Casein Derived Peptides And Uses Thereof in Therapy

Abstract

Biologically active peptides that are derived from or are similar to sequences identical with the N-terminus of the oS1 fraction of milk casein. These peptides are capable of stimulating and enhancing immune response, protecting against viral infection, normalizing serum cholesterol levels, and stimulating hematopoiesis. The casein-derived peptides are non-toxic and can be used to treat and prevent immune pathologies, hypercholesterolemia, hematological disorders and viral-related diseases.

1 . A method for inducing or increasing hematopoiesis in a subject, comprising administering to the subject casecidin peptide preparation derived from natural casein. 
     
     
         2 . The method of  claim 1 , wherein said casecidin peptide preparation derived from natural casein is prepared according to a preparation method comprising proteolytic digestion of said natural casein in solution to form a digested material solution; and
 centrifugation of said digested material solution to obtain said casecidin peptide preparation derived from natural casein.   
     
     
         3 . The method of  claim 2 , wherein the treatment increases or induces at least one of hematopoietic stem cell proliferation; hematopoietic stem cell differentiation; megakaryocytopoiesis; leukocytopoiesis, erythrotopoiesis and thrombopoiesis. 
     
     
         4 . The method of  claim 3 , wherein the treatment increases or induces thrombopoiesis for treating thrombocytopenia. 
     
     
         5 . The method of  claim 2 , wherein the treatment is for treating a disorder selected from the group consisting of pancytopenia, granulocytopenia, helper T-cell disorders, dendrite cell deficiencies, macrophage deficiencies, hematopoietic stem cell disorders, pre-leukemic conditions, leukemic conditions and a blood cell disorder resulting from chemotherapy or radiation therapy. 
     
     
         6 . The method of  claim 5 , wherein said hematopoietic stem cell disorders are selected from the group consisting of platelet, lymphocyte, plasma cell and neutrophil disorders. 
     
     
         7 . The method of  claim 2 , wherein said preparation method further comprises a method of low-temperature processing of casein, the method comprising: a) obtaining a casein proteolytic hydrolysate comprising proteolytic enzymes; b) cooling said casein proteolytic hydrolysate so as to inactivate said proteolytic enzymes; c) adjusting the pH of said casein protein hydrolysate to an acid pH; d) filtering said acidic casein protein hydrolysate, collecting the filtrate, and further acidifying said filtrate so as to precipitate proteins derived from natural casein; e) separating and collecting said precipitate; f) adjusting the pH of said precipitate to an alkaline pH so as to irreversibly inactivate said proteolytic enzymes; and g) adjusting the pH of said precipitate to pH 7-9; thereby processing said casein protein hydrolysate at low temperature to form said casecidin peptide preparation derived from natural casein. 
     
     
         8 . The method of  claim 7 , wherein said stage b comprises cooling to about 10 C. 
     
     
         9 . The method of  claim 8 , wherein said adjusting said pH of stage c comprises addition of acid to 2% (w/v) acid, and whereas said further acidifying said filtrate of stage d comprises additional addition of acid to about 10% (w/v) acid. 
     
     
         10 . The method of  claim 9 , wherein said alkaline pH of stage f is at least pH 9. 
     
     
         11 . A method of treating a disease selected from the group consisting of glucosuria, hyperglycemia and diabetes, comprising administering to a subject in need thereof casecidin peptide preparation derived from natural casein. 
     
     
         12 . The method of  claim 11 , wherein said casecidin peptide preparation derived from natural casein is prepared according to a preparation method comprising proteolytic digestion of said natural casein in solution to form a digested material solution; and centrifugation of said digested material solution to obtain said casecidin peptide preparation derived from natural casein. 
     
     
         13 . The method of  claim 12 , wherein said preparation method further comprises a) obtaining a casein proteolytic hydrolysate comprising proteolytic enzymes; b) cooling said casein proteolytic hydrolysate so as to inactivate said proteolytic enzymes; c) adjusting the pH of said casein protein hydrolysate to an acid pH; d) filtering said acidic casein protein hydrolysate, collecting the filtrate, and further acidifying said filtrate so as to precipitate proteins derived from natural casein; e) separating and collecting said precipitate; f) adjusting the pH of said precipitate to an alkaline pH so as to irreversibly inactivate said proteolytic enzymes; and g) adjusting the pH of said precipitate to pH 7-9; thereby processing said casein protein hydrolysate at low temperature to form said casecidin peptide preparation derived from natural casein. 
     
     
         14 . The method of  claim 13 , wherein said stage b comprises cooling to about 10 C. 
     
     
         15 . The method of  claim 14 , wherein said adjusting said pH of stage c comprises addition of acid to 2% (w/v) acid, and whereas said further acidifying said filtrate of stage d comprises additional addition of acid to about 10% (w/v) acid. 
     
     
         16 . The method of  claim 15 , wherein said alkaline pH of stage f is at least pH 9.