Process for the preparaton of dispersible colloidal systems of a substance in the form of nanocapsules

• US 5,049,322 A
• Filed: 12/31/1987
• Issued: 09/17/1991
• Est. Priority Date: 12/31/1986
• Status: Expired due to Term

• Current Assignee: Centre National De La Recherche Scientifique
• Original Assignee: Centre National De La Recherche Scientifique
• Inventors: Fessi, Hatem, Puisieux, Francis, Devissaguet, Jean-Philippe
• Primary Examiner(s): Lovering, Richard D.
• Assistant Examiner(s): COVERT, JOHN
• Application Number:
  US07/140,246
• Time in Patent Office: 1,356 Days
• Field of Search: 264/4.3, 264/4.33, 264/4.1, 264/4.6, 427/213.31, 427/213.32, 427/213.3, 427/213.36, 424/450
• US Class Current: 264/4.1
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

The process according to the invention comprises:

(1) the preparation of a liquid phase consisting essentially of a solution of a substance A in a solvent or in a mixture of solvents, and containing the substance B in solution or as a dispersion,

(2) the preparation of a second liquid phase consisting essentially of a non-solvent or a mixture of non-solvents for the substances A and B, and supplemented with one or more surfactants, the solvent or mixture of solvents of the first phase being miscible in all proportions with the non-solvent or mixture of non-solvents of the second phase,

(3) the addition of the first phase to the second phase with moderate agitation so as to produce a colloidal suspension of nanocapsules, the wall of which is constituted by the substance A and the core by the substance B,

(4) if desired, the removal of all or part of the solvent or the mixture of solvents and of the non-solvent or the mixture of non-solvents so as to produce a colloidal suspension of nanocapsules of the desired concentration or to produce a powder of nanocapsules following the addition of stabilizing substances.

Claims

1. A process for the preparation of dispersible colloidal systems in the form of spherical particles of the vesicular type and of a size less than 500 nm (nanocapsules), the wall of which is constituted by a substance A having film-forming properties and the core by a liquid substance B capable of being encapsulated by the substance A, comprising:

combining (1) a first liquid phase consisting essentially of a solution of the substances A and B in a solvent for the substances A and B or in a mixture of solvents for the substances A and B, and (2) a greater amount of a second liquid phase consisting essentially of a non-solvent or a mixture of non-solvents for the substances A and B and including one or more surfactants, the solvent or the mixture of solvents of the first phase being miscible in all proportions with the non-solvent or mixture of non-solvents of the second phase,

comprising a core of said liquid substance B surrounded by a layer of said substance A.

2. A process according to claim 1, wherein said combining step comprises adding the first liquid phase to the second liquid phase.

3. A process according to claim 1, wherein surfactant(s) are present in a proportion of 0.1 to 10% by weight of the colloidal suspension.

4. A process according to claim 3, wherein the surfactant(s) are present in a proportion of 0.2 to 2% by weight.

5. A process according to claim 1, wherein substance A is a polymer.

6. A process according to claim 5, wherein said polymer is present in said solvent in a concentration of between 0.1 and 10% by weight.

7. A process according to claim 6, wherein said polymer is present in a concentration of between 0.2 and 2% by weight.

8. A process according to claim 1, wherein substance B is a biologically active substance.

9. A process according to claim 1, wherein substance B is an oil.

10. A process according to claim 8, wherein substance B is a biologically active substance in solution in an oil.

11. A process according to claim 13, further comprising removing by lyophilization all of the solvents and non-solvents.

12. A process according to claim 1, wherein said nanocapsules are of a size of about 150 to 450 nm.

13. A process according to claim 1, further comprising removing at least a portion of the solvent or mixture of solvents and non-solvent or mixture of non-solvents to produce a concentrated colloidal suspension of nanocapsules or a powder of nanocapsules.