US 12,440,447 B2
Drug-loaded microbead compositions, embolization compositions and associated methods
Hiep Do, Chandler, AZ (US); and Michael Randall, Gilbert, AZ (US)
Assigned to C.R. Bard, Inc., Franklin Lakes, NJ (US)
Filed by C.R. Bard, Inc., Franklin Lakes, NJ (US)
Filed on Feb. 7, 2023, as Appl. No. 18/165,597.
Application 18/165,597 is a division of application No. 16/955,275, granted, now 11,607,388, previously published as PCT/US2018/066232, filed on Dec. 18, 2018.
Claims priority of provisional application 62/607,080, filed on Dec. 18, 2017.
Prior Publication US 2023/0172859 A1, Jun. 8, 2023
Int. Cl. A61K 9/16 (2006.01); A61K 9/00 (2006.01); A61K 31/351 (2006.01)
CPC A61K 9/1652 (2013.01) [A61K 9/0019 (2013.01); A61K 9/1635 (2013.01); A61K 9/1647 (2013.01); A61K 9/1682 (2013.01); A61K 31/351 (2013.01)] 10 Claims
OG exemplary drawing
 
1. A method for preparing a drug-loaded microbead composition, the method comprising:
dissolving a carrier and a therapeutic agent in an aqueous solvent to form an initial mixture, the initial mixture comprising a complex of the carrier and the therapeutic agent, wherein the therapeutic agent is chosen from doxorubicin, sorafenib, vandetanib, nivolumab, ipilimumab, regorafenib, irinotecan, epirubicin, pirarubicin, 5-fluorouracil, cisplatin, floxuridine, mitomycin C, derivatives of any of the foregoing, prodrugs of any of the foregoing, therapeutically acceptable salts of any of the foregoing, or combinations of any of the foregoing;
combining the initial mixture with a first solvent composition in which the therapeutic agent is less soluble than in the aqueous solvent to form a second mixture;
stirring the second mixture rapidly to form particles of the complex in the second mixture;
combining the particles of the complex with a hydrogel of a water-swellable polymer material to form a hydrogel mixture, wherein the water-swellable polymer is a biodegradable polymer material chosen from poly(4hydroxybutyrate), methacrylated hyaluronic acids, chitosan-alginate, poly(N isopropylacrylamide) copolymers, poly(N isopropylacrylamide) alginates, poly(N isopropylacrylamide) peptides, poly(N isopropylacrylamide) a acryloyloxy-β,βdimethyl-γ butyrolactone-hydrophilic Jeffamine, poly(N isopropylacrylamide)-poly(ethylene glycol) diacrylate-pentaerythritol tetrakis(3 mercaptopropionate), derivatives of any of the foregoing, or combinations of any of the foregoing;
combining the hydrogel mixture with a second solvent composition to form a synthesis mixture;
stirring the synthesis mixture rapidly to form drug-loaded microbeads in the synthesis mixture;
recovering the drug-loaded microbeads from the synthesis mixture; and
removing water from the drug-loaded microbeads to form a drug-loaded microbead composition having a water content of less than 1% by weight, based on the total weight of the drug-loaded microbeads in the drug-loaded microbead composition.