JPH031984B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a surgical suture made of polyester containing an organosilicon polymer in its main chain. [Prior art] Surgical sutures are made of many types of base materials, ranging from natural polymer compounds such as silk to synthetic polymer compounds such as polypropylene. used for. Examples of the suture thread include natural fibers such as silk and cotton; synthetic fibers such as polyester, polyamide, and polyolefin; and absorbable fibers such as catgut and polyglycolic acid. However, with the recent advances in medical science, there are times when these conventional sutures cannot be used in sophisticated and complex surgeries, and there is currently a need for the development of even better sutures. be. [Problems to be solved by the invention] In particular, sutures used for anastomosis of blood vessels or anastomosis of blood vessels and artificial blood vessels must (a) have excellent antithrombotic properties; (b) stress-distortion of the blood vessel wall; It is desired to have three properties: (c) flexibility that approximates that of a wire, and (c) excellent operability (especially slipperiness) during surgery. The present invention has been made with the object of providing a novel surgical suture having all of these three properties. [Means for Solving the Problem] The present inventors have discovered that polyester containing an organosilicon polymer in its main chain has excellent antithrombotic properties and slipperiness, and that the polyester fibers are threaded. They discovered that a flexibility similar to the stress-strain curve of a blood vessel wall appears, and completed the present invention. That is, the present invention has a molecular weight of 200 to 10,000 in the main chain.
The present invention relates to a surgical suture made of a polyester containing 1 to 50% by weight of an organosilicon polymer, and further containing polyether and/or polyester having a molecular weight of 500 or more as a soft segment other than the organosilicon polymer. [Example] The surgical suture of the present invention has a molecular weight of 200 in the main chain.
~10,000, and a polyester containing 1 to 50% by weight of an organosilicon polymer and a polyether and/or polyester having a molecular weight of 500 or more as a soft segment other than the organosilicon polymer. The content of organosilicon polymer in the polyester is preferably 1 to 50% by weight, especially 2 to 30% by weight, especially 3 to 20% by weight. If the content of the organosilicon polymer is less than 1% by weight, the antithrombotic properties and slipperiness will be poor, and if it exceeds 50% by weight, the tensile strength and antithrombotic properties will be poor. The molecular weight of the organosilicon polymer is preferably 200 to 10,000, and in consideration of the balance of mechanical properties and antithrombotic properties, the molecular weight is preferably 400 to 5,000, particularly 500 to 3,000. When the molecular weight of the organosilicon polymer is less than 200, its antithrombotic properties are poor;
Moreover, when it exceeds 10,000, the mechanical properties tend to be inferior. The binding method of the organosilicon polymer is not particularly limited as long as it contains organosilicon, but in order to exhibit antithrombotic properties, it may be further combined with the general formula (): (In the formula, R ¹ and R ² are each hydrogen, an alkyl group, a phenyl group, an alkylphenyl group, a phenylalkyl group, or a fluorinated group thereof, and n represents an integer of 1 or more) Among the polysiloxanes represented, polydimethylsiloxane is particularly preferred. Furthermore, polydimethylsiloxane can be expressed by the general formula (): (In the formula, R ₃ to _{R 6} are alkylene groups having 2 or more carbon atoms,
(a and e are integers of 0 to 30, b and d are 0 or 1, and c is an integer of 2 to 134), preferably contained in the main chain of the polyester elastomer. Further, in the general formula (), R ₃ to _{R 6} are groups selected from alkylene groups having 2 or more carbon atoms, and ethylene, propylene, butylene, or hexamethylene groups are particularly preferred. Furthermore, a and e are preferably integers of 0 to 20. b and d are 0 or 1, but considering the safety when used in the body over a long period of time, it is desirable that they do not contain Si-O-C bonds that are susceptible to hydrolysis, and in this sense b and d are preferably 1. c is determined by selection of the molecular weight of the polydimethylsiloxane moiety. The molecular weight of the polydimethylsiloxane portion is
Preferably from 200 to 10,000, more preferably from 400 to
5000, particularly preferably 500 to 3000. The polyester used in the surgical suture of the present invention contains polyether and/or polyester having a molecular weight of 500 or more as a soft segment other than the organosilicon polymer. The soft segment in the present invention refers to a diol compound containing an organosilicon polymer and a molecular weight
It is a residue obtained by removing hydrogen from the hydroxyl group of a long-chain diol compound consisting of polyether and/or polyester of 500 or more, and has a glass transition point (hereinafter referred to as
(referred to as T _g ) is below room temperature. The molecular weight of the polyether and/or polyester used as the soft segment is
It is preferably 500 to 6000, particularly 500 to 3000. Considering hydrolyzability in vivo and thermal stability during production, polyether is more preferable than polyester. Soft segment ratio (S) in the present invention
is determined by the following formula: S = (molecular weight of total soft segments) / (total molecular weight)
% by weight, especially 25-45% by weight is preferred. If the proportion of the soft segment is less than 10% by weight, the flexibility will be insufficient, and if it exceeds 70% by weight, the tensile strength will be poor. The reduced specific viscosity (η _sp /C) of the polyester used in the present invention is 0.5 to 3.0 (polymer concentration c
= 0.5/dl measured at 25°C), and further
0.7-2.5 is preferred. Of course, a composition of the polyester and a polyester containing no other organosilicon polymer can also be used in the present invention, as long as the properties of the polyester are exhibited. The surgical suture of the present invention is made by spinning the polyester and then stretching it, but the optimal stretching ratio cannot be determined unconditionally because it changes depending on the properties of the polyester, especially the soft segment ratio. It is preferably 3 to 15 times, more preferably 5 to 12 times, particularly 6 to 10 times. By this stretching, the polyester molecules are strongly oriented, and a material having a flexibility similar to that of a blood vessel wall and a tensile strength sufficiently large as a suture thread can be obtained. Therefore, if the stretching ratio is less than 3 times, it will become too flexible and the tensile strength will be insufficient, and if it exceeds 15 times, the flexibility will be poor. As used herein, flexibility similar to a blood vessel wall means:
This means that the material has a stress-strain curve that shows a small elastic modulus up to a certain strain in the range of 10 to 15%, and that shows a rapidly high elastic modulus beyond that strain. Next, one embodiment of the method for manufacturing a surgical suture according to the present invention will be described, but the present invention is not limited to this embodiment. First, the polyester used in the surgical suture of the present invention is composed of a dicarboxylic acid compound, a short chain diol compound with a molecular weight of 300 or less, a diol compound containing an organosilicon polymer with a molecular weight of 200 to 10,000, and a molecular weight
A long chain diol compound consisting of 500 or more polyethers and/or polyesters is polymerized as an essential component. The dicarboxylic oxidized compound means a dicarboxylic acid or an ester-forming equivalent thereof, such as an aromatic dicarboxylic acid or an aliphatic (including alicyclic)
(same hereinafter) refers to dicarboxylic acids, their dialkyl esters, halides, acid anhydrides, etc. Specific examples of the dicarboxylic acid compounds include terephthalic acid, phthalic acid, isophthalic acid, 4,4'-biphenyldicarboxylic acid, 4,4'-biphenyldicarboxylic acid,
4'-sulfonyl dibenzoic acid, 2,6-naphthalene dicarboxylic acid, cyclohexanedicarboxylic acid, adipic acid, sebacic acid, succinic acid, fumaric acid, etc., or one type of dialkyl ester, halide, or acid anhydride thereof Alternatively, a mixture of two or more types can be mentioned, and among these, terephthalic acid and its dialkyl ester are particularly preferred from the viewpoint of moldability and physical properties based on the crystallinity of the hard segment. The short chain diol compound with a molecular weight of 300 or less is
Refers to short-chain diols or their ester-forming equivalents with a molecular weight of 300 or less. For example, ethylene glycol, propylene glycol, 1,4'-butanediol, 1,3'-butanediol, 2,
One or a mixture of two or more of 3'-butanediol, diethylene glycol, dipropylene glycol, triethylene glycol, 1,5-pentanediol, 1,6-hexyldiol, neopentyl glycol, hydrogenated bisphenol A, etc. Can be used. Among these, ethylene glycol and 1,4-butanediol are more preferred in order to obtain a suture having excellent mechanical properties. Considering that the heating temperature during polycondensation and molding is low and the crystallization rate is high, 1,4-butanediol is particularly preferred. The diol compound containing an organosilicon polymer used in the present invention has the general formula (): −(R ₇ ) _f −
(OR ₈ ) _g -OH (R ₇ and R ₈ are alkylene groups with 2 or more carbon atoms, f is 0 or 1, and g is an integer from 0 to 30)
or its ester-forming equivalent. In order to obtain excellent antithrombotic properties, the general formula (): (In the formula, R ₃ to _{R 6} are alkylene groups having 2 or more carbon atoms,
A diol compound containing an organosilicon polymer represented by (a and e are integers of 0 to 30, b and d are 0 or 1, and C is an integer of 2 to 134) is preferred. Further, in the general formula (), R ₃ to _{R 6} are groups selected from alkylene groups having 2 or more carbon atoms, and ethylene, propylene, butylene, or hexamethylene groups are particularly preferred. Furthermore, a and e are preferably integers of 0 to 20. b and d are 0 or 1, but considering the safety when used in the body over a long period of time, it is desirable that they do not contain Si-O-C bonds that are susceptible to hydrolysis, and in this sense b and d are preferably 1. c is determined by the selection of the molecular weight of the polydimethylsiloxane moiety, and this molecular weight is preferably from 200 to 10,000, more preferably from 400 to 10,000.
5000, particularly preferably 500 to 3000. The long-chain diol compound made of polyether and/or polyester with a molecular weight of 500 or more used in the present invention has hydroxyl groups at both ends (or as close as possible to both ends), and the T _g of the polymer is below room temperature. or a diol compound of a polyether, polyester or block polymer thereof, or an ester-forming equivalent thereof. Considering its properties as an elastomer, it has a molecular weight of 500 to 6000, especially a molecular weight of 500 to 6000.
Preferably it is 3000. Examples of the long-chain diol compound include polyethylene glycol, polypropylene glycol, polytetramethylene glycol, glycols composed of block polymers thereof, and general formula (): (In the formula, R is an alkylene group having 2 to 6 carbon atoms, h is an integer of 1 or more) such as polyethers such as polyalkylene oxide adducts of bisphenol A, and polyesters such as polylactone. However, it is particularly preferable that R is an ethylene group. Considering stability against hydrolysis and ease of polycondensation, polyethers are more preferred. Among polyethers, polytetramethylene glycol and polyalkylene oxide adducts of bisphenol A represented by the general formula () are particularly preferred from the viewpoint of antithrombotic properties, mechanical properties, and heat resistance. The content ratio of long chain diol compound and diol compound containing organosilicon polymer is 1/5 to 69/1
is preferable, more preferably 1/1 to 30/1, particularly preferably 2/1 to 20/1. If this ratio exceeds 69/1, the antithrombotic properties and slipperiness will be poor, and if this ratio is less than 1/5, the tensile strength and antithrombotic properties will be poor. The polyester can be manufactured by a normal polyester manufacturing method. for example,
Direct esterification reaction using glycol and polybasic acid, direct esterification reaction using glycol and acid anhydride, transesterification reaction between dicarboxylic acid ester and glycol, polycondensation reaction of dicarboxylic acid ester, metathesis reaction between dicarboxylic acid chloride and diol. There are various methods such as Among these, the most common is the transesterification reaction between a dicarboxylic acid ester and a glycol, so this method will be explained. In this method, raw materials are transesterified and then the transesterified products are polycondensed.
The transesterification reaction is carried out at a high temperature of about 150 to 250° C. in an atmosphere of an inert gas such as nitrogen gas in the presence of a catalyst between a dicarboxylic acid dialkyl ester and a glycol. As a catalyst, organic titanium, antimony,
Known transesterification catalysts can be used, such as compounds such as lead, zinc, magnesium, germanium, calcium and manganese. The polycondensation reaction is carried out under reduced pressure of about 1 mmH _g or less and heated to a temperature within the range of the melting point of the resulting copolymer to 300°C, but the thermal decomposition of diol compounds containing long chain diol compounds and organic silicon polymers is Taking this into consideration, a range of the melting point of the produced copolymer to 260°C is more preferable. Further, in the polycondensation reaction step, a compound such as lead, titanium, antimony, niobium, germanium or the like may be added as a catalyst if necessary. The surgical suture of the present invention can be obtained by melt-extruding the polyester thus produced, quenching it, and then stretching it. Melt extrusion of polyester may be carried out using a conventional melt spinning method for synthetic fibers. After extrusion, after quenching with water or glycerin, the
It is preferable to stretch the film 12 times, particularly 6 to 10 times. Although this stretching method is not particularly limited, it is usually preferable to perform the stretching in two stages. This description will be explained in more detail below using examples. Note that "parts" used in Examples and Comparative Examples means parts by weight, and the reduced specific viscosity (η _sp /
C) is a 1:1 ratio of phenol and tetrachloroethane
Polymer concentration (C: 0.5g/
dl) at 25°C. Example 1 and Comparative Example 1 960 parts of dimethyl terephthalate, 810 parts of 1,4-butanediol, 375 parts of polytetramethylene glycol with a molecular weight of 1025, formula: 75 parts of the compound shown by, 1.5 parts of tetra-n-butyl titanate, antioxidant (Irganox 1010,
3.8 parts (manufactured by Ciba Geigy) was heated to a jacket temperature of 200°C.
The mixture was added to an autoclave under a nitrogen gas atmosphere and stirred. The temperature was raised to 250°C for 100 minutes at normal pressure, and methanol was distilled off. After reaching 250℃, 10
Polycondensation was carried out under reduced pressure of 0.5 _mmHg or less for 1 minute. Polycondensation reaction was carried out for 100 minutes to obtain polyester. The reduced specific viscosity of this polyester was 1.0. After thoroughly drying this polyester, it was thread-proofed at a temperature of 220 to 240°C and at an extrusion speed of 15 m/min. The extruded thread passed through hot water at 60°C, was stretched 4.7 times in hot water at 90°C, and then stretched 1.5 times in glycerin at 120°C. Finally, it was thoroughly washed with water, dried, and then rolled up. The antithrombotic properties of this surgical suture were measured using the polyester material as follows. Make this polyester sheet, 3cm x 3
After cutting into cm squares, they were placed on a watch glass with a lid maintained at 37°C. After placing a certain amount of dog ACD blood (preserved blood made non-coagulable by adding sodium citrate, glucose, etc.) on the sheet and the glass of the watch glass, an aqueous calcium chloride solution is added,
The amount of clotted blood (thrombus) was measured at predetermined intervals. Thrombus formation rate (%) was calculated using the following formula. Thrombus formation rate (%) = (Weight of thrombus formed after a certain period of time on the sheet) / (Final weight of thrombus formed on glass) ×
100 For comparison, the polydimethylsiloxane compound was removed from the composition of Example 1, and polytetramethylene glycol (molecular weight:
1025) was used, and the other conditions were the same as in Example 1 (reduced specific viscosity: 1.0). A sheet made from polyester and glass were simultaneously tested using blood (Comparative Example 1). . The results (thrombus formation rate) are shown in Table 1. As can be seen from the above results, the polyester sheet used in the surgical suture of the present invention has excellent antithrombotic properties. Next, the tensile strength, elongation, and stress-strain curve of the produced yarn were measured using Shimadzu Autograph IS-2000. The measurement results of tensile strength and elongation are shown in Table 2, and the measurement results of the stress-strain curve are shown in It is shown in Figure 1. The fabricated thread has excellent operability as a surgical suture, especially in the tie-down test (a test in which two knots are tied at the top, and both ends of the thread are pulled and pulled down to the bottom). It showed ease. When this thread was used to suture the femoral artery of an adult mongrel dog and the subcutaneous tissue surrounding the femoral artery, excessive force was applied to the blood vessel wall and soft tissues of the living body, or these tissues were cut. I was able to suture with good workability. In particular, when suturing blood vessels, the adhesion of the sutured portion was good, and there was very little leakage from the sutured portion after blood flow was resumed.

【table】

[Table] Example 2 In place of polytetramethylene glycol with a molecular weight of 1025 in Example 1, the same number of moles of a compound of the following formula (molecular weight: 1000): Reduced specific viscosity under the same conditions as Example 1 except that
A polyester of 1.2 was synthesized. Using this polyester, a thread was made in the same manner as in Example 1, and as a result of evaluation, it was found to have excellent antithrombotic properties and slipperiness, and stress-
The strain curve approximated the blood vessel wall. [Effects of the Invention] As explained above, the surgical suture of the present invention has (a)
It has excellent antithrombotic properties, (b) has flexibility that approximates the stress-strain curve of the blood vessel wall, and (c) has excellent operability during surgery such as slipperiness, making it suitable for normal surgery. Of course, it has the effect of being particularly suitable for use in revascularization surgery.

[Brief explanation of the drawing]

FIG. 1 is a graph showing the measurement results of the stress-strain curve of the surgical suture of the present invention obtained in Example 1.

Claims (1)

[Claims] 1 Surgery made of polyester containing 1 to 50% by weight of an organosilicon polymer with a molecular weight of 200 to 10,000 in the main chain, and further containing polyether and/or polyester with a molecular weight of 500 or more as a soft segment other than the organosilicon polymer for sutures.