Pharmaceutical and cosmetic preparations must be formulated so as to assure elegance of appearance, efficacy of ingredients and a satisfactory shelf life as the product. If the formulation is not self-preserving and if it contains material which could act as a substrate for growth of micro-organisms, the shelf life aspect involves, in addition to several other factors, the choice of a suitable antimicrobial preservative. Such preservatives, when present in the minimum effective concentration, are unfortunately prone to interact with many other materials. A number of papers on the inactivation of preservatives by containers, filters and formulation components have been published. The field has been adequately reviewed by de Navarre (1962), Wedderburn (1964) and, more recently, by Coates (1973). From these reviews and from a study of the literature it became apparent that relatively little work had been done on interactions between preservatives and solid particles in aqueous suspension. Consequently, a range of preservatives not previously investigated in this respect was tested for loss of activity in the presence of fifteen powders commonly used in aqueous suspension in pharmaceutical and cosmetic formulations. In view of the information obtained in this preliminary study and after the development of more satisfactory analytical techniques it was decided to study in greater depth the interaction between these powders and selected organomercurials and quaternary ammonium compounds.

Cette thèse de doctorat a été réalisée dans le cadre du projet NATUBAVAL visant à découvrir de nouveaux conservateurs naturels pour l’industrie cosmétique, à partir de plantes issues d’un des hotspots mondiaux de biodiversité : le bassin méditerranéen. Dix-sept extraits ont ainsi été obtenus et évalués quant à leurs propriétés antimicrobiennes contre Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus brasiliensis et Candida albicans, ainsi que leur capacité antioxydante. Santolina chamaecyparissus a démontré des propriétés remarquables, et a été sélectionnée pour une étude plus approfondie. Une approche par fractionnement bioguidé a permis l’isolement du composé majoritaire de la fraction la plus active, également identifié comme actif : un spirokétal énol connu de la famille des polyacétylènes. Une optimisation de l’extrait brut d’intérêt a alors été entreprise dans le but de maximiser son activité et de faire face au challenge d’une transposition industrielle et de son incorporation dans un produit cosmétique. En définitive, cette étude introduit une stratégie de développement d’un ingrédient naturel pouvant potentiellement être utilisé comme une alternative aux conservateurs de synthèse dans les produits cosmétiques. / This PhD thesis is part of the NATUBAVAL project that aims at discovering new natural preservatives for the cosmetics industry, issued from one of the world’s biodiversity hotspots: the Mediterranean Basin. Seventeen plant extracts were obtained and screened for their antimicrobial properties against Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus brasiliensis and Candida albicans and their antioxidant capacity. Santolina chamaecyparissus extract was found to present superior properties and selected for further investigation. A bioguided fractionation permitted to isolate the major compound of the most active fraction, that was identified as the active compound, a known spiroketal enol from the polyacetylenes family. An optimization of the crude extract of interest was then performed in order to maximize its activity and to face the challenge of an industrial scale-up and its incorporation in a cosmetic formulation. Finally, this study introduces a natural ingredient development strategy that might potentially be used as an alternative to synthetic preservatives in cosmetics.