Claims for Patent: 9,877,971

Summary for Patent: 9,877,971

Title:	Soft lozenges comprising corticosteroids
Abstract:	Described herein are oral pharmaceutical compositions suitable for chewing, sucking, or buccal dissolution comprising non-systemic corticosteroid soft lozenges, methods for making the same, and methods for treating subjects in need thereof with such lozenges. In particular, the oral composition provides topical, non-systemic administration of one or more active pharmaceutical ingredients to the oral cavity and upper gastrointestinal track, including the esophagus. In one embodiment, the oral pharmaceutical compositions comprise chewable, suckable, or buccally-dissolvable soft lozenges for the treatment of esophageal lesions. The soft lozenges provide topical, non-systemic delivery of corticosteroids to the esophagus and oral cavity.
Inventor(s):	Zhao; Yinyan (Greensboro, NC), Hughey; Justin (Asheboro, NC), Vaughn; Jason (Browns Summit, NC), Fang; Qi (Oak Ridge, NC)
Assignee:	Banner Life Sciences LLC (High Point, NC)
Application Number:	15/181,462
Patent Claims:	1. An oral, topical, slow releasing, non-systemic, solid, soft lozenge pharmaceutical composition comprising: (a) about 10% to about 40% by mass of one or more film-forming polymers comprising gelatins; (b) about 1% to about 5% by mass of one or more release modifiers comprising polyethylene oxide having a molecular weight (M.sub.v) of about 900,000 to about 8,000,000; (c) about 5% to about 20% by mass of one or more plasticizers comprising glycerol, sorbitol, mannitol, maltitol, xylitol, or combinations thereof; (d) about 20% to about 60% by mass of one or more sweeteners comprising maltitol, xylitol, mannitol, sucralose, aspartame, stevia, or a combination thereof; (e) about 0.1% to about 5% by mass of one or more pH modifiers comprising one or more organic acids (f) less than 1% by mass of one or more corticosteroids; and (g) water; wherein the composition orally disintegrates within about 30-45 minutes upon oral administration to a subject in need thereof. 2. The composition of claim 1, further comprising: (h) one or more opacifiers, coloring agents, flavorings, or combinations thereof; (i) one or more solubilizing agents; and (j) one or more second active pharmaceutical ingredients. 3. The composition of claim 2, further comprising one or more pharmaceutically acceptable excipients. 4. The composition of claim 1, wherein the one or more of gelatins comprises gelatin, partially hydrolyzed gelatin, hydrolyzed gelatin, hydrolyzed collagen, or combination thereof. 5. The composition of claim 1, wherein the one or more gelatins has a Bloom value of about 50 Bloom to about 150 Bloom. 6. The composition of claim 1, wherein the one or more organic acids comprises citric acid, acetic acid, lactic acid, malic acid, tartaric acid, fumaric acid, or combinations thereof. 7. The composition of claim 1, wherein the release modifier comprises polyethylene oxide having a molecular weight (M.sub.v) of about 7,000,000. 8. The composition of claim 2, wherein the solubilizing agent comprises poloxamer, polyoxyethylene 50 stearate, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, propylene glycol diacetate, propylene glycol monostearate, sodium lauryl sulfate, sodium stearate, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, or combinations thereof. 9. The composition of claim 1, wherein the corticosteroid comprises one or more of alclometasone, amcinonide, beclometasone, betamethasone, budesonide, ciclesonide, clobetasol, clobetasone, clocortolone, cloprednol, cortivazol, deflazacort, deoxycorticosterone, desonide desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, fluclorolone, fludrocortisone, fludroxycortide, flumetasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin, fluocortolone, fluorometholone, fluperolone, fluticasone, fluticasone propionate, fluprednidene, formocortal, halcinonide, halometasone, hydrocortisone aceponate, hydrocortisone buteprate, hydrocortisone butyrate, loteprednol, medrysone, meprednisone, methylprednisolone, methylprednisolone aceponate, mometasone furoate, paramethasone, prednicarbate, prednisone, prednisolone, prednylidene, rimexolone, tixocortol, triamcinolone, ulobetasol, combinations thereof, pharmaceutically acceptable salts thereof, or esters thereof. 10. The composition of claim 1, wherein the corticosteroid comprises fluticasone or a salt thereof. 11. The composition of claim 1, wherein the corticosteroid comprises fluticasone proprionate. 12. The composition of claim 1, wherein the corticosteroid comprises about 0.025% or about 0.05% fluticasone. 13. The composition of claim 1, wherein the corticosteroid comprises about 0.5 mg or about 1.0 mg of fluticasone. 14. The composition of claim 2, wherein the second active pharmaceutical ingredient comprises lidocaine, prilocaine, or a combination thereof. 15. The pharmaceutical composition of claim 1, wherein the composition is administered for treating or reducing the symptoms of one or more of esophageal, oral, or buccal inflammation, eosinophilic esophagitis, oral lichen planus, aphthous stomatitis, odynophagia, acid reflux, dysphagia, oral, esophageal or peptic ulcers, heart burn, chest pain, abdominal pain, nausea, vomiting, coughing, sore throat, decrease in appetite, or failure to thrive. 16. The pharmaceutical composition comprising the compositions of claim 1 for treating a subject suffering from one or more of oral or esophageal inflammation, eosinophilic esophagitis, inflammatory bowel disease involving the esophagus, oral lichen planus, aphthous stomatitis, Crohn's disease, esophageal inflammation secondary to caustic/irritant ingestion, recurrent esophageal strictures of any cause and including irritant ingestion, pill-induced esophagitis, systemic diseases, congential diseases, epidermolysis bullosa, trauma, or post-surgery inflammation. 17. A topical, non-systemic oral, slow releasing, solid, soft lozenge pharmaceutical composition comprising a shell and a fill, the shell comprising: (a) about 10% to about 40% by mass of one or more gelatins, gelatin hydrolysates, or combinations thereof; (b) about 5% to about 20% by mass of glycerol; (c) about 0.1% to about 5% by mass of citric acid; (d) about 20% to about 60% by mass of one or more of maltitol, xylitol, sucralose, or combinations thereof; (e) about 5% to about 30% by mass of water; and the fill comprising: (f) about 5% to about 30% by mass of gelatins; (g) about 1% to about 5% by mass of one or more polyethylene oxides comprising a molecular weight (M.sub.v) of about 7,000,000; (h) about 5% to about 20% by mass of glycerol; (i) about 0.5% to about 5% by mass of citric acid; (j) about 20% to about 60% by mass of one or more of maltitol, xylitol, sucralose, or combinations thereof; (k) about 0.1% to about 5% by mass of polysorbate 80; (l) about 5% to about 30% by mass of water; and (m) about 0.001% to about 1% by mass of fluticasone propionate. 18. A method for treating, retarding the progression of, prophylaxis of, delaying the onset of, ameliorating, or reducing the symptoms of one or more of esophageal, oral, or buccal inflammation, eosinophilic esophagitis, oral lichen planus, aphthous stomatitis, odynophagia, acid reflux, dysphagia, oral, esophageal or peptic ulcers, heart burn, chest pain, abdominal pain, nausea, vomiting, coughing, sore throat, decrease in appetite, or failure to thrive comprising administering to a subject in need thereof the pharmaceutical composition of claim 1. 19. A method for treating or reducing the symptoms of one or more of esophageal, oral, buccal, gastrointestinal or stomach inflammation comprising administering to a subject in need thereof a topical, non-systemic oral, slow releasing, solid, soft lozenge pharmaceutical composition comprising: (a) about 10% to about 40% by mass of one or more film-forming polymers comprising gelatins; (b) about 5% to about 20% by mass of one or more plasticizers comprising glycerol, sorbitol, mannitol, maltitol, xylitol, or combinations thereof; (c) about 0.1% to about 5% by mass of one or more pH modifiers comprising one or more organic acids; (d) about 20% to about 60% by mass of one or more sweeteners comprising maltitol, xylitol, mannitol, sucralose, aspartame, stevia, or combination thereof; (e) water; (f) about 1% to about 5% by mass of one or more release modifiers comprising polyethylene oxide polymers comprising a molecular weight of about 900,000 to about 8,000,000; and (g) less than 1% by mass of one or more corticosteroids; wherein the composition orally disintegrates within about 30-45 minutes upon administration to a subject in need thereof. 20. A pharmaceutical combination comprising the composition of claim 1 and one or more additional therapeutic compounds. 21. The pharmaceutical combination of claim 20, wherein the one or more additional therapeutic compound comprises one or more of antacids (e.g., calcium hydroxide, magnesium hydroxide, alluminum hydroxide, sodium bicarbonate, calcium carbonate, bismuth sub salicylate, or others; Maalox, Mylanta, Gaviscon, Kaopectate, Pepto-Bismol) sucralfate, esomeprazole, omeprazole, lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, rabeprazole, ilaprazole, cimetidine, ranitidine, famotidine, lafutidine, nizatidine, roxatidine, tiotidine, salmeterol, albuterol, aclidinium, ipratropium, tiotropium, umeclidinium, acrivastine, azelastine, bilastine, brompheniramine, buclizine, bromodiphenhydramine, carbinoxamine, chlorpromazine, cyclizine, chlorphenamine, chlorodiphenhydramine, clemastine, cyproheptadine, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimetindene, diphenhydramine, doxylamine, ebastine, embramine, fexofenadine, hydroxyzine, loratadine, meclozine, mirtazapine, olopatadine, orphenadrine, phenindamine pheniramine, phenyltoloxamine, promethazine, quetiapine, rupatadine, tripelennamine, triprolidine, clobenpropit, ciproxifan, conessine, thioperamide, montelukast, zafirlukast, pranlukast, mepolizumab, reslizumab, omalizumab, infliximab, azathioprine, 6-mercaptopurine, thioguanine, aspirin (acetylsalicylic acid), ibuprofen, naproxen, ketoprofen, celecoxib, diclofenac, amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, streptomycin, spectinomycin, geldanamycin, herbimycin, rifaximin, loracarbef, ertapenem, doripenem, imipenem/cilastatin, meropenem, cefadroxil, cefazolin, cefalotin, cefalexin, cefaclor, cefamandole, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefepime, ceftaroline fosamil, ceftobiprole, teicoplanin, vancomycin, telavancin, dalbavancin, oritavancin, clindamycin, lincomycin, daptomycin, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, spiramycin, aztreonam, furazolidone, nitrofurantoin, linezolid, posizolid, radezolid, torezolid, amoxicillin, ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, temocillin, ticarcillin, amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate, bacitracin, colistin, polymyxin B, ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, trovafloxacin, grepafloxacin, sparfloxacin, temafloxacin, mafenide, sulfacetamide, sulfadiazine, silver sulfadiazine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, sulfanilimide, sulfasalazine, sulfisoxazole, trimethoprim-sulfamethoxazole, sulfamidochrysoidine, demeclocycline, doxycycline, minocycline, oxytetracycline, tetracycline, clofazimine, dapsone, capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, pyrazinamide, rifampicin, rifabutin, rifapentine, streptomycin, arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin/dalfopristin, thiamphenicol, tigecycline, tinidazole, trimethoprim, or combinations thereof.

Details for Patent 9,877,971

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2035-06-15
Genentech, Inc.	XOLAIR	omalizumab	For Injection	103976	06/20/2003		2035-06-15
Genentech, Inc.	XOLAIR	omalizumab	Injection	103976	09/28/2018		2035-06-15