Use of derivatives containing C—O—P bonds in patients with kidney failure
Inventors
Perello Bestard, Joan • Salcedo Roca, Carolina • FERRER REYNES, Miguel David • Isern Amengual, Bernat • JOUBERT, Pieter H.
Assignees
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Publication Number
US-9364490-B2
Publication Date
2016-06-14
Expiration Date
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 calcimirnetic, vitamin, phosphate binder, thiosulfate, bisphosphonate, pyrophosphate, citrate, diuretic, antihypertensive and anticholesteraemic agent.
Core Innovation
The invention relates to methods for the treatment and/or inhibition of a kidney failure-related disease by administering to a subject with kidney failure an effective amount of a medicament containing at least one compound of formula I, or a pharmaceutically acceptable salt thereof. At least one of R1, R3, R5, R7, R9 and R11 independently represents a compound of formula II, with the remaining radicals defined as specified for the formula relationship.
A core feature is administration of the medicament in a non bolus prolonged release form, and the medicament is suitable for parenteral, topical or enteral administration. The document contrasts the C–O–P bond compounds with non-hydrolyzable P–C–P bisphosphonates and with P–O–P pyrophosphates, and links the compounds to hydrolysis and affinity behavior relevant under uraemia-associated changes.
The document further describes reversible calcium crystal interaction and calcium disorder-related disease control, including cardiovascular calcification and chronic kidney disease mineral bone disease (CKD-MBD). Non-bolus prolonged release dosing is presented as supporting restoration and maintenance of efficacy despite uraemia-related pharmacokinetic effects, while bolus administration is contrasted as failing to inhibit calcification in uraemic models.
Claims Coverage
The independent claim coverage comprises one independent method claim directed to administering a specific class of formula I compounds in a non-bolus prolonged release form for kidney failure-related diseases, with defined formula II-containing structural relationships. Dependent claims refine the composition, add an additional active substance, and narrow the disease scope to enumerated calcium disorder-related diseases, while also listing selectable co-therapy agent classes.
Treatment and/or inhibition of kidney failure-related disease with formula I medicament
A method for the treatment and/or inhibition of a kidney failure-related disease comprising administering to a subject with kidney failure an effective amount of a medicament comprising at least one compound of formula I, or a pharmaceutically acceptable salt thereof.
Non bolus prolonged release administration
Administering the medicament in a non bolus prolonged release form.
Formula I radicals including at least one formula II radical
At least one of the radicals R1, R3, R5, R7, R9 and R11 represents a compound of formula II, with the remaining radicals defined as specified for the formula relationship.
Medicament suitable for multiple administration routes
The medicament is found in a form suitable for parenteral, topical or enteral administration.
Combination with another active substance in a non-bolus prolonged release medicament
Administering an effective amount of a medicament containing at least one compound of general formula I and another active substance, delivered as a non-bolus prolonged release form suitable for parenteral, topical, or enteral administration.
Selected additional agents for co-therapy
Administering the medicament comprising at least one selected additional agent in a non-bolus prolonged-release form, where the additional agent is chosen from a specified group including calcimimetic, vitamin, phosphorus chelator, thiosulfate, bisphosphonate, pyrophosphate, citrate, diuretic, antihypertensive, and anticholesteraemic agent.
Disease scope narrowed to enumerated calcium disorder-related diseases
Calcium disorder-related diseases are selected from a defined list of specific conditions, as specified in the claim refinement.
Overall, the claim set centers on treating and/or inhibiting kidney failure-related disease using a formula I compound medicament administered as a non-bolus prolonged release form, with the medicament suitable for parenteral, topical or enteral administration. Refinements add an additional active substance and narrow the calcium disorder-related disease scope to an explicit list of conditions.
Stated Advantages
Reduced hypocalcaemia and reduced QTc effects associated with non-bolus dosing.
Improved efficacy in uraemia-associated faster metabolism and reduced plasma exposure by using non-bolus prolonged release.
Non-bolus prolonged release dosing supports inhibition of calcification in uraemic rat models, contrasted with bolus dosing.
Documented Applications
Treatment and/or inhibition of kidney failure-related disease in subjects with kidney failure.
Management of calcium disorder-related diseases including cardiovascular calcification and chronic kidney disease mineral bone disease (CKD-MBD).
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