was added. At this time, the health, wet strength, and knot strength were average 5..5, 3.2, and 4.3 g / d, respectively. As a comparative example, the chitin fibers to which cellulose was not added were 1.5, 1.4 and 1.4 g / d.

The results of the physical properties of these kitulose sutures are shown in Tables 3 and 4 below.

a: elongation (%), b: breaking force (g), c: denier, d: strength (g / d)

Example 2 10 liters of distilled water was put in a 15 liter container and kept at 95 ° C. for 30 minutes in a state in which the fibers prepared as in Example 1 and Example 1 were squeezed tightly and then immersed in a healthy state with an Instron taken out. The results of the measurement are described in Table 5, where the physical property increase rate of the conventional chitin suture was increased, but the final physical properties were still less than the chitulose suture before heat treatment. Chitulose sutures significantly increased the strength of the fiber by water bath treatment.

a: fiber strength before bath treatment (g / d), b: fiber strength after bath treatment (g / d)

Example 3 Chitin extracted from crab shell (supplied by Sigma Co.) was milled [Cutting Mill Willy, Model No. C-CMA (Cheil Science 11-06)] to powder to 100 mesh. 10 kg of this powder was treated with 200 liter of 2N aqueous hydrochloric acid solution at room temperature for 4 hours, neutralized with 1N aqueous sodium hydroxide solution, washed with distilled water sufficiently, filtered and dried. 10 kg of α-cellulose from cellulose Sigma Co. was immersed in 200 liters of distilled water for 24 hours, and then filtered and immersed in methanol for 5 hours. Subsequently, in a solvent [dimethylimidolidome (DAI): lithium chloride = 20: 0.6 (weight ratio)], the weight ratio of chitin and cellulose was mixed at 0%, 10%, 20%, and 35% to be solution at room temperature. Filtration and defoaming resulted in a homogeneous solution with a transparent spinnable viscosity (about 360 poise). The solution was placed in a spinneret and nitrogen gas was fed at a pressure of approximately 8.4 kg / cm 2 (120 psi), discharged into a methanol from a nozzle of 0.15 mm ψ, 300 holes, and coagulated, followed by winding up at a speed of 10 m / min. A chitulose fiber of d was obtained.

The health of chitin fibers averaged 3.9 g / d. In the case of chitulose fibers, the health level was changed according to the cellulose content. Among them, the health level was the highest when the cellulose was added 35%, and the average health level was 5.2 g / d. At least 35% by weight to chitin did not dissolve the cellulose. The overall results are shown in Table 6 below.

a: elongation (%), b: breaking force (g), c: denier, d: strength (g / d)

Example 4 After sterilizing the sutures (kinin: cellulose-1.5: 2.0, weight ratio) of Example 1, they were buried in the back muscles of rats each weighing 400-500 g and sieved over time to decompose the sutures. Was observed with a scanning electron microscope. As a result, it started to decompose | disassemble from 14 days after burial, and disappeared completely after 40 days. As can be seen from Table 3 showing the results of Example 1, the health of chitulose sutures increased by two or more compared to chitin main yarn. Thus, chitulose sutures are ideal as bioabsorbable sutures. In addition, since the degree of decomposition varies with time, it is possible to manufacture a suitable suture depending on the surgical site by changing the content of cellulose added to the chitin.

Example 5 The single yarn C of Example 1 was made into 30 strands, and after sterilization, it was buried in the back muscles of a rat weighing 400 to 500 g, collected over time, and the degree of degradation was examined by scanning microscope and instron. After 15 days, the original strength was maintained at 625, after 30 days, 20%, and after 40 days, the strength was almost lost (Table 7). Comparing this result with the degree of degradation of the conventional chitin fibers (Table 1), the degradation rate of the chitulose fibers of the present invention could be controlled gently. The biodegradable absorbency was 50% degraded after 40 days and completely degraded after 70 days.

a: elongation (%), b: breaking force (g), c: denier, d: strength (g / d)

Example 6 In the soil of the fibers of Example 1 (collected from wild), the change was observed over time after being buried in a 3 liter flowerpot to determine the degree of decomposition. After one month, it degraded by about 20%, after two months it was degraded by 30%, and after six months it completely disintegrated. According to Table 8, the biodegradability in the soil of the conventional chitin fiber A and the chitulose fibers of the present invention was similar. The degree of degradation was evaluated according to the degree of change of the fiber observed under the microscope.

Example 7 In order to investigate the applicability of chitulose resin to artificial skin, the following experiment was conducted. Various solutions were prepared in the same manner as in Example 1. The composition of the solution had a weight ratio of chitin and cellulose to a solvent of 1.0%: 0%, 1.5%: 0.5%, 1.0%: 0.5%, 1.5%: 1.0% and 0%: 2.0%, respectively. These solutions were cast on a glass plate to push out Doctor5s Knife, then methanol was immersed, and the solvent was removed to obtain a film of a constant thickness (about 5 μm). The results of examining the permeation amount of various organic compounds on these films are shown in Table 9 below. In Table 9, the film obtained from the solution of the composition of chitin 1.0% and cellulose 0.5% had the highest biochemical activity.

In order to investigate the possibility of application as artificial skin, two-degree burns on the back of the body are artificially burned, and one side is left but the other is a chitulose film with high biochemical activity (chitin 1.0%: cellulose 0.5) %) Was attached. The upper body of the site where it was left appeared to be slightly inflamed and healed only after 50 days.However, the wound with the chitulose film attached did not appear to be inflamed.After 6 days, the wound began to heal and the wound was reduced, and after 15 days The scab fell off and after 20 days the hair was sprouting and after 30 days it was restored to its former state.

Example 8 The following experiment was conducted to investigate the applicability of the chitulose resin to the food packaging material suitable for living beings and having bioabsorbability. Various aqueous solutions were prepared in the same manner as in Example 1, but the composition of the solution was 1.0%: 0%, 1.0%: 0.5%, 1.0%: 1.0%, 1.0%: 2.0 in the weight ratio of chitin and cellulose to the solvent, respectively. % And 0%: 1.3%. These solutions were cast on a glass plate to push out a doctor knife, then methanol was immersed, and the solvent was removed to prepare a film of a constant thickness (about 5 mu m). Table 10 shows the results of examining the amount of oxygen permeation for these films.

The oxygen permeability was the lowest in the chitulose film prepared from a solution of 1.0% chitin and cellulose 1.0 composition, and the chitulose film prepared from a solution of 1.0% chitin and 0.5% cellulose.

This means that the oxygen permeation amount can be controlled by adjusting the composition. Therefore, it is possible to extend the shelf life of fresh vegetables (when high oxygen permeability) or as a food packaging material for preventing fat oxidation (when low oxygen permeability).

Claims (9)

The chitin and the plant-based cellulose are dissolved in a solvent capable of dissolving all of them in order to obtain a chitin-cellulose complex (chitulose) solution, and the wet spinning is characterized in that the high-molecular-weight chitose fibers Manufacturing method. The method of claim 1, wherein the solvent is selected from a mixed solution of dimethylimidazolidon / lithium chloride, acetic acid dichloride / hydrochloric chloride, dimethylacetamide / lithium chloride, and N-methylpyrrolidone / lithium chloride. . The method according to claim 2, wherein the solvent is a mixed solvent of dimethylimidazolidon / lithium chloride and dimethylacetamide / lithium chloride. The method of claim 1 wherein the cellulose is added to the chitin in an amount of 6-15%. It is produced by the method according to any one of claims 1 to 4, the health is 2g / d or more, the wet strength is 1.9-4.4g / d, the knot strength is 2.4-5.5g / d Phosphorus biodegradable chitulose fibers. A bioabsorbable chitulose suture comprising the chitulose fibers of claim 5 and having a bioabsorption rate controlled according to the amount of cellulose added. The bioabsorbable chitulose suture of claim 6, wherein the chitulose fibers are bathed to increase the strength of the fibers. A bioabsorbable chitulose artificial skin prepared from the kitulose solution of claim 1 and whose function is adjusted according to the amount of cellulose added. A kitulose food packaging material prepared from the kitulose solution of claim 1 and whose oxygen permeability is adjusted according to the amount of cellulose added.