Desmopressin oral compositions
Inventors
Tu, Yu-Hsing • Kathala, Kalyan • BHATTACHARYA, Romona • Fan, Yingjun • Perumal, Ashok
Assignees
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Publication Number
US-12343372-B2
Publication Date
2025-07-01
Expiration Date
Abstract
Provided herein are desmopressin oral liquid formulations. Also provided herein are methods of making and using desmopressin oral liquid compositions for the treatment of certain diseases including diabetes insipidus, enuresis, hemophilia A, von willebrand disease, high blood urea levels and others.
Core Innovation
The invention provides a method of treating a disease or condition, or symptoms thereof, by administering a therapeutically effective amount of a liquid pharmaceutical composition to a subject in need thereof. The liquid pharmaceutical composition comprises desmopressin acetate, water, and a two-component, dual-functional preservative-buffer system that comprises sodium benzoate and benzoic acid. The composition is described as a ready-to-use oral liquid with a pH about 4.0 to about 6.0, including about 5.0, and is configured to provide buffering capacity while limiting preservative and buffer levels.
The described formulation approach uses sodium benzoate and benzoic acid as the two-component dual-functional preservative-buffer system within the liquid pharmaceutical composition. The composition includes stability and quality attributes for desmopressin retention and impurity control, with peptide-related desmopressin impurities, assay recovery after storage, and impurity limits reported under room temperature, ambient, refrigerated, and accelerated conditions. Comparative pharmacokinetic and bioequivalence results are also described using AUC and/or Cmax relative to a reference oral tablet composition containing desmopressin acetate, DDAVP.
The invention further describes use via direct dosing devices such as an oral syringe with graduations and indicates reduced need for dilution. The method is defined for multiple diseases and conditions selected from diabetes insipidus, nocturnal enuresis, nocturia, hypothalamic injury-induced obesity, hemophilia A, von willebrand disease, postoperative bleeding, polyurea, and high blood urea levels. Additional dependent embodiments refine quantitative constraints for desmopressin acetate and preservative-buffer components, and mention optional preservative systems such as parabens.
Claims Coverage
The document provides one independent method claim covering administration of a liquid pharmaceutical composition with three core composition elements. The inventive features include desmopressin acetate, water, and a dual-functional sodium benzoate and benzoic acid preservative-buffer system, with treatment limited to specified diseases or conditions.
Dual-functional preservative-buffer system with sodium benzoate and benzoic acid
Administering a therapeutically effective amount of a liquid pharmaceutical composition comprising a two-component, dual-functional preservative-buffer system that comprises sodium benzoate and benzoic acid.
Desmopressin acetate liquid in water
Administering a therapeutically effective amount of a liquid pharmaceutical composition comprising desmopressin acetate and water.
Therapeutic administration for selected diseases or conditions
The disease or condition, or symptoms thereof, is selected from diabetes insipidus, nocturnal enuresis, nocturia, hypothalamic injury-induced obesity, hemophilia A, von willebrand disease, postoperative bleeding, polyurea, and high blood urea levels.
Claim coverage centers on administering a desmopressin acetate liquid composition containing water and a two-component dual-functional preservative-buffer system of sodium benzoate and benzoic acid for treatment of a defined group of diseases or conditions. Dependent claims further refine pH, optional preservatives, impurity limits after storage, stability retention, and bioequivalence metrics using AUC and/or Cmax versus a reference oral tablet.
Stated Advantages
Reduced need for dilution and reduced microbial contamination risk.
Improved dosing accuracy using direct dosing devices such as an oral syringe with graduations.
Improved oral performance versus reference oral tablets, including bioavailability and bioequivalence based on AUC and/or Cmax.
Shelf stability at room temperature, ambient, refrigerated, and accelerated conditions while maintaining quality attributes and peptide impurity limits.
Retention of at least 95 wt% (or at least 90 wt%) of initial desmopressin under room temperature/ambient storage for up to 120 days.
Resistance to pH drift greater than 0.5 units over long term for the benzoic acid/sodium benzoate buffering system.
Documented Applications
Treating diabetes insipidus, nocturnal enuresis, nocturia, hypothalamic injury-induced obesity, hemophilia A, von willebrand disease, postoperative bleeding, polyurea, and high blood urea levels, and related symptoms, by administering the defined desmopressin acetate oral liquid.
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