JP2023012477A - 消化酵素の腸内放出のための製剤、調製方法およびガレヌス製剤 - Google Patents
消化酵素の腸内放出のための製剤、調製方法およびガレヌス製剤 Download PDFInfo
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Abstract
Description
- 胃で遭遇する状態からの消化酵素の保護(胃保護)、
- 味がマスキングされた即時水性形態の調製を可能とする、味のマスキング、
- 腸内への迅速な放出、
- 粘膜刺激作用のマスキング
を可能とする、消化酵素の投与のための新規な製剤を提案することを対象とする。
固体脂質粒子が、
- サイズが50μm~1200μm(マイクロメートル)であり、
- 厳密に疎水性であり、
- 水、有機溶媒、界面活性剤化合物およびポリマー、特に表面ポリマーを含有せず、
- 少なくとも1種の消化酵素、特に、パンクレリパーゼ、膵酵素およびそれらのアナログからなる群から選択される少なくとも1種の消化酵素、ならびに
- 厳密に疎水性の、非吸湿性のワックス状マトリックスを含み、
前記少なくとも1種の消化酵素が、
- 製剤の各固体脂質粒子中に均一に分布し、
- ワックス状マトリックスの内部に向かう分布勾配を伴わずに分布し、
- 製剤の質量の0.1%~90%を占め、
製剤の融点が20℃~65℃である、
製剤に関する。
- 厳密に疎水性かつ非吸湿性のワックス状マトリックスを含み、
- 厳密に疎水性であり、胃保護されており、
- 微量の水性または有機溶媒も含有せず、
- 界面活性剤または両親媒性もしく洗浄剤化合物を含まず、
- ポリマー、特に表面ポリマーおよびこのようなポリマー剤の残留物を含まない
ことを特徴とする。固体脂質粒子は、このようなポリマーを使用する必要なく生成され、
- 前記少なくとも1種の消化酵素が、半径方向の勾配を伴わずにワックス状マトリックス中に均一に分布することを特徴とし、
- 生体適合性かつ腸内分散性であり、
- 非経口投与することができず、
- 単独でまたは混合物として、前記少なくとも1種の消化酵素、特にパンクレリパーゼ、または1種以上の膵酵素もしくは膵臓抽出物、または同様の酵素、ならびに任意選択で補助因子および補酵素を含有し、
- 胃保護をもたらす他に、前記少なくとも1種の消化酵素の安定性を向上させ、腸内への放出を促進すると同時に、味および匂いを確実にマスキングすることが可能である。
- a/ワックス状マトリックスを撹拌しながら溶融した後、ワックス状マトリックスの温度を、ワックス状マトリックスの融点より少なくとも3℃高い温度に低下させる工程、
- b/前記少なくとも1種の消化酵素を、溶融したワックス状マトリックスに添加しおよび分散させる工程、
- c/形成された混合物を、ワックス状マトリックスの融点より少なくとも15℃低い温度に冷却することによって固化する工程、
- e/(前記少なくとも1種の消化酵素を含有するワックス状マトリックスの)固化した混合物の融点より少なくとも10℃、好ましくは20℃低い温度で機械的粉砕を行い、それにより粉末形態の固体脂質粒子の製剤を形成する工程。
- 1.有効成分の味は検出されない、
- 2.有効成分の味がわずかに感知される、
- 3.有効成分の味が検出される、
- 4.有効成分の味は依然として許容される、
- 5.有効成分の味は許容されない。
速度:3000(rpm)、
時間:90秒
粒径:平均直径565ミクロン(μm)。
腸内への放出が促進された、胃保護された、安定化された、味マスキングされたパンクレアチンを含有する粉剤の調製
この製剤化は、膵外分泌不全を処置するための生成物の生成を目的とする。
- 予備粉砕:1500rpmで20秒
- 粉砕:3000rpmで70秒
- 基質240ml、そのうち24.5%のオリーブ油はアカシアガムで乳化した;
- H2Od:140ml
- タウロコール酸ナトリウム溶液(0.5%):20ml
- パンクレアチン量:500IU。
Claims (12)
- 少なくとも1種の消化酵素の製剤であって、製剤が固体脂質粒子を含み、
固体脂質粒子が、
- サイズが50μm~1200μmであり、
- 厳密に疎水性であり、
- 水、有機溶媒、界面活性剤化合物およびポリマーを含有せず、
- 少なくとも1種の消化酵素、
- 厳密に疎水性の、非吸湿性のワックス状マトリックスを含み、
前記少なくとも1種の消化酵素が、
- 製剤の各固体脂質粒子中に均一に分布し、
- ワックス状マトリックスの内部に向かう分布勾配を伴わずに分布し、
- 製剤の質量の0.1%~90%を占め、
製剤の融点が20℃~65℃である、
製剤。 - 固体脂質粒子が、サイズが150μm~800μm、特に250μm~550μmであることを特徴とする、請求項1に記載の製剤。
- 融点が20℃~55℃であることを特徴とする、請求項1または2に記載の製剤。
- ワックス状マトリックスが、植物ワックス、ミツロウ、変性ミツロウ、パラフィンおよびパラフィン誘導体、オゾケライト、ポリオレフィン、脂肪酸、脂肪酸エステル、トリグリセリド、トリグリセリド誘導体、パーム油ならびにカカオバターからなる群から選択される少なくとも1種の脂肪性物質からなることを特徴とする、請求項1から3のいずれか一項に記載の製剤。
- 脂肪酸または脂肪酸エステルを、製剤の0.5%~75%の質量割合で含有することを特徴とする、請求項1から4のいずれか一項に記載の製剤。
- 各固体脂質粒子が消化酵素を1種のみ含むことを特徴とする、請求項1から5のいずれか一項に記載の製剤。
- 製剤が固体脂質粒子の混合物の形態であり、各固体脂質粒子が消化酵素を1種のみ含み、固体脂質粒子の混合物が消化酵素の混合物を形成することを特徴とする、請求項1から6のいずれか一項に記載の製剤。
- 請求項1から7のいずれか一項に記載の製剤を含むガレヌス製剤であって、滑沢剤、均一化剤、薬学的に許容される結合剤、安定剤、分解剤、崩壊剤、着色剤、保存剤、甘味剤、希釈剤および増粘剤からなる群から選択される少なくとも1種の追加化合物を含有することを特徴とする、ガレヌス製剤。
- 前記追加化合物が、ガレヌス組成物における質量割合が約0.1%~99%であることを特徴とする、請求項8に記載のガレヌス製剤。
- 粉剤、錠剤、ロゼンジ剤、ゲルカプセル剤およびウエハーカプセル剤からなる群から選択される形態であることを特徴とする、請求項8または9に記載のガレヌス製剤。
- 請求項1から7のいずれか一項に記載の製剤を調製するための方法であって、以下の工程:
- a/ワックス状マトリックスを撹拌しながら溶融した後、ワックス状マトリックスの温度を、ワックス状マトリックスの融点より少なくとも3℃高い温度に低下させる工程、
- b/前記少なくとも1種の消化酵素を、溶融したワックス状マトリックスに添加しおよび分散させる工程、
- c/形成された混合物を、ワックス状マトリックスの融点より少なくとも15℃低い温度に冷却することによって固化する工程、
- e/固化した混合物の融点より少なくとも10℃、好ましくは20℃低い温度で機械的粉砕を行い、それにより粉末形態の固体脂質粒子の製剤を形成する工程
を含むことを特徴とする、方法。 - 予備粉砕工程d/を含むことを特徴とし、かつ固化工程c/、予備粉砕工程d/および粉砕工程e/のうち少なくとも1つの工程が、ドライアイスまたは液体窒素で冷却することによって行われることを特徴とする、請求項11に記載の方法。
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PCT/FR2019/050557 WO2019180351A1 (fr) | 2018-03-23 | 2019-03-14 | Formulation de libération intestinale d'enzyme digestive, procédé de préparation et préparation galénique |
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