JPH0634813B2 - Surgical bioabsorbable blue fiber and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention makes surgical fibers such as sutures obtained from polyglycolic acid, poly L-lactic acid or glycolic acid-L-lactic acid copolymer blue. The present invention relates to a colored bioabsorbable fiber and a method for producing the same.

[Conventional technology and its problems]

Polyglycolic acid, poly L-lactic acid, and glycolic acid-
The L-lactic acid copolymer is a solid bioabsorbable and hydrolyzable polymer, and a polymer having a high degree of polymerization is used for surgery after being spun, knitted or processed into filament. It is used as a surgical material such as sutures and gauze.

This is because these bioabsorbable polymer materials have a pale yellow or almost translucent gray color when spun for sutures, for example. When used as a suture in surgery, it is contaminated in red by blood and it is difficult to identify the sutured portion, which often causes difficulty during surgery.

Therefore, it is known that sutures made of materials other than bioabsorbable polymer materials such as nylon and tetron are colored with various desired pigments so that they can be distinguished at a glance even if they are contaminated with blood. .

However, sutures made of bioabsorbable polymeric material
Taking advantage of the advantage, it is not removed by removing the thread after suturing the surgical site. Therefore, the dye for coloring the suture made of the bioabsorbable polymer material is non-toxic to the human body and needs to be absorbed and metabolized promptly, so that the usable dye is naturally limited.

Therefore, United States Food and Drug Administration proposes that bioabsorbable surgical sutures can be colored only with dyes that are recognized as non-toxic by the association. In Japan as well, standard standards for tar dyes for foods, pharmaceuticals and cosmetics are established, and tar dyes that can be used as external medicines and quasi-drugs are listed. (Handbook of Dyes, pp. 222-223) Among them, certain oil-soluble dyes are already known for bioabsorbable sutures and the like, and as a polyglycolic acid dye in JP-A-48-33687. 1,4-bis (p-toluidino) anthraquinone (CISolvent Green3) is used. Further, Japanese Patent Publication No. 56-14688 discloses a dye for sutures made of a glycolic acid-lactic acid copolymer, which includes 1-hydroxy-4-p-toluidinoanthraquinone (CISolv).
The disclosure using ent Violet 13) is also made.

However, these dyes are oil-soluble dyes used as resin colorants and are not necessarily nontoxic when used directly in the human body. Further, the dye described in JP-A-48-33687 is also a green dye, and therefore, when blood adheres, it becomes black and difficult to see.

Thus, these known dyes have not been satisfactory as bioabsorbable polymer dyes.

[Means for solving problems]

Based on the above-mentioned problems, the present inventors diligently studied a coloring method using a safer dye for coloring a bioabsorbable polymer material, and said one of the tar dyes that can be used in a surgical drug. It was found that a clear blue colored product can be obtained by using Indigo, which is one of the two, and the application was filed earlier.

Indigo has long been a vat dye (CI Vat Blu
It is known as e1), is a component of natural supervision, and is completely harmless to the human body. Moreover, the colored product using this is blue, and even if blood adheres, it becomes purple, so that the advantages such as easy identification are easily conceivable.

Nevertheless, since indigo is a vat dye,
It is made into an aqueous solution at the time of dyeing, and is usually used for cotton, and bioabsorbable polymers such as polyglycolic acid and polylactic acid are hydrolyzed even in the presence of a trace amount of water.
It is known that the strength is decreased, and therefore it is considered that indigo has been regarded as a dye that is completely unsuitable for coloring these bioabsorbable polymers.

However, the present inventors previously prepared a masterbatch in which the indigo and the polymer are dispersed in this using a non-aqueous organic solvent that does not dissolve the bioabsorbable polymer,
When kneaded with a polymer, bright blue colored pellets are obtained, and surprisingly, despite the fact that indigo is a vat dye, it does not affect bioabsorbable polymers such as polyglycolic acid and polylactic acid. It was found that the coloring property was very good.

Further, the present inventors, as a result of examining the coloring method using indigo, even when using a purified indigo containing no additives other than indigo, the colored polymer obtained depending on the lot of indigo slightly deteriorates the physical properties or It was found to have a brown color other than blue.

The main cause is indirubin, which is a by-product of indigo production. Or indoxyl red It is estimated that impurities such as
It is considered that these impurities are also oil-soluble and cannot be removed by ordinary purification of indigo.

The present inventors show that indigo used for removing these impurities is washed and purified with concentrated hydrochloric acid in advance, and if the purified indigo that is dried is used, the obtained colored polymer exhibits a light brown color without deterioration. It was found that there is no such thing, and the present invention has been reached.

That is, the present invention uses indigo obtained by purifying a bioabsorbable polymer selected from polyglycolic acid, poly L-lactic acid, or glycolic acid-L-lactic acid copolymer used as a surgical fiber with concentrated hydrochloric acid. The present invention provides a bioabsorbable blue fiber for surgery, which is colored blue, and when coloring blue, indigo purified using concentrated hydrochloric acid is used, and indigo and the polymer are non-aqueous systems that do not dissolve the polymer. Mix and disperse in an organic solvent, heat at a temperature of 120 ° C or less, degas the solvent to obtain a masterbatch with high concentration of indigo, knead this with a polymer and spin it into a bioabsorbable blue for surgery. It is intended to provide a coloring method for obtaining fibers.

The bioabsorbable polymer used for spinning in the present invention is polyglycolic acid, poly L-lactic acid, or glycolic acid-L-lactic acid copolymer.

These polymers used in the present invention preferably have the following physical properties, and even when these polymers contain a copolymerization component or an additive, as long as they have the same physical properties. Can be used if

The intrinsic viscosity ([η]) and melt index (MI) of these polymers are measured as follows.

◎ Intrinsic viscosity ([η]) Dissolve the polymer in a mixed solvent of phenol (10 parts by weight) and trichlorophenol (7 parts by weight) and measure with a Ubbelohde viscometer at 30 ± 0.1 ° C and a concentration of 0.5%.

◎ Melt Index (MI) American Society for Testing Mat
according to ASTM method D1238-65T issued by erials), that is, 325 g and 2.1 by melt indexer.
Extrusion at 230 ° C. using mm orifice and label MI in grams per 10 minutes.

Polyglycolic acid [η] = 0.8 to 1.3 MI = 0.1 to 5.0 Poly L-lactic acid [η] = 1.0 to 2.0 MI = 0.1 to 5.0 Glycolic acid-L-lactic acid copolymer [η] = 1.0 to 2.0 MI = 0.1 ~ 5.0 The bioabsorbable polymer having these physical properties can be obtained by a conventional method, and for example, those obtained as follows are preferable.

A stannous octoate catalyst prepared by charging glycolide or 1-lactide in a polymerization vessel and dissolving it in a solvent such as chloroform was added to the glycolide in an amount of about 0.00
3% by weight (about 0.03% is used in the conventional method), and linear aliphatic alcohols such as lauryl alcohol are used in glycolide in an amount of about 0.3% by weight (about 0.06% in the conventional method), which is higher than that in the conventional method. It is used to some extent.) After addition, degas in a vacuum. Substituting with nitrogen or argon, under a nitrogen or argon atmosphere, the reaction temperature is slightly higher than the conventional method, that is, heated to about 200 ° C for lactide polymerization and about 230 ° C for glycolide polymerization, and kept at a constant temperature for 2 to 6 hours. Polymerize. After completion of the polymerization, the product is directly removed from the lower part of the container, introduced into a pelletizer and pelletized.

The polymer thus obtained has a very low tin content, and has a molecular weight of about 10,000 to about 100,000, and when measured under the conditions as described above, in the case of polyglycolic acid, 0.8 or more, In the case of polylactic acid, at least about 1.0
As the bioabsorbable polymer having the above intrinsic viscosity, a polymer suitable for use in surgical sutures and the like can be obtained. Further, when a copolymer is obtained, the copolymer having the above physical properties can be obtained by a method according to these.

In the present invention, the bioabsorbable polymer thus obtained is preferably used for coloring by pelletizing it into granules having a particle size of 3 mm or less. If the particle size is 5 mm or more, uneven dyeing occurs when spinning after coloring, which is not preferable.

In the present invention, the method for coloring a polymer using indigo is carried out as follows.

As for indigo, a powder having an average particle size of 5 μm or less which is normally available can be used as it is. However, in that case, since a dispersant for water is usually mixed, it is washed with hot water and dried,
Completely remove the dispersant. Then concentrated hydrochloric acid, preferably 35
After stirring and washing in concentrated hydrochloric acid at a concentration of not less than%, completely dehydrate before use. By this purification treatment, the impurities such as indirubin and indoxyl red become hydrochlorides and are removed in the aqueous layer.

The indigo treatment with hydrochloric acid of the present invention is not effective with dilute hydrochloric acid, and mineral acids other than hydrochloric acid such as hydrochloric acid cannot be used because they cause sulfonation of indigo.

The amount of indigo used is 0.01 to 1.0% by weight, preferably 0.05 to 0.3% by weight, based on the polymer. If it is less than 0.01%, the coloring effect is poor and 1.0
If it is used at a high concentration of at least%, the strength of the yarn will be slightly reduced when spun.

As a method of adding indigo to the pelletized polymer, indigo may be directly mixed with a polymer without a solvent, or a method of directly adjusting a masterbatch without a solvent may be carried out, but such a direct mixing may be performed. In that case, since the loss of the indigo dye during coloring and mixing is large and the coloring property is not always sufficient, in the present invention, the method of dispersion dyeing using a non-aqueous organic solvent is preferable.

That is, in the present invention, ethyl acetate, toluene, xylene, using a non-aqueous solvent such as hexane, to prepare a high-concentration dispersion of indigo dispersed in it, a high concentration of some used polymer added It is recommended to prepare a masterbatch of 1) and dilute it with a polymer before use.

The solvent for the indigo dispersion is preferably a low boiling point solvent that does not dissolve the polymer at all, and desolvation becomes difficult when a solvent that dissolves the polymer used is used. Therefore DM
SO, DMF and the like dissolve the polymer and are not suitable for the method of the present invention.

Ethyl acetate is particularly preferable for coloring polyglycolic acid, and hexane is preferable for polylactic acid.

In the present invention, a high-concentration masterbatch in which indigo is attached to the polymer is prepared in advance by adding a desired polymer as a masterbatch to the indigo dispersion using such an indigo dispersion and heating the solvent to almost completely remove the solvent. Adjusted. In the adjustment, when the indigo concentration is suture, the indigo concentration during spinning (0.01 to 1.0% by weight)
While indigo was added and mixed thoroughly so as to be 0.05 to 10.0% by weight, which is equivalent to 5 to 10 times, while heating to 50 to 70 ° C,
The wet cake masterbatch obtained by removing most of the solvent under reduced pressure is further heated to 120 ° C or lower to 20 m.
By heating under a vacuum of about mHg for about 3 hours, a dried masterbatch containing less than 0.1% of solvent can be obtained. Then 120
It is necessary to degas below ℃, and above 120 ℃,
Since deaeration takes a long time, it causes thermal deterioration of the polymer during deaeration.

The masterbatch thus obtained is kneaded with an uncolored polymer according to a conventional method to obtain a blue-colored primary polymer.

In the mixing of the masterbatch and the uncolored polymer, it is preferable to mix 5 to 10 parts by weight of the uncolored polymer with 1 part by weight of the masterbatch, so that the concentration of indigo dispersed in the colored polymer is 0.01 to 1.0. weight%
You can get

In the spinning for obtaining, for example, a suture, using the thus obtained primary polymer, melt spinning is performed using a conventional melt extruder through a nozzle having 8 to 40 holes to produce a multifilament. Extrusion pressure is 10 by the extrusion screw
-200 kg / cm < ² >, extrusion temperature is carried out at 230-250 degreeC.

After spinning, it is continuously introduced onto a hot plate kept at 120 ° C., where it is stretched about 4 times to obtain a good blue multifilament having a tensile strength of 6.5 g / denier. This is braided, sterilized and sealed according to a conventional method, and used as a surgical suture.

〔Example〕

Examples will be shown below, but the indigo content in the examples was quantified as follows.

Indigo Quantitative Method Colored polymer or 1g of fiber after spinning and drawing 20m
Boiled with dimethylformamide for 10 minutes and cooled to 50 ° C. or lower, the filtered solution was diluted as needed, the absorption peak intensity at 610 nm was measured using a visible absorption device, and the content was calculated from this.

Reference example 20 g of glycolide (mp83.5-84.5 ° C) obtained from oxyacetic acid (glycolic acid) was placed in a thick cylindrical stainless steel polymerization container (separable type: main body and cover can be separated), and octane Stannous acid 0.6 mg (0.003% by weight, 1.5 ×
Chloroform solution (10 ^-6 mol) 0.3 m and lauryl alcohol 48.0 mg (0.24 wt%, 28 x 10 ^-4 mol, 80 wt times stannous octoate catalyst) chloroform solution 0.3 m
And were added to a container, and the mixture was degassed under vacuum (1 to 5 mmHg) for 2 hours and then replaced with nitrogen gas. This mixture is heated under a nitrogen atmosphere using a mantle heater for 2 to 6 hours at 200 to 230 ° C.
And heat to polymerize. After completion of the polymerization, the product was taken out from the lower part of the container as it was, introduced into a pelletizer and pelletized to obtain 19 g of colorless polyglycolic acid. When the viscosity of this polyglycolic acid was measured, the intrinsic viscosity was [η] inh = 1.06 and MI = 2.0. In the same manner, a total of 200 g of polyglycolic acid was obtained.

〔Example〕

20 g of indigo powder (Indigo Pure EX manufactured by Mitsui Toatsu Dye) washed with hot water and dried was added to 100 m of 35% hydrochloric acid and stirred at room temperature for 30 minutes. The product was filtered under reduced pressure with a Nutsche equipped with a glass filter, and the filtered product was washed with distilled water until the pH of the washing solution became 6 or more.

The cake obtained is dried and crushed to produce 19.4 g of purified indigo.
Got

1.0 g of the refined indigo powder thus obtained was mixed and dispersed in 200 m of ethyl acetate, and 200 g of the polyglycolic acid pellet obtained in the above Reference Example was added and thoroughly mixed, followed by vacuum desorption at 50 to 55 ° C. The obtained wet masterbatch was further heated to 120 ° C. under vacuum to completely remove the ethyl acetate solvent to 0.1% or less to prepare a masterbatch to which 0.5% of indigo was attached.

100 g of this masterbatch was sufficiently kneaded with 900 g of polyglycolic acid, and then dried at 120 ° C. under a vacuum of 20 mmHg for 3 hours to obtain 1 kg of colored polyglycolic acid.

The colored pellets were spun at a temperature of 245 ° C. using a normal melt spinning machine and then stretched 4 times on a hot plate at 120 ° C. As a result, a blue filament for suture having good tensile strength of 6.5 g / denier was obtained. Obtained. [Η] of this blue filament is
It was 0.90.

The indigo was 0.05 in the obtained blue filament.
%, It was found that the indigo used was all present in the polymer.

Comparative Example 1.0 g of commercially available indigo powder that had been treated with boiling water and then dried
1 kg of colored polyglycolic acid was obtained in exactly the same manner as in the example except that was used.

The colored pellets were spun at a temperature of 245 ° C. using an ordinary melt spinning machine in the same manner as in Example, and then stretched 4 times at 120 ° C. As a result, a filament having a tensile strength of 5.0 g / denier was obtained. It was bad and could not be obtained as a slightly bluish filament. Further, a thermal decomposition product of the polymer adhered to the nozzle portion during spinning.

The result of measuring the viscosity of the filament. [Η] = 0,85, and it was found that it was clearly deteriorated as compared with the examples.

Claims (2)

[Claims] 1. An indigo obtained by purifying a bioabsorbable polymer selected from polyglycolic acid, poly L-lactic acid, or glycolic acid-L-lactic acid copolymer used as a surgical fiber with concentrated hydrochloric acid. Surgical bioabsorbable blue fiber colored blue using. 2. When a bioabsorbable polymer selected from polyglycolic acid, poly L-lactic acid, or glycolic acid-L-lactic acid copolymer used as a surgical fiber is colored blue, concentrated hydrochloric acid is used. Using indigo purified using, indigo and polymer are mixed in a non-aqueous organic solvent that does not dissolve the polymer, dispersed and heated at a temperature of 120 ℃ or less, solvent degassing, indigo in high concentration master A method for producing a bioabsorbable blue fiber for surgery, which is obtained by obtaining a batch, kneading it with a polymer, and spinning the mixture.