Pyrazole derivative and use thereof for medical purposes
Inventors
Isaji, Masayuki • Takemura, Masaaki • Isawa, Hidetoshi • Hotei, Yukihiko • Miyashita, Itaru
Assignees
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Publication Number
US-9694027-B2
Publication Date
2017-07-04
Expiration Date
Abstract
The present invention provides pyrazole derivatives, uses thereof for medical purposes and so on. More particularly, the present invention relates to pharmaceuticals useful for the prevention or treatment of constipation, which comprise as an active ingredient 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide, or a pharmaceutically acceptable salt thereof. The pharmaceuticals of the present invention exert an effect of increasing the frequency of bowel movement or the like, and are useful for the prevention or treatment of constipation.
Core Innovation
The invention relates to a constipation pharmaceutical. A pharmaceutical composition is described that comprises as an active ingredient 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide, or a pharmaceutically acceptable salt thereof, together with an appropriate pharmaceutical carrier.
The invention addresses constipation as a medical condition by providing a method for the treatment of constipation. The document defines constipation subtypes including functional constipation, chronic idiopathic constipation, drug-induced constipation, and IBS-C, and describes treating constipation by administering the specified active ingredient and carrier to a patient in need thereof.
The method further specifies a daily dose range of 1 to 60 mg of 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide. The document also describes specific salts/forms such as bis[3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide]monosebacate and hemifumarate dihydrate, and characterizes stool form using the Bristol Stool Form Scale and diagnostic criteria including Rome III.
Claims Coverage
The partial content includes one independent claim covering treatment of constipation by administering a pharmaceutical composition with a defined active ingredient (or pharmaceutically acceptable salt) plus an appropriate pharmaceutical carrier, with a specified daily dose range. The independent claim is refined by dependent claims that specify an additional salt/form and narrow the treated constipation type to functional constipation, chronic idiopathic constipation, and drug-induced functional constipation.
Constipation treatment with a defined pyrazole derivative active ingredient and carrier
A method for the treatment of constipation comprising administering to a patient in need thereof a pharmaceutical composition comprising as an active ingredient 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide, or a pharmaceutically acceptable salt thereof, and an appropriate pharmaceutical carrier.
Specified daily dose range for the active ingredient in constipation therapy
The daily dose is 1 to 60 mg of 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide.
Use of a specific pharmaceutically acceptable salt/form (monosebacate) for constipation treatment
The method where the active ingredient is bis[3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide]monosebacate.
Treatment limited to functional constipation
The method wherein the constipation is functional constipation.
Treatment limited to chronic idiopathic constipation
The method wherein the constipation is chronic idiopathic constipation.
Treatment limited to drug-induced functional constipation
The method wherein the constipation is drug-induced functional constipation.
Across the claims in the partial content, the core coverage is a constipation treatment method using a defined pyrazole derivative active ingredient (or pharmaceutically acceptable salt) with an appropriate pharmaceutical carrier, together with a specified daily dose range. Dependent claim coverage further specifies a monosebacate salt/form and narrows the treated condition to functional constipation, including chronic idiopathic and drug-induced functional constipation.
Stated Advantages
Increased bowel movement frequency and softer stools as characterized in the studies described in the document.
Improved spontaneous bowel movement frequency and stool form in chronic constipation patients in the clinical trial described.
Mild gastrointestinal adverse events were reported in connection with the human studies described.
No hypoglycemia was reported in the clinical trial described.
Documented Applications
Prevention/treatment of constipation in patients, including functional constipation, chronic idiopathic constipation (CIC), drug-induced constipation, and IBS-C, as described in the document and supported by animal and human study examples.
Use in a loperamide-induced dog constipation model, described as showing dose-dependent increases in fecal weight and bowel movement frequency versus control.
Use in a low-fiber diet rat model, described as showing dose-dependent fecal weight increases versus a positive control (MgSO4).
Use in single-dose and multiple-dose human studies, described as increasing bowel movement frequency and affecting stool form (including Bristol types) with mild GI adverse events.
Use in a clinical trial in chronic constipation patients, described as improving spontaneous bowel movement frequency and stool form with Compound 2 across dosing regimens.
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