Biodegradable photoluminescent polymers

Patent metadata

Field	Value
Publication number	US-9611354-B2
Application number	US-201514863889-A
Country	US
Kind code	B2
Filing date	Sep 24, 2015
Priority date	Jun 20, 2008
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

Biodegradable photoluminescent polymer (BPLP) which comprises an oligomer synthesized from a multifunctional monomer, a diol, and an amino acid by reacting (i) a multifunctional monomer comprising citric acid or triethyl citrate with (ii) a diol to form a reaction product, and further reacting the reaction product with (iii) an amino acid, wherein the amino acid is linked as a side group to the oligomer backbone. The BPLP of the present invention poses tunable fluorescence emission characteristics and are cell-compatible and biodegradable. The BPLP can serve as both implant materials and bioimaging probes.

First claim

The invention claimed is:

1. A polymer composition comprising:
an oligomer synthesized from monomers comprising (i) a multifunctional monomer comprising citric acid or triethyl citrate, (ii) a diol, and (iii) an amino acid, wherein the amino acid is linked as a side group to the oligomer backbone.

2. The composition of claim 1 , wherein the diol is selected from 1,8-octanediol, ethylene glycol, propylene glycol, poly(ethylene glycol), polypropylene glycol), 1,3-propanediol, ethanediol, and cis-1,2-cyclohexanediol.

3. The composition of claim 1 , wherein the amino acid comprises alanine, arginine, asparagine, aspartic acid, cysteine, glycine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, threonine, tyrosine, tryptophan, valine, or a combination thereof.

4. The composition of claim 1 , wherein the amino acid comprises an L-amino acid, D-amino acid, D,L-amino acid, or a derivative thereof.

5. The composition of claim 1 , wherein an acid anhydride or a multifunctional acid chloride is used in addition to the citric acid or triethyl citrate.

6. The composition of claim 1 , wherein maleic acid, maleic anhydride, fumaric acid, fumaryl chloride, acryloylchloride, itaconic acid, or allylmalonic acid is used in addition to the citric acid or triethyl citrate.

7. The composition of claim 1 , wherein the oligomer is crosslinked.

8. A composition comprising:
an oligomer synthesized from monomers comprising (i) a multifunctional monomer comprising citric acid or triethyl citrate, (ii) a diol, (iii) an amino acid, and (iv) a di-isocyanate wherein the amino acid is linked as a side group to the oligomer backbone.

9. The composition of claim 8 , wherein the multifunctional monomer comprises citric acid.

10. The composition of claim 8 , wherein the diol is selected from 1,8-octanediol, ethylene glycol, propylene glycol, poly(ethylene glycol), poly(propylene glycol), 1,3-propanediol, ethanediol, and cis-1,2-cyclohexanediol.

11. The composition of claim 8 , wherein the amino acid comprises alanine, arginine, asparagine, aspartic acid, cysteine, glycine, glutamine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, proline, phenylalanine, serine, threonine, tyrosine, tryptophan, valine, or a combination thereof.

12. The composition of claim 8 , wherein the amino acid comprises an L-amino acid, D-amino acid, D,L-amino acid, or a derivative thereof.

13. The composition of claim 8 , wherein the multifunctional monomer comprises citric acid, the diol comprises 1,8-octanediol, the amino acid comprises cysteine or serine, and the di-isocyanate comprises hexamethylene-1,6-di-isocyanate or 1,4-butane-di-isocyanate.

14. A method of making a crosslinked urethane-doped biodegradable photoluminescent polyester (CUBPLP) comprising:
mixing (i) a multifunctional monomer comprising citric acid or triethyl citrate and (ii) a diol to form a mixture;
raising the temperature of the mixture to melt the mixture;
lowering the temperature of the mixture with stirring to form an oligomer;
adding an amino acid to the oligomer with stirring to form a pre-BPLP-amino acid;
purifying the pre-BPLP-amino acid;
dissolving the purified pre-BPLP-amino acid to form a solution;
adding a di-isocyanate to the pre-BPLP-amino acid solution to form a pre-CUBPLP (UBPLP);
casting a film of the pre-CUBPLP (UBPLP); and
drying the pre-CUBPLP (UBPLP) film to obtain the CUBPLP.

15. The method of claim 14 , wherein the diol is selected from 1,8-octanediol, ethylene glycol, propylene glycol, poly(ethylene glycol), poly(propylene glycol), 1,3-propanediol, ethanediol, and cis-1,2-cyclohexanediol.

16. The method of claim 14 , wherein the multifunctional monomer comprises citric acid, the diol comprises 1,8-octanediol, the amino acid comprises cysteine or serine, and the di-isocyanate comprises hexamethylene-1,6-di-isocyanate or 1,4-butane-di-isocyanate.

17. The method of claim 14 , wherein purifying the pre-BPLP-amino acid comprises:
adding the pre-BPLP-amino acid to deionized water;
collecting an undissolved pre-BPLP-amino acid portion from the deionized water; and
lyophilizing the collected pre-BPLP-amino acid to obtain purified pre-BPLP-amino acid.

18. The method of claim 14 , wherein dissolving the purified pre-BPLP-amino acid to form a solution comprises dissolving the purified pre-BPLP-amino acid in 1,4-dioxane.

19. The method of claim 14 , wherein the film of the pre-CUBPLP (UBPLP) is cast in a laminar airflow.

20. The method of claim 14 , wherein forming the pre-BPLP-amino acid solution further comprises adding one or more catalysts to the solution, the one or more catalysts being selected from tin octanoate, dibutyl tin dilaurate, and 1,4-diazabicyclo[2.2.2]octane.

Assignees

• Univ Texas

Inventors

• Yang Jian
• Gautam Santosh

Classifications

• C08G63/914 Primary

  derived from polycarboxylic acids and polyhydroxy compounds · CPC title

• C08G63/6854

  derived from polycarboxylic acids and polyhydroxy compounds · CPC title

• A61L27/50

  Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} · CPC title

• C08J2367/04

  Polyesters derived from hydroxy carboxylic acids, e.g. lactones (C08J2367/06 takes precedence) · CPC title

• C12N5/0691

  Vascular smooth muscle cells; 3D culture thereof, e.g. models of blood vessels · CPC title