THERMAL RESPONSIVE COMPOSITION FOR TREATING BONE DISEASES

• US 20120010139A1
• Filed: 06/29/2011
• Published: 01/12/2012
• Est. Priority Date: 06/30/2010
• Status: Active Grant

• Current Assignee: Industrial Technology Research Institute
• Original Assignee: Industrial Technology Research Institute
• Inventors: Shen, Hsin-Hsin, Hsieh, Meng-Yow, Li, Pei-Shan, Lin, Tsai-Yu, Lai, Po-Liang, Sun, Jui-Sheng, Lin, Yi-Hung, Peng, Shen-Hua, Yang, Liang-Yo, Yu, Wei-Lin, Chang, Chih-Hung
• Granted Patent: US 8,614,190 B2
• Time in Patent Office: Days
• US Class Current: 514/8.1
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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 27/54 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: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease

Abstract

Thermal responsive compositions for treating bone diseases are provided. The thermal responsive composition for treating bone diseases includes a bone growth factor and a biodegradable copolymer. The biodegradable copolymer has a structure of Formula (I) or Formula (II):

A-B-BOX-B-A  (Formula I)

and

B-A-B-(BOX-B-A-B)_n-BOX-B-A-B  Formula (II),

wherein, A includes a hydrophilic polyethylene glycol polymer, B includes a hydrophobic polyester polymer, BOX is a bifunctional group monomer of 2,2′-Bis(2-oxazoline) and used for coupling the blocks A-B or B-A-B, and n is an integer and the same or more than 0.

Claims

1. A thermal responsive composition for treating bone diseases, comprising:

a biological activity factor, wherein the biological activity factor is bone growth factor, hydroxyapatite (HAp), tri-calcium phosphate (TCP), demineralized bone matrix (DBM); and

a biodegradable copolymer, wherein the biodegradable copolymer has a structure represented by Formula (I) or Formula (II);

A-B-BOX-B-A 

 

(Formula I)

and

B-A-B-(BOX-B-A-B)_n-BOX-B-A-B 

 

(Formula II)

wherein, A comprises a hydrophilic polyethylene glycol polymer, B comprises a hydrophobic polyester polymer, BOX is a bifunctional group monomer of 2,2′

-Bis(2-oxazoline) and used for coupling the blocks A-B or B-A-B, and n is an integer and the same or more than 0.

2. The thermal responsive composition for treating bone diseases as claimed in claim 1, wherein an end of the hydrophobic polyester polymer (B) which is not bonded with the hydrophilic polyethylene glycol polymer (A) has an end capping/coupling functional group.

3. The thermal responsive composition for treating bone diseases as claimed in claim 2, wherein the hydrophobic polyester polymer (B) is bonded with the BOX via the end capping/coupling functional group.

4. The thermal responsive composition for treating bone diseases as claimed in claim 2, wherein the end capping/coupling functional group is derived from an end capping/coupling agent, and the end capping/coupling agent comprises an anhydride.

5. The thermal responsive composition for treating bone diseases as claimed in claim 4, wherein the end capping/coupling agent comprises succinic anhydride, maleic anhydride, phthalic anhydride, or sebacic anhydride.

6. The thermal responsive composition for treating bone diseases as claimed in claim 1, wherein the hydrophilic polyethylene glycol polymer (A) comprises methoxy-poly(ethylene glycol) (mPEG).

7. The thermal responsive composition for treating bone diseases as claimed in claim 1, wherein the hydrophobic polyester polymer (B) comprises polymers or copolymers derived from D,L-Lactide, D-Lactide, L-Lactide, D,L-Lactic acid, D-Lactic acid, L-Lactic acid, glycolide, β

-propiolactone, δ

-valerolactone, or ε

-caprolactone.

8. The thermal responsive composition for treating bone diseases as claimed in claim 1, wherein the hydrophobic polyester polymer (B) comprises poly(lactide-co-glycolide) (PLGA), poly(propionic-co-lactic (PPLA), poly(valeric-co-lactic) (PVLA), or poly(caproic-co-lactic) (PCLA).

9. The thermal responsive composition for treating bone diseases as claimed in claim 1, wherein the bone growth factor comprises bone morphogenetic protein, transforming growth factor-β

, fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, or combinations thereof.

10. The thermal responsive composition for treating bone diseases as claimed in claim 9, wherein the bone morphogenetic protein comprises BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, BMP-19, BMP-20, BMP-21, or combinations thereof.

11. The thermal responsive composition for treating bone diseases as claimed in claim 1, wherein the ratio of hydroxyapatite (HAp), and tri-calcium phosphate (TCP) is 7:

3 to 5;

5.

12. The thermal responsive composition for treating bone diseases as claimed in claim 1, wherein the thermal responsive composition for treating bone diseases serves as a carrier of an injection, pastille, powder, gel or oral liquid.

13. A method for the treatment of bone diseases, comprising:

administering the thermal responsive composition of claim 1 to a subject suffering from bone diseases.

14. The method as claimed in claim 13, wherein an end of the hydrophobic polyester polymer (B) which is not bonded with the hydrophilic polyethylene glycol polymer (A) has an end capping/coupling functional group.

15. The method as claimed in claim 13, wherein the hydrophilic polyethylene glycol polymer (A) comprises methoxy-poly(ethylene glycol) (mPEG).

16. The method as claimed in claim 13, wherein the hydrophobic polyester polymer (B) comprises polymers or copolymers derived from D,L-Lactide, D-Lactide, L-Lactide, D,L-Lactic acid, D-Lactic acid, L-Lactic acid, glycolide, β

-propiolactone, δ

-valerolactone, or ε

-caprolactone.

17. The method as claimed in claim 13, wherein the bone growth factor comprises bone morphogenetic protein, transforming growth factor-β

, fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, or combinations thereof.

18. The method as claimed in claim 13, wherein the bone morphogenetic protein comprises BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, BMP-19, BMP-20, BMP-21, or combinations thereof.

19. The method as claimed in claim 13, wherein the ratio of hydroxyapatite (HAp), and tri-calcium phosphate (TCP) is 7:

3 to 5;

5.

20. The method as claimed in claim 13, wherein the thermal responsive composition for treating bone diseases serves as a carrier of an injection, pastille, powder, gel or oral liquid.