Processes for the preparation of soluble salts of inositol phosphates
Inventors
Isern Amengual, Bernat • Moreno Santurino, Marco Antonio • Perelló Bestard, Joan
Assignees
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Publication Number
US-12049476-B2
Publication Date
2024-07-30
Expiration Date
Abstract
The present invention provides processes for preparing soluble salts of inositol phosphate characterized by a low level of impurities. Processes for preparing soluble salts (e.g., alkali-metal or ammonium) of inositol phosphates (e.g., hexasodium or dodecasodium salts), and of inositol hexaphosphate in particular (e.g., Na6IP6 and Na12IP6), are described. Also provided are pharmaceutical compositions, methods of use, combination treatments, kits, and articles of manufacture comprising soluble salts of inositol phosphates prepared according to the method of the invention.
Core Innovation
The invention relates to processes for preparing a purified inositol phosphate (IP) salt. The process includes an ion removal step in which an IP salt is dissolved in water to obtain an IP solution, contacted with an ion exchange medium to yield an ion exchanged IP solution, and concentrated to obtain an IP syrup containing a soluble IP salt. The soluble IP salt from the IP syrup is separated in the presence of an alkoxide.
After the ion removal step, the process further includes a purification step comprising dissolving the soluble IP salt separated from the syrup in water to obtain an IP solution, converting the IP solution to an IP suspension, washing the IP suspension with an alcohol solution to obtain an IP solid, and drying the IP solid to obtain the purified IP salt. Dependent refinements specify particular purified IP salt identities, including inositol hexaphosphate.
The disclosed subject matter also supports pharmaceutical compositions and formulations containing Na6IP6 (hexasodium phytate) with defined concentration ranges. The compositions can include tonicity agents and optional pH buffers and are described as having stability at 25°C and 60% RH. The document describes parenteral dosage forms such as sterile solutions and suspensions, and lyophilized reconstitutable powders, together with therapeutic use for treating or preventing ectopic calcification, including calciphylaxis in dialysis/end-stage renal disease subjects.
Claims Coverage
The provided claims include two independent claims. Across these claims, the inventive coverage focuses on ion removal using water dissolution, ion exchange, concentration to an IP syrup, and alkoxide-assisted separation, with one independent claim further requiring suspension conversion, alcohol washing, and drying to obtain a purified IP salt.
Alkoxide-assisted separation during ion removal
An ion removal step comprising dissolving an IP salt in water to obtain an IP solution; contacting the IP solution with an ion exchange medium to yield an ion exchanged IP solution; concentrating to obtain an IP syrup containing a soluble IP salt; and separating the soluble IP salt from the IP syrup in the presence of an alkoxide.
Alcohol washing and drying after converting to an IP suspension
A purification step comprising dissolving the soluble IP salt separated from the IP syrup in water to obtain an IP solution; converting the IP solution to an IP suspension; washing the IP suspension with an alcohol solution to obtain an IP solid; and drying the IP solid to obtain the purified IP salt.
Claim coverage is anchored in alkoxide-assisted separation of a soluble IP salt formed during concentration after ion exchange, and in producing a purified IP salt by converting to an IP suspension, washing with an alcohol solution, and drying the resulting IP solid. Dependent claims further narrow features such as specific purified IP salt identity, alkoxide class, pH windows, and specific constraints for distillation and syrup water content.
Stated Advantages
Produces a purified inositol phosphate (IP) salt with low impurity levels, including IP6 purity targets and pentaphosphate impurity limits as described.
Improves purification outcomes compared with failed antisolvent crystallization examples described in purification-screening results.
Documented Applications
Pharmaceutical composition including injectable intravenous infusion use for ectopic calcification and calciphylaxis as described in the partial content.
Use in combination treatments as described in the partial content.
Provision of kits as described in the partial content.
Parenteral dosage forms such as sterile solutions and suspensions.
Lyophilized reconstitutable powders.
Therapeutic use for treating or preventing ectopic calcification, including calciphylaxis in dialysis/end-stage renal disease subjects.
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