JP2021529205A - 腸管吸収が改善されたナノ粒子形態のペントサンポリ硫酸塩の経口投与用組成物 - Google Patents
腸管吸収が改善されたナノ粒子形態のペントサンポリ硫酸塩の経口投与用組成物 Download PDFInfo
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Abstract
Description
本発明は、ペントサンポリ硫酸ナトリウム(PPS)の経口送達用の医薬組成物に関する。特に本発明は、小腸におけるPPSの吸収を改善し、結腸における副作用を低減又は消失させることを目的とする、ナノ粒子形態のPPSと適切なポリマーとの組成物を開示する。
ペントサンポリ硫酸ナトリウムは、ヘパリン及びグリコサミノグリカン(GAG)に化学的及び構造的に類似する半合成硫酸化多糖である。これは間質性膀胱炎(IC)の患者における抗炎症薬として使用され、尿路上皮を覆う、損傷したグリコサミノグリカン(GAG)層を修復して、バリアの損傷部における透過性を低減し、尿からの毒素が尿路上皮を刺激するのを防止する。これはまた、結合組織及び粘膜マスト細胞の阻害を通じて炎症応答及びヒスタミン分泌を低減することもできる。
本発明は、ペントサンポリ硫酸ナトリウム(PPS)とキトサンとの複合体のナノ粒子を含む経口組成物に関する。本発明の組成物は、好ましくは錠剤、硬カプセル剤、分包の顆粒剤又は散剤、液剤又はシロップ剤の用時調製用の散剤の形態である。ナノ粒子は、PPSとキトサンのイオン化可能な官能基との間のイオン相互作用による溶液中での自己集合により得られる。水溶液中のそのような相互作用の結果として、分子量、置換度、出発溶液中の濃度などのポリマーの特徴及びパラメータのみならず、製造工程のパラメータに寸法が依存する粒子の自然形成が生じる。動的光散乱法により測定される80から220nmの間の直径を好ましくは有する本発明のナノ粒子は、遊離薬物の拡散よりもナノ粒子全体のエンドサイトーシスにより上皮細胞膜を通過して活性成分を運ぶことができる安定な分子間複合体の形態で上部腸管の上皮を直接透過する(A. Dube et al. Chitosan nanoparticles enhance the intestinal absorption of the green tea catechins (+)-catechin and (-)-epigallocatechin gallate, Eur. J. Phar, Sci. 41, 2019-225, 2010)。このように、大腸に達する未吸収の薬物量は有意に低減し、結腸の刺激は低下する。この特徴は、吸収改善の結果として、投与された用量が顕著に低減することを可能にする。
入口温度 140℃;
気流 600L/時間;
懸濁液供給速度 2mL/min;
アスピレータ 35m3/時間
である。
実施例15と同様の粉末 413.44mg
結晶セルロース 90mg
ステアリン酸マグネシウム 2.5mg
Claims (6)
- ペントサンポリ硫酸ナトリウムとキトサンとの複合体のナノ粒子を含む経口組成物。
- ナノ粒子が、80〜220nmの間の直径を有する、請求項1記載の組成物。
- キトサンが、78〜99%の間の脱アセチル化度及び30〜400kDaの間に含まれる分子量を有する、請求項1又は2記載の組成物。
- 20重量%未満の非複合体化ペントサンポリ硫酸ナトリウムを含有する、請求項1〜3のいずれか一項記載の組成物。
- 錠剤、硬カプセル剤、顆粒剤若しくは散剤、液剤の用時調製用の散剤、液剤、又はシロップ剤の形態の、請求項1〜4のいずれか一項記載の組成物。
- 間質性膀胱炎の処置に使用するための、請求項1〜5記載の組成物。
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EP18180223.2 | 2018-06-27 | ||
EP18180223.2A EP3586851A1 (en) | 2018-06-27 | 2018-06-27 | Compositions for oral administration of pentosan polysulfate and chitosan in form of nanoparticles with improved intestinal absorption |
PCT/EP2019/062662 WO2020001852A1 (en) | 2018-06-27 | 2019-05-16 | Compositions for oral administration of pentosan polysulfate in form of nanoparticles with improved intestinal absorption |
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US (1) | US12005126B2 (ja) |
EP (2) | EP3586851A1 (ja) |
JP (1) | JP2021529205A (ja) |
CN (1) | CN112423734A (ja) |
AU (1) | AU2019295349A1 (ja) |
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JP2014520889A (ja) * | 2011-07-19 | 2014-08-25 | バクスター・インターナショナル・インコーポレイテッド | 非抗凝固性硫酸化多糖の経口製剤を改善するための添加剤としての吸収促進剤 |
JP2017512757A (ja) * | 2014-02-24 | 2017-05-25 | ウリゲン ファーマシューティカルズ、インコーポレイテッド | 経口投与するためのペントサンポリ硫酸塩の組成物および使用の方法 |
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US20070141181A1 (en) | 1998-02-13 | 2007-06-21 | Nutramax Laboratories, Inc. | Use of anabolic agents, anti-catabolic agents, antioxidant agents, and analgesics for protection, treatment and repair of connective tissues in humans and animals |
CN1454588A (zh) * | 2003-01-30 | 2003-11-12 | 沈阳药科大学 | 一种多肽蛋白质类口服纳米粒制剂 |
EP1774971A1 (en) * | 2005-10-14 | 2007-04-18 | Advanced in Vitro Cell Technologies, S.L. | Chitosan and heparin nanoparticles |
US20070243218A1 (en) * | 2006-04-03 | 2007-10-18 | Ellinghuysen Jerry A | Stabilized pentosan polysulfate (PPS) formulations and methods of analyzing them |
WO2012027797A1 (en) * | 2010-09-02 | 2012-03-08 | David Charles James | Anti-inflammatory compostion |
KR20140051182A (ko) * | 2011-05-24 | 2014-04-30 | 폴리발러 에스.이.씨. | 특정한 키토산-기재의 나노복합체를 사용하여 sirna를 효과적이고 안전하게 전달하기 위한 조성물 및 방법 |
EP3302705A4 (en) | 2015-05-27 | 2019-01-23 | Vanguard Therapeutics, Inc. | PENTOSAN SODIUM POLYSULFATE FOR THE TREATMENT OF DRÉPANOCYTOSE |
WO2016199161A2 (en) | 2015-06-12 | 2016-12-15 | Swati Vishal Jajodia | A composition comprising pentosan polysulfate sodium for use in treatment of bladder outlet obstruction and/or lower urinary tract symptoms |
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JP2014520889A (ja) * | 2011-07-19 | 2014-08-25 | バクスター・インターナショナル・インコーポレイテッド | 非抗凝固性硫酸化多糖の経口製剤を改善するための添加剤としての吸収促進剤 |
JP2017512757A (ja) * | 2014-02-24 | 2017-05-25 | ウリゲン ファーマシューティカルズ、インコーポレイテッド | 経口投与するためのペントサンポリ硫酸塩の組成物および使用の方法 |
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EP3586851A1 (en) | 2020-01-01 |
EP3813787A1 (en) | 2021-05-05 |
US12005126B2 (en) | 2024-06-11 |
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EP3813787B1 (en) | 2023-10-04 |
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