200927269 九、發明說明： 【發明所屬之技術領域】 有關於一種分離物質之方法’特別是一種分離二溶 質之製造方法。 【先前技術】 Ο _首2物ΐϊί奈米材料或超細微粒之製備為廣受討論於研究 領域，s物質涵微細化製程後，大幅增加粒子㈣表面積，原 顯著的變化及獨特的物理性質。目前傳統的製程 ί ί 的結晶顆粒，經由研磨方式將原料減積達一定 的粒徑分佈’以總體密度的需求。雖然，此一方法過錄 但由於原料進入研磨前的結晶粒徑大小常因批次生產而 因進料晶粒粒徑分佈較廣，難單藉由研磨便獲得粒徑分佈^ =佈：準化之要求;另一問題點在於研磨過程中需 作動力，嫉麵應力料使晶觀成蚊形 穩定性，且由於機械功而產生_齡破麵㈣粉3 原料中有效成份之活性。 视寅降低 ▲從醫.藥研究發現㈣的雛大小是蚊該物f絲被人 效吸收利用_鍵之―’當絲子微細化後，可以增進其溶解速 率、附著性增強:吸㈣增高，在生物_更驗速鱗而有= ，收利用，增賴物本身朗效率，同_少藥物的使用劑量， 提升療效。 、奈米材料鮮定義為尺寸具有奈狀度之籠、薄膜 或疋塊體。此種材料具有許多超越傳統塊材物質的特性，其應用 5 200927269 Ο 〇 =域相當廣泛；經由科學實驗證實，當常態物質經由微細化製程 、到不米尺度時，會現特異的表面效應、體積效度和量子效應， 其物理化子乃至醫藥性質均產生十分顯著的變化。例如： ，爆裂，物質或推補’能促賴燒效果；聚合物與生物高分子 S ’是良好的吸附劑、觸媒與藥物釋放系統的優異載體；藥物 太^可提升生物攝取度、降制藥量、改善藥轉放的可控性； 微減增紗紐與歡性；奈糊雜粒可增大表面 ，提痛媒雜，奈米超導先趨物微粒，具有提升超導物的性 此等。因此’奈料料製備的技術開發，甚具有產業價值性。 超臨界流體的相關報導最早於西元1822年時，由學者Charles ⑯la TQUr於實驗時所發現的—個物理現象；當流體溫 '、綱達臨界·叫液_氣兩相的密度將趨於相同；此時， ^論改變溫奴壓力，流體不會因壓力的增加硫化也不會因 =度的增加轉致氣化，使缝魏-液兩相合併成為-均句 μ目\此一均勻的相便是所謂的超臨界相（Supercritical 由於流體的溫度或壓力由超臨界狀態回復到液-氣相 ^ 相之間的變化是不易被觀察或觀察不到相之間的變化，因 臨界流義為—定義的㈣[8]。超臨界趣技術製備細微 化顆粒之研究在聰年代_才漸受重視 醫藥與化輋的斜柄工夕社 攸遲用於展備 二^ 年，由許多不同的超臨界流體製備微粒子 技術因廷目而被發明。 壯曰^在化學、醫藥紅業上_粒製備方法為糊粉碎或是 於=方i獲得所需的顆粒與顆粒尺度的分佈。然而，傳統的 二大二i噴霧乾燥法與再結晶技術’無法有效的控制顆粒尺度 、/、刀佈。利用超臨界流體技術製備微粒子技術，除可由操 6 200927269 作條件的細微變化便能改變超臨界流體的物理特性進而達到 粒子尺度大㈣尺度分佈鶴，_兼觸環猶料，能 無溶劑殘㈣粉體’並且不會破壞物質本身的活性， 贺 熱敏性物質的微粒子，衫需再、_繁複的後處理等優點。4備 以超臨界技術鶴微細難的駿本質上_於傳統結晶操 作’不_是可藉由超臨界流體的使用在極短__到物 超飽和，進而生成齡小且分佈均勻的顆粒，同時所獲得之粉體 f有理想的結晶體與幾乎無溶綱㈣特性，更可省去冷朴 燥、粉碎等繁鎖的後處理程序。錄超臨界流體的相變化可以藉 由溫度與壓力進行調控以操控相在相圖上的轉變，進而利用此— 特性，來獲得齡與控繼㈣_職學與狹窄的粒徑分佈， 使所獲得_粒大小、幾何形狀及顆錄徑的分佈達到均句的目 的。因為超臨界流體是·種介於氣相與液相之間的流體，因而避 免結晶過程中相之間的衝突，也消除表面張力產生的影響使生 成的細微化固體顆粒不易發生聚集現象。 、近年陸續有學者針對超臨界频技術在材料製備技術上的應 ❹㈣彳T研究絲討’-般雜界紐在雛製備·術分類是以 超臨界流體所扮演的角色加以區分’以超臨界紐做為溶劑的有 快速膨脹法（Rapid Expansion of Supercritical Solution，RESS) 與氣體飽和溶液沉積法（Particle fr〇m Gas Saturated Solution，PGSS);以超臨界流體做為反溶劑使用的技術稱為超 臨界反溶劑沉積法（Supercritical AntiSolvent，SAS)。在幾 種微粒子製備技術中，RESS通常被列入首先的考量，這是由於在 /谷質溶入超臨界流體中所添加的修飾劑均可經由以二氧化碳做為 超臨界流體的RESS程序被消除。當溶質在超臨界流體中的溶解能 200927269 力較低時，例如醫藥化合物，才會改由SAS的技術製備微粒子。這 - 些微粒製備技術，均利用溶劑本身的溶解能力的改變，使溶質達 高度過飽和狀態而析出，進而獲得細微粒子。 超臨界溶液快速膨脹法（RESS)最早是由Mats〇n等人在1987 年提出實驗程序’並成功針對—些有機物和無機物做快速膨脹製 備微粒實驗。其後許多學者紛紛投入研究不同的操作參數對於微 粒的晶體成型的影響、晶體的成核理論和晶粒成長理論。200927269 IX. Description of the invention: [Technical field to which the invention pertains] A method for separating a substance, in particular, a method for producing a separation solute. [Prior Art] _ _ first two objects ΐϊ 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈 奈. At present, the conventional process ί ί crystal particles, through the grinding method, reduce the raw material to a certain particle size distribution 'to the overall density demand. Although this method has been recorded, the size of the crystal grain before the raw material enters the grinding is often due to the batch production. Because of the wide distribution of the grain size of the feed, it is difficult to obtain the particle size distribution by grinding alone. The other problem lies in the need to use the power during the grinding process. The surface stress material makes the crystal form a mosquito-like stability, and the activity of the active ingredient in the raw material is generated due to mechanical work.寅 寅 ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ ▲ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ In the biological _ more test speed scales have =, take advantage of, increase the efficiency of the material itself, with the use of less drugs, improve efficacy. Nanomaterials are rarely defined as cages, membranes or lumps with dimensions. This material has many characteristics beyond the traditional bulk material, and its application 5 200927269 Ο 〇 = domain is quite extensive; through scientific experiments, it is confirmed that when the normal substance passes through the micronization process to the non-meter scale, it will have a specific surface effect, Volumetric validity and quantum effects, both physicochemical and even medical properties, have produced significant changes. For example: , burst, substance or tonic 'can promote the effect of burning; polymer and biopolymer S ' is a good carrier of good adsorbent, catalyst and drug release system; drug too ^ can improve biological uptake, drop The amount of pharmaceuticals, improve the controllability of drug transfer; slightly reduce the yarn and the joy; the paste can increase the surface, painful media, nano-superconducting precursor particles, with the promotion of superconductors Sex like this. Therefore, the development of technology for the preparation of nanomaterials is of great industrial value. The correlation report of supercritical fluids was first discovered in the 1822 AD by the scholar Charles 16la TQUr. When the temperature of the fluid, the density of the fluid, the liquid phase and the gas phase will tend to be the same. At this time, on the change of Wennuo pressure, the fluid will not be vulcanized due to the increase of pressure, nor will it be converted into gasification due to the increase of = degree, so that the two phases of the split-wei-liquid merge into one--------- The phase is the so-called supercritical phase (Supercritical due to the change of the temperature or pressure of the fluid from the supercritical state to the liquid-gas phase. The change between the phases is not easy to observe or observe the change between the phases due to the critical flow. Yi Wei—Defined (4) [8]. The research on the preparation of fine particles by supercritical interest technology in the era of Cong _ is gradually gaining attention to the treatment of medicine and phlegm. The slash handle is used for the exhibition of two years, many Different microcritical fluid preparation microparticle technology was invented by Tingmu. In the chemical and pharmaceutical red industry, the particle preparation method is paste pulverization or the desired particle-particle size distribution is obtained. , the traditional two big two i spray drying method and The crystallization technology 'cannot effectively control the particle size, /, knife cloth. Using the supercritical fluid technology to prepare the microparticle technology, in addition to the slight changes in the conditions of the operation of 200927269 can change the physical properties of the supercritical fluid and reach the particle size (four) scale The distribution of cranes, _ also touched the ring, can be solvent-free (four) powder 'and does not destroy the activity of the substance itself, the heat-sensitive substance of the particles, the shirt needs to be, _ complicated post-treatment and other advantages. 4 prepared with supercritical The technical crane is very difficult to use in the essence of the _ in the traditional crystallization operation 'no _ can be used by the use of supercritical fluid in a very short __ to super-saturated, and then to generate small and evenly distributed particles, while the powder obtained The body f has ideal crystals and almost no solute (four) characteristics, and can eliminate the complicated post-processing procedures such as cold and dry, crushing, etc. The phase change of the supercritical fluid can be controlled by temperature and pressure to control the phase. The transformation on the phase diagram, and then the use of this - characteristics, to obtain the age and control (four) _ vocational and narrow particle size distribution, so that the _ particle size, geometry and particle diameter The cloth reaches the purpose of the average sentence. Because the supercritical fluid is a kind of fluid between the gas phase and the liquid phase, it avoids the conflict between the phases in the crystallization process, and also eliminates the influence of the surface tension to make the generated fine solid. Particles are not prone to aggregation. In recent years, some scholars have applied the supercritical frequency technology to the material preparation technology. (4) 彳T research 讨 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Distinguish between 'Rapid Expansion of Supercritical Solution (RESS) and Particle Fractional Gas Saturated Solution (PGSS) with supercritical fluid as solvent; use supercritical fluid as anti-solvent The technique used is called Supercritical AntiSolvent (SAS). Among several microparticle preparation techniques, RESS is generally considered as the first consideration because the modifier added in the /grain-dissolved supercritical fluid can be eliminated via the RESS procedure using carbon dioxide as the supercritical fluid. When the solute dissolves in a supercritical fluid 200927269 When the force is low, such as a pharmaceutical compound, the microparticles are prepared by the SAS technique. This - some particle preparation techniques use the change in the solubility of the solvent itself to cause the solute to be highly supersaturated and precipitate, thereby obtaining fine particles. The supercritical solution rapid expansion method (RESS) was first proposed by Mats〇n et al. in 1987 and successfully developed microparticle experiments for rapid expansion of some organic and inorganic substances. Since then, many scholars have devoted themselves to studying the effects of different operating parameters on the crystal formation of microparticles, the nucleation theory of crystals and the theory of grain growth.
Debendetti借由流體力學與熱力學的理論，對膨脹前後的溫度' ❹ 壓力、飽和度與溶解度的變化針對晶核最小可逆功、成核速^、 臨，晶核^寸做-分析討論。當超臨界溶液膨_低溫與低壓而 成氣相狀態，溶質的過飽和度瞬間提升，此時若溶液以單相喷出 時將會析出大量微核’在等熵區域内微核快速生長形成粒度 =勻的超細職。在定溫條件下’改㈣力或觸脹溫度使溶^ 溶解度增加，經過喷嘴時溶_過飽和度增大，成核速率增加， 所獲得之晶核更小。 〃仙快速膨脹法不需賴—般的有機賴，且a作為溶劑的 公超臨界流體進入收集槽後快速膨脹而揮發，可以直接得到無溶劑 t留的顆粒’不需再經繁複的後處理以清除顆粒中的殘餘溶劑， 且能藉由操作條件的改變控制產生顆粒的粒徑以及分布而得到 平均粒徑在微米或奈米等級且粒徑分布集中的材料顆粒。快速膨 ，法最主要的限制為溶質在超臨界流體中的溶解度，若溶質在超 臨界流體巾触解度太低，聽速膨脹法的效率與產量可能 降低，必須藉由添加共溶劑以克服此問題。 雖然傳統物理方法與化學方法均可獲得奈米粒子，也均具有 200927269 其各自優異性。但傳統的物理與化學此兩種造粒技術也存在著相 當的缺點存在，例如高機械應力、使用大量溶劑、熱不德定物質 的熱分解、藥物的化學性質改變、微量殘留溶劑、溶劑污染、研 磨破壞表面與結晶性質、顆粒大小及分佈不易控制等問題存在。 因此開發一套對環境衝擊小、生成之固體顆粒性質穩定、能有效 控制粒子尺寸與分佈的造粒技術’勢必將成為一門受到注意的技 術研究。Debendetti relies on the theory of fluid mechanics and thermodynamics to analyze the temperature, pressure, saturation and solubility of the nucleus before and after expansion for the minimum reversible work of the crystal nucleus, nucleation rate, pro, and nucleation. When the supercritical solution swells from low temperature and low pressure to form a gas phase, the supersaturation of the solute is instantaneously increased. At this time, if the solution is ejected in a single phase, a large number of micronuclei will be precipitated. In the isentropic region, the micronucleus rapidly grows to form a particle size. = even super fine job. Under constant temperature conditions, the (four) force or the swelling temperature increases the solubility of the solution. When the nozzle passes, the dissolution_supersaturation increases, the nucleation rate increases, and the obtained crystal nucleus is smaller. The rapid expansion method of Zhuxian does not depend on the organic susceptibility, and a public supercritical fluid as a solvent enters the collecting tank and rapidly expands and volatilizes, and can directly obtain the particles without solvent t-remaining without complicated post-treatment. In order to remove residual solvent in the particles, and to control the particle size and distribution of the particles by changing the operating conditions, material particles having an average particle diameter on the order of micrometers or nanometers and having a particle size distribution can be obtained. Rapid expansion, the most important limitation of the method is the solubility of the solute in the supercritical fluid. If the solute is too low in the supercritical fluid towel, the efficiency and yield of the swell expansion method may be reduced, and it must be overcome by adding a cosolvent. This problem. Although both traditional physical and chemical methods can obtain nanoparticles, they all have their own superiority in 200927269. However, traditional physical and chemical granulation techniques also have considerable disadvantages, such as high mechanical stress, the use of large amounts of solvents, thermal decomposition of thermophilic substances, chemical changes in drugs, trace residual solvents, solvent contamination. Problems such as grinding damage surface and crystallization properties, particle size and distribution are difficult to control. Therefore, the development of a granulation technology with small environmental impact, stable solid particle formation, and effective particle size and distribution control is bound to become a technical study that has received attention.
【發明内容】 本發明之主要目的，在於提供一種分離二溶質之製造方法， 以超臨界溶液膨脹法，利用不同溶質（例如咖啡因或兒茶素）的凝 聚力不同，使得凝聚力較強的溶質先凝結成液體，而凝聚力較弱 的溶質隨著氣相被收集，藉此以分離不同溶質之為用者。 本發明之次要目的，在於提供一種分離二溶質之製造方法， 以超臨界溶液膨脹法，以防止使職械設健生高溫破壞物質内 所含有之至少二溶質之成份。 本發明之又—目的，在於提供—種分離二溶質之製造方法， 不:r機溶觸嶋取賴 射，導·再將該 氣-液相之_，其响_蝴咐SUMMARY OF THE INVENTION The main object of the present invention is to provide a method for producing a separation solute, which uses a supercritical solution expansion method to utilize different cohesive forces of different solute (for example, caffeine or catechin) to make a solute having a strong cohesive force Condensed into a liquid, and a weakly cohesive solute is collected along the gas phase, thereby separating the different solutes. A secondary object of the present invention is to provide a method for producing a separation of two solutes by a supercritical solution expansion method to prevent the components of the at least two solutes contained in the material from being destroyed by the high temperature. A further object of the present invention is to provide a method for producing a separation of two solutes, which is not: r-dissolved and absorbed, and then the gas-liquid phase, which sounds _
之 200927269 體，其包含該些溶質之一第—溶質. /奋買，5亥第一收集槽所產生之氣相 二二 讓該第二收集槽之該氣相、流體快速膨 之Λ\其巾該第二收_所產生之餘流體為一第 ^ 溶質之―第二溶f。最後抽出該第二收集槽 所產生之氣相流體，而留下該第二液體 出第一溶質與第二溶質，而不殘留溶劑。 有效刀離 實施方式】 錄為使貝審查委員對本發明之結構特徵及所達成之功 效更進-步之瞭解與認識，謹佐以較佳之實施例及配細 說明，說明如後： 請參閱第-圖，其係本發明之分離裝置之方塊圖；如圖所示， 本發明為-種分離二溶質之製造方法，其所顧之分離裝置係包 含-膨脹轉…冷凝㈣_與_減幫雜，其中膨服 收集槽1G設置-噴嘴12與-連接管14，冷凝收集槽置一冷凝 管22 ’抽氣幫賴設置—抽氣管32，連接扣係連接膨脹收集槽 10與冷凝管22 ’減管獅連接冷凝轉獅與減幫浦3〇。至 2二溶質溶解於-賴而成為―舰，其巾該賴於臨界壓力與 臨界溫度下即為-超臨界溶液（supercHtieal sQlui：i〇n)。該 流體經喷嘴12注入膨脹收集槽1〇，膨脹收集槽1〇快速膨脹該流體 為氣-液相之流體。 膨脹收集槽10所產生之氣相流體為經連接管14注入冷凝收集 槽20，並經由冷凝管22冷凝冷凝收集槽20之氣相流體為液相流 體，如此未冷凝為液相流體之氣相流體則由抽氣幫浦3〇經抽氣管 200927269 32抽出。 _雜财二®，其係本發明之—健實補之流糊，·如圖 所示’本發明為-種分離二溶質之製造方法，其利用超臨界溶液 膨脹法分離溶質。步驟一開始按步驟sl〇〇所示，提供至少二溶質， ，係具不同之凝聚力。再按步驟S12G所示，提供一溶劑溶解該二 洛質而為該關為在臨界壓力與臨界溫度下，即為 了超臨界溶液。按步驟_所示，注入該流體至一第一收集槽:、 ❹ 並讓該第-收集槽之流體快速膨脹為氣一液相之流體，其中該第一 收集槽所產生之液相流體為—第—液體，其係包含該些溶質之一 第二溶質。按步驟所示，該第―㈣槽所產生讀相流體注 入-第二收集槽，並讓該第二收集槽之氣相流體快速膨脹為氣-液 相之机體，其中該第二收集槽所產生之液相流體為一第二液體。 按步驟S18G所示’抽取該第二收賴所產生之氣相流體。 本發明更可再_雜界溶隸賴驗（Rapid E聊si〇n ^Supercritical Solution ’ RESS)讓該第-液體與該第二液體 :氣液i目，而取其液相，以提升溶質於該第一液體之純度，以及 奋質於4第—液體之純度’如第三圖與第四圖所示，其係該第一 液體與該第二液體經快速祕提升溶f純度之步驟絲。如第三 =所其係本發明之—較佳實細之快速膨脹第—液體之流程 ，按步驟S142所示，加熱加壓該第一液體至臨界溫度與臨界壓 力下：以讓第一液體成為一超臨界液體，接續按步驟S144所示， 、:該第液體至一第三收集槽，並讓該第一液體快速膨脹為氣— 人目六其中該第二收集槽所產生之之液相為—第三液體，其所包 =办質的比例係大於該第—液體。'然後按步驟&46所示，柚出 二收集槽所產生之氣相流體。 ❹ ❹ 200927269 如第四圖所示，复在士双nn 液體之#鞀_.& /糸本發明之一較佳實施例之快速膨脹第二 度與臨轉力下乡驟S162所示，加熱加屢該第二液體至臨界溫 s:所示，注入為-超臨界液體’接績按步驟 ΠΐΓΓ其中該第四收集槽所產生之之液相為一第四液 所示:、抽：二，：質的比例係大於該第二液體。然後按步驟S166 第二收集槽所m相流體。因此該第-液體與該 摇斗:，哲：J由重複執行如第三圖與第四圖所示之步驟而大幅 徒升洛質之純度，且不會破壞溶質之本質。 如第五圖與第六圖所示，本發明之方法接續自該第一液體與 “了液體過滤出該第一溶質與該第二溶質之步驟流程。如第五 ，所不’其縣發明之—較佳實酬之取得第—溶質之流程圖,· t步驟S15G所示’讓该第—液體成為液_固相，接續按步驟SB?所 示，過濾液-固相而取得該第一溶質。如第六圖所示其係本發明 <較佳實施例之取得第二溶質之流程圖；按步驟sl7〇所示，讓 該第二液體成為液—固相，接續按步驟S172所示，過濾液-固相而 取得該第二溶質。 另外，以下實施例為本發明之實驗數據，藉由實驗數據加以 說明本發明之優點： 請參閱第七圖’其係本發明之超臨界溶液相變化的示意圖； 如圖所示，在超臨界狀態下’溶質的溶解度會隨溫度和壓力在較 大範圍内產生變化，利用降低壓力使溶質經由氣-液相界線從超臨 界狀態變為液一氣態，或利用降低溫度以使溶質經由液—固相界線 攸超臨界狀態變為液一固態’此過程將導致過飽和或達到高产過 12 200927269 Ο 飽和狀態’固體溶質從超臨界流體巾析出，職平均粒徑报 均勻粒子。而本發明所朗之超臨界溶液快速膨脹技術為新 細微粒的製備驗，此驗是核料祕於雜界流體中，缺 後將/谷有飽和⑷質的超臨界溶液在極短時間内通過喷嘴或毛細 管，並讓超臨界溶液於低壓或常_收#_快速膨脹，藉由= 烈的機械擾動與超臨界流體的溶解能力驟降，使溶f在溶液 到極高過飽械，麟携械贿件，使縣鱗於容液中的 溶質快速沉崎出，而制雌微小且分佈均勻的溶質顆粒。 本實施例係選用二氧化碳做為超臨界流體的溶劑，並以綠茶 ，取液為溶質’實施步驟如第二_示，紐行溶質的製備，再 著手wh實驗參數，本實驗的參數設定主要是以定溫㈣的條件 及疋壓變溫的餅做為錄設計。當溶該由超臨界溶液快速膨 脹法製備獲得粉體後，將收制的綠茶粉，利时射粒徑分析儀 ，掃描式電子酿鏡分析峨得__綠度大小，與顆粒的 晶體結構’來觸及獲得在不同操作條件下顆粒尺寸的分佈情形 與添加修飾劑對超臨界流體結晶的影響。 $中超臨界流體在定溫條件下，壓力越高密度越大，同時也 會使各解度增加，且超臨界㈣由超臨界壓力膨關常壓狀態 下，結晶成核速率增快，使顆粒成長變緩，因而可以獲得粒徑較 J且刀佈較集中的顆粒。如第八圖所示由雷射粒徑分析儀所獲 得的粒控分佈顯示，壓力在2_加時所獲得結晶顆粒粒徑較大， 且粒徑分佈較廣，當壓力提升到25GGpsi、3GGGpsi及35_si時， 可以發現雛尺寸不但隱力的提升崎小，目時也因壓力的提 升而使粒分佈更為狹窄，此—特性乃符合超臨界流體結晶技術 同時亦與H. Kwak，J.W. Jung, S. Y. BaseandH. Kumazawa 13 200927269 等人所提出之文獻「Preparation of Anthracene Fine Particles by Rapid Expansion of a Supercritical Process Utilizing Supercritical C02」有相同之結論。 然而如第九圖所示，當操作溫度由55°c降為45〇c時，其壓力 對粒徑之變化呈現相反趨勢，當操件壓力提升時其粒徑卻有增大 之趨勢，此一現象與張鏡澄先生之「超臨界流體萃取」之書中所 提之「濁點曲線」現象有關；同時在圖中可發現系統操作溫度為 45C時所獲得之顆粒尺度明顯變小，且粒徑分佈也變的較狹窄； ❹ 並在此操作條件下麟本研究巾最小的粒徑尺度，因此可知當操 作溫度在45 C且操作壓力在_Gpsi時，可獲得綠茶粉末之最小粒 徑。 -般在RESS操作過財是保持超臨界越溶㈣壓力條件不 變’藉由溫^控制而使超臨界溶液呈現出不_溶解能力。假 點曲_對應之溫度為L，系統操作溫度為 出二一3統處在溶解和析出的臨界狀態；在叫時則析 〇 !ί蜀二二，=中的溶液與溶質將溶解成均相溶液。假 辅舰界雜進人健之前健保持溶 ===/獅_峨磁生與聚= 個_里序便已經完成，而獲得小的_立徑。 整 若ΔΓ<0 ’ 谷液將需在更低 嘴後才開崎出溶質難，伽f力相，也就聽液通過喷 獲得更小的粒徑。當ΔΓ>0時，、、j^成長和聚合時間更短，因而 、4液在未進入噴嘴前便已分相，使 14 200927269 析出的溶質微粒有充足的時間可以 獲得之顆粒尺度較大。 生長和聚合成較大的顆粒， 所 圖所：其係本發明之溫度對溶質顆粒粒徑之相對變 _ °本⑯例所顯示之操作溫度對溶質之顆粒粒徑的影 ❹The 200927269 body, which contains one of the solute, the first solute. / Fenbu, the gas phase generated by the first collection tank of the 5th sea allows the gas phase and the fluid of the second collection tank to rapidly expand. The remaining fluid produced by the second _ is the second sol of the first solute. Finally, the vapor phase fluid generated by the second collection tank is withdrawn, leaving the second liquid out of the first solute and the second solute without remaining solvent. Effective Knife Separation Method] Recorded as a more in-depth understanding and understanding of the structural features and achieved effects of the present invention, please refer to the preferred embodiment and detailed description, as explained below: - Figure, which is a block diagram of the separation device of the present invention; as shown in the figure, the present invention is a method for producing a separation of two solutes, the separation device of which comprises - expansion to condense (four) _ and _ reduction Miscellaneous, wherein the expansion collecting tank 1G is provided - the nozzle 12 and the - connecting tube 14, the condensing collecting tank is provided with a condensing tube 22 'the pumping aid is provided - the exhaust pipe 32, the connecting buckle is connected to the expansion collecting tank 10 and the condensing duct 22' The reduced lion connection is connected to the condensed lion and the reduced pump 3 〇. The solute dissolves in the solute and becomes the ship. The towel depends on the critical pressure and the critical temperature is the supercritical solution (supercHtieal sQlui: i〇n). The fluid is injected into the expansion collection tank 1 through the nozzle 12, and the expansion collection tank 1 rapidly expands the fluid into a gas-liquid phase fluid. The vapor phase fluid generated by the expansion collecting tank 10 is injected into the condensing collecting tank 20 through the connecting pipe 14, and the vapor phase fluid of the condensing collecting tank 20 is condensed as a liquid phase fluid via the condensing pipe 22, so that it is not condensed into a gas phase of the liquid phase fluid. The fluid is pumped out by the pumping pump 3 through the suction pipe 200927269 32. _ Miscellaneous®, which is a solid paste of the present invention, is shown in the drawings. The present invention is a method for producing a separated solute which separates a solute by a supercritical solution expansion method. At the beginning of the step, according to the step sl1, at least two solutes are provided, and the system has different cohesive forces. Further, as shown in step S12G, a solvent is provided to dissolve the ruthenium which is at a critical pressure and a critical temperature, i.e., a supercritical solution. Injecting the fluid into a first collection tank as shown in step _, ❹ and allowing the fluid of the first collection tank to rapidly expand into a gas-liquid phase fluid, wherein the liquid phase fluid produced by the first collection tank is a first liquid comprising a second solute of one of the solute. According to the step, the phase-reading fluid generated by the first (four) tank is injected into the second collecting tank, and the gas phase fluid of the second collecting tank is rapidly expanded into a gas-liquid phase body, wherein the second collecting tank The liquid phase fluid produced is a second liquid. The gas phase fluid generated by the second retraction is extracted as shown in step S18G. The invention can further improve the solute by taking the liquid phase and the second liquid: the liquid and the liquid, and the liquid phase to obtain the liquid sol. The purity of the first liquid, and the purity of the liquid of the fourth liquid, as shown in the third and fourth figures, is a step of rapidly increasing the purity of the first liquid and the second liquid. wire. For example, in the third embodiment, the flow of the rapidly expanding first liquid of the present invention is as shown in step S142, heating and pressurizing the first liquid to a critical temperature and a critical pressure: to make the first liquid Forming a supercritical liquid, and then, as shown in step S144, the liquid is discharged to a third collecting tank, and the first liquid is rapidly expanded into a gas-human phase, wherein the liquid phase generated by the second collecting tank For the third liquid, the ratio of the package to the medium is greater than the first liquid. 'The gas phase fluid produced by the two collection tanks is then shown in steps & 46. ❹ ❹ 200927269 As shown in the fourth figure, the re-expansion of the second embodiment of the preferred embodiment of the invention is shown in Figure 162. Heating and repeating the second liquid to a critical temperature s: as shown, the injection is a -supercritical liquid's step by step, wherein the liquid phase produced by the fourth collection tank is a fourth liquid: Second, the ratio of the mass is greater than the second liquid. Then, according to step S166, the m phase fluid of the second collecting tank is used. Therefore, the first liquid and the cradle: J: J is substantially excised from the purity as shown by the steps shown in the third and fourth figures, and does not destroy the essence of the solute. As shown in the fifth and sixth figures, the method of the present invention is continued from the first liquid and the step of "filtering out the first solute and the second solute by the liquid. For example, the fifth, the not" invention of the county - the preferred remedy to obtain the first - solute flow chart, · t step S15G shown 'to make the first liquid into a liquid _ solid phase, followed by step SB?, the filtrate - solid phase to obtain the first a solute. As shown in the sixth figure, it is a flow chart of obtaining a second solute according to the preferred embodiment of the present invention; as shown in step s17, the second liquid is made into a liquid-solid phase, followed by step S172. The second solute is obtained by the filtrate-solid phase. The following examples are experimental data of the present invention, and the advantages of the present invention are illustrated by experimental data: Please refer to the seventh figure, which is the super Schematic diagram of the phase change of the critical solution; as shown in the figure, in the supercritical state, the solubility of the solute changes with a large range of temperature and pressure, and the pressure is reduced to change the solute from the supercritical state via the gas-liquidus boundary. For liquid-gas, or use temperature reduction In order to make the solute change to a liquid-solid state via the liquid-solid phase boundary 攸 supercritical state, this process will lead to supersaturation or high yield. 12 200927269 饱和 Saturated state 'Solid solute precipitates from supercritical fluid towel, average particle size is reported as uniform particle The rapid expansion technology of the supercritical solution of the present invention is a preparation test of new fine particles, which is a secret material in a heterogeneous fluid, and a supercritical solution having a saturated (4) mass in a short period of time. Pass the nozzle or capillary inside, and let the supercritical solution expand rapidly at low pressure or constant__, with the mechanical disturbance of the strong and the solvency of the supercritical fluid dip, so that the solution f is extremely high in the solution. Lin, with the bribes, makes the solute in the squama in the liquid quickly and intensively, and produces solute particles that are small and evenly distributed. In this embodiment, carbon dioxide is used as a solvent for the supercritical fluid, and green tea is used. The liquid extraction is the solute' implementation step, such as the second _, the preparation of the new solute, and then the wh experimental parameters, the parameter setting of this experiment is mainly based on the conditions of constant temperature (four) and the rolling temperature change cake. When the powder is prepared by the rapid expansion method of the supercritical solution, the green tea powder, the Li-time particle size analyzer, and the scanning electron beam mirror are analyzed to obtain the __greenness size and the crystal structure of the particles. 'To reach the distribution of particle size under different operating conditions and the effect of adding modifier on the crystallization of supercritical fluid. In the supercritical fluid, the higher the pressure, the higher the density, and the solution Increase, and supercritical (four) by supercritical pressure swelling under normal pressure, the crystallization nucleation rate increases, so that the particle growth becomes slower, so that particles with a larger particle size than J and a more concentrated cloth can be obtained. The particle-controlled distribution obtained by the laser particle size analyzer shows that the particle size of the crystal particles obtained at 2_addition is larger, and the particle size distribution is wider. When the pressure is increased to 25 GGpsi, 3GGGpsi and 35_si, It is found that the size of the chicks is not only a small increase in the invisibility, but also a narrower particle distribution due to the increase in pressure. This characteristic is in line with the supercritical fluid crystallization technology and also with H. Kwak, JW Jung, SY Baseand H. K. Umazawa 13 200927269 et al., "Preparation of Anthracene Fine Particles by Rapid Expansion of a Supercritical Process Utilizing Supercritical C02" has the same conclusion. However, as shown in the ninth figure, when the operating temperature is lowered from 55 ° C to 45 〇 c, the pressure has an opposite trend to the change of the particle size, and the particle size tends to increase as the operating pressure increases. A phenomenon is related to the phenomenon of "cloud point curve" mentioned in the book "Supercritical Fluid Extraction" by Mr. Zhang Jingcheng. At the same time, it can be found that the particle size obtained by the system operating temperature is 45C is significantly smaller, and the particle size is smaller. The distribution also becomes narrower; ❹ and under this operating condition, the minimum particle size of the lining study towel, so that the minimum particle size of the green tea powder can be obtained when the operating temperature is 45 C and the operating pressure is _Gpsi. Generally, in the RESS operation, the supercritical solution is kept in a supercritical state. (4) The pressure condition does not change. The supercritical solution exhibits a non-dissolving ability by temperature control. The false point _ corresponds to the temperature of L, the system operating temperature is in the critical state of dissolution and precipitation; when it is called, it will be resolved! 蜀 蜀 ,, = solution and solute will dissolve into Phase solution. False auxiliary ship industry mixed with people before the health to keep dissolved === / lion _ 峨 magnetic and poly = _ 里 sequence has been completed, and get a small _ vertical diameter. If the ΔΓ<0 ’ 谷谷液 will need to open the solute after the lower mouth, the gamma force phase will also get a smaller particle size by the liquid. When ΔΓ>0, , j^ growth and polymerization time are shorter, so that the four liquids have been phase-separated before entering the nozzle, so that the solute particles precipitated in 14200927269 have sufficient time to obtain a larger particle size. Growth and polymerization into larger particles, which is the relative change of the temperature of the present invention to the particle size of the solute _ ° The effect of the operating temperature shown in the 16 cases on the particle size of the solute
二，、^^卿1^23]所述相符，*於操作溫度越接近溶劑的彿 .，八命酵發的速度增快，使其雌成長的時間更為短暫，因 此=操作溫度越接近修_之_ (本實施綱使狀修飾劑為 酒精’其雜為78.3°c)而溶質雛越趨於微細化的結果。 如此本發明彻超臨界流體結晶技術巾的超臨界溶液快速膨 脹法t備t微化綠余粉’可降低傳統技術因使用機械設備產生高 二破壞綠*巾的兒*讀茶㈣的成份，也避免有機溶賊留與 萃取液後續齡魏燥粉碎科的繁複處理問題。因减效提升 細微化綠·之鶴轉，且更聽關殘留。 惟以上所述者’僅為本發明之—較佳實施例而已，並非 用來限定本發明實施之_，舉凡依本發明巾請專娜圍所述之 形狀、構造、特徵及精神所為之均㈣倾修飾，均應包括於本 發明之申請專利範圍内。 【圖式簡單說明】 第一圖係本發明之分離裝置的方塊圖； 第二圖係本發明之—錄實_之流程圖； 第二圖係本發明之快速膨脹第一液體之流程圖； 第四圖係本發明之快物脹第二液體之流程圖； 15 200927269 第五圖係本翻之取科—溶質之流程圖； 第六圖係本翻之取得第二溶質之流程圖； 第七圖係本發明之溫度與壓力對相變化的示意圖； 第八圖係本發明之溫度錢力對獅綠之相錢化的曲線圖； 第九圖係本發明之溫度與壓力對顆粒粒徑之相對變化的曲線圖 以及 ❹ 第十®1係本發明之溫度與壓力對顆粒粒徑之相㈣化的曲線圖。 【主要元件符號說明】 10 :膨脹收集槽； 12 :喷嘴； 14 :連接管； 20 :冷凝收集槽； 22 :冷凝管； 30 :抽氣幫浦； 32:抽氣管； S100〜S180 :流程步驟； S142〜S146 :流程步驟；以及 S150〜S152 :流程步驟。Second, ^^qing 1^23] said the match, * at the operating temperature is closer to the solvent of the Buddha. The speed of the eight life yeast is increased, making the time for female growth more transient, so the closer the operating temperature is修__ (This embodiment makes the modifier is alcohol 'the miscellaneous is 78.3 ° c) and the solute chicks tend to be finer. Thus, the supercritical solution rapid expansion method of the supercritical fluid crystallization technology towel of the present invention can reduce the composition of the tea (four) of the traditional technology caused by the use of mechanical equipment to produce the high-grade green* towel. Avoid the complicated treatment of organic thieves and the subsequent age of the extract. Due to the reduction in efficiency, the green crane is turned, and the residual is more. However, the above description is only for the preferred embodiment of the present invention, and is not intended to limit the practice of the present invention, and the shapes, structures, features, and spirits of the invention according to the present invention are all (4) The tilting modification should be included in the scope of the patent application of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS The first drawing is a block diagram of a separating apparatus of the present invention; the second drawing is a flow chart of the present invention - a second embodiment is a flow chart of the rapidly expanding first liquid of the present invention; The fourth figure is a flow chart of the second liquid of the fast material expansion of the present invention; 15 200927269 The fifth figure is a flow chart of the solute-solute; the sixth figure is a flow chart of obtaining the second solute; Figure 7 is a schematic diagram showing the phase change of temperature and pressure of the present invention; the eighth figure is a graph of the temperature and the force of the present invention on the phase of the lion green; the ninth is the temperature and pressure of the present invention. A graph of the relative change and ❹ Tenth® 1 is a graph of the phase (four) of the temperature and pressure of the present invention on the particle size. [Description of main component symbols] 10: expansion collection tank; 12: nozzle; 14: connection pipe; 20: condensation collection tank; 22: condensation pipe; 30: suction pump; 32: suction pipe; S100~S180: process steps S142~S146: process steps; and S150~S152: process steps.