Component of bromelain

Abstract

The invention relates to a component of bromelain which is largely responsible for the ability of bromelain to interrupt the MAP kinase cascade. The component contains ananain and comosain and is useful in the treatment or prevention of diseases and conditions mediated by T cell activation or by activation of the MAP kinase pathway.

1 . A component of bromelain which contains proteins having molecular weights of about 15.07 kDa, 25.85 kDa and 27.45 kDa as determined by SDS-PAGE, has isoelectric points of 10.4 and 10.45 and is obtainable by the following method: 
 i. dissolving bromelain in acetate buffer at pH 5.0;    ii. separating the components of the bromelain by fast flow high performance liquid chromatography on S-sepharose eluting with a linear gradient of 0 to 0.8 M sodium chloride in acetate buffer over 300 ml;    iii. collecting the fraction corresponding to the final double peak off the column; and    iv. isolating the protein from the fraction collected in (iii).    
     
     
         2 . A component of bromelain as claimed in  claim 1 , for use in medicine, particularly in the treatment or prevention of diseases and conditions mediated by: 
 i. activation of T cells;    ii. activation of the MAP kinase pathway; or    iii. the production of growth factors or cytokines;    or in the treatment or prevention of cancer.    
     
     
         3 . A component of bromelain as claimed in  claim 1  for modulating pathways controlling cell growth and proliferation.  
     
     
         4 . A component of bromelain as claimed in  claim 1  for inhibiting the production of growth factors or cytokines by cells.  
     
     
         5 . A component of bromelain as claimed in  claim 1  for inhibiting the activation of the MAP kinase pathway.  
     
     
         6 . A component of bromelain as claimed in  claim 1  for inhibiting the activation of T cells.  
     
     
         7 . A component of bromelain as claimed in  claim 1  for use as an immunosuppressant.  
     
     
         8 . A component of bromelain as claimed in  claim 1  for blocking the production of growth factors and cytokines or for the treatment or prevention of autoimmune diseases, graft or transplant rejection by a host, allergic reactions, toxic shock, apoptosis, parasite or pathogen infections or cancer.  
     
     
         9 . The use of ananain, comosain, a mixture of ananain and comosain or a component of bromelain as claimed in  claim 1  in the preparation of an agent for modulating intracellular signalling pathways which control cell growth and proliferation.  
     
     
         10 . The use of ananain, comosain, a mixture of ananain and comosain or a component of bromelain as claimed in  claim 1  in the preparation of an agent for inhibiting the production of growth factors and cytokines by cells.  
     
     
         11 . The use of ananain, comosain, a mixture of ananain and comosain or a component of bromelain as claimed in  claim 1  in the preparation of an agent for reducing or preventing the activation of the MAP kinase pathway.  
     
     
         12 . The use of ananain, comosain, a mixture of ananain and comosain or a component of bromelain as claimed in claim  1 in the preparation of an agent for reducing or preventing the activation of T cells.  
     
     
         13 . The use of ananain, comosain, a mixture of ananain and comosain or a component of bromelain as claimed in  claim 1 , wherein the agent is an immunosuppressive agent.  
     
     
         14 . The use of ananain, comosain, a mixture of ananain and comosain or the CCS fraction of bromelain in the preparation of an agent for the treatment or prevention of diseases and conditions mediated by 
 i. the activation of T cells;    ii. activation of the MAP kinase pathway; or    ii. the production of growth factors or cytokines;    or in the treatment or prevention of cancer.    
     
     
         15 . The use of ananain, comosain, a mixture of ananain and comosain or a component of bromelain as claimed in  claim 1  in the preparation of an agent for blocking the production of growth factors and other cytokines or for the treatment or prevention of autoimmune diseases, graft or transplant rejection by a host, allergic reactions, toxic shock, apoptosis, parasite or pathogen infections or cancer.  
     
     
         16 . A pharmaceutical or veterinary composition comprising the CCS fraction of bromelain together with a pharmaceutically or veterinarily acceptable excipient.  
     
     
         17 . A pharmaceutical or veterinary composition as claimed in  claim 16 , which is adapted for enteral, for example oral, nasal, buccal, topical or anal administration.  
     
     
         18 . A pharmaceutical or veterinary composition as claimed in  claim 16 , which is adapted for parenteral administration, for example by the intravenous, subcutaneous, intramuscular or intraperitoneal routes.  
     
     
         19 . A pharmaceutical or veterinary composition as claimed in  claim 16  which is adapted for oral administration and which is an enteric coated preparation.