Injectable scaffold composition

• US 10,195,309 B2
• Filed: 02/01/2008
• Issued: 02/05/2019
• Est. Priority Date: 02/01/2007
• Status: Active Grant

• Current Assignee: Locate Therapeutics Limited
• Original Assignee: Locate Therapeutics Limited
• Inventors: Ginty, Patrick, Quirk, Robin Andrew, Shakesheff, Kevin Morris
• Primary Examiner(s): Yoon, Tae H
• Application Number:
  US12/525,195
• Publication Number:
  US 20100063175A1
• Time in Patent Office: 4,022 Days
• Field of Search: 523113, 424501, 524537, 514785
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• 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 27/502 Plasticizers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

A composition comprising polymer particles and a carrier, wherein the polymer particles are a mixture of at least a first polymer and a second polymer, wherein the first polymer is at least partially soluble or dispersible in the carrier, and wherein the polymer particles are arranged such that they can join together to form a scaffold of polymer particles, and wherein the composition is administrable to a human or non-human animal.

Claims

1. An injectable composition administrable to a human or non-human animal consisting of polymer particles capable of cross-linking and an aqueous carrier, wherein the polymer particles consist of a first polymer and a second polymer,

wherein the first polymer is a plasticizer having a molecular weight of 800 Da or less and is soluble or dispersible in the carrier, such that 1 wt % or more of the first polymer will leach into the carrier within 20 hours at 25°

C. immediately after combining the first and second polymers with the carrier,

wherein the second polymer is an amorphous or semi-crystalline polymer,

wherein the amount of the first polymer present in the polymer particles is from 1 to 20% by weight and the ratio of polymer to carrier is from 4;

1 to 1;

4,

wherein the polymer particles have a glass transition temperature lower than the glass transition temperature of the second polymer on its own,

wherein the polymer particles cross-link in vivo by one or more of fusion, adhesion, cohesion, and entanglement to form a scaffold of polymer particles; and

wherein removal of the first polymer from the scaffold of polymer particles in vivo by leaching results in a hardened scaffold structure.

2. The composition of claim 1, wherein the polymer particles have a glass transition temperature of 45°

C. or less.

3. The composition of claim 2, wherein the polymer particles have a glass transition temperature of 37°

C. or less and wherein the glass transition temperature of the polymer particles is lower than the glass transition temperature of the second polymer particle on its own.

4. The composition of claim 1, wherein the plasticizer having a molecular weight of 800 Da or less is selected from the group consisting of:

polyethylene glycol (PEG), poly(propylene adipate) (PPA), polyt(butylene adipate) (PBA), poly lactic acid (PLA), polyglycolic acids (PGA), poly(D,Lvlactide-co-glycolide)(PLGA), poly propylene glycol, poly capralactone, polyethylene glycol polypropylene block co-polymers.

5. The composition of claim 4, wherein the plasticizer having a molecular weight of 800 Da or less is PEG.

6. The composition of claim 5, wherein the plasticiser is PEG having a molecular weight of 400 Da or less.

7. The composition of claim 1, wherein the amount of the first polymer present in the polymer particles is from 3% to 10% by weight.

8. The composition of claim 1, wherein the second polymer is selected from the group comprising poly lactic acid (PLA), polyglycolic acids, poly(D,L-Iactide-co-glycolide)(PLGA), poly D,L-Iactic acid (PDLLA), poly-Iactide poly-glycolide copolymers and combinations thereof.

9. The composition of claim 7, wherein the first polymer is PEG and the second polymer is PLGA.

10. A kit for use in producing a tissue scaffold comprising a composition according to claim 1, instructions to use the composition, and optionally further comprising a syringe for use in injecting the composition.

11. A method of producing a scaffold in vivo in a human or non-human animal, comprising:

(a) administering an injectable composition according to claim 1 to a human or non-human animal.

12. The method of claim 11, wherein the polymer particles have a glass transition temperature of 45°

C. or less.

13. The method of claim 12, wherein the polymer particles have a glass transition temperature of 37°

C. or less and wherein the glass transition temperature of the polymer particles is lower than the glass transition temperature of the second polymer particle on its own.

14. The method of claim 11, wherein the plasticizer having a molecular weight of 800 Da or less is selected from the group consisting of:

polyethylene glycol (PEG), poly(propylene adipate) (PPA), polyt(butylene adipate) (PBA), poly lactic acid (PLA), polyglycolic acids (PGA), poly(D,Lvlactide-co-glycolide)(PLGA), poly propylene glycol, poly capralactone, polyethylene glycol polypropylene block co-polymers.

15. The method of claim 14, wherein the plasticizer having a molecular weight of 800 Da or less is PEG.

16. The method of claim 15, wherein the plasticiser is PEG having a molecular weight of 400 Da or less.

17. The method of claim 11, wherein the amount of the first polymer present in the polymer particles is from 3% to 10% by weight.

18. The method of claim 11, wherein the second polymer is selected from the group comprising poly lactic acid (PLA), polyglycolic acids, poly(D,L-Iactide-co-glycolide)(PLGA), poly D,L-Iactic acid (PDLLA), poly-Iactide poly-glycolide copolymers and combinations thereof.

19. The method of claim 17, wherein the first polymer is PEG and the second polymer is PLGA.