JP2017206535A - 非アルコール性脂肪性肝疾患及び非アルコール性脂肪性肝炎の処置方法 - Google Patents
非アルコール性脂肪性肝疾患及び非アルコール性脂肪性肝炎の処置方法 Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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Abstract
Description
(式中、mは2〜5の整数であり、そしてnは3〜8の整数であり、X1及びX2は、X1及びX2が同時に酸素原子でなければ、それぞれ独立して硫黄原子、酸素原子、スルフィニル(−S(O)−)基又はスルホニル(−S(O)2−)基を表す。)
若しくはその代謝産物、又は式(I)の化合物のエステル若しくはその代謝産物、或いはこれらそれぞれの薬学的に許容可能な塩を投与する工程を含む方法を提供する。
本明細書及び添付の特許請求の範囲で使用する場合、文脈上に特に明確な定めがない限り、単数形「a」、「an」及び「the」には複数形が包含される。
一態様において、本発明は、非アルコール性脂肪性肝疾患(NAFLD)又は非アルコール性脂肪性肝炎(NASH)に罹患した患者の処置方法であって、処置を必要とする患者に有効量の式(I)の化合物:
若しくはその代謝産物、又は式(I)の化合物のエステル若しくはその代謝産物、或いはこれらそれぞれの薬学的に許容可能な塩を投与する工程を含む方法を提供する。
式(I)の化合物の合成及び特定の生物学的活性については、米国特許第4,985,585号に記載されており、その全体を本明細書に参照として組み込む。例えば、式(IA)の化合物は、式(II)のフェノール:
を式(III)の化合物:
本明細書で使用される化合物は、経口投与されてもよく、又は静脈注射、筋肉注射及び皮下注射によって投与されてもよく、或いは経皮手段によって投与されてもよい。有効な投与量は、例えば1日当たり約100〜4000mgまで変化に富む。一実施態様では、1日の投与量は250〜2,000mg程度であり、これを1回で又は2回若しくは3回に分けて与える。別の実施態様では、投与量は1000mgを1日2回である。他の実施態様では、好適な投与量としては、1000mgを毎日、1000mgを1日2回、及び750mgを1日3回が挙げられる。
非アルコール性脂肪性肝炎に罹患した成人250名に、MN−001又はMN−002或いはプラセボをそれぞれ毎日500mg最長6ヶ月間与えるように無作為に割り当てた。脂肪肝、小葉炎症、肝細胞の肥大化及び/又は線維症に関する標準得点の合計を用いて評価したところ、主要な結果は、非アルコール性脂肪性肝炎の組織学的特徴の改善であった。結果は、当業者に周知の方法に従って解析した。
超音波試験(US)でNAFLDと診断されかつ肝生検(患者40名)でNAFLDを確認した患者50名に対して、プラセボ対照無作為化二重盲検比較試験を行った。患者には、MN−001又はMN−002(それぞれ毎日500mgを最長6カ月間)或いはプラセボを与えるように無作為に割り当てた。患者は全員、同じ行動減量プログラムに参加した。患者は全員、月一回、腹部US検査を受けた。さらに肝臓酵素量、脂質状態、インスリン量及び身体測定パラメータもモニターして、患者全員が栄養追跡検査を受けた。患者は試験の最後にも2度目の肝生検を受けた。血清アラニントランスアミナーゼの量及びUSによる脂肪変性を、非限定的な評価項目として測定した。結果は、当業者に周知の方法に従って解析した。
Claims (20)
- 前記患者がNAFLDに罹患している、請求項1に記載の方法。
- 前記患者がNASHに罹患している、請求項1に記載の方法。
- 前記化合物が経口投与される、請求項1に記載の方法。
- 前記化合物が錠剤又はカプセルとして投与される、請求項6に記載の方法。
- 前記化合物が、他の多形形態を実質上含まない斜方晶の多形形態Aを呈している、請求項2に記載の方法。
- 前記化合物が液状剤形として投与される、請求項1に記載の方法。
- 前記化合物が、1日当たり100〜4000mgの量を1回で又は2回若しくは3回に分けて投与される、請求項1に記載の方法。
- 前記患者がNAFLDに罹患している、請求項11に記載の方法。
- 前記患者がNASHに罹患している、請求項11に記載の方法。
- 前記化合物が経口投与される、請求項11に記載の方法。
- 前記化合物が錠剤又はカプセルとして投与される、請求項16に記載の方法。
- 前記化合物が、他の多形形態を実質上含まない斜方晶の多形形態Aを呈している、請求項12に記載の方法。
- 前記化合物が液状剤形として投与される、請求項11に記載の方法。
- 前記化合物が、1日当たり100〜4000mgの量を1回で又は2回若しくは3回に分けて投与される、請求項11に記載の方法。
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US8962687B2 (en) * | 2012-12-05 | 2015-02-24 | Medicinova, Inc. | Method of treating liver disorders |
US9346754B2 (en) | 2014-05-08 | 2016-05-24 | Medicinova, Inc. | Method of treating advanced non-alcoholic steatohepatitis |
US20150321989A1 (en) * | 2014-05-08 | 2015-11-12 | Medicinova, Inc. | Method of treating idiopathic pulmonary fibrosis |
CA2950909C (en) * | 2014-06-02 | 2023-03-28 | Medicinova, Inc. | Method of inhibiting or treating fibrosis |
WO2016085954A1 (en) * | 2014-11-26 | 2016-06-02 | Medicinova, Inc. | Geranygeranylacetone and analogs thereof and phenoxyalkylcarboxlic acids for treating fibrosis |
RU2702003C1 (ru) * | 2019-03-18 | 2019-10-03 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Санкт-Петербургский государственный химико-фармацевтический университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО СПХФУ Минздрава России) | Антистеатозное средство |
CN117320701A (zh) * | 2021-05-28 | 2023-12-29 | 美迪诺亚公司 | 一种降低肝脏中甘油三酯合成的方法 |
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