Biodegradable poly(ester amide) elastomers and uses therefor

Patent metadata

Field	Value
Publication number	US-10039858-B2
Application number	US-201615227187-A
Country	US
Kind code	B2
Filing date	Aug 3, 2016
Priority date	Aug 3, 2015
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

Provided herein are biodegradable poly(ester amide) elastomers, methods of making the elastomers, and methods of using the elastomers, for example for tissue engineering. The elastomers can be used for preparation of tissue prostheses, such as a heart valve leaflet, a heart valve, cartilage, myocardium, blood vessels, smooth muscle, skeletal muscle, or other tissues. Also provided herein are semiquantitative FTIR methods for determining structure of a poly(ester amide) elastomer.

First claim

We claim:

1. A polymer composition comprising a copolymer comprising residues of polyethylene glycol, glycerol, sebacic acid, and 1,3-diamino-2-hydroxy-propane, wherein the feed ratios of sebacic acid:glycerol:DAHP:PEG are (2.5-3.5):(0.5 to 1.2):(1.2 to 1.7):(0.45 to 1.26).

2. The polymer composition of claim 1 , wherein the polyethylene glycol has a M n of from 200D (Daltons) to 10 kD (kiloDaltons).

3. The polymer composition claim 1 , wherein the molar feed percentage of the polyethylene glycol to the sebacic acid ranges from 15% to 40%.

4. The polymer composition of claim 1 , wherein the polyethylene glycol has a Mn of from 400D to 4 kD, and the feed percentage of polyethylene glycol to sebacic acid ranges from 15% to 40%.

5. The polymer composition of claim 1 , having a Mn of from 3 kD to 10 kD and/or a polydispersity index of less than 2.

6. The polymer composition of claim 1 , further comprising an active agent.

7. The polymer composition of claim 6 , wherein the active agent is an antioxidant.

8. The polymer composition of claim 7 , wherein the active agent is a cerium nanoparticle.

9. A method of preparing a biocompatible elastomer copolymer, comprising:
a. condensing in a reaction mixture a sebacic acid with a polyethylene glycol to produce a first product; and
b. adding glycerol and 1,3-diamino-2-hydroxy-propane to the reaction mixture and condensing the first product with the glycerol and 1,3-diamino-2-hydroxy-propane (DAHP) to produce the elastomer copolymer, wherein the feed ratios of sebacic acid:glycerol:DAHP:PEG are (2.5-3.5):(0.5 to 1.2):(1.2 to 1.7):(0.45 to 1.26).

10. The method of claim 9 , wherein the feed molar ratio of the sebacic acid ranges between 90% and 110% of the sum of the feed molar ratios of the polyethylene glycol, the glycerol, and the DAHP in the reaction mixture.

11. The method of claim 9 , wherein the feed molar ratio of the polyethylene glycol is between 15% and 40% of the feed molar ratio of the sebacic acid.

12. The method of claim 9 , wherein the molar ratio of the DAHP is between 1- and 3-times the molar ratio of the glycerol.

13. The method of claim 9 , wherein the polyethylene glycol has a Mn of from 200D to 10 kD.

14. The method of claim 9 , wherein the condensation is performed by heating the reaction mixture in an inert atmosphere, e.g. argon, optionally under reduced (less than atmospheric, e.g., less than 0.001 atm (atmosphere), e.g., 300 mTorr) pressure.

15. A method of culturing cells, comprising placing a composition of claim 1 in a suitable cell growth medium; contacting cells with the composition;
and culturing cells under conditions suitable for cell growth.

16. A tissue prosthesis comprising the polymer composition of claim 1 .

17. The tissue prosthesis of claim 16 , comprising at least a heart valve leaflet with anisotropic fiber orientation.

18. The polymer composition of claim 1 , wherein the feed ratio of sebacic acid:glycerol:DAHP:PEG is 3:0.85:1.7:0.45.

19. The polymer composition of claim 1 , wherein the feed ratio of sebacic acid:glycerol:DAHP:PEG is 3:0.75:1.5:0.75.

20. The polymer composition of claim 1 , wherein the feed ratio of sebacic acid:glycerol:DAHP:PEG is 3:0.6:1.2:1.2.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education
• Univ Of Pittsburgh—Of The Commonweatlh System Of Higher Education

Inventors

• Sant Shilpa
• Sant Vinayak

Classifications

• A61L27/18 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• C08G69/48

  Polymers modified by chemical after-treatment · CPC title

• A61L2430/20

  for reconstruction of the heart, e.g. heart valves · CPC title

• C08G2230/00

  Compositions for preparing biodegradable polymers · CPC title

• A61L2300/102

  Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates · CPC title