Crosslinked hyaluronic acid-collagen gels for improving tissue graft viability and soft tissue augmentation

Patent metadata

Field	Value
Publication number	US-9782517-B2
Application number	US-201715494991-A
Country	US
Kind code	B2
Filing date	Apr 24, 2017
Priority date	Sep 6, 2011
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

Hydrogels comprising a macromolecular matrix and water may be used to augment soft tissue of a human being, promote or support cell or tissue viability or proliferation, create space in tissue, and for other purposes. A macromolecular matrix may comprise a hyaluronic acid component crosslinked to a collagen component.

First claim

What is claimed is:

1. A method of grafting fat in a human subject, the method comprising administering a composition to a soft tissue of the subject, wherein the composition comprises:
(i) a hydrogel comprising:
(a) water; and
(b) a crosslinked macromolecular matrix comprising hyaluronic acid crosslinked to collagen via a plurality of crosslink units, wherein at least a portion of the crosslink units comprise an amide bond; and the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the collagen of 1:1 to 7:1;

wherein said hydrogel has a hyaluronic acid concentration of 6 mg/mL to 21 mg/mL, a collagen concentration of 3 mg/mL to 12 mg/mL, and a storage modulus value of between 850 Pa and 5,000 Pa; and
(ii) a fat component, comprising adipose tissue, adipocytes, or both, wherein the fat component has been explanted from the human subject;

thereby increasing the volume of fat in the soft tissue of the subject.

2. The method of claim 1 , wherein the administration of the composition results in an increase in fat graft volume retention as compared to administering the fat component alone.

3. The method of claim 2 , wherein the administration of the composition reduces variability in the retained fat graft volume as compared to administering the fat component alone.

4. The method of claim 1 , wherein the hyaluronic acid is crosslinked to the collagen using a coupling agent which is not part of the crosslink unit.

5. The method of claim 1 , wherein the composition has a fat: hydrogel weight ratio of 1:1 to 5:1.

6. The method of claim 1 , wherein the hydrogel has a storage modulus value of between 1,000 Pa and 4,000 Pa.

7. The method of claim 1 , wherein the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the collagen of 1:1 to 2:1.

8. The method of claim 1 , wherein the hydrogel has a collagen concentration of greater than or equal to 6 mg/mL.

9. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of at least 9 mg/mL.

10. The method of claim 1 , wherein the hydrogel has a collagen concentration of 6 mg/mL, 8 mg/mL or 12 mg/mL.

11. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 6 mg/mL.

12. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 12 mg/mL.

13. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of 16 mg/mL and a collagen concentration of 8 mg/mL.

14. The method of claim 1 , wherein the hydrogel has a hyaluronic acid concentration of at least 9 mg/mL and a collagen concentration of greater than or equal to 6 mg/m L.

15. The method of claim 1 , wherein the hyaluronic acid is crosslinked to the collagen using hyaluronic acid having a molecular weight of 1,000,000 to 5,000,000 daltons.

16. The method of claim 1 , wherein the hyaluronic acid is crosslinked to the collagen using hyaluronic acid having a molecular weight of 1,000,000 daltons to 3,000,000 daltons.

17. The method of claim 1 , wherein the collagen is porcine or human collagen type I.

18. The method of claim 1 , wherein the administering comprises injecting or implanting the composition into the soft tissue of the subject.

19. The method of claim 1 , wherein the fat component contains adipocytes, and wherein the administration of the composition enhances adipocyte proliferation as compared to administering adipocytes alone.

20. The method of claim 1 , wherein the fat component contains adipose tissue, and wherein the administration of the composition enhances adipose tissue growth as compared to administering adipose tissue alone.

21. A method of grafting fat in a soft tissue of a human subject, the method comprising:
(i) injecting a hydrogel component into the soft tissue of the subject, wherein the hydrogel component comprises:
(a) water; and
(b) a crosslinked macromolecular matrix comprising hyaluronic acid crosslinked to collagen via a plurality of crosslink units, wherein at least a portion of the crosslink units comprise an amide bond; and the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the collagen of 1:1 to 7:1;

wherein said hydrogel component has a hyaluronic acid concentration of 6 mg/mL to 21 mg/mL, a collagen concentration of 3 mg/mL to 12 mg/mL, and a storage modulus value of between 850 Pa and 5,000 Pa; and
(ii) administering a fat component to the soft tissue of the subject, wherein the fat component contains adipose tissue, adipocytes, or both, and wherein the fat component has been explanted from the human subject;
thereby increasing the volume of fat in the soft tissue of the subject.

22. The method of claim 21 , wherein the injection of the hydrogel component and the administration of the fat component to the soft tissue is performed sequentially.

23. The method of claim 22 , wherein the injection of the hydrogel component to the soft tissue precedes the administration of the fat component to the soft tissue.

24. The method of claim 21 , wherein the fat component is injected into the soft tissue.

25. The method of claim 24 , wherein the hydrogel component is contacted with the fat component prior to the injection to provide a single composition, which is injected into the soft tissue of the subject.

26. The method of claim 25 , wherein the composition has a fat:hydrogel weight ratio of 1:1 to 5:1.

27. The method of claim 21 , wherein fat graft volume retention is increased as compared to administering the fat component alone.

28. The method of claim 27 , wherein variability in the retained fat graft volume is reduced as compared to administering the fat component alone.

29. The method of claim 21 , wherein the hyaluronic acid is crosslinked to the collagen using a coupling agent which is not part of the crosslink unit.

30. The method of claim 21 , wherein the hydrogel component has a storage modulus value of between 1,000 Pa and 4,000 Pa.

31. The method of claim 21 , wherein the crosslinked macromolecular matrix has a weight ratio of the hyaluronic acid to the collagen of 1:1 to 2:1.

32. The method of claim 21 , wherein the hydrogel component has a collagen concentration of greater than or equal to 6 mg/m L.

33. The method of claim 21 , wherein the hydrogel component has a hyaluronic acid concentration of at least 9 mg/mL.

34. The method of claim 21 , wherein the hydrogel component has a collagen concentration of 6 mg/mL, 8 mg/mL or 12 mg/mL.

35. The method of claim 21 , wherein the hydrogel component has a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 6 mg/m L.

36. The method of claim 21 , wherein the hydrogel component has a hyaluronic acid concentration of 12 mg/mL and a collagen concentration of 12 mg/mL.

37. The method of claim 21 , wherein the hydrogel component has a hyaluronic acid concentration of 16 mg/mL and a collagen concentration of 8 mg/mL.

38. The method of claim 21 , wherein the hydrogel component has a hyaluronic acid concentration of at least 9 mg/mL and a collagen concentration of greater than or equal to 6 mg

Assignees

• Allergan Inc

Inventors

• Pollock Jacob F
• Kokai Lauren E
• Cui Cunqi
• Yu Xiaojie
• Van Epps Dennis E
• Messina Darin J

Classifications

• A61L27/52 Primary

  Hydrogels or hydrocolloids · CPC title

• A61K2800/91

  Injection · CPC title

• A61Q19/08

  Anti-ageing preparations · CPC title

• A61L27/3604

  characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel · CPC title

• A61L2300/412

  Tissue-regenerating or healing or proliferative agents · CPC title