Pharmaceutical compositions comprising a statin and a cannabinoid and uses thereof
Inventors
Smeeding, James • Sherwood, Mathew
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10835501-B2
Publication Date
2020-11-17
Expiration Date
Abstract
The invention relates to pharmaceutical compositions comprising a statin and a cannabinoid, and their use for the treatment of hypercholesterolemia and atherosclerosis. It has been found that compositions combining a statin and a cannabinoid are improved over existing statin formulations. The compositions of the invention for example allow for a lower effective dose of statin and a reduction of the adverse effects seen with statins taken alone. Dosing ranges and formulations suitable for oral, buccal, and sublingual administration are disclosed. Various specific cannabinoids such as cannabidiol and synthetic cannabidiols selected for their anti-inflammatory, antioxidant, and anti-atherosclerotic effect are shown to be particularly advantageous.
Core Innovation
The disclosed invention is directed to pharmaceutical compositions in unit dosage form and methods for treating a lipid disorder in a patient by providing a statin-cannabidiol combination. The composition contains a reduced daily dosage amount of a statin and an amount of cannabidiol, together with a pharmaceutically acceptable carrier, diluent, or excipient. The statin is specified as atorvastatin in the disclosed combinations.
The reduced daily dosage amount of the statin is less than the lowest standard daily dosage amount for the statin when taken alone, while the statin-cannabidiol combination confers a synergistic effect compared to the statin and the cannabidiol administered alone in the same amounts. The synergistic effect is described as responsible for the reduced daily dosage amount of the statin without loss of therapeutic effect. The claimed compositions are formulated for oral or mucosal administration and are useful in once daily dosing.
The disclosure further emphasizes selection and interaction based on cannabidiol and CYP-related processing, including oral use with first-pass metabolism and cannabidiol being a substrate and/or inhibitor associated with CYP enzymes. In this context, shared CYP enzyme interactions are identified for CYP3A4, CYP2C19, and CYP2C9, and cannabidiol selection includes synthetic/engineered cannabidiols having increased CYP affinity and/or enhanced anti-inflammatory, antioxidant, and anti-atherosclerotic activity.
The invention also encompasses a method of treating medical conditions in a human by administering, in combination, synergistically and therapeutically effective amounts of atorvastatin and cannabidiol. The medical conditions are selected from dysregulation of cholesterol metabolism, myositis, rhabdomyolysis, and statin-associated myopathy, with hypercholesterolemia and atherosclerosis identified as further refinements of the treated conditions.
Claims Coverage
The independent claims cover pharmaceutical compositions and a method, each centered on a synergistic atorvastatin-cannabidiol combination enabling reduced statin dosing without loss of therapeutic effect. Across the independent claims, at least five inventive feature themes are repeated: reduced daily statin dose below the lowest standard dose taken alone, cannabidiol content limits, oral or mucosal formulation with once daily dosing, synergistic effect relative to monotherapies, and method-level treatment of specified cholesterol/metabolic and statin-associated adverse conditions.
Reduced statin daily dosage below lowest standard dose with synergistic effect
The pharmaceutical composition is formulated such that the reduced daily dosage amount of a statin is less than the lowest standard daily dosage amount for the statin when taken alone, and the statin-cannabidiol combination confers a synergistic effect compared to the statin and the cannabidiol administered alone in the same amounts, said synergistic effect responsible for the reduced daily dosage amount of the statin without loss of therapeutic effect.
Cannabidiol amount constraint (≤500 mg) in unit dosage form
The pharmaceutical composition in unit dosage form contains less than or equal to 500 mg of a cannabidiol together with a pharmaceutically acceptable carrier, diluent, or excipient.
Once daily oral or mucosal formulation with unit dosage form
The pharmaceutical composition is formulated for oral or mucosal administration and is useful in once daily dosing, including a unit dosage form for such dosing.
Atorvastatin as the statin
The statin is specified as atorvastatin in the statin-cannabidiol combination.
Shared CYP enzyme interaction and first-pass metabolism after administration
The pharmaceutical composition includes conditions wherein the atorvastatin and cannabidiol are metabolized as substrates of the same CYP enzyme, leading to first-pass metabolism after administration by that CYP enzyme.
Cannabidiol selection with greater affinity for a CYP enzyme
Cannabidiol is selected to have greater affinity for a CYP enzyme.
Once daily oral or mucosal formulation with synergistic reduced dose in lipid disorder treatment
A pharmaceutical composition for once daily dosing useful in treating a patient with a lipid disorder consists essentially of a statin-cannabidiol combination of therapeutically effective amounts, with the reduced daily dosage amount less than the lowest standard daily dosage amount for the statin when taken alone, and with a synergistic effect compared to statin and cannabidiol alone in the same amounts, responsible for reduced statin dosage without loss of therapeutic effect.
Method of treating specified medical conditions with synergistic atorvastatin and cannabidiol
A method of treating a medical condition in a human comprises administering in combination to the human a synergistically and therapeutically effective amount of atorvastatin and a cannabidiol, wherein the medical condition is selected from dysregulation of cholesterol metabolism, myositis, rhabdomyolysis, and statin-associated myopathy.
The independent claims consistently require a synergistic atorvastatin-cannabidiol combination that enables a reduced daily statin dosage below the lowest standard daily dose for the statin when taken alone, with specified cannabidiol limits and oral/mucosal once-daily formulation for lipid disorder treatment. The independent method claim extends the same combination concept to treatment of cholesterol dysregulation and statin-associated adverse conditions, including myositis, rhabdomyolysis, and statin-associated myopathy, with further refinements disclosed as hypercholesterolemia and atherosclerosis.
Stated Advantages
Reduced effective statin dose while maintaining therapeutic effect through the claimed synergistic effect.
Reduced statin-related adverse effects, including myositis/rhabdomyolysis (statin-associated myopathy).
Improved bioavailability (AUC) via shared CYP enzyme interactions (CYP3A4, CYP2C19, CYP2C9) associated with cannabidiol as a CYP substrate/inhibitor.
Documented Applications
Treating a patient with a lipid disorder using an atorvastatin-cannabidiol pharmaceutical composition for once daily dosing.
Treating dysregulation of cholesterol metabolism in a human by administering synergistically and therapeutically effective amounts of atorvastatin and cannabidiol.
Treating myositis, rhabdomyolysis, and statin-associated myopathy in a human by administering synergistically and therapeutically effective amounts of atorvastatin and cannabidiol.
Treating hypercholesterolemia and atherosclerosis using the claimed statin-cannabidiol combination.
Interested in licensing this patent?