Plastic and nonmetallic article shaping or treating: processes – Encapsulating normally liquid material – Liquid encapsulation utilizing an emulsion or dispersion to...
Patent
1996-07-22
1998-12-22
Mullis, Jeffrey C.
Plastic and nonmetallic article shaping or treating: processes
Encapsulating normally liquid material
Liquid encapsulation utilizing an emulsion or dispersion to...
42721336, 4272133, 42721331, 42721332, A61K 951
Patent
active
058514520
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION
The present invention is comprised within the technical field of microencapsulation, particularly, in the coating of droplets of particles with sizes comprised within the nanometric range, using biodegradable and bio-compatible polymers of different nature. The thus obtained products have important applications in pharmacy, medicine, cosmetics, veterinary, chemical industry, agriculture etc.
BACKGROUND OF THE ART
The obtention of a fine suspension of particles formed by a biodegradable polymer, polycaprolactone, by means of precipitation due to a change of solvent, has been described in the scientific work "Mechanism of the biodegradable of polycaprolactone" (1983), Jarret, P. et al. Polym Prep. (Am. Chem. Soc. Div. Polym. Chem.) Vol. 24 No. 1, page 32-33.
EP Patent 0274961B1 (which corresponds to U.S. Pat. No. 5,049,322) describes a method for the obtention of vesicular type, spherical particles having a size less than 500 nm. The method comprises the preparation of a phase containing a polymer, an oil and a substance to be encapsulated in a solution or dispersion. The phase is added, under agitation, to another phase formed by a non solvent of the polymer and of the oil, producing the precipitation of the polymer and subsequently the removal of the solvents by lyophilization. On incorporation of one phase over another, the size of the reactor which contains the mixture is increased depending on the final volume desired. This implies the necessity of a scaling to adapt the manufacturing conditions. There exists the difficulty in large volumes in that, once the mixture is formed, the polymer solvent must be in contact with the nanocapsules for a long period, with the possibility of producing the re-dissolution of the same, or the extraction of the active substance to the external phase. On the other hand, the removal of solvents by means of lyophilization is a slow and expensive process, with the additional disadvantage that when inflammable solvents are involved, it is highly dangerous.
The present invention relates to the coating of already formed droplets or particles, so that it is not necessary to agitate the mixture, which is effected by incorporation of the two phases in a device in which the mixture flows continuously, with the immediate production of the evaporation of the solvents. The elaboration and facility conditions (reaction volume) is always the same, independent of the final volume to be obtained, so that it does not require scaling for the obtention of industrial quantities. The solvent remains in contact with the recently coated vesicules during a very short period, so that the re-dissolution of the coating and the possible extraction of the active principle to the external phase is avoided, whatever the volume to be prepared.
The process described in FR A2 515960 allows the obtention of poly alkyl-cyanoacrylate biodegradable nanocapsules, which separate from the polymerization of the corresponding monomer. These nanocapsules contain a biologically active substance. The disadvantage of this method is that it requires a polymerization stage, so that it can only be used with specific polymers. Besides this important limitation, it involves the difficulty of controlling the polymerization and the possible existence of residual monomers which may, in some cases, be toxic. The present invention has the advantage that it does not require a polymerization, being a more rapid process and being applicable to a great number of polymers of diverse nature.
The process described in EP 0480 729 A1 consists of the coating of droplets in oil, containing active principles for oral administration, with a polysaccharide with chelator capacity (sodium alginate) which hardens on the addition of multivalent cations, resulting in micro-capsules with sizes over 1 .mu.m. Finally, it is lyophilized to obtain a product in powder form. This method is limited to the employment of polysaccharides with chelator capacity. Likewise, sonication is necessary, not being applicable for
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Jarret et al. (1983) "Mechanism of bioderadation of polycaprolactone". Polum Prep. (Am. Chem. Soc. div. Polum. Chem.) vol. 24, No. 1:32-3.
Carreras Perdiguer Nuria
Galan Valdivia Francisco Javier
Mas Jose Alberto Vallet
Laboratorios Cusi, S.A.
Mullis Jeffrey C.
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