AU2003203627B2 - Method of Manufacturing A Monofilament Suture From A Resin of A Random Copolymer - Google Patents

Description

S&F Ref: 554227D1

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD

PATENT

Name and Address of Applicant: Actual Inventor(s): Address for Service: Invention Title: United States Surgical Corporation 150 Glover Avenue Norwalk Connecticut 06856 United States of America Rooma Mehta, Lydmilla K. Kokish, Jerry Y. John, Mark S. Roby Spruson Ferguson St Martins Tower Level 31 Market Street Sydney NSW 2000 (CCN 3710000177) Method of Manufacturing A Monofilament Suture From A Resin of A Random Copolymer The following statement is a full description of this invention, including the best method of performing it known to me/us:- 5845c Method Of Manufacturing A Monofilament Suture From A Resin Of A Random Co- Polymer Technical Field Absorbable polymers of randomly polymerised glycolide, lactide, trimethylene carbonate, and caprolactam are described. Process for making the polymers and surgical articles made totally or in part from such polymers, including sutures, are also described.

Background Bioabsorbable surgical devices made from copolymers derived from glycolide and E caprolactone are known in the art. Such bioabsorbable surgical devices include sutures.

A desirable characteristic of a bioabsorbable suture is its ability to exhibit and maintain desirable tensile properties for a predetermined time period followed by rapid absorption of the suture mass (hereinafter "mass loss").

Synthetic absorbable sutures are known in the art. Absorbable multifilament sutures such as DEXON sutures (made from glycolide homopolymer and commercially available from Davis Geck, Danbury Connecticut), VICRYL sutures (made from a copolymer of glycolide and lactide and commercially available from Ethicon, Inc., Sommerville, New Jersey), and POLYSORB sutures (made from a copolymer of glycolide and lactide and commercially available from United States Surgical Corporation, Norwalk, Connecticut) are known in the industry as short term absorbable sutures. The term short term absorbable sutures generally refers to surgical sutures which retain at least about percent of their original strength at three weeks after implantation, with the suture mass being essentially absorbed in the body within about 60 to 90 days post implantation.

PALSpecificationsf554227OlI sped Long term absorbable sutures are generallyclassified as sutures capable of retaining at least about 20 percent of their original strength for six or more weeks after implantation, with the suture mass being essentially absorbed in the body within about 180 days post implantation. For example, PDS II sutures (commercially available from Ethicon, Inc., Sommerville, New Jersey), are synthetic absorbable monofilament sutures that reportedly retain at least about 20 to 30 percent of their original strength six weeks after implantation.

However, PDS II reportedly exhibits minimal mass loss until days after implantation with the suture mass being essentially absorbed in the body about 180 days after implantation.

MAXON

suture (commercially available from Davis Geck, Danbury, Connecticut) is another absorbable synthetic monofilament..that reportedly generally fits this absorption profile.

Recently, United States Surgical Corporation has introduced BIOSYN monofilament sutures which exhibit good flexibility, handling characteristics, knot strength and absorption characteristics similar to those of presently available short term absorbable multifilament sutures.

Another attempt to provide an acceptable synthetic absorbable monofilament sutures resulted in MONOCRYL, a suture fabricated from an absorbable block copolymer containg glycolide and epsilon-caprolactone, commercially available from Ethicon, S Inc.

However, no synthetic absorbable monofilament sutures exist today which approximate the strength retention, mass loss, and modulus of sutures commonly referred to in the art as "catgut" or "gut" sutures. It is well known in the art that the 23) term gut suture refers to a collagen based suture of any type or origin often fabricated from the mammalian intestines, such as the serosal layer of bovine intestines or the submucosal fibrous layer of sheep intestines. Gut sutures exhibit the unique combination of two week strength retention and about 75 day mass loss while maintaining acceptable modulus and tensile strength; and thus are still widely used in gynecological surgery.

It would be advantageous to provide a synthetic absorbable suture which exhibits physical propertfes-similar or superior to the gut suture.

U.S. Patent N6. 4,700,704 to Jamiolkowski does teach that sutures can be fabricated from random copolymers of glycolide and epsilon-caprolactone, and more specifically from S, random copolymers containing from 20 to 35 weight percent epsilon-caprolactone and from 65 to 80 weight percent glycolide.

Moreover, Jamiolkowski reports that sutures fabricated from glycolide/epsilon-caprolactone copolymers containing over caprolactone are not orientable to a dimensionally stable fiber.

Jamiolkowski further reports that some sutures fabricated from glycolide/epsilon-caprolactone copolymers containing caprolactone are also not orientable to a dimensionally stable fiber. Furthermore, Jamiolkowski also reports the undesirable 2) combination of low modulus and low tensile strength for the glycolide/epsilon-caprolactone copolymers which he was able to fabricate into sutures.

C U.S. Patents 4,045,418 and 4,057,537 disclose random copolymers obtained by copolymerizing lactide and epsiloni 3 caprolactone as well as- terpolymers obtained by polymerizing lactide, epsilon-caprolactone, and glycolide. The copolymers as well as the terpolymers disclosed in U.S. Patents 4,045,418 and 4,057,537 have at least 60% by weight lactide. These copolymers have been described in the literature as having "one major 3 drawback which has prevented their wide spread use. Although the copolymers can be literally interpreted to be 'bioabsorbable', the rate of absorption is so slow that it renders the copolymers practically useless for numerous medical 4 applications" (see US 5 468 253 at column 2, lines 24 et seq.). In fact, US 5 468 253 addresses this problem by disclosing medical devices formed from a random copolymer of: a) from about 30 to about weight percent of epsilon-caprolactone, trimethylene carbonate, an ether lactone and combinations thereof, and b) the balance being substantially glycolide or para-trimethylene carbonate.

Therefore, it would be unexpected that medical devices such as sutures made from random copolymer of glycolide, epsilon-caprolactone, trimethylene carbonate, and lactide would provide the strength retention and mass loss characteristics approximating those of gut sutures while maintaining an acceptable modulus and tensile strength.

Disclosure Of The Invention According to this invention there is provided a method of manufacturing a monofilament suture from a resin of a random copolymer, the random copolymer comprising caprolactone, trimethylene carbonate, lactide, and glycolide, which comprises: a) extruding the copolymer to provide a molten monofilament; b) quenching the molten monfilament to provide a solidified monfilament; c) drawing the solidified monofilament through an air oven maintained at a temperature of about 250C to about 35 0 C at a draw ratio of about 6:1 to about 8:1; d) drawing the monofilament through an air oven maintained at a temperature of about 800C to about 1000C at a draw ratio of about 1.2:1 to about 2.5:1; e) drawing the monofilament through an air oven maintained at a temperature of about 900C to about 1100C at a draw ratio of about 0.85:1 to about 1.05:1; and f) annealing the monofilament.

Summary It has now surprisingly been found that absorbable surgical articles formed from a random polymer of glycolide, caprolactone, trimethylene carbonate and lactide exhibit strength retention, mass loss and modulus similar to that of gut sutures. In one embodiment, the polymers used in forming surgical articles include between about 12 and about 17 weight percent of units derived from caprolactone, about 5 to about 8 weight percent of units derived from trimethylene carbonate, between about 68 and 75 weight percent of units derived from glycolide, and between about 5 to about 8 weight percent of units derived from lactide. In another embodiment, the polymers used in forming surgical articles include between about 12 and about 17 weight percent of units derived from caprolactone, about 1 to about 19 weight percent of units derived from trimethylene carbonate, between about 68 and 75 weight percent of units derived from glycolide, and between about 1 to about 19 weight percent of units derived from lactide.

In particularly useful embodiments, the random polymers can be spun into fibres. The fibres can be advantageously PALSpecifications/554227D1 sped

I

S

l0 fabricated into either monofilament or multifilament sutures having physical properties similar to those of gut sutures.

In addition, a process of making such synthetic absorbable monofilament sutures from the above described trimethylene carbonate/caprolactone/glycolide/lactide random polymers has been found. The process, for a given size suture, comprises the operations of extruding the random caprolactone/glycolide/trimethylene carbonate/lactide copolymer at an extrusion temperature of from about 140°C to about 180 C to provide a monofilament fiber, passing the solidified monofilament through water (or other suitable liquid medium) quench bath at a temperature of from about 150 C to about 250 C or through air (or other suitable gaseous medium) at from about 15°C to about 25 0 C, stretching the monofilament through a series of air ovens at an overall stretch ratio of from about 8:1 to about 11:1 to provide a stretched monofilament. In a particularly useful embodiment, the monofilament is stretched through three air ovens by four godet stations. The first air oven is maintained at about 25 0 C to about 35 0 C temperature, whereas the second air oven is heated to a temperature above the crystalization temperature of the glycolide/lactide/epsilon-caprolactone/trimethylene carbonate copolymer at about 80 0 C to about 100°C, and the third air oven is set at about 90 0 C to about 110 0 C. The draw ratio between the first and second godet station ranges between about 6:1 to about 8:1. The draw ratio between the second and third godet station ranges between about 12:1 to about 2.5:1. The draw ratio between the third and fourth godet station ranges between about 0.85:1 to about 1.05:1.

The suture then may be annealed with or without relaxation at a temperature of from about 80 0 C to about 110 0 C to provide the finished suture.

BRIEF DESCRIPTION OF THE DRAWINGS I I Fig. 1A is a schematic illustration of an apparatus which is suitable for manufacturing of monofilament sutures disclosed herein; Fig. 1B is a modification of the apparatus shown in Fig. 1A which is particularily suitable for manufacturing monofilament sutures of smaller size; e.g. sizes 4/0 and smaller.

Fig. 2 is a perspective view of a suture attached to a needle.

(0 Fig. 3A 3C illustrate the formation of the knot which was employed in the loop pull test used in Table IV.

DESCRIPTION OF THE PREFERRED EMBODIMENTS It has been found that glycolide, epsilon-caprolactone, trimethylene carbonate, and lactide monomers can advantageously be combined to form a random polymer useful in forming surgical articles having strength retention, mass loss, and modulus characteristics similar to or superior to gut sutures.

The random polymer can be prepared using conventional techniques. For example, monomers can be dried, mixed in a reaction vessel with an initiator (either a single or multifunctional initiator) and a suitable polymerization catalyst and polymerized at temperatures from about 160'C to about 190'C for a period of time ranging from about 12 hours to about 48 hours.

The polymer has randomly combined repeating units derived from glycolide, lactide, trimethylene carbonate, and epsilon-caprolactone. In one embodiment, repeating units derived from glycolide comprise about 68 to about 75 weight percent of the polymer, while repeating units derived from lactide comprise about 5 to about 8 weight percent of the i polymer, units derived from caprolactone comprise about 12 to about 17 weight percent of the polymer, and units derived from trimethylene carbonate comprise about 5 to about 8 weight percent of the polymer. Polymers of trimethylene carbonate, caprolactone, glycolide, and lactide having an inherent viscosity of from about 1 to about 1.5 dl/g measured at 30'C and at a concentration of 0.25 g/dl in chloroform or HFIP may generally be used. In another embodiment, repeating units derived from glycolide comprise about 68 to about 75 weight percent of the polymer, while repeating units derived from lactide comprise about 1 to about 19 weight percent of the polymer, units derived from caprolactone comprise about 12 to about 17 weight percent of the polymer, and units derived from trimethylene carbonate comprise about 1 to about 19 weight percent of the polymer. Polymers of trimethylene carbonate, caprolactone, glycolide, and lactide having an inherent viscosity of from about 1 to about 1.5 dl/g measured at 30'C and at a concentration of 0.25 g/dl in chloroform or HFIP may generally be used.

The random polymers provided herein can be blended or copolymerized with other known absorbable polymers and/or coploymers derived from materials such as glycolide, lactide, caprolactone, trimethylene carbonate, dioxanone, alkylene oxides, absorbable amides and the like. It should be understood that the above list of materials with which the random copolymer can be either blended or copolymerized is provided for illustrative purposes and is not to be construed as limiting.

The random polymers can be formed into surgical articles using any known technique, such as, for example, extrusion, molding and/or solvent casting. The copolymers can >0 be used alone, blended with other absorbable compositions, or in combination with non-absorbable components. A wide variety of surgical articles can be manufactured from the copolymers described herein. These include but are not limited to clips and other fasteners, staples, sutures, pins, screws, prosthetic devices, wound dressings, drug delivery devices, anastomosis rings, and other implantable devices. Fibers made from the copolymers can be knitted, woven or made into non-woven materials with other fibers, either absorbable or nonabsorbable to form fabrics, such as meshes and felts. Compositions including these random copolymers can also be used as an absorbable coating for surgical devices. Preferably, however, the polymers are spun into fibers to be used in making sutures.

Multifilament sutures of the present invention may be made by methods known in the art. Braid constructions such as those disclosed and claimed in U.S. Patent No. 's 5,059,213 and 5,019,093 are suitable for the multifilament suture of the present invention.

Fig. 1A substantially illustrates the extruding, I quenching and stretching operations of the monofilament manufacturing operation herein. Extruder unit 10 is of a known or conventional type and is equipped with controls for regulating the temperature of barrel 11 in various zones thereof, progressively higher temperatures in three consecutive zones A, B and C along the length of the barrel.

Pellets or powder of resins of the present invention are introduced to the extruder through hopper 12. Any of the above described polymers which are useful for the formation of fibers can be used herein.

Z2 Motor-driven metering pump 13 delivers melt extruded resin at a constant rate to spin pack 14 and thereafter through spinneret 15 possessing one or more orifices of desired diameter to provide a molten monofilament 16 which then enters quench bath 17, containing water, where the monofilament 2) solidifies. The distance .monofilament 16 travels after emerging from spinneret 15 to the point where it enters quench bath 17, the air gap, can vary and can advantageously be from about 1 to about 5cm and preferably from about 2 to about 3cm. If desired, a chimney (not shown), or shield, can be provided to isolate monofilament 16 from contact with air currents which might otherwise affect the cooling of the monofilament in an unpredictable manner. In general, barrel S zone A of the -extruder can be maintained at a temperature of from about 140 0 C to 160 0 C, zone B at from about 140 0 C to 165 0

C

and zone C at from about 145 0 C to about 170 0 C. Additional temperature parameters include: metering pump block 13 at from about 140 0 C to about 170 0 C, spinneret 15 at from about 150°C to 0 about 180 0 C and quench bath at from about 15 0 C to about 25 0

C.

Monofilament 16 is passed through quench bath 17 around driven roller 18 and over idle roller 19. Optionally, a wiper (not shown) may remove excess water from the monofilament CJ as it is removed from quench bath 17. On exiting the quench J1 bath the monofilament is passed through first godet station 1, which is equiped with five individual godets, i.e. godets 101, 102, 103, 104 and 105. Upon entering godet station 1, monofilament 16 is wrapped around a first godet .101 provided with nip roll 22 to prevent slippage which might otherwise 2) result from the subsequent stretching operation; and subsequently passed over godet 101, under godet 102, over godet 103, under godet 104, and over godet 105 to godet station 2, containing godets 106, 107, 108, 109, and 110, where it is wrapped over godet 106, under godet 107, over godet 108, under godet 109, and over godet 110. Monofilament 16 passing from godet station 1 to godet station 2 is drawn through air oven 23 at a temperature ranging form about 25 0 C to about 35°C by the godets of godet station 2 which rotate at speeds faster than the speed of the godet station 1 to provide the desired draw S0 ratio, which is from about 6:1 to about 8:1 and preferably from about 6.5:1 to about 7.5:1, to effect the molecular orientation of the copolymer from which it is fabricated and thereby increase its tensile strength.

Following the initial draw at about 25 0 C to about S 35 0 C temperature, monofilament 16 is then subjected to a second and a third drawing operation. Monofilament 16 is subsequently drawn from godet 110 through air oven 24, which is maintained at from about 80 0 C to about 100 0 C, to godet station 3 containing godets 111, 112, 113, 114, and 115 where it is wrapped over godet 111, under godet 112, over godet 113, under godet 114, and over godet 115. Godet station 3 spins faster than godet station 2 to provide the desired draw ratio, which is from about 1.2:1 to about 2.5:1. Monofilament 16 is then drawn from godet 115 through air oven 25, which is maintained at from about 90°C to about 110 0 C, by godet station 4, I0 containing godets 116, 117 118, 119, and 120 where it is wrapped over godet 116, under godet 117, over godet 118, under godet 119, and over godet 120. Godet station 4 spins at a variable rate, (preferably faster than godet station 3) to provide the desired draw ratio, which is from about 0.85:1 to \c about 1.05:1. It should be understood that the godet arrangements in each of godet stations 1, 2, 3, and 4, respectively should not be limited to the above described arrangement and that each godet station may have any suitable godet arrangement.

In an alternative operation for sutures for smaller size sutures, e.g. sizes 4/0 to 8/0, as showm in Fig. 1B monofilament 16 is only passed through godet stations 1 and 2 and not subjected to any further stetching operations.

Annealing of the suture also may be accomplished with or without shrinkage of the suture. In carrying out the annealing operation, the desired length of suture may be wound around a creel and the creel placed in a heating cabinet under nitrogen flow maintained at the desired temperature, e.g. about to about 110'C, as described in U.S. Patent No. 3,630,205.

O After a suitable period of residency in the heating cabinet, for up to about 18 hours or so, the suture will have undergone essentially no shrinkage. As shown in U.S. Patent No.

3,630,205, the creel may be rotated within the heating cabinet in order to insure uniform heating of the monofilament or the 23 cabinet may be of the circulating hot air type in which case uniform heating of the monofilament will be achieved without the

IM

need to rotate the creel. Thereafter, the creel with its annealed suture is removed from the heating cabinet and when returned to room temperature, the suture is removed from the creel, conveniently by cutting the wound monofilament at opposite ends of the creel. The annealed sutures, optionally attached to surgical needles, are then ready to be packaged and sterilized.

Alternatively, the suture may be annealed on line with or without relaxation. For relaxation, the fourth godet station I0 rotates at a slower speed than the third godet station thus relieving tension on the filament.

The suture disclosed herein, suture 101, may be attached to a surgical needle 100 as shown in Fig. 2 by methods well known in the art. Wounds may be sutured by passing the i needled suture through tissue to create wound closure. The needle preferably is then removed from the suture and the suture tied.

One or more medico-surgically useful substances can be incorporated into the presently disclosed polymers and ?i surgical articles, those medico-surgically useful substances which accelerate or beneficially modify the healing process when particles are applied to a surgical repair site.

So, for example, the suture can carry a therapeutic agent which will be deposited at the repair site. The therapeutic agent can be chosen for its antimicrobial properties, capability for promoting repair or reconstruction and/or new tissue growth.

Antimicrobial agents such as broad spectrum antibiotic (gentamycin sulfate, erythromycin or derivatized glycopeptides) which are slowly released into the tissue can be applied in 3Q this manner to aid in combating clinical and sub-clinical infections in a tissue repair site. To promote repair and/or tissue growth, one or several growth promoting factors can be introduced into the sutures, fibroblast growth factor, bone growth factor, epidermal growth factor, platelet derived growth factor, macrophage derived growth factor, alveolar derived growth factor, monocyte derived growth factor, magainin, and so forth. Some therapeutic indications are: glycerol with tissue or kidney plasminogen activator to cause thrombosis, superoxide dimutase to scavenge tissue damaging free radicals, tumor necrosis factor for cancer therapy or colony stimulating factor and interferon, interleukin-2 or other lymphokine to enhance the immune system.

1C It is contemplated that it may be desirable to dye the sutures in order to increase visibility of the suture in the surgical field. Dyes known to be suitable for incorporation in sutures can be used. Such dyes include but are not limited to carbon black, bone black, D&C Green No. 6, I\ and D&C Violet No. 2 as described in the handbook of U.S.

Colorants for Food, Drugs and Cosmetics by Daniel M. Marrion (1979). Preferably, sutures in accordance with the invention are dyed by adding up to about a few percent and preferably about 0.2% dye, such as D&C Violet No. 2 to the resin prior to extrusion, although addition of the dye during polymerization is also suitable.

In order that those skilled in the art may be better able to practice the compositions and methods described.herein, the following examples are given as an illustration of the preparation of random polymers as well as of the preparation and superior characteristics of sutures made from the random copolymers. It should be noted that the invention is not limited to the specific details embodied in the examples and further that all ratios or parts recited are by weight, unless otherwise indicated.

EXAMPLE 1 Dry glycolide (4140 grams), dry 1-lactide (420 grams), trimethylene carbonate (420grams) and distilled epsiloncaprolactone (1020 grams) were added to a reactor along with 0.72 grams of distilled stannous octoate and 1.2 grams of distilled diethylene glycol (DEG). The mixture was dried for about 22.5 hours with agitation under flow of nitrogen. The reactor temperature was then set at 100'C. When the temperature of the reaction vessel reached 100*C, the temperature was maintained for about 15 minutes. Then the temperature of the Sreaction vessel was raised to 150'C and then the reaction vessel heated for about an additional 15 minutes. The temperature of the reactants was then raised to about 180'C and polymerization conducted with stirring under a nitrogen atmosphere for about 18 hours.

The reaction product is then isolated, comminuted, and treated to remove residual reactants using known techniques.

The treatment to remove residual reactants occurred at 90'C for 48 hours under vacuum. NMR analysis, using a commercially available Bruker NMR, model number DPX-300, revealed the 170 resultant polymer contained 7.25 weight percent lactide, 15.87 weight percent caprolactone, 6.84 weight percent trimethylenecarbonate, and 70.04 weight percent glycolide.

EXAMPLE 2 Dry glycolide (4260 grams), dry 1-lactide (420 grams), trimethylene carbonate (420 grams) and distilled epsilon- .23 caprolactone (900 grams) were added to a reactor along with 0.72 grams of distilled stannous octoate and 1.2 grams of distilled diethylene glycol (DEG). The mixture was dried for about 6 hours with agitation under flow of nitrogen. The reactor temperature was then set at 100'C. When the temperature of the reaction vessel reached 100'C, the temperature was maintained for about 15 minutes. Then the temperature of the reaction vessel was raised to 150'C and then the reaction vessel heated for about an additional 15 minutes. The temperature of the reactants was then raised to about 180C and polymerization conducted with stirring under a nitrogen atmosphere for about 18 hours.

The reaction product is then isolated, comminuted, and treated to remove residual reactants using known techniques.

The treatment to remove residual reactants occurred at 90'C for 48 hours under vacuum. NMR analysis, using a commercially available Bruker NMR, model number DPX-300, revealed the resultant polymer contained 7.2 weight percent lactide, 13.9 weight percent caprolactone, 6.8 weight percent trimethylene carbonate, and 72.1 weight percent glycolide.

TABLE I CONDITIONS OF MANUFACTURING VARIOUS SIZES I 5 OF MONOFILAMENT OF THE PRESENT INVENTION 2i Example Suture Size Process Conditions extruder screw, rpm pump, rpm driven roller, mpm barrel temp., zone A barrel temp., zone B barrel temp., zone C clamp temp., 'C, adapter temp., "C spinneret temp., 'C 1 3/0 Extrusion 4.4 12.9 2.5 140 143 146 153 153 153 2 8.4 1.9 140 145 147 155 157 160 block temp., "C 153 160 barrel melt temp., "C 152 154 pump melt temp., 'C 157 163 spinneret melt temp., 'C 159 166 S barrel pressure, psi 550 540 pump pressure, psi 500 500 spinneret pressure, psi 730 580 pump size, cc per revolution 0.16 0.16 diameter of spinneret, orifices, mm 1.2 1.2 O1 no. of spinneret orifices 1 1 quench bath temp., "C 27 Stretching (Orienting) Operation Example 1 2 draw bath temp., "C N/A N/A first godet station, mpm 2.7 1 2 I) second godet, mpm 17.7 13.3 third godet station, mpm 24.9 17.5 fourth godet station,mpm 25.2 15.6 first oven temp, 'C 29 31 second oven temp, C 94 96 third oven temp, 'C 90 100 overall draw ratio 9.33:1 8.75:1 Relaxation N/A 11% Annealing Operation Example 1 2 annealing temp., *C 90 2 time (hrs.) 6 6 The physical properties of the sutures and the procedures employed for their measurement are set forth in Table II as follows: TABLE II PROCEDURES FOR MEASURING PHYSICAL

PROPERTIES

OF MONOFILAMENT SUTURES OF THE PRESENT INVENTION Physical Property knot-pull strength, kg straight-pull strength, kg elongation, tensile strength, kg/mm 2 Young's Modulus Test Procedure U.S.P. XXI, tensile strength, sutures (881) ASTM D-2256, Instron Corporation ASTM D-2256 ASTM D-2256, Instron Corporation Series IX Automated Materials Testing System 1.03A Instron Merlin Software version 2000 Series IX calculation. 18.3 (commercially available from Instron Corporation) 0 Table III below sets forth the physical properties of the size 3/0 suture of the present invention.

TABLE III Physical Property diameter (mm) knot-pull strength (kg) Young's Modulus (kpsi) Elongation Tensile Strength (kpsi) Example 1 Example 2 0.325 2.58 229 26 88.3 0.32 3.15 453 29 103.6 As the data in Tables III illustrates, the suture made of the copolymer provided herein shows a desired physical properties, such as modulus and tensile strength.

IN VITRO STRENGTH RETENTION Monofilament sutures manufactured in accordance with the above described process using the copolymer of Example 1 were tested for in vitro strength retention. In c vitro loop-pull strength retention is indicative of in vivo strength retention. The in vitro strength retention of the suture was tested as follows: To simulate in vivo conditions, the suture samples were stored in a container filled with Sorenson's buffer solution at 37'C. After various periods of time, the suture samples were then removed from the container to test their loop-pull strength as follows. A knotted loop was formed in a test suture in three steps as shown in FIGS. 3A 3C. As shown in step 1 of FIG 3A each suture was given a double throw IE (left over right around a 2 cm diameter cylinder. In Step 2, the free ends of the suture were-set in a single throw (right over left) onto the initial throw of step 1. Finally, in step 3, another double throw left over right) was set onto the single throw of Step 2 to complete the knot. The free ends of the suture were cut to approximately 0.5 inches and the loop was carefully eased from the cylinder.

Testing of the loop was carried out using an Instron Tensile Tester Model No. 4307 (commercially available from Instron Corporation, Canton, Massachusetts), operated with a 2 crosshead speed of 51 mm/min and equipped with flat grips, (9 each having a pin over which the loop is positioned.

The results of the tests are presented in Table IV hereinbelow. In the strength retention data reported in Table IV, Tn represents the time elapsed in weeks since the sample was placed in the solution, with n representing the number of weeks.

TABLE IV PERCENTAGE OF IN VITRO STRENGTH RETAINED COMPOSITION T1 T2 T3 EXAMPLE 1 73.7 15.7 0 EXAMPLE 2 83.9 18.8 0 SMonocryl 58 26 3 IN VITRO MASS LOSS Monofilament sutures manufactured in accordance with the above described process'using the polymer of Examples 1-3 were tested for in vitro mass retention. In vitro mass retention is indicative of in vivo mass retention. The in vitro strength retention of the suture was tested as follows: To simulate in vivo conditions, the suture samples were weighed and stored in a fritted microencapsulation thimble (commercially available from Chemglass, Inc., Vineland, New Jersey), which was placed in a scintillation vial filled with I Sorenson's buffer solution. The scintillation vials were then placed in a water bath at 80'C. After various periods of time, the microextraction thimbles containing the suture samples were then removed from the scintillation vial, vacuum filtered, rinsed with distilled water, vacuum filtered, and D r dried for about 6 hours at about 40'C under vacuum and subsequently the suture and thimble were weighed. The weight of the suture remaining was calculated by subtracting the weight of the thimble from the weight of the thimble containing the remaining suture. The percentage of the suture retained was calculated by dividing the weight of the remaining suture by the original weight of the suture and multiplying the result by 100.

The results of the tests are presented in Table V hereinbelow. In the mass retention data reported in Table V, Tn represents the time elapsed in hours since the sample was placed in the solution, with n representing the number of hours. It is well known in the art that one hour of immersion in the container filled with Sorenson's buffer solution at approximates about one day of in vivo mass loss. For comparison purposes, the same tests were conducted on Monocryl sutures.

All comparative tests were performed on size 3/0 sutures.

TABLE V Time (hr) EXAMPLE 1 EXAMPLE 2 Monocryl T1 T2 8 24 92.8 58.34 92.11 59.62 94.86 74.79

PERCENTAGE

T3 32 42.14 45.08 66.83 OF IN VITRO MASS T4 T6 48 72 29.09 21.91 32.96 25.18 47.95 35.31

RETAINED

T8 96 18.01 20.62 27.32

T

1 0 120 13.58 16.26 17.37 It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments.

Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.

19 r r

Claims (3)

1. A method of manufacturing a monofilament sulure from a resin of a random copolymer, the random copolymer comprising caprolactone, trimethylene carbonate, lactide, and glycolide, which comprises: a) extruding the copolymer to provide a molten monofilament; b) quenching the molten monfilament to provide a solidified monfilament; c) drawing the solidified monofilament through an air oven maintained at a temperature of about 25 0 C to about 350C at a draw ratio of about 6:1 to about 8:1; d) drawing the monofilament through an air oven maintained at a temperature of about 800C to about 1000C at a draw ratio of about 1.2:1 to about 2.5:1; e) drawing the monofilament through an air oven maintained at a temperature of about 900C to about 1100C at a draw ratio of about 0.85:1 to about 1.05:1; and f) annealing the monofilament.

2. The method of claim 1 wherein the random copolymer comprises from about 68 about weight percent glycolide, about 12 to about 17 weight percent epsilon-caprolactone, about 1 to about 19 weight percent trimethylene carbonate, and about 1 to about 19 weight percent lactide.

3. A monofilament suture prepared by the method according to claim 1 or claim 2. Dated 9 April 2003 UNITED STATES SURGICAL CORPORATION Patent Attorneys for the Applicant/Nominated Person SPRUSON&FERGUSON PALSpecifications/55422 7 D speci