# US 5,703,200 A · Absorbable copolymers and blends of 6,6-dialkyl-1,4-dioxepan-2-one and its cyclic dimer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,703,200 A - Document ID: US5703200A - Status: Granted - Kind: A - Application number: 08/616,799 - Filed: 1996-03-15 - Granted: 1997-12-30 - Earliest claimed: 1996-03-15 - Assignees: Ethicon, Inc. - Inventors: Rao S. Bezwada; Steven C. Arnold; Constance Ace - Web page: https://patentgrep.com/patent/US5703200A ## CPC - C08G 63/664: derived from hydroxy carboxylic acids - A61L 17/105: {Polyesters not covered by A61L17/12} - A61L 17/12: Homopolymers or copolymers of glycolic acid or lactic acid - A61L 17/145: {Coating} - A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds - A61L 31/06: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)} - C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) ## Abstract This invention provides various copolymers comprising a first repeating unit of the chemical formula: ##STR1## in which R.sub.1 and/or R.sub.2 are alkyl groups and a second repeating units generally having the chemical formula: ##STR2## and combinations of two or more thereof wherein R is a hydrogen atom or a methyl group and the first repeating unit is less than 45 weight percent of the total weight of the copolymer. This invention also relates to use of these copolymers in the fabrication of absorbable surgical devices such as sutures and as coatings for medical devices. Additionally, described are blends and polyoxaesters containing the first repeating unit. ## Claims ### Claim 1 A copolymer comprising a first repeating unit of the chemical formula: ##STR9## in which R.sub.1 and R.sub.2 are independently alkyl groups selected from the group consisting of methyl, ethyl and propyl groups and a second repeating unit is generated from a monomer selected from the group of glycolic acid, lactic acid, glycolide, lactide (1, d, dl and meso), 3-methyl-1,4-dioxan-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, delta-valerolactone, epsilon-decalactone, pivalolactone, gamma-butyrolactone, ethylene carbonate, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, epsilon-caprolactone and combinations thereof and the first repeating unit is less than 45 weight percent of the total weight of the copolymer. ### Claim 2 (depends on 1) The copolymer of claim 1 wherein R.sub.1 and R.sub.2 are the same alkyl group. ### Claim 3 (depends on 2) The copolymer of claim 2 wherein the second repeating unit has a chemical formula selected from the group consisting of: ##STR10## combinations of two or more thereof wherein R is a hydrogen atom or methyl group. ### Claim 4 (depends on 3) The copolymer of claim 3 wherein the copolymer is selected from the group consisting of: a) a copolymer comprising the reaction product of a prepolymer of the first repeating unit the remainder of the copolymer being the second repeating unit; b) a random copolymer comprising the first repeating unit and the second repeating unit; c) a copolymer comprising the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit; and d) a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 5 (depends on 1) The copolymer of claim 1 wherein the copolymer is the reaction product of a prepolymer of the first repeating unit and the remainder of the copolymer is the second repeating unit. ### Claim 6 (depends on 1) The copolymer of claim 1 wherein the copolymer is the statistically random copolymer of the first repeating unit and the second repeating unit. ### Claim 7 (depends on 1) The copolymer of claim 1 wherein the copolymer comprises the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit. ### Claim 8 (depends on 1) The copolymer of claim 1 wherein the copolymer is the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 9 (depends on 3) The copolymer of claim 3 wherein the second repeating unit is of the chemical formula: ##STR11## ### Claim 10 (depends on 7) The copolymer of claim 7 wherein additionally present with the first repeating unit in the remainder of the copolymer is the second repeating unit. ### Claim 11 A surgical device comprising a copolymer composed of a first repeating unit of the chemical formula: ##STR12## in which R.sub.1 and R.sub.2 are independently alkyl groups selected from the group consisting of methyl, ethyl and propyl groups and a second repeating unit is generated from a monomer selected from the group of glycolic acid, lactic acid, glycolide, lactide (1, d, dl and meso), 3-methyl-1,4-dioxan-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, delta-valerolactone, epsilon-decalactone, pivalolactone, gamma-butyrolactone, ethylene carbonate, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, epsilon-caprolactone and combinations thereof and the first repeating unit is less than 45 weight percent of the total weight of the copolymer. ### Claim 12 (depends on 11) The surgical device of claim 11 wherein R.sub.1 and R.sub.2 are the same alkyl group. ### Claim 13 (depends on 12) The surgical device of claim 12 wherein the second repeating unit has a chemical formula selected from the group consisting of: ##STR13## and combinations of two or more thereof wherein R is a hydrogen atom or a methyl group. ### Claim 14 (depends on 13) The surgical device of claim 13 wherein the copolymer is selected from the group consisting of: a) a copolymer comprising the reaction product of a prepolymer of the first repeating unit the remainder of the copolymer being the second repeating unit; b) a random copolymer comprising the first repeating unit and the second repeating unit; c) a copolymer comprising the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit; and d) a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 15 (depends on 11) The surgical device of claim 11 wherein the surgical device is selected from the group consisting of sutures, ligaments, ribbons, pins, screws, clamps, plates, films, medical dressings, hernia patches, gauze, meshes, fabrics, felts, sponges, surgical staples, hemostatic clips, suture knot clips, hooks, buttons, snaps, bone substitutes and vascular implants. ### Claim 16 (depends on 11) The surgical device of claim 11 wherein the copolymer is the reaction product of a prepolymer of the first repeating unit and the remainder of the copolymer is the second repeating unit. ### Claim 17 (depends on 11) The surgical device of claim 11 wherein the copolymer is a statistically random copolymer comprising the first repeating unit and the second repeating unit. ### Claim 18 (depends on 11) The surgical device of claim 11 wherein the copolymer is the reaction product of a prepolymer containing the second repeating unit the remainder of the copolymer being the first repeating unit. ### Claim 19 (depends on 11) The surgical device of claim 11 wherein the copolymer is a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 20 (depends on 11) The surgical device of claim 11 wherein the surgical device is a suture. ### Claim 21 (depends on 13) The surgical device of claim 13 wherein the surgical device is a suture. ### Claim 22 (depends on 21) The surgical device of claim 21 wherein the suture is attached to at least one needle. ### Claim 23 (depends on 11) The surgical device of claim 11 wherein additionally present with the first repeating unit in the remainder of the copolymer is the second repeating unit. ### Claim 24 A suture coated with a copolymer composed of a first repeating unit of the chemical formula: ##STR14## in which R.sub.1 and R.sub.2 are independently alkyl groups selected from the group consisting of methyl, ethyl and propyl groups and a second repeating unit is generated from a monomer selected from the group of glycolic acid, lactic acid, glycolide, lactide (1, d, dl and meso), 3-methyl-1,4-dioxan-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, delta-valerolactone, epsilon-decalactone, pivalolactone, gamma-butyrolactone, ethylene carbonate, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, epsilon-caprolactone and combinations thereof and the first repeating unit is less than 45 weight percent of the total weight of the copolymer. ### Claim 25 (depends on 24) The suture coated with the copolymer of claim 24 wherein R.sub.1 and R.sub.2 are the same alkyl group. ### Claim 26 (depends on 25) The suture coated with the copolymer of claim 25 wherein the second repeating unit has a chemical formula selected from the group consisting of: ##STR15## and combinations of two or more thereof wherein R is a hydrogen atom or a methyl group. ### Claim 27 (depends on 26) The suture coated with the copolymer of claim 26 wherein the copolymer is selected from the group consisting of: a) a copolymer comprising the reaction product of a prepolymer of the first repeating unit the remainder of the copolymer being the second repeating unit; b) a random copolymer comprising the first repeating unit and the second repeating unit; c) a copolymer comprising the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit; and d) a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 28 (depends on 24) The coated suture of claim 24 wherein the copolymer is the reaction product of a prepolymer of the first repeating unit and the remainder of the copolymer is the second repeating unit. ### Claim 29 (depends on 24) The coated suture of claim 24 wherein the copolymer is a statistically random copolymer comprising the first repeating unit and the second repeating unit. ### Claim 30 (depends on 24) The coated suture of claim 24 wherein the copolymer is the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit. ### Claim 31 (depends on 24) The coated suture of claim 24 wherein the copolymer is a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 32 (depends on 26) The copolymer of claim 26 wherein the second repeating unit is of the formula: ##STR16## ### Claim 33 (depends on 24) The coated suture of claim 24 wherein the suture is attached to at least one needle. ### Claim 34 A surgical device having at least a part thereof made from a polymeric blend composed of at least one first polymer selected from the group consisting of homopolymers and copolymers (including segmented block copolymers and graft copolymers) prepared from monomers selected from the group consisting of glycolic acid, lactic acid, glycolide, L-lactide, D-lactide, D,L-lactide, meso-lactide, 1,4-dioxan-2-one, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, .epsilon.-caprolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and combinations thereof; and a second polymer having a first repeating unit of the chemical formula: ##STR17## in which R.sub.1 and R.sub.2 are independently alkyl groups selected from the group consisting of methyl, ethyl and propyl groups and optionally a second repeating unit is generated from a monomer selected from the group of glycolic acid, lactic acid, glycolide, lactide (1, d, dl and meso), 3-methyl-1,4-dioxan-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, delta-valerolactone, epsilon-decalactone, pivalolactone, gamma-butyrolactone, ethylene carbonate, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, epsilon-caprolactone and combinations thereof and the first repeating unit is less than 45 weight percent of the total weight of the copolymer. ### Claim 35 (depends on 34) The surgical device of claim 34 wherein R.sub.1 and R.sub.2 are the same alkyl group. ### Claim 36 (depends on 35) The surgical device of claim 35 wherein the second repeating unit has a chemical formula selected from the group consisting of: ##STR18## and combinations of two or more thereof wherein R is a hydrogen atom or a methyl group. ### Claim 37 (depends on 34) The surgical device of claim 34 wherein the copolymer is selected from the group consisting of: a) a copolymer comprising the reaction product of a prepolymer of the first repeating unit the remainder of the copolymer being the second repeating unit; b) a statistically random copolymer comprising the first repeating unit and the second repeating unit; c) a copolymer comprising the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit; and d) a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 38 (depends on 34) The surgical device of claim 34 wherein the surgical device is selected from the group consisting of sutures, ligaments, ribbons, pins, screws, clamps, plates, films, medical dressings, hernia patches, gauze, meshes, fabrics, felts, sponges, surgical staples, hemostatic clips, suture knot clips, hooks, buttons, snaps, bone substitutes and vascular implants. ### Claim 39 (depends on 34) The surgical device of claim 34 wherein the second polymer is the reaction product of a prepolymer of the first repeating unit and the remainder of the copolymer is the second repeating unit. ### Claim 40 (depends on 34) The surgical device of claim 34 wherein the second polymer is a statistically random copolymer comprising the first repeating unit and the second repeating unit. ### Claim 41 (depends on 34) The surgical device of claim 34 wherein the second polymer is the reaction product of a prepolymer containing the second repeating unit the remainder of the copolymer being the first repeating unit. ### Claim 42 (depends on 34) The surgical device of claim 34 wherein the copolymer is a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 43 (depends on 36) The surgical device of claim 36 wherein the surgical device is selected from the group consisting of sutures, ligaments, ribbons, pins, screws, clamps, plates, films, medical dressings, hernia patches, gauze, meshes, fabrics, felts, sponges, surgical staples, hemostatic clips, suture knot clips, hooks, buttons, snaps, bone substitutes and vascular implants. ### Claim 44 (depends on 43) The surgical device of claim 43 wherein the surgical device is a surgical staple. ### Claim 45 (depends on 44) The surgical device of claim 44 wherein the surgical device is a hemostatic clip. ### Claim 46 (depends on 34) The surgical device of claim 34 wherein additionally present with the first repeating unit in the remainder of the copolymer is the second repeating unit. ### Claim 47 A polymeric blend composed of at least one first polymer selected from homopolymers and copolymers (including segmented block copolymers and graft copolymers) prepared from monomers selected from the group consisting of glycolic acid, lactic acid, glycolide, L-lactide, D-lactide, D,L-lactide, meso-lactide, 1,4-dioxan-2-one, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, .epsilon.-caprolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one and combinations thereof; and a second polymer having a first repeating unit of the chemical formula: ##STR19## in which R.sub.1 and R.sub.2 are independently alkyl groups selected from the group consisting of methyl, ethyl and propyl groups and a second repeating unit is generated from a monomer selected from the group of glycolic acid, lactic acid, glycolide, lactide (1, d, dl and meso), 3-methyl-1,4-dioxan-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, delta-valerolactone, epsilon-decalactone, pivalolactone, gamma-butyrolactone, ethylene carbonate, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, epsilon-caprolactone and combinations thereof and the first repeating unit is less than 45 weight percent of the total weight of the copolymer. ### Claim 48 (depends on 47) The polymeric blend of claim 47 wherein R.sub.1 and R.sub.2 are the same alkyl group. ### Claim 49 (depends on 48) The polymeric blend of claim 48 wherein the second repeating unit has a chemical formula selected from the group consisting of: ##STR20## and combinations of two or more thereof wherein R is a hydrogen atom or a methyl group. ### Claim 50 (depends on 47) The polymeric blend of claim 47 wherein the copolymer is selected from the group consisting of: a) a copolymer comprising the reaction product of a prepolymer of the first repeating unit the remainder of the copolymer being the second repeating unit; b) a statistically random copolymer comprising the first repeating unit and the second repeating unit; c) a copolymer comprising the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit; and d) a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 51 A polyoxaester having a formula selected from the group consisting of ›(--C(O)--C(R.sub.3) (R.sub.4)--O--R.sub.5 --O--C(R.sub.3) (R.sub.4)--C(O)--(O--R.sub.6).sub.A --O).sub.S (Q).sub.B !.sub.WXII and ›(--C(O)--C(R.sub.3) (R.sub.4)--O--R.sub.5 --O--C(R.sub.3) (R.sub.4)--C(O)--(O--R.sub.6).sub.A --O).sub.S (›Q!.sub.P --O--).sub.L G!.sub.W XIII wherein R.sub.3 and R.sub.4 are independently selected from the group consisting of hydrogen or an alkyl group containing from 1 to 8 carbon atoms and R.sub.5 is an alkylene containing from 2 to 12 carbon atoms or is an oxyaIkylene group of the following formula: --›(CH.sub.2)C--O--!.sub.D --(CH.sub.2).sub.E IV wherein C is an integer in the range of from about 2 to about 5, D is an integer in the range of from about 0 to about 2,000, and E is an integer in the range of from about 2 to about 5 except when D is zero in which event E is an integer from 1 to 12; R.sub.6 is an alkylene unit containing from 2 to 8 methylene units; A is an integer in the range of from 1 to about 2,000; B is an integer in the range of from 1 to n such that the number average molecular weight of Q is less than about 100,000; Q is an aliphatic polyester having at least a first repeating unit of the chemical formula: ##STR21## wherein R.sub.1 and R.sub.2 are independently alkyl groups selected from the group consisting of methyl, ethyl and propyl groups; P is an integer in the range of from 1 to m such that the number average molecular weight of the formula: (›Q!.sub.P --O--).sub.L G is less than about 100,000; G represents the residue minus from 1 to L hydrogen atoms from the hydroxyl groups of an alcohol previously containing from 1 to about 200 hydroxyl groups; L is an integer from about 1 to about 200; and S is an integer in the range of from about 1 to about 1,000; and W is an integer in the range of from about 1 to about 1,000. ### Claim 52 (depends on 51) The polyoxaester of claim 51 wherein the aliphatic polyester additionally contains a second repeating unit generated from a monomer selected from the group of glycolic acid, lactic acid, glycolide, lactide (1, d, dl and meso), 3-methyl-1,4-dioxan-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-one, 1,4-dioxan-2-one, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, delta-valerolactone, epsilon-decalactone, pivalolactone, gamma-butyrolactone, ethylene carbonate, 1,3-dioxan-2-one, 4,4-dimethyl-1,3-dioxan-2-one, epsilon-caprolactone and combinations thereof. ### Claim 53 (depends on 52) The polyoxaester of claim 52 wherein the first repeating unit is less than 45 weight percent of the total weight of the copolymer. ### Claim 54 (depends on 51) The polyoxaester of claim 51 wherein R.sub.1 and R.sub.2 are the same alkyl group. ### Claim 55 (depends on 54) The polyoxaester of claim 54 wherein the second repeating unit has a chemical formula selected from the group consisting of: ##STR22## and combinations of two or more thereof wherein R is a hydrogen atom or a methyl group. ### Claim 56 (depends on 47) The polyoxaester of claim 47 wherein the aliphatic polyester is a copolymer selected from the group consisting of: a) a copolymer comprising the reaction product of a prepolymer of the first repeating unit the remainder of the copolymer being the second repeating unit; b) a statistically random copolymer comprising the first repeating unit and the second repeating unit; c) a copolymer comprising the reaction product of a prepolymer containing the second repeating unit and the remainder of the copolymer being the first repeating unit; and d) a copolymer comprising the reaction product of a prepolymer containing less than 45 weight percent of the first repeating unit and greater than 55 weight percent of the second repeating unit in the prepolymer and the remainder of the copolymer being the second repeating unit. ### Claim 57 (depends on 1) The copolymer of claim 1 wherein R.sub.1 and R.sub.2 are methyl groups. ### Claim 58 (depends on 11) The surgical device of claim 11 wherein R.sub.1 and R.sub.2 are methyl groups. ### Claim 59 (depends on 24) The suture coated with a copolymer of claim 24 wherein R.sub.1 and R.sub.2 are methyl groups. ### Claim 60 (depends on 34) The surgical device of claim 34 wherein R.sub.1 and R.sub.2 are methyl groups. ### Claim 61 (depends on 47) The polymeric blend of claim 47 wherein R.sub.1 and R.sub.2 are methyl groups. ### Claim 62 (depends on 51) The polyoxaester of claim 51 wherein R.sub.1 and R.sub.2 are methyl groups.