Absorption enhancers such as E.G. BHT, BHA or propyl gallate

Abstract

The invention provides a pharmaceutical composition comprising a mixture of (a) an active macromolecular principle, and (b) an aromatic alcohol absorption enhancer chosen from butylated hydroxy toluene, butylated hydroxy anisole and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, and further comprises a pharmaceutical composition comprising a mixture of (a) an active macromolecular principle, (b) an aromatic alcohol absorption enhancer chosen from propyl gallate, butylated hydroxy toluene, butylated hydroxy anisole and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, and (c) a solubilisation aid capable of increasing the solubility of the aromatic alcohol absorption enhancer in aqueous media.

1 - 29 . (canceled) 
   
   
       30 . A pharmaceutical composition comprising a mixture of:
 (a) an active macromolecular principle, and   (b) an aromatic alcohol absorption enhancer chosen from propyl gallate, butylated hydroxy toluene, butylated hydroxy anisole and analogues and derivatives thereof, wherein the aromatic alcohol absorption enhancer is present in an amount by weight greater than or equal to that of the active macromolecular principle, and wherein when the aromatic alcohol absorption enhancer is propyl gallate or an analogue or derivative thereof, the composition further comprises:   (c) a solubilisation aid capable of increasing the solubility of the aromatic alcohol absorption enhancer in aqueous media.   
   
   
       31 . A composition according to  claim 30 , wherein the mixture comprises less than 5% by weight of water. 
   
   
       32 . A composition according to  claim 30 , wherein the composition is coated with an enteric coating which becomes permeable at a pH of from 3 to 7. 
   
   
       33 . A composition according to  claim 30 , wherein the mixture comprises at least 1% by weight of the aromatic alcohol absorption enhancer. 
   
   
       34 . A composition according to  claim 30 , wherein the ratio by weight of the aromatic alcohol absorption enhancer to active macromolecular principle is at least 5:1. 
   
   
       35 . A composition according to  claim 30 , wherein the mixture is in the form of a solution or a microparticulate dispersion. 
   
   
       36 . A composition according to  claim 30 , wherein the mixture is in solid form. 
   
   
       37 . A composition according to  claim 30 , wherein the active macromolecular principle is a polypeptide or protein, polynucleotide, polysaccharide or a mixture thereof. 
   
   
       38 . A composition according to  claim 30 , wherein the aromatic alcohol absorption enhancer is chosen from BHT, BHA and analogues and derivatives of hydroxy toluene or hydroxy anisole where the methyl group or the methoxy group linked to the aromatic ring and/or the hydrogen ortho to the hydroxyl group are replaced by linear or branched chain C 1-12  alkyl, C 1-12  alkyloxy, C 1-12  alkylthio or C 2-12  alkenyl, either unsubstituted or substituted in any position, especially by halogen atoms. 
   
   
       39 . A composition according to  claim 30 , wherein the aromatic alcohol absorption enhancer is propyl gallate or a linear or branched chain C 1-12  alkyl, C 1-12  alkyloxy, C 1-12  alkylthio or C 2-12  alkenyl ester of gallic acid, and the compounds are optionally substituted with halogen, linear or branched chain C 1-12  alkyl, C 1-12  alkyloxy, C 1-12  alkylthio or C 2-12  alkenyl. 
   
   
       40 . A composition according to  claim 30 , where the solubilisation aid is chosen from a bile acid or salt, benzyl alcohol, phenyl ethanol, phenoxyethanol, transcutol and isopropanol. 
   
   
       41 . A composition according to  claim 30 , where the active macromolecular principle is insulin, calcitonin, growth hormone, parathyroid hormone, or erythropoeitin, and derivatives and analogues, either synthetic or from natural sources, conforming to structures derived from either human or animal origin. 
   
   
       42 . A composition according to  claim 30 , where the active macromolecular principle is insulin, calcitonin, parathyroid hormone or a derivative or an analogue thereof, either synthetic or from natural sources, conforming to structures derived from either human or animal origin. 
   
   
       43 . A composition according to  claim 42 , where the active macromolecular principle is insulin or a derivative or an analogue thereof, either synthetic or from natural sources, conforming to structures derived from either human or animal origin and the composition further comprises an insulin sensitizing agent. 
   
   
       44 . A composition according to  claim 30 , for use in the therapeutic or diagnostic treatment of the human or animal body.