Sustained release microspheres

摘要

A microsphere comprising: (1) a carrier protein selected from the group consisting of HAS; BSA; IgG; IgM; insulin; hGH; lysozyme; alpha-lactoglobulin; basic fibroblast growth factor; VEGF; chymotrypsin; trypsin; carbonic anhydrase; ovalbumin; phosphorylase b; alkaline phosphatase; beta-galactosidase; fibrinogen; poly-1-lysine; DNA; immunoglobulins (e.g. antibodies); casein; collagen; soy protein; and gelatin; (2) a water soluble polymer; (3) a first complexing agent that is a polyanionic polysaccharide; and (4) a second complexing agent that is a divalent metal cation selected from the group consisting of calcium and magnesium. A microsphere comprising: (1) a carrier protein; (2) a water soluble polymer selected from the group consisting of: a) carbohydrate-based polymers, such as methylcellulose, carboxymethyl cellulose-based polymers, dextran, polydextrose, derivatized chitins, chitosan, and derivatives thereof; b) PEG-acrylates, polyethylene imine, polyvinyl acetate, and derivatives thereof; c) poly(vinyl) alcohol, poly(vinyl) phosphate, poly(vinyl) phosphonic acid, and derivatives thereof; d) polyacrylic acids and derivatives thereof; e) polyorganic acids, such as polymaleic acid, and derivatives thereof; f) polyamino acids, such as polylysine, and polyimino acids, such as polyimino tyrosine, and derivatives thereof; g) co-polymers and block co-polymers, such as poloxamer 407 or Pluronic L-101 TM polymer, and derivatives thereof; h) tert-polymers and derivatives thereof; i) polyethers, such as poly(tetramethylene ether glycol), and derivatives thereof; j) naturally occurring polymers, such as zein and pullulan, and derivatives thereof; k) polyimids, such as poly n-tris (hydroxymethyl) methylmethacrylate, and derivatives thereof; l) surfactants, such as polyoxyethylene sorbitan, and derivatives thereof; m) polyesters such as poly(ethylene glycol)(n)monomethyl ether mono (succinimidylsuccinate) ester, and derivatives thereof; n) branched and cyclo-polymers, such as cyclodextrins, and derivatives thereof; and o) polyaldehydes, such as poly(perfluoropropyleneoxide-b-perfluoroformaldehyde), and derivatives thereof; (3) a first complexing agent that is a polyanionic polysaccharide; and (4) a second complexing agent that is a divalent metal cation selected from the group consisting of calcium and magnesium. A microsphere comprising: (1) a carrier protein; (2) a water soluble polymer; (3) a first complexing agent that is a polyanionic polysaccharide selected from the group consisting of galacturonic acids, alginates, mannuronic acid, guluronic acid, hyaluronic acid, chondroitin sulfates, chitin, chitosan, glycosaminoglycans, proteoglycans; and (4) a second complexing agent that is a divalent metal cation selected from the group consisting of calcium and magnesium. Methods of forming the microspheres are also disclosed.