Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11390620-B2
Publication Date
2022-07-19
Expiration Date
Abstract
Provided herein are novel polymorphic forms of metopimazine mesylate. These polymorphic forms are useful in methods, compositions, and kits for the treatment of an enteric nervous system disorder.
Core Innovation
The invention relates to a crystalline form of metopimazine mesylate for treating gastroparesis. The crystalline form is characterized by an X-ray powder diffraction pattern comprising two or more specified 2b8 values within a defined tolerance, and the crystalline material is formulated with a pharmaceutically acceptable carrier for administration to a subject in need thereof.
Metopimazine mesylate is provided as crystalline form A and crystalline form B. Crystalline form A is described as being characterized and confirmed by HRMS, 1H and 13C NMR, single-crystal structure confirmation, and XRPD, together with reported thermal behavior by TGA. Crystalline form B is described as humidity-induced from crystalline form A and is confirmed by HRMS, 1H and 13C NMR, and XRPD, including reported XRPD peak lists.
The invention also relates to polymorphic crystalline forms of metopimazine mesylate, including a crystalline-form pharmaceutical composition defined by XRPD peak sets, thermal profiles, and thermogravimetric analysis. Crystal Form A is characterized by a DSC single endotherm, while Crystal Form B is characterized by DSC two endotherms and one exotherm, together with specified TGA weight-loss behavior.
Claims Coverage
The coverage centers on treating gastroparesis with a metopimazine mesylate crystalline form defined by an XRPD pattern and a pharmaceutically acceptable carrier. The claimed themes present one core inventive feature with dependent refinements that narrow the XRPD requirements and composition constraints.
Xrpd-defined crystalline form metopimazine mesylate for gastroparesis treatment
A method of treating gastroparesis by administering a pharmaceutical composition comprising a crystalline form of metopimazine mesylate, where the crystalline form is characterized by an X-ray powder diffraction pattern comprising two or more of the listed 2b8 values within the stated tolerance, and a pharmaceutically acceptable carrier.
Minimum number and tolerance of xrpd peaks
The crystalline form has an X-ray powder diffraction pattern with three or more of the listed 2b8 peak values, each within b10.2b0 of the stated value.
Limited other crystalline forms
The pharmaceutical composition contains less than 10 wt. % of other crystalline forms of metopimazine mesylate.
Permissible administration routes
The pharmaceutical composition is suitable for administration by multiple routes, including oral, intraduodenal, intracolonic, enteral, topical, intranasal, non-oral, buccal, sublingual, by inhalation, or rectal delivery.
Specified dosage forms and modified-release formats
The pharmaceutical composition is formulated in one of several dosage forms including tablet, capsule, paste, powder, suspension, suppository, extended-release, or modified-release formats.
Daily dosing amount threshold
The method includes administering more than 20 mg per day of the crystalline form of metopimazine mesylate.
The claims coverage focuses on an XRPD-defined metopimazine mesylate crystalline form for treating gastroparesis, with further limitations on the number of peaks, other crystalline forms, administration routes, dosage forms, and daily dose amount.
Stated Advantages
Potential safety advantages via peripheral restriction relative to dopamine-modulating therapies.
Crystalline form A shows lower Tmax variance than metopimazine free base in the reported crossover pharmacokinetic study.
Reduced food effect is reported for crystalline form A, with Cmax/AUC comparisons between fasted and fed conditions.
Thermal characterization is reported to show minimal weight loss for crystalline form A up to 150b0C compared with humidity-induced crystalline form B.
Documented Applications
Treatment of gastroparesis, including diabetic gastroparesis and idiopathic gastroparesis.
Treatment of functional dyspepsia.
Treatment of irritable bowel syndrome (IBS).
Treatment of gastroesophageal reflux disease (GERD).
Treatment of nausea, vomiting, and delayed gastric emptying.
Treating gastroparesis in a subject in need thereof by administering a pharmaceutical composition comprising a crystalline form of metopimazine mesylate defined by an XRPD pattern.
Interested in licensing this patent?