201010614 六、發明說明： 【發明所屬之技術領域】 本發明係關於一種殺生物劑組合物，該等組合物之製備 方法及其用途。特定言之，本發明係關於一種具有選自抗 病毒、抗細菌、抗真菌性質中之至少兩種性質的微粒狀殺 生物劑組合物。 【先前技術】 環境中所存在危害人類健康的微生物正日受關注。該等 微生物包括細菌、病毒及真菌。其中特別關注毒性致病性 微生物之傳播，包括細菌，諸如抗甲氧苯青黴素金黃色葡 萄球菌awrewsXMRSA)、銅綠假單胞菌 {Pseudomonas aeruginosa (P. aeruginosa))及大腸埃希氏菌 (Esc/zen'c/z/a 〇?// (E. coli));病毒，諸如 SARS冠狀病毒（SARS-CoV)、禽流感病毒H5N1、及人類免疫缺陷病毒（HIV)。亦 希望限制真菌種屬之生長，諸如白色念珠菌 α/Mcims (C. albicans))及釀酒酵母（iSacc/zaromyce·? cereWWae (S. cerevisiae)) ° 因此仍舊需要一種可透過提供新穎之殺生物及/或抑制 生物之產品來預防該等微生物之生長及其傳播的方法。該 等產品之有利用途在於減少致病性微生物透過直接接觸傳 播，或與環境中表面、水中發現的生物、空氣中生物或媒 介（諸如蚊子或肉類）中所攜帶的生物相互作用所造成間接 接觸之傳播。 已知一些金屬具有殺細菌性質。例如銀離子與銅離子用 142207.doc 201010614 於水處理，其係透過破壞細胞壁引起革蘭氏陰性菌（諸如 退伍軍人病菌（Legionella))細胞溶解。該等金屬常呈細粒形 式使用，以使暴露於環境之金屬表面積最大化。必需使用 可達到所需殺菌效果的最低金屬量。然而’存在一些與彼 等產品相關之問題，例如必須平衡所用之金屬量與消耗 率。存在金屬越多，產品成本越高，而存在金屬越少，消 耗率或因與其他化學物相互反應的鈍化率越高。鈍化問題 係使用該等金屬所固有的問題，因彼等通常自然反應容 易形成氧化物、氫氧化物或其他鹽類。該等副反應會抑制 金屬的殺細菌效果。另外，在熱處理含銀及銅物質時，很 難避免發生降解或反應，因此限制彼等於需要高溫處理之 顆粒中之用途。 另外，已知銀、銅及金會從彼等計晝產生活性之位點遷 移，滲濾入其環境中。不希望此現象發生，因其不僅損失 金屬之殺生物效益，而且汙染鄰近物質。因此，在某些範 圍内限制該等元素作為殺生物劑使用。 宜解決或改進一些或全部上述問題。 已發現奈米顆粒可用於醫藥調配物，以改善藥物之可溶 性及/或生物活性。奈米顆粒亦可用於醫學目的。例如銀 奈米顆粒已用於殺滅細菌（Furn〇等人j Antimicrob201010614 VI. Description of the Invention: [Technical Field] The present invention relates to a biocide composition, a preparation method of the composition and use thereof. In particular, the present invention relates to a particulate biocide composition having at least two properties selected from the group consisting of antiviral, antibacterial, and antifungal properties. [Prior Art] Microorganisms that are harmful to human health in the environment are receiving attention. Such microorganisms include bacteria, viruses and fungi. Particular attention is paid to the spread of toxic pathogenic microorganisms, including bacteria such as methicillin-resistant Staphylococcus aureus awrewsXMRSA, Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (Esc/). Zen'c/z/a 〇?// (E. coli)); viruses such as SARS coronavirus (SARS-CoV), avian influenza virus H5N1, and human immunodeficiency virus (HIV). It is also desirable to limit the growth of fungal species such as Candida albicans alpha/Mcims (C. albicans) and Saccharomyces cerevisiae (iSacc/zaromyce·? cereWWae (S. cerevisiae)). Therefore, there is still a need to provide novel killing organisms. And/or methods of inhibiting the growth of biological products and their propagation. The beneficial use of these products is to reduce the indirect contact of pathogenic microorganisms through direct contact or in interaction with organisms found in surfaces, water found in organisms, or organisms in the air, such as mosquitoes or meat. Spread. Some metals are known to have bactericidal properties. For example, silver ions and copper ions are treated with water at 142207.doc 201010614, which causes cell lysis of Gram-negative bacteria (such as Legionella) by disrupting the cell wall. These metals are often used in the form of fine particles to maximize the surface area of the metal exposed to the environment. It is necessary to use the minimum amount of metal that will achieve the desired germicidal effect. However, there are some problems associated with their products, such as the need to balance the amount of metal used and the rate of consumption. The more metal present, the higher the product cost, and the less metal there is, the higher the rate of depletion or the rate of passivation with other chemicals. Passivation problems are problems inherent in the use of such metals, as they are generally naturally reactive to form oxides, hydroxides or other salts. These side reactions inhibit the bactericidal effect of the metal. In addition, when heat-treating silver-containing and copper-containing materials, it is difficult to avoid degradation or reaction, thus limiting the use in which particles are required to be treated at high temperatures. In addition, it is known that silver, copper and gold migrate from their sites of activity and percolate into their environment. This phenomenon is not expected to occur because it not only loses the biocidal benefits of metals, but also contaminates adjacent substances. Therefore, these elements are restricted to be used as biocides in certain ranges. Some or all of the above issues should be addressed or improved. Nanoparticles have been found to be useful in pharmaceutical formulations to improve the solubility and/or biological activity of the drug. Nanoparticles can also be used for medical purposes. For example, silver nanoparticles have been used to kill bacteria (Furn〇 et al. j Antimicrob
Chemother，54(6)，1019-24 (2004))。 已於 WO 2007/093808(Queen Mary & Westfield College 等人）中論述奈米顆粒作為抗病毒劑之用途，其描述奈米 顆粒金屬鹽於減少及預防病毒傳播上之用途。該文獻中， 142207.doc 201010614 描述通式MnXy化合物’其中μ為⑴由下列各鈣、鋁、 鋅、鎳、鎢、或銅組成之群中選出之金屬；或（ii)由下列 各矽、棚或碳組成之群中選出之非金屬；其中η等於i、 2、或3，且X為（Ui)由下列各氧、氮或碳組成之群中選出 之非金屬；或（iv)由下列各磷酸根、磷酸氫根、磷酸二氫 根、碳酸根、矽酸根、硫酸根、硝酸根、亞硝酸根組成之 群中選出之陰離子；其中y等於〇、i、2、3、或4;其用於 減少及/或預防病毒傳播。然而，此文所揭示者俱限於抗 病毒劑’且未提出抗病毒劑、抗菌劑及抗真菌劑之組合需 求。 GB 071 5728.2(Qinetiq Nanomaterials有限公司）亦教示以 金屬（特定言之，鎮）於抗病毒上之用途。其提供通式 WnXy之鎢化合物’其中X為非金屬、類金屬或陰離子，且 其中η等於1或2且y等於0、1、2或3。此文教示由所揭示的 鎢化合物（抗病毒性）與第二種已知具有抗微生物或抗真菌 性質的化合物混合’可獲得超過一種形式之殺生物劑。此 等化合物組合可應用於多種物品，而不損失殺生物活性。 然而，SARS、禽流感及人類流感之病毒爆發之影響， 及從醫院消除MRS A時持續存在問題及由此導致的相關結 果顯示，目前所有抗感染之防禦範圍有限。因此，需要一 種改良方法，以預防細菌、病毒及真菌之生長及/或傳 播。 【發明内容】 本發明之第一態樣中’提供以包含顆粒的組合物作為殺 142207.doc 201010614 生物劑之用途，該顆粒包含： a) —種通式MnXy化合物’其中Μ係選自鈣、鋁、辞、 錄、鎢、銅、石夕、棚、碳及其組合；且X係選自氧、氮 碳、磷酸根、磷酸氫根、磷酸二氫根、碳酸根、梦酸根、 硫酸根、硝酸根、亞硝酸根及其組合；其中η為於1至3範 圍内且y為於1至4範圍内；及 b) 選自銅、釕、錄、纪、銀、銖、锇、銀、鉑、金、 汞及其組合之貴金屬； 其中’作為殺生物劑之該組合物之殺生物效應包括殺病 毒、殺細菌及殺真菌效應中之兩種或更多種。 上述組合物提供一種顆粒，其中由無機基質承載責金 屬。已發現在該基質存在下所產生組合物在稀釋使用時， 會展現高於僅使用貴金屬時所期望之效應。 如上所述’本發明組合物之殺生物效應係選自殺病毒、 殺細菌及殺真菌中之兩種或更多種。許多例子中，該組合 物具有抗病毒性質，及抗菌性質與抗真菌性質中之至少一 種。例如，該組合物之殺生物效應可包括殺病毒與殺細菌 效應；殺病毒與殺真菌效應；或殺病毒、殺細菌與殺真菌 效應。或者’亦希望該組合物具有殺細菌與殺真菌組合效 應。 殺生物效應可包括殺病毒效應（H5N1、貓卡里西病毒）與 殺細菌效應（金黃色葡萄球菌、MRSA '綠膿桿菌及大腸桿 函）及/或权真菌效應（白色念珠菌及釀酒酵母）之組合。該 組合物之殺真菌用途通常用於控制酵母菌。宜提供一種可 142207.doc 201010614 作為殺多種生物之製劑使用之單一組合物，因為病毒、細 菌及真菌之區別極大且屬性不同，故通常難以製備殺病毒 及/或殺細菌及/或殺真菌之組合物。此點尤其考驗當試圖 組合抗病毒性質與抗菌及/或抗真菌性質時。廣譜性殺生 物劑通常由數種組分組成，其中每一種分別針對攻擊特定 生物。當必須包含多於一種活性時，藉由此種方式製備之 殺生物劑可能在安定性（不同活性成分通常不能穩定相容） 及生產成本增加上出現問題。文中描述之組合物藉由某些 方法解決此問題。 本發明之第二態樣中，提供殺生物劑組合物，其包含至 少兩種不同組成之顆粒（第一微粒組成及第二微粒組成）， 該第一微粒組成包括： a) 通式MnXy化合物，其中Μ係選自鈣、鋁、鋅、鎳、 鎢、銅、矽、硼、碳及其組合；且X係選自氧、氮、碳、 鱗酸根、磷酸氫根、磷酸二氫根、碳酸根、矽酸根、硫酸 根、硝酸根、亞硝酸根及其組合；其中η為於1至3範圍内 且y為於1至4範圍内；及 b) 選自銅、釕、錢、把、銀、銖、锇、銀、鉑、金、 汞及其組合之貴金屬； 及第二微粒組成包括： 選自銅、釕、铑、鈀、銀、銖、餓、銥、鉑、金、汞及 其組合之責金屬； 其中第二微粒組成大體上不含通式Mnxy化合物，其中 M係選自鈣、鋁、鋅、鎳、鎢、銅、矽、硼、碳及其組 142207.doc 201010614 合’及x係選自氧、氮、碳、碟酸根、填酸氫根、礙酸二 氫根、碳酸根、矽酸根、硫酸根、硝酸根、亞硝酸根及其 組合；其中n為於1至3範圍内且y為於1至4範圍内。 本發明之第三態樣中，提供一種製備殺生物劑組合物之 方法’其由通式MnXy化合物與貴金屬進入電漿流中，且 所得蒸汽在離開電漿流時冷卻；其中 Μ係選自鈣、鋁、鋅、鎳、鎢、銅、矽、硼、碳及其組 合； X係選自氧、氮、碳、磷酸根、磷酸氫根、磷酸二氫根、 碳酸根、矽酸根、硫酸根、硝酸根、亞硝酸根及其組合； η為於1至3範圍内且y為於1至4範圍内；及 該貴金屬係選自銅、釕、铑、鈀、銀、銖、锇、錶、 鉑、金、汞及其組合。 本發明之第四態樣中，提供一種經過包括顆粒之殺生物 劑組合物塗覆或浸潰過之物品或表面，該顆粒包含： a) 通式MnXy化合物，其中μ係選自鈣、鋁、辞、鎳、 鎢、銅、矽、硼、碳及其組合；且X係選自氧、氮、碳、 磷酸根、磷酸氫根、磷酸二氫根、碳酸根、矽酸根、硫酸 根、硝酸根、亞硝酸根及其組合；其中η為於1至3範圍内 且y為於1至4範圍内；及 b) 選自銅、釘、錢、把、銀、鍊、鐵、銀、始、金、 汞及其組合之貴金屬； 其中該組合物之殺生物效應包括殺病毒、殺細菌及殺真 菌效應中之兩種或更多種。 142207.doc -9- 201010614 本發明之第五態樣包括—種以根據本發明之第四態樣之 表面或物品於減少及/或預防細菌、病毒或真菌中之一種 或多種（通常兩種或更多種）傳播上之用途。本發明之第六 態樣係關於—種以如第二態樣中所述之殺生物劑組合物作 為抗病毒劑、&菌劑或抗真菌劑中—種或多種（通常兩種 或更多種）之用途。 主本發明之第七態樣亦說明一種減少及/或預防細菌、病 毒及真菌中之一種或多種(通常兩種或更多種)傳播之方 法，該方法包括本發明第—態樣之用㉟，施用該組合物至 物品或表面。 【實施方式】 組合物 、本發明組合物通常包括奈米顆粒。奈米顆粒意為具有奈 米尺寸大小之顆粒，且奈米顆粒可具有例如約幾奈米至幾 微米之尺寸大小。奈米顆粒之平均粒度可等於或小於之 等於或小於200碰，在許多例子中等於或小於2〇請。在 許多例子下，該組合物由實質上所有顆粒均落於小於2㈣ 尺寸範圍’或落於小於200 nm尺寸_，或小於2〇謹尺 寸範圍内之奈米顆粒所組成。過渡前，奈米顆粒之一般尺 寸範圍為⑴⑼^通常為⑴⑽心然而若顆粒在 製造後過瀘'，則其可在組合物中呈2至5〇⑽，或甚至2至 20 run尺寸範圍存在。 為了本申請案之目的，術語「實質上所有」意指9〇%或 以上’通常95。/。或以上，最”98%或以上之顆粒或所述 142207.doc •10、 201010614 之其他特性。平均粒度係關於該顆粒最寬處之直徑。 所述顆粒之比表面積可為15〇 m2/g至約丨4” m2/g，通常 200 m2/g至約 700 m2/g，適宜之數值可包括 15〇 m2/g、64〇 m2/g、 700 m /g。顆粒中存在之空隙可為〇」至約〇 8 ml/g，適宜 為0.2至約〇.7 ml/g ’通常為約0.6 mi/g。 該顆粒（包括奈米顆粒）通常呈乾燥粉末形式，但亦可呈 液體、溶膠-凝膠體或多聚物及奈米管形式。該等顆粒可 團聚或自由結合。 在許多例子中，通式MnXy化合物係呈化學計量，在該 等情況下’ η等於1、2或3且y等於丨、2、3或4。在化學計 量之化合物中，η及y之數值可取決於Μ&γ之相對價數而 變化。但亦可能為非化學計量之化合物。 顆粒結構通常為通式MnXy與貴金屬之密切混合。例 如’顆粒分析顯示MnXy與貴金屬係均勻分配於顆粒中。 該等顆粒實質上均質化。或者該等顆粒可製成層合（核心/ 鲁 外殼）顆粒，其包括貴金屬外殼及單獨或與貴金屬混合之 通式MnXy化合物内核心。在該等實例中，可發現至少一 部分貴金屬位於顆粒表面；通常該貴金屬至少部分塗覆顆 粒表面。例如，在至少10%之顆粒表面積上塗覆貴金屬， 通常在至少25%，或50%之顆粒表面積上塗覆貴金屬。可 能需要以責金屬塗覆50至1〇〇%之顆粒表面積，可能需要 塗覆70至1〇〇%或最佳μ至i〇〇0/。之範圍。 通式MnXy與貴金屬之相對比例，可由熟悉此技術者根 據顆粒每一組分之性質及殺生物劑組合物所應用之特定用 142207.doc 201010614 途而變化。 在論述顆粒之混合及結構時，通常任一組合物中至少 50 /〇顆粒具有上述性質，有些實例中占顆粒之⑽至丨, 通常90或95至100%。 組合物可另外包含第二微粒組成之第二類型顆粒，其不 同於第-類型顆粒之組成。第二類型顆粒可為如上述之大 小、形狀及結構。 第二微粒組成之顆粒包括選自銅、釕、铑、鈀、銀、 銖、餓、銥、鉑、金、汞及其組合之貴金屬；其中顆粒實籲 質上不含通式MnXy化合物，其中¥係選自鈣、鋁、鋅、 鎳、鴻、銅、矽、硼、碳及其組合；且乂係選自氧、氮、 碳、磷酸根、磷酸氫根、磷酸二氫根、碳酸根、矽酸根、 硫酸根、靖酸根、亞墙酸根及其組合；其中η為於⑴範 圍内且y為於1至4範圍内。 文中所使用之術語「實質上不含」意指僅含微量之通式 MnXy化合物。例如’通式MnXy化合物可占第二微粒組成 之〇至1重量。/。，經常在〇至〇_5重量％ ’更經常在〇至〇 2重量參 %，通常o-o.i wt%，在許多例子中，通式MnXy化合物不 存在於第二微粒組成中。 已驚奇發現，第一微粒組成之顆粒與第二微粒組成之顆 粒=組合當用在殺生物劑組合物中時，所提供之殺生物效 * 應间於所有顆粒實質上為相同組成時所觀察到效應。最顯 著的殺細菌及殺真菌劑效應出現在顆粒稀釋液遠高於實質 上所有顆粒同時包含由通式ΜηΧ_合物所形成基質與責 142207.doc •12- 201010614 金屬二者時所觀察之效應。另外，若通式MnXy化合物與 貴金屬皆具有獨立可觀察到之殺生物效應，則這兩種顆粒 類型之組合所提供的協同殺生物效應將大於兩種獨立可觀 察到之效應之總和。 每一組成的顆粒相對比例將取決於殺生物劑組合物所要 求之最終性質。例如，如果要求組合物之殺細菌效應大於 殺病毒效應’則第二微粒組合物之顆粒所占含量可大於第 一微粒組合物之顆粒’反之亦然。然而，通常希望同時存 在兩種顆粒，該組合物將包括40至60重量％之每一種顆粒 類型’經常為45至55重量％，更經常為兩種顆粒實質上占 相等數量。 有些情況下，Μ可為早一元素且X為單一陰離子或類金 屬或非金屬。在該等情況下，Μ係選自飼、铭、鋅、錄、 嫣、銅、矽、硼、碳；且X係選自氧、氮、碳、磷酸根、 磷酸氫根、磷酸二氫根、碳酸根、矽酸根、硫酸根、确酸 根與亞硝酸根。 許多例子十，選擇Μ及X以提供物理性堅固且耐高溫之 通式MnXy化合物。通常Μ包括鎢，因為鎢化合物對高溫 安定’且本發明者已發現，即使在加工時暴露於嚴酷條件 下’其仍具有實質之殺細菌及殺真菌效應。X可為碳及/或 氧。經常Μ為鎢且X為碳，因而MnXy包括鎢碳化物，換言 之’ MnXy可選自WC、W2C及其組合。 貴金屬經常獨立選自銀、銅、金及其組合。已發現鎢碳 化物與銅、銀或其組合之組合在抗病毒及抗細菌用途上提 142207.doc •13· 201010614 供特別有效之殺生物效應。 製法 可藉由例如氣相合成或溶膠-凝膠方法製備微粒組合 物。在氣相合成中’顆粒（經常為奈米顆粒）可在低於常壓 之惰性氣體環境中’藉由蒸發及冷凝（成核及生長）產生。 可使用多種氣溶膠加工技術來改善奈米顆粒之產量。其包 括利用燃燒火焰、電漿、雷射燒蝕、化學蒸汽冷凝、喷灑 熱解、電喷灑及電漿喷灑之合成法。 亦可使用球磨或其他研磨形式’產生顆粒（包括奈米顆 粒）°在研磨技術中，最終粒度取決於下列因素，包括研 磨介質之尺寸、外型及組成，製程變數、磨具之設計與操 作。 若需要使所產生顆粒間之尺寸達最低變化程度時，氣相 合成法為達到目的之一種可靠方法。通常利用嚴格控制成 核-冷凝生長及藉由擴散與渦流避免凝集之組合法，之後 並有效收集顆粒與後續處理，來獲得粒度均一性。可於液 態懸浮液中收集顆粒，保證所收集顆粒粉末具有抵抗凝 聚、燒結及組成變化之安定性。 適於生產奈米顆粒之製造方法之—為Tesima⑧方法（描述 於WO 01/78471及WO 01/58625) ’其使用高溫DC電漿（電 聚火炬）在氣體包圍環境巾產生電㈣。該氣體包圍環境 可為惰性，例如包括氣氣或氦氣；或可含有反應性氣體， 例如氮氣。氮氣含量可占〇至2〇重量％，重量％或2至 5重量％。材料（預製原料或混合原料）（或液體）可放置於電 142207.doc •14- 201010614 聚中’引起快速蒸發。所得蒸汽隨後逸出電漿，此時可利 用大量冷氣體冷卻。該等氣體可為惰性氣體（諸如氩氣或 氦氣）、空氣，或可包括為了發展出化學/外型/尺寸所需之 微量組分。快速冷卻（每秒超過1〇〇 〇〇〇度），隨後冷凍顆 粒，供繼續冷卻及利用可能包括@體或纖維過遽、、氣旋及 液體系統之組合技術進行收集。材料亦可於惰性氣體下直 接收集至容器内或進入多種液體中。 本發明包括一種方法，其包括由通式MnXy化合物與貴 金屬進入電漿流’且所得蒸汽在離開該物流時冷卻。該電 漿流（在某些實例中）可為熱電漿流。在該方法中，通式 MnXy化合物與貴金屬在進入電漿流前組合、在進入電漿 時組合，或根本不組合。另外，該貴金屬（在某些實例 中）可在通式MnXy化合物暴露於電漿流後，但在所得蒸汽 冷卻前，與通式MnXy化合物組合。結果產生之顆粒具有 至少部分塗覆貴金屬之通式MnXy化合物核心。 通常’通式MnXy化合物與貴金屬共同送入如上所述之 熱電漿火炬中。 通常’會產生顆粒的原料係呈小粒形式。此點可能需要 前處理步驟（諸如研磨步驟），以製備用於反應之原料。許 多例子中，原料顆粒之尺寸為直徑小於1〇 μπι ,經常為】 至5 μηι範圍内，或2 μηι至4 μΓη範圍内。使用細粒形式之 原料可增加用於反應之表面積，且因此提高反應速率。組 分之更緊密混合亦有利。然而已發現，使用尺寸小於丨μιη 或2 μηι之顆粒不利於加工，因為新的材料開始互相黏合或 142207.doc -15· 201010614 結塊。其降低材料通過加工設備之流動速率，且增加管道 堵塞之風險，造成中止生產，直至清理加工設備為止。 有些實例中，在顆粒形成前，貴金屬至少部分與通式 MnXy化合物組合。有些實例中，在顆粒形成前，貴金屬 實質上全部與通式MnXy化合物組合，例如藉由使用研磨 方法。或者，在顆粒形成前，通式MnXyi合物與貴金屬 皆至少部分或實質上全部溶解於替代性溶劑中。如文中所 用，術語「至少部分」及「實質上全部」意欲具有相關技 藝中之一般通用含義。例如，如文中所用之「實質上全 部」意指其在宏觀尺度上，僅可見到極少量溶質呈與溶 質-溶劑溶液之分離相。 顆粒可藉由簡單摻合通式MnXy化合物與貴金屬而形 成。或者可使用如上所述之研磨方法。該研磨法通常產生 機械性連接通式MnXy化合物與責金屬。 使用熱電漿火炬可促進產生具有高表面積且實質上均一 尺寸之顆粒，其對高溫安定。其使所得殺生物劑組合物可 用於尚溫下之處理法’例如，可用於將殺生物劑組合物加 至塑膠產物中，以產生具有本質上抗微生物的表面的產 物。 已驚奇發現藉由通式MnXy化合物與責金屬進入電漿流 中’且所得蒸汽在離開電漿流時冷卻，所製成之顆粒當用 於殺生物劑組合物時，所提供之殺生物劑效應大於使用其 他製備技術（例如機械研磨）時所觀察到效應。最顯著的殺 細菌劑與殺真菌劑效應出現在顆粒稀釋液，遠大於使用研 142207.doc -16- 201010614 磨或其他簡單共同混合通式MnXy化合物與貴金屬之技術 所形成之顆粒。 在不受理論束缚下，此可能因為利用電漿火炬所製得顆 粒係雙重組合物。更特定言之，所產生之顆粒具有至少兩 種不同組成（第一微粒組成與第二微粒組成），該第一微粒 組成包含貴金屬與通式MnXy基質材料，該第二微粒組成 包含沒有基質材料之貴金屬。明確言之，第一微粒組成包 括： a) 通式MnXy化合物，其中μ係選自鈣、鋁、鋅、鎳、 鶴、銅、矽、硼、碳及其組合；且X係選自氧、氮、碳、 鱗酸根、磷酸氫根、磷酸二氫根、碳酸根、矽酸根、硫酸 根、硝酸根、亞硝酸根及其組合；其中η為於丨至3範圍内 且y為於1至4範圍内；及 b) 選自銅、釕、铑、鈀、銀、銖、锇、銥、鉑、金、 采及其組合之貴金屬； 及第一微粒組成包括： 選自銅、釕、铑、鈀、銀、鍊、锇、銥、鉑、金、汞及 其組合之貴金屬； 其中第二微粒組成實質上不含通式MnXy化合物，其中 Μ係選自鈣、鋁、鋅、鎳、鎢、銅、矽、硼、碳及其組 合；且X係選自氧、氮、碳、磷酸根、磷酸氫根、磷酸二 氫根、碳酸根、矽酸根、硫酸根、硝酸根、亞硝酸根及其 組合，其中η為於1至3範圍内且y為於丨至4範圍内。 利用其他方法（特定言之，研磨）所製得顆粒被認為具有 142207.doc 17 201010614 -致結構’其中每—顆粒包含通式MnXy化合物與貴金 屬。 另外，若通式MnXy化合物與責金屬皆獨立具有可觀察 到之殺生物效應時，此兩種基f之組合可提供大於兩種獨 立觀察效應總和之協同殺生物效應。 該組合物可調配用於適宜載體、塗層或溶劑（諸如水、 曱酵、乙醇、丙酮）、水溶性多聚黏合劑(諸如聚乙酸乙烯 醋、環氧樹脂、聚酯等）及耦合劑、抗靜電劑。亦可使用 生物性材料溶液，如：磷酸鹽緩衝生理食鹽水（pBs)或擬 似生物體液（SBF)。 顆粒之濃度可位於0.001至20重量％，經常在〇〇1至1〇重 量％ ’偶爾0.1至5重量％範圍内。 或者，該等顆粒呈粉末形式包含於組合物中。彼等可塗 覆或浸潰至表面或物品中，或與諸如漂白土或砂之吸收性 粉末混合。 用途 減少及/或預防致病性微生物傳播之作法除了預防從一 地區傳播至另一地區，或預防透過媒介材料傳播外，尚包 括預防個趙感染病毒、細菌或真菌。該個體可為人類或非 人類動物’以非人類哺乳動物為宜。本發明因此可用於人 類醫學與動物獸醫學領域’並用於在非醫學環境中控制感 &之領域’諸如對抗微生物傳播及/或擴散之預防性藥 物。 所述之組合物可用於密閉公共建築之通風結構，及交通 142207.doc 18 201010614 工具(諸如汽車、火車、船及飛機)。該組合物亦可用於醫 學應用，諸如於過渡材料中（亦即諸如血毁、血液、奶或 ***之生物流體之《)’以使存在的任何病毒、細菌及/ 或真菌失活。 該抗病毒顆粒可塗覆於紡織品及不同產品之表面，諸如 傢倶、塗料/塗層、書籍封面及電腦鍵盤，以產生具有殺 生物劑性質之產品。該等產品將以較低成本之方式為醫Chemother, 54(6), 1019-24 (2004)). The use of nanoparticles as antiviral agents has been discussed in WO 2007/093808 (Queen Mary & Westfield College et al.), which describes the use of nanoparticulate metal salts for reducing and preventing viral transmission. In this document, 142207.doc 201010614 describes a compound of the formula MnXy where μ is (1) a metal selected from the group consisting of calcium, aluminum, zinc, nickel, tungsten, or copper; or (ii) a non-metal selected from the group consisting of sheds or carbon; wherein η is equal to i, 2, or 3, and X is (Ui) a non-metal selected from the group consisting of the following oxygen, nitrogen, or carbon; or (iv) An anion selected from the group consisting of phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, citrate, sulfate, nitrate, and nitrite; wherein y is equal to 〇, i, 2, 3, or 4 It is used to reduce and/or prevent the spread of the virus. However, all of the disclosures herein are limited to antiviral agents' and no combination of antiviral, antibacterial and antifungal agents has been proposed. GB 071 5728.2 (Qinetiq Nanomaterials Co., Ltd.) also teaches the use of metals (specifically, towns) for antiviral purposes. It provides a tungsten compound of the formula WnXy where X is a non-metal, metalloid or anion, and wherein n is equal to 1 or 2 and y is equal to 0, 1, 2 or 3. This teaching teaches that more than one form of biocide can be obtained by mixing the disclosed tungsten compound (antiviral) with a second compound known to have antimicrobial or antifungal properties. These combinations of compounds can be applied to a wide variety of articles without loss of biocidal activity. However, the impact of SARS, avian influenza and human influenza outbreaks, and the persistence of problems with MRS A removal from hospitals and the associated results indicate that all current anti-infective defenses are limited. Therefore, an improved method is needed to prevent the growth and/or spread of bacteria, viruses and fungi. SUMMARY OF THE INVENTION In a first aspect of the invention, the invention provides a composition comprising particles as a biological agent for killing 142207.doc 201010614, the particles comprising: a) a compound of the formula MnXy wherein the lanthanide is selected from the group consisting of calcium , aluminum, rhetoric, recorded, tungsten, copper, stone shed, shed, carbon and combinations thereof; and X is selected from the group consisting of oxygen, nitrogen, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, dream acid, sulfuric acid Root, nitrate, nitrite, and combinations thereof; wherein η is in the range of 1 to 3 and y is in the range of 1 to 4; and b) is selected from the group consisting of copper, ruthenium, ruthenium, silver, ruthenium, osmium, A noble metal of silver, platinum, gold, mercury, and combinations thereof; wherein the biocidal effect of the composition as a biocide comprises two or more of a virucidal, bactericidal, and fungicidal effect. The above composition provides a granule in which the inorganic substrate is carried by the inorganic substrate. It has been found that compositions produced in the presence of the matrix exhibit a higher than expected effect when only the precious metal is used, when used in diluted form. As described above, the biocidal effect of the composition of the present invention is selected from two or more of virucidal, bactericidal and fungicidal. In many instances, the composition has antiviral properties, and at least one of antibacterial and antifungal properties. For example, the biocidal effects of the composition can include viricidal and bactericidal effects; viricidal and fungicidal effects; or viricidal, bactericidal and fungicidal effects. Alternatively, the composition is also expected to have a bactericidal and fungicidal combination. Biocidal effects may include viricidal effects (H5N1, cat Carrisi virus) and bactericidal effects (Staphylococcus aureus, MRSA 'Pseudomonas aeruginosa and large intestine) and/or fungal effects (Candida albicans and Saccharomyces cerevisiae) a combination of). The fungicidal use of the composition is typically used to control yeast. It is desirable to provide a single composition that can be used as a multi-biological preparation. Because viruses, bacteria and fungi are very different and have different properties, it is often difficult to prepare virucidal and/or bactericidal and/or fungicidal. combination. This is especially true when trying to combine antiviral properties with antibacterial and/or antifungal properties. A broad spectrum biocide typically consists of several components, each of which is directed against a particular organism. When more than one activity must be included, biocides prepared in this manner may present problems in stability (different active ingredients are generally not compatible) and increased production costs. The compositions described herein solve this problem by some means. In a second aspect of the invention, there is provided a biocide composition comprising particles of at least two different compositions (a first particle composition and a second particle composition), the first particle composition comprising: a) a compound of the formula MnXy Wherein the lanthanide is selected from the group consisting of calcium, aluminum, zinc, nickel, tungsten, copper, lanthanum, boron, carbon, and combinations thereof; and the X system is selected from the group consisting of oxygen, nitrogen, carbon, sulphate, hydrogen phosphate, dihydrogen phosphate, a carbonate, a citrate, a sulfate, a nitrate, a nitrite, and combinations thereof; wherein η is in the range of 1 to 3 and y is in the range of 1 to 4; and b) is selected from the group consisting of copper, bismuth, money, and a precious metal of silver, ruthenium, iridium, silver, platinum, gold, mercury, and combinations thereof; and a second particulate composition comprising: selected from the group consisting of copper, ruthenium, rhodium, palladium, silver, osmium, hunger, ruthenium, platinum, gold, mercury And a combination thereof; wherein the second particulate composition is substantially free of a compound of the formula Mnxy, wherein the M is selected from the group consisting of calcium, aluminum, zinc, nickel, tungsten, copper, lanthanum, boron, carbon, and combinations thereof 142207.doc 201010614 ' and x are selected from the group consisting of oxygen, nitrogen, carbon, acid acid, hydrogenate, dihydrogen chloride, carbonate, and citrate Sulfate, nitrate, nitrite and combinations thereof; wherein n is in the range of from 1 to 3 and y is in the range of 1-4. In a third aspect of the invention, there is provided a method of preparing a biocide composition which is passed from a compound of the formula MnXy and a noble metal into a plasma stream, and the resulting vapor is cooled as it exits the plasma stream; wherein the lanthanide is selected from the group consisting of Calcium, aluminum, zinc, nickel, tungsten, copper, strontium, boron, carbon and combinations thereof; X is selected from the group consisting of oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, citrate, sulfuric acid Root, nitrate, nitrite, and combinations thereof; η is in the range of 1 to 3 and y is in the range of 1 to 4; and the noble metal is selected from the group consisting of copper, ruthenium, rhodium, palladium, silver, osmium, iridium, Table, platinum, gold, mercury, and combinations thereof. In a fourth aspect of the invention, there is provided an article or surface coated or impregnated with a biocide composition comprising particles, the particles comprising: a) a compound of the formula MnXy, wherein the μ is selected from the group consisting of calcium and aluminum , nickel, tungsten, copper, bismuth, boron, carbon and combinations thereof; and X is selected from the group consisting of oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, citrate, sulfate, Nitrate, nitrite and combinations thereof; wherein η is in the range of 1 to 3 and y is in the range of 1 to 4; and b) is selected from the group consisting of copper, nail, money, handle, silver, chain, iron, silver, A noble metal of priming, gold, mercury, and combinations thereof; wherein the biocidal effect of the composition includes two or more of a virucidal, bactericidal, and fungicidal effect. 142207.doc -9- 201010614 A fifth aspect of the invention includes a surface or article according to the fourth aspect of the invention for reducing and/or preventing one or more of bacteria, viruses or fungi (usually two More or more) the purpose of communication. A sixth aspect of the invention relates to a biocide composition as described in the second aspect as one or more of an antiviral agent, an <bacterial agent or an antifungal agent (usually two or more) A variety of uses. The seventh aspect of the invention also describes a method for reducing and/or preventing the spread of one or more (usually two or more) of bacteria, viruses and fungi, including the first aspect of the invention 35. Applying the composition to an article or surface. [Embodiment] The composition, the composition of the invention generally comprises nanoparticle. The nanoparticle means a particle having a nanometer size, and the nanoparticle may have a size of, for example, about several nanometers to several micrometers. The average particle size of the nanoparticles may be equal to or less than or equal to 200 hits, and in many cases equal to or less than 2 Å. In many instances, the composition consists of nanoparticle having substantially all of the particles falling within a size range of less than 2 (four) or falling within a size of less than 200 nm, or less than 2 inches. Prior to the transition, the general size of the nanoparticles is (1) (9) ^ usually (1) (10). However, if the particles pass the 泸 after manufacture, they can be present in the composition in the range of 2 to 5 〇 (10), or even 2 to 20 run size. . For the purposes of this application, the term "substantially all" means 9 % or more 'usually 95'. /. Or above, the most "98% or more of the particles or other characteristics of the 142207.doc • 10, 201010614. The average particle size is about the diameter of the widest part of the particle. The specific surface area of the particle may be 15〇m2 / g To about 4" m2/g, usually from 200 m2/g to about 700 m2/g, suitable values may include 15 〇 m2/g, 64 〇 m2/g, 700 m/g. The voids present in the granules may range from about ml8 to about 8 ml/g, suitably from 0.2 to about 7.7 ml/g', typically about 0.6 mi/g. The granules (including the nanoparticles) are usually in the form of a dry powder, but may also be in the form of a liquid, a sol-gel or a polymer and a nanotube. The particles may be agglomerated or freely bonded. In many instances, the compound of the formula MnXy is stoichiometric, in which case 'η is equal to 1, 2 or 3 and y is equal to 丨, 2, 3 or 4. In stoichiometric compounds, the values of η and y may vary depending on the relative valence of Μ & γ. However, it may also be a non-stoichiometric compound. The particle structure is usually intimately mixed with the noble metal of the formula MnXy. For example, 'particle analysis shows that MnXy and the noble metal are evenly distributed in the particles. The particles are substantially homogenized. Alternatively, the particles may be formed into a laminated (core/lube shell) particle comprising a noble metal shell and an inner core of the formula MnXy compound, either alone or in combination with a noble metal. In such instances, at least a portion of the precious metal may be found to be on the surface of the particle; typically the precious metal is at least partially coated with the surface of the particle. For example, the precious metal is coated on at least 10% of the surface area of the particles, typically at least 25%, or 50% of the surface area of the particles. It may be necessary to coat 50 to 1% of the surface area of the particles with a metal, which may require coating of 70 to 1% or optimum μ to i〇〇0/. The scope. The relative proportions of the formula MnXy to the noble metal can be varied by the skilled artisan depending on the nature of each component of the particle and the particular application of the biocide composition 142207.doc 201010614. In discussing the mixing and structure of the granules, typically at least 50 Å of the granules in any of the compositions have the above properties, and in some instances occupies (10) to bismuth, typically 90 or 95 to 100%. The composition may additionally comprise a second type of particles of the second particle composition, which is different from the composition of the first type of particles. The second type of particles may be of a size, shape and structure as described above. The particles composed of the second particles comprise a noble metal selected from the group consisting of copper, ruthenium, rhodium, palladium, silver, iridium, osmium, iridium, platinum, gold, mercury, and combinations thereof; wherein the particles are substantially free of the compound of the formula MnXy, wherein ¥ is selected from the group consisting of calcium, aluminum, zinc, nickel, hong, copper, lanthanum, boron, carbon and combinations thereof; and the lanthanide is selected from the group consisting of oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, and carbonate. , citrate, sulfate, sulphate, sulphate and combinations thereof; wherein η is in the range of (1) and y is in the range of 1 to 4. The term "substantially free" as used herein means a trace amount of a compound of the formula MnXy. For example, the compound of the formula MnXy may constitute from 1% by weight of the second particle composition. /. It is often in the range of 〇 to 5% by weight ‘ more often in 〇 to 〇 2 重量%, usually o-o.i wt%, in many instances, the compound of the formula MnXy is not present in the second particle composition. Surprisingly, it has been found that the particles of the first particle composition and the particles of the second particle combination are used when used in a biocide composition, and the biocidal effect provided should be observed when all particles are substantially identical in composition. To the effect. The most significant bactericidal and fungicidal effects occur when the granular diluent is much higher than substantially all of the particles and contains both the matrix formed by the general formula and the 142207.doc •12- 201010614 metal. effect. In addition, if the compound of the formula MnXy and the noble metal have independently observed biocidal effects, the combination of the two types of particles provides a synergistic biocidal effect that is greater than the sum of the two independently observable effects. The relative proportion of particles of each composition will depend on the desired properties of the biocide composition. For example, if the bactericidal effect of the composition is desired to be greater than the viricidal effect' then the particles of the second particulate composition may comprise more than the particles of the first particulate composition' and vice versa. However, it is generally desirable to have both particles at the same time, which composition will comprise from 40 to 60% by weight of each particle type' often from 45 to 55% by weight, more often the two particles will be substantially equal. In some cases, Μ may be an early element and X is a single anion or metalloid or non-metal. In such cases, the lanthanide is selected from the group consisting of feed, inscription, zinc, lanthanum, cerium, copper, cerium, boron, and carbon; and X is selected from the group consisting of oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, and dihydrogen phosphate. , carbonate, citrate, sulfate, acid and nitrite. In many instances X, X and X are selected to provide a physically strong and high temperature resistant compound of the formula MnXy. Typically, ruthenium includes tungsten because the tungsten compound is stable to high temperatures' and the inventors have discovered that it has substantial bactericidal and fungicidal effects even when exposed to harsh conditions during processing. X can be carbon and/or oxygen. Often tanning is tungsten and X is carbon, and thus MnXy includes tungsten carbides, in other words, MnXy may be selected from the group consisting of WC, W2C, and combinations thereof. The precious metals are often independently selected from the group consisting of silver, copper, gold, and combinations thereof. The combination of tungsten carbide with copper, silver or a combination thereof has been found to provide a particularly effective biocidal effect in antiviral and antibacterial applications. 142207.doc •13· 201010614. Process The particulate composition can be prepared by, for example, gas phase synthesis or a sol-gel process. In gas phase synthesis, 'particles (often nano-particles) can be produced by evaporation and condensation (nucleation and growth) in an inert gas atmosphere below atmospheric pressure. A variety of aerosol processing techniques can be used to improve the production of nanoparticle. It includes synthesis using combustion flames, plasma, laser ablation, chemical vapor condensation, spray pyrolysis, electrospray, and plasma spray. Ball milling or other abrasive forms can also be used to produce particles (including nanoparticles). In grinding technology, the final particle size depends on the following factors, including the size, shape and composition of the grinding media, process variables, design and operation of the tool. . The gas phase synthesis method is a reliable method for achieving the purpose if it is desired to minimize the size of the particles produced. Particle size uniformity is typically obtained by a combination of strict control of nucleation-condensation growth and avoidance of agglutination by diffusion and vortex, followed by efficient collection of particles and subsequent processing. The particles can be collected in a liquid suspension to ensure that the collected particulate powder has stability against aggregation, sintering and compositional changes. A method suitable for the production of nanoparticles is the Tesima8 process (described in WO 01/78471 and WO 01/58625) which uses a high temperature DC plasma (electrothermal torch) to generate electricity in a gas enveloped environmental wipe (4). The gas entraining environment may be inert, including, for example, gas or helium; or may contain a reactive gas such as nitrogen. The nitrogen content may be from 2% by weight, % by weight or from 2% to 5% by weight. The material (pre-formed or mixed) (or liquid) can be placed in electricity 142207.doc •14- 201010614 in the polymerization to cause rapid evaporation. The resulting steam then escapes the plasma where it can be cooled with a large amount of cold gas. The gases may be inert gases (such as argon or helium), air, or may include minor components required to develop a chemical/profile/size. Rapid cooling (more than 1 每秒 per second), followed by freezing of the pellets for continued cooling and collection using a combination of techniques that may include @body or fiber over-the-counter, cyclone and liquid systems. The material can also be collected directly into the container under inert gas or into a variety of liquids. The invention includes a process comprising entering a slurry stream from a compound of the formula MnXy with a noble metal and the resulting vapor is cooled as it exits the stream. The slurry stream (in some instances) can be a hot plasma stream. In this method, the compound of the formula MnXy is combined with the precious metal before entering the plasma stream, combined upon entering the plasma, or not combined at all. Alternatively, the noble metal (in some instances) may be combined with a compound of the formula MnXy after the compound of the formula MnXy is exposed to the plasma stream, but prior to cooling of the resulting vapor. The resulting particles have a core of the general formula MnXy compound at least partially coated with a noble metal. Typically, the 'formula MnXy compound is co-fed with a noble metal into a hot plasma torch as described above. Usually, the raw material which produces particles is in the form of small particles. This may require a pre-treatment step, such as a milling step, to prepare the starting material for the reaction. In many instances, the size of the raw material particles is less than 1 〇 μπι in diameter, often in the range of 5 μηι, or 2 μηι to 4 μΓη. The use of a raw material in a fine particle form increases the surface area for the reaction and thus increases the reaction rate. A closer mix of components is also advantageous. However, it has been found that the use of particles having a size smaller than 丨μιη or 2 μηι is not conducive to processing because the new materials begin to bond to each other or agglomerate at 142207.doc -15· 201010614. It reduces the flow rate of material through the processing equipment and increases the risk of pipe blockage, causing production to be suspended until the processing equipment is cleaned. In some instances, the noble metal is at least partially combined with the compound of the formula MnXy prior to particle formation. In some instances, the noble metal is substantially all combined with the compound of the formula MnXy prior to particle formation, for example by using a milling process. Alternatively, the MnXyi compound and the noble metal are at least partially or substantially completely dissolved in the alternative solvent prior to particle formation. As used herein, the terms "at least a portion" and "substantially all" are intended to have the generic meaning of the art. For example, "substantially all" as used herein means that on a macroscopic scale, only a very small amount of solute is observed as a separate phase from the solute-solvent solution. The particles can be formed by simply blending a compound of the formula MnXy with a noble metal. Alternatively, a grinding method as described above can be used. This milling process typically produces a mechanical linkage of the compound of the formula MnXy with the responsible metal. The use of a hot plasma torch promotes the production of particles having a high surface area and a substantially uniform size which is stable to high temperatures. It allows the resulting biocide composition to be used in a treatment at room temperature', e.g., for the biocide composition to be added to a plastic product to produce a product having an antimicrobial surface. It has been surprisingly found that by the addition of the compound MnXy compound and the responsible metal into the plasma stream and the resulting vapor is cooled as it leaves the plasma stream, the resulting pellets, when used in a biocide composition, provide the biocide The effect is greater than that observed when using other preparative techniques such as mechanical milling. The most significant bactericidal and fungicidal effects occur in granular diluents, much larger than those formed by the technique of grinding or other simple techniques of simply mixing a compound of the formula MnXy with a noble metal. Without being bound by theory, this may be due to the use of a plasma torch to produce a granule double composition. More specifically, the resulting particles have at least two different compositions (a composition of a first particle and a second particle), the first particle composition comprising a noble metal and a matrix material of the formula MnXy, the second particle composition comprising no matrix material Precious metal. Specifically, the first particulate composition comprises: a) a compound of the formula MnXy wherein the μ is selected from the group consisting of calcium, aluminum, zinc, nickel, crane, copper, cerium, boron, carbon, and combinations thereof; and the X is selected from the group consisting of oxygen, Nitrogen, carbon, sulphate, hydrogen phosphate, dihydrogen phosphate, carbonate, citrate, sulfate, nitrate, nitrite, and combinations thereof; wherein η is in the range of 丨 to 3 and y is in 1 to a range of 4; and b) a noble metal selected from the group consisting of copper, ruthenium, rhodium, palladium, silver, iridium, ruthenium, osmium, platinum, gold, and combinations thereof; and the first particulate composition comprising: selected from the group consisting of copper, ruthenium, iridium a noble metal of palladium, silver, chain, ruthenium, rhodium, platinum, gold, mercury, and combinations thereof; wherein the second particulate composition is substantially free of a compound of the formula MnXy, wherein the lanthanide is selected from the group consisting of calcium, aluminum, zinc, nickel, tungsten , copper, bismuth, boron, carbon and combinations thereof; and X is selected from the group consisting of oxygen, nitrogen, carbon, phosphate, hydrogen phosphate, dihydrogen phosphate, carbonate, citrate, sulfate, nitrate, nitrite And combinations thereof, wherein η is in the range of 1 to 3 and y is in the range of 丨 to 4. The particles obtained by other methods (specifically, grinding) are considered to have a structure of 142207.doc 17 201010614, wherein each particle contains a compound of the formula MnXy and a noble metal. Alternatively, if the compound of the formula MnXy and the responsible metal are both independently observable for biocidal effects, the combination of the two groups f provides a synergistic biocidal effect greater than the sum of the two independent observation effects. The composition can be formulated for use in a suitable carrier, coating or solvent (such as water, fermentation, ethanol, acetone), water-soluble multi-adhesive (such as polyvinyl acetate, epoxy, polyester, etc.) and coupling agent , antistatic agent. Biomaterial solutions such as phosphate buffered saline (pBs) or pseudo-biological fluids (SBF) can also be used. The concentration of the granules may be in the range of 0.001 to 20% by weight, often in the range of 〇〇1 to 1% by weight, occasionally 0.1 to 5% by weight. Alternatively, the particles are included in the composition in powder form. They may be coated or impregnated onto surfaces or articles or mixed with absorbent powder such as bleaching earth or sand. Uses In addition to preventing transmission from one area to another, or preventing transmission through media, it is also necessary to prevent the spread of viruses, bacteria or fungi. The individual may be a human or non-human animal 'as a non-human mammal. The present invention is thus applicable to the field of human medicine and animal veterinary medicine' and is used in the field of controlling sensation & in a non-medical environment such as a prophylactic drug against the spread and/or spread of microorganisms. The composition can be used to ventilate structures in public buildings, and to transport 142207.doc 18 201010614 tools (such as cars, trains, boats, and airplanes). The compositions may also be used in medical applications, such as in transition materials (i.e., "such as blood, blood, milk, or semen, biological fluids") to inactivate any viruses, bacteria, and/or fungi present. The antiviral particles can be applied to textiles and surfaces of different products, such as furniture, coatings/coatings, book covers, and computer keyboards to produce products having biocide properties. These products will be treated at a lower cost
院、兒童、患者及老人提供較安全m步的用途 y包括用於密閉環境（諸如客機）之空調系統，例如預防空 瑕*中病毒進入或排出。 本發明之物品可塗覆或浸漬過上述殺生物劑组合物。若 之至乂塗覆或浸潰過之表面與待移除之微生 物直接接觸時，該組合物將發揮最大效力。例如，保護性 布料可匕括已塗覆抗病毒劑組合物之纺織品及，或纖維， 且k I用之暴露表面可以塗覆該組合物。同樣地植棱桌 面亦可浸潰過或塗覆殺生物劑組合物，以產生本質上抗微 生物之表面。醫院中可使用該表面以幫助改善手術過程之 安全性，4用於家庭中，減少透過家t存在致病性微生物 之疾病傳播。 可使用之塗覆及浸潰方法為彼等相關技藝中常見並為熟 心、此技術者所熟知者。其包括噴塗法、擠出層壓法、共擠 出法t噴灑塗覆法、浸潰或電漿鑛膜法。The use of safer m-steps for hospitals, children, patients and the elderly y includes air-conditioning systems for confined environments such as passenger aircraft, such as preventing the entry or exit of viruses in airspace*. The article of the invention may be coated or impregnated with the above biocide composition. The composition will exert maximum effectiveness if the coated or impregnated surface is in direct contact with the microorganism to be removed. For example, the protective cloth can include textiles and/or fibers that have been coated with an antiviral composition, and the exposed surface for the coating can be applied to the composition. Similarly, the ribbed surface can also be impregnated or coated with a biocide composition to produce an anti-microbial surface. This surface can be used in hospitals to help improve the safety of the surgical procedure. 4 It is used in the home to reduce the spread of disease-causing microorganisms through the home. Coating and impregnation methods that can be used are common to those skilled in the art and are well known to those skilled in the art. It includes spray coating, extrusion lamination, coextrusion t spray coating, impregnation or plasma film.
示了塗覆或次潰物品本身外’物品之組分亦可使用組合 物則處理。你丨L J如’物可由已塗覆殺生物劑組合物之纖維 142207.doc •19- 201010614 組成。該等物品纟s。i 彳物°°通常選自過濾網、面軍、外科手術口罩、 呼吸器面罩、帽子、 评丁觀衫、手套、連褲戎工 作服及外科手術服。亦可使 I,... 于/、獸醫器材或預防器 :。二者，人們經常接觸之表面(特別為公共區域 t門、開關等）)均可塗覆及/或浸潰過該組合物。食品製 2域及其所使用器皿或設備同樣可根據本發明之化合物 過濾網可由任何適宜的天然或人造材料製造。過滤網可 為工孔過;f網。空氣過滤網為移除空氣中雜質（通常為固 體顆粒)之器材。空氣過濾網通常用於潛水空氣壓縮器、 ，風系統及任何其他重視空氣品質之環境（諸如线調節 早心空氣過渡網包括在密閉空間（諸如建築物或房間）及 處理病毒材料之裝置或區域中過濾空氣之器材。因此其他 具有保護功旎之物品(;諸如窗簾或篩網）亦可視為空氣過濾 網。 空氣過濾網可由紙、發泡體、棉濾網、或紡絲玻璃纖維 過濾70件組成。或者，空氣過濾網亦可使用具有靜態電荷 之纖維或元素。四種主要類型之機械式空氣過濾網為紙、 發泡體、合成物及棉。 設計用於家庭取暖、通風及空調（HVAC)系統之管道内 用途的褶紙式空氣過濾網之一實例為3]^之「Fihrete」產 品° 聚醋纖維可用於製造用於過濾空氣之網狀形成物。聚酯 可與棉或其他纖維摻合’以產生廣泛的性能。有些例子可 142207.doc •20· 201010614 使用聚丙烯。被稱為微纖維之微小合成纖維可用於多種類 型之高效微粒空氣（HEPA)過濾網。高效空氣過濾網可使用 棉花紗布之塗油層。 或者，過濾網可用於過濾液體。該等過濾網可由如上述 任一適宜纖維組成。用於過濾液體之過濾網可用於過濾供 人類或動物食用之飲用液體、一般家庭用水、醫學用途之 液體（諸如血漿或生理食鹽水）或注射用醫藥調配物、或其The components of the article which are shown as coated or sub-cracked items may also be treated using the composition. Your 丨L J such as ' can be composed of the fiber 142207.doc •19- 201010614 which has been coated with the biocide composition. These items are 纟s. i 彳°°° are usually selected from filters, facials, surgical masks, respirator masks, hats, spectacles, gloves, romper, and surgical gowns. Can also make I,... in /, veterinary equipment or preventive devices: Both, surfaces that are often in contact with people (especially for public areas, doors, switches, etc.) can be coated and/or impregnated with the composition. The food product 2 field and the utensils or equipment used therewith may likewise be made in accordance with the compounds of the invention. The filter screen may be made of any suitable natural or man made material. The filter can be a work hole; f network. Air filters are equipment that removes impurities (usually solid particles) from the air. Air filters are commonly used in submersible air compressors, wind systems, and any other environment where air quality is important (such as line-regulated early-air air transition networks included in confined spaces (such as buildings or rooms) and devices or areas that handle viral materials. Equipment for filtering air. Therefore, other items with protective functions (such as curtains or screens) can also be regarded as air filters. Air filters can be filtered by paper, foam, cotton filter, or spun glass. Alternatively, the air filter can also use statically charged fibers or elements. The four main types of mechanical air filters are paper, foam, composites and cotton. Designed for home heating, ventilation and air conditioning. An example of a pleated air filter for in-pipe use of a (HVAC) system is the "Fihrete" product of 3]^ Polyvinyl acetate fiber can be used to make a mesh formation for filtering air. Polyester can be used with cotton or Other fibers blend 'to produce a wide range of properties. Some examples can be used 142207.doc •20· 201010614 to use polypropylene. Microfibers called microfibers It is used in many types of high efficiency particulate air (HEPA) filters. High efficiency air filters can use oil coatings of cotton gauze. Alternatively, filters can be used to filter liquids. These filters can be composed of any suitable fiber as described above. The filter screen for filtering liquid can be used for filtering drinking liquid for human or animal consumption, general household water, liquid for medical use (such as plasma or physiological saline) or pharmaceutical preparation for injection, or
他可能與患者接觸之生物液體。 保護性布製品宜由已塗覆如上定義之顆粒之纖維組成。 保護性布料產物可為面罩。該等面罩可覆蓋使用者之整個 面部或其一部分’以佩戴者之鼻及/或嘴的外部區域為 宜。 保護性布製品可由任一適宜纖維或織物製得，且可包括 天然及/或造纖維。適宜的天然纖維包含棉、羊毛、纖維 素（包含紙原料）、絲、毛髮、黃麻、***、劍麻、亞麻、 木、竹、金屬或碳。適宜的人造纖維包含聚酯、人造絲、 尼龍、Kevlar®、溶媒纖維（ly〇ceU)(Tencei⑧卜聚乙烯、 聚丙烯、聚醯亞胺、聚甲基丙烯酸甲酯、聚(苯氧羧酸)磷 腈（PCPP)、纖維玻璃（玻璃）或陶瓷。布製品可選自下列各 物所組成群中：面罩(外科手術口罩、呼吸器面罩）、帽 子、頭巾、褲子、概衫、手套、裙子、連褲式工作服及外 科手術服（刷手服）。可發現該箄.姐_财 J赞現通寻帝枓可用於醫院中以控制 感染為首要工作的特定用途。 關於保4性布製品或過濾'網之本發明態樣中，應注意布 142207.doc -21 - 201010614 製品或過滤網可自上述之任何來源之混合纖維製得。 殺生物劑效應測量 文中所述顆粒及組合物之殺生物劑效應至少為雙重性。 明確言之，本發明之組合物顯示抗病毒效應、抗細菌效應 或抗真菌劑效應中之至少兩種。 如文中所用，術語「微生物」意欲包括病毒、細菌及真 菌；其通常為致病微生物’經常為毒性微生物。 傳播 減少及/或預防病毒、細菌及/或真菌傳播可定義為在對 一種或多種該等微生物製劑投與如文中定義之奈米顆粒組 合物後’使微生物效價減少至少90%。較佳使效價減少至 少93。/。、94%或95% ’最佳為98%、99%或100%。減少及/ 或預防傳播係藉由微生物與顆粒接觸時之失活來證實。 效價減少70%或以下並非足以避免感染之有效減少。本 發明提供減少效價’以顯著預防感染或避免感染之方法。 效價為測定指定樣本中之微生物數量。可利用血球凝集 素試驗（HA)測定效價。HA試驗特別適合檢測病毒，因為 病毒家族具有能夠凝集動物紅血液細胞（RBc)且與Rbc之 細胞表面上N-乙醯神經胺酸殘基鍵合之表面或被膜蛋白。 病毒鍵合之後，RBC將形成一種可以定量之格架。 HA方法係一種容易、簡單及快速之方法，並可應用於 大量樣本。詳細條件取決於微生物種類。例如，有些病毒 僅在—定pH值下鍵合RBC，另一些則在一定離子強度下鍵 合。然而彼等為熟悉此技術者所熟知，且很容易根據所 142207.doc -22· 201010614 a微生物判定。在適宜條件下添加微生物稀釋液至RBC 稀釋液，彳2 、寺適宜時間。隨後，計算格架形成數，並計算 效價。 5、可利用生物發光分析法。例如水中細菌污染物可藉 亦述方法測定：培養水，過濾所得細菌懸浮液，利用試 ” ^ 甲基亞硬）釋出細菌ATP，並利用發光計數檢測 ATP濃度。 亦可利用β-D·葡聚糖分析法測定效價。該分析法係於培 養的血液或血漿樣本上進行。添加鱟變形血球溶胞液至樣 本中，並利用分光光度技術測定光學密度之變化。卜D_葡 聚糖分析法常用於獲得真菌及細菌之效價。 本發明可提供一種減少病毒之病毒效價之方法，該病毒 車乂佳為選自流行性感冒病毒、麻療病毒、冠狀病毒、腿腺 炎病毒、馬爾堡病毒、伊波拉病毒、風疹病毒、鼻病毒、 小兒麻痹病毒、A型肝炎病毒、天花病毒、水痘病毒、嚴 重心丨生呼吸综合症病毒或SARS病毒、HIV及相關之非人類 動物免疫缺陷逆轉錄病毒（諸如狼免疫缺陷病毒（Sly)、輪 狀病毒、諾沃克病毒與腺病毒）之病毒。諾沃克病毒包含 其仿病毒猫卡里西病毒（feline calicivims)。流行性感冒病 毒包含病毒之人類與鳥類形式。 除另說明，如熟悉此技術者所理解，本發明所述之每一 整數可與任一其他整數組合。另外，雖然本發明之所有態 樣較佳「包括」與該態樣相關之特性，但是其明確言之 「包括」或「基本上包括」彼等由請求項中所列之特性。 142207.doc -23- 201010614 除非另外指出，否則本說明書中出現之所有百分比係所 述凡素之重量百分比。另外，除非另外說明，否則本申請 中出現之所有數量數值均理解為由術語「約」修飾。 實例 使用穿透式電子顯微鏡（ΤΕΜ)分析一系列之含銀/銅及鎢 碳化物之顆粒。利用Tesima®方法製造顆粒。原料包括： 奈米顆粒分散於多孔碳鋁架上之方式係藉由超聲波在乙 醇中攪拌粉末，隨後藉由吸液管分散於該架上。讓該溶液 靜置兩分鐘，以避免任何大團塊進入吸液管中。利用帶有 直徑小於5 nm之探測之Philips Techni F20，於200 Kv下產 生顯微圖。隨後以點模式取得元素EDX圖譜及圖。所有影 像均在明視野且係自STEM模式中獲得。 區域1 於此區域檢測鋁、矽、銀、銅、鎢、氧及碳（如圖丨及2 所示）。進一步的EDX圖譜分析（圖3&至3(1)顯示存在含矽、 銅及鎢組合之顆粒。亦觀察到分離的銀顆粒（3〇至5〇 nm)。其示於圖譜中。因此可能存在通式MnXy與貴金屬之 顆粒’及僅包括貴金屬之顆粒。 區域2 區域2之EDX圖譜顯示存在由單一元素組成之顆粒彼 等之實例示於銀及鎢圖譜（圖4及5a-c)另外，存在包括兩種 或更多種元素之區域，該等區域可為由超過一種元素組成 之顆粒，且可含有通式MnXy化合物。 區域3 142207.doc -24- 201010614 如區域2觀察到彳能為單一元素之顆粒（包括鎢及貴金 屬銀與銅)。然而’區域3中更多顆粒包括呈組合存在之兩 種或更多種7L素（圖6及7以）’使得單—顆粒中可能存在通 式MnXy化合物與貴金屬。 區域4 圖及9a d囷解區域4之顆粒分佈。銀顆粒係存在於該區 域，且可能為單獨的含鎢及銀之顆粒。銅存在時，主要與 鎢共存，表示可能存在含有通式MnXy之鎢化合物與責金 屬銅之顆粒，及僅含貴金屬（銀）之顆粒。 區域5 區域5(圖1〇_12)為該組合物中單獨之含銅顆粒提供證 據。自其中一種顆粒（實例中強調之顆粒）得到點模式圖 谱，圖譜中出現的主要元素為銅。該區域之分析亦說明存 在氧化物（可能為通式MnXy化合物），因為樣本中之氧濃度 係不均勻分佈。 區域6 該區域（圖13)所獲之圖譜清晰顯示存在含銅及矽之顆粒 (圖14a’可此含呈元素形式存在之銅）’及含鎢、銅及石夕之 顆粒（圖14b，可能為通式MnXy化合物與責金屬之組合）。 區域7 該區域（圖15)所獲之圖譜顯示存在含矽、銅及鎢之顆粒 (圖16a’可能為通式MnXy化合物與責金屬之組合），及含 銀及銅之顆粒（圖16b)。 區域8 142207.doc -25- 201010614 圖17所示之顆粒圖譜說明此顆粒含有銅、鎢及矽（圖 18，可能為通式MnXy化合物與貴金屬之組合卜 一般觀察 據觀察’銀顆粒係呈尺寸範圍小於丨〇 ηιη之分離的顆粒 存在。偶爾存在尺寸範圍為30至50 nm之更大的銀顆粒。 含銅及鶴之顆粒的尺寸範圍通常為2〇至5〇 nm，該等元素 經常混合出現在單一顆粒中，雖然亦觀察到各種元素之分 離顆粒。鋁及矽亦混合出現在單一顆粒中。 【圖式簡單說明】 圖1為區域1之EDX圖譜，其顯示緊密堆積之顆粒。該圖 譜提供可分析個別顆粒之背景資料； 圖2為點模式圖譜，其說明區域1之元素組成； 圖3a至3d為放大的區域1之EDX圖譜，其說明含石夕、 銀、銅及鎢顆粒之存在； 圖4為區域2之EDX圖譜，其係選自該區域所獲之元素圖 譜之一部分； 圖5a至5c為放大的區域2之EDX圖譜，其說明含石夕、 銀、銅及鎢顆粒之存在； 圖6為區域3之EDX圖譜，其為選自該區域所獲之元素圖 之一部分； 圖7a至7d為放大的區域2之EDX圖譜’其說明含石夕、 銀、銅及鶴顆粒之存在， 圖8為區域4之EDX圖譜，其為選自該區域所獲之元素圖 之一部分； 142207.doc -26- 201010614 圖9a至9d為放大的區域4之EDX圖譜，其說明含石夕、 銀、銅及鎢顆粒之存在； 圖10為區域5之EDX圖譜，其為選自該區域所獲之元素 圖之一部分； 圖11為放大的區域5之EDX圖譜，其說明含銅顆粒之存 在；He may be in contact with the patient's biological fluid. The protective cloth product is preferably composed of fibers which have been coated with granules as defined above. The protective cloth product can be a mask. The masks may cover the entire face of the user or a portion thereof, preferably in the outer region of the wearer's nose and/or mouth. The protective cloth product can be made from any suitable fiber or fabric and can include natural and/or fiber-making. Suitable natural fibers include cotton, wool, cellulose (including paper stock), silk, hair, jute, hemp, sisal, linen, wood, bamboo, metal or carbon. Suitable rayon fibers include polyester, rayon, nylon, Kevlar®, solvent fiber (ly〇ceU) (Tencei8 polyethylene, polypropylene, polyimine, polymethyl methacrylate, poly(phenoxycarboxylic acid) Phosphazene (PCPP), fiberglass (glass) or ceramic. The cloth product can be selected from the group consisting of: masks (surgical masks, respirator masks), hats, headscarves, pants, general shirts, gloves, Skirts, trousers overalls and surgical gowns (brushing clothes). You can find this 箄. Sister _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ In the aspect of the invention of the article or filter 'net, it should be noted that the article 142207.doc -21 - 201010614 article or filter can be made from the mixed fiber of any of the above sources. Biocide effect measurement of the particles and compositions described herein The biocide effect is at least dual. In particular, the composition of the invention exhibits at least two of an antiviral, antibacterial or antifungal effect. As used herein, the term "microorganism" is intended to include Viruses, bacteria and fungi; which are usually pathogenic microorganisms 'often toxic microorganisms. Reduced transmission and/or prevention of viral, bacterial and/or fungal transmission may be defined as the administration of one or more of such microbial preparations as defined herein. After the nanoparticulate composition, the microbial titer is reduced by at least 90%. Preferably, the potency is reduced by at least 93%, 94% or 95% 'best 98%, 99% or 100%. Reduction and / or Prophylactic transmission is confirmed by the inactivation of the microorganisms in contact with the particles. A 70% reduction in potency or less is not sufficient to avoid an effective reduction in infection. The present invention provides a method of reducing the potency to significantly prevent infection or avoid infection. To determine the number of microorganisms in a given sample, the hemagglutinin test (HA) can be used to determine titer. The HA test is particularly suitable for detecting viruses because the virus family has the ability to agglutinate animal red blood cells (RBc) and N on the cell surface with Rbc - Surface or envelope protein bound to the acetaminophen residue. After virus binding, RBC will form a quantifiable lattice. The HA method is an easy, simple and fast method. The method can be applied to a large number of samples. The detailed conditions depend on the type of microorganism. For example, some viruses only bind RBC at a certain pH, while others bind at a certain ionic strength. However, those who are familiar with this technology It is well known and can be easily determined according to the microorganisms of 142207.doc -22· 201010614 a. Add the microbial dilution to the RBC dilution under suitable conditions, 彳2, and the appropriate time of the temple. Then, calculate the grid formation number and calculate the effect. 5. Bioluminescence analysis can be used. For example, bacterial contaminants in water can be determined by the method described below: culture water, filtration of the resulting bacterial suspension, release of bacterial ATP by test "^ methyl hard", and counting by luminescence The ATP concentration was measured. The titer can also be determined by the β-D·glucan assay. This assay is performed on cultured blood or plasma samples. The sputum hematopoietic lysate was added to the sample and the change in optical density was measured by spectrophotometry. D-glucan assays are commonly used to obtain the potency of fungi and bacteria. The invention can provide a method for reducing the virus titer of a virus, which is selected from the group consisting of influenza virus, aphrodisiac virus, coronavirus, leg adenitis virus, Marburg virus, Ebola virus, rubella virus, Rhinovirus, poliovirus, hepatitis A virus, variola virus, varicella virus, severe heartburn respiratory syndrome virus or SARS virus, HIV and related non-human animal immunodeficiency retroviruses (such as wolf immunodeficiency virus (Sly) ), rotavirus, norovirus and adenovirus). Norwalk virus contains its pseudo-virus feline calicivims. Influenza viruses contain human and bird forms of the virus. Unless otherwise stated, as understood by those skilled in the art, each integer described herein can be combined with any other integer. In addition, while all aspects of the invention are susceptible to "comprising" the features of the invention, the <RTIgt; </ RTI> <RTIgt; 142207.doc -23- 201010614 Unless otherwise stated, all percentages appearing in this specification are percentages by weight of the stated elements. In addition, all numerical values appearing in this application are understood to be modified by the term "about" unless otherwise stated. Example A series of particles containing silver/copper and tungsten carbides were analyzed using a transmission electron microscope (ΤΕΜ). Granules are produced using the Tesima® method. The raw materials include: The method in which the nanoparticles are dispersed on the porous carbon aluminum frame is by ultrasonically stirring the powder in ethanol, and then dispersed on the frame by a pipette. Allow the solution to stand for two minutes to avoid any large agglomerates entering the pipette. Micrographs were generated at 200 Kv using a Philips Techni F20 with a probe with a diameter of less than 5 nm. The element EDX map and graph are then taken in dot mode. All images are in bright field and are obtained from the STEM mode. Zone 1 This area detects aluminum, tantalum, silver, copper, tungsten, oxygen, and carbon (as shown in Figure 丨 and 2). Further EDX pattern analysis (Fig. 3 & to 3 (1) shows the presence of particles containing a combination of bismuth, copper and tungsten. Separated silver particles (3 〇 to 5 〇 nm) were also observed. This is shown in the spectrum. There are particles of the general formula MnXy and precious metals' and particles comprising only precious metals. The EDX spectrum of the region 2 region 2 shows that there are particles composed of a single element, and examples of such particles are shown in the silver and tungsten maps (Figs. 4 and 5a-c). There are regions including two or more elements, which may be particles composed of more than one element, and may contain a compound of the formula MnXy. Region 3 142207.doc -24- 201010614 As observed in region 2 Particles of a single element (including tungsten and precious metals such as silver and copper). However, more particles in Zone 3 include two or more 7Ls in combination (Figures 6 and 7), making it possible in single-particles. There is a compound of the formula MnXy and a noble metal. The particle distribution of the region 4 and the 9a d decomposed region 4. The silver particles are present in this region and may be separate tungsten and silver particles. When copper is present, it mainly coexists with tungsten. , indicating that there may be There are tungsten compounds of the general formula MnXy and particles of metallic copper, and particles containing only precious metals (silver). Region 5 Region 5 (Fig. 1〇_12) provides evidence for the individual copper-containing particles in the composition. A particle (the particle highlighted in the example) is obtained from a dot pattern map, and the main element appearing in the spectrum is copper. The analysis of this region also indicates the presence of an oxide (possibly a compound of the general formula MnXy) because the oxygen concentration in the sample is not Uniform distribution. Region 6 The map obtained in this region (Fig. 13) clearly shows the presence of particles containing copper and antimony (Fig. 14a' can contain copper in the form of elements) and particles containing tungsten, copper and Shixi ( Figure 14b, which may be a combination of a compound of the formula MnXy and a responsible metal.) Region 7 The map obtained in this region (Fig. 15) shows the presence of particles containing antimony, copper and tungsten (Fig. 16a' may be a compound of the formula MnXy and Combination of metals) and particles containing silver and copper (Fig. 16b). Region 8 142207.doc -25- 201010614 The particle map shown in Figure 17 indicates that the particles contain copper, tungsten and rhenium (Figure 18, possibly a general formula Group of MnXy compounds and precious metals It has been observed that the 'silver particles are in the form of separated particles having a size range smaller than 丨〇ηιη. Occasionally there are larger silver particles ranging in size from 30 to 50 nm. The size of the copper-containing and crane particles is usually 2 〇 to 5〇nm, these elements are often mixed in a single particle, although separate particles of various elements are also observed. Aluminum and bismuth are also mixed in a single particle. [Simplified schematic] Figure 1 is the region 1 EDX map showing closely packed particles. The map provides background data for analyzing individual particles; Figure 2 is a dot pattern map illustrating the elemental composition of region 1; Figures 3a to 3d are enlarged EDX spectra for region 1, Explain the presence of particles containing stellite, silver, copper and tungsten; FIG. 4 is an EDX spectrum of region 2 selected from a portion of the elemental map obtained in the region; FIGS. 5a to 5c are enlarged EDX spectra of region 2, It illustrates the presence of particles containing stellite, silver, copper and tungsten; Figure 6 is an EDX spectrum of region 3, which is part of the elemental map selected from the region; Figures 7a to 7d are EDX spectra of enlarged region 2. 'its Figure 8 is an EDX spectrum of region 4, which is part of the elemental map selected from the region; 142207.doc -26- 201010614 Figures 9a to 9d are enlarged The EDX spectrum of region 4, which indicates the presence of particles containing stellite, silver, copper, and tungsten; FIG. 10 is an EDX spectrum of region 5, which is a portion of the elemental map selected from the region; The EDX spectrum of region 5, which illustrates the presence of copper-containing particles;
圖12為點模式圖譜，其說明以圖u所示之放大的edx圖 譜為特徵之顆粒的元素組成； 圖13為區域6之EDX圖譜，點模式圖譜係獲自該區域； 圖14a及14b為點模式圖譜，其說明區域6中出現之顆粒 的元素組成； 圖15為區域7之酿圖譜，點模式圖譜係獲自該區域’· 圖祕⑽為點模式圖譜，其說明區域7中出現之顆粒 的元素組成； 圖17為區域8之EDX圖譜，點握+ w曰點模式圖譜係獲自該區域；及 圖18為點模式圖譜，苴呤 曰，、况明區域8中出現之顆粒的元素 組成。 142207.doc .27-Figure 12 is a dot pattern map illustrating the elemental composition of particles characterized by the enlarged edx pattern shown in Figure u; Figure 13 is an EDX spectrum of region 6, from which the dot pattern is obtained; Figures 14a and 14b are Point mode map, which illustrates the elemental composition of the particles appearing in region 6; Figure 15 is the brewing pattern of region 7, which is obtained from the region's image (10) as a point pattern map, which shows the presence in region 7. The elemental composition of the particles; Figure 17 is the EDX spectrum of the region 8, the point grip + w曰 point pattern is obtained from the region; and Figure 18 is the dot pattern map, 苴呤曰, the particles appearing in the region 8 Elemental composition. 142207.doc .27-