Compositions of hyaluronan with high elasticity and uses thereof

• US 10,383,890 B2
• Filed: 10/11/2016
• Issued: 08/20/2019
• Est. Priority Date: 07/10/2013
• Status: Active Grant

• Current Assignee: Matrix Biology Institute
• Original Assignee: Matrix Biology Institute
• Inventors: Balazs, Endre A., Belmonte, Carlos
• Primary Examiner(s): Maier, Leigh C
• Application Number:
  US15/290,107
• Publication Number:
  US 20170071974A1
• Time in Patent Office: 1,043 Days
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates

Abstract

The present invention provides compositions comprising hyaluronan with high elasticity, as well as methods for improving joint function, reducing pain associated with joint function and treating osteoarthritis by introducing into a joint a therapeutically effective amount of a composition comprising hyaluronan with high elasticity.

Claims

1. A method of inhibiting activation of an ion channel involved in pain transduction in a subject in need thereof, the method comprising administering to the subject a high elasticity composition comprising hyaluronan, wherein:

the hyaluronan is not cross-linked and/or is substantially free of chemical modifications;

wherein the composition is substantially free of a pharmaceutically active substance selected from the group consisting of a protein, a glycosaminoglycan that is different from hyaluronan, hydroxypropyl methyl cellulose and a local anesthetic; and

wherein the composition has an elasticity (G′

) of at least about 900 Pascal when measured at a frequency of 5.0 Hz, thereby inhibiting activation of the ion channel involved in pain transduction in the subject.

2. The method of claim 1, wherein hyaluronan is present in the high elasticity composition at a concentration of greater than 30 mg/mL.

3. The method of claim 2, wherein hyaluronan is present in the high elasticity composition at a concentration of 40 mg/mL to 60 mg/mL.

4. The method of claim 1, wherein the hyaluronan has an average molecular weight of between 1 million and 2 million.

5. The method of claim 1, wherein the hyaluronan has an average molecular weight of less than 2 million.

6. The method of claim 1, wherein the high elasticity composition is sterile.

7. The method of claim 1, wherein the high elasticity composition further comprises a buffer.

8. The method of claim 7, wherein the buffer is phosphate buffered saline (PBS).

9. The method of claim 8, wherein the buffer comprises NaCl, NaH₂PO₄.H₂O, and Na₂HPO₄.

10. The method of claim 9, wherein the buffer comprises 8.47 g/L NaCl, 0.047 g/L NaH₂PO₄H₂O and 0.213 g/L Na₂HPO₄.

11. The method of claim 1, wherein the ion channel involved in pain transduction is a TRPV1 ion channel.

12. The method of claim 1, wherein administering the high elasticity composition results in inhibition of an increase in cytosolic Ca²⁺following a nociceptive stimulus in a neuron expressing the ion channel involved in pain transduction.

13. The method of claim 1, wherein administering the high elasticity composition results in a decrease in a whole-cell current following a nociceptive stimulus in a neuron expressing the ion channel involved in pain transduction.

25. The method of claim 1, wherein the ion channel involved in pain transduction is in a nerve of a joint of the subject.

26. The method of claim 25, wherein the joint is selected from the group consisting of a knee joint, an elbow joint, a hip joint and a shoulder joint.

14. A method of treating pain in a subject in need thereof, the method comprising administering to the subject a high elasticity composition comprising hyaluronan, wherein:

the hyaluronan is not cross-linked and/or is substantially free of chemical modifications;

wherein the composition is substantially free of a pharmaceutically active substance selected from the group consisting of a protein, a glycosaminoglycan that is different from hyaluronan, hydroxypropyl methyl cellulose and a local anesthetic; and

wherein the composition has an elasticity (G′

) of at least about 900 Pascal when measured at a frequency of 5.0 Hz, thereby treating pain in the subject.

15. The method of claim 14, wherein hyaluronan is present in the high elasticity composition at a concentration of greater than 30 mg/mL.

16. The method of claim 15, wherein hyaluronan is present in the high elasticity composition at a concentration of 40 mg/mL to 60 mg/mL.

17. The method of claim 14, wherein the hyaluronan has an average molecular weight of between 1 million and 2 million.

18. The method of claim 14, wherein the hyaluronan has an average molecular weight of less than 2 million.

19. The method of claim 14, wherein the high elasticity composition is sterile.

20. The method of claim 14, wherein the high elasticity composition further comprises a buffer.

21. The method of claim 20, wherein the buffer is phosphate buffered saline (PBS).

22. The method of claim 21, wherein the buffer comprises NaCl, NaH₂PO₄.H₂O, and Na₂HPO₄.

23. The method of claim 22, wherein the buffer comprises 8.47 g/L NaCl, 0.047 g/L NaH₂PO₄.H₂O and 0.213 g/L Na₂HPO₄.

24. The method of claim 14, wherein administering the high elasticity composition results in a decrease in a mean number of pain nerve impulses in the subject.

27. The method of claim 14, wherein the pain is in a joint of the subject.

28. The method of claim 27, wherein the joint is selected from the group consisting of a knee joint, an elbow joint, a hip joint and a shoulder joint.