Multi-phase emulsions based on amphiphilic block copolymers

Abstract

An composition comprises (a) a continuous aqueous phase; (b) an oily phase; and (c) an amphiphilic emulsifying system comprising a block copolymer having the formula (A)p-(B)q-(C)r, in which (B)q is a hydrophilic block and (C)r is a hydrophobic block; wherein p, q and r are integers with the proviso that: if p is 0, then A is other than hydroxyl or reactive functional groups and the block copolymer is a diblock copolymer; B and C are each individual repeating) units; if p is >1, then the block copolymer is a triblock copolymer, in which (A)p is a hydrophobic block; the hydrophobic blocks (A)p and (C)r are each homopolymers or heteropolymers; the repeating units A and C are the same or different; and wherein the ratio q/(p+r) is sufficient high so that the hydrophilic-lipophilic balance value of the block copolymer is >10.

1 . A composition comprising:
 (d) a continuous aqueous phase comprising H, O,   (e) an oily phase comprising oil; and   (f) an amphiphilic emulsifying system stabilizing the interface between the oily phase and the continuous aqueous phase, comprising a block copolymer having the formula
   (A)p-(B)q-(C)r 
 wherein:
 p, q and r are integers with the proviso that:
 if p is 0, then A is other than hydroxyl or reactive functional groups and the block copolymer is a diblock copolymer, in which (B)q is a hydrophilic block and (C)r is a hydrophobic block, B and C are each individual repeating units; if p is >1, then the block copolymer is a triblock copolymer, in which (B)q is a hydrophilic block and (A)p and (C)r are each hydrophobic blocks; the hydrophobic blocks (A)p and (C)r are each homopolymers or heteropolymers; A, B and C are each individual repeating units; the repeating units A and C are the same or different; 
 
 and wherein the ratio q/(p+r) is sufficient high so that the hydrophilic-lipophilic balance (HLB) of the block copolymer is >10. 
 
   
     
     
         2 . The composition of  claim 1 , wherein p is 0 and A is methoxy. 
     
     
         3 . The composition of  claim 1 , wherein the continuous aqueous phase comprises an antigen and/or a bioactive substance. 
     
     
         4 . The composition of  claim 1 , wherein the oily phase entraps or encapsulates an antigen and/or a bioactive agent. 
     
     
         5 . The composition of claim i, wherein the oily phase further comprises an emulsion comprising:
 (c) an internal aqueous phase comprising H 2 O, being dispersed in the oily phase; and   (d) a lipophilic emulsifying system stabilizing the interface between the inner aqueous phase and the oily phase to form a water-in-oil (W/O) emulsion;   wherein the composition is in the form of a W/O/W emulsion.   
     
     
         6 . The composition of  claim 5 , wherein the lipophilic emulsifying system comprises at least one physiologically acceptable emulsifier selected from the group consisting of mannide monooleat and sorbitan esters. 
     
     
         7 . The composition of  claim 5 , further comprising an antigen and/or a bioactive agent dissolved in the internal aqueous phase and/or in the continuous aqueous phase. 
     
     
         8 . The composition of  claim 1 , wherein the block copolymer is bioresorbable. 
     
     
         9 . The composition of  claim 1 , wherein the hydrophilic block (B)q is a liner polymer. 
     
     
         10 . The composition of  claim 1 , wherein the repeating unit B is selected from the group consisting of ethylene oxide, vinylpyroolidone, and acrylamide. 
     
     
         11 . The composition of  claim 1 , wherein the hydrophobic blocks (A)p and (C)r are each polyester polymers. 
     
     
         12 . The composition of  claim 1 , wherein the hydrophobic blocks (A)p and (C)r are each aliphatic polyesters. 
     
     
         13 . The composition of  claim 12 , wherein the aliphatic polyesters are polymers of dicarboxylic acids and a diols. 
     
     
         14 . The composition of  claim 12 , wherein the repeating units A and C are each selected from the group consisting of hydroxyacids, lactones, and combinations thereof. 
     
     
         15 . The composition of  claim 14 , wherein the hydroxyacids are selected from the group consisting of lactic acid, 6-hydroxycaproic acid, glycolic acid, malic acid monoesters, and combinations thereof. 
     
     
         16 . The composition of  claim 14 , wherein the lactones are selected from the group consisting of ε-caprolactone, lactide, glycolide, para-dioxanones, and combinations thereof. 
     
     
         17 . The composition of  claim 1 , wherein the hydrophobic blocks (A)p and (C)/r are each comprises a polymer selected from the group consisting of:
 (i) a hydroxyacid-containing polymer: poly(lactide), poly(lactic acid), poly(lactide-co-glycolide), poly(glycolide), poly(lactic acid-co-glycolic acid), poly(malic acid), poly(malic acid ester), or poly(glycolic acid);   (ii) a lactone-containing polymer: poly(lactide-co-ε-caprolactone), poly(ε-caprolactone), or poly(glycolide-co-ε-caprolactone); and   (iii) a hydroxycaproic acid-containing polymer: poly(lactic acid-co-6-hydroxycaproic acid), or poly(glycolic acid-co-6-hydroxycaproic acid).   
     
     
         18 . The composition of  claim 1 , wherein the block copolymer is selected from the group consisting of poly(ethylene glycol)-block-poly(lactide-co-ε-caprolactone), poly(ethylene glycol)-block-polylactide, and poly(ethylene glycol)-block-poly(ε-caprolactone). 
     
     
         19 . A block copolymer comprising the formula
   (A)p-(B)q-(C)r   wherein:
 p, q and r are integers with the proviso that:
 if p is 0, then A is other than hydroxyl or reactive functional groups and the block copolymer is a diblock copolymer, in which (B)q is a hydrophilic block and (C)r is a hydrophobic block; B and C are each individual repeating units; 
 if p is >1, then the block copolymer is a triblock copolymer, in which (B)q is a hydrophilic block and (A)p and (C)r are each hydrophobic blocks; the hydrophobic blocks (A)p and (C)r are each homopolymers or heteropolymers; A, B and C are each individual repeating units; the repeating units A and C are the same or different; 
 and wherein the ratio q/(p+r) is sufficient high so that the hydrophilic-lipophilic balance (1-1.03) of the block copolymer is >10. 
 
   
     
     
         20 . The block copolymer of  claim 19 , wherein the hydrophilic block (B)q constitutes at least 50% by weight of the block copolymer.