BONE FILLING COMPLEX AND METHOD FOR FABRICATING THE SAME

• US 20100249059A1
• Filed: 08/27/2007
• Published: 09/30/2010
• Est. Priority Date: 08/31/2006
• Status: Active Grant

• Current Assignee: Megagen Implant Co., Ltd., Pohang University of Science and Technology (Posco Holdings Incorporated)
• Original Assignee: Megagen Implant Co., Ltd., Pohang University of Science and Technology (Posco Holdings Incorporated)
• Inventors: Park, Jung Kyu, Yang, Dong Jun, Oh, Eun Ju, Choi, Seok Kyu, An, Hyun Wook, Hahn, Sei Kwang, Park, Kwang Bum, Ryoo, Kyoung Ho
• Granted Patent: US 8,183,229 B2
• Time in Patent Office: Days
• US Class Current: 514/54
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Provided is a bone filling complex and a method of preparing the same. The bone filling complex includes a matrix including a hydrogel-type hyaluronic acid derivative; and a bone derivative filling the matrix, and thus adhesion can be prevented and excellent bone generation property can be obtained. For example, the bone filling complex can be used to an injured portion of alveolar bone to derive an regeneration of the alveolar bone.

Claims

1. A bone filling complex comprising:

a matrix comprising a hydrogel-type hyaluronic acid derivative; and

a bone derivative filling the matrix.

2. The bone filling complex of claim 1, wherein the hydrogel-type hyaluronic acid derivative is obtained by reacting a hyaluronic acid with suberate.

3. The bone filling complex of claim 2, wherein the suberate is bis(sulfosuccinimmidyl)suberate.

4. The bone filling complex of claim 2, wherein the suberate is bonded to a carbonyl group of the hyaluronic acid through a linker.

5. The bone filling complex of claim 4, wherein the linker comprises at least two amino groups, wherein one amino group of the amino groups is bonded to the carboxylic group of the hyaluronic acid and another amino group of the amino groups is bonded to a carbonyl group of the suberate.

6. The bone filling complex of claim 5, wherein the matrix comprises at least one unit represented by Formula 1:

7. The bone filling complex of claim 6, wherein each of R₁ and R₂ is hydrogen atom and R₃ is —

NHCO—

(CH₂)y—

CONH—

.

8. The bone filling complex of claim 1, wherein the hydrogel-type hyaluronic acid derivative is obtained by reacting a hyaluronic acid to which a methacrylic anhydride is introduced with a dithiol-based crosslinker.

9. The bone filling complex of claim 8, wherein the methacrylic anhydride is bonded to a carboxylic group of the hyaluronic acid through a linker.

10. The bone filling complex of claim 9, wherein the linker comprises at least two amino groups, wherein one amino group of the amino groups is bonded to the carboxylic group of the hyaluronic acid and another amino group of the amino groups is bonded to a carbonyl group of the methacrylic anhydride.

11. The bone filling complex of claim 8, wherein the dithiol-based crosslinker is a peptide which has cysteine at its opposite ends and an arginin-glycine-aspartic acid sequence interposed between the ends.

12. The bone filling complex of claim 11, wherein

the matrix comprises at least one unit represented by Formula 2.

13. The bone filling complex of claim 12, wherein each of R₁ and R₂ is hydrogen atom and R₃ is —

NHCO—

(CH₂)y—

CONH—

.

14. The bone filling complex of claim 1, wherein the matrix has a network structure.

15. The bone filling complex of claim 1, wherein the bone derivative is a calcium phosphate-based compound.

16. The bone filling complex of claim 1, wherein the bone filling complex is formulated into blocks, granules, or an injectable form.

17. A method of preparing a bone filling complex, the method comprising:

forming a matrix comprising a hydrogel-type hyaluronic acid derivative; and

filling the matrix with a bone derivative.

18. The method of claim 17, wherein the forming of a matrix comprises reacting a hyaluronic acid with suberate.

19. The method of claim 18, wherein the suberate is bis(sulfosuccinimmidyl)suberate.

20. The method of claim 18, wherein the suberate is bonded to a carbonyl group of the hyaluronic acid through a linker.

21. The method of claim 20, wherein the linker comprises at least two amino groups, wherein one amino group of the amino groups is bonded to the carboxylic group of the hyaluronic acid and another amino group of the amino groups is bonded to a carbonyl group of the suberate.

22. The method of claim 21, wherein the matrix comprises at least one unit represented by Formula 1:

23. The method of claim 22, wherein each of R₁ and R₂ is hydrogen atom and R₃ is —

NHCO—

(CH₂)y—

CONH—

.

24. The method of claim 20, wherein the linker is bonded to the carboxylic group of the hyaluronic acid in a solution comprising at least one organic solvent in an amount ranging from 0 to 60 vol %.

25. The method of claim 24, wherein the organic solvent is ethanol.

26. The method of claim 17, wherein the forming of the matrix comprises:

introducing methacrylic anhydride to a hyaluronic acid; and

reacting the hyaluronic acid to which the methacrylic anhydride is introduced with a dithiol-based crosslinker.

27. The method of claim 26, wherein the methacrylic anhydride is bonded to a carboxylic group of the hyaluronic acid through a linker.

28. The method of claim 27, wherein the linker comprises at least two amino groups, wherein one amino group of the amino groups is bonded to the carboxylic group of the hyaluronic acid and another amino group of the amino groups is bonded to a carbonyl group of the methacrylic anhydride.

29. The method of claim 26, wherein the dithiol-based crosslinker is a peptide which has cysteine at its opposite ends and an arginin-glycine-aspartic acid sequence interposed between the ends.

30. The method of claim 29, wherein the matrix comprises at least one unit represented by Formula 2:

31. The method of claim 30, wherein each of R₁ and R₂ is hydrogen atom and R₃ is —

NHCO—

(CH₂)y—

CONH—

.

32. The method of claim 27, wherein the linker is bonded to the carboxylic group of the hyaluronic acid in a solution comprising at least one organic solvent in an amount ranging from 0 to 60 vol %.

33. The method of claim 32, wherein the organic solvent is ethanol.

34. The method of claim 17, wherein the bone derivative is a calcium phosphate-based compound.

35. The method of claim 17, wherein the forming of the matrix and the filling with the bone derivative are performed substantially in situ.