JP2021506894A - 固体送達組成物 - Google Patents
固体送達組成物 Download PDFInfo
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- JP2021506894A JP2021506894A JP2020534241A JP2020534241A JP2021506894A JP 2021506894 A JP2021506894 A JP 2021506894A JP 2020534241 A JP2020534241 A JP 2020534241A JP 2020534241 A JP2020534241 A JP 2020534241A JP 2021506894 A JP2021506894 A JP 2021506894A
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Abstract
Description
本明細書において、「一つの実施形態(one embodiment)」、「一実施形態(an embodiment)」、「一つの態様(one aspect)」、「一態様(an aspect)」の言及及び同様の言及は、記載した実施形態又は態様が特定の態様、特徴、構造又は特性を含みうることを示す。更に、かかる表現は、本明細書の他の部分で言及されたのと同じ実施形態又は態様いうが、必ずしもそうであるとは限らない。更に、特定の態様、特徴、構造又は特性が一実施形態又は一態様と共に記載されている場合、前記態様、特徴、構造又は特性が他の実施形態又は態様に影響すること、又は関連することは、明示的に記載されているかどうかにかかわらず、当業者の知識の範囲内である。単数の形態「a」、「an」及び「the」は、その文脈が明確に指示していない限り、複数の言及を含む。従って、例えば「一化合物(a compound)」の言及は、複数のかかる化合物を含む。更に、特許請求の範囲は、任意選択的な要素を排除するように草案されうることに注意されたい。従って、この記述は、請求項の要素の記載又は「負」の限定の使用と関連して「もっぱら(solely)」、「単に(only)」などのような排他的な用語を使用するための先行詞として機能することを意図する。
トリス(TRIS):トリス(ヒドロキシメチル)アミノメタン
EDTA:エチレンジアミン四酢酸
EDPA:ジエチレントリアミン五酢酸
本発明によれば、活性物質の標的化された放出及び制御された放出のための固体組成物が提供される。この組成物は、
送達される少なくとも1種の活性物質、
少なくとも1種の熱応答性ポリマー、
少なくとも1種のイオン感受性ポリマー、及び
少なくとも1種の親油性化合物
を含む。
送達される少なくとも1種の活性物質、及び
少なくとも1種の親油性化合物に分散された少なくとも1種の熱応答性ポリマーと少なくとも1種のイオン感受性ポリマーとの組み合わせを含む、親水性マトリックス
を含む。
送達に適した活性物質は、治療クラスの小さい化学化合物若しくは生物学的物質、例えば、タンパク質、ペプチド、モノクローナル抗体、抗−TNFs、免疫調節剤、サイトカイン、ケモ−サイトカイン、抗−新生物剤、鎮痛剤、抗炎症薬、抗生物質、抗アドレナリン薬、局所麻酔剤、非ステロイド性抗炎症薬、ステロイド性抗炎症薬、抗下痢薬、腸抗炎症剤、抹消オピオイド受容体拮抗剤、緩下剤、鎮痙剤、3−ヒドロキシ−3−メチルグルタリル−コエンザイムA(HMG−CoA)リダクターゼ阻害剤、胆汁酸抑制剤(bile acid sequestrants)に属し、全身活性の見地で経口標的投与に適しているか、ヒト身体、好ましくは胃腸管の幾つかの領域で局所的に作用するのに適している。
− タンパク質、ペプチド、抗−TNFアルファー剤及びモノクローナル抗体、例えばコロストラム(初乳、colostrum)、セルトリズマブペゴル(certolizumab pegol)、インフリキシマブ、アダリムマブ、ウステキヌマブ、
− サイトカイン、例えばアルファ−1、アルファ−2、ベータ−1及びガンマ−1インターフェロン、インターロイキン−2(IL−2)、インターロイキン−11(IL−11)、血小板由来成長因子(PDGF)、トランスフォーミング成長因子β(TGFβ)
− 抗−新生物剤、例えばアルキル化剤、代謝拮抗物質、インターフェロン、抗新生物性モノクローナル抗体、BCR−ALBチロシンキナーゼ阻害剤、EGRF阻害剤、HER2阻害剤、分裂抑制剤、5−FU、パクリタキセル、エトポシド、フルタミド、エンザルタミドなど、
− 鎮痛剤、例えばアセトアミノフェン、フェナセチン、サリチル酸ナトリウム、
− 抗生物質、例えばアミノグリコシド、カルバペネム、セファロスポリン、ペニシリン、マクロライド、アンサマイシン、テトラサイクリン、スルホンアミド、テトラサイクリン、
− 抗アドレナリン薬、例えばドキサゾシン、プラゾシン、テラゾシン、
− 局所麻酔剤、例えばブピバカイン、リドカイン、メピバカイン、アルチカイン、これらの塩など、
− 非ステロイド性抗炎症薬、例えばケトプロフィン、イブプロフェン、ジクロフェナク、ジフルニサル、ピロキシカム、フルビプロフェン、ナプロキセン、ケトロラク、ニメスリド、チアプロフェン酸、メサラジン(5−アミノサリチル酸)、
− ステロイド性抗炎症薬、例えばプレドニゾロン、ブデソニド、ヒドロコルチゾン、ベタメタゾン、トリアムシノロン、これらの塩又はエステルなど、
− 抗下痢薬、例えば次没食子酸ビスマス、ロペラミド及びその塩、ラクトバチルス アシドフィルス(Lactobacillus acidophilus)、
− 腸抗炎症剤、例えばロペラミド、5−アミノサリチル酸、オルサラジン、スルファサラジン、ブデソニド、
− 抹消オピオイド受容体拮抗剤、例えばメチルナルトレキソン、ナロキセゴルなど、
− 緩下剤、例えばマグネシウム塩、(クエン酸塩、硫酸塩、リン酸塩、重炭酸塩など)、センナ、ビサコジル、ラクツロース、ポリエチレングリコール(PEGs)、リン酸塩、ドクサート塩など、
− 鎮痙剤、例えば臭化オクチロニウム、ヒヨスチアミン、メトスコポラミン、
ロバスタチン及びシンバスタチンなどの3−ヒドロキシ−3−メチルグルタリル−コエンザイムA(HNG−CoA)リダクターゼ阻害剤、及び
コレスチラミン及びコレセベラムなどの胆汁酸抑制剤(bile acid sequestrants)。
驚くことに、同じ組成物中における少なくとも1種の熱応答性ポリマー、少なくとも1種のイオン感受性ポリマー及び少なくとも1種の親油性化合物の組み合わせが、典型的には経口投与での改良された制御された放出の固体処方剤を得ることに繋がることが発見された。本発明の処方剤は、事前に特定された作用部位に活性物質の放出を標的化でき、長期間所望の範囲、好ましくは胃腸管内で活性成分の放出を保証することができる。
送達されるべき少なくとも1種の活性物質
少なくとも1種の熱応答性ポリマー、
少なくとも1種のイオン感受性ポリマー、
少なくとも1種の親油性化合物、
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマーと少なくとも1種のイオン感受性ポリマーの組み合わせを含む親水性マトリックス、
(c) 少なくとも1種の親油性化合物、
(d) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマー
(c) 及び少なくとも1種のイオン感受性ポリマー、
(d) 少なくとも1種の親油性化合物、
(e) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマーと少なくとも1種のイオン感受性ポリマーの組み合わせを含む親水性マトリックス、
(c) 少なくとも1種の親油性化合物、
(d) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマー
(c) 少なくとも1種のイオン感受性ポリマー、
(d) 少なくとも1種の親油性化合物、
(e) 少なくとも一種の樹脂、
(f) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマーと少なくとも1種のイオン感受性ポリマーの組み合わせを含む親水性マトリックス、
(c) 少なくとも1種の親油性化合物、
(d) 少なくとも一種の樹脂、
(e) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマー
(c) 及び少なくとも1種のイオン感受性ポリマー、
(d) 少なくとも1種の親油性化合物、
(e) 少なくとも一種の樹脂、
(f) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマーと少なくとも1種のイオン感受性ポリマーの組み合わせを含む親水性マトリックス、
(c) 少なくとも1種の親油性化合物、
(d) 少なくとも一種の樹脂、
(e) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマー
(c) 及び少なくとも1種のイオン感受性ポリマー、
(d) 少なくとも1種の親油性化合物、
(e) 少なくとも1種の生体接着性化合物
(f) 任意選択的に、少なくとも一種の樹脂、
(g) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマーと少なくとも1種のイオン感受性ポリマーの組み合わせを含む親水性マトリックス、
(c) 少なくとも1種の親油性化合物、
(d) 少なくとも1種の生体接着性化合物
(e) 任意選択的に、少なくとも一種の樹脂、
(f) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマー
(c) 及び少なくとも1種のイオン感受性ポリマー、
(d) 少なくとも1種の親油性化合物、
(e) 少なくとも1種の生体接着性化合物
(f) 任意選択的に、少なくとも一種の樹脂、
(g) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
(a) 少なくとも1種の活性物質、
(b) 少なくとも1種の熱応答性ポリマーと少なくとも1種のイオン感受性ポリマーの組み合わせを含む親水性マトリックス、
(c) 少なくとも1種の親油性化合物、
(d) 少なくとも1種の生体接着性化合物
(e) 任意選択的に、少なくとも一種の樹脂、
(f) 任意選択的に、他の生理学的に許容しうる賦形剤
を含む。
Claims (14)
- 活性物質の標的化及び制御された放出のための固体組成物であって、前記組成物が、
送達される少なくとも1種の活性物質、
少なくとも1種の熱応答性ポリマー
少なくとも1種のイオン感受性ポリマー、及び
少なくとも1種の親油性化合物、
を含む、固体組成物。 - 送達される少なくとも1種の活性物質、及び
少なくとも1種の親油性化合物に分散された、少なくとも1種の熱応答性ポリマー及び少なくとも1種のイオン感受性ポリマーの組み合わせを含む親水性マトリックス、
を含む、請求項1に記載の固体組成物。 - 樹脂を更に含む、請求項1又は請求項2に記載の固体組成物。
- 錠剤の形態、ミニタブレットの形態、カプセルの形態、顆粒の形態又は他の固体組成物形態である、請求項1〜3のいずれか一項に記載の固体組成物。
- 前記組成物が、生体接着性ポリマー、両親媒性化合物、胃耐性コーティング、及び他の賦形剤のいずれか又は全てを含む1以上の他の任意の置換体をさらに含む、請求項1〜4のいずれか一項に記載の固体組成物。
- 前記少なくとも1種の熱応答性ポリマーは、ポロキサマー124、ポロキサマー188、ポロキサマー237、ポロキサマー338、ポロキサマー407からなる群から選択されるポリオキシエチレン−ポリオキシプロピレンブロックコポリマー(PEO−PPO−PEO)、ポリ(エチレングリコール)/ポリ(ラクチド−コグリコリド)ブロックコポリマー(PEG−PLGA)、ポリ(エチレングリコール)−ポリ(乳酸)−ポリ(エチレングリコール)(PEG−PLA−PEG)、ポリ(N−イソプロピルアクリルアミド)、及びメチルセルロース、ヒドロキシプロピルメチルセルロース、エチル(ヒドロキシエチル)セルロースからなる群から選択される熱応答性セルロース誘導体、並びにこれらの混合物からなる群から選択される、請求項1〜5のいずれか1項に記載の固体組成物。
- 前記少なくとも1種のイオン感受性ポリマーは、カラギーナン、ゲランガム、ペクチン、アルギン酸及びその塩、及びこれらの混合物からなる多糖類の群から選択される、請求項1〜6のいずれか一項に記載の固体組成物。
- 前記少なくとも1種の親油性化合物は、ステアリルアルコール、セチルアルコール又はセテアリルアルコール(これらに限定されない)を含む群から選択される、脂肪酸、それらの塩、エステル又はアミドの不飽和又は水素化されたアルコール、脂肪酸のモノ−、ジ−若しくはトリグリセリド、それらのポリエトキシル化誘導体、ワックス、セラミド、コレステロール誘導体、ステアリン酸及びその塩、パルミチン酸及びその塩、セチル酸及びその塩、アラキドン酸及びその塩、ベヘン酸及びその塩、及びこれらの混合物からなる群から選択される、請求項1〜7のいずれか一項に記載の固体組成物。
- 送達のための前記少なくとも1種の活性物質は、治療クラスの、タンパク質、ペプチド、モノクローナル抗体、抗−TNFs、免疫調節剤、サイトカイン、ケモ−サイトカイン、抗−新生物剤、鎮痛剤、抗炎症薬、抗生物質、抗アドレナリン薬、局所麻酔剤、非ステロイド性抗炎症薬、ステロイド性抗炎症薬、抗下痢薬、腸抗炎症剤、抹消オピオイド受容体拮抗剤、緩下剤、鎮痙剤、3−ヒドロキシ−3−メチルグルタリル−コエンザイムA(HMG−CoA)リダクターゼ阻害剤、胆汁酸抑制剤(bile acid sequestrants)に属し、全身活性の見地で経口標的投与に適しているか、又は人体、好ましくは胃腸管の幾つかの領域で局所的に作用するのに適している、請求項1〜8のいずれか一項に記載の固体組成物。
- 送達のための前記少なくとも1種の活性物質が、タンパク質、ペプチド、モノクローナル抗体、抗−TNFα抗体、又は免疫調節剤である、請求項1〜9のいずれか一項に記載の固体組成物。
- 送達のための前記少なくとも1種の活性物質が、インフリキシマブ、又はアダリムマブ、又はセルトリズマブペゴル、又はこれらの生体類似化合物である、請求項1〜10のいずれか一項に記載の固体組成物。
- 身体に影響する病状又は障害の、診断、予防、緩和、処理、減少及び/又は緩解の誘導若しくは維持に使用するための、請求項1〜11のいずれか一項に記載の固体組成物。
- 経口投与のための、請求項1〜12のいずれか一項に記載の固体組成物。
- 錠剤、ミニタブレット、カプセル、顆粒又はペレットである、請求項1〜13のいずれか一項に記載の固体組成物。
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RU2020124114A3 (ja) | 2022-01-24 |
KR20200103731A (ko) | 2020-09-02 |
CN111491620A (zh) | 2020-08-04 |
MX2020006663A (es) | 2020-08-31 |
CA3079541A1 (en) | 2019-06-27 |
EP3727343A1 (en) | 2020-10-28 |
RU2020124114A (ru) | 2022-01-24 |
WO2019122258A1 (en) | 2019-06-27 |
EP3501503A1 (en) | 2019-06-26 |
BR112020012510A2 (pt) | 2020-11-24 |
US20210007993A1 (en) | 2021-01-14 |
JP2023153395A (ja) | 2023-10-17 |
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