Liposomal composition containing mild acidic active agent

Abstract

Provided is a method for preparing a liposomal composition. The method comprises the step of contacting a liposome solution with a mild acidic agent for a limited time. The liposome solution comprises a weak acid salt encapsulated within an aqueous interior space separated from the aqueous medium by a membrane comprised of a lipid mixture containing one or more lipids and a hydrophilic polymer conjugated lipid at a molar percentage of less than 3% based on the total amount of the lipid mixture. The time for encapsulating the agent to a desired amount at a predetermined ratio to lipids is dramatically reduced even under a condition without elevating the temperature to above ambient environment.

1 - 5 . (canceled) 
     
     
         6 . A delivery vehicle, said delivery vehicle comprising a liposome in an aqueous medium, wherein the liposome comprises a combination of a weak acid salt and a polyprotic acid encapsulated within the liposome. 
     
     
         7 . The delivery vehicle according to  claim 6 , wherein the polyprotic acid is an organic tribasic acid. 
     
     
         8 . The delivery vehicle according to  claim 6 , wherein the polyprotic acid is selected from the group consisting of citric acid, succinic acid, tartaric acid or a combination thereof. 
     
     
         9 - 33 . (canceled) 
     
     
         34 . A liposomal composition, comprising a liposome-encapsuled mild acidic agent in an aqueous medium and prepared by the steps:
 contacting the liposome of the delivery vehicle according to  claim 6     with a mild acidic agent to obtain the liposome-encapsulated mild acidic agent.   
     
     
         35 . The liposomal composition according to  claim 34 , wherein the liposome comprises a lipid mixture; and the lipid mixture contains one or more lipids and a polyethylene glycol-derived lipid. 
     
     
         36 . The liposomal composition according to  claim 34 , wherein the polyethylene glycol-derived lipid is at a molar percentage ranging from 0.1% to 3% based on the total amount of the lipid mixture; preferably from 0.5% to 3%; and more preferably, from 0.5% to 1%. 
     
     
         37 . The liposomal composition according to  claim 34 , wherein the weak acid salt is sodium acetate, potassium acetate or calcium acetate. 
     
     
         38 . The liposomal composition according to  claim 34 , wherein the weak acid salt is at a concentration of at least 100 mM; and typically, between 100 mM and 800 mM; preferably between 200 mM and 800 mM; and most preferably between 400 mM and 800 mM. 
     
     
         39 - 41 . (canceled) 
     
     
         42 . The liposomal composition according to  claim 34 , wherein the polyprotic acid is at a concentration less than 50 mM, preferably less than 10 mM, more preferably between 0.01 mM and 5 mM, much more preferably between 0.1 mM and 3 mM, and most preferably between 1.5 mM and 2.5 mM. 
     
     
         43 . The liposomal composition according to  claim 34 , wherein the molar ratio of the mild acidic agent to the amount of lipids of the liposomal composition is at least 0.001:1 and preferably from 0.001:1 to 0.05:1. 
     
     
         44 . The delivery vehicle according to  claim 6 , wherein the combination of the weak acid salt and the polyprotic acid is at a molar ratio no less than 8:1. 
     
     
         45 . The delivery vehicle according to  claim 6 , wherein the combination of the weak acid salt and the polyprotic acid is at a molar ratio ranging from 8:1 to 80000:1. 
     
     
         46 . The delivery vehicle according to  claim 6 , wherein the combination of the weak acid salt and the polyprotic acid is at a molar ratio ranging from 8:1 to 200:1. 
     
     
         47 . The delivery vehicle according to claim  1 , wherein the weak acid salt is sodium acetate, potassium acetate or calcium acetate. 
     
     
         48 . The delivery vehicle according to  claim 6 , wherein the weak acid salt is at a concentration of at least 100 mM; and typically, between 100 mM and 800 mM; preferably between 200 mM and 800 mM; and most preferably between 400 mM and 800 mM. 
     
     
         49 . The delivery vehicle according to  claim 6 , wherein the liposome comprises a lipid mixture; and the lipid mixture contains one or more lipids and a polyethylene glycol-derived lipid. 
     
     
         50 . The liposomal composition according to  claim 34 , wherein the mild acidic agent is arachidonic acid metabolite. 
     
     
         51 . The liposomal composition according to  claim 34 , wherein the mild acidic agent is a prostaglandin. 
     
     
         52 . A liposomal composition, comprising
 a delivery vehicle, said delivery vehicle comprising a liposome in an aqueous medium, wherein the liposome comprises a combination of a weak acid salt and an organic tribasic acid encapsulated within the liposome, wherein the weak acid salt is sodium acetate, potassium acetate or calcium acetate; and   an arachidonic acid metabolite.   
     
     
         53 . The liposomal composition according to  claim 52 , wherein the molar ratio of the arachidonic acid metabolite to the amount of lipids of the liposomal composition is at least 0.001:1.