Pharmaceutical composition for treatment and prevention of chronic disease

Abstract

An object of the present invention is to develop a novel treatment method for chronic diseases for which conventional treatment methods are either ineffective or for which efficacy is low. The present invention provides a pharmaceutical composition for the treatment and/or prevention of an inflammatory chronic disease that is used in combination with a biological preparation that inhibits leukocyte tissue invasion. The pharmaceutical composition of the present invention contains as an active ingredient thereof siRNA suppressing the expression of CHST15 gene that contains a structure formed by the hybridization of RNA containing the base sequence represented by SEQ ID NO: 1 with RNA complementary thereto.

1 . A pharmaceutical composition, comprising, as an active ingredient thereof:
 (i) a siRNA suppressing an expression of CHSTI5 gene comprising a structure formed by hybridizing an RNA comprising a base sequence represented by SEQ ID NO: I with an RNA comprising a base sequence represented by SEQ ID NO: 2 complementary thereto,   (ii) the siRNA of (i) having a structure in which one or a plurality of nucleic acids overhang from an end thereof, or   (iii) a DNA vector capable of expressing the siRNA of (i) or (ii).   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition comprises the si RNA of (ii), and the siRNA of (ii) has a structure formed by hybridizing an RNA composed of a base sequence represented by SEQ ID NO: 3 with an RNA composed of a base sequence represented by SEQ ID NO: 4 complementary thereto. 
     
     
         3 . The method of  claim 15 , wherein the biological preparation inhibiting leukocyte tissue invasion inhibits a function of at least one molecule selected from the group consisting of an integrin and a chemokine receptor on surfaces of leukocytes circulating in blood and adhesion molecules on surfaces of vascular endothelial cells. 
     
     
         4 . The method of  claim 3 , wherein the biological preparation inhibiting leukocyte tissue invasion is at least one member selected from the group consisting of Etrolizumab, Vedolizumab, Natalizumab, PF-00547659 and Vercirnon. 
     
     
         5 . The method of  claim 15 , wherein the biological preparation inhibiting inflammatory cytokines inhibits a function of at least one molecule selected from the group consisting of TNF-α, IL-17 and IL-23. 
     
     
         6 . The method of  claim 1 , wherein the administering is administering, in need thereof, the pharmaceutical composition in combination with at least one of the biological preparations as well as at least one member selected from the group consisting of a 5-aminosalicyclic acid preparation, a steroid preparation, a thiopurine preparation and an immunosuppressant. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 17 , wherein the pharmaceutical composition comprises the si RNA of (ii), and the siRNA of (ii) has a structure formed by hybridizing an RNA composed of a base sequence represented by SEQ ID NO: 3 with an RNA composed of a base sequence represented by SEQ ID NO: 4 complementary thereto. 
     
     
         9 . The method of  claim 15 , wherein the chronic disease is an autoimmune disease. 
     
     
         10 . The method of  claim 9 , wherein the autoimmune disease is at least one disease selected from the group consisting of inflammatory colitis, Crohn's disease, ulcerative colitis, autoimmune pancreatitis, chronic rheumatoid arthritis, bronchial asthma, chronic interstitial pneumonia, Grave's disease, Hashimoto's thyroiditis, chronic thyroiditis and atopic dermatitis. 
     
     
         11 . The method of  claim 15 , wherein the administering comprises administering the pharmaceutical composition and at least one of the biological preparations systemically or locally. 
     
     
         12 . The method of  claim 11 , wherein the chronic disease is a disease selected from the group consisting of inflammatory colitis, Crohn's disease and ulcerative colitis, and
 the administering is a local administration, which is a submucosal administration into an intestine of the patient.   
     
     
         13 . The method of  claim 11 , wherein the administration is a systemic administration, which is an oral administration and/or an intravenous injection. 
     
     
         14 . The method of  claim 13 , wherein the administering is an oral administration of a complex,
 the complex comprises an active ingredient and N-acetvlated chitosan and the active ingredient is:   (i) the siRNA suppressing the expression of CHST15 gene, or   (ii) the siRNA of (i) having a structure in which one or a plurality of nucleic acids overhang from the end thereof.   
     
     
         15 . A method for treating or preventing a chronic disease of a patient, the method comprising:
 administrating the pharmaceutical composition of  claim 1  in combination with a biological preparation inhibiting leukocyte tissue invasion and/or a biological preparation inhibiting inflammatory cytokines, in need thereof.   
     
     
         16 . The method of  claim 6 , wherein the immunosuppressant is tacrolimus or cyclosporine. 
     
     
         17 . A method for treating and/or preventing an inflammatory disease in which 6-sulfosiallyl Lewis X of L-selectin ligand is expressed on surfaces of vascular endothelial cells of a patient, the method comprising:
 administrating the pharmaceutical composition of  claim 1  in need thereof.