Condensed-phase microparticle composition and method

• US 5,654,006 A
• Filed: 05/27/1994
• Issued: 08/05/1997
• Est. Priority Date: 02/12/1993
• Status: Expired due to Fees

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Original Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Inventors: Knudson, Mark B., Fernandez, Julio M.
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US08/250,464
• Time in Patent Office: 1,166 Days
• Field of Search: 424/489, 424/499, 424/500, 424/501, 424/484-488, 264/4.1-4.3
• US Class Current: 424/489
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1664 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/1617
• CPC Class Codes: A61K 9/5176 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/5123
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/586 Liposomes, microcapsules or cells
• CPC Class Codes: Y10S 977/906 Drug delivery
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition

Abstract

An microparticle composition and its method of use in drug delivery and diagnostic applications are disclosed. Also disclosed are methods of storing and administering drug compounds at high concentration in condensed-phase microparticles.

Claims

1. A method of achieving controlled release of a cationic therapeutic compound from microparticles made from anionic polymers, said microparticles having the property that they undergo transition from a swelled, decondensed state to a condensed state in the presence of Ca⁺² ions, and rapid transition back to the decondensed state when exposed to monovalent cations, said method comprising

mixing said cationic therapeutic compound with a suspension of microparticles (i) having average sizes in a selected size range between 0.05 and 5.0 microns, and (ii) composed of a condensed-phase matrix of crosslinked polyionic polymer filaments capable of expanding to a decondensed phase in the presence of monovalent counterions, said mixing being carried out with the particles in their decondensed state, such that said cationic therapeutic compound becomes incorporated into the matrix of the microparticles, and

condensing the microparticles by addition of polycations containing at least three charged groups, said polycations being effective to delay the release of the compound from the microparticles when the microparticles are exposed to monovalent cations.

2. The method of claim 1, wherein the polymer filaments forming the microparticle matrix are selected from the group consisting of sulfated, sulfonated, carboxylated, and polyphosphated polyanionic polymers.

3. The method of claim 1, wherein said condensing further comprises adding a divalent cation to the microparticles after the polycations have produced partial condensation of the microparticles.