GB1604177A

GB1604177A - Surgical articles formed from copolymeric lactide polyesters

Info

Publication number: GB1604177A
Application number: GB17108/78A
Authority: GB
Original assignee: American Cyanamid Co
Current assignee: Wyeth Holdings LLC
Priority date: 1977-05-23
Filing date: 1978-04-28
Publication date: 1981-12-02
Also published as: DK225978A; AR218303A1; HU180198B; DE2821570C2; GB1604178A; NL185493B; FI65443B; NO152791C; RO85051A; JPS53145899A; FR2391734A1; NO152791B; CA1128231A; NO812911L; RO85051B; NL7805276A; DE2821570A1; IT7849479A0; EG14151A; SE7805831L

Description

(54) SURGICAL ARTICLES FORMED FROM COPOLYMERIC LACTIDE POLYESTERS (71) We, AMERICAN CYANAMID COMPANY, a Corporation organized and existing under the laws of the State of Maine, United States of America, of Berdan Avenue, Township of Wayne, State of New Jersey, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: This invention relates to synthetic polyester surgical articles, and to a method for preparing such articles.

The use of lactide polyesters in the fabrication of synthetic surgical articles is known in the art. In conjunction therewith, comonomers have often been employed to modify the characteristics of the various polyesters. The conventional polymerization method for forming the polyesters is through ring opening polymerizations of the appropriate cyclic lactides. Usually where copolymers are prepared, one lactide is copolymerized with another. Other cyclic materials have also optionally been employed as comonomers. These include other lactones and compounds such as trimethylene carbonate.

Useful polymerization and post-treatment methods as well as fabrication procedures for the surgical articles are also known in the art. The surgical articles produced include both absorbable and non-absorbable articles.

The following patents are of interest in this respect: United States Patents 3,268,486 and 3,268,487.

It has now been found in accordance with the present invention that synthetic polyester surgical articles advantageously can be manufactured by employing in conjunction therewith a polymerization procedure whereby copolymeric lactide polyesters are formed through a ring opening polymerization wherein the polymerization is sequentially carried out by adding the comonomers used to form the copolymer chain in at least two stages. By conducting the polymerization procedure in such a stepwise or staged manner, the in vivo characteristics of the surgical articles produced can more broadly be modified prior to encountering the usual degree of interference of the ability of the polymer to form dimensionally stable, highly crystalline, or highly oriented molecular structures.

More specifically, in accordance with one aspect, the present invention provides a method for the manufacture of a sterile absorbable surgical article, comprising the steps of: 1) preparing a synthetic absorbable copolymeric lactide ester from copolymerizable monomers comprising at least one lactide monomer, the polymerization being conducted in two or more stages employing sequential addition of the comonomers whereby there is formed in each stage a polymeric chain of different composition from the polymeric chain formed in the or each other stage; and 2) forming a sterile surgical article from the copolymeric lactide polyester obtained in step 1).

The present invention further provides a sterile absorbable surgical article formed from a synthetic absorbable copolymeric lactide polyester prepared from copolymerizable monomers comprising at least one lactide monomer by conducting the polymerization in two or more stages employing sequential addition of the comonomers whereby there is formed in each stage a polymeric chain of different composition from the polymeric chain formed in the or each other stage.

The method of the present invention can be employed in two or more stages using two or more comonomers in the polymerization procedure. In one or more of the stages, two monomers can be employed simultaneously. A different catalyst may be employed at each stage if desired.

It is generally preferred to conduct the consecutive polymerizations in the same reaction vessel by sequentially adding the comonomers thereto; however, if desired one or more of the polymer segments can be prepared and used as such for further chemical reaction to form the polyesters in a different reaction vessel of choice while still retaining the advantages of and falling within the present invention.

The two lactides conventionally preferred for use in preparing surgical articles are L(-) lactide and glycolide. They are also preferred for use in the present invention.

Furthermore, it is generally preferred, herein, to employ them together in a sequential polymerization procedure. Other cyclic comonomers conventionally employed therewith such as trimethylene carbonate, 2-keto-1,4-dioxane and one or more of the following compounds may also be used as one of the comonomers to copolymerize with a lactide in the practice of the present invention: ss-propiolactone, tetramethylglycolide, t3- butyrolactone, gammabutyrolactone, delta-valerolactone, epsilon-caprolactone, pivalolactone and intermolecular cyclic esters of a-hydroxybutyric acid, a-hydroxyisobutyric acid, a-hydroxyvaleric acid, a-hydroxyisovaleric acid, a-hydroxycaproic acid, a-hydroxy-aethylbutyric acid, a-hydroxyisocaproic acid, a-hydroxy-B-methylvaleric acid, ahydroxyheptanoic acid, a-hydroxyoctanoic acid, a-hydroxydecanoic acid, ahydroxymyristic acid, a-hydroxystearic acid, a-hydroxylignoceric acid, a,adiethylpropiolactone, ethylene carbonate, 2,5-diketomorpholine, ethylene oxalate, 6,8 dioxabicyclo[3,2,1l-octane-7-one, di-salicylide, trioxane, 3-methyl-1,4-dioxane-2,5-dione, 3 ,5-dimethyl-1 ,4-dioxane-2-one.

One of the generally preferred embodiments of the present invention relates to the preparation of sterile, synthetic, absorbable, surgical articles (especially sutures) wherein glycolide is employed as the predominant lactide comonomer in preparing the polyesters.

The present state of the art is such that detailed absorption mechanisms and details of the polymer structures on the molecular levels are not known with certainty.

More specifically, a preferred embodiment of the present invention relates to sequentially copolymerizing lactide [preferably L(-) lactide] with glycolide. Triblock structures formed by sequentially and consecutively copolymerizing (L(-) lactide, glycolide and L(-) lactide respectively are also of interest. In the latter case, the polyester produced has lactic acid units predominating on both ends of the glycolide polymer chain.

It is believed that the three usual morphological units, namely spheres, rods (or cylinders) and lamellae which are well known in AB and ABA type poly(styrene-bbutadiene) (PSB) would be exhibited in the polyesters of the present invention. In films of ABA PSB where the mole ratio of styrene units to butadiene units is 80/20, spherical domains have been observed by electron micrograph. As the mole ratio decreases with relatively greater quantities of butadiene units the morphology of the microphase separation is altered from spheres of butadiene units in a matrix of styrene units to rods of butadiene units in a matrix of styrene units and then to alternate lamellae of the units.

When the mole ratio is further decreased until the butadiene predominates, the styrene units are first presented as cylindrical or rod-like microphase separations in a matrix of butadiene units whereafter, as the mole ratio is further decreased, the styrene units are presented as spheres in a matrix of butadiene units. For a disclosure of this, see M. Matsuo, S. Sagae and H. Asai, Polymer, 10, p. 79, 1969.

In the preparation of absorbable sutures, in accordance with the preferred practice of the present invention, one may employ polyesters wherein minor amounts of a monomer segment of an inert homopolymer such as an L(-) lactide segment is incorporated at one or both ends of a chain of glycolide units. The stable segment or segments may be employed in relatively minor amounts whereby it is believed that the morphology of microphase separation would, for example, exist as rods of L(-) lactide units in a matrix of glycolide units or more preferably spherical domains of L(-) lactide units in a matrix of glycolide units.

The sterile surgical articles may be fabricated from the copolymeric lactide polyesters using the procedures conventionally employed with lactide polyesters. Likewise, the resulting surgical articles may be employed in a conventional manner.

The following examples illustrate procedures which are useful in conjunction with the practice of the present invention. Unless otherwise specified, all parts and percentages mentioned are by weight.

Examples 1 - 2 An ether solution of SnCI2-2H2O was prepared together with an ether solution of lauryl alcohol containing 10 mg/ml of lauryl alcohol. A sufficient volume of the above solutions was added to two polymerization tubes so that when the solvent was removed the final weights of catalyst and lauryl alcohol per 20.0 g of L(-) lactide monomer were: TABLE I Tube No. mg Sn C12.2H2O mg Lauryl Alcohol 1 2.0 125 2 4.0 250 After the solvent was removed, 20.0 g of L(-) lactide was added to each tube. The tubes were evacuated and sealed under vacuum. They were then placed in an oil bath at 1800C.

for 24 hours. They were removed from the oil bath and let cool to room temperature. The tubes were opened, the polymer ground in a Wiley mill through a 20 mesh screen, and dried for 24 hours at 50"C. at 0.1 mm Hg. The resultant polymers from tubes 1 and 2 were formed in 86% and 89% conversion and had I.V.'s of 0.33 and 0.27, respectively. The percent conversion to polymer was obtained by dividing the weight of polymer after drying by the weight of polymer before drying. I.V. means the inherent viscosity of a solution of 0.5 g of dried polymer/100 ml of hexafluoroacetone sesquihydrate, measured at 300C.

Into a three neck 100 ml round bottom blask equipped with a glass shaft and a polytetrafluoroethylene paddle stirrer, attached to a stirring motor and a gas inlet tube connected to an argon cylinder, was added 7.0 g of the 0.33 I.V. poly L(-) lactide described above. The flask was flushed with argon gas for 15 minutes. The flush was maintained throughout the polymerization. The flask was placed in a 1900C oil bath. The pot contents reached 1800 + 2"C. within 15 minutes. Then 3.5 g of glycolide was added with stirring and the oil bath temperature was adjusted to keep the temperature of the pot contents at 180 + 2"C. for 30 minutes with continuous stirring. The temperature of the oil bath was then raised so that during 30 minutes the temperature of the pot contents reached 220 + 2 C.

Then, the remainder of the glycolide, 31.5 g, was added and the temperature of the pot contents was maintained at 220 + 2"C. for 1 1/2 hours with continuous stirring. At this time the oil bath was removed, the stirring was stopped, and the pot contents were allowed to cool to approximately room temperature under the argon flush. This flush was then stopped. The glass flask was then broken and the polymer was removed and ground in a Wiley mill through a 20 mesh screen. 3.0 g of the ground polymer were fabricated into a fibrous sheet for implantation by first dissolving the polymer in 60 ml of 60"C.

hexafluoroacetone sesquihydrate (HFAS). The polymer was precipitated by dripping this solution into 600 ml of methanol with stirring. The polymer was collected by filtration and extracted with acetone in a Soxhlet extractor for 2 days to remove the residue of fluorinated solvent. The polymer was then dried in a vacuum oven overnight at 50"C. at 0.1 mm Hg.

The yield of polymer was 95%. The I.V. in HFAS was 0.77. The mole percent of the lactic acid units in the polymer chain as determined by NMR was 8.8. The melting point as determined from the peak endotherm observed in a differential thermal analysis (D.T.A.) apparatus was 218"C.

A second two-stage copolymer was prepared as follows. Into a three neck 100 ml. round bottom flask equipped with a glass shaft and a polytetrafluoroethylene paddle stirrer attached to a stirring motor, and a gas inlet tube connected to an argon cylinder, was added 4.0 g of the poly L(-) lactide whose I.V. was 0.27, with stirring. This was flushed with argon gas for 15 minutes. This argon gas flush was maintained throughout the following polymerization. The flask was placed in a 1900C. oil bath. The pot contents reached 1800 + 2"C. within 15 minutes. Then, 3.6 g. of glycolide were added with stirring and the oil bath temperature was adjusted to keep the temperature of the pot contents at 1800 + 2"C. for 30 minutes with continuous stirring. The temperature of the oil bath was then raised so that at the end of 30 minutes the temperature of the pot contents reached 220 + 2"C. Then, 31.4 g of glycolide was added and the temperature of the pot contents was maintained at 2200 + 2"C. for 1 1/2 hours with continuous stirring. At this time the oil bath was removed, the stirring was stopped and the pot contents were allowed to cool to approximately room temperature under the argon flush. The flush was then stopped. The glass flask was broken and the polymer was removed and ground in a Wiley mill through a 20 mesh screen. 3.0 g of this polymer were dissolved in 60 ml. of 60"C. hexafluoroacetone sesquihydrate (HFAS) and the polymer was precipitated by dripping this solution into 600 ml of methanol with stirring. The polymer was collected by filtration and extracted with acetone in a Soxlet extractor for 2 days. The polymer was then dried in a vacuum oven overnight at 500C. at 0.1 mm Hg. The yield of polymer was 95%. The I.V. in HFAS was 0.82. The mole percent of lactic acid units in the polymer as determined by NMR was 5.9. The melting point as determined by the peak endotherm observed in a D.T.A. apparatus was 219"C.

Example 3 A sample of poly L(-) lactide was prepared by the procedure of Examples 1-2 except that it was formed in 98% conversion with a 0.5 I.V. using 1.2 mg of Sn Cl2-2H2O and 7.5 mg of lauryl lacohol. Into a three neck 100 ml round bottom flask equipped with a glass shaft and a polytetrafluoromethylene paddle stirrer attached to a stirrin motor and a gas inlet tube attached to an argon cylinder, was added 10.0 g of the polyL(- lactide. This was flushed with argon for 15 minutes. This argon flush was maintained through the following polymerization. The flask was placed in a 1900C. oil bath. The pot contents reached 1800 + 2"C. within 15 minutes. Then 2 g of glycolide was added with stirring and the oil bath temperature was adjusted to keep the temperature of the pot contents at 1800 + 2"C. for 30 minutes with continuous stirring. The temperature of the oil bath was then raised so that at the end of 30 minutes the temperature of the pot contents reached 220 i 2 C. Then, 18.0 g, of glycolide were added and the temperature of the pot contents was maintained at 2200 + 2"C. for 1 1/2 hours with continuous stirring. At this time the oil bath was removed, the stirring was stopped and the pot contents were allowed to cool to approximately room temperature under argon flush. This flush was then stopped. The glass flask was broken and the polymer was ground up in a Wiley mill through a 20 mesh screen.

20.0 . of this polymer was dissolved in 400 ml of 60"C. hexafluoroacetone sesquihydrate (HFAS and the polymer was precipitated by dripping this solution into 4,000 ml of methanol with stirring. The polymer was collected by filtration and extracted with acetone in a Soxhlet extractor for 2 days. The polymer was then dried in a vacuum oven overnight at 50 at 0.1 mm Hg. The yield of polymer was 72%. The I.V. in HFAS was 0.60. The mole percent of lactic acid units in the polymer as determined by NMR was 33. The melting point as determined from the peak endotherm observed in a differential thermal analysis (D.T.A.) apparatus was 219 C.

Example 4 Into a three neck 100 ml round bottom flask equipped with a glass shaft and a polytetrafluoroethylene paddle stirrer attached to a stirring motor and a gas inlet tube attached to an argon cylinder, was added 6.0 g of a 0.29 I.V. poly L(-) lactide prepared as in Example 3 except that a heating period of 1.5 hours at 2000C. was used. The flask was flushed with argon for 15 minutes. This argon flush was maintained throughout the following polymerization. The flask was placed in a 200"C. oil bath and the bath temperature was raised until the temperature of the pot contents reached 200 + 2"C. This occurred within 15 minutes. Then, 48.0 g. of glycolide were added with stirring and the temperature of the oil bath was raised until the temperature of the pot contents was 225 + 2"C. This occurred within 30 minutes. Stirring was continued for 1 1/2 hours at this temperature. Then, 6.0 g of L(-) lactide were added (with stirring of the pot contents) and stirring was continued for 1 1/2 hours at this temperature. At this time, the oil bath was removed, the stirring was stopped and the pot contents were allowed to cool to approximately room temperature under the argon flush. This flush was then stopped. The glass flask was broken and the polymer was removed and ground in a Wiley mill through a 20 mesh screen. 5.0 g. of this polymer were dissolved in 100 ml of hexafluoroacetone sesquihydrate (HFAS) and the polymer was precipitated by dripping this solution in 1,000 ml of methanol with stirring. The polymer was collected by filtration and extracted with acetone in a Soxhlet extractor for 2 days. The polymer was dried in a vacuum oven overnight at 50"C. at 0.1 mm Hg. The yield of polymer was 82%. The I.V. in HFAS was 0.81. The mole percent of lactic acid units in the polymer chain as determined by NMR was 11.2. The melting point as determined from the peak endotherm in a differential thermal analysis (.D.T.A.) apparatus was 216"C.

Example 5 Into a three neck 100 ml round bottom flask equipped with a glass shaft and a polytetrafluoromethylene paddle attached to a stirring motor and a gas inlet tube attached to an argon cylinder, was added 4.5 g. of poly(epsilon-caprolactone) whose I.V. was 0.42.

The poly(epsilon-caprolactone) polymer was prepared as in Example 1 except that 8.0 mg.

of Sn C12 2H2O and 500 mg. of lauryl alcohol were employed and epsilon-caprolactone was used in place of the L(-) lactide. The flask was flushed with argon for 15 minutes. The argon flush was maintained throughout the following polymerization. The flask was placed in a 1900C. oil bath. The pot contents reached 1800 + 2 C. within 15 minutes. Then, 1.35 g of glycolide were added with stirring and the oil bath temperature was adjusted to keep the temperature of the pot contents at 180 + 2 C. for 30 minutes with continuous stirring. The temperature of the oil bath was then raised so that at the of 30 minutes the temperature of the pot contents was 220 + 2 C. Then, 12.15 g of glycolide were added with stirring and the temperature of the pot contents was maintained at 2200 + 2 C. for 1 1/2 hours with continuous stirring. At this time the oil bath was removed, the stirring was stopped and the pot contents were allowed to cool to approximately room temperature under the argon flush. This flush was then stopped. The glass flask was broken and the polymer was removed and ground in a Wiley mill through a 20 mesh screen. 4.0 g. of this polymer was dissolved in 80 ml. of 60 C. HFAS and the polymer was precipitated by dripping this solution into 1000 ml of methanol with stirring. The polymer was collected by filtration and extracted with acetone in a Soxhlet extractor for 2 days. The polymer was then dried overnight in a vacuum oven at 500C. at 0.1 mm Hg. The yield of polymer was 73%. The I.V.

in HFAS was 0.77. The mole percent of epsilon-hydroxy caproic acid units in the polymer chain as determined by NMR was 12.3. This corresponds to 12.1 weight percent caprolactone units. The melting point as determined from the peak endotherm in a differential thermal analysis (D.T.A.) apparatus was 218 C.

Example 6 L(-) lactide (1612 g.), SnCI2-2H2O (0.204 g.) and lauryl alcohol (4.77 g.) were added to a stirred reactor which had been preheated to 140 C. The reactants were heated with stirring under a nitrogen atmosphere over a 30 minute period to 2000C. and then held at that temperature for 2 hours.

The reactor was evacuated to a pressure of 50 mm Hg and the mixture was stirred for 30 minutes during which time the temperature of the mixture was allowed to fall to 1800C.

Atmospheric pressure was restored by introducing nitrogen into the reaction vessel and the temperature was raised to 2000C. over a 5 minute period. The molten glycolide (5198 g.) preheated to 1000C. was added and the temperature was raised over a 15 minute period to 225 C. and held at this temperature for an additional 20 minutes.

The contents of the reactor were discharged and the polymeric mass was broken up after it had cooled to room temperature. The polymer was then ground and vacuum dried at 8-10 mm Hg for 11 hours at 140 C. to remove all volatiles preparatory to spinning and determining the polymer's viscosity.

The inherent viscosity of the polymer was determined to be 1.14, measured at 300C. in a 0.5% solution in hexafluoroacetone sesquihydrate. The mole % of lactic acid units in the finished polymer was determined to be 20.3% by NMR. The melting range of the product was determined to be 215 -223.5 C. using a hot stage polarizing microscope.

A portion of the dried polymer was added to the feed hopper of a small continuous extruder operating at about 230 C. The extruder was equipped with a die having a 60 mil cylindrical orifice and a length to diameter ratio of 4 to 1. The extrudate was water quenched and collected at 44 feet per minute. It was then drawn to about 4.5 times its original length at 55 C. in a hot air draw unit. A sample of glycolide homopolyrner having a 1.05 I.V. was extruded and drawn in the same way and then post treated along with the above copolymer fiber, for 3 hours at 1350C. at a pressure of 1 mm Hg.

The copolymer fiber which was 2.45 mils in diameter was found to have exceptional tensile-strength retention properties (34,600 p.s.i.) in an accelerated strength retention test and very good initial tensile strength (96,500 p.s.i.) notwithstanding its high comonomer content (20.3 mole%). In the contrast, the initial strength of the homopolymer fiber which was 2.10 mils in diameter was 140,000 p.s.i. and the counterpart strength retained in an accelerated test was 25,300 p.s.i.

As mentioned above, it is believed that such copolymeric polyesters are characterized by microphase separations having spherical domains in the molten state, prior to orientation wherein the chain segments composed of lactic acid units are overlapped with themselves in a matrix of glycolic acid units. It is believed that polyesters having such microphase separation would exist where the mole percentage of L(-) lactide incorporated into the polymer chains ranged up to about 25 percent. From about 25 percent to about 40 percent lactic acid units it is believed that cylindrical domains of lactic acid units would predominate. This would likewise be the case where the lactic acid units prevailed on both ends of the polyester chains as a result of sequentially and consecutively polymerizing L(-) lactide, glycolide and then L(-) lactide.

Although the geometry of the domains in the molten state is speculative, evidence for the existence of phase separation or precipitation of the polymers may be seen by comparing their melting points with that of the homopolymer of the major component.

Accordingly, preferred surgical articles prepared in accordance with the present invention are sterile synthetic absorbable surgical sutures prepared from a lactide polyester said polyester being composed of a copolymer having cylindrical or more preferably spherical domains of L(-) lactide units in a matrix of glycolide units. The polyesters employed can have the relative quantities of glycolide units and L(-) lactide units indicated above. The sutures may be in the form of a sterile surgical needle and suture combination.

Conventional suture constructions and sterilization methods may be used. Preferably a monofilament or polyfilamentary braided polyester yarn is crimped into the butt of a surgical needle and the needled suture is then sterilized using a toxidant such as ethylene oxide. Polyesters formed by sequentially and consecutively polymerizing L(-) lactide and glycolide are most preferred for use therein.

While the surgical articles of the present invention are generally useful in conventional manners for retaining living tissure in a desired location and relationship during a healing process by positioning and emplacing living tissue therewith, as in ligation of blood vessels, the needled sutures are especially adapted for the closing of wounds of living tissue by sewing together the edges thereof using conventional suturing techniques.

The reader's attention is directed to our co-pending Application No. 8034213 Serial No 1604178 divided herefrom and which describes and claims copolymers characterized by a content of sequential units of Formula I and Formula II fO-CH2-CO-O-CH2-CO) (I) {OrCH2-CH2-CH2-O-COf (11) and sterile surgical articles fabricated from such copolymers. We make no claim herein to a sterile absorbable surgical article which is fabricated from a copolymer characterized by a content of sequential units of Formula I and Formula II above.

Subject to the foregoing disclaimer: WHAT WE CLAIM IS: 1. A method for the manufacture of a sterile absorbable surgical article, comprising the steps of: 1) preparing a synthetic absorbable copolymeric lactide ester from copolymerizable monomers comprising at least one lactide monomer, the polymerization being conducted in two or more stages employing sequential addition of the comonomers whereby there is formed in each stage a polymeric chain of different composition from the polymeric chain formed in the or each other stage; and 2) forming a sterile surgical article from the copolymeric lactide polyester obtained in step 1).

2. A method according to Claim 1, wherein said lactide monomer or monomers is (are) selected from L(-)lactide and glycolide.

3. A method according to Claim 2, wherein L(-)lactide is polymerized in a first stage and glycolide is polymerized in a second stage.

4. A method according to Claim 3, wherein L(-)lactide is polymerized in a third stage.

5. A method according to any preceding claim, wherein a sterile surgical suture is formed in step 2).

6. A sterile absorbable surgical article formed from a synthetic absorbable copolymeric lactide polyester prepared from copolymerizable monomers comprising at least one lactide monomer by conducting the polymerization in two or more stages employing sequential addition of the comonomers whereby there is formed in each stage a polymeric chain of different composition from the polymeric chain formed in the or each other stage.

7. A surgical article according to Claim 6, wherein said copolymeric lactide polyester contains units derived from the polymerization of a lactide monomer or monomers selected from L(-)lactide and glycolide.

8. A surgical article according to Claim 7, wherein said copolymeric lactide polyester contains units derived from the polymerization of L(-)lactide in a first stage of polymerization and units derived from the polymerization of glycolide in a second stage of polymerization.

9. A surgical article according to Claim 8, wherein said copolymeric lactide polyester further contains units derived from the polymerization of L(-)lactide in a third stage of polymerization.

10. A surgical article according to any one of Claims 7-9, wherein said copolymeric lactide polyester contains up to 25 percent of units derived from L(-)lactide.

**W

Claims

**WARNING** start of CLMS field may overlap end of DESC **. Accordingly, preferred surgical articles prepared in accordance with the present invention are sterile synthetic absorbable surgical sutures prepared from a lactide polyester said polyester being composed of a copolymer having cylindrical or more preferably spherical domains of L(-) lactide units in a matrix of glycolide units. The polyesters employed can have the relative quantities of glycolide units and L(-) lactide units indicated above. The sutures may be in the form of a sterile surgical needle and suture combination. Conventional suture constructions and sterilization methods may be used. Preferably a monofilament or polyfilamentary braided polyester yarn is crimped into the butt of a surgical needle and the needled suture is then sterilized using a toxidant such as ethylene oxide. Polyesters formed by sequentially and consecutively polymerizing L(-) lactide and glycolide are most preferred for use therein. While the surgical articles of the present invention are generally useful in conventional manners for retaining living tissure in a desired location and relationship during a healing process by positioning and emplacing living tissue therewith, as in ligation of blood vessels, the needled sutures are especially adapted for the closing of wounds of living tissue by sewing together the edges thereof using conventional suturing techniques. The reader's attention is directed to our co-pending Application No. 8034213 Serial No 1604178 divided herefrom and which describes and claims copolymers characterized by a content of sequential units of Formula I and Formula II fO-CH2-CO-O-CH2-CO) (I) {OrCH2-CH2-CH2-O-COf (11) and sterile surgical articles fabricated from such copolymers. We make no claim herein to a sterile absorbable surgical article which is fabricated from a copolymer characterized by a content of sequential units of Formula I and Formula II above. Subject to the foregoing disclaimer: WHAT WE CLAIM IS:

1. A method for the manufacture of a sterile absorbable surgical article, comprising the steps of: 1) preparing a synthetic absorbable copolymeric lactide ester from copolymerizable monomers comprising at least one lactide monomer, the polymerization being conducted in two or more stages employing sequential addition of the comonomers whereby there is formed in each stage a polymeric chain of different composition from the polymeric chain formed in the or each other stage; and 2) forming a sterile surgical article from the copolymeric lactide polyester obtained in step 1).

11. A suture according to any one of Claims 6-10.

12. A suture according to Claim 11 in combination with a sterile needle.

13. A method for the manufacture of a sterile absorbable surgical article according to Claim 1, wherein said synthetic absorbable copolymeric lactide ester is prepared sqbstantially as described in any one of the Examples herein.

14. A sterile absorbable surgical article according to Claim 6, and formed from a synthetic absorbablecopol meric lactide ester which has been prepared substantially as ascribed in any one of the Examples herein.