JP5704623B2 - Anti-Legionella material carrying metal-tropolone complex between inorganic layers - Google Patents
Anti-Legionella material carrying metal-tropolone complex between inorganic layers Download PDFInfo
- Publication number
- JP5704623B2 JP5704623B2 JP2008128941A JP2008128941A JP5704623B2 JP 5704623 B2 JP5704623 B2 JP 5704623B2 JP 2008128941 A JP2008128941 A JP 2008128941A JP 2008128941 A JP2008128941 A JP 2008128941A JP 5704623 B2 JP5704623 B2 JP 5704623B2
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- Prior art keywords
- legionella
- metal
- complex
- tropolone
- layers
- Prior art date
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- Agricultural Chemicals And Associated Chemicals (AREA)
Description
本発明は、所定の生理活性機能を有する金属−トロポロン錯体を無機層状化合物の層間に挿入、担持した抗レジオネラ属菌材料に関するものであり、更に詳しくは、無機層状化合物を主原料とし、その層間に、植物生長調節機能、病害虫防除機能、雑草防除機能、抗微生物機能等の所定の生理活性作用を有する金属−トロポロン錯体を挿入、担持させてその生理活性機能の徐放性を向上させた新規な生理活性機能を有する抗レジオネラ属菌材料、その製造方法、及び当該抗レジオネラ属菌材料を有効成分として含有する抗レジオネラ属菌加工製品に関するものである。 The present invention relates to an anti- Legionella genus material in which a metal-tropolone complex having a predetermined physiological activity function is inserted and supported between layers of an inorganic layered compound, and more specifically, an inorganic layered compound as a main raw material, A metal-tropolone complex having a predetermined physiological activity such as a plant growth regulation function, pest control function, weed control function, antimicrobial function, etc. is inserted and supported to improve the sustained release of the physiological activity function The present invention relates to an anti-Legionella material having a novel physiologically active function, a production method thereof, and an anti-Legionella bacterium processed product containing the anti-Legionella material as an active ingredient.
本発明は、所定の生理活性機能を有する金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料を提供するものであり、特に、浴場施設や、我々の生活環境において大量の水を溜めて利用する場所、給湯設備、冷却塔、加湿装置、水景施設に好適に利用可能であり、更に優れた所定の生理活性機能の持続性や保水性、耐候性及び環境親和性を有し、生活環境や医療福祉環境、植物の組織培養、農業、植林をはじめとする林業全般、植物栽培などに応用可能な新規抗レジオネラ属菌剤を提供するものである。 The present invention provides an anti-Legionella genus material in which a metal-tropolone complex having a predetermined physiological activity function is supported between layers, and in particular, a large amount of water is accumulated and used in a bath facility or our living environment. It is suitable for use in places, hot water supply facilities, cooling towers, humidifiers, and waterscape facilities, and has excellent durability and water retention, weather resistance, and environmental compatibility, as well as living environment and medical care. The present invention provides novel anti-Legionella bacteria that can be applied to the welfare environment, plant tissue culture, agriculture, general forestry including plantation, and plant cultivation.
エネルギー利用の高効率化を図る目的で、多くの公衆浴場には、大型の循環式浴槽が設置されている。業務用の大型循環式浴槽には、濾過装置の前に殺菌装置が組み込まれ、濾過装置にレジオネラ属菌や大腸菌などの人に危害を及ぼす細菌類の繁殖を防ぐ配慮がなされている場合が多い。最近では、一般家庭向けの循環式浴槽（２４時間風呂）も普及してきており、販売台数が伸張している。循環式浴槽は、浴槽水を濾過して再利用するため、有機物をろ過・分解して水質を長持ちさせる保存性と、それに伴う浴槽の清掃頻度低下と水資源の節約が、従来型の浴槽には無い利点として挙げられる。 In order to increase the efficiency of energy use, many public baths are equipped with large circulation bathtubs. Large circulatory tubs for business use are equipped with a sterilization device in front of the filtration device, and the filtration device is often designed to prevent the growth of bacteria such as Legionella spp. . Recently, circulation bathtubs (24-hour baths) for general households have become widespread, and the number of units sold has increased. Since the recirculating bathtub is used by filtering and reusing the bath water, the preservation of the water quality by filtering and decomposing the organic matter, and the associated less frequent cleaning of the bathtub and saving of water resources, is the conventional bathtub. There is no advantage to mention.
しかし、この循環式浴槽を設置した浴槽水中において、レジオネラ属菌（感染時の主要症状は肺炎等で、重症者は致死率が高い。）の高いレベルでの繁殖が高確率で観察される事例が学会等で報告されており、また、家庭用２４時間風呂では、レジオネラ属菌に限らず、大腸菌等のその他の雑菌によると思われる細菌汚染等のクレームが各地の消費生活センター等に寄せられている。こうした点を踏まえ、厚生労働省では、平成１１年に、「建築物等におけるレジオネラ症防止対策について」を、生活衛生局長より、各都道府県及び政令市市長に通知し、指導を行っている。 However, in the bath water in which this circulating bath is installed, cases of high-level reproduction of Legionella spp. (Major symptoms at the time of infection are pneumonia, etc., severe cases are fatal) In the 24-hour bath for home use, complaints such as bacterial contamination that seems to be caused not only by Legionella spp. But also other bacteria such as Escherichia coli are sent to consumer centers in various regions. ing. Based on these points, in 1999, the Ministry of Health, Labor and Welfare notified the prefectural and mayoral mayors of “Regional Disease Prevention Measures in Buildings” from the Director of the Health Sanitation Bureau.
家庭用循環式浴槽の場合、浴槽水に微生物が繁殖する原因として、（１）繁殖に適した水温、（２）低い加熱温度、（３）浴槽水の循環路長、（４）微生物を利用した生物浄化方式、等が挙げられる。入浴に快適な水温は、多くの微生物の繁殖・増殖に格好の条件となる。レジオネラ属菌は、７０℃に加温すると短時間で死滅するが、家庭用循環式浴槽での加熱温度は４０℃前後である。また、浴槽水の循環路には、浴槽水を運ぶ配管が長いものが多く、徹底的な清掃が困難となり、配管壁面には微生物が付着して生物膜（バイオフィルム）を形成して増殖し易くなる。このような場所にアメーバなどの原生動物が定着し、更にレジオネラ属菌が混入すると、レジオネラ属菌がアメーバを利用して爆発的に増殖する。 In the case of household circulation bathtubs, there are (1) water temperature suitable for breeding, (2) low heating temperature, (3) bath water circulation path length, and (4) use of microorganisms. Bioremediation methods, etc. The water temperature that is comfortable for bathing is a favorable condition for the propagation and growth of many microorganisms. Legionella spp. Die in a short time when heated to 70 ° C., but the heating temperature in a household circulation bath is around 40 ° C. In addition, there are many pipes that carry bathtub water in the circulation path of bathtub water, and thorough cleaning becomes difficult. Microorganisms adhere to the wall of the pipe to form a biofilm (biofilm). It becomes easy. When a protozoan such as an amoeba settles in such a place and further Legionella spp. Is mixed, the Legionella spp. Grows explosively using the amoeba.
レジオネラ属菌は、レジオネラ症と呼ばれる感染症を引き起こすことが知られている。レジオネラ属菌を含む微細な水滴（エアロゾル）を直接肺に吸入することや、菌を含む水を誤飲することにより感染し、発症する。症状には、急性肺炎に似たレジオネラ肺炎と、インフルエンザに似たポンティアック熱がある。こうしたレジオネラ属菌に対する被害は、上記の浴場施設だけではなく、我々の生活環境において、大量の水を溜めて利用する場所、給湯設備、冷却塔、加湿装置、水景施設等でも発生しており、深刻な問題となっている。 Legionella is known to cause an infection called Legionellosis. Infected by inhalation of fine water droplets (aerosol) containing Legionella spp. Directly into the lungs or accidental ingestion of water containing bacteria. Symptoms include Legionella pneumonia resembling acute pneumonia and Pontiac fever resembling influenza. Such damage to Legionella spp. Occurs not only in the bath facilities mentioned above, but also in places where water is stored and used in our living environment, hot water supply facilities, cooling towers, humidifiers, aquatic facilities, etc. It has become a serious problem.
このレジオネラ属菌による問題の対策として、循環水系に抗菌剤を注入して細菌類の増殖を抑制する方法や、装置内を機械的に清掃洗浄し、あるいは洗浄剤を用いて洗浄する方法などが用いられてきた。そして、従来から、レジオネラ属菌を防除する殺菌剤として、例えば、５−クロロ−２−メチル−４−イソチアゾリン−３−オンなどのイソチアゾロン系化合物や、２−ブロモ−２−ニトロプロパン−１，３−ジオールなどのニトロアルコール系化合物等、種々の化合物が提案されている。しかし、これらの従来から提案されている薬剤は、実験室内では有効な殺菌性能を示しても、実際に稼働している水系に使用してみると、必ずしも十分な効果が得られないことが多かった。 As countermeasures against problems caused by Legionella, there are a method of injecting an antibacterial agent into the circulating water system to suppress the growth of bacteria, a method of mechanically cleaning the inside of the apparatus, or a method of cleaning with a cleaning agent, etc. Has been used. Conventionally, as bactericides for controlling Legionella, for example, isothiazolone compounds such as 5-chloro-2-methyl-4-isothiazolin-3-one, 2-bromo-2-nitropropane-1, Various compounds such as nitroalcohol compounds such as 3-diol have been proposed. However, even if these conventionally proposed drugs show effective sterilization performance in the laboratory, they are often not always effective when used in water systems that are actually in operation. It was.
ヒノキチオールをはじめとするトロポロン類化合物は、台湾檜油、青森産檜葉油及びウェスタンレッドセダーオイル等に含有する結晶性物質である。この天然由来の化合物は、現在では、合成品としても入手可能であり、抗菌防カビ剤や養毛育毛剤、アロマテラピー用芳香剤、歯磨や食品添加物等の様々な分野で広く利用されている。しかし、このトロポロン類化合物は、融点が５２−５３℃と低いことと、昇華性や光分解性が高いために、上記効果を長期間持続させることが困難であった。そのため、こうした生理活性物質あるいは薬剤が徐々に供給されるように、それらを徐放性にした内服又は外用の製剤が、徐放薬、徐放錠、徐放製剤、持効性製剤等と称されて、盛んに用いられている。 Tropolones such as hinokitiol are crystalline substances contained in Taiwan coconut oil, Aomori coconut oil, Western red cedar oil, and the like. This naturally derived compound is now available as a synthetic product and is widely used in various fields such as antibacterial and antifungal agents, hair restoring agents, aromatherapy fragrances, toothpaste and food additives. Yes. However, since this tropolone compound has a low melting point of 52-53 ° C. and high sublimation and photodegradability, it has been difficult to maintain the above effects for a long time. Therefore, such a physiologically active substance or drug is gradually supplied so that internal or external preparations in which they are sustained-released are referred to as sustained-release drugs, sustained-release tablets, sustained-release preparations, sustained-release preparations, etc. It has been actively used.
これまでに、薬剤を無機層状物質と組み合わせて、徐放性、耐熱性あるいは分散性を改善する製薬に関する幾つかの手段が報告されている。トロポロン類化合物であるヒノキチオールを含む製品として、先行技術文献には、例えば、ヒノキチオール−粘土複合体を含む成形品、ヒノキチオールを含む粘土複合物、ヒノキチオールを含む殺菌剤組成物、ヒノキチオールを混合した品質保存剤（特許文献１〜４参照）や、セラミックス中の金属イオンにヒノキチオールを配位させることにより得られるセラミックス系組成物（特許文献５〜６参照）等が報告されている。 So far, several means relating to pharmaceuticals have been reported to improve sustained release, heat resistance or dispersibility by combining a drug with an inorganic layered substance. As a product containing hinokitiol which is a tropolone compound, the prior art documents include, for example, a molded article containing hinokitiol-clay complex, a clay compound containing hinokitiol, a fungicide composition containing hinokitiol, and a quality preservation mixed with hinokitiol. Agents (see Patent Documents 1 to 4), ceramic compositions obtained by coordinating hinokitiol to metal ions in ceramics (see Patent Documents 5 to 6), and the like have been reported.
そこで、これらの手段について詳しくみてみると、例えば、層状粘土成分の層間空隙中に、ヒノキチオールをゲストとして導入させる手段（特許文献１参照）、が提案されている。しかし、これは、熱可塑性樹脂に配合して成形することが困難であったヒノキチオールを粘土と複合し、成形品としたものに過ぎない。 Therefore, when these means are examined in detail, for example, means for introducing hinokitiol as a guest into the interlayer void of the layered clay component has been proposed (see Patent Document 1). However, this is merely a product obtained by combining hinokitiol, which has been difficult to be molded into a thermoplastic resin, with clay.
また、例えば、ヒノキチオールを油溶性抗菌防黴剤として含む粘土複合物（特許文献２参照）、ヒノキチオールを含む殺菌剤組成物（特許文献３参照）、ヒノキチオールとニンニク成分や唐辛子成分を含む品質保存剤（特許文献４参照）、が提案されている。しかし、これらは、上記生理活性物質を混合するのみであり、徐放性については考慮されておらず、これらの成分を無機層状化合物の層間に導入するものではない。 Further, for example, clay composite comprising hinokitiol as the oil soluble antimicrobial antifungal agent (see Patent Document 2), (see Patent Document 3) fungicidal composition comprising hinokitiol, quality preservation including hinokitiol and garlic ingredients and pepper component An agent (see Patent Document 4) has been proposed. However, these are only mixed with the above-mentioned physiologically active substance, and the sustained release property is not considered, and these components are not introduced between the layers of the inorganic layered compound.
また、セラミックス中に含まれるカルシウムイオン又はマグネシウムイオンにヒノキチオールを配位させて得られるセラミックス系組成物（特許文献５参照）、が提案されている。しかし、得られたヒノキチオール包接セラミックスは、セラミックスであるトバモライト、ゾノトライト等の層間にヒノキチオールを取り込んだという相互関係が明らかとされておらず、また、組成物のヒノキチオール含有率が数％程度と極めて低い。 A ceramic composition obtained by coordinating hinokitiol to calcium ions or magnesium ions contained in ceramics (see Patent Document 5) has been proposed. However, the obtained hinokitiol inclusion ceramics have not been shown to have a mutual relationship that hinokitiol is incorporated between layers of ceramics such as tobermorite and zonotolite, and the hinokitiol content of the composition is as high as several percent. Low.
更に、セラミックス中のカルシウムイオン又はマグネシウムイオンを他の金属イオンと交換し、導入された金属イオンにヒノキチオールを配位させて得られるヒノキチオール包接セラミックス（特許文献６参照）、が提案されている。しかし、これも、同様に、セラミックスである粘土鉱物の層間にヒノキチオールが挿入されたことを示す明確な実証はなされておらず、導入されたとされる金属イオン及びヒノキチオールの含有率も数％程度であり、積極的に粘土鉱物層間に生理活性物質を挿入するものではない。 Furthermore, hinokitiol inclusion ceramics obtained by exchanging calcium ions or magnesium ions in ceramics with other metal ions and coordinating hinokitiol to the introduced metal ions (see Patent Document 6) have been proposed. However, there is no clear demonstration that hinokitiol has been inserted between the layers of ceramic clay mineral, and the content of metal ions and hinokitiol that have been introduced is about several percent. Yes, it does not actively insert physiologically active substances between clay mineral layers.
また、金属イオンと粘土鉱物を複合化させることにより得られる抗菌性消臭剤（特許文献７参照）、が提案されている。しかし、これは、金属イオン溶液を粘土鉱物に噴霧して添着させるのみであり、層間担持や徐放性については特に考慮されていない。また、粘土鉱物と有機系塩基性物質の複合体にヒノキチオールやフラボノイド類を担持させて得られる抗菌防カビ剤（特許文献８参照）、が提案されている。しかし、これは、油溶性であるヒノキチオールやフラボノイド類を、塩基性物質で複合化して親油性を賦与した粘土鉱物複合体に混練する手段を採用しており、抗菌防カビ剤の積極的な粘土層間への固定化を行うものではない。 In addition, an antibacterial deodorant (see Patent Document 7) obtained by combining metal ions and clay minerals has been proposed. However, this only involves spraying the metal ion solution onto the clay mineral and attaching it, and no particular consideration is given to interlayer support and sustained release. Further, an antibacterial and antifungal agent obtained by supporting hinokitiol and flavonoids on a complex of a clay mineral and an organic basic substance (see Patent Document 8) has been proposed. However, this employs a means of kneading oil-soluble hinokitiol and flavonoids into a clay mineral complex that has been combined with a basic substance to impart lipophilicity, and is an active antibacterial and antifungal agent. It is not intended to fix between layers.
また、金属成分とヒノキチオール類成分を反応させた抗生物剤で、多孔質物質を処理して得られる材料（特許文献９参照）、が提案されている。しかし、これは、単に多孔質物質の表面に抗生物剤を固着させているのみであり、効果の持続性や徐放性について特に検討されていない。更に、ヒノキチオールの金属錯体を、多孔質表面に含浸処理を行うことで得られる材料（特許文献１０参照）、が提案されている。しかし、これも、物理的な表面処理を行うに留まっており、化学的あるいは電気的な手法を用いた固定化を行うものではない。 In addition, a material obtained by treating a porous substance with an antibiotic agent obtained by reacting a metal component and a hinokitiol component (see Patent Document 9) has been proposed. However, this is merely an antibiotic agent fixed on the surface of the porous material, and the sustainability of the effect and the sustained release property are not particularly examined. Furthermore, a material obtained by impregnating a porous surface with a metal complex of hinokitiol (see Patent Document 10) has been proposed. However, this is also only a physical surface treatment, and does not perform immobilization using a chemical or electrical technique.
更に、温水循環型の２４時間風呂等での使用を念頭に置いて、アメーバなどとの共存状態にあるレジオネラ属菌を制御する目的として、それらが共存している水系に対してヒノキチオール及びヒノキチオール金属錯体等を添加して制御する方法（特許文献１１、１２、１３参照）が提案されている。しかし、これらは、単にレジオネラ属菌を殺菌するために水系中に薬剤を添加するのみであり、抗レジオネラ属活性効果の徐放性については全く考慮していない。
Furthermore, with the aim of controlling Legionella spp. Coexisting with amoeba etc. with the use in a hot water circulation type 24-hour bath, etc., hinokitiol and hinokitiol metal for the water system in which they coexist A method of controlling by adding a complex or the like (see
また、レジオネラ属菌に対する殺菌剤として、ヒノキチオールをはじめとするトロポロン化合物の金属錯体の使用（特許文献１４参照）が提案されているが、その抗菌効果のみに着目しており、効果の持続性について言及していない。 In addition, the use of metal complexes of tropolone compounds such as hinokitiol has been proposed as a bactericidal agent against Legionella spp. (See Patent Document 14). Not mentioned.
更に、ヒノキチオールをはじめとするトロポロン骨格を有する有機物とフィトンチッドを、ゲル化剤並びに吸水性樹脂と混合して得られる抗レジオネラ属菌剤（特許文献１５参照）が提案されている。これは、ゲル状物質内にヒノキチオール類を封じ込めることにより、ゲル状物質からのヒノキチオール類の拡散を狙ったものである。しかし、ゲル状物質の含水率を制御することが困難であるため、ヒノキチオール類の拡散速度を自在に制御することは困難であり、ただ有効成分を揮発させるのみに留まる。その上、光分解性の高いヒノキチオールを錯体化せずにそのままの状態でゲル状物質に混合しているため、抗レジオネラ属菌効果の持続性に問題がある。 Furthermore, an anti-legionella bacterium (see Patent Document 15) obtained by mixing an organic substance having a tropolone skeleton such as hinokitiol and phytoncide with a gelling agent and a water-absorbing resin has been proposed. This aims at diffusion of hinokitiols from the gel material by enclosing the hinokitiols in the gel material. However, since it is difficult to control the moisture content of the gel substance, it is difficult to freely control the diffusion rate of hinokitiols, and only the active ingredient is volatilized. In addition, since hinokitiol, which has high photodegradability, is mixed with the gel-like substance as it is without being complexed, there is a problem in the durability of the anti-legionella genus effect.
このような状況の中で、本発明者らは、上記従来技術に鑑みて、有効成分の長期持続性、徐放性、耐熱性及び耐候性を兼備した機能性材料を開発することを目標として鋭意研究を積み重ねた結果、層状粘土鉱物の層間に、所定の生理活性機能を有するトロポロン化合物と抗レジオネラ属菌機能を有する金属イオンからなる有機金属錯体を層間挿入し、その層間からの有機金属錯体の放出量を制御することで、所期の目的を達成し得ることを見出し、本発明を完成するに至った。 Under such circumstances, the present inventors have aimed at developing a functional material that combines the long-term sustainability, sustained release, heat resistance and weather resistance of the active ingredient in view of the above-described conventional technology. intensive result of stacked studies, between layers of the layered clay mineral, and intercalated organic metal complex comprising a metal ion having a Toroporo emissions of compounds with anti-Legionella function having a predetermined physiologically active functions, from the interlayer The inventors have found that the intended purpose can be achieved by controlling the release amount of the organometallic complex, and the present invention has been completed.
すなわち、本発明は、低コストでかつ安全に、目的に応じた機能を賦与させることを可能とする、生理活性機能を有する抗レジオネラ属菌材料の製造方法、当該方法で製造される、生理活性機能の優れた持続性あるいは生理活性物質の徐放性とともに、耐熱性、耐候性、保水性、環境親和性を有する新規抗レジオネラ属菌材料、及びそれを有効成分として用いた抗レジオネラ菌加工製品を提供することを目的とするものである。また、本発明は、層間挿入の利点として、２５０℃付近の熱処理後においても明確な抗レジオネラ属効果の発現を可能とする耐熱性を賦与した抗レジオネラ属菌材料を提供することを目的とするものである。 That is, the present invention provides a method for producing an anti-Legionella material having a physiologically active function, which is capable of imparting a function according to the purpose at a low cost and safely, and a physiological activity produced by the method. A new anti-Legionella genus material that has heat resistance, weather resistance, water retention, environmental compatibility, as well as long-lasting functions or sustained release of physiologically active substances, and processed products of anti-Legionella bacteria using them as active ingredients Is intended to provide. Another object of the present invention is to provide an anti- Legionella bacterium material imparted with heat resistance that enables a clear anti- Legionella genus effect even after heat treatment at around 250 ° C. as an advantage of intercalation. Is.
上記課題を解決するための本発明は、以下の技術的手段から構成される。
（１）トロポロン化合物と抗菌性金属カチオンを錯体化した金属−トロポロン錯体を無機層状化合物の層間に担持してその生理活性機能の徐放性を向上させた抗レジオネラ属菌材料であって、
上記金属−トロポロン錯体が、金属カチオンに有機配位子のトロポロン化合物を配位させた、生理活性機能を有する金属−トロポロン錯体からなり、かつ、上記有機配位子のトロポロン化合物がヒノキチオールであり、上記無機層状化合物が、層間に交換性陽イオンを有するスメクタイト族粘土鉱物、バーミキュライト、膨潤性雲母のいずれか１種からなり、その陽イオン交換容量（ＣＥＣ）はＣＥＣ＝３０〜４００ミリ等量／１００ｇの範囲であり、かつ脱イオン水あるいは有機溶媒により膨潤させたものであり、
この無機層状化合物の層間に上記トロポロン化合物が該層間に存在する交換性陽イオンとの交換反応により金属−トロポロン錯体の形で挿入、担持されていて、粉末Ｘ線回折による（００１）回折線から計算される基底面間隔値が反応前の無機層状化合物の基底面間隔値より拡大し、かつ層構造に起因する（００３）回折線を示し、３００℃までの熱処理（空気中、昇温速度１０℃／分、保持１時間）に対して抗レジオネラ属菌活性を示すことを特徴とする金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料。
（２）生理活性機能を有する金属−トロポロン錯体を形成する金属カチオンが、Ｃｕ、Ｚｎ、ＮｉもしくはＡｌ又は遷移金属群の中から選ばれた少なくとも一種以上の金属イオンである、前記（１）に記載の金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料。
（３）スメクタイト族粘土鉱物が、モンモリロナイト、バイデライト、ノントロナイト、サポナイト、ヘクトライトもしくはスティーブンサイトであり、膨潤性雲母が、雲母粘土鉱物もしくはフッ化雲母である、前記（１）に記載の金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料。
（４）抗レジオネラ属菌材料が、銅−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料であって、粉末Ｘ線回折による層間内間隔が１．３１ｎｍ、低角度側に２．２８ｎｍ（００１）回折線を示し、又は、
ニッケル−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料であって、低角度側に１．５１ｎｍの（００１）回折線を示し、又は、
亜鉛−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料であって、低角度側に１．５２ｎｍの（００１）回折線を示し、又は、
アルミニウム−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料であって、低角度側に１．５９ｎｍの（００１）回折線を示す、前記（１）に記載の金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料。
（５）前記（１）から（４）のいずれかに記載の金属−トロポロン錯体を無機層状化合物の層間に担持させてその生理活性機能の徐放性を向上させた抗レジオネラ属菌材料を製造する方法であって、
上記無機層状化合物として、層間に交換性陽イオンを有するスメクタイト族粘土鉱物、バーミキュライト、膨潤性雲母のいずれか１種であり、その陽イオン交換容量（ＣＥＣ）がＣＥＣ＝３０〜４００ミリ等量／１００ｇの範囲のものを使用し、かつ脱イオン水あるいは有機溶媒により膨潤させ、
上記金属−トロポロン錯体として、金属カチオンに有機配位子のトロポロン化合物を配位させた金属−トロポロン錯体を使用し、かつ、上記有機配位子のトロポロン化合物として、ヒノキチオールを用いて、
上記無機層状化合物と、上記金属−トロポロン錯体を、有機溶媒の存在下で混合撹拌し、かつ５〜９０℃に加熱して、上記無機層状化合物の層間に存在する交換性陽イオンと、上記金属−トロポロン錯体との交換反応を進行させることにより、この無機層状化合物の層間に上記トロポロン化合物を金属−トロポロン錯体の形で挿入、担持させて、粉末Ｘ線回折による（００１）回折線から計算される基底面間隔値が反応前の無機層状化合物の基底面間隔値より拡大し、かつ層構造に起因する（００３）回折線を示し、３００℃までの熱処理（空気中、昇温速度１０℃／分、保持１時間）に対して抗レジオネラ属菌活性を示し、かつ、その生理活性機能の徐放性を向上させた抗レジオネラ属菌材料を製造することを特徴とする金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料の製造方法。
（６）生理活性機能を有する金属−トロポロン錯体を形成する金属カチオンが、Ｃｕ、Ｚｎ、ＮｉもしくはＡｌ又は遷移金属群の中から選ばれた少なくとも一種以上の金属イオンである、前記（５）に記載の金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料の製造方法。
（７）スメクタイト族粘土鉱物が、モンモリロナイト、バイデライト、ノントロナイト、サポナイト、ヘクトライトもしくはスティーブンサイトであり、膨潤性雲母が、雲母粘土鉱物もしくはフッ化雲母である、前記（５）に記載の金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料の製造方法。
（８）前記（１）から（４）のいずれかに記載の金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料を有効成分として含有し、製剤加工されていることを特徴とする抗レジオネラ属菌加工製品。
The present invention for solving the above-described problems comprises the following technical means.
(1) An anti-Legionella genus material in which a metal-tropolone complex obtained by complexing a tropolone compound and an antibacterial metal cation is supported between layers of an inorganic layered compound to improve the sustained release of its bioactive function,
The metal-tropolone complex is composed of a metal-tropolone complex having a physiologically active function in which an organic ligand tropolone compound is coordinated to a metal cation , and the organic ligand tropolone compound is hinokitiol , The inorganic layered compound is composed of any one of smectite group clay mineral having an exchangeable cation between layers , vermiculite, and swellable mica, and its cation exchange capacity (CEC) is CEC = 30 to 400 milliequivalent / It is in the range of 100 g and is swollen with deionized water or an organic solvent,
Metal above preparative Roporon compound between layers of the inorganic layered compound by exchange reaction between exchangeable cations present between the layers - insert in the form of tropolone complex, be supported, by powder X-ray diffraction (001) diffraction line basal spacing value calculated is larger than the basal plane spacing value of the inorganic layered compound before the reaction from, and due to the layer structure (003) diffraction line shows, heat treatment up to 300 ° C. (in air, Atsushi Nobori rate 10 ° C. / min, metal and wherein indicates Succoth anti Legionella activity against 1 hour) - anti Legionella materials interlayer carrying tropolone complex.
(2) In the above (1), the metal cation forming the metal-tropolone complex having a physiologically active function is at least one metal ion selected from Cu, Zn, Ni, Al, or a transition metal group An anti-legionella bacterium material carrying an interlayer-supported metal-tropolone complex as described.
( 3 ) The metal according to (1), wherein the smectite group clay mineral is montmorillonite, beidellite, nontronite, saponite, hectorite, or stevensite, and the swellable mica is mica clay mineral or fluorinated mica. -Anti-legionella genus material carrying a tropolone complex as an interlayer.
( 4 ) The anti-legionella genus material is an anti-legionella genus material in which a copper -hinokitiol complex is supported between layers, and the interlayer distance by powder X-ray diffraction is 1.31 nm, and the lower angle side is 2.28 nm (001) Shows diffraction lines, or
An anti-Legionella material carrying an interlayer-supported nickel-hinokitiol complex, showing a (001) diffraction line of 1.51 nm on the low angle side, or
An anti-legionella genus material intercalated with a zinc-hinokitiol complex, which exhibits a (001) diffraction line of 1.52 nm on the low angle side, or
An anti-legionella genus material carrying an aluminum-hinokitiol complex as an interlayer, and showing an (001) diffraction line at 1.59 nm on the low angle side, the interlayer-supporting anti-legionella complex according to (1) above Genus material.
( 5 ) An anti-Legionella material that improves the sustained release of the physiologically active function by supporting the metal-tropolone complex according to any one of (1) to ( 4 ) between layers of an inorganic layered compound. A way to
As above-inorganic layered compound is any one of the smectite group clay minerals, vermiculite, swellable mica having an exchangeable cation between layers, the cation exchange capacity (CEC) is CEC = 30 to 400 milliequivalents / use 100g range ones, or one swollen with deionized water or an organic solvent,
As the metal-tropolone complex, a metal-tropolone complex in which an organic ligand tropolone compound is coordinated to a metal cation, and using hinokitiol as the organic ligand tropolone compound,
And the inorganic layered compound, the metal - the tropolone complex, were mixed and stirred in the presence of an organic solvent, and heated to 5 to 90 ° C., and exchangeable cations present between layers of the inorganic laminar compound, the metal - the Rukoto allowed to proceed exchange reaction between tropolone complex, the interlayer metal the tropolone compound of the inorganic layered compound - insert in the form of tropolone complex, by collateral lifting, by powder X-ray diffraction (001) diffraction line The basal plane spacing value calculated from the equation is larger than the basal plane spacing value of the inorganic layered compound before the reaction, and shows (003) diffraction lines due to the layer structure, and heat treatment up to 300 ° C. (in air, rate of temperature increase) Metal-tropolone characterized by producing an anti-Legionella bacterium material exhibiting anti-Legionella bacterium activity at 10 ° C./min, holding 1 hour) and having improved sustained release of its physiological activity function A method for producing an anti-Legionella material carrying a complex between layers.
( 6 ) In the above ( 5 ), the metal cation forming the metal-tropolone complex having a physiologically active function is at least one or more metal ions selected from Cu, Zn, Ni, Al, or a transition metal group. A method for producing an anti-Legionella material comprising an interlayer-supported metal-tropolone complex as described.
( 7 ) The metal according to ( 5 ), wherein the smectite group clay mineral is montmorillonite, beidellite, nontronite, saponite, hectorite, or stevensite, and the swellable mica is mica clay mineral or fluorinated mica. A method for producing an anti-Legionella material having an interlayer-supported tropolone complex.
( 8 ) An anti-Legionella genus characterized in that it contains an anti-Legionella genus bacterial material that carries the metal-tropolone complex according to any one of (1) to ( 4 ) above as an active ingredient and is processed into a preparation. Bacteria processed product.
次に、本発明について更に詳細に説明する。
本発明の生理活性機能を有する抗レジオネラ属菌材料では、特に、主原料として、無機層状化合物、例えば、層状粘土鉱物、モンモリロナイト、バイデライト、ノントロナイト、サポナイト、ヘクトライト、スティーブンサイト等のスメクタイト族粘土鉱物、バーミキュライト、又は天然もしくは合成の膨潤性雲母鉱物もしくはフッ化雲母等を用いている。本発明は、この無機層状化合物の層間に、Ｃｕ、Ｚｎ、ＮｉもしくはＡｌ等又は遷移金属群の中から選ばれた少なくとも一種以上の金属イオンと、トロポロン化合物で形成された金属−トロポロン錯体を層間挿入、担持したことを特徴としている。
Next, the present invention will be described in more detail.
In the anti-Legionella material having a physiologically active function of the present invention, in particular, as a main raw material, an inorganic layered compound, for example, a layered clay mineral, montmorillonite, beidellite, nontronite, saponite, hectorite, stevensite, etc. Clay minerals, vermiculite, natural or synthetic swelling mica minerals or fluorinated mica are used. In the present invention, the interlayer of the inorganic layered compound, Cu, Zn, Ni or Al or the like, or at least one or more metal ions selected from among the transition metal group, a metal formed by Toroporo emissions of compounds - tropolone It is characterized by intercalation and support of the complex.
本発明は、金属−トロポロン錯体を無機層状化合物の層間に挿入、担持することにより、その層間からの金属−トロポロン錯体の放出量を制御することを可能としている。本発明は、無機層状化合物の層間と金属−トロポロン錯体の静電的な相互作用により、抗レジオネラ属菌機能の優れた持続性あるいは抗レジオネラ属菌物質の徐放性とともに、耐熱性、耐候性、保水性、環境親和性を有する新規抗レジオネラ属菌材料及びそれを用いた抗レジオネラ菌加工製品を製造し、提供することを可能とするものである。 The present invention makes it possible to control the release amount of the metal-tropolone complex from the interlayer by inserting and supporting the metal-tropolone complex between the layers of the inorganic layered compound. The present invention is based on the electrostatic interaction between the layer of the inorganic layered compound and the metal-tropolone complex, and has excellent durability of the anti-Legionella genus function or sustained release of the anti-Legionella genus substance, as well as heat resistance and weather resistance. It is possible to produce and provide a novel anti-Legionella material having water retention and environmental compatibility, and a processed product of anti-Legionella using the same.
本発明の主原料の無機層状化合物について詳しく説明する。粘土鉱物は、無機結晶物質であり、組成や構造によって様々な種類が存在するが、その基本構造は、どれも類似している。ここでは、これらの粘土鉱物の構造について説明する。粘土鉱物は一部の例外を除いて全て層状構造を有している。層状構造とは、無機結晶層が多数積み重なった積層構造である。 The inorganic layered compound as the main raw material of the present invention will be described in detail. Clay minerals are inorganic crystal substances, and there are various types depending on the composition and structure, but the basic structures are all similar. Here, the structure of these clay minerals will be described. All clay minerals have a layered structure with some exceptions. The layered structure is a laminated structure in which a large number of inorganic crystal layers are stacked.
例えば、ベントナイトの主成分であるモンモリロナイトを代表例として説明すると、モンモリロナイトは、層状ケイ酸塩鉱物の１種であるスメクタイト族に分類される粘土鉱物である。ケイ酸塩鉱物の結晶構造は、イオン半径の大きい酸素原子の数と配置により決まる。ケイ酸塩鉱物の基本構造は、１個のケイ酸原子を中心とした四面体の各頂点に酸素原子を有する正四面体である。大部分のケイ酸塩鉱物は、この正四面体の３個の原子を隣接した各々の四面体と共有することにより、１次元的な六角網目状の層を形成している。 For example, montmorillonite, which is the main component of bentonite, will be described as a representative example. Montmorillonite is a clay mineral classified into the smectite group, which is a kind of layered silicate mineral. The crystal structure of a silicate mineral is determined by the number and arrangement of oxygen atoms having a large ionic radius. The basic structure of a silicate mineral is a regular tetrahedron having an oxygen atom at each vertex of a tetrahedron centered on one silicate atom. Most silicate minerals share the three tetrahedron atoms with each adjacent tetrahedron to form a one-dimensional hexagonal network layer.
この四面体層の他に、Ｏ２−やＯＨ−などの陰イオンが八面体の各頂点に各々１個ずつ位置し、その中心にＡｌ３＋、Ｍｇ２＋などの陽イオンが存在し、各頂点の陰イオンが隣接した八面体同士を結びつけ、二次元的な網状をなす八面体層がある。これは、Ｍｇ、Ａｌなどの原子を中心とし、酸素原子が六配位している八面体と、その八面体が稜共有（酸素原子と酸素原子を結んだ辺を共有している）によって二次元的な網目状を形成している八面体層である。 In addition to this tetrahedral layer, one anion such as O 2− and OH − is located at each vertex of the octahedron, and cations such as Al 3+ and Mg 2+ are present at the center. There is an octahedral layer in which two anions connect adjacent octahedrons to form a two-dimensional network. This is because the octahedron is centered on atoms such as Mg and Al and the oxygen atoms are six-coordinated, and the octahedron shares a ridge (the side that connects the oxygen atom and the oxygen atom is shared). It is an octahedral layer forming a dimensional network.
これらの四面体層と八面体層との結びつきは、各層が１枚ずつの二層構造（１：１型）、二枚の四面体層の間に八面体層が挟まった構造（２：１型）、２：１型の層間域に八面体層が位置する構造（２：１：１型）、等があり、四面体層と八面体層の様々な組み合わせ方で、一組の単位層を形成している。 The connection between these tetrahedral layers and octahedral layers is a two-layer structure (1: 1 type) in which each layer is one, and a structure in which an octahedral layer is sandwiched between two tetrahedral layers (2: 1 Type), a structure in which an octahedral layer is located in an interlayer region of 2: 1 type (2: 1: 1 type), etc., and a combination of tetrahedral layer and octahedral layer, a set of unit layers Is forming.
モンモリロナイトの結晶構造は、ケイ酸四面体層−アルミナ八面体層−ケイ酸四面体層の３層が積み重なっており（２：１型）、その単位層は、厚さ約１０Å（１ｎｍ）、広がり０．１〜１μｍという極めて薄い板状になっている。アルミナ八面体層の中心原子であるＡｌ３＋の１部がＭｇ２＋に置換されることで陽電荷不足となり、各結晶層自体は負に帯電しているが、結晶層間にＮａ＋、Ｋ＋、Ｃａ２＋、Ｍｇ２＋等の陽イオンを挟むことで電荷不足を中和し、モンモリロナイトは、安定状態となる。 The montmorillonite crystal structure is composed of three layers of silicate tetrahedral layer-alumina octahedral layer-silicate tetrahedral layer (2: 1 type), and the unit layer is about 10 mm (1 nm) thick and spreads. It has a very thin plate shape of 0.1 to 1 μm. A portion of Al 3+ that is the central atom of the alumina octahedral layer is replaced with Mg 2+ , resulting in insufficient positive charge, and each crystal layer itself is negatively charged, but Na + , K + , By sandwiching cations such as Ca 2+ and Mg 2+ , neutralization of charge shortage is achieved, and montmorillonite becomes stable.
そのため、モンモリロナイトは結晶層が何層も重なり合った状態で存在しており、層と層の間には、陽イオンと空隙が存在している。層表面の負電荷及び層間陽イオンが様々な作用を起こすことによって、モンモリロナイトの特異的性質は発揮される。モンモリロナイト単位層表面の負電荷と層間陽イオンとの結合力は弱いため、他のイオンを含む溶液と接触すると、層間陽イオンと液中の陽イオンは瞬間的に交換反応を起こし、陽イオン交換反応が生じる。 Therefore, montmorillonite is present in a state in which a number of crystal layers overlap each other, and cations and voids exist between the layers. The specific properties of montmorillonite are exhibited by the negative charge on the surface of the layer and interlayer cations causing various actions. Since the binding force between the negative charge on the surface of the montmorillonite unit layer and the interlayer cation is weak, when it comes into contact with a solution containing other ions, the interlayer cation and the cation in the liquid instantaneously undergo an exchange reaction, resulting in cation exchange. A reaction occurs.
水中に放出された陽イオンの量を測定すれば、モンモリロナイトの反応関与電荷量（陽イオン交換容量：ＣＥＣ）を知ることができる。陽イオン交換容量は、溶液のｐＨや濃度によって変わり、モンモリロナイトは、ｐＨ６以上になると陽イオン交換容量が増加することが知られている。モンモリロナイトは層状構造を成しているため、極めて大きな表面積を有している。その表面上において、層表面の酸素原子や水酸基との水素結合、層間において、層間負電荷や層間陽イオンとの静電気的結合などが生じ、吸着能を発揮し、それは、特に極性分子に対して作用しやすい。 By measuring the amount of cations released into water, the amount of charge involved in the reaction (cation exchange capacity: CEC) of montmorillonite can be known. It is known that the cation exchange capacity varies depending on the pH and concentration of the solution, and montmorillonite is known to increase the cation exchange capacity when the pH is 6 or more. Since montmorillonite has a layered structure, it has a very large surface area. On the surface, hydrogen bonds with oxygen atoms and hydroxyl groups on the surface of the layer, and electrostatic bonds with interlayer negative charges and interlayer cations occur between layers, exhibiting adsorptive capacity, especially for polar molecules Easy to act.
本発明において、無機層状化合物とは、層間に交換性陽イオンを有する層状ケイ酸塩鉱物を意味する。層状ケイ酸塩としては、特に限定されないが、例えば、モンモリロナイト、バイデライト、ノントロナイト、サポナイト、ヘクトライト、スティーブンサイト等のスメクタイト族粘土鉱物、バーミキュライト、膨潤性雲母として雲母粘土鉱物もしくはフッ化雲母等が例示される。層状ケイ酸塩及び膨潤性雲母は、天然物でも合成物であっても良く、これらの１種又は２種以上を併用して用いることも適宜可能である。 In the present invention, the inorganic layered compound means a layered silicate mineral having an exchangeable cation between layers. The layered silicate is not particularly limited. For example, smectite group clay minerals such as montmorillonite, beidellite, nontronite, saponite, hectorite, and stevensite, vermiculite, swellable mica, mica clay mineral or fluorinated mica Is exemplified. The layered silicate and the swellable mica may be natural products or synthetic products, and one or more of these may be used in combination as appropriate.
このような層状ケイ酸塩の中でも、スメクタイト族のモンモリロナイト及び膨潤性雲母が好ましい。上記層状ケイ酸塩及び膨潤性雲母は、水と接触すると、水を吸着して膨らむ（膨潤する）作用があり、これは、層間陽イオンと水分子との相互作用によって生じる。上記層状ケイ酸塩及び膨潤性雲母の単位層表面の負電荷と層間陽イオンとの結合力は、層間陽イオンと水分子の相互作用エネルギーより弱いため、層間陽イオンが水分子を引き寄せる力により層間が押し広げられる。この層間陽イオンと水分子の相互作用により層間挿入反応が容易に進行しやすくなる。 Among such layered silicates, smectite montmorillonite and swellable mica are preferred. When the layered silicate and the swellable mica are in contact with water, the layered silicate and the swellable mica have an action of adsorbing and swelling (swell) water, and this is caused by the interaction between interlayer cations and water molecules. The binding force between the negative charge on the unit layer surface of the layered silicate and swellable mica and the interlayer cation is weaker than the interaction energy between the interlayer cation and water molecule, so the interlayer cation attracts water molecules. The layers are spread out. The intercalation reaction easily proceeds due to the interaction between the interlayer cations and water molecules.
三次元結晶層が負電荷を帯びているモンモリロナイトに代表されるスメクタイト族粘土鉱物や膨潤性雲母等は、イオン交換性、膨潤性、有機あるいは無機複合体形成能等の化学的活性が顕著であり、これらの交換反応が自然界の物質循環に果たす役割は大きく、また、粘土鉱物や膨潤性雲母の工業的利用面でもイオン交換能は直接的間接的に用いられている。粘土鉱物や膨潤性雲母と様々な物質との複合体の形成は、極性分子の吸着や、イオン交換能等を含めた粘土層内表面による吸着現象である。 Smectite clay minerals such as montmorillonite, which has a negative three-dimensional crystal layer, and swellable mica have remarkable chemical activities such as ion exchange, swelling, and organic or inorganic complex formation ability. These exchange reactions play a large role in the natural material circulation, and the ion exchange capacity is directly and indirectly used in industrial applications of clay minerals and swellable mica. The formation of complexes between clay minerals and swellable mica and various substances is an adsorption phenomenon by the surface of the clay layer including the adsorption of polar molecules and ion exchange ability.
代表的な複合体は、粘土と各種の有機化合物との複合体であり、スメクタイト族粘土鉱物や膨潤性雲母等の利用をはじめ、自然現象の解釈等にも広く利用されている。すなわち、モンモリロナイト以外の、イオン交換能を有するスメクタイト族粘土鉱物や、イオン交換能を有する膨潤性雲母等を本発明に用いた場合でも、本発明による金属−トロポロン錯体を無機層間に担持した抗レジオネラ属菌材料を、イオン交換反応を用いて形成し得ることは可能であり、それらは同様に実施が可能である。 A typical composite is a composite of clay and various organic compounds, and is widely used for interpretation of natural phenomena, including the use of smectite group clay minerals and swellable mica. That is, even when a smectite group clay mineral having ion exchange ability or swelling mica having ion exchange ability other than montmorillonite is used in the present invention, the anti-legionella carrying the metal-tropolone complex according to the present invention between inorganic layers. It is possible that the genus material can be formed using an ion exchange reaction and they can be implemented as well.
層状ケイ酸塩の層間に存在する交換性陽イオンとは、結晶表面上のナトリウム、カルシウム等のイオンであり、これらのイオンは、カチオン性物質に対してイオン交換性を有するので、カチオン性を有する種々の物質を層状ケイ酸塩の層間に挿入することができる。層状ケイ酸塩の陽イオン交換容量（ＣＥＣ）は、特に限定されないが、ＣＥＣ＝３０〜４００ミリ等量／１００ｇであることが好ましい。 The exchangeable cation existing between the layers of the layered silicate is an ion such as sodium or calcium on the crystal surface, and these ions have an ion exchange property with respect to the cationic substance. Various materials can be inserted between the layered silicate layers. The cation exchange capacity (CEC) of the layered silicate is not particularly limited, but is preferably CEC = 30 to 400 milliequivalent / 100 g.
３０ミリ等量／１００ｇ未満であると、陽イオン交換によって結晶層間に挿入できる生理活性物質の量が少なくなるので、生理活性機能の発現と持続性が充分に発揮できない可能性がある。一方、４００ミリ等量／１００ｇを超えると、層状ケイ酸塩の層間の結合力が強固となり、生理活性物質の層間挿入が困難になることがある。 If the amount is less than 30 milliequivalents / 100 g, the amount of the physiologically active substance that can be inserted between the crystal layers by cation exchange decreases, so that the expression and sustainability of the physiologically active function may not be sufficiently exhibited. On the other hand, when it exceeds 400 milliequivalents / 100 g, the bonding strength between the layers of the layered silicate becomes strong, and the intercalation of the physiologically active substance may be difficult.
無機層状化合物は、市販されているものを使用することができ、市販されているスメクタイト系層状ケイ酸塩としては、例えば、「クニピアシリーズ」、「スメクトンシリーズ」（クニミネ工業株式会社）や、市販されている膨潤性マイカやスメクタイト系層状ケイ酸塩としては、例えば、「ＴＮシリーズ」、「ＴＳシリーズ」、「ＮＨＴシリーズ」（トピー工業株式会社）、「ルーセンタイトシリーズ」「ミクロマイカシリーズ」「ソマシフシリーズ」（コープケミカル株式会社）等を挙げることができる。いずれの市販品も、結晶構造、陽イオン交換容量や比表面積等その性質に応じて種々のグレードがあるが、本発明では、いずれも用いることができる。 Commercially available inorganic layered compounds can be used. Examples of commercially available smectite layered silicates include “Kunipia Series”, “Smecton Series” (Kunimine Industries Co., Ltd.) and Examples of commercially available swellable mica and smectite layered silicates include “TN series”, “TS series”, “NHT series” (Topy Industries, Ltd.), “Lucentite series” and “Micro mica series”. "Somasif series" (Coop Chemical Co., Ltd.). Any commercially available product has various grades depending on its properties such as crystal structure, cation exchange capacity and specific surface area, but any of them can be used in the present invention.
本発明において、生理活性機能を有する金属−トロポロン錯体については、錯体を形成する有機配位子であるトロポロン化合物として、ヒノキチオールが使用される。錯体を形成する中心金属としては、Ｃｕ、Ｚｎ、ＮｉもしくはＡｌ等又は遷移金属の群の中から選ばれた少なくとも一種以上の金属イオンのオキシ塩化物、塩化物、硝酸塩、硫酸塩、炭酸塩、酢酸塩、塩酸塩等の水和物等が例示される。 In the present invention, a metal having a physiologically active functions - For tropolone complex, as Toroporo emissions of compound is an organic ligand which forms a complex, hinokitiol is used. As the central metal forming the complex, Cu, Zn, Ni, Al or the like, or at least one metal ion selected from the group of transition metals, oxychloride, chloride, nitrate, sulfate, carbonate, Examples thereof include hydrates such as acetates and hydrochlorides.
本発明において、生理活性機能を有する金属−トロポロン錯体は、無機層状化合物の層間に物理的あるいは静電的に保持されている。すなわち、無機層状化合物の層間は、一般には、陽イオンが静電的に保持されているが、本発明においては、層間に生理活性機能を有する金属−トロポロン錯体が保持されている。 In the present invention, the metal-tropolone complex having a physiologically active function is physically or electrostatically held between the layers of the inorganic layered compound. That is, in general, a cation is electrostatically held between layers of an inorganic layered compound, but in the present invention, a metal-tropolone complex having a physiologically active function is held between layers.
本発明の生理活性機能を有する金属−トロポロン錯体を層間に取り込んだ抗レジオネラ属菌材料を製造するには、例えば、次のような方法によることができる。先ず、無機層状化合物を任意の重量分計量する。これに脱イオン水を適量添加し、充分に撹拌を行い、無機層状化合物の重量濃度が０．１〜１０ｗｔ％程度となる無機層状化合物懸濁液を調製する。次に、使用する無機層状化合物の陽イオン交換容量に対し、０．１〜３倍量分の脱イオン水あるいは有機溶媒の金属塩溶液を調製する。 In order to produce an anti-Legionella material that incorporates a metal-tropolone complex having a physiologically active function of the present invention between layers, for example, the following method can be used. First, the inorganic layered compound is weighed arbitrarily. An appropriate amount of deionized water is added thereto, and the mixture is sufficiently stirred to prepare an inorganic layered compound suspension in which the inorganic layered compound has a weight concentration of about 0.1 to 10 wt%. Next, 0.1 to 3 times the amount of deionized water or a metal salt solution of an organic solvent is prepared with respect to the cation exchange capacity of the inorganic layered compound to be used.
一方で、この陽イオン交換容量当量に対し、０．３〜９倍量分のトロポロン化合物を秤量し、脱イオン水あるいは有機溶媒に溶解し、トロポロン化合物溶液を得る。この時使用する有機溶媒は、金属塩あるいはトロポロン化合物が溶解すれば良く、例えば、メタノール、エタノール、１−プロパノール、２−プロパノール及びアセトン等が使用できる。次に、金属塩溶液とトロポロン化合物溶液を充分に混合撹拌し、金属−トロポロン錯体を得る。必要であれば、加熱により、錯体形成反応を促進しても良い。 On the other hand, with respect to the cation exchange capacity equivalent, it was weighed Toroporo emissions of compounds of 0.3 to 9 times amount, dissolved in deionized water or an organic solvent to give a Toroporo emissions of compound solution. The organic solvent used at this time may be dissolved metal salt or Toroporo emissions of compounds, such as methanol, ethanol, 1-propanol, 2-propanol and acetone or the like can be used. Then, the metal salt solution and Toroporo emissions of compound solution was thoroughly mixed and stirred, metal - obtain tropolone complex. If necessary, the complex formation reaction may be accelerated by heating.
合成された金属−トロポロン錯体は、使用する金属溶液や溶媒の種類により、溶液状態あるいは懸濁液状態として得ることができる。この金属−トロポロン錯体をあらかじめ分散させておいた無機層状化合物懸濁液中に投入し、撹拌しながら陽イオン交換反応を行うことで、金属−トロポロン錯体を無機層状化合物の層間に挿入する。交換反応速度は、混合した上記懸濁液を加熱することで、早めることができる。反応は、懸濁液温度が５℃付近からでも進行するが、５〜９０℃付近までの加熱を行い、交換反応を円滑に進行させることが望ましい。反応時間は、設定した温度条件によって変化するが、０．５〜７２時間程度が適当である。 The synthesized metal-tropolone complex can be obtained in a solution state or a suspension state depending on the type of metal solution or solvent used. The metal-tropolone complex is put into an inorganic layered compound suspension in which the metal-tropolone complex is dispersed in advance, and a cation exchange reaction is performed with stirring, whereby the metal-tropolone complex is inserted between the layers of the inorganic layered compound. The exchange reaction rate can be accelerated by heating the mixed suspension. Although the reaction proceeds even when the suspension temperature is around 5 ° C., it is desirable to heat the suspension up to about 5 to 90 ° C. to smoothly advance the exchange reaction. The reaction time varies depending on the set temperature condition, but about 0.5 to 72 hours is appropriate.
使用する中心金属イオンや有機配位子の種類によって、最適反応温度や反応時間は勿論異なる。加熱反応中には、反応系の水分が蒸発しないように、反応容器上部に水冷の冷却管を装備するのが好ましい。反応終了後、固液を分離洗浄して金属−トロポロン錯体を層間に取り込んだ抗レジオネラ属菌材料を得ることができる。乾燥方法は、特に限定されるものではないが、凍結乾燥、噴霧乾燥あるいは加熱乾燥等が挙げられる。更に、金属−トロポロン錯体を層間に取り込んだ抗レジオネラ属菌材料懸濁液を平面に展開・乾燥し、キャスト膜として得ることもできる。 Of course, the optimum reaction temperature and reaction time vary depending on the type of central metal ion and organic ligand used. It is preferable to equip the upper part of the reaction vessel with a water-cooled cooling tube so that the water in the reaction system does not evaporate during the heating reaction. After completion of the reaction, the solid-liquid is separated and washed to obtain an anti-Legionella material that incorporates the metal-tropolone complex between the layers. The drying method is not particularly limited, and examples thereof include freeze drying, spray drying, and heat drying. Furthermore, the anti- Legionella genus material suspension in which the metal-tropolone complex is taken in between the layers can be developed and dried on a flat surface to obtain a cast film.
本発明の生理活性機能を有する金属−トロポロン錯体を層間に担持した抗レジオネラ属菌材料は、そのままでの使用も勿論可能であるが、軟膏剤、クリーム剤、乳剤、ペレット等の、散布又は塗布に適した形態に製剤加工することができる。これらの加工製品を製造する方法は、特に限定されず、生理活性機能を有する金属−トロポロン錯体を層間に担持した抗レジオネラ属菌材料を油性基剤中に混合溶解する方法や、一般に用いられる方法により適宜製造することができる。 The anti-legionella bacterium material carrying the metal-tropolone complex having a physiologically active function of the present invention between layers can of course be used as it is, but it can be applied or applied to ointments, creams, emulsions, pellets, etc. The preparation can be processed into a form suitable for the above. The method for producing these processed products is not particularly limited, and a method of mixing and dissolving an anti-Legionella bacterium material carrying a metal-tropolone complex having a bioactive function between layers in an oily base or a generally used method Can be produced as appropriate.
本発明の生理活性機能を有する抗レジオネラ属菌材料は、無機層間に所定の生理活性機能を有する金属−トロポロン錯体がイオン化して存在している。そのため、生理活性機能を有する金属−トロポロン錯体の系外への徐放速度を制御できるため、抗レジオネラ属菌効果の持続性が極めて高い。目的や使用環境に応じて、生理活性機能を有する金属−トロポロン錯体を層間に担持した抗レジオネラ属菌材料と、他の有機あるいは無機材料と混合して成形体を形成して使用することも可能である。 In the anti-Legionella material having a physiologically active function of the present invention, a metal-tropolone complex having a predetermined physiologically active function is ionized between inorganic layers. Therefore, the sustained release rate of the metal-tropolone complex having a physiologically active function to the outside of the system can be controlled, so that the anti-Legionella effect is extremely high. Depending on the purpose and environment of use, it is also possible to mix and use anti-Legionella material that has a metal-tropolone complex with a bioactive function between layers and other organic or inorganic materials to form a molded body. It is.
本発明の生理活性機能を有する金属−トロポロン錯体を層間に担持した抗レジオネラ属菌材料は、無機層間に金属−トロポロン錯体が、静電的に固定化されて存在している。そのため、本発明の抗レジオネラ属菌材料の合成に使用する無機層状化合物を、陽イオン交換容量や結晶構造、比表面積等から適宜選択して、層の荷電量と電荷分布割合を考慮することにより、層間内における生理活性機能を有する金属−トロポロン錯体の保有量や、層間内における生理活性機能を有する金属−トロポロン錯体の保持力を制御することができる。 The anti-Legionella genus material carrying the metal-tropolone complex having a physiologically active function of the present invention between layers has the metal-tropolone complex electrostatically immobilized between the inorganic layers. Therefore, by selecting the inorganic layered compound used for the synthesis of the anti-legionella material of the present invention from the cation exchange capacity, crystal structure, specific surface area, etc., and considering the charge amount and charge distribution ratio of the layer The amount of the metal-tropolone complex having a physiologically active function in the interlayer and the retention force of the metal-tropolone complex having a physiologically active function in the interlayer can be controlled.
すなわち、本発明では、上記因子を選択、制御することで、生理活性作用を有する金属−トロポロン錯体が徐々に放たれて行く徐放速度を制御することが可能であるから、生理活性効果の程度及び持続性を制御することができ、また、持続性を極めて長くすることもできる。目的や使用環境に応じて、生理活性機能を有する金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料と、他の有機あるいは無機材料と混合して成形体を形成して使用することも可能である。 That is, in the present invention, by selecting and controlling the above factors, it is possible to control the sustained release rate at which the metal-tropolone complex having a physiological activity is gradually released. And the persistence can be controlled, and the persistence can be very long. Depending on the purpose and environment of use, it is also possible to mix the anti-legionella genus material with a layer-supported metal-tropolone complex with bioactive function and other organic or inorganic materials to form a molded product. is there.
従来、層間支柱を有する層状粘土成分と、その層間空隙中にゲストとしてヒノキチオールを導入したヒノキチオール−粘土複合体や、塩基交換能を有する膨潤性粘土に抗菌防黴剤及び塩基性物質を含有させた粘土複合物、ヒノキチオール等の殺菌剤と水膨潤性粘土鉱物との複合体、セラミックス中に含まれるカルシウムイオン又はマグネシウムイオンにヒノキチオールを配位、包接させたセラミックス系組成物等が提案されている。しかし、それらは、ヒノキチオール単体を粘土ないしセラミックスに混合又は配位させたものであり、その徐放効果は限られたものであり、高い徐放性を付与することは困難であった。 Conventionally, an antibacterial antifungal agent and a basic substance are contained in a layered clay component having interlayer struts, a hinokitiol-clay complex in which hinokitiol is introduced as a guest in the interlayer gap, and a swellable clay having base exchange ability. Clay composites, composites of fungicides such as hinokitiol and water-swellable clay minerals, ceramic compositions in which hinokitiol is coordinated and included in calcium ions or magnesium ions in ceramics, etc. have been proposed. . However, they are those in which hinokitiol alone is mixed or coordinated with clay or ceramics, and its sustained release effect is limited, and it has been difficult to impart high sustained release properties.
これに対して、本発明では、主原料として、層間に交換性陽イオンを有し、所定の陽イオン交換容量（ＣＥＣ）を有する無機層状化合物を用いること、無機層状化合物の層間に生理活性機能を有する金属−トロポロン錯体を挿入して、そのカチオン交換性を利用してこの無機層状化合物の層間に存在する交換性陽イオンと、生理活性機能を有する金属−トロポロン錯体を交換すること、それにより、トロポロン化合物を金属−トロポロン錯体の形で層間に担持させること、が重要であり、それにより、金属−トロポロン錯体を無機層状化合物の層間に安定に担持させて、著しく徐放性を向上させた有機無機複合材料を合成することを実現可能としたものである。
In contrast, in the present invention, an inorganic layered compound having an exchangeable cation between layers and having a predetermined cation exchange capacity (CEC) is used as a main raw material, and a physiologically active function is provided between layers of the inorganic layered compound. A metal-tropolone complex having a bioactive function by exchanging the exchangeable cation existing between layers of this inorganic layered compound by utilizing its cation exchange property, thereby the Toroporo emissions of compounds metals - be supported between the layers in the form of tropolone complex, is important, thereby, the metal - and stably supported on the interlayer of tropolone complex inorganic layered compound, a significantly slow release This makes it possible to synthesize improved organic-inorganic composite materials.
本発明は、天然由来成分のトロポロン化合物と抗菌性金属イオンを錯体化し、静電的に粘土層間に固定化する技術と、高効率の生理活性効果の確認技術を確立した点において新規である。これまでのトロポロン化合物に関する既報特許のほとんどは、当該化合物の無機多孔質担体表面への物理的な吸着あるいは単純な混練手段を採用するに留まり、化学的手法による層間担持や徐放性制御について考慮されていない。生理活性物質は、この陽イオン交換反応を利用することで粘土層間に固定化されるため、生理活性機能の制御された持続性（生理活性物質の徐放性）とともに、耐熱・耐候・環境親和性の向上や、他構造部材との複合化による加工製品への展開等が達成される。 The present invention is novel in that it has established a technology for complexing a naturally derived tropolone compound and an antibacterial metal ion and electrostatically immobilizing them between clay layers, and a technology for confirming a highly efficient physiological activity effect. Most of the published patents related to tropolone compounds so far only employ physical adsorption or simple kneading means of the compounds on the inorganic porous support surface, and consider interlayer loading and controlled release control by chemical methods. It has not been. Since bioactive substances are immobilized between clay layers using this cation exchange reaction, the bioactive function is controlled (sustained release of bioactive substances), heat resistance, weather resistance, and environmental compatibility. The improvement of the property and the development to the processed product by combining with other structural members are achieved.
この粘土鉱物の層間内に金属−トロポロン錯体を担持した試剤は、トロポロン化合物の生理活性機能のみならず、金属イオン由来の生理活性機能をも同時に発現させることができるため、トロポロン化合物と結合させる金属イオンを適宜選択することで、抗菌能力や防カビ能力を自在に制御することが可能となる。更に、粘土鉱物層間内に陽イオン交換反応により担持できる金属錯体含有量を変化させることが可能であるため、使用目的に応じた試剤の材料設計が可能となる。すなわち、本発明では、使用環境中において問題視されていた生理活性成分の残効性、徐放性を改善し、必要とされる活性成分の施用量を制御し、かつ天候や利用形態等の外因性の環境変化に対して安定な活性を実現可能となるため、本発明の抗レジオネラ属菌材料は、生活、環境、農業及び医療福祉等の広範囲の分野での応用が期待される。 The reagent carrying a metal-tropolone complex between the layers of this clay mineral can simultaneously express not only the physiologically active function of the tropolone compound but also the physiologically active function derived from the metal ion. By appropriately selecting ions, it is possible to freely control the antibacterial ability and the antifungal ability. Furthermore, since it is possible to change the metal complex content that can be supported by the cation exchange reaction in the clay mineral layer, it is possible to design the material of the reagent according to the purpose of use. That is, in the present invention, it is possible to improve the residual effect and sustained release of a physiologically active ingredient that has been regarded as a problem in the environment of use, to control the required application amount of the active ingredient, and to adjust the weather, usage pattern, etc. Since it becomes possible to realize stable activity against exogenous environmental changes, the anti-Legionella material of the present invention is expected to be applied in a wide range of fields such as life, environment, agriculture and medical welfare.
本発明により、次のような効果が奏される。
（１）本発明により、生理活性機能を有する金属−トロポロン錯体を層間担持した新規抗レジオネラ属菌材料、及びそれを用いた加工製品を提供することができる。
（２）本発明の抗レジオネラ属菌材料は、特に、浴場施設や、我々の生活環境において大量の水を溜めて利用する場所、給湯設備、冷却塔、加湿装置、水景施設に利用可能であり、更に優れた生理活性機能、例えば、病害虫防除機能、雑草防除機能、抗微生物機能等の持続性や保水性、耐候性及び環境親和性を有し、生活環境や医療福祉環境、植物の組織培養、農業、植林をはじめとする林業全般、植物栽培などに応用可能である。
（３）本発明の抗レジオネラ属菌材料の層間では、生理活性機能を有する金属−トロポロン錯体が、ナノメートルオーダーで均一に分散しているため、抗レジオネラ属菌材料を培地表面あるいは田畑などに使用する場合でも、均一に散布又は塗布し、培地あるいは土などと均一に混合できるので、植物生長調節機能、病害虫防除機能、雑草防除機能、抗微生物機能等の生理活性作用を有効に及ぼすことができる。
（４）本発明の生理活性機能を有する金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料は、そのままでの使用も勿論可能であるが、活性機能を有する有機物や金属イオン、有機金属錯体の徐放速度を制御できるため、抗レジオネラ属菌効果の持続性が極めて高く、例えば、任意の形態に製剤加工した加工製品とすることもできる。
（５）低コストでかつ安全に、目的に応じた機能を賦与させた加工製品とすることができる。
（６）加工製品を製造する方法は、特に限定されず、生理活性機能を有する抗レジオネラ属菌材料を油性基剤中に混合溶解する方法や、一般に用いられている方法により製造することができる。
（７）加工製品は、使用環境に応じた合目的な設計が可能であるため、広範な産業分野での利用が可能となる。
The present invention has the following effects.
(1) According to the present invention, it is possible to provide a novel anti-Legionella material that carries a metal-tropolone complex having a physiologically active function as an interlayer, and a processed product using the same.
(2) The anti-Legionella material of the present invention can be used particularly for bath facilities, places where large amounts of water are stored and used in our living environment, hot water supply equipment, cooling towers, humidifiers, and waterscape facilities. Furthermore, it has superior physiological activity functions such as pest control function, weed control function, antimicrobial function, etc., sustainability, water retention, weather resistance and environmental compatibility, living environment, medical welfare environment, plant tissue culture It can be applied to agriculture, general forestry including plantation, and plant cultivation.
(3) Since the metal-tropolone complex having a physiologically active function is uniformly dispersed in the nanometer order between the layers of the anti-legionella genus material of the present invention, the anti-legionella genus material is applied to the surface of the culture medium or the field. Even when used, it can be sprayed or applied uniformly and mixed uniformly with culture medium or soil, etc., so that it can effectively exert physiological activities such as plant growth regulation function, pest control function, weed control function, antimicrobial function, etc. it can.
(4) The anti-legionella bacterium material carrying the intercalated metal-tropolone complex having a physiologically active function of the present invention can of course be used as it is, but organic substances, metal ions, organometallic complexes having an active function can be used. Since the sustained release rate can be controlled, the effect of anti-Legionella spp. Is extremely high, and for example, it can be a processed product that has been processed into a desired form.
(5) A processed product can be provided with functions according to the purpose at low cost and safely.
(6) The method for producing a processed product is not particularly limited, and can be produced by a method of mixing and dissolving an anti-Legionella material having a physiologically active function in an oily base or a commonly used method. .
(7) The processed product can be designed in a suitable manner according to the usage environment, so that it can be used in a wide range of industrial fields.
次に、実施例に基づいて本発明を具体的に説明するが、本発明は、以下の実施例によって何ら限定されるものではない。 EXAMPLES Next, although this invention is demonstrated concretely based on an Example, this invention is not limited at all by the following Examples.
（１）銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の製造
モンモリロナイト粉末（（株）クニミネ工業製、クニピアＦ）を丸底フラスコ中に所定量秤量し、脱イオン水を適量添加した後、充分に撹拌して、１〜２ｗｔ％のモンモリロナイトゾルを調製した。一方、陽イオン交換容量（ＣＥＣ）当量の塩化銅２水和物水溶液と、ＣＥＣに対して２倍量のヒノキチオール（Ｃ１０Ｈ１２Ｏ２）エタノール溶液を混合撹拌して、黄緑色の銅−ヒノキチオール錯体を得た。
(1) Production of anti-legionella genus material carrying a copper-hinokitiol complex between layers of inorganic layered compound montmorillonite A montmorillonite powder (Kunimine Industries, Ltd., Kunipia F) is weighed in a round bottom flask and removed. After adding an appropriate amount of ionic water, the mixture was sufficiently stirred to prepare a montmorillonite sol of 1 to 2 wt%. On the other hand, a copper chloride dihydrate aqueous solution equivalent to a cation exchange capacity (CEC) and a hinokitiol (C 10 H 12 O 2 ) ethanol solution twice as much as CEC were mixed and stirred, and a yellow-green copper- A hinokitiol complex was obtained.
この錯体を、あらかじめ調製しておいたモンモリロナイトゾルに添加し、４０℃で撹拌しながら４８時間保持して交換反応を行った。反応終了後、得られた生成物を脱イオン水により洗浄した後、４０℃電気乾燥機中で乾燥させ、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した生理活性機能を有する粉末状の抗レジオネラ属菌材料を得た。 This complex was added to a montmorillonite sol prepared in advance, and the exchange reaction was carried out with stirring at 40 ° C. for 48 hours. After completion of the reaction, the resulting product was washed with deionized water and then dried in an electric dryer at 40 ° C., and a powdery anti-legionella genus having a physiologically active function in which a copper-hinokitiol complex was supported between montmorillonite layers. A fungal material was obtained.
（２）銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料の確認試験
得られた銅−ヒノキチオール／粘土複合体は、原料モンモリロナイトよりも疎水性が高く、有機金属錯体の層間挿入が行われたことが示唆された。図１に、得られた銅−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料の粉末Ｘ線回折の結果を示す。この抗レジオネラ属菌材料の粉末Ｘ線回折の結果より、低角度側に２．２８ｎｍの（００１）回折線が確認された。この時の層間内間隔は１．３２ｎｍ程度であり、この層間距離は、銅−ヒノキチオール錯体が、銅を中心としてその周囲を包囲する配位子である２分子のヒノキチオールの七員環が、層平面に対して縦に直立している距離にほぼ相当する。
(2) Confirmation test of anti-legionella genus material carrying a copper-hinokitiol complex between montmorillonite layers The obtained copper-hinokitiol / clay complex is more hydrophobic than the raw material montmorillonite, and the intercalation of organometallic complexes is It was suggested that it was done. In FIG. 1, the result of the powder X-ray diffraction of the anti- Legionella genus material which carry | supported the obtained copper- hinokitiol complex between layers is shown. From the results of powder X-ray diffraction of the anti-Legionella material, (001) diffraction lines of 2.28 nm were confirmed on the low angle side. The inter-layer spacing at this time is about 1.32 nm, and this inter-layer distance is such that the seven-membered ring of two molecules of hinokitiol, which is a ligand surrounding the copper-hinokitiol complex around copper, is a layer. It corresponds approximately to the distance that stands vertically with respect to the plane.
更にまた、低角度側に１．３１ｎｍの回折線が確認されるが、これは、銅−ヒノキチオール錯体が層間内で平行に配列している距離にほぼ等しい。この系においては、銅−ヒノキチオール錯体は、２種類の立体配置でモンモリロナイトの層間に存在していることが判る。銅−ヒノキチオール錯体は、平面正方形の立体配座を示すが、ｔｒａｎｓ−型異性体は、広い抗菌スペクトルを示すことが知られている。 Furthermore, a diffraction line of 1.31 nm is confirmed on the low angle side, which is almost equal to the distance at which the copper-hinokitiol complexes are arranged in parallel between the layers. In this system, it can be seen that the copper-hinokitiol complex exists between montmorillonite layers in two different configurations. Copper-hinokitiol complexes exhibit a planar square conformation, but trans-type isomers are known to exhibit a broad antimicrobial spectrum.
比較のために、対照試料として図１に示した、無機層間にＮａ＋のみを担持した原料モンモリロナイトの粉末Ｘ線回折の結果より、モンモリロナイトの回折図形からは、粘土鉱物特有の回折ピークが多数確認された。基底面間隔とそれに起因する（００ｌ）の回折線と（０ｋｌ）回折線が確認され、（００１）回折線から計算された基底面間隔値は水一分子層を含む１．２４ｎｍであった。層間内の水分子のサイズを考慮すると、粘土層一層の厚さは０．９６ｎｍ程度となることが判った。 For comparison, a number of diffraction peaks peculiar to clay minerals were confirmed from the diffraction pattern of montmorillonite, based on the results of powder X-ray diffraction of raw material montmorillonite supporting only Na + between inorganic layers as shown in FIG. It was done. The basal plane spacing, the (00 l) diffraction line and the (0 kl) diffraction line resulting therefrom were confirmed, and the basal plane spacing value calculated from the (001) diffraction line was 1.24 nm including the water monomolecular layer. Considering the size of water molecules in the interlayer, it was found that the thickness of one clay layer was about 0.96 nm.
得られた銅−ヒノキチオール／粘土複合体について、ＣＨＮコーダーを用いた炭素含有率測定を行い、使用したモンモリロナイトの陽イオン交換容量に対して、挿入された銅−ヒノキチール錯体の交換率を計算した。その結果、交換性ナトリウムイオンとの交換率は８０％以上と見積もられ、目的とする抗レジオネラ属菌材料が合成されたことが確認された。 The obtained copper-hinokitiol / clay composite was measured for carbon content using a CHN coder, and the exchange rate of the inserted copper-hinokitiol complex was calculated with respect to the cation exchange capacity of the used montmorillonite. As a result, the exchange rate with exchangeable sodium ions was estimated to be 80% or more, and it was confirmed that the desired anti-legionella material was synthesized.
図２に、原料モンモリロナイトの赤外吸収スペクトルを示す。原料モンモリロナイトからは粘土鉱物特有の吸収である、３６２４ｃｍ−１に八面体のＡｌ−ＯＨ伸縮による吸収、３４３４ｃｍ−１に層間水分子のＯＨ伸縮振動による吸収が見られた。１６３９ｃｍ−１の吸収も吸着水のＯＨ伸縮振動による。また、１０３８ｃｍ−１には四面体Ｓｉ−Ｏ−Ｓｉ伸縮振動、９１４ｃｍ−１には八面体Ａｌ−ＯＨ変角振動、及び８４７ｃｍ−１には（Ａｌ、Ｍｇ）−ＯＨ変角振動に帰属する強い吸収が確認された。更に、５２０、４６７ｃｍ−１にはＳｉ−Ｏ−Ａｌ変角振動とＳｉ−Ｏ−Ｍｇ変角振動がそれぞれ確認された。 FIG. 2 shows an infrared absorption spectrum of the raw material montmorillonite. From the raw material montmorillonite, absorption due to octahedral Al—OH stretching was observed at 3624 cm −1, and absorption due to OH stretching vibration of interlaminar water molecules was observed at 3434 cm −1 , which are absorptions specific to clay minerals. Absorption at 1639 cm −1 is also due to OH stretching vibration of adsorbed water. Further, 1038 cm −1 is attributed to tetrahedral Si—O—Si stretching vibration, 914 cm −1 to octahedral Al—OH variable vibration, and 847 cm −1 to (Al, Mg) —OH variable vibration. Strong absorption was confirmed. Furthermore, Si-O-Al deformation vibration and Si-O-Mg deformation vibration were respectively confirmed at 520 and 467 cm- 1 .
図３に、得られた銅−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料と錯体の配位子であるヒノキチオールの赤外吸収スペクトルの結果を示した。銅−ヒノキチオール担持モンモリロナイトの赤外吸収スペクトルの結果より、２９６５、２８７３ｃｍ−１にＣＨ３基及び七員環のＣ−Ｈ伸縮振動、１５９３、１５１３ｃｍ−１の七員環分子骨格に帰属するＣ＝Ｃ伸縮振動が存在し、１４３４及び１３５６ｃｍ−１にＣＨ３基及び七員環のＣ−Ｈ変角振動、また、８１２、７４１ｃｍ−１には芳香環Ｃ−Ｈ変角振動による吸収が確認された。上記複合体の系についても、挿入有機物に特有の吸収と、それらの層間担持に伴う若干のシフトが確認され、これらのことからも、目的とする抗レジオネラ属菌材料が合成されたことが確認された。 FIG. 3 shows the results of the infrared absorption spectrum of the obtained anti-Legionella material carrying the copper-hinokitiol complex as an interlayer and hinokitiol, which is a ligand of the complex. From the results of the infrared absorption spectrum of the copper-hinokitiol-supported montmorillonite, 2965, 2873 cm −1 CH 3 group and seven-membered CH stretching vibration, 1593, 1513 cm −1 belonging to the seven-membered ring molecular skeleton C stretching vibration is present, and absorption due to CH 3 radicals and seven-membered C—H bending vibrations are observed at 1434 and 1356 cm −1 , and aromatic ring C—H bending vibrations are observed at 812 and 741 cm −1. It was. As for the above complex system, absorption specific to the inserted organic matter and a slight shift accompanying their interlaminar loading were confirmed, and from these, it was confirmed that the desired anti-legionella material was synthesized It was done.
（アルミニウム−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料の製造）
モンモリロナイト粉末（（株）クニミネ工業製、クニピアＦ）を丸底フラスコ中に所定量秤量し、脱イオン水を適量添加した後、充分に撹拌して、１〜２ｗｔ％のモンモリロナイトゾルを調製した。一方、陽イオン交換容量（ＣＥＣ）当量の塩化アルミニウム６水和物水溶液と、ＣＥＣに対して３倍量のヒノキチオール（Ｃ１０Ｈ１２Ｏ２）エタノール溶液を混合撹拌して、白色のアルミニウム−ヒノキチオール錯体を得た。
(Production of anti-legionella genus material carrying an aluminum-hinokitiol complex between montmorillonite layers)
A predetermined amount of montmorillonite powder (Kunipia F, manufactured by Kunimine Kogyo Co., Ltd.) was weighed into a round bottom flask, and after adding an appropriate amount of deionized water, the mixture was sufficiently stirred to prepare a 1-2 wt% montmorillonite sol. On the other hand, an aluminum chloride hexahydrate aqueous solution having an equivalent cation exchange capacity (CEC) and a hinokitiol (C 10 H 12 O 2 ) ethanol solution three times as much as CEC were mixed and stirred to produce white aluminum-hinokitiol. A complex was obtained.
この錯体を、あらかじめ調製しておいたモンモリロナイトゾルに添加し、４０℃で撹拌しながら４８時間保持して交換反応を行った。反応終了後、得られた生成物を脱イオン水により洗浄した後、４０℃電気乾燥機中で乾燥させ、粉末状のアルミニウム−ヒノキチオール錯体をモンモリロナイトの層間に担持した生理活性機能を有する抗レジオネラ属菌材料を得た。 This complex was added to a montmorillonite sol prepared in advance, and the exchange reaction was carried out with stirring at 40 ° C. for 48 hours. After completion of the reaction, the resulting product was washed with deionized water and then dried in an electric dryer at 40 ° C., and a powdery aluminum-hinokitiol complex was supported between layers of montmorillonite and had a physiologically active function. A fungal material was obtained.
（亜鉛−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料の製造）
モンモリロナイト粉末（（株）クニミネ工業製、クニピアＦ）を丸底フラスコ中に所定量秤量し、脱イオン水を適量添加した後、充分に撹拌して、１〜２ｗｔ％のモンモリロナイトゾルを調製した。一方、陽イオン交換容量（ＣＥＣ）当量の硝酸亜鉛６水和物水溶液と、ＣＥＣに対して２倍量のヒノキチオール（Ｃ１０Ｈ１２Ｏ２）エタノール溶液を混合撹拌して、亜鉛−ヒノキチオール錯体を得た。
(Production of anti-legionella genus material carrying zinc-hinokitiol complex between montmorillonite layers)
A predetermined amount of montmorillonite powder (Kunipia F, manufactured by Kunimine Kogyo Co., Ltd.) was weighed into a round bottom flask, and after adding an appropriate amount of deionized water, the mixture was sufficiently stirred to prepare a 1-2 wt% montmorillonite sol. On the other hand, an aqueous solution of zinc nitrate hexahydrate having an equivalent cation exchange capacity (CEC) and a hinokitiol (C 10 H 12 O 2 ) ethanol solution twice the amount of CEC are mixed and stirred to obtain a zinc-hinokitiol complex. Obtained.
この錯体を、あらかじめ調製しておいたモンモリロナイトゾルに添加し、４０℃で撹拌しながら４８時間保持して交換反応を行った。反応終了後、得られた生成物を脱イオン水により洗浄した後、４０℃電気乾燥機中で乾燥させ、亜鉛−ヒノキチオール錯体をモンモリロナイトの層間に担持した生理活性機能を有する粉末状の抗レジオネラ属菌材料を得た。 This complex was added to a montmorillonite sol prepared in advance, and the exchange reaction was carried out with stirring at 40 ° C. for 48 hours. After completion of the reaction, the obtained product was washed with deionized water and then dried in an electric dryer at 40 ° C., and a powdery anti-legionella genus having a bioactive function in which a zinc-hinokitiol complex was supported between montmorillonite layers. A fungal material was obtained.
（１）ニッケル−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料の製造
モンモリロナイト粉末（（株）クニミネ工業製、クニピアＦ）を丸底フラスコ中に所定量秤量し、脱イオン水を適量添加した後、充分に撹拌して、１〜２ｗｔ％のモンモリロナイトゾルを調製した。一方、陽イオン交換容量（ＣＥＣ）当量の硝酸ニッケル６水和物水溶液と、ＣＥＣに対して３倍量のヒノキチオール（Ｃ１０Ｈ１２Ｏ２）エタノール溶液を混合撹拌して、黄色のニッケル−ヒノキチオール錯体を得た。
(1) Production of anti-legionella genus material carrying nickel-hinokitiol complex between montmorillonite layers A predetermined amount of montmorillonite powder (Kunimine Industries, Ltd., Kunipia F) is weighed in a round bottom flask, and an appropriate amount of deionized water is obtained. After the addition, the mixture was thoroughly stirred to prepare a 1-2 wt% montmorillonite sol. On the other hand, a nickel nitrate hexahydrate aqueous solution having a cation exchange capacity (CEC) equivalent and a quinolthiol (C 10 H 12 O 2 ) ethanol solution three times as much as CEC were mixed and stirred to produce a yellow nickel-hinokitiol. A complex was obtained.
この錯体を、あらかじめ調製しておいたモンモリロナイトゾルに添加し、４０℃で撹拌しながら４８時間保持して交換反応を行った。反応終了後、得られた生成物を脱イオン水により洗浄した後、４０℃電気乾燥機中で乾燥させ、ニッケル−ヒノキチオール錯体をモンモリロナイトの層間に担持した生理活性機能を有する粉末状の抗レジオネラ属菌材料を得た。 This complex was added to a montmorillonite sol prepared in advance, and the exchange reaction was carried out with stirring at 40 ° C. for 48 hours. After completion of the reaction, the resulting product was washed with deionized water and then dried in an electric dryer at 40 ° C., and a powdery anti-legionella genus having a physiologically active function in which a nickel-hinokitiol complex was supported between montmorillonite layers. A fungal material was obtained.
（２）実施例２、３及び４のアルミニウム、亜鉛及びニッケル−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料の確認試験
上記実施例２、３及び４のアルミニウム、亜鉛及びニッケル−ヒノキチオール錯体を層間担持した抗菌抗レジオネラ属菌材料の粉末Ｘ線回折を行った。図４に、その結果を示す。粉末Ｘ線回折の結果より、モンモリロナイトの基底面間隔値は、層間のナトリウムイオンに水分子が配位した水分子１層分にほぼ相当する１．２４ｎｍであり、（００ｌ）と（ｈｋ０）回折線が確認された。
(2) Confirmation test of anti-Legionella material carrying the aluminum, zinc and nickel-hinokitiol complexes of Examples 2, 3 and 4 between montmorillonite layers Aluminum, zinc and nickel-hinokitiol of Examples 2, 3 and 4 Powder X-ray diffraction of the antibacterial anti-Legionella material carrying the complex between layers was performed. FIG. 4 shows the result. From the results of powder X-ray diffraction, the basal plane spacing value of montmorillonite is 1.24 nm, which is almost equivalent to one layer of water molecules in which water molecules are coordinated to sodium ions between layers, and (001) and (hk0) diffraction. The line was confirmed.
上記金属−ヒノキチオール錯体をモンモリロナイト懸濁液に投入すると、凝集塩効果による相分離が観察されたことにより、層間挿入反応が生じたことが示唆された。アルミニウム−ヒノキチオール錯体を挿入した試料は、層間距離が１．５９ｎｍにまで拡大した。この時の層間内距離は０．６３ｎｍであり、ヒノキチオールの７員環が層内に対して平行に２層配列した距離にほぼ等しい。また、長周期構造に起因する（００３）回折線と原料モンモリロナイトの（ｈｋ０）回折線も確認された。 When the metal-hinokitiol complex was added to the montmorillonite suspension, it was suggested that an intercalation reaction occurred due to the observed phase separation due to the aggregated salt effect. The sample in which the aluminum-hinokitiol complex was inserted expanded the interlayer distance to 1.59 nm. The distance between layers at this time is 0.63 nm, which is substantially equal to the distance in which two layers of 7-membered rings of hinokitiol are arranged in parallel to the inside of the layer. Moreover, the (003) diffraction line resulting from a long-period structure and the (hk0) diffraction line of raw material montmorillonite were also confirmed.
亜鉛−ヒノキチオール錯体を挿入した試料についても、同様の挙動が確認され、基底面間隔値は１．５２ｎｍであった。ニッケル−ヒノキチオール錯体を反応させた系では、基底面間隔値が１．５１ｎｍとなり、層構造に起因する（００３）と（００５）回折線も確認された。 The same behavior was confirmed for the sample in which the zinc-hinokitiol complex was inserted, and the basal plane spacing value was 1.52 nm. In the system in which the nickel-hinokitiol complex was reacted, the basal plane spacing value was 1.51 nm, and (003) and (005) diffraction lines due to the layer structure were also confirmed.
合成された複合体の基底面間隔値は、いずれも１．５ｎｍ程度であり、使用した遷移金属イオンの水和半径は、およそ水２分子に相当することを考えると、配位子が層間に対して（屈曲しながら）平行に配列した距離とほぼ等しい。この基底面間隔値は、金属錯体との反応前のモンモリロナイトの基底面間隔値である０．９６ｎｍと比較して、明らかに拡大しているため、これらの金属錯体が、モンモリロナイトの層間に挿入されたことが判明した。 Considering that the basal plane spacing values of the synthesized composites are all about 1.5 nm, and the hydration radius of the transition metal ions used is approximately equivalent to two molecules of water, the ligand is between the layers. On the other hand, it is almost equal to the distance arranged in parallel (while bending). Since this basal plane spacing value is clearly larger than 0.96 nm, which is the basal plane spacing value of montmorillonite before the reaction with the metal complex, these metal complexes are inserted between montmorillonite layers. Turned out to be.
（銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の抗レジオネラ属菌試験）
抗レジオネラ属菌試験のための供試菌として、レジオネラ属菌の１種であるレジオネラニューモフィラ株（Ｌｅｇｉｏｎｅｌｌａ ｐｎｅｕｍｏｐｈｉｌａ ＡＴＣＣ（アメリカンタイプカルチャーコレクション）３３１５２）を用いた。Ｌ字型試験管に１０ｍｌの滅菌リン酸緩衝生理食塩水（ｐＨ７．０±０．１）を用いて最終濃度５０、２５、１２．５、７．２５、３．１２、及び１．５６ｍｇ／ｌの銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の懸濁液を調製した。
(Anti-legionella bacterium test of anti-legionella genus material carrying copper-hinokitiol complex between layers of inorganic layered compound montmorillonite)
A Legionella pneumophila strain (Legionella pneumophila ATCC (American Type Culture Collection) 33152), which is one species of Legionella, was used as a test bacterium for the anti-Legionella genus test. Final concentrations of 50, 25, 12.5, 7.25, 3.12, and 1.56 mg / L using 10 ml of sterile phosphate buffered saline (pH 7.0 ± 0.1) in an L-shaped test tube. A suspension of anti-Legionella material carrying 1 copper-hinokitiol complex between layers of the inorganic layered compound montmorillonite was prepared.
約１０７ＣＦＵ／ｍｌに調製したレジオネラ属菌０．１ｍｌをそれぞれの管に接種して、３０℃、２４時間、１００ｒｐｍで振とう培養した後に、各管の上清５０μｌを新しいＢＣＹＥα培地に移植して、３７℃、７２時間培養した。培養後、菌の発育を阻止した最小濃度を最小殺菌濃度（ＭＢＣ）と判定した。対照試料として、モンモリロナイト層間に銅イオンのみを担持した試剤についても同様の試験を行った。 Each tube is inoculated with 0.1 ml of Legionella spp. Prepared to approximately 10 7 CFU / ml, cultured at 30 ° C. for 24 hours with shaking at 100 rpm, and then 50 μl of the supernatant of each tube is transferred to a new BCYEα medium. And cultured at 37 ° C. for 72 hours. After the culture, the minimum concentration at which the growth of the bacteria was inhibited was determined as the minimum bactericidal concentration (MBC). As a control sample, a similar test was also performed on a reagent carrying only copper ions between montmorillonite layers.
表１から明らかなように、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、明確な抗レジオネラ属菌効果を示し、銅イオンのみを担持した試剤と比較して高い抗レジオネラ属菌活性を示すことが明らかとなった。 As is clear from Table 1, the anti-legionella genus material in which the copper-hinokitiol complex is supported between the layers of montmorillonite exhibits a clear anti-legionella genus effect, and is higher in anti-legionella compared to the reagent supporting only copper ions. It became clear that it showed genus activity.
（銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の徐放性試験）
レジオネラ属菌の１種であるレジオネラニューモフィラ株（Ｌｅｇｉｏｎｅｌｌａ ｐｎｅｕｍｏｐｈｉｌａ ＡＴＣＣ３３１５２）を用いて、徐放性試験を行った。銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、１００．０ｍｇを秤量し、１０ｍｌの５％ＤＭＳＯ溶液に分散させて試験原液（１００００ｐｐｍ）を調製した。試験原液をローターミックス（ＡＴＲ）を用いて２０ｒｐｍの速度で常時回転させた。調製後、１、２０、４０、及び５０日目にサンプルの２ｍｌを用いて抗菌活性を測定した。試験方法は段落００７３、００７４に記載したとおりで、２０日目以降は、試料に対して活性測定の１日前に洗浄操作を行った。洗浄操作は、試験原液の２ｍｌを１５０００ｒｐｍ、５分間遠心分離した後、上澄みを除去し滅菌蒸留水に再懸濁する操作を３回繰り返し、１日間徐放させた後に抗菌活性試験に供した。
(Sustained release test of anti-Legionella material with copper-hinokitiol complex supported between layers of inorganic layered compound montmorillonite)
A sustained-release test was conducted using Legionella pneumophila strain (Legionella pneumophila ATCC33152), which is one species of the genus Legionella. 100.0 mg of the anti-legionella material carrying the copper-hinokitiol complex between the layers of the inorganic layered compound montmorillonite was weighed and dispersed in 10 ml of 5% DMSO solution to prepare a test stock solution (10000 ppm). The test stock solution was always rotated at a speed of 20 rpm using a rotor mix (ATR). After preparation, antibacterial activity was measured using 2 ml of the sample at 1, 20, 40, and 50 days. The test method was as described in paragraphs 0073 and 0074. From the 20th day onward, the sample was washed one day before the activity measurement. The washing operation was performed by centrifuging 2 ml of the test stock solution at 15000 rpm for 5 minutes, then removing the supernatant and resuspending in sterilized distilled water three times.
表２から明らかなように、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、徐放期間５０日まで１２．５ｐｐｍの濃度で抗レジオネラ属菌活性を示すことが明らかとなった。２０日目以降で、洗浄操作時の上澄みの中にヒノキチオールと銅イオンが有効量残留していることを確認しており、活性中心は良好な錯体を形成している銅−ヒノキチオールであることが示唆された。 As is clear from Table 2, the anti-legionella material carrying the copper-hinokitiol complex between the layers of montmorillonite exhibits the anti-legionella activity at a concentration of 12.5 ppm up to 50 days of sustained release period. It was. On and after the 20th day, it has been confirmed that hinokitiol and copper ions remain in the supernatant at the time of the washing operation, and the active center is copper-hinokitiol forming a good complex. It was suggested.
（銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の耐洗浄試験）
レジオネラ属菌の１種であるレジオネラニューモフィラ株（Ｌｅｇｉｏｎｅｌｌａ ｐｎｅｕｍｏｐｈｉｌａ ＡＴＣＣ３３１５２）を用いて、耐洗浄試験を行った。銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、１００．０ｍｇを秤量し、１０ｍｌの５％ＤＭＳＯ溶液に分散させて試験原液（１００００ｐｐｍ）を調製した。（１）調製した懸濁液をローターミックス（ＡＴＲ）を用いて２０ｒｐｍの速度で１日間以上撹拌し、（２）この懸濁液を３０００ｒｐｍ１０分遠心後に上澄みを除去し２０％ＤＭＳＯ溶液で再懸濁し、（３）同様に、遠心後の上澄みを除去し滅菌蒸留水で再々懸濁し、（４）ローターミックス（ＡＴＲ）を用いて、２０ｒｐｍの速度で１日間以上撹拌した。（１）〜（４）の操作を１洗浄操作とし、１、３、５、１０、１５及び２０洗浄操作後の懸濁液を試料として採取し、抗菌活性試験に供した。
(Cleaning resistance test of anti-Legionella spp. Material with copper-hinokitiol complex supported between layers of inorganic layered compound montmorillonite)
A washing resistance test was performed using a Legionella pneumophila strain (Legionella pneumophila ATCC 33152), which is one species of the genus Legionella. 100.0 mg of the anti-legionella material carrying the copper-hinokitiol complex between the layers of the inorganic layered compound montmorillonite was weighed and dispersed in 10 ml of 5% DMSO solution to prepare a test stock solution (10000 ppm). (1) Stir the prepared suspension at a speed of 20 rpm for 1 day or more using a rotor mix (ATR). (2) After centrifuging the suspension at 3000 rpm for 10 minutes, remove the supernatant and resuspend it in a 20% DMSO solution. In the same manner as in (3), the supernatant after centrifugation was removed and suspended again with sterilized distilled water. (4) Using a rotor mix (ATR), the mixture was stirred for 1 day or more at a speed of 20 rpm. The operations (1) to (4) were set as one washing operation, and the suspensions after the 1, 3, 5, 10, 15 and 20 washing operations were collected as samples and subjected to an antibacterial activity test.
表３から明らかなように、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、洗浄回数２０回後でも２５ｐｐｍの濃度で抗レジオネラ属菌活性を示すことが明らかとなった。 As is apparent from Table 3, it was revealed that the anti-Legionella material having a copper-hinokitiol complex supported between montmorillonite layers exhibits anti-Legionella activity at a concentration of 25 ppm even after 20 washings.
（銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の温泉水を用いた抗レジオネラ属菌試験）
検水として、温泉（泉質は、ナトリウム塩化物・炭酸水素塩泉）の泉源から得られた湧出水（以下、泉源水という）及び泉源水を一時的に貯湯させておくタンクから得られた貯湯水（以下、貯湯タンク水という）を用いた。これらの検水は、予め新版レジオネラ症防止指針に基づくレジオネラ属菌検査を行い、検出限界以下（１０ＣＦＵ／１００ｍｌ未満）であることを確かめている。
(Anti-legionella bacterium test using hot spring water of anti-legionella genus material carrying a copper-hinokitiol complex between layers of montmorillonite, an inorganic layered compound)
As test water, it was obtained from spring water (hereinafter referred to as spring water) obtained from the hot spring (spring quality is sodium chloride / bicarbonate spring) and from a tank that temporarily stores the hot spring water. Hot water (hereinafter referred to as hot water tank water) was used. These water samples are preliminarily tested for Legionella genus based on the new edition of Legionellosis prevention guidelines and confirmed to be below the detection limit (less than 10 CFU / 100 ml).
抗レジオネラ属菌試験のための供試菌として、レジオネラ属菌の一種であるレジオネラニューモフィラ株（Ｌｅｇｉｏｎｅｌｌａ ｐｎｅｕｍｏｐｈｉｌａ ＡＴＣＣ（アメリカンタイプカルチャーコレクション）３３１５２）を用いた。１０ｍｌのＬ字型試験管に、泉源水及び貯湯タンク水を用いて、最終濃度５０、２５、１２．５、６．２５、３．１２、及び１．５６ｍｇ／ｌの銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の懸濁液を調製した。 A Legionella pneumophila strain (Legionella pneumophila ATCC (American Type Culture Collection) 33152), which is a kind of Legionella, was used as a test bacterium for the anti-Legionella genus test. In a 10 ml L-shaped test tube, using the spring water and hot water tank water, inorganic copper-hinokitiol complexes with final concentrations of 50, 25, 12.5, 6.25, 3.12, and 1.56 mg / l A suspension of anti-legionella material carried between layers of the layered compound montmorillonite was prepared.
約１０７ＣＦＵ／ｍｌに調製したレジオネラ属菌０．１ｍｌをそれぞれの管に接種して、３０℃、２４時間、１００ｒｐｍで振とう培養した後、更に、各管の上清５０μｌを新しいＢＣＹＥα培地に移植して、３７℃、４８時間培養した。培養後、菌の発育を阻止した最小濃度を最小殺菌濃度（ＭＢＣ）と判定した。 Each tube is inoculated with 0.1 ml of Legionella spp. Prepared at about 10 7 CFU / ml, cultured at 30 ° C. for 24 hours with shaking at 100 rpm, and then 50 μl of the supernatant of each tube is added to fresh BCYEα medium. And cultured at 37 ° C. for 48 hours. After the culture, the minimum concentration at which the growth of the bacteria was inhibited was determined as the minimum bactericidal concentration (MBC).
表４から明らかなように、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、温泉水中にあっても明確な抗レジオネラ属菌効果を示し、滅菌リン酸緩衝生理食塩水を用いたときと変わらない強い抗レジオネラ属菌活性を示すことが明らかとなった。 As is clear from Table 4, the anti-legionella genus material carrying the copper-hinokitiol complex between the layers of montmorillonite exhibits a clear anti-legionella bacterium effect even in hot spring water, and sterilized phosphate buffered saline It became clear that it showed strong anti- Legionella genus activity which is not different from the one used.
（銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の温泉水中持続性試験１）
レジオネラ属菌の一種であるレジオネラニューモフィラ株（Ｌｅｇｉｏｎｅｌｌａ ｐｎｅｕｍｏｐｈｉｌａ ＡＴＣＣ３３１５２）を用いて、抗レジオネラ属菌材料の温泉水中殺菌力持続性試験を行った。泉源水及び貯湯タンク水それぞれに、銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料を添加して、最終濃度５０ｍｇ／ｌの試験原液を３ｌずつ調製し、マグネチックスターラーを用いて、約１００ｒｐｍの速度で常時回転させた。
(Hot spring water sustainability test 1 of anti-Legionella spp. Material carrying copper-hinokitiol complex between layers of inorganic layered compound montmorillonite)
Using a Legionella pneumophila strain (Legionella pneumophila ATCC 33152), which is a kind of Legionella sp. Anti-Legionella material containing a copper-hinokitiol complex supported between layers of montmorillonite, an inorganic layered compound, is added to each source water and hot water tank water to prepare 3 liters of a test stock solution having a final concentration of 50 mg / l. Using a stirrer, it was always rotated at a speed of about 100 rpm.
調製日からの経過日の、１、３、４、８、１０、１１、１５、１７、２４、３０、３２、３６、３９、４３、４６、５０、５２、５７、６４、６７、及び９５日目の試験原液における抗レジオネラ属菌材料の抗菌活性を測定した。それぞれの経過日に、試験原液の１０ｍｌをＬ字型試験管に移し、レジオネラ属菌を接種して約１０５ＣＦＵ／ｍｌの菌液として、３０℃、２４時間、１００ｒｐｍで振とう培養した。更に、各管の上清５０μｌを新しいＢＣＹＥα培地に移植して、３７℃、４８時間培養した。培養後、菌の発育が認められなかった場合に、殺菌力ありと判定した。 1, 3, 4, 8, 10, 11, 15, 17, 24, 30, 32, 36, 39, 43, 46, 50, 52, 57, 64, 67, and 95 from the date of preparation The antibacterial activity of the anti-Legionella material in the day test stock solution was measured. On each elapsed day, 10 ml of the test stock solution was transferred to an L-shaped test tube, inoculated with Legionella spp., And cultured as a solution of about 10 5 CFU / ml with shaking at 30 ° C. for 24 hours at 100 rpm. Furthermore, 50 μl of the supernatant of each tube was transplanted to a new BCYEα medium and cultured at 37 ° C. for 48 hours. When the growth of the bacteria was not observed after the culture, it was determined that there was bactericidal activity.
表中の＋は、１０５ＣＦＵ／ｍＬのレジオネラ属菌を、２４時間の各試験原液との接触により、殺菌力試験の検出限界以下（２０ＣＦＵ／ｍｌ未満）まで減数させたことを示す。表５から明らかなように、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、各種温泉水の中で、９５日まで５０ｐｐｍの濃度で抗レジオネラ属菌活性を示すことが明らかとなった。 + In the table indicates that 10 5 CFU / mL of Legionella was reduced to below the detection limit of the bactericidal test (less than 20 CFU / ml) by contact with each test stock solution for 24 hours. As is apparent from Table 5, it is clear that the anti-legionella material carrying the copper-hinokitiol complex between the layers of montmorillonite exhibits anti-legionella activity at a concentration of 50 ppm up to 95 days in various hot spring waters. It became.
（銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の温泉水中持続性試験２）
レジオネラ属菌の一種であるレジオネラニューモフィラ株（Ｌｅｇｉｏｎｅｌｌａ ｐｎｅｕｍｏｐｈｉｌａ ＡＴＣＣ３３１５２）を用いて、抗レジオネラ属菌材料の温泉水中殺菌力持続性試験を行った。泉源水及び貯湯タンク水それぞれに、銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料を添加して最終濃度５０ｍｇ／ｌの試験原液を３ｌずつ調製し、マグネチックスターラーを用いて、約１００ｒｐｍの速度で常時回転させて、調製日からの経過日の、６４、及び９５日目の試験原液における抗レジオネラ属菌材料の抗菌活性を測定した。
(Hot spring water sustainability test 2 for anti-Legionella spp. Material carrying copper-hinokitiol complex between layers of inorganic layered compound montmorillonite)
Using a Legionella pneumophila strain (Legionella pneumophila ATCC 33152), which is a kind of Legionella sp. Anti-Legionella material containing a copper-hinokitiol complex between layers of montmorillonite, an inorganic layered compound, was added to each spring water and hot water storage tank water to prepare 3 liters of a test stock solution having a final concentration of 50 mg / l, and a magnetic stirrer. Was used to measure the antibacterial activity of the anti-Legionella material in the test stock solution on the 64th and 95th day after the preparation date.
それぞれの経過日に、試験原液の５００ｍｌを滅菌採水瓶に移して試験液とし、レジオネラ属菌を接種して約１０５ＣＦＵ／ｍｌの菌液を調製して、３０℃、２４時間、１００ｒｐｍで振とう培養した。培養後の試験液について、新版レジオネラ症防止指針に準拠してレジオネラ属菌検査を行った。 On each elapsed day, transfer 500 ml of the test stock solution to a sterile water collection bottle to make a test solution, inoculate with Legionella spp. To prepare a bacterial solution of about 10 5 CFU / ml at 30 ° C. for 24 hours at 100 rpm. Cultured with shaking. About the test liquid after culture | cultivation, the Legionella genus microbe test | inspection was performed based on the new edition Legionella disease prevention guideline.
すなわち、試験液を、直径４７ｍｍ、孔径０．４５μｍのポリカーボネートメンブランフィルター（ミリポア）で吸引ろ過した後、滅菌蒸留水５ｍｌに浮遊させて十分に撹拌し、５０℃、２０分間加温した上清の０．１ｍｌをＧＶＰＣ培地（日本ビオメリュー）に接種した。３５℃で数日間好気培養し、レジオネラ属菌を疑うコロニーが検出された場合は、システイン要求性試験、血清型別試験及びＰＣＲ試験を用いて同定した。最終的に１０日間まで培養して、レジオネラ属菌の発育を認めなかったものを検出限界以下とし、殺菌力ありと判定した。 Specifically, the test solution was suction filtered through a polycarbonate membrane filter (Millipore) having a diameter of 47 mm and a pore size of 0.45 μm, suspended in 5 ml of sterilized distilled water, sufficiently stirred, and heated at 50 ° C. for 20 minutes. 0.1 ml was inoculated into GVPC medium (Nihon Biomeryu). When a colony suspected to be Legionella was detected after aerobic culture at 35 ° C. for several days, it was identified using a cysteine requirement test, a serotype test, and a PCR test. Finally, the cells were cultured for up to 10 days, and those in which no growth of Legionella was recognized were determined to be below the detection limit, and determined to have bactericidal activity.
表中の＋＋は、１０５ＣＦＵ／ｍＬのレジオネラ属菌を、２４時間の各試験原液との接触によりレジオネラ属菌検査の検出限界以下（１０ＣＦＵ／１００ｍｌ未満）まで減数させたことを示す。表６から明らかなように、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、９５日まで、各種温泉水中５０ｐｐｍの濃度で、１ｍｌあたり約１０万個存在するレジオネラ属菌を一般に用いられているレジオネラ属菌検査の検出限界以下（１０ＣＦＵ／１００ｍｌ未満）まで減数させるほどの強い抗レジオネラ属菌活性を示すことが明らかとなった。 ++ in the table indicates that 10 5 CFU / mL of Legionella was reduced to below the detection limit of Legionella test (less than 10 CFU / 100 ml) by contact with each test stock solution for 24 hours. As is apparent from Table 6, the anti- Legionella genus material in which the copper-hinokitiol complex is supported between the layers of montmorillonite is a genus of about 100,000 Legionella genus per ml at a concentration of 50 ppm in various hot spring waters up to 95 days. It was revealed that the anti-Legionella bacterium activity was strong enough to reduce the number to below the detection limit of the commonly used Legionella bacterium test (less than 10 CFU / 100 ml).
（銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の熱処理後の抗菌試験）
銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ材料の耐熱性を検討するために、熱処理後の試料についての抗菌試験を行った。実施例１で得られた銅−ヒノキチオール粘土複合体について、電気炉を用いた熱処理（空気中、昇温速度１０℃／分、保持１時間）を行った。処理温度は、それぞれ２００、２５０、３００、４００及び５００℃とした。
(Antimicrobial test after heat treatment of anti-Legionella spp. Material carrying copper-hinokitiol complex between layers of inorganic layered compound montmorillonite)
In order to examine the heat resistance of the anti-legionella material in which the copper-hinokitiol complex is supported between the layers of montmorillonite, an antibacterial test was performed on the sample after the heat treatment. The copper-hinokitiol clay composite obtained in Example 1 was subjected to heat treatment using an electric furnace (in air, heating rate 10 ° C./min, holding 1 hour). The processing temperatures were 200, 250, 300, 400 and 500 ° C., respectively.
各熱処理温度にて得られた試料について、粉末Ｘ線回折による分析を行った。図５に、その結果を示す。粉末Ｘ線回折の結果より、未処理試料からは、２．２８ｎｍの基底面間隔値を示す回折線と、それに隣接して層構造に起因すると思われる回折線が確認された。配位子であるヒノキチオールは、銅イオンと２：１型の平面錯体を形成することが知られており、層間に対し直立して配置していると仮定すると、基底面間隔値は２．４５ｎｍとなる。 Samples obtained at each heat treatment temperature were analyzed by powder X-ray diffraction. FIG. 5 shows the result. From the result of the powder X-ray diffraction, a diffraction line having a basal plane spacing value of 2.28 nm and a diffraction line which is considered to be attributed to the layer structure were confirmed from the untreated sample. The hinokitiol, a ligand, is known to form a 2: 1 type planar complex with copper ions, and assuming that it is placed upright with respect to the interlayer, the basal plane spacing value is 2.45 nm. It becomes.
（００１）回折線は、２５０℃処理まで２．２ｎｍ程度の数値を示していたが、３００℃処理で１．４６ｎｍまで低下した。これに伴い、（００２）と思われる回折線も高角度側にシフトした。４００〜５００℃処理では、層内有機物の離脱に伴い、１．３ｎｍまで減少したが、中心化学種である銅の酸化還元状態は、Ｘ線的には確認されなかった。 The (001) diffraction line showed a value of about 2.2 nm until the treatment at 250 ° C., but decreased to 1.46 nm after the treatment at 300 ° C. Along with this, the diffraction line considered to be (002) also shifted to the high angle side. In the treatment at 400 to 500 ° C., it decreased to 1.3 nm with the separation of organic substances in the layer, but the redox state of copper as the central chemical species was not confirmed by X-ray.
抗レジオネラ属菌試験のための供試菌として、レジオネラ属菌の１種であるレジオネラニューモフィラ株（Ｌｅｇｉｏｎｅｌｌａ ｐｎｅｕｍｏｐｈｉｌａ ＡＴＣＣ（アメリカンタイプカルチャーコレクション）３３１５２）を用いた。Ｌ字型試験管に１０ｍｌの滅菌リン酸緩衝生理食塩水（ｐＨ７．０±０．１）を用いて、最終濃度５０、２５、１２．５、７．２５、３．１２、及び１．５６ｍｇ／ｌの銅−ヒノキチオール錯体を無機層状化合物のモンモリロナイトの層間に担持した抗レジオネラ属菌材料の懸濁液を調製した。 A Legionella pneumophila strain (Legionella pneumophila ATCC (American Type Culture Collection) 33152), which is one species of Legionella, was used as a test bacterium for the anti-Legionella genus test. Using 10 ml sterile phosphate buffered saline (pH 7.0 ± 0.1) in an L-shaped test tube, final concentrations 50, 25, 12.5, 7.25, 3.12, and 1.56 mg A suspension of anti-Legionella material carrying 1 / l copper-hinokitiol complex between layers of montmorillonite, an inorganic layered compound, was prepared.
約１０７ＣＦＵ／ｍｌに調製したレジオネラ属菌０．１ｍｌをそれぞれの管に接種して、３０℃、２４時間、１００ｒｐｍで振とう培養した後に、各管の上清５０μｌを新しいＢＣＹＥα培地に移植して、３７℃、７２時間培養した。培養後、菌の発育を阻止した最小濃度を最小殺菌濃度（ＭＢＣ）と判定した。 Each tube is inoculated with 0.1 ml of Legionella spp. Prepared to approximately 10 7 CFU / ml, cultured at 30 ° C. for 24 hours with shaking at 100 rpm, and then 50 μl of the supernatant of each tube is transferred to a new BCYEα medium. And cultured at 37 ° C. for 72 hours. After the culture, the minimum concentration at which the growth of the bacteria was inhibited was determined as the minimum bactericidal concentration (MBC).
表７から明らかなように、銅−ヒノキチオール錯体をモンモリロナイトの層間に担持した抗レジオネラ属菌材料は、レジオネラ属菌に対して、熱処理温度が３００℃まで、好ましくは２５０℃まで、明確な抗レジオネラ属菌活性を示すことが明らかとなった。 As is clear from Table 7, the anti-legionella material carrying the copper-hinokitiol complex between the layers of montmorillonite has a clear heat-resistant temperature up to 300 ° C., preferably up to 250 ° C., against the Legionella genus. It became clear that it showed genus activity.
以上詳述したように、本発明は、生理活性機能を有する金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料に係るものであり、本発明により、浴場施設や、我々の生活環境において大量の水を溜めて利用する場所、給湯設備、冷却塔、加湿装置、水景施設に利用可能であり、更に、優れた生理活性機能、例えば、病害虫防除機能、雑草防除機能、抗微生物機能等の持続性や保水性、環境親和性を有し、生活環境や医療福祉環境、植物の組織培養、農業、植林をはじめとする林業全般、植物栽培などに応用可能な抗レジオネラ属菌材料を提供することができる。 As described above in detail, the present invention relates to an anti-legionella genus material having an interlayer-supported metal-tropolone complex having a physiologically active function, and according to the present invention, a large amount of it can be used in bath facilities and in our living environment. It can be used in places where water is collected and used, hot water supply facilities, cooling towers, humidifiers, aquatic facilities, and also has excellent physiological activity functions such as pest control functions, weed control functions, and antimicrobial functions. Providing anti-Legionella material that has water retention and environmental compatibility, and can be applied to living environment, medical welfare environment, plant tissue culture, agriculture, forestry including plantation, plant cultivation, etc. it can.
本発明の抗レジオネラ属菌材料は、無機層状化合物の層間では、生理活性機能を有する有機金属錯体がナノメートルオーダーで均一に分散しているため、培地表面や田畑へ使用された場合でも分散性に優れている。また、生理活性機能を有する金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料は、そのままでの使用も勿論可能であるが、活性機能を有する金属−トロポロン錯体の系外への徐放速度を制御できるため、生理活性効果の持続性が極めて高く、任意の形態に製剤加工した加工製品とすることができる。 The anti-legionella genus material of the present invention has a dispersibility even when it is used on the surface of a medium or a field because an organometallic complex having a physiologically active function is uniformly dispersed on the nanometer order between layers of an inorganic layered compound. Is excellent. In addition, the anti-legionella genus material carrying the intercalated metal-tropolone complex having a physiologically active function can be used as it is, but the sustained release rate of the metal-tropolone complex having an active function to the outside of the system is increased. Because it can be controlled, the physiologically active effect is extremely high, and a processed product that has been processed into a desired form can be obtained.
更に、本発明の、任意の形態に製剤加工した加工製品は、通常の製剤製品を製造する方法を用いて、生理活性機能を有する抗レジオネラ属菌材料を油性基剤中に混合溶解する方法や、一般に用いられる方法により製造することができる。こうした加工製品は、使用環境に応じた合目的な設計が可能であるため、広範な産業分野での利用が可能となる。本発明は、上述の抗レジオネラ属菌材料に関する新製品・新技術を提供するものとして有用である。 Furthermore, the processed product of the present invention processed into an arbitrary form is prepared by mixing and dissolving an anti-Legionella material having a physiologically active function in an oily base using a method for producing an ordinary pharmaceutical product. It can be produced by a generally used method. Since such a processed product can be designed in a suitable manner according to the use environment, it can be used in a wide range of industrial fields. The present invention is useful as providing a new product and a new technology relating to the above-mentioned anti-legionella genus material.
Claims (8)
上記金属−トロポロン錯体が、金属カチオンに有機配位子のトロポロン化合物を配位させた、生理活性機能を有する金属−トロポロン錯体からなり、かつ、上記有機配位子のトロポロン化合物がヒノキチオールであり、上記無機層状化合物が、層間に交換性陽イオンを有するスメクタイト族粘土鉱物、バーミキュライト、膨潤性雲母のいずれか１種からなり、その陽イオン交換容量（ＣＥＣ）はＣＥＣ＝３０〜４００ミリ等量／１００ｇの範囲であり、かつ脱イオン水あるいは有機溶媒により膨潤させたものであり、
この無機層状化合物の層間に上記トロポロン化合物が該層間に存在する交換性陽イオンとの交換反応により金属−トロポロン錯体の形で挿入、担持されていて、粉末Ｘ線回折による（００１）回折線から計算される基底面間隔値が反応前の無機層状化合物の基底面間隔値より拡大し、かつ層構造に起因する（００３）回折線を示し、３００℃までの熱処理（空気中、昇温速度１０℃／分、保持１時間）に対して抗レジオネラ属菌活性を示すことを特徴とする金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料。 An anti-Legionella material that improves the sustained release of its bioactive function by supporting a metal-tropolone complex formed by complexing a tropolone compound and an antibacterial metal cation between layers of an inorganic layered compound,
The metal-tropolone complex is composed of a metal-tropolone complex having a physiologically active function in which an organic ligand tropolone compound is coordinated to a metal cation , and the organic ligand tropolone compound is hinokitiol , The inorganic layered compound is composed of any one of smectite group clay mineral having an exchangeable cation between layers , vermiculite, and swellable mica, and its cation exchange capacity (CEC) is CEC = 30 to 400 milliequivalent / It is in the range of 100 g and is swollen with deionized water or an organic solvent,
Metal above preparative Roporon compound between layers of the inorganic layered compound by exchange reaction between exchangeable cations present between the layers - insert in the form of tropolone complex, be supported, by powder X-ray diffraction (001) diffraction line basal spacing value calculated is larger than the basal plane spacing value of the inorganic layered compound before the reaction from, and due to the layer structure (003) diffraction line shows, heat treatment up to 300 ° C. (in air, Atsushi Nobori rate 10 ° C. / min, metal and wherein indicates Succoth anti Legionella activity against 1 hour) - anti Legionella materials interlayer carrying tropolone complex.
ニッケル−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料であって、低角度側に１．５１ｎｍの（００１）回折線を示し、又は、
亜鉛−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料であって、低角度側に１．５２ｎｍの（００１）回折線を示し、又は、
アルミニウム−ヒノキチオール錯体を層間担持した抗レジオネラ属菌材料であって、低角度側に１．５９ｎｍの（００１）回折線を示す、請求項１に記載の金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料。 The anti-legionella genus material is an anti-legionella genus material in which a copper -hinokitiol complex is supported between layers, and the inter-layer spacing by powder X-ray diffraction is 1.31 nm, and the 2.28 nm (001) diffraction line on the low angle side Showing or
An anti-Legionella material carrying an interlayer-supported nickel-hinokitiol complex, showing a (001) diffraction line of 1.51 nm on the low angle side, or
An anti-legionella genus material intercalated with a zinc-hinokitiol complex, which exhibits a (001) diffraction line of 1.52 nm on the low angle side, or
The anti- Legionella genus material which carried | supported the aluminum- hinokitiol complex between layers, Comprising: The anti- Legionella genus which carried | supported the metal- tropolone complex of Claim 1 which shows the (001) diffraction line of 1.59 nm on the low angle side Fungus material.
上記無機層状化合物として、層間に交換性陽イオンを有するスメクタイト族粘土鉱物、バーミキュライト、膨潤性雲母のいずれか１種であり、その陽イオン交換容量（ＣＥＣ）がＣＥＣ＝３０〜４００ミリ等量／１００ｇの範囲のものを使用し、かつ脱イオン水あるいは有機溶媒により膨潤させ、
上記金属−トロポロン錯体として、金属カチオンに有機配位子のトロポロン化合物を配位させた金属−トロポロン錯体を使用し、かつ、上記有機配位子のトロポロン化合物として、ヒノキチオールを用いて、
上記無機層状化合物と、上記金属−トロポロン錯体を、有機溶媒の存在下で混合撹拌し、かつ５〜９０℃に加熱して、上記無機層状化合物の層間に存在する交換性陽イオンと、上記金属−トロポロン錯体との交換反応を進行させることにより、この無機層状化合物の層間に上記トロポロン化合物を金属−トロポロン錯体の形で挿入、担持させて、粉末Ｘ線回折による（００１）回折線から計算される基底面間隔値が反応前の無機層状化合物の基底面間隔値より拡大し、かつ層構造に起因する（００３）回折線を示し、３００℃までの熱処理（空気中、昇温速度１０℃／分、保持１時間）に対して抗レジオネラ属菌活性を示し、かつ、その生理活性機能の徐放性を向上させた抗レジオネラ属菌材料を製造することを特徴とする金属−トロポロン錯体を層間担持した抗レジオネラ属菌材料の製造方法。 A method for producing an anti-Legionella material in which the metal-tropolone complex according to any one of claims 1 to 4 is supported between layers of an inorganic layered compound to improve the sustained release of the physiologically active function ,
As above-inorganic layered compound is any one of the smectite group clay minerals, vermiculite, swellable mica having an exchangeable cation between layers, the cation exchange capacity (CEC) is CEC = 30 to 400 milliequivalents / use 100g range ones, or one swollen with deionized water or an organic solvent,
As the metal-tropolone complex, a metal-tropolone complex in which an organic ligand tropolone compound is coordinated to a metal cation, and using hinokitiol as the organic ligand tropolone compound,
And the inorganic layered compound, the metal - the tropolone complex, were mixed and stirred in the presence of an organic solvent, and heated to 5 to 90 ° C., and exchangeable cations present between layers of the inorganic laminar compound, the metal - the Rukoto allowed to proceed exchange reaction between tropolone complex, the interlayer metal the tropolone compound of the inorganic layered compound - insert in the form of tropolone complex, by collateral lifting, by powder X-ray diffraction (001) diffraction line The basal plane spacing value calculated from the equation is larger than the basal plane spacing value of the inorganic layered compound before the reaction, and shows (003) diffraction lines due to the layer structure, and heat treatment up to 300 ° C. (in air, rate of temperature increase) Metal-tropolone characterized by producing an anti-Legionella bacterium material exhibiting anti-Legionella bacterium activity at 10 ° C./min, holding 1 hour) and having improved sustained release of its physiological activity function A method for producing an anti-Legionella material carrying a complex between layers.
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