Composition of dialysis liquid comprising crystallisation inhibitor substances

Abstract

This invention relates to a composition that comprises inositol phosphates and/or bisphosphonates, and to the use thereof to prevent the loss of substances of biological interest in the body of patients subjected to dialysis and to maintain sufficient physiological levels of said substances to regulate physiological and/or pathological processes, these substances being inhibitors of pathological crystallisation.

1 - 20 . (canceled) 
     
     
         21 . A method to treat or prevent cardiovascular calcification comprising administering to a subject in need thereof:
 (a) a dialysis liquid comprising a crystallization inhibitory substance wherein (i) the crystallization inhibitory substance is chosen from inositol phosphate, bisphosphonate, their pharmaceutically acceptable salts, and combinations thereof, and (ii) the crystallization inhibitory substance maintains, in the body of the subject, an effective physiological concentration of at least one substance that contributes to regulate at least a physiological or pathological crystallization or calcification process in said subject; or,   (b) an intravenous composition comprising at least one of inositol phosphate and any of its pharmaceutically acceptable salts, in a form adapted for intravenous administration; or,   (c) a preparation comprising (i) a composition that comprises crystallization inhibitory substances selected from among inositol phosphate, bisphosphonate, their pharmaceutically acceptable salts, and any combinations thereof, and (ii) a dialysis liquid administered to said subject separately, simultaneously or sequentially from said composition; or,   (d) combinations thereof,   wherein the administration of the dialysis liquid, intravenous composition, preparation, or combination thereof treats or prevents cardiovascular calcification in the subject.   
     
     
         22 . A method to regulate a physiological or pathological crystallization or calcification process in a subject having a cardiovascular disease comprising administering to the subj ect:
 (a) a dialysis liquid comprising a crystallization inhibitory substance wherein (i) the crystallization inhibitory substance is chosen from inositol phosphate, bisphosphonate, their pharmaceutically acceptable salts, and combinations thereof, and (ii) the crystallization inhibitory substance maintains, in the body of the subject, an effective physiological concentration of at least one substance that contributes to regulate at least one physiological or pathological crystallization or calcification process in said subject; or,   (b) an intravenous composition comprising at least one of inositol phosphate and any of its pharmaceutically acceptable salts, in a form adapted for intravenous administration; or,   (c) a preparation comprising (i) a composition that comprises crystallization inhibitory substances selected from among inositol phosphate, bisphosphonate, their pharmaceutically acceptable salts and any combinations thereof, and (ii) a dialysis liquid administered to said subject separately, simultaneously or sequentially from said composition; or,   (d) combinations thereof   wherein the administration of the dialysis liquid, intravenous composition, preparation, or combination thereof regulates the physiological or pathological crystallization or calcification process in the subject having the cardiovascular disease.   
     
     
         23 . A method to treat or prevent a cardiovascular disease associated with pathological crystallization or calcification comprising administering to a subject in need thereof
 (a) a dialysis liquid comprising a crystallization inhibitory substance wherein (i) the crystallization inhibitory substance is chosen from inositol phosphate, bisphosphonate, their pharmaceutically acceptable salts, and combinations thereof, and (ii) the crystallization inhibitory substance maintains, in the body of the subject, an effective physiological concentration of at least one substance that contributes to regulate at least one physiological or pathological crystallization or calcification process in said subject; or,   (b) an intravenous composition comprising at least one of inositol phosphate and any of its pharmaceutically acceptable salts, in a form adapted for intravenous administration; or,   (c) a preparation comprising (i) a composition that comprises crystallization inhibitory substances selected from among inositol phosphate, bisphosphonate, their pharmaceutically acceptable salts, and any combinations thereof, and (ii) a dialysis liquid administered to said subject separately, simultaneously or sequentially from said composition; or,   (d) combinations thereof,   wherein the administration of the dialysis liquid, intravenous composition, preparation, or combination thereof treats or prevents the symptoms of the cardiovascular disease associated with pathological crystallization or calcification in the subject.   
     
     
         24 . The method according to  claims 23 , wherein the cardiovascular disease is selected from the group consisting of hypertension, aortic stenosis, cardiac hypertrophy, myocardial ischemia, lower-limb ischemia, congestive heart failure, stroke, atherosclerotic calcification, arterial medial calcification, and calcific uremic arteriolopathy (calciphylaxis). 
     
     
         25 . The method according to  claim 23 , wherein the inositol phosphate is inositol mono phosphate, inositol diphosphate, inositol triphosphate, inositol tetraphosphate, inositolpenta phosphate, inositol hexaphosphate, or a combination thereof 
     
     
         26 . The method according to  claim 25 , wherein the inositol phosphate is inositol hexaphosphate. 
     
     
         27 . The method according to  claim 26 , wherein the inositol hexaphosphate is myo-inositol hexaphosphate. 
     
     
         28 . The method according to  claim 23 , wherein the bisphosphonate is etidronic acid, alendronic acid, risedronic acid, zoledronic acid, tiludronic acid, pamidronic acid, clodronic acid, ibandronic acid, the salts thereof, or a combination thereof 
     
     
         29 . The method according to  claim 23 , wherein the dialysis liquid, intravenous composition, or preparation further comprises pyrophosphate. 
     
     
         30 . The method according to  claim 23 , wherein the dialysis liquid, intravenous composition, or preparation further comprises dextrose, heparin, lactate, antibiotics, or combinations thereof. 
     
     
         31 . The method according to  claim 23 , wherein the concentration of inositol phosphate is between 0.01 μM and 0.1 M, between 0.1 μM and 10 mM, or between 0.1 μM and 5 mM. 
     
     
         32 . The method according to  claim 23 , wherein the concentration of bisphosphonate is between 0.01 μM and 0.1 M, between 0.1 μM and 10 mM, or between 0.1 μM and 5 mM. 
     
     
         33 . The method according to  claim 23 , wherein the intravenous composition is administered by bolus injection or intravenous infusion. 
     
     
         34 . The method according to  claim 23 , wherein the dialysis liquid is used in heamodialysis or peritoneal dialysis. 
     
     
         35 . The method according to  claim 23 , wherein the amount of inositol phosphate in the dialysis liquid, intravenous composition, or preparation is between 1 nmol/kg and 0.1 mol/kg of the body weight of the subject. 
     
     
         36 . The method according to  claim 35 , wherein the amount of inositol phosphate in the dialysis liquid, intravenous composition, or preparation is between 0.01 μmol/kg and 10 mmol/kg of the body weight of the subject. 
     
     
         37 . The method according to  claim 36 , wherein the amount of inositol phosphate in the dialysis liquid, intravenous composition, or preparation is between 0.1 μmol/kg and 1 mmol/kg of the body weight of the subject. 
     
     
         38 . The method according to  claim 23 , wherein the dialysis liquid, intravenous composition, or preparation is administered in a single dose. 
     
     
         39 . The method according to  claim 23 , wherein the dialysis liquid, intravenous composition, or preparation is administered in more than one dose. 
     
     
         40 . The method according to  claim 23 , wherein the dialysis liquid, intravenous composition, or preparation is administered to the subject as at least one dose of inositol phosphate between 1 nmol/kg of body weight of the subject/day and 0.1 mol/kg of body weight of the subject/day.