GB1604178A - Lactide polyester copolymer - Google Patents

Description

PATENT SPECIFICATION ( 11) 1 604 178

X ( 21) Application No 34213/80 ( 22) Filed 28 Apr 1978 ( 19) % ( 62) Divided out of No 1604177 ( 31) Convention Application No 799836 ( 32) Filed 23 May 1977 in l ( 33) United States of America (US) ú ( 44) Complete Specification Published 2 Dec 1981 ( 51) INT CL 3 CO 8 G 63/64 ( 52) Index at Acceptance C 3 R 3 D 20 3 D 24 3 D 2 A 3 N 7 3 P 2 3 T 1 C SM C 3 Y B 120 B 126 B 262 B 284 G 230 G 315 ( 54) LACTIDE POLYESTER COPOLYMER ( 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: 5

This invention relates to a novel lactide polyester copolymer from which surgical articles, particularly sutures, can be fabricated The Application has been divided from our co-tending Application No 17108/78 Serial No 1604177.

The use of lactide polyesters in the fabrication of synthetic surgical articles is known in the art The two lactides conventionally preferred for use in preparing surgical articles are 10 L(-) lactide and glycolide In conjunction with the lactide monomers comonomers have been employed to modify the characteristics of the resulting 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 15 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: U S Patents Nos 3, 268,486 and 3,268,487 20 The present invention provides a novel lactide polyester copolymer which is useful for the fabrication of surgical articles such as sutures.

The copolymer of the present invention is characterized by a content of sequential units of Formula I and Formula II:

25 t O-CH 2-CO-O-CH 2-CO i I t O-CH 2-CH 2 CH 2-O-CO i II 30 The novel copolymers of the present invention may be prepared by the sequential ring-opening coploymerization procedure which forms the subject of the Parent Application No 17108/78, Serial No 1604177 supra, employing glycolide and trimethylene 35 carbonate as the monomers It is preferred to sequentially polymerize first the trimethylene carbonate and then the glycolide By thus conducting the polymerization procedure in 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 40 molecular structures.

One of the preferred areas for use of the copolymers of the present invention relates to the preparation of sterile, synthetic, absorbable, surgical articles (especially sutures) wherein glycolide is employed as the predominant comonomer in preparing the polyesters, giving rise to a predominant content of units of Formula I The present state of the art is 45 1 604 178 such that detailed absorption mechanisms and details of the polymer structure on the molecular levels are not known with certainty.

The surgical articles may be fabricated from the novel polyesters using the procedures conventionally employed with the known lactide polyesters Likewise, the resulting surgical articles are employed in a conventional manner 5 Sutures formed from the novel copolymer may be in the form of a sterile surgical needle and suture combination Conventional suture constructions and sterilization methods may be employed 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 toxicant such as ethylene oxide 10 While the surgical articles of the present invention are generally useful in conventional manners for retaining living tissue 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 15 An example of the preparation of a copolymer of this invention from glycolide and trimethylene carbonate by the method in accordance with the parent Application No.

17108/78, Serial No 1604177 supra, will now be given.

Example 20

Into a three neck 100 ml round bottom flask equipped with a glass shaft and a polytetrafluroethylene paddle attached to a stirring motor and a gas inlet tube attached to an argon cylinder 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 1 of the parent Application No 17108/78 serial no 1604177 except that trimethylene carbonate was 25 used in place of the L(-) lactide and 4 0 mg of Sn C 12 H 20 were used with 250 mg of lauryl alcohol The conversion was 48 % The flask was flushed with argon for 15 minutes The argon flush was maintained throughout the following polymerization The flask was placed in a 1900 C oil bath The pot contents reached 1800 20 C within 15 minutes Then, 3 5 g.

of glycolide were added with stirring and the oil bath temperature was adjusted to keep the 30 temperature of the pot contents at 1800 20 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 was 220 20 C Then, 31 5 g of glycolide were added with stirring and the temperature of the pot contents was maintained at 2200 20 C for 1 1/2 hours with continuous stirring At this time the oil bath was removed, the stirring was stopped and the 35 pot contents were allowed to cool to apporoximately 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 ml of 600 C HFAS and the polymer was precipitated by dripping this solution into 1,000 ml of methanol with stirring The polymer was collected by filtration and extracted 40 with acetone in a Soxhlet extractor for 2 days The polymer wa dried overnight in a vaccum oven at 500 C at 0 1 mm Hg The yield of polymer was 86 % The I V in HFAS (hexafluoroacetone sesquihydrate) was 0 64 The mole percent of units derived from trimethylene carbonate in the polymer chain as determined by NMR was 16 4 This figure corresponds to 14 7 weight percent trimethylene carbonate units The melting point as 45 determined from the peak endotherm in a differential thermal analysis (D T A) apparatus was 218 C.

Claims (8)

WHAT WE CLAIM IS:-

1 A copolymer characterized by a content of sequential units of Formula I and Formula II: 50 t O-CH 2-CO-O-CH 2-CO + (I) 55 t O-CH 2-CH 2-CH 2-O-CO 1 (II)

2 A copolymer according to Claim 1 and formed by copolymerizing glycolide with trimethylene carbonate 60

3 A copolymer according to Claim 2 and formed by sequentially polymerizing first the trimethylene carbonate followed by the glycolide.

4 A copolymer according to any preceding Claim and having a predominant content of units of Formula (I).

5 A copolymer according to Claim 1 and substantially as described in the Example 65 3 1 604 178 3 herein.

6 A sterile surgical article fabricated from a copolymer according to any preceding Claim.

7 An article according to Claim 6 in the form of a mono or multifilament suture.

8 An article according to Claim 7 in the form of a needled suture 5 9 An article according to any one of Claims 6 to 8 and fabricated from a copolymer having a content of units of Formula (I) such that the article is absorbable in vivo.

LLOYD WISE, TREGEAR & CO, Norman House, 10 105-109 Strand, London, WC 2 R OAE.

Printed for Her Majesty's Stationery Office by Croydon Printing Company Limited Croydon, Surrey, 1981.

Published by The Patent Office 25 Southampton Buildings, London, WC 2 A l AY, from which copies may be obtained.