Absorbable polyalkylene diglycolates

• US 5,696,178 A
• Filed: 07/22/1996
• Issued: 12/09/1997
• Est. Priority Date: 01/19/1995
• Status: Expired due to Term

• Current Assignee: Ethicon Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Cooper, Kevin, Scopelianos, Angelo
• Primary Examiner(s): BUTTNER, DAVID J
• Application Number:
  US08/681,135
• Time in Patent Office: 505 Days
• Field of Search: 525/34, 525/41, 525/42, 525/411, 525/412, 525/413, 525/415, 522/44, 522/48, 522/43, 522/68, 522/104, 522/108, 522/63
• US Class Current: 522/43
• CPC Class Codes: A61L 15/225 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 15/26 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 26/0019 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: C08G 63/66 Polyesters containing oxygen in the form of ether groups C08G63/42, C08G63/58 take precedence
• CPC Class Codes: C08G 63/668 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08G 63/672 Dicarboxylic acids and dihydroxy compounds
• CPC Class Codes: C08G 63/914 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08L 67/00 Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds C08L67/06 takes precedence
• CPC Class Codes: C08L 67/025 containing polyether sequences
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 67/07 having terminal carbon-to-carbon unsaturated bonds

Abstract

Absorbable polymers and blends of acrylated poly(alkylene diglycolate)s and aliphatic polyesters based on lactone monomers such as lactide, glycolide, e-caprolactone, p-dioxanone, and trimethylene carbonate are described. The polymers and blends exhibit a broad range of properties, useful in a variety of medical devices.

Claims

1. An absorbable, block segmented statistically random, or graft copolymer comprising the reaction product of:

a) an absorbable, biocompatible poly(alkylene diglycolate) comprising the reaction product of;

1. an acid or ester of diglycolic acid; and

,

2. an alcohol selected from the group consisting of glycerol, pentaerythitol, trimethylolpropane, hydroxyl terminated poly(ethylene glycol)s, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butylene glycol, dipropylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, and 1,8-octanediol,

wherein the poly(alkylene diglycolate) comprises about 10 mole percent to about 90 mole percent of repeating units with tri-, tetra-alcohols, and hydroxyl terminated poly(ethylene glycol)s, and wherein the balance of the poly(alkylene diglycolate) comprises repeating units with diol alcohols, and,

b) a polyester formed from lactone monomers selected from the group consisting of p-dioxanone, e-caprolactone, delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, 6,8-dioxabicycloctane-7-one, and combinations of two and more thereof,

wherein the copolymer is comprised of about 10 weight percent to about 90 weight percent of poly(alkylene diglycolate), and

wherein the poly(alkylene diglycolate) additionally comprised pendant acrylate groups.

2. The copolymer of claim 1 wherein the polyester is formed from lactone monomers selected from the group consisting of glycolide and lactide,

wherein the copolymer comprises about 55 weight percent to about 95 weight percent of poly(alkylene diglycolate).

3. The graft copolymer of claim 2 wherein the pendant acrylate groups are formed from an unsaturated acid halide comprising acryloyl chloride.

4. The graft copolymer of claim 1 wherein the pendant acrylate groups are formed from an unsaturated acid halide comprising acryloyl chloride.

5. The copolymer of claim 1 wherein the copolymer is cured via free radical photopolymerization, utilizing irradiation selected from the group consisting of visible and long wavelength ultraviolet radiation at a wavelength of about 150 to about 750 nm and laser light at about 514 nm, and free radical, photosensitive initiators selected from the group consisting of ethyl eosin, 2-methoxy-2-phenyl acetophenone, 2,2-dimethoxy-2-phenyl acetophenone, other acetophenone derivatives, and camphorquinone.

6. An absorbable polymer blend, comprising:

a) an absorbable, biocompatible poly(alkylene diglycolate) of comprising the reaction product of;

1. an acid or ester of diglycolic acid; and

,

2. an alcohol selected from the group consisting of glycerol, pentaerythitol, trimethylolpropane, hydroxyl terminated poly(ethylene glycol)s, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butylene glycol, dipropylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, and 1,8-octanediol,

wherein the poly(alkylene diglycolate) comprises about 10 mole percent to about 90 mole percent of repeating units with tri-, tetra-alcohols, and hydroxyl terminated poly(ethylene glycol)s, and wherein the balance of the poly(alkylene diglycolate) comprises repeating units with diol alcohols, and,

b) a polyester formed from lactone monomers selected from the group consisting of p-dioxanone, e-caprolactone, delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, 6,8-dioxabicycloctane-7-one, and combinations of two and more thereof,

wherein the blend is comprised of about 10 weight percent to about 90 weight percent of poly(alkylene diglycolate), and

wherein the poly(alkylene diglycolate) additionally comprises pendant acrylate groups.

7. The blend of claim 6 wherein the polyester is formed from lactone monomers selected from the group consisting of glycolide and lactide,

wherein the blend comprises about 55 weight percent to about 95 weight percent of poly(alkylene diglycolate).

8. The blend of claim 7 wherein the pendant acrylate groups are formed from an unsaturated acid halide comprising acryloyl chloride.

9. The blend of claim 6 wherein the pendant acrylate groups are formed from an unsaturated acid halide comprising acryloyl chloride.

10. The blend of claim 6 wherein the blend is cured via free radical photopolymerization, utilizing irradiation selected from the group consisting of visible and long wavelength ultraviolet radiation at a wavelength of about 150 to about 750 nm and laser light at about 514 nm, and free radical, photosensitive initiators selected from the group consisting of ethyl eosin, 2-methoxy-2-phenyl acetophenone, 2,2-dimethoxy-2-phenyl acetophenone, other acetophenone derivatives, and camphorquinone.

11. An absorbable device for use in medical applications, the medical device comprising a block, segmented, statistically random, or graft copolymer comprising the reaction product of:

a) an absorbable, biocompatible poly(alkylene diglycolate) of comprising the reaction product of;

1. an acid or ester of diglycolic acid; and

,

2. an alcohol selected group consisting of glycerol, pentaerythitol, trimethylolpropane, hydroxyl terminated poly(ethylene glycol)s, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butylene glycol, dipropylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, and 1,8-octanediol,

wherein the poly(alkylene diglycolate) comprises about 10 mole percent to about 90 mole percent of repeating units with tri-, tetra-alcohols, and hydroxyl terminated poly(ethylene glycol)s, and wherein the balance of the poly(alkylene diglycolate) comprises repeating units with diol alcohols, and,

b) a polyester formed from lactone monomers selected from the group consisting of p-dioxanone, e-caprolactone, delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, and combinations of two and more thereof,

wherein the copolymer is comprised of about 10 weight percent to about 90 weight percent of poly(alkylene diglycolate),

wherein the poly(alkylene diglycolate) additionally comprises pendant acrylate groups.

12. The absorbable device of claim 11 wherein the polyester formed from lactone monomers comprising a monomer selected from the group consisting of glycolide and lactide,

wherein the copolymer is comprised of about 55 weight percent to about 95 weight percent of poly(alkylene diglycolate).

13. An absorbable device for use in medical applications, the medical device comprising a blend of:

a) an absorbable, biocompatible poly(alkylene diglycolate) comprising the reaction product of;

1. an acid or ester of diglycolic acid; and

,

2. an alcohol selected from the group consisting of glycerol, pentaerythitol, trimethylolpropane, hydroxyl terminated poly(ethylene glycol)s, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butylene glycol, dipropylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, and 1,8-octanediol,

wherein the poly(alkylene diglycolate) comprises about 10 mole percent to about 90 mole percent of repeating units with tri-, tetra-alcohols, and hydroxyl terminated poly(ethylene glycol)s, and wherein the balance of the poly(alkylene diglycolate) comprises repeating units with diol alcohols, and,

b) a polyester formed from lactone monomers selected from the group consisting of p-dioxanone, e-caprolactone, delta-valerolactone, beta-butyrolactone, epsilon-decalactone, 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, gamma-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 1,4-dioxan-2-one, and combinations of two and more thereof,

wherein the blend is comprised of about 10 weight percent to about 90 weight percent of poly(alkylene diglycolate),

wherein the poly(alkylene diglycolate) additionally comprises pendant acrylate groups.

14. The absorbable device of claim 13 wherein the polyester is formed from lactone monomers comprising a monomer selected from the group consisting of glycolide and lactide,

wherein the blend is comprised of about 55 weight percent to about 95 weight percent of poly(alkylene diglycolate).