Mixtures and formulations comprising an alkyl ammonium EDTA salt
Inventors
Barauskas, Justas • NISTOR, Catalin • Johnsson, Markus
Assignees
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Publication Number
US-11241476-B2
Publication Date
2022-02-08
Expiration Date
Abstract
The present invention relates to mixtures comprising: i) at least one lipid and/or at least one oil; and ii) an alkyl ammonium EDTA salt; wherein the mixture has a water content in the range of 0 to 1.0 wt %. The invention further relates to mixtures which are pre-formulations, methods of treatment comprising administration of such pre-formulations, to pre-filled administration devices and kits containing the formulations, to the use of an alkylammonium EDTA salt to reduce the decomposition of the lipid components and/or any active agent contained within the pre-formulation, and to alkyl ammonium EDTA salts as described herein.
Core Innovation
The invention relates to a pre-formulation comprising a lipid mixture and an antioxidant system, where the lipid mixture comprises glycerol dioleate (GDO), at least one phosphatidyl choline (PC), and ethanol or mixtures of ethanol and propylene glycol. The pre-formulation further comprises ethylenediaminetetraacetic acid (EDTA) and ethanolamine (ETA), has a water content of 0 to 1.0 wt%, and the molar amount of ETA relative to the molar amount of EDTA is at least 3.5 (mol/mol).
The invention also addresses oxidation in formulations that include at least one active agent. A method is provided for reducing oxidation of at least one active agent in a pre-formulation that contains the same defined lipid mixture together with EDTA and ETA, with the same water content and ETA:EDTA molar ratio.
The document further characterizes the composition as including very low-water pre-formulations and indicates that the lipid component can form non-lamellar liquid-crystalline depots upon exposure to an aqueous fluid. The antioxidant system is based on EDTA and ETA and includes alkylammonium EDTA salts and EDTA analogues as described in the document content provided.
Claims Coverage
The partial content provides two independent claims: one directed to a specific pre-formulation composition and one directed to a method of reducing oxidation of an active agent using that pre-formulation. The independent claims center on a low-water pre-formulation containing a defined lipid mixture together with EDTA and ETA, including a required molar ETA:EDTA ratio of at least 3.5 (mol/mol).
Very low-water lipid pre-formulation with EDTA and ETA
A pre-formulation comprising a lipid mixture of glycerol dioleate (GDO), at least one phosphatidyl choline (PC), and ethanol or mixtures of ethanol and propylene glycol; ethylenediaminetetraacetic acid (EDTA) and ethanolamine (ETA); wherein the pre-formulation has a water content of 0 to 1.0 wt% and the molar amount of ETA relative to the molar amount of EDTA is at least 3.5 (mol/mol).
Reducing oxidation of an active agent using the defined EDTA/ETA pre-formulation
A method of reducing oxidation of at least one active agent in a pre-formulation comprising the defined lipid mixture, the at least one active agent, EDTA and ETA; wherein the pre-formulation has a water content in the range of 0 to 1.0 wt% and the molar amount of ETA relative to the molar amount of EDTA is at least 3.5 (mol/mol).
Both independent claims are centered on a low-water pre-formulation containing a defined lipid mixture together with EDTA and ETA, including the required ETA:EDTA molar ratio. The method claim applies this same formulation framework to reduce oxidation of at least one active agent.
Stated Advantages
Improved resistance to lipid and active-agent oxidation/decomposition.
Reduced oxidation of at least one active agent.
Improved stability of peptide active agents.
Documented Applications
Depot-forming treatment methods and delivery formats, including pre-filled administration devices and kits, where non-lamellar liquid-crystalline depots form upon exposure to aqueous fluid [procedural detail omitted for safety].
Use of the pre-formulation with active agents including peptides/proteins/APIs, with assay stability support described for peptide APIs such as octreotide and somatostatin analogues, as well as examples listed in the provided content such as goserelin, oxytocin, and granisetron [procedural detail omitted for safety].
Application of the antioxidant pre-formulation strategy in the presence of iron (Fe3+) to address oxidation and decomposition stability support described in the provided content [procedural detail omitted for safety].
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