IP Library Granted Patent US 8,895,054
Granted Patent B2
US 8,895,054 · App. 12/411,855 · Granted Nov 25, 2014

Methods for joint lubrication and cartilage wear prevention making use of glycerophospholipids

Inventors: Yechezkel Barenholz (Jerusalem, IL); Dorit Nitzan (Bargiora, IL); Izhak Etsion (Haifa, IL); Avi Schroeder (Moshav Massuot Yitzhak, IL); Grigory Halperin (Or-Akiva, IL); Sarit Sivan (Zichron Yaakov, IL)
Assignees: Technion Research and Development Foundation Ltd.; Hadasit Medical Research Services & Development Limited; Yissum Research Development Company of the Hebrew University of Jerusalem
A61K31/685A61K9/127A61K9/0019A61L27/50A61L2430/24A61K9/1271
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Quick Facts
Patent No.
US 8,895,054
App. No.
12/411,855
Granted
Nov 25, 2014
Kind
B2
Abstract

The present invention concerns methods of joint lubrication and/or prevention of cartilage wear making use of liposomes having membranes with at least one phospholipid (PL) of the group consisting of a glycerophospholipid (GPL) having two, being the same or different, C 12 -C 16 hydrocarbon chain and a sphingolipid (SPL) having a C 12 -C 15 hydrocarbon chain, the one or more membranes having a phase transition temperature in which solid ordered (SO) to liquid disordered (LD) phase transition occurs, the phase transition temperature being within a temperature of about 20° C. to about 39° C. for lubrication of joints.

Claims (20)

1. A method for lubricating a joint of a mammal, the method comprising: administering into a cavity of the joint having a first temperature a composition consisting essentially of liposomes, wherein said liposomes are multilamellar vesicles (MLV) dispersed in a fluid medium, the liposomes having a mean diameter of between about 0.8 μm to about 10 μm and consisting essentially of membranes including at least one phospholipid (PL) selected from the group consisting of dimyristoylphosphatidylcholine (DMPC) and a mixture of DMPC and dipalmitoyl-phosphatidylcholine (DPPC), the membranes having a phase transition temperature in which solid ordered (SO) to liquid disordered (LD) phase transition occurs, the phase transition temperature being at a temperature of about 20° C. to about 39° C.; the phase transition temperature being lower than the first temperature.

2. The method of claim 1 , wherein said PL is dimyristoylphosphatidylcholine (DMPC).

3. The method of claim 1 , wherein said PL is the mixture of DMPC and DPPC.

4. The method of claim 3 , wherein the ratio of DMPC to DPPC is at least 0.6/1.0 (mole/mole).

5. The method claim 1 , wherein said liposomes do not include a membrane active sterol.

6. The method of claim 1 , for the treatment of or prevention of an articular disorder or symptoms arising therefrom or for the treatment, management or prevention of deterioration of locked joints, sports injury or traumatic injury towards osteoarthritis (OA).

7. The method of claim 6 , wherein said articular disorder is selected from arthritis, osteoarthritis, osteoarthritis in rheumatoid arthritis patients, traumatic joint injury, locked joint, sports injury, status post arthrocentesis, arthroscopic surgery, open joint surgery, and joint replacement.

8. A method for reducing or preventing a mammal's cartilage wear, the method comprising: administering into a cavity of a mammal's joint having a first temperature a composition consisting essentially of liposomes, wherein said liposomes are multilamellar vesicles (MLV) dispersed in a fluid medium, the liposomes having a mean diameter of between about 0.8 μm to about 10 μm and consisting essentially of membranes including at least one phospholipid (PL) selected from the group consisting of dimyristoylphosphatidylcholine (DMPC) and a mixture of DMPC and dipalmitoyl-phosphatidylcholine (DPPC), the membranes having a phase transition temperature in which solid ordered (SO) to liquid disordered (LD) phase transition occurs, the phase transition temperature being at a temperature of about 20° C. to about 39° C.; the phase transition temperature being lower than the first temperature.

9. The method of claim 8 , wherein said PL is dimyristoylphosphatidylcholine (DMPC).

10. The method of claim 8 , wherein said PL is the mixture of DMPC and DPPC.

11. The method of claim 10 , wherein the ratio of DMPC to DPPC is at least 0.6/1.0 (mole/mole).

12. The method claim 8 , wherein said liposomes do not include a membrane active sterol.

13. The method of claim 8 , for the treatment of or prevention of an articular disorder or symptoms arising therefrom or for the treatment, management or prevention of deterioration of locked joints, sports injury or traumatic injury towards osteoarthritis (OA).

14. The method of claim 13 , wherein said articular disorder is selected from arthritis, osteoarthritis, osteoarthritis in rheumatoid arthritis patients, traumatic joint injury, locked joint, sports injury, status post arthrocentesis, arthroscopic surgery, open joint surgery, and joint replacement.

15. The method of claim 1 , wherein the liposomes do not include dextran.

16. The method of claim 8 , wherein the liposomes do not include dextran.

17. A method for lubricating a joint of a mammal for reducing or preventing cartilage wear, the method comprising:

selecting phospholipids that form liposomes having a phase transition temperature that is in the range of about 20° C. to about 39° C.;

forming a composition consisting essentially of liposomes of multilamellar vesicles (MLV) dispersed in a fluid medium and having a mean diameter of between about 0.8 μm to about 10 μm, wherein the liposomes are formed from phospholipid (PL) membranes consisting essentially of dimyristoylphosphatidylcholine (DMPC) or a mixture of DMPC and another PL, provided that in the mixture the DMPC and other PL are present in a ratio of at least 0.6/1.0 (mole/mole) and that the membranes have a phase transition temperature in which solid ordered (SO) to liquid disordered (LD) phase transition occurs in the in the selected range of about 20° C. to about 39° C.; and

administering the selected compositions into a cavity of the joint, wherein the joint has a first temperature and the phase transition temperature of the selected composition is lower than the first temperature.

Assignments (2)
RE-RECORD TO CORRECT THE ADDRESS OF THE ASSIGNEE ON AN ASSIGNMENT DOCUMENT RECORDED ON MARCH 15, 2010, PREVIOUSLY RECORDED ON REEL 024081 FRAME 0826. Recorded Mar 24, 2010
From: BARENHOLZ, YECHEZKEL; NITZAN, DORIT; ETSION, IZHAK; SCHROEDER, AVI; HALPERIN, GRIGORY; SIVAN, SARIT
To: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION LTD.; HADASIT MEDICAL RESEARCH SERVICES & DEVELOPMENT LIMITED; YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM
Reel/Frame 024155/0172 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 15, 2010
From: BARENHOLZ, YECHEZKEL; NITZAN, DORIT; ETSION, IZHAK; SCHROEDER, AVI; HALPERIN, GRIGORY; SIVAN, SARIT
To: TECHNION RESEARCH AND DEVELOPMENT FOUNDATION LTD.; HADASIT MEDICAL RESEARCH SERVICES & DEVELOPMENT LIMITED; YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM
Reel/Frame 024081/0826 →
Continuity (3)
Continuation In Part PCTIL2007001215 · Oct 7, 2007
Provisional Application 60847651 · Sep 28, 2006
Related Publication 20100098749A1 · Apr 22, 2010