Degradable thiol-ene polymers

• US 8,859,716 B2
• Filed: 07/25/2013
• Issued: 10/14/2014
• Est. Priority Date: 10/10/2001
• Status: Active Grant

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Bowman, Christopher, Anseth, Kristi, Hacioglu, Bilge, Nuttelman, Charlie
• Primary Examiner(s): ZIMMER, MARC S
• Application Number:
  US13/951,268
• Publication Number:
  US 20140039085A1
• Time in Patent Office: 446 Days
• Field of Search: None
• US Class Current: 528/376
• CPC Class Codes: A01N 25/04 Dispersions, emulsions, suspoemulsions, suspension concentrates or gels foams A01N25/16
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61L 2300/62 Encapsulated active agents, e.g. emulsified droplets
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C05G 5/23 Solutions
• CPC Class Codes: C05G 5/37 layered or coated with a polymer
• CPC Class Codes: C08G 2261/126 block
• CPC Class Codes: C08G 75/045 from mercapto compounds and unsaturated compounds
• CPC Class Codes: C08G 81/00 Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers involving only carbon-to-carbon unsaturated bond reactions C08F299/00 ; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42
• CPC Class Codes: C08G 81/025 containing polyether sequences
• CPC Class Codes: C08G 81/027 containing polyester or polycarbonate sequences
• CPC Class Codes: C08J 2329/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08J 2367/04 Polyesters derived from hydroxy carboxylic acids, e.g. lactones C08J2367/06 takes precedence
• CPC Class Codes: C08J 2371/02 Polyalkylene oxides
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08L 2205/05 containing polymer components which can react with one another
• CPC Class Codes: C08L 2666/22 : Macromolecular compounds not provided for in C08L2666/16 - C08L2666/20
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C08L 81/02 : Polythioethers; Polythioether-ethers
• CPC Class Codes: C08L 83/00 : Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 89/00 : Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10S 524/916 : Hydrogel compositions
• CPC Class Codes: Y10S 525/936 : Encapsulated chemical agent

Abstract

A thiol-ene polymeric material is disclosed. The material is produced by the photopolymerization of reactants having thiol and olefin moieties. The material can incorporate encapsulated components, including cells. Additionally, the material can be derivatized by reacting the polymeric material with components such as proteins.

Claims

1. A hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer comprising a —

C—

C—

moiety derived from an olefinic portion of a norbornene moiety.

2. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 1, wherein the —

C—

C—

moiety derived from an olefinic portion of a norbornene moiety is linked to a polymeric moiety selected from the group consisting of poly(lactic acid) (PLA);

polyglycolide (PGA);

a copolymer of PLA and PGA (PLGA);

poly(vinyl alcohol) (PVA);

poly(ethylene glycol) (PEG);

poly(ethylene oxide);

a poly(ethylene oxide)-co-poly(propylene oxide) block copolymer;

a poloxamine;

a polyanhydride;

a polyorthoester;

a poly(hydroxy acids);

a polydioxanone;

a polycarbonate;

a polyaminocarbonate;

a poly(vinyl pyrrolidone);

a poly(ethyl oxazoline);

a carboxymethyl cellulose;

a hydroxyalkylated cellulose;

a polypeptide;

a polysaccharide;

a carbohydrate;

heparan sulfate;

chondroitin sulfate;

heparin, alginate; and

a combination thereof.

3. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 1, wherein the —

C—

C—

moiety derived from an olefinic portion of a norbornene moiety is bound to a sulfur atom derived from a thiol moiety to provide a moiety of the formula —

S—

C≡

C—

.

4. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 3, wherein the sulfur atom derived from a thiol moiety is linked to a polymeric moiety selected from the group consisting of poly(lactic acid) (PLA);

polyglycolide (PGA);

a copolymer of PLA and PGA (PLGA);

poly(vinyl alcohol) (PVA);

poly(ethylene glycol) (PEG);

poly(ethylene oxide);

a poly(ethylene oxide)-co-poly(propylene oxide) block copolymer;

a poloxamine;

a polyanhydride;

a polyorthoester;

a poly(hydroxy acids);

a polydioxanone;

a polycarbonate;

a polyaminocarbonate;

a poly(vinyl pyrrolidone);

a poly(ethyl oxazoline);

a carboxymethyl cellulose;

a hydroxyalkylated cellulose;

a polypeptide;

a polysaccharide;

a carbohydrate;

heparan sulfate;

chondroitin sulfate;

heparin, alginate; and

a combination thereof.

5. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 3, wherein sulfur atom is derived from a branched thiol moiety.

6. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 1, further comprising at least one biologically active component encapsulated within the polymer.

7. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 6, wherein the biologically active component is selected from the group consisting of cells, tissues, and tissue aggregates.

8. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 6, wherein the biologically active component is selected from the group consisting of chondrocytes, immortalized cell lines, stem cells, hormone-producing cells and fibroblasts.

9. The hydrogel comprising a biocompatible crosslinked degradable thiol-ene polymer of claim 1, further comprising at least one pharmacologically active agent encapsulated within the polymer.

10. The hydrogel comprising a biocompatible cross-linked degradable thiol-ene polymer of claim 1, wherein the polymer is derivatized with a functional molecule selected from the group consisting of adhesion peptides, growth factors, hormones, antihormones, signaling compounds, serum proteins, albumins, macroglobulins, globulins, agglutinins, lectins, antibodies, antigens, enzymes and extracellular matrix proteins.

11. The hydrogel comprising a biocompatible cross-linked degradable thiol-ene polymer of claim 1, wherein the polymer comprises a segment selected from the group consisting of a moiety of poly(lactic acid) (PLA), polyglycolide (PGA), copolymers of PLA and PGA (PLGA), poly(vinyl alcohol)(PVA), poly(ethylene glycol)(PEG), poly(ethylene oxide), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers, polyoxamines, polyanhydrides, polyorthoesters, poly(hydroxyl acids), polydioxanones, polycarbonates, polyaminocarbonates, poly(vinyl pyrrolidone), poly(ethyl oxazoline), carboxymethyl cellulose, a hydroxyalkylated cellulose, a polypeptide, a polysaccharide, a carbohydrate, heparin sulfate, chondroitin sulfate, heparin, alginate, gelatin, collagen, albumin and ovalbumin.

12. The hydrogel comprising a biocompatible cross-linked degradable thiol-ene polymer of claim 11, wherein the segment has a molecular weight ranging from about 30 Da to about 50,000 Da.

13. The hydrogel comprising a biocompatible cross-linked degradable thiol-ene polymer of claim 11, wherein the segment is biodegradable.

14. The hydrogel comprising a biocompatible cross-linked degradable thiol-ene polymer of claim 11, wherein the polymer comprises a PLA, PVA or PEG segment.