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

Abstract

A method for lubricating a joint of a mammal by administering into a cavity of the joint a composition of liposomes that 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 including membranes of at least one glycerophospholipid (GPL) having two C12-C16 hydrocarbon chains which are the same or different. These membranes have 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. and being lower than the temperature of the joint.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 12 / 411,855 filed Mar. 26, 2009, which is a continuation-in-part of International application no. PCT / IL2007 / 001215 filed Oct. 7, 2007, which claims priority to U.S. provisional application No. 60 / 847,651 filed Sep. 28, 2006, the entire content of each of which are incorporated herein by reference thereto.FIELD OF THE INVENTION[0002]This invention generally concerns liposomes and methods for their therapeutic use.LIST OF PRIOR ART[0003]The following is a list of prior art, which is considered to be pertinent for describing the state of the art in the field of the invention.[0004]Hills, B. A. Phospholipid and propylene glycol based lubricant. U.S. Pat. No. 6,133,249, 1998.[0005]Hills, B. A. Lubricant Composition for Rheumatism. U.S. Pat. No. 5,403,592, 1990. Hills, B. A.; Monds, M. K., Enzymatic identification of the load-bearing boundary lubricant in the joint. Br. J. R...

AI Technical Summary

Benefits of technology

[0030]Thus, in accordance with the invention, a novel formulation based on a liposome system comprising PL is proposed, for introduction into synovial joints in order to improve or restore joint mobility. It was been found that the novel liposomal platform is effective as a lubricant as well as for reducing cartilage wear.

[0031]Thus, in accordance with a first of its aspects, there is provided the use of liposomes comprising one or more membranes with at least one phospholipid (PL) of the group consisting of a glycerophospholipid (GPL) having two, being the same or different, C12-C16 hydrocarbon chain and a sphingolipid (SPL) having a C12-C18 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., the use being for lubrication and / or reducing wear rate of joints (cartilage) having a joint temperature which is above the phase transition temperature of the membrane.

[0033]In accordance with yet another aspect there is provided a method for preventing or reducing a mammal's cartilage wear, comprising: administering into a cavity of the joint having a joint temperature a therapeutically effective amount of liposomes comprising one or more membranes with at least one phospholipid (PL) of the group consisting of glycerophospholipid (GPL) having two, being the same or different C12-C16 hydrocarbon chain and a sphingolipid (SPL) having a C12-C18 hydrocarbon chain, the one or more membranes having a phase transition temperature (Tm, the temperature in which the maximum change in the heat capacity during the phase transition from solid ordered (SO) to liquid disordered (LD) 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 joint temperature.

[0036]By a still further aspect of the invention there is provided a pharmaceutical composition for joint lubrication and / or reducing wear rate of joints having a joint temperature and comprising a physiologically acceptable carrier and liposomes; the liposomes comprising one or more membranes with at least one phospholipid (PL) of the group consisting of glycerophospholipid (GPL) having two, being the same or different, C12-C16 hydrocarbon chains and a sphingolipid (SPL) having a C12-C18 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. and being below said joint temperature.

Problems solved by technology

Joint dysfunctions affect a very large portion of the population.

Due to problems of acquiring suitable human specimens and the complicated nature of the experiments, most of the studies addressing this issue used animal cartilage.

It was found that severe depletion of the SAPL layer, which is strongly related to osteoarthritis, resulted in accelerated wear of the articular cartilage.

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