TW448157B

TW448157B - Method for producing particles of pyrithione salts

Info

Publication number: TW448157B
Application number: TW87103850A
Authority: TW
Inventors: George A Polson; Richard H Dumas; Rahim Hani
Original assignee: Arch Chem Inc
Priority date: 1997-03-14
Filing date: 1998-03-16
Publication date: 2001-08-01

Abstract

The present invention relates to a method for producing submicron-sized particles of pyrithione salts, comprising reacting pyrithione or a water-soluble salt of pyrithione and a water-soluble polyvalent metal salt in a pressurized turbulent flow reactor that generates pulverizing forces, the reaction producing submicron sized particles of pyrithione salt. The present invention also relates to particles made by the above method, and products, such as shampoos, soaps, and skin care medicaments made using these particles.

Description

經濟部中央標準局員工消費合作社印製 448157 A7 _ B7 五、發明説明（1 ) 本發明通常係關於一種製備羥基吡啶硫酮鹽粒子的方法 ,而且尤其關於在加餮、湍流狀態下製備次微米大小之羥基〃比淀硫嗣鹽粒子的方法〇>本發明也關於以此方法製成粒子，以及由該方法製造之粒子所生成的產物。羥基吡症硫_的多價金屬鹽（也以h羥基_2_吡啶硫酮； 2-吡啶硫醇-1 -氧化物；2-吡啶硫酮；2_氫硫基吡啶_N_氧化物；吡啶硫酮；和吡啶硫酮_N_氧化物聞名）已知是有效的生物殺菌劑’而且廣泛用於塗料中做爲殺眞菌劑和殺細菌劑，以及個人保養產物，如止頭皮屑洗髮精。羥基吡啶硫酮的多價金屬鹽僅稍溶於水，而且包括羥基毗啶硫酮鎂 ’喪基p比症硫_鎖’經基p比喊硫鲷總，經基被症硫酮銅，羥基吡啶硫酮鋅，羥基吡啶硫酮鎘，和羥基吡啶硫銅锆。使用最廣泛的二價羥基吡啶硫酮鹽是羥基吡啶硫酮鋅和羥基P比淀硫嗣銅。羥基吡啶硫酮鋅和羥基吡啶硫酮鋼能用來做爲積極對抗格蘭氏陽性和陰性細菌、眞菌及酵母菌的殺菌劑。羥基吡淀硫鲷鋅用於洗髮精中做爲止頭皮屑成份，而羥基吡啶硫酮鋅和/或幾基峨淀硫酮銅的懸浮液則用於塗料和聚合物中做爲防腐劑和防污劑。多價經基P比喊硫酮鹽的合成载於 Berstein等人的美國專利第2,809,97ι號中。其它揭示相似化合物和製造彼等之方法的專利，包括美國專利第 2,768,847 ; 3,589,999 ; 3,590,035 ; 3,773,770 號。已知有一種會造成平均大小大於2微米之固體大粒子而生成不溶的多價羥基吡啶硫酮鹽的方法。然而，通常需要 ϋ張尺度適f中國國CNsyA4聽_ ( 21〇Χ297公釐) ^~ ^^1 ^^ΙΒ1 n^— l * (請先閱讀背面之注意事項再填寫本頁) 448 15 7 經濟部中央標準局貝Η消費合作社印製 A7 B7 五、發明説明（2 ) 較小的羥基吡啶硫酮鹽粒子（即，低於1微米或次微米），因爲彼等比較容易形成懸浮液，並提供較大表面積因而加強生物殺菌活性。此外，光線能穿透較小粒子，特別是低次微米範園（如，低於0.2微米），因此提供製造目前市場上常見的「透明」產物，像透明洗髮精和香皂的機會。較小的羥基吡啶硫酮鹽粒子通常是以傳統方法製成的較大粒子或結晶上，由個別機械操作之步驟（如，研磨或壓碎 )製成。例如，歐洲專利第70046號敘述利用有機溶劑製備羥基吡啶硫酮鋅。此方法會製造出很容易由過濾作用分離出來的羥基吡啶硫酮鋅大結晶。個別、視情況研磨的步驟係用來研磨大結晶’而五製造較小的幾基p比咬硫酮鋅粒子。如同另一個實施例，美國專利第4,670,430號敘述以研磨較大羥基吡啶硫酮鋅粒子製造約0.2微米中等大小之幾基口比喊硫銅辞粒子的方法。目前無法僅由一個步驟就能製造次微米大小範圍的羥基 p比喊疏酮鹽粒子的方法。研磨較大粒子製造較小粒子的個別步驟，如前藝所敘述，通常會造成有用產物的實質損失，而且就所需儀器、時間和能量而言，其成本昴貴。此外，本藝所需的是不需要經個別機械壓碎或研磨步驟就可製備次微米大小範圍的經基？比淀硫啊鹽粒子之方法。本發明咸信可以符合該需求。本發明一方面係關於製造次微米大小之羥基吡啶硫_鹽粒子的方法’包括羥基吡啶硫酮或羥基吡啶硫酮的水溶性鹽和水溶性多價金屬鹽在會產生霧化力的加壓湍流連續反 _____-5- 本紙張尺度適用中國國家操準（CNS ) A#規格（21〇><297公釐） (請先閱讀背面之注^'項再填寫本頁) /裝- 448157 經濟部中央標準41貝工消费合作社印掣 A7 B7 五、發明説明（3 ) 應器中反應，該反應產生次微米大小之輕基峨症硫酮鹽粒 0 本發明另一方面係關於製造次微米大小之幾基P比虎硫酮鋅粒子的方法’其包含趣基P比峻硫酮或經基p比症網的水溶性鹽和選自含有硫酸鋅、氣化鋅、醋酸鋅及其组合物之水溶性鋅鹽’在會產生霧化力的加壓湍流連續反應器中反應，該湍流反應器的壓力維持在约1 8,000镑/平方英寸至約 23,000磅/平方英寸而溫度維持在约〇。〇至約23 °C，該反應製造次微米大小的經基吡啶硫酮鋅粒子。本發明還有一方面係關於由上述方法製成的粒子，和利用由本發明方法製成粒子而製成的產物。一旦讀了以下本發明之詳細敘述後，就會明暸此等和其它方面。目前意外地發現’根據本發明之溶液會產生在單次操作下有效製造次微米大小之羥基吡啶酮鹽粒子的問題。而本發明以經基t»比咬硫酮或輕基峨淀硫闕的水溶性鹽和水溶性多價金屬鹽’在會產生霧化力的加壓湍流連續反應器中反應，也解決了此問題。由加壓湍流連反應器製造的霧化力 ’不靠個別機械研磨或壓碎步驟，就能有效地生成次微米大小之羥基毗啶硫酮鹽粒子。以本發明方法製造之次微米大小的趣基p比咬疏嗣鹽粒子，其大小分佈有而且均勾，並且由於次微米粒子群提供大表面積而具有優異的表面沉積特性。此大表面積因而改良了洗髮精、香皀和塗料的生物殺菌效果。此外，根據本發明方法製造的次微米大小粒子 -6- 本紙乐尺度適用中國國家標準（CNS ) A4*格（210X297公釐） m n^i > n l V (請先閱讀背面之注項再填寫本頁) 448 15 7 A7 B7 經濟部中央標準局員工消費合作社印繁五、發明説明（4 ) ，當與其它化合物組合時，更容易形成懸浮液，而因此形成的懸浮液對於粒子沉降有較大的物理安定性。本文中使用的術語「羥基吡啶硫酮的水溶性鹽」或「水溶性羥基吡啶硫酮鹽」包括其中硫醇基的氫子經單價陽離子取代的該些經基说遠硫酮I鹽。「水溶性多價金屬鹽」〜詞指其中陽離子具有+2或以上電荷的該些鹽。「高壓」和 /或「加壓」一詞在本文中的定義爲大於約1大氣壓的任何壓力。「湍動的」和「湍流」一詞指的是與平靜流動的液體迴異，其速度在某一點時大小和方向變化不規律之液艘。「連續反應器」一詞係指可以操縱含有反應原，產物、反應介質或其組合物之液體流量的裝置。「霧化力」在本文中的定義爲該些在湍流狀態下會使粒子變小的力，像剪切力、衝摯力、空化力、聲波振盪力或此等之組合物。「次微米」一詞在本文中的定義爲大小低於1微米的任何粒子。次微米粒子的較佳範圍爲約0,01微米至約0.99微米。本文使用的「輕基11比淀硫酮的粒子」和「幾基P比淀硫ϋ同粒子」係指會形成沉澱，而且基本上不溶或稍溶於周圍介質中的該些羥基吡啶硫酮鹽。根據本發明方法’輕基ρ比淀硫_或經基Ρ比咬硫酮的水溶性鹽係與選自多價金屬的水溶性鹽在會產生霧化力的加壓湍流連續反應器中反應。由該連續反應器的壓力和湍流下生成的霧化力，在由反應製造而形成羥基吡啶硫酮鹽粒子時，能有效地使次微米變小。反應中可以使用酸性形態的經基峨淀硫·或經基11比淀硫酮的水溶性鹽。可用的巍基比本紙張尺度適用中國國家標隼（CNS ) Α4規格（210Χ297公釐） I ~^iln n 訂 (辞先閱讀背面之注意事碩再填寫本頁) 448 I 5 7 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明（5 ) 啶硫酮水溶性鹽最好包括銨離子或鹼金屬離子。另外，實施例中的羥基吡啶硫酮水溶性鹽包括羥基吡啶硫酮鈉、羥基吡啶硫酮鉀、經基被啶硫酮鐘、經基峨啶硫酮銨和其組合物。本發明中最佳的羥基吡啶硫酮水溶性鹽是鈉鹽（即，羥基吡啶硫酮鈉）。羥基吡啶硫酮或羥基吡啶硫酮之水溶性鹽的量變化範圍很廣，而且所制定以反應的化學計量學爲主，以及必須生成次微米之羥基吡啶硫酮鹽粒子所需的量，當然要在一般熟於此藝之操作者能力内。羥基吡啶硫酮或水溶性羥基吡啶硫酮鹽的較佳量是約佔反應混合物總重的3至52重量％。根據本發明方法之實施例的水溶性多價金屬鹽包括鋅鹽、錫鹽、鎘鹽、銅鹽、結鹽、鎂鹽、鋁鹽和其類似物。也可以使用這些鹽的组合物。這些金屬的有效抗衡離子包括硝酸鹽、醋酸鹽、硫酸鹽、自化物或其組合物。較佳的水各性多價金屬鹽包括鼠化鋅（ZnC〗2)、氯化鋼（CuCD、醋酸鋅（Zn〇2CCH3)和酼酸鋅（ZnS〇4)。水溶性多價金屬鹽的量會隨著反應中使用的輕基p比淀硫g同或經基u比喊硫酮之水溶性鹽的量而異。經基P比淀硫酮或經基p比喊疏酮的水溶性鹽與水溶性多價金屬鹽之莫耳比率通常在約i : 2至約1 : 8 的範圍内。爲了確保反應完全，在化學計量上稍微超量（如，水溶性多價金屬鹽比羥基吡啶硫酮或羥基吡啶硫酮的水溶性鹽多5重量。/〇)是必要的。可用於反應之介質包括水性介質，像水或水與一種或多種有機溶劑的组合物。有用的有機溶劑包括醇類，像甲醇 -8 - 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） Γ r---.)¾------,tT (#先閱讀背面之注意事項再填寫本頁) 4 48 15 7 A7 ____.__B7___ 五、發明説明（6 ) 、乙醇；胺類，像二乙醇胺、醚、酯和其類似物。其它物質’像分散劑，可以在沉澱反應期間添加至反應内，以防止羥基吡啶硫酮鹽粒子的附聚作用。分散劑也可以在反應完成時添加而防止粒子的附聚作用。分散劑最好是聚合燒基莕續酸鹽，像「DARVAN 1 J (荅續酸甲酿鈉， R. T· Vanderbilt Co. Inc.的產物），「DEMOL N」（蓁磺酸的鈉鹽，Kao Chemicals的產物），「DAXAD 11」（聚合烷基莕績酸的鈉鹽’ W_ R. Grace Co.的產物），「TAMOL N 」（縮合莕績酸的鈉鹽’ Rohm和Hass Co.的產物），「HAROL KG J (聚合跪基莕績酸的軒鹽，Graden Chemical Co.的產物）’ 「HAROL· RG-71」（聚合烷基葚磺酸的鈉鹽，Graden Chemical Co.的產物），Γ LOMAR LS」（縮合單葚磺酸的納鹽，Henkel Corp.的產物）和其類似物。其它可用的分散劑揭示於McCutcheons之功能物質手册中（北美第i册，1992 ’第11 7-137頁）。根據本發明，也可以使用本文敘述的兩種、三種、四種或多種分散劑的组合。經濟部中央標準局員工消費合作社印製 n I I . m 111 ^ I- i _ -1 I —— 1^1 - * \ ,-5° {請先閲讀背面之注意事項再填寫本頁) 本發明方法的分散劑也適合與界面活性劑组合使用。有用的界面活性劑可以選自稱爲非離予、陰離子、陽離子和兩性離子（後者也通常稱爲「兩性的離子」）類的界面活性劑。該界面活性劑適合單獨使用，或與選自上述四種中的兩種、三種或甚至四種或多種界面活性劑组合。可用的非離子界面活性劑包括直鏈狀醇烷氧基化物，像直鍵狀醇乙氧基化物’乙氧基/丙氧基嵌斷共聚物，乙氧基 /丙氧基脂肪醇’和聚氧乙缔基十六乾酸和其類似物。可用 -9- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐）經濟部中央標準局負工消費合作社印製 A7 B7 五、發明説明（7 ) 的直鏈狀醇燒氧基化物已有市售，例如註册商標爲 POLYTERGENT SL-42之〇lin公司產物。若有需要，醇燒氧基化物適合以低碳烷基封端，而且這種產物係以p〇LY_ TERGENTSLF-18市售，以環氧丙烷_封端的直鏈狀醇烷氧基化物也是ΟΗη公司產物，而這些封端的直鏈狀醇規氧基化物在使用時泡沬格外少。使用根據本發明中以p〇LY_ TERGENT SLF-18B系列販售之界面活性劑也有效，該界面活性劑的特性爲可以加強生物降解能力（也是〇Ηη公司產物），是一種環氧烷基-封端的直鏈狀醇烷氧基化物，其主要成份中含有環氧乙坑部份’而在主要成份也含有至少一個環氧丙坑部份也適用，如同例如美國專利第4,925 587 和4,898,621號所揭示者。其它有用的非離子界面活性劑包括一種Shell Chemical 的產物，以註册商標NEODOL91-6販售之界面活性劑。此界面活性劑是平均每莫耳醇中含有六莫耳環氧乙烷之 C! i直鏈狀初級醚乙氧化物的除垢類混合物。其它有用的非離子界面活性劑包括彼等含有直鏈狀Cg-C〗！碳鏈和每莫耳五或六個環氧乙烷或環氧丙烷基。有用的陰離予界面活性劑包括烷基二苯醚二磺酸鹽，貌基苯基乙氧化磷酸酯，羧化直鏈狀醇烷氧基化物，直鏈狀烷基苯磺酸，二異丁基磺基琥珀酸鹽，和烷基磺酸鹽。有用的，離子界面活性劑也包括烷基化二苯基氧化物磺酸鹽，而且其製備方法非常有名，其說明揭示於美國專利第 3,264,242 ·’ 3,634,272 ;和 3,945,437。市面上製備烷基 ____ 10- 本紙張尺度適用中關家標準（CNS ) A4規格（2】GX297公麓） (請先閲讀背面之注意事項再填寫本頁)Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 448157 A7 _ B7 V. Description of the invention (1) The present invention is generally related to a method for preparing hydroxypyridinethione salt particles, and in particular, it is related to the preparation of submicrons in a turbulent and turbulent state. Method for preparing sulfonium sulfonium salt particles of different sizes. The present invention also relates to particles produced by this method and the products produced by the particles produced by this method. Polyvalent metal salt of hydroxypyridine sulfur (also referred to as h hydroxy_2_pyridinethione; 2-pyridinethiol-1 -oxide; 2-pyridinethione; 2-hydrothiopyridine_N_oxide ; Pyridhione; and Pyridhione _N_ oxides are known) are known to be effective biocides' and are widely used in coatings as fungicides and bactericides, as well as personal care products such as scalp Shampoo. The polyvalent metal salt of hydroxypyridine thione is only slightly soluble in water, and includes magnesium hydroxypyridinium thioketone. Zinc hydroxypyridine, cadmium thiopyridone, and copper zirconium thiopyridine. The most widely used divalent pyrithione salts are zinc pyrithione and copper thiopyridine copper. Zinc pyrithione and pyrithione steel can be used as a fungicide to actively fight Gram-positive and negative bacteria, tadpoles and yeasts. Zinc hydroxypyridine is used as a dandruff ingredient in shampoos, while suspensions of zinc hydroxypyridine and / or copper thioacetone are used in coatings and polymers as preservatives and Antifouling agent. The synthesis of the polyvalent thiopyridine salt is described in Berstein et al., U.S. Patent No. 2,809,97m. Other patents that disclose similar compounds and methods of making them include U.S. Patent Nos. 2,768,847; 3,589,999; 3,590,035; 3,773,770. A method is known which causes large solid particles having an average size larger than 2 m to form an insoluble polyvalent hydroxypyridinethione salt. However, it is usually necessary to use a standard size of CNsyA4 in China_ (21〇 × 297mm) ^ ~ ^^ 1 ^^ ΙΒ1 n ^ — l * (Please read the precautions on the back before filling out this page) 448 15 7 Printed by the Central Bureau of Standards of the Ministry of Economic Affairs, Behr Consumer Cooperative, A7 B7 V. Description of the invention (2) Small hydroxypyridine salt particles (ie, less than 1 micron or submicron), because they are more likely to form suspensions, It provides a larger surface area and thus enhances the biocidal activity. In addition, light can penetrate smaller particles, especially low-order micron range (eg, less than 0.2 micron), thus providing the opportunity to make “transparent” products such as transparent shampoos and soaps that are currently on the market. Smaller hydroxypyridine salt particles are usually larger particles or crystals made by traditional methods, and are made by individual mechanical operations such as grinding or crushing. For example, European Patent No. 70046 describes the preparation of zinc pyrithione using an organic solvent. This method produces large crystals of zinc pyrithione that can be easily separated by filtration. The individual, as appropriate, grinding step is used to grind large crystals' and to produce smaller zinc particles with a few p-bithione ratios. As another example, U.S. Patent No. 4,670,430 describes a method of making approximately 0.2 micron medium-sized copper sulfide particles by grinding larger zinc pyrithione particles. There is currently no way to make submicron-sized hydroxyl p-pyridoxone salt particles in one step. The individual steps of grinding larger particles to produce smaller particles, as described in the previous art, usually result in substantial loss of useful products, and are expensive in terms of the required equipment, time, and energy. In addition, what is needed in the art to prepare warp substrates in the sub-micron size range without the need for individual mechanical crushing or grinding steps? Than the method of sulphur salt particles. The present invention can meet this need. One aspect of the present invention relates to a method for manufacturing submicron-sized hydroxypyridinethio salt particles. The method includes a water-soluble salt of hydroxypyridine or hydroxypyridine and a water-soluble polyvalent metal salt under pressure that generates atomization force. Turbulent continuous inversion _____- 5- This paper size is applicable to China National Standards (CNS) A # specifications (21〇 > < 297mm) (Please read the note ^ 'on the back before filling this page) / Installation- 448157 Central Standard of the Ministry of Economic Affairs 41 Shellfish Consumer Cooperative Press A7 B7 V. Description of the invention (3) The reaction in the reactor, the reaction produces submicron-sized light erythrothiophene thione salts 0 Another aspect of the present invention relates to manufacturing Method for sub-micron-sized zinc particles of P ratio thiophosphatonone, which comprises a water-soluble salt of p-thiopyridine or thiopyridine and selected from the group consisting of zinc sulfate, zinc gasification, zinc acetate, and The water-soluble zinc salt of the composition is reacted in a pressurized turbulent continuous reactor that generates atomization force. The pressure of the turbulent reactor is maintained at about 18,000 pounds per square inch to about 23,000 pounds per square inch and the temperature is maintained. At about 0. 0 to about 23 ° C, this reaction produces submicron-sized zinc pyrithione particles. Still another aspect of the present invention relates to particles made by the above method, and products made by using the method of the present invention to make particles. These and other aspects will become apparent upon reading the following detailed description of the invention. It has now been unexpectedly discovered that the solution according to the present invention causes a problem of efficiently producing submicron-sized hydroxypyridone salt particles in a single operation. The present invention also solves the problem by using a water-soluble salt and a water-soluble polyvalent metal salt of thiopyridine or light-based dianthizone in a pressurized turbulent continuous reactor that generates atomization force, and solves the problem. This problem. The atomizing force produced by the pressurized turbulent flow reactor ′ can effectively generate submicron-sized hydroxypyridinethione salt particles without relying on individual mechanical grinding or crushing steps. The submicron-sized p-base bituminate salt particles produced by the method of the present invention have a size distribution and are uniform, and have excellent surface deposition characteristics because the submicron particle group provides a large surface area. This large surface area thus improves the biocidal effect of shampoos, perfumes and coatings. In addition, the submicron-sized particles produced according to the method of the present invention-6- The paper scale is applicable to China National Standard (CNS) A4 * (210X297 mm) mn ^ i > nl V (Please read the note on the back before filling (In this page) 448 15 7 A7 B7 Yin Fan, the Consumer Cooperative of the Central Standards Bureau, Ministry of Economic Affairs. 5. Description of the Invention (4) When combined with other compounds, it is easier to form a suspension, and the resulting suspension is more likely to settle particles. Great physical stability. The term "water-soluble salt of hydroxypyridine thioketone" or "water-soluble hydroxypyridine thioketone salt" as used herein includes those thioketone I salts in which hydrogen atoms of a thiol group are replaced with monovalent cations. "Water-soluble polyvalent metal salts" ~ words refer to those salts in which the cation has a charge of +2 or more. The term "high pressure" and / or "pressurized" is defined herein as any pressure greater than about 1 atmosphere. The terms "turbulent" and "turbulent" refer to liquid vessels that are different from calm flowing liquids and whose velocity and size change irregularly at a certain point. The term "continuous reactor" refers to a device that can manipulate the flow of a liquid containing a reactant, a product, a reaction medium, or a combination thereof. "Atomization force" is defined in this paper as those forces that will make particles smaller in a turbulent state, such as shear force, impact force, cavitation force, acoustic wave force, or a combination of these. The term "submicron" is defined herein as any particle having a size below 1 micron. The preferred range of sub-micron particles is from about 0.01 micrometers to about 0.99 micrometers. As used herein, "light-based 11 ratio thiosulfone particles" and "isopropyl P ratio thiosulfone particles" refer to those hydroxypyridine thiones that will form a precipitate and are substantially insoluble or slightly soluble in the surrounding medium. salt. According to the method of the present invention, the water-soluble salt of the light-based ρ ratio thiosulfate or the thiopyridine-based thione is reacted with a water-soluble salt selected from a polyvalent metal in a pressurized turbulent continuous reactor that generates atomization force. . The atomization force generated by the pressure and turbulence of the continuous reactor can effectively reduce the submicron size when hydroxypyridinethione salt particles are formed by the reaction. In the reaction, a water-soluble salt of ketothione or keto 11-thione can be used in an acidic form. Available paper size is applicable to China National Standards (CNS) Α4 size (210 × 297 mm) I ~ ^ iln n (please read the notes on the back before filling in this page) 448 I 5 7 Central Ministry of Economic Affairs Printed by the Consumer Bureau of Standards Bureau A7 B7 V. Description of the invention (5) The water-soluble salt of pyrithione preferably includes ammonium ion or alkali metal ion. In addition, the water-soluble salts of hydroxypyridine in the examples include sodium thiopyridine, potassium thiopyridine, thiopyridine, thiopyridinium ammonium, and combinations thereof. The most water-soluble salt of pyrithione in the present invention is a sodium salt (ie, sodium pyrithione). The amount of hydroxypyridinethione or thiopyridine's water-soluble salts varies widely, and the formulation is mainly based on the stoichiometry of the reaction and the amount required to form submicron hydroxypyridinethione particles, of course Be within the capabilities of an operator generally familiar with the art. The preferred amount of hydroxypyridine or water-soluble thiopyridine is about 3 to 52% by weight based on the total weight of the reaction mixture. Water-soluble polyvalent metal salts according to embodiments of the method of the present invention include zinc salts, tin salts, cadmium salts, copper salts, knot salts, magnesium salts, aluminum salts, and the like. Combinations of these salts can also be used. Effective counter ions for these metals include nitrates, acetates, sulfates, compounds, or combinations thereof. Preferred water anisotropic polyvalent metal salts include zinc ratate (ZnC2), steel chloride (CuCD, zinc acetate (ZnO2CCH3), and zinc acetate (ZnS04). Water-soluble polyvalent metal salts The amount will vary with the amount of the water-soluble salt of the p-based thiosulfate g or the p-thiopyridone used in the reaction. The molar ratio of the alkaline salt to the water-soluble polyvalent metal salt is usually in the range of about i: 2 to about 1: 8. In order to ensure the reaction is complete, a slight excess in stoichiometry (for example, the ratio of water-soluble polyvalent metal salt) Hydroxypyridine or a water-soluble salt of hydroxypyridine is 5 weights more. / 0) is necessary. The medium that can be used for the reaction includes an aqueous medium, such as water or a combination of water and one or more organic solvents. Useful organic Solvents include alcohols, such as methanol-8-This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) Γ r ---.) ¾ ------, tT (#Read the note on the back first Please fill in this page again for matters) 4 48 15 7 A7 ____.__ B7___ 5. Description of the invention (6), ethanol; amines, such as diethanolamine, ether, ester and the like Thing. Other substances', like dispersants, can be added to the reaction during the precipitation reaction to prevent agglomeration of the hydroxypyridinethione salt particles. A dispersant may be added at the completion of the reaction to prevent agglomeration of particles. The dispersant is preferably a polymerized alkanoate, such as "DARVAN 1 J (a product of sodium methylate, a product of R. T. Vanderbilt Co. Inc.)," DEMOL N "(a sodium salt of sulfonic acid) , A product of Kao Chemicals), "DAXAD 11" (a sodium salt of polymerized alkyl acetic acid 'W_R. Grace Co.), "TAMOL N" (a sodium salt of condensed acetic acid' Rohm and Hass Co. Product), "HAROL KG J (Polyuric acid salt of polymerized glutamic acid, product of Graden Chemical Co.)" "HAROL · RG-71" (Polyalkylated sulfonic acid sodium salt, of Graden Chemical Co. Products), Γ LOMAR LS "(a sodium salt of condensed monofluorenesulfonic acid, a product of Henkel Corp.), and the like. Other useful dispersants are disclosed in McCutcheons 'Handbook of Functional Substances (North American Book I, 1992', pp. 11 7-137). According to the present invention, a combination of two, three, four or more dispersants described herein may also be used. Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs n II .m 111 ^ I- i _ -1 I —— 1 ^ 1-* \, -5 ° {Please read the precautions on the back before filling this page) The present invention The dispersant of the method is also suitable for use in combination with a surfactant. Useful surfactants can be selected from the group of surfactants called non-ionizing, anionic, cationic, and zwitterionic (the latter is also commonly referred to as "zwitterionic"). The surfactant is suitable for use alone or in combination with two, three, or even four or more surfactants selected from the above four. Useful non-ionic surfactants include linear alcohol alkoxylates, like linear alcohol ethoxylates 'ethoxy / propoxy intercalation copolymers, ethoxy / propoxy fatty alcohols', and Polyoxyethylene hexadecanoic acid and its analogs. Available -9- This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) A7 B7 printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Linear Invention Alcohol Burning Oxygenate (7) It is commercially available, for example, it is a product of Olin Corporation with a registered trademark of POLYTERGENT SL-42. If necessary, the alcohol alkoxide is suitable for capping with a lower alkyl group, and this product is commercially available as POLY_TERGENTSLF-18, and the linear alcohol alkoxylate terminated with propylene oxide is also ΗΗη Company products, and these end-capped linear alcohol gauge oxylates have extremely low foaming when used. It is also effective to use the surfactant sold in the POLY_TERGENT SLF-18B series according to the present invention. The characteristic of the surfactant is that it can enhance the biodegradability (also a product of 〇ηη company), which is an epoxy alkyl group- A capped linear alcohol alkoxylate containing an ethylene oxide pit moiety in its main component and at least one propylene oxide pit moiety in its main component is also suitable, such as, for example, U.S. Patent Nos. 4,925 587 and 4,898,621 Revealed. Other useful non-ionic surfactants include a product of Shell Chemical, a surfactant sold under the registered trademark NEODOL 91-6. This surfactant is a descaling mixture containing an average of C! I linear primary ether ethoxylates of six mol ethylene oxide per mol alcohol. Other useful non-ionic surfactants include those that contain linear Cg-C! Carbon chain and five or six ethylene oxide or propylene oxide per mole. Useful anionic surfactants include alkyl diphenyl ether disulfonates, aryl phenyl ethoxylated phosphates, carboxylated linear alcohol alkoxylates, linear alkyl benzene sulfonic acids, diisocyanates Butylsulfosuccinate, and alkylsulfonate. Usefully, ionic surfactants also include alkylated diphenyl oxide sulfonates, and their methods of preparation are well known, and their descriptions are disclosed in U.S. Patent Nos. 3,264,242 · '3,634,272; and 3,945,437. Alkyl on the market ____ 10- This paper size is applicable to Zhongguanjia Standard (CNS) A4 specification (2) GX297 male foot (Please read the precautions on the back before filling this page)

、1T 經濟部中央標準局員工消費合作社印製 448157 A7 -----5Z__ 五、發明説明（8 ) 二苯基氧化物續酸鹽的方法通常無法製造出單烷化基化、單績化、二燒基化或二磺化系列。市售系列典型上主要（大於90%)是二磺化，而且是以約μ至約25%的二烷基化作用，和約75和85%單烷基化作用形成的單_和二·烷基化之混合。最典型的是’市售系列是約8〇%經單烷基化和2〇% 經二烷基化。兩種説明用含有烷基化二苯基氧化磺酸鹽界面活性劑之市售溶液爲DOWFAX 8390和DOWFAX 8390A界面活性劑 ’其係Dow化學公司的註册商標產物。在每一種中，烷基王要是Cie十六烷基。若有需要，這些產物適用於以氫氧化氨完全或部份中和的溶液中。也可由上述燒基化二苯基氧化物績酸鹽與六氫井化合反應，生成績酸鹽化合物與六氛比呼化合物之莫耳比率呈约10 ·· 1和約1 ·· 10，而最好介於約2 : J和約i · 2之有效陰離子界面活性劑。雖然任何的六氫吡畊化合物皆適用於該反應中，但較佳的化合物包括彼等選自含有丨，2•胺基乙基六農说呼、1,4-六氫吡畊二乙烷磺酸、無水六氫吡畊、含水六氫P比呼和其組合物。其它可用的陰離子爲多羧化醇烷氧基化物，最好是該些選自以下的酸或有機或無機鹽•多羧化直鏈狀醇烷氧基化物’多幾化分枝狀醇燒氧基化物，多羧化環狀醇烷氧基化物，和其组合物。這些多羧化醇烷氧基化物典型上每莫耳 .含有至少兩個琥珀酸基。較佳的多羧化醇烷氧基化物爲該些具有包含多（環氧丙烷）和多（環氧乙烷）嵌斷物之主鏈，而 —_____- 11 - 本紙張尺ϋ用中國國家標準（CNS ) A4规格（210X297公釐) " —---- n I - n^i· ^^1 - - ii ^^1 ! i In - . I Jl^i 一~' (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局κ工消費合作社印製 448 15 7 A7 *---_ ____B7___ 五、發明説明（9 ) JL這些較佳的多羧化醇烷氧基化物已經上市販售，例如〇】in公司生產商標名爲p〇LY_TERGEMT CS-1的界面活性劑。若有需要，至少在多羧化醇烷氧基化物上的部份酸性基能與鹼中和產生對應的鹽。適宜的鹼包括鹼金屬氫氧化物、驗土金屬氫氧化物和游離金屬氫氧化物，包括氫氧化卸、氫氧化銨、氫氧化鈣、氫氧化鎂、錄、單_、二-和三_ 乙醇胺，及其組合物。雖然可以使用氫氧化鉀，但卻非較佳奐擇，以氫氧化鈉較佳。所用的有機或無機鹼的量最好至吵與多羧化醇烷氧基化物使用的莫耳數相等。多幾化醇也可以含有多羧化酸，例如聚丙烯酸，與起始醇烷氧基化物和該多羧化酸的烷氧基化之酯。雖然本發明方法接受個別使用陽離子和兩性離子界面活 =劑，但彼等也可以與其它種類中至少一種界面活性劑组 «使用。供説明用之陽離子界面活性劑包括烷基鹵化三銨二非直鏈狀烷基二甲基闺化物和含界面活性劑之烷基甲基苄基南化銨。供説明用之兩性離子界面活性劑包括聚乙二醇醚知生物、乙氧基噁唑啉衍生物、月桂醯胺基丙基三甲銨乙内酯和卵磷脂。、本發明方法可以使用以上述界面活性劑的各種組合物爲王的通宜摻合物。這些摻合物可以是任兩種或多種介於上述四種廣泛界面活性劑之間或之内之界面活性劑的組合物。組合物可包括摻入：陰離子與陰離子、陰離子與非離子、，離子與陽離子、陰離子與兩性離子、陽離子與陽離子、陽離子與兩性離子、非離子與非離子、非離子與兩 ---,--^---_}裝------ΐτ (請先鬩讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 448157 A7 ___B7_ 五、發明説明（1〇 ) 子、以及兩性離子與兩性離子。同樣地，界面活性劑的第三和第四摻合物可分別選自上述種類中的三種或四種界面活性劑。根據以下出示的名單中，適用的任何單獨或二、三或四種界面活性劑的組合物有：（a)非離子的，包括烷基化直鏈狀醇（像Olin公司的產物，POLY-TERGENT SLF-18界面活性劑），直鏈狀醇乙氧化物（像Shell公司的產物，NEODOL 91-8界面活性劑），乙氧基化直鏈狀烷基苯（像Union Carbide公司的產物，TRITON X-100界面活性劑），和EO /PO嵌斷共聚物（像Olin公司的產物，POLY-TERGENT Τ-ΐ 7 A 界面活性劑）；（b) 陰離子的，包括烷基二苯基醚二磺酸鹽（像Olin公司的產物，POLY-TERGENT 2A1界面活性劑），娱·基苯基乙氧化鱗酸酿（像Olin公司的產物，Wayfos M-60界面活性劑），羧化直鏈狀烷氧化物（像Olin公司的產物，POLY-TERGENT CS-1界面活性劑），直鏈狀烷基苯磺酸（像Stepan公司的產物，BIOS OFT S-130界面活性劑）， ot-稀屬績酸醋（像Stepan公司的產物，BIO TERG AS-40界面活性劑），二烷基磺基琥珀酸鹽（像Arol化學產物的產物，AROWET SC-75界面活性劑），和烷基硫酸鹽（像Stepan 公司的產物，STEPANOL SLS界面活性劑）；（c)陽離子的，包括烷基齒化三銨（像VWR科學公司的產物，CTAB界面活性劑），聚伸氧乙烯椰基胺（像PPG工業的產物， MAZEEN界面活性劑），初級烷基胺（像Akzo化學公司的產物，ARMEEN界面活性劑），二椰基二曱基鹵化銨（像Jetco __- 13-_ 本紙張尺度適用中國國家標率（CNS ) A4規格（2]〇X297公釐）. (請先閱讀背面之注意事項再填寫本頁)1. 1T printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 448157 A7 ----- 5Z__ 5. Description of the invention (8) Diphenyl oxide continuum methods usually cannot produce mono-alkylated, single-performance , Di-calcination or disulfonation series. Commercially available series are typically mainly (greater than 90%) disulfonated, and are mono- and di · formed from about μ to about 25% dialkylation and about 75 and 85% monoalkylation. Alkylated blend. The most typical is the 'commercially available series' which is about 80% monoalkylated and 20% dialkylated. Two commercially available solutions containing alkylated diphenyl oxide sulfonate surfactants are DOWFAX 8390 and DOWFAX 8390A surfactants, which are registered trademarks of Dow Chemical Company. In each case, the alkyl king is Cie hexadecyl. If desired, these products are suitable for use in a solution that is completely or partially neutralized with ammonia hydroxide. It is also possible to react the above-mentioned calcined diphenyl oxide salt with a hexahydrogen well, and the molar ratios of the chromate compound to the hexamethylene compound are about 10 ·· 1 and about 1 ·· 10, and Effective anionic surfactants preferably between about 2: J and about i · 2. Although any hexahydropyridine compound is suitable for use in this reaction, preferred compounds include those selected from compounds containing 1,2, aminoethylhexanon, 1,4-hexahydropyridine Sulfuric acid, anhydrous hexahydropyridine, hydrated hexahydropeptone, and combinations thereof. Other useful anions are polycarboxylated alcohol alkoxylates, preferably those acids or organic or inorganic salts selected from the following: • polycarboxylated linear alcohol alkoxylates Oxide, polycarboxylated cyclic alcohol alkoxylate, and combinations thereof. These polycarboxylated alcohol alkoxylates typically contain at least two succinate groups per mole. The preferred polycarboxylated alcohol alkoxylates are those which have poly (propylene oxide) and poly (ethylene oxide) interrupts, and —_____- 11-This paper uses China Standard (CNS) A4 specification (210X297 mm) " —---- n I-n ^ i · ^^ 1--ii ^^ 1! I In-. I Jl ^ i 一 ~ '(Please read first Note on the back, please fill in this page again) Printed by the Central Standards Bureau of the Ministry of Economic Affairs κ Industrial Consumer Cooperative 448 15 7 A7 * ---_ ____B7___ V. Description of the invention (9) JL These better polycarboxylated alcohol alkoxylates It has been sold on the market, for example, 〇] in company produces a surfactant named p〇LY_TERGEMT CS-1. If desired, at least part of the acidic groups on the polycarboxylated alcohol alkoxylate can neutralize with the base to produce the corresponding salt. Suitable bases include alkali metal hydroxides, soil metal hydroxides, and free metal hydroxides, including hydrogen hydroxide, ammonium hydroxide, calcium hydroxide, magnesium hydroxide, mono, mono-, di-, and tri- Ethanolamine, and combinations thereof. Although potassium hydroxide can be used, it is not preferred, and sodium hydroxide is preferred. The organic or inorganic base is preferably used in an amount equal to the number of moles used for the polycarboxylated alcohol alkoxylate. The polyalkylated alcohol may also contain a polycarboxylated acid, such as polyacrylic acid, with the starting alcohol alkoxylate and the alkoxylated ester of the polycarboxylated acid. Although the method of the present invention accepts the individual use of cationic and zwitterionic surfactants, they can also be used with at least one surfactant group of other species. Illustrative cationic surfactants include triammonium alkyl halides, di-non-linear alkyl dimethyl compounds, and alkyl methyl benzyl ammonium sulfides containing surfactants. Illustrative zwitterionic surfactants include polyethylene glycol ethers, ethoxy oxazoline derivatives, laurylaminopropyltrimethylammonium lactone, and lecithin. 2. The method of the present invention may use a Tongyi blend in which various compositions of the above-mentioned surfactants are king. These blends can be any combination of two or more surfactants between or within the four broad range of surfactants. Compositions can include incorporation: anions and anions, anions and non-ions, ions and cations, anions and zwitterions, cations and cations, cations and zwitterions, nonions and nonions, nonions and two ---,- -^ ---_} Installation ------ ΐτ (Please read the notes on the back before filling out this page) Printed by the Employees' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 448157 A7 ___B7_ V. Description of the invention (1〇) Daughter, as well as zwitterions and zwitterions. Likewise, the third and fourth blends of surfactants may be selected from three or four surfactants, respectively, of the aforementioned species. According to the list presented below, any suitable single or two, three, or four surfactant compositions are: (a) Non-ionic, including alkylated linear alcohols (like products from Olin Corporation, POLY- TERGENT SLF-18 surfactant), linear alcohol ethoxylates (like products from Shell, NEODOL 91-8 surfactant), ethoxylated linear alkylbenzenes (like products from Union Carbide, TRITON X-100 surfactant), and EO / PO intercalation copolymer (like Olin's product, POLY-TERGENT Τ-ΐ 7 A surfactant); (b) anionic, including alkyl diphenyl ether Disulfonate (like Olin's product, POLY-TERGENT 2A1 surfactant), entertainment · phenylphenyl ethoxylated scale acid (like Olin's product, Wayfos M-60 surfactant), carboxylated linear Alkoxides (like products from Olin, POLY-TERGENT CS-1 surfactant), linear alkylbenzene sulfonic acids (like products from Stepan, BIOS OFT S-130 surfactant), ot-dilute Sour vinegar (like the product of Stepan company, BIO TERG AS-40 surfactant), Dialkyl sulfosuccinates (like products of Arol chemical products, AROWET SC-75 surfactant), and alkyl sulfates (like products of Stepan company, STEPONOL SLS surfactant); (c) cationic, Including alkyl triammonium (like VWR Scientific's product, CTAB surfactant), polyoxyethylene cocoamine (like PPG's industrial product, MAZEEN surfactant), primary alkylamine (like Akzo Chemical) Product, ARMEEN surfactant), dicocodifluorenyl ammonium halide (like Jetco __- 13-_ This paper size is applicable to China National Standard (CNS) A4 specifications (2) 〇297mm). (Please first (Read the notes on the back and fill out this page)

448 1 5 7 經濟部中央標準局負工消費合作社印繁 A7 B7 五、發明説明（11 ) 化學公司的產物，JET QUAT界面活性劑），二異癸基二甲基卤化銨（像Stepan公司的產物，ΑΜΜΟΝΥΧ K9界面活性劑），和二乙基胺乙基硬脂酸酯（像ISP Van Dyke的產物， CERASYNT 303界面活性劑）；和（d)兩性離子的，包括聚乙醇醚衍生物（像Ciba-Geigy的產物，ALBEGAL A界面活性劑），乙氧基化噁唑啉衍生物（像Angus化學的產物 ALKATERG T-IV界面活性劑），月桂醯胺基丙基三甲銨乙内酿（像Inolex化學的產物，LEXAINE C界面活性劑），卵鱗脂（像Can Amoral的產物，CANASPERSE界面活性劑），椰基丙性二醋酸二鈉（像 Mona工業的產物， MONATERICS界面活性劑），複合脂肪胺鹽（像PPG工業的產物，MAFO 13界面活性劑），和椰基氧化胺（像McIntyre Group公司的產物，MACKAMINE CO界面活性劑）。所用的分敎劑或分散劑/界面活性劑組合物，最好佔反應混合物總重之約〇.〇5至10重量％，約0.1至5重量％更佳，而約0.5至約1.5重量％最佳。爲能有效製造次微米大小的羥基吡啶硫酮鹽粒子，反應原係呈高壓和湍流狀態下的連續反應器内反應。高壓和湍流的组合在連續反應器内生成霧化力，並在由反應形成羥基吡啶硫酮鹽粒子的同時影響其變小。在較佳具體實施例中，羥基吡啶硫酮鈉係與氯化鋅、硫酸鋅、醋酸鋅或其組合物在會生成霧化力的連續反應器中反應（如 Microfluidics 國際公司，Newton MA，販售 M-140K 模式之實驗室微流體處理機）。反應產物爲次微米大小的羥基吡 -14 - 本紙張尺度適用中國國家標率（CNS ) A4規格（210X297公釐） ---Γ------(J装------訂 (讀先閱讀背面之注意事項再填寫本頁) 44815? 經濟部中央標隼局員工消費合作社印製 A7 B7 五、發明説明（12 ) 啶硫酮鋅粒子，並生成氯化鈉水溶液，硫酸鈉水溶液或醋酸鈉水溶液之副產物。在連續反應器中以本藝已知之任何方法，例如幫浦、活塞和其類似物可以生成壓力。在—個具體實施例中，反應原是由空氣傳動幫浦以高壓抽進混合室内。幫浦的高壓能力使得反應原上生成高達5 0, 〇〇〇磅/平方英寸的壓力。反應使用的壓力最好是在10,000至50,00〇磅/平方英寸的範圍内’在18,000至23,000的範園内較佳，而18 〇〇〇至2〇〇〇〇磅/平方英寸的範圍内更佳。當反應混合物的加壓層流通過連續反應器時，利用擾動可以產生ΐίϋ流。？而流可以由本藝已知之任何方法產生。然而，反應混合物的加壓層流必須經擾動至足以生成會影塑羥基吡啶硫鹽粒子變小之霧化力的程度。在一個具體實施例中’連續反應器内可以放置擾流板，使反應原的層流在高壓通過連續反應器時受擾動。在另一個具體實施例中，加壓反應混合物（可以包括經基吡啶硫酮鹽粒子和水溶液狀副產物）係通過可使水流分爲數道，例如兩道水流之固定幾.何：ic互作用Α。水波繼而經匯集’高壓和水流的瑞流力因而聚集於一處生成霧化力使總粒子變小。由水流聚集生成使其變小的力包括，例如剪切力、衝搫力、空化力和其類似物，或彼等之组合，而且導致粒子大小有效地變小。在Γ單程」模式中使用的交互作用室裝置能使剛生成的羥基吡啶硫鹽粒子變小的力量只有一次。羥基吡啶硫酮鹽粒子也可以在交互作用室裝置内，以重覆分離的方式反覆 -15- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐） {諳先鬩讀背面之注意事項再填寫本買) ,ya 448157 Α7 Β7 五、發明説明（Ί3 生成的力作用，再會聚而使反應混合物進入「多程」模式中β父互作用室裝置可以配置冷卻或加熱線圈以維持必要的溫度。通常，根據本發明方法較高壓力會生成較小粒子。舉例來說，約10,000磅/平方英寸的壓力生成的〇7至〇95微米範園内的粒予。約18,000磅/平方英寸的壓力通常生成約 0.3至0.4微米範園内的粒子。此外，熟於此藝者能輕易地改良壓力而獲得所需大小的粒子。反應和連續反應器的溫度可以維持在會使經基峨淀硫面同鹽沉澱的任何溫度下。通常，較低溫會促進較小粒子形成 ;因此，較低溫較佳《此外，反應溫度最好介於水性介質的凝固點和室溫（約23 °C )之間，約〇和約15 °C間較佳，而约0 C和7 °c之間最佳。特別有用的溫度範圍爲約5至约7 °c。經濟部中央標準扃員工消費合作社印家 ο装— (請先閱讀背面之注意事項再填寫本頁) 由本發明方法製成之不溶的經基p比淀破鲷鹽粒子具有狹小的次微米大小範園，在約〇. 〇 3微米至約〇. 9 5微米的範圍内較佳，在約0,04微米至約0.88微米的範圍内更佳，而在约0.3 0微米至約〇. 4 5微米的範圍内最佳。經基5比唆硫自同鹽粒子能以過濾作用或本藝中已知之其它分離方法由副產中分離出來。粒子的混合物和副產物也可以不經進一步純化而直接添加到市售產物内。副產物（如，氣化鈉水溶液、硫酸鈉水溶液或醋酸鈉水溶液）可用於洗髮精和香电調配物中做爲增稠劑。由於不經分離、離析和純化步驟，所以在添加根據本發明製成的羥基吡啶硫酮鹽粒子和副產物之級合物時，能節省大量的製造成本β -16- 本紙張尺度適用中國國家標隼（（：>15)久4規格（2丨0\297公釐） 448157 A7 一________B7 五、發明説明（14 ) ' 根據本發明方法製造的粒子可以在許多項目上做爲添加劑，像個人保養品（香皀、洗髮精和其類似物），塗料、塗層、肥料和食品工業。例如，根據本發明方法製造的羥基吡啶硫酮鋅粒子可以添加至止頭皮屑洗髮精内做爲止頭皮屑添加劑。實施例以下κ施例係用於説明，但絕不侷限於本發明範圍内。所有的部份和百分比爲重量比，而除非另外明白地敘述，否則全郅的溫度皆爲攝氏度數。以下實施例中「q s」指足量，通常爲重量百分比0.1至2。實施蚵1 :次微米經基p比啶硫綢鋅粒子之製造經濟部中央標準局貝工消費合作社印製 (諳先閱讀背面之注意事項再填寫本頁) 倒入24克20% ZnS〇4，0,5克「DARVAN」（聚合規基荅磺酸的鈉鹽）和25.5克水，而且經由包括固定幾何交互作用室的M-140K模式之實驗室微流化處理器（Microfluidics 國際公司，Newton ΜΑ)再循環。將全部裝置冷卻至約7 ，並使微流化器的壓力維持在約18,000磅/平方英寸。將經基吡啶硫酮鈉溶液（45毫升16.3%的溶液）加至微流化器的儲畜器入口 ’費時8分鐘以上，而且使反應原持續循環5 _ 10分鐘。當反應混合物在微流化器裝置内循環時，固定幾何交互作用室會將反應混合物分成兩股流體。該流體繼而於壓力下聚集生成湍流及造成使經基吡啶硫銅鋅粒子變小的霧化力。以雷射光散射粒子大小分析儀（Horiba LA9 1 〇) 測量因而形成的禮基桃咬硫輞鋅粒子。表I顯示粒子的大小分佈和頻率。中等粒子大小約爲0,3 13微米。粒子大小 -17- 本纸張尺度適用中國國家標準（CNS ) A4規格（2[0X297公釐）第871〇385〇號專利申請安邊48 ί 5 了中文說明書修正頁(89月） --- 五、發明説明（15: Α7 Β7 _丨丨丨_丨1丨_| ί 分佈呈狹幅分散（幾乎為單分.·……-ΤΤΤ…' 為0.30至約0.45綠米。〕大小圍约表I 大小(微米）頻率 --—--- 累積f%、 0.445 0.25 ----- 100.0 0.389 22.41 99.75 0.339 64.35 77.34 0.296 —------ 13.00 13.00 經濟部中央標準局貝工消費合作社印袈實.m.次微米羥基吡啶硫酮铜粒子之製造與實施例1万法相似，倒入100毫升3%趣基峨咬麵納水溶液，並於維持約汕”㈧磅/平方英寸和大約5充的微流化器裝置内再循環。將50 $升2 42% CuCl2、溶液加入約維持在5°C.的此循環溶液内。利用H〇riba LA910雷射測量由單程微流化器生成的羥基吡啶硫酮鋼粒子之大小和分佈。分析顯示粒子大小範圍為0 04至〇 88微米，而中等大小為約0 · 0 9微米。 I施1例？.. ·(建議實施例）去頭皮屑的洗髮精調配物I 去頭皮屑的洗髮精组成份係根據實施例1和2敘述製成的羥基吡啶硫酮鋼粒子與以下成份組合一起製成： 18- 本紙張尺度適用中國國家標隼（CNS ) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁)448 1 5 7 Central Government Bureau of Standards, Ministry of Economic Affairs, Consumer Cooperatives, Infanches A7 B7 V. Description of Invention (11) Product of Chemical Company, JET QUAT Surfactant, Diisodecyldimethylammonium halide (like Stepan's Product, AMMONIX K9 surfactant), and diethylamine ethyl stearate (like the product of ISP Van Dyke, CERASYNT 303 surfactant); and (d) zwitterionic, including polyethanol ether derivatives ( Products like Ciba-Geigy, ALBEGAL A surfactant), ethoxylated oxazoline derivatives (like ALKATERG T-IV surfactant from Angus Chemistry), laurylamine trimethylammonium betaine ( Like products of Inolex chemistry, LEXAINE C surfactant), egg scale lipids (like Can Amoral products, CANASPERSE surfactants), coconut sodium diacetate disodium (like products of Mona Industries, MONATERICS surfactants), Complex fatty amine salts (like products from the PPG industry, MAFO 13 surfactant), and cocoamine oxides (like the product from McIntyre Group, MACKAMINE CO surfactant). The tiller or dispersant / surfactant composition used is preferably about 0.05 to 10% by weight, more preferably about 0.1 to 5% by weight, and about 0.5 to about 1.5% by weight of the total weight of the reaction mixture. optimal. In order to effectively produce sub-micron-sized hydroxypyridine salt particles, the reaction system is a continuous reactor reaction under high pressure and turbulent conditions. The combination of high pressure and turbulence generates an atomizing force in a continuous reactor, and affects the reduction of hydroxypyridinethione salt particles while reacting. In a preferred embodiment, sodium pyrithione is reacted with zinc chloride, zinc sulfate, zinc acetate, or a combination thereof in a continuous reactor that generates atomization power (eg, Microfluidics International, Newton MA, M-140K model laboratory microfluidic processor). The reaction product is sub-micron-sized hydroxypyridine-14-This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) --- Γ ------ (J Pack ------ Order (Read the precautions on the back before you fill out this page) 44815? Printed by A7 B7 of the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (12) Zinc pyrithione particles, and generate sodium chloride aqueous solution, sodium sulfate Aqueous products or by-products of aqueous sodium acetate. Pressure can be generated in a continuous reactor by any method known in the art, such as pumps, pistons, and the like. In a specific embodiment, the reactants are powered by air. The pump is pumped into the mixing chamber at high pressure. The high pressure of the pump causes the reactor to generate a pressure of up to 50,000 psi. The pressure used for the reaction is preferably 10,000 to 50,000 psi The range is preferably within the range of 18,000 to 23,000, and more preferably in the range of 18,000 to 20,000 pounds per square inch. When a pressurized laminar flow of the reaction mixture passes through the continuous reactor, use Disturbance can produce a stream. Produced by any method known in the art. However, the pressurized laminar flow of the reaction mixture must be perturbed to a degree sufficient to generate a nebulizing force that will reduce the size of the hydroxypyridine sulfide particles. In one embodiment, the 'continuous reaction A spoiler can be placed in the reactor, so that the laminar flow of the reactant is disturbed when passing through the continuous reactor under high pressure. In another specific embodiment, the pressurized reaction mixture (which may include via The product) is made by dividing the water flow into several channels, such as the fixed number of two water flows. Ho: ic interaction A. The water waves are then brought together to gather the high-pressure and the current of the stream, so that they gather together to generate an atomizing force to make the total Particles become smaller. The forces generated by the aggregation of water currents to make them smaller include, for example, shear, impact, cavitation, and the like, or a combination thereof, and cause the particle size to effectively become smaller. The interaction chamber device used in the "one way" mode can make the newly generated hydroxypyridine sulfide salt particles smaller in size only once. The hydroxypyridine thione salt particles can also be used in the interaction room device. -15- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) {谙 Read the precautions on the back before filling in this purchase), ya 448157 Α7 Β7 V. Description of the invention (Ί3 The force generated by the Ί3 is re-converged to bring the reaction mixture into "multi-pass" mode. The β-parent interaction chamber device can be equipped with cooling or heating coils to maintain the necessary temperature. Generally, the higher pressure according to the method of the present invention will Generates smaller particles. For example, a pressure of about 10,000 pounds per square inch generates particles in the range of 0.77 to 0.95 micron range. A pressure of about 18,000 pounds per square inch typically generates particles in the range of about 0.3 to 0.4 micron range. . In addition, those skilled in the art can easily improve the pressure to obtain particles of the desired size. The temperature of the reaction and the continuous reactor can be maintained at any temperature that will cause precipitation of the same salt through the sulfur surface of Chiede. Generally, lower temperatures promote the formation of smaller particles; therefore, lower temperatures are preferred. Furthermore, the reaction temperature is preferably between the freezing point of the aqueous medium and room temperature (about 23 ° C), and between about 0 and about 15 ° C. Good, and best between about 0 C and 7 ° C. A particularly useful temperature range is about 5 to about 7 ° c. Central Standards of the Ministry of Economic Affairs, Consumer Consumption Cooperatives, Printing— (Please read the precautions on the back before filling out this page) The insoluble crystalline particles produced by the method of the present invention have a narrower submicron size range than the yakisho salt. Orbital, preferably in the range of about 0.03 micrometers to about 0.95 micrometers, more preferably in the range of about 0.04 micrometers to about 0.88 micrometers, and in the range of about 0.3 micrometers to about 0.45 Best in the micrometer range. The sulfenyl group can be separated from by-products by filtration or other separation methods known in the art. The mixture of particles and by-products can also be added directly to the commercial product without further purification. By-products (such as aqueous vaporized sodium, aqueous sodium sulfate, or aqueous sodium acetate) can be used as thickeners in shampoos and fragrance formulations. Due to the absence of isolation, isolation and purification steps, a large amount of manufacturing cost can be saved when adding the hydroxypyridinethione salt particles and by-products produced according to the present invention β -16- This paper is applicable to China Standard ((: > 15) Jiu 4 specifications (2 丨 0 \ 297 mm) 448157 A7 _________B7 V. Description of the invention (14) 'The particles manufactured according to the method of the present invention can be used as additives in many items, Like personal care products (citron, shampoo, and the like), coatings, coatings, fertilizers, and the food industry. For example, zinc pyrithione particles made according to the method of the present invention can be added to antidandruff shampoos Additives for dandruff. Examples The following kappa examples are for illustration, but are by no means limited to the scope of the present invention. All parts and percentages are weight ratios, and unless explicitly stated otherwise, the full temperature All are in degrees Celsius. "Qs" in the following examples refers to a sufficient amount, usually 0.1 to 2 weight percent. Implementation 蚵 1: Submicron-based p-pyridine sulfur silk zinc particles manufacturing Ministry of Economic Central Standards Bureau Printed by the Industrial and Consumer Cooperative (please read the precautions on the back before filling this page). Pour 24 g of 20% ZnS0, 0,5 g "DARVAN" (sodium salt of polymerized gadolinium sulfonic acid) and 25.5 g of water And recirculated via a laboratory microfluidizer (Microfluidics International, Newton MA) in the M-140K mode including a fixed geometry interaction chamber. The entire unit was cooled to approximately 7 and the pressure of the microfluidizer was maintained At about 18,000 pounds per square inch. Adding sodium pyrithione solution (45 ml of 16.3% solution) to the inlet of the microfluidizer's stocker 'took more than 8 minutes, and the reactor was continuously circulated 5 _ 10 Minutes. As the reaction mixture circulates in the microfluidizer device, the fixed geometric interaction chamber divides the reaction mixture into two fluids. This fluid then aggregates under pressure to create turbulence and cause the copper pyrithione copper zinc zinc particles to become smaller The atomization force is measured by a laser light scattering particle size analyzer (Horiba LA9 1 0). The resulting ritual peach bite zinc sulphate zinc particles are measured. Table I shows the particle size distribution and frequency. The medium particle size is about 0,3 13 M. Particle size -17- This paper scale applies Chinese National Standard (CNS) A4 specification (2 [0X297 mm) Patent Application No. 871〇385〇 Anbian 48 ί 5 Chinese manual revision page (89 months)- -V. Description of the invention (15: Α7 Β7 _ 丨丨丨 _ 丨 1 丨 _ | ί The distribution is narrowly dispersed (almost single points ..........- TTTT ... 'is 0.30 to about 0.45 green rice.) Size Table I Size (micron) Frequency ------ Cumulative f%, 0.445 0.25 ----- 100.0 0.389 22.41 99.75 0.339 64.35 77.34 0.296 -------- 13.00 13.00 Shellfish Consumption cooperatives. Indica.m. Sub-micron copper pyrithione copper particles are manufactured similarly to the method of Example 10,000. Pour 100 ml of a 3% aqueous solution of Quercus octopus, and maintain about shank lb / sq. Recirculate inside the microfluidizer unit at approximately 5 inches and approximately 5 charges. Add 50 $ L 2 42% CuCl2, solution to this circulating solution maintained at about 5 ° C. Horiba LA910 laser was used to measure the size and distribution of hydroxypyridine steel particles generated by a single-pass microfluidizer. Analysis showed particle sizes ranging from 0 04 to 0 88 microns, while medium sizes were about 0.99 microns. I apply 1 case? .. (Recommended Example) Anti-dandruff shampoo formulation I Anti-dandruff shampoo composition is made of hydroxypyridine steel particles made according to the descriptions of Examples 1 and 2 and combined with the following ingredients Cheng: 18- This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page)

448157 A7 B7 五、發明説明（16 ) 成份A : 水矽酸銨鎂羥基丙基曱基纖維素成份B : 羥基吡啶硫酮鋼 (針狀/桿狀’ 25%分散水溶液）成份C : 挪基酿胺DEA 成份D : 月桂基三乙醇胺硫酸鹽，4〇0/〇三乙醇胺，99% FD&C Blue No.l (0.2%) FD&C Yellow No.5 (0.1%) 香料 41.0% 1.0% 0.8% 4.0% 1.0% 40.0% 3.2% 1.5% 0.5%適量 (請先閲讀背面之注意事項再填寫本頁) ,裝. 、-° 經濟部中央標準局員工消費合作社印製去頭皮屑的洗髮精组成份製法如下：水加熱至70 C並且攪拌（約丨5 〇〇 rpm)溶解其它兩種成份以製備。將遇合物溫度降低至5代，而且添加成份接著持續攪拌5分鐘。減緩攪拌速度至〜3〇〇 RpM ◎在單獨合器内熔解成份c，然後加入A/B混合物。移開熱源，一旦混合物冷卻，即加入成份D。表紙張尺度適用中國國 -19- 210X297 公楚） 448157 經濟部中央摞準局員工消費合作社印掣 A7 B7 五、發明説明（17) 實施例4 :(建議實施例）去頭皮屑的洗髮精調配物11 另一種去頭皮屑的洗髮精組成份係根據實施例1和2敘述製成的經基p比峻硫銅鋅粒子與以下成份組合製成：成份A : 去離子水 76.0% 月桂基硫酸銨 15.0% 椰基醯胺DEA 2.0% 成份B : 二（氧化）牛脂苯二曱酸醯胺 5.0% 經基吡啶硫酮銅 (針狀/捍狀，25%分散水溶液） 4.0% 成份C : 防腐劑適量成份D : 檸1樣酸，5 0 %適量溶液，或氫氧化鈉，50%水溶液適量成份E · 氣化铵適量去頭皮屑的洗髮精组成份製法如下：在單獨容器内，使混合物A和B充份混合。將成份A加熱至60 °C後加入成份B。攪拌混合物30分鐘。然後冷卻混合物至50 °C，繼而添加成份C。以成份D調整生成的混 _ -20- 本紙張尺度適用中國國家標率（CNS ) A4規格（210X297公釐） (請先閱讀背面之注意事項再填寫本頁)448157 A7 B7 V. Description of the invention (16) Ingredient A: Hydrogen ammonium silicate magnesium hydroxypropyl fluorenyl cellulose Ingredient B: Hydroxypyridhione steel (acicular / rod-shaped 25% dispersed aqueous solution) Ingredient C: Noryl Fermented amine DEA Ingredient D: Lauryl triethanolamine sulfate, 400 / 〇 triethanolamine, 99% FD & C Blue No.l (0.2%) FD & C Yellow No.5 (0.1%) perfume 41.0% 1.0% 0.8% 4.0% 1.0% 40.0% 3.2% 1.5% 0.5% Appropriate amount (please read the precautions on the back before filling out this page), and install.,-° Dandruff shampoo printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs The refined components are prepared as follows: The water is heated to 70 C and stirred (about 5,000 rpm) to dissolve the other two components to prepare. The temperature of the compound was reduced to 5 generations, and the ingredients were added, followed by continuous stirring for 5 minutes. Slow down the stirring speed to ~ 300 RpM ◎ Melt ingredient c in a separate combiner, then add the A / B mixture. Remove heat source and add component D once the mixture has cooled. The paper size is applicable to China 19-210X297 (Gongchu) 448157 Printed A7 B7 by the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs V. Description of Invention (17) Example 4: (Recommended Example) Shampoo for Dandruff Formulation 11 Another anti-dandruff shampoo composition is made by combining p-sulfur copper-zinc particles with the following ingredients according to Examples 1 and 2: Ingredient A: Deionized water 76.0% Laurel Ammonium sulfate 15.0% cocoamide DEA 2.0% ingredient B: ammonium di (oxidized) tallow benzenediacetate 5.0% copper dipyridylthione (acicular / protective, 25% dispersed aqueous solution) 4.0% ingredient C : Preservative proper amount D: Citric 1 acid, 50% proper solution, or sodium hydroxide, 50% aqueous solution, proper ingredient E · Ammonium vaporized shampoo with the right amount of dandruff Ingredients are prepared as follows: In a separate container , Mix A and B thoroughly. Heat ingredient A to 60 ° C and add ingredient B. The mixture was stirred for 30 minutes. The mixture was then cooled to 50 ° C and component C was added. Mixture generated by adjustment of component D _ -20- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page)

44δ 1 5 7 經濟部中央標準局員工消費合作社印製 Α7 Β7 •五、發明説明（18) 合物酸鹼値至5.0-6.2，爾後以成份e調整黏稠度。實施例5 :(建議實施例）去治頭皮屑的洗髮精與潤髮乳I 去頭皮屑的洗髮精與潤髮乳组成份係根據實施例1和2 叙述製成的起基p比淀破銅辞粒子與以下成份組合製成：成份A : 去離子水 77.0% 月桂基硫酸銨 20.0% 椰基醯胺DEA 2.0% 成份Β : 二（氧化）牛脂苯二曱酸醯胺 4.0% 經基被淀硫酮銅 (針狀/桿狀，25%分散水溶液） 4.0% Dimethicone， 12,000 cps 0.5% 成份C : 防腐劑適量成份D : 檸檬酸，50%適量溶液，或氫氧化鈉，50%水溶液適量成份E : 氯化銨適量去頭皮屑的洗髮精與潤髮劑組成份製法如下：在單獨容器内，使混合物A和B充份混合。將成份a加 -21 - 本紙張尺度適用中國國家標準（CNS ) A4規格（2IOX：297公釐） (讀先閱讀背面之注意事項再填寫本頁〕訂 448157 A7 B7 -------------—__________ 五、發明说明（I9 ) ---：—-----C""}裝------訂 (#先閲讀背面之注意事項再填寫本頁) 熱至6 0 °C後加入成份B。攪拌混合物3 0分鐘。然後冷卻混合物至5 0 C ’再添加成份C。以成份D調整生成的混•合物酸驗値至5.0-6.2 ’繼而以成份e調整黏稠度。實施例6 :(建議實施例）去治頭皮屑的洗髮精與潤髮乳il 另一種去頭皮屑的洗髮精與潤髮劑組成份係根據實施例 1和2敘述製成的羥基吡啶硫酮鋅粒子與以下成份組合製成：成份A : 21.75% 0.3 0% 0.70% 4.0% 3 0.0% 02.0% 0.5 0% 0.40% 0.40% 2.00% 去離子水瓜耳經基丙基氯化三銨矽酸銨鎂趣基p比喊硫酮鋼 (針狀/桿狀，25%分散水溶液）成份B :44δ 1 5 7 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs Α7 Β7 • V. Description of the invention (18) The pH of the compound is 5.0-6.2, and then the viscosity is adjusted by component e. Example 5: (Recommended Example) Shampoo and conditioner for dandruff I Shampoo and conditioner for dandruff The precipitated copper particles are combined with the following ingredients: Ingredient A: deionized water 77.0% lauryl ammonium sulfate 20.0% cocamidonium DEA 2.0% ingredient B: di (oxidized) tallow benzenediacetate ammonium amine 4.0% via Copper thioketone (acicular / rod-shaped, 25% dispersed aqueous solution) 4.0% Dimethicone, 12,000 cps 0.5% Ingredient C: Preservative amount D: Citric acid, 50% solution, or sodium hydroxide, 50% Amount of water solution E: Amount of ammonium chloride and antidandruff shampoo and hair conditioner are prepared as follows: In a separate container, the mixtures A and B are fully mixed. Add -21 to component a-This paper size applies the Chinese National Standard (CNS) A4 specification (2IOX: 297 mm) (read the precautions on the back before filling this page) Order 448157 A7 B7 ------- ------—__________ V. Description of the invention (I9) ---: ------- C " "} Installation ------ Order (#Read the precautions on the back before filling in this page ) After heating to 60 ° C, add component B. Stir the mixture for 30 minutes. Then cool the mixture to 50 C 'and then add component C. Adjust the acid of the resulting mixture with component D to 5.0-6.2' and then The viscosity is adjusted by ingredient e. Example 6: (Recommended Example) Shampoo and conditioner for dandruff treatment Another composition of shampoo and conditioner for dandruff treatment is based on Examples 1 and 2 The prepared zinc pyrithione particles are combined with the following ingredients: Ingredient A: 21.75% 0.3 0% 0.70% 4.0% 3 0.0% 02.0% 0.5 0% 0.40% 0.40% 2.00% deionized water Guar Classic Propyltriammonium chloride, ammonium silicate, magnesium sulphate, p-thioneone steel (acicular / rod-shaped, 25% dispersed aqueous solution) Ingredient B:

Sodium laureth sulfate 二甲苯硫酸銨成份C : 經濟部中央標举局員工消費合作社印製Sodium laureth sulfate Ingredient C: Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs

三十六烷基氯化銨十六娱:醇NF 硬脂醯醇乙二醇二硬脂酸酯成份D · _______-22- 本紙張尺度適用中國國家梯準{ CNS ) A4規格（210X297公釐） 448 ί 5 7 Α7 Β7 五、發明説明（20 ) 椰基醯胺MEA 月桂基硫酸銨成份E : 防腐劑香料和染料成份F : 檸檬酸，2 5:%水溶液 1.70% 36.00% 0.05% 適量適量經濟部中央標率局貝工消費合作社印架去頭皮屑的洗髮精與潤髮乳組成份製法如下：將水加熱至50 °C，並快速攪動分散瓜耳羥基丙基氯化三按和矽酸録鎂。一邊攪拌將羥基吡啶硫銅鋅分散加至此組合物内。以成份F調整成份A之酸鹼値至4.5-5.0。將成份 B緩慢加至成份A中，充份混合。以成份ρ調整該混合物的酸鹼値至5.7-6.3。在單獨容器内，將成份c加熱至7〇_ 75 °C。繼而使A/B混合物加熱至60 °C，而且以成份c換合，充份混合°將成份D加入熱的混合物内，並且充份授掉。以成份F調整混合物的酸鹼値至5.7-6.3。使混合物冷卻至.40-45 °C，一邊攪拌加入成份E。若有需要，可以加入 0.05-1 %的氣化鈉以增加產物的黏稠度。實施例7 :(建議實施例）「特效」去頭皮屑的洗髮精利用根據實施例1和2敘述製成的羥基吡啶硫酮鋅粒予與以下成份組合，製成「特效」去頭皮屑的洗髮精和潤髮乳組成份： -23- 本紙乐尺度適用中國國家標準（CNS ) Α4规格（210x297公楚） ----—1---裝------訂 (諳先閔讀背面之注意事項再填寫本頁〕 448 1 5 7 A7 B7 五、發明説明（21 ) 成份A : 去離子水 62.6% 羥基吡啶硫酮銅 4.0% (針狀/桿狀，25%分散水溶液）Hexadecyl Ammonium Chloride Hexadecyl: Alcohol NF Stearyl Alcohol Glycol Distearate Composition D · _______- 22- This paper size is applicable to China National Standard {CNS) A4 (210X297 mm) ) 448 ί 5 7 Α7 Β7 V. Description of the invention (20) Cocoamine MEA Lauryl ammonium sulfate Ingredient E: Preservative flavor and dye ingredient F: Citric acid, 2 5:% aqueous solution 1.70% 36.00% 0.05% The method of preparing the dandruff shampoo and conditioner for the scalp and the dandruff of the print shelf of the Central Standards Bureau of the Ministry of Economic Affairs is as follows: Heat water to 50 ° C, and quickly stir and disperse the guar hydroxypropyl chloride. Silicate records magnesium. Dispersely add copper pyrithione to this composition with stirring. Use ingredient F to adjust the pH of ingredient A to 4.5-5.0. Add ingredient B slowly to ingredient A and mix well. The pH of the mixture is adjusted to 5.7-6.3 with the component ρ. In a separate container, heat component c to 70-75 ° C. Then, the A / B mixture is heated to 60 ° C, and the component c is exchanged, and the mixture is fully mixed. The component D is added to the hot mixture, and the mixture is fully dispensed. Use ingredient F to adjust the pH of the mixture to 5.7-6.3. Allow the mixture to cool to .40-45 ° C and add ingredient E while stirring. If necessary, 0.05-1% sodium gasification can be added to increase the viscosity of the product. Example 7: (Recommended example) "Special effect" anti-dandruff shampoo Use the zinc pyrithione granules prepared according to Examples 1 and 2 to combine with the following ingredients to make "special effect" anti-dandruff Shampoo and conditioner composition: -23- The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210x297). Please read the notes on the back before filling this page] 448 1 5 7 A7 B7 V. Description of the invention (21) Ingredient A: Deionized water 62.6% Copper pyrithione 4.0% (acicular / rod-shaped, 25% dispersed Aqueous solution)

成份B 甲基派柱平（paraben) 0.30% 丙基派拉平 0.10% 聚丙二醇 0.5 0% 氯化鈉 0.50% 成份C : 月桂基三乙醇胺硫酸銨 20.0% 椰基酿胺MEA 4.0% 伸乙二醇二硬脂酸酯 7.0% 成份D : 椰基二銨水解動物蛋白質 1,00% 成份E : 經濟部中央標準局員工消費合作社印製 - -1 - -. - I - J_ I - I 1:1 I- I 一 I I (請先閱讀背面之注意事項再填寫本頁) FD & C Blue No. 1 適量成份F : 檸檬酸，50%水溶液適量去頭皮屑的洗髮精與潤髮乳组成份製法如下：將成份A加熱至60 °C。充份攪拌加入成份B的成分直到 _-24- 本紙張尺度適用中國國家標準（CNS ) A4規格（210X297公釐〉 448 1 5 7 A7 ----—_____B7 五、發明説明（22 ) 一Ingredient B: methyl paraben 0.30% propylpyrazine 0.10% polypropylene glycol 0.5 0% sodium chloride 0.50% ingredient C: lauryl triethanolamine ammonium sulfate 20.0% coco-based melamine MEA 4.0% ethylene glycol Distearate 7.0% Ingredient D: Coconut diammonium hydrolyzed animal protein 1,00% Ingredient E: Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs--1--.-I-J_ I-I 1: 1 I- I-II (Please read the precautions on the back before filling out this page) FD & C Blue No. 1 Ingredients F: Citric acid, 50% aqueous solution, appropriate amount of anti-dandruff shampoo and conditioner composition The method is as follows: Ingredient A is heated to 60 ° C. Add the ingredients of ingredient B until it is _-24- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 448 1 5 7 A7 ----——_____ B7 V. Description of the invention (22)

'谷解爲止。依序將成份C的成分加入混合物内，並且在60 °C 時混S加熱。—邊榄拌使混合物冷卻至4 0 °C，繼而繼續攪拌加入成份Π)和E。利用成份F調整最終組合物的酸驗値至 4.7。雖然本發明已顯示和敘述關於其具體實施例的説明，但應茲明瞭前述和各種其它變化、省略和添加形態及其詳細 j明，必需不悸離中請專利範圍中詳載之本發明精神與範 -1〇装-- (請先閲讀背面之注意事項存填??本頁) •Λ 經濟部中央標準局員工消費合作衽印製 25- _---- 本紙張尺度適用+國國家榇準（CNS ) A4规格（2!0X297公嫠）'So far. Add the ingredients of ingredient C into the mixture in sequence, and mix with S at 60 ° C to heat. —Blank to cool the mixture to 40 ° C, then continue to add ingredients Π) and E. Use ingredient F to adjust the pH of the final composition to 4.7. Although the present invention has shown and described the description of its specific embodiments, the foregoing and various other changes, omissions, and added forms and their detailed descriptions should be made clear, and the spirit of the present invention, which is detailed in the scope of the patent, must be kept. With Fan-1〇 Pack-(Please read the precautions on the back and fill in this page) • Λ Consumption Cooperation with Employees of the Central Standards Bureau of the Ministry of Economic Affairs 衽 Printed 25- _---- This paper is applicable to + country countries Standard (CNS) A4 specifications (2! 0X297 male)

Claims

A8 B8

4 48 1 $ " | 71〇385〇 Chinese Patent Application Scope Amendment (I-89, February) 诘 Sixth, apply-please patent Fan Yuan 〇 (Please read the "% attention notice" Fill in this education] 1.-A method for making sub-micron-sized hydroxypyridine thione salt particles, which is characterized in that the p-based thiopyridine or the water-soluble salt and the water-soluble polyvalent metal salt of thiopyridine Reaction in a pressurized turbulent reactor that generates atomization force 'The reaction will produce sub-micron-sized p-pyridone salt particles ranging in size from about 0.03 microns to about 0.95 microns. 2. According to The method of claim 1 is characterized in that the water-soluble salt of cyprobenone is selected from the group consisting of sodium hydroxypyridine thione, hydroxypyridine thiosulfone, sulfone, and thiophenone. Copper pyrite thiosulfate and its combination. 3. According to the method of _Please Patent Fan Yuan, characterized in that the water-soluble polymetallic salt is a bi-salt salt, and is selected from the group consisting of zinc salt, tin salt, and salt. , Syria, copper, knot, iron, salt, nitrate, acetate, sulfate 'halide salts and combinations thereof 4. Method according to item 3 of the scope of patent application, characterized in that the divalent salt system is selected from the group consisting of zinc sulfate, zinc chloride, zinc acetate, copper chloride and combinations thereof. 5. According to the scope of patent application! The method of item, characterized in that the reaction step further comprises adding a dispersant 'selected from the group consisting of sodium salts of polymerized alkylbenzenesulfonic acid and combinations thereof. Printed by Zhengong Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 6. According to the application The method according to item 5 of the patent, characterized in that the dispersant is present in a blend with a surfactant. 7. The method according to item 丨 of the application, is characterized in that the hydroxypyridine or The ratio of the water-soluble salt of pyridylthione to the water-soluble polyvalent metal salt is in the range of about 1: 2 to about 1: 8. 8. According to the method of item 丨 of the application scope, its further features In order to separate the submicron hydroxypyridine thione salt particles. —- This paper size is free from the Chinese national standard (CNS > A4 size (210X297) 嫠 448157 Α8 Β8 C8 D8 Cooperative printed oxygen The scope of the patent application 9 'The method according to the scope of the patent application No.!, Characterized in that the pressure maintained in the pressurized reactor is greater than 1000 psi. 10. According to the patent application The method of item i is characterized in that the reaction step is performed at a temperature of about ot: and about 23. (:). 1L according to the method of the scope of patent application item !, characterized in that the atomizing force is selected from the group including shear Shear force, impact force, cavitation force, acoustic vibration force, and combinations thereof. 12. The method according to item (1) of the patent application park, characterized in that the size range of the submicron-sized hydroxypyridine salt particles is about 0. 〇4 microns to about 0.88 microns. The method according to item 12 of the patent application is characterized in that the submicron-sized hydroxypyridine thione salt particles have a size ranging from about 0.30 micrometers to about 0.45 micrometers. 14. A shampoo or skin care composition, characterized in that it is a base money and a hydroxypyridine salt having a size in the range of about 0.003 micrometers to about 0-95 micrometers made by the method of patent application No. 1 particle. 15. The composition according to item 14 of the Patent Application, characterized in that the matrix flow system is selected from the group consisting of a surfactant, a dispersant, and a combination thereof. 16. A method for manufacturing submicron-sized zinc pyrithione particles, characterized in that a water-soluble salt of hydroxypyridine or pyrithione is selected from the group consisting of zinc sulfate, zinc chloride, zinc acetate, and combinations thereof The water-soluble zinc salt is reacted in a pressurized turbulent reactor that generates atomization force, and the pressure of the turbulent reactor is maintained at about: ^ "pounds per square inch to about 23,000 pounds per square inch = inch And, the temperature is about 0. (: to about 23t, the reaction will produce a size of less than 2 meters. Fanyuan is about 0.03 microns to about 0.95 microns light (please read the precautions on the back before filling in (This page) _, ιτ SS home paper used in this paper size push f 2 · A ΛΑ /, ν ΛΛτ V i af% A8 Βδ C8 D8 448 157 6. Apply for a patent scope based on U than thiosulfur zinc particles D 17 The method according to item 16 of the application, wherein the water-soluble salt of hydroxypyridine is selected from the group consisting of sodium hydroxypyridine, potassium thiopyridine, lithium thiopyridine, ammonium hydroxypyridine, and The combination 18. Method according to item 16 of the Patent Scope It is characterized in that the reaction step further comprises adding a dispersant selected from the group consisting of sodium salts of polymerized alkyl sulfonic acid and combinations thereof. 19. The method according to item 18 of the scope of patent application, characterized in that the dispersant system It exists in the blend with the surfactant. 20. The method according to item 16 of the scope of application for patent, characterized in that the water-soluble salt of hydroxypyridine or hydroxypyridine The ratio is in the range of about 1: 2 to about 1: 8. 21. According to the method of the patent application No. 16, its further feature is the step of separating the submicron zinc hydroxypyridinethione particles. 22. The method according to item 16 of the patent application park, characterized in that the atomizing force is selected from the group consisting of a shear force, an impact force, a cavitation force, a sonic force, and a combination thereof. The method according to item 16, characterized in that the submicron size of the zinc pyrithione particles is too small in the range of about 0.003 micrometers to about 0.95 micrometers. According to the method in claim 23, the method is characterized in that Submicron zinc pyrithione The size of the particles ranges from about 0.004 micrometers to about 0.88 micrometers. According to the method of patent application Fanyuan f 24, it is characterized in that the size range of the submicron zinc hydroxypyridhione zinc particles is About 0 30 microns to about In--I i nt— 1-nn n ^ i I — ^ nn ^ 111 Jan -1, 3-δ (Please read the notes on the back before filling out this page) Central Ministry of Economic Affairs The printed paper produced by the Employees' Cooperative of the China Bureau is applicable to the standard (CNS) A4g -3- A8 B8 C8 D8 ^ 48 1 5 7 6. The scope of patent application is 0.45 microns. 26. A shampoo or skin care composition characterized by having a matrix fluid and a size range of about 0.03 micrometers to about 0.95 micrometers with a base fluid and a ratio of about 0.03 micrometers to about 0.95 micrometers. Zinc thioketone particles. 27. The composition according to item 26 of the application, wherein the matrix sweat system is selected from the group consisting of surfactants, dispersants, and combinations thereof. (Please read the notes on the back before filling out this page) Order the printed sample of the Central Ministry of Economic Affairs, the Ministry of Economic Affairs, the Ministry of Economic Affairs, the Fifth Cooperative Cooperative Society I, the country, the country, the country, the country, the country, the country, and the country. 97 2 X

Application Date-6 'Case No. 87103850 Class Amendment Supplement A4 C4 Chinese Manual Correction Page (December 88) Economy Zou Zhi 4 Industry Consumer Cooperative Co., Ltd. Printed as * j Patent Specification 448 丄 57 Invention I. New Name Made in Chinese Method for making particles of hydroxypyridine thiamine in English METHOD FOR PRODUCING PARTICLES OF PYRITHIONE SALTS Name 1. George A. Posen 2. Richard H. Dumas' 3. Invented and created nationality in the United States 1. No.131 Campivila Hills Road, Harwindon, Connecticut, USA 2. No. 2 Brocade Village, East Haven, Connecticut, USA 3. City Fees, Ques, Connecticut, USA No. 148, Erwei Road Name (Name) American Business Yaqi Chemical Company Nationality US 3 'Applicant's Residence, Domicile (Office) Post Office Box 5204 Merritt 5 01, New York, Connecticut, USA Name of Representative Sarah O'Connor · -1-This paper size applies Chinese National Standard (CNS) A4 (210X; 297 mm) Patent Application No. 871〇385〇 Anbian 48 ί 5 Chinese manual amendment page (89 Month)- -V. Description of the invention (15: Α7 Β7 _ 丨丨丨 _ 丨 1 丨 _ | ί The distribution is narrowly dispersed (almost single points ..........- TTTT ... 'is 0.30 to about 0.45 green rice.) Size Table I Size (micron) Frequency ------ Cumulative f%, 0.445 0.25 ----- 100.0 0.389 22.41 99.75 0.339 64.35 77.34 0.296 -------- 13.00 13.00 Shellfish Consumption cooperatives. Indica.m. Sub-micron copper pyrithione copper particles are manufactured similarly to the method of Example 10,000. Pour 100 ml of a 3% aqueous solution of Quercus octopus, and maintain about shank lb / sq. Inch and approximately 5 charge microfluidizer recirculation. 50 $ L 2 42% CuCl2, the solution was added to this circulating solution maintained at about 5 ° C. Measured by a single pass micro with Horiba LA910 laser Size and distribution of hydroxypyridine steel particles generated by the fluidizer. Analysis shows that the particle size ranges from 0 04 to 088 micrometers, while the medium size is about 0. 0 9 micrometers. 1 case of 1 application? .. (recommended Example) Anti-dandruff shampoo formulation I Anti-dandruff shampoo composition is described according to Examples 1 and 2 The prepared hydroxypyridine steel particles are made together with the following ingredients: 18- This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page)

A8 B8

4 48 1 $ " | 71〇385〇 Chinese Patent Application Scope Amendment (I-89, February) 诘 Sixth, apply-please patent Fan Yuan 〇 (Please read the "% attention notice" Fill in this education] 1.-A method for making sub-micron-sized hydroxypyridine thione salt particles, which is characterized in that the p-based thiopyridine or the water-soluble salt and the water-soluble polyvalent metal salt of thiopyridine Reaction in a pressurized turbulent reactor that generates atomization force 'The reaction will produce sub-micron-sized p-pyridone salt particles ranging in size from about 0.03 microns to about 0.95 microns. 2. According to The method of claim 1 is characterized in that the water-soluble salt of cyprobenone is selected from the group consisting of sodium hydroxypyridine thione, hydroxypyridine thiosulfone, sulfone, and thiophenone. Copper pyrite thiosulfate and its combination. 3. According to the method of _Please Patent Fan Yuan, characterized in that the water-soluble polymetallic salt is a bi-salt salt, and is selected from the group consisting of zinc salt, tin salt, and salt. , Syria, copper, knot, iron, salt, nitrate, acetate, sulfate 'halide salts and combinations thereof 4. Method according to item 3 of the scope of patent application, characterized in that the divalent salt system is selected from the group consisting of zinc sulfate, zinc chloride, zinc acetate, copper chloride and combinations thereof. 5. According to the scope of patent application! The method of item, characterized in that the reaction step further comprises adding a dispersant 'selected from the group consisting of sodium salts of polymerized alkylbenzenesulfonic acid and combinations thereof. Printed by Zhengong Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 6. According to the application The method according to item 5 of the patent, characterized in that the dispersant is present in a blend with a surfactant. 7. The method according to item 丨 of the application, is characterized in that the hydroxypyridine or The ratio of the water-soluble salt of pyridylthione to the water-soluble polyvalent metal salt is in the range of about 1: 2 to about 1: 8. 8. According to the method of item 丨 of the application scope, its further features In order to separate the submicron hydroxypyridine thione salt particles. —- This paper size is based on the Chinese national standard (CNS > A4 specification (210X297))