Methods of treating heart failure with reduced ejection fraction using modified forms of trimetazidine
Inventors
Patel, Jaikrishna • CHAMBERLIN, Paul
Assignees
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Publication Number
US-11969422-B2
Publication Date
2024-04-30
Expiration Date
Abstract
The invention provides methods of treatment of heart failure with reduced ejection fraction (HFrEF) using modified forms of trimetazidine, such as CV-8972 and CV-8814.
Core Innovation
The document describes a method of treating heart failure associated with reduced ejection fraction (HFrEF) in a subject by providing a compound represented by formula (X) or a pharmaceutically acceptable salt thereof. It further describes that CV-8972 corresponds to the compound of formula (X) and that a hydroxyethyl precursor/metabolite relationship exists between CV-8972 and CV-8814, which corresponds to formula (IX). The therapeutic context is explicitly linked to HFrEF and reduced left ventricular ejection fraction (LVEF).
The disclosed mechanism shifts myocardial energy metabolism from fatty-acid oxidation to glucose oxidation by inhibiting long-chain 3-ketoacyl-CoA thiolase. For CV-8972, the document also states that nicotinic acid/NAD+ precursor activity supports mitochondrial respiration and ATP production, connecting the metabolism shift to mitochondrial metabolism and ATP generation.
The document additionally describes patient association categories for subjects having HFrEF and provides pharmaceutical composition and administration concepts, including oral formulations. It also describes formulation concepts involving erodible swelling polymers, including hydroxypropyl methylcellulose (HPMC), and options for polymorphs, salts, and hydrates for CV-8972.
Claims Coverage
The claim set includes two independent method claims, each directed to treating HFrEF by administering a specific represented compound or its pharmaceutically acceptable salt. Across the dependent claims, the coverage adds inventive features concerning the HFrEF subject population, oral administration, and specific erodible swelling-polymer formulation details including HPMC, as well as unit-dose and formulation-type refinements.
Treating HFrEF with a compound of formula (X)
Providing to a subject having HFrEF a compound represented by formula (X) or a pharmaceutically acceptable salt thereof.
Treating HFrEF with a compound of formula (IX)
Providing to a subject having HFrEF a compound represented by formula (IX) or a pharmaceutically acceptable salt thereof.
HFrEF subject associated with specified conditions
The HFrEF is associated with one selected condition from a list of cardiovascular and related diseases or patient factors, as specified in the dependent claims.
Oral pharmaceutical composition administration
The method provides a pharmaceutical composition and administering the pharmaceutical composition orally.
Erodible swelling polymer mixture formulation
The pharmaceutical composition includes a mixture of the compound with an erodible polymer that promotes swelling of the mixture in an aqueous environment.
Hydroxypropyl methylcellulose (HPMC) erodible swelling polymer
The erodible polymer is hydroxypropyl methylcellulose (HPMC).
Unit dosage range for the compound
Providing a pharmaceutical unit dosage containing about 10 mg to about 500 mg of the compound.
Specific oral formulation dosage forms
Providing a formulation selected from tablet, troche, lozenge, aqueous suspension, oily suspension, emulsion, hard capsule, soft capsule, or syrup.
Overall, the claims cover treating HFrEF by providing either formula (X) (CV-8972) or formula (IX) (CV-8814) as pharmaceutically acceptable salts, with dependent claim coverage that further specifies an HFrEF subject population associated with enumerated conditions, oral pharmaceutical composition delivery, and erodible swelling-polymer formulations using HPMC, together with unit-dose and selected oral dosage-form types.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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