Usage and dosage of therapeutic agents for endometriosis
Inventors
Dan, Takuro • Takahashi, Hideomi • Kuramochi, Yu
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10646491-B2
Publication Date
2020-05-12
Expiration Date
Abstract
An object of the present invention is to provide pharmaceutical agents that reduce risk for decrease in bone mineral density due to their effect of reducing estrogen levels and exert excellent therapeutic effects on endometriosis. The present invention relates to pharmaceutical compositions for treating endometriosis comprising 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid or a pharmaceutically acceptable salt thereof, which are administered orally once a day at a daily dose of between 50 mg and 75 mg calculated as a free form.
Core Innovation
The invention relates to pharmaceutical compositions containing a compound represented by 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid or a pharmaceutically acceptable salt thereof, preferably a choline salt (Compound 2). The compositions are orally administrable and include the compound in an amount of from 50 mg to 75 mg calculated as a free form. The composition is therapeutically effective for treating endometriosis or endometriosis-associated pain in a patient.
The invention further provides methods for treating endometriosis and endometriosis-associated pain by administering orally a therapeutically effective amount of the pharmaceutical composition once a day at a daily dose of from 50 mg to 75 mg calculated as a free form. The disclosed approach is directed to maintaining estradiol within an “appropriate” range while providing therapeutic efficacy.
The disclosed clinical context includes estradiol reduction and assessment of endometriosis-related symptoms, including NRS pelvic pain improvement. The document describes a correlation of hypoestrogenic side effects with E2 <20 pg/mL and discusses risk of decreased bone mineral density, including outcomes measured by DXA bone density and biomarkers such as serum NTX and bone alkaline phosphatase (BAP).
Claims Coverage
The partial content identifies three independent claims: one for a pharmaceutical composition, and two for treatment methods. Across these claims, the core inventive features focus on the specific compound (or pharmaceutically acceptable salt) and orally administered once-daily dosing at 50 mg to 75 mg calculated as a free form for treating endometriosis or endometriosis-associated pain.
Orally administrable pharmaceutical composition for treating endometriosis or endometriosis-associated pain
A pharmaceutical composition comprising a compound represented by 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is orally administrable and comprises the compound in an amount of from 50 mg to 75 mg calculated as a free form, the amount being therapeutically effective for treating endometriosis or the endometriosis-associated pain.
Oral once-a-day dosing method for treating endometriosis
A method for treating endometriosis comprising administering a therapeutically effective amount of a pharmaceutical composition comprising the compound represented by 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof to a patient, wherein the compound is administered orally once a day at a daily dose of from 50 mg to 75 mg calculated as a free form.
Oral once-a-day dosing method for treating endometriosis-associated pain
A method for treating endometriosis-associated pain comprising administering a therapeutically effective amount of a pharmaceutical composition comprising the compound represented by 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof to a patient, wherein the compound is administered orally once a day at a daily dose of from 50 mg to 75 mg calculated as a free form.
Across the independent claims, the coverage centers on orally administrable pharmaceutical compositions and corresponding treatment methods using the specified tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid compound (or a pharmaceutically acceptable salt) with once-daily administration at 50 mg to 75 mg calculated as a free form for treating endometriosis or endometriosis-associated pain.
Stated Advantages
Therapeutic efficacy for treating endometriosis or endometriosis-associated pain.
Maintains estradiol within an “appropriate” range to reduce risk of decreased bone mineral density.
Documented Applications
Treating endometriosis in a patient using an orally administrable pharmaceutical composition containing the specified compound (or salt) once daily at 50–75 mg calculated as free form.
Treating endometriosis-associated pain in a patient using an orally administrable pharmaceutical composition containing the specified compound (or salt) once daily at 50–75 mg calculated as free form.
Interested in licensing this patent?