Treatment of diseases involving mucin

Abstract

The present invention relates to compositions containing one or more of the compounds contained in bromelain, or salts, solvates or prodrugs thereof, and one or more mucolytic agents, or salts, solvates or prodrugs thereof, for treatment of diseases involving mucin, especially mucin secreting cancers, or diseases involving blood clots (thrombi).

1 . A composition comprising:
 one or more compounds in bromelain, or a metabolite(s), pharmaceutically acceptable salt(s), solvate(s) or prodrug(s) thereof; and   at least one mucolytic agent, or a metabolite, pharmaceutically acceptable salt, solvate or prodrug thereof.   
     
     
         2 . A composition according to  claim 1 , wherein the at least one mucolytic agent is a compound of formula (I): 
       
         
           
           
               
               
           
         
       
       or a metabolite, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein
 L 1  to L 6  are independently selected from CR 5 R 6 , S, O, CO, N(R 7 )CO and NR 8 ; 
 Z 1  and Z 2  are independently selected from O, S, Se and NR 9 ; 
 Y 1  and Y 2  are independently selected from O and S; 
 X is selected from NR 10 , O and S; 
 R 1  to R 10  are independently selected from H, alkyl, aryl and heteroaryl; and 
 p to u are independently selected from 0 to 20. 
 
     
     
         3 . A composition according to  claim 1 , wherein the at least one mucolytic agent is a compound of formula (Ia): 
       
         
           
           
               
               
           
         
       
       or a metabolite, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R 1 , Y 1 , X, L 5  and t are defined according to  claim 1 . 
     
     
         4 . A composition according to  claim 1 , wherein the at least one mucolytic agent is N-acetylcysteine: 
       
         
           
           
               
               
           
         
       
       or a metabolite, pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         5 . The composition according to  claim 1  any preceding claim, additionally comprising at least one further biologically active compound, or a metabolite, pharmaceutically acceptable salt, solvate or prodrug thereof. 
     
     
         6 . The composition according to  claim 5 , wherein the biologically active compound is selected from any one of chemotherapeutic agent, N-glycosylation inhibitor, silyltransferase inhibitor, multi-drug transport inhibitor, NSAID, antibiotic, and anti-inflammatory agent. 
     
     
         7 . The composition according to  claim 6 , wherein the biologically active agent is a chemotherapeutic agent. 
     
     
         8 . The composition according to  claim 7 , wherein the chemotherapeutic agent is cisplatin. 
     
     
         9 . The composition according to  claim 1 , wherein the composition is a synergistic combination. 
     
     
         10 . A combined preparation of one or more compounds in bromelain, at least one mucolytic agent according to  claim 1 , and optionally at least one biologically active compound, or a metabolite, pharmaceutically acceptable salt, solvate or prodrug thereof, for simultaneous, separate or sequential use in therapy. 
     
     
         11 . The composition according to  claim 1  for use as a medicament. 
     
     
         12 . The composition according to  claim 1  for the treatment of one or more diseases involving mucin or for the treatment of one or more diseases involving thrombi. 
     
     
         13 . Use of the composition of  claim 1  for the manufacture of a medicament for the treatment of one or more diseases involving mucin or for the treatment of one of more diseases involving thrombi. 
     
     
         14 . A method for the treatment of one or more diseases involving mucin or for the treatment of one or more diseases involving thrombi, the method comprising administering a therapeutically effective amount of the composition of  claim 1  to a patient in need thereof. 
     
     
         15 . The method according to  claim 14 , wherein the disease involving mucin is selected from cancer, pseudomyxoma peritoneii, glue ear, cystic fibrosis, sputum retention, chest infection and mucus associated with biliary/pancreatic stents, and wherein the disease involving thrombi is selected from haemophilia, myocardial infarction, coronary artery disease, stroke, massive pulmonary embolism and acute limb ischaemia, stent-related thrombosis or haemarthrosis. 
     
     
         16 . The method according to  claim 15 , wherein the cancer is selected from lung cancer, breast cancer, colorectal cancer, thyroid cancer, prostate cancer, stomach cancer, pancreatic cancer, cancer of the appendix and ovarian cancer. 
     
     
         17 . The method according to  claim 15 , wherein the cancer is signet ring cell carcinoma. 
     
     
         18 . A method for removing mucin from a patient in need thereof comprising administering to the patient the composition according to  claim 1 .