JOINT LUBRICANT

Abstract: A composition for lubricating a joint is disclosed which comprises a solution or suspension of a phospholipid together with gelatin. The gelatin is preferably succinylated gelatin. The phospholipid, may be phosphatidic acid, phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol, phosphatidylglycerol and cardiolipin, especially phosphatidyl choline. The composition of the invention is useful in reducing wear in simulator studies of artificial joints.

Description: JOLNT LUBRICANT This invention relates to a composition for use in the lubrication of biomechanical joints such as hip joints, knee joints, shoulder joints, ankle joints and the like. It relates to an assembly for use in lubricating a biomechanical joint, and to a method of lubricating a biomechanical joint. Synovial fluid acts in biomechanical joints to lubricate the articulating bone surfaces. Osteo-arthritis and other rheumatic diseases result in degeneration of a joint, when the natural lubricating effect provided by the synovial fluid is unable to lubricate the joint satisfactorily. These problems arising from the inability of the synovial fluid to lubricate a joint satisfactorily can also arise in artificial joints such as those in which the articulating surfaces are provided by metal, polymeric or ceramic materials. The present invention provides a joint lubricant which relies on a combination of a phospholipid and gelatin for its lubricating effect. Accordingly, in one aspect, the invention provides composition for the lubrication of biomechanical joints, which comprises a solution or suspension of a phospholipid together with gelatin. In another aspect, the invention provides the use of gelatin and a phospholipid in the manufacture of the composition of the invention. In a further aspect, the invention provides a method of lubricating a biomechanical joint, which comprises applying the composition of the invention to the articulating surfaces of the joint. The gelatin is preferably succinylated gelatin. This gives the protein polar side groups which probably makes it more soluble in saline. Preferably the average molecular weight of the succinylated gelatin is at least about 10000 daltons, more preferably 15000 daltons, especially at least about 20000 daltons, for example about 30000 daltons. A particularly preferred proprietary solution is sold under the trade mark Gelofusine (Braun) which contains 5% (w/v) of succinylated gelatin in 0.9% (w/v) aqueous sodium chloride solution. A phospholipid, or in more correct terminology a phosphoglyceride, comprises four basic units: 1. a molecule of glycerol; 2. two fatty acid side chains at the first and second carbon atoms normally containing from 15 to 22 carbons (other than that in the carboxyl group); 3. a phosphate group attached to the third carbon of the glycerol backbone; 4. a substituent of the phosphate. It is the latter which gives the phosphoglyceride its name, and suitable phosphoglycerides can be selected from, without limitation: phosphatidic acid, phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol, phosphatidylglycerol and cardiolipin. The fatty acids in the phospholipid may be the same or different. A preferred example phospholipid is di-palmitoyl phosphatidyl choline (DPPC) which is phosphatidyl choline with two palmitic acid moieties (C 16 ) as the fatty acids at carbons 1 and 2. The gelatin is preferably present in the composition in the range from approximately 1.0 to 5.0 wt-%, based on the total weight of the composition. Preferably the amount of gelatin that is present in the composition is at least about 0.3 wt-%, more preferably at least about 0.5 wt-%, especially at least about 1.0 wt-%. Preferably, the amount of gelatin that is present in the composition is not more than about 8.0 wt-%, more preferably not more than about 5.0 wt-%, for example not more than about 3.0 wt-%. Around 1.25 wt-% has been found effective, and this may be achieved by using 25% v/v of a solution of a gelatin with a concentration of 5% w/v. The gelatin is preferably present in the composition in the range from approximately 1.0 to 5.0 g.lOO cm '3 of the composition. Preferably the amount of gelatin that is present in the composition is at least about 0.3 g.lOO cm "3 , more preferably at least about 0.5 g.lOO cm "3 , especially at least about 1.0 g.lOO cm "3 . Preferably, the amount of gelatin that is present in the composition is not more than about 8.0 g.100 cm "3 , more preferably not more than about 5.0 g.100 cm "3 , for example not more than about 3.0 g.100 cm "3 . Around 1.25 g.100 cm "3 has been found effective. The amount of phospholipid present can vary greatly. For example, it can vary between 0.01 wt-%) to 10 wt-%). Preferably, the amount of the phospholipid that is present in the composition is at least about 0.01 wt-%, more preferably at least about 0.05 wt-%. Preferably, the amount of the phospholipid that is present in the composition is not more than about 10.0 wt-%, more preferably not more than about 8.0 wt-%o, especially not more than about 5.0 wt-%>. For most purposes, between 0.05 and 5 wt-%> will be employed. Preferably, the amount of the phospholipid that is present in the composition is at least about 0.01 g.100 cm "3 of the composition, more preferably at least about 0.05 g.100 cm "3 . Preferably, the amount of the phospholipid that is present in the composition is not more than about 10.0 g.100 cm "3 , more preferably not more than about 8.0 g.100 cm "3 , especially not more than about 5.0 g.100 cm "3 . For most purposes, between 0.05 and 5 g.100 cm "3 will be employed. The solvent or carrier for the composition will often be water based. It can however consist of or include non-aqueous materials, including for example propylene glycol, ethylene glycol and polymers thereof. The composition can include other components to enhance its biocompatibility. For example, a water based composition can be based on a saline solution of appropriate concentration. Preferably, the composition is homogeneous so that all components are dissolved. However, the composition might be non-homogeneous, for example in the manner of a suspension, or a dispersion. The concentration of the composition will generally be such that the amount that is injected into a joint to provide appropriate lubrication is at least about 0.1 cm 3 , preferably at least about 0.2 cm 3 . The concentration will generally be such that the amount is not more than about 4.0 cm 3 , preferably not more than about 2.0 cm 3 . The composition of the invention has been found dramatically useful in reducing wear in simulator studies of artificial joints. It has been found that the lubricating effects of the phospholipid and gelatin components interact in a synergistic way to enhance the overall lubricating effect of the composition. The composition of the invention can be used to treat biomechanical joints in which the articulating bone surfaces have become damaged. Use of the composition involves injecting the composition into the joint cavity so that it becomes distributed over the joint surfaces. Apparatus is known for gaining access to the cavity of a biomechanical joint such as a hip, knee, shoulder or ankle joint, for example to inspect components of the joint, or to conduct surgery within the joint. The composition of the invention can be injected into a biomechanical joint using a portal of this kind for gaining access to a joint cavity. Accordingly, in another aspect, the invention provides an assembly for use in lubricating a biomechanical joint, which comprises a portal which can be used to gain access to the joint cavity to inject a composition into the cavity, and a quantity of the composition of the invention for injection into the cavity. The following examples illustrate the invention. Examples Materials and methods Five identical acetabular cups of ultra high molecular weight polyethylene and cobalt chrome 28 mm heads were tested in a total hip simulator. Three of the femoral heads were smooth, with a mean Ra of 0.007 ± 0.003 μm and a mean Rp of 0.085 ± 0.049 μm. The other two femoral heads were deliberately scratched with a diamond stylus. Three scratches were made to form at "*" at the pole extending down towards the equator. The diamond stylus had an included angle of 90° and a tip radius of 20 μm and was used with a load of 2.5 N. This produced a scratch with an Ra of 0.035 ± 0.009 μm and a mean Rp of 2.909 ± 1.067 μm. The scratching was carried out in order to represent damage that had been categorised from explanted heads that had suffered third body damage. A Prosim™ hip joint simulator was used to apply flexion/extension and internal/external rotation with superior/inferior load cycle to the prostheses. The cups were measured before and at 1 million cycle intervals throughout the test period using a co-ordinated measuring machine (CMM) to obtain wear volumes. Wear tests were carried out sequentially in 25% (v/v) new born calf serum in 0.1%) (w/v) sodium azide (2 million cycles); 25% (v/v) Gelofusine (a protein-based solution) + 5% (w/v) commercial phosphatidyl choline (a phospholipid) in 0.1%) (w/v) sodium azide and 25%) Gelofusine + 0.5%> (w/v) phosphatidyl choline in 0.1 % sodium azide (1 million cycles each). (Sodium azide is included as an antibacterial agent to preserve the serum in the tests.) Results The mean wear rates after testing in the three different lubricants are presented in Figure 1. There was a substantial reduction in wear as a result of the phospholipid. The impact of the phospholipid on the wear of the acetabular cups was phenomenal and was demonstrated for both counterface topographies. Thus, the composition of the invention reduces the wear in artificial hips dramatically. It is also useful for the lubrication of natural mammalian joints, for example by injection.

Claims: CLAIMS: 1. A composition for the lubrication of biomechanical joints, which comprises a solution or suspension of a phospholipid together with gelatin. 2. A composition as claimed in claim 1, in which the gelatin comprises succinylated gelatin. 3. A composition as claimed in claim 2, in which the gelatin is present in a solution which contains 5% (w/v) of succinylated gelatin in 0.9%) (w/v) aqueous sodium chloride solution. 4. A composition as claimed in any of claims 1 to 3, in which the phospholipid is selected from phosphatidic acid, phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol, phosphatidylglycerol and cardiolipin. 5. A composition as claimed in claim 5, in which the phospholipid comprises phosphatidyl choline. 6. A composition as claimed in any of claims 1 to 5, in which the amount of the gelatin that is present in the composition is at least about 0.3 g.100 cm "3 . 7. A composition as claimed in any of claims 1 to 6, in which the amount of the gelatin that is present in the composition is not more than about 8.0 g.100 cm "3 . 8. A composition as claimed in any of claims 1 to 7, in which the amount of the phospholipid that is present in the composition is at least about 0.01 g.100 cm "3 . 9. A composition as claimed in any of claims 1 to 7, in which the amount of the phospholipid that is present in the composition is not more than about 10.0 g.100 cm "3 . 10. A composition as claimed in claim 9, in which the amount of the phospholipid that is present in the composition is not more than about 8.0 g.100 cm "3 . 11. An assembly for use in lubricating a biomechanical joint, which comprises a portal which can be used to gain access to the joint cavity to inject a composition into the cavity, and a quantity of a composition as claimed in any one of claims 1 to 10 for injection into the cavity. 12. Use of gelatin and a phospholipid in the manufacture of a composition as claimed in any one of claims 1 to 10. 13. A method of lubricating a biomechanical j oint, which comprises applying to the articulating surfaces of the joint a composition as claimed in any one of claims 1 to 10.

Inventors: FISHER JOHN, INGHAM EILEEN, FISHER, JOHN, INGHAM, EILEEN
Applicants: DEPUY INT LTD, FISHER JOHN, INGHAM EILEEN, DEPUY INTERNATIONAL LIMITED, FISHER, JOHN, INGHAM, EILEEN
Application year: 2000
Main classification: A61L27
IPC codes: A61F2, A61L27, A61L31, A61P41