DK152336B - STERILE ABSORBABLE SURGICAL SUTURE - Google Patents

Description

in

DK 152336B

The present invention relates to a novel absorbable surgical suture in the form of a stretched, preferably colored, multifilament structure that retains at least 50% of its original tensile strength for 15 days and at least 20% of its original tensile strength for 21 days after implantation into living animal tissue.

Catgut monofilaments (collagen derived from beef or sheep intestines) are the most commonly used absorbable suture on the market. Collagen sutures are also prepared by extrusion of acid-swollen collagen fibrils originating from sheep tendons into a dehydration bath to form filaments which are stretched to further orient the collagen fibrils and co-cure to form a strand. The preparation of regenerated collagen sutures is disclosed in United States Patent Nos. 3,114,372 and 3,114,593.

Absorbable sutures may also be prepared from polyhydric acetic acid ester as described in U.S. Patent No. 3,297,033. However, such polyhydroxyacetic acid ester homopolymer sutures are a serious drawback that they rapidly lose tensile strength when implanted in an animal body, and in this respect are less desirable than tanned catgut.

According to United States Patent No. 3,422,181, polyglycolic acid homopolymer filaments can be appreciably improved in their in vivo absorption characteristics by heat treatment at temperatures of 50 to 190 ° C for a time varying inversely with temperature and extending say from approx. 5 hours to approx. 5 minutes. Table I of the above patent describes braided sutures made from heat-treated monofilament. The sutures listed in Table I have a direct tensile strength of 385 N / mm and a knuckle strength of 261 N / mm. After 15 days of implantation in rabbits, the tensile strength of this suture material is 54 N / mm or 13.9% of the original tensile strength.

Another disadvantage of the polyglycolide suture made as described in U.S. Patent No. 3,297,033 is that the color of the extruded filament varies from off-white to light yellow-brown. Such a bright color is undesirable in a suture due to the so-called "chameleon effect". The suture will how-

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2 will be stained red when placed in the operating cavity and are not easily distinguishable from the operating surgeon in a bloody area. Although numerous methods of dyeing textile filaments are known, the current regulations of the United States Food & Drug Administration state that an absorbable surgical suture can only be stained with the materials approved by the said authority as non-toxic . The problem of staining polyglycolic acid sutures is further complicated by the fact that such sutures are easily hydrolyzed with consequent loss in tensile strength in the presence of moisture, especially at the elevated temperatures frequently used in dyeing textiles.

Dr. I.L. Lichtenstein has in Jour. A. Med. Assoc., Vol. 24, page 760 (1970) commented on the importance of sutures 15 retaining a high percentage of their initial tensile strength during the later stages of the healing process. Surgical sutures consisting of copolymers having a predominant content of polylactide are known from French Patent No. 1,478,694 and US Patent No. 3,531,561. Such copolymers may have a glycolide content of up to 15% according to claim 1 of the French patent and column 1, line 40 of the US patent.

Finally, British Patent No. 988,939 discloses a process for polymerizing glycolide, optionally in the presence of some homologues of the general formula set out on page 1, lines 12-16. As an example, citation is mentioned. To effect the softening point, approx. 15% lactide (cf. page 1, lines 47-62).

The invention according to said British patent is based on the discovery that long polymerization times can be avoided by polymerizing the glycolide in a screw extruder if desired, with the addition of a homologue thereof in the presence of stannous ethate as a catalyst, the temperature of the screw extruder being arranged so that it rises from approx. At the feed side to a maximum in the range of 190 ° to 225 ° C, depending on the amount of homolog initially present in the glycolide, also decreases towards the discharge side.

3

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Ov · '... . Λ_ν; ^ i;

Under the polymerization, a dye can also be added.

According to Example 5, polymerization can be carried out in the extruder and then molding into foils or filaments. The polymericates obtained are insoluble and do not swell 05 in water or other solvents.

The technical problem underlying the present invention is to produce a absorbable suture based on L (-) - lactide and glycolide for a surgical purpose, which has the greatest possible initial tensile strength and knot strength, which tensile strength even after use during wound healing for up to 21 days, to a large extent, after which the suture after these 21 days is rapidly absorbed.

This technical problem is solved in the manner specified in the characterizing part of claim 1.

The suture of the invention consists of a heat-treated copolymer isate which is obtained by reacting at least 85 mole percent and not more than 90 mole percent glycolide with at least 10 mole percent and not more than 15 mole percent L (-) lactide in the presence of 20 a stannous octoate catalyst. are braided, heat treated and sterilized to produce a suture characterized by improved tensile strength retention for 15 and 21 days, respectively, after implantation. This suture material can also be stained for internal use by adding from 0.1% to 0.5% by weight by D&C Violet No. 2 to the monomer mixture prior to polymerization without adversely affecting the retaining strength of the colored suture.

This advantage that a large portion of the initial tensile strength is retained after 15-21 days of implantation into living tissue, seems to be characteristic of the above described L (-) - lactide / glycolide copolymer material when extruded, stretched, is braided, heat treated and sterilized according to the procedures described below.

The invention will become more apparent from the following detailed description when coupled with the drawing which shows, by way of example, a preferred embodiment of the invention.

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4 In the drawing, FIG. 1 shows an apparatus for extruding and stretching poly- [L (-) - lactide-co-glycolide]; FIG. Fig. 2 is a diagram showing the loss in tensile strength 05 when braided sutures originating from poly- [L (-) - lactide-co-glycolide] are implanted in animals; 3 is a graph showing the molecular weight distribution of a braided poly- [L (-) - lactide-co-glycolide] suture made in accordance with the present invention; FIG. 4 is a thermogram for the embodiment of FIG. 3, braided po ly [L (-) - late-time co-glycolide] suture, and FIG. 5 is a diagram showing the loss in tensile strength resulting from the FIG. 3 and 4, braided poly- [L (-) - lactide-co-glycolide] suture is implanted in an animal.

The material for the preparation of poly [L (-) - lactide-co-glycolide] sutures, as described herein, is a copolymer prepared by reacting at least 10 mole percent and not more than 15 mole percent L (-) - lactide with at least 85 mole percent and not more than 90 mole percent glycolide.

Both the L (-) lactide and the glycolide used in the polymerization reaction should be clean and dry. The reaction is carried out in a dry container under a dry nitrogen jacket.

Stannous ethate is used to catalyze the polymerization. It is desirable that the ratio of monomer to catalyst (mol / mol) is 50,000-150,000: 1. A smaller amount of glycolic acid may be present to regulate the molecular weight. The monomer-glycolic acid ratio ranges from 400: 1 to 2000: 1.

To induce polymerization, the mixture of L (-) - lactide and glycolide is heated at a temperature of approx. 200 ° C for approx. 5 hours until a sample of the polymer has a logarithmic viscosity number of at least 1.4 at 0.1% concentration in hexafluoro isopropanol at 25 ° C.

If the copolymer is to be used in the preparation of 35 colored sutures, the dye (from 0.1 wt.% To 0.5 wt.% D&C Violet No. 2) is added to the reaction flask prior to polymerization. D&C Violet No. 2 is 1-hydroxy-4-p-toluene

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5 idino-anthraquinone. This dye is uniformly dispersed throughout the monomer mixture and has little adverse effect on the polymerization reaction. After the polymerization reaction, the colored polymeric material can be extruded into air 05 to form a multifilament and the multifilament can be stretched and heat treated prior to the braid. After the braiding step, the braided multifilament is stretched again and heat treated prior to sterilization.

The apparatus used for extruding the copolymer materials of the present invention is illustrated in FIG. 1 of the drawing, to which reference is made to understanding the physical steps involved in the extrusion of the copolymer to form a multifilament. An extruder 10 used for the formation of the multifilament 15 has a vertical container 11 supported on its lower end with a cylindrical drum 12. A screw 14 a little smaller in diameter than the drum 12 , is mounted for rotation therein and is driven by a variable speed motor 16 via a shaft 18.

20 A finely divided copolymer material 20 to be extruded is fed into the hopper through a side arm 21 under dry nitrogen and moisture is excluded from the extruder by a continuous stream of dry nitrogen entering the hopper through an opening 22 and flowing through an opening 24.

To conclude the description of the extrusion step, the finely divided copolymer flows from the bottom of the hopper into the cylindrical drum of the extruder where it is melted and forced by the screw through a bore 26 into the chamber of a gear pump 28. The gear pump is rotated by a not shown. variable speed motor for passing the molten copolymer through a bore 30 to a die 32. Immediately prior to this die is a filter 34 consisting of small classified sand particles held up on a sieve.

35 The extrusion die is designed with a long landing length and a variety of openings. The opening in the matrix preferably has an input angle of 20 °. With this one in

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6, a streamlined stream is obtained which ensures a uniform extrudate.

During operation of the extruder described above, the temperature in the screw (zone 1), in the gear measuring pump 05 (zone 2) and in the matrix (zone 3) is continuously controlled by three electric heating units surrounding the screw, the measuring pump and the matrix respectively. Furthermore, precautions are taken to continuously monitor the pressure applied to the molten copolymer by the screw 14 and by the measuring pump 10 28.

By extruding the copolymers described in the examples below, the dried copolymer powder is placed in the hopper container 11 and flows due to gravity into the drum 12 of the extruder. Screw 14 guides the polymer through zone 1 where it is melted, forcing the molten polymer at pressures as high as 20.6 MPa through the opening 26 into the gear pump 28, which measures the volume of material passing through die 32. The temperature of molten copolymers is controlled as it passes through the metering pump (zone 2) and the extrusion matrix (zone 3).

In normal operation, the screw (zone 1) is kept at approx. 244 ± 3 ° C; the measuring pump (zone 2) of between 202 and 220 ° C; and the matrix (zone 3) of between 202 and 230 ° C. Extruded filaments 33 are stretched approx. 200 times as they leave the die and quench-cooled in air at room temperature. The stretching occurs within the first 10-12 cm after the filaments leave the surface of the matrix.

The multifilament passes around an intermediate wheel 35, over a roller 36, and is wound around tension cylinders 37 and 38 to prevent any slippage that could result in variations in the stretching that takes place between the steel mold surface and the intermediate wheel 35. The stretch cylinder 37 is collected on a collector roll 40.

As stated above, the multifilament 33 can be stretched and heat-treated both before and after the braid. The braided suture can be sterilized with only a slight decrease in tensile strength by exposing the braided suture to a wet atmosphere of FREON and

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7 ethylene oxide.

The present invention will be further illustrated by the following examples which describe the preparation of braided copolymer sutures, all retaining at least 50% of their original tensile strength for 15 days and at least 20% of their original tensile strength for 21 days after implantation in animals. .

Example 1

Preparation of a poly [L (-) - lactide co-glycolide] from 10 10 mole percent L (-) - lactide and 90 mole percent glycolide (1023-86)

A 1-liter stainless steel reactor vessel equipped with a stirrer, a stirrer and a gas outlet is heated to 110 ° C under vacuum to remove moisture from the inside of the container.

A mixture of 80.6 g (0.56 mol, 12.2% by weight) of pure L (-) lactide with m.p. 97-99 ° C (specific rotation at least 282 °) and 580 g (5.0 mol, 87.8% by weight) of pure glycolide, m.p.

82.5-84-5 ° C is prepared using dry glass apparatus in an atmosphere of dry nitrogen. This mixture of 10 mole percent L (-) lactide and 90 mole percent glycolide is transferred to the container under a dry nitrogen sheath. To this reaction vessel is added 0.34 ml of a 0.33 molar catalyst solution containing 13.41 g of stannous octoate in 100 ml of toluene 25 (1.11 x 10 4 mol) using a dry glass syringe.

The mole ratio of monomer to catalyst is 50,000: 1. Then 0.5283 g (6.95 x 10 6 · mole) of glycolic acid is added. The mole ratio of monomer to glycolic acid is 800: 1.

The reaction vessel is closed and a high vacuum (0.1-0.2 mm of mercury pressure) is used to remove toluene. The container is flushed with dry nitrogen by evacuation and release of the vacuum twice with the gas. The container is then filled again with dry nitrogen until the pressure inside the container is approx. 1Q5 kPa and the outlet valve closes.

The container and its contents are immersed in a silicone bath preheated to a temperature of 200 ° C and heated below 35 ° C.

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Stir at this temperature for 1 hour and 20 minutes. The stirrer is raised above the liquid and heating at 200 ° C is continued for an additional 4 hours. The unit is cooled and the polymeric mass is removed from the opened unit. This is cooled with dry ice, 05 cut into quarters with a hand saw, ground with dry ice in a Cumberland mill and dried in vacuum for 48 hours at 0.1 mm Hg and 25 ° C. The yield of the copolymer obtained (product 1023-86) is 617 g. This product has a hardness of 92-94, a transition temperature (becomes soft) in the range of 193 to 196 ° C, a sticking point of 199 ° C, a stretch point. of 207 ° C and a melting point (flow point) of 218-219 ° C. The logarithmic viscosity number of this copolymer is 1.55 at 0.1% concentration in hexafluoro isopropanol at 25 ° C.

The polymerization reaction described above in this example is repeated four times (heating at 200 ° C for about 1 hour with stirring and for a further 4 hours without stirring) with the following results:

Product 1023-88 20 Yield 621 g Hardness 92-94

Softening point 193-196 ° C

Adhesive point 197-199 ° C

Melting point 206-207 ° C

Melting point 218-219 ° C

Logarithmic Viscosity Number 1.55

Product 1023-92

Yield 618 g 30 Hardness 92-94

Softening point 194-197 ° C

Adhesive point 198-199 ° C

Melting point 207 ° C

Melting point 219 ° C

Logarithmic Viscosity Number 1.54

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9

Product 1023-93

Yield 616 g Hardness 92-94

Softening point 193-197 ° C

05 Sticking point 198-199 ° C

Melting point 207-208 ° C

Melting point 219-220 ° C

Logarithmic Viscosity Number 1.49 Product 1023-94

Yield 620 g Hardness 92-94

Softening point 194-197 ° C

Adhesive point 199 ° C

Melting point 207-208 ° C

Melting point 218-219 ° C

Logarithmic Viscosity Number 1.49

The five products identified above (1023-86, 88, 20 92, 93 and 94) are ground in a Cumberland mill with dry ice so that they can pass through a screen with a mesh width of 4.76 mm. The mixture is de-metallized with a magnet and carefully dried in a vacuum oven. The combined product (1023-101) weighs 2,883 g and has the following physical properties: 25

Softening point 190-195 ° C

Melting point 196-197 ° C

Melting point 207-208 ° C

Melting point 217-2190 ^ 30 Logarithmic viscosity number 1.57

The melt index of an aliquot sample of the combined products is determined by a method similar to ASTM Method D 1238-65T published by the American Society for 35 Testing Materials, 1916 Race Street, Philadelphia, Pennsylvania 19103, using an extrusion plastometer (melt index meter) manufactured by Tinius Olsen

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10

Testing Machine Co., Easton Road, Willow Grove, Pennsylvania 19090. Using 3,800 g of weight and an opening of 0.635 mm, the melt index at 235 ° C is 0.7 (grams / 10 minutes at 900 seconds).

05

Example 2

Extrusion of poly- [L (-) - lactide-co-glycolide] (1038-53, 56)

The polymer blend (1023-101) described in Example 1 is extruded under dry nitrogen using a screw extruder of the type shown in FIG. 1 illustrated type for making an eight-strand multifilament. A filter of sand classified to pass a No. 30 screen and held back on a No. 50 screen is held up on a No. 30 screen.

15 60 sieves (U.S. Standard) disposed between the metering pump and die 32. The steel mold used has eight apertures with a diameter of 0.635 mm.

The screw in the extruder is operated to maintain a pressure of 10.3 MPa r and the metering pump is operated to maintain a pressure at the matrix of 2-21 MPa, the extrusion rate being 30 g / m 2. hour.

Throughout the extrusion, the screw feed section of the extruder, zone 1, is maintained at 245 ° C, the temperature of the metering pump, zone 2, is 205 ° C, and the temperature of the die, zone 3, is maintained at 210 ° C. The eight-stranded multifilament is collected on a collector coil 40 at a rate of 21 m per second. minute.

The multifilament thus obtained is oriented by stretching over a stretching cylinder heated to 52-54 ° C, 3 to 3.5 times. The collection rate for the oriented multifilament is 160 m / s. minute. The tensile strength of this oriented multifilament is 3.5 g / ml. denier. The oriented multifilament is then heat treated by placing the coil with the multifilament in an oven heated to 113 ° C for 20 minutes. After this heat treatment step, the tensile strength of the multifilament is 5.1-5.3 g / ml. denier.

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11

Example 3

Braid of a poly [L (-) - lactide-co-glycolide] yarn (P-240A 1045-98) 05 The eight-strand yarn described in Example 2 (total yarn 59 ± 12) is applied to braid machine bobbins on a machine with 16 support rollers and a three-layer core. The braid is made with 51 ± 3 shots per 2.5 cm to produce a braided multifilament suture of size 2/0. The braided 10 multifilament suture (average diameter 0.368 mm) has a tensile strength of 54.25 M (510 N / mm) and a knot strength (average diameter 0.370 mm) of 34.72 N (322 N / mm "). The braided multifilament is stretched by twisting around a frame, c which is then expanded 20% to produce a 1.2 fold stretch 15 in the braid * The frame on which the stretched braid is still in place is then heat treated in a furnace for 24 hours at 105 ° C. A useful apparatus for stretching and heat treating the copolymer braid is illustrated in U.S. Patent Application No. 846,412.

20

Example 4

Sterilization and Packing of Poly [L (-) - Lactide-Co-Glycolide] Sutures (1045-132, 134B; 1039-99) The stretched and standardized multifilament braid described in Example 3 above is cut into appropriate lengths for use as a suture, and sterilized with ethylene oxide in open-air gaskets by exposing the braided sutures to an atmosphere of FREON and ethylene oxide (500 mg ethylene oxide per liter of gas) at 70% relative humidity and 38 ° C. 6 hours.

The packages of sterilized braided sutures are sealed to preserve sterility until use. The sterile packed sutures (diameter 0.328 mm) have a direct tensile strength 35 of 50.72 N (600 N / mm2) and a dry knot strength (diameter 0.333 mm) of 31.98 N (366 N / mm2).

Absorption characteristics of this product (tensile strength

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12 duration in rats after 5 days) is determined by implanting ten samples in five different animals. Similarly, tensile strength retention is determined 10, 15, and 21 days after implantation. The average of 10 fractures using a 05 iNSTRON tester operating at a cross head speed of 2.5 cm per second. A minute of a 1.3 cm sample is given in Table I below and illustrated in FIG. 2

Table I

10

Days after implantation_ 0 5 10 15 21

Direct tensile strength in 50.69 44.52 37.95 29.22 10.30 15% tensile strength 100 87.8 75 57.8 20.3

Example 5

Preparation of poly- [L (-) - lactide-co-glycolide] containing 0.1% by weight D&C Violet No. 2 (1023-74) 20 _

A 1-liter stainless steel reactor vessel equipped with a stirrer, a stirrer and a gas outlet is heated to 110 ° C under vacuum to remove moisture from the interior surface of the container.

A mixture of 80.6 g (0.56 mol, 12.2% by weight) of pure lactide with m.p. 97-99 ° C (specific rotation at least 282 °) and 580 g (5.0 mol, 87.8% by weight) of pure glycolide, m.p.

82.6-84.5 ° C is prepared using dry glass apparatus in an atmosphere of dry nitrogen. This mixture of 10 30 mole percent L (-) lactide and 90 mole percent glycolide is transferred to the reactor vessel under a jacket of nitrogen. To this reaction mixture is added 0.34 ml of a 0.33 molar catalyst solution containing 13.41 g of stannous octoate in 100 ml of toluene (1.11 x 10-4 mol) using a dry glass syringe.

The monomer to catalyst molar ratio is 50,000: 1. Then 0.5283 g (6.93 x 10 10 · mol) of glycolic acid and 0.6611 g (0.1% by weight) of D&C Violet No. 2. The mole ratio of mono-

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13 more and glycolic acid is 800: 1.

The reactor vessel is closed and a high vacuum (0.1-0.2 mm Hg) is used to remove toluene. The container is flushed with dry nitrogen by evacuation and release of the vacuum twice with the gas. The container is then filled again with dry nitrogen until the pressure inside the container is approx.

0.07 kg / cm2 above atmospheric pressure and the outlet valve is closed.

The container and its contents are immersed in a silicone bath preheated to a temperature of 200 ° C and heated under stirring at this temperature for 1 hour and 2 minutes. The stirrer is raised above the liquid and heating at 200 ° C is continued for an additional 4 hours and 18 minutes. The unit is cooled and the polymeric mass is removed from the opened unit. The pulp is cooled with dry ice, cut into quarters with a hand saw, ground with dry ice on a Cumberland mill and dried in vacuum for 48 hours at 0.1 mm Hg and 25 ° C. The yield of the copolymer obtained (product 1023-74) is 620 g. -202 ° C, a stretch point of 206-207 ° C and a melting point (flow point) of 217 ° C. The logarithmic viscosity of this copolymer at 0.1% concentration in hexafluoro isopropanol at 25 ° C is 1.43.

The polymerization reaction described above in this example is repeated four times (heating at 200 ° C for 1 hour with stirring and for an additional 4 hours without stirring) with the following results:

Product 1023-76 Yield 618 g Hardness 92-94

Softening point 195-198 ° C

Adhesive point 199-200 ° C

Melting point 206 ° C

Melting point 217-2190 * 2

Logarithmic Viscosity Number 1.35

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14

Product 1023-79

Odor exchange 615 g Hardness 92-94

Softening point 195-198 ° C

05 Adhesive point 199-201 ° C

Melting point 205-206 ° C

Melting point 217-219 ° C

Logarithmic Viscosity Number 1/46 Product 1023-81

Yield 621 g Hardness 92-94

Softening point 195-198 ° C

Adhesive point 200 ° C

Melting point 206-207 ° C

Melting point 215-218 ° C

Logarithmic Viscosity Number 1/37

Product 1023-83 20 Yield 621 g Hardness 92-94

Softening point 195-198 ° C

Adhesive point 200 ° C

Melting point 205-206 ° C

Melting point 215-216 ° C

Logarithmic Viscosity Number 1.29

The five products identified above (1023-74 / 76, 79, 81 and 83) are ground in a dry ice Cumberland mill so that they can pass through a screen with a mesh width of 4.76 mm. The mixture (1023-85) is de-metallized with a magnet and carefully dried in a vacuum oven. The combined product weighs 2,879 g and has the following physical characteristics:

35 Softening point 190-197 ° C

Adhesive point 200-202 ° C

Melting point 205-206 ° C

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15

Melting point 217-218 ° C

Logarithmic Viscosity Number 1.41

The melt index of an aliquot sample of the combined 05 products as determined by the method described in Example 1 is 1.2.

Example 6

Extrusion of poly- [L (-) - lactide-co-glycolide J containing 10 0.1% by weight of D&C Violet No. 2 (1038-49,55; 2661-130957-61)

The polymer blend (1023-85) described in Example 5 is extruded as described in Example 2 to produce an octagonal multifilament.

The screw in the extruder is operated to maintain a pressure of 10.3 MPa, and the metering pump is operated to maintain a pressure at the steel mold of 1-19 MPa, the extrusion rate being 30 gm. hour.

During the entire extrusion, the screw feed section of the extruder, zone 1, is maintained at 245 ± 2 ° C, the temperature of the metering pump, zone 2, is 202-207 ° C, and the temperature of the die, zone 3, is maintained at 203-211 ° C. The eight-stranded multifilament is collected on the collector coil 40 at a rate of 21 m per second.

25 minutes.

The multifilament thus obtained is oriented by stretching 3.5 times over a stretch cylinder heated to 52 ° C. The collection speed of the oriented multifilament is 160 m per second. minute. The oriented multifilament heat is then treated by placing the coil with the multifilament in place in an oven heated to 113 ° C for 20 minutes. After this heat treatment step, the multifilament denier is -56 ± 4 and the tensile strength is 5.2 ± 0.8 g per minute. denier.

35 16

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Example 7

Braiding a poly [L (-) - lactide-co-glycolide] yarn containing 0.1% by weight of D&C Violet No. 2 (P-239A - 1045 p. 96, 96A) 05 __

The eight-stranded yarn described in Example 6 (total yarn denotes 56 ± 4) is placed on braid machine bobbins on a machine with 16 support rollers and a three-layer core. The braid is made at 51 ± 3 shots per 2.5 cm to produce 10 320 m braided multifilament suture size 2/0. The braided multifilament suture (average diameter 0.348 mm) 2 has a tensile strength of 46.3 N (486.2 N / mm) and a knot strength (average diameter 0.343 mm) of 30.7 N (332.4 N / mm).

The braided multifilament is stretched by twisting around a frame, which is then expanded 20% to produce a 1.2 fold stretch in the braid. The frame on which the stretched braid is still in place is then heat treated in an oven for 24 hours at 105 ° C. After heat treatment, the braid (diameter 2 0.317 mm) has a direct tensile strength of 45.81 N (579.3 N / mm) and a dry knot strength (diameter 0.310 mm) of 27.66 N (366.2 N / mm2).

Example 8

Sterilization and packing of poly- [L (-) - lactide-co-glycolide] -25 sutures containing 0.1% by weight D&C Violet No. 2 (1045-132, 134A; 1039-99)

The stretched and normalized multifilament braid described in Example 7 above is cut into lengths suitable for use as a suture and sterilized with ethylene oxide in open-air packages by exposing the braided sutures to an atmosphere of FREON and ethylene oxide (500 mg of ethylene oxide per liter of gas at 70% relative humidity and 38 ° C for 6 hours.

35 The packs of sterilized braided sutures are sealed to maintain sterility until use. The sterile packed sutures have a direct tensile strength of 44.54 N and one

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17 dry knot strength of 29.14 N.

The absorption characteristics of this product (tensile strength retention in rats after 5 days) are determined by implanting ten samples in five different animals. Similarly, the tensile strength retention is determined 10, 15 and 21 days after implantation. The average of ten fractures using an INSTRON tester operating at a cross-head speed of 2.5 cm per second. per minute, on a 1.3 cm sample is listed below in Table II and illustrated in FIG. 2nd

10

Table II

Days after implantation_ 15 0 5 10 15 21

Direct tensile strength iN 44.52 39.13 33.34 24.42 13.29% tensile strength retention 100 88.08 75.0 55.0 29.7 ^ Average of 9 fractures

Aliquot samples of the sterile braid are hydrolyzed in methanolic potassium hydroxide. The resulting glycolate and lactate are then esterified with methanol, and the methyl esters are simultaneously determined on a gas chromatograph with a thermal conductivity detector (HEWLETT PACKARD 5750 or an equivalent). The average glycolide content (six samples) is 91.1% by weight 25 with a standard deviation of 1.3. The average lactide content in the braid (six samples analyzed) is 10.0% by weight with a standard deviation of 0.33.

Example 9 Preparation of a poly [L (-) - lactide-co-glycolide] containing 0.3% by weight of D&C Violet No. 2 (1023-110)

A 1-liter stainless steel reactor vessel equipped with a stirrer, a stirrer motor and a gas outlet is heated to 110 ° C under vacuum to remove moisture from the interior surface of the container. A mixture of 80.6 g (0.56 mol; 12.2% by weight) of pure L (-) lactide, m.p. 97-99 ° C (

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18 were turned at least 282 °) and 580 grams (5.0 moles; 87.8 wt.%) Of pure glycolide, m.p. 82.5-84.5 ° C is prepared using dry glass apparatus in an atmosphere of dry nitrogen. This mixture of 10 mole percent L (-) lactide and 90 05 mole percent glycolide is transferred to the container under a jacket of nitrogen. To this reaction mixture is added 0.34 ml of a 0.33 molar catalyst solution containing 13.41 g of stannous octoate in 100 ml of toluene (1.11 x 10-4 mol) using a dry glass syringe. The mole ratio of monomer to catalyst is 50,000: 1. Then 0.5283 g (6.95 x 10 -6 mole) of glycolic acid and 1.9834 g (0.3% by weight) of D&C Violet No. 2. The mole ratio of monomer to glycolic acid is 800: 1.

The reaction vessel is closed and a high vacuum (0.1-0.2 mm Hg) is used to remove toluene. The container is flushed with dry nitrogen by evacuation and release of the vacuum twice with the gas. The container is then refilled with dry nitrogen until the pressure inside the container is approx.

105 kPa and the exhaust valve closes.

The container and its contents are immersed in a silicone bath 20 preheated to a temperature of 200 ° C and heated under stirring at this temperature for 1 hour. The stirrer is raised above the liquid and heating at 200 ° C is continued for 4 hours. The unit is cooled and the copolymeric mass is removed from the opened unit. The color of the copolymer is intensely violet and the yield obtained (Proc. 1023-110) is 626 g. The copolymer is cooled with dry ice, cut into quarters with a hand saw, ground with dry ice in a Cumberland mill so that it can pass a screen having a mesh width of 4.76 mm, and de-metallized with a magnet. The ground copolymer is dried in vacuo for 48 hours at 0.1 mm Hg and 25 ° C. The copolymers thus obtained have a hardness of 92-94, a transition temperature (softening point) in the range of 190-195 ° C, a sticking point of 197 ° C, a tensile point of 206 ° C and a melting point of 219 ° C.

The logarithmic viscosity number of the colored copolymer at 0.1% concentration in hexafluoro isopropanol at 25 ° C is 1.41.

The melt index of the colored copolymer, determined as

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19 written above in Example 1 is 1.84.

Example 10

Extrusion of poly- [L (-) - lactide-co-glycolide] containing 05 0.3% by weight D&C Violet No. 2 (1038-54, 57)

The polymer (1023-110) described in Example 9 is extruded using a screw extruder of the type shown in FIG.

1 illustrated for producing an eight-stranded multifilament. A filter of sand classified to pass a No. 30 sieve and retained on a No. 50 sieve is held up on a No. 60 sieve (U.S. Standard) disposed between the measuring pump 28 and the die 32. The die used has eight apertures with a diameter of 0.635 mm.

The screw in the extruder is operated to maintain a pressure of 10.3 MPa, and the metering pump is operated to maintain a pressure at the die of 5-20 MPa, the extrusion rate being 30 g / m 2. hour.

Throughout the extrusion, the extruder screw section, zone 1, is maintained at 241-245 ° C, the temperature of the metering pump, zone 2 is 205 °, and the temperature in the matrix, zone 3, is maintained at 204-207 ° C. The eight-stranded multifilament is collected on a collector coil 40 at a speed of 21 m per minute.

The multifilament thus obtained is oriented at 25 stretches 3.5 times over a stretch cylinder heated to 52 ° C. The collection speed of the oriented multifilament is 160 m per second. minute. The oriented multifilament is then heat treated by placing the coil with the multifilament in place in an oven heated to 113 ° C for 20 minutes.

After this normalization step, the tensile strength of the multifilament (51 ± 1 denier) is 5.8 + 0.7g per second. denier.

Example 11

Braid of a poly-y [L (-) - lactide-co-glycolide] yarn containing 0.3% by weight of D&C Violet No. 2 (P-244A? 1045-114B)

The eight-strand yarn described in Example 10 above

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20 (total yarn 51 ± 1) are applied to braid machine bobbins on a machine with 16 support rollers and a three-layer core. The braid is performed at 51 ± 3 shots per 2.5 cm to produce a braided multifilament suture of size 2/0. The braided 05 multifilament suture (average diameter 0.340 mm) has a 2 tensile strength of '46.70 N (510.1 N / mm) and a knot strength (average diameter 0.335 mm) of 29.92 N (338.6 N / mm2). The braided multifilament is stretched by twisting around a frame which is then expanded 20% to produce a 1.2 fold stretch 10 of the braid. The frame with the stretched braid still in place thereafter is heat treated in an oven for 24 hours at 105 ° C. After heat treatment, the braid (average diameter 0.282 mm) has a direct tensile strength of 45.42 N (726.9 N / mm) and a dry knot strength of 28.45 N (439.3 N / mm 2).

15

Example 12

Sterilization and packing of poly [L (-) - lactide-co-glycolide] sutures containing 0.3% by weight of D&C Violet No. 2 (1045-98, 132, 134C)

The stretched and normalized multifilament braid described in Example 11 above is cut into lengths suitable for use as a suture, and sterilized with ethylene oxide in open-air packages by exposing the braided suits to an atmosphere of FREON and ethylene oxide. (500 ml of ethylene oxide per liter of gas) at 70% relative humidity and 38 ° C for 6 hours.

The packages of sterilized braided sutures are sealed to maintain sterility until use. The 30-pack packed sutures have a direct tensile strength of 49.54 N and a dry knot strength of 27.25 N.

The absorption characteristics of this product (tensile strength retention in rats after five days) are determined by implanting ten samples in five different animals. Similarly, tensile strength retention is determined 10, 15 and 21 days after implantation. The average of ten fractures using an INSTRON tester operating with a

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21 main speed of 2.5 cm per per minute on a 1.3 cm sample is listed in Table III below and illustrated in FIG. 2nd

Table III 05

Days after implantation_ 0 5 10 15 21

Direct tensile strength in, N 49.52 40.50 35.89 25.69 14.51 10% tensile strength retention 100 81.6 72.4 51.8 29.2 * Average for nine fractures

Example 13 Absorption Characteristics of a Braided Sterile Polyglycolic Acid Homopolymer Suture

A box of three dozen individually wrapped braided polyglycolic acid sutures size 00 (size 2/0), manufactured by Davis & Geck, Cyanamid of Great Britain Ltd., London, England, and identified by the trade mark DEXON is purchased in England. The box with sutures is identified by the number 7002-51 and lot number 6384. The sutures, which are approx. 152 cm long and 0.328 mm in diameter, has a direct tensile strength of o 25 43.06 N (511.7 N / mm) and a dry knot strength (diameter 0.328 mm) of 30.90 N ('364.2 N / mm2) .

The absorption characteristics of this product (tensile strength retention in rats after five days) are determined by implanting eight samples in eight different animals. Similarly, tensile strength retention is determined 10, 15 and 21 days after implantation. The average of eight fractures using an INSTRON tester operating at a cross-head speed of 2.5 cm per second. per minute on a 1.3 cm sample is given in Table IV below and illustrated in FIG. 2nd

35

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22

Table IV

Days after implantation_ 05 O 5 10 15 21

Direct tensile strength in N 46> 38 42.95 29.42 17.65 3.23% tensile strength retention 100 92.3 63.2 37.9 6.88

It will be apparent from FIG. 2, that the braided sutures made from a copolymer of 10 mole percent L (-) - lactide and 90 mole percent glycolide as described in Examples 1-12 above are extremely superior to braided polyglycolic acid homopolymer. sutures with respect to the percentage of initial tensile strength retained 15 and 21 days after 15 implantation.

Example 14

Preparation of a poly- [L (-) - lactide-co-glycolide] containing 0.1% by weight of D&C Green No. 6 (1014-120-6? 121, 139; 20 145)

By the method described in Example 5 above. a green-colored copolymer is prepared by adding to the reaction mixture of 10 mole percent L (-) lactide and 90 mole percent 25 glycolide 0.1 wt.% 1,4-bis- (p-toluino) anthraquinone (D&C Green No. 6 ). The polymer thus obtained has a logarithmic viscosity number of 1.41 and a melt viscosity (determined in the manner described in Example 1 above) of 0.9.

The thus obtained green colored polymer can be extruded as a multifilament, drawn, plaited, heat treated, sterilized and packaged as a suture useful in surgery.

Similarly, any non-toxic dye that retains its color and strength under the polymerization conditions and does not adversely affect the polymerization reaction can be used to stain the sutures of the present invention.

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23 of the present invention.

Many of the dyes listed as baits for food, pharmaceuticals and cosmetics in the regulations issued under the Federal Food, Drug, and Cosmetic 05 Act of 1938 cannot be used because they adversely affect it copolymerization reaction which produces low molecular weight poly [L (-) - lactide-co-glycolide] characterized by a low logarithmic viscosity number and tensile strength. Other non-toxic dyes themselves are adversely affected under the polymerization conditions, with the result that the desired clear color is not achieved.

Example 15

Preparation of a poly- [L (-) - lactide-co-glycolide] (1078-21B)

A 1-liter stainless steel reactor vessel equipped with a stirrer, a stirrer motor and a gas outlet is heated to 110 ° C under vacuum to remove moisture from the interior surfaces of the container.

A mixture of 80.6 g (0.56 mol; 12.2 wt.%) Of pure L (-) lactide with m.p. 97-99 ° C (specific rotation at least 282 °) and 580 g (5.0 mol; 87.8 wt.%) Of pure glycolide, m.p. 82.5-84.25 ° C is prepared using dry glass apparatus in an atmosphere of dry nitrogen. This mixture of 25 10 mole percent L (-) lactide and 90 mole percent glycolide is transferred to the container under a dry nitrogen sheath. To this reaction mixture is added 0.34 ml of a 0.33 molar catalyst solution containing 13.41 g of stannous octoate in 100 ml of toluene (1.11 x 10-4 mol) using a dry glass syringe.

The monomer to catalyst molar ratio is 50,000: 1. Then 0.5283 g (6.95 x 10 6 · mole) of glycolic acid is added. The mole ratio of monomer to glycolic acid is 800: 1.

The reaction vessel is closed and a high vacuum (0.1-0.2 mm Hg) is used to remove toluene. The container is flushed with dry nitrogen by evacuating and releasing the vacuum twice with the gas. The container is filled again with dry nitrogen until the pressure inside the container is approx. J.05 kPa

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24 and the discharge valve closes.

The container and its contents are immersed in a silicone bath preheated to a temperature of 200 ° C and heated under stirring at this temperature for 1 hour. The stirrer is raised above the liquid and heating at 200 ° C is continued for a further four hours. The unit is cooled and the polymeric mass is removed from the opened unit. The pulp is cooled with dry ice, cut into quarters with a hand saw, ground with dry ice on a Cumberland mill and dried in vacuum for 72 hours at 0.1 mm Hg 10 and 25 ° C. The yield of the copolymer obtained (polymer 1078-21B) is 545.9 g (82.9%). This product has a sticking point of 210 ° C, a tensile point of 214 ° C and a melting point (flow point) of 234 ° C. The logarithmic viscosity number of this copolymer at 0.1% concentration in hexafluoroisopropanol at 25 ° C is 1.54.

The melt index of an aliquot sample of this product as described in Example 1 above is 0.36 (grams / 10 minutes at 900 seconds).

Example 16

Extrusion of a poly- [L (-) - lactide-co-glycolide] (1038-153)

The polymer (1078-21-B2) described in Example 15 above is extruded under dry nitrogen using a screw extruder to produce an eight-stranded multifilament. A filter of sand classified to pass a No. 40 screen and retained on a No. 60 screen is held up on a No. 80 screen (U.S. Standard) disposed between the metering pump in the extruder and the die. The die used has eight openings with a diameter of 0.635 mm.

The screw in the extruder is operated to maintain a pressure of 13.7 MPa, and the measuring pump in the extruder is operated to maintain a pressure at the matrix of 1-5.6 MPa. Throughout the extrusion, the screw feed section of the extruder is maintained at 245 ° C; The temperature of the measuring pump is 210 ° C and the temperature of the matrix is maintained at 215 ° C. The eight-stranded multifilament is collected at the collector coil at a rate of 21 m per second. minute.

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25

The multifilament thus obtained is oriented by stretching over a stretch cylinder / heated to 57 ° C, 4.5 times. The oriented multifilament is then heat treated by placing the coil with the multifilament in place thereon in an oven heated to 105 ° C for 45 minutes. After this normalization step, the tensile strength of the multifilament (54.8 denier) is 4.8 g. denier.

Example 17 Braiding of a poly [L (-) - lactide-co-glycolide] yarn (P-331)

The eight-stranded yarn (54.8 denier) described in Example 16 above is placed on braid machine bobbins on a machine with 16 support rollers and a three-layer core. The braid is performed at 15 51 ± 3 shots per second. 2.5 cm to produce a braided multi-filament suture size 2/0 (average diameter 0.345 mm) 2 with a tensile strength of 61.41 N (655.11 N / mm) and a knot strength o of 37.87 N (403, 5 N / mm). The braided multifilament is heat-stretched by twisting around a frame placed in an oven heated to slightly above room temperature and stretched 10% to produce a 1.1 fold stretch in the braid. The frame with the stretched braid still in place is then heat treated in the oven in an inert atmosphere for 24 hours at 105 °.

Example 18

Sterilization and packaging of poly [L (-) - lactide-co-glycolide] sutures (1095-39A)

The multifilament braid, described in Example 17, described above, is cut into lengths suitable for use as a suture and sterilized with ethylene oxide in open-air gaskets by exposing the braided sutures to an atmosphere containing ethylene oxide in an amount of 1,000 mg per ml. liter at a relative humidity of 35 100% for 3 hours at 25 ° C. The sterilization process is repeated by subjecting the product to the same conditions for an additional 3 hours at 25 ° C. The gaskets are then degassed under

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26 cum (0.5 mm Hg) for 16 hours at 40 ° C and sealed. The sterile packed sutures (diameter 0.335 mm) have a nodal strength of 2 36.00 N (407.6 N / mm) when tested on a SCOTT Model No.

IP-4 Incline Plane Tests on the one in United States 05 Pharmacopoeia, Vol. XVIII, page 921 described. The direct tensile strength of the sterile suture (diameter 0.335 mm) is 2 57.00 N (645.5 N / mm) determined on the aforementioned SCOTT Incline Plane Tester.

The absorption characteristics of this product (tensile strength retention in rats after 7, 14, 21 and 28 days) are determined by implanting ten samples in five different animals. The average of ten fractures using an INSTRON test machine operating at a cross head speed of 2.5 cm per second. per minute on a 1.3 cm sample is listed below in Table V and illustrated in FIG. 5th

Table V

Days after implantation_ 20 0 7 14 21 28

Direct tensile strength of N 55.60 47.56 36.77 23.63 9.61% tensile strength preservation 100 84.32 65.09 41.8 17.06 25 A representative sample of the braided suture is examined by gel penetration chromatography to information on the molecular weight and molecular weight distribution of the copolymer can be obtained. FIG. 3 is a schematic view of the chain length distribution data thus obtained. It will be seen that the ratio of average molecular weight by weight to average molecular weight by number is 72,000: 33,000 or approx. 2: 1.

A representative sample of the sterile braided suture according to this example is evaluated using a differential scanning calorimeter (duPont Instruments model # 500). The thermograms are shown in FIG. 4. It will be seen from curve A that the glass transition temperature of the normalized and

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27 braided sutures are indicated by the number 10 and are approx. 55 ° C. The melting point indicated by the number 12 is approx. 205 ° C. After . melting is quenched in the copolymer suture and a different thermogram (curve B) is obtained. On this quenched material, the glass-05 transition temperature is indicated by the number 14, and it is at approx. 43 ° C. The crystallization temperature is indicated by the number 16, and it is at ca. 112 ° C. The melting point is indicated by the number 18 and occurs at ca. 205 ° C.

Example 19

Preparation of a poly- [L (-) - lactide-co-glycolide] (1078-16A and 1078-16B)

A 1-liter stainless steel reactor vessel equipped with a stirrer, a stirrer motor and a gas outlet is heated to 110 ° C under vacuum to remove moisture from the inside surface of the container.

A mixture of 126.7 g (0.88 mole; 17.93 wt%) pure L (-) lactide and 580 g (5.0 mole; 82.07 wt%) pure glycolide with m.p. 82.5-84.5 ° C is prepared using dry glass apparatus in an atmosphere of dry nitrogen. This mixture of 15 mole percent L (-) lactide and 85 mole percent glycolide is transferred to the container under a dry nitrogen sheath.

To this reaction mixture is added 0.36 ml of a 0.33 molar catalyst solution containing 13.41 g of stannous octoate in 100 ml of toluene (1.18 x 10 10³ mol) using a dry glass syringe. The mole ratio of monomer to catalyst is 50,000: 1. Then 0.5586 g (7.35 x 10 10 · mole) of glycolic acid is added. The mole ratio of monomer to glycolic acid is 800: 1.

The reaction vessel is closed and a high vacuum (0.1-0.2 mm Hg) is used to remove toluene. The container is flushed with dry nitrogen by evacuation and release of the vacuum twice with the gas. The container is then refilled with dry nitrogen until the pressure in the container is approx. 105 kPa, 35 and the exhaust valve closes.

The container and its contents are immersed in a silicone bath preheated to a temperature of 200 ° C and heated

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28 with stirring at a temperature of 193-200 ° C for 55 minutes. The stirrer is raised above the reaction mixture and heating at 200 ° C is continued for a further 4 hours and 5 minutes. The reactor is raised from the silicone bath and allowed to cool overnight 05. The reactor and its contents are cooled with dry ice, and the polymer is removed from the reactor vessel, cut into quarters with a hand saw, milled with dry ice in a Cumberland mill and dried in vacuo at 0.1 mm Hg and 25 ° C. The yield of the copolymer obtained (product 1078-12) is 512.4 g. This product has a hardness of 90-91, a sticking point of 195 °, a tensile point of 205 ° C and a melting point (flow point) of 225 ° C . The logarithmic viscosity number of this copolymer at 0.1% concentration in hexafluoro isopropanol at 25 ° C is 1.51.

The melt index of an aliquot sample of the vacuum-dried product of this example is determined by the method described in Example 1 above. The melt index at 235 ° C using a weight of 3,800 g and an opening of 0.635 mm is 0.33 (grams / 10 minutes at 900 seconds).

Example 20

Extrusion of a poly- [L (-) - lactide-co-glycolide] (1038-143? 1095-12-B)

The polymer described above in Example 19 is extruded 25 under dry nitrogen using a screw extruder of the type shown in FIG. 1 illustrated for making a twelve-stranded multifilament. A filter of sand classified to pass a No. 80 sieve and retained on a No. 100 sieve is held up on a No. 100 sieve located 30 between the metering pump and die 32. The die used has 12 openings with a diameter of 0.508 mm.

The screw in the extruder is operated to maintain a pressure of 10.3 MPa,. and the measuring pump is operated to maintain a pressure at the matrix of 5.2-13.7 MPa.

35 Throughout the extrusion, the extruder screw section, zone 1, is held at 245 ° C; the temperature in the measuring pump, zone 2, is 220 ° C; and the temperature in the matrix, zone 3, is maintained

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29 230 ° C. The twelve-stranded multifilament is collected on the collector coil 40.

The multifilament thus obtained is oriented by stretching over a stretch cylinder heated to 54 ° C, 4.5 times. The tensile strength of this oriented multifilament (40 ± 5 denier) is 4.0 g / ml. denier.

Example 21

Braided poly [L (-) - lactide-co-glycolide] yarn (braid 299A; 1095-12-B)

The twelve-strand yarn (total yarn 40 ± 5 yarn) is placed on braid machine bobbins on a machine with 16 support rollers with a three-layer core. The braid is done with 49 ± 3 shots 15 per. 2.5 cm to make a braided multifilament suture size 2/0. The braided multifilament suture (average 2 diameter 0.330 mm) has a tensile strength of 38 * 75 N (448.3 N / mm) and a knot strength of 23.54 N (275.7 N / mm2). The braided multifilament is stretched by twisting around a frame which is widened 15% 20 to produce a 1.15 fold stretch in the braid.

The frame with the stretched braid still in place is then heat treated in an oven for 24 hours at 105 ° C.

Example 22 Sterilization and packing of poly [L (-) - lactide-co-glycolide] suture (1095-12-B, ERF 71-81, P-299A)

The stretched and normalized multifilament braid described in Example 21 above is cut into lengths suitable for use as a suture and sterilized with ethylene oxide in open-air gaskets by exposing the braided sutures to an atmosphere of FREON qg ethylene oxide ( 500 mg of ethylene oxide per liter of gas) at 70% Eelative humidity and 25 ° C for 6 hours. The gaskets are then degassed under 35 vacuum (0.5 mm Hg) for 1 hour at 40 ° C and sealed to maintain sterility until use.

The sterile packed sutures (average diameters 0.291 30

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mm) has a direct tensile strength (determined on a SCOTT Model IP-4 Incline Plane Tester) of 45.62 N (694.5 N / mm) 'and a dry knot strength of 28 * 45 N (431 * 64 N / mr /) .

The absorption characteristics of this product (tensile strength retention in rats after 7 days) are determined by implanting twelve samples in twelve different animals. Similarly, tensile strength retention is determined 14 * 21 and 28 days after implantation. The average for twelve fractures using an iNSTRON tester * operating at a cross head speed of 2 * 5 cm per second. per minute on a 1.3 cm sample * is given in Table VI below.

Table VI

15 days after implantation

Direct tensile strength iN 42 * 95 37.66 25, '40 16 * 57, 6 * 28% tensile strength retention 100 79 * 5 59 * 1 38.1 14 * 6 20

Aliquot samples of the sterile braid are hydrolyzed in methanolic potassium hydroxide. The resulting glycolate and lactate are then esterified with methanol, and the methyl esters are simultaneously determined on a gas chromatograph with a thermal conductivity detector (HEWLETT PACKARD 5750 or an equivalent). The average glycol content (six samples) is 86.8% by weight with a standard deviation of 1 * 4. The average lac time content of the braid (six samples analyzed) is 14.7% by weight with a standard deviation of 0.2.

30 35

Claims (2)

1. Sterile absorbable surgical suture in the form of a stretched, preferably colored, multifilament structure consisting of a heat-treated copolymer in the form of L (-) - lactide and glycolide FEATURED by the proportion of L (-) - lactide being 10-15% by weight , That a 0.1% solution of the copolymer in hexa-fluoroisopropanol at 25 ° C prior to extrusion has a logarithmic viscosity number of at least 1.4, and that the surgical suture 10 after sterilization has a nodal strength of at least 345N / mm2 and a direct tensile strength at least 552N / mm2 and after implantation in animal tissues for 15 days retains at least 50% and after 21 days at least 20% of the direct tensile strength. Suture according to claim 1, characterized in that the copolymer satin mass is stained with 0.1 to 0.3% by weight of 1-hydroxy-4- p-toluidinoanthraquinone or by 0.1% by weight of 1,4-bis- (p-toluidino ) -anthraqinon. 20 25 30 35