JP2019151592A - Antiviral agent - Google Patents
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- JP2019151592A JP2019151592A JP2018038346A JP2018038346A JP2019151592A JP 2019151592 A JP2019151592 A JP 2019151592A JP 2018038346 A JP2018038346 A JP 2018038346A JP 2018038346 A JP2018038346 A JP 2018038346A JP 2019151592 A JP2019151592 A JP 2019151592A
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- silica
- mesoporous silica
- platinum
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- 239000003443 antiviral agent Substances 0.000 title claims abstract description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 251
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 123
- 239000011148 porous material Substances 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 18
- 238000002441 X-ray diffraction Methods 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 8
- 238000009826 distribution Methods 0.000 claims abstract description 5
- 238000002429 nitrogen sorption measurement Methods 0.000 claims abstract description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 88
- 229910052697 platinum Inorganic materials 0.000 claims description 40
- 239000000843 powder Substances 0.000 claims description 12
- 239000008188 pellet Substances 0.000 claims description 4
- 230000000840 anti-viral effect Effects 0.000 description 19
- 239000002994 raw material Substances 0.000 description 19
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- 210000004027 cell Anatomy 0.000 description 13
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- 241000700605 Viruses Species 0.000 description 9
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- 206010022000 influenza Diseases 0.000 description 5
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- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 description 2
- 229910052911 sodium silicate Inorganic materials 0.000 description 2
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- NOEGNKMFWQHSLB-UHFFFAOYSA-N 5-hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 description 1
- 238000004438 BET method Methods 0.000 description 1
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- 229910002651 NO3 Inorganic materials 0.000 description 1
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- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical group [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
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- 229910045601 alloy Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 238000011951 anti-virus test Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- IXSUHTFXKKBBJP-UHFFFAOYSA-L azanide;platinum(2+);dinitrite Chemical compound [NH2-].[NH2-].[Pt+2].[O-]N=O.[O-]N=O IXSUHTFXKKBBJP-UHFFFAOYSA-L 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- XKXHCNPAFAXVRZ-UHFFFAOYSA-N benzylazanium;chloride Chemical compound [Cl-].[NH3+]CC1=CC=CC=C1 XKXHCNPAFAXVRZ-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
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- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- RJGBSYZFOCAGQY-UHFFFAOYSA-N hydroxymethylfurfural Natural products COC1=CC=C(C=O)O1 RJGBSYZFOCAGQY-UHFFFAOYSA-N 0.000 description 1
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- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
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- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- CLSUSRZJUQMOHH-UHFFFAOYSA-L platinum dichloride Chemical compound Cl[Pt]Cl CLSUSRZJUQMOHH-UHFFFAOYSA-L 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- NFOHLBHARAZXFQ-UHFFFAOYSA-L platinum(2+);dihydroxide Chemical compound O[Pt]O NFOHLBHARAZXFQ-UHFFFAOYSA-L 0.000 description 1
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 1
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- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本発明は、新規な抗ウイルス剤に関する。 The present invention relates to a novel antiviral agent.
メソポーラスシリカ（Ｍｅｓｏ Ｐｏｒｏｕｓ Ｓｉｌｉｃａ）は、二酸化ケイ素（シリカ）を材質として、均一で規則的な細孔（メソ孔）を持つ物質のことである。メソポーラスシリカの粉末は、触媒や吸着材料として、薄膜は光学デバイスやガスセンサー、分離膜などとして研究が行われている。製造例の一つに、界面活性剤のミセルを鋳型として合成する方法があり、ハニカム（蜂の巣）状の均一なメソポアを有するシリカ多孔体（メソポーラスシリカ）が製造されている（特許文献１、特許文献２）。
メソポーラスシリカは、大きな比表面積（最大１３００ｍ２／ｇ）と細孔容積（最大１．５ｃｍ３／ｇ）を有していることが知られている。この細孔に白金を担持させた白金担持メソポーラスシリカは、水素中の一酸化炭素除去能を有する触媒や、エチレン分解触媒として利用することが提案されている（特許文献１、特許文献３、非特許文献１）。また、金属粒子は、ナノ細孔内で金属還元生成を行なうことで高度にメソポーラスシリカ内に均一に分散した金属ナノ粒子担持メソポーラスシリカが得られる。さらに、この技術の応用として、白金担持メソポーラスシリカを冷蔵庫内の野菜や果物の鮮度保持剤として使用する技術が開発されている（非特許文献２）。
Mesoporous silica is a substance having uniform and regular pores (mesopores) made of silicon dioxide (silica). Research has been conducted on mesoporous silica powders as catalysts and adsorbing materials, and thin films as optical devices, gas sensors, separation membranes, and the like. One of the production examples is a method of synthesizing a surfactant micelle as a template, and a porous silica body (mesoporous silica) having a honeycomb (honeycomb) -like uniform mesopore is produced (Patent Document 1, Patent). Reference 2).
Mesoporous silica is known to have a large specific surface area (maximum 1300 m 2 / g) and pore volume (maximum 1.5 cm 3 / g). It has been proposed that platinum-supported mesoporous silica in which platinum is supported in the pores is used as a catalyst capable of removing carbon monoxide in hydrogen or as an ethylene decomposition catalyst (Patent Document 1, Patent Document 3, Patent Document 1). In addition, the metal particles are reduced to metal in the nanopores to obtain metal nanoparticle-supported mesoporous silica that is highly uniformly dispersed in the mesoporous silica. Furthermore, as an application of this technique, a technique has been developed in which platinum-supported mesoporous silica is used as a freshness-preserving agent for vegetables and fruits in a refrigerator (Non-patent Document 2).
また、メソポーラスシリカに潮解性物質として塩化カルシウムなどを担持させ、さらに抗菌性物質を同時に担持させ、これを除湿又は加湿機能を有する再生可能な吸湿剤として利用する提案がなされている（特許文献４）。 In addition, proposals have been made that mesoporous silica is loaded with calcium chloride or the like as a deliquescent substance and further an antibacterial substance is loaded at the same time, and this is used as a renewable moisture absorbent having a dehumidifying or humidifying function (Patent Document 4). ).
白金担持メソポーラスシリカや金属粒子担持メソポーラスシリカは、その他ヒドロキシメチルフルフラールの還元（特許文献５）、アセトニトリルの二量体化反応（特許文献６）、α−ヒドロキシカルボン酸の製造（特許文献７）、芳香族水酸化物の製造（特許文献８）など各種の化学反応の触媒として利用されている。 Platinum-supported mesoporous silica and metal particle-supported mesoporous silica include other reductions of hydroxymethylfurfural (Patent Document 5), dimerization reaction of acetonitrile (Patent Document 6), production of α-hydroxycarboxylic acid (Patent Document 7), It is used as a catalyst for various chemical reactions such as the production of aromatic hydroxide (Patent Document 8).
またメソポーラスシリカのような多孔質構造を有さない１〜６０ｎｍのシリカ含有微粒子を分散させたコロイダルシリカに抗インフルエンザウイルス作用があることが知られている（特許文献９参照）。このシリカ含有粒子としては、具体的にはアモルファスシリカや結晶性シリカが例示されている。 Further, it is known that colloidal silica in which 1 to 60 nm silica-containing fine particles having no porous structure such as mesoporous silica are dispersed has an anti-influenza virus action (see Patent Document 9). Specific examples of the silica-containing particles include amorphous silica and crystalline silica.
本発明者らは、白金担持メソポーラスシリカや金属粒子担持メソポーラスシリカの利用について研究を行っている。この研究過程で、メソポーラスシリカ及び／又は白金担持メソポーラスシリカに強い抗ウイルス作用を有することを見いだした。そしてメソポーラスシリカ及び／又は白金担持メソポーラスシリカの新たな用途として、抗ウイルス剤として利用することを着想し、本発明をなした。
すなわち、本発明は、メソポーラスシリカ及び／又は白金担持メソポーラスシリカを有効成分として含有する抗ウイルス剤を提供することを課題とする。
The present inventors have been studying the use of platinum-supported mesoporous silica and metal particle-supported mesoporous silica. In the course of this research, it was found that mesoporous silica and / or platinum-supported mesoporous silica has a strong antiviral effect. And as a new use of mesoporous silica and / or platinum-supported mesoporous silica, it was conceived to be used as an antiviral agent, and the present invention was made.
That is, an object of the present invention is to provide an antiviral agent containing mesoporous silica and / or platinum-supported mesoporous silica as an active ingredient.
本発明は以下の構成である。
（１）メソポーラス構造を有することを特徴とするシリカを有効成分として含有する抗ウイルス剤。
（２）前記シリカのメソポーラス構造が規則性の構造である（１）に記載の抗ウイルス剤。
（３）前記シリカが窒素吸着測定においてＢＪＨ法による細孔分布で０．５〜１５ｎｍの範囲にピークトップを有し、比表面積が３００〜２０００ｍ２／ｇであることを特徴とする（１）又は（２）に記載の抗ウイルス剤。
（４）前記シリカがＸ線回折の回折強度において、ｄ値が２．０ｎｍより大きい位置に少なくとも１つのピークを有することを特徴とする（１）〜（３）のいずれかに記載の抗ウイルス剤。
（５）前記シリカのメソ孔がヘキサゴナル状に規則的に配列していることを特徴とする（１）〜（４）のいずれかに記載の抗ウイルス剤。
（６）前記シリカに白金を担持した（１）〜（５）のいずれかに記載の抗ウイルス剤。
（７）粉末状の形態である（１）〜（６）のいずれかに記載の抗ウイルス剤。
（８）ペレット状の形態である（１）〜（６）のいずれかに記載の抗ウイルス剤。
The present invention has the following configuration.
(1) An antiviral agent containing silica as an active ingredient, which has a mesoporous structure.
(2) The antiviral agent according to (1), wherein the mesoporous structure of silica is a regular structure.
(3) The silica has a peak top in the range of 0.5 to 15 nm in pore distribution by BJH method in nitrogen adsorption measurement, and has a specific surface area of 300 to 2000 m 2 / g (1) Or the antiviral agent as described in (2).
(4) The antivirus according to any one of (1) to (3), wherein the silica has at least one peak at a position where the d value is larger than 2.0 nm in the diffraction intensity of X-ray diffraction. Agent.
(5) The antiviral agent according to any one of (1) to (4), wherein the silica mesopores are regularly arranged in a hexagonal form.
(6) The antiviral agent according to any one of (1) to (5), wherein platinum is supported on the silica.
(7) The antiviral agent according to any one of (1) to (6), which is in a powder form.
(8) The antiviral agent according to any one of (1) to (6), which is in a pellet form.
本発明により新規な抗ウイルス剤が提供される。本発明の抗ウイルス剤は、メソポーラスシリカ及び／又は白金担持メソポーラスシリカからなり、抗ウイルス作用に加えて水分吸収性を有し、皮膚に付着しても刺激性が少ない。また飲食品や口腔内洗浄液に配合することができる。
また水不溶性のため、衣類などの抗ウイルス剤として使用した場合、洗浄によって抗ウイルス性が低下しない。
The present invention provides a novel antiviral agent. The antiviral agent of the present invention comprises mesoporous silica and / or platinum-supported mesoporous silica, has water absorption in addition to antiviral action, and has little irritation even if it adheres to the skin. Moreover, it can mix | blend with food-drinks and an intraoral washing | cleaning liquid.
Moreover, since it is insoluble in water, when used as an antiviral agent for clothing, the antiviral properties are not reduced by washing.
本発明は、メソポーラスシリカ及び／又は白金又は白金含有化合物を担持させたメソポーラスシリカを有効成分として含有する抗ウイルス剤に係る発明である。
本発明におけるメソポーラス構造を有することを特徴とするシリカとは、多孔質構造を持つケイ素酸化物を主成分とし、規則的な細孔を有する水不溶性物質を意味し、メソポーラスシリカと称する。
また本発明で言う抗ウイルス作用とは、ウイルスの増殖の抑制又は減少作用をいう。
The present invention relates to an antiviral agent containing mesoporous silica and / or mesoporous silica supporting platinum or a platinum-containing compound as an active ingredient.
The silica characterized by having a mesoporous structure in the present invention means a water-insoluble substance mainly composed of a silicon oxide having a porous structure and having regular pores, and is called mesoporous silica.
In addition, the antiviral action referred to in the present invention refers to the action of suppressing or reducing the growth of viruses.
メソポーラスシリカの平均細孔直径は、０．５ｎｍ以上が好ましく、白金を粒子状で担持する観点から、１５ｎｍ以下が好ましい。より好ましくは１〜１０ｎｍ、さらに好ましくは１〜７ｎｍ、特に好ましくは１．５〜５ｎｍである。本発明において、多孔質シリカの平均細孔直径は、窒素吸脱着によるＢＪＨ法により算出することができる。 The average pore diameter of mesoporous silica is preferably 0.5 nm or more, and preferably 15 nm or less from the viewpoint of supporting platinum in the form of particles. More preferably, it is 1-10 nm, More preferably, it is 1-7 nm, Most preferably, it is 1.5-5 nm. In the present invention, the average pore diameter of the porous silica can be calculated by the BJH method based on nitrogen adsorption / desorption.
メソポーラスシリカの比表面積は、白金担持量を高める観点から、３００ｍ２／ｇ以上が好ましく、製造が実現可能である観点から、２０００ｍ２／ｇ以下が好ましい。これらの観点から、メソポーラスシリカの比表面積は、好ましくは３００〜２０００ｍ２／ｇ、より好ましくは６００〜１５００ｍ２／ｇである。本発明において、メソポーラスシリカの比表面積は、窒素吸脱着によるＢＥＴ法により算出することができる。
本発明のメソポーラスシリカは、窒素吸着測定においてＢＪＨ法による細孔分布で０．５〜１５ｎｍの範囲にピークトップを有し、比表面積が３００〜２０００ｍ２／ｇであることが好ましい。
The specific surface area of the mesoporous silica is preferably 300 m 2 / g or more from the viewpoint of increasing the amount of platinum supported, and preferably 2000 m 2 / g or less from the viewpoint that the production can be realized. From these viewpoints, the specific surface area of the mesoporous silica is preferably 300 to 2000 m 2 / g, more preferably 600 to 1500 m 2 / g. In the present invention, the specific surface area of mesoporous silica can be calculated by the BET method by nitrogen adsorption / desorption.
The mesoporous silica of the present invention preferably has a peak top in the range of 0.5 to 15 nm in the pore distribution according to the BJH method in nitrogen adsorption measurement, and the specific surface area is preferably 300 to 2000 m 2 / g.
また、メソポーラスシリカは、Ｘ線回折のｄ値が２．０ｎｍより大きい位置に少なくとも１ピークを有することが好ましい。Ｘ線回折ピークは、そのピーク角度に相当するｄ値の周期構造が試料中にあることを意味する。従って、２．０ｎｍ以上のｄ値に相当する回折角度に１以上のピークがあることは、細孔が２．０ｎｍ以上の間隔で規則的に配列していることを意味する。このように規則的に配列した細孔をもつものが、本発明におけるメソポーラスシリカである。本発明のメソポーラスシリカはＸ線回折の回折強度において、ｄ値が２．０ｎｍより大きい位置に少なくとも１つのピークを有することが好ましい。ｄ値は、好ましくは２．０〜２５ｎｍ、より好ましくは３．０〜２０ｎｍである。本発明において、メソポーラスシリカのＸ線回折パターンは粉末Ｘ線回折装置により測定することができる。
本発明のメソポーラスシリカのメソ孔はヘキサゴナル状に規則的に配列している。
The mesoporous silica preferably has at least one peak at a position where the d-value of X-ray diffraction is larger than 2.0 nm. The X-ray diffraction peak means that there is a periodic structure having a d value corresponding to the peak angle in the sample. Therefore, the presence of one or more peaks at the diffraction angle corresponding to a d value of 2.0 nm or more means that the pores are regularly arranged at intervals of 2.0 nm or more. The mesoporous silica in the present invention has such regularly arranged pores. The mesoporous silica of the present invention preferably has at least one peak at a position where the d value is larger than 2.0 nm in the diffraction intensity of X-ray diffraction. The d value is preferably 2.0 to 25 nm, more preferably 3.0 to 20 nm. In the present invention, the X-ray diffraction pattern of mesoporous silica can be measured with a powder X-ray diffractometer.
The mesopores of the mesoporous silica of the present invention are regularly arranged in a hexagonal form.
メソポーラスシリカの製造方法としては、特に限定されるものではない。特許文献１、特許文献２及び特許文献３に記載された方法が、本発明の目的とする細孔径を有するメソポーラスシリカを製造するために適している。
例えば次のようにして製造できる。まず、無機原料と有機原料を混合し、反応させることにより、有機物を鋳型としてそのまわりに無機物の骨格が形成された有機物と無機物の複合体を形成させる。次いで、得られた複合体から有機物を除去することにより、メソポーラスシリカが得られる。
The method for producing mesoporous silica is not particularly limited. The methods described in Patent Document 1, Patent Document 2 and Patent Document 3 are suitable for producing mesoporous silica having a pore diameter which is an object of the present invention.
For example, it can be manufactured as follows. First, an inorganic raw material and an organic raw material are mixed and reacted to form an organic matter-inorganic matter composite in which an inorganic matter skeleton is formed around the organic matter as a template. Subsequently, mesoporous silica is obtained by removing organic substances from the obtained composite.
無機原料としては、テトラメトキシシラン、テトラエトキシシラン、テトラプロポキシシラン等のアルコキシシラン、ケイ酸ソーダ、カネマイト（ｋａｎｅｍｉｔｅ、ＮａＨＳｉ２Ｏ５・３Ｈ２Ｏ）、シリカ、シリカ−金属複合酸化物等が挙げられる。これらの無機原料はシリケート骨格を形成する。これらは、単独で又は２種以上を混合して用いることができる。 Examples of inorganic raw materials include alkoxysilanes such as tetramethoxysilane, tetraethoxysilane, and tetrapropoxysilane, sodium silicate, kanemite (Kanemite, NaHSi 2 O 5 .3H 2 O), silica, and silica-metal composite oxide. It is done. These inorganic raw materials form a silicate skeleton. These can be used alone or in admixture of two or more.
鋳型として使用される有機原料は、特に限定されるものではないが、例えば界面活性剤等が挙げられる。界面活性剤は陽イオン性、陰イオン性、非イオン性のうちのいずれであってもよく、具体的には、アルキルトリメチルアンモニウム（好ましくはアルキル基の炭素数が８〜１８のアルキルトリメチルアンモニウム）、アルキルアンモニウム、ジアルキルジメチルアンモニウム、ベンジルアンモニウムの塩化物、臭化物、ヨウ化物又は水酸化物の他、脂肪酸塩、アルキルスルホン酸塩、アルキルリン酸塩、ポリエチレンオキサイド系非イオン性界面活性剤、一級アルキルアミン、トリブロックコポリマー型のポリアルキレンオキサイド、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル等が挙げられる。これらは、単独で又は２種以上を混合して用いることができる。 Although the organic raw material used as a casting_mold | template is not specifically limited, For example, surfactant etc. are mentioned. The surfactant may be any of cationic, anionic, and nonionic, specifically, alkyltrimethylammonium (preferably alkyltrimethylammonium having an alkyl group having 8 to 18 carbon atoms). , Alkylammonium, dialkyldimethylammonium, benzylammonium chloride, bromide, iodide or hydroxide, fatty acid salt, alkylsulfonate, alkylphosphate, polyethylene oxide nonionic surfactant, primary alkyl Examples include amines, triblock copolymer type polyalkylene oxides, glycerin fatty acid esters, and polyglycerin fatty acid esters. These can be used alone or in admixture of two or more.
無機原料と有機原料を混合する場合、適当な溶媒を用いることができる。溶媒としては、特に限定されるものではないが、例えば水、有機溶媒、水と有機溶媒との混合物等が挙げられる。 When mixing an inorganic raw material and an organic raw material, a suitable solvent can be used. Although it does not specifically limit as a solvent, For example, water, an organic solvent, the mixture of water and an organic solvent, etc. are mentioned.
無機物と有機物の複合体の形成方法は特に限定されるものではないが、例えば、有機原料を溶媒に溶解後、無機原料を添加し、所定のｐＨに調製した後に、反応混合物を所定の温度に保持して縮重合反応を行う方法が挙げられる。縮重合反応の反応温度は使用する有機原料や無機原料の種類や濃度によって異なるが、通常０〜１００℃程度が好ましく、より好ましくは３５〜８０℃である。 The formation method of the complex of inorganic and organic is not particularly limited. For example, after dissolving the organic raw material in a solvent, adding the inorganic raw material and adjusting to a predetermined pH, the reaction mixture is brought to a predetermined temperature. A method of carrying out the condensation polymerization reaction while holding is mentioned. The reaction temperature of the polycondensation reaction varies depending on the type and concentration of the organic raw material and inorganic raw material to be used, but is usually preferably about 0 to 100 ° C, more preferably 35 to 80 ° C.
縮重合反応の反応時間は、通常１〜２４時間程度が好ましい。また、上記の縮重合反応は、静置状態、撹拌状態のいずれで行ってもよく、またそれらを組み合わせて行ってもよい。 The reaction time for the polycondensation reaction is usually preferably about 1 to 24 hours. In addition, the above condensation polymerization reaction may be performed either in a stationary state or in a stirring state, or may be performed in combination.
縮重合反応後に得られる複合体から有機原料を除去することによって、メソポーラスシリカが得られる。有機物と無機物の複合体からの有機物の除去は、４００〜８００℃で焼成する方法、水やアルコール等の溶媒で処理する方法等の方法により行うことができる。 By removing the organic raw material from the composite obtained after the condensation polymerization reaction, mesoporous silica is obtained. The removal of the organic substance from the complex of the organic substance and the inorganic substance can be performed by a method such as a method of baking at 400 to 800 ° C. or a method of treating with a solvent such as water or alcohol.
本発明に使用するメソポーラスシリカは、例えば、珪酸ソーダを、界面活性剤を含む水溶液中に分散させ、加熱撹拌しながら塩酸を添加して分散液のｐＨを調整し、得られた固形生成物を洗浄・乾燥した後、４００〜８００℃程度で焼成することにより得られる。本発明に適したメソポーラスシリカとしては、例えば特許文献２（特開２００６−２４８８３２号公報）に開示された方法で製造することができる。
斯くして得られたメソポーラスシリカは、必要に応じて粉砕し、微粉末とする。得られるメソポーラスシリカは水不溶性であるため、これを有効成分とする抗ウイルス剤も水に不溶性である。
The mesoporous silica used in the present invention is prepared by, for example, dispersing sodium silicate in an aqueous solution containing a surfactant, adding hydrochloric acid while heating and stirring to adjust the pH of the dispersion, and obtaining the obtained solid product. After washing and drying, it is obtained by firing at about 400 to 800 ° C. The mesoporous silica suitable for the present invention can be produced by, for example, the method disclosed in Patent Document 2 (Japanese Patent Laid-Open No. 2006-248832).
The mesoporous silica thus obtained is pulverized as necessary to obtain a fine powder. Since the obtained mesoporous silica is insoluble in water, an antiviral agent containing this as an active ingredient is also insoluble in water.
なお、本発明の抗ウイルス剤は、吸着剤や吸湿剤、触媒などの用途で市販されているメソポーラスシリカを、本発明の目的に使用することもできる。このようなメソポーラスシリカとしては、太陽化学株式会社製メソポーラスシリカＴＭＰＳ−２、太陽化学株式会社製メソポーラスシリカＴＭＰＳ−２．７、太陽化学株式会社製メソポーラスシリカＴＭＰＳ−４Ｒを例示できる。 In addition, as the antiviral agent of the present invention, mesoporous silica marketed for applications such as an adsorbent, a hygroscopic agent, and a catalyst can be used for the purpose of the present invention. Examples of such mesoporous silica include mesoporous silica TMPS-2 manufactured by Taiyo Kagaku Co., Ltd., mesoporous silica TMPS-2.7 manufactured by Taiyo Kagaku Co., Ltd., and mesoporous silica TMPS-4R manufactured by Taiyo Chemical Co., Ltd.
メソポーラスシリカに担持される白金含有化合物としては、塩化白金、酸化白金、水酸化白金、塩化白金酸塩のほかに、その他金属との合金等が挙げられる。
メソポーラスシリカに担持された白金又は白金含有化合物の粒子は、好ましくは０．５〜７ｎｍであり、より好ましくは１〜４ｎｍである。
斯くして得られる白金担持メソポーラスシリカは、抗ウイルス作用に加えてエチレン分解作用や一酸化炭素除去能などの触媒作用を有している。
Examples of platinum-containing compounds supported on mesoporous silica include platinum chloride, platinum oxide, platinum hydroxide, chloroplatinate, and alloys with other metals.
The particles of platinum or a platinum-containing compound supported on mesoporous silica are preferably 0.5 to 7 nm, more preferably 1 to 4 nm.
The platinum-supported mesoporous silica thus obtained has a catalytic action such as an ethylene decomposition action and a carbon monoxide removal ability in addition to the antiviral action.
メソポーラスシリカに白金又は白金含有化合物を担持させるには、白金原子を含む白金化合物、白金錯体等の白金原料とメソポーラスシリカとの混合物を還元することにより得られる。具体的には、例えば、白金原料を含む水溶液を調製し、メソポーラスシリカを含浸させ、乾燥した後、還元して、メソポーラスシリカに白金又は白金含有化合物を担持させることができる。
白金原料は、塩化白金酸、ジニトロジアンミン白金、硝酸テトラアンミン白金等を例示できる。
白金原料を含む水溶液に含浸したメソポーラスシリカは、５０〜２００℃程度の温度で乾燥させ、ついで還元条件で白金原料を還元させる。
還元は、還元剤、熱、光等の条件で実施するが、メソポーラスシリカに含まれる白金原料が分解して白金粒子を生成する条件を還元方法に応じて適宜設定することができる。
塩化白金酸を白金原料として用いた場合には、還元剤に水素を使用し、１００〜４００
℃の温度条件下で、処理することが好ましい。
In order to support platinum or a platinum-containing compound on mesoporous silica, it is obtained by reducing a mixture of a platinum raw material such as a platinum compound containing a platinum atom or a platinum complex and mesoporous silica. Specifically, for example, an aqueous solution containing a platinum raw material is prepared, impregnated with mesoporous silica, dried, and then reduced to support platinum or a platinum-containing compound on the mesoporous silica.
Examples of the platinum raw material include chloroplatinic acid, dinitrodiammine platinum, and tetraammineplatinum nitrate.
The mesoporous silica impregnated in the aqueous solution containing the platinum raw material is dried at a temperature of about 50 to 200 ° C., and then the platinum raw material is reduced under reducing conditions.
The reduction is carried out under conditions such as a reducing agent, heat, and light, but the conditions under which the platinum raw material contained in the mesoporous silica is decomposed to produce platinum particles can be appropriately set according to the reduction method.
When chloroplatinic acid is used as a platinum raw material, hydrogen is used as the reducing agent, and 100 to 400
The treatment is preferably performed under a temperature condition of ° C.
白金又は白金含有化合物は、メソポーラスシリカの細孔外よりも細孔内に担持されていることが好ましい。細孔外に担持（付着）した白金、白金粒子あるいは白金含有化合物は、流水等により洗浄除去することができる。 Platinum or a platinum-containing compound is preferably supported in the pores rather than outside the pores of mesoporous silica. Platinum, platinum particles or platinum-containing compounds supported (attached) outside the pores can be removed by washing with running water or the like.
斯くして得られた白金担持メソポーラスシリカは、必要に応じて粉砕し、粉末とする。得られる白金担持メソポーラスシリカは水不溶性であるため、これを有効成分とする抗ウイルス剤も水に不溶性である。
なお、本発明の抗ウイルス剤は、触媒として市販されている白金担持メソポーラスシリカを、本発明の目的に使用することもできる。このような白金担持メソポーラスシリカとしては、太陽化学株式会社製プラチナ触媒ＴＭＰＳ−Ｐｔを例示できる。
The platinum-supported mesoporous silica thus obtained is pulverized as necessary to obtain a powder. Since the obtained platinum-supported mesoporous silica is insoluble in water, an antiviral agent containing this as an active ingredient is also insoluble in water.
In addition, as the antiviral agent of the present invention, platinum-supported mesoporous silica that is commercially available as a catalyst can be used for the purpose of the present invention. As such platinum-supported mesoporous silica, Taiyo Kagaku Co., Ltd. platinum catalyst TMPS-Pt can be exemplified.
本発明の抗ウイルス剤を構成するメソポーラスシリカ及び／又は白金担持メソポーラスシリカは、０．５〜１５ｎｍの平均細孔直径を有し、３００〜２０００ｍ２／ｇの比表面積を有し、Ｘ線回折のｄ値が２．０ｎｍより大きい位置に少なくとも１つのピークを有することが好ましい。また白金担持メソポーラスシリカは、白金又は白金含有化合物を含有し、その含有量は、０．１〜５質量％であることが好ましい。白金又は白金化合物は、メソポーラスシリカの細孔中に担持されている。
本発明の抗ウイルス剤の有効成分である、メソポーラスシリカ及び／又は白金担持メソポーラスシリカは、０．０１〜２００μｍの粒径を有する粉末、或いは、賦形剤を添加して成形して得られるペレット状の形態を有することが好ましい。
The mesoporous silica and / or platinum-supported mesoporous silica constituting the antiviral agent of the present invention has an average pore diameter of 0.5 to 15 nm, a specific surface area of 300 to 2000 m 2 / g, and X-ray diffraction It is preferable to have at least one peak at a position where the d value of is greater than 2.0 nm. Moreover, platinum carrying | support mesoporous silica contains platinum or a platinum containing compound, and it is preferable that the content is 0.1-5 mass%. Platinum or a platinum compound is supported in the pores of mesoporous silica.
The mesoporous silica and / or platinum-supported mesoporous silica, which is an active ingredient of the antiviral agent of the present invention, is a powder having a particle diameter of 0.01 to 200 μm, or a pellet obtained by molding by adding an excipient It is preferable to have a shape.
本発明の抗ウイルス剤は抗菌性も併せ持っており、これを殺菌や細菌増加抑制を目的とする抗菌・抗ウイルス剤として使用する場合は、平均粒子径が１０μｍ以下の微小粒子のものを用いて、水やアルコールに分散させて用時振盪混合して使用する形態の容器に充填した溶液とするか、或いはタンパク質やその他コロイド分散溶液、又は増粘多糖類などの粘性物質を添加した粘性溶液とすることで白金担持メソポーラスシリカの沈降を抑制し、手指の抗菌・抗ウイルス用除菌液として使用することができる。手指の除菌剤とする場合は、溶液中に白金担持メソポーラスシリカを０．０１〜１０質量％含有させることが好ましい。 The antiviral agent of the present invention also has antibacterial properties, and when it is used as an antibacterial / antiviral agent for the purpose of sterilization or suppression of bacterial growth, use a microparticle having an average particle size of 10 μm or less. A solution in which it is dispersed in water or alcohol and mixed by shaking at the time of use and filled into a container, or a viscous solution to which a viscous substance such as a protein or other colloid dispersion solution or a thickening polysaccharide is added By doing so, sedimentation of platinum-supported mesoporous silica can be suppressed, and it can be used as an antibacterial / antiviral disinfectant solution for fingers. When it is used as a hand sanitizer, it is preferable to contain 0.01 to 10% by mass of platinum-supported mesoporous silica in the solution.
多糖類などの賦形剤を添加して、打錠成形するか或いは造粒した後打錠成形したメソポーラスシリカ及び／又は白金担持メソポーラスシリカのペレットは、空気清浄機などの空気濾過槽の抗菌・抗ウイルス剤として用いることもできる。加湿器用の抗菌・抗ウイルス剤として用いることもできる。
また平均粒子径を２μｍ以下の微粉末とすると、化粧水や化粧用乳液など、粘性を有する溶液においては、沈降せずに分散するため、これらの化粧水や乳液、或いはクリームに添加して抗ウイルス用途の化粧料として使用することができる。洗口液などの抗ウイルス用途の口腔ケア化粧料としてもよい。また化粧石鹸に練りこみ抗菌・抗ウイルス作用を有する石鹸としたり、粉末洗剤にビルダーの一部とともに混合するかあるいは液体洗剤に混合して、洗浄後の衣類に抗ウイルス作用を付与したりすることもできる。さらに化粧水や乳液、洗口液等の抗ウイルス用途の化粧料として使用する場合は、メソポーラスシリカ及び／又は白金担持メソポーラスシリカを０．０１〜１０質量％含有させることが好ましい。
メソポーラスシリカ及び／又は白金担持メソポーラスシリカを配合したトローチなどの打錠菓子としてもよい。
Pellets of mesoporous silica and / or platinum-supported mesoporous silica that have been tableted or granulated after adding excipients such as polysaccharides are antibacterial products for air filtration tanks such as air purifiers. It can also be used as an antiviral agent. It can also be used as an antibacterial / antiviral agent for humidifiers.
If the average particle size is a fine powder of 2 μm or less, a viscous solution such as lotion or cosmetic emulsion will disperse without settling, so it can be added to these lotions, emulsions or creams to resist. It can be used as a cosmetic for virus use. It may be an oral care cosmetic for antiviral use such as mouthwash. Also, kneading into cosmetic soap to make soap with antibacterial and antiviral action, or mix with powder detergent with part of builder or liquid detergent to give anti-virus action to washed clothes You can also. Furthermore, when using as cosmetics for antiviral uses such as lotion, milky lotion, mouthwash, etc., it is preferable to contain 0.01 to 10% by mass of mesoporous silica and / or platinum-supported mesoporous silica.
It is good also as tableting confectionery, such as a troche which mix | blended mesoporous silica and / or platinum carrying | support mesoporous silica.
また、水分散溶液などに適宜バインダー成分を添加し、この溶液に布、紙、木材、樹脂、セラミックなどを浸漬するか、或いは本発明の抗ウイルス剤分散溶液を噴霧して、乾燥させることで抗菌・抗ウイルス性を有するメソポーラスシリカ及び／又は白金担持メソポーラスシリカが付着した布、紙、木材、樹脂、セラミックを得ることができる。この場合に抗ウイルス性を付与するためには、それぞれの素材の表面積当たり、メソポーラスシリカ及び／又は白金担持メソポーラスシリカを０．０１〜５．０ｇ／ｍ２付着させることが必要である。また抗菌・抗ウイルス性付与方法としては、布、紙、樹脂、セラミック等を作成する工程で、メソポーラスシリカ及び／又は白金担持メソポーラスシリカを練り込んでも良い。 In addition, a binder component is appropriately added to an aqueous dispersion and the like, and cloth, paper, wood, resin, ceramic, etc. are immersed in this solution, or the antiviral agent dispersion of the present invention is sprayed and dried. A cloth, paper, wood, resin, or ceramic to which mesoporous silica having antibacterial / antiviral properties and / or platinum-supported mesoporous silica is attached can be obtained. In this case, in order to impart antiviral properties, it is necessary to attach 0.01 to 5.0 g / m 2 of mesoporous silica and / or platinum-supported mesoporous silica per surface area of each material. In addition, as a method for imparting antibacterial / antiviral properties, mesoporous silica and / or platinum-supported mesoporous silica may be kneaded in a step of creating cloth, paper, resin, ceramic, or the like.
以下に抗ウイルス作用を確認した試験例を示し、本発明をより具体的に説明する。
＜抗ウイルス試験例＞
１．試験試料
（１）メソポーラスシリカ及び白金担持メソポーラスシリカ粉末
試験で使用する試料は、市販のメソポーラスシリカ粉末及びメソポーラスシリカに白金を担持した粉末を用いた。
本発明品１：メソポーラスシリカ：太陽化学株式会社製 メソポーラスシリカ ＴＭＰＳ−４Ｒ（以下「ＴＭＰＳ−４Ｒ」）
本発明品２：白金担持メソポーラスシリカ：太陽化学株式会社製 ＴＭＰＳ−Ｐｔ（以下「ＴＭＰＳ−Ｐｔ」）白金１０ｍｇ／ｇ含有
なお、メソポーラスシリカＴＭＰＳ−４Ｒは、窒素吸着測定においてＢＪＨ法による細孔分布で３．８７ｎｍにピークトップを有し、９２９ｍ２／ｇの比表面積を有し、細孔容積が０．９１１ｃｍ３／ｇであり、外表面積は５６．６ｍ２／ｇであった。
白金を担持したメソポーラスシリカＴＭＰＳ−Ｐｔは、窒素吸着測定においてＢＪＨ法による細孔分布で３．４５ｎｍにピークトップを有し、６７８ｍ２／ｇの比表面積を有し、細孔容積が０．５９３ｃｍ３／ｇであり、外表面積は５３．２ｍ２／ｇであった。
そして、いずれもＸ線回折の回折強度において、ｄ値が２．０ｎｍより大きい位置に少なくとも１つのピークを有し、ｄ値が１．０ｎｍより小さい位置にピークはなかった。そしてメソポーラス構造は規則性であり、ヘキサゴナル状に規則的に配列していた。
Hereinafter, the present invention will be described in more detail by showing test examples in which antiviral action has been confirmed.
<Antivirus test example>
1. Test sample (1) Mesoporous silica and platinum-supported mesoporous silica powder Samples used in the test were commercially available mesoporous silica powder and mesoporous silica-supported powder.
Invention product 1: Mesoporous silica: Taiyo Kagaku Co., Ltd. Mesoporous silica TMPS-4R (hereinafter "TMPS-4R")
Invention product 2: Platinum-supported mesoporous silica: manufactured by Taiyo Kagaku Co., Ltd. TMPS-Pt (hereinafter “TMPS-Pt”) containing 10 mg / g of platinum. And had a peak top at 3.87 nm, a specific surface area of 929 m 2 / g, a pore volume of 0.911 cm 3 / g, and an outer surface area of 56.6 m 2 / g.
The mesoporous silica TMPS-Pt supporting platinum has a peak top at 3.45 nm in the pore distribution by the BJH method in nitrogen adsorption measurement, a specific surface area of 678 m 2 / g, and a pore volume of 0.593 cm. 3 / g and the outer surface area was 53.2 m 2 / g.
All of them had at least one peak at a position where the d value was greater than 2.0 nm and no peak at a position where the d value was smaller than 1.0 nm in the diffraction intensity of X-ray diffraction. The mesoporous structure was regular and regularly arranged in a hexagonal form.
（２）比較対照
比較試料１：粉末状多孔質シリカ：豊田化工株式会社製 トヨタシリカゲルＡ形シロ（以下「Ａ形シリカ」）
比較試料２：白金ナノコロイド：アプト株式会社製 Ｃ−Ｐｔ−Ｃｏｓ（以下「Ｃ−Ｐｔ−Ｃｏｓ」 白金０．２ｍｇ／ｇ含有
なお「Ａ形シリカ」は規則的なメソポーラス構造を有しない多孔性シリカ、「Ｃ−Ｐｔ−Ｃｏｓ」はメソポーラス構造を有しないが、抗ウイルス作用が確認されている物質である。
(2) Comparative control Comparative sample 1: Powdered porous silica: Toyota silica gel A type white (hereinafter referred to as “A type silica”) manufactured by Toyoda Chemical Co., Ltd.
Comparative Sample 2: Platinum Nanocolloid: C-Pt-Cos (hereinafter “C-Pt-Cos” manufactured by APT Co., Ltd.) 0.2 mg / g of platinum Note that “A-type silica” is porous without a regular mesoporous structure. Silica, “C-Pt-Cos” does not have a mesoporous structure, but has been confirmed to have an antiviral effect.
（３）試験試料の調製
各試験試料は、２倍段階希釈系列を計１０濃度（非添加群を除く）調製する。希釈には感染維持培地（ビタミン含有無血清MEM培地）を使用し、希釈用の９６−ｗｅｌｌ ｐｌａｔｅを使用して実施する。試験最高濃度は、ＴＭＰＳ−４Ｒ：１０質量％、ＴＭＰＳ−Ｐｔ：１０質量％、Ａ形シリカ：１０質量％、Ｃ−Ｐｔ−Ｃｏｓ：１００％（原液）とする。
(3) Preparation of test sample Each test sample is prepared in a 10-fold concentration (excluding the non-addition group) in a 2-fold serial dilution series. Dilution is performed using an infection maintenance medium (vitamin-containing serum-free MEM medium) and a 96-well plate for dilution. The highest test concentrations are TMPS-4R: 10% by mass, TMPS-Pt: 10% by mass, A-type silica: 10% by mass, and C-Pt-Cos: 100% (stock solution).
（４）抗ウイルス試験−１
１）試験用ウイルス
試験用ウイルスとしてヒトインフルエンザウイルスＡ型Ｈ１Ｎ１型（Ａ／ＷＳＮ／３３，Ｈ１Ｎ１）を使用した。
２）試験用細胞
イヌ腎臓由来細胞株ＭＤＣＫ細胞（Madin-Darby canine kidney cell）を用いた。
３）試験方法
ＭＤＣＫ細胞を１０％血清含有ＭＥＭ（ＭＥＭ−１０％ＦＢＳ）で３．０×１０５ｃｅｌｌｓ／ｍＬに調製し、１００μＬ／ｗｅｌｌで９６−ｗｅｌｌ ｐｌａｔｅへ播種した。なお、プレート左端１列目（計８ｗｅｌｌｓ）には細胞を播種せず、解析時の補正用のブランク群とした。
次いで３７℃−５％ＣＯ２下で２４時間培養後、培養液を除去し、１００μＬ／ｗｅｌｌの無血清ＭＥＭで各ｗｅｌｌの細胞単層を１回洗浄した。
ウイルス接種量は、予め、試験に用いるウイルスのＭＤＣＫ細胞に対するＴＣＩＤ５０（Ｍｅｄｉａｎ ｔｉｓｓｕｅ ｃｕｌｔｕｒｅｉｎｆｅｃｔｉｏｕｓ ｄｏｓｅ， ５０％感染量）を測定しておき、これに基づいて、ウイルス接種量を決定した。
細胞洗浄後、調製した試験液１００μＬ／ｗｅｌｌ添加し、続けて、抗ウイルス活性評価群には感染維持培地で２５０TCID50／ｍＬ、ないしは、１，０００TCID50／ｍＬに調製したインフルエンザウイルス溶液を１００μＬ／ｗｅｌｌで添加した。
一方、細胞毒性評価群には感染維持培地を１００μＬ／ｗｅｌｌで添加した。試験試料並びにウイルス添加後の９６−ｗｅｌｌ ｐｌａｔｅは、室温下で３０秒間撹拌し、３７℃−５％ＣＯ２下で３日間（７２ｈｒｓ）培養した。なお、試験はＮ＝２（ｄｕｐｌｉｃａｔｅ）で実施した。
(4) Antiviral test-1
1) Test virus Human influenza virus type A H1N1 (A / WSN / 33, H1N1) was used as a test virus.
2) Test cells A canine kidney-derived cell line MDCK cell (Madin-Darby canine kidney cell) was used.
3) Test method MDCK cells were prepared to 3.0 × 10 5 cells / mL with 10% serum-containing MEM (MEM-10% FBS), and seeded on 96-well plate at 100 μL / well. Note that cells were not seeded in the first column on the left end of the plate (total 8 wells), and a blank group for correction during analysis was used.
Subsequently, after culturing at 37 ° C.-5% CO 2 for 24 hours, the culture solution was removed, and the cell monolayer of each well was washed once with 100 μL / well of serum-free MEM.
The virus inoculation amount was determined in advance by measuring TCID50 (Media tissue cultureinfectious dose, 50% infection amount) against MDCK cells of the virus used in the test, and based on this, the virus inoculation amount was determined.
After washing the cells, 100 μL / well of the prepared test solution was added, and then the influenza virus solution prepared at 250 TCID50 / mL or 1,000 TCID50 / mL in the infection maintenance medium was added to the antiviral activity evaluation group at 100 μL / well. Added.
On the other hand, the infection maintenance medium was added to the cytotoxicity evaluation group at 100 μL / well. The test sample and the 96-well plate after addition of the virus were stirred at room temperature for 30 seconds and cultured at 37 ° C. under 5% CO 2 for 3 days (72 hrs). The test was performed at N = 2 (duplicate).
（５）結果
試験試料の希釈系列からＩＣ５０（％）を求めた。
結果を下記の表１に示す。
(5) Result IC50 (%) was calculated | required from the dilution series of the test sample.
The results are shown in Table 1 below.
表１に示すように、ＴＭＰＳ−４Ｒ及びＴＭＰＳ−Ｐｔは低濃度でヒトインフルエンザウイルスに対して抗ウイルス作用を示した。この抗ウイルス作用は、公知の粉末状多孔質シリカや白金ナノコロイドよりも強いことが明らかとなった。 As shown in Table 1, TMPS-4R and TMPS-Pt exhibited antiviral activity against human influenza virus at low concentrations. It was revealed that this antiviral action is stronger than known powdered porous silica and platinum nanocolloid.
（６）抗ウイルス試験―２
１）試験用ウイルス
試験用ウイルスとしてヒトインフルエンザウイルスＡ型 Ｈ１Ｎ１ Ａ／ＰＲ／８３４ ＡＴＣＣ ＶＲ−１４６９を使用した。
(6) Antiviral test-2
1) Test virus Human influenza virus type A H1N1 A / PR / 834 ATCC VR-1469 was used as a test virus.
２）試験用細胞
イヌ腎臓由来細胞株ＭＤＣＫ細胞（Madin-Darby canine kidney cell）ＡＴＣＣ ＣＣＬ−３４を用いた。
2) Test cells Canine kidney-derived cell line MDCK cells (Madin-Darby canine kidney cell) ATCC CCL-34 were used.
３）試験試料
・本発明品１（メソポーラスシリカ：製品名 ＴＭＰＳ−４Ｒ、メーカー：太陽化学株式会社）比表面積：９２９ｍ２／ｇ、細孔直径：３．８７ｎｍ、細孔容積：０．９１１ｃｍ３／ｇ、外表面積：５６．６ ｍ２／ｇ
・本発明品２（白金担持メソポーラスシリカ：製品名：ＴＭＰＳ−Ｐｔ、メーカー：太陽化学株式会社）比表面積：６７８ｍ２／ｇ、細孔直径：３．４５ｎｍ、細孔容積：０．５９３ｃｍ３／ｇ、外表面積：５３．２ｍ２／ｇ、白金１０ｍｇ／ｇ含有
3) Test sample-Invention product 1 (Mesoporous silica: Product name TMPS-4R, manufacturer: Taiyo Kagaku Co., Ltd.) Specific surface area: 929 m 2 / g, pore diameter: 3.87 nm, pore volume: 0.911 cm 3 / G, outer surface area: 56.6 m 2 / g
Invention product 2 (platinum-supported mesoporous silica: product name: TMPS-Pt, manufacturer: Taiyo Kagaku Co., Ltd.) Specific surface area: 678 m 2 / g, pore diameter: 3.45 nm, pore volume: 0.593 cm 3 / g, outer surface area: 53.2 m 2 / g, platinum 10 mg / g
４）試験方法
試験試料を４００ｍｇ秤量し、５ｍＬチューブに加えた。別途準備したインフルエンザウイルス（１−５×１０６ｐｆｕ／ｍＬ、滅菌水溶液）０．４ｍＬを、上記５ｍＬチューブに加え、撹拌を行い、１５分間不活化処理を行った。不活化処理後、ＳＣＤＬＰ培地を３．６ｍＬ添加し、撹拌抽出後、４０００ｒｐｍ、３分間遠心分離した。遠心分離後の上清を、ＳＣＤＬＰ培地を用いて１０倍段階希釈系を作成した。この段階希釈液をＭＤＣＫ細胞とともに３７℃１時間インキュベートした。その後、オキサイドアガー溶液（０．８％寒天、０．０６％ダルベッコ改変イーグル培地）１ｍＬを細胞上に重層し、３７℃のインキュベータ中で、２−３日間静置した。その後、５％グルタルアルデヒド溶液で固定し、メチレンブルー染色によってプラーク数をカウントし、インフルエンザウイルス感染力価を測定した。
4) Test method 400 mg of the test sample was weighed and added to a 5 mL tube. 0.4 mL of separately prepared influenza virus (1-5 × 10 6 pfu / mL, sterile aqueous solution) was added to the 5 mL tube, stirred, and inactivated for 15 minutes. After the inactivation treatment, 3.6 mL of SCDLP medium was added, followed by extraction with stirring, followed by centrifugation at 4000 rpm for 3 minutes. A 10-fold serial dilution system was prepared for the supernatant after centrifugation using SCDLP medium. This serial dilution was incubated with MDCK cells for 1 hour at 37 ° C. Thereafter, 1 mL of an oxide agar solution (0.8% agar, 0.06% Dulbecco's modified Eagle medium) was layered on the cells and allowed to stand for 2-3 days in a 37 ° C. incubator. Thereafter, the plate was fixed with a 5% glutaraldehyde solution, the number of plaques was counted by methylene blue staining, and the influenza virus infection titer was measured.
（７）結果
試験試料の希釈系列から、感染力価を求めた。また感染力の減少値を計算し、下記
表２に示す。
(7) Results The infectious titer was determined from the dilution series of the test sample. In addition, the decrease in infectivity was calculated and shown in Table 2 below.
表２に示すように、メソポーラスシリカ、白金担持メソポーラスシリカはヒトインフルエンザウイルスの感染を抑制した。 As shown in Table 2, mesoporous silica and platinum-supported mesoporous silica suppressed infection with human influenza virus.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006069824A (en) * | 2004-08-31 | 2006-03-16 | Univ Of Miyazaki | Mesoporous silica nanoparticle having micropore and method for producing the same |
| JP2006248832A (en) * | 2005-03-10 | 2006-09-21 | Taiyo Kagaku Co Ltd | Substance-supporting porous silica |
| JP2009155262A (en) * | 2007-12-26 | 2009-07-16 | Lion Corp | Antiviral agent |
| JP2011056509A (en) * | 2004-02-05 | 2011-03-24 | Taiyo Kagaku Co Ltd | Adsorptivity imparting agent containing porous silica |
| JP2014098546A (en) * | 2010-12-24 | 2014-05-29 | Bioface Co Ltd Tokyo Research Laboratory | Home electric appliance using one of platinum shield technology, platinum catalyst chemistry technology and platinum fixation technology, and humidifier |
| JP2015195827A (en) * | 2014-03-31 | 2015-11-09 | 株式会社Ｎｂｃメッシュテック | Antiviral member |
| JP2017150117A (en) * | 2016-02-26 | 2017-08-31 | 独立行政法人国立高等専門学校機構 | Antiviral stock |
| JP2017206489A (en) * | 2016-05-13 | 2017-11-24 | 稚内市 | Environment improvement material and method for producing the same |
-
2018
- 2018-03-05 JP JP2018038346A patent/JP7085860B2/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011056509A (en) * | 2004-02-05 | 2011-03-24 | Taiyo Kagaku Co Ltd | Adsorptivity imparting agent containing porous silica |
| JP2006069824A (en) * | 2004-08-31 | 2006-03-16 | Univ Of Miyazaki | Mesoporous silica nanoparticle having micropore and method for producing the same |
| JP2006248832A (en) * | 2005-03-10 | 2006-09-21 | Taiyo Kagaku Co Ltd | Substance-supporting porous silica |
| JP2009155262A (en) * | 2007-12-26 | 2009-07-16 | Lion Corp | Antiviral agent |
| JP2014098546A (en) * | 2010-12-24 | 2014-05-29 | Bioface Co Ltd Tokyo Research Laboratory | Home electric appliance using one of platinum shield technology, platinum catalyst chemistry technology and platinum fixation technology, and humidifier |
| JP2015195827A (en) * | 2014-03-31 | 2015-11-09 | 株式会社Ｎｂｃメッシュテック | Antiviral member |
| JP2017150117A (en) * | 2016-02-26 | 2017-08-31 | 独立行政法人国立高等専門学校機構 | Antiviral stock |
| JP2017206489A (en) * | 2016-05-13 | 2017-11-24 | 稚内市 | Environment improvement material and method for producing the same |
Non-Patent Citations (4)
| Title |
|---|
| ACS OMEGA, vol. 3, JPN6021052482, February 2018 (2018-02-01), pages 1689 - 1699, ISSN: 0004675793 * |
| J.JPN.SOC.COLOUR MATER., vol. 82(10), JPN6021035436, 2009, pages 454 - 460, ISSN: 0004675791 * |
| NANOSCALE, vol. 8, JPN6021052480, 2016, pages 16192 - 16196, ISSN: 0004675794 * |
| 雪氷, vol. 78(5), JPN6021052478, 2016, pages 281 - 290, ISSN: 0004675792 * |
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