Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12226408-B2
Publication Date
2025-02-18
Expiration Date
Abstract
Co-crystals of itanapraced; methods of preparation of the co-crystals; uses of the co-crystals as APIs; formulations containing the co-crystals; uses of the co-crystals and formulations for prevention and treatment of neurodegeneration disorders, infections, dementias, inflammation, and injuries; and methods of prevention and treatment of neurodegeneration disorders, infections, dementias, inflammation, and injuries are described.
Core Innovation
The invention relates to co-crystals of an AICD inhibitor, wherein the AICD inhibitor is provided as a co-crystal comprising a crystal lattice of molecules of the AICD inhibitor and a coformer. The AICD inhibitor interacts nonionically with the coformer in the crystal lattice, and the AICD inhibitor and the coformer are associated only by non-ionic and noncovalent bonds. The coformer is not a solvent, and the co-crystal includes at least an AICD inhibitor interacting in a supramolecular crystal lattice.
In particular, the AICD inhibitor is itanapraced, and the coformer is selected from citric acid, nicotinamide, saccharin, and vanillin. A further embodiment specifies that the AICD inhibitor includes a carboxylic acid moiety and that the coformer is a nonvolatile heterocyclic organic compound having a pyridinyl moiety, with nicotinamide as the coformer. The document reports evidence of supramolecular interaction between the nicotinamide pyridinyl moiety and the itanapraced carboxylic acid moiety.
The invention includes co-crystal screening and characterization for itanapraced, including qualitative solubility and slurry investigations with multiple coformers, and identifies itanapraced:nicotinamide as a co-crystal with a distinctive XRPD pattern and crystal habit. The co-crystal is characterized using XRPD and solid-state behavior, including hygroscopicity and water sorption/desorption behavior, with reported formulation performance goals such as improved water solubility, reduced hygroscopicity, enhanced bioavailability/dissolution, and faster Tmax/Cmax.
Claims Coverage
The independent claims define pharmaceutical formulations containing itanapraced as an AICD inhibitor in co-crystal form with specified non-solvent coformers, where the co-crystal lattice is characterized by non-ionic/noncovalent association. Across the independent claims, the main inventive features include six merged features.
Non-solvent coformer co-crystal with nonionic/noncovalent lattice association
A pharmaceutical formulation comprising a therapeutically effective amount of an AICD inhibitor, wherein the AICD inhibitor is in a form of a co-crystal comprising a crystal lattice of molecules of the AICD inhibitor and a coformer, the AICD inhibitor interacting nonionically with the coformer in the crystal lattice, and the AICD inhibitor and the coformer being associated only by non-ionic and noncovalent bonds, wherein the coformer is not a solvent; the pharmaceutical formulation consists of the AICD inhibitor, the coformer, the crystal lattice, and optional pharmaceutically acceptable excipient(s).
Coformer selection with specified coformer set
The co-crystal pharmaceutical formulation where the AICD inhibitor is itanapraced and the coformer is selected from a group consisting of citric acid, nicotinamide, saccharin, and vanillin.
Pyridinyl heterocycle coformer co-crystal with defined XRPD peaks
A pharmaceutical formulation comprising a therapeutically effective amount of an AICD inhibitor in co-crystal form, where the AICD inhibitor includes a carboxylic acid moiety and the coformer is a nonvolatile heterocyclic organic compound having a pyridinyl moiety; the AICD inhibitor and the coformer are associated only by non-ionic and noncovalent bonds; the coformer is not a solvent; the AICD inhibitor is itanapraced; the coformer is nicotinamide; a stoichiometric ratio of itanapraced to nicotinamide is from about 0.8:1.2 to about 1.2:0.8; and the co-crystal comprises an X-ray Powder Diffraction Pattern (XRPD) with specified peaks in 2θ space.
Itanapraced–nicotinamide nonionic/noncovalent co-crystal formulation
A pharmaceutical formulation comprising a therapeutically effective amount of an AICD inhibitor in co-crystal form, where the AICD inhibitor includes a carboxylic acid moiety and the coformer is a nonvolatile heterocyclic organic compound having a pyridinyl moiety; the AICD inhibitor and the coformer are associated only by non-ionic and noncovalent bonds; the coformer is not a solvent; and wherein the AICD inhibitor is itanapraced and the coformer is nicotinamide.
Defined XRPD peak pattern from a Cu radiation source
The co-crystal comprises an XRPD pattern with specific peaks, expressed in 2θ produced from a Cu radiation source (λ=1.54 Å after Ni filtering), at about 14.63°; 14.90°; 15.56°; 16.71°; 18.24°; 18.46°; 20.03°; 20.27°; 22.01°; 22.27°; 24.17°; 24.47°; 26.14°; 26.47°; 27.83°; 28.85°; 29.97°; 30.64°; 32.42°; 34.07°; and 39.14°, all ±0.2 degrees 2θ.
Defined stoichiometric ratio for itanapraced and nicotinamide
A stoichiometric ratio of itanapraced to nicotinamide is from about 0.8:1.2 to about 1.2:0.8.
The independent claims focus on pharmaceutical formulations where itanapraced is delivered as a co-crystal with a nonvolatile, non-solvent coformer, and where the crystal lattice association between itanapraced and the coformer is limited to non-ionic and noncovalent bonds. Coverage further specifies which coformers are allowed, identifies nicotinamide as a pyridinyl heterocyclic coformer for embodiments, constrains a stoichiometric ratio, and in one claim family requires an XRPD pattern defined by specific 2θ peaks.
Stated Advantages
Improved water solubility
Reduced hygroscopicity
Enhanced bioavailability/dissolution
Faster Tmax/Cmax
Non-hygroscopic behavior and no solid-state form changes after two 5–95% RH cycles.
The co-crystal is less hygroscopic than itanapraced but more water soluble than itanapraced.
Documented Applications
Therapeutic use for neurodegeneration disorders, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis
Therapeutic use for dementias and inflammation
Therapeutic use for related injuries including COVID-19 neurological infection and acute respiratory stress syndrome (ARDS)
Microglial modulation and inflammation inhibition
Interested in licensing this patent?