Methods of treating non-obstructive hypertrophic cardiomyopathy using modified forms of trimetazidine
Inventors
Patel, Jaikrishna • CHAMBERLIN, Paul
Assignees
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Publication Number
US-12233058-B2
Publication Date
2025-02-25
Expiration Date
Abstract
The invention provides methods of treatment of non-obstructive hypertrophic cardiomyopathy using modified forms of trimetazidine, such as CV-8972 and CV-8814.
Core Innovation
The invention relates to a method of treating hypertrophic cardiomyopathy (HCM) by administering a compound represented by formula (IX) to a subject having non-obstructive HCM, including administration of the compound and a pharmaceutically acceptable salt thereof. The disclosed compounds are modified trimetazidine compounds, including CV-8972 and CV-8814.
The described treatment mechanism is shifting cardiac metabolism from fatty-acid oxidation to glucose oxidation. The disclosure includes inhibition of long-chain 3-ketoacyl-CoA thiolase and a CV-8972-derived nicotinic acid as a precursor for NAD+ to support mitochondrial ATP production and mitochondrial respiration.
The invention also discloses pharmaceutical compositions containing the compound or salts, including polymorph and hydrate forms, suitable for administration by selected routes and in oral dosage forms. The disclosure includes mixtures with an erodible swelling polymer, hydroxypropyl methylcellulose (HPMC), together with compound:HPMC weight ratios, and specific compound solid-form examples such as a polymorph Form A, trihydrochloride, and monohydrate.
Claims Coverage
The independent claim covers a method of treating non-obstructive hypertrophic cardiomyopathy by providing a specific formula (IX) compound, or a pharmaceutically acceptable salt, to a subject. The claim set further includes six inventive features through dependent claim limitations.
Treating non-obstructive hypertrophic cardiomyopathy using formula (IX) compound
Providing to a subject having non-obstructive HCM a compound represented by formula (IX), or a pharmaceutically acceptable salt thereof.
Symptom-based subject selection for non-obstructive HCM treatment
The subject has at least one selected symptom from angina, atrial fibrillation, dizziness, fainting, fatigue, heart palpitation, leg swelling, light-headedness, shortness of breath, and stroke.
Use as a pharmaceutical composition
The compound is provided as part of a pharmaceutical composition.
Oral administration of the pharmaceutical composition
The pharmaceutical composition is administered orally.
HPMC as an erodible swelling polymer
The erodible swelling polymer is hydroxypropyl methylcellulose (HPMC).
Compound-to-HPMC weight ratio mixture constraint
A mixture comprises the compound and HPMC in a weight ratio ranging from about 1:10 to about 10:1.
Overall, the claims are directed to administering the formula (IX) modified trimetazidine compound, or a pharmaceutically acceptable salt, for non-obstructive HCM, with additional coverage for symptom-defined subject selection and pharmaceutical composition features including oral administration and HPMC-based erodible swelling polymer mixtures with defined compound:HPMC weight ratios.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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