Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...
Reexamination Certificate
2000-12-14
2003-01-07
Short, Patricia A. (Department: 1712)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Mixing of two or more solid polymers; mixing of solid...
C525S411000, C525S439000, C528S302000, C606S151000, C606S154000, C606S230000
Reexamination Certificate
active
06503991
ABSTRACT:
BACKGROUND OF THE INVENTION
Since the successful development of the crystalline thermoplastic polyglycolide (PG) and 10/90 poly(1-lactide-co-glycolide) (PLG) as absorbable suture materials, there have been many successful attempts to prepare a number of new absorbable, crystalline homopolymers as well as segmented and block copolymers by ring-opening or condensation polymerization for use in a variety of biomedical and pharmaceutical applications Meanwhile, a few monomers have been considered to be the necessary precursors for the production of truly absorbable polyesters by ring-opening polymerization. These monomers are glycolide, lactide, and p-dioxanone Of the condensation-type absorbable polymers, only certain polyanhydrides and polyalkylene oxalates have been recognized as crystalline thermoplastic materials. Most pertinent to the copolymers, subject of this invention, are crystalline absorbable thermoplastic copolymers made by end-grafting low Tg (glass transition temperature) absorbable, so-called “soft” blocks or segments with relatively high Tg crystallizable, chains usually denoted as “hard” blocks or segments. See, for example, U.S Pat Nos. 5,554,170; 5,431,679; 5,403,347, 5,236,444; 5,133,739; and 4,429,080. The terms segment and block are used to denote relatively short and long structures of repeat units in the polymeric chain, respectively In designing the soft segments, or blocks, of the prior art, polar cyclic monomers have been used as precursors to produce these moieties in essentially amorphous, highly flexible form by ring-opening polymerization However, most of the segments or blocks of the prior art were made to contain small amounts of hydrolytically labile ester linkages derived from glycolide or p-dioxanone to attain a timely absorption of the entire block/segmented copolymer. And in commercial products having the hard-soft segment/block molecular architecture, the hard component of the copolymers have been made primarily or totally of glycolide-derived chains. Unfortunately, having the labile linkage in the soft segments or blocks not only facilitates their absorption, but also causes a premature or early and sudden reduction in the molecular weight of the load-bearing long chains and, hence, an early reduction in breaking strength and related physicomechanical properties of implants based on these copolymers. This provided the incentive to develop the new, linear, semi-crystalline block/segmented copolymers, subject of this invention, wherein the soft blocks or segments are designed to comprise less polar chain sequences formed by step-growth polymerization of acyclic precursors, which are not expected to be absorbable as homopolymers, in order to minimize the hydrolytic instability of the entire block/segmented systems having the more traditional hard components. Accordingly, one aspect of this invention deals with block/segmented copolymers having the soft segment made by step-growth polymerization of an alkane diol and diester which are not known as the common precursors of absorbable homopolymers. In another aspect of this invention, the soft segment/block is made by further end-grafting the aforementioned step-growth alkylene dicarboxylate prepolymer with a cyclic ester and/or carbonate other than those known to provide labile ester linkages such as glycolide and p-dioxane.
SUMMARY OF THE INVENTION
The present invention is directed to a crystalline, absorbable block/segmented copolymer which is the reaction product of (a) a linear prepolymer comprising a polyalkylene dicarboxylate, preferably a polytrimethylene of one or more acids selected from the group consisting of succinic acid, glutaric acid, sebacic acid and adipic acid; and (b) a monomer selected from the group consisting of glycolide, lactide, and mixtures thereof Preferably, prior to reaction with the glycolide, lactide or mixtures thereof, the prepolymer is end-grafted with a monomer selected from the group consisting of aliphatic carbonate, cyclic carbonate, caprolactone, and 1,5-dioxapan-2-one. Most preferably, the prepolymer is first end-grafted with trimethylene carbonate, &egr;-caprolactone, or a mixture of the two With or without preliminary end-grafting, the polymer comprises from about 20% to about 80% by weight of the overall copolymer and preferably from about 30% to about 70% by weight.
It is preferred that the prepolymer is amorphous or that the prepolymer has a melting temperature at or below 50° C., most preferably at or below 37° C.
The copolymers of the present invention may be used in the production of a variety of bioabsorble medical devices. Certain types of the present copolymers are especially suited for forming monofilament sutures
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The present invention is directed to the design of segmented/block copolymeric chains to provide absorbable materials for the production of biomedical articles with controlled absorption and strength retention profiles. The copolymers of the present invention have an amorphous or low melting temperature phase that is based primarily on soft segments or blocks whose chains are essentially devoid of distinctly hydrolytically labile ester linkages and, hence, provide an overall minimized hydrolytic instability.
The present copolymers are defined as blocked or segmented because they are of the type having blocks or segments made from “hard” phase forming monomers and one or more blocks or segments made from “soft” phase forming monomers. Generally, the hard phase blocks or segments lend mechanical strength to the overall copolymer and the soft phase blocks or segments render the copolymer compliant. The term “block copolymer” typically refers to a copolymer having two or more blocks or long structures of repeat units such as the general form A-B, A-B-A, or (A-B)
n
. A “segmented copolymer” is typically considered to be one with multiple relatively short structures such as a-b-a-b . . . or a-b-c-a-b . . . , where the a, b, and c are shorter than the A and B of the block copolymers. The present copolymers are referred to as “block/segmented copolymers” herein because they may contain a limited number of long blocks or several short segments per chain. These terms are intended to distinguish the present copolymers from random copolymers.
The copolymers of the present invention are formed by the copolymerization of a prepolymer, which will ultimately form the soft block or segments, with one or more monomers which will ultimately form the hard blocks or segments. The prepolymer of the present invention is, at least, a polyalkylene dicarboxylate, preferably a polytrimethylene dicarboxylate of glutaric, adipic, sebacic and/or succinic acid. More preferably, the polytrimethylene dicarboxylate is end-grafted with at least one or more monomers of the group a cyclic carbonate, &egr;-caprolactone, and 1,5-dioxapan-2-one. The preferred cyclic carbonate is trimethylene carbonate. Thus, in one preferred embodiment a polytrimethylene dicarboxylate of succinic acid is end-grafted with trimethylene carbonate. In another preferred embodiment a polytrimethylene dicarboxylate of succinic acid is end-grafted with a mixture of trimethylene carbonate and &egr;-caprolactone.
Generally, the soft block or segments must be incapable of crystallization between 25-50° C. and display a high degree of chain mobility at about room temperature. That is, preferably the prepolymer which will ultimately form the soft block is either amorphous or has a melting temperature of 50° C. or less. Most preferably, it is either amorphous or has a melting temperature of 37° C. or less. Optionally, the prepolymer is a liquid.
Attached to soft block or segments is one or more blocks or segments that are capable of crystallization under prevailing processing conditions to form the crystalline or hard component of the final copolymeric system. Preferably, hard components are composed primarily of repeat units derived from glycolide, lactide, or mixtures thereof. Optionally, minor co-repeat units (or sequences) in the hard segments are deriv
Gregory Leigh P.
Poly-Med, Inc.
Short Patricia A.
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