Therapeutic Compositions and Uses Thereof

Abstract

The invention provides pharmaceutical compositions, including anti-gastrointestinal cancer compositions, containing propolis and cyclodextrin. Methods of using such compositions, in particular in the treatment or prevention of gastrointestinal cancers, and in the resenitisation of gastrointestinal cancers to therapy, are also provided.

1 . A method of treating or preventing a gastrointestinal cancer in a subject or of inducing apoptosis of one or more neoplastic gastrointestinal cells in a subject, the method comprising administering an effective amount of a composition comprising, consisting essentially or, or consisting of propolis and cyclodextrin, to a subject in need thereof. 
     
     
         2 . A method of inhibiting gastrointestinal tumour formation, inhibiting gastrointestinal tumour growth, inhibiting gastrointestinal tumour metastasis, or treating or preventing a gastrointestinal cancer in a subject, the method comprising separate, simultaneous or sequential administration of an effective amount of a composition comprising, consisting essentially or, or consisting of propolis and cyclodextrin, to a subject in need thereof. 
     
     
         3 . A method of increasing the responsiveness of a subject to a gastrointestinal cancer therapy or of increasing the sensitivity of a gastrointestinal tumour in a subject to a gastrointestinal cancer therapy, the method comprising administration to the subject of a composition comprising, consisting essentially or, or consisting of propolis and cyclodextrin. 
     
     
         4 . A method of resensitising one or more gastrointestinal cancer cells that are resistant to treatment, the method comprising administering an effective amount of a composition comprising, consisting essentially or, or consisting of propolis and cyclodextrin to the one or more cancer cells. 
     
     
         5 . A method of at least partially reversing the resistance of a neoplastic cell in a subject suffering from gastrointestinal cancer to a gastrointestinal cancer therapy, or of reversing, wholly or in part, the resistance of a gastrointestinal cancer-burdened patient to a gastrointestinal cancer therapy, or of re-sensitising one or more tumours of a gastrointestinal cancer-burdened patient which are, or are predicted to either be or become, resistant to treatment with a gastrointestinal cancer therapy, the method comprising administration to the subject of a composition comprising, consisting essentially or, or consisting of propolis and cyclodextrin. 
     
     
         6 . A method of improving gut health, the method comprising administering to a subject in need thereof a composition comprising, consisting essentially of, or consisting of propolis and cyclodextrin; and in particular, propolis and gamma-cyclodextrin, for example European propolis and gamma-cyclodextrin. 
     
     
         7 . The method according to any one of  claims 1  to  6 , wherein the composition consists of propolis and cyclodextrin. 
     
     
         8 . The use of propolis and cyclodextrin in the manufacture of a composition for use in inhibiting gastrointestinal tumour formation, inhibiting gastrointestinal tumour growth, inhibiting gastrointestinal tumour metastasis or treating or preventing gastrointestinal cancer in a subject; inducing apoptosis of one or more neoplastic gastrointestinal cells in a subject; increasing the responsiveness of a subject to a gastrointestinal cancer therapy; increasing the sensitivity of a gastrointestinal tumour in a subject to a gastrointestinal cancer therapy; resensitising one or more gastrointestinal cancer cells in a subject that are resistant to treatment; at least partially reversing the resistance of a neoplastic cell in a subject suffering from gastrointestinal cancer to a gastrointestinal cancer therapy; reversing, wholly or in part, the resistance of a gastrointestinal cancer-burdened patient to a gastrointestinal cancer therapy; or re-sensitising one or more tumours of a gastrointestinal cancer-burdened patient which are, or are predicted to either be or become, resistant to treatment with a gastrointestinal cancer therapy to treatment with a gastrointestinal cancer therapy. 
     
     
         9 . The use according to  claim 8  wherein the cyclodextrin is gamma-cyclodextrin. 
     
     
         10 . The use according to  claim 8  or  9  wherein the composition comprises at least one additional therapeutic agent. 
     
     
         11 . An anti-gastrointestinal cancer composition comprising propolis and cyclodextrin. 
     
     
         12 . The method of any one of  claims 1  to  7 , the use of any one of  claims 8  to  10 , or the composition of  claim 11 , wherein the cyclodextrin is gamma-cyclodextrin, or the cyclodextrin is present as a combination of cyclodextrins comprising gamma-cyclodextrin. 
     
     
         13 . The method of any one of  claim 1  to  7  or  12 , the use of any one of  claim 8  to  10  or  12 , or the composition of  claim 11  or  12 , wherein the cyclodextrin is chemically-modified cyclodextrin. 
     
     
         14 . The method of any one of  claim 1  to  7 ,  12  or  13 , the use of any one of  claim 8  to  10 ,  12 , or  13 , or the composition of any one of  claims 11  to  13 , wherein the propolis is a propolis extract or fraction. 
     
     
         15 . The method, use, or composition of  claim 14  wherein the propolis is free of wax. 
     
     
         16 . The method of any one of  claims 1  to  7 , or  12  to  14 , the use of any one of  claim 8  to  10 , or  12  to  14 , or the composition of any one of  claims 11  to  14 , wherein the propolis is European or Poplar propolis. 
     
     
         17 . The method of any one of  claims 1  to  7 , or  12  to  14 , the use of any one of  claim 8  to  10 , or  12  to  14 , or the composition of any one of  claims 11  to  14 , wherein the propolis is Brazilian Green propolis. 
     
     
         18 . The method, use, or composition of  claim 17  wherein the Brazilian Green propolis is at least in part obtained by bees from leaf exudates of the tree  Baccharis dracanculifolia.    
     
     
         19 . The method of any one of  claims 1  to  7 , or  12  to  18 , the use of any one of  claim 8  to  10 , or  12  to  18 , or the composition of any one of  claims 11  to  18 , wherein the composition comprises from about 1.0% wt to about 99% wt propolis. 
     
     
         20 . The method of any one of  claims 1  to  7 , or  12  to  18 , the use of any one of  claim 8  to  10 , or  12  to  18 , or the composition of any one of  claims 11  to  18 , wherein the composition comprises from about 1.0% wt to about 99% wt propolis resin. 
     
     
         21 . The method, use, or composition of  claim 19  wherein the composition comprises from about 1% wt to about 99% wt propolis, from about 1% wt to about 25% wt propolis, from about 1% wt to about 30% wt propolis, from about 5% wt to about 25% wt propolis, from about 5% wt to about 30% wt propolis, from about 5% wt to about 99% wt propolis, from about 10% wt to about 25% wt propolis, from about 10% wt to about 30% wt propolis, from about 10% wt to about 99% wt propolis, from about 15% wt to about 25% wt, from about 15% wt to about 30% wt, from about 15% wt to about 99% wt, from about 20% wt to about 25% wt, from about 20% wt to about 30% wt, from about 20% wt to about 99% wt, or about 25% wt propolis, or about 30% wt propolis. 
     
     
         22 . The method, use, or composition of  claim 20  wherein the composition comprises from about 1% wt to about 99% wt propolis resin, from about 1% wt to about 25% wt propolis resin, from about 1% wt to about 30% wt propolis resin, from about 5% wt to about 25% wt propolis resin, from about 5% wt to about 30% wt propolis resin, from about 5% wt to about 99% wt propolis resin, from about 10% wt to about 25% wt propolis resin, from about 10% wt to about 30% wt propolis resin, from about 10% wt to about 99% wt propolis resin, from about 15% wt to about 25% wt, from about 15% wt to about 30% wt, from about 15% wt to about 99% wt, from about 20% wt to about 25% wt, from about 20% wt to about 30% wt, from about 20% wt to about 99% wt, or about 25% wt propolis resin, or about 30% wt propolis resin. 
     
     
         23 . The method of any one of  claims 1  to  7 , or  12  to  22 , the use of any one of  claims 8  to  10 , or  12  to  22 , or the composition of any one of  claims 11  to  22 , wherein the propolis in the composition is entirely encapsulated within the cyclodextrin. 
     
     
         24 . The method of any one of  claims 1  to  7 , or  12  to  23 , the use of any one of  claims 8  to  10 , or  12  to  23 , or the composition of any one of  claims 11  to  23 , wherein the molar ratio of propolis to cyclodextrin in the composition is no greater than about 1:1. 
     
     
         25 . A composition comprising, consisting essentially of or consisting of propolis and gamma-cyclodextrin. 
     
     
         26 . A composition of any one of the preceeding claims for use in inhibiting gastrointestinal tumour formation, inhibiting gastrointestinal tumour growth, inhibiting gastrointestinal tumour metastasis or treating or preventing gastrointestinal cancer in a subject; inducing apoptosis of one or more neoplastic gastrointestinal cells in a subject; increasing the responsiveness of a subject to a gastrointestinal cancer therapy; increasing the sensitivity of a gastrointestinal tumour in a subject to a gastrointestinal cancer therapy; resensitising one or more gastrointestinal cancer cells in a subject that are resistant to treatment; at least partially reversing the resistance of a neoplastic cell in a subject suffering from gastrointestinal cancer to a gastrointestinal cancer therapy; reversing, wholly or in part, the resistance of a gastrointestinal cancer-burdened patient to a gastrointestinal cancer therapy; or re-sensitising one or more tumours of a gastrointestinal cancer-burdened patient which are, or are predicted to either be or become, resistant to treatment with a gastrointestinal cancer therapy to treatment with a gastrointestinal cancer therapy. 
     
     
         27 . The composition of  claim 26  for use in the treatment or prevention of gastrointestinal cancer. 
     
     
         28 . An anti-gastrointestinal cancer composition comprising cyclodextrin. 
     
     
         29 . The method, use, or composition as claimed in  claim 16 , wherein the European propolis has a caffeic acid phenylether ester concentration of greater than about 1 mg/g. 
     
     
         30 . The method, use, or composition as claimed in  claim 16  or  claim 29 , wherein the European propolis has a pinocembrin concentration of greater than about 10 mg/g. 
     
     
         31 . The method, use, or composition as claimed in  claim 16 ,  29  or  30 , wherein the European propolis has a galangin concentration of greater than about 5 mg/g. 
     
     
         32 . The method, use, or composition as claimed in  claim 16  or any one of  claims 29  to  31 , wherein the European propolis has chrysin concentration of greater than about 3.5 mg/g. 
     
     
         33 . The method, use, or composition as claimed in any one of  claims 1  to  32 , wherein the composition comprises two or more of caffeic acid phenylether ester (CAPE), caffeic acid, pinocembrin, benzyl caffeate, chrysin, galangin, and pinobanksin. 
     
     
         34 . The method, use, or composition as claimed in any one of  claims 1  to  33 , wherein the composition is one to which has been added one or more of CAPE, caffeic acid, pinocembrin, benzyl caffeate, chrysin, galangin, and pinobanksin. 
     
     
         35 . The method, use, or composition as claimed in any one of  claims 1  to  34 , wherein the composition has a CAPE concentration of greater than about 1 mg/g. 
     
     
         36 . The method, use, or composition as claimed in any one of  claims 1  to  35 , wherein composition has a pinocembrin concentration of greater than about 1 mg/g. 
     
     
         37 . The method, use, or composition as claimed in any one of  claims 1  to  36 , wherein the composition has a galangin concentration of greater than about 1 mg/g. 
     
     
         38 . The method, use, or composition as claimed in any one of  claims 1  to  37 , wherein the composition has a chrysin concentration of greater than about 1 mg/g. 
     
     
         39 . The method, use, or composition as claimed in any one of  claims 1  to  38 , wherein the composition has a pinobanksin concentration of greater than about greater than about 1 mg/g. 
     
     
         40 . The method, use, or composition as claimed in any one of  claims 1  to  39 , wherein the composition has a caffeic acid concentration of greater than about greater than about 1 mg/g.