4 4 200302115 玖、發明說明 • ， ，. · .· - . . . ... · .. »: . -- - · ··.···- .......... ......... ...... .... ............. · · (發明說明應敘明：發明所屬之技術領域、先前技術、內容、實施方式及圖式簡單說明） (一） 發明所屬之技術領域 本發明係一般係關於一種氣溶膠（a e r 〇 s ο 1 )產生。更具體 地，本發明係關於一種氣溶膠產生器，在使用時，其可提 供藥物之控制劑量。 (二） 先前技術 由病人本身吸入用之輸送氣溶膠的計量藥劑吸入器已被 φ 揭示於美國專利 Nos.5, 487, 378; 5, 522, 378;5, 622, 162; 5,83 9,43 0;5,89 4,84 1;及6，152，130中。一些吸入器使用 推進劑系統，例如液化氟氯化碳之混合物之推進力。其他 之吸入器超音波噴霧器系統將在載氣流中之液體霧化，或 者吸入空氣之爆裂而使流體化，而將粉末劑拉入支氣管中 。共同擁有之美國專利Nos.5, 743, 251及6，234, 167揭示 一種氣溶膠產生器，其中一種液體配方被蒸發以形成一中 吸入用氣溶膠。 φ 爲了使氣溶膠從吸入器產生輸送，許多種呼吸致動系統 已被提議出來。依照美國專利No· 5, 622, 162， 一些呼吸 致動系統需要病人本身呼吸之努力，以移動一個機柄或產 生上升到預設界限之受檢測流動。此系統之一個問題爲，個 人呼吸狀況各不相同，而且一些病人無法產生足夠的氣流 以作動該單元。 雖然有許多嘗試用來改善呼吸致動系統，檢測方面仍以 一 6- 200302115 由病人本身產生氣流爲主，因而往往在氣溶膠被送到之前 都會吸入一些空氣。因此，病人可能無法全部之藥劑。 其他用來產生氣溶膠之技術，習知如美國專利No s . 4,811,731及4,627, 432中揭示有用來管理藥劑施予病人 之裝置，其中一個膠囊被針刺穿，以使藥劑成粉末狀釋出 。然後使用者經由裝置之開口而吸入釋出之藥劑。 (三）發明內容 依照第1實施例，本發明之一種氣溶膠產生器，其包括 有：一個吸嘴，其具有出口可使氣溶膠被輸送到氣溶膠產 生器之使用者；一個空氣通道，空氣可通過此通道而被輸 送到吸嘴之內部；以及一個感測器，用來檢測在吸嘴內部 之壓力降。 氣溶膠產生器可包括有：一個外殼；一個毛細通道，其 被設置在外殼中；一個儲存器，其被設置在外殼中；一個 計量室，其被設置在外殼中，流體經由第1流動通道而從 儲存器中被輸送到該計量室，並且流體經由第2流動通道 而從計量室被輸送到毛細通道；電源，用來供應電力到加 熱器；第1閥，用來將第1流動通道打開及關閉；第2閥， 用來將第2流動通道打開及關閉；第3閥，用來將空氣通 道打開及關閉。閥可由馬達或凸輪軸打開及關閉。凸輪軸 包含有多數個凸輪軸突出部，其與第1，第2及第3閥在 操作上相連，凸輪軸突出部在一個氣溶膠輸送周期中可作 用以關閉第1閥並且打開第2及第3閥，使流體被輸送到 毛細通道。凸輪軸突出部在塡充周期中可作用，以打開第 一 7 - 200302115 1閥並且關閉第2及第3閥，以使流體被輸送到計量室。 一個步進馬達可在操作上與凸輪軸相聯結，其中步進馬達 可轉動凸輪軸，以打開及關閉第1閥，第2及第3閥。儲 存器可移除地被固定到外殼，並且/或者儲存器可包含有 一個活塞，其可操作而對儲存器中之流體加壓。 依照一個較佳實施例，外殼可包括有一個蓋子，其可滑 動地被固定到外殼，蓋子之一端有吸嘴。並且，一個液晶 顯示器，其位於外殼之一個部份上，當蓋子被移動到氣溶 膠輸送位置時，其可被暴露出來。當使用者在吸嘴之出口 上開始吸入時，感測器可作用送出一個信號到控制器。感 測器包括有一個換能器，其可在當使用者在吸嘴之出口上 開始吸入時，檢測吸嘴內部之壓力降。控制器可用來監視 加熱器之參數，並且從電源處輸送電力到加熱器，使加熱 器可在氣溶膠輸送周期中被保持在所需之溫度範圍。 在另一個較佳實施例中，氣溶膠產生器爲手持式吸入器， 僅空氣可經由空氣通道而被供應到吸嘴之內部，並且氣溶 膠產生器包含有一個閥，其可在使用者於出口開始吸入之 後一段預定時間內打開空氣通道。 在第2實施例中，氣溶膠產生器包括有：一個吸嘴，其 具有出口可使氣溶膠被輸送到氣溶膠產生器之使用者；一 個氣溶膠產生器系統，其可作用而供應氣溶膠到吸嘴之內 部；一個空氣通道，空氣可通過此通道而被輸送到吸嘴之 內部；一個壓力感測器，其可在檢測到吸嘴內部之壓力降 時產生作用而輸出一個信號；一個控制器，其可作用而作 一 8- 200302115 動氣溶膠產生器系統，以反應於壓力感測器之信號輸出而 供應氣溶膠到吸嘴之內部；以及一個閥，其可作用以打開 及關閉空氣通道，控制器可反應於壓力感測器之信號輸出 而作用以打開閥。氣溶膠產生器系統包括有一個推進劑爲 主之氣溶膠產生器，噴灑藥水爲主之氣溶膠產生器，或是 揮發爲主之氣溶膠產生器。 在第2實施例中，氣溶膠產生器包含有外殼及一個蓋子， 其可滑動地被固定到外殼，蓋子之一端有吸嘴，蓋子可從 氣溶膠被防止被輸送到吸嘴內部之關閉位置滑動到氣溶膠 輸送位置，使氣溶膠產生器系統於此可位於呼吸作動模式 狀態，其中使用者可由在出口上之吸入而獲得所需之氣溶 膠劑量。較佳爲，氣溶膠產生器包含有手持式吸入器，並 且氣溶膠產生器系統包括有具毛細管尺寸大小之流動通道 及一個加熱器，其被配置成可使流動通道中之流體揮發， 以在吸嘴內部產生氣溶膠。氣溶膠產生器可包括有一個投 藥件及計量室，計量室包括一個凹部及蓋住凹部之彈性 壁，投藥件可從相對於彈性壁之第1位置移動到第2位置， 使彈性壁在此變形進入凹部中，計量室提供流體源與流動 通道之間的流體相通，並且投藥件可以一個方式移動，而 提供流體在流動通道中之恆定流量。 在第3實施例中，一種氣溶膠產生器，其包括有：一個 計量室，其包含有一個凹部在其材料之第一層，以及一個 彈性層覆蓋在凹部上；投藥件，其可從相對於彈性壁之第 1位置移動到第2位置，使彈性壁在此變形進入凹部中； 一 9- 200302115 一個流動通道，其可與計量室做流體相通；一個吸嘴，其 內部可與流動通道之出口做流體相通；加熱器，其可與流 動通道之至少一部份做熱傳遞相通，加熱器可作用而使流 動通道中之流體揮發，使揮發之流體在吸嘴內部形成氣溶 膠。 依照第3實施例，一個控制器電氣地操作一個致動機構， 其可使投藥件從第1位置移動到第2位置，以使預定體積 之流體通過流動通道而提供一個恆定流量。流動通道較佳 爲毛細管尺寸大小之流動通道，並且材料之第1層包括一 個入口，伸設於入口與計量室之間的第1通道，出口及伸 設於計量室與出口之間的第2通道，彈性層覆蓋入口，第 1通道，第2通道，及出□。第1及第2柱塞可被用來打 開及關閉入口及出口，第1柱塞可從入口被打開之第1位 置移動第2位置，在此彈性層被壓抵住第1閥座以關閉入 口，並且第2柱塞可從出口被打開之第1位置移動到第2 位置，在此彈性層在此彈性層被壓抵住第2閥座以關閉出 口。一個致動機構可被用來將第1柱塞移動到第2位置，而 仍使第2柱塞保持在第1位置。 在第4實施例中，本發明提供一種以氣溶膠產生器產生 氣溶膠之方法，氣溶膠具有吸嘴使氣溶膠可被輸送到使用 者，該方法包括有：當使用者在吸嘴之出口上吸入時，感 測吸嘴內部之壓力降；當壓力降被檢測到之時，使氣溶膠 被供應到吸嘴內部；當壓力降被檢測到之時，打開空氣通 道而使空氣被供應到吸嘴內部。 -10- 200302115 在較佳實施例中，氣溶膠產生器包括有一個具有可滑動 蓋子之手持式吸入器，該方法另外包括有：使蓋子從關閉 位置滑動到打開位置，當壓力降被檢測到之時，打開位置 可作動氣溶膠產生器之元件而輸送氣溶膠到使用者。氣溶 膠產生器最好包括有一個加熱器及毛細通道，其等足以使 其中之流體揮發，此揮發之流體與空氣混合而形成氣溶膠 。氣溶膠產生器可包括有一個控制器，加熱器及毛細通道， 控制器用來監視加熱器之參數，並且控制輸送電力到加熱 器，使流體通過毛細通道時，加熱器可被保持在所需之溫 度範圍，流體揮發成氣溶膠。 在這個較佳方法中，氣溶膠產生器包括有一個外殼；一 個毛細通道，其被設置在外殼中，毛細通道具有出口與吸 嘴內部做流體相通；一個加熱器被設置在外殻中；一個儲 存器，其被設置在外殻中；一個計量室被設置在外殼中，流 體經由第1流動通道而從儲存器中被輸送到該計量室，並 且流體經由第2流動通道而從計量室被輸送到毛細通道； 一個電源，用來供應電力到加熱器；第1閥，用來將第1 流動通道打開及關閉；第2閥，用來將第2流動通道打開 及關閉；第3閥，用來將空氣通道打開及關閉，氣溶膠是 由：輸送電力到加熱器，關閉第1閥，打開第2及第3閥， 將流體從計量室移除，供應預定體積之流體到毛細通道且 使毛細通道中之流體揮發。一個馬達驅動之凸輪軸可被用 來打開及關閉第1，第2及第3閥，其方法包括：轉動凸 輪軸到第1位置，使第1閥在此被關閉並且第2及第3閥 -11 - 200302115 被打開，以在氣溶膠輸送周期時達成預定體積之流體被輸 送到毛細通道，進一步轉動凸輪軸到第2位置，使第2及 第3閥在此被關閉並且第1閥被打開，因而在塡充周期中 可達成流體從儲存器被輸送到計量室中。 依照另一個較佳之方法，氣溶膠產生器包括有一個儲存 器，其容納有至少1 〇劑之藥用流體，該方法另外包括： 將預定體積之藥用流體塡充了計量室，並且將預定體積之 藥用流體輸送到毛細通道。此方法可包括有一個位移活塞， 該方法包括：將位移活塞從使計量室塡充流體之第1位置， 移動到第2位置，位移活塞在此可使計量室之彈性壁偏斜 。一個控制電路可被用來使電力被供應到加熱器，而使流 體在通過毛細通道時可加熱毛細通道，因而控制毛細通道 中之流體的溫度，流體被揮發並且在吸嘴中形成氣溶膠。 最好，吸嘴內部經由空氣通道僅被供應空氣，空氣通道由 一個閥所打開及關閉，閥在感測到壓力降時被關閉，並且 閥在感測到壓力降之後，並且氣溶膠被輸送到吸嘴內部之 後被打開一段時間。 (四）實施方式 整體言之，本發明提供一種如手持式吸入器之氣溶膠產 生器，以及當壓力降在吸嘴內被檢測到之時輸送氣溶膠到 在吸嘴之出口上進行吸入之使用者。通過一個毛細通道之 藥物流體被加熱到足夠使流體蒸發，並且當其與空氣混合 之時，使揮發之流體凝縮，而形成氣溶膠。空氣經由一個 空氣通道被輸送到吸嘴，該空氣通道起初在壓力降之檢測 -12- 200302115 時被關閉。一個計量室使流體劑量很精確地被不斷地輸送 。壓力降在空氣被輸送到吸嘴之前被檢測，結果爲氣溶膠 可以在使用者開始在吸嘴上吸入時很快地被輸送到使用者 。氣溶膠之快速輸送對使用者胸腔容量可提供更有效之使 用。 本發明一個較佳實施例之氣溶膠產生器包括有外殼，壓 力換能器以及可輸送控制量之藥物配方到使用者之流體及 空氣輸送系統。在氣溶膠產生器之使用時，使用者移動外 殼上之滑動蓋子，因而作動一個主開關，其可將氣溶膠產 生器置於隨時可被使用之情況。在主開關作動之後，當使 用者在氣溶膠產生器之吸嘴上進行吸入時，一壓力感測器 感測到吸嘴中之壓力降。壓力換能器送出一信號到控制器， 因而作動一個步進馬達，以轉動一個與入口閥、計量室、 投藥活塞、出口閥、以及空氣通道閥相連之凸輪軸。當凸 輪軸轉動時，流體從計量室移動到一個已被加熱之毛細通 道中，其中流體會在此揮發。在已揮發流體從毛細通道出 來並且進入吸嘴內部之後，周遭空氣與揮發流體混合，因 而提供了氣溶膠。 第1圖爲本發明一個實施例之氣溶膠產生器101之槪圖 。氣溶膠產生器1 0 1包含有外殼1 0 3，毛細通道1 〇 2，流 體及空氣輸送系統100及儲存器118。除此之外，氣溶膠 產生器101包含有一個（ΟΝ/OFF)主開關142,壓力換能器 1 3 8，電池組1 4 0及控制電路1 3 6。外殼1 0 3包括有一個滑 動蓋子1 0 3 a，其在操作上與氣溶膠產生器1 〇 1聯結，因而 200302115 在氣溶膠產生器1 0 1被使用之時，使用者可使蓋子1 0 3 a 沿著如箭頭A所指示之方向而向上方移動。在本發明一個 實施例中，外殻103及蓋子103a可使用塑膠射出成型製 造。 氣溶膠產生器101之毛細通道102可包括有一小段金屬 配管，其可使經過第1電極106及第2電極108之電流通 過。但是，流動通道可設置在其他之配置中，如在高分子， 玻璃，金屬及/或陶瓷薄片中且具有一層電阻式加熱材料 製成之加熱器之通道。通道102之最大寬度可爲0.01到1〇 公厘，較佳爲0.05到1公厘，更佳爲0.1至0.5公厘。 或者，毛細通道之通道橫向橫剖面可被形成爲8x1 CT5平方 公厘，較佳爲2x10·3平方公厘，更佳爲8χ1(Τ3至2x1〇·1 平方公厘。以此配置，毛細通道1 02可在氣溶膠產生器1 0 1 使用時加熱從儲存器1 1 8來之藥劑1 1 2 (參照第2圖）。依 照本發明一個實施例，儲存器1 1 8具有藥劑容量爲可輸送 5 // 1劑量，較佳爲在1 0劑量到約5 0 0劑量之間，例如5 0 至250劑量。但是藥劑容量是視所需劑量體積而定，並且 所需劑量可視氣溶膠產生器之施打量而預先設定。而且，儲 存器118可被設計成爲可移除之部分，以便在氣溶膠產生 器101使用時可與替換用儲存器互相更換。如此，氣溶膠 產生器101之使用壽命由於儲存器Π8及裝在內部之藥劑 112之更換而可增加。 氣溶膠產生器101亦包含有壓力換能器138，其可經由 通路1 〇 9而與吸嘴1 0 5相通。使用者可在吸嘴1 0 5之出口 200302115 上進行吸入而作動氣溶膠產生器1 ο 1。在進行吸入時，由 吸入造成之壓力變化可作動壓力換能器138。壓力換能器 1 3 8經由通路1 0 9而感測壓力變化，因而作動流體及空氣 輸送系統1 0 0。如下列將述及者，流體及空氣輸送系統1 〇 〇 可促進藥劑1 1 2進入毛細通道1 〇 2中。 除此之外，流體及空氣輸送系統1〇〇可使周遭空氣進入 凝縮區域1 0 7中，而與從毛細通道1 〇 2來做藥物配方用之 蒸發藥劑進行混合。氣溶膠產生器1 〇 1包括周遭空氣通道 110a，其可使周遭空氣通過進入氣溶膠產生器ι〇1。周遭 空氣通道110a進給到空氣通道11〇，其可使凝縮區域1〇7 中之周遭空氣與跑出毛細通道1 〇 2之蒸發藥劑進行混合。 須提及者，在本發明另一個實施例中，可使用加壓空氣源 提供稀釋用空氣而與蒸發藥劑進行混合，如設置在氣溶膠 產生器內之壓縮空氣源（未顯示），風扇/鼓風機使空氣流 入吸嘴，或其類同物。 除了周遭空氣通道ll〇a之外，氣溶膠產生器101亦包 括有控制電路1 3 6。如下列將參照第5圖所敘述者，控制 電路1 3 6在氣溶膠產生器1 〇 1操作時用來控制毛細通道1 0 2 的溫度。控制電路1 3 6亦可監視一個液晶顯示器，其被用 來顯示剩餘之藥劑量，在氣溶膠產生器丨〇丨操作時用來控 制流體及空氣輸送系統1〇〇之一個步進馬達丨34(參考第2 圖），監視一個光學感測器，其與步進馬達丨3 4合作以確 保馬達之精確定位，監視起初之壓力降，監視電池組1 40 之情況，監視已被加熱之毛細通道丨〇2之操作等等。 200302115 氣溶膠產生器1 ο 1也包括有電池組1 40。在第1圖所顯 示之實施例中，電池組1 4 0可爲使用5個電池之充電式6 伏特鎳氫電池。在此實施例中，電池組14 0可使用5個串 聯之三洋HF-CIU，600mAh之鎳氫電池，其可使1〇〇劑之5 // 1體積之藥劑被輸送。電池組1 4 0可提供電力到氣溶膠產 生器1 0 1之元件（如控制電路1 3 6，壓力換能器1 3 8等）以 及（ΟΝ/OFF)主開關142。 (ON/OFF)主開關142控制氣溶膠產生器101在操作時之 電力提供或切斷。再者，本發明一個實施例中，（0N/0FF) 主開關142作動一個在LCD(未顯示），使其可提供訊息，如 儲存器118中剩餘之藥劑含量，是否加熱器失效，是否電 池組1 40被檢測到低電壓，及其他等。 在氣溶膠產生器1 0 1操作時，使用者移動蓋子1 0 3 a到 在方向A中之打開位置，以作動氣溶膠產生器1〇1之元件 。蓋子1 Q 3 a在打開位置時，使用者可在吸嘴1 〇 5上進行 吸入藥劑。當使用者在吸嘴1 0 5上進行吸入藥劑時，會在 吸嘴內部造成壓力降，此可由壓力換能器1 3 8檢測出來。 在感測壓力降時，壓力換能器1 3 8送出一個信號到控制器， 其可用來操作流體及空氣輸送系統1 0 0，如第2圖中淸楚 地顯示。 第2圖爲顯示參照第1圖之本發明一個實施例的流體及 空氣輸送系統100之槪圖。流體及空氣輸送系統1〇〇包括 有上述之毛細通道102，第1及第2電極106及108，以 及儲存器118。儲存器118包括有壓縮彈簧116，柱塞114 -16- 200302115 及藥劑1 1 2。壓縮彈簧1 1 6在方向箭頭B所示之方向上提 供壓力到柱塞1 1 4上，當入口閥1 20被打開之時，可以保 持液體藥劑1 12流動通過通道1 18a且進入計量室122中。 入口閥1 20形成氣溶膠產生器1 0 1之流體及空氣輸送系 統1 0 0的一'部份。在本發明一*個貫施例中，流體及空热車目！ J 送系統1 0 0包括有許多由凸輪軸1 3 2所作動之閥，凸輪軸 1 3 2具有凸輪軸突出部及啣接齒輪1 3 2 a。 啣接齒輪1 3 2 a與步進馬達1 3 4之啣接齒輪1 3 4 a聯結。 如此情況下，當步進馬達1 3 4轉動時，凸輪軸1 3 2亦經由 啣接齒輪1 3 2 a與1 3 4 a而轉動。當凸輪軸1 3 2轉動時，凸 輪軸突出部132b至132e亦轉動。凸輪軸132轉動時，凸 輪軸突出部132b至132e選擇地與閥柱塞120a，124a及 130a，以及投藥柱塞122a聯結，投藥柱塞122a由彈簧（ 未顯示）加壓，以壓抵住凸輪軸突出部。在轉動之時，凸 輪軸突出部132b至132e依照由凸輪軸突出部之構造所決 定之所需順序而作動閥柱塞1 2 0 a，1 2 4 a及1 3 0 a，以及投 藥柱塞122a。例如，凸輪軸突出部132b在操作上與閥柱 塞120a聯結，因而在凸輪軸轉動時可打開及關閉閥120。 凸輪軸突出部1 3 2 c在操作上與投藥柱塞1 2 2 a聯結，因而 在凸輪軸轉動時可將計量室丨22放空。較佳者，投藥柱塞 可以恆定流量將流體從計量室1 22中射出。凸輪軸突出部 132d在操作上與閥柱塞124a聯結，因而可打開及關閉閥 124，而凸輪軸突出部I32e在操作上與閥柱塞130a聯結， 因而在凸輪軸轉動時可打開及關閉閥1 3 〇。 -17- 200302115 如前所述，當蓋子1 03 a在打開位置並且使用者在在吸 嘴1 05上進行吸入藥劑時，吸嘴內部之壓力降可由壓力換 能器1 3 8檢測出來。在壓力換能器1 3 8感測壓力降時，壓 力換能器1 3 8可送出一個信號到控制電路1 3 6，接著其可 造成步進馬達134被作動。在本發明一個實施例中，步進 馬達1 34可爲美國佛羅里達州，淸水市之麥克羅模電子公 司所生產之類型者。 計量室122可由移動投藥柱塞122a而被放空。例如，當 凸輪軸突出部1 3 2 c與投藥柱塞1 2 2 a啣接時，投藥柱塞1 2 2 a 之一端抵住計量室1 22之彈性壁，直到彈性壁抵住室之對 向壁爲止。因此，室中之流體被迫入通道100b中，而通 道1 00b中之流體被迫入毛細通道中。彈性壁最好在通道 100a，100b，入口閥120及出口閥124之上方形成密封，使 出入口閥可在閥柱塞120a，124a將彈性壓抵住閥開口周圍 之閥座時被打開或關閉。計量室1 22可確保所需要量之藥 劑1 1 2可由氣溶膠產生器1 〇 1而被輸送給病人。在本發明 一個實施例中，計量室具有預定之體積（例如，5 // 1 )。但 是須了解，計量室122可視氣溶膠產生器101之應用而定， 而被設計成任何需要量之體積。在預定體積之藥劑被輸送 到毛細通道1 0 2之後，出口閥1 2 4由凸輪軸突出部1 3 2 d 與柱塞124a之啣接而關閉。 凸輪軸1 3 2也包括有凸輪軸突出部1 3 2 e ,其在操作上與 閥柱塞1 3 0 a聯結。柱塞1 3 0 a操作上連接到空氣閥1 3 0，當 凸輪軸突出部1 3 2 e轉動而使閥柱塞1 3 0 a移動之時，空氣 200302115 閥1 3 0會打開。空氣閥1 3 0使周遭空氣經由周遭空氣通道 110a而進入氣溶膠產生器101中。空氣閥13〇進入將周遭 空氣通道110a與空氣通道110連接，因而在由空氣閥13〇 打開時，進入周遭空氣通道ll〇a之周遭空氣繼續通過空 氣通道110，而與從凝縮區域1〇7(參考第1圖中之顯示） 內之毛細通道102跑出之蒸發藥劑混合。空氣閥130亦可 使加壓空氣進入，而取代周遭空氣。 第2圖顯示流體及空氣輸送系統1 〇 〇在計量室被充塡流 體時之充塡周期時之情況。在充塡周期時，凸輪軸丨3 2轉 動而使凸輪軸突出部1 3 2 b將閥1 2 0打開，並且凸輪軸突 出部132d將閥124關閉，而仍然保持投藥柱塞i22a在一 個位置上，使藥劑1 12可塡充計量室122。 第3圖爲流體及空氣輸送系統1 〇 〇之槪圖，其中流體及 空氣輸送系統100爲在氣溶膠輸送周期之開始。在此操作 中，凸輪軸矢出η卩132b將閥120關閉。當閥120關閉時，凸 輪軸突出部1 3 2 d及1 3 2 e使閥1 2 4及1 3 0保持在關閉位置， 而凸輪軸突出部1 3 2 c仍然保持投藥柱塞1 2 2 a在非投藥位 置上。 第4圖爲流體及空氣輸送系統1 〇 〇之槪圖，其中流體及 空氣輸送系統100爲在氣溶膠輸送周期之終了。在氣溶膠 輸送周期之中，凸輪軸突出部132c使投藥柱塞122a移動 到投藥位置上，其中半球形柱塞頭將計量室之彈性壁壓住 朝向對向壁，因而使半球形計量室1 2 2被放空。當投藥柱 塞1 2 2 a開始壓住彈性壁時，凸輪軸突出部} 3 2 d及1 3 2 e 200302115 將柱塞124a及130a移動到打開位置，因而將閥124及130 打開。 當藥劑1 1 2流入被加熱之毛細通道1 02並且以蒸發之流 體跑出時，周遭空氣由於使用者之吸入作用而從周遭空氣 通道1 1 0 a進入空氣通道1 1 0。將空氣閥1 3 0保持關閉直到 氣溶膠在吸嘴中產生爲止，氣溶膠可在病人吸入呼吸周期 中之早期被供應到病人，因而可將藥劑之正確劑量輸送到 病人之胸腔中。 第5圖顯示入口閥，出口閥，栗致動器（投藥柱塞），步 進馬達，呼吸致動感測器以及聯結到步進馬達之光學感測 器之時程順序槪圖。如圖所示，在200毫秒檢測使用者拉 動吸嘴之中，入口閥被關閉，隨後出口閥被打開。同時，空 氣通道閥被打開，使周遭空氣被病人在吸嘴出口上之吸入 作用而拉入吸嘴中。在出口閥打開之情況下，泵致動器（ 投藥柱塞）將流體之精確體積之恆定流量提供到被加熱之毛 細通道2秒鐘。周遭空氣與被加熱之毛細通道所輸送之蒸 發流體混合而形成氣溶膠，並且病人可因而吸入氣溶膠。 隨後，出口閥關閉並且然後入口閥打開，以再塡充計量室 。因爲氣溶膠在病人之吸入開始時被輸送，氣溶膠中之藥 劑配方可有效地被管理。 第6圖爲本發明較佳之加熱器裝置的一個實施例，其中 毛細通道包括有具第1電極1 〇6之電導管，其爲下游電極， 以及第2電極1 〇 8，其爲上游電極。在此實施例中，毛細 通道102爲一個被控制溫度之外形設計，如於西元200 1 200302115 年9月21日而仍待審中之共同提出的專利申請案 N 〇 · 0 9 / 9 5 7，0 2 6中所揭示者。在被控制溫度之外形的毛細 管中，下游電極具有電阻，其値足以在裝置之使用時造成 電極之加熱，因而減少在毛細管之出口端的熱損失。 依照本發明之一個實施形態，毛細通道是由不銹鋼或其 他導電材料製成之管子，或非導體或半導電管加入一個由 導電材料如白金所製成之電熱器所形成。兩個電極沿著管 長度方向在隔開位置上相連接，使加熱部被形成於兩個電 極之間。施加到兩個電極之間的電壓可依照不銹鋼或其他 製成管子或電熱器之材料的電阻，以及如加熱部之橫剖面 積及長度之其他參數，而在加熱部上產生熱。當流體流經 毛細管而進入第1及第2電極之間的加熱部之時，流體被 加熱並且轉換成蒸氣。蒸氣從毛細管之加熱部通過而到毛 細管之頂端，並且從毛細管之出口端跑出。若揮發之流體 從毛細管之頂端進入周遭空氣中之時，揮發之流體會凝縮 成小滴，因而形成較佳爲具有所需小滴尺寸爲0 . 5至2 . 5 # m的氣溶膠。 毛細管流動通道中之液體溫度可根據加熱元件的測量或 計算出來之電阻而計算之。在本發明一個較佳實施例中，加 熱器爲金屬管之一部份，或者加熱器可爲帶狀或螺旋狀電 阻加熱材料。控制器較佳爲可由監視加熱器之電阻而調節 流動通道之溫度。 電阻控制爲根據一個簡單之原理：電熱器之電阻在其溫 度增加之時會提高。因爲電力被施加到加熱元件，其溫度 -21- 200302115 由於電阻式加熱而提高，並且電熱器之實際電阻値亦會增 加。當電力被關閉時，電熱器之溫度會降低，相對地其電 阻亦降低。因而，監視電熱器之參數（例如使用已知電流 及通過電熱器之電壓以計算電阻）並且控制電力施加之時， 控制器可維持電熱器在一個相當於具體化電阻目標之溫度 上。若電阻式加熱器並不被用來加熱流動通道中之液體之 時，一或多個電阻之使用亦可被用來監視被加熱液體之溫 度。 電阻目標値被選定成可對應於足以引起到液體之熱傳遞 的溫度，使液體被揮發並且從毛細管之開口端膨脹出來。 控制器可使作動電熱器之開關被閉路，因而通電到電熱器 一段時間，並且在此段時間之後，使用測量裝置之輸入値 而可決定電熱器之瞬時電阻値。在一個較佳實施例中，電 熱器之電阻是由測量通過與電熱器串聯之分流電阻（未顯示） 的電壓（因而可決定流到電熱器之電流），並且測量通過電 熱器之電壓降（因而可根據測量電壓及流過分流電阻之電流 而求出電阻値）而計算出來。爲了得到連續之測量，可使 小量之電流連續地通過分流電阻且加熱，以方便電阻計算， 並且使較高電流可被用來加熱該加熱器到所需之溫度。 若需要的話，電熱器之電阻可從通過電熱器之電流的測 量而求得，或者其他技術亦可用來獲得相同訊息。然後控 制器可根據電熱器之所需電阻目標値與由控制器所決定之 實際電阻値之間的差異，而決定是否送出另一段時間之電 力。 -22- 200302115 在一個發展模式中，供應到電熱器之電力的時間被設定 爲1毫秒。若電熱器之被監視電阻減去調整値小於目標値 的話，控制器之程式會使開關進入閉路（ο η )之位置而輸送 出另一段時間之電力。調整値考慮一些因素，例如電熱器 在未被致動之時的熱損失，測量裝置，及控制及開關裝置 之循環期之誤差，等等。實際上，因爲電熱器之電阻隨其 溫度而變化，電阻控制可被用來達成溫度控制。 依然本發明一個實施例，毛細通道1 02使用標準規格爲 32的SS304配管，其具有12公厘之流體加熱部。除此之 外，在此實施例中，下游電極1 0 6是標準規格爲2 9號配 管3 · 5公厘長，而上游電極108可爲任何幾何形狀，只要 其可減少電極1 0 8之電阻，如鍍金之銅銷。 控制電路136可由監視被加熱之毛細通道102的電阻而 控制毛細通道1 02之溫度。在本發明一個實施例中，毛細 通道102之目標溫度較佳爲約22(TC。在此實施例中，一 個被加熱毛細通道102的已測量之電阻對目標溫度爲22CTC 而言較佳爲0.4歐姆。爲了達成0.4歐姆之電阻値，控制 電路136測量電壓及電流，以計算通過毛細通道102長度 之電阻。若控制電路1 3 6計算出，最終電阻在目標値之下 時，控制電路1 3 6會使電力ON大約1 0毫秒。控制電路1 36 繼續重覆此程序直到毛細通道1 02之目標電阻値達到爲止 。同樣地，若控制電路1 3 6測量電阻値高出毛細通道1 02 溫度之所需時，控制電路1 3 6會使電力OFF大約1 0毫秒 。在此實施例中，控制電路1 3 6可包含有任何處理器，只 200302115 要其可經由電極106及丨08控制毛細通道102之電阻，例 如美國亞利桑那州張德勒市之微晶片公司所販賣之微晶片 PIC16F8 7 7，其以組合語言寫入程式。須提及者， 控制電 路1 3 6包括有控制步進馬達1 3 4 ,光學及壓力感測器，檢 查電池組140及含在（ON/OFF)主開關142中之LCD的功能 。控制電路1 3 6亦可包含有經由處理器而顯示剩餘藥劑數 目，病人順從訊息，投藥完了時間及/或兒童安全鎖之功 能。毛細通道1 02内的藥劑1 1 2蒸發之後，蒸發之藥劑膨 脹到凝縮區域1 0 7中，而與周遭空氣混合以達到凝縮。 氣溶膠產生器可產生凝縮之氣溶膠，其具有高數量之濃 度及尺寸約爲0 . 5 # m與約2 . 5 # m範圍之間的微粒。氣溶 膠產生器可小型化成手持式，可攜帶式之裝置，其具有相 當的藥劑目標値輸送到胸腔深度之潛力。這些氣溶膠提供 了輸送藥劑到胸膛深度之優許多點。例如，嘴及喉嚨之沉 積可被減少，而沉積到胸腔深度則可增加。再者，當使用 適當的親水載體之時，沉積可進一步地由濕度之成長而被 強化。 氣溶膠之中間値微粒尺寸可由增加毛細管尺寸，及/或 減少通過毛細通道之流體流速而提高。氣溶膠產生器較佳 爲產生氣溶膠，其中9 5%之氣溶膠粒子（氣溶膠滴）小於 5.6//m，更佳爲在〇.5//m與約2.5/zm範圍之間。氣溶膠 產生器較佳爲含有處理器晶片，以用來控制產生之程序。 具有適當感測器之處理器亦可在任何所需時間病人進行吸 入時啓動氣溶膠之產生。處理器亦可儲存且報告病人回饋 -24- 200302115 之順從性訊息。在氣溶膠產生器使用之時，待噴霧之藥劑 被溶解到載體之中。適當地選擇親水性載體之時，此氣溶 膠產生器可充分利用到呼吸系統之濕度成長之優點。 較佳氣溶膠產生器之操作如下。首先，一種流體載體連 同藥物一起被泵唧通過已加熱之毛細通道。流體在通道中 蒸發，並且從通道之開口端以蒸發噴射而跑出。蒸發噴射 輸送且與周遭空氣混合，冷卻然後凝縮成高濃縮之細微氣 溶膠。已加熱之毛細通道可包括許多形式，包括使用玻璃 毛細管由加電熱器所纏繞，以及由不銹鋼所形成之毛細管 。使氣溶膠產生蒸發之熱的施加通常是由通電到金屬毛細 管，使電阻性電熱器加熱而達成。施加之電力被調整，以 增加流體變成氣溶膠之轉換。 氣溶膠產生器視毛細管尺寸及使流體蒸發所需電力而定， 可在一個流體流量範圍內產生氣溶膠。可被用來產生氣溶 膠之流體可爲美國喬治亞州亞特蘭大市之費雪科技公司所 生產之USP等級（CAS#5 7 - 5 5 - 6 )之乙二醇（PG)。乙二醇之沸 點爲189°C，並且其密度爲1.0 3 6克/毫升。做爲藥劑模式 之溶液化合物亦爲費雪科技公司所生產之三苯基甲烷 (CAS#519-73-3)，及油醇（CAS#143-28-2)。 由氣溶膠產生器所生產之氣溶膠的質量中間値空氣動力 直徑（MMAD)爲已加熱毛細管尺寸大小之流動通道以及輸入 流量之函數。第7圖顯示對許多毛細管直徑，其MMAD與PG 流量之曲線關係。參考第7圖所顯不之資料反應未含溶解 物之PG。當流量增加時，氣溶膠之MMAD首先減少，然後 200302115 成水平而趨向恆定値。當毛細管直徑增加時，整個流量範 圍之微粒尺寸亦增加。在本發明一個實施例中，這兩個效 果可被用來減少氣溶膠之MMAD。 加入如藥物之溶質到PG之時，可改變凝縮程序，因爲 溶質可做爲PG之核形成劑。若溶質之蒸氣壓等於PG時，溶 質在氣溶膠中與PG凝縮之相同時間上進行凝縮。當三苯基 甲烷（TPM)在PG中具有0，28%之濃度時，TPM活動類似PG， 並且TPM及PG兩者形成一種氣溶膠，其中TPM具有與所 有氣溶膠相同之化學分佈，如第8圖中淸楚地顯示。在第 8圖所顯示之曲線中，流體進給速率爲2 . 5克/秒，並且PG 具有之MMAD爲在約1 . 1 /z m與1 . 5 /z m之間。 在一個溶質比PG更易揮發之實施例中，溶質可較早開 始凝縮程序，並且做爲隨後PG凝縮所用之核生長劑。在 此實施例中，會產生溶質之化學分佈與整體氣溶膠之質量 分佈之間的差異。此可證明溶質及PG本身之不同的MMADs 。須提及者，沒有兩種分別的氣溶膠。相反地，一種氣溶 膠被生產出，其具有隨尺寸變化的可變化學成分。MMADs 可爲溶質濃度之函數，如第9圖中淸楚顯示，含在PG中 之油醇（0A)由於PG氣溶膠核生長之溶質效應者。在第9圖 所顯示之實施例中，流體進給速率爲3 · 3克/秒。須提及 者，做爲PG之核生長之溶質的存在會造成氣溶膠中MMAd 値之減少。在此實施例中，具有溶液重量之1 0%的〇A之串 級衝擊器及USP電導口之總恢復値爲泵唧到毛細管之量的 95 . 1± 1.2% - 26 - 200302115 如眾人可能有興趣者，本發明一個較佳實施例提供一種 氣溶膠產生器，其可控制蒸發及藥物配方之凝縮。除此之 外，本發明一個較佳實施例提供可更換之儲存器，其具有 預定量之藥劑。氣溶膠產生器之一個較佳實施例可將氣溶 膠立即輸送到病人，以不浪費由於病人健康情況而受限之 胸腔容量。而且，氣溶膠產生器之一個較佳實施例可提供 ®定輸送控制量之藥劑配方給病人。如此情況下，與此氣 溶膠產生器之較佳實施例相關之整體成本可減少，因爲使 用者可連續地更換儲存器及電池，因而增加氣溶膠產生器 之使用壽命。 上述爲執行本發明之舉例模式，並且並不意在限制本發 明。明顯地，對熟於此技術者而言，在不違反本發明之精 神及由隨附申請專利範圍所規定之範圍之下，可從事許多 改變。例如，雖然已加熱的毛細管已被敘述爲較佳之氣溶 膠產生器，但是氣溶膠亦可以其他技術產生，例如以推進 劑爲主之氣溶膠產生器，或噴灑藥水爲主之氣溶膠產生器， 其中液體或粉末可由加壓氣體或經由超音波振動而被形成 氣溶膠。另外，雖然已加熱的毛細管已被敘述爲較佳之被 加熱毛細通道，但是毛細通道可被設置成在薄層中之一或 多個通路，此薄層中具有逼個加熱器沿著通路而配置，或 多數個毛細管配置，或一個具有加熱器裝設在通道內側之 通道，或同心配置，其中流體可流動通過環狀通道等。另 外，雖然凸輪配置已被敘述做爲較佳之閥操作機構，但是 個別之電磁閥或其他閥作動裝置亦可取代而使用。 -27 - 200302115 (五）圖示簡單說明 桌1圖爲本發明一個實施例之氣溶膠產生器之槪圖； 桌2圖爲梦^桌1圖之本發明一個實施例的流體及空氣 輸送系統之槪圖； 第3圖爲爹照第2圖之流體及空氣輸送系統之槪圖，其 中流體及空氣輸送系統在儲存器封閉操作中； 第4圖爲參照第3圖之本發明一個實施例的流體及空氣 輸送系統之槪圖，其中流體及空氣輸送系統在投藥周期中 9 第5圖爲本發明一個較佳實施例之氣溶膠產生器的操作 之時程順序之槪圖； 第6圖爲本發明一個實施例，顯示具有第1電極及第2 電極之毛細管之槪圖； 第7圖係顯示本發明一個實施例中丙二醇氣溶膠之微粒 尺寸上之毛細管直徑及質量流速之效應的曲線圖； 第8圖是顯示丙二醇及三苯甲烷與微粒尺寸之化學分佈 曲線圖，顯示當溶液與液體媒介物具有相等的蒸發壓力之 活動狀態。 $胃§ILia 符號說ro 100 100b 101 102 103a 流體及空氣輸送系統 通道 氣溶膠產生器 毛細通道 蓋子 200302115 105 106 107 108 109 110a 110 112 114 116 118 118a 120 122 122a 124 120a，124a，130a 130 132 132a 132b， 132e 134 136 138 140 吸嘴 第1電極 凝縮區域 第2電極 通路 周遭空氣通道 空氣通道 藥劑 柱塞 壓縮彈簧 儲存器 通道 入口閥 計量室 投藥柱塞 出口閥 閥柱塞 空氣閥 凸輪軸 啣接齒輪 凸輪軸突出部 步進馬達 及控制電路 壓力換能器 電池組 (ΟΝ/OFF)主開關4 4 200302115 发明, description of the invention •,,. ·. ·-. . . . . . ·. . »:. --... ··-. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . · (The description of the invention should state: the technical field to which the invention belongs, the prior art, the content, the embodiments, and the drawings are briefly explained) (1) The technical field to which the invention belongs The present invention relates generally to an aerosol (aerosol) 1) Generate. More specifically, the present invention relates to an aerosol generator which, when used, can provide a controlled dose of a drug. (2) Prior art The metered dose inhaler for aerosol delivery by the patient himself has been disclosed in U.S. Patent Nos. 5, 487, 378; 5, 522, 378; 5, 622, 162; 5,83 9,43 0; 5,89 4,84 1; and 6,152,130. Some inhalers use the propelling power of a propellant system, such as a mixture of liquefied CFCs. Other inhaler ultrasonic atomizer systems atomize the liquid in the carrier gas stream, or inhale the burst of air to fluidize, and pull the powder into the bronchi. U.S. Patent Nos. 5, 743, 251 and 6,234, 167 disclose an aerosol generator in which a liquid formulation is evaporated to form an aerosol for inhalation. φ In order for aerosols to be delivered from inhalers, many respiratory actuation systems have been proposed. According to US Patent No. 5, 622, 162, some respiratory actuation systems require the patient's own breathing effort to move a handle or generate a detected flow that rises to a preset limit. One problem with this system is that individual breathing conditions vary and some patients are unable to generate enough airflow to actuate the unit. Although there have been many attempts to improve the respiratory actuation system, the detection is still based on the 6-200302115 air flow generated by the patient itself, so often some air is inhaled before the aerosol is sent. As a result, patients may not be able to get all the medicine. Other technologies used to generate aerosols are known as U.S. Patent No.s. 4,811,731 and 4,627, 432 disclose devices for administering medications to patients. One of the capsules is pierced by a needle to release the medication in powder form. The user then inhales the released medicament through the opening of the device. (3) Summary of the Invention According to a first embodiment, an aerosol generator of the present invention includes: a suction nozzle having an outlet for aerosol to be delivered to a user of the aerosol generator; an air passage, Air can be delivered to the inside of the nozzle through this channel; and a sensor to detect the pressure drop inside the nozzle. The aerosol generator may include: a housing; a capillary channel provided in the housing; a reservoir provided in the housing; a metering chamber provided in the housing, and the fluid passing through the first flow channel The fluid is transferred from the reservoir to the metering chamber, and the fluid is transferred from the metering chamber to the capillary channel through the second flow channel; the power source is used to supply electricity to the heater; and the first valve is used to transfer the first flow channel Opening and closing; the second valve is used to open and close the second flow channel; the third valve is used to open and close the air channel. The valve can be opened and closed by a motor or camshaft. The camshaft includes a plurality of camshaft protrusions, which are operatively connected to the first, second, and third valves. The camshaft protrusions can act during an aerosol delivery cycle to close the first valve and open the second and third valves. The third valve allows fluid to be delivered to the capillary channel. The camshaft protrusion can function during the filling cycle to open the first 7-200302115 1 valve and close the second and third valves so that fluid is delivered to the metering chamber. A stepper motor can be operatively connected to the camshaft, wherein the stepper motor can rotate the camshaft to open and close the first valve, the second valve, and the third valve. The reservoir is removably secured to the housing and / or the reservoir may include a piston operable to pressurize the fluid in the reservoir. According to a preferred embodiment, the housing may include a cover that is slidably secured to the housing, with a suction nozzle at one end of the cover. Also, a liquid crystal display, which is located on a part of the housing, can be exposed when the cover is moved to the aerosol delivery position. When the user starts inhaling at the mouthpiece of the nozzle, the sensor can send a signal to the controller. The sensor includes a transducer which detects the pressure drop inside the nozzle when the user starts inhalation at the outlet of the nozzle. The controller can be used to monitor the parameters of the heater and transfer power from the power source to the heater, so that the heater can be maintained in the required temperature range during the aerosol delivery cycle. In another preferred embodiment, the aerosol generator is a hand-held inhaler, only air can be supplied to the inside of the nozzle through the air passage, and the aerosol generator includes a valve which can be The air passage is opened for a predetermined time after the outlet starts to inhale. In the second embodiment, the aerosol generator includes: a suction nozzle having an outlet to allow the aerosol to be delivered to a user of the aerosol generator; and an aerosol generator system that can function to supply the aerosol To the inside of the nozzle; an air channel through which air can be transported to the inside of the nozzle; a pressure sensor that outputs a signal when it detects the pressure drop inside the nozzle; A controller that functions as an 8-200302115 moving aerosol generator system that supplies aerosol to the interior of a nozzle in response to a signal output from a pressure sensor; and a valve that functions to open and close air Channel, the controller can respond to the signal output of the pressure sensor to open the valve. The aerosol generator system includes a propellant-based aerosol generator, a spray-based aerosol generator, or a volatilized aerosol generator. In the second embodiment, the aerosol generator includes a housing and a cover which is slidably fixed to the housing, and one end of the cover has a suction nozzle, and the cover can be prevented from being transported from the aerosol to the closed position inside the suction nozzle. Slide to the aerosol delivery position, so that the aerosol generator system can be in the breathing mode, where the user can get the required aerosol dose by inhaling on the outlet. Preferably, the aerosol generator includes a hand-held inhaler, and the aerosol generator system includes a capillary channel-sized flow channel and a heater configured to volatilize the fluid in the flow channel to Aerosol is generated inside the nozzle. The aerosol generator may include a medicine injection member and a measuring chamber. The measuring chamber includes a concave portion and an elastic wall covering the concave portion. The medicine injection member may be moved from the first position to the second position relative to the elastic wall so that the elastic wall is here. Deformed into the recess, the metering chamber provides fluid communication between the fluid source and the flow channel, and the medication can be moved in one way to provide a constant flow of fluid in the flow channel. In a third embodiment, an aerosol generator includes: a metering chamber including a recessed portion in a first layer of its material, and an elastic layer covering the recessed portion; Move from the first position to the second position of the elastic wall, so that the elastic wall deforms into the recess; a 9- 200302115 a flow channel that can communicate with the metering chamber in fluid; a suction nozzle whose interior can communicate with the flow channel The outlet is in fluid communication; the heater can communicate with at least a part of the flow channel for heat transfer. The heater can function to volatilize the fluid in the flow channel, so that the volatilized fluid forms an aerosol inside the nozzle. According to a third embodiment, a controller electrically operates an actuating mechanism that can move a drug-administering member from a first position to a second position so that a predetermined volume of fluid passes through the flow channel to provide a constant flow. The flow channel is preferably a capillary-sized flow channel, and the first layer of the material includes an inlet, a first channel extending between the inlet and the measuring room, and an outlet and a second channel extending between the measuring room and the outlet. Passage, elastic layer covers entrance, pass 1, pass 2, and exit. The first and second plungers can be used to open and close the inlet and outlet. The first plunger can be moved from the first position where the inlet is opened to the second position, where the elastic layer is pressed against the first valve seat to close. The inlet, and the second plunger can be moved from the first position where the outlet is opened to the second position, where the elastic layer is pressed against the second valve seat to close the outlet. An actuation mechanism may be used to move the first plunger to the second position while still keeping the second plunger in the first position. In a fourth embodiment, the present invention provides a method for generating aerosol with an aerosol generator. The aerosol has a suction nozzle so that the aerosol can be delivered to the user. The method includes: when the user is at the outlet of the nozzle When inhaling, the pressure drop inside the nozzle is sensed; when the pressure drop is detected, aerosol is supplied to the inside of the nozzle; when the pressure drop is detected, the air passage is opened to allow air to be supplied to Nozzle inside. -10- 200302115 In a preferred embodiment, the aerosol generator includes a hand-held inhaler with a slidable lid. The method additionally includes sliding the lid from the closed position to the open position when a pressure drop is detected At this time, the open position can act as an element of the aerosol generator to deliver the aerosol to the user. The aerosol generator preferably includes a heater and a capillary channel, which are sufficient to volatilize the fluid therein, and the volatilized fluid is mixed with air to form an aerosol. The aerosol generator may include a controller, a heater, and a capillary channel. The controller is used to monitor the parameters of the heater and control the delivery of electricity to the heater so that the fluid can be maintained at the required level when the fluid passes through the capillary channel. At temperature ranges, the fluid evaporates into an aerosol. In this preferred method, the aerosol generator includes a casing; a capillary channel disposed in the casing, the capillary channel having an outlet in fluid communication with the interior of the nozzle; a heater disposed in the casing; and a storage A metering chamber is provided in the housing; a metering chamber is provided in the housing; the fluid is transferred from the reservoir to the metering chamber via the first flow channel; and the fluid is transferred from the metering chamber to the metering chamber through the second flow channel Capillary channel; a power supply to supply power to the heater; a first valve to open and close the first flow channel; a second valve to open and close the second flow channel; a third valve to The air channel is opened and closed. The aerosol is made by: sending electric power to the heater, closing the first valve, opening the second and third valves, removing the fluid from the metering chamber, supplying a predetermined volume of fluid to the capillary channel and making the capillary The fluid in the channel evaporates. A motor-driven camshaft can be used to open and close the first, second, and third valves. The method includes turning the camshaft to the first position so that the first valve is closed here and the second and third valves are closed. -11-200302115 is opened so that a predetermined volume of fluid is delivered to the capillary channel during the aerosol delivery cycle, and the cam shaft is further rotated to the second position, so that the second and third valves are closed here and the first valve is closed Open, so that fluid can be delivered from the reservoir into the metering chamber during the filling cycle. According to another preferred method, the aerosol generator includes a reservoir containing at least 10 doses of the medicinal fluid, the method further comprising: filling a predetermined volume of the medicinal fluid into the metering chamber, and filling the predetermined volume A volume of medicinal fluid is delivered to the capillary channel. This method may include a displacement piston. The method includes moving the displacement piston from a first position where the metering chamber is filled with fluid to a second position, where the displacement piston may deflect the elastic wall of the metering chamber. A control circuit can be used to supply power to the heater so that the fluid can heat the capillary channel as it passes through the capillary channel, thereby controlling the temperature of the fluid in the capillary channel, the fluid is volatilized and an aerosol is formed in the nozzle. Preferably, the inside of the nozzle is only supplied with air through an air channel, the air channel is opened and closed by a valve, the valve is closed when a pressure drop is sensed, and the valve is sensed after the pressure drop, and the aerosol is delivered It is opened for a while after reaching the inside of the nozzle. (IV) Embodiments In summary, the present invention provides an aerosol generator such as a hand-held inhaler, and when the pressure drop is detected in the mouthpiece, the aerosol is delivered to the mouthpiece for inhalation. user. The drug fluid passing through a capillary channel is heated enough to cause the fluid to evaporate, and when mixed with air, the volatilized fluid condenses to form an aerosol. Air is delivered to the suction nozzle via an air channel, which is initially closed at the detection of the pressure drop -12-200302115. A metering chamber allows the fluid dose to be delivered continuously and precisely. The pressure drop is detected before the air is delivered to the nozzle, with the result that the aerosol can be delivered to the user quickly when the user begins to inhale on the nozzle. The rapid delivery of aerosols provides a more effective use of the user's chest volume. An aerosol generator according to a preferred embodiment of the present invention includes a housing, a pressure transducer, and a fluid and air delivery system capable of delivering a controlled amount of a pharmaceutical formulation to a user. During the use of the aerosol generator, the user moves the sliding cover on the housing, thereby activating a main switch, which can place the aerosol generator in a ready-to-use condition. After the main switch is actuated, when a user inhales on the nozzle of the aerosol generator, a pressure sensor senses the pressure drop in the nozzle. The pressure transducer sends a signal to the controller, thereby actuating a stepper motor to rotate a camshaft connected to the inlet valve, the metering chamber, the dosing piston, the outlet valve, and the air passage valve. As the camshaft rotates, the fluid moves from the metering chamber into a heated capillary channel where the fluid will evaporate. After the volatile fluid comes out of the capillary channel and enters the inside of the nozzle, the surrounding air is mixed with the volatile fluid, thus providing an aerosol. FIG. 1 is a schematic diagram of an aerosol generator 101 according to an embodiment of the present invention. The aerosol generator 101 includes a housing 103, a capillary channel 102, a fluid and air delivery system 100, and a reservoir 118. In addition, the aerosol generator 101 includes a (ON / OFF) main switch 142, a pressure transducer 1 38, a battery pack 140 and a control circuit 136. The housing 10 3 includes a sliding cover 1 0 3 a which is operatively connected to the aerosol generator 1 01. Therefore, when the aerosol generator 1 0 1 is used, the user can make the cover 1 0 3 a Move up in the direction indicated by arrow A. In one embodiment of the present invention, the case 103 and the cover 103a can be made by plastic injection molding. The capillary channel 102 of the aerosol generator 101 may include a small section of metal piping that allows the current passing through the first electrode 106 and the second electrode 108 to pass. However, the flow channel may be provided in other configurations, such as a channel of a heater made of a resistive heating material in a polymer, glass, metal and / or ceramic sheet. The maximum width of the channel 102 can be 0. 01 to 10 mm, preferably 0. 05 to 1 mm, more preferably 0. 1 to 0. 5 mm. Alternatively, the transverse cross section of the capillary channel can be formed as 8x1 CT5 square millimeters, preferably 2x10 · 3 square millimeters, and more preferably 8 × 1 (T3 to 2x10.1 square millimeters. In this configuration, the capillary channel 1 02 The aerosol generator 1 0 1 can be used to heat the medicine 1 1 2 from the reservoir 1 1 8 (refer to FIG. 2). According to an embodiment of the present invention, the reservoir 1 1 8 has a medicine capacity. Delivery of 5 // 1 dose, preferably between 10 doses to about 500 doses, such as 50 to 250 doses. However, the volume of the medicament depends on the required dose volume, and the required dose can be generated by the aerosol The dosage of the device is preset. Moreover, the storage 118 can be designed as a removable part so that it can be replaced with the replacement storage when the aerosol generator 101 is used. Thus, the use of the aerosol generator 101 The life can be increased due to the replacement of the reservoir Π8 and the internal medicine 112. The aerosol generator 101 also includes a pressure transducer 138, which can communicate with the suction nozzle 105 through the passage 1009. The user Can be performed on the outlet of the nozzle 1 0 5 200302115 The aerosol generator 1 ο 1. is actuated. During the inhalation, the pressure change caused by the inhalation can actuate the pressure transducer 138. The pressure transducer 1 3 8 senses the pressure change through the passage 1 0 9 and thus actuates. Fluid and air delivery system 100. As will be described below, fluid and air delivery system 1000 can facilitate the entry of medicament 1 12 into the capillary channel 100. In addition, fluid and air delivery system 10 〇 Allow the surrounding air to enter the condensation area 107, and mix it with the evaporating agent used for the pharmaceutical formulation from the capillary channel 102. The aerosol generator 101 includes the surrounding air channel 110a, which allows the surrounding air By entering the aerosol generator ι01. The surrounding air channel 110a is fed to the air channel 110, which can mix the surrounding air in the condensation area 107 with the evaporation agent running out of the capillary channel 100. It must be mentioned Moreover, in another embodiment of the present invention, a pressurized air source may be used to provide dilution air to be mixed with the evaporating agent, such as a compressed air source (not shown) provided in the aerosol generator. / The blower causes air to flow into the suction nozzle, or the like. In addition to the surrounding air passage 110a, the aerosol generator 101 also includes a control circuit 1 36. As will be described below with reference to FIG. 5, the control Circuit 1 36 is used to control the temperature of the capillary channel 10 2 when the aerosol generator 10 is in operation. The control circuit 1 36 can also monitor a liquid crystal display, which is used to display the remaining dose of the drug in the aerosol. Generator 丨 〇 丨 A stepping motor used to control the fluid and air delivery system 100 (refer to Figure 2) during operation. It monitors an optical sensor, which cooperates with the stepping motor to ensure that The precise positioning of the motor, monitoring the initial pressure drop, monitoring the condition of the battery pack 1 40, monitoring the operation of the capillary channel that has been heated, etc. 200302115 Aerosol generator 1 ο 1 also includes battery pack 1 40. In the embodiment shown in FIG. 1, the battery pack 140 can be a rechargeable 6-volt nickel-metal hydride battery using five batteries. In this embodiment, the battery pack 140 can use five tandem Sanyo HF-CIU, 600mAh nickel-metal hydride batteries, which can deliver 5 // 1 volume of medicament of 100 doses. The battery pack 140 can provide power to the components of the aerosol generator 101 (such as the control circuit 1 36, the pressure transducer 1 38, etc.) and the (ON / OFF) main switch 142. (ON / OFF) The main switch 142 controls the power supply or cut-off of the aerosol generator 101 during operation. Furthermore, in one embodiment of the present invention, the (0N / 0FF) main switch 142 operates an LCD (not shown) so that it can provide information such as the remaining pharmaceutical content in the storage 118, whether the heater has failed, and whether the battery Group 1 40 was detected with low voltage, among others. When the aerosol generator 101 is in operation, the user moves the cover 103a to the open position in the direction A to actuate the element of the aerosol generator 101. When the lid 1 Q 3 a is in the open position, the user can inhale the medicine on the suction nozzle 105. When the user inhales the medicine on the suction nozzle 105, a pressure drop will be caused inside the suction nozzle, which can be detected by the pressure transducer 138. When sensing the pressure drop, the pressure transducer 138 sends a signal to the controller, which can be used to operate the fluid and air delivery system 100, as shown clearly in Figure 2. Fig. 2 is a diagram showing a fluid and air delivery system 100 according to an embodiment of the present invention with reference to Fig. 1; The fluid and air delivery system 100 includes the capillary channel 102 described above, the first and second electrodes 106 and 108, and the reservoir 118. The reservoir 118 includes a compression spring 116, a plunger 114 -16-200302115, and a medicine 1 1 2. The compression spring 1 1 6 provides pressure to the plunger 1 1 4 in the direction shown by the directional arrow B. When the inlet valve 12 is opened, the liquid medicine 1 12 can be kept flowing through the channel 1 18a and enter the metering chamber 122. in. The inlet valve 120 forms a part of the fluid and air delivery system 100 of the aerosol generator 101. In one * embodiment of the present invention, fluid and air-heated cars! The J delivery system 1 0 0 includes a number of valves actuated by a cam shaft 1 2 2. The cam shaft 1 3 2 has a cam shaft protrusion and an engaging gear 1 3 2 a. The engagement gear 1 3 2 a is connected to the engagement gear 1 3 4 a of the stepping motor 1 3 4. In this case, when the stepping motor 1 3 4 rotates, the cam shaft 1 3 2 also rotates through the engagement gears 1 3 2 a and 1 3 4 a. When the camshaft 1 2 2 is rotated, the cam shaft projections 132b to 132e are also rotated. When the camshaft 132 rotates, the camshaft protrusions 132b to 132e are selectively connected to the valve plungers 120a, 124a, and 130a, and the dosing plunger 122a. The dosing plunger 122a is pressurized by a spring (not shown) to press against the cam Shaft protrusion. At the time of rotation, the camshaft protrusions 132b to 132e actuate the valve plungers 1 2 a, 1 2 4 a, and 1 3 0 a in the required order determined by the structure of the cam shaft protrusions, and the dosing plunger. 122a. For example, the camshaft protrusion 132b is operatively coupled to the spool plug 120a, so that the valve 120 can be opened and closed when the camshaft is rotated. The cam shaft protrusion 1 3 2 c is operatively coupled to the dosing plunger 1 2 2 a, so that the metering chamber 22 can be emptied when the cam shaft is rotated. Preferably, the dosing plunger can eject fluid from the metering chamber 1 22 at a constant flow rate. The camshaft protrusion 132d is operatively connected to the valve plunger 124a, so that the valve 124 can be opened and closed, and the camshaft protrusion I32e is operatively connected to the valve plunger 130a, so that the valve can be opened and closed when the camshaft is rotated 1 3 0. -17- 200302115 As mentioned before, when the lid 103a is in the open position and the user is inhaling the medicine on the nozzle 105, the pressure drop inside the nozzle can be detected by the pressure transducer 13.8. When the pressure transducer 1 38 senses the pressure drop, the pressure transducer 1 38 can send a signal to the control circuit 1 36, which can then cause the stepping motor 134 to be activated. In one embodiment of the present invention, the stepping motor 134 may be a type produced by Macromolectronics Corporation of Lashui, Florida. The metering chamber 122 can be emptied by moving the dosing plunger 122a. For example, when the camshaft protrusion 1 3 2 c is engaged with the dosing plunger 1 2 2 a, one end of the dosing plunger 1 2 2 a is against the elastic wall of the metering chamber 1 22 until the elastic wall abuts the opposite side of the chamber. To the wall. Therefore, the fluid in the chamber is forced into the channel 100b, and the fluid in the channel 100b is forced into the capillary channel. The elastic wall preferably forms a seal above the passages 100a, 100b, the inlet valve 120 and the outlet valve 124, so that the inlet and outlet valves can be opened or closed when the valve plungers 120a, 124a press the elasticity against the valve seat around the valve opening. The metering chamber 1 22 can ensure that the required amount of medicine 1 12 can be delivered to the patient by the aerosol generator 101. In one embodiment of the invention, the metering chamber has a predetermined volume (e.g., 5 // 1). It should be understood, however, that the metering chamber 122 may be designed to any desired volume depending on the application of the aerosol generator 101. After a predetermined volume of the medicine is delivered to the capillary channel 102, the outlet valve 1 2 4 is closed by the engagement of the cam shaft protrusion 1 3 2 d with the plunger 124a. The camshaft 1 3 2 also includes a camshaft protrusion 1 3 2e, which is operatively coupled to the valve plunger 130a. The plunger 1 3 0 a is operatively connected to the air valve 1 3 0. When the camshaft protrusion 1 3 2 e is rotated and the valve plunger 1 3 0 a is moved, the air 200302115 valve 1 3 0 is opened. The air valve 130 causes ambient air to enter the aerosol generator 101 through the ambient air passage 110a. The air valve 13o enters and connects the surrounding air passage 110a with the air passage 110. Therefore, when the air valve 13o is opened, the surrounding air entering the surrounding air passage 110a continues to pass through the air passage 110, and is connected with the air from the condensation area 107. (Refer to the display in Figure 1.) The evaporating agent running out of the capillary channel 102 inside is mixed. The air valve 130 may also allow pressurized air to enter instead of surrounding air. Figure 2 shows the condition of the fluid and air delivery system 1000 during the charge cycle when the metering chamber is filled with fluid. During the charging cycle, the camshaft 32 rotates to cause the camshaft protrusion 1 3 2 b to open the valve 120, and the camshaft protrusion 132d closes the valve 124 while still maintaining the dosing plunger i22a in one position. Then, the measuring chamber 122 can be filled with the medicine 1 12. Fig. 3 is a schematic diagram of the fluid and air delivery system 100, where the fluid and air delivery system 100 is at the beginning of the aerosol delivery cycle. In this operation, the camshaft y 132n closes the valve 120. When the valve 120 is closed, the camshaft protrusions 1 3 2 d and 1 3 2 e keep the valves 1 2 4 and 1 3 0 in the closed position, while the camshaft protrusions 1 3 2 c still maintain the dosing plunger 1 2 2 a in the non-administered position. Fig. 4 is a schematic diagram of the fluid and air delivery system 100, where the fluid and air delivery system 100 is at the end of the aerosol delivery cycle. During the aerosol delivery cycle, the camshaft protrusion 132c moves the dosing plunger 122a to the dosing position, in which the hemispherical plunger head presses the elastic wall of the metering chamber toward the opposing wall, thereby causing the hemispherical dosing chamber 1 2 2 is vented. When the dosing plug 1 2 2 a starts to press the elastic wall, the camshaft protrusion} 3 2 d and 1 3 2 e 200302115 moves the plungers 124a and 130a to the open position, thereby opening the valves 124 and 130. When the medicament 1 1 2 flows into the heated capillary channel 102 and runs out as an evaporated fluid, the surrounding air enters the air channel 1 1 0 from the surrounding air channel 1 1 0 a due to the inhalation effect of the user. Keep the air valve 130 closed until the aerosol is generated in the nozzle. The aerosol can be supplied to the patient early in the patient's inhalation breathing cycle, so that the correct dose of the medicament can be delivered to the patient's chest. Figure 5 shows the time sequence diagram of the inlet valve, outlet valve, pump actuator (medicine plunger), stepping motor, respiratory actuation sensor, and optical sensor connected to the stepping motor. As shown in the figure, during the 200 millisecond detection user pulls the nozzle, the inlet valve is closed, and then the outlet valve is opened. At the same time, the air channel valve is opened, so that the surrounding air is drawn into the nozzle by the patient's suction effect on the nozzle outlet. With the outlet valve open, the pump actuator (dosing plunger) provides a constant flow of a precise volume of fluid to the heated capillary channel for 2 seconds. The surrounding air is mixed with the evaporative fluid delivered by the heated capillary channel to form an aerosol, and the patient can inhale the aerosol. The outlet valve is then closed and then the inlet valve is opened to refill the metering chamber. Because the aerosol is delivered at the beginning of the patient's inhalation, the pharmaceutical formulation in the aerosol can be effectively managed. FIG. 6 is an embodiment of a preferred heater device according to the present invention, wherein the capillary channel includes an electrical conduit with a first electrode 106, which is a downstream electrode, and a second electrode 108, which is an upstream electrode. In this embodiment, the capillary channel 102 is a temperature-controlled external shape design, such as the co-filed patent application No. 0 9/9 5 7 which was pending on September 21, 20011 200302115. , As disclosed in 0 2 6. In a capillary outside the controlled temperature, the downstream electrode has resistance, which is sufficient to cause the electrode to heat up during use of the device, thereby reducing heat loss at the exit end of the capillary. According to an embodiment of the present invention, the capillary channel is a tube made of stainless steel or other conductive material, or a non-conductive or semi-conductive tube is formed by adding an electric heater made of a conductive material such as platinum. The two electrodes are connected at spaced positions along the length of the tube so that a heating portion is formed between the two electrodes. The voltage applied between the two electrodes can generate heat on the heating portion in accordance with the resistance of stainless steel or other materials made of a tube or heater, and other parameters such as the cross-sectional area and length of the heating portion. When the fluid flows through the capillary tube and enters the heating portion between the first and second electrodes, the fluid is heated and converted into vapor. Vapor passes through the heating part of the capillary tube to the top of the capillary tube and runs out from the outlet end of the capillary tube. If the volatilized fluid enters the surrounding air from the top of the capillary, the volatilized fluid will condense into droplets, so it is preferred to have a desired droplet size of 0. 5 to 2. 5 #m of aerosol. The temperature of the liquid in the capillary flow channel can be calculated based on the measured or calculated resistance of the heating element. In a preferred embodiment of the present invention, the heater is part of a metal pipe, or the heater may be a strip-shaped or spiral-shaped resistive heating material. The controller preferably adjusts the temperature of the flow channel by monitoring the resistance of the heater. The resistance control is based on a simple principle: the resistance of an electric heater increases as its temperature increases. Because electricity is applied to the heating element, its temperature is increased by -21-200302115 due to resistance heating, and the actual resistance of the heater is also increased. When the power is turned off, the temperature of the heater will decrease, and its resistance will decrease accordingly. Therefore, the controller can maintain the heater at a temperature equivalent to the specified resistance target while monitoring the parameters of the heater (for example, using a known current and the voltage across the heater to calculate the resistance) and controlling the application of power. The use of one or more resistors can also be used to monitor the temperature of the heated liquid if the resistance heater is not used to heat the liquid in the flow channel. The resistance target 値 is selected to correspond to a temperature sufficient to cause heat transfer to the liquid, so that the liquid is volatilized and expands from the open end of the capillary. The controller can make the switch of the electric heater to be closed, so that the electric heater is powered on for a period of time, and after this period of time, the instantaneous resistance of the electric heater can be determined using the input 値 of the measuring device. In a preferred embodiment, the resistance of the electric heater is measured by measuring the voltage through a shunt resistor (not shown) in series with the electric heater (thereby determining the current flowing to the electric heater), and measuring the voltage drop through the electric heater ( Therefore, the resistance 値) can be calculated based on the measured voltage and the current flowing through the shunt resistor. In order to obtain continuous measurement, a small amount of current can be continuously passed through the shunt resistor and heated for convenient resistance calculation, and a higher current can be used to heat the heater to the required temperature. If necessary, the resistance of the heater can be obtained from the measurement of the current through the heater, or other techniques can be used to obtain the same information. The controller can then decide whether to send power for another period of time based on the difference between the required resistance target 値 of the heater and the actual resistance 决定 determined by the controller. -22- 200302115 In a development mode, the time for supplying power to the heater is set to 1 millisecond. If the monitored resistance of the electric heater minus the adjustment 値 is smaller than the target ，, the program of the controller will cause the switch to enter the closed circuit (ο η) position and transmit power for another period of time. Adjustment: Consider factors such as the heat loss of the electric heater when it is not actuated, the error in the cycle time of the measuring device, and the control and switching devices, and so on. In fact, because the resistance of a heater varies with its temperature, resistance control can be used to achieve temperature control. In still another embodiment of the present invention, the capillary channel 102 uses a SS304 pipe with a standard size of 32, which has a fluid heating section of 12 mm. In addition, in this embodiment, the downstream electrode 106 is a standard specification with a pipe length of 2.5 mm, and the upstream electrode 108 can have any geometric shape, as long as it can reduce the electrode 108 length. Resistors, such as gold-plated copper pins. The control circuit 136 can control the temperature of the capillary channel 102 by monitoring the resistance of the heated capillary channel 102. In one embodiment of the present invention, the target temperature of the capillary channel 102 is preferably about 22 ° C. In this embodiment, the measured resistance of a heated capillary channel 102 is preferably 0 for a target temperature of 22 CTC. . 4 ohms. To reach 0. With a resistance of 4 ohms, the control circuit 136 measures the voltage and current to calculate the resistance through the length of the capillary channel 102. If the control circuit 1 36 calculates that when the final resistance is below the target value, the control circuit 1 36 will turn the power on for about 10 milliseconds. The control circuit 1 36 continues to repeat this procedure until the target resistance 毛 of the capillary channel 102 is reached. Similarly, if the control circuit 1 36 measures the resistance 値 higher than the temperature of the capillary channel 102, the control circuit 1 36 will turn the power OFF for about 10 milliseconds. In this embodiment, the control circuit 136 may include any processor, and only 200302115 requires that it can control the resistance of the capillary channel 102 through the electrodes 106 and 08, for example, sold by the microchip company of Zhangdler, Arizona, USA The microchip PIC16F8 7 7 writes the program in a combined language. It should be mentioned that the control circuit 1 3 6 includes the functions of controlling the stepping motor 1 3 4, optical and pressure sensors, checking the battery pack 140 and the LCD included in the (ON / OFF) main switch 142. The control circuit 1 3 6 may also include the function of displaying the number of remaining medicines through the processor, the patient's compliance message, the time after the administration of the medicine and / or the child safety lock. After the medicament 1 12 in the capillary channel 102 is evaporated, the evaporated medicament swells into the condensation area 107 and is mixed with the surrounding air to achieve condensation. The aerosol generator can produce condensed aerosols, which have a high concentration and a size of about 0. 5 # m with about 2. 5 # m range of particles. The aerosol generator can be miniaturized into a hand-held, portable device with the potential to deliver equivalent drug targets to the depth of the chest cavity. These aerosols offer many advantages over delivering medicament to the depth of the chest. For example, the deposition in the mouth and throat can be reduced, while the depth to the chest can be increased. Furthermore, when a suitable hydrophilic carrier is used, the deposition can be further enhanced by the growth of humidity. The size of the interstitial particles of the aerosol can be increased by increasing the size of the capillary and / or reducing the flow velocity of the fluid through the capillary channel. The aerosol generator preferably produces aerosols, of which 95% of the aerosol particles (aerosol droplets) are less than 5. 6 // m, more preferably at 0. 5 // m and about 2. 5 / zm range. The aerosol generator preferably contains a processor chip to control the generation process. A processor with appropriate sensors can also initiate aerosol generation at any time the patient is inhaling. The processor may also store and report patient compliance messages from -24- 200302115. When the aerosol generator is used, the agent to be sprayed is dissolved in the carrier. When a hydrophilic carrier is appropriately selected, this aerosol generator can take full advantage of the humidity growth of the respiratory system. The preferred aerosol generator operates as follows. First, a fluid carrier is pumped with the drug through a heated capillary channel. The fluid evaporates in the channel and runs off as an evaporative jet from the open end of the channel. Evaporative spray is transported and mixed with the surrounding air, cooled and condensed into a highly concentrated fine aerosol. Heated capillary channels can include many forms, including the use of glass capillaries wrapped around a heater and capillaries formed of stainless steel. The application of heat to evaporate the aerosol is usually achieved by applying electricity to a metal capillary tube and heating a resistive heater. The applied power is adjusted to increase the conversion of fluid to aerosol. Aerosol generators produce aerosols over a range of fluid flows, depending on the size of the capillary tube and the power required to evaporate the fluid. The fluid that can be used to generate aerosol can be ethylene glycol (PG) of USP grade (CAS # 5 7-5 5-6) produced by Fisher Technology Corporation of Atlanta, Georgia, USA. The boiling point of ethylene glycol is 189 ° C, and its density is 1. 0 3 6 g / ml. The solution compounds used as a pharmaceutical model are also triphenylmethane (CAS # 519-73-3) and oleyl alcohol (CAS # 143-28-2) produced by Fisher-Tech. The aerosol diameter produced by the aerosol generator is a function of the aerodynamic diameter (MMAD) as a function of the size of the heated capillary flow channel and the input flow. Figure 7 shows the relationship between MMAD and PG flow for many capillary diameters. Refer to the information shown in Figure 7 to reflect the PG without dissolved matter. When the flow rate increases, the MMAD of the aerosol first decreases, and then 200302115 becomes level and tends to be constant. As the capillary diameter increases, so does the particle size over the entire flow range. In one embodiment of the invention, these two effects can be used to reduce the MMAD of an aerosol. When a solute such as a drug is added to PG, the condensation procedure can be changed because the solute can be used as a nucleating agent for PG. If the vapor pressure of the solute is equal to PG, the solute will condense in the aerosol at the same time as the PG condenses. When triphenylmethane (TPM) has a concentration of 0,28% in PG, TPM activity is similar to PG, and both TPM and PG form an aerosol, where TPM has the same chemical distribution as all aerosols, as Figure 8 shows clearly. In the curve shown in Figure 8, the fluid feed rate is 2. 5 g / s, and PG has a MMAD of about 1. 1 / z m and 1. 5 / z m. In an embodiment where the solute is more volatile than PG, the solute can begin the condensation process earlier and serve as a nuclear growth agent for subsequent PG condensation. In this embodiment, a difference occurs between the chemical distribution of the solute and the mass distribution of the entire aerosol. This proves the different MMADs of solute and PG itself. It must be mentioned that there are no two separate aerosols. Instead, an aerosol is produced that has a variable chemical composition that changes with size. MMADs can be a function of solute concentration. As clearly shown in Figure 9, oleyl alcohol (0A) contained in PG is due to the solute effect of PG aerosol core growth. In the embodiment shown in Figure 9, the fluid feed rate is 3.3 g / sec. It must be mentioned that the presence of solutes as PG's nuclear growth will cause a decrease in MMAd in aerosols. In this embodiment, the total recovery of the cascade impactor and USP conductivity port with 10% of the solution weight is 95% of the amount pumped to the capillary. 1 ± 1. 2%-26-200302115 If everyone may be interested, a preferred embodiment of the present invention provides an aerosol generator, which can control evaporation and condensation of a pharmaceutical formula. In addition, a preferred embodiment of the present invention provides a replaceable reservoir having a predetermined amount of a medicament. A preferred embodiment of the aerosol generator can deliver the aerosol to the patient immediately without wasting the thorax volume limited by the patient's health condition. Moreover, a preferred embodiment of the aerosol generator may provide the patient with a controlled delivery of a pharmaceutical formulation. In this case, the overall cost associated with this preferred embodiment of the aerosol generator can be reduced because the user can continuously replace the storage and battery, thereby increasing the life of the aerosol generator. The foregoing is an exemplary mode for carrying out the invention and is not intended to limit the invention. Obviously, for those skilled in the art, many changes can be made without departing from the spirit of the present invention and the scope prescribed by the scope of the accompanying patent application. For example, although heated capillaries have been described as preferred aerosol generators, aerosols can also be produced by other technologies, such as propellant-based aerosol generators, or spray-based aerosol generators. Wherein a liquid or powder can be formed into an aerosol from a pressurized gas or via ultrasonic vibration. In addition, although the heated capillary has been described as a preferred heated capillary channel, the capillary channel can be arranged in one or more channels in a thin layer with a heater disposed along the channel. , Or a plurality of capillary configurations, or a channel with a heater installed inside the channel, or a concentric configuration in which fluid can flow through the annular channel, etc. In addition, although the cam arrangement has been described as the preferred valve operating mechanism, individual solenoid valves or other valve actuating devices may be used instead. -27-200302115 (five) Illustrations Brief description Table 1 is a diagram of an aerosol generator according to an embodiment of the present invention; Table 2 is a dream ^ Table 1 is a fluid and air delivery system according to an embodiment of the present invention Figure 3; Figure 3 is a diagram of the fluid and air delivery system according to Figure 2, where the fluid and air delivery system is in the closed operation of the reservoir; Figure 4 is an embodiment of the invention with reference to Figure 3 Figure 5 of the fluid and air delivery system, wherein the fluid and air delivery system is in the dosing cycle 9 Figure 5 is a schematic diagram of the time sequence of the operation of the aerosol generator according to a preferred embodiment of the present invention; Figure 6 This is an embodiment of the present invention, showing a capillary diagram of a capillary having a first electrode and a second electrode; FIG. 7 is a graph showing the effect of capillary diameter and mass flow rate on the particle size of propylene glycol aerosol in an embodiment of the present invention Fig. 8 is a graph showing the chemical distribution curve of propylene glycol, triphenylmethane and particle size, showing the activity state when the solution and the liquid medium have the same evaporation pressure. $ Stomach§ILia symbol says ro 100 100b 101 102 103a fluid and air delivery system channel aerosol generator capillary channel cover 200302115 105 106 107 108 109 110a 110 112 114 116 118 118a 120 122 122a 124 120a, 124a, 130a 130 132 132a 132b, 132e 134 136 138 140 Nozzle 1st electrode condensation area 2nd electrode path surrounding air passage air passage medicine plunger compression spring reservoir passage inlet valve metering chamber medicine plunger outlet valve plunger air valve camshaft engagement gear Camshaft protrusion stepper motor and control circuit pressure transducer battery pack (ON / OFF) main switch
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