Composition intended to vectorise an anti-cancer agent
Inventors
Robic, Caroline • MAYER, Jean-François
Assignees
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Publication Number
US-10716861-B2
Publication Date
2020-07-21
Expiration Date
Abstract
A composition in the form of a water-in-oil emulsion comprising: from 20% to 40% (v/v) of aqueous phase, in the form of droplets, comprising an anti-cancer agent and a densifying agent chosen from the complexes of nonionic macrocyclic chelate with a paramagnetic metal,from 60% to 80% (v/v) of lipid phase comprising an iodized oil and at least one surfactant of formula (I) in a proportion, by weight of surfactant relative to the total volume of the composition, of 0.3% to 5%, formula (I) of said surfactant being the following: in which: s is 0 or 1,m is an integer from 2 to 30,R1 represents a group of formula (II) in which n is an integer from 4 to 10, o is an integer from 1 to 4, p is an integer from 3 to 7, q is an integer from 2 to 10, and r is 0 or 1,R2 represents a hydrogen atom or is identical to R1, andeach R3 independently represents a hydrogen atom or is identical to R1.
Core Innovation
The invention relates to a composition in the form of a water-in-oil emulsion for an anti-cancer agent. The composition includes from 20% to 40% (v/v) of aqueous phase in droplets, where the droplets comprise an anti-cancer agent and a densifying agent selected from Gd-HP-DO3A, Gd-BT-DO3A, and a complex of formula (XI).
The emulsion further includes from 60% to 80% (v/v) of a lipid phase comprising an iodized oil and at least one surfactant of formula (I) in a proportion by weight such that the surfactant is 0.3% to 5% relative to the total volume of the composition. The composition is visually stable, with less than 5% by volume phase separation within 24 hours following preparation at 20°C.
The composition is configured such that, at 20°C and 1 bar and within 24 hours following its preparation, a visual phase separation of less than 5% by volume relative to the total composition is observed. The described emulsion addresses stability and imaging/therapeutic correlation, including improved MRI and X-ray correlation and reduced systemic release as compared to non-compliant formulations.
The document describes compliance criteria and emulsion sense verification, including that non-compliant formulations may show instability or an inversion of emulsion sense and poor MRI visibility, whereas compliant formulations maintain the specified stable water-in-oil emulsion characteristics.
Claims Coverage
The independent claim is claim 1. It combines five main inventive features: a water-in-oil emulsion structure, aqueous droplets with an anti-cancer agent and a gadolinium-based densifying agent identity, a lipid phase with iodized oil, a defined surfactant of formula (I), and explicit stability/phase-separation performance at defined conditions.
Water-in-oil emulsion composition with defined aqueous and lipid fractions
A composition in the form of a water-in-oil emulsion comprising from 20% to 40% (v/v) aqueous phase in droplets and from 60% to 80% (v/v) lipid phase.
Aqueous droplets containing an anti-cancer agent and a gadolinium-based densifying agent
The aqueous droplets comprise an anti-cancer agent and a densifying agent selected from Gd-HP-DO3A, Gd-BT-DO3A, and a complex of formula (XI) where M is a gadolinium ion.
Lipid phase comprising an iodized oil
The lipid phase comprises an iodized oil.
Low-concentration surfactant of formula (I) in lipid phase
The lipid phase comprises at least one surfactant of formula (I) in a proportion, by weight of surfactant relative to the total volume of the composition, of 0.3% to 5%.
Visual phase separation performance within 24 hours
At 20°C and 1 bar and within 24 hours following preparation, a visual phase separation of less than 5% by volume relative to the total composition is observed.
Claim 1 is directed to a stabilized water-in-oil emulsion whose aqueous droplets contain a specified anti-cancer agent together with specified gadolinium-based densifying agents, and whose lipid phase contains an iodized oil and a surfactant of formula (I) at 0.3% to 5%, while maintaining less than 5% visual phase separation within 24 hours under defined conditions.
Stated Advantages
Improved MRI and X-ray correlation.
Reduced systemic release.
Documented Applications
Use for transarterial chemoembolization (TACE).
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