Highly water-soluble salts of a short acting phenylalkylamine calcium channel blocker and uses thereof
AssigneeMilestone Pharmaceuticals Inc.
InventorMartin P. Maguire
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Abstract
The present invention includes surprisingly water-soluble salts of a phenylalkylamine compound that are potent antagonists of L-type calcium channels. Aqueous solutions including salts of the instant invention are formulated for nasal administration and provide a novel therapeutic platform for the treatment of stable angina, migraine, and cardiac arrhythmia, such as paroxysmal supraventricular tachycardia.
Claims39
An aqueous composition formulated for nasal administration comprising a pharmaceutically acceptable salt or free base of compound I:
- or a racemate or enantiomer thereof, wherein compound I, or the racemate or enantiomer thereof, is dissolved in the aqueous composition at a concentration of between 150 mg/mL and 600 mg/mL.
A method of treating a disease selected from the group consisting of cardiac arrhythmia, stable angina, and migraine, said method comprising nasally administering to a patient in need thereof an aqueous composition comprising a pharmaceutically acceptable salt of compound I:
- or a racemate or enantiomer thereof, wherein compound I, or the racemate or enantiomer thereof, is dissolved in the aqueous composition at a concentration of between 150 mg/mL and 600 mg/mL.
An aqueous composition formulated for nasal administration comprising the acetate salt of the S-enantiomer of compound I:
- dissolved in the aqueous composition at a concentration of 350 mg/mL±25 mg/mL.
A method of treating PSVT, said method comprising nasally administering to a patient in need thereof an aqueous composition comprising the acetate salt of the S-enantiomer of compound I:
- wherein the compound is dissolved in the aqueous composition at a concentration of 350 mg/mL±25 mg/mL.
A method of making a solution formulated for nasal administration to a patient, the method comprising the steps of
- a) adding a solution comprising acidic acid to the free base of the S-enantiomer of compound I:
- to form a mixture;
- b) adding to the mixture a solution comprising ethylenediaminetetracetic acid;
- c) heating and mechanically stirring the resulting mixture until the S-enantiomer of compound I has fully dispersed within the mixture;
- d) adjusting the pH of the mixture to be 4.5±0.1 by adding a solution comprising sulfuric acid to the mixture;
- and
- e) diluting the mixture such that the final concentration of the S-enantiomer of compound I in solution is 350 mg/mL±25 mg/mL.
Dependencies are inferred from the claim text.