GB888180A - - Google Patents

Abstract

888,180. Vaccines, oil in water emulsions. GLAXO LABORATORIES Ltd. Feb. 26, 1959 [Feb. 27, 1958; Aug. 14, 1958], Nos. 6396/58 and 26186/58. Class 81 (1). An injectable pharmaceutical or veterinary vaccine comprises an antigenic material dispersed in a stable, parenterally acceptable emulsion comprising at least 30% by weight of an oil in a continuous aqueous phase. The antigenic material may be: (a) a bacterial toxoid from which the dead bacteria have been removed, e.g. toxoids from Staphylococcus aureus, clostridial toxoids, e.g. from Cl. welchii types B, C and D, toxoids from Cl. tetani; (b) bacterial vaccines containing dead bacteria, e.g. preparations from Erysipelothrix rhusiopathiae and Brucella, Salmonella, Leptospiral vaccines, e.g. from Leptrospira pomona; (c) viral vaccines, e.g. Swine fever virus, Foot and Mouth virus, Louping ill virus, Enzootic abortion virus, Infectious Larynys tracheitis virus. Vaccines for human use mentioned are those for diphtheria, Salmonella, cholera, poliomyelitis and influenza. The oil may be a vegetable oil, e.g. arachis, olive, sesame, soya bean, castor or cottonseed oil; an oily ester, e.g. ethyl oleate, dibutyl sebacate, isoamyl salicylate; or (preferably) a mineral oil, e.g. light liquid paraffin. The proportion of oil to water should lie between 30 and 65% (by weight) and is desirably between 40 and 60%. The emulsions may be stabilized by the addition of one or more wetting-agents, preferably of the non-ionic type. Preferably a two-component system is used comprising a water-soluble or preferentially water-soluble wetting-agent (Type A) which serves primarily to assist the formation of the emulsion and an oil-soluble or preferentially oilsoluble wetting-agent (Type B) serving primarily to stabilize the emulsion when formed. Examples of those of Type A given are : polyoxyalkylene derivatives of esters of polyhydric alcohols, e.g. polyoxyethylene sorbitan monostearate, water-soluble fatty acid esters of polyethylene glycol, e.g. nonaethylene glycol monooleate, fatty alcohols condensed with ethylene oxide, e.g. " Collone A.C." Examples of those of Type B given are: polyhydric alcohols and their anhydrides esterified with fatty acids, e.g. sorbitan sesquioleate, pentaerythritol dioleate. In general from 0.5 to 1.5% of Type A with from 0.5 to 1.5% of Type B are used. Preparation of the vaccines may be carried out by preparing the emulsion of the water, oil and wetting- agents by homogenization, or from water and a gel of the oil using as gelling agent a metal soap of a long-chain fatty acid, e.g. aluminium stearate, or calcium oleate, sterilizing and adding the antigenic material. The antigenic material may be used in any convenient form, e.g. a dried solid, an adsorbate on a parenterally acceptable adsorbant, e.g. aluminium phosphate or hydroxide, pumice or kieselguhr, or a suspension in a parenterally acceptable liquid. Sodium chloride may be added as an isotonicizing agent. Preservatives may also be added.