Biodegradable submicroscopic particles containing a biologically active substance and compositions containing them

• US 4,329,332 A
• Filed: 07/16/1979
• Issued: 05/11/1982
• Est. Priority Date: 07/19/1978
• Status: Expired due to Term

• Current Assignee: NV Sopar SA Rue de Thyle 3A 6328 Sart-Dames-Avelines Belgium
• Original Assignee: Michel Roland, Patrick Couvreur, Peter Speiser
• Inventors: Couvreur, Patrick, Speiser, Peter, Roland, Michel
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US06/057,767
• Time in Patent Office: 1,030 Days
• Field of Search: 252/316, 424/33, 424/9, 424/22, 424/1, 526/297
• US Class Current: 424/9.6
• 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: C08F 22/32 Alpha-cyano-acrylic acid; Esters thereof
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

Biodegradable particles, with a diameter smaller than 500 nanometers, formed by the micellar polymerization of an alkyl-cyano-acrylate where the term "alkyl" means a lower alkyl radical having 1 to 4 carbon atoms and containing a biologically active substance.

Claims

1. Biodegradable particles having a diameter less than 500 nanometers for oral or parenteral administration in a human or animal host, said particles comprising a substantially spherical, dense, filamentous, polymeric network, wherein the polymeric network has dispersed therethrough a biologically active substance, and wherein said polymer is biodegradable in said host and is formed by the micellar polymerization of an alkyl cyano-acrylate said alkyl group containing 1 to 4 carbon atoms, and when said polymer particles are biodegraded in said host, the biologically active substance is progressively released into said host at a rate substantially corresponding to the rate of biodegradation of said polymer.

2. Biodegradable particles according to claim 1, which have a diameter of less than 200 nanometers.

3. Biodegradable particles according to claim 1 or 2 in which the biologically active substance is a product with antimitotic, antineoplastic, antibiotic or hormonal properties, a virus, a virus component, a bacterium component, a cell component, an antigen, an allergen or an enzyme.

4. A pharmaceutical composition containing biodegradable particles as defined according to claim 3 and an excipient for orally, subcutaneously, intradermally, intramuscularly or intraveneously administering said composition.

5. Biodegradable particles according to claim 1 or 2 formed by the polymerization of methyl-cyano-acrylate.

6. A pharmaceutical composition containing biodegradable particles as defined according to claim 5 and an excipient for orally, subcutaneously, intradermally, intramusuclarly or intraveneously administering said composition.

7. Biodegradable particles according to claim 5 in which the biologically active substance is a product with antimitotic, antineoplastic, antibiotic or hormonal properties, a virus, a virus component, a bacterium component, a cell component, an antigen, an allergen or an enzyme.

8. A pharmaceutical composition containing biodegradable particles as defined according to claims 1, 2 or 5 and an excipient for orally, subcutaneously, intradermally, intramuscularly or intraveneously administering said composition.

9. Biodegradable particles having a diameter less than 500 nanometers for parenteral administration in a human or animal host, said particles comprising a substantially spherical, dense, filamentous, polymeric network wherein the polymeric network has dispersed therethrough a biologically active substance, and wherein said polymer is biodegradable in said host and is formed by the micellar polymerization of an alkyl cyano-acrylate in an aqueous solution of a non-ionic surface active agent and at a pH less than 7, said alkyl containing 1 to 4 carbon atoms, and when said polymer particles are biodegraded in said host, the biologically active substance is progressively released into said host at a rate substantially corresponding to the rate of biodegradation of said polymer.

10. Biodegradable particles according to claim 9 in the form of a mixture of nanoparticles formed from different alkyl cyano-acrylates to thereby provide nanoparticles in said mixture having different degradability kinetics in the host.

11. Biodegradable particles having a diameter less than 500 nanometers for use as a diagnostic agent, said particles comprising a substantially spherical, dense, filamentous, polymeric network wherein the polymeric network has dispersed therethrough a biologically active substance, and wherein said polymer is biodegradable and is formed by the micellar polymerization of an alkyl cyano-acrylate in an aqueous solution of a surface active agent and at a pH less than 7, said alkyl containing 1 to 4 carbon atoms, and wherein said polymer particles are biodegraded in use as a diagnostic agent whereby the biologically active substance is progressively released at a rate substantially corresponding to the rate of biodegradation of said polymer.

12. Biodegradable particles according to claim 11 in the form of a mixture of nanoparticles formed from different alkyl cyano-acrylates to thereby provide nanoparticles in said mixture having different degradability kinetics.