Biodegradable photoluminescent polymers

• US 9,611,354 B2
• Filed: 09/24/2015
• Issued: 04/04/2017
• Est. Priority Date: 06/20/2008
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Yang, Jian, Gautam, Santosh
• Primary Examiner(s): Choi, Ling
• Assistant Examiner(s): Mesh, Gennadiy
• Application Number:
  US14/863,889
• Publication Number:
  US 20160075822A1
• Time in Patent Office: 558 Days
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/3891 as distinct cell layers
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: C08F 283/00 Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
• CPC Class Codes: C08F 283/006 on to polymers provided for in C08G18/00 C08F283/004 takes precedence
• CPC Class Codes: C08F 289/00 Macromolecular compounds obtained by polymerising monomers on to macromolecular compounds not provided for in groups C08F251/00 - C08F287/00
• CPC Class Codes: C08F 290/00 Macromolecular compounds obtained by polymerising monomers on to polymers modified by introduction of aliphatic unsaturated end or side groups
• CPC Class Codes: C08G 18/4236 containing only aliphatic groups
• CPC Class Codes: C08G 18/4283 Hydroxycarboxylic acid or ester
• CPC Class Codes: C08G 18/4646 containing one nitrogen atom in the ring
• CPC Class Codes: C08G 18/4676 containing sulfur
• CPC Class Codes: C08G 18/73 acyclic
• CPC Class Codes: C08G 2230/00 Compositions for preparing biodegradable polymers
• CPC Class Codes: C08G 63/6854 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08G 63/6858 Polycarboxylic acids and polyhydroxy compounds in which at least one of the two components contains aliphatic unsaturation
• CPC Class Codes: C08G 63/914 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08J 2367/04 Polyesters derived from hydroxy carboxylic acids, e.g. lactones C08J2367/06 takes precedence
• CPC Class Codes: C08J 5/18 Manufacture of films or sheets
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0691 : Vascular smooth muscle cells; 3D culture thereof, e.g. models of blood vessels

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.

Claims

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.