Biocompatible materials containing stable complexes method of TSG-6 and hyaluronan and method of using same
View Patent ↗The present invention provides a biocompatible material in the form of a solid, a water insoluble cross-linked gel or a liposome, which contains a stable complexes of TNF-stimulated gene protein (TSG-6) and hyaluronan.
1. A biocompatible material in the form of a water insoluble covalently cross-linked gel, comprising:
hyaluronan (HA), as a water insoluble covalently cross-linked HA gel or mutually cross-linked with at least one other polymer in a water insoluble covalently cross-linked gel; and
TNF-stimulated gene 6 protein (TSG-6) in a stable complex with said HA, wherein said TSG-6 in said stable complex is capable of transferring heavy chains (HCs) of inter-α-inhibitor (IαI) to bound or free HA.
2. The biocompatible material of claim 1 , wherein said HA is the water insoluble covalently cross-linked HA gel to which TSG-6 is complexed.
3. The biocompatible material of claim 1 , wherein the stable complex of TSG-6 and HA is resistant to treatment with 6M guanidine HCl containing 8% lauryl sulfobetain (3-(Dodecyldimethylammonio)propanesulfonate, ZWITTERGENT®) for 30 minutes at ambient temperature or is resistant to boiling in reducing SDS-PAGE sample buffer of 0.25 M Tris pH 6.8, 2% sodium dodecylsulfate, 5% 2-mercapto ethanol, and 10% glycerol.
4. The biocompatible material of claim 1 , which is present on the surface of a solid medical device that is implantable or in-dwelling in a patient or is transiently introduced into a patient during the course of a medical procedure.
5. The biocompatible material of claim 1 , wherein said HA is mutually cross-linked with at least one other polymer in a water insoluble covalently cross-linked gel.
6. The biocompatible material of claim 1 , which is biodegradable.
7. The biocompatible material of claim 1 , wherein said stable complex of TSG-6 and HA is capable of being released in a soluble form.
8. A soluble stable complex of TSG-6 and HA that is released from the biocompatible material of claim 7 .
9. A biocompatible material in the form of a solid, comprising:
hyaluronan (HA) bound to the surface of a water insoluble solid biocompatible or pharmaceutically acceptable carrier, but not to a liposome or a water insoluble covalently cross-linked gel; and
TNF-stimulated gene 6 protein (TSG-6) in a stable complex with said HA, wherein said TSG-6 in said stable complex is capable of transferring heavy chains (HCs) of inter-α-inhibitor (IαI) to bound or free HA.
10. The biocompatible material of claim 9 , wherein said water insoluble solid biocompatible or pharmaceutically acceptable carrier is a nanoparticle.
11. The biocompatible material of claim 9 , wherein HA is bound to the surface of a solid medical device that is implantable or in-dwelling in a patient or is transiently introduced into a patient during the course of a medical procedure.
12. The biocompatible material of claim 9 , which is biodegradable.
13. The biocompatible material of claim 9 , wherein said stable complex of TSG-6 and HA is capable of being released in a soluble form.
14. The biocompatible material of claim 9 , wherein the stable complex of TSG-6 and HA is resistant to treatment with 6M guanidine HCl containing 8% lauryl sulfobetain (3-(Dodecyldimethylammonio)propanesulfonate, ZWITTERGENT®) for 30 minutes at ambient temperature or is resistant to boiling in reducing SDS-PAGE sample buffer of 0.25 M Tris pH 6.8, 2% sodium dodecylsulfate, 5% 2-mercapto ethanol, and 10% glycerol.
15. A biocompatible material in the form of a liposome, comprising:
hyaluronan (HA) bound to the surface of a liposome; and
TNF-stimulated gene 6 protein (TSG-6) in a stable complex with said HA, wherein said TSG-6 in said stable complex is capable of transferring heavy chains (HCs) of inter-α-inhibitor (IαI) to bound or free HA.
16. The biocompatible material of claim 15 , which is present on the surface of a solid medical device that is implantable or in-dwelling in a patient or is transiently introduced into a patient during the course of a medical procedure.
17. The biocompatible material of claim 15 , which is biodegradable.
18. The biocompatible material of claim 15 , wherein said stable complex of TSG-6 and HA is capable of being released in a soluble form.
19. The biocompatible material of claim 15 , wherein the stable complex of TSG-6 and HA is resistant to treatment with 6M guanidine HCl containing 8% lauryl sulfobetain (3-(Dodecyldimethylammonio)propanesulfonate, ZWITTERGENT®) for 30 minutes at ambient temperature or is resistant to boiling in reducing SDS-PAGE sample buffer of 0.25 M Tris pH 6.8, 2% sodium dodecylsulfate, 5% 2-mercapto ethanol, and 10% glycerol.