Modified polylactide polymers

Patent metadata

Field	Value
Publication number	US-9669137-B2
Application number	US-201514613304-A
Country	US
Kind code	B2
Filing date	Feb 3, 2015
Priority date	Feb 4, 2014
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

It is provided herein modified polylactide (PLA) polymers comprising biocompatibile functional group(s) on the polymers and methods of making and using the modified PLA polymers.

First claim

What is claimed is:

1. A modified polylactide (PLA) polymer comprising a biocompatible functional group (BFG) on a PLA polymer, wherein the BFG is at one or both ends of the polymer backbone or in the polymer backbone;
wherein the modified polylactide polymer is according to one of the following formulae:
polylactide polymer-BFG3-polylactide polymer,
BFG1-polylactide polymer-BFG3-polylactide polymer-BFG2,
BFG1-polylactide polymer-BFG3-polylactide polymer,
polylactide polymer-BFG3-polylactide polymer-BFG2;

wherein
BFG1 and BFG2 are independently selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH═CH 2 , —CH═CH 2 CH 3 ,

wherein y is an integer ranging from 0 to 4 inclusive, and z is an integer ranging from 0 to 15 inclusive;
BFG3 is selected from the group consisting of

wherein p is an integer ranging from 0 to 3 inclusive, q is an integer ranging from 3 to 0 inclusive, provided p+q=3; and
wherein the molecular weight of the polylactide polymer is from about 2,000 Daltons to about 2,000,000 Daltons.

2. The modified polylactide polymer of claim 1 , wherein the PLA polymer is a homopolymer of lactide or a copolymer of lactide and at least one monomer.

3. The modified polylactide polymer of claim 2 , wherein the at least one monomer is a hydroxy alkanoate monomer selected from the group consisting of glycolic acid, 3-hydroxypropanoate, 3-hydroxybutyrate, 3-hydroxyvalerate, 3-hydroxyhexanoate, 3-hydroxyheptanoate, 3-hydroxyoctanoate, 4-hydroxybutyrate, 4-hydroxyvalerate, 4-hydroxyhexanote, 4-hydroxyheptanoate, and 4-hydroxyoctanoate.

4. The modified polylactide polymer of claim 1 , wherein the PLA polymer is selected from the group consisting of poly(L-lactide), poly(D-lactide), poly(D,L-lactide), poly(L-lactide-co-D,L-lactide), poly(D-lactide-co-D,L-lactide), poly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide), poly(L-lactide-co-caprolactone), poly(D-lactide-co-caprolactone), poly(L-lactide-co-trimethylene carbonate), poly(D-lactide-co-trimethylene carbonate), poly(D,L-lactide-co-glycolide), poly(D,L-lactide-co-caprolactone), poly(D,L-lactide-co-trimethylene carbonate), a combination thereof, and a blend thereof.

5. The modified polylactide polymer of claim 1 , comprising a structure according to the following formula:

wherein
m and n are independently a positive integer.

6. The modified polylactide polymer of claim 1 , comprising, in part, a structure according to the following formula:

wherein
m and n are independently a positive integer,
x is an integer ranging from 1 to 5 inclusive,
p is an integer ranging from 0 to 3 inclusive, q is an integer ranging from 3 to 0, provided p+q=3.

7. A modified polylactide polymer conjugate produced by reacting the biocompatible functional group of the modified polylactide polymer of claim 1 with a therapeutic agent, a diagnostic agent, a hydrophilic component, a hydrophobic component, or a combination thereof.

8. The modified polylactide polymer conjugate of claim 7 , wherein the therapeutic agent is selected from the group consisting of paclitaxel, rapamycin, rapamycin derivative, everolimus, zotarolimus, temsirolimus, deforolimus, merilimus, novolimus, myolimus, umirolimus, biolimus, tacrolimus, pimecrolimus, 16-pent-2-ynyloxy-32(S)-dihydro-rapamycin, and ridaforolimus.

9. The modified polylactide polymer conjugate of claim 7 , wherein the diagnostic agent is a radiocontrast agent.

10. The modified polylactide polymer conjugate of claim 7 , wherein the hydrophilic component is selected from the group consisting of poly(ethylene glycol) (PEG), a copolymer of PEG, a polymer of hydroxyethyl methacrylate (HEMA), a polymer of hydroxypropyl methacrylate (HPMA), a polymer of hydroxypropyl methacrylamide, a polymer 2-methacryloyloxyethylphosphorylcholine (MPC), a polymer of methacrylic acid (MA), a polymer of acrylic acid (AA), a polymer of alkoxymethacrylate, a polymer of alkoxyacrylate, polymer of 3-trimethylsilylpropyl methacrylate (TMSPMA), a polymer of vinyl alcohol, a polymer of allyl alcohol, a polymer of N-vinyl pyrrolidone (VP), a copolymer of HEMA, a copolymer of HPMA, a copolymer of hydroxypropyl methacrylamide, a copolymer MPC, a copolymer of MA, a copolymer of AA, a copolymer of alkoxymethacrylate, a copolymer of alkoxyacrylate, a copolymer of TMSPMA, a copolymer of vinyl alcohol, a copolymer of allyl alcohol, a copolymer of VP, collagen, chitosan, alginate, fibrin, fibrinogen, cellulose, starch, dextran, dextrin, hyaluronic acid, fragments of hyaluronic acid, derivatives of hyaluronic acid, heparin, fragments of heparin, derivatives of heparin, glycosamino glycan (GAG), GAG derivatives, polysaccharide, elastin, and combinations thereof.

11. The modified polylactide polymer conjugate of claim 7 , wherein the hydrophobic component is selected from the group consisting of saturated fatty acids, unsaturated fatty acids, saturated fatty alcohols, unsaturated fatty alcohols, and hydrophobic polymers.

12. A polymer blend comprising the modified polylactide polymer according to claim 1 .

13. The polymer blend of claim 12 , further comprising poly(L-lactide), poly(L-lactide-co-caprolactone), or a combination thereof.

14. An implantable medical device comprising a device body and optionally a coating, wherein the device body or the coating comprises the modified polylactide polymer according to claim 1 .

15. The implantable medical device of claim 14 , which is a stent.

16. The implantable medical device of claim 14 , which is a bioabsorbable stent.

17. The implantable medical device of claim 14 , wherein the device body or the coating further comprises a therapeutic agent.

18. An implantable medical device comprising a device body and optionally a coating, wherein the device body or the coating comprises the modified polylactide polymer conjugate according to claim 7 .

19. An implantable medical device comprising a device body and optionally a coating, wherein the device body or the coating comprises the polymer blend according to claim 12 .

Assignees

• Abbott Cardiovascular Systems Inc

Inventors

• Pacetti Stephen
• Tang Fuh-Wei
• Ma Xiao
• Ding Ni
• Mortisen Derek

Classifications

• C08G63/912 Primary

  derived from hydroxycarboxylic acids · CPC title

• B29C2035/0877

  using electron radiation, e.g. beta-rays · CPC title

• B29C2035/085

  using gamma-ray · CPC title

• B29B13/08

  by using wave energy or particle radiation · CPC title

• A61F2/91

  made from perforated sheets or tubes, e.g. perforated by laser cuts or etched holes · CPC title