INJECTABLE MELPHALAN COMPOSITIONS COMPRISING CYCLODEXTRIN DERIVATIVE AND METHODS OF PRODUCING AND USING THE SAME

• Main Authors: JAMES D PIPKIN, STEPHEN G MACHATHA
• Format: Patent
• Language: English; Japanese
• Published: 30.06.2016
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

PROBLEM TO BE SOLVED: To provide a melphalan formulation that can minimize a toxicology and side effect profile of intravenous melphalan (2-amino-3-[4-[bis(2-chloroethyl)phenyl]-propionic acid).SOLUTION: The invention provides a pharmaceutical composition containing melphalan and cyclodextrin derivative, wherein 25-125 mg of melphalan as a hydrochloride, any buffer, and a cyclodextrin derivative represented by the formula I are contained, the composition being a dilute pharmaceutical composition. The invention discloses a method for administering a dilute pharmaceutical composition to a subject in need thereof by injection, wherein the dilute pharmaceutical composition has a pH of 4-6; the cyclodextrin derivative is present in a concentration of at least 50:1 (w/w) with respect to the melphalan; and the melphalan in the dilute pharmaceutical composition degrades by 2% or less at 25°C within 5 hours after the diluting.SELECTED DRAWING: None 【課題】静脈内メルファラン（２−アミノ−３−［４−［ビス（２−クロロエチル）フェニル］−プロピオン酸）の毒物学及び副作用プロフィールを最小限にすることができるメルファラン製剤の提供。【解決手段】メルファラン及びシクロデキストリン誘導体を含んでなる薬学的組成物であって、塩酸塩としてのメルファラン２５ｍｇ〜１２５ｍｇ、任意の緩衝剤、及び式Ｉで表されるシクロデキストリン誘導体を含む希釈薬学的組成物。希釈薬学的組成物はｐＨ４〜６を有し、シクロデキストリ誘導体がメルファランに対して少なくとも５０：１（ｗ／ｗ）の濃度で存在し、希釈後５時間以内に２５℃で２％以下分解し、必要対象に対して注射により希釈薬学的組成物を投与する方法。【選択図】なし