Histaminase of vegetable origin for use in the treatment of allergic and septic shock and of allergic asthma

Abstract

The present invention relates to a histaminase of vegetable origin to be used in the treatment of allergic and septic shock and inallergic asthma. The invention also regards the preparation of the histaminase for pharmaceutical use and the corresponding pharmaceutical compositions.

1 . A histaminase of vegetable origin to be used as medicament.  
     
     
         2 . A histaminase of vegetable origin to be used for the treatment of histamine-mediated affections.  
     
     
         3 . The histaminase according to  claim 2  for the treatment of at least one of the following affections: allergic shock, septic shock, allergic asthma, anaphylaxis, rhinitis, allergic conjunctivitis, urticaria, atopic dermatitis, pruritus.  
     
     
         4 . Pharmaceutical compositions comprising an histaminase of vegetable origin to be used as medicament.  
     
     
         5 . The pharmaceutical compositions according to  claim 4  to be used for the treatment of histamine-mediated affections.  
     
     
         6 . The pharmaceutical compositions according to  claim 5  for the treatment of at least one of the following affections: allergic shock, septic shock, allergic asthma, anaphylaxis, rhinitis, allergic conjunctivitis, urticaria, atopic dermatitis, pruritus.  
     
     
         7 . The pharmaceutical compositions according to claims  4 - 6  in injectable formulation.  
     
     
         8 . The pharmaceutical compositions according to  claim 7 , in which the histaminase is in lyophilized form and, at the moment of use, is dissolved in the solvent comprising apyrogenic physiological solution, buffered at pH 7.4 or other iso-osmotic solutions.  
     
     
         9 . The pharmaceutical compositions according to claims  4 - 6  in spray formulation.  
     
     
         10 . The pharmaceutical compositions according to claims  4 - 6 , in which the histaminase is immobilized on a biocompatible insoluble matrix.  
     
     
         11 . The pharmaceutical compositions according to  claim 10 , in which the histaminase is bound on a matrix selected between: CNBr-activated Sepharose 4B® and on activated CH-Sepharose 4B®.M.  
     
     
         12 . A method for preparation of histaminase of vegetable origin for pharmaceutical use, characterized in that the starting vegetable material undergoes homogenization in conditions of pH<7, the homogenate thus treated being then subjected to subsequent stages of extraction and purification.  
     
     
         13 . The method according to  claim 12 , in which homogenization is conducted at pH<5.5 in phosphate buffer with ionic force<100 mM.  
     
     
         14 . The method according to  claim 12 , in which homogenization is conducted in phosphate buffer, approximately 50 mM at pH 3.5-5.  
     
     
         15 . The method according to claims  12 - 14 , in which the starting vegetable material is selected from among  Pisum sativum L., Lens culinaris, Cicer arietinum, Latirus sativus  and corresponding mixtures.  
     
     
         16 . The method according to  claim 15 , in which the starting vegetable material consists of etiolated seedlings of approximately 10 days old.  
     
     
         17 . The method according to claims  12 - 16 , in which the histaminase undergoes lyophilization starting from a solution thereof in phosphate buffer 10 mM pH 7.4 containing NaCl 0.15 M.  
     
     
         18 . The histaminase obtained according to the method described in claims  12 - 17 , characterized by a specific activity in the region of 60 UE/mg, where by enzymetic unit (UE) is meant the quantity of protein that catalyses the conversion of one μmole of substrate per minute.  
     
     
         19 . The histaminase according to  claim 18  in lyophilized form.  
     
     
         20 . The histaminase according to  claim 18 , to be used in concentrations ranging between 0.01 mg and 1 mg per administration.  
     
     
         21 . Use of histaminase of vegetable origin for the preparation of a medicament for the treatment of histamine-mediated affections.  
     
     
         22 . The use according to  claim 21  for the treatment of at least one of the following affections: allergic shock, septic shock, allergic asthma, anaphylaxis, rhinitis, allergic conjunctivitis, urticaria, atopic dermatitis, pruritus.  
     
     
         23 . The use according to claims  21  and  22  for the preparation of a medicament in injectable formulation.  
     
     
         24 . The use according to claims  21  and  22  for the preparation of a medicament in spray formulation.  
     
     
         25 . The use according to claims  21  and  22 , in which the histaminase is immobilized on a biocompatible insoluble matrix.  
     
     
         26 . The use according to claims  21  and  22 , in which the histaminase is bound on a matrix chosen from between: CNBr-activated Sepharose 4B® and on activated CH-Sepharose 4B®.M.