Development of Microencapsulated Peptide Drugs with Specific Controlled Release Functions by Air Suspension Coating Process

空气悬浮包衣工艺开发具有特定控释功能的微囊化多肽药物

基本信息

  • 批准号:
    12672098
  • 负责人:
  • 金额:
    $ 2.18万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2000
  • 资助国家:
    日本
  • 起止时间:
    2000 至 2003
  • 项目状态:
    已结题

项目摘要

The aim of the present research project is to develop microcapsules with specific controlled release functions for peptide drug delivery. Three types of microcapsules with different drug-release mode were newly designed and their preparation was accomplished by the air suspension coating process. The proposed systems are directed to long-term delayed release for peroral colon-specific peptide delivery, periodically pulsatile release for chronophermacological peptide delivery and thermo-sensitive release for externally temperature-activated peptide delivery. The results obtained through this research project are summarized asfollows :1.The microcapsules composed of a lactose core, a drug-layer and a coat of newly synthesized acrylic terpolymer made it possible to achieve a pH-independent delayed-release even for a macromolecular water-soluble substance with MW of 20,000. The microencapsulated insulin with this formulation was found to be released in a same manner and stable even after t … More he storage at 4℃ for 12 months. In vivo oral administration studies of the microcapsules revealed a relatively good correlation between in vitro drug-release profiles and in vivo drug-absorption behaviors.2.Novel nano-sized components, i.e. poly(N-isbpropylacrylamide) with grafted poly(ethylene glycol)(p(NIPAAm-g-EG)) nanoparticles and biodegradable poly(e-caprolactone)(PCL), were prepared to fabricate the periodically pulsatile release microcapsules. The p(NIPAAm-g-EG) nanospheres had an ability to protect the incorporated insulin from high temperature and high shear stress that made the system a good candidate as a carrier for insulin for air suspension coating technology. The PCL nanoparticles showing a good film-formability could be prepared by a solvent-evaporation method, though further formulation studies are yet needed to reduce the water-permeability.3.The microcapsules having an ability to thermosensitively control drug-release could be achieved by fabricating an ethylcellulose matrix coat containing nano-sized p(NIPAAm) hydrogels onto a drug-layered core. The microcapsules demonstrated a positively thermosensitive drug-release as expected. The present microcapsule membrane made it possible to obtain an 'on-off' pulsatile release, which could alter the release rate in the order of a minute, in response to stepwise temperature changes between 37 and 42℃. Less
本课题的目的是研制具有特定控释功能的多肽药物微囊。设计了三种不同释药方式的微囊,并采用空气悬浮包衣法制备了微囊。所提出的系统涉及用于经口结肠特异性肽递送的长期延迟释放、用于时辰性肽递送的周期性脉冲释放和用于外部温度激活肽递送的热敏性释放。1.以乳糖为芯材、药物层和新型丙烯酸酯为包衣的微囊,即使是分子量为20,000的大分子水溶性物质,也能实现非pH依赖性的缓释。发现该制剂的微囊化胰岛素以相同的方式释放,即使在注射后也保持稳定。 ...更多信息 在4℃下储存12个月。2.以聚N-异丙基丙烯酰胺接枝聚乙二醇(p(NIPAAm-g-EG))纳米粒和可生物降解的聚己内酯(PCL)为纳米组分,制备了周期性脉冲释药微囊。p(NIPAAm-g-EG)纳米球具有保护掺入的胰岛素免受高温和高剪切应力的能力,这使得该系统成为用于空气悬浮包衣技术的胰岛素载体的良好候选者。通过溶剂挥发法可以制备成膜性良好的PCL纳米粒,但需要进一步的处方研究来降低水的渗透性。3.通过在药物层芯上制备含有纳米级p(NIPAAm)水凝胶的乙基纤维素基质包衣,可以获得具有温敏控制药物释放能力的微囊。该微囊表现出正的温度敏感性药物释放,如预期的。本发明的微胶囊膜使得有可能获得“开-关”脉冲释放,其可以响应于37 ℃和42℃之间的逐步温度变化而在一分钟内改变释放速率。少

项目成果

期刊论文数量(35)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
H.Ichikawa, N.A.Peppas: "New Trends in Polymer for Oral and Parental Administration from Design to Receptors"Editions De Sante. 401 (2001)
H.Ich​​ikawa,N.A.Peppas:“从设计到受体的口服和家长给药聚合物的新趋势”De Sante 版本。
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    0
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福森義信: "ナノパーティクル・テクノロジー"日刊工業新聞社. 257 (2003)
福森庆信:《纳米粒子技术》日刊工业新闻社 257 (2003)。
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    0
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Hideki Ichikawa, Masahiro Arimoto, Yoshinobu Fukumori: "Design of microcapsules with hydrogel as a membrane component and their preparation by a spouted bed."Powder Technol.. 130. 189-192 (2003)
Hideki Ichikawa、Masahiro Arimoto、Yoshinobu Fukumori:“以水凝胶作为膜成分的微胶囊的设计及其通过喷射床的制备。”Powder Technol.. 130. 189-192 (2003)
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    0
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W.Leobandung, H.Ichikawa, Y.Fukumori, N.A.Peppas: "Preparation of stable insulin-loaded nanospheres of poly(ethylene glycol) macromers and N-isopropyl acrylamide"Journal of Controlled Release. 80. 357-363 (2002)
W.Leobandung、H.Ich​​ikawa、Y.Fukumori、N.A.Peppas:“聚乙二醇大分子单体和 N-异丙基丙烯酰胺的稳定胰岛素负载纳米球的制备”控释杂志。
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    0
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Hideki Ichikawa, Yoshinobu Fukumori: "A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix."J.Controlled Release. 63. 107-119 (2000)
Hideki Ichikawa、Yoshinobu Fukumori:“一种新型正热敏控释微胶囊,其膜是分散在乙基纤维素基质中的纳米级聚(N-异丙基丙烯酰胺)凝胶。”J.Controlled Release。
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    0
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ICHIKAWA Hideki其他文献

ICHIKAWA Hideki的其他文献

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{{ truncateString('ICHIKAWA Hideki', 18)}}的其他基金

Structural Design of Micro-and Nano-gel Particles for Appropriate Controlled Release of Peptide Drugs
用于适当控制释放肽类药物的微米和纳米凝胶颗粒的结构设计
  • 批准号:
    16590038
  • 财政年份:
    2004
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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