Macromolecular microparticles and methods of production and use

• US 5,981,719 A
• Filed: 12/14/1998
• Issued: 11/09/1999
• Est. Priority Date: 03/09/1993
• Status: Expired due to Term

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Original Assignee: Epic Therapeutics, Inc. (Baxter International Inc.)
• Inventors: Brown, Larry R., Scott, Terrence L., Blizzard, Charles D., Di, Jie, Woiszwillo, James E., Riske, Frank J., Sudhalter, Judith
• Primary Examiner(s): LEITH, NANCY JILL
• Application Number:
  US09/211,018
• Time in Patent Office: 330 Days
• Field of Search: 530/350, 530/402, 530/812, 530/410, 530/409, 530/810, 530/811, 530/813, 436/523, 436/528, 436/518, 436/529, 436/535
• US Class Current: 530/410
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: C07K 1/32 as complexes
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/54346 Nanoparticles
• CPC Class Codes: Y10S 530/812 Peptides or proteins is immobilized on, or in, an organic carrier

Abstract

Microparticles formed by mixing a macromolecule with a polymer at a pH near the isoelectric point of the macromolecule and incubating the mixture in the presence of an energy source for a predetermined length of time. The microparticles are composed of homogeneously distributed, intertwined macromolecule and polymer. Each microparticle allows aqueous fluids to enter and allows solubilized macromolecule and polymer to exit the microparticle and may be formulated to provide a sustained release of macromolecule and polymer from the interior of the microparticle when placed in an appropriate aqueous medium, such as under physiological conditions. Methods of production and methods of use for research, diagnostics and therapeutics are provided.

Claims

1. A microparticle comprising a macromolecule and polymer in an aqueous solution, wherein the concentration of macromolecule in the microparticle is at least 40% and less than 100% by weight and wherein the microparticle does not contain any oil.

2. The microparticle of claim 1 wherein the concentration of polymer in the microparticle is greater than 0% and less than or equal to 30% by weight.

3. The microparticle of claim 1 wherein the macromolecule is a molecule having or capable of having a tertiary and quaternary structure.

4. The microparticle of claim 3 wherein the macromolecule is selected from the group-consisting of a protein, peptide, polypeptide, carbohydrate, polysaccharide, protein conjugate, nucleic acid, virus, virus particle, and mixtures thereof.

5. The microparticle of claim 1 further comprising a pharmaceutical compound.

6. The microparticle of claim 1 wherein the polymer is water soluble or soluble in a water miscible solvent.

7. The microparticle of claim 1 wherein the polymer is selected from the group consisting of carbohydrate-based polymers, polyaliphatic alcohols, poly(vinyl) polymers, polyacrylic acids, polyorganic acids, polyamino acids, co-polymers and block co-polymers, tert-polymers polyethers, naturally occurring polymers, polyimids, surfactants, polyesters, branched and cyclo-polymers, polyaldehydes, and mixtures thereof.

8. The microparticle of claim 1 further comprising a biomolecule bound insideor on the surface of the microparticle.

9. The microparticle of claim 1 wherein the macromolecule is released from the microparticle under physiological conditions.

10. The microparticle of claim 9 wherein the released macromolecule is biologically active.

11. The microparticle of claim 1 further comprising luteinizing hormone releasing hormone (LHRH) or an analog thereof, wherein the analog has LHRH agonist or antagonist activity.

12. The microparticle of claim 11 wherein the luteinizing hormone releasing hormone analog is leuprolide.

13. The microparticle of claim 1 wherein the polymer is selected from the group consisting of dextrans, polydextroses, chitins, starches, and hetastarch.

14. The microparticle of claim 1 further comprising a small molecule or compound bound inside or on the surface of the microparticle by non-covalent interactions.

15. The microparticle of claim 1 further comprising dextran sulfate.