JPH0696633B2 - Process for producing copolymer of glycolide and ε-caprolactone - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method of making a copolymer of glycolide and ε-caprolactone useful as synthetic surgical products with improved properties, particularly oriented filaments and sutures.

Homopolymers and copolymers of lactide and glycolide,
For example, U.S. Pat.Nos. 3,636,956; 2,703,316; 3,468,
853; 3,865,869; and 4,137,921 are known in the manufacture of synthetic absorbable sutures. Also, in US Pat. No. 3,867,190, it is known to include certain cyclic comonomers with glycolide containing ε-caprolactone. Indeed, the use of cyclic ester monomers in the production of polyesters for the production of synthetic surgical articles is known in the art. A common polymerization method for producing a polymer of cyclic ester is by ring-opening polymerization. U.S. Pat. No. 4,300,565 discloses surgical articles made from synthetic absorbable copolymers produced by specially copolymerizing glycolide and cyclic ester monomers. That is, widely ε
It should be appreciated that copolymers of caprolactone with other cyclic esters such as lactide or glycolide are known and described in the literature along with various methods for their preparation.

Synthetic absorbable sutures are already well accepted in the surgical field. However, “easy handling” or compliance, ie flexibility and “flexibility”,
Is not always satisfactory in the monofilament form. The monofilament configuration is considered more suitable for surgery than the multifilament or braided form because it is less prone to infection and trauma at the wound closure site. However, monofilaments tend to be stiffer and more difficult to handle than braided forms of the same diameter. Over the years, various polymer combinations have been tried in an attempt to achieve a very subtle interaction between desirable suture absorbency, in vivo strength retention, initial knot strength and high compliance or low modulus properties. Has been done. These desirable properties have been found in several suture materials, with the exception of absorbability,
This has been achieved, for example, in those described in US Patent Application Nos. 311,829 (filed October 16, 1981) and 338,407 (filed January 8, 1982). While the suture materials described have desirable strength, compliance and flexibility, they are not absorbable, which limits their use. To our knowledge, the only absorbable sutures that may possibly have the above properties are those consisting of polydioxanone as described in US Pat. No. 4,052,988.

The obvious means for designing the molecular chains required for the production of highly flexible absorbable materials is to use the appropriate comonomers according to methods similar to those used in the production of flexible, non-absorbable sutures. Or copolymerizing a mixture of prepolymer and monomer. However, AA-BB
This is not the case for non-absorbent type polymers. Moreover, U.S. Pat.No. 3,867, which describes copolymers containing up to 15% ε-caprolactone moieties.
Copolymerization of both glycolide and ε-caprolactone comonomers according to the description of 190 does not give a flexible material. 15
Copolymers containing less than 10% caprolactone are random in nature, and monofilaments made therefrom exhibit high modulus and low compliance. Copolymers with random microstructures containing less than 85% glycolide moieties generally do not give good fiber forming polymers due to inadequate levels of crystallinity. Thus,
Copolymers containing more than 15% caprolactone sequence have poor crystallinity and are almost amorphous, and are expected to be unsuitable for the production of strong monofilament suture materials .

The present invention describes novel copolymers containing a specific weight percentage of epsilon (ε) -caprolactone and a specific weight percentage of glycolide or a mixture of glycolide and lactide. These novel copolymers provide a synthetic absorbable surgical article with new and unknown properties and exhibit desirable linear and knot tensile strength, controllable absorbency, suitable absorption while exhibiting unexpectedly unique high compliance and low modulus. Provide a filament or suture material having in-vivo strength. The novel copolymer according to the invention has at least 30,000 ps
It has a tensile strength of i and a Young's modulus of less than 350,000 psi. When in filamentary form, the novel copolymer of the present invention comprises about 20 to 35 weight percent ε-caprolactone and 65 to 80 weight percent glycolide or a mixture of glycolide and lactide. When a mixture of glycolide and lactide is used in a preferred embodiment of the invention, the mixture should contain less than 20 parts by weight of L (-) lactide. The novel copolymers can be used as molded articles or can be processed into filaments and suitable sutures by methods known in the art and needles can be attached to the sutures if desired. . The filament can be heat treated to provide a material having a tensile strength of at least 50,000 psi while retaining a Young's modulus of less than 250,000 psi. The novel copolymers of the present invention can be designed to be completely absorbed in vivo in less than 150 days while maintaining in vivo strength of at least 40 percent after 7 days. In certain embodiments of the present invention, the novel copolymers have an inherent viscosity of at least 0.8 dl / g as measured at 25 ° C. for a solution of 0.1 g / dl in hexafluoroisopropanol (HFIP). There is. In certain embodiments of the invention,
The novel polymers of the present invention have a crystallinity of at least 5%, preferably at least 10%.

Also in accordance with the present invention, the novel copolymers of the present invention comprise a mixture of glycolide and ε-caprolactone, preferably about 0.
Produced by polymerizing in the presence of catalyst, 004 to 0.02 weight percent. The catalyst is a metal salt or metal oxide,
Preferably, it may be a salt or oxide of tin, such as stannous octoate, dibutyltin oxide and the like. The polymerization is conducted at a temperature below 250 ° C. for a time sufficient to result in at least 80% conversion of monomer to polymer. Another novel method for making the copolymers of the present invention uses the first step, which should yield a low molecular weight copolymer of ε-caprolactone and glycolide. In this first step, the copolymer must contain at least 50% by weight of ε-caprolactone in order to obtain a ε-caprolactone-rich prepolymer. After carrying out the first stage at a temperature below 220 ° C., in the second stage additional glycolide is added to the prepolymer. The addition and mixture are polymerized at a temperature above 120 ° C. for a time sufficient to produce a conversion of at least 80%.

The polymer produced by the above method can be easily extruded and stretched by a known method to obtain an oriented filament-like material. Oriented filaments can be used to make sutures with or without heat treatment. Needles can be attached to oriented filaments to form sutures with needles. A suture with or without a needle can be sterilized by a known sterilization method to obtain a novel sterilized surgical suture. The polymer can also be processed by other methods, such as injection molding, and then sterilized by known methods to provide new, sterilized synthetic medical devices.

In the following description and examples, the number of copies and percentage are
All are by weight unless otherwise noted.
The process of the present invention comprises either a one-step or two-step polymerization process. In a one-step polymerization process, an essentially random copolymer of glycolide monomer and ε-caprolactone results. Polymerization is carried out in a conventional manner using a polymerization reactor equipped with heating and stirring means. Polymerization is about 0.
Performed in the presence of 004 to 0.02 weight percent metal salt or metal oxide, preferably dibutyltin oxide or stannous octoate. The polymerization is carried out with a pure dry reactant under a dry, inert atmosphere at a temperature sufficient to keep the reaction mixture at a temperature close to the melting point of the resulting polymer. The amount of .epsilon.-caprolactone used should be sufficient such that about 20 to 35 percent by weight of .epsilon.-caprolactone moieties are present in the final polymer. The amount of glycolide used is approximately
It should be sufficient so that 62 weight percent to about 80 weight percent glycolide moieties are present. The polymerization must be carried out for a sufficient time to achieve at least 80%, preferably greater than 90 percent conversion of monomer to copolymer.

The following examples illustrate preferred copolymers of the invention and preferred methods for making the copolymers.

Example 1 Flame dried 100 m with Teflon coated magnetic stirrer
l In a glass ampoule 14.27 g (0.125 mol) ε-caprolactone, 43.53 g (0.375 mol) glycolide, 0.0591 g
Charge 1,6-hexanediol and a catalytic amount of stannous octoate (0.25 ml of 0.033 molar solution in toluene). The pressure in the ampoule is reduced to evaporate the toluene. After replacing the ampoule with dry nitrogen and vacuum suction several times, the pressure is adjusted to 3/4 of atmospheric pressure with dry nitrogen. Seal the ampoule with flame. Immerse the sealed ampoule in a silicone oil bath preheated to 100 ° C. Keep this temperature for 15 minutes, stirring for as long as possible, then
Raise to 0 ° C and hold it for 15 minutes. The temperature is raised to 190 ° C and the polymerization is continued at 190 ° C for 18 hours. The copolymer produced is isolated, cooled, ground and then dried under reduced pressure at room temperature.
Some unreacted monomer is removed by heating the milled copolymer under reduced pressure at 110 ° C. for 16 hours. A conversion of monomer to copolymer of about 95 percent is obtained. The resulting copolymer is composed of 23 percent by weight ε-caprolactone moieties and 77 percent by weight glycolide moieties. The inherent viscosity of the resulting copolymer was 25 ° C using a 0.1g / dl solution in hexafluoroisopropanol.
It is 1.66 dl / g when measured at.

Example 2 For comparison, US Pat. No. 3,863, which describes a copolymer of glycolide with 15 weight percent ε-caprolactone.
Example 6 in 7,190 is performed.

Flame dried 100 m with Teflon coated magnetic stir bar
In a glass ampoule of 1 l, 6.0 g (0.053 mol) of ε-caprolactone, 34.
Charge 0 g (0.293 mol) of glycolide and 0.12 g of lead monoxide. After repeating nitrogen substitution, adjust the pressure with nitrogen to about 3/4 of atmospheric pressure and seal the ampoule with a flame. Immerse the sealed ampoule in a silicone oil bath and heat to 145-150 ° C. Keep ampoules in this temperature range for 31 hours. The copolymer is isolated, ground and then dried under reduced pressure at room temperature. Some unreacted monomer is removed by heating the milled copolymer under reduced pressure at 110 ° C. for 16 hours. The conversion of monomer to copolymer is about 97 percent. The resulting copolymer consists of 15 percent by weight ε-caprolactone moieties and 85 percent by weight glycolide moieties. The resulting copolymer is almost insoluble in hexafluoroisopropanol.

Attempts to extrude and stretch into oriented filaments are unsuccessful because the copolymer decomposes at the temperatures required to obtain a uniform melt.

Example 3 Attempts are made to produce a suitable filament forming copolymer as described in US Pat. No. 3,867,190, using the amount and type of catalyst according to the method of the present invention.

Flame dried 100 m with Teflon coated magnetic stir bar
In a glass ampoule of 1 l, 6.0 g (0.053 mol) of ε-caprolactone, 34.
Charge 0 g (0.293 mol) of glycolide and 0.90 ml of a 0.33 mol stannous octoate solution as a solution in toluene. The pressure in the ampoule is reduced to remove toluene.
After repeated nitrogen replacement and suction, the pressure was adjusted to about 3/4 of atmospheric pressure with nitrogen, and then the ampoule was sealed. Immerse the sealed ampoule in a silicone oil bath and heat to 145-150 ° C. Keep this temperature range for 31 hours. The copolymer is isolated, ground and dried under reduced pressure at room temperature. Some unreacted monomer is removed by heating the milled copolymer under reduced pressure at 110 ° C. for 16 hours. About monomer to copolymer
A conversion of 97% is obtained. The resulting copolymer consists of 15 percent by weight ε-caprolactone moieties and 85 percent by weight glycolide moieties. The resulting copolymer is almost insoluble in hexafluoroisopropanol. The resulting copolymer cannot be extruded and oriented to provide a satisfactory filament for suture manufacture. In an attempt to extrude the resulting copolymer, it undergoes decomposition in the temperature range necessary to obtain a homogeneous melt.

In a preferred embodiment of the single-step process for making the copolymers of the present invention, it is desirable to obtain about 22-32 percent by weight of ε-caprolactone moieties in the final polymer.

As mentioned above, another novel method for making the novel copolymers of the present invention is to first produce a low molecular weight prepolymer of ε-caprolactone and glycolide. This prepolymer is rich in ε-caprolactone; that is, it contains at least 50 weight percent ε-caprolactone. 220 prepolymer
It is manufactured at a temperature of ℃ or below. After forming the prepolymer, additional glycolide or glycolide / caprolactone or glycolide-rich lactide mixture is added to the prepolymer, and the mixture thus obtained is further polymerized at a temperature of about 180-240 ° C. This two-step polymerization is conducted up to a conversion of at least 85 percent.

Following are specific examples of this alternative method for making the novel copolymers of the present invention.

Example 4 In a flame dried multi-neck glass reactor, under dry and oxygen-free conditions, 71.8 g (0.629 mol) ε-caprolactone, 31.3 g (0.27 mol) glycolide, 0.0882 g glycolic acid. And 0.43 ml of a 0.33 molar stannous octoate toluene solution. The reactor is equipped with an adapter connected to a hose and a dry mechanical stirrer. The pressure in the reactor is reduced to remove toluene. After flushing and evacuating the reactor with nitrogen, it is kept at a pressure of 1 atmosphere with nitrogen for the rest of the operation. Immerse the reactor in a silicone oil bath and heat to 120 ° C. and hold it for 10 minutes. Raise the temperature to 200 ° C over 30 minutes and hold it for 20 minutes. Bath 1
Allow to cool to 50 ° C, stop stirring and remove reactor from bath. About 0.2 g of a small sample of the reaction product is taken out under a nitrogen atmosphere. The sample has an inherent viscosity of 0.51 dl / g.
In the reactor, 45.6 g (0.399 mol) of ε-caprolactone and 18
Add 5.6 g (1.599 mol) glycolide. Place the reactor back in the silicone oil bath. The temperature drops to 120 ° C,
Hold at that temperature for 10 minutes with good stirring. Raise the temperature to 205 ° C over 15 minutes and hold at that temperature for 4 hours.

The copolymer is isolated, ground and dried under reduced pressure at room temperature. Some unreacted monomer is removed by heating the milled copolymer at 100 ° C. under reduced pressure to a constant weight. A conversion of monomer to copolymer of about 87% is achieved. The resulting copolymer consisted of 26 percent by weight ε-caprolactone moieties and 74 percent by weight glycolide moieties. The resulting copolymer has an inherent viscosity of 1.53 dl / g when measured at 25 ° C using a 0.1 g / dl solution in hexafluoroisopropanol.

Example 5 17.1 g (0.150 mol) of ε-caprolactone on ampoule,
Essentially the procedure described in Example 1 except that 40.6 g (0.350 mol) of glycolide, 0.1182 g (0.001 mol) of 1,6-hexanediol and 0.25 ml of 0.033 mol stannous octoate toluene solution were charged. Obey. Immerse the sealed ampoule in a silicone oil bath preheated to 100 ° C. Hold this temperature for 30 minutes with stirring as long as possible. Raise the temperature to 190 ° C over 50 minutes and hold it for 7 hours. The conversion of the monomer to the copolymer was about 90 percent, and the resulting copolymer was 0.1% in hexafluoroisopropanol.
It has an inherent viscosity of 1.24 dl / g measured at 25 ° C. using a 1 g / dl solution. The resulting copolymer contains 23 percent by weight of ε-caprolactone moieties.

Example 6 14.3 g (0.125 mol) of ε-caprolactone on ampoule,
The procedure described in Example 1 was followed except that 43.5 g (0.35 mol) glycolide, 0.0591 g (0.0005 mol) 1,6-hexanediol and 0.51 ml 0.033 mol stannous octoate toluene solution were charged. Obey. The sealed ampoule
Immerse in a silicone oil bath preheated to 100 ° C. After holding the temperature for 15 minutes, the temperature is raised to 195 ° C in less than 1 hour. The copolymer is isolated, ground and dried under reduced pressure at room temperature. Some unreacted monomer is removed by heating the milled copolymer at 110 ° C. under reduced pressure.
The conversion of monomer to copolymer is about 90%. The copolymer produced is 0.1 g in hexafluoroisopropanol.
It has an inherent viscosity of 1.62 dl / g measured at 25 ° C at a concentration of / dl. The resulting copolymer contains 17 percent by weight of ε-caprolactone moieties.

Example 7 22.8 g (0.200 mol) of ε-caprolactone, 10 in a reactor
g (0.0862 mol) glycolide, 33.8 g (0.286 mmol) 1,6-hexanediol and 0.216 ml 0.33 mol stannous octoate toluene solution were charged,
Follow the procedure described in Example 4. The charged reactor is immersed in a silicone oil bath and heated to 190 ° C for 35 minutes.
The heating is discontinued and the reactor in the bath is allowed to cool to 120 ° C for 30 minutes. Under a nitrogen atmosphere while maintaining a temperature of 120 ° C
6.5 g (0.057 mol) of ε-caprolactone and 59.7 g (0.51 mol)
4 mol) glycolide is added to the reactor. The reaction is kept at 120 ° C for 40 minutes with good stirring. Increase the temperature to 1 over 15 minutes
Raise to 90 ° C and hold it for 2.5 hours. Isolate the copolymer,
Grind and dry at room temperature under reduced pressure. Some unreacted monomer is removed by heating the milled copolymer under reduced pressure at 85 ° C. for 16 hours. Achieve greater than 90% conversion of monomer to copolymer. The resulting copolymer has an inherent viscosity of 1.60 dl / g measured at 25 ° C. at a concentration of 0.1 g / dl in hexafluoroisopropanol. The resulting copolymer contains 26 percent by weight of ε-caprolactone moieties.

Example 8 22.8 g (0.200 mol) of ε-caprolactone, 7.
7 g (0.066 mol) glycolide, 0.1182 g (0.001 mol)
The procedure described in Example 7 is followed, except that the 1,6-hexanediol of 1. and 0.25 ml of a 0.033 molar solution of stannous octoate in toluene are charged. The initial polymerization is carried out at 150 ° C. and then the reactor is charged with a further 27.1 g (0.233 mol) of glycolide. Polymerization is continued at a temperature of 190-205 ° C for about 2.5 hours. Conversion rates of over 80% are obtained. The resulting copolymer has an inherent viscosity of 1.00 dl / g measured at 25 ° C. in hexafluoroisopropanol with a solution of 0.1 g / dl. The resulting copolymer contains 23 percent by weight of ε-caprolactone moieties.

Example 9 17.12 g ε-caprolactone and 10.15 g glycolide are used first, 30.47 g glycolide is added before the second polymerization and the second polymerization is carried out at 205 ° C. for 6 1/4 hours, Follow the procedure described in Example 8. Achieving a conversion of about 90%. The resulting copolymer was 1.23d measured at 25 ° C using a 0.1g / dl solution in hexafluoroisopropanol.
It has a viscosity of l / g. The resulting copolymer contains 22 percent by weight of ε-caprolactone moieties.

Example 10 A series of experiments are conducted with various ratios of ε-caprolactone and glycolide as shown in Table 1 below. In a flame-dried 100 ml glass ampoule equipped with a Teflon-coated magnetic stir bar, the amounts of ε-caprolactone and glycolide shown in the table below and 0.1182 g of 1,6-hexanediol and a catalytic amount of stannous tin (in toluene) were used. 0.033 molar solution of 0.25 m
Charge l). The pressure in the ampoule is reduced to evaporate the toluene. After repeating nitrogen replacement and suction, the pressure is adjusted to about 3/4 of atmospheric pressure by nitrogen and the ampoule is sealed. Immerse the reactor in a silicone oil bath preheated to 100 ° C. Keep this temperature for 15 minutes with stirring, then 150
Raise to ℃. Hold this temperature for 15 minutes, then raise to 190 ° C. and hold it for 18 hours. In Examples ah this procedure is followed, but in Example i the temperature is 20
Raise to 5 ° C and hold it for 2 hours. Allow the bath to cool to 190 ° C,
The temperature is maintained during the final heating time; the cooling time and the final heating time are 18 hours in total. The polymer from each example is isolated, cooled and ground. Table 1 shows the conversion ratio of each copolymer and the inherent viscosity when measured at 25 ° C. using a 0.1 g / dl solution in hexafluoroisopropanol.

Example 11 In a 100 ml glass ampoule equipped with a magnetic stir bar coated with Teflon, 22.8 g (0.200 mol) of ε-caprolactone, 3
Charge 4.8 g (0.300 mol) of glycolide, 0.1182 g (0.001 mol) of 1,6-hexanediol and 0.25 ml of a 0.033 molar stannous octoate solution in toluene. Immerse the reactor in a silicone oil bath preheated to 100 ° C. Hold this temperature for 15 minutes with stirring. Raise the temperature to 150 ° C and
After holding for 0 minutes, raise to 190 ° C and hold it for 17 hours. The polymer is isolated, ground and dried under reduced pressure at room temperature. Some unreacted monomer is removed by heating the milled polymer under reduced pressure at 110 ° C. for 16 hours. Achieve greater than 90% conversion of monomer to polymer. The resulting copolymer has an inherent viscosity of 1.39 dl / g at 25 ° C. in hexafluoroisopropanol at a concentration of 0.1 g / dl.

In this example, the resulting copolymer has an ε of about 37% by weight.
The copolymer which contains the caprolactone moiety and is almost amorphous. This is unsuitable for the production of dimensionally stable oriented filaments and surgical sutures.

Example 12 Flame dried 100 m with Teflon coated magnetic stir bar
In an ampoule, 11.41 g (0.4 mol) ε-caprolactone, 0.0739 g (0.625 mmol) 1,6-hexanediol and a catalytic amount of stannous octoate (0.03 in toluene).
Charge 3 molar solution 0.25 ml). The pressure in the ampoule is reduced to evaporate the toluene. After the ampoule was repeatedly replaced with dry nitrogen, the pressure was
Adjust to 3/4 atmosphere. Seal the ampoule with flame. Immerse the sealed ampoule in a silicone oil bath preheated to 100 ° C. This temperature is maintained for 15 minutes, possibly with stirring, then the temperature is raised to 150 ° C and maintained for 15 minutes. Temperature 190
C. and the polymerization is continued at 190.degree. C. for 18 hours. The resulting terpolymer is isolated, cooled, ground and then dried under reduced pressure at room temperature. The pulverized terpolymer was dried under reduced pressure at 110 ° C for 16
Some unreacted monomer is removed by heating for a period of time. A weight loss of 2.8% occurs. The resulting terpolymer has an inherent viscosity of 1.48 dl / g at 25 ° C. as a 0.1 g / dl solution in hexafluoroisopropanol. The novel synthetic absorbent copolymers of the present invention can be converted to compounded filament materials by known extrusion and drawing methods for producing filamentary materials. The filaments can be sterilized with or without needles to give surgical sutures sterilized as known in the art. A preferred method for extruding and stretching the copolymers of this invention is described in the examples below.

Example 13 At a temperature of at least 10 ° C. above the melting temperature of the copolymer,
Melt spinning the copolymer in an Instron rheometer. A 40 mil die with a length / width ratio of 24 is used.
A shear rate of 213 sec ^-1 is used for extrusion. Take the extrudate in ice water and wind on a spool. The wound fiber is stored under vacuum for 2-24 hours. The monofilament is oriented by one or two stages of stretching. Stretch filament 5%
Heat set by heating at a desired temperature under constant strain, with or without relaxation of.

The filamentous material is typically heat treated under conditions that improve the properties of the suture, as is known in the art. The filament is placed under tension at a temperature of about 50-120 ° C. for 1-48
Heat treatment may be performed for a period of time. In a preferred embodiment, the filamentary material of the present invention is heat treated under tension at a temperature of 60 to 110 ° C. for 4 to 16 hours.

The filament material is tested for various physical properties such as knot tensile strength, linear tensile strength, elongation and Young's modulus. The copolymer is also tested for inherent viscosity, melting point and crystallinity.

The various test methods used to measure the properties of filament materials and / or copolymers are set forth below.

The characteristics of the filament of the present invention can be easily measured by a conventional test method. These properties are measured using an Instron tensile tester under the following conditions: Crosshead speed (XH): 2 inches / min Chart speed (CS): 10 inches / min Sample length (GL): 2 inches Scale load (SL): 21 lbs / inch Young's modulus is calculated from the slope of the initial linear elastic region of the stress-strain curve of the sample as follows: Θ is each degree between tilt and horizontal, XS is the initial cross-sectional area of the fiber (in ² ), SL is the scale load and XH, CS and GL are as above.

Linear tensile strength is calculated by dividing the force required to cut (pounds) by the initial cross-sectional area of the fiber (in ² ).
Elongation at break is read directly from the stress-strain curve of the sample, allocating 10% per anti-horizontal displacement.

The knot tensile strength of filament is measured in another experiment. The test product is wrapped around a soft tube (1/4 inch ID, 1/16 inch wall thickness) with one wrap of filament and tied to the surgeon's knot. The surgeon's knot should be squeezed by pulling the free end first twice between the annuli rather than once, then between the second annulus.
Overlap the single nodule on the composite nodule by wrapping around and pulling strongly on both ends. The first nodule starts with the left end on the right end and applies sufficient force to ensure the knot is tied. Place the specimen on the Instron tester with the nodule approximately midway between the clamps. Knot tensile strength is calculated by dividing the force required to cut (pounds) by the initial cross-sectional area of the fiber (in ² ).

The temperature profile of the copolymer is determined using a differential scanning calorimeter by first heating the copolymer to its melting point (initial Tm) and then rapidly cooling the molten sample. The quenched copolymer is then reheated at a rate of 20 ° C. for 1 minute and the glass transition temperature (Tg), crystallization temperature (Tc) and melting point (Tm) are observed. The crystallinity of the polymers described is measured by the known X-ray diffraction method.

In each case, the stated inherent viscosities are measured in hexafluoroisopropanol at a concentration of 0.1 g / dl at 25 ° C.

The composition of the final copolymer is determined by NMR analysis.

The various copolymers prepared in Examples 1-12 are measured for one or more of the following properties: inherent viscosity, melting point and crystallinity. The results are shown in Table 2: The inventive copolymers prepared according to Examples 1 to 12 above are converted to filamentous materials, if possible, as described above. In some cases the filaments are heat treated, in others they are not. The filamentous materials produced are measured for one or more of the following properties: linear tensile strength, knot tensile strength, elongation and Young's modulus.

The results of these tests are shown in Table 3 below: Fibers made from copolymers made according to some of the above examples are heat treated and sterilized and tested for absorbency. The cut strength is tested for retention after various times.

The cut strength of the samples is measured by implanting two samples subcutaneously on the back of each of eight Long-Evans rats. Thus, 16 samples of each are transplanted (2 samples for each period) corresponding to 2 transplant periods. The residence time in vivo is 7 days and 14 days. The average value (average of 8 measurements) of the breaking strength (measured using an Instron tester according to the standard test method) in each period with respect to the average value (average of 8 measurements) obtained for the sample before transplantation The ratio is defined as the cutting strength retention rate for that period.

Table 4 shows the results of the cutting strength retention rate for each example.

The filaments of the present invention can be used as monofilament or multifilament sutures and can be woven, knitted or braided. The polymers of the present invention are also useful in making cast films and other solid surgical articles as are known in the art.

Many different embodiments of the invention will be apparent to those skilled in the art and could be made without departing from the spirit and scope of the invention. The invention is not limited to the specific embodiments except as set forth in the claims.

Claims (10)

[Claims] 1. A mixture of glycolide and ε-caprolactone is polymerized in the presence of a metal salt or metal oxide catalyst,
The polymerization is carried out at a temperature below 250 ° C. for a time sufficient to provide at least 80 percent conversion of monomer to copolymer, thereby producing a copolymer having a crystallinity of at least 5 percent. A process for producing a copolymer of glycolide and ε-caprolactone, which can be thermoformed into a strong filament having a Young's modulus of 300,000 psi or less. 2. A method according to claim 1 wherein 20 to 30 weight percent ε-caprolactone is used. 3. A method according to claim 1 wherein 0.004 to 0.02 weight percent catalyst is used. 4. The method of claim 1 wherein the catalyst is stannous octoate. 5. The method according to any one of claims 1 to 4, wherein the polymerization is carried out at a temperature of 190 ° C. 6. The method according to claim 5, wherein the polymerization is carried out for 10 hours or more. 7. The method of claim 6 wherein the conversion of monomer to copolymer is at least 90 percent. 8. The method of claim 7 wherein the copolymer has a crystallinity of at least 10 percent. 9. First, by polymerizing ε-caprolactone and glycolide at a temperature lower than 220 ° C., a low molecular weight prepolymer of ε-caprolactone and glycolide containing more than 50 weight percent ε-caprolactone is prepared.
Additional glycolide is then added to the prepolymer and the mixture containing the additional glycolide is polymerized at a temperature above 120 ° C. for a time sufficient to provide at least 80 percent conversion to copolymer. The method of claim 1 wherein the copolymer yields a copolymer having a crystallinity of at least 5 percent. 10. The method of claim 9 wherein the prepolymer contains at least 60 weight percent ε-caprolactone.