iiililiili^ @ EuroPean Patent Office ^-S Office europeen des brevets (fi) Publication number : 0 559 404 A1 @ EUROPEAN PATENT APPLICATION @ Application number : 93301510.9 @ Int. CI.5 : C08K 5/14, C08K 5/1 1 , C08G 69/44, C08G 69/48, (§) Date of filing : 26.02.93 A61L 1 7/00, A61 L 27/00, //(C08K5/14, C08L77:00), (C08K5/27, C08L77:00) (30) Priority : 06.03.92 US 847969 (72) Inventor : Holy, Norman Lee 901 Cherry Lane Penns Park, Pennsylvania 18943 (US) @ Date of publication of application : Inventor : Bortnick, Newman Mayer 08.09.93 Bulletin 93/36 509 Oreland Mill Road Oreland, Pennsylvania 19075 (US) (S) Designated Contracting States : DE ES FR GB IE IT PT @ Representative : Angell, David Whilton et al ROHM AND HAAS (UK) LTD. European Operations Patent Department Lennig House © Applicant : ROHM AND HAAS COMPANY 2 Mason's Avenue Independence Mall West Croydon CR9 3NB (GB) Philadelphia Pennsylvania 19105 (US) (S) Degradable polyamides. (57) Compositions comprising polyamide rendered hydrolytically labile by the incorporation of certain alkyl esters therein are useful in or as articles intended for degradation by water. Certain of the hydrolytically labile polyamides are novel compounds. O 10 10 LU Jouve, 18, rue Saint-Denis, 75001 PARIS EP 0 559 404 A1 This invention is concerned with biodegradable polymeric articles and certain amide polymers useful therein. The polymers and articles become brittle after long exposure to water and are especially useful as biodegradable fiber and netting, degradable plastic dishware, and degradable films for packaging. Another use of interest is in biological implants. 5 Japanese Kokai No. 56 022324 describes the production of alternate block copolymers of low molecular weight aliphatic polyesters and low molecular weight aliphatic polyamides by ester-amide interchange which are useful for mulch films biodegradable via enzyme digestion (Rhizopus delemar lipase). In this polymer, the polyester to polyamide ratio is high in polyester, for example, 4 to 1 mole % polyester to nylon 6. Japanese Kokai No. 54 119594 describes the production of a biodegradable low molecular weight aliphatic 10 polyester amide alternate block copolymer from polycaprolactone and nylon 6 in the presence of zinc acetate. The polyester to polyamide ratio is near 1 to 1 . Again, the product polymer is subject to enzymatic (lipase) deg- radation. Japanese Kokai No. 54 120727 describes polyester polyamide block copolymers, high in the polyester component, which are useful for production of biodegradable films orf ibers. There is no mention of marine uses 15 of the copolymers. US-A3,592,873 describes the preparation of polyamide esters as interpolymers to provide thermal stability in polyoxymethylenes. The polyamide esters are prepared by reacting lactams oralkyl substituted lactams with at least a four membered ring with lactones or alkyl substituted lactones, again with at least a four membered ring. 20 JAppl. Polymer Sci., 24(7), 1701-11 (1979) describes the synthesis of copolyamide-esters via amideester interchange of polycaprolactone with nylon 6, 66, 69, 11 , 12, or 612. It also describes degradation of the poly- mers by Rhizopus delemar lipase digestion or alcoholic alkali hydrolysis. The effect of nylon/polycaprolactone ratio on the biodegradability was examined and biodegradability was found to decrease as the polyamide con- tent increased and/or as the polyamide blocks shortened. 25 Eur. Polym. J., 529-557 (1984) describes the preparation of copolyesteramides by anionic ring opening copolymerization of s-caprolactam with s-caprolactone. Alternating copolymers or random multiblock copoly- mers with amide to ester ratios of 90/1 0 to 1 0/90 were prepared. In addition, the reference describes cleavage by alkaline hydrolysis as well as tensile properties of films and fibers fabricated from the copolymers. Chemtech, 21_, 26-30 (January, 1991) describes the biodegradability of a variety of commercial plastics 30 and compares their utility for medical applications. Medical uses are related to mechanical and degradative properties of many of the commercial materials. The combination of properties which polyamides (or, more specifically, nylons) exhibit make them ideal for use in fibers. Furthermore, nylon fibers have many properties which make them ideal for use in netting, including strength, light weight, and resistance to degradation, However, some of these desirable properties 35 also result in a significant environmental problem. The lifetime for nylon netting in the ocean has been estimated as over ten years; and may be closer to thirty years. Netting which has been abandoned either intentionally or by accident continues to capture marine fish and mammals. These "ghost" nets account for enormous kills offish, seals, whales, and dolphins. Seal deaths alone are estimated to be about 40,000 annually off the coast of Alaska alone. A similar situation is found in abandoned lobster traps where any captured lobsters are unable 40 to free themselves from the trap's netting. Analogous situations exist in fresh water lakes, many being contam- inated with fishing line either lost or abandoned. Commercial nylons are also used in biological implants. However, because of their biological inertness, uses are limited to those in which the implant is permanent or in which it can be mechanically removed. Polymers of lactic acid are well-known for their degradability under microbial attack. Acopolyester of lactic and 45 glycolic acid is used as a biodegradable suture in repairing soft tissue wounds. These polymers have also been used to fabricate degradable bone plate which is used to reinforce a broken bone during its healing period. There is no record of lactic acid/nylon copolymers being used in a similar manner. Oxalate substitution for adipate units in nylon 66, or similar units in other bi-directional polyamides for the purpose of rendering the material more degradable is not reported. Oxalate esters are highly reactive hydrol- 50 ytically. Thus, incorporation of oxalate units into nylon provides sites for attack and chain cleavage, whether biologically or by simple hydrolysis. We have now found amide polymers which will degrade at a controlled rate in fresh or ocean water and which can be used as degradable nylon useful for biological implants or as degradable nylon film. The invention also provides a process for the efficient production of the degradable nylon. 55 The invention involves incorporating into a nylon, or reacting with a nylon precursor, an appropriate ester, cyclic ester, or polyester such that the ester functionality is incorporated into the polymer backbone. Incorporation can be accomplished via three major routes; reaction of preformed polymers, for example, nylon 6 with poly- caprolactone; reaction of a prepolymer with a monomer, for example, nylon 6 with dimethylglycolide; orcopo- 2 EP 0 559 404 A1 lymerization of two monomers, for example, caprolactam with caprolactone. We have discovered that by con- trolling the extent of incorporation, the desirable properties of the nylon are largely maintained while at the same time the nylon becomes subject to hydrolysis by water, presumably (although we are not to be bound by such theoretical considerations) at the incorporated ester functionality. These ester functionalities, which 5 are hydrolytically unstable, act as weak links. The strength of the nondegradable nylon is preserved. However, as the ester functionalities are hydrolyzed, the chain falls apart. The hydrolysis may be uncatalyzed, catalyzed by acids or bases, or biologically catalyzed. Furthermore, since the hydrolysis results in creation of an acidic polymer end group, it can also be autocatalyzed. As the polymer chain length becomes shorter due to the hydrolytic degradation, the nylon becomes em- 10 brittled and, therefore, weaker. Thus, netting produced from ester modified nylon fibers becomes so weak over time that the struggles of a captured animal are sufficient to break the fiber, freeing the animal; biological im- plants degrade at a rate commensurate with their replacement by normal tissue; and films degrade at a pre- determined rate. Although some of the explanation in this disclosure refers to nylon as the polymer, the invention is appli- 15 cable generally to polyamides. Novel hydrolytically labile polyamides of this invention comprise: (a) from about 80 to about 99.99 weight percent of polyamide, such as nylon, including nylons 6, 6/6, 6/12, 6/9, 6/10, 11, 12, 4/12, 12/12, and the like; and (b) from about 0.01 to about 20 weight percent (based on (a) plus (b) ) of ester comprising oxalate of formula I (bidirectional esters) and/or dimethylglycolide of formula II (unidir- 20 ectional esters): 00 J I Ri0_lLU_OR2 0^o^R2 I II wherein R1 and R2 are the same or different radicals selected from hydrogen and - C20 alkyl such as, for 30 example, dibutyl oxalate, dimethyl oxalate, lactic acid cyclic dimer, and the like. The oxalate ester can also be in the form of a polymer (that is where the R1 and R2 radicals form connecting links between oxalate units). Examples of these polymeric oxalates include those wherein R1 and R2 are derived from ethylene glycol, pro- pylene glycol, 1 ,4-butanediol, and the like. The oxalate, oxalate polymer, or glycolide dimer is randomly incor- porated into the polyamide chain as single, diad, triad, or oligomeric units. This invention also extends to the 35 use in biodegradable articles of the novel polyamides or of polyamides which have been made hydrolytically labile by randomly incorporating into the polymer chains of the polyamide, singularly or in combination, of from about 0.01 to about 20 weight percent of alkyl ester selected from compounds of the formula III, IV, V, or VI; 40 u II HO-(CR1R2)n-C-OR3 -[-(CR1R2)n-C-0-]x- III IV 45 � O 0 R30-C— (CR1R2)n-C-OR3 V VI wherein R1 and R2 are the same or different radicals selected from H, or C^-C4 alkyl; R3 is selected from hy- drogen or CrC2o alkyl; n is 1 - 10; m is 2 - 6; and x varies with the polymer molecular weight range; such as, for example, 3-hydroxybutyric esters, polycaprolactone, caprolactone, adipic esters, and the like.