Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
15 巻, 6 号
選択された号の論文の7件中1~7を表示しています
  • —その現状と将来—
    高山 幸三
    2000 年 15 巻 6 号 p. 487
    発行日: 2000/11/10
    公開日: 2008/12/26
    ジャーナル フリー
  • 永井 恒司
    2000 年 15 巻 6 号 p. 489
    発行日: 2000/11/10
    公開日: 2008/12/26
    ジャーナル フリー
  • 薬物の経皮経粘膜吸収—Overview
    杉林 堅次
    2000 年 15 巻 6 号 p. 492-498
    発行日: 2000/11/10
    公開日: 2008/12/26
    ジャーナル フリー
    In most drug formulations except injections, the drug must be absorbed through skin or epithelial mucosa. The drug may have a local effect in the skin, mucosae or their surrounding area, or a systemic action after taking up by the local vessels to migrate into the systemic circulation. Sustained drug action can be achieved by controlling the drug release from the formulations. Much success has already been made in the oral and topical formulations. On the other hand, increase in the transdermal and transrrnucosal absorption is achieved by enhancement of the membrane permeability. Prodrug approach, use of chemical enhancers and application of iontophcresis are the examples to improve the absorption rate of drugs. Active transport of drugs through the membranes has also been paid attention, since biological or biotechnological advances were made on the drug transporters in the epithelial membranes. Broad and active efforts for the moment on this area may give future development of many transdermal and transmucosal DDSs.
  • pH応答性高分子のインスリン経口製剤への応用
    森下 真莉子, 永井 恒司, 高山 幸三
    2000 年 15 巻 6 号 p. 499-506
    発行日: 2000/11/10
    公開日: 2008/12/26
    ジャーナル フリー
    The potential of graft copolymer networks with poly (methacrylic acid-g-ethylene glycol ; P(MAA-g-EG) for oral dosage forms to enhance insulin absorption is reviewed. The polymer exhibited unique pH-responsive characteristics in which interpolymer complexes were formed and dissociated, respectively, in acidic and neutral/basic environments ; the latter forming hydrogels. Correspondingly, the polymer was capable of highly incorporating (94%) and rapidly releasing (<20 min) insulin in vitro. The swelling ratio, mesh size of the gel structure, and insulin incorporation of P (MAA-g-EG) were maximized when the polymer contained equimolar MAA and PEG (molecular weight=1000). This insulin loaded polymer was orally administered to both diabetic and non-diabetic rats. The polymer successfully enhanced insulin absorption in both animal groups, achieving 4.2% bioavailability(relative to subcutaneous administration) with significant hypoglycemic effects. Enhanced insulin absorption was demonstrated with direct intestinal administration (in situ closed loop) with a maximum effect seen in the ileum. This implies that the polymer has a direct absorption enhancing effect local to the intestine in addition to the protective effect (inhibition of insulin release) as the insulin loaded polymer passes through the low pH environment of the stomach. Indeed, it was shown in vitro that enzymatic degradation of insulin in intestinal fluid (pH=7.4) was inhibited in the presence of P (MAA-g-EG). The polymer was also shown to possess mucoadhesive properties, when the hydrogels were formed. Furthermore, the polymer demonstrated high calcium binding and water absorption, which may affect the proteolytic activity of calcium-dependent enzymes and/or reduce transepithelial resistances. Consequently, it was suggested that P (MAA-g-EG) was advantageous by virtue of pH-responsive interpolymer complexation (protection from enzymatic digestion and rapid release on absorption site), mucaadhesion, and protease inhibition and/or tight junction opening due to calcium-binding. Thus, the polymer has the potential to be used as a carrier for oral dosage forms of insulin to enhance its absorption following administration.
  • ペプチド性医薬品の経粘膜吸収改善
    山本 昌
    2000 年 15 巻 6 号 p. 507-519
    発行日: 2000/11/10
    公開日: 2008/12/26
    ジャーナル フリー
    Peptide and protein drugs are becoming a very important class of therapeutic agents. However, the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract and impermeable through the intestinal mucosa. For systemic delivery of peptide and protein drugs, parenteral administration is currently required to achieve their therapeutic activities. However, these administration are poorly accepted by patients and may cause allergic reactions and serious side effects. Therefore, various strategies have been examined to overcome the delivery problems of these peptides when they administered orally. These strategies include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to develop an administration method for peptides that can serve as an alternative to oral and injection administration, (3) to modify the molecular structure of peptide and protein drugs to produce prodrugs and analogues, and (4) to use the dosage forms to these peptide drugs. Of all these strategies, we demonstrated that transmucosal absorption of various peptides including insulin, calcitonin, tetragastrin and thyrotropin releasing hormone (TRH) could be improved by using these approaches. Therefore, these approaches may give us basic information to improve the transmucosal absorption of peptide and protein drugs.
  • 経粘膜ワクチンの臨床応用
    檜垣 惠
    2000 年 15 巻 6 号 p. 521-524
    発行日: 2000/11/10
    公開日: 2008/12/26
    ジャーナル フリー
    Most human pathogens initiate their infectious processes at mucosal surfaces, but most of the licensed vaccines available against these agents are usually given parentally. This is due in part to the relative difficulty in achieving effective mucosal immunization. Future progress in vaccination will be significantly advanced by application of emerging technologies for immunization of inucosal surfaces. Although living vaccines have been the most promising candidates for mucosal vaccination, development of microencapsulated delivery system and adjuvants has made non-living iactivated or subunit vaccines reasonable options for mucosal immunization. Furthermore, such vaccinations should be developed as combined agent vaccines, possibly deliverable by multiple mucosal routes.
  • インスリン製剤への経皮·経粘膜応用
    山崎 義光
    2000 年 15 巻 6 号 p. 525-532
    発行日: 2000/11/10
    公開日: 2008/12/26
    ジャーナル フリー
    In order to control diabetic patients, basal and postprandial insulin supplementation must be needed. To facilitate rapid delivery or stabilize delivery of subcutaneous insulin, biotechnology realizes ultra-rapid delivered insulin and slowly delivered insulin. Ultra-rapid insulin well controlled postprandial hyperglycemia of diabetics by injection immediately before meal-intake. Slowly-delivered insulin may stabilize insulin delivery from subcutaneous depot of insulin and reduce the frequency of hypoglycemia. Various types of transmucosal delivery of insulin are established, such as insulin suppository, intranasal insulin, inhaled insulin, etc. Insulin suppository can be absorbed rapidly as intramuscular injection of insulin and control daily glycemic excursion by applying insulin suppository after every meal. As inhaled insulin, crystalline powder is inhaled for 3 minutes and insulin is appeared immediately in plasma. Insulin action lasts for more than 5 hours after inhalation. Thus, these approaches may improve “quality of life” of diabetic patients.
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