FLOWABLE FORMULATIONS FOR TISSUE REPAIR AND REGENERATION

• US 20130096064A1
• Filed: 10/09/2012
• Published: 04/18/2013
• Est. Priority Date: 10/07/2011
• Status: Active Grant

• Current Assignee: Olaregen Therapeutix, Inc. (Generex Biotechnology Corp.)
• Original Assignee: Tissue Repair Company
• Inventors: Chandler, Lois
• Granted Patent: US 9,782,457 B2
• Time in Patent Office: Days
• US Class Current: 514/17.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 36/39 Convolvulaceae (Morning-glory family), e.g. bindweed
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 26/0033 Collagen
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 27/24 Collagen

Abstract

The present invention relates generally to flowable tropocollagen formulations and uses of such formulations for promoting healing and tissue repair and/or regeneration in wounds induced by, for example, trauma or injury, a disease state, bed sores or other pressure ulcers, or surgery.

Claims

1. A formulation comprising (i) a tropocollagen, (ii) at least one adjuvant, and (iii) a physiologically acceptable excipient, wherein said formulation is a selectively flowable colloid.

2. A formulation according to claim 1, wherein the tropocollagen is an atelopeptide renatured tropocollagen.

3. A formulation according to claim 1, wherein the tropocollagen is non-aggregated and is dispersed within the excipient to form a homogeneous dispersion.

4. A formulation according to claim 1, wherein the formulation at a temperature of approximately 15°

C. exhibits sufficient flow to be extruded through a syringe, cannula, applicator tip, or any device used to deliver a colloid to a wound.

5. A formulation according to claim 1, wherein at least one adjuvant is a structural modulator.

6. A formulation according to claim 5, wherein the structural modulator is a tropocollagen stabilizer.

7. A formulation according to claim 6, wherein the tropocollagen stabilizer is a polyol.

8. A formulation according to claim 5, wherein the structural modulator is a formulation modulator.

9. A formulation according to claim 1, wherein the tropocollagen is capable of promoting the release of PDGF by platelets.

10. A formulation according to claim 1, wherein at least one adjuvant is an enhancer.

11. A formulation according to claim 10, wherein the enhancer is an antimicrobial agent.

12. A formulation according to claim 10, wherein the enhancer is an MMP inhibitor.

13. A formulation according to claim 12, wherein the MMP inhibitor is a zinc chelating agent.

14. A formulation according to claim 1, wherein the formulation is sterile.

15. A formulation according to claim 1, wherein the tropocollagen is bovine type I tropocollagen.

22. A device comprising a formulation according to claim 1.

23. A device of claim 22, wherein the device is a syringe barrel containing the formulation.

24. A kit comprising a device of claim 22, further comprising instructions for use of the device in the treatment of a wound.

25. A method of preparing a formulation according to claim 1, comprising the following steps:

(i) a collagen grindate is denatured and solubilized in a first solution resulting in a solubilized collagen in solution, (ii) a renaturing agent is added to the solubilized collagen in solution resulting in the formation of renatured tropocollagen, (iii) the renatured tropocollagen is dispersed in a pharmaceutically acceptable excipient.

26. A method of claim 25, wherein the first solution is an acidic solution comprising pepsin, wherein the renaturing agent is a base added to the solution to increase the pH to neutral range and the solution is mixed to allow renatured tropocollagen to form, and wherein the renatured tropocollagen is isolated from the solution by centrifugation before being dispersed in a pharmaceutically acceptable excipient.

27. A method of claim 25, wherein the tropocollagen formulation is approximately 2.6% bovine atelopeptide tropocollagen in the form of a selectively flowable sol.

16. A use of a selectively flowable colloid formulation comprising (i) a tropocollagen, (ii) at least one adjuvant, and (iii) a physiologically acceptable excipient, for treating a wound.

17. A use according to claim 16, wherein the tropocollagen is an atelopeptide renatured tropocollagen.

18. A method of treating a wound comprising applying to the wound a selectively flowable formulation comprising (i) a tropocollagen, (ii) at least one adjuvant, and (iii) a physiologically acceptable excipient.

19. A method according to claim 18, wherein the tropocollagen is an atelopeptide tropocollagen.

20. A method according to claim 18, wherein the tropocollagen is capable of promoting the release of PDGF by platelets.

21. A method according to claim 18, wherein the wound is selected from the group consisting of a traumatic injury wound,

a diseased state, an iatrogenic wound, a soft tissue wound, a chronic wound, a diabetic foot ulcer.