著者

藤堂 浩明 齋藤 美幸 鈴木 宏宙 井上 裕 高山 幸三 杉林 堅次

出版者

公益社団法人 日本薬剤学会

雑誌

薬剤学 (ISSN:03727629)

巻号頁・発行日

vol.81, no.1, pp.111-120, 2021 (Released:2021-01-01)

参考文献数

6

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It is important when developing effective and safe pharmaceutical products to select adequate active components and formulations as well as to design their containers and devices. Minoxidil was developed as a direct over-the-counter (OTC) drug in 1999 and has long been marketed only by one original company. Recently, many generic products have been marketed. However, the shape and type of the containers for these generic products differ from that of the original product, leading to a possibility that the amount of minoxidil applied by patients may differ. In the present study, the original and three typical generic products with 5% minoxidil external formulations were evaluated for their filling amounts, single application amounts, extent of distribution on application, ability to reach the scalp, and dripping properties. As a result, statistically significant differences were found in the filling amounts and ability to reach to the scalp between the products due to differences in the nozzle shape of the container. In addition, a large variation was observed in some of the generic products in terms of the drug liberation. These results indicate that it is important to suitably design and adequately evaluate the container for OTC products such as minoxidil formulations, which can exhibit toxicity from overuse, and that are easily purchased by consumers.

著者

木村 恵理子 藤堂 浩明 杉林 堅次

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.132, no.3, pp.319-324, 2012-03-01 (Released:2012-03-01)

参考文献数

19

被引用文献数

2 2

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Human beings are exposed or otherwise a subjected to a various chemical compounds. Various nanomaterials are contained in the chemical compounds which are used in many fields. Nanomaterials are also used in cosmetics: titanium dioxide and zinc oxide are examples. Consumers who apply cosmetics to their skin as well as workers at industrial plants may thus be exposed to these nanoparticles. Therefore, it is of great importance to evaluate the safety of these nanoparticles. In this review, we describe the possibility of nanoparticle penetration to skin following exposure, which makes it urgent to evaluate the safety factors. In general, it is necessary to take account of the desquamation rate of the stratum corneum and the permeation pathway and size of nanoparticles when considering such penetration. One layer of the human stratum corneum is peeled off per day. Therefore, a chemical compound of which the skin penetration is lower than the desquamation rate does not permeate through the skin, when the compound infiltrates the stratum corneum. Hence, compounds with a molecular weight of more than 500 Daltons do not permeate through the stratum corneum. However, we must also pay attention to the appendage routes, although the aforementioned layer is the primary permeation route of nanoparticles. The contribution of appendage routes must be taken into consideration.

著者

杉林 堅次

出版者

公益社団法人 日本油化学会

雑誌

オレオサイエンス (ISSN:13458949)

巻号頁・発行日

vol.17, no.11, pp.549-558, 2017 (Released:2019-08-05)

参考文献数

23

被引用文献数

1

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簡便なDDSとしての外用剤と経皮吸収型製剤(TDDS)を今後さらに開発・発展させていくためには,皮膚の構造について理解し,薬物の経皮吸収について十分理解することが必要である。ここでは,経皮吸収経路とその速度論について,さらには特に外用剤の評価で重要となる皮膚中濃度動態について解説した。また,実用化に当たって重要である吸収促進剤の利用や外部エネルギーを利用した製剤化に関しても説明した。今後は,AIやIoTの発展に伴い全く新しいタイプのTDDSが世に出ると期待される。今はまさに将来のために過去を振り返る時であると思われる。

著者

杉林 堅次

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.37, no.5, pp.385-387, 2001

参考文献数

21

被引用文献数

1

著者

杉林 堅次

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.31, no.3, pp.201-209, 2016

被引用文献数

1

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経皮吸収型製剤(TDDS)を多くの薬物に応用するためには、皮膚透過促進技術の利用が必須となる。一方で、最終的な医薬品とするためには、バイオアベイラビリティや吸収速度をあらかじめ予測した値にするため、コントロールドリリースの機能も必要となる。本稿では、TDDSのこの40年の開発研究から、経皮吸収促進剤の利用研究やイオントフォレシスやマイクロニードルなどの物理的吸収促進法の研究までについて紹介する。また、これら吸収促進法との併用により、ようやく本来の意味のコントロールドリリース能を持ち、高いバイオアベイラビリティを有するTDDSの開発が可能になりつつあること、さらにはモノのインターネット(IoT)の概念を導入したTDDSについて述べ、これら新規なTDDS(TDDS-IoT)が医薬品製剤の中心を担う可能性について論述する。

著者

杉林 堅次

出版者

The Society of Cosmetic Chemists of Japan

雑誌

日本化粧品技術者会誌 (ISSN:03875253)

巻号頁・発行日

vol.41, no.4, pp.241-245, 2007-12-20 (Released:2010-08-06)

参考文献数

17

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化粧品には, その目的により, 有効成分を角層中に浸透させたり, 表皮細胞層や真皮細胞層に吸収させるべく設計されたものがある一方で, 有効成分を皮膚に浸透させずに皮膚をカバーすることによって目的を達成できるものがある。また, 有効成分を皮膚の実質層ではなく毛髪や毛嚢にのみに集中的に移行させることを企図した化粧品もある。したがって, 化粧品の有効性を高める場合には, その化粧品の目的にあった有効成分の浸透・吸収性を示すことが望まれる。ここでは, 有効成分の皮膚への浸透・分配性, また皮膚透過性の実験・評価方法, さらには, 皮膚浸透・分配性や皮膚透過性の制御や改善 (促進) 技術について主にQ/A形式で紹介する。

著者

杉野 雅浩 藤堂 浩明 杉林 堅次

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.12, pp.1453-1458, 2009-12-01 (Released:2009-12-01)

参考文献数

14

被引用文献数

12 14

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Transdermal Drug Delivery Systems (TDDS), where active drugs must be absorbed into the systemic circulation after penetrating the skin barrier, were first launched in 1979, and about 10 TDDS containing different kinds of drugs were developed during the initial decade. Interestingly, a developmental rush has come again in the present century. Various penetration-enhancing approaches to improve drug permeation of the skin (stratum corneum) have been attempted. These approaches are of two types: chemical and physical. Examples of the chemical approach are enhancers such as alcohol, monoterpenes and fatty acid esters, as well as chemical modification of prodrugs. In contrast, physical approaches include the use of electrical-, thermal- and mechanical-energy, as well as microneedles, needle-free injectors or electroporation to completely or partially evade the barrier function in the stratum corneum. The chemical approaches are mainly effective in increasing the skin permeation of low-molecular chemicals, whereas physical means are effective for these chemicals but also high-molecules like peptides, proteins and nucleotides (DNA or RNA). Marked development has been observed in these physical means in the past decade. In addition, recent developments in tissue engineering technologies enables the use of cultured skin containing keratinocytes and fibroblasts as a TDDS. An effective “cell delivery system” may be a reality in the near future. This paper will look back on the 30-year history of TDDS and evaluate the feasibility of a new generation of these systems.

著者

杉林 堅次

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.31, no.3, pp.201-209, 2016-07-25 (Released:2016-10-25)

参考文献数

26

被引用文献数

1

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経皮吸収型製剤(TDDS)を多くの薬物に応用するためには、皮膚透過促進技術の利用が必須となる。一方で、最終的な医薬品とするためには、バイオアベイラビリティや吸収速度をあらかじめ予測した値にするため、コントロールドリリースの機能も必要となる。本稿では、TDDSのこの40年の開発研究から、経皮吸収促進剤の利用研究やイオントフォレシスやマイクロニードルなどの物理的吸収促進法の研究までについて紹介する。また、これら吸収促進法との併用により、ようやく本来の意味のコントロールドリリース能を持ち、高いバイオアベイラビリティを有するTDDSの開発が可能になりつつあること、さらにはモノのインターネット(IoT)の概念を導入したTDDSについて述べ、これら新規なTDDS(TDDS-IoT)が医薬品製剤の中心を担う可能性について論述する。

著者

杉林 堅次

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.15, no.6, pp.492-498, 2000-11-10 (Released:2008-12-26)

参考文献数

30

被引用文献数

2 1

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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.

著者

杉林 堅次 東條 角治 寺原 孝明 大谷 道輝 徳留 嘉寛 Sugibayashi Kenji / Tojo Kakuji / Terahara Takaaki / Ootani Michiteru / Tokudome Yoshihiro スギバヤシ ケンジ トウジョウ カクジ テラハラ タカアキ オオタニ ミチテル トクドメ ヨシヒロ

出版者

出版者:日本薬剤学会

雑誌

薬剤学 (ISSN:03727629)

巻号頁・発行日

vol.69,

著者

杉林 堅次

出版者

日本薬剤学会

雑誌

薬剤学 (ISSN:03727629)

巻号頁・発行日

vol.67, no.2, pp.89-95, 2007

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皮膚局所に適用する医薬品製剤には, 皮膚組織やその周辺部位での薬効(局所作用)を期待するものだけでなく, いわゆる全身作用を期待する経皮吸収型製剤(Transdermal Drug Delivery Systems, TDS)があり, さらに, 最近では機能性を有する化粧品も市場を賑わすようになってきた. したがって, 現在では, 治療薬だけでなく化粧品有効成分の皮膚透過性や経皮吸収性を正しく評価する方法論の確立が以前にも増して必要とされるようになった. また一方で, 効果が高くなれば皮膚局所での刺激性などの副作用についても正しく予測することが重要となり, 加えて, 主薬およびその濃度, さらには基剤の選択基準の確立が必要となってきた. 現在, 薬物の皮膚透過量や透過速度はヒト皮膚を用いて主にin vitro実験法で評価されている. しかし, 特に本邦では新鮮なヒト皮膚が必要な量を入手できるとは限らない. そこで, 動物皮膚や人工膜が使われることとなるが, 動物皮膚使用に当たっては動物愛護の問題を回避することができないし, また, 人工膜の使用では代謝酵素やトランスポーターが関与する皮膚透過を表現することができない.

著者

藤堂 浩明 齋藤 美幸 鈴木 宏宙 井上 裕 高山 幸三 杉林 堅次

出版者

日本薬剤学会

雑誌

Journal of Pharmaceutical Science and Technology, Japan (ISSN:03727629)

巻号頁・発行日

vol.81, no.1, pp.111-120, 2021-01

---

It is important when developing effective and safe pharmaceutical products to select adequate active components and formulations as well as to design their containers and devices. Minoxidil was developed as a direct over-the-counter (OTC) drug in 1999 and has long been marketed only by one original company. Recently, many generic products have been marketed. However, the shape and type of the containers for these generic products differ from that of the original product, leading to a possibility that the amount of minoxidil applied by patients may differ. In the present study, the original and three typical generic products with 5% minoxidil external formulations were evaluated for their filling amounts, single application amounts, extent of distribution on application, ability to reach the scalp, and dripping properties. As a result, statistically significant differences were found in the filling amounts and ability to reach to the scalp between the products due to differences in the nozzle shape of the container. In addition, a large variation was observed in some of the generic products in terms of the drug liberation. These results indicate that it is important to suitably design and adequately evaluate the container for OTC products such as minoxidil formulations, which can exhibit toxicity from overuse, and that are easily purchased by consumers.

著者

杉林 堅次

出版者

The Japanese Society for the Study of Xenobiotics

雑誌

薬物動態 (ISSN:09161139)

巻号頁・発行日

vol.2, no.1, pp.71-80, 1987 (Released:2007-03-29)

参考文献数

37

被引用文献数

1

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Transdermal absorption of drugs, i.e. nitroglycerin and scoporamine, from marketed transdermal therapeutic systems (TTS) has been evaluated mainly according to T. Higuchi's theory. This theory, at first, was reviewed from the thermodynamic point of view. Much attention is paid to the enhanced transdermal absorption to expand the utility of TTS to many drugs and it becomes realistic by use of prodrugs as esters of viderabine, an antivirus drug, by the application of penetration-enhancers such as Azone, and/or by appearance of iontophoresis. Secondly, such enhancing systems were summarized theoretically and the differences between them and Higuchi's theory on the absorption rates were discussed. The route for transdermal absorption and its kinetic model might be modified in such enhancing systems, since the systems affect the skin barrier function. Reasonable absorption routes and skin model were discussed, thirdly. These three considerations could be useful for the development and evaluation of new TTS.

著者

藤堂 浩明 杉林 堅次

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.20, no.4, pp.452-459, 2005-07-10 (Released:2008-12-09)

参考文献数

31

被引用文献数

2 2

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薬物の皮膚適用は, 肝初回通過効果を回避でき, 長期連続投与が可能であるなどの理由から, 全身治療を目的とした薬物投与法として注目されている. しかしながら, 多くの薬物において皮膚透過性はきわめて低いという問題点があり, 実用化には吸収促進法の利用が不可欠である. 現在までに確立されている吸収促進法は, 大きく物理学的促進法と化学的方法の二つがあげられる. これらの技術の進歩により, 従来型低分子有機化合物のみならず, ペプチド, 蛋白質, 核酸医薬品などの高分子量物質に対しても経皮薬物送達システムの適用が可能になりつつある.

著者

井上 裕 森田 夕貴 斉藤 麗美 天野 留美子 沼尻 幸彦 金本 郁男 杉林 堅次

出版者

日本社会薬学会

雑誌

社会薬学 (ISSN:09110585)

巻号頁・発行日

vol.33, no.1, pp.30-35, 2014-06-10 (Released:2015-08-11)

参考文献数

17

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In 2012, the external prescription rate was 66.1% of the national average. A dispensing doctor is recognized by the escape clauses of Article 22 of the Medical Law, Article 21 of the Dentist Medical Law, and Article 19 of the Pharmacists Act. In this study, the medicine inventories of dispensing doctors and pharmacies were compared. The medicine supplies of 7 dispensing doctors and 11 pharmacies in Saitama were classified according to the medicinal effects. We also investigated the conditions in which high-risk medicines, poisons, or drugs were stored. The average number of medicines in the medicine inventory of a dispensing doctor was 262.3 (range : 99, 439), whereas the average number of medicines in the medicine inventory of a pharmacy was 1179.7 (minimum, 275 ; maximum, 1980). Further, among these medicines, there were an average of 41.0 high-risk medicines (minimum, 18 ; maximum, 76) in the inventory of a dispensing doctor and an average of 176.7 high-risk medicines (minimum, 5 ; maximum, 299) in the inventory of a pharmacy. In addition, poisons (average, 0.3) and narcotics (average, 0.9) were found to be stored by dispensing doctors. The study results revealed that pharmacies as well as dispensing doctors stored high-risk medicines. The dispensing doctor may be indirectly associated with critical medical accidents to need cross-check by pharmacist exceedingly high-risk medicine. Thus, for patients to use medicines appropriately and for them to be reassured of the safety of medicines, only professionals such as pharmacists, rather than doctors, should dispense medicines.