Statins of omega-3 polyunsaturated acids for treating hypercholesterolemia
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Publication Number
US-9540307-B2
Publication Date
2017-01-10
Expiration Date
Abstract
The present invention relates to novel statin derivatives of omega-3 fatty acids, and their use in treating hypercholesterolemia, obesity, hypertriglyceridemia, cardiovascular diseases, and metabolic diseases, and Alzheimer's disease.
Core Innovation
The invention relates to compounds of Formula (I) or Formula (II) having R joined from the aldehyde group formed by the partial reduction of the carboxylic acid of specified omega-3 polyunsaturated fatty acids, and includes pharmaceutically-acceptable salts of Formula (II). The compounds are described as trans-β-hydroxy-δ-lactone compounds or corresponding (3R,5R)-3,5-dihydroxy pentanoic acid compounds, with the PUFA-derived tail joined as part of the structure generated from the aldehyde group.
The specified fatty acids include HTA, ALA, SDA, ETE, ETA, EPA, HPA, DPA, DHA, TPA, and THA. The content also focuses on EPA/ALA-derived statin-like aldehyde condensation products referred to as Hytra, including EPA-Hytra condensation product and ALA-Hytra condensation product, and further includes aldol products, hydroxy methyl esters, keto esters, dihydroxy t-butyl esters, lactones, and alcohol/aldehyde precursors.
The document states intended therapeutic uses for hypercholesterolemia and related metabolic and cardiovascular conditions. It also indicates potential for Alzheimer’s disease and dementia-related slowing, including references to amyloid beta, β-secretase, γ-secretase, and γ-secretase modulator relationships.
Claims Coverage
The claims coverage centers on one independent compound claim with dependent claims that add purity, formulation, dosage presentation, and effective-amount limitations. Across the set, the inventive features focus on Formula (I) and Formula (II) compounds in which R is joined from an aldehyde formed by partial reduction of specified polyunsaturated fatty acids, plus pharmaceutically-acceptable salts of Formula (II).
A compound of Formula (I) or Formula (II) with aldehyde-derived R
A compound of Formula (I) or Formula (II), wherein R is joined from the aldehyde group formed by the partial reduction of the carboxylic acid of specified polyunsaturated fatty acids, including HTA, ALA, SDA, ETE, ETA, EPA, HPA, DPA, DHA, TPA, and THA, or the pharmaceutically-acceptable salts of Formula (II).
At least 95% chemical purity for the Formula (I) or Formula (II) compound
The compound of Formula (I) or (II) has at least 95% chemical purity.
Pharmaceutical formulation with specified active ingredient and excipient classes
A pharmaceutical formulation containing, as active ingredient, one or more compounds of Formula (I) or Formula (II), their pharmaceutically-acceptable salts, and pharmaceutically-acceptable adjuvants, binders, desiccants, diluents, and excipients.
Dosage presentation as capsule/tablet or injectable solution/emulsion/suspension
A pharmaceutical formulation containing, as active ingredient, a compound of Formula (II) or a pharmaceutically-acceptable salt, presented as a soft or hard gelatin capsule or tablet, or as an injectable solution, ampule, emulsion, or suspension.
Effective amount range about 10 mg to about 500 mg per day
An effective amount ranging from about 10 mg to about 500 mg per day.
Overall, the claims cover Formula (I)/(II) compounds where R is linked to an aldehyde derived from partial reduction of specified polyunsaturated fatty acids, optionally including pharmaceutically-acceptable salts. Dependent claims further constrain the compound by chemical purity, define pharmaceutical formulations with specified excipient classes, narrow presentation to capsules/tablets or injectable solution/emulsion/suspension, and specify an effective-amount range.
Stated Advantages
Not explicitly described in patent.
Documented Applications
The document states intended therapeutic uses for hypercholesterolemia and related metabolic/cardiovascular conditions.
The document indicates potential for Alzheimer’s disease and dementia-related slowing.
Utility data for HMG-CoA reductase inhibition comparing Na+ salts of EPA-statin and ALA-statin versus pravastatin, including IC50 and Hill coefficient reporting.
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