Use of derivatives containing c-o-p bonds in patients with kidney failure

Abstract

Use of a derivative containing C—O—P bonds in a controlled release form to treat patients with kidney failure. Moreover, it comprises the use of said derivatives together with other active substances, which particularly may be selected from a list comprising a calcimimetic, vitamin, phosphate binder, thiosulfate, bisphosphonate, pyrophosphate, citrate, diuretic, antihypertensive and anticholesteraemic agent.

1 - 14 . (canceled) 
     
     
         15 . A method for the treatment of a kidney failure-related disease or condition in a subject in need thereof comprising administering to the subject an effective amount of a composition comprising an inositol phosphate selected from the group consisting of inositol hexaphosphate (IP6), inositol pentaphosphate (IP5), inositol tetraphosphate (IP4), inositol triphosphate (IP3), inositol diphosphate (IP2), inositol monophosphate (IP1), a pharmaceutical acceptable salt thereof, and any combination thereof, wherein the composition is administered by intravenous infusion over more than 3 minutes. 
     
     
         16 . The method of  claim 15 , wherein the inositol phosphate is IP6. 
     
     
         17 . The method of  claim 15 , wherein the intravenous infusion is administered over more than 5 minutes, over more than 20 minutes, over more than 4 hours, or over more than 24 hours. 
     
     
         18 . The method of  claim 15 , wherein the composition comprises between 1 mg/kg and 100 mg/kg of inositol phosphate. 
     
     
         19 . The method of  claim 15 , wherein the composition comprises between 10 mg/kg and 60 mg/kg of inositol phosphate. 
     
     
         20 . The method of  claim 15 , wherein the composition comprises at least 10 mg/kg of inositol phosphate. 
     
     
         21 . The method of  claim 15 , wherein the intravenous infusion is (i) administered over more than 5 minutes, over more than 20 minutes, over more than 4 hours, or over more than 24 hours, and (ii) comprises at least 10 mg/kg of inositol phosphate. 
     
     
         22 . The method of  claim 15 , wherein the administration of the composition to the subject results in therapeutic levels of the inositol phosphate in blood plasma of at least 0.15 micromolar, at least 0.3 micromolar, or at least 0.6 micromolar. 
     
     
         23 . The method of  claim 22 , wherein the therapeutic level of the inositol phosphate in blood plasma is maintained for at least 30 minutes, at least 1 hour, at least 3 hours, or at least 4 hours after administration. 
     
     
         24 . The method of  claim 15 , wherein the composition further comprises another active substance. 
     
     
         25 . The method of  claim 24 , wherein the another active substance is selected from the group consisting of a calcimimetic, a vitamin, a phosphorus chelator, a thiosulfate, a bisphosphonate, a pyrophosphate, a citrate, a diuretic, an antihypertensive, and an anticholesteraemic agent. 
     
     
         26 . The method of  claim 15  further comprising separately, simultaneously or sequentially administering a compound selected from the group consisting of a calcimimetic, a vitamin, a phosphorus chelator, a thiosulfate, a bisphosphonate, a pyrophosphate, a citrate, a diuretic, an antihypertensive, and an anticholesteraemic agent. 
     
     
         27 . The method of  claim 26 , wherein the vitamin comprises vitamin B, vitamin D, vitamin K, or a combination thereof. 
     
     
         28 . The method of  claim 26 , wherein the calcimimetic is selected from the group consisting of cinacalcet ((R)-N-[1-(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine, KAI-4169 (etelcalcetide), NPS R-467 (((R)-N-(3-phenylpropyl)-1-(3-methoxyphenyl)ethylamine)), NPS R-568 ((R)-2-chloro-N-(1-(3-methoxyphenyl)ethyl)benzenepropanamine), and a combination thereof. 
     
     
         29 . The method of  claim 26 , wherein the phosphorus chelator comprises a calcium salt, an iron salt, a lanthanum salt, an aluminum salt, a magnesium salt, or a combination thereof. 
     
     
         30 . The method of  claim 26 , wherein the bisphosphonate is selected from the group consisting of etidronate, alendronate, risedronate, zoledronate, tiludronate, pamidronate, monidronate, neridronate, pamidronate, olpadronate, clodronate, ibandronate, and a combination thereof. 
     
     
         31 . The method of  claim 15 , wherein the kidney failure-related disease is a calcium disorder-related disease. 
     
     
         32 . The method of  claim 31 , wherein the calcium disorder-related disease is selected from the group consisting of renal lithiasis, cardiovascular disease, osteoporosis, bone cancer, podagra, calcific tendinitis, calcinosis cutis, rheumatoid arthritis, bone mineral disease, osteomalacia, adynamic bone, and calciphylaxis. 
     
     
         33 . The method of  claim 32 , wherein the cardiovascular disease is cardiovascular calcification. 
     
     
         34 . The method of  claim 33 , wherein the cardiovascular calcification is aortic calcification, heart calcification, or coronary artery calcification. 
     
     
         35 . The method of  claim 33 , wherein the cardiovascular disease is cardiac disease, coronary disease, heart failure, myocardial infarction, angina pectoris, cerebrovascular disease, atherosclerosis, arteriosclerosis, thrombosis, hypertension, aneurysm, peripheral vascular disease, ischaemia, arrhythmia, stroke, or cardiac death. 
     
     
         36 . A method to treat and/or inhibit the progression of a calcification process in a subject having a cardiovascular disease comprising administering to the subject an effective amount of a composition comprising an inositol phosphate selected from the group consisting of IP6, IP5, IP4, IP3, IP2, IP1, a pharmaceutical acceptable salt thereof, and any combination thereof, wherein the composition is administered by intravenous infusion over more than 3 minutes. 
     
     
         37 . The method of  claim 36 , wherein the inositol phosphate is IP6. 
     
     
         38 . The method of  claim 15 , wherein the intravenous infusion is (i) over more than 5 minutes, over more than 20 minutes, over more than 4 hours, or over more than 24 hours, and (ii) comprises at least 10 mg/kg of inositol phosphate. 
     
     
         39 . The method of  claim 36 , wherein the calcification process is cardiovascular calcification. 
     
     
         40 . A method to increase inositol phosphate levels in the bloodstream of subject with a kidney failure-related disease or condition comprising administering to the subject an effective amount of a composition comprising an inositol phosphate selected from the group consisting of IP6, IP5, IP4, IP3, IP2, IP1, a pharmaceutical acceptable salt thereof, and any combination thereof, wherein the composition is administered by intravenous infusion over more than 3 minutes, and wherein the subject has a higher inositol phosphate metabolic rate than a subject without the kidney failure-related disease or condition. 
     
     
         41 . The method of  claim 40 , wherein the inositol phosphate is IP6. 
     
     
         42 . The method of  claim 40 , wherein the intravenous infusion is (i) administered over more than 5 minutes, over more than 20 minutes, over more than 4 hours, or over more than 24 hours, and (ii) comprises at least 10 mg/kg of inositol phosphate. 
     
     
         43 . The method of  claim 40 , wherein the kidney failure-related disease is a calcium disorder-related disease selected from the group consisting of renal lithiasis, cardiovascular disease, osteoporosis, bone cancer, podagra, calcific tendinitis, calcinosis cutis, rheumatoid arthritis, bone mineral disease, osteomalacia, adynamic bone, and calciphylaxis. 
     
     
         44 . The method of  claim 43 , wherein the cardiovascular disease is cardiovascular calcification.