ES2355699T3 - REABSORBABLE POLYMERS AND SURGICAL ITEMS MANUFACTURED OF THEM. - Google Patents

Abstract

A medical device manufactured entirely or in part from a random polymer comprising 70 to 76 percent by weight of glycolide, 14 to 17 percent by weight of epsilon-caprolactone and 9 to 15 percent by weight of lactide.

Description

TECHNICAL FIELD

Resorbable terpolymers of glycolide, lactide and caprolactone randomly polymerized are described. Processes for making terpolymers and surgical articles made entirely or in part from such terpolymers, including sutures, are also described. 5

BACKGROUND

Bio-absorbable surgical devices made from copolymers derived from glycolide and epsilon-caprolactone are known in the art. Resorbable surgical devices of this type include surgical sutures.

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

Synthetic resorbable sutures are known in the art. Absorbable multifilament sutures such as DEXON II sutures (made from glycolide homopolymer and commercially available from United States Surgical Corporation, North Haven, Connecticut), VICRYL sutures (made from a glycolide and lactide copolymer and commercially available from Ethicon, Inc., Sommerville, New Jersey), and POLYSORB sutures (also made from a glycolide and lactide copolymer and commercially available from United States Surgical Corporation, North Haven, Connecticut) are known in the industry as absorbable sutures short term. The classification of reabsorbable sutures in the short term refers, in general, to surgical sutures that retain at least about 20 percent of their original resistance at three weeks after implantation, the suture mass being practically reabsorbed into the body. within about 60 to 90 days after implantation.

Long-term reabsorbable sutures are generally classified as sutures capable of retaining at least about 20 percent of their original strength for six or more weeks after implantation, the suture mass being reabsorbed into the body within about 180 days after implantation. For example, PDS II sutures (commercially available from Ethicon, Inc., Sommerville, New Jersey), are synthetic resorbable monofilament sutures that are reported to retain at least about 20 to 30 percent of their original strength six weeks after implantation. However, PDS II reportedly shows a minimum loss of mass up to 90 days after implantation, the suture mass being practically reabsorbed in the body about 180 days after implantation. The MAXON suture (commercially available from United States Surgical Corporation, North Haven, Connecticut) is another resorbable synthetic monofilament that, according to reports, 30 generally conforms to this resorption profile.

More recently, United States Surgical Corporation has introduced the BIOSYN monofilament sutures which show good flexibility, handling characteristics, knot strength and resorption characteristics similar to those of currently available short-term absorbable multifilament sutures.

Another attempt to provide an acceptable synthetic resorbable monofilament suture resulted in MONOCRYL, a suture made from a block copolymer containing glycolide and epsilon-caprolactone, commercially available from Ethicon, Inc.

However, today there are no synthetic resorbable monofilament sutures which approximate resistance retention, mass loss and modulus of elasticity of sutures that are commonly referred to in the art as "gut" or "sutures." catgut. " It is well known in the art that the term "gut suture" refers to a collagen-based suture of any type or origin often made from mammalian intestines, such as the serous layer of bovine intestines or the layer. fibrous submucosa of lamb intestines. Gut sutures show the only combination of strength retention for two weeks and about 75 days of mass loss while maintaining an acceptable modulus of elasticity and tensile strength; and therefore they are still widely used in gynecological surgery. Four. Five

It would be advantageous to provide a synthetic resorbable suture that shows physical properties similar to the gut suture.

US Patent documents 5,236,444 and 5,322,925 describe block copolymers used to produce suture, the copolymer comprises a block made of glycolide and epsilon-caprolactone and a second block made of trimethylene and glycolide carbonate or epsilon-caprolactone. fifty

US Patent 4,605,730 describes a process for producing a glycolide and epsilon-caprolactone copolymer having a Young's modulus of less than 1,724 MPa and US Patent document 5,713,920 describes medical devices, such as sutures, formed from bioabsorbable elastomers comprising random copolymers made of epsilon-caprolactone.

US Patent No. 4,700,704 to Jamiolkowski publishes that 55 can be manufactured.

sutures from random copolymers of glycolide and epsilon-caprolactone and, more specifically, from random copolymers containing from 20 to 35 percent by weight of epsilon-caprolactone and from 65 to 80 percent by weight of glycolide. In addition, Jamiolkowski reports that sutures made from glycolide / epsilon-caprolactone copolymers containing more than 35% caprolactone cannot be oriented to obtain a dimensionally stable fiber. Jamiolkowski also reports that some sutures made from glycolide / epsilon-caprolactone copolymers containing 15% caprolactone cannot be oriented to produce a dimensionally stable fiber. In addition, Jamiolkowski also reports the undesirable combination of low modulus of elasticity and low tensile strength for glycolide / epsilon-caprolactone copolymers with which he was able to make sutures.

US Patent 4,045,418 and 4,057,537 describe random copolymers 10 obtained by the copolymerization of lactide and epsilon-caprolactone as well as terpolymers obtained by polymerization of lactide, epsilon-caprolactone and glycolide. The copolymers as well as the terpolymers described in US Patent 4,045,418 and 4,057,537 have at least 60% lactide by weight. These copolymers have been described in the literature as having "an important drawback that has prevented their widespread use. Although it can be interpreted that the copolymers are literally "bioabsorbable," the rate of resorption 15 is so slow that it makes the copolymers virtually useless for numerous medical applications "(see US Patent 5,468,253 in column 2, lines 24 And next). In fact, US Patent 5,468,253 addresses this problem by describing medical devices formed from a random copolymer of: a) from about 30 to about 50% by weight of epsilon-caprolactone, trimethylene carbonate and lactone ether , and their combinations, and b) the remaining weight being substantially glycolide or para-dioxanone.

Therefore, it would be unexpected that medical devices of the type of sutures made from random copolymers of glycolide, epsilon-caprolactone and lactide could provide the characteristics of strength retention and mass loss that approximate those of gut sutures at the same time. that maintain an acceptable modulus of elasticity and tensile strength. 25

COMPENDIUM

It has now been found, surprisingly, that resorbable surgical articles formed from a random glycolide, caprolactone and lactide terpolymer show a strength retention, a loss of mass and a modulus of elasticity similar to those of gut sutures. Preferably, the terpolymers used to form surgical articles include between 14 and 17 percent by weight of units derived from caprolactone, between 70 and 76 percent by weight of units derived from glycolide and between 9 to 15 percent by weight of units derived of lactide

In particularly useful embodiments, random terpolymers can be spun into fibers. The fibers can be advantageously manufactured in either monofilament or multifilament sutures that have physical properties similar to those of gut sutures.

In addition, a process has been found to make such synthetic resorbable monofilament sutures from the random terpolymers of caprolactone / glycolide / lactide described above. The process, for a suture of a given caliber, comprises the operations of extruding the random copolymer of caprolactone / glycolide / lactide at an extrusion temperature of between 130 ° C and 190 ° C to provide a monofilament fiber, passing the solidified monofilament through a water cooling bath (or other suitable liquid medium) at a temperature between 15º C and 28º C or through air (or other suitable gaseous medium) between 15º C and 30º C, stretch the monofilament through 40 of a series of air convection ovens at a global draw ratio between 6: 1 and 13: 1 to provide a stretched monofilament. In a particularly useful embodiment, the monofilament is stretched through three air convection ovens by four stations of stretching cylinders. The first air convection oven is kept at room temperature, while the second air convection oven is heated to a temperature above the crystallization temperature of the glycolide / lactide / epsilon-caprolactone copolymer between 45 80 ° C and 115 ° C, and the third air convection furnace is set between 80º C and 125º C. The stretching ratio between the first and second stations of stretching cylinders varies between 5: 1 and 12: 1. The stretching ratio between the second and third station of stretching cylinders varies between 1.1: 1 and 2.6: 1. The stretching ratio between the third and fourth stations of stretching cylinders varies between 0.75: 1 and 1.05: 1. The suture can then be tempered with or without relaxation at a temperature between 80º C and 125º C to provide the finished suture. fifty

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1A is a schematic illustration of an apparatus that is suitable for the manufacture of monofilament sutures described herein;

Figure 1B is a modification of the apparatus shown in Figure 1A that is particularly suitable for manufacturing monofilament sutures of smaller caliber; for example, sizes 4/0 and smaller. 55

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

Figure 3A-3C illustrates the formation of the knot that was used in the tensile test of the loop used in Table IV .;

DESCRIPTION OF THE PREFERRED EMBODIMENTS

It has been found that glycolide, epsilon-caprolactone and lactide monomers can be advantageously combined to form a random polymer useful for forming surgical articles that have strength retention characteristics, mass loss and elastic modulus similar to or greater than sutures of gut.

The random polymer can be prepared using conventional techniques. For example, monomers 5 can be dried, mixed in a reaction vessel with an initiator (a very mono or multifunctional initiator) and a suitable polymerization catalyst and polymerized at temperatures from 170 ° C to 200 ° C for a period of time that It varies from 10 hours to 30 hours.

The polymer has randomly combined repeating units derived from glycolide, lactide and epsilon-caprolactone. Repetitive units derived from glycolide comprise between 70 and 76 percent by weight of the polymer, 10 while repetitive units derived from lactide comprise 9 to 15 percent by weight of the polymer and units derived from caprolactone comprise 14 to 17 percent by weight. polymer weight In general, caprolactone, glycolide and lactide polymers having an intrinsic viscosity between 0.9 and 1.8 dl / g measured at 30 ° C and at a concentration of 0.25 g / dl in chloroform or HFIP can be used

The random polymers given herein may be mixed or copolymerized with other known resorbable polymers and / or copolymers derived from materials such as glycolide, lactide, caprolactone, dioxanone, trimethylene carbonate, alkylene oxides, resorbable amides and the like. It should be understood that the above list of materials with which the random copolymer can be either mixed or copolymerized is given for illustrative purposes and should not be considered as limiting.

Random polymers can be shaped into surgical articles using any known technique, such as, for example, extrusion, molding and / or solvent casting. The copolymers can be used alone, mixed with other resorbable compositions, or in combination with non-absorbable components. A wide variety of surgical items can be manufactured from the copolymers described herein. These include, but are not limited to, forceps and other fasteners, staples, sutures, nails, screws, prosthetic devices, wound dressings, medication dispensing devices, anastomosis rings and other 25 implantable devices. Fibers made from copolymers can be braided, woven or transformed into nonwoven materials with other fibers, either reabsorbable or non-absorbable to form structures such as meshes and felts. Compositions that include these random copolymers can also be used as a resorbable coating for surgical devices. Preferably, however, the polymers are spun into fibers to be used in making sutures. 30

The multifilament sutures of the present invention can be made by methods known in the art. Braided constructions of the type described and claimed in US Patent Nos. 5,059,213 and 5,019,093 are suitable for the multifilament suture of the present invention.

Figure 1A substantially illustrates the extrusion, cooling and stretching operations of the monofilament manufacturing operation of this document. The extruder unit 10 is of a known or conventional type and is equipped with controls to regulate the drum temperature 11 in various areas thereof, for example, progressively higher temperatures in three consecutive zones A, B and C along the drum length Pellets or resin powder of the present invention are introduced into the extruder, through hopper 12. Any of the polymers described above that are useful for fiber formation can be used herein.

The metering pump 13 supplies molten extruded resin at a constant speed to the set of 40 rotary discs 14 and then through the row 15 which has one or more holes of desired diameter to provide a molten monofilament 16 which then enters the bath cooling 17, which for example contains water, where the monofilament solidifies. The distance that the monofilament 16 travels after leaving row 15 to the point where it enters the cooling bath 17, that is the open space, can vary and can be advantageously from 0.5 to 100 cm and preferably from 1 to 20 cm. If desired, a vault (not shown), or screen, can be provided to isolate monofilament 16 from contact with air currents which could otherwise affect cooling of the monofilament in an unpredictable manner. In general, zone A of the extruder drum can be maintained at a temperature between 130º C and 180º C, zone B at one between 135º C and 190º C and zone C at one between 135º C and 190º C. Parameters Additional temperatures include: block 13 of the metering pump between 135º C and 190º C, row 15 between 140º C and 190º C and cooling bath 50 between 15º C and 25º C.

The monofilament 16 is passed through the cooling bath 17 around a driven roller 18 and above the guide roller 19. Optionally, a brush (not shown) can remove excess water from the monofilament as it is removed from the cooling bath 17. Upon exiting the cooling bath the monofilament is passed through the first station 1 of stretching cylinders, which is equipped with five individual stretching cylinders 55, ie stretching cylinders 101, 102, 103, 104 and 105. Upon entering the station 1 of stretching cylinders, the monofilament 16 is wrapped around a first stretching cylinder 101 provided with a pressure roller. 22 to prevent slippage which could otherwise occur as a result of the subsequent stretching operation; and then passed over the stretching cylinder 101, below the stretching cylinder 102, by

above the stretching cylinder 103, below the stretching cylinder 104 and above the stretching cylinder 105 to the station 2 of stretching cylinders, which contains the stretching cylinders 106, 107, 108, 109 and 110, where it is wrapped above the cylinder stretcher 106, below the stretch cylinder 107, above the stretch cylinder 108, below the stretch cylinder 109 and above the stretch cylinder 110. The monofilament 16 which passes from station 1 of stretching cylinders to station 2 of stretching cylinders it is stretched through an oven 23 of 5 air convection at a temperature ranging from 25 ° C to 40 ° C by the stretching cylinders of station 2 of stretching cylinders which rotate at speeds faster than the speed of station 1 of stretching cylinders to provide the desired drawing ratio, which is from 5: 1 to 12: 1 and, preferably, from 6: 1 to 10: 1, to effect the molecular orientation of the copolymer from which it is manufactured and thereby increase its tensile strength. 10

Following the initial stretching at a temperature between about 20 ° C and about 40 ° C, the monofilament 16 is then subjected to a second and a third stretching operations. The monofilament 16 is then stretched from the stretching cylinder 110 through the air convection oven 24, which is maintained between about 80 ° C and about 115 ° C, to the stretching cylinder station 3 containing the stretching cylinders 111, 112, 113, 114 and 115 where it is wrapped above the stretching cylinder 111, below the stretching cylinder 112, above the stretching cylinder 113, below the stretching cylinder 114 and above the stretching cylinder 115. Station 3 of stretching cylinders rotates faster than station 2 of stretching cylinders to provide the desired stretch ratio, which is from about 1.3: 1 to about 2.6: 1. The monofilament 16 is then stretched from the stretching cylinder 115 through the air convection oven 25, which is maintained between about 80 ° C and about 125 ° C, by the station 4 of stretching cylinders 20 containing the stretching cylinders 116 , 117, 118, 119 and 120 where it is wrapped above the stretching cylinder 116, below the stretching cylinder 117, above the stretching cylinder 118, below the stretching cylinder 119 and above the stretching cylinder 120. Station 4 of stretching cylinders rotates faster than station 3 of stretching cylinders to provide the desired drawing ratio, which is from 0.75: 1 to 1.05: 1. It should be understood that the arrangements of stretching cylinders in each of the stations 1, 2, 3 and 4 of stretching cylinders, 25 respectively, should not be limited to the arrangement described above and that each station of stretching cylinders may have any applicable arrangement.

In an alternative suture operation for smaller caliber sutures, for example 4/0 to 8/0 gauges, as shown in Figure 1B, monofilament 16 is passed only through stations 1 and 2 of stretching cylinders and not is subjected to no further stretching operation. 30

The suture tempering can also be performed with or without suture contraction. When performing the tempering operation, the desired length of suture can be wound around a fillet and the fillet placed in a heating booth under nitrogen flow maintained at the desired temperature, for example between 80 ° C and 125 ° C, as It is described in US Patent No. 3,630,205. After a suitable period of residence in the heating cabin, for example for up to 18 hours or so, the suture will have undergone virtually no contraction. As shown in US Patent 3,630,205, the fillet can be rotated inside the heating cabin in order to ensure uniform heating of the monofilament or the cabin can be of the type of circulating hot air in which case the heating Monofilament uniform will be achieved without the need to rotate the fillet. After this, the fillet with its tempered suture is removed from the heating booth and when it returns to room temperature, the suture 40 is removed from the fillet, conveniently by cutting the wound monofilament at opposite ends of the fillet. The tempered sutures, optionally attached to surgical needles, are then ready to be packaged and sterilized.

As an alternative, the suture can be tempered in line with or without relaxation. For relaxation, the fourth station of stretching cylinders rotates at a slower speed than the third station of stretching cylinders thereby relieving tension in the filament.

The suture described herein, suture 101, can be attached to a surgical needle 100 as shown in Figure 2 by methods well known in the art. The wounds can be sutured by passing the threaded suture in the needle through the tissue to create a wound closure. The needle is preferably removed from the suture and the suture attached. fifty

It is also within the scope of this invention to incorporate one or more substances useful from the medical-surgical point of view in the polymers and surgical articles described herein, for example, those substances useful from the medical-surgical point of view that accelerate or beneficially modify the healing process when particles are applied to a surgical repair site. Thus, for example, the suture can carry a therapeutic agent that will be deposited at the repair site. The therapeutic agent can be chosen for its antimicrobial properties or its ability to promote repair or reconstruction and / or growth of new tissue. Antimicrobial agents such as broad-spectrum antibiotics (gentamicin sulfate, erythromycin or derived glycopeptides) which are slowly released into the tissue can be applied in this way to help fight clinical and subclinical infections at a tissue repair site.

To promote tissue repair and / or growth, one or more growth promotion factors 60 may be introduced into the sutures, for example, 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 on. Some therapeutic indications are: glycerol with tissue or renal plasminogen activator to cause thrombosis, superoxide dimutase to eliminate free radicals that damage tissues, tumor necrosis factor for cancer therapy or colony and interferon stimulation factor, interleukin-2 or other lymphokines to boost the immune system.

It is contemplated that it may be desirable to dye the sutures in order to increase the visibility of the suture in the surgical field. Dyes known as suitable for incorporation into sutures can be used. Such dyes include, but are not limited to, carbon black, bone black, D&C Green No. 6 and D&C Violet No. 2 as described in the U.S. manual. Colorants for Food, Drugs and Cosmetics by Daniel M. Marrion (1,979). Preferably, the sutures according to the invention are stained by adding up to about a small percentage and, preferably, about 0.2% dye, such as Violet D&C No. 2 to the resin before extrusion, although The addition of the dye during polymerization is also acceptable.

In order that those skilled in the art can better implement the compositions and methods described herein, the following examples are given as an illustration of the preparation of random polymers as well as 15 of the preparation and superior characteristics of sutures made to from random copolymers. It should be appreciated that the invention is not limited to the specific detailed embodiments of the examples and furthermore that all the relationships or parts set forth are by weight, unless otherwise indicated.

EXAMPLE 1

Dry glycolide (1,320 grams), dry 1-lactide (300 grams) and distilled epsilon-caprolactone (380 grams) were added to a reactor along with 0.24 grams of distilled stannous octoate and 0.2 grams of diethylene glycol (DEG) distilled. The mixture was dried for 21 hours and 40 minutes with stirring under nitrogen flow. 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 was heated for an additional 15 minutes. The temperature of the reaction was then raised to about 190 ° C and the polymerization carried out with stirring under nitrogen atmosphere for 25 hours and 40 minutes.

The reaction product was then isolated, crushed and treated to extract residual reagents using known techniques. The treatment to extract the residual reagents takes place at 100 ° C for 48 hours under vacuum. Analysis by RNM, using a team of RNM Bruker, model number DPX-300, commercially available, revealed that the resulting polymer contained 12.9 percent by weight of lactide, 16.6 percent by weight of caprolactone and 70 , 5 percent by weight glycolide.

EXAMPLE 2

Dry glycolide (4,080 grams), dry 1-lactide (900 grams) and distilled epsilon-caprolactone (1,020 grams) were added to a reactor along with 0.72 grams of distilled stannous octoate and 1.2 grams of diethylene glycol (DEG) 35 distilled. The mixture was dried for 18.75 hours with stirring under nitrogen flow. 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 reaction temperature was raised to 150 ° C and then the reaction vessel was heated for an additional 15 minutes. The reaction temperature was then raised to about 190 ° C and the polymerization carried out with stirring under nitrogen atmosphere for 23 hours and 10 minutes.

The reaction product was then isolated, crushed and treated to extract residual reagents using known techniques.

The treatment to extract the residual reagents takes place at 90 ° C for 48 hours under vacuum. NMR analysis, using a Bruker NMR kit, commercially available DPX-300 model number, revealed that the resulting polymer contained 12.5 percent by weight of lactide, 15.3 percent by weight of caprolactone and 72 , 2 percent by weight glycolide.

EXAMPLE 3

Dry glycolide (3,960 grams), dry 1-lactide (1,020 grams) and distilled epsilon-caprolactone (1,020 grams) were added to a reactor along with 0.72 grams of distilled stannous octoate and 0.6 grams of diethylene glycol (SDR) 50 distilled. The mixture was dried for 10 hours with stirring under nitrogen flow. The reactor temperature was then set at 100 ° C. When the temperature of the reaction vessel reached 100 ° C, the temperature was maintained for one 15 minutes. Then, the reaction temperature was raised to 150 ° C and then the reaction vessel was heated for an additional 15 minutes. The temperature of the reagents was then raised to about 190 ° C and the polymerization carried out with stirring under nitrogen atmosphere for 22 hours and 55 minutes.

The reaction product was then isolated, crushed and treated to extract residual reagents using

known techniques The treatment to extract the residual reagents takes place at 90 ° C for 48 hours under vacuum. NMR analysis, using a Bruker NMR kit, commercially available DPX-300 model number, revealed that the resulting polymer contained 14.5 percent by weight of lactide, 14.9 percent by weight of caprolactone and 70, 6 percent by weight glycolide.

EXAMPLE 4 5

Dry glycolide (4,200 grams), dry 1-lactide (780 grams) and distilled epsilon-caprolactone (1,020 grams) were added to a reactor along with 0.72 grams of distilled stannous octoate and 0.6 grams of distilled diethylene glycol (DEG) . The mixture was dried for 5.75 with stirring under nitrogen flow. The reactor temperature was then set at 100 ° C. When the temperature of the reaction vessel reached 100 ° C, the temperature was maintained for one 15 minutes. Then, the reaction temperature was raised to 150 ° C and then the reaction vessel was heated for an additional 15 minutes. The temperature of the reaction vessel was then raised to about 190 ° C and the polymerization carried out with stirring under nitrogen atmosphere for 23 hours and 15 minutes.

The reaction product was then isolated, crushed and treated to extract residual reagents using known techniques. The treatment to extract the residual reagents takes place at 100 ° C for 48 hours under vacuum. 15 NMR analysis, using a Bruker NMR kit, commercially available DPX-300 model number, revealed that the resulting polymer contained 12.9 percent by weight of lactide, 16.6 percent by weight of caprolactone and 70 , 5 percent by weight glycolide.

Table I, which follows, shows the typical conditions for extrusion and stretching of 3/0 size sutures. All monofilament sutures were manufactured from resins of Examples 1-4, respectively. twenty

TABLE I

 MANUFACTURING CONDITIONS OF VARIOUS CALIBER MONOFILAMENT OF THIS INVENTION

 Example

 1 2 3 4

 Suture gauge

 3/0 3/0 3/0 3/0

 Process conditions

 EXTRUSION

 spindle extruder, rpm

 4.6 3.0 2.1 3.8

 pump, rpm

 10.9 7.8 6.0 5.1

 active roller, mpm

 2.21 0 0 0

 temp. of drum, º C, zone A

 143 137 136 150

 temp. of the drum, º C, zone B

 146 143 140 155

 temp. of drum, º C, zone C

 150 143 144 156

 temp. of the clamp, º C

 151 143 140 155

 temp. of adapter, º C

 151 144 143 158

 temp. of row, º C

 151 149 148 162

 temp. of the block, º C

 151 146 140 160

 temp. of the melt in the drum, º C

 165 160 156 173

 temp. of the melt in the pump, º C

 157 149 143 163

 temp. of the melt in the row, º C

 N / A 158 155 174

 pressure in the drum, kPa (psi)

 7,310 (1,060) 3,793 (550) 4,000 (580) 3,586 (520)

 pump pressure, kPa (psi)

 6,900 (1,000) 3,450 (500) 3,450 (500) 3,450 (500)

 row pressure, kPa (psi)

 10,207 (1,480) 3,241 (470) 5,586 (810) 2,965 (430)

 pump size, cc per revolution

 0.16 0.16 0.16 0.16

 row hole diameter, mm

 1.2 1.2 1.2 1.2

 number of holes in the row

 1 1 1 1

 temp. of the cooling bath, º C

 25 25 25 25

 Stretching operation (Orientation)

 temp. Stretch bath, º C

 N / A N / A N / A N / A

 Example

 1 2 3 4

 first station of stretching cylinders, mpm

 2.34 1.5 1.2 1.2

 Example

 1 2 3 4

 second stretching cylinder, mpm

 15.8 12.2 9.6 9.1

 third station of stretching cylinders, mpm

 23.0 16.5 13.1 11.9

 4th station of stretching cylinders, mpm

 19.0 15.2 11.7 9.5

 temp. first oven, º C

 40 38 38 38

 temp. second oven, º C

 85 109 92 108

 temp. third oven, º C

 105 105 98 110

 global stretch ratio

 9.82: 1 11: 1 10.92: 1 9.9: 1

 relaxation

 17% 10.7% 10% 20%

 Tempering operation

 Example

 1 2 3 4

 temp. tempering, º C

 105 110 100 110

 time (hours)

 6 6 6 6

The physical properties of the sutures and the procedures used for their measurement are shown in Table II as follows:

TABLE II

 PROCEDURES FOR MEASURING PHYSICAL PROPERTIES OF MONOFILAMENT SUTURES OF THE PRESENT INVENTION

 Physical property

 Test procedure

 tensile strength of the knot, kg

 U.S.P. XXI, tensile strength, sutures (881)

 direct tensile strength, kg

 ASTM D-2256, Instron Corporation

 elongation,%

 ASTM D-2256

 tensile strength, kg / mm2

 ASTM D-2256, Inston Corporation Series IX Automated Testing System 1.03A

 Young's module

 Instron Merlin Software version 2000 Series IX calculation 18.3 (commercially available from Instron Corporation)

Table III, below, presents the physical properties of the 3/0 gauge suture of the present invention.

TABLE III

 Physical property

 Example 1 Example 2 Example 3 Example 4

 diameter (mm)

 0.324 0.316 0.319 0.319

 tensile strength of the knot (kg)

 2.64 2.51 2.29 2.99

 Young's module (MPa (kpsi))

 2,620 (380) 4,557 (661) 3,606 (523) 5,061 (734)

 Elongation%

 38 19 27 29

 Tensile strength (MPa (kpsi))

 443 (64.3) 564 (81.8) 509 (73.9) 651 (94.5)

As the data in Table III illustrate, the suture made of the copolymer provided herein shows desired physical properties, such as modulus of elasticity and tensile strength. 5

IN VITRO RESISTANCE RETENTION

Tests were performed on monofilament sutures manufactured in accordance with the process described above using the copolymer of Example 1 to evaluate resistance retention in vitro. The retention of tensile strength of the lacing in vitro is indicative of the retention of resistance in vivo. In vitro resistance retention of the suture was tested as follows: 10

To simulate the conditions in vivo, the suture samples were placed in a container filled with Sorenson's buffer solution at 37 ° C. After several periods of time, the suture samples were then removed from the container to test their tensile strength. the loop as follows. A loop was formed in a three-step test suture as shown in Figures 3A-3C. As shown in step 1 of Figure 3A, each suture was double-turned (left over right) around a cylinder of 2 15 cm in diameter. In step 2, the free ends of the suture were given a single turn (right over left) on the initial turn of step 1. Finally, in step 3, another double turn (left over right) was given over the Simple turn of step 2 to complete the knot. The free ends of the suture were cut to approximately 1.3 cm (0.5 inches) and the loop was carefully released from the cylinder.

The loop test was carried out using an Instron Model No. 4307 20 tensile test apparatus (commercially available from Instron Corporation, Canton, Massachusetts), operated with a crosshead speed of 51 mm / min and equipped with flat jaws, each having a pin on which the loop is located.

The results of the tests are presented in Table IV below. In the resistance retention data presented 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. 25

TABLE IV

 PERCENTAGE OF RESISTANCE CONSERVED IN VITRO

 COMPOSITION

 T1 T2 T3

 EXAMPLE 1

 23 15 0

 EXAMPLE 2

 34 3 0

 EXAMPLE 3

 32 0

 MONOCRYL

 58 26 3

IN VITRO MASS LOSS

Tests were performed on monofilament sutures manufactured in accordance with the process described above using the copolymer of Examples 1-4 to assess in vitro mass conservation. In vitro mass conservation is indicative of in vivo mass conservation. In vitro mass preservation of the suture was tested as

follow:

To simulate the conditions in vivo, the suture samples were weighed and placed in a fritted microencapsulation thimble (commercially available from Chemglass, Inc., Vineland, New Jersey), which was placed in a scintillation vial filled with buffer solution. Sorenson The scintillation vials were then placed in a water bath at 80 ° C. After several periods of time, the microextraction thimbles 5 containing the suture samples were then removed from the scintillation vial, vacuum filtered, rinsed with distilled water , filtered under vacuum and dried about 6 hours at about 40 ° C under vacuum and then the suture and thimble were heavy. The weight of the remaining suture was calculated by subtracting the weight of the thimble from the weight of the thimble that contained the remaining suture. The percentage of preserved suture was calculated by dividing the weight of the suture that remained by the original weight of the suture and multiplying the result by 100. 10

The results of the tests are presented in Table V below. In the mass conservation data presented 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 80 ° C approximates about one day of mass loss in vivo. For the purpose of comparison, the same tests were performed on Monocryl sutures. fifteen

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

TABLE V

 CONSERVATION PERCENTAGE OF MASS IN VITRO

 COMPOSITION

 T1 T2 T3 T4 T6 T8 T10 T12

 Time (hours)

 8 24 32 48 56 72 96 120

 EXAMPLE 1

 90.52 42.58 35.35 25.54 23.50 19.56 12.94 11.43

 EXAMPLE 2

 88.32 43.96 33.77 24.83 22.63 18.7 14.76 11.72

 EXAMPLE 3

 92.05 40.91 28.26 21.56 18.36 15.0 12.71 8.73

 EXAMPLE 4

 89.28 54.15 42.95 32.81 29.24 23.74 18.68 13.33

 Monocryl

 94.86 74.79 66.83 47.95 42.63 35.31 32.14 27.32

Modifications and variations of the compositions and processes described here are possible in light of the teachings that go above. It should be understood therefore that changes can be made in the particular embodiments described which are within the intended full scope of the invention as defined by the claims.

Claims (22)

1. A medical device manufactured entirely or in part from a random polymer comprising 70 to 76 percent by weight of glycolide, 14 to 17 percent by weight of epsilon-caprolactone and 9 to 15 percent by weight of lactide .

2. The medical device of claim 1 wherein the device is a surgical suture. 5

3. The suture of claim 2 wherein the random polymer comprises 70.6 percent by weight of glycolide, 14.9 percent by weight of caprolactone and 14.5 percent by weight of lactide.

4. The suture of claim 2 or 3 wherein the suture shows a 15% strength retention at two weeks, as measured in Sorenson buffer at 37 ° C.

5. The suture of any one of claims 2-4 wherein the suture shows a mass loss of 10 91% in 96 hours as measured in Sorenson buffer at 80 ° C.

6. The suture of any of claims 2-5 wherein the suture shows a module ranging from 2,620 MPa (380 kpsi) to 5,240 MPa (760 kpsi).

7. The suture of any of claims 2-6 wherein the suture shows a tensile strength of the knot from 2.0 to 3.0 kg.

8. The suture of any of claims 2-7 wherein the suture is a 3/0 size suture showing a module of 3,605 MPa (523 kpsi).

9. The suture of any of claims 2-8 wherein the suture is a 3/0 size suture showing a tensile strength of the knot of 2.3 Kg.

10. The suture of any of claims 2-9 wherein the suture is a 3/0 size suture that shows a tensile strength of 690 MPa (100 kpsi).

11. The suture of any of claims 2-10 wherein the suture is a 3/0 size suture showing the following characteristics;

module 2,400 to 5,170 MPa (350 to 750 kpsi) tensile strength of the knot 2.2 to 3 Kg. 25 tensile strength 440 to 720 MPa (64 to 105 kpsi)

12. The suture of any of claims 2-11 wherein the random polymer has an intrinsic viscosity of 0.9 to 1.8 dl / g at 30 ° C and at a concentration of 0.25 g / dl in HFIP.

13. The suture of any of claims 2-12 wherein the suture is a 3/0 size suture showing a 50% mass loss after 24 hours in Sorenson buffer at 80 ° C. 30

14. The suture of any of claims 2-13 wherein the suture is a 3/0 size suture showing a 70% mass loss after 48 hours in Sorenson buffer at 80 ° C.

15. The suture of any of claims 2-14 wherein the suture is a 3/0 size suture showing a mass loss greater than 85% after 120 hours in Sorenson buffer at 80 ° C.

16. The medical device of claim 1 comprising a substance useful from a medical-surgical point of view.

17. The medical device of claim 1 wherein the device is a clip, clip, other fastener, nail, screw, prosthetic device, mesh or felt.

18. The medical device of claim 1 or 17 wherein the random polymer is mixed with at least one other absorbable composition. 40

19. The medical device of claim 17 or 18 wherein the random copolymer is copolymerized with another resorbable composition.

20. A process for manufacturing a monofilament suture from a random copolymer resin, random polymer comprising 70 to 76 percent by weight of glycolide, 14 to 17 percent by weight of epsilon-caprolactone and 9 to 15 percent weight percent of lactide, which includes the operations of: 45

to. extruding said resin at an extrusion temperature between 130 ° C and 190 ° C to provide a monofilament; b. Stretching the solidified monofilament at a stretch ratio between 5: 1 and 13: 1 to provide a stretched monofilament.

21. The process of claim 20 further comprising the steps of:

to. tempering said stretched monofilament at a temperature between 80 ° C and 125 ° C to provide a finished suture. 5

22. A method of making a monofilament suture from a resin of a random copolymer, random copolymer comprising 70 to 76 percent by weight of glycolide, 14 to 17 percent by weight of epsilon-caprolactone and 9 to 15 percent weight percent of lactide, method comprising:

a) extrude the copolymer to provide a molten monofilament; b) cooling the molten monofilament to provide a solidified monofilament; 10 c) stretching the solidified monofilament through an air convection oven maintained at a temperature of 25 ° C to 40 ° C at a drawing ratio of 5: 1 to 10: 1; d) stretching the monofilament through an air convection oven maintained at a temperature of 80º C to 115º C at a stretching ratio of 1.1: 1 to 2.6: 1; e) stretching the monofilament through an air convection oven maintained at a temperature of 80º C to 15 125º C at a stretching ratio of 0.75: to 1.05: 1; Y f) temper the monofilament.