ID | JOS-s40780-019-0151-5 |
著者:名前 | |
著者:別形式 | Ohno, Yui / Seki, Tomohiro / Kojima, Yu / Miki, Ryotaro / Egawa, Yuya / Hosoya, Osamu / Kasono, Keizo / Seki, Toshinobu |
著者:カナ | |
著者:所属 | 城西大学薬学部 / 城西大学薬学部 / 城西大学薬学部 / 城西大学薬学部 / 城西大学薬学部 / 日本赤十字社医療センター薬剤部 / 城西大学薬学部 / 城西大学薬学部 |
著者:所属(別形式) | Josai University, Faculty of Pharmacy and Pharmaceutical Sciences / Josai University, Faculty of Pharmacy and Pharmaceutical Sciences / Josai University, Faculty of Pharmacy and Pharmaceutical Sciences / Josai University, Faculty of Pharmacy and Pharmaceutical Sciences / Josai University, Faculty of Pharmacy and Pharmaceutical Sciences / Japanese Red Cross Medical Center, Department of Pharmacy / Josai University, Faculty of Pharmacy and Pharmaceutical Sciences / Josai University, Faculty of Pharmacy and Pharmaceutical Sciences |
著者版フラグ | publisher |
出版者 | BioMed Central |
電子ISSN | 20550294 |
掲載誌名 | |
巻 | 5 |
刊行年月 | 2019-10 |
開始ページ | 1 |
終了ページ | 11 |
コンテンツ作成日 | 2019-06-13 |
コンテンツ修正日 | 2019-09-05 |
コンテンツ登録日 | 2020-03-21 |
識別番号:DOI | info:doi/10.1186/s40780-019-0151-5 |
識別番号:DOI(リンク) | |
抄録 | Background: Multiple daily subcutaneous injections (MDSIs) are mainly used for formulating an insulin therapy for diabetic patients; however, they also cause insulin-derived amyloidosis (IDA) and lead to poor glycemic control. In addition, for the continuous subcutaneous insulin infusion system (CSII), precipitation frequently causes catheter occlusion and, if the precipitate in the formulations is amyloid, the injection of the insoluble amyloid into the subcutaneous tissue leads to IDA. The aim of this study was to conduct in vitro experiments and present a situation where insulin formulations cause precipitation and amyloid formation. Methods: Humulin®R and NovoRapid® were used as model formulations for MDSIs and CSII, respectively. The generation of the precipitation was evaluated by measuring turbidity, and amyloid formation was evaluated by using Thioflavin T.Humulin®R was mixed with saline buffer solutions and glucose solutions to evaluate the effect of dilution. In addition, we created an experimental system to consider the effect of the time course of condition changes, and investigated the effects of insulin concentration, m-cresol existence, and pH change on the generation of the precipitate and amyloid in the formulation. Results: In both the original and diluted formulations, physical stimulation resulted in the formation of a precipitate, which in most cases was an amyloid. The amyloid was likely to be formed at a near neutral pH. On the contrary, although a precipitate formed when the pH was decreased to near the isoelectric point, this precipitate was not an amyloid. Further decreases in pH resulted in the formation of amyloids, suggesting that both the positive and negative charged states of insulin tended to form amyloids. The formulation additive m-cresol suppressed amyloid formation. When additives were removed from the formulation, the amyloid-containing gel was formed in the field of substance exchange. Conclusions: To consider changes in conditions that may occur for insulin formulations, the relationship between the formation of precipitates and amyloids was demonstrated in vitro by using insulin formulations. From the in vitro study, m-cresol was shown to have an inhibitory effect on amyloid formation. |
キーワード | |
注記 | 11p. Article number: 22, This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
言語 | eng |
資源タイプ | text |
ジャンル | |
フォーマット | application/pdf |
権利 | Copyright © The Author(s).2019 |
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