Occidiofungin formations and uses thereof

Patent metadata

Field	Value
Publication number	US-10265374-B2
Application number	US-201515510801-A
Country	US
Kind code	B2
Filing date	Sep 14, 2015
Priority date	Sep 12, 2014
Publication date	Apr 23, 2019
Grant date	Apr 23, 2019

Abstract

Disclosed are occidiofungin formulations and uses thereof for the treatment of proliferative disorders, such as cancer. Methods of producing the disclosed occidiofungin formulations are also provided. Further, methods of treating a subject with the formulations are provided. In some embodiments, the formulations include occidiofungin and one or more cyclodextrins. The formulations may optionally further comprise an additional chemotherapeutic agent for treating the proliferative disease, lipid vesicles, and/or aqueous solvents (including pharmaceutically acceptable buffers and/or exceipients).

First claim

We claim:

1. A formulation comprising occidiofungin, and one or more cyclodextrins and an aqueous solvent, wherein either
a) said occidiofungin is present in an amount ranging from about 20 μg/mL to about 1 g/mL; or
b) said one or more cyclodextrins comprise between about 0.5% to about 10% weight/volume (w/v) of said formulation.

2. The formulation according to claim 1 , wherein said occidiofungin is present in an amount ranging from about 20 μg/mL to about 1 g/mL.

3. The formulation according to claim 1 , wherein said one or more cyclodextrins comprise between about 0.5% to about 10% weight/volume (w/v) of said formulation.

4. The formulation according to claim 1 , wherein said one or more cyclodextrins is selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, cyclomaltonose, variants thereof, and any combination thereof.

5. The formulation according to claim 1 , wherein said one or more cyclodextrins is selected from the group consisting of hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, hydroxyethyl β-cyclodextrin, methyl-β-cyclodextrin, dimethyl-β-cyclodextrin, randomly dimethylated-β-cyclodextrin, randomly methylated-β-cyclodextrin, carboxymethyl-β-cyclodextrin, carboxymethyl ethyl-β-cyclodextrin, diethyl-β-cyclodextrin, tri-O-methyl-β-cyclodextrin, tri-O-ethyl-β-cyclodextrin, tri-O-butyryl-β-cyclodextrin, tri-O-valeryl-β-cyclodextrin, di-O-hexanoyl-β-cyclodextrin, glucosyl-β-cyclodextrin, maltosyl-β-cyclodextrin, and 2-hydroxy-3-trimethyl-ammoniopropyl-β-cyclodextrin, or combinations thereof.

6. The formulation according to claim 1 , wherein said one or more cyclodextrins is hydroxypropyl-β-cyclodextrin.

7. The formulation according to claim 1 , further comprising lipid vesicles.

8. The formulation according to claim 7 , wherein said lipid vesicles comprise lipids selected from the group consisting of 1,2-Dioleoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(3-lysyl(1-glycerol))], and combinations thereof.

9. The formulation according to claim 1 , wherein said aqueous solvent is a pharmaceutically acceptable buffer, excipient, or combination thereof.

10. The formulation according to claim 9 , wherein said pharmaceutically acceptable buffer, excipient, or combination thereof is selected from the group consisting of Ringer's solution, isotonic saline, isotonic glucose solutions, distilled water, and phosphate buffered saline.

11. The formulation according to claim 1 , further comprising at least one chemotherapeutic agent.

12. The formulation according to claim 11 , wherein said at least one chemotherapeutic agent is selected from the group consisting of:
analogs of gonadotropin releasing hormone;
nitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), 1,3-bis (2-chloroethyl)-1-nitroso-urea (BCNU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), N-hydroxyethylnitroso-N′-chloroethylurea (HCNU);
cytostatic antibiotics, doxorubicin, pegylated liposomal doxorubicin, 5-fluorodeoxyuridine, 5-fluoro-2′-deoxyuridine 5′-monophosphate (5-FdUMP), 5-fluorouracil, 5-fluorouridine, procarbazine, docetaxel, gemcitabine, gemcitabine hydrochloride, telozolomide, epirubicin, epirubicin hydrochloride, idarubicin hydrochloride, zorubicin hydrochloride, aclarubicin, amrubicin, nemorubicin, pirarubicin;
vinca alkaloids, vinblastine, vincristine, vindesine; and
acivicin, acodazole hydrochloride, acronine, ambomycin, ametantrone acetate, aminoglutethimide, anthramycin, asparaginase, asperlin, bevacizumab (Avastin™), azacitidine, azetepa, azotomycin, benzodepa, bisantrene hydrochloride, bisnafide dimesylate, bleomycin sulfate, brequinar sodium, busulfan, cactinomycin, calusterone, caracemide, carbetimer, carboplatin, carmustine, carubicin hydrochloride, cedefingol, cetuximab, chlorambucil, cirolemycin, cisplatin, crisnatol mesylate, cyclophosphamide, cytarabine, dacarbazine, N-[2-(dimethyl-amino)ethyl]acridine-4-carboxamide (DACA), dactinomycin, daunomycin, dexormaplatin, dezaguanine, dezaguanine mesylate, droloxifene citrate, dromostanolone propionate, duazomycin, edatrexate, eflornithine hydrochloride, elsamitrucin, enloplatin, enpromate, epipropidine, erbulozole, erlotinib, esorubicin hydrochloride, estramustine, estramustine phosphate sodium, ethiodized oil I 131 , etoposide phosphate, etoprine, fadrozole hydrochloride, fludarabine phosphate, flurocitabine, fosquidone, fostriecin sodium, gefitinib (Iressa™), gold (Au) 198, hydroxyurea, ifosfamide, imatinib mesylate, interferon alfa-2a, interferon alfa-2b, interferon alfa-n1, interferon alfa-n3, interferon beta-I a, interferon gamma-I b, iproplatin, irinotecan hydrochloride, lanreotide acetate, leuprolide acetate, liarozole hydrochloride, lometrexol sodium, lomustine, losoxantrone hydrochloride, maytansine, mechlorethamine hydrochloride, megestrol acetate, melengestrol acetate, melphalan, mercaptopurine, methotrexate, methotrexate sodium, metoprine, meturedepa, mitindomide, mitocarcin, mitocromin, mitogillin, mitomalcin, mitomycin, mitosper, mitotane, mitoxantrone hydrochloride, mycophenolic acid, nocodazole, nogalamycin, oxisuran, paclitaxel, peliomycin, pentamustine, peplomycin sulfate, pipobroman, piposulfan, piroxantrone hydrochloride, plicamycin, plomestane, prednimustine, procarbazine hydrochloride, puromycin, puromycin hydrochloride, pyrazofurin, riboprine, rituximab, safinol, safingol hydrochloride, simtrazene, sparfosate sodium, sparsomycin, spirogermanium hydrochloride, spiromustine, spiroplatin, streptonigrin, streptozocin, strontium 89 (Sr) chloride, sulofenur, talisomycin, tamoxifen, taxane, taxoid, teloxantrone hydrochloride, teroxirone, testolactone, thiamiprine, thioguanine, thiotepa, nolatrexed (Thymitaq™), tiazofurin, raltitrexed (Tomudex™), 4beta-aminoalkyl-4′-O-demethyl-4-desoxypodophyllotoxin (TOP-53), topotecan hydrochloride: toremifene citrate, trastuzumab, trestolone acetate, triciribine phosphate, trimetrexate, trimetrexate glucuronate, tubulozole hydrochloride, uracil mustard, uredepa, vinblastine sulfate, vincristine sulfate, vindesine sulfate, vinepidine sulfate, vinglycinate sulfate, vinleurosine sulfate, vinorelbine tartrate, vinrosidine sulfate, vinzolidine sulfate, zeniplatin, zinostatin, 2-chlorodeoxyadenosine, 2′-deoxformycin, 9-aminocamptothecin, raltitrexed, N-propargyl-5,8-dideazafolic acid, 2-chloro-2′-arabino-fluoro-2′-deoxyadenosine, 2-chloro-2′-deoxyadenosine, anisomycin, trichostatin A, hPRL-G129R, CEP-751, linomide, 20-epi-1,25 dihydroxyvitamin D3, 5-ethynyluracil, abiraterone, acylfulvene, adecypenol, adozelesin, aldesleukin, ALL-tyrosine kinase (TK) antagonists, altretamine, ambamustine, amidox, amifostine, aminolevulinic acid, amsacrine, anagrelide, anastrozole, andrographolide, antagonist D, antagonist G, teverelix (Antarelix™), anti-dorsalizing morphogenetic protein-1, antineoplaston, aphidicolin glycinate, apoptosis gene modulators, apoptosis regulators, apurinic acid, 1-beta-D-Arabinofuranosylcytosine 5′-diphosphate-rac-1-S-octadecyl-2-O-palmitoyl-1-thioglycerol (ara-CDP-DL-PTBA), arginine deaminase, asulacrine, atamestane, atrimustine, axinastatin 1, axinastatin 2, axinastatin 3, azasetron, azatoxin, azatyrosine, baccatin III derivatives, balanol, batimastat, breakpoint cluster region/abelson murine leukemia viral oncogene homolog 1 (BCR/ABL) antagonists, benzochlorins, benzoylstaurosporine, beta lactam derivatives, beta-alethine, betaclamycin B, betulinic acid, basic fibroblast growth factor (bFGF) inhibitor, bicalutamide, bisaziridinylspermine, bisnafide, bistratene A, bizelesin, breflate, bropirimine, budotitane, buthionine sulfoximine, calcipotriol, calphostin C, camptothecin derivatives, cana

Assignees

• Univ Mississippi State
• Texas A & M Univ Sys

Inventors

• Smith James L
• Pruett Stephen
• Austin Frank
• Lu Shien
• Akshaya Ravichandran
• Laihing Steven

Classifications

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title