Sterically stabilized carrier for subcutaneous, sublingual and oral therapeutics, compositions and methods for treating a mammal

Abstract

Disclosed herein are pharmaceutical compositions and methods for oral, sublingual or subcutaneous administration comprising a sterically stabilized liposome carrier comprising: i) poly (ethylene glycol) distearoylphosphatidylethanolamine (PEG-DSPE); and ii) at least one of phosphatidylglycerol and phosphatidylcholine. Compositions and methods for treatment of food allergy and eosinophilic esophagitis are also described.

1 .- 151 . (canceled) 
     
     
         152 . A method for treating inflammation associated with an allergy or a disease in a subject in need thereof, the method comprising administering, orally or sublingually, a pharmaceutical composition comprising a therapeutically effective amount of an active agent, wherein the active agent is encapsulated in a sterically stabilized liposome carrier that comprises: i) poly (ethylene glycol) distearoylphosphatidylethanolamine (PEG-DSPE); and ii) phosphatidylglycerol, phosphatidylcholine, or a combination thereof, wherein the pharmaceutical composition is devoid of cholesterol and further comprises a pH sensitive component which causes the liposome to release the active agent in the stomach. 
     
     
         153 . The method of  claim 152 , wherein the active comprises a proton pump inhibitor, a corticosteroid, an antihistamine, a bronchodilator, a mast cell stabilizer, a leukotriene inhibitor, an allergen, an anti-inflammatory agent, or any combination thereof. 
     
     
         154 . The method of  claim 152 , wherein the pH sensitive component comprises an acylated amino acid, a phospholipid, a fatty acid, a double chain amphiphile, cholesteryl hemisuccinate, or any combination thereof. 
     
     
         155 . The method of  claim 154 , wherein the pH sensitive component comprises N-palmitoyl homocysteine (PHC). 
     
     
         156 . The method of  claim 152 , wherein the active agent comprises an anti-inflammatory agent that comprises theophylline, budesonide, flunisolide, triamcinolone, beclomethasone, fluticasone, mometasone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, cortisone, or betamethasone, or any combination thereof. 
     
     
         157 . The method of  claim 152 , wherein the allergy comprises a food allergy and the active agent comprises a grass pollen allergen, a weed pollen allergen, an indoor allergen, a mold allergen, a tree pollen allergen, a stinging insect allergen, a food allergen, or any combination thereof. 
     
     
         158 . The method of  claim 152 , wherein the allergy is a food allergy, and wherein the active agent comprises peanut, tree nut, egg, shellfish, soy, milk, gluten, or any combination thereof. 
     
     
         159 . The method of  claim 158 , wherein the peanut comprises whole peanut, peanut powder, peanut butter, or any combination thereof. 
     
     
         160 . The method of  claim 152 , wherein the method treats allergy, and wherein the active agent comprises an H1-antihistamine, H2-antihistamine, H3-antihistamine, H4-antihistamine, or any combination thereof. 
     
     
         161 . The method of  claim 160 , wherein the active agent comprises the H1-antihistamine that is 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, or any combination thereof. 
     
     
         162 . The pharmaceutical composition of  claim 152 , wherein the pharmaceutical composition contains about 60% to about 99% phosphatidylcholine, phosphatidylglycerol, or combination thereof. 
     
     
         163 . The pharmaceutical composition of  claim 152 , wherein the pharmaceutical composition contains about 1% to about 5% PEG-DSPE. 
     
     
         164 . The pharmaceutical composition of  claim 152 , wherein the pharmaceutical composition contains about 1% to about 33% of the active agent. 
     
     
         165 . The method of  claim 152 , further comprising administering a second pharmaceutical composition, the second pharmaceutical composition comprising at least one active agent encapsulated in a second population of liposome carriers, wherein the second population of liposome carriers are stable in the stomach and release the at least one active agent in the small intestine of the subject. 
     
     
         166 . The method of  claim 165 , wherein the at least one active agent comprises the active agent of  claim 152 . 
     
     
         167 . The method of  claim 165 , wherein the at least one active agent is different from the active agent of  claim 152 . 
     
     
         168 . The method of  claim 152 , wherein the active agent comprises an anti-IgE antibody or a fragment thereof. 
     
     
         169 . The method of  claim 165 , wherein the active agent is in a form of a lyophilized powder. 
     
     
         170 . The method of  claim 152 , wherein the phosphatidylglycerol or phosphatidylcholine contains an acyl group comprising from about 8 to about 24 carbon atoms. 
     
     
         171 . The method of  claim 152 , wherein the phosphatidylglycerol or phosphatidylcholine contains an acyl chain comprising distearoyl, dipalmitoyl, or stearoyl palmitoyl.