CA1128231A

CA1128231A - Sequentially polymerizable block lactide copolyesters and surgical articles thereof

Info

Publication number: CA1128231A
Application number: CA300,986A
Authority: CA
Inventors: Michael N. Rosensaft; Richard L. Webb
Original assignee: American Cyanamid Co
Current assignee: Wyeth Holdings LLC
Priority date: 1977-05-23
Filing date: 1978-04-12
Publication date: 1982-07-20
Also published as: DK225978A; AR218303A1; HU180198B; DE2821570C2; GB1604178A; GB1604177A; NL185493B; FI65443B; NO152791C; RO85051A; JPS53145899A; FR2391734A1; NO152791B; NO812911L; RO85051B; NL7805276A; DE2821570A1; IT7849479A0; EG14151A; SE7805831L

Abstract

A B S T R A C T

A method employing the sequential addition of comonomers to form copolymeric lactide polyesters in the manufacture of surgical articles is disclosed.

Description

~lZl~Z3~
- \ This invention relates to a method for preparing synthetic polyester surgical articles, as well as the art-icles produced thereby and methods for using them.
The use of lactide polyesters in the fabrication of synthetic surgical articles is known in the art~ In con-junction therewith, comonomers have often been employe~ to modify the characteristics of -the various polyesters. rrhe conventional polymerization method for forming the polyest-ers i5 through ring opening polymerizations of the appropri-ate cyclic lactides. Usually where copolymers are prepaxed,one lactide is copolymerized with another. Other cyclic materials have also optionally been employed as comonomers.
These include other lactones, compounds such as trimethylene carbonate and the like.
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 articlesO
The following patents are of interest in this re-spect: United States Patents 3,268,486 and 3,268,487 issuedAugust 23, 1966 to inventor A. Klootwijk and assigned to Shell Oil Company,New York, N.Y., U.S.A.
It has now been found that syn-thetic polyester surgical articles can advantageously be manufactured by em-ploying in conjunction therewith a polymerization procedurewhereby copolymeric lactide polyesters are formed through a -` ring opening polymerization wherein the polymerization is sequentially or incrementally carried out. This is achieved by consecutively adding the comonomers used to form the co-polymer chain. By conducting the polymerization procedure in a stepwise or staged manner, the ln vivo characteristics of the surgical articles produced can more broadly be modi-L28~31.
fied p~or to encounteri~n~ the usual degree of interference of the ability of the paly~er to fo~m dimensionally stable, highly crystalline, or highly oriented molecular structures.
Accordingly, the present invention provides in one aspec-t, a method for -the manufacture of a sterile absorbable surgical article, ccmpris-ing the steps of:
(1) preparing a snythetic absorbable copolymeric lactide ester from copolymerizable manQmerS comprising at least one lactide mDnomer, the polymerization being donducted in two or m~re 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 cop~lymeric lactide polyester obtained in step (1).
In another aspect, the present invention provides a copolymer comprising a proportion of sequential units having the formula:

- O O
u "
-C ~ -C (I) and a proportion of sequential units having the formula:
, ~ O ' -O-(CH2)3-o~c (II) m e process of the present invention can be employed in two or ; more stages using two or more cOmOnQmerS in the polymerizationprocedure.
In one or more of the stages, tw~ 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;
~- hcwever, if desired one or more of the polymer segments can be prepared and uscd as such for fuxther chemical reaction to form the polyesters in a different reaction vessel of choice while still retaining the advantages of and falling with m the present invention.
m e two lactides conventionally preferred for use in preparin~

3 --~L~Z8Z3~

surgical articles a~e L(-) lactide and glycolide. They are also preferred for use in the present in~ention. Furthermore, i-t is generally preferred, herein to employ them together in a sequential polymerization procedure.
Other cyclic comDncmers conventionally employed therewith ~uch as tri-methylene carbonate, 2-keto-1,4-dioxane and one or more of th~ Eollowing compounds may also be u æ d as one of the comDnomers to copolymerize with a lactide in the practice of the present invention: ~-prOpiolactone, tetra-methylglycolide, ~-butyrolactone, ganmabutyrolactone, delta-valerolactone, e~silon-caprolactone, pivalolactone and intermolecular cyclic esters of ~-hydroxybutyric acid, ~-hydroxyisobutyric acid, ~-hydroxyvaleric acid, ~-hydroxyiso-- 3a -~Z8~

1 valeric acid, a-hydroxycaproic acid, a-hydroxy-a-ethylbu-tyric acid, a-hydroxyisocaproic acid, a-hydroxy-~-me-thyl-valeric acid, a-hydroxyheptanoic acid, ~hydroxyoct~noic acid, a-hyclroxydecanoic acid, ~~hydroxymyristic acid, ~~h~~
droxystearic acid, ~-hydroxylignoceric acid, ~ dieth~1-propiolactone, ethylene carbonate, 2,5-diketomorpholine, ethylene oxalate, 6,8-dioxabicyclo[3,2,1]-octane-7-one, di-salicylide, trioxane, 3-methyl-1,~-dioxane-2,5-dione, 3,5---dimethyl-1,4-dioxane-2-one.
One of the preferred areas ~or use 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.
One of the preferred embodiments of the present nvention relates to sequentially copolymerizing lactide [preferably L(-3 lactide] with glycolide. Triblock struc-tures formed by sequentially and consecutively copolymeriz-ing (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-b-buta-diene~ (PSB) would be exhibited in the polyesters of the present units to butadiene units in 80/20~ spherical domains ~2 8~3 1 have been observed by electron micrograph. Ag the mole ratio decreases with relatively g.reater quantities of buta-diene units the morphology o:E the microphase separation is altered from spheres of butadiene units in a mat,ri~ of st~-rene units to rods of butadiene units in a ma~rix o~ styreneunits and then to alternate lamellae of the units~ When the mole ratio is further decreased until the butadiene predom-inates, 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 the absorbable sutures, in accordance with the 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 se~-., .
ment is incorporated at one or both ends of a chain o~ gly-colide units. The stable segment or segments may be employ-ed 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 Lt-) lactide units in a matrix of glycolide units.
The surgical articles are fabricated from the poly-`~: esters using the procedures conventionally employed with the polyesters disclosed in the reference above. Likewise, the resulting surgical articles are employed in a conventional manner.
The following examples illustrate procedures which ~L~Z8;~3~L

1 are useful in conjunction with the practice of the present invention but are not to be taken as being limiting thereof.
Unless o-therwise specified, all parts and percen-tages men-tioned are by weight.
Examples 1 - 2 An ether solution of SnC12.2H2O was prepared -to-gether 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 polymerizatian tubes so that when the solvent was removed the final weights of cata-lyst 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 180C.
for 24 hours. They were removed from the oil bath and let cool to room temperature. The tubes were opened, the poly-mer ground in a Wiley mill through a 20 mesh screen, and - dried for 24 hours at 50C. at 0.1 mm Hg. The resultant polymers from tubes 1 and 2 were formed in 86% and 89~ con-version and had I.V.'s of 0.33 and 0.27, resp~ctively. The percent conversion to polymer was obtained by dividing the weight of polymer after drying by the weight of polymer be-fore drying. I.V. means the inhe~ent viscosity of a solu-tion of 0.5 g of dried polymer/100 ml of hexafluoroacetone 8Z3~l 1 sesquihydrate, measured at 30C.
Into a three neck 100 ml round bottom blask equip-ped with a glass shaf~ and Teflon~ (DuPont Company, Wilminy-ton, Delaware, U.S.A.) paddle stirrer, attach~d ~o a stirr-ing motor and a gas inlet tube connected to an argon cylin~er,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 190C. oil bath. l'he pot contents reached 180 + 2C. within 15 minutes. Then 3.5 g of glyco-lide was added with stirring and the oil bath temperature was adjusted to keep the temperature of the pot contents at 180 - 2C. 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 - 2C. Then, the remainder of the glycolide, 31.5 g, was added and the temperature of the pot contents was maintained ; at 220 - 2C. for 1 1/2 hours with continuous stirring. At this time the oil bath was removed t 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 60C. hexafluoroacetone sesquihydrate (HFAS). The polymer was precipitated by dripping this solu-tion into ~00 ml of methanol with stirring. The polymer was collected by filtration and extracted with acetone in a Soxh-let extractor for 2 days to remove the residue of fluorinated ~2~3~L

1 solvent. The polymer was then dried in a vacuum oven over-rlight at 50C. at 0.1 mm Hg. The yield of polymer was 95~6.
The I.V. in HFAS was 0.77. The mole percent of the lactic acid units in the polymer chain as determined by ~IMR wa~ ~.g.
The melting point as determined from the peak endotherm ob-served in a differential thermal analysis (D.T.A.j appara-tus was 218C.
A second two-stage copolymer was prepared as fol-lows. Into a three neck 100 ml. round bottom flask equipped with a glass shaft and a Teflon~ 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 Lt-) lactide whose I.V.
was 0.27, with stirring. This was flushed with argon gas for 15 minutes. This argon gas flush was maintained through-out the following polymerization. The flask was placed in a190C. oil bath. The pot contents reached 180 - 2C. with-in 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 180 + 2C. 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 + 2C.
Then, 31.4 g of glycolide was added and the temperature of the pot contents was maintained at 220 + 2C. 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 poly-~2 1 mer were dissolved in 60 ml. of 60C. hexafluoroacetone ses~quihydrate (HFAS) and the polymer was precipitated by dri,pp-ing this solution into 600 ml of methanol with stirring. The polymer was collected by filtration and extrac-~ed with ace~
tone in a Soxlet extractor for 2 days. The polymer was then dried in a vacuum oven overnight at 50C. 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 deter-mined by NMR was 5.9. The melting point as determined by the peak endotherm observed in a D.T.A. apparatus was 219C.
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 C12-2H2O and 7.5 mg of lauryl lacohol. Into a three neck 100 ml round bottom flask equipped with a glass shaft and a Teflon~ paddle stirrer attached to a stirring motor and a gas inlet tube attached to an argon cylinder, was added 10.0 g of the poly Lt-) lactide. This was flushed with argon for 15 minutes.
This argon flush was maintained through the following poly-merization. The flask was placed in a 190C. oil bath. The pot contents reached 180 - 2C. within 15 minutes. Then 2 g of glycolide was added with stirring and the oil bath temp-erature was adjusted to keep the temperature of the pot con-tents at 180 + 2C. 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 po-t contents reached 220 - 2C. Then, 18.0 g. of glycolide were added and the temperature of the pot contents was maintained at 220 + 2C. for 1 1/2 hours with continuous stirring. At . g _ ~2~Z3~

1 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 ~he polymer w~
ground up in a Wiley mill through a 20 mesh screen.
20.0 g. of this polymer was dissolved in ~00 ml of 60C. hexafluoroacetone sesquihydrate (HFAS) and the poly-mer 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 219C.
~xample 4 Into a three neck 100 ml round bottom flask e~uip-ped with a glass shaft and a Teflon~ paddle stirrer attachedto 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 ~(-) lactide prepared as in Example 3 except that a heating period of 1.5 hours at 200C. 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 200C. oil bath and the bath temperature was raised until the temperature of the pot contents reached 200 - 2C. This occurred within 15 minutes. Then, 48.0 g. of glycolide were added with stirring and the temperature of the oil ~ath was ~13z33L

1 raised until the temperature of the pot contents was 225~
+ 2C. This occurred within 30 minutes. Stirr:ing was con-tinued for 1 1/2 hours at this temperaturc. Then, 6.0 g of L(-) lac-tide were added (with stirring of -the pot contents) and stirring was continued for 1 1/2 hours at th:is temper-ature. At this time, the oil bath was removed, the stirring was stopped and the pot contents were allowed to cool to ap-proximately 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 poly-mer 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 extrac-tor for 2 days. The polymer was dried in a vacuum oven overnight at 50C. at 0.1 mm Hy. The yield of polymer was 82%. The I.V. in HEAS 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 endo-therm in a differential thermal a~alysis (.D.T.A.~ apparatus was 216C.
Example 5 .
Into a three neck 100 ml round bottom flask equip-ped with a glass shaft and a Teflon~ paddle attached to a stirring motor and a gas inlet tube attached to an argon cyl-inder, was added ~.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 2~2O
and 500 mg. of lauryl alcohol were employed and epsilon-cap-~12i!3,'~3~

1 rolactone was used in place of the L(-) lactide. The flask was flushed with argon for 15 minutes. The argon flush was maintained throughout the followiny polymeriza~ion. rl'he flask was placed in a 190C. oil bath. The pot con-ten-ts reached 180 ~ 2C. within 15 minutes. Then, 1.35 g of gly-colide were added with stirring and the oil bath temperature was adjusted to keep the temperature of the pot contents at 180 + 2C. 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 - 2C. Then, 12.15 g of glycolide were added with stirring and the temperature of the pot contents was maintained at 220 + 2C. 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 re-moved and ground in a Wiley mill through a 20 mesh screen.

4.0 g. of this polymer was dissolved in 80 ml. of 60C. HFAS
and the polymer was precipitated by dripping this solution into 1000 ml of methanol with stirring. The polymer was col-lected by filtration and extracted with acetone in a Soxhlet extractor for 2 days. The polymer was then dried overnight in a vacuum oven at 50C. at 0.1 mm Hg. The yield of poly-mer was 73%. The I.V. in HFAS was 0.77. The mole percentof 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 218C.

~21~3~

l Example 6 Into a three neck 100 ml round bottom flas~ e~uip-ped with a glass shaft and a Teflon~ paddle attached to a stirring motor and a gas inlet tube attached to an argon c~l-inder was added 7.0 g. of poly(trimethylene carbonate) whose I.V. was 0.34. The poly(trimethylene carbonate) was prepared by the procedure of Example l except that trimethylene car-~onate was used in place of the L(-) lactide and 4.0 mg. of SnC12 H2O were used with 250 mg. of lauryl alcohol. The con-version was 48%. The flask was flushed with argon for 15minutes. The argon flush was maintained throughout the fol-lowing polymerization. The flask was placed in a 190C. oil - bath. The pot contents reached 180 2C. within 15 min-utes. Then, 3.5 g. of glycolide were added with stirring and the oil bath temperature was adjusted to keep the temp-erature o~ the pot contents at 180 + 2C. for 30 minutes with continuous stirring. The temperature of the oil bath was then raised so~ that at the end of 30 minutes the temper-ature of the pot contents was 220 ~ 2C. Then, 31.5 g of glycolide were added with stirring and the temperature of the pot contents was maintained at 220 - 2C. 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 removed and ground in a Wiley mill through a 20 mesh screen. 5.0 g. of this polymer were dissolved in lO0 ml~ of 60C. HFAS and the polymer was pre-cipitated by dripping this solution into 1,000 ml. of meth-anol with stirring. The polymer was collected by filtration ~Z823J~

1 and extracted with acetone in a ~o~hlet extractor for 2 da~s.
The polymer was dried overnight in a vacuum oven at 50C. at 0.1 mm. Hg. The yield o~ polymer was 86%. The I.V. in HFAS
was 0.64. The mole percent of units deriv~d ~rom trimethyl-; 5 ene carbonate in the polymer chain as de-termined b~ NMR was 16,4. This figure corresponds to 14.7 weiyht percent -tri-methylene carbonate units. The melting point as determined from the peak endotherm in a differential thermal analysis (D.T.A.) apparatus was 218C.
Example_7 L~-) lactide (1612 g.), SnC12 2H2O (0.204 g.) and lauryl alcohol (4.77 g.) were added to a stirred reactor which had been preheated to 140C. The reactants were heat-ed with stirring under a nitrogen atmosphere over a 30 min-ute period to 200C. and then held at that temperature for 2hours.
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 180C.
Atmospheric pressure was restored by introducing nitrogen into the reaction vessel and the temperature was raised to 200C. over a 5 minute period. The molten glyco-lide (5198 g.) preheated to 100C. was added and the temper-ature was raised over a 15 minute period to 225C. and heldat this temperature for an additional 20 minutes.
The contents of the reactor were discharged and the pol~meric mass was broken up after it had cooled to room temperature. The polym~r was then ground and vacuum dried at 8-10 mm Hg for 11 hours at 140C. to remove all volatiles Z3~

l preparatory to spinning and determin:ing the polymer'.s vis-cosity.
The inherent viscosity of the polymer was det~r-mined to be 1.14, measured at 30C. in a 0.5~ solu~ion in ; 5 hexafluoroacetone sesquihydrate. The mole % of lactic acid units in the finished polymer was determined to be 20.3% by ~MR. The n~elting range of the product was determined to be 215-223.5C. 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 230C. 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 orig-inal length at 55C~ in a hot air draw unit. A sample of glycolide homopolymer 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 135C. at a pressure of l mm ~g.
The copolymer fiber which was 2.45 mils in diam-eter was found to have exceptional tensile-strength retention properties (34,600 p.s.i.) in an accelerated strength reten-tion 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 homo-polymer fiber which was 2.10 mils in diameter was 140,000 p.s.i. and the counterpart strength retained in an acceler-ated test was 25,300 p.s.io As mentioned above, it is believed that such co-polymeric polyesters are characterized by microphase separa-~28;~3il l tions having spherical domains in -the molten state, prior to orientation wherein the chain segments composed o~ lac-tic acid units are overlapped with themselves irl a matri~
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 poly-mer 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 predom-inate. This would likewise be the case where the lacticacid 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 syn-thetic absorbable surgical sutures prepared from a lactide polyester said polyester being composed of a copolymer hav-ing cylindrical or more preferably spherical dominions of L(-) lactide units in a matrix of glycolide units. The poly-esters employed can have the relative quantities of glycolideunits 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 sterili-zation methods may be used. Preferahly a monofilament or polyfilamentary braided polyester yarn is crimped into the 1 butt of a surgical needle and the needled suture is then sterilized using a toxidant such as ethylene oxide. Poly-esters ~ormed by sequentially and consecutively polymeriGing L(-) lactide and glycolide are most preferred ~or use -there-in.
While the surgical articles of the present inven-tion are generally useful in conventional manners for retain-ing living tissue in a desired location and relationship dur-ing a healing process by positioning and emplacing living tissue therewith, as in ligation of blood vessels, the need led sutures are especially adapted for the closing of wounds of living tissue by sewing together the edges thereof using conventional suturing techniques.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

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, further characterized in the use of L(-) lactide as a comonomer in the polymerization.

3. A method according to claim 1, further characterized in that the comonomers sequentially and consecutively polymerized are L(-) lactide and glycolide respectively.

4. A method according to claim 1, further characterized in that glycolide is employed as a comonomer in the polymerization.

5. A method according to claim 1, further characterized m that the comonomers sequentially and consecutively polymerized are L(-) lactide, glycolide and then L(-) lactide respectively.

6. A sterile surgical article fabricated from a synthetic absorbable copolymeric lactide polyester prepared according to the method of claim 1.

7. A suture according to claim 6 wherein the polyester is prepared by sequentially and consecutively polymerizing L(-) lactide, glycolide and L(-) lactide respectively.

8. A method according to claim 1, further characterized in that the comonomers sequentially and consecutively polymerized are trimethylene carbonate and glycolide respectively.

9. A copolymer comprising a proportion of sequential units having the formula:

(I) and a proportion of sequential units having the formula:

(II)

10. A copolymer according to claim 9 and formed by copolymerizing glycolide with trimethylene carbonate.

11. A copolymer according to claim 10 and formed by sequentially polymerizing first the trimethylene carbonate followed by glycolide.

12. A copolymer according to claim 9 and having a predominant content of units of formula (I).

13. A copolymer according to claim 12 where the units of formula (II) comprise from about 15% to less than 50% by weight of the copolymer.

14. A copolymer according to claim 13 wherein the units of formula (II) comprise about 15% by weight of the copolymer.

15. A copolymer according to claim 9 having a melting point in the range of 216 to 221°C as described by the peak endotherm in a differential thermal analysis apparatus.

16. A copolymer according to claim 9 or 15 having an inherent viscosity of about 0.6 to 2 dl/g (measured at a concentration of 0.5 g/100 ml hexafluoroacetone sesquihydrate at 30°C).

17. A copolymer according to claim 9 or 15 having an inherent viscosity of about 0.6 dl/g (measured at a concentration of 0.5 g/100 ml hexafluoro-acetone sesquihydrate at 30°C) and wherein the units of formula (II) comprise about 15% by weight of the copolymer.