著者

下石 和樹 安楽 誠 庵原 大輔 平山 文俊 門脇 大介 陣上 祥子 丸山 徹 小田切 優樹

出版者

一般社団法人日本医療薬学会

雑誌

医療薬学 (ISSN:1346342X)

巻号頁・発行日

vol.44, no.2, pp.55-60, 2018-02-10 (Released:2019-02-10)

参考文献数

8

---

Because it is essential to restrict phosphorus intake in dialysis patients, we investigated the phosphorus content per daily standard dose for eight different types of Chinese medicine and 12 different supplements, all of which are typically used by dialysis patients. Phosphorous contents in the range of 3-12 mg were detected in all of the Chinese medicines. Although 11 of the 12 kinds of supplements contained phosphorous, the levels were less than those in the Chinese medicines. The highest phosphorus content among those supplements was found in glucosamine, with a phosphorous content of 6 mg per dose. The phosphorous contents of glucosamine samples obtained from five different companies were all different. Taking these findings together, the intake of phosphorus by dialysis patients heeds to be restricted and the phosphorus contents of Chinese medicines and supplements need to be taken into consideration, by evaluating the total phosphorus intake per day for such patients. Pharmacists should pay attention to maintaining the serum phosphorus level within a reference value by effectively using a phosphate binder if necessary.

著者

小田切 優樹

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.4, pp.413-425, 2009-04-01 (Released:2009-04-01)

参考文献数

103

被引用文献数

21 35

---

After being distributed in the circulating blood, drugs bind to serum proteins varying degrees. In general, such binding is reversible, and a dynamic equilibrium exists between the bound and unbound molecular species. It is believed that unless there is a specific transport system (e.g. receptor-mediated endocytosis, protein-mediated transport), only unbound drugs are able to penetrate through biomembranes, are distributed to tissues, and undergo metabolism and glomerular filtration. It is also believed that only unbound molecules present in target tissues can exert their pharmacological effects, and that the concentration of unbound molecules in tissues is in proportion to the drug serum concentration. Therefore, drug-serum protein binding is critically involved in the manifestation of the pharmacological effects of a drug as well as its pharmacokinetics. Among serum proteins, human serum albumin (HSA) and α1-acid glycoprotein (AGP) play important roles in protein binding for many drugs, which is of key importance to drug distribution in the body. In addition, they are widely used in clinical settings as blood preparations and drug delivery system carriers. It is thus of great importance from the viewpoint of pharmaceutical science to clarify the structure, function, and pharmaceutical properties of HSA and AGP. Accordingly, since starting my laboratory, the focus of my research has involved molecular pharmaceutical studies on the interactions of drugs and HSA and AGP for the purpose of applying these findings to clinical fields, such as drug treatment, diagnosis and drug discovery. In this review, the molecular properties of HSA and AGP will be briefly outlined. The static and dynamic topology of drug binding sites on these proteins, investigated by various spectroscopic techniques, X-ray crystallography, quantitative structure-activity relationships, molecular modeling, photo affinity labeling, site-directed mutagenesis etc., changes in the serum protein binding of drugs in pathological conditions, such as liver and kidney failure and various inflammation diseases and factors contributing to the changes will then be summarized. Finally, cases in which protein binding displacement can be applied to medical fields will also be introduced.

著者

佐藤 弘希 丸山 徹 小田切 陽子 三村 絵美子 河上 恵子 池田 倫子 岡山 善郎 安楽 誠 小田切 優樹

出版者

一般社団法人日本医療薬学会

雑誌

医療薬学 (ISSN:1346342X)

巻号頁・発行日

vol.32, no.9, pp.940-945, 2006-09-10 (Released:2007-11-09)

参考文献数

25

被引用文献数

2 3

---

The results of a population pharmacokinetic (PPK) analysis for Japanese suggest that smoking and gender difference are factors influencing the clearance of olanzapine, an atypical antipsychotic drug. However, no post-marketing verification has been conducted regarding how these factors affect the prescribing of this drug by practicing physicians. We therefore conducted a retrospective analysis on the effects of smoking and gender difference on olanzapine dosages. The results showed that smokers received significantly higher doses of olanzapine than non-smokers and that males tended to receive higher doses of olanzapine than females. The dosage for male smokers, the highest dose group, was 1.3 times that for female non-smokers, the lowest dose group. These results showed good correspondence with those of the PPK analysis given in the package insert and suggests that PPK data could be useful information for the community pharmacist.

著者

安楽 誠 小田切 優樹 上釜 兼人

出版者

崇城大学

雑誌

基盤研究(C)

巻号頁・発行日

2014-04-01

---

慢性腎不全モデルを利用した検討において,天然糖類であるシクロデストリン(CD)において,その包接能による尿毒症物質インドキシル硫酸の血中濃度低下が観察された.さらに天然多糖であるキチンを部分的に脱アセチル化したカチオン性高分子であるキトサンナノファイバー(CSNF)においてもキトサン粉末と比較して顕著なインドキシル硫酸の血中濃度低下に加えた血中抗酸化効果も観察された.そこで,CDとCSNFを素材とした薬物含有ゲルを作成した結果,CDの包接能による薬物の高い封入率とCDNFとCDの静電相互作用による薬物の徐放化が観察された.今回作成した複合ゲルの腎不全などの病態への応用が今後期待される.

著者

平山 文俊 小田切 優樹 上釜 兼人 和久田 徹 稲葉 光治

出版者

公益社団法人 高分子学会

雑誌

高分子論文集 (ISSN:03862186)

巻号頁・発行日

vol.39, no.10, pp.643-648, 1982-10-25 (Released:2010-02-26)

参考文献数

19

被引用文献数

2 5

---

水溶液中ならびに固体状態における16, 16-Dimethyl-trans-Δ2-prostaglandin E1 methylester (ONO-802) とα-, β-, γ-シクロデキストリン (α-, β-, γ-CyD) との複合体形成を溶解度法並びに粉末X線回折法により検討した. 複合体の安定度定数の大きさはβ-CyD複合体>α-CyD複合体>γ-CyD複合体の順であった. 溶解度相図に基づきモル比1: 2 (ONO-802: 2CyD) のβ-及びγ-CyD固体複合体を調製し, それらの溶解性, セロハン膜透過性, 坐剤基剤 (Witepsol H15) からの放出性を検討し, ONO-802の場合と比較した. ONO-802の見掛けの溶解速度並びに膜透過速度は包接複合体形成により著しく増加した. また, CyD複合体の坐剤基剤からの放出性はONO-802単独に比べて著しく優れていた. これらの知見はONO-802のバイオアベイラビリティの向上及び製剤化に際してCyDの有効利用を示唆するものである.

著者

瀬尾 量 鶴岡 道雄 橋本 強 藤永 稔夫 小田切 優樹 上釜 兼人

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.1, pp.286-291, 1983-01-25 (Released:2008-03-31)

参考文献数

15

被引用文献数

48 62

---

Inclusion complex formations of spironolactone (SP) with three cyclodextrins (α-, β-, γ-CyDs) in aqueous solution and in the solid state were studied by the solubility method, by spectroscopic methods (UV, CD, IR) and by X-ray diffractometry, and their modes of interaction were assessed. The solid complexes of SP with β- and γ-CyDs were obtained in molar ratios of 1 : 2 and 2 : 3, respectively, and their dissolution, membrane permeation and oral absorption properties were examined. The rates of dissolution and permeation through a cellophane membrane in water were significantly increased by inclusion complexation (γ-CyD complex>β-CyD complex>SP alone), depending upon the solubility of the test samples. The serum levels of SP following oral administration of CyD complexes were found to be greater than those after administration of SP alone. The results indicated that the γ-CyD complex rather than β-CyD complex may have great utility as a faster dissolving form of SP able to produce higher serum levels.

著者

小田切 優樹 丸山 徹 渡邊 博志

出版者

崇城大学

雑誌

挑戦的萌芽研究

巻号頁・発行日

2011

---

本研究では標的分子をBRに絞り込み、BR捕獲型HSAドメインの設計と新規BR除去療法としての有用性を評価するため、以下の検討を行った。得られた知見を要約する。(1)進化工学的手法であるファージディスプレイ法を駆使してBRの詳細な結合部位の同定を可能にし、さらに1.6×105個の変異体の中からBR高親和性HSAドメインII変異体を拾い上げることに成功した。(2)今回作製した新規BR尿中排泄促進剤pan3_3-13は、抗体製剤よりも製造コストが低く、従来の血液浄化法の基盤を成す血液透析に替わり、侵襲性の低い新たな血液浄化法の道を拓くことが大いに期待される。