Sterilisable lubricant

Abstract: A radiation sterilisable surgical gel comprises a carbomer, glycerol and water.

Description: This invention relates to sterilisation of gels of the kind having surgical and external uses as a lubricant, emolient or both. Sterilisation of lubricant gels for surgical applications has presented problems. Thermal sterilisation can cause tubes or other containers to burst unless air ballasted autoclaves are employed. Glycosidic links of conventional cellulosic gels are cleaved by gamma radiation. The viscosity of the gel is reduced, destroying the lubricity characteristic. In the sterilisation method defined in claim 1, a lubricant gel is sterilesed by exposure to ionising radiation. Other compounds may be present in the gel. The acrylic acid polymer may be a homopolymer or copolymer of acrylic acid or a derivative thereof. Acrylic acid polymers cross-linked with allylsucrose, known as carbomers are preferred. Carbomers, discussed in Martindale (The Extra Pharmacopoeia) 27th ed. Pharmaceutical Press p919, are powders which dissolve in water to give acidic solutions. Neutralisation of the solutions may be necessary to form a gel. Preferred carbomers are manufactured under the Trade Mark CARBOPOL (BF Goodrich). Preferred acrylic acid polymers have molecular weights of 1 million or greater, preferably 2 million or greater but also preferably less than 4 million. Preferred acrylic acid polymers afford aqueous solutions having a viscosity of 50-150,000 cps at 1% concentration. Use of CARBOPOL 934,940 or 954 is particularly preferred. The hydroxy compound having two or more hydroxyl groups may comprise a diol, triol or polyol. Presence of 1,2-diol groupings is preferred. Hydroxy compounds, having 2-4 carbon atoms have been found to be particularly useful. Glycerol is expecially preferred. Other preferred compounds include ethane-1,2-diol; propane-1,2-diol, butane-1,3-diol and butane-1,4-diol. Mixtures of hydroxy compounds may be employed, especially mixtures of glycerol and one or more diols. A base, for example, sodium hydroxide, may be provided in an amount to neutralise the acrylic acid polymer. Methods in accordance with this invention have been found to result in sterilisation without a significant decrease in rheological properties. The need for autoclaving is avoided. The gels are preferably thixotropic, facilitating adhesion to surfaces after application. The proportion of hydroxy compound or compounds in the gel preferably in the range from a trace to 15%. Percentages referred to in the specification are by weight unless indicated otherwise. Preferred gels include 4-8% or hydroxy compound, particularly approximately 5%. Corrosion inhibitors may be included in the gels. These are preferably radiation stable. Use of sodium nitrite is preferred. Use of a corrosion inhibitor is useful in preventing corrosion of surgical instruments or other apparatus. Such gels may be intended for external use only, dependent on the nature or the inhibitor. An anaesthetic, for example lignocaine, may be incorporated in the gel. A preservative may be used to prevent bacterial spoilage of the gel. NIPAGIN M or NIPOLSOL M (Nipa Laboratories) have been found to be efficacious. Conductive salts, for example potassium chloride, potassium nitrate, potassium nitrite, sodium chloride, sodium nitrate and sodium nitrite may be included to facilitate use as an electrode gel or ultrasound gel. Sequestering agents are employed to protect the gel from the destructive effects of polyvalent cations. Any suitable sequestering agent may be used, for example: disodium hydroxy ethane-1,1-diphosphonate (HYQUEST 20, S G Stead). Polyvalent ions may be leached in use from the surfaces of the instruments or other materials. The invention is further described by means of the following examples which are not limitative. EXAMPLE 1 A gel was compounded with the following ingredients. The ingredients, excluding CARBOPOL were mixed in the aqueous phase. CARBOPOL was added under high shear and the mixture was allowed to stand for one minute. Aqueous sodium hydroxide was added to bring the PH to 6.5. Carbopol 934P 0.75% Glycerol 5.00% Nipagen M Sodium 0.03% Hiquest 20 100ppm Water to balance 100% Viscosities before and after irradiation were 112,000 and 103,000 cps respectively. The composition of Example 1 exhibited excellent retention of viscosity upon storage after one or two cycles of radiation sterilization. Results are set out in Tables 1, 2 and 3. The product was stored in a laquered metalic tube, the preservatives Nipagen and Nipasol were added in the proportions shown. TIME CONTROL 1 RADIATION CYCLE 10°C 2 RADIATION CYCLES INITIAL pH 6.33 pH 6.20 pH 6.19 121,280cps 97,680cps 100,720cps 0.140% Nipagin 0.131% Nipagin 0.132% Nipagin 0.029% Nipasol 0.037% Nipasol 0.028% Nipasol 1 MONTH pH 6.26 pH 6.27 pH 6.35 115,680cps 99,520cps 94,720cps 0.147% Nipagin 0.148% Nipagin 0.143% Nipagen 0.025% Nipasol 0.036% Nipasol 0.028% Nipasol 3 MONTHS pH 6.52 pH 6.55 pH 6.61 120,560cps 96,560cps 98,360cps 0.142% Nipagin 0.146% Nipagin 0.148% Nipagin 0.022% Nipasol 0.042% Nipasol 0.031% Nipasol TIME CONTROL 1 RADIATION CYCLE Room Temperature 2 RADIATION CYCLES INITIAL pH 6.33 pH 6.20 pH 6.19 12,1280cps 97,680cps 100,720cps 0.140% Nipagin 0.131% Nipagin 0.132% Nipagin 0.029% Nipasol 0.037% Nipasol 0.028% Nipasol 1 MONTH pH 6.33 pH 6.35 pH 6.33 116,560cps 97,520cps 95,200cps 0.162% Nipagin 0.142% Nipagin 0.143% Nipagin 0.025% Nipasol 0.020% Nipasol 0.051% Nipasol 3 MONTHS pH 6.45 pH 6.48 pH 6.60 121,680cps 96,560cps 93,760cps 0.159% Nipagin 0.150% Nipagin 0.148% Nipagin 0.050% Nipasol 0.035% Nipasol 0.031% Nipasol 6 MONTHS pH 6.52 Not Available pH 6.45 106,320cps 76,560cps 0.148% Nipagin 0.130% Nipagin 0.026% Nipasol 0.023% Nipasol TIME CONTROL 1 RADIATION CYCLE 37°C 2 RADIATION CYCLES INITIAL pH 6.33 pH 6.20 pH 6.19 12,1280cps 97,680cps 100,720cps 0.140% Nipagin 0.131% Nipagin 0.132% Nipagin 0.029% Nipasol 0.037% Nipasol 0.028% Nipasol 1 MONTH pH 6.29 pH 6.36 pH 6.38 109,120cps 98,240cps 96,800cps 0.140% Nipagin 0.143% Nipagin 0.145% Nipagin 0.032% Nipasol 0.032% Nipasol 0.031% Nipasol 3 MONTHS pH 6.56 pH 6.44 pH 6.47 102,720cps 92,640cps 86,720cps 0.154% Nipagin 0.147% Nipagin 0.148% Nipagin 0.035% Nipasol 0.015% Nipasol 0.036% Nipasol 6 MONTHS pH 6.51 Not Available pH 6.44 90,400cps 69,920cps 0.144% Nipagin 0.131% Nipagin 0.026% Nipasol 0.022% Nipasol

Claims: A method of forming a sterile lubricant gel which comprises the steps of (a) forming the gel so that it contains an acrylic acid polymer, a hydroxy compound, a sequestering agent for polyvalent cations and water, (b) placing a quantity of the gel in a sealed container, and (c) exposing the gel to a sterilising intensity of ionising radiation. A method as claimed in claim 1, characterised in that the polymer is a carbomer. A method as claimed in claim 1 or 2, characterised in that the polymer has a molecular weight of 10 6 or greater. A method as claimed in claim 3, characterised in that the polymer has a molecular weight of 2 × 10 6 or greater. A method as claimed in any preceding claim, characterised in that the polymer affords an aqueous solution with a viscosity of 50 to 150,000 cps at 1% concentration. A method as claimed in any preceding claim, characterised in that the hydroxy compound is a 1,2-diol. A method as claimed in any preceding claim, characterised in that the hydroxy compound has 2 to 4 carbon atoms. A method as claimed in claim 6 or 7, wherein the hydroxy compound is selected from the group comprising glycerol, ethane-1,2-diol, propane-1,2-diol, butane-1,3-diol and butane-1,4-diol. A method as claimed in any preceding claim, characterised by including two or more hydroxy compounds. A method as claimed in claim 9 characterised by including glycerol and a diol. A method as claimed in any preceding claim, characterised by including up to 15% of hydroxy compound. A method as claimed in claim 11, characterised by including 4 to 8% of hydroxy compound. A method as claimed in claim 12, characterised by including 5% of hydroxy compound. A method as claimed in any preceding claim, characterised by further including sodium nitrite. A method as claimed in any preceding claim, characterised by further including an anaesthetic. A method as claimed in any preceding claim, characterised by including a conductive salt.

Inventors: GREEN DAVID ROBERT JOHN, SMITH RORY JAMES MAXWELL, GREEN, DAVID ROBERT JOHN, SMITH, RORY JAMES MAXWELL
Applicants: DEPUY INT LTD, DEPUY INTERNATIONAL LIMITED
Application year: 1990
Main classification: A61K31
IPC codes: A61K31, A61L2