Compositions containing HC-HA/PTX3 complexes and methods of use thereof

1. A method of reducing pain in an individual in need thereof, comprising administering to an individual having a chemical burn, severe bacterial keratitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, irradiation of ocular tumors, arthritis, or bone spurs, a therapeutically effective amount of a composition comprising (i) a reconstituted HC-HA/PTX3 (rcHC-HA/PTX3) (heavy chain-hyaluronic acid/pentraxin3) complex; and (ii) a natural polymer, adjuvant, excipient, preservative, agent for delaying absorption, filler, binder, adsorbent, buffer, or combination thereof, thereby reducing pain associated with chemical burns, severe bacterial keratitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, irradiation of ocular tumors, arthritis, or bone spurs.

2. The method of claim 1 , wherein the rcHC-HA/PTX3 complex comprises hyaluronic acid (HA), heavy chain 1 (HC1) and heavy chain 2 (HC2) of inter-α-inhibitor (IαI) protein, and pentraxin 3 (PTX3).

3. The method of claim 1 , wherein the administering is to an epidermis, dermis, hypodermis, sclera, cornea, retina, choroid, vitreous, optic nerve, nerve, tendon, tissue surrounding tendon, joint, or spine.

4. The method of claim 1 , wherein the administering is by topical administration, injection, infusion, inhalation, or implantation.

5. The method of claim 4 , wherein the injection is a subconjunctival injection, intracorneal injection, intravitreal injection, intrastromal injection, intraarterial injection, intracardiac injection, intraduodenal injection, intramedullary injection, intraosseous injection, intraperitoneal injection, intrathecal injection, intravascular injection, epidural injection, parenteral injection, enteral injection, subcutaneous injection, percutaneous injection, transdermal injection, intradermal injection, or injection into a joint.

6. The method of claim 1 , wherein the composition is a solution, suspension, gel, powder, ointment, tablet, capsule, cream, lotion, paste, stick, syrup, granule, pill, aerosol, injectable depot preparation, or combinations thereof.

7. The method of claim 1 , wherein the complex further comprises a small leucine rich proteoglycan (SLRP).

8. The method of claim 1 , wherein the natural polymer comprises hyaluronic acid, collagen, fibrin, fibronectin, laminin, keratin, fibrinogen, heparan sulfate, chondroitin sulfate, or combinations thereof.

9. The method of claim 1 , wherein the excipient is a tonicity agent.

10. The method of claim 9 , wherein the tonicity agent is sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfate, or ammonium sulfate.

11. The method of claim 1 , wherein the excipient is a clarifying agent.

12. The method of claim 11 , wherein the clarifying agent is polysorbate 20, polysorbate 80, or combinations thereof.

13. The method of claim 1 , wherein the excipient is a viscosity enhancer.

14. The method of claim 13 , wherein the viscosity enhancer is carboxymethylcellulose, carbomer (acrylic acid polymer), poly(methylmethacrylate), polyacrylamide, polycarbophil, acrylic acid/butyl acrylate copolymer, sodium alginate, or dextran.

15. The method of claim 1 , wherein the excipient is a solubilizing agent.

16. The method of claim 15 , wherein the solubilizing agent is glucan sulfate, cyclodextrin, derivatives thereof, or a combination thereof.

17. The method of claim 1 , further comprising administering to the individual an additional therapeutic agent.

18. The method of claim 1 , wherein the composition comprises liposomes, niosomes, pharmacosomes, microspheres, microparticles, or nanoparticles.

19. The method of claim 1 , wherein the rcHC-HA/PTX3 complex consists of HMW HA, HC1, HC2, and PTX3.

20. The method of claim 1 , wherein the rcHC-HA/PTX3 complex consists of HMW HA, HC1, HC2, PTX3, and TSG-6.