JPS6160705B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a surgical suture, and more particularly to a surgical suture that is made of chitin fiber and has high strength, flexibility, and good absorbability. Absorbable surgical sutures must have good biocompatibility, be absorbed after retaining their strength within the body for a certain period of time, and be sterilizable, as well as being easy to sew and tie. It must be easy to use and have suitable physical properties as a suture thread, such as tensile strength and flexibility. Conventionally, as absorbable surgical suture threads, cutlets made from regenerated sheep intestines have been known, and polyglycolic acid suture threads are newer. These are currently used by surgeons, but
Each of these does not satisfy all of the conditions that should be met by the absorbable surgical suture described above. For example, katsutogutsuto has disadvantages in usability such as ease of sewing and tying, is prone to antigen-antibody reactions and is therefore not biocompatible, and is quickly absorbed in the body, so it retains its strength for a short period of time. It has many drawbacks such as: In addition, polyglycolic acid suture thread has a high coefficient of surface friction, which makes it difficult to sew and tie, and it also tends to break down in the air, making it difficult to store. It has its drawbacks. Chitin is a polysaccharide consisting of poly(N-acetyl-D-glucosamine), a substance widely distributed in nature such as the exoskeleton of crustaceans, and has one aminoacetyl group in each repeating unit of its molecule. It has many interesting and unique properties. One of its properties is that it undergoes enzymatic decomposition within the human body and is absorbed into tissues, and that it has good stainability.For this reason, chitin is turned into fibers and used as absorbable surgical sutures. It is proposed to do so. However, to date, no absorbable surgical suture thread with sufficient performance for practical use has been obtained from chitin fibers. For example, JP-A No. 51-133367 describes that a chitin dope was prepared by dissolving chitin in a solution containing trichloroacetic acid, which was wet-spun and then cold-stretched to obtain high-strength chitin fibers. However, the fibers obtained are very thick. In other words, Example 2 has a tensile strength of
It is shown that a filament of 63Kg/mm ² was obtained, which is 5 if the density is calculated as 1.4.
g/d (knot strength of about 3 g/d), and it is clear that highly strong chitin fibers have been obtained, but the thickness is equivalent to the diameter as seen in Example 3. It is 0.25 mm thick, which is equivalent to 618 denier if the density is calculated as 1.4. Additionally, Tokusekki No. 53-127500 describes that chitin was dissolved in a solvent such as dichloroacetic acid to prepare chitin dope, which was wet-spun and then drawn to obtain fine denier chitin fibers. However, the strength of the obtained fibers is low. i.e. 3.0 for that example
It has been shown that chitin fibers of ~3.5 denier were obtained, but the strength was 1.2~1.5 g/
d (knot strength 0.6 to 0.7 g/d). As described above, the chitin fibers known up to now had high strength and were thick, while thin chitin fibers had low strength. Even if a suture is made using such chitin fibers, it is difficult to obtain a suture that has appropriate physical properties and usability as a suture and can be used practically. It was true. In view of the current situation, the present inventors have conducted intensive research with the aim of providing an ideal absorbable surgical suture thread that does not have the above-mentioned drawbacks. a suture having a knot strength of at least 1.4;
The present invention was achieved by discovering that a suture having a g/d ratio can achieve the above object. That is, the present invention provides a suture thread composed of chitin fibers, which has good absorbability, characterized in that the thickness of the chitin fibers is 20 d or less, and the knot strength of the suture thread is 1.4 g/d or more. This is a surgical suture thread. The suture thread of the present invention has sufficient strength and flexibility as a surgical suture thread, and has good ease of sewing and knotting due to its low coefficient of surface friction. Furthermore, the suture of the present invention maintains the necessary strength for about 10 days and then is absorbed by the living body, meaning that it has moderate bioabsorbability as an absorbable suture. It is ideal as an absorbable surgical suture thread as it has good resistance to bacteria, is difficult to cause antigen-antibody reactions and is biocompatible, and is also difficult to decompose in the air and is easy to store. . The chitin fibers constituting the suture of the present invention have a thickness of
It is 20 d or less, preferably 0.5 to 5 d. 20d
If the suture thread exceeds this value, it will not only lack flexibility and usability, but also have poor bioabsorbability and biocompatibility. The chitin fiber used in the present invention needs to have a thickness of 20 d or less as described above, but also 2 g/d or more, further 2.5 g/d or more, further 3 g/d or more, and even 3.5 g /d
It is preferable to have a dry strength equal to or higher than that. Such chitin fibers are produced by, for example, extruding a chitin dope consisting of chitin and a solvent into a coagulation bath through a nozzle and taking it off to form threads containing the solvent, and then applying tension to the threads. It can be manufactured by processing with a coagulating liquid in the absence of force. Chitin in the present invention includes not only chitin itself but also chitin derivatives. Such chitin can be prepared, for example, by treating crustaceans, insects, etc. with hydrochloric acid and caustic soda to separate and purify protein and calcium components, or by etherifying, esterifying, etc. can. Examples of chitin derivatives include etherified chitins such as carboxymethylated chitin and hydroxyethylated chitin, and esterified chitins such as acetylated chitin and sulfonated chitin. Examples of esterified products include formic acid, acetic acid, butyric acid, valeric acid, isobutyric acid, isovaleric acid, benzoic acid, cinnamic acid, salicylic acid, anthranilic acid,
Carboxylic acids such as phthalic acid, sulfonic acids such as sulfuric acid, trienesulfonic acid, and sulfanilic acid,
Examples include esters of carbonates or their anhydrides. To prepare these esterified products, for example, chitin powder may be treated with the above-mentioned acids or their aqueous solutions, and if necessary, sulfuric acid, hydrochloric acid, toluenesulfonic acid, etc. can also be used as a catalyst. The degree of esterification can be adjusted by changing the composition, temperature, or treatment time of the treatment solution. For example, acetylation can be carried out in a relatively short time. For example, chitin powder is soaked in 90% acetic acid for 10 minutes at room temperature, thoroughly washed with water, then neutralized with ammonium hydroxide to completely remove free acetic acid, and dried to achieve an acetylation degree of approximately 6%. Acetylated chitin can be adjusted. Although various known chitin solvents can be used as the solvent for preparing the chitin dope, trichloroacetic acid is preferably used. Since the melting point of trichloroacetic acid is 57°C, it is necessary to maintain the temperature at least above 57°C in order to obtain chitin dope. Since chitin decomposes to some extent at such temperatures, it is desirable to use trichloroacetic acid as a solvent together with an organic solvent that can dissolve trichloroacetic acid, preferably at 50° C. or lower, more preferably at room temperature or lower. Examples of solvents that can dissolve trichloroacetic acid and provide a uniform chitin dope at room temperature include chlorinated hydrocarbons. Preferred chlorinated hydrocarbons include, for example, chloromethane, dichloromethane, chloroform,
Carbon tetrachloride, 1,2-dichloroethane, 1,1,
Examples include 1-trichloroethane and 1,1,2-trichloroethane, which may be used alone or in combination of two or more. The mixing ratio of trichloroacetic acid and chlorinated hydrocarbon is preferably in the range of 25-75:75-25 (weight ratio).
The higher the proportion of trichloroacetic acid, the better the solubility of chitin, but in order to avoid a decrease in the molecular weight due to the decomposition of chitin, the above range in which the mixed solvent is liquid at room temperature or lower is preferable. In the present invention, chitin dope can be prepared, for example, as follows. In other words, if only trichloroacetic acid is used as a solvent, the temperature of trichloroacetic acid at least 57°C
Gradually add chitin powder while heating to above temperature.
What is necessary is just to stir and mix and dissolve. In addition, when using a mixed solvent of trichloroacetic acid and chlorinated hydrocarbon as a solvent, add and mix trichloroacetic acid to the chlorinated hydrocarbon in advance to obtain a liquid mixed solvent at as low a temperature as possible, preferably below 10°C. Chitin powder may be gradually added to the mixed solvent and dissolved by stirring and mixing. The concentration of chitin in the chitin dope is preferably 0.5-20% by weight, more preferably 0.5-10% by weight, even more preferably 1-10% by weight. If the concentration of chitin becomes too high, it will be difficult to dissolve it and it will also be difficult to produce fibers from such chitin dope.
If it is too low, it becomes difficult to obtain fibers with excellent mechanical properties, which is not preferable. Chitin dope contains, for example, dyes, pigments, stabilizers, antioxidants,
Additives such as heat resistant agents, bactericidal agents, preservatives, anesthetics, and fillers can be added as necessary. To produce chitin fibers, first, the chitin dope prepared as described above is extruded through a nozzle into a coagulation bath and taken off to form a thread containing a solvent. Coagulation baths include organic ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, diethyl ketone, and cyclopentanone, chlorinated hydrocarbons such as ethylene chloride, carbon tetrachloride, trichlorethylene, and tetrahydrofuran, cyclohexane, hexane, and petroleum. Hydrocarbons such as ether, alcohols such as methanol, ethanol, isopropyl alcohol, and n-butyl alcohol, esters such as ethyl acetate, and amides such as dimethylformamide and N-methylpyrrolidone can be used, but in particular, Anhydrous acetone, anhydrous methanol, anhydrous ethanol, etc. are preferred. The temperature of the coagulation bath is preferably about 10 to 25°C. The chitin dope is filtered and defoamed if necessary, and then extruded from a nozzle into a coagulation bath and taken off. For this purpose, a conventional wet spinning device and method can be employed. At this time, the pulled yarn contains a solvent, that is, is in a state of incomplete coagulation, but the yarn thus formed is then subjected to a substantial tension force. Treat it with a coagulating solution without washing. As mentioned above, the taken yarn still contains some solvent,
In order to treat this material with a coagulating liquid in a state where no tension is applied to it, for example, after spinning, the yarn, which is taken up by a roll through a coagulating bath (first coagulating bath), is introduced into a second coagulating bath. It is possible to adopt a method of processing For example, the yarn is extruded from a nozzle into the first coagulation bath and then taken off by a roller.
It is shaken down onto the conveyor by an introduction roller to form a thread pile. the conveyor is in a second coagulation bath;
The yarn moves at a speed slower than the introduction speed of the yarn, and after the yarn is coagulated in the second coagulation bath, it is returned to a yarn state from the thread pile and taken off by a take-up roller. In addition, the yarn extruded from the nozzle into the first coagulation bath and then taken up by a roller is dropped by an introduction roller into a device having a curved pipe shape capable of packing the yarn, such as a U-shaped tube, and is laminated. Ru. The U-shaped tube is filled with a coagulating liquid, and the yarn is moved to the other opening of the U-shaped tube due to the lamination pressure and coagulated. After that, it is returned to a yarn state and is taken up by a take-up roller. It will be done. Second
It is possible to provide a plurality of coagulation baths, and it is also possible to stack the yarns introduced into the second coagulation bath as they are in the coagulation bath and then take them out. Any method can be adopted as long as it can be processed in a state where the yarn is not substantially subjected to tension, such as processing in the first coagulation bath without providing any. As the coagulating liquid used in this treatment, those used in the above-mentioned coagulating bath (spinning bath) can be used. When treating with a coagulating liquid, the amount of solvent remaining in the yarn is preferably in the range of 10 to 50% by weight (based on the polymer) before treatment and 10% by weight or less after treatment.
It is desirable that the treatment time be 1 minute or more, particularly 10 minutes or more. Another preferred method is to leave it for one night or more. The fibers obtained as described above have a dryness of 2 g/d or more as is, but by stretching them, fibers with even higher strength can be obtained. Stretching may be carried out subsequent to treatment with a coagulating solution, or may be carried out after neutralization and washing, and various known devices may be used; be able to. The yarn treated with the coagulation liquid is neutralized, washed, and dried as necessary. Various known devices and methods can be used for neutralization, washing, and drying. The suture of the present invention can be obtained by twisting or braiding a plurality of these chitin fibers, for example 6 to 16. The thickness of the suture thread can be adjusted as appropriate depending on the denier of the chitin fibers used, the number of threads, etc., but the
USP size 1, 2, 3, 4, 1-0, 2-0, 3
-0, 4-0, 5-0, 6-0, 7-0, 8-
0, 9-0, etc. are preferably used. The thus obtained suture of the present invention has a weight loss of 1.4 g/d or more, preferably 1.8 g/d or more, more preferably 2.1 g/d or more.
It has a knot strength of d or more, more preferably 2.4 g/d or more. The suture of the present invention can be treated with, for example, dyes, pigments, stabilizers, antioxidants, heat resistant agents, bactericidal agents, preservatives, anesthetics, etc., so after being subjected to the necessary treatments depending on the purpose. Can be put to practical use. The suture thread of the present invention not only has sufficient physical properties and usability as a surgical suture thread, but also has appropriate bioabsorbability and good biocompatibility, as well as excellent resistance to germs and storage stability. It is ideal as an absorbable surgical suture. The present invention will be explained in more detail below by giving examples. The knot strength of the suture is USP <
881＞Tensile Strength - tying defined by surgical sutures, commonly known as surgical knots
Measured using an Instron tensile tester at ℃ and 60% RH. Example 1, Comparative Examples 1 and 2 Chitin powder [manufactured by Kyowa Yushi Co., Ltd., degree of polymerization approximately 1 million]
A chitin dope was obtained by dissolving 3 parts by weight in a mixed solvent consisting of 50 parts by weight of trichloroacetic acid and 50 parts by weight of methylene chloride at 5°C. The dope obtained was a clear and viscous solution. This dope was filtered under a pressure of 4 kg/cm ² using a stainless wire mesh of 1480 mesh, and then thoroughly defoamed under reduced pressure. After the defoamed dope was transferred to a tank, it was pumped with a gear pump under a pressure of 2.5 kg/cm ² to form a hole with a pore diameter of 0.08 mm and 40 holes.
The yarn was spun into acetone (first coagulation bath) whose temperature was controlled at 14° C. at a discharge rate of 2.3 ml/min from a nozzle, and the yarn was drawn onto a roller at a speed of 10 ml/min. The collected yarn was then treated in methanol (second coagulation bath) whose temperature was controlled to 15°C for 5 minutes on a conveyor moving at a speed of 0.5 m/min, and then wound into a winder at a speed of 9 m/min. . The density of the thread that has been wound up
After neutralizing by immersing in 0.3 g/aqueous caustic soda solution for 1 hour, washing with ion-exchanged water until the pH of the washing water becomes neutral, then dehydrating with a centrifugal dehydrator, and drying under reduced pressure at room temperature overnight. Thus, chitin fibers were obtained (sample A). The obtained chitin fiber had a denier of 65 d (single yarn 1.62 d) and a dry strength of 3.10 g/d. For comparison, without using a belt conveyor,
Chitin fibers were obtained in the same manner as in Example 1, except that the fibers were simply passed through the second coagulation bath under tension (Sample B). The obtained chitin fiber had a denier of 64 d (single yarn 1.60 d) and a dry strength of 1.65 g/d. Also,
For comparison, chitin fibers were obtained in the same manner as in Example 1 except that a nozzle with a hole diameter of 0.15 mm and 3 holes was used (Sample C). The resulting chitin fiber has a denier of 71d.
(single yarn 35.5 d), and the dry strength was 2.9 g/d. For Samples A, B, and C, 16 threads were each braided to create a 3-0 (thread diameter: approximately 0.32 mm) suture thread according to the USP XX edition collagen suture thread standard. The knot strength of the obtained suture was measured and the results were as shown in Table 1.

[Table] The three types of suture threads A, B, and C were dyed, sterilized, and used to suture the abdominal muscles of domestic rabbits, but sample B was not able to be sutured because it was frequently cut during suturing. However, Sample C was rigid, difficult to handle, and difficult to tie. On the other hand, sample A had low intramuscular resistance during suturing, was easy to handle, did not slip, and could be sutured well. Furthermore, the nodule was removed at intervals of 5, 15, and 30 days after implantation, and the retention rate of the nodule strength was measured.
It was 74% after 5 days, 18% after 15 days, and 0% after 30 days, indicating good bioabsorption. Example 2, Comparative Examples 3 and 4 The chitin fiber of Example 1 was stretched 1.4 times to obtain a chitin fiber having a denier of 46 d (single yarn 1.16 d) and a dry strength of 4.1 g/d. One or two of these were braided to create a USP size 4-0 suture thread. This suture was used to suture the back muscles of a domestic rabbit, and after 5, 10, 20, and 30 days, the suture was taken out from the sutured area, and the retention rate of the knot strength was determined. I checked the reaction. For comparison, similar tests were conducted on polyglycolic acid suture thread (Comparative Example 3) and Katsutogut (chromic processed) (Comparative Example 4). First, when we compared the usability of the three types of sutures during suturing, we found that polyglycolic acid sutures had poor slippage and were difficult to enter tissue, while cut-off sutures were wire-like and difficult to suture, making it difficult to create knots. In contrast, the suture thread of the present invention had a feel similar to silk thread, was smooth to handle, easily entered tissue, and was easy to knot. In addition, the results of bioabsorption were as shown in Table 2.

[Table] As is clear from the results in Table 2, the suture of the present invention was absorbed too quickly, whereas the suture of the present invention
This is a favorable result for an absorbable surgical suture in that it is slowly absorbed until the first day and then rapidly absorbed.

Claims (1)

[Claims] 1. A suture made of chitin fibers,
A surgical suture having good absorbability, characterized in that the thickness of chitin fibers is 20 d or less and the knot strength of the suture is 1.4 g/d or more. 2. The suture according to claim 1, wherein the thickness of the chitin fibers is 5 d or less.