IP Library › Granted Patent US 11,607,386
Granted Patent B2
US 11,607,386 · App. 17/601,032 · Granted Mar 21, 2023

Liposomes encapsulating adenosine

Inventors: Siddhesh R. Angle (Jersey City, NJ); Carmen Corciulo (Gothenburg, SE); Bruce N. Cronstein (New York, NY); Jonathan Kaufman (Pittsburgh, PA)
Assignee: New York University
A61K9/1274A61K9/0019A61K31/7076
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Quick Facts
Patent No.
US 11,607,386
App. No.
17/601,032
Granted
Mar 21, 2023
Kind
B2
Abstract

Provided are liposomes that encapsulate adenosine. The liposomes may be formed from sphingomyelin or a combination of sphingomyelin and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or a combination of sphingomyelin and 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) or a combination of sphingomyelin, DMPG, and DMPC. The liposomes encapsulating adenosine may be used to induce cartilage regeneration, treat osteoarthritis, alleviate joint pain, and/or slow, arrest, and/or reverse progressive structural tissue damage associated with osteoarthritis or treat osteoarthritis, rheumatoid arthritis, acute gouty arthritis, and/or synovitis. The liposomes may release adenosine for up to two weeks.

Claims (25)

1. An injectable formulation comprising saline and liposomes comprising one or more lamellae, wherein the liposome lamellae comprise 70 to 100% by mass sphingomyelin and when there is less than 100% by mass sphingomyelin the remainder is 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) or DMPC and DMPG together, wherein the liposomes

(a) have a diameter of 50 nm to 150 μm; and

(b) encapsulate adenosine in the aqueous compartment of the liposome, wherein the concentration of adenosine is 3 mg/mL.

2. The injectable formulation of claim 1 , wherein the adenosine or a portion thereof is released for up to two weeks.

3. The injectable formulation of claim 1 , further comprising an excipient.

4. The injectable formulation of claim 1 , wherein the formulation is suitable for intra-articular injection.

5. The injectable formulation of claim 1 , wherein the ratio of DMPC and DMPG is from 6:4 to 8:2.

6. The injectable formulation of claim 5 , wherein the ratio of DMPC and DMPG is 7:3.

7. The injectable formulation of claim 1 , wherein the total lipid concentration is 7 to 12 mg/mL.

8. The injectable formulation of claim 1 , wherein one or more of the liposomes have a diameter of 50 nm to 100 μm.

9. The injectable formulation of claim 1 , wherein one or more of the liposomes have a diameter of 100 nm to 150 μm.

10. The injectable formulation of claim 1 , wherein the liposomes collapse at a temperature of 35 to 45° C.

11. The injectable formulation of claim 1 , wherein at least a portion of the adenosine is released within 1 second to 1 hour of administration to a joint of an individual.

12. The injectable formulation of claim 11 , wherein at least a portion of the adenosine is released within 1 minute to 1 hour of administration to the joint of the individual.

13. The injectable formulation of claim 12 , wherein at least 1 to 20% of the adenosine is released within 1 minute to 1 hour of administration to the joint of the individual.

14. The injectable formulation of claim 11 , wherein at least a portion of adenosine or at least 1 to 20% of adenosine is released within 1 second to 10 minutes of administration to the joint of the individual.

15. The injectable formulation of claim 1 , wherein the liposomes have a diameter of 50 nm to 1 μm.

16. The injectable formulation of claim 1 , wherein the liposomes have a diameter of 1 μm to 150 μm.

17. The injectable formulation of claim 1 , wherein the liposome lamellae comprise 75 to 100% by mass sphingomyelin.

18. A method of i) inducing cartilage regeneration and/or ii) alleviating joint pain and/or inflammation and/or iii) slowing and/or arresting and/or reversing progressive structural tissue damage comprising administering to an individual an injectable formulation of claim 1 , wherein i) cartilage regeneration is induced and/or ii) joint pain and/or inflammation is alleviated or partially alleviated and/or iii) progressive structural tissue damage is slowed or partially slowed and/or arrested or partially arrested and/or is reversed or partially reversed.

19. The method of claim 18 , wherein the injectable formulation is administered via intra-articular injection to a joint of the individual.

20. The method of claim 18 , wherein the injectable formulation is administered in one or more injections.

21. The method of claim 18 , wherein the injectable formulation is administered multiple times, wherein each administration occurs once every 10 days.

22. The method of claim 18 , wherein the individual has osteoarthritis, rheumatoid arthritis, acute gouty arthritis, and/or synovitis.

23. The method of claim 19 , wherein the individual is a human or a non-human mammal.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 13, 2022
From: ANGLE, SIDDHESH R.; CORCIULO, CARMEN; CRONSTEIN, BRUCE N.; KAUFMAN, JONATHAN
To: NEW YORK UNIVERSITY
Reel/Frame 062073/0027 →
Continuity (2)
Provisional Application 62828916 · Apr 3, 2019
Related Publication 20220168223A1 · Jun 2, 2022
Cited By (1)
US 12,734,129