著者

山本 恵司

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.52, no.5, pp.373-373, 2016

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昭和の時代だった頃に見た映画「Back to the future part 2」で,よれよれの白衣のドクとマクフライ少年を乗せたデロリアン号が大嵐の中向かった未来は,半年ほど前の過去となってしまった2015年10月21日でした.彼らは30年先の未来世界に到着してあらゆることにビックリ,特にinnovationの進展で人々の生活は様変わりしていました.医薬品製剤の世界も30年前と比べてみると貼付剤,口腔内崩壊(OD)錠はライフサイクルマネージメント(LCM)の中に定着し,経肺吸収製剤,コクリスタル製剤,イオントフォレーシスや薬剤溶出型ステントの出現までドク,マクフライが知ったとしたらその驚愕ぶりが想像できます.これらはアイデアの創出から,new product,new market,new material supplier等の有機的結合・発展,つまりinnovationの結果と言えます.我が国では安倍首相が次々と成長戦略の一環として「健康・医療戦略」を発表しており,先日のスピーチでは「医療関係産業の活性化は安倍政権の成長戦略の要であり,特にバイオ医薬品はその柱として健康長寿社会実現の鍵と言えます」と述べています.一貫した医療分野の研究開発の推進とその環境整備を総合的に行うことを目指す日本医療研究開発機構(AMED)の昨年4月の発足はその象徴と言えます.しかし現実には明るい未来が待っているとは限りません.昨年9月に出された医薬品産業強化総合戦略には「我が国として産業構造やinnovationを生み出す力が現状のままでは,日本の創薬産業は生き残りが困難な状況となる.」とあります.事実,先日発表された世界のグローバルイノベーター100社中に日本企業が40社を占めたとの発表の中で,いわゆる製薬会社がその中に1社も入っていない事実からも読み取れます.一方,USFDAは一貫してinnovationに強い意識を持っており,Statement of FDA missionの中にも「各種innovationを加速することでpublic healthを促進する」と記載されています.この流れは医薬品の生産についても確実に及んできており,マインドセットシフト(頭の構造の大転換)を要するinnovationが求められています.繁用される固形製剤の生産を例とすれば,従来からその生産方法は単位操作の積み重ねで構成されており,操作ごとに品質管理検査を行い最終的に優れた品質の製品を提供してきました.しかしinnovationの進展に伴い,これまでのquality by testingから現代ではquality by design(QbD)が主流となり,さらに昔のサンプル検査に代わってprocess analytical technology(PAT)などの技術によりreal time release testing(RTRT)が実現しています.その基礎となるのがrisk managementです.USFDAの医薬品評価研究センター(CDER)長のJanet Woodcock氏は昨春,議会で製剤プロセスを従来のバッチ式から連続プロセスにスイッチしていくことがinnovationであり,将来のあるべき姿であると発言しています.原料の医薬品,医薬品添加剤等を装置に投入して全てをコントロール,テストしながら連続プロセスにより高品質な製剤が生産されるinnovationは実は既に実現しつつあります.我らが得意とする"改善・改良"でガラパゴスへの道を再度たどること無く,世界の動きをリードするためのマインドセットシフトは待ったなしと感じられます.

著者

荒井 研祐 三堀 将寛

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.138, no.4, pp.525-527, 2018 (Released:2018-04-01)

参考文献数

2

被引用文献数

1

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Within school classrooms, Active Learning has been receiving unprecedented attention. Indeed, Active Learning's popularity does not stop in the classroom. As more and more people argue that the Japanese government needs to renew guidelines for education, Active Learning has surfaced as a method capable of providing the necessary knowledge and training for people in all areas of society, helping them reach their full potential. It has become accepted that Active Learning is more effective over the passive listening of lectures, where there is little to no interaction. Active Learning emphasizes that learners explain their thoughts, ask questions, and express their opinions, resulting in a better retention rate of the subject at hand. In this review, I introduce an Active Learning support tool developed at Digital Knowledge, “Clica”. This tool is currently being used at many educational institutions. I will also introduce an online questionnaire that Digital Knowledge provided at the 10th Annual Meeting of the Japanese Society for Pharmaceutical Palliative Care and Sciences.

著者

杉原 数美

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.138, no.3, pp.277-280, 2018 (Released:2018-03-01)

参考文献数

10

被引用文献数

6

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In recent years, pharmaceuticals and personal care products (PPCPs) have emerged as significant pollutants of aquatic environments and have been detected at levels in the range of ng/L to μg/L. The source of PPCPs is humans and livestock that have been administered pharmaceuticals and subsequently excreted them via urine and feces. Unlike agricultural chemicals, the environmental dynamics of PPCPs is not examined and they would undergo structural transformation by environmental factors, e.g., sunlight, microorganisms and treatments in sewage treatment plants (STPs). Processing at STPs can remove various PPCPs; however, they are not removed completely and some persist in the effluents. In this study, we examined the degradation of 9 pharmaceuticals (acetaminophen, amiodarone, dapsone, dexamethasone, indomethacin, raloxifene, phenytoin, naproxen, and sulindac) by sunlight or UV, and investigated the ecotoxicological variation of degradation products. Sunlight (UVA and UVB) degraded most pharmaceuticals, except acetaminophen and phenytoin. Similar results were obtained with UVB and UVA. All the pharmaceuticals were photodegraded by UVC, which is used for sterilization in STPs. Ecotoxicity assay using the luminescent bacteria test (ISO11348) indicated that UVC irradiation increased the toxicity of acetaminophen and phenytoin significantly. The photodegraded product of acetaminophen was identified as 1-(2-amino-5-hydroxyphenyl)ethanone and that of phenytoin as benzophenone, and the authentic compounds showed high toxicity. Photodegraded products of PPCPs are a concern in ecotoxicology.

著者

秋山 卓美

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.48, no.8, pp.792-792, 2012

参考文献数

5

著者

加藤 隆弘 兵藤 文紀 大和 真由実 内海 英雄 神庭 重信

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.135, no.5, pp.739-743, 2015 (Released:2015-05-01)

参考文献数

36

被引用文献数

2 5

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Altered antioxidant status has been implicated in schizophrenia. Microglia are major sources of free radicals such as superoxide in the brain, and play crucial roles in various brain diseases. Recent postmortem and imaging studies have indicated microglial activation in the brain of schizophrenia patients. Animal models that express some phenotypes of schizophrenia have revealed the underlying microglial pathology. In addition, minocycline, an antibiotic and the best known inhibitor of microglial activation, has therapeutic efficacy in schizophrenia. We have recently revealed that various antipsychotics directly affect microglia via proinflammatory reactions such as oxidative stress, by in vitro studies using rodent microglial cells. Based on these findings, we have suggested that microglia are crucial players in the brain in schizophrenia, and modulating microglia may be a novel therapeutic target. In this review paper, we introduce our hypothesis based on the above evidence. The technique of in vivo molecular redox imaging is expected to be a powerful tool to clarify this hypothesis.

著者

笹岡 沙也加 畠平 春奈 長谷川 栞 元岡 佑美 福田 昌穂 長沼 美紗 梅津 亮冴 中尾 智史 島内 あかり 上田 夏実 平出 耕石 井口 和弘 中村 光浩

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.138, no.1, pp.123-134, 2018 (Released:2018-01-01)

参考文献数

22

被引用文献数

8

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OTC combination cold remedies are widely used in Japan. In the present study, we aimed to evaluate the adverse event profiles of OTC combination cold remedy based on the components using the Japanese Adverse Drug Event Report (JADER) database. The JADER database contained 430587 reports between April 2004 and November 2016. 1084 adverse events associated with the use of OTC combination cold remedy were reported. Reporting odds ratio (ROR) was used to detect safety signals. The ROR values for “skin and subcutaneous tissue disorders”, “hepatobiliary disorders”, and “immune system disorders” stratified by system organ class of the Medical Dictionary for Regulatory Activities (MedDRA) were 9.82 (8.71-11.06), 2.63 (2.25-3.07), and 3.13 (2.63-3.74), respectively. OTC combination cold remedy containing acetaminophen exhibited a significantly higher reporting ratio for “hepatobiliary disorders” than OTC combination cold remedy without acetaminophen. We demonstrated the potential risk of OTC combination cold remedy in a real-life setting. Our results suggested that the monitoring of individuals using OTC combination cold remedy is important.

著者

見坂 武彦 片岡 憲司 藤光 隆司 谷 佳津治

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.138, no.1, pp.117-122, 2018 (Released:2018-01-01)

参考文献数

21

被引用文献数

5

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Migratory birds are considered as vectors of infectious diseases, owing to their potential for transmitting pathogens over large distances. The populations of barn swallow (Hirundo rustica) migrate from Southeast Asia to the Japanese mainland during spring and migrate back to Southeast Asia during autumn. This migratory population is estimated to comprise approximately hundreds to thousands of individuals per year. However, to date, not much is known about the gastrointestinal microbiota of the barn swallow. In this study, we characterized the fecal bacterial community in barn swallow. Using 16S rRNA gene metagenomic sequencing analysis, we examined the presence and composition of potentially pathogenic bacteria in the fecal samples, which were collected during spring season from Osaka. The number (±S.D.) of total bacteria was approximately 2.1(±3.4)×108 per gram of feces. In most samples, the bacterial community composition was dominated by families, such as Enterobacteriaceae, Pseudomonadaceae, Mycoplasmataceae, Enterococcaceae, Streptococcaceae, and Alcaligenaceae. However, no relationship was found between the bacterial community composition and geographical area in the fecal samples. Potentially pathogenic bacteria were detected at the rate of >0.1%, which included Pseudomonas spp., Escherichia/Shigella spp., Enterobacter spp., Yersinia spp., Mycoplasma spp., Enterococcus spp., Achromobacter spp., and Serratia spp. Our results suggested that barn swallow is instrumental in the transmission of these genera over large distances.

著者

武富 芳隆 村上 誠

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.131, no.1, pp.73-84, 2011 (Released:2011-01-01)

参考文献数

71

被引用文献数

2 3

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Tissue-resident mast cells are derived from circulating committed progenitors, which are originated from pluripotential hematopoietic stem cells in bone marrow. These progenitors migrate into extravascular tissues, where they undergo differentiation and maturation into tissue-specific mature phenotypes. When activated by IgE/antigen, stem cell factor, neuropeptides, or other stimuli, mature mast cells release three classes of biologically active products, including pre-formed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo synthesized lipid mediators. Therefore, these cells have been implicated as major effector cells in acute and chronic inflammatory diseases. In recent years, it has become clear that lipid mediators including arachidonic acid metabolites (prostaglandins and leukotrienes) and lysophospholipid-derived products play crucial roles in mast cell-associated pathology. In this article, we will provide an overview of the roles of various lipid mediators in allergic diseases fueled by studies of their biosynthetic enzymes or receptors. In the latter part, we will make a particular focus on phospholipase A2 enzymes, which are placed at the bottleneck (rate-limiting) step of the lipid mediator-biosynthetic pathways.

著者

堀 誠治

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.131, no.10, pp.1423-1428, 2011 (Released:2011-10-01)

参考文献数

13

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Many antibiotics have been developed and used for the treatment of infectious diseases. Although they have been known to have various adverse effects, most of the mechanisms remain still unknown. New quinolones are well known to induce convulsions and their convulsant activity enhanced by concurrent administration of anti-inflammatory drugs. Each new quinolone has an individual convulsant activity with individual drug-interaction with anti-inflammatory drugs. And enoxacin, lomefloxacin and gatifloxacin have been reported to decrease blood glucose levels in a dose-depend- ent manner, but ciprofloxacin and levofloxacin had no effect on the levels. It should be important to know the safety profile of antimicrobial agents before doctors administer these agents to the patients with infectious diseases.

著者

舩田 正彦

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.136, no.1, pp.65-72, 2016 (Released:2016-01-01)

参考文献数

17

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Cases of people experiencing disturbed consciousness or dyspnea, causing traffic accidents, or requiring ambulance transport to hospital due to abuse of law-evading chemical substances have become a serious social problem in Japan. Most law-evading herbal products are marketed as incense or herbs and consist of finely chopped, dry vegetative matter mixed with chemical substances (drugs). Analysis of the chemical substances in these herbal products has demonstrated that they contain synthetic cannabinoids. Because there are many cannabinoid compounds, even if a particular drug is regulated, similar compounds that differ only slightly in structure may be added in their place. Therefore a cat-and-mouse game exists between regulations on chemical substances and their propagation. This paper summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids, as a group of chemical substances contained in these products. Furthermore, comprehensive designations of synthetic cannabinoids have been introduced as a new method of regulation that emphasizes the similarity of chemical structures; this paper also outlines the comprehensive designations. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids using animals (behavioral analysis in vivo) and cell cultures (cytotoxicity analysis in vitro). With our drug-screening system, we were able rapidly to evaluate and quantify psychic-dependence liabilities and cytotoxicity of synthetic cannabinoids contained in law-evading herbal products. These scientific data using our screening system contributed to the establishment of legislation for comprehensive designations of synthetic cannabinoids.

著者

石井 敬 戸田 雄大 五十嵐 信智 落合 和 杉山 清

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.301-310, 2012 (Released:2012-03-01)

参考文献数

36

被引用文献数

2 14

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Living organisms eliminate foreign low-antigenic substances, such as drugs and environmental pollutants, by detoxification mediated by metabolizing cytochrome P450 (CYP). We have examined the possible regulation of CYP expression by enteric bacteria. Cyp mRNA expression levels, Cyp3a protein expression level, and the activity of Cyp3a in hepatic microsomal fractions were compared in germ-free (GF) and specific pathogen-free (SPF) mice. We evaluated hepatic Cyp3a11 mRNA expression levels and Cyp3a metabolic activity in GF and SPF mice after five days of antibiotic administration. The fecal levels of lithocholic acid (LCA)-producing bacteria and hepatic taurolithocholic acid (TLCA) were also measured. Cyp mRNA expression levels, Cyp3a protein expression level, and the activity of Cyp3a in SPF mice were higher than those in GF mice, indicating that enteric bacteria increases hepatic Cyp3a expression. The effects of enteric bacteria-reducing antibiotics on Cyp3a expression were examined. We observed that decreasing enteric bacteria with antibiotics in SPF mice caused a significant decrease in the hepatic Cyp3a11 mRNA expression, TLCA, and fecal LCA-producing bacteria compared to the group that did not receive antibiotics. No change in Cyp3a11 expression was observed in GF mice that were treated with antibiotics. Administration of LCA to GF mice showed an increase in Cyp3a11 expression similar to that of SPF mice. The enzymes of the enteric bacteria are believed to metabolize and detoxify drugs by either reduction or hydrolysis. The results of this study indicate that changes in enteric bacteria may alter the expression and activity of hepatic drug metabolizing enzymes and pharmacokinetics. Therefore, enteric bacteria should be closely monitored to ensure the safe use of drugs.

著者

大友 千絵子

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.52, no.9, pp.863-865, 2016

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全米の医療大麻人口はおよそ260万人と推計されている。50州から構成される連邦国家であるアメリカ合衆国で、医療大麻(医療マリファナ)が合法とされている州はそのうち24州と連邦政府直轄地区であるワシントンD.C地区である。その先陣を切り、最も早く医療大麻が合法化されたのがカリフォルニア州(加州)だ。規制薬物法で最も規制の厳しいスケジュールIに分類されている医療大麻の現状を紹介する。

著者

宝田 剛志

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.133, no.7, pp.799-802, 2013 (Released:2013-07-01)

参考文献数

13

被引用文献数

1

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In this review, we would outline the possible signaling system for three types of amino acids including glutamate (Glu), γ-aminobutyric acid (GABA) and D-serine (D-Ser) to play a role as an extracellular signal mediator in mechanisms underlying maintenance of the cellular homeostasis in skeletal tissues. Although Glu and GABA has been thought to be an excitatory/inhibitory amino acid neurotransmitter in the mammalian central nervous system, our molecular biological analyses give rise to a novel function for Glu and GABA as an autocrine and/or paracrine factor in three types of distinct cell types including osteoblasts, osteoclasts and chondrocytes in bone tissues. Moreover, D-Ser plays a pivotal role in osteoclastogenesis through a mechanism related to the incorporation of serine enantiomers in osteoclasts after the synthesis and subsequent release from adjacent osteoblasts. Accordingly, bone formation and maintenance seems to be under control by amino acid signaling in skeletal tissues as seen with neurotransmission in the brain.

著者

岸本 桂子 竹内 智重 福島 紀子

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

pp.17-00114, (Released:2017-09-05)

参考文献数

18

被引用文献数

4

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In Japan, a pharmacy or drug store license is required for selling pharmaceutical products. However, civilians without a pharmacy or drug store license are displaying pharmaceutical products for sale on a flea market application, which is illegal dealing. This study discussed the modality for implementing countermeasures for the illicit selling of pharmaceutical products. We extracted pharmaceutical products displayed for sale on three flea market applications (Mercari, Rakuma, Fril) on one day. One hundred and eighty-one pharmaceutical products were displayed (49 on Mercari, 86 on Rakuma, and 46 on Fril). There were 6.1% (11/181) domestically prescribed drugs, 69.1% (125/181) domestic over-the-counter (OTC) drugs, 23.8% (43/181) foreign-made prescribed drugs, and 1.1% (2/181) foreign-made OTC drugs. The seller could display the product for sale without confirming whether it is prohibited. We alerted the service providers of this illicit selling at flea markets at three different instances. The pharmaceutical product displays were deleted by the service providers at a rate of 55.1% (27/49) for Mercari and 51.2% (44/86) for Rakuma. The average number of drugs that were displayed for sale by each seller was 1.4 and the average number of total products that were displayed for sale by each seller was 100. The seller could have unintentionally displayed the pharmaceutical products for sale, without the knowledge that it is illegal. The service providers of flea market applications should create mechanisms to alert the sellers that displaying pharmaceutical products for sale is an illicit act and regulate these violations.

著者

小林 長夫

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.52, no.6, pp.507-509, 2016 (Released:2016-06-01)

参考文献数

11

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動植物中には多くの機能中心として金属ポルフィリンが存在し、又類縁体である人工のフタロシアニンは多方面で応用され“機能性色素の王様”と呼ばれるにふさわしい化合物である。機能にはしばしば色が関係しており、色は更に吸収スペクトルと関係している。ポルフィリン類の幾何構造と分光学的データからそれらの相関を理論的に解釈し、未知ポルフィリン色素をデザインする際の指針とする事を目指した。

著者

鈴木 康男 宇田 裕 奥井 誠一

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.85, no.1, pp.72-76, 1965-01-25 (Released:2010-02-19)

参考文献数

15

被引用文献数

3

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Lipid component, extracted from dried cells of Torulopsis utilis was examined by means of chromatography. It was found that lipid content in dried cells was 3% and this lipid consisted mainly of phospholipid (84%), which was largely composed of lecithin, phosphatidylethanolamine and lysolecithin, however neutral lipids are formed mainly of free fatty acid, triglyceride and sterol.Analysis of the fatty acid composition of the isolated lipid fractions by gas-liquid chromatography showed that acid neutral lipids and phospholipids contained mainly linoleic acid, oleic acid and palmitic acid, while free fatty acid fraction had a very low content of linoleic acid. The lysolecithin fraction contained considerably larger amounts of linoleic acid than the other lipid fractions.

著者

井上 圭三

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.48, no.8, pp.772-774, 2012-08-01 (Released:2016-12-16)

著者

大嶋 直浩

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.50, no.11, pp.1143-1143, 2014 (Released:2016-09-30)

参考文献数

2

被引用文献数

14

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伝統薬は長い使用経験の中でその有効性が確認されたものであり,より効果的にするために複数の生薬を組み合わせていることが多い.そのため,伝統薬の有効性を理解するためには,生薬の相乗作用を明らかにすることが重要である.しかし,これまでに様々な生薬から有効成分が見いだされてきたものの,複数の生薬の相乗作用を成分レベルで明らかにした研究報告は少なく,生薬を組み合わせる意義が科学的に理解されているとは言い難いのが現状である.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Wang F. et al., PLOS ONE, 9, e87221 (2014).2) Chou T. C., Talalay P., Trends Pharmacol Sci., 4, 450-454 (1983).

著者

設楽 研也

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.1, pp.3-9, 2009 (Released:2009-01-01)

参考文献数

19

被引用文献数

6 11

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Antibody-dependent cellular cytotoxicity (ADCC), a lytic attack on antibody-targeted cells, is triggered upon binding of lymphocyte receptors (FcγRs) to the antibody constant region. ADCC is considered to be a major therapeutic function of antibodies. ADCC requires the presence of oligosaccharides in the Fc region and is sensitive to change in the oligosaccharide structure. We have demonstrated that fucose is the most critical IgG1 oligosaccharide component, and the removal of fucose from IgG1 oligosaccharides results in a very significant enhancement of ADCC and anti-tumor activity in vivo. Many therapeutic antibodies approved or clinical development are produced using Chinese hamster ovary (CHO) cells that express high level of α1,6-fucosyltransferase and consequently produce highly fucosylated antibodies. We have established the fucosyltransferase knockout CHO cells which could stably produce non-fucosylated antibodies, designated as Potelligent antibodies. Potelligent antibodies show potent ADCC upon target cells through the effective and antigen-specific activation of NK cells due to augmented binding to FcγRIIIa. Moreover, Potelligent antibodies can evade the inhibitory effect of plasma IgG on ADCC through its high FcγRIIIa binding. Thus, the application of Potelligent antibodies is expected to be a promising approach as next-generation therapeutic antibodies with improved efficacy, even when administered at low doses in humans in vivo.

著者

早河 輝幸

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.53, no.5, pp.462-463, 2017 (Released:2017-05-01)

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あらゆる学問は、先人の研究成果を礎としその上に新たな発見がなされることの繰り返しで進展する。私はその礎を書籍出版という形で築き、学問の発展に貢献すべく、専門出版社にて編集に携わっている。書籍の企画立案や校閲においては、薬学分野で培ったジェネラリストとしての観点が有用であると実感している。