WO1995021637A1

WO1995021637A1 - Membrane with anti-viral properties

Info

Publication number: WO1995021637A1
Application number: PCT/GB1995/000194
Authority: WO
Inventors: Michael Charles Petty; Martin Robert Bryce; Geoffrey Williams
Original assignee: British Technology Group Limited
Priority date: 1994-02-10
Filing date: 1995-01-31
Publication date: 1995-08-17
Also published as: GB9402581D0

Abstract

A condom with anti-viral properties is made by Langmuir-Blodgett coating onto latex rubber of 1 mole part C60 fullerene and 4 mole parts arachidic acid.

Description

MEMBRANE WITH ANTI- VIRAL PROPERTIES

This invention relates to a membrane with anti-viral properties, to a method of imparting anti-viral properties to a membrane, and to products such as surgical gloves and condoms made of such a membrane, which itself may typically be of rubber, such as latex rubber, or polyurethane. An important virus whose activity it would be appropriate to curb with such products is the human immuno-deficiency virus HIV.

It had been thought from laboratory studies in the mid-1980s that the spermicide nonoxynol-9 killed this virus, but more recent studies suggest that this compound can increase the chance of HUV transmission compared with using a placebo (Guardian, 3 November 1993). Therefore the search for a different anti-viral agent is urgent.

It has been suggested by a group from Emory University, Atlanta, Georgia, USA, that the football-shaped carbon compound buckminsterfullerene Cgø should block the action of the enzyme "reverse transcriptase", with which the virus converts its RNA into the DNA essential for replication (Neue Zϋrcher Zeitung 1 December 1993). Independently, Friedman et al. from the University of California postulated and verified that Cgø was of just the right size to block the enzyme HIV-protease, which has the form of an open cylinder in the bore of which is a site where two aspartic acid groups catalyse the hydrolysis (i.e. destruction) of the peptide bonds of the protein being attacked by the enzyme. The Cgø molecule snugly fits this site, stopping the enzyme from functioning (J. American Chemical Society, 1993, pp 6510-2).

However, the possibility of exploiting these welcome properties in the context of membrane products has not been considered because it is such an improbable combination technically, in that a strong chemical bond uncharacteristic of buckminsterfullerene is normally required for a monomolecular layer to adhere to a substrate.

Independently of this, Williams et al of the University of Durham have succeeded in forming Langmuir-Blodgett films of fullerenes on to various rigid bulk substrates, namely glass, single-crystal silicon, quartz and aluminium-coated glass (Synthetic Metals.

55-57 (1993) 2955-2960), and Goldenberg et aL (J. Chem. Soc, Chem. Comm.. 1993. p 1310) have improved on this, but still on rigid bulk substrates only, by using the substituted compound l-tertbutyl-l,9-dihydrofullerene-60. A membrane of for example polyurethane or rubber, e.g. latex rubber, according to the invention carries a coating of from one to ten, preferably 1 or 2, layers of one or more fullerenes. The fullerene(s) may be applied by way of dispersion in a gel or lubrication layer, applied conventionally to the membrane, or as follows.

A method of coating a membrane, according to the invention, comprises applying one or more Langmuir-Blodgett coatings of fullerene to the membrane. The fullerene may be dissolved in an aromatic and/or hydrophobic compound on a hydrophilic (e.g. water) subphase. The fullerene may be codissolved with a phospholipid or fatty acid, e.g. arachidic acid, in a mole proportion of 1 :(1-10) and/or may be substituted with alkyl chains C_j-C_jg or with functionalised chains containing amine, hydroxyl or carboxy lie acid groups, e.g. may be 1 -tertbutyl- 1.9-dihydrofullerene-60.

The invention extends to products such as surgical gloves and condoms made of a membrane which has a coating as set forth above.

The invention will now be described by way of example.

A Langmuir-Blodgett trough of a constant perimeter design of floating boom was housed in a microelectronics-grade clean room. The subphase in the trough was ultra-pure water (pH 5.7 ± 0.1, temperature 20 ± 2°C) obtained by reverse osmosis, deionization and

UV sterilization.

Onto the subphase and inside the adjustable perimeter floating on the surface of the subphase were placed a few drops (150 μl) of a concentrated solution of 1 mole part Cgø fullerene and 4 parts arachidic acid in benzene. One hour was allowed to pass, to ensure complete evaporation of the benzene. The perimeter was adjusted until the fullerene plus arachidic acid formed a close-packed and ordered arrangement, this being established by compressing the perimeter such as to maintain a surface pressure of 30 milliNewtons/m.

This arrangement is believed to be of vertically aligned fatty acid molecules in a close-packed ordered arrangement on the subphase (water) surface, with the fullerene molecules on tog. This arrangement is transferred "as is" to a solid substrate dipped into the Langmuir-Blodgett trough.

When a substrate is dipped into the trough and removed, it may have adhering to it a layer of aligned molecules which became attached: on the downstroke only (X-type deposition), on the downstroke and again on the upstroke (Y-type deposition), or on the upstroke only (Z-type deposition). The thoroughness or efficiency of deposition is measured by the deposition ratio, defined as (change in enclosed surface area of trough)/(dipped area of substrate).

Initially, attempts were made to dip on to commercially available condoms, which were first washed in a mild detergent/warm water solution to remove any lubrication. Dipping was, however, unsuccessful as residual lubrication turned out to have remained on the condom, transferring to the subphase surface as the substrate was lowered into the subphase. This was monitored by an increase in surface area of the floating film, instead of the expected decrease which accompanies loss of material from the subphase surface. Further attempts to clean the condoms resulted in a deterioration of the latex rubber. LB film transfer was unsuccessful.

A pair of hospital-grade starch-free latex rubber surgeon gloves was obtained and a finger was removed from a glove. The finger was stretched over a 1 cm diameter glass test tube. Once again, on transferring the substrate through the subphase a surface area increase was monitored. It was, however, found possible to remove this unknown coating by repeatedly dipping the substrate through a clean subphase/air interface. Following this cleaning procedure, Y-type Langmuir-Blodgett deposition occurred at a dipping speed of - 7.5 mm min"*. The deposition ratio was 1.0 ± 0.05 and the film thickness estimated to be 7.2 nm. This was too thin to affect the appearance of the substrate. Z-type deposition was recorded for a dry condom, supplied by the London Rubber

Company, with a deposition ratio approaching 1.0.

Claims

1. A membrane carrying a coating of from one to ten layers of one or more fullerenes.

2. A membrane according to Claim 1 , wherein the coating is of one or two said layers.

3. A membrane according to Claim 1 or 2, wherein the membrane is of polyurethane or rubber.

4. A membrane according to Claim 3, wherein the membrane is of latex rubber;.

5. A method of coating a membrane, comprising applying one or more Langmuir-Blodgett layers of fullerene to the membrane.

6. A method of making a membrane according to any of Claims 1 to 4, comprising applying one or more Langmuir-Blodgett layers of fullerene to the membrane.

7. A method according to Claim 5 or 6, wherein the fullerene is dissolved in an aromatic and/or hydrophobic compound on a hydrophilic subphase.

8. A method according to Claim 7, wherein the fullerene is codissolved with a phospholipid or fatty acid.

9. A method according to Claim 8, wherein the fullerene and the phospholipid/fatty acid are present in a mole ratio of 1 :(1-10).

10. A method according to Claim 8 or 9, wherein the fatty acid is arachidic acid.

11. A method according to any of Claims 5 to 10, wherein the fullerene is substituted with a C_j_ιg alkyl chain or with a functionalised chain containing an amine, hydroxyl or carboxylic acid group.

12. A method according to Claim 11, wherein the fullerene is l-tertbutyl-1,9- dihy drofullerene-60.

13. A membrane coated by the method of any of Claims 5 to 12.

14. A surgical glove or condom comprising a membrane according to any of Claims 1 to 4 or 13.