JPWO2019142799A1 - 潰瘍性大腸炎治療カプセル剤 - Google Patents
潰瘍性大腸炎治療カプセル剤 Download PDFInfo
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- JPWO2019142799A1 JPWO2019142799A1 JP2019566477A JP2019566477A JPWO2019142799A1 JP WO2019142799 A1 JPWO2019142799 A1 JP WO2019142799A1 JP 2019566477 A JP2019566477 A JP 2019566477A JP 2019566477 A JP2019566477 A JP 2019566477A JP WO2019142799 A1 JPWO2019142799 A1 JP WO2019142799A1
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- ulcerative colitis
- indigo
- soluble polymer
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Abstract
Description
該内容物が、潰瘍性大腸炎を治療する薬剤であるインジゴを分散または溶解したものであり、
該保護層が、油性物質を含有し、
該皮膜が、天然水溶性高分子の皮膜基材にキトサン粉末を分散させたものであり、
該天然水溶性高分子が、第1天然水溶性高分子と第2天然水溶性高分子との混合物であり、該第1天然水溶性高分子がゼラチン、カラギーナン、デンプン、寒天、プルラン、変性デンプン、アルギン酸およびマンナンから成る群から選択される1種または2種以上の混合物であり、該第2天然水溶性高分子がペクチン、ジェランガムおよびカードランから成る群から選択される1種または2種以上の混合物である、ことを特徴とする大腸で局所的に崩壊する潰瘍性大腸炎治療カプセル剤を提供する。
(1)薬剤を含有する内容物、該内容物を被覆する保護層および保護層の外側に形成された皮膜が同心円状に存在するカプセル剤であって、
該内容物が、潰瘍性大腸炎を治療する薬剤であるインジゴを分散または溶解したものであり、
該保護層が、油性物質を含有し、
該皮膜が、天然水溶性高分子の皮膜基材にキトサン粉末を分散させたものであり、
該天然水溶性高分子が、第1天然水溶性高分子と第2天然水溶性高分子との混合物であり、該第1天然水溶性高分子がゼラチン、カラギーナン、デンプン、寒天、プルラン、変性デンプン、アルギン酸およびマンナンから成る群から選択される1種または2種以上の混合物であり、該第2天然水溶性高分子がペクチン、ジェランガムおよびカードランから成る群から選択される1種または2種以上の混合物である、
ことを特徴とする大腸で局所的に崩壊する潰瘍性大腸炎治療カプセル剤、
(2)皮膜が、可塑剤を更に含む前記(1)に記載の潰瘍性大腸炎治療カプセル剤、
(3)前記キトサン粉末が動物由来または植物由来であり、乾燥後の皮膜総重量を基準として、前記キトサン粉末の配合量が1〜27質量%であり、かつ前記第2天然水溶性高分子の配合量が1〜24質量%である前記(1)または(2)に記載の潰瘍性大腸炎治療カプセル剤、
(4)前記天然水溶性高分子の皮膜基材がゼラチンおよびペクチンの混合物である前記(1)〜(3)のいずれかに記載の潰瘍性大腸炎治療カプセル剤、
(5)あらかじめ、酸性溶液で処理したものである、前記(1)〜(4)に記載の潰瘍性大腸炎治療カプセル剤、
(6)前記内容物、保護層および皮膜のいずれかまたはそれらの組合せが、更に、大腸上皮付着性物質、大腸内滞留時間増加物質またはそれらの組合せを含有する、前記(1)〜(5)のいずれかに記載の潰瘍性大腸炎治療カプセル剤、
(7)前記皮膜の外表面に、大腸上皮付着性物質、大腸内滞留時間増加物質またはそれらの組合せを存在させる、前記(1)〜(5)のいずれかに記載の潰瘍性大腸炎治療カプセル剤、
(8)前記大腸上皮付着性物質をインジゴ粉末に配合または被覆して成る内容物を包含する、前記(1)〜(5)のいずれかに記載の潰瘍性大腸炎治療カプセル剤、
(9)経口投与用である前記(1)〜(8)のいずれかに記載の潰瘍性大腸炎治療カプセル剤、
(10)成人(60kg)1人あたりインジゴの量で0.05〜120mg/day服用する前記(1)〜(9)のいずれかに記載の潰瘍性大腸炎治療カプセル剤、
(11)成人(60kg)1人あたりインジゴの量で0.05〜20mg/day服用する前記(1)〜(9)に記載の潰瘍性大腸炎治療カプセル剤、である。
を有する化合物であり、藍色を示す染料としても用いられている。インジゴは、藍の色素成分であって、植物(リュウキュウアイ、タデアイ)等から抽出されていたが、現在ではアニリンから合成される。青黛はインジゴを含む生薬で、これを内容物として用いてもよいが、合成品が好ましく用いられ、特に好ましくは窒素分析法による純度が95%以上の合成品が用いられる。
インジゴ配合カプセル剤Aの形成
(a)内容物液:インジゴ(東京化成工業株式会社製、純度97%)8.33gを、融点32℃の油性物質(グリセリン脂肪酸エステル)91.67gを融解した中に分散したものを内容物液とした。
(b)保護層液:グリセリン脂肪酸エステル(融点42℃)90.00g、レシチン7.00gおよび微粒二酸化ケイ素3.00gを混合して保護層液とした。
(c)皮膜液:豚皮由来酸処理ゼラチン(ゼリー強度:240ブルーム(Bloom))67.00g、食品添加物濃グリセリン24.00g、低メトキシル(LM)ペクチン(エステル化度DE値:27)3.00gおよびイカキトサン(アセチル化度:80以上;粒度:JIS Z8801標準ふるい試験規格準拠、目開き250μm(60mesh)の篩で90%以上パス)6.00gを混合して、皮膜液とした。
動物試験に用いるマウスとしてはC57BL/6Jを、購入後3日間の予備飼育後に使用を開始した。先ず、マウスにDSS(デキストラン硫酸ナトリウム塩、分子量36,000〜44,000)の2.0%溶液を与えて腸炎を発生させ、大腸炎モデルマウスを作製した。
上記の大腸炎モデルマウスの滅菌水のみを投与して、コントロールマウスとした。尚、7日間マウスの腸炎状態を維持するため、減菌水投与時に前記2.0%DDS(デキストラン硫酸ナトリウム塩)溶液を同時に経口投与した。
上記インジゴ配合カプセル剤Aを、5粒(インジゴ量0.5mg相当)と15粒(インジゴ量1.5mg相当)をそれぞれ5検体の腸炎マウスに7日間経口投与した。尚、7日間マウスの腸炎状態を維持するため、該カプセル剤Aの経口投与時に前記2.0%DDS(デキストラン硫酸ナトリウム塩)溶液も同時に経口投与した。
インジゴによる腸炎抑制作用は、体重(Body Weight(BW))の減少、腸炎活動性スコア(Disease Activity Index Score(DAI)スコア:排便回数、血便、粘膜所見、全般的評価の各項目を0〜3の4段階でスコア付けし、合計したスコア(0〜12))および腸管長さ(Colon length)で評価した。大腸炎病態の進行に伴い、体重の減少、腸炎活動スコアの上昇、腸管長さの短縮が見られるので、投与後のマウスの腸を検査して、前記の評価項目で腸炎有無を判断した。
低酸症による高いpHに対応するために、調製例1のインジゴ配合カプセル剤Aを、あらかじめ酸処理をして再乾燥したカプセル剤を作成し、崩壊試験を行った。
酸性溶液に3分以上間浸漬処理したインジゴを含むカプセル剤を用意し、マウスの胃内を想定したpHであるpH4.0で37℃60分間浸漬し崩壊試験を行った。60分後にカプセルをシャーレに取り出し、写真撮影をし、カプセルの状態を確認した。カプセルの崩壊、さらにカプセル内のインジゴの流出はみられなかった。
調製例1のインジゴ配合カプセル剤Aの形成と同様に下記のインジゴ配合カプセル剤Bを形成した。
(a)内容物液:インジゴ(東京化成株式会社製、純度97%)8.33gを、融解した32 ℃の油性物質(グリセリン脂肪酸エステル)85.67g、レシチン3.00及びトコフェロール3.00を融解した中に分散したものを内容液とした。
(b)保護層液:インジゴ配合カプセル剤Aと同じ。
(c)皮膜液:インジゴ配合カプセル剤Aと同じ。
(1)BioCoatTM Fibronectin 6・well plate(コーティング成分:フィブロネクチン)
(2)BioCoatTM Poly・D・Lysine/Laminin 6・well plate(コーティング成分:ポリ-D-リシン/ラミニン)
Claims (11)
- 薬剤を含有する内容物、該内容物を被覆する保護層および保護層の外側に形成された皮膜が同心円状に存在するカプセル剤であって、
該内容物が、潰瘍性大腸炎を治療する薬剤であるインジゴを分散または溶解したものであり、
該保護層が、油性物質を含有し、
該皮膜が、天然水溶性高分子の皮膜基材にキトサン粉末を分散させたものであり、
該天然水溶性高分子が、第1天然水溶性高分子と第2天然水溶性高分子との混合物であり、該第1天然水溶性高分子がゼラチン、カラギーナン、デンプン、寒天、プルラン、変性デンプン、アルギン酸およびマンナンから成る群から選択される1種または2種以上の混合物であり、該第2天然水溶性高分子がペクチン、ジェランガムおよびカードランから成る群から選択される1種または2種以上の混合物である、
ことを特徴とする大腸で局所的に崩壊する潰瘍性大腸炎治療カプセル剤。 - 皮膜が、可塑剤を更に含む請求項1記載の潰瘍性大腸炎治療カプセル剤。
- 前記キトサン粉末が動物由来または植物由来であり、乾燥後の皮膜総重量を基準として、前記キトサン粉末の配合量が1〜27質量%であり、かつ前記第2天然水溶性高分子の配合量が1〜24質量%である請求項1または2に記載の潰瘍性大腸炎治療カプセル剤。
- 前記天然水溶性高分子の皮膜基材がゼラチンおよびペクチンの混合物である請求項1〜3のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
- あらかじめ、酸性溶液で処理したものである、請求項1〜4のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
- 前記内容物、保護層および皮膜のいずれかまたはそれらの組合せが、更に、大腸上皮付着性物質、大腸内滞留時間増加物質またはそれらの組合せを含有する、請求項1〜5のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
- 前記皮膜の外表面に、大腸上皮付着性物質、大腸内滞留時間増加物質またはそれらの組合せを存在させる、請求項1〜5のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
- 前記大腸上皮付着性物質をインジゴ粉末に配合または被覆して成る内容物を包含する、請求項1〜5のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
- 経口投与用である請求項1〜8のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
- 成人(60kg)1人あたりインジゴの量で0.05〜120mg/day服用する請求項1〜9のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
- 成人(60kg)1人あたりインジゴの量で0.05〜20mg/day服用する請求項1〜9のいずれかに記載の潰瘍性大腸炎治療カプセル剤。
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JP2019566477A Active JP7325753B2 (ja) | 2018-01-18 | 2019-01-16 | 潰瘍性大腸炎治療カプセル剤 |
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CN113599364A (zh) * | 2021-08-26 | 2021-11-05 | 贵州医科大学 | 一种左金果胶胶囊的制作方法 |
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JP2013209297A (ja) * | 2012-03-30 | 2013-10-10 | Morishita Jintan Co Ltd | 大腸特異崩壊性カプセル |
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JPS512401B1 (ja) | 1970-12-29 | 1976-01-26 | ||
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JPS518176A (ja) | 1974-07-11 | 1976-01-22 | Morishita Jintan Co | Tsugimenashitankakunijukapuserunoseizohohotokono hohoo jitsushisurutameno seizosochi |
JPS60172343A (ja) | 1984-02-15 | 1985-09-05 | Akira Horikawa | 多重マイクロカプセルの製造法およびその装置 |
JP2987576B2 (ja) | 1998-03-11 | 1999-12-06 | ユーナイテッド ネイションズ デベロップメント プログラム | 消化性潰瘍治療用の植物薬剤、その製造法と用途 |
US20050154046A1 (en) | 2004-01-12 | 2005-07-14 | Longgui Wang | Methods of treating an inflammatory-related disease |
US8563525B2 (en) * | 2004-01-12 | 2013-10-22 | Natrogen Therapeutics International, Inc. | Methods of treating an inflammatory-related disease |
US7582670B2 (en) * | 2001-12-13 | 2009-09-01 | Natrogen Therapeutics, Inc. | Methods of treating an inflammatory-related disease |
CN100512834C (zh) * | 2004-10-25 | 2009-07-15 | 江西本草天工科技有限责任公司 | 八味锡类散口服制剂及其结肠靶向口服制剂与制备方法 |
CN1660357A (zh) * | 2005-01-24 | 2005-08-31 | 王小平 | 锡类散结肠定位释放胶囊及制备方法 |
CA2691132C (en) * | 2007-06-13 | 2016-01-12 | Jay Pravda | Materials and methods for treatment and diagnosis of disorders associated with oxidative stress |
CA2706272C (en) * | 2010-06-03 | 2020-05-05 | Accucaps Industries Limited | Multi phase soft gel capsules, apparatus and method thereof |
WO2014097664A1 (ja) * | 2012-12-21 | 2014-06-26 | 日清ファルマ株式会社 | 大腸送達カプセル及びその製造方法 |
EP3015111B1 (en) * | 2013-06-26 | 2018-01-10 | Tasly Pharmaceutical Group Co., Ltd. | Use of chinese medicine preparation in preparing drug for preventing and/or treating crohn's disease |
JP2019515917A (ja) * | 2016-04-19 | 2019-06-13 | コナリス リサーチ インスティチュート アーゲー | シェラックマイクロカプセル製剤および組成物 |
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EP3741368A4 (en) | 2021-12-22 |
JP7325753B2 (ja) | 2023-08-15 |
KR102597785B1 (ko) | 2023-11-02 |
EP3741368A1 (en) | 2020-11-25 |
CN111867583A (zh) | 2020-10-30 |
EP3741368B1 (en) | 2024-03-06 |
WO2019142799A1 (ja) | 2019-07-25 |
KR20200118813A (ko) | 2020-10-16 |
US20230263740A1 (en) | 2023-08-24 |
US20200352868A1 (en) | 2020-11-12 |
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