Thermal responsive composition for treating bone diseases
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) 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.
1. A thermal responsive composition for treating bone diseases, comprising:
a biological activity factor, wherein the biological activity factor is a bone growth factor, hydroxyapatite (HAp), tri-calcium phosphate (TCP), demineralized bone matrix (DBM), or combinations thereof; and
a biodegradable copolymer, wherein the biodegradable copolymer has a structure represented by Formula (I):
A-B-BOX-B-A Formula (I)
wherein, A comprises a hydrophilic polyethylene glycol polymer, B comprises a hydrophobic polyester polymer, and BOX is a bifunctional group monomer of 2, 2′-Bis(2-oxazoline) and used for coupling the blocks A-B.
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-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, 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 is formulated as an injectable form, pastille, powder, gel or oral liquid.
13. A method for the treatment of bone diseases, comprising:
locally 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 17 , wherein the bone morphogenetic protein comprises BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, 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 is formulated as an injectable form, pastille, powder, gel or oral liquid.