JP2004002296A - Chemical substance-embedded particle, method for producing the particle and production apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing chemical substance-embedded particles, which shortens a production process, reduces a manufacturing cost and is suitable for mass-production of the particles. <P>SOLUTION: The chemical substance-embedded particles comprises 300-99.9 wt.% of a base material and 0.1-70 wt.% of a chemical substance embedding substance. The method for producing the particles comprises a process of melting the base material, a process of uniformly mixing the molten base material with the chemical substance embedding material and a process which casts the mixture of the molten base material and the chemical substance embedding material from a nozzle in a duct into a medium solution that is maintained at a temperature lower at least 5°C than the melting point of the base material and has 0.6 g/cm<SP>3</SP>-1.5 g/cm<SP>3</SP>specific gravity. <P>COPYRIGHT: (C)2004,JPO

Description

【００１２】
本発明の化学物質埋め込み粒子を製造するために使用される装置は、図１に示すように、溶融状態の基材を蓄積する容器（１０２）と、化学物質埋込材を蓄積する容器（１０４）と、容器（１０２）と容器（１０４）とを夫々接続し、容器（１０２）からの溶融状態の基材と容器（１０４）からの化学物質埋込材とを混合する容器（１０１）と、媒体溶液を蓄積する容器（１０７）と、ダクト（１０５）により容器（１０１）と容器（１０７）に接続され、そのダクト（１０５）に溶融状態の基材と化学物質埋込材との混合物を移送する駆動手段（１０９）と、ダクト（１０５）における、容器（１０７）と接続する端に配設され、駆動手段（１０９）からの溶融状態の基材と化学物質埋込材との混合物を、容器（１０７）に蓄積される媒体溶液に注入するノズル（１１１）とを備えている。
更に詳しく説明すると、容器（１０２）からの溶融状態の基材と容器（１０４）からの化学物質埋込材とは容器（１０１）において混合された後、駆動手段（１０９）によりダクト（１０５）を介して容器（１０７）における媒体溶液に注入される。この駆動手段（１０９）は、蠕動式ポンプであってもギヤポンプであってもよく、又、中空管状のダクト（１０５）はプラスチック管、ＰＥ管、テフロン管、銅管、ステンレス管などの軟質或いは硬質の管を採用できる。更に、ダクト（１０５）における、容器（１０７）と接続する端には、容器（１０７）における媒体溶液と接するようにノズル（１１１）が配置され、該ノズル（１１１）はプラスチック、ＰＥ、テフロン、銅、ステンレスなどの軟質或いは硬質のものを採用することができる。又、ノズル（１１１）の口径は、粒径が０．０１〜５．０ｍｍの粒子を造粒する場合は、０．９〜５．０ｍｍであることが好ましく、又、粒径が２０〜１０００ｎｍの粒子を造粒する場合は、０．０１〜０．８ｍｍであることが好ましい。
又、溶融状態の基材と化学物質埋込材との混合物、媒体溶液夫々の温度が一定値である場合は、該混合物の注入速度が速ければ速いほど、ノズル（１１１）の口径が小さければ小さいほど、粒径の小さい粒子を形成することができる。
【００１３】
更に、基材の材質である水素添加植物油、水素添加動物油及び飽和脂肪酸の性質は、温度やｐＨ値により影響されやすいので、使用される化学物質埋込材の材質により植物油や動物油の水素添加量、飽和脂肪酸の炭素数を調整することが好ましく、凝固後の基材は化学物質埋込材を外気、水分から保護することができ、又胃内などの酸性環境においての安定性も優れているので、下記の各用途において適用することができる。
【００１４】
（Ａ）医薬品においての用途
本発明の薬剤を被覆する基材には、薬剤を外気、水分から保護できる水素添加油類や脂肪酸類が使用されているので、該薬剤の外気や水分による酸化、潮解を防止することができる。又、水素添加油類や脂肪酸類は特に胃内などの酸性環境においての安定性に優れているので、それを基材とする薬剤は胃内においての胃酸による分解を防止することができる。更に、苦味を有する経口薬剤は外部に水素添加油類や脂肪酸類を被覆することによりその苦味を抑えることができる。
【００１５】
（Ｂ）食品においての用途
本発明の香料、食用料を被覆する基材においては、香料、食用料を外気、水分から保護できる水素添加油類や脂肪酸類が使用されることから、該香料、食用料の外気や水分による酸通し、潮解を防止することができると共に、該香料、食用料の香りをそのまま被覆層下に密封することができ、更に、得られる食品の外観をより綺麗に見せることができるので、食品の付加価値を高めることができる。
【００１６】
（Ｃ）水産・畜産用途
水素添加油類や脂肪酸類は安定な化学的性質を有していると共に、化学物質埋込材を外気、水分から保護できる特性を有しているので、ワクチン、抗体、営養品の基材として好適に使用できる。
更に、水産用途において、水素添加油類や脂肪酸類は比重において水と異なる非水溶性物であり、それにより被覆されるワクチン、抗体、その他の薬品は、被覆した脂肪酸の種類により水面、水中に懸濁させたり、水底に沈積させたりすることができるので、給餌する魚類の棲息水域を考量して選択することができる。又、ワクチン、抗体、その他の薬品以外に、魚の食欲を促進するための飼料を適量混入してもよい。更に、活性物質を被覆する水素添加油類や脂肪酸類として特定の融点を有するものを使用した場合、所定の水温以上の水に投入することで該活性物質に被覆される脂肪酸類などは水により溶けるので、活性物質を水中に解き放つことができる。
又、畜産用途においては、畜産動物に与える、水素添加油類や脂肪酸類により被覆した抗体や営養物質を飼料調理過程において破壊することなく、そのまま畜産動物が摂食することができる。
【００１７】
（Ｄ）その他の用途
プリント産業において使用するカーボン粉や顔料を、特定の融点の水素添加油類や脂肪酸類により被覆した場合、該水素添加油類や脂肪酸を融点以上に加熱した時に溶融させて、内含するカーボン粉や顔料を外部環境に釈放することができる。
【００１８】
以下、本発明を、実施例を参照して更に詳細に説明するが、本発明の請求範囲は当該実施例により制限されるものではない。又、特に説明がない限り、％は重量％を指すものである。
【００１９】
（実施例１）
選用材質
ステアリン酸７５％＋フィッシュ・プロテイン２０％＋キトサン（ｃｈｉｔｏｓａｎ）５％
作業条件
ダクト管径：７．９ｍｍ
注入速度：２５Ｌ／ｈｒ
ノズル口径：１．６ｍｍ
製造方法
前記ステアリン酸、フィッシュ・プロテイン及びキトサンを７０±３℃の温度下で、十分に均一攪拌した後、蠕動式ポンプにより４９±１℃の水溶液に注入し造粒する。
結果
粒度分布範囲が０．５±０．２ｍｍの正球体の粒子が得られる。又、その粒子の比重は水より小さく、融点は５５℃であり、１時間に２５ｋｇ生産できる。
効果
フィッシュ・プロテインによる臭みを有効に密封できると共に、その空気や水分との接触により生じる酸通しや潮解を防止でき、更に食品の外観をより綺麗に見せることができる（図２参照）。
【００２０】
（実施例２）
選用材質
ステアリン酸６３％＋ラウリン酸３２％＋乳酸菌５％
作業条件
ダクト管径：７．９ｍｍ
注入速度：３８Ｌ／ｈｒ
ノズル口径：２．７ｍｍ
製造方法
前記ステアリン酸、ラウリン酸及び乳酸菌を５５±３℃の温度下で、十分に均一攪拌した後、蠕動式ポンプにより３８±１℃の水溶液に注入し造粒した後、水溶液中から掬い取って４℃の環境下で保存する。
結果
粒度分布範囲が１．０±０．２ｍｍの正球体の粒子が得られる。又、その粒子の比重は水より小さく、融点は４３℃であり、１時間に３８ｋｇ生産できる。
効果
乳酸菌を空気、水分、及び胃酸による酸性環境から保護できると共に、製品としての外観を改良してその附加価値をより高めることができる（図３参照）。
【００２１】
（実施例３）
選用材質
精製水素添加パームステアリン油（ステアリン酸４１％、パーム酸５７％及びミリスチン酸２％）９０〜５５％＋ビール酵母とスピルリナ抽出物（Ｂｅｅｒ　ｙｅａｓｔ＋Ｓｐｉｒｕｌｉｎａ　ｅｘｔｒａｃｔ）５〜４０％＋キトサン５％
作業条件
ダクト管径：７．９ｍｍ
注入速度：４４．８Ｌ／ｈｒ
ノズル口径：１．８ｍｍ
製造方法
前記精製水素添加パームステアリン油、ビール酵母とスピルリナ抽出物、及びキトサンを７０±３℃の温度下で、十分に均一攪拌した後、蠕動式ポンプにより４４．３±１℃の水溶液に注入し造粒した後、水溶液中から掬い取って４０℃の環境において乾燥する。
結果
粒度分布範囲が０．５±０．２ｍｍの正球体の粒子が得られる。又、その粒子の比重は水より大きく、融点は５５℃であり、１時間に４５ｋｇ生産できる。
効果
ビール酵母とスピルリナ抽出物による臭みを有効に密封できると共に、ビール酵母とスピルリナ抽出物を空気や水分から保護でき、更に製品としての外観を改良してその附加価値をより高めることができる。
【００２２】
（実施例４）
選用材質
ステアリン酸６３％＋ラウリン酸３２．０％＋水産ワクチン５％
作業条件
ダクト管径：７．９ｍｍ
注入速度：３８Ｌ／ｈｒ
ノズル口径：２．７ｍｍ
製造方法
前記ステアリン酸、ラウリン酸及び水産ワクチンを５５±３℃の温度下で、十分に均一攪拌した後、蠕動式ポンプにより３８±１℃の水溶液に注入し造粒した後、水溶液中から掬い取って４℃の環境下で保存する。
結果
粒度分布範囲が１．０±０．２ｍｍの正球体の粒子が得られる。又、その粒子の比重は水より小さく、融点は４３℃であり、１時間に３８ｋｇ生産できる。
効果
水産ワクチンを空気や水分から保護できると共に、該水産ワクチンは水面上に長時間浮遊することができるので、主に水面上に浮遊する餌を摂食する魚類に対し好適な飼料として提供することができる。
【００２３】
（実施例５）
選用材質
ステアリン酸４４．６％＋ラウリン酸２２．３％＋グリセリン２８．６％＋水産ワクチン４．５％
作業条件
ダクト管径：７．９ｍｍ
注入速度：３８Ｌ／ｈｒ
ノズル口径：２．７ｍｍ
製造方法
前記ステアリン酸、ラウリン酸、グリセリン及び水産ワクチンを５５±３℃の温度下で、十分に均一攪拌した後、蠕動式ポンプにより３８±１℃の水溶液に注入し造粒した後、水溶液中から掬い取って４℃の環境下で保存する。
結果
粒度分布範囲が１．０±０．２ｍｍの正球体の粒子が得られる。又、その粒子の比重は水より大きく、融点は４３℃であり、１時間に３８ｋｇ生産できる。
効果
水産ワクチンを空気や水分から保護できると共に、該水産ワクチンは水底層に長時間滞留することができるので、水底に存在する餌を摂食する魚類に対し好適な飼料として提供することができる。
【００２４】
（実施例６）
選用材質
基材：水素添加パームステアリン油６０％＋水素添加椰子油４０％
化学物質埋込材：ＴＧＩＶ不活性化ワクチン１０％
作業条件
ダクト管径：２０ｎｍ
注入速度：１５０Ｌ／ｈｒ
ノズル口径：０．８ｍｍ
製造方法
前記水素添加パームステアリン油、水素添加椰子油及びＴＧＩＶ不活性化ワクチンを５５±３℃の温度下で、十分に均一攪拌した後、ポンプにより３８±１℃の水溶液に注入し造粒させ、冷凍乾燥機に移送し乾燥させる。
結果
前記方法により製造される粒子は、図４に示すように、何れも正球体を呈すると共に、その比重は水より小さいことから、水中に懸濁分散状態となる。又、粒子の融点は４３℃であり、１ロット毎に１０００ｇ生産できる。
効果
上記方法により製造される、ホルマリンやβ−プロピオラクトン（β−ｐｒｏｐｉｏｌａｃｔｏｎｅ、ＢＰＬ）含有ＴＧＩＶ不活性化ワクチン（７×１０^２ＴＣＩＤ_５０／ｍｌ／ｆｉｓｈ）にハタの稚魚を１回浸漬し免疫を生じさせ、１５日経過後再び浸漬処理を追加し、流水環境において１０日間飼育した後、ＴＧＩＶ（１０^４．０ＴＣＩＤ_５０／ｍｌ／ｆｉｓｈ）を用いて攻撃試験を行い、前記ワクチンによる免疫効果を判定する。その結果は図５に示すようである。
【００２５】
（実施例７）
選用材質
基材：水素添加パームステアリン油６０％＋水素添加椰子油３０％
化学物質埋込材：ＴＧＩＶ不活性化ワクチン１０％
作業条件
ダクト管径：２０ｎｍ
注入速度：３００Ｌ／ｈｒ
ノズル口径：０．８ｍｍ
製造方法
前記水素添加パームステアリン油、水素添加椰子油及びＴＧＩＶ不活性化ワクチンを５５±３℃の温度下で、十分に均一攪拌した後、ポンプにより３８±１℃の水溶液に注入し造粒させ、冷凍乾燥機に移送し乾燥させる。
結果
粒径が３０〜１８０ｎｍの範囲の粒子が得られる。
【００２６】
（実施例８）
選用材質
基材：水素添加パームステアリン油１００％
作業条件
ダクト管径：２０ｎｍ
注入速度：３００Ｌ／ｈｒ
ノズル口径：０．８ｍｍ
製造方法
前記水素添加パームステアリン油を７０±３℃の温度下で、十分に均一攪拌した後、ポンプにより４５±１℃の水に注入し造粒させ、冷凍乾燥機に移送し乾燥させる。
結果
前記方法により粒径が３０〜１８０ｎｍの範囲の粒子が得られる（図６参照）と共に、その比重は水より小さいので、水中に懸濁分散状態となる。又、粒子の融点は５３℃であり、１ロット毎に１０００ｇ生産できる。
【００２７】
（実施例９）
選用材質
基材：１％アルギン酸ナトリウム水溶液
作業条件
ダクト管径：２０ｎｍ
注入速度：３００Ｌ／ｈｒ
ノズル口径：０．７ｍｍ
製造方法
前記１％アルギン酸ナトリウム水溶液を室温下、十分に均一攪拌した後、ポンプにより室温の３％乳酸カルシウム水溶液に注入し造粒させる。
結果
水と同様の比重を有するナノ級の粒子を１ロット毎に１０００ｇ生産できる。又、所定時間放置した後、粒子は集結し混濁物となる。
効果
水溶性ナノ粒子が得られる。
【００２８】
（実施例１０）
選用材質
基材：４％Ａｇａｒ水溶液
作業条件
ダクト管径：２０ｎｍ
注入速度：３００Ｌ／ｈｒ
ノズル口径：０．７ｍｍ
製造方法
前記４％Ａｇａｒ水溶液を６０℃温度下、十分に均一攪拌した後、ポンプにより室温の水に注入し造粒させる。
結果
水と同様の比重を有するナノ級の粒子を１ロット毎に１０００ｇ生産でき、又、所定時間放置した後、粒子は集結し混濁物となる。
効果
水溶性ナノ粒子が得られる。
【００２９】
上記実施例からも分かるように、従来のコアセルベーション（Ｃｏａｃｅｒｖａｔｉｏｎ）法や噴霧懸濁流体床法に比べて、本発明の粒子の製造方法では、物化性において安定し、化学物質を安定に被覆できる粒子を製造できると共に、粒子の融点や比重を調整することにより、医薬、食品、水産などの分野に適用できる粒子を得ることができる。
更に、コアセルベーション法では、粒子を製造するために煩雑な製造工程が必要であると共に、粒子を連続的に生成することは困難である。又、噴霧懸濁流体床法では、設備コストが高く、高品質の粒子を高生産で短時間に製造することは困難である。これに対し、本発明の粒子の製造方法を用いれば、前記諸問題を一挙に解決することができる。
【００３０】
以下、本発明のナノ粒子を、魚類のＴＧＩＶ感染予防に適用する実験について説明する。
【００３１】
一．ＴＧＩＶ不活性化ワクチンの量産
ＴＧＩＶを、ＭＯＩ＝０．１〜１により単層培養されるハタのスウィンブレーダ・セル・ライン（ｓｗｉｍｂｌａｄｄｅｒ（ＳＢ）　ｃｅｌｌ　ｌｉｎｅ）に接種し、２５℃の温度下で、７〜１４日間培養した後、ウィルス液を採取し、凍結及び解凍を繰り返し行なった後、４℃の温度下のホルマリンに４日間含浸させ、或いは２０℃の温度下のＢＰＬに４日間含浸させた後に使用する。
【００３２】
二．被覆層を有する及び有しないＴＧＩＶ不活性化ワクチンにより浸漬法を用いてハタに免疫を生じさせた場合の効果
１、上記ＴＧＩＶ不活性化ワクチンを海水により希釈した後、ハタの稚魚をその希釈液に１時間浸漬し免疫を生じさせ、流水飼育により１５日間の飼育を行った後、再び１時間の浸漬処理を追加し、海水飼育槽に移して１０日間の飼育を行う（Ａグループ）。或いは、ハタの稚魚をウィルス免疫用液に１時間浸漬した後、流水飼育により２５日間の飼育を行う（Ｂグループ）。そして、前記各グループのハタの稚魚に対し１０^４．０ＴＣＩＤ_５０／ｍｌＴＧＩＶにより攻撃試験を行い、２週間後におけるハタの稚魚の死亡率を記録する。
２、前記ＴＧＩＶ不活性化ワクチンを実施例２に記載される方法に基づいてナノ粒子に造粒した後に海水により希釈し、その希釈液にハタの稚魚を１時間浸漬し免疫を生じさせ、流水飼育により１５日間の飼育を行った後、再び１時間の浸漬処理を追加し、海水飼育槽に移して１０日間の飼育を行う（Ａグループ）。或いは、ハタの稚魚をウィルス免疫用液に１時間浸漬した後、流水飼育により２５日間の飼育を行う（Ｂグループ）。そして、前記各グループのハタの稚魚に対し１０^４．０ＴＣＩＤ_５０／ｍｌＴＧＩＶにより攻撃試験を行い、２週間後におけるハタの稚魚の死亡率を記録する。
図７は、ホルマリン又はＢＰＬをカプセル化せず、又はカプセル化させたＴＧＩＶ不活性化ワクチン（７×１０^２ＴＣＩＤ_５０／ｍｌ）の浸漬液にハタの稚魚（平均体長２．３ｃｍ、体重約１．８ｇ）を浸漬し免疫を生じさせた後、免疫後のハタの稚魚の腹腔にＴＧＩＶ（１０^４ＴＣＩＤ_５０／ｆｉｓｈ）を注射した場合の、攻撃試験の結果を示す図である。未免疫グループ（コントロールグループ）（黒菱形）からも分かるように、検体は攻撃試験後１０日内に全滅し、経時生存率は０％であった。一方、免疫グループにおいて、色が塗り潰された所定形状の符号は、ナノカプセル化ワクチンにより免疫を生じさせた結果であり、その中の白抜きされた所定形状の符号は、ナノカプセル化されていないワクチンにより免疫を生じさせた結果を示している。図７に示すように、カプセル化したＢＰＬのワクチンにより免疫処理された稚魚の経時生存率（１０日）は９０％（ライン１参照）であり、カプセル化されずＢＰＬのワクチンにより免疫処理された稚魚の経時生存率（１０日）は７０％（ライン２参照）であった。これに対し、ホルマリンによる不活性化ワクチンはカプセル化するかしないかに拘わらずＢＰＬのワクチンに比べて免疫効果において劣っていた（ライン５、ライン８参照）。
このように、ナノカプセル化されていないワクチンの浸漬液により免疫処理された稚魚の２５日経過後の生存率は約７０％であるのに対し、ナノカプセル化ワクチンの浸漬液により免疫処理された稚魚の生存率は依然として９０％以上であることから見れば、ワクチンをカプセル化することは、魚類のウィルス感染の予防において有効な方法であることが分かる。
【００３３】
上記説明においては本発明の好ましい実施例が開示されているが、本発明は当該実施例により限定されるものではなく、請求の範囲のみにより制限されるものであり、本案の要旨を脱逸しない範囲内の種々の変更も本案に含まれることは言うまでもない。
【００３４】
【発明の効果】
本案の構成により、以下の効果を達成できる。
１．　食品、製薬、水産業又は半導体ウエハ材に幅広く適用でき、安価な基材で簡単な作業により、低コスト且つ高生産性で製造できる、化学物質埋め込み粒子、該粒子の製造方法及び製造装置を提供することができる。
２．　台湾ハタのイリドウイルス感染の予防に有効である化学物質埋め込み粒子を提供することができる。
【図面の簡単な説明】
【図１】本発明の粒子の製造装置の好ましい実施例を示す図である。
【図２】実施例１により製造される正球体粒子の外観写真の図である。
【図３】実施例２により製造される正球体粒子の外観写真の図である。
【図４】実施例６により製造される正球体のナノ粒子のＳＥＭ写真の図である。
【図５】実施例６により製造されるナノ級ワクチンによる台湾ハタの稚魚へのウィルス免疫効果を示す図であり、ホルマリン又はＢＰＬのＴＧＩＶ不活性化ワクチン（７×１０^２ＴＣＩＤ_５０／ｍｌ）の浸漬液にハタの稚魚を浸漬し免疫を生じさせ、１５日経過後に再び浸漬処理を追加し、流水飼育により１０日間飼育した後、ハタの稚魚の腹腔にＴＧＩＶ（１０^４ＴＣＩＤ_５０／ｆｉｓｈ）を注射した場合の、攻撃試験の結果を示す図である。
【図６】実施例８により製造されるナノ粒子の寸法分布を示す図である。
【図７】ホルマリンやＢＰＬをカプセル化せず、又はカプセル化させたＴＧＩＶ不活性化ワクチン（７×１０^２ＴＣＩＤ_５０／ｍｌ）の浸漬液にハタの稚魚を浸漬し免疫を生じさせ、ハタの稚魚の腹腔にＴＧＩＶ（１０^４．０ＴＣＩＤ_５０／ｆｉｓｈ）を注射した場合の、攻撃試験の結果を示す図である。
【符号の説明】
１０１、１０２、１０４、１０７　　　容器
１０５　　　ダクト
１０９　　　駆動手段
１１１　　　ノズル[0001]
[Industrial application fields]
The present invention particularly relates to chemical substance-embedded particles, a method for producing the particles, and a production apparatus.
[0002]
[Prior art]
Conventionally, the coacervation method and the spray suspension fluid bed method have been mainly used as methods for producing non-nanoparticles (for example, those having a particle size larger than that of nanoparticles such as microparticles) by oil and fat production technology. In addition, as a method for producing nanoparticles using a water-soluble substance or a water-insoluble substance, a coacervation method or a homogenization method is mainly employed.
For example, in US Pat. No. 6,153,657, an oil (liquid phase) having a low melting point is put in an aqueous phase solvent to which a surfactant is added, and stirred at a stirring speed of 3000 rpm to 15000 rpm in a high temperature environment. (O / W) type is changed to (W / O) type, and further changed to (O / W) type by lowering the temperature, at a temperature of 40 ° C. or lower and at a stirring speed of 3000 rpm to 15000 rpm. A method for producing the required particles by stirring is disclosed.
In US Pat. No. 6,015,773, a mixture consisting of a wax, a fatty acid derivative, a long-chain solid alcohol derivative and a water-insoluble substance is placed in a mixing zone simultaneously with water vapor and sprayed onto a fluidized bed so that the particle size is 0.5. A method for producing particles of ˜50 mu (* 1 mu = 1/1000 mm) is disclosed.
In US Pat. No. 6,087,003, a granular, droplet-like or gaseous chemical substance embedding material is suspended in a fluidized bed of a base material atmosphere, and the base material has a thickness on the surface of the chemical substance embedding material. A method of forming a coating layer that is 0 to 1000 mu is disclosed.
In US Pat. No. 6,197,349, a supercooled soluble substance (for example, phospholipid) as a base material, a chemical, an insecticide or a fertilizer as a chemical embedding material, a surfactant or an emulsifier as a stabilizer Are mixed 10 times with a homogenizer at a pressure of 1200 bar or with a centrifugal stirrer at a rotational speed of 4000 rpm for 20 minutes to produce particles having a particle size of 30 nm to 50 nm, and then cooled to room temperature.
In US Pat. No. 6,395,302, as a substrate, a first phase, a polymer aqueous phase (eg, dextran), a second phase, an emulsion phase (eg, fine lipid granules) and a crosslinkable polymer (eg, methacrylate) An organic solvent is mixed and stirred in a W / W phase mixed system composed of an active substance as a chemical substance embedding material to form particles having a particle size of 100 nm to 100 μm, followed by washing with water and freeze drying. Disclosed.
In US Pat. No. 6,395,300, a porous material such as hydrophilic polyvinyl ethylene glycol or hydrophobic phospholipid as a base material and a poorly water-soluble drug as a chemical substance embedding material are coagulated. After mixing the agent such as ammonia and the volatile solvent such as acetone and chloroform and stirring for 5 minutes at a rotation speed of 16000 rpm to produce particles having a particle size of 100 nm to 5 μm, conditions such as 60 kg / hr and 36 ° C. Discloses a method for obtaining tablets and encapsulating agents by removing volatile solvents by spray drying.
Further, in US Pat. No. 6,190,692, a swelling polymer such as methylcellulose or phospholipid as a base material and a drug or active substance as an embedding agent is mixed with an aqueous solution such as a polyvinyl compound. Disclosed is a method for producing particles on which a film having an effect of controlling the drug release rate is formed by an O / W type method of adding and stirring.
In US 6,387,409, by mixing and homogenizing vinyl or propene as a stabilizer in a mixture of a phospholipid as a base material and a water-soluble or water-insoluble drug as a chemical substance embedding material, A method for producing particles having a particle size of 50 nm to 10 μm is disclosed.
In US Pat. No. 6,146,663, for example, a phospholipid or vinyl polymer as a base material is mixed with sucrose as a dispersant and homogeneously emulsified to produce particles having a particle size of 100 nm, and then a filter membrane having a mesh size of 220 nm is used. A method of removing bacteria and then lyophilizing to a product is disclosed.
[0003]
However, in any of the above methods, a complicated manufacturing process is required, and a number of conditions such as reaction temperature, equipment operation method, and blending components must be adjusted. In addition, it is necessary to work for a long time at high temperature using an organic solvent, so it can be said that it is a preferable method for coating heat-sensitive substances such as bacteria, vaccines and proteins. Absent.
In addition, a method for producing edible particles, in which a base material and a chemical substance embedding material are mixed and dropped into a liquid, has also been developed. Since the yield of the product is low, it cannot be said to be an industrially suitable production method.
Therefore, shortening the manufacturing process, reducing the manufacturing cost, and developing a method for producing particles suitable for mass production of particles, development of a technology capable of generating particles in a stable phase state without using a blend in the manufacturing method, etc. Is an urgent need.
[0004]
Related to the above technique is aquaculture, but for example, the Taiwan grouper (Epinephelus sp.), Which has a high occupation rate in the aquaculture industry in Taiwan, is a high-class fish, but its survival rate is very low. This is because Taiwan grouper is easily infected with Iridovirus, which has a fatal infection rate of 90% or more during the fry season. For this reason, there is an urgent need to prevent the infection problem of grouper iridovirus, but there have been almost no attempts to solve the problem by using the chemical embedded particles as described above. Not.
[0005]
[Problems to be solved by the invention]
Accordingly, the present invention provides a particle embedded with a chemical, which can be produced at a low cost and with a high productivity by producing a particle having a good quality produced by a simple operation using an inexpensive base material. It is an object of the present invention to provide a manufacturing method and a manufacturing apparatus, and particles that are effective in preventing infection by Taiwan grouper iridovirus.
[0006]
[Means for Solving the Problems]
The present invention relates to hydrogenated vegetable oil, hydrogenated animal oil and C ₈ ~ C ₆₄ A particle size comprising at least one selected from saturated fatty acids, a base material having a blending amount of 30 to 99.9% by weight, and a chemical substance embedding material having a blending amount of 0.1 to 70% by weight. Chemical substance embedded particles in the range of 0.01 to 5.0 mm, hydrogenated vegetable oil, hydrogenated animal oil, C ₈ ~ C ₆₄ A water-insoluble substrate group consisting of a saturated fatty acid and a derivative thereof, or a water-soluble substrate group consisting of a temperature-change gel body, a divalent ion gel body and a derivative thereof, and the blending amount is 30 to 99.9. Provided is a chemical substance-embedded particle having a particle size in the range of 20 to 1000 nm, comprising a base material having a weight percentage of 0.1% and a chemical substance-embedding material having a blending amount of 0.1 to 70% by weight.
The present invention also provides hydrogenated vegetable oil, hydrogenated animal oil and C ₈ ~ C ₆₄ The step of melting at least one substrate selected from saturated fatty acids of the above, and the mixed substrate and the chemical substance embedding material are mixed in a proportion of 30 to 99.9% by weight: 0.1 to 70% by weight. The mixture of the melted base material and the chemical substance embedding material with a nozzle having a diameter of 0.9 to 5.0 mm in the duct at an injection rate of 5 to 100 L / hr. The temperature is maintained at least 5 ° C. lower than the melting point of the material, and the specific gravity is 0.6 g / cm. ³ ~ 1.5g / cm ³ And a step of granulating particles having a particle size of 0.01 to 5.0 mm.
Furthermore, the present invention connects a container (102) for accumulating a base material in a molten state, a container (104) for accumulating a chemical substance embedding material, a container (102) and a container (104). A container (101) for mixing the molten substrate from (102) and the chemical embedding material from the container (104), a container (107) for accumulating the medium solution, and a duct (105) 101) and a container (107), a drive means (109) for transferring a mixture of a molten base material and a chemical embedding material to the duct (105), and a container (107) in the duct (105). And a nozzle (111) for injecting a mixture of the molten base material and the chemical substance embedding material from the driving means (109) into the medium solution accumulated in the container (107). Of chemical embedded particles To provide a concrete apparatus.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
According to the present invention, hydrogenated vegetable oil, hydrogenated animal oil and C ₈ ~ C ₆₄ Particle size comprising at least one substrate selected from saturated fatty acids of the above, a base material having a blending amount of 30 to 99.9% by weight, and a chemical substance embedding material having a blending amount of 0.1 to 70% by weight Embedded in a chemical substance having a diameter of 0.01 to 5.0 mm, hydrogenated vegetable oil, hydrogenated animal oil, C ₈ ~ C ₆₄ A water-insoluble substrate group consisting of a saturated fatty acid and a derivative thereof, or a water-soluble substrate group consisting of a temperature-change gel body, a divalent ion gel body and a derivative thereof, and the blending amount is 30 to 99.9. Two kinds of chemical substances consisting of a base material having a weight% and a chemical substance embedded material having a compounding amount of 0.1 to 70% by weight and a chemical substance embedded particle having a particle diameter in the range of 20 to 1000 nm Embedded particles can be produced.
“Temperature change gel body” in the present proposal is gel-like in an environment at room temperature or lower, but refers to a gel body that becomes a fluid substance in an environment at room temperature or higher, and “divalent ion gel body” Ca ²⁺ , Mg ²⁺ It refers to a gel body that forms a gel when it comes into contact with ions such as. As said gel body, sodium alginate, pectin, agar, or a young cloth can be used conveniently.
The hydrogenated vegetable oil is preferably hydrogenated palm oil, hydrogenated palm oil, hydrogenated bean oil, hydrogenated peanut oil or hydrogenated vegetable oil.
The hydrogenated animal oil is preferably applied with hydrogenated butter, hydrogenated cream, hydrogenated fish oil or hydrogenated lard.
C ₈ ~ C ₆₄ The saturated fatty acid is not particularly limited as long as it exhibits a solid state at room temperature. One or more selected from acids, margaric acid, stearic acid, nonadecyl acid, arachidic acid, heneicosanoic acid, behenic acid, or derivatives thereof can be suitably used.
It is preferable that the chemical substance embedding material is a drug (for example, antibiotic), a physiologically active substance (hormone, vaccine), an inorganic or organic compound (for example, mineral or vitamin).
[0008]
In order to produce the particles, in the method for producing particles of the present invention,
(A) melting the substrate;
(B) uniformly mixing the molten base material and the chemical substance embedding material;
(C) The specific gravity of the mixture of the molten base material and the chemical substance embedding material is 0.6 g / cm by the nozzle in the duct. ³ ~ 1.5g / cm ³ Injecting into a liquid medium,
The temperature of the liquid medium is at least 5 ° C. lower than the temperature at which the substrate is melted.
Usually, the temperature which melt | dissolves a base material is 10 to 200 degreeC, More preferably, it is 40 to 80 degreeC.
Moreover, the temperature of a liquid medium is adjusted based on the temperature which fuse | melts the said base material, and is normally -10 degreeC-150 degreeC, More preferably, it is 20 degreeC-60 degreeC.
When producing particles having a particle diameter of 0.01 to 5.0 mm according to the present proposal, the injection speed of the mixed liquid by the nozzle may be 0.01 L / hr or more, and more preferably 5 L / hr to 100 L / hr. The nozzle diameter is preferably 0.9 mm to 5.0 mm.
On the other hand, when producing particles having a particle diameter of 20 to 1000 nm according to the present proposal, the injection rate of the mixed liquid by the nozzle may be 10 L / hr or more, and more preferably 150 L / hr to 300 L / hr. Moreover, the nozzle diameter should just be 0.01 mm or more, More preferably, it is 0.1 mm-0.8 mm.
[0009]
Hereinafter, the principle of the method for producing chemical substance-embedded particles of the present invention will be described.
When an oil substance is injected into a medium solution having an appropriate temperature difference, the oil substance is rapidly agitated in the medium phase due to the injection rate of the oil substance and the difference in specific gravity between the oil substance and the medium solution. A large amount of fine oil droplets are generated by decomposition, and the fine oil droplets become regular spheres due to the influence of the interfacial tension with the medium phase and the cohesive force of the medium solution itself. It becomes solid particles rapidly due to the temperature difference.
[0010]
Hereinafter, Table 1 compares the advantages and disadvantages of the method for producing particles of the present invention and the conventional method.
[0011]
[Table 1]

[0012]
As shown in FIG. 1, an apparatus used for producing chemical substance-embedded particles of the present invention includes a container (102) for accumulating a molten base material and a container (104) for accumulating a chemical substance-embedded material. ), The container (102) and the container (104), respectively, and the container (101) for mixing the molten base material from the container (102) and the chemical embedding material from the container (104) , A container (107) for accumulating the medium solution, and connected to the container (101) and the container (107) by a duct (105), and the duct (105) is a mixture of the molten base material and the chemical substance embedding material. A mixture of the molten base material and the chemical substance embedding material from the driving means (109), disposed at the end of the duct (105) connected to the container (107). Is stored in the container (107) And a nozzle (111) to be injected into the liquid.
More specifically, after the molten base material from the container (102) and the chemical embedding material from the container (104) are mixed in the container (101), the duct (105) is driven by the driving means (109). Into the medium solution in the container (107). This drive means (109) may be a peristaltic pump or a gear pump, and the hollow tubular duct (105) is a soft or plastic tube, PE tube, Teflon tube, copper tube, stainless tube or the like. A rigid tube can be used. Further, a nozzle (111) is disposed at the end of the duct (105) connected to the container (107) so as to contact the medium solution in the container (107), and the nozzle (111) is made of plastic, PE, Teflon, Soft or hard materials such as copper and stainless steel can be used. The diameter of the nozzle (111) is preferably 0.9 to 5.0 mm when granulating particles having a particle diameter of 0.01 to 5.0 mm, and the particle diameter is 20 to 1000 nm. When the particles are granulated, it is preferably 0.01 to 0.8 mm.
Further, when the temperature of each of the mixture of the molten base material and the chemical substance embedding material and the medium solution is a constant value, the faster the injection rate of the mixture, the smaller the nozzle (111) diameter. The smaller the particle size, the smaller the particle size.
[0013]
Furthermore, the properties of the hydrogenated vegetable oils, hydrogenated animal oils and saturated fatty acids that are the materials of the base material are easily affected by temperature and pH value, so the amount of hydrogenated vegetable oil or animal oil depending on the material of the chemical embedding material used It is preferable to adjust the carbon number of the saturated fatty acid, and the base material after solidification can protect the chemical implant from the outside air and moisture, and has excellent stability in an acidic environment such as the stomach. Therefore, it can be applied to the following uses.
[0014]
(A) Use in pharmaceuticals
Since the base material for coating the drug of the present invention uses hydrogenated oils and fatty acids that can protect the drug from the outside air and moisture, it is possible to prevent oxidation and deliquescence of the drug by the outside air and moisture. . In addition, hydrogenated oils and fatty acids are particularly excellent in stability in an acidic environment such as in the stomach, so that a drug based on the oil can prevent degradation by gastric acid in the stomach. Furthermore, an oral medicine having a bitter taste can suppress the bitter taste by coating the exterior with a hydrogenated oil or a fatty acid.
[0015]
(B) Use in food
In the base material for coating the fragrance and edible material of the present invention, since hydrogenated oils and fatty acids that can protect the fragrance and edible material from the outside air and moisture are used, it depends on the outside air and moisture of the fragrance and edible material. While preventing acidification and deliquescence, the fragrance of the fragrance and edible food can be sealed as it is under the coating layer, and the appearance of the resulting food can be shown more beautifully. Added value can be increased.
[0016]
(C) Fishery and livestock applications
Hydrogenated oils and fatty acids have stable chemical properties, and can protect chemical embedding materials from the outside air and moisture. Can be suitably used.
Furthermore, in marine products, hydrogenated oils and fatty acids are non-water-soluble substances that are different from water in specific gravity, and vaccines, antibodies, and other chemicals that are coated with them are on the surface and in water depending on the type of fatty acid coated. Since it can be suspended or deposited on the bottom of the water, it is possible to consider and select the habitat area of the fish to be fed. In addition to vaccines, antibodies, and other chemicals, an appropriate amount of feed for promoting fish appetite may be mixed. Furthermore, when hydrogenated oils or fatty acids that coat the active substance are used that have a specific melting point, the fatty acids that are coated on the active substance by being poured into water at a predetermined water temperature or higher are water-based. Because it dissolves, the active substance can be released into the water.
Moreover, in livestock applications, livestock animals can be fed as they are without destroying the antibodies and nutrient substances coated with hydrogenated oils and fatty acids, which are given to livestock animals, in the course of feed preparation.
[0017]
(D) Other uses
When carbon powder or pigment used in the printing industry is coated with hydrogenated oils or fatty acids having a specific melting point, the carbon powder contained by melting the hydrogenated oils or fatty acids when heated to the melting point or higher. And pigments can be released to the outside environment.
[0018]
EXAMPLES Hereinafter, although this invention is demonstrated further in detail with reference to an Example, the claim of this invention is not restrict | limited by the said Example. Further, unless otherwise specified, “%” means “% by weight”.
[0019]
(Example 1)
Material for selection
Stearic acid 75% + fish protein 20% + chitosan 5%
Process conditions
Duct pipe diameter: 7.9 mm
Injection speed: 25L / hr
Nozzle diameter: 1.6mm
Production method
The stearic acid, fish protein and chitosan are sufficiently homogeneously stirred at a temperature of 70 ± 3 ° C., and then injected into a 49 ± 1 ° C. aqueous solution by a peristaltic pump and granulated.
result
Regular spherical particles having a particle size distribution range of 0.5 ± 0.2 mm are obtained. Further, the specific gravity of the particles is smaller than that of water, the melting point is 55 ° C., and 25 kg can be produced per hour.
effect
The odor caused by fish protein can be effectively sealed, acidification and deliquescence caused by contact with the air and moisture can be prevented, and the appearance of the food can be made more beautiful (see FIG. 2).
[0020]
(Example 2)
Material for selection
63% stearic acid + 32% lauric acid + 5% lactic acid bacteria
Process conditions
Duct pipe diameter: 7.9 mm
Injection speed: 38L / hr
Nozzle diameter: 2.7 mm
Production method
The stearic acid, lauric acid and lactic acid bacteria are sufficiently uniformly stirred at a temperature of 55 ± 3 ° C., poured into a 38 ± 1 ° C. aqueous solution by a peristaltic pump, granulated, and then sprinkled from the aqueous solution. Store in an environment of ℃.
result
Regular spherical particles having a particle size distribution range of 1.0 ± 0.2 mm are obtained. Further, the specific gravity of the particles is smaller than that of water, the melting point is 43 ° C., and 38 kg can be produced per hour.
effect
Lactic acid bacteria can be protected from an acidic environment caused by air, moisture, and stomach acid, and the added value can be further improved by improving the appearance of the product (see FIG. 3).
[0021]
(Example 3)
Material for selection
Refined hydrogenated palm stearin oil (41% stearic acid, 57% palm acid and 2% myristic acid) 90-55% + brewer's yeast and spirulina extract (Beer yeast + Spirulina extract) 5-40% + chitosan 5%
Process conditions
Duct pipe diameter: 7.9 mm
Injection rate: 44.8 L / hr
Nozzle diameter: 1.8mm
Production method
The purified hydrogenated palm stearin oil, brewer's yeast and spirulina extract, and chitosan are sufficiently uniformly stirred at a temperature of 70 ± 3 ° C., and then injected into an aqueous solution of 44.3 ± 1 ° C. by a peristaltic pump. After granulation, it is scooped out from the aqueous solution and dried in an environment of 40 ° C.
result
Regular spherical particles having a particle size distribution range of 0.5 ± 0.2 mm are obtained. Further, the specific gravity of the particles is larger than that of water and the melting point is 55 ° C., and 45 kg can be produced in one hour.
effect
The odor due to brewer's yeast and Spirulina extract can be effectively sealed, and the brewer's yeast and Spirulina extract can be protected from air and moisture, and the appearance of the product can be improved to further increase its added value.
[0022]
Example 4
Material for selection
Stearic acid 63% + Lauric acid 32.0% + Marine vaccine 5%
Process conditions
Duct pipe diameter: 7.9 mm
Injection speed: 38L / hr
Nozzle diameter: 2.7 mm
Production method
The stearic acid, lauric acid and aquatic vaccine are sufficiently uniformly stirred at a temperature of 55 ± 3 ° C., injected into a 38 ± 1 ° C. aqueous solution by a peristaltic pump, granulated, and then taken out from the aqueous solution. Store in an environment of 4 ° C.
result
Regular spherical particles having a particle size distribution range of 1.0 ± 0.2 mm are obtained. Further, the specific gravity of the particles is smaller than that of water, the melting point is 43 ° C., and 38 kg can be produced per hour.
effect
The marine vaccine can be protected from air and moisture, and since the aquatic vaccine can float on the water surface for a long time, it can be provided as a suitable feed for fish that mainly feed on food that floats on the water surface. it can.
[0023]
(Example 5)
Material for selection
Stearic acid 44.6% + Lauric acid 22.3% + Glycerol 28.6% + Marine vaccine 4.5%
Process conditions
Duct pipe diameter: 7.9 mm
Injection speed: 38L / hr
Nozzle diameter: 2.7 mm
Production method
The stearic acid, lauric acid, glycerin and the aquatic vaccine are sufficiently homogeneously stirred at a temperature of 55 ± 3 ° C., injected into a 38 ± 1 ° C. aqueous solution by a peristaltic pump, granulated, and then sprinkled from the aqueous solution. And store in a 4 ° C environment.
result
Regular spherical particles having a particle size distribution range of 1.0 ± 0.2 mm are obtained. Further, the specific gravity of the particles is larger than that of water, the melting point is 43 ° C., and 38 kg can be produced per hour.
effect
The aquatic vaccine can be protected from air and moisture, and the aquatic vaccine can stay in the bottom layer for a long time. Therefore, the aquatic vaccine can be provided as a suitable feed for fish that feed on the bottom.
[0024]
(Example 6)
Material for selection
Base material: 60% hydrogenated palm stearin oil + 40% hydrogenated palm oil
Chemical implants: TGIV inactivated vaccine 10%
Process conditions
Duct pipe diameter: 20 nm
Injection speed: 150 L / hr
Nozzle diameter: 0.8mm
Production method
The hydrogenated palm stearin oil, hydrogenated coconut oil and TGIV inactivated vaccine are sufficiently uniformly stirred at a temperature of 55 ± 3 ° C., and then injected into a 38 ± 1 ° C. aqueous solution by a pump, granulated, and frozen. Transfer to a dryer and dry.
result
As shown in FIG. 4, all the particles produced by the above method have regular spheres and their specific gravity is smaller than that of water, so that they are suspended and dispersed in water. The melting point of the particles is 43 ° C., and 1000 g can be produced per lot.
effect
Formalin and β-propiolactone (BPL) -containing TGIV inactivated vaccine (7 × 10 6) produced by the above method ² TCID ₅₀ / Ml / fish) was once immersed in larvae to raise immunity. After 15 days, an immersion treatment was added again, and the animals were reared for 10 days in a flowing water environment. ^4.0 TCID ₅₀ / Ml / fish) is used to determine the immune effect of the vaccine. The result is as shown in FIG.
[0025]
(Example 7)
Material for selection
Base material: 60% hydrogenated palm stearin oil + 30% hydrogenated palm oil
Chemical implants: TGIV inactivated vaccine 10%
Process conditions
Duct pipe diameter: 20 nm
Injection speed: 300L / hr
Nozzle diameter: 0.8mm
Production method
The hydrogenated palm stearin oil, hydrogenated coconut oil and TGIV inactivated vaccine are sufficiently uniformly stirred at a temperature of 55 ± 3 ° C., and then injected into a 38 ± 1 ° C. aqueous solution by a pump, granulated, and frozen. Transfer to a dryer and dry.
result
Particles with a particle size in the range of 30-180 nm are obtained.
[0026]
(Example 8)
Material for selection
Base material: 100% hydrogenated palm stearin oil
Process conditions
Duct pipe diameter: 20 nm
Injection speed: 300L / hr
Nozzle diameter: 0.8mm
Production method
The hydrogenated palm stearin oil is sufficiently uniformly stirred at a temperature of 70 ± 3 ° C., poured into 45 ± 1 ° C. water by a pump, granulated, transferred to a freeze dryer and dried.
result
By the above method, particles having a particle size in the range of 30 to 180 nm are obtained (see FIG. 6), and the specific gravity is smaller than that of water, so that the particles are suspended and dispersed in water. The melting point of the particles is 53 ° C., and 1000 g can be produced per lot.
[0027]
Example 9
Material for selection
Base material: 1% sodium alginate aqueous solution
Process conditions
Duct pipe diameter: 20 nm
Injection speed: 300L / hr
Nozzle diameter: 0.7mm
Production method
The 1% sodium alginate aqueous solution is sufficiently uniformly stirred at room temperature, and then poured into a 3% calcium lactate aqueous solution at room temperature by a pump and granulated.
result
1000g of nano-grade particles having the same specific gravity as water can be produced per lot. In addition, after being allowed to stand for a predetermined time, the particles collect and become turbid.
effect
Water-soluble nanoparticles are obtained.
[0028]
(Example 10)
Material for selection
Base material: 4% Agar aqueous solution
Process conditions
Duct pipe diameter: 20 nm
Injection speed: 300L / hr
Nozzle diameter: 0.7mm
Production method
The 4% Agar aqueous solution is sufficiently uniformly stirred at a temperature of 60 ° C., and then poured into water at room temperature by a pump and granulated.
result
1000 g of nano-grade particles having a specific gravity similar to that of water can be produced for each lot, and after standing for a predetermined time, the particles collect and become turbid.
effect
Water-soluble nanoparticles are obtained.
[0029]
As can be seen from the above examples, compared with the conventional coacervation method and spray suspension fluid bed method, the particle production method of the present invention is stable in physical properties and stably coated with chemical substances. Particles that can be produced, and by adjusting the melting point and specific gravity of the particles, particles that can be applied in fields such as medicine, food, and fisheries can be obtained.
Furthermore, in the coacervation method, a complicated manufacturing process is required to manufacture the particles, and it is difficult to continuously generate the particles. In addition, the spray suspension fluid bed method has a high equipment cost, and it is difficult to produce high quality particles in a high production time in a short time. On the other hand, if the manufacturing method of the particle | grains of this invention is used, the said problems can be solved at a stretch.
[0030]
Hereinafter, an experiment in which the nanoparticles of the present invention are applied to prevention of TGIV infection in fish will be described.
[0031]
one. Mass production of TGIV inactivated vaccine
TGIV was inoculated into a swineblader (SB) cell line that was monolayer-cultured at MOI = 0.1-1 and cultured for 7-14 days at a temperature of 25 ° C. Thereafter, the virus solution is collected, repeatedly frozen and thawed, and then impregnated with formalin at a temperature of 4 ° C. for 4 days, or after impregnated with BPL at a temperature of 20 ° C. for 4 days.
[0032]
two. Effect of immunization of grouper using immersion method with TGIV inactivated vaccine with and without coating layer
1. After diluting the above TGIV inactivating vaccine with seawater, larvae of groupers are immersed in the diluted solution for 1 hour to immunize them, and after 15 days of breeding by running under running water, they are again immersed for 1 hour. Is added to the seawater breeding tank and reared for 10 days (Group A). Alternatively, grouper fry is soaked in a virus immunization solution for 1 hour, and then reared for 25 days by running under water (Group B). And 10 for each group of grouper fry ^4.0 TCID ₅₀ Attack test with / ml TGIV and record the mortality of grouper fry after 2 weeks.
2. The TGIV inactivated vaccine is granulated into nanoparticles based on the method described in Example 2 and then diluted with seawater. A grouper fry is immersed in the diluted solution for 1 hour to generate immunity. After breeding for 15 days by breeding, a 1 hour immersion treatment is added again, and it is transferred to a seawater breeding tank for 10 days (Group A). Alternatively, grouper fry is soaked in a virus immunization solution for 1 hour, and then reared for 25 days by running under water (Group B). And 10 for each group of grouper fry ^4.0 TCID ₅₀ Attack test with / ml TGIV and record the mortality of grouper fry after 2 weeks.
FIG. 7 shows TGIV inactivated vaccine with or without formalin or BPL encapsulated (7 × 10 ² TCID ₅₀ / Ml) soaked fry of grouper (average body length 2.3 cm, body weight about 1.8 g) to raise immunity, and then TGIV (10 ⁴ TCID ₅₀ / Fish) is a figure which shows the result of an attack test at the time of injecting. As can be seen from the non-immunized group (control group) (black rhombus), the specimen was completely annihilated within 10 days after the challenge test, and the survival rate with time was 0%. On the other hand, in the immunity group, the symbol of the predetermined shape filled with color is the result of immunization caused by the nanoencapsulated vaccine, and the symbol of the predetermined shape outlined therein is not nanoencapsulated The result of raising immunity with the vaccine is shown. As shown in FIG. 7, the time course survival rate (10 days) of fry immunized with the encapsulated BPL vaccine was 90% (see line 1) and was not encapsulated and immunized with the BPL vaccine The survival rate (10 days) of the fry was 70% (see line 2). In contrast, the inactivated vaccine with formalin was inferior in immune effect compared to the BPL vaccine, whether encapsulated or not (see lines 5 and 8).
Thus, the survival rate after 25 days of the fry immunized with the non-nanoencapsulated vaccine immersion liquid is about 70%, whereas the fry immunized with the nanoencapsulated vaccine immersion liquid. In view of the fact that the survival rate is still over 90%, encapsulating the vaccine proves to be an effective method for the prevention of fish virus infection.
[0033]
In the above description, preferred embodiments of the present invention are disclosed. However, the present invention is not limited to the embodiments, but is limited only by the scope of the claims, and does not depart from the gist of the present invention. It goes without saying that various modifications within the scope are also included in this proposal.
[0034]
【The invention's effect】
The following effects can be achieved by the configuration of the present plan.
1. Provided with chemical embedded particles, a method for producing the particles, and a production apparatus that can be widely applied to food, pharmaceutical, marine industry, or semiconductor wafer materials, and can be produced at low cost and high productivity by a simple operation with an inexpensive substrate can do.
2. It is possible to provide chemical embedded particles that are effective in preventing Taiwan Grouper's iridovirus infection.
[Brief description of the drawings]
FIG. 1 is a view showing a preferred embodiment of the apparatus for producing particles of the present invention.
2 is a photograph of the appearance of regular spherical particles produced according to Example 1. FIG.
3 is a photograph of an external appearance photograph of regular spherical particles produced according to Example 2. FIG.
4 is an SEM photograph of regular spherical nanoparticles produced in Example 6. FIG.
FIG. 5 is a graph showing the viral immunity effect on Taiwanese grouper fry by the nano-grade vaccine produced according to Example 6; formalin or BPL TGIV inactivated vaccine (7 × 10 ² TCID ₅₀ / Ml) soaked fry of grouper to raise immunity. After 15 days, dipping treatment was added again, and after 10 days of breeding under running water, TGIV (10 ⁴ TCID ₅₀ / Fish) is a figure which shows the result of an attack test at the time of injecting.
6 is a graph showing the size distribution of nanoparticles produced according to Example 8. FIG.
FIG. 7: TGIV inactivated vaccine with or without encapsulation of formalin or BPL (7 × 10 ² TCID ₅₀ / Ml) soaking the grouper's larvae to immunize them, and TGIV (10 ^4.0 TCID ₅₀ / Fish) is a figure which shows the result of an attack test at the time of injecting.
[Explanation of symbols]
101, 102, 104, 107 containers
105 duct
109 Driving means
111 nozzles

Claims (19)

At least one base selected from hydrogenated vegetable oils, hydrogenated animal oils and C ₈ -C ₆₄ saturated fatty acids, with a blending amount of 30-99.9% by weight,
Chemical substance-embedded particles comprising a chemical substance-embedded material having a blending amount of 0.1 to 70% by weight and having a particle size in the range of 0.01 to 5.0 mm. Water-insoluble substrate group consisting of hydrogenated vegetable oil, hydrogenated animal oil, C ₈ -C ₆₄ saturated fatty acid and derivatives thereof, or temperature-change gel body, divalent ion gel body and derivatives thereof A base material selected from the group having a blending amount of 30 to 99.9% by weight;
Chemical substance-embedded particles having a particle diameter in the range of 20 to 1000 nm, comprising a chemical substance-embedded material having a blending amount of 0.1 to 70% by weight. The chemical substance-embedded particles according to claim 1 or 2, wherein the hydrogenated vegetable oil is selected from the group consisting of hydrogenated palm oil, hydrogenated palm oil, hydrogenated bean oil, hydrogenated peanut oil, and hydrogenated vegetable oil. . The chemical-embedded particles according to claim 1 or 2, wherein the hydrogenated animal oil is selected from the group consisting of hydrogenated butter, hydrogenated cream, hydrogenated fish oil, and hydrogenated lard. The C ₈ -C ₆₄ saturated fatty acid is caprylic acid, pelargonic acid, capric acid, undecyl acid, dodecyl acid (lauric acid), tridecyl acid, myristic acid, pentasilic acid, palmitic acid, margaric acid, stearic acid, nonadecylic acid The chemical substance-embedded particles according to claim 1 or 2, which are selected from the group consisting of arachidic acid, heneicosanoic acid, behenic acid, and derivatives thereof. The chemical substance embedding particle according to claim 1, wherein the chemical substance embedding material is a drug, a physiologically active substance, an inorganic compound, or an organic compound. The chemical substance embedding particle according to claim 2, wherein the chemical substance embedding material is a marine vaccine. The chemical-implanted particles according to claim 7, wherein the aquatic vaccine is an iridovirus inactivated vaccine. The chemical substance-embedded particles according to claim 2, wherein the gel body is sodium alginate, pectin, agar, or agar weed. The chemical substance-embedded particles according to claim 1 or 2, wherein the base material comprises stearic acid and lauric acid, and the chemical substance-embedded material is an animal or human vaccine. The chemical substance-embedded particles according to claim 10, wherein the base material further contains glycerin. 2. The chemical substance-embedded particles according to claim 1, wherein the base material is stearic acid, and the chemical substance-embedded material is composed of fish protein and chitosan. 3. The chemical substance-embedded particles according to claim 1, wherein the base material is refined hydrogenated palm stearin oil, and the chemical substance-embedded material is composed of brewer's yeast and a spirulina extract. Hydrogenated vegetable oil, a step of melting at least one substrate selected from a saturated fatty acid of hydrogenated animal oils and C ₈ -C _64,
A step of uniformly mixing the melted base material and the chemical substance embedding material so that the blending proportion is 30 to 99.9% by weight: 0.1 to 70% by weight;
The mixture of the molten base material and the chemical substance embedding material is brought to a temperature at least 5 ° C. lower than the melting point of the base material at an injection rate of 5 to 100 L / hr with a nozzle having a diameter of 0.9 to 5.0 mm in the duct. is maintained, the specific gravity is injected into the medium solution is ^{0.6g / cm 3 ~1.5g / cm 3} , a particle size and a step of granulating the particles of 0.01～5.0Mm, chemicals Method for producing embedded particles. Hydrogenated vegetable oil, hydrogenated animal oil, water-insoluble substrate group consisting of C _{8 to} C ₆₄ saturated fatty acids and derivatives thereof, or divalent ion gels and derivatives thereof, water-soluble groups consisting of temperature-change gels and derivatives thereof Melting a substrate selected from a group of materials;
A step of uniformly mixing the melted base material and the chemical substance embedding material so that the blending proportion is 30 to 99.9% by weight: 0.1 to 70% by weight;
The mixture of the molten base material and the chemical substance embedding material is brought to a temperature at least 5 ° C. lower than the melting point of the base material at an injection rate of 150 to 300 L / hr by a nozzle having a diameter of 0.01 to 0.8 mm in the duct. is maintained, the specific gravity is injected into the medium solution is ^{0.6g / cm 3 ~1.5g / cm 3} , a particle size and a step of granulating the particles of 20 to 1000 nm, producing chemicals embedded particles Method. A container (102) for accumulating a molten substrate;
A container (104) for storing chemical embedding material;
A container (101) for connecting the container (102) and the container (104), respectively, and mixing the molten substrate from the container (102) and the chemical embedding material from the container (104);
A container (107) for accumulating a medium solution;
A driving means (109) connected to the container (101) and the container (107) by a duct (105), and transferring a mixture of the molten substrate and the chemical embedding material to the duct (105);
In the duct (105), the mixture of the molten base material and the chemical substance embedding material, which is disposed at the end connected to the container (107) in the duct (105), is accumulated in the container (107). An apparatus for producing chemical substance-embedded particles, comprising a nozzle (111) for injecting into a medium solution. The apparatus for producing chemical substance-embedded particles according to claim 16, wherein the driving means (109) is a peristaltic pump or a gear pump. 17. The chemical substance embedded particle manufacturing apparatus according to claim 16, wherein the duct (105) is a plastic tube, a PE tube, a Teflon tube, a copper tube, or a stainless tube. The apparatus for producing chemical substance-embedded particles according to claim 16, wherein a material of the nozzle (111) is plastic, PE, Teflon, copper or stainless steel.

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