Controlled release compositions
View Patent ↗The compositions disclosed herein are for use as controlled release therapeutics for the treatment of a wide variety of diseases. In particular, the compositions provide water soluble bioactive agents, organic ions and polymers where the bioactive agent is efficiently released over time with minimal degradation products. The resulting controlled release composition is capable of administration in a decreased dose volume due to the high drug content and predominance of non-degraded bioactive agent after release. Additionally, the compositions, of the present invention are capable of long term, sustained releases.
1. A composition comprising a bioactive agent and a biodegradable polymer in an organic phase; and an organic ion in an aqueous phase that forms a complex with the bioactive agent,
wherein the organic ion comprises trifluoromethyl-p-toluate, 2-naphthalene sulfonate, 2,3-naphthalene dicarboxylate, 1-hydroxy-2-naphthoate, 3-hydroxy-2-naphthoate, 2-naphthoate, or salicylsalicylate, or a mixture thereof, and
wherein the stoichiometry of the bioactive agent relative to the organic ion ranges from about 1.0 to 1.5.
2. The composition of claim 1 , wherein said biodegradable polymer comprises poly(lactide)s, poly(glycolide)s, poly(lactide-co-glycolide)s, poly(lactic acid)s poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s, polycaprolactone, polycarbonates, polyesteramides, polyanhydrides, poly(amino acids), polyorthoesters, polyacetyls, polycyanoacrylates, polyetheresters, poly(dioxanone)s, poly(alkylene alkylate)s, copolymers of polyethylene glycol or polyorthoester, biodegradable polyurethanes, blends or copolymers thereof.
3. The composition of claim 1 , wherein said bioactive agent comprises proteins, nucleic acids, carbohydrates, peptides, LHRH agonists, leuprolide, oxytocin, somatostatin, small molecule pharmaceutical substances, immunogens, metabolic precursors capable of promoting growth and survival of cells and tissues, antineoplastic agents, hormones, antihistamines, cardiovascular agents, anti-ulcer agents, bronchodilators, vasodilators, central nervous system agents or narcotic antagonists or a mixture thereof.
4. The composition of claim 1 , wherein the bioactive agent comprises octreotide or octreotide acetate or a mixture thereof.
5. The composition of claim 1 , wherein the organic ion interacts with the bioactive agent to form a charged or neutral complex.
6. The composition of claim 1 , wherein the organic ion comprises trifluoromethyl-p-toluate, 2,3-naphthalene dicarboxylate, 1-hydroxy-2-naphthoate, 3-hydroxy-2-naphthoate, 2-naphthoate, or salicylsalicylate or a mixture thereof.
7. The composition of claim 1 , wherein the organic phase comprises a solvent and a co-solvent.
8. The composition of claim 1 , wherein the organic phase comprises methylene chloride, ethyl acetate, benzyl alcohol, acetone, acetic acid or propylene carbonate or a mixture thereof.
9. The composition of claim 7 , wherein the co-solvent comprises methyl alcohol, ethyl alcohol, isopropyl alcohol, N-methyl pyrrolidinone, dimethyl sulfoxide, N,N-dimethyl formamide, PEG 200, PEG 400 or benzyl alcohol or a mixture thereof.
10. The composition of claim 1 , wherein the aqueous phase comprises methanol, benzyl alcohol, isopropyl alcohol, water, dimethylsulfoxide, N,N-dimethylformamide or methylene chloride, or mixtures thereof.
11. The composition of claim 1 , wherein the composition produces a controlled release composition.
12. The composition of claim 11 , wherein said controlled release composition comprises microparticles or nanoparticles or a mixture thereof.
13. The composition of claim 12 , wherein said microparticles and nanoparticles are biodegradable.