Formulation of liposome rehydration salts

Abstract

A liposomal rehydration salt formulation comprising phosphatidylcholine liposomes, salts, water, and a percentage inclusion ratio of salts (salts retained within said liposomes/total salts) of at least 40%; and a process for preparing said formulation using tangential ultrafiltration.

1 . A liposomal rehydration salt formulation, characterized in that it comprises phospholipids at a concentration of 1 g/l to 60 g/l, salts, water, and a percentage inclusion ratio of salts (salts retained within total salts/liposomes) of at least 40%. 
     
     
         2 . The liposomal rehydration salt formulation of  claim 1 , characterized in that said percentage inclusion ratio comprises a value of at least 50%. 
     
     
         3 . The liposomal rehydration salt formulation of  claim 1 , characterized in that said percentage inclusion ratio comprises a value of at least 52%. 
     
     
         4 . The liposomal rehydration salt formulation of  claim 1 , characterized in that said percentage inclusion ratio comprises a value of at least 56%. 
     
     
         5 . The liposomal rehydration salt formulation of  claim 1 , characterized in that said phospholipids are selected from the group consisting of phosphatidylcholines (PCs), phosphatidylserines (PSs), phosphatidylethanolamines (PEs), phosphatidylglycerols (PGs), phosphatidylinositols (PIs), phosphatidic acids (PAs), and mixtures thereof. 
     
     
         6 . The formulation of  claim 1 , characterized in that it further comprises an antioxidant selected from the group consisting of phytosterol, tocopherol, and mixtures thereof. 
     
     
         7 . The formulation of  claim 1 , characterized in that said salts are selected from the group consisting of sodium chloride at a concentration of 0.7 g/l to 2.8 g/l, potassium citrate at a concentration of 0.8 g/l to 2.5 g/l, sodium citrate at a concentration of 0.5 g/l to 2.9 g/l, and mixtures thereof. 
     
     
         8 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it further comprises carbohydrates at a concentration of up to 6 g/l. 
     
     
         9 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it further comprises carbohydrates at a concentration of up to 30 g/l. 
     
     
         10 . The liposomal rehydration salt formulation of  claim 9 , characterized in that said carbohydrates are selected from the group consisting of glucose, fructose, dextrose, high fructose corn syrup, and mixtures thereof. 
     
     
         11 . The liposomal rehydration salt formulation of  claim 9 , characterized in that said carbohydrate is glucose. 
     
     
         12 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it comprises an osmolality lower than 190 mmol/L. 
     
     
         13 . The liposomal rehydration salt formulation of  claim 1 , characterized in that said liposomes comprise a particle diameter ranging from 200 nm to 500 nm. 
     
     
         14 . The liposomal rehydration salt formulation of  claim 1 , characterized in that said liposomes comprise a particle diameter ranging from 225 nm to 450 nm. 
     
     
         15 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it comprises an oral administration infusion for oral replacement of fluids and electrolyte salts drinkable by people with dehydration caused by diarrhoea and vomiting, thus preventing severe dehydration, and maintaining body electrolytes and fluids. 
     
     
         16 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it comprises an oral administration infusion for use in sport activities. 
     
     
         17 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it further comprises Stevia at a concentration of 0.1 g/l to 0.2 g/l; sucrose at a concentration of 20 g/l to 50 g/l; citric acid at a concentration of 3 g/l to 4 g/l; and natural flavours at a concentration of 1 g/l to 2 g/l, and it is a formulation for rehydration in children. 
     
     
         18 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it further comprises sucralose at a concentration of 0.1 g/l to 1.5 g/l; high fructose corn syrup 55° Brix at a concentration of 20 g/l to 50 g/l; citric acid at a concentration of 3 gl to 5 g/l; and natural flavours at a concentration of 1 g/l to 2 g/l; and it comprises a paediatric formula for acute hypotonic dehydration. 
     
     
         19 . The liposomal rehydration salt formulation of  claim 1 , characterized in that it further comprises Stevia at a concentration of 0.1 g/l to 0.2 g/l; sucrose at a concentration of 20 g/l to 25 g/l; citric acid at a concentration of 3 g/l to 4 g/l; and natural flavours at a concentration of 1 g/l to 2 g/l; and it comprises a formulation for rehydration in sport activities. 
     
     
         20 . A process for preparing the formulation of  claim 1 , characterized in that it comprises the following steps:
 a. preparing an aqueous phase (AP) or buffer comprising sodium chloride, potassium citrate, sodium citrate dissolved in distilled water;   b. separately preparing an ethanol phase (EP) by dissolving said phospholipid at a concentration of 0.1% to 6% (W/V) and optionally an antioxidant at a concentration of 0.2% to 0.5% (W/V), in alcohol;   c. inducing formation of liposomes by injecting said EP into said AP at room temperature, while stirring;   d. subjecting the liposomal solution obtained in step c to a tangential ultrafiltration (TUF) concentration process, removing the buffer and maintaining the liposomes and their contents, thus reducing the volume at least by 10-fold; and   e. subjecting the liposomal solution obtained in step d to a tangential ultrafiltration (TUF) concentration process,   wherein ethanol is removed and the buffer is replaced by a saline solution, maintaining the liposomes and the contents therein.   
     
     
         21 . The process of  claim 20 , characterized in that in step “a” said aqueous phase (AP) or buffer comprises sodium chloride at a concentration of 6 mmol/l to 20 mmol/l:
 potassium citrate at a concentration of 1 mmol/l and 7 mmol/l: sodium citrate at a concentration of 2 mmol/l to 5 mmol/l; and distilled water. 
 
     
     
         22 . The process of  claim 20 , characterized in that in step “a” said phospholipids are selected from the group consisting of phosphatidylcholines (PCs), phosphatidylserines (PSs), phosphatidylethanolamines (PEs), phosphatidylglycerols (PGs), phosphatidylinositols (PIs), phosphatidic acids (PAs), and mixtures thereof. 
     
     
         23 . The process of  claim 20 , characterized in that in step “b” said alcohol comprises ethyl alcohol. 
     
     
         24 . The process of  claim 20 , characterized in that in step “e” said saline solution comprises a sodium concentration of 12 mmol/l to 50 mmol/l; a potassium concentration of 3 mmol/l to 14 mmol/l; a chloride concentration of 5 mmol/l to 40 mmol/l; a citrate concentration of 3 mmol/l to 10 mmol/l; and it further comprises a glucose concentration of 17 mmol/l to 45 mmol/l. 
     
     
         25 . The process of  claim 20 , characterized in that the AP:EP volume ratio in step c is at least 10:1. 
     
     
         26 . The process of  claim 20 , characterized in that the AP:EP volume ratio in step c is at least 10:0.5. 
     
     
         27 . The process of  claim 20 , characterized in that the AP:EP volume ratio in step c is at least 10:0.4. 
     
     
         28 . The process of  claim 20 , characterized in that it comprises a perpendicular flow process, wherein the ethanol phase is added on the aqueous phase by perpendicular coupling to the flow of the former, and with a linear velocity ratio REP/RAP of no more than 1/200. 
     
     
         29 . A method of treating a human suffering from dehydration caused by diarrhoea and vomiting, comprising orally administering the liposomal rehydration salt formulation of  claim 1  to the human. 
     
     
         30 . A method of preventing severe dehydration of, and maintaining body electrolytes and fluids in, a human, comprising orally administering the liposomal rehydration salt formulation of  claim 1  to the human.