Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1993-02-09
1996-06-11
Venkat, Jyothsna
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424401, 424489, 4284022, 264 43, A61K 952
Patent
active
055253598
DESCRIPTION:
BRIEF SUMMARY
The present invention essentially concerns microcapsules having a combined atelocollagen/polyholoside wall coagulated by a divalent cation, a method for manufacturing the microcapsules and cosmetic or pharmaceutical or food compositions containing them.
It is known that, for pharmaceutical and cosmetic applications, numerous research workers are working on the development of encapsulation of active substances. Among the effects sought for such work, particular mention may be made of the improvement in bio-availability, the protection of the active principle in a finished formula, the protection of the active principle in the organism in order to avoid in particular its degradation in the stomach, the deferred release or slow release for prolonged effect.
This encapsulation may be produced by incorporating these active principles in microcapsules for introduction thereof in cosmetic products, pharmaceutical preparations or food products intended for various routes of administration such as the oral route, parenteral route, application on the skin and the mucous membranes.
In the prior state of the art, various techniques have already been proposed for manufacturing microcapsules with the aid of synthetic polymers. These latter substances allow easy industrial manufacture but the microcapsules obtained are generally not easily biodegradable and, when they are, they produce products of degradation which may be toxic or whose toxicity is not known.
Thus, research work has been oriented towards the production of microcapsules with the aid of biocompatible or biodegradable natural substances. Within this scope, the research workers have used proteins. Reference may be made for example to document FR-A-2 444 497 MARS as well as to document FR-A-2 527 438 CNRS.
In both documents, the technique used comprises three steps: organic solvent non-miscible in water; cross-linking agent which is generally an organic acid dichloride; and finally appropriate solvents.
In the first document, the membrane is constituted solely by protein, whilst, in the second document, it is composed of a mixture of proteins and polyholosides.
Another method known under the name of EXTRAMET process carried out by the firm EXTRAMET makes it possible to obtain microcapsules by mechanically cutting with the aid of a vibrator a laminar flow produced by extrusion of a solution of polymerizable materials through a nozzle, which provokes the formation of vesicles or droplets which may then be rigidified by drying or by cross-linking in a bath containing a cross-linking agent into which the vesicles or droplets drop. This technique may be applied to synthetic polymers or to proteins. The encapsulation of a hydrosoluble active substance in a protein capsule will be obtained by dissolution in the solution of proteins before extrusion. If the active substance is of oily form or if it is in solution in oil, it will be encapsulated thanks to a co-extrusion with the protein solution which lies outside the laminar flow.
It will be observed that, in neither of the documents of the prior state of the art relative to the manufacture of microcapsules and in particular in the two documents mentioned above, FR-A-2 444 497 and FR-A-2 527 438, although the methods are generally applied to proteins, has the use of collagen ever been mentioned or hinted at.
The inventors of the present invention have tried to use collagen in the methods described in the prior documents and by using the EXTRAMET technique.
These experiments resulted in failure as these techniques are not applicable to collagen. In fact, in order to obtain an efficient cross-linking, it is necessary to prepare solutions of collagen in a strongly buffered medium at pH's higher than or equal to 5.5.
Now, the usual collagen, i.e. native collagen, precipitates partly and it is then very difficult to obtain homogeneous mixtures. Emulsion with an organic liquid cannot be produced, with the result that the methods described in prior documents FR-A-2 444 497 and FR-A-2 527 438 cannot be employed. The same app
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Allard Roland
Huc Alain
Coletica
Venkat Jyothsna
LandOfFree
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