Stable amorphous calcium carbonate comprising synthetic phosphorylated peptides

Abstract

Provided are compositions containing amorphous calcium carbonate (ACC), and at least one phosphorylated peptide which stabilizes the amorphous form of said calcium carbonate. Particularly, the peptide can be selected from crustacean proteins, also provided by the invention, namely GAP65, GAP22, GAP21, and GAP12 (also indicated herein as GAP10). The compositions are useful in pharmaceutical and nutraceutical formulations.

1 - 38 . (canceled) 
     
     
         39 . A composition comprising amorphous calcium carbonate (ACC) and at least one component selected from phosphorylated peptides comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:17, SEQ ID NO:24, SEQ ID NO:25, and any homologues, variants, derivatives and fragments thereof. 
     
     
         40 . A peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:17, SEQ ID NO:24, SEQ ID NO:25, and any homologues, variants, derivatives and fragments thereof. 
     
     
         41 . A peptide being an isolated and purified peptide from crustacean gastrolith or cuticle comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:17, SEQ ID NO:24, SEQ ID NO:25, and any homologues, variants, derivatives and fragments thereof. 
     
     
         42 . A nucleic acid sequence encoding a peptide according to  claim 41 . 
     
     
         43 . A method of preparing stable amorphous calcium carbonate, comprising mixing in aqueous phase in any order a soluble salt comprising calcium, a carbonate source and at least one phosphorylated peptide. 
     
     
         44 . A pharmaceutical formulation comprising a composition according to  claim 39  and further optionally other components selected from the group consisting of chitin, chitosan, and fillers. 
     
     
         45 . A nutraceutical formulation comprising a composition according to claim  1  and further optionally other components selected from the group consisting of chitin, chitosan, and fillers. 
     
     
         46 . A pharmaceutical formulation according to  claim 44 , for treating conditions selected from the group consisting of bone metabolism disorders, pain, proliferative diseases, neurological disorders, immunologic disorders, cardiovascular diseases, pulmonary diseases, nutritional disorders, reproductive disorders, musculoskeletal disorders, and dental problems. 
     
     
         47 . A pharmaceutical formulation according to  claim 46 , wherein said proliferative disease is breast carcinoma or bronchogenic carcinoma. 
     
     
         48 . A pharmaceutical formulation according to  claim 46 , wherein said pain is selected from postoperative pain, pain after injury, pain associated with cancer, and neuropathic pain. 
     
     
         49 . A pharmaceutical formulation according to  claim 46 , wherein said neurologic disorder is selected from demyelinating diseases, dementias, and movement disorders. 
     
     
         50 . A pharmaceutical formulation according to  claim 46 , wherein said condition is a degenerative disease selected from multiple sclerosis, Alzheimer's disease, and Parkinson's disease. 
     
     
         51 . A pharmaceutical formulation according to  claim 46 , wherein said condition comprises a bone disorder or a bone marrow disorder. 
     
     
         52 . A pharmaceutical formulation according to  claim 46 , wherein said disorder comprises fracture or osteoporosis. 
     
     
         53 . A pharmaceutical formulation according to  claim 46 , wherein said condition is a neurodegenerative disorder. 
     
     
         54 . An isolated and purified peptide comprising in its sequence a fragment of a crustacean peptide according to  claim 41 , said fragment consisting of at least ten amino acids. 
     
     
         55 . A peptide having an amino acid sequence selected from SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:17 or SEQ ID NO:24, or SEQ ID NO:25 or a sequence homologous thereto at least by 90%. 
     
     
         56 . A calcium carbonate preparation according to  claim 39 , which is stable at least for between about one month to one year. 
     
     
         57 . A pharmaceutical formulation comprising a composition according to  claim 39 . 
     
     
         58 . A nutraceutical formulation comprising the composition of  claim 39 . 
     
     
         59 . A food additive or functional food comprising a mixture of calcium carbonate and a peptide having a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:17, SEQ ID NO:24, SEQ ID NO:25, and homologues or fragments thereof.