JP2018516929A - 吸入、舌下又は頬側投与のための非晶質炭酸カルシウムの組成物 - Google Patents
吸入、舌下又は頬側投与のための非晶質炭酸カルシウムの組成物 Download PDFInfo
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Abstract
Description
一実施形態によれば、疾患又は病態は、疼痛、増殖性疾患、皮膚疾患、神経障害、免疫障害、心血管疾患、肺疾患、栄養障害、繁殖障害、筋骨格障害、感染症、及び歯科疾患からなる群から選択される。特定の一実施形態によれば、疾患又は病態は疼痛である。他の実施形態によれば、疾患又は病態は癌である。いくつかの実施形態によれば、癌は、肺癌、乳癌、及び骨癌からなる群から選択される。
実施例
材料及び方法
安定化剤濃度の定義
安定化剤(%)=(最初に添加された安定化剤の量(g)/最初に添加されたCaCl2の量(g))×100
安定性評価
実施例1ポリリン酸塩、一塩基性リン酸又はクエン酸で安定化したACCの粉末組成物の安定性
実施例3再懸濁ACCの安定性に及ぼす異なるポリリン酸塩の効果
実施例4ビスホスホネートで安定化したACCの安定性
実施例6ACC乾燥粉末の含量
実施例7ACC−TP10%粉末のスケールアップ生産
実施例10吸入毒性試験
結論
実施例11癌患者へのACCの頬側投与
実施例12癌患者へのACCの経口投与と組み合わせた吸入投与
試験対象母集団:
試験手順
エンドポイント
VASスコアに基づく疼痛の軽減
鎮痛薬の用量及び/又は回数ごとのオピエート離脱
ECOG PSに基づく機能の改善
医師の推定又はホスピス履歴データと比較した生存率
パルスオキシメータによる動脈酸素飽和度の変化
評価エンドポイント(安全性):
用量あたりの高カルシウム血症DLT対象者の割合
用量あたりのDLT対象者の割合
身長及び体重は、プロトコルごとに測定する(このような評価が行われたときの場所と時間を挿入する(例えば、休憩後X分)。
全試験段階を通して、対象者は5分間休憩後、バイタルサイン(体温、末梢動脈血圧、心拍数、及び呼吸数)を得る。
体温は、全試験段階を通して温度計によって得る。
末梢動脈血圧(収縮期血圧、拡張期血圧)は、全試験段階を通して血圧計によって得る。
心拍数は較正済み標準測定装置を用いて得る。
呼吸数は、最小30秒間の胸郭可動域を観察することによって得る。
理学的検査は、直腸及び骨盤の検査を除く、主要な全臓器系で実施される。身長及び体重は、プロトコルごとに測定し、記録する。
治験責任医師は、任意の理学的検査所見の臨床的意義を決定する際に臨床判断を使用するものとする。
−ECOG PSに基づく機能の改善
−医師の推定又はホスピス履歴データの少なくとも1つと比較した際の生存率の延長
−パルスオキシメータにより判定された動脈酸素飽和度の上昇
−強度、頻度及び持続時間の少なくとも1つにおいて、疼痛の軽減(VASスケール)
実施例13癌患者へのACCの吸入投与
Claims (41)
- 少なくとも1種の安定化剤によって安定化された活性剤として非晶質炭酸カルシウム(ACC)を含む組成物であって、前記ACCが粒子の形態であり、前記組成物は、吸入、頬側、舌下及び歯肉投与からなる群から選択される投与様式のために配合される、組成物。
- 前記ACCが天然ACC又は合成ACCである、請求項1に記載の組成物。
- 前記ACCが合成ACCである、請求項1又は2に記載の組成物。
- 前記安定化剤が、ポリリン酸塩、リン酸化アミノ酸、ビスホスホネート、クエン酸、酒石酸、及びこれらの任意の組み合わせからなる群から選択される、請求項3に記載の組成物。
- 前記ポリリン酸塩がトリリン酸塩、ピロリン酸塩、及びヘキサメタリン酸塩からなる群から選択され、前記リン酸化アミノ酸がホスホセリン又はホスホトレオニンであり、前記ビスホスホネートは、アレンドロン酸塩、エチドロン酸、ゾレドロン酸、及びメドロン酸からなる群から選択される、請求項4に記載の組成物。
- 前記安定化剤がポリリン酸塩又はビスホスホネートであり、前記安定化剤のP原子と前記ACCのCa原子との前記モル比が約1:90〜1:1である、請求項4又は5に記載の組成物。
- 前記安定化剤のP原子と前記ACCのCa原子との間の前記モル比が、約1:30〜約1:3又は1:25〜約1:5である、請求項6に記載の組成物。
- 前記組成物が乾燥粉末の形態である、請求項1〜7のいずれか一項に記載の組成物。
- 前記乾燥粉末中の含水量が30%(w/w)を超えない、請求項8に記載の組成物。
- 前記乾燥粉末中の前記含水量が20%(w/w)未満、15%(w/w)未満、又は10%(w/w)未満である、請求項9に記載の組成物。
- 固体分散体又は懸濁液として配合された、請求項1〜10のいずれか一項に記載の組成物。
- 前記組成物が増量剤を更に含む固体分散体である、請求項11に記載の組成物。
- 前記組成物が液体担体中においてACC懸濁液の形態である、請求項11に記載の組成物。
- 前記液体担体が少なくとも80重量%の水を含む、請求項15に記載の組成物。
- 前記ACCが少なくとも1時間安定したままである、請求項13及び14のいずれか一項に記載の組成物。
- 前記ACCが少なくとも1日、7日、14日、1ヶ月、3ヶ月、又は6ヶ月間安定したままである、請求項17に記載の組成物。
- 前記組成物が約0.1%(w/w)〜約30%(w/w)のACCを含む、請求項13〜16のいずれか一項に記載の組成物。
- 少なくとも1種の追加の活性剤を更に含む、請求項1〜17のいずれか一項に記載の組成物。
- 吸入投与用に配合された、請求項1〜18のいずれか一項に記載の組成物。
- 前記粒子の少なくとも70%、少なくとも80%、少なくとも90%、又は少なくとも95%が20μm以下の粒子径を有する、請求項19に記載の組成物。
- 前記粒子の少なくとも70%、少なくとも80%、少なくとも90%、又は少なくとも95%が15μm以下の粒子径を有する、請求項19に記載の組成物。
- 前記粒子の少なくとも70%、少なくとも80%、少なくとも90%、又は少なくとも95%が10μm以下の粒子径を有する、請求項19に記載の組成物。
- 前記粒子の少なくとも70%が5μm以下の粒子径を有する、請求項19に記載の組成物。
- 前記粒子の少なくとも80%が5μm以下の粒子径を有する、請求項23に記載の組成物。
- 前記粒子の少なくとも90%が5μm以下の粒子径を有する、請求項24に記載の組成物。
- 前記組成物が乾燥粉末吸入用に構成された乾燥粉末の形態である、請求項19及び25に記載の組成物。
- 炭酸カルシウム治療に応答する疾患又は病態の治療に使用するための、請求項1〜26のいずれか一項に記載の組成物及び薬学的に許容される担体を含む医薬組成物であって、吸入、頬側、歯肉、及び舌下投与からなる群から選択される投与様式のために配合される、医薬組成物。
- 前記疾患又は前記病態が、疼痛、過剰増殖性疾患、皮膚疾患、神経障害、免疫障害、心血管疾患、肺疾患、栄養障害、繁殖障害、筋骨格障害、感染症、及び歯科疾患からなる群から選択される、請求項27に記載の医薬組成物。
- 前記疾患又は病態が癌である、請求項28に記載の医薬組成物。
- 吸入投与用に配合された、請求項27〜29のいずれか一項に記載の医薬組成物。
- 乾燥粉末吸入器と共に使用されるように構成されたパッケージに包装された、少なくとも1種の一定量の請求項30に記載の前記医薬組成物を含む容器。
- 前記少なくとも1種の一定量の医薬組成物の吸入投与を可能にするように構成された、請求項31に記載の容器を含む吸入器。
- 少なくとも1種の安定化剤によって安定化されたACCを、吸入投与、頬側投与、舌下投与、歯肉投与、及びこれらの任意の組み合わせから選択される投与経路により、その必要がある対象に投与することを含む、前記対象における炭酸カルシウム治療に応答する疾患又は病態を治療する方法。
- 請求項1〜26のいずれか一項に記載の組成物を前記対象に投与することを含む、請求項33に記載の方法。
- 前記疾患又は前記病態が、疼痛、過剰増殖性疾患、皮膚疾患、神経障害、免疫障害、心血管疾患、肺疾患、栄養障害、繁殖障害、筋骨格障害、感染症、及び歯科の問題からなる群から選択される、請求項34に記載の方法。
- 前記疾患又は前記病態が疼痛である、請求項35に記載の方法。
- 前記疾患又は前記病態が癌である、請求項35に記載の方法。
- 前記癌は、肺癌、乳癌、及び骨癌からなる群から選択される、請求項37に記載の方法。
- 前記疾患が感染症である、請求項35に記載の方法。
- 前記安定化されたACCが0.1〜5%ACCを8mlの用量で吸入投与される、請求項33に記載の方法。
- 頬側及び/又は舌下投与されるACCの前記用量がACC2000mg/日以下である、請求項33に記載の方法。
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