技術説明

天然成分(緑茶カテキンEGCg)でウイルスの不活化に新展開!

社会生活を一変させた新型コロナウイルスの発生。

ワクチンや治療薬の開発が進む中、また新たな変異株の発生でますます予防対策が求められる現在、天然成分で抗ウイルス効果が期待できるとして、緑茶カテキンEGCgは国内はもとより海外でもウイルスに対する不活化効果が検証され発表されている。

しかし、抗酸化作用の強いカテキンEGCgは酸化劣化が激しく保存安定性に欠けるため、各種製品開発においてその点が大きな欠点でとなっていた。

この安定性に欠ける欠点を克服し、水中で高濃度のまま安定化させた製剤が開発され、インフルエンザをはじめ新型コロナウイルスなど変異を繰り返す様々なウイルスに対して、ウイルスたんぱく質に結合することで細胞への侵入を防ぎ、不活化効果があることが検証実験で明らかになった。

 

●各種インフルエンザウイルスへの不活化効果については、九州保健福祉大学副学長・薬学部長・薬学科長の黒川昌彦教授を中地とした研究チームにて検証実験を実施。

●新型コロナウイルス及びSARSウイルスなど他のウイルスについての不活化効果は、国立大学大学院の研究チームにて検証実験を実施。

 

いずれのウイルスに対しても有効な不活化効果を確認!予防対策に新展開

保存安定性に優れた高濃度カテキンEGCgの水溶性製剤技術の開発は株式会社HPG(東京都中央区・代表取締役 金山正則)が成功し、水溶液中で高濃度のまま安定させる世界初の加工技術として、特許出願申請を開始した。

現在、この水溶液製剤は、10000ppmの高濃度で安定化されており、稀釈により容易に濃度調整ができる。

また、安定化を実現させているすべての構成成分が厚生労働省が許認可する食品添加成分であるため、体内に入っても副反応などの心配もなく、お子様から高齢者まで安心して口腔ケアなどによる服用も可能。

また、添加濃度にもよるが、不活化効果を示す濃度であれば、カテキンEGCg特有の渋みや苦み、変色等で既存製品本来の味わいや香り・色合いに与えるダメージはほとんどなく、様々な分野の製品に展開できる。

 

●高濃度カテキンEGCg製剤の可能性

現在、ウイルス感染予防対策商品が各種販売されているが、当該技術製品はウイルスは勿論、菌にも強い効果がある為、手荒れの心配なアルコール製剤の代替品としての活用や台所や食品取扱の分野、さらには人だけではなく鳥インフルエンザや豚インフルエンザなどの予防対策としての活用など、幅広く展開できるものと考えられる。

 

黒川研究チームの検証データ概要

緑茶にはカテキン類が多く含まれており、カテキン類の一種であるepigallocatechin gallate(EGCg)はウイルスの増殖過程において、細胞への吸着過程を阻害し、抗ウイルス効果を示すことが知られている。そこで、EGCgの抗インフルエンザウイルス効果とその作用機序を検証した。In vitroにおいて4種のA型、B型インフルエンザウイルス株に対してMDCK(Madin-Darby canine kidney)細胞を用いたプラーク減少法を行うことで、EGCgの抗インフルエンザウイルス効果を検討した。その結果、4種のインフルエンザウイルスに対して、ウイルス粒子の細胞への吸着あるいは侵入過程をEGCgが阻害することを確認した。

 

プロフィール

黒川昌彦(くろかわ まさひこ)

九州保健福祉大学副学長・薬学部長・薬学科長

大学院医療薬学研究科 生化学講座 教授

 

研究内容:

これまで伝統医薬物やサプリメント等から新規抗ウイルス薬の開発やウイルス感染病態および宿主感染免疫防御機序の解析に関する研究とともに、遺伝子治療への応用に向けたウイルスベクターの基礎研究を進展してきた。さらに、これらの研究に加えQOLの維持・増進に貢献できる研究として、ウイルス感染動物を用いて、胎児期・新生児期環境化学物質暴露やメタボリックシンドロームによる感染症増悪化現象の立証とその解析研究を進めている。近年では、生化学、分子・細胞生物学、遺伝子工学、細菌学、ウイルス学、免疫学などの知識と実験手技を駆使して、感染症や生活習慣病の病態メカニズムの解明と新規予防・治療法の開発、環境化学物質の宿主免疫機構に対するリスク評価などの研究を行っています。これらの研究は、学内外の研究者(大学、研究所、企業)との共同研究体制を構築しており、研究成果を効率的に社会に還元することで、国民のQOL維持・増進に寄与することを目的としています。 

国立大学大学院チームの検証データ概要

 

 「感染症パニック」という言葉に代表されるように、様々な感染症が生命と社会・経済に大きな打撃を与え続けている。そのため、現代社会において、感染症に対抗するための手段の確立は重要な課題であり、近年、様々な素材の抗ウイルス効果が注目をされ、EGCgをはじめとする植物由来成分も盛んに研究がおこなわれている。本研究では、現在、世界中で問題となっているSARS-CoV-2に近縁で、ヒトに風邪症状を引き起こすhuman coronavirusHCoV-229Eに対するEGCgの抗ウイルス効果を50% Tissue Culture Infectious DoseTCID50)を指標に測定した。その結果、直接不活化効果と吸着阻害効果との相乗効果によって、10ppmという低濃度のEGCgによって、一定の感染阻害効果が確認された。

A new development in virus inactivation with a natural ingredient - green tea catechin (EGCg)

Patent application 〈Processing technology to stabilize green tea catechins (EGCg) at high concentrations in aqueous solutions〉 started in August 2021

The outbreak of the novel coronavirus (COVID-19) has completely changed social life.

While the development of vaccines and therapeutic agents is progressing, the outbreak of new mutant virus strains is requiring increasingly strong preventive measures. In such a situation, green tea catechin (Epigallocatechin gallate, EGCg), as a natural ingredient with potential antiviral effects, has been verified and published for its inactivating effects against viruses in Japan and overseas.

However, catechins and EGCg, which have a strong antioxidant effect, are highly susceptible to oxidative deterioration and lack storage stability, which is a major drawback in the development of various products.

To overcome this lack of stability, a formulation that is stabilized at a high concentration in water has been developed, and verification experiments have shown that it is effective in inactivating various viruses that repeatedly mutate, such as influenza and novel coronaviruses, by binding to viral proteins and preventing them from entering cells. It has also been shown in verification experiments that it has an inactivating effect by binding to viral proteins.

 

- A research team led by Professor Masahiko Kurokawa, Vice President, Dean of the Faculty of Pharmaceutical Sciences, Kyushu University of Health and Welfare, conducted verification experiments on the inactivation effects of various influenza viruses.

- The inactivation of other viruses, such as the novel coronavirus and SARS virus, was verified by a research team led by the National University.

 

Effective inactivation of all viruses confirmed

New development in preventive measures

HPG Co., Ltd. (Chuo-ku, Tokyo; Masanori Kanayama, President) has successfully developed a water-soluble formulation technology of highly concentrated catechin EGCg with excellent storage stability and has started to apply for a patent as the world's first processing technology to stabilize the product at a high concentration in aqueous solution.

Currently, this aqueous solution formulation is stabilized at a high concentration of 10,000 ppm, and the concentration can be easily adjusted by dilution.

In addition, since all the components that stabilize the product are food additives approved by the Ministry of Health, Labor and Welfare, there is no need to worry about adverse reactions if they enter the body, and children and the elderly can take the product through oral care without anxiety.

Furthermore, depending on the concentration added, if the concentration shows an inactivation effect, there is almost no damage to the original taste, aroma, or color of existing products due to astringency, bitterness, or discoloration peculiar to catechin EGCg, and the product can be used in a variety of fields.

 

- Potential of highly concentrated catechin, EGCg pharmaceutical preparations

 

At present, there are a variety of products on the market to prevent viral infections, but since this technological product is highly effective against bacteria as well as viruses, it can be used as a substitute for alcohol products that can cause rough hands, in the kitchen and food handling fields, and as a preventive measure against not only human but also bird flu and swine flu.

 

Summary of verification data from the Kurokawa Research Team

 

Green tea is rich in catechins, and epigallocatechin gallate (EGCg), one of the catechins, is known to have an antiviral effect by inhibiting the adsorption process of the virus to cells during the replication process. In this study, we examined the anti-influenza effect of EGCg and its mechanism of action by performing plaque reduction assay using MDCK (Madin-Darby canine kidney) cells against four kinds of influenza A and B virus strains in vitro. They investigated the anti-influenza effect of EGCg by performing plaque reduction assay using MDCK (Madin-Darby canine kidney) cells. As a result, they confirmed that EGCg inhibited the adsorption or entry process of virus particles into the cells for four kinds of influenza virus strains.

 

Profile of Masahiko Kurokawa:

Vice President, Dean, Director of Pharmaceutical Sciences, Kyushu University of Health and Welfare

Professor, Department of Biochemistry, Graduate School of Medical and

Pharmaceutical Sciences

 

Research Description:

We have been conducting research on the development of new antiviral drugs from traditional medicines and supplements, the pathogenesis of viral infections and the analysis of host immune defense mechanisms, as well as basic research on viral vectors for gene therapy. In addition to these studies, we have been conducting research to prove and analyze the exacerbation of infectious diseases caused by exposure to environmental chemicals in the fetal and neonatal period and metabolic syndrome using virus-infected animals as research that can contribute to the maintenance and improvement of QOL. In recent years, we have been conducting research on elucidation of pathological mechanisms of infectious diseases and lifestyle-related diseases, development of novel preventive and therapeutic methods, and risk assessment of environmental chemicals on host immune mechanisms by using knowledge and experimental techniques in biochemistry, molecular and cellular biology, genetic engineering, bacteriology, virology, and immunology. For these research, we have established a collaborative research system with internal and external researchers (universities, research institutes, and companies), with the aim of contributing to the maintenance and improvement of the quality of life of the people by efficiently returning the research results to society.

 

Summary of verification data of the National University Research Team

 

As typified by the term " Infectious disease panic," various infectious diseases continue to inflict serious damage on life, society, and the economy. In recent years, attention has been focused on the antiviral effects of various materials, and plant-derived ingredients such as EGCg have been actively studied. In this study, the antiviral effect of EGCg against human coronavirus (HCoV)-229E, which is closely related to SARS-CoV-2 and causes cold symptoms in humans, was measured using 50% Tissue Culture Infectious Dose (TCID50) was used as an indicator. The results showed that EGCg at a low concentration of 10 ppm had a certain inhibitory effect on the infection due to the synergistic effects of direct inactivation and adsorption inhibition.