Utilization of a transacylation reaction between an esterified p

Stock material or miscellaneous articles – Coated or structually defined flake – particle – cell – strand,... – Particulate matter

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528272, 424408, 424451, 424455, 424457, 424468, 424491, 424493, 424497, 424499, 264 432, 264 433, 264 44, 42840221, B32B 900

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active

056910606

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BRIEF SUMMARY
The present invention relates essentially to the use of a transacylation reaction between an esterified polysaccharide and a polyamino or polyhydroxylic substance for the manufacture of microparticles, to the microparticles, to the processes for their manufacture and to compositions in which they are present.
More precisely, the present invention relates essentially to the use of a transacylation reaction between on the one hand a polysaccharide carrying esterified carboxyl groups and on the other hand either a polyamino substance, in particular a protein, or a polyhydroxylic substance, in particular a polysaccharide, for the manufacture of microparticles, in particular microcapsules, to the microparticles produced in this way, to the processes for the manufacture of such microparticles, in particular microcapsules, and to the compositions in which they are present, such as cosmetic, pharmaceutical, food, enzyme, reagent or diagnostic compositions.
The development of biocompatible microparticles, in particular microcapsules, is of great interest especially in the fields of cosmetics, pharmaceuticals and foodstuffs. When charged with one or more active substances, these vesicles can in fact make it possible to mask an unpleasant taste or odor, to increase the stability of the encapsulated substances, to prevent their evaporation or to ensure their sustained release in situ. If the membrane is enteric, the microparticles, in particular the microcapsules, can also protect the active substance from degradation in the stomach or protect the gastric mucous membrane from an irritant effect.
Such microcapsules can be administered by a variety of routes, such as the oral route, application to the skin or mucous membranes, or the parenteral route.
Proteins and polysaccharides have been studied most among the various candidate materials. A variety of processes have thus been described for the preparation of microcapsules from proteins or polysaccharides or associations of proteins and polysaccharides. Some processes comprise a first stage involving emulsification of an aqueous solution of protein or polysaccharide within a hydrophobic phase, followed by a stage involving crosslinking with a difunctional agent such as acid dichlorides. Examples of documents which may be cited are FR-A-2 444 497 Mars or else FR-A-2 527 438 CNRS, in which interfacial crosslinking is applied to mixtures of proteins and polysaccharides.
To encapsulate hydrophobic liquids emulsified as the disperse phase in an aqueous solution of protein or polysaccharide, the existing processes generally consist either in heating the emulsion if the protein can be denatured by heat (for example the document US 3 137 631 Soloway), or in incorporating a crosslinking agent into the hydrophobic phase (the document US 4 138 362 Vassiliades).
Furthermore, the so-called complex coacervation processes are well known to those skilled in the art. They are applicable especially to aqueous solutions of a protein or a polyanionic substance, for example a polysaccharide carrying carboxyl groups. The substance to be encapsulated is dispersed in the aqueous phase either in the form of a solid, or in the form of droplets of an immiscible liquid. The principle is to acidify the aqueous solution so as to bring the pH to a value such that the protein is positively charged and forms with the polyanionic substance an electrically neutral complex, which deposits on the disperse phase to be encapsulated.
The processes which use difunctional crosslinking agents have the disadvantage of necessitating repeated washing of the resulting microcapsules in order to remove all the excess crosslinking agent. Moreover, the chemical crosslinking reaction substantially degrades the structure of proteins. For pharmaceutical applications, such degradations are to be avoided since they can be the cause of immunogenic properties of the microparticles. Likewise, if it is desired to preserve the specific biological properties of the protein used to prepare the microparticles, such as enzymic prope

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