TWI660789B - Particle forming apparatus with the nozzle and particle forming method - Google Patents
Particle forming apparatus with the nozzle and particle forming method Download PDFInfo
- Publication number
- TWI660789B TWI660789B TW106124957A TW106124957A TWI660789B TW I660789 B TWI660789 B TW I660789B TW 106124957 A TW106124957 A TW 106124957A TW 106124957 A TW106124957 A TW 106124957A TW I660789 B TWI660789 B TW I660789B
- Authority
- TW
- Taiwan
- Prior art keywords
- phase fluid
- tank
- particle
- fluid
- oil
- Prior art date
Links
Abstract
一種微粒成形裝置及其微粒成形方法，係用以大量生產微粒，以解決習知微粒噴頭所生產之微粒均一性差、粒徑難以控制及生產效率低落等問題，該微粒成形裝置包含一微粒噴頭，且該微粒噴頭係包含：一噴頭本體，該噴頭本體內部具有一流道，該流道之一端連接數個延伸管，各該延伸管遠離該流道之一端形成一流出口，且各該延伸管之流出口係間隔設置。 A particle forming device and a particle forming method are used for mass production of particles to solve the problems of poor uniformity of particles produced by a conventional particle nozzle, difficulty in controlling particle size, and low production efficiency. The particle forming device includes a particle nozzle. In addition, the particle spray head includes: a spray head body, which has a first-class channel inside, one end of the flow channel is connected to a plurality of extension tubes, and each of the extension tubes forms a first-class outlet away from one end of the flow channel, and each of the extension tubes The outlets are set at intervals.
Description
本發明係關於一種微粒成形裝置及其微粒成形方法，特別關於一種用以大量生產微粒的微粒成形裝置及其微粒成形方法。 The invention relates to a particle forming device and a particle forming method, and more particularly to a particle forming device and a particle forming method for mass production of particles.
微粒(microparticle)又稱為微球(microsphere)，係泛指粒徑小於1000μm之小型球型顆粒，常被應用作為藥劑釋放之微載體(microcarrier)，藉由其靶向性、控釋性、穩定性、安定性及表面可修飾性等特點，成為新興的給藥技術之一。 Microparticles, also known as microspheres, refer to small spherical particles with a particle size of less than 1000 μm. They are often used as microcarriers for drug release. With their targeting, controlled release, Stability, stability, and surface modifiability have become one of the emerging drug delivery technologies.
由於微粒的粒徑較小且所需數量龐大，因此如何大量生產微粒，成為微粒成形技術的重要目標；舉例而言，藉由如第1圖所示之習知微粒噴頭9，即可量產成形微粒。 Due to the small particle size and the large number of particles required, how to mass-produce particles has become an important goal of particle forming technology; for example, by using the conventional particle nozzle 9 shown in Figure 1, mass production can be achieved Shaped particles.
詳言之，該習知微粒噴頭9具有一流道91及連通該流道91的數個開口92。該流道91供注入一油相溶液，所述油相溶液可經由各該開口92流出該微粒噴頭9，並且受表面張力作用而於各該開口92位置聚積形成液滴。當液滴重量足以克服表面張力時將脫離該開口92，藉由使液滴落入一水相溶液中，即可利用該水相溶液包覆油相溶液所形成的液滴，以輔助液滴固化定型，最終量產成形微粒。 In detail, the conventional particle spray head 9 has a first channel 91 and a plurality of openings 92 communicating with the flow channel 91. The flow channel 91 is used for injecting an oil phase solution, and the oil phase solution can flow out of the particulate spray head 9 through each of the openings 92 and is accumulated at the positions of each of the openings 92 to form droplets under the action of surface tension. When the weight of the droplet is sufficient to overcome the surface tension, the opening 92 will be released. By dropping the droplet into an aqueous solution, the droplet formed by the aqueous solution can be coated with the aqueous solution to assist the droplet Cure and shape, and finally mass-produce shaped particles.
儘管藉由上述習知微粒噴頭9可以大量生產微粒，惟，位在不同開口92處的液滴所承受之表面張力或壓力等條件可能有所差異，導致所生產之微粒的粒徑分布較為分散，使得微粒均一性差，將會造成每一顆 微粒所具有的藥劑釋放效果不一致。 Although a large number of particles can be produced by the conventional particle spray head 9 described above, the conditions such as the surface tension or pressure experienced by the droplets located at different openings 92 may be different, resulting in a dispersed particle size distribution. Makes poor particle uniformity, will cause each Microparticles have inconsistent drug release effects.
再者，微粒的粒徑亦受該油相溶液的黏度影響，使得利用該習知微粒噴頭9生產微粒時難以控制微粒的粒徑。更甚者，當該流道91所填充之油相溶液的黏度過高(例如：高分子材料黏度>9wt%)時，將造成液滴需聚積較重的重量始能脫離該開口92，因而形成粒徑過大的微粒，可能不符合微粒生產需求而使得該習知微粒噴頭9無法用以生產高黏度油相溶液的微粒。據此，該習知微粒噴頭9所生產之微粒的粒徑難以控制且適用範圍較小。 In addition, the particle size of the particles is also affected by the viscosity of the oil phase solution, which makes it difficult to control the particle size of the particles when using the conventional particle spray head 9 to produce particles. What's more, when the viscosity of the oil phase solution filled in the flow channel 91 is too high (for example, the viscosity of the polymer material is> 9wt%), it will cause the droplets to accumulate a heavier weight before they can leave the opening 92, so The formation of particles with an excessively large particle size may not meet the requirements for the production of particles, making the conventional particle spray head 9 unable to produce particles with a high viscosity oil phase solution. According to this, the particle diameter of the particles produced by the conventional particle spray head 9 is difficult to control and the applicable range is small.
此外，所述油相溶液於各該開口92位置聚積形成液滴，直至液滴重量足以脫離該開口92的過程冗長，使得利用該習知微粒噴頭9生產微粒的效率較低。又，由於該水相溶液為靜止流體，上述液滴落入該水相溶液後容易團聚，導致液滴無法個別為水相溶液包覆定型，使得利用該習知微粒噴頭9生產微粒的良率較差。 In addition, the oil phase solution accumulates at each of the openings 92 to form droplets, and the process until the weight of the droplets is sufficient to leave the openings 92 is tedious, so that the efficiency of producing particles using the conventional particle nozzle 9 is low. In addition, since the aqueous phase solution is a stationary fluid, the droplets are likely to agglomerate after falling into the aqueous phase solution, resulting in that the droplets cannot be individually shaped and shaped for the aqueous phase solution, so that the yield of fine particles produced by the conventional fine particle nozzle 9 Worse.
有鑑於此，習知微粒噴頭9及微粒成形方法確實仍有加以改善之必要。 In view of this, the conventional particle spray head 9 and the particle forming method do still need to be improved.
為解決上述問題，本發明係提供一種微粒成形裝置及其微粒成形方法，以成形粒徑均一的微粒。 To solve the above problems, the present invention provides a particle forming apparatus and a particle forming method for forming particles having a uniform particle diameter.
本發明之一種微粒成型裝置，係包含：一噴頭本體，該噴頭本體內部具有一流道，該流道之一端連接數個延伸管，各該延伸管遠離該流道之一端形成一流出口，且各該延伸管之流出口係間隔設置，各該延伸管之流出口具有一口徑，各該延伸管之管壁具有一厚度，該厚度小於該口徑；一容槽，該噴頭本體之延伸管係伸入該容槽內部；一流體剪切裝置，該流體剪切裝置設置於該容槽；及一溫度控制系統，該容槽設置於該溫度控制系統中。 The particle forming device of the present invention comprises a nozzle body having a first-class channel inside, one end of the flow channel is connected to a plurality of extension tubes, and each of the extension tubes forms a first-class outlet away from one end of the flow channel, and The outlets of each extension tube are arranged at intervals. The outlets of each extension tube have a diameter, and the wall of each extension tube has a thickness that is less than the diameter. A tank, the extension tube system of the nozzle body. Project into the tank; a fluid shearing device, the fluid shearing device is set in the tank; and a temperature control system, the tank is set in the temperature control system.
其中，該容槽供裝載一水相流體，該水相流體的液面所在位置為一液面高度，各該延伸管之流出口位於該液面高度與該容槽的一底面之間，藉以使該流出口位於該水相流體中。 Wherein, the tank is used for loading an aqueous phase fluid, the liquid level of the aqueous phase fluid is at a liquid level, and the outlets of the extension tubes are located between the liquid level and a bottom surface of the tank, thereby The outflow port is positioned in the aqueous phase fluid.
其中，另設有一集收槽，且該容槽設有一入口管及一出口管，該入口管及該出口管係貫穿該容槽外壁，該集收槽連通該容槽之出口管。藉此，該容槽中的水相流體連帶該微粒半成品係經由該出口管流向該集收槽，使工者可利用該集收槽收集該微粒半成品；且該入口管可供注入該水相流體，以保持該容槽中的水相流體具有該液面高度，進而確保各該延伸管之流出口位於該水相流體中。 Wherein, another collecting tank is provided, and the receiving tank is provided with an inlet pipe and an outlet pipe, the inlet pipe and the outlet pipe run through the outer wall of the receiving tank, and the collecting tank communicates with the outlet pipe of the receiving tank. As a result, the aqueous phase fluid in the tank and the particulate semi-finished product flow to the collecting tank via the outlet pipe, so that workers can use the collecting tank to collect the particulate semi-finished product; and the inlet pipe can be injected into the aqueous phase. Fluid to keep the water-phase fluid in the tank having the liquid surface height, thereby ensuring that the outlet of each extension tube is located in the water-phase fluid.
其中，該流體剪切裝置包含設置於該容槽內部之一攪拌裝置。藉此，該攪拌裝置能夠驅動該水相流體流動，以利用該水相流體流動時的剪切力打斷流出該噴頭本體的油相流體。 Wherein, the fluid shearing device includes a stirring device disposed inside the tank. Thereby, the stirring device can drive the water-phase fluid to flow, so as to interrupt the oil-phase fluid flowing out of the nozzle body by using the shear force when the water-phase fluid flows.
其中，該流體剪切裝置包含結合於該容槽外壁之一超音波產生器。藉此，該超音波產生器能夠使該水相流體產生振動，以打斷由各流出口流出的連續油相流體。 The fluid shearing device includes an ultrasonic generator coupled to an outer wall of the cuvette. Thereby, the ultrasonic generator can cause the water-phase fluid to vibrate to interrupt the continuous oil-phase fluid flowing out of each outflow port.
本發明之一種微粒成型方法，係利用如上所述之微粒成型裝置執行，該微粒成型方法包含：於該容槽中裝載一水相流體，使各該延伸管之流出口位於該水相流體中；於該噴頭本體之流道中通入一油相流體，使該油相流體經由各該延伸管之流出口流出該噴頭本體；帶動該攪拌裝置旋轉以驅動該水相流體流動或是啟動該超音波產生器使該水相流體產生振動，以於該容槽中形成微粒半成品；收集該微粒半成品，該微粒半成品包含由該油相流體所形成之內層，以及由該水相流體所形成之外層；及去除該微粒半成品之外層。 A particle forming method according to the present invention is performed by using the particle forming device as described above. The particle forming method includes: loading a water-phase fluid in the tank so that the outlets of the extension tubes are located in the water-phase fluid. ; Passing an oil-phase fluid into the flow path of the nozzle body, so that the oil-phase fluid flows out of the nozzle body through the outlet of each extension tube; driving the stirring device to rotate to drive the water-phase fluid to flow or start the supersonic fluid; The sonic generator vibrates the aqueous phase fluid to form a particulate semi-finished product in the tank; collects the particulate semi-finished product, the particulate semi-finished product includes an inner layer formed by the oil-phase fluid, and a particle formed by the aqueous-phase fluid An outer layer; and an outer layer from which the particulate semi-finished product is removed.
其中，該油相流體係將聚合物加熱至玻璃轉移溫度製成，藉以使該油相流體能夠通入該噴頭本體之流道。 Wherein, the oil phase flow system is made by heating the polymer to a glass transition temperature, so that the oil phase fluid can pass into the flow channel of the shower head body.
其中，在將該油相流體通入該流道前，啟動該溫度控制系統以保持該水相流體於一預定溫度，該預定溫度等於或低於該油相流體之玻璃轉移溫度溫度。藉此，該油相流體形成微液滴時，該水相流體之溫度能夠輔助該微液滴固化定型。 Before the oil-phase fluid is passed into the flow channel, the temperature control system is activated to maintain the water-phase fluid at a predetermined temperature that is equal to or lower than a glass transition temperature of the oil-phase fluid. Therefore, when the oil-phase fluid forms micro-droplets, the temperature of the water-phase fluid can assist the micro-droplet to solidify and shape.
其中，該油相流體係將聚合物加入有機溶劑製成，藉以使該油相流體能夠通入該噴頭本體之流道。 Wherein, the oil phase flow system is made by adding a polymer to an organic solvent, so that the oil phase fluid can pass into the flow channel of the shower head body.
其中，所述聚合物為一可生物降解高分子材料，且於其中混參一藥物活性成分或。藉此，當該微粒成品投予一生物體時，即可以藉由該可生物降解高分子材料的包覆，達成緩慢釋放該藥物活性成分的效果。 Wherein, the polymer is a biodegradable high-molecular material, and a pharmaceutical active ingredient or a polymer is mixed therein. Therefore, when the fine particle product is administered to an organism, the effect of slowly releasing the active pharmaceutical ingredient can be achieved by coating the biodegradable polymer material.
其中，所述聚合物為一可生物降解高分子材料，且於其中混參氣體。藉此，可使該微粒成品包含數個空氣微泡，以提升該微粒成品的藥物釋放效果。 Wherein, the polymer is a biodegradable polymer material, and a reference gas is mixed therein. As a result, the microparticle finished product can include several air microbubbles, so as to improve the drug release effect of the microparticle finished product.
其中，在將該油相流體通入該流道時，對該流道加壓，使該油相流體流經由各該流出口被打入該水相流體中，以產生連續油相流體。藉此，可利用該水相流體的剪切力或振動打斷所述連續油相流體，使該油相流體形成微液滴，並使該水相流體可包覆於該微液滴的外層，而可以於該容槽中形成微粒半成品。 Wherein, when the oil phase fluid is passed into the flow channel, the flow channel is pressurized, and the oil phase fluid flow is driven into the water phase fluid through each of the outflow ports to generate a continuous oil phase fluid. Thereby, the shear force or vibration of the aqueous phase fluid can be used to interrupt the continuous oil phase fluid, the oil phase fluid can form micro-droplets, and the aqueous phase fluid can be coated on the outer layer of the micro droplets. , And a semi-finished particle product can be formed in the container.
其中，該水相流體為濃度1~15%的聚乙烯醇溶液，故能夠將該數個微粒半成品以乾燥法處理，或者利用水溶液對該微粒半成品進行洗滌，以去除該微粒半成品之外層，進而使該微粒半成品之內層成形為微粒成品。 Wherein, the aqueous phase fluid is a polyvinyl alcohol solution having a concentration of 1 to 15%, so the several semi-finished products of microparticles can be processed by a drying method, or the semi-finished products of microparticles can be washed with an aqueous solution to remove the outer layer of the semi-finished products of particles, and further The inner layer of the fine particle semi-finished product is formed into a fine particle finished product.
本發明上述微粒成形裝置及微粒成形方法，藉由該噴頭本體設有數個延伸管，能夠使得所成形之微粒成品的粒徑分布集中，具有提升微粒均一性功效。再者，透過調整該攪拌裝置或超音波產生器，即可精確控制所成形之微粒成品的粒徑，並且適用於生產高黏度油相流體的微粒， 具有提升微粒粒徑的控制精確度及微粒成形裝置與方法的適用範圍功效。此外，透過讓該油相流體以連續形式較快地流出該噴頭本體，能夠縮減該微粒成形方法的製程時間，具有提升微粒生產效率之功效。又，該水相流體的流動及振動能夠確保所述微液滴個別為水相流體包覆定型，具有提升微粒的生產良率之功效。 According to the above particle forming device and the particle forming method of the present invention, the nozzle body is provided with several extension tubes, which can make the particle size distribution of the formed particle finished product concentrated, and has the effect of improving particle uniformity. Furthermore, by adjusting the stirring device or the ultrasonic generator, the particle size of the formed fine particle product can be precisely controlled, and it is suitable for producing fine particles of high viscosity oil phase fluid. It has the functions of improving the control precision of the particle size and the applicable scope of the particle forming device and method. In addition, by allowing the oil-phase fluid to flow out of the nozzle body relatively quickly in a continuous form, the process time of the particle forming method can be reduced, and the effect of improving particle production efficiency can be achieved. In addition, the flow and vibration of the aqueous phase fluid can ensure that the micro-droplets are individually shaped and shaped by the aqueous phase fluid, and have the effect of improving the production yield of the particles.
1‧‧‧噴頭本體 1‧‧‧ Nozzle body
1a‧‧‧模仁 1a‧‧‧mould
1b‧‧‧座體 1b‧‧‧ seat
11‧‧‧流道 11‧‧‧ runner
12‧‧‧延伸管 12‧‧‧ extension tube
13‧‧‧組裝部 13‧‧‧Assembly Department
14‧‧‧鎖固元件 14‧‧‧Locking element
121‧‧‧流出口 121‧‧‧ Outlet
2‧‧‧容槽 2‧‧‧ tank
21‧‧‧液面高度 21‧‧‧Liquid level
22‧‧‧底面 22‧‧‧ underside
23‧‧‧入口管 23‧‧‧Inlet tube
24‧‧‧出口管 24‧‧‧Export tube
3‧‧‧流體剪切裝置 3‧‧‧fluid shearing device
31‧‧‧攪拌裝置 31‧‧‧mixing device
32‧‧‧超音波產生器 32‧‧‧ Ultrasonic generator
4‧‧‧溫度控制系統 4‧‧‧Temperature Control System
5‧‧‧集收槽 5‧‧‧ collection tank
F1‧‧‧油相流體 F1‧‧‧oil phase fluid
F2‧‧‧水相流體 F2‧‧‧Aqueous fluid
S‧‧‧微粒半成品 S‧‧‧Particle semi-finished product
S1‧‧‧內層 S1‧‧‧Inner layer
S2‧‧‧外層 S2‧‧‧ Outer
M‧‧‧微粒成品 M‧‧‧ Particle Finished Product
M1‧‧‧藥物活性成分 M1‧‧‧pharmaceutical active ingredient
M2‧‧‧空氣微泡 M2‧‧‧Air Microbubbles
D1‧‧‧口徑 D1‧‧‧ caliber
D2‧‧‧厚度 D2‧‧‧thickness
D3‧‧‧最小間距 D3‧‧‧minimum distance
9‧‧‧習知微粒噴頭 9‧‧‧ Known particle spray head
91‧‧‧流道 91‧‧‧ runner
92‧‧‧開口 92‧‧‧ opening
第1圖：習知微粒噴頭結構的示意圖。 Fig. 1: Schematic diagram of the structure of a conventional particle sprayer.
第2圖：本發明一實施例的微粒噴頭之立體分解圖。 FIG. 2 is an exploded perspective view of a particle sprayer according to an embodiment of the present invention.
第3圖：本發明一實施例的微粒噴頭之組合剖視圖。 FIG. 3 is a sectional view of a particle sprayer according to an embodiment of the present invention.
第4圖：本發明一實施例的微粒成型裝置之組合剖視圖。 FIG. 4 is a sectional view of a microparticle molding device according to an embodiment of the present invention.
第5圖：本發明一實施例的微粒成型裝置之局部放大剖視圖。 FIG. 5 is a partially enlarged cross-sectional view of a particle molding apparatus according to an embodiment of the present invention.
第6圖：經本發明一實施例的微粒成型裝置所製得的微粒半成品示意圖。 FIG. 6 is a schematic diagram of a semi-finished particle produced by a particle molding device according to an embodiment of the present invention.
第7圖：經本發明一實施例的微粒成型裝置所製得的微粒成品示意圖。 FIG. 7 is a schematic diagram of a finished fine particle produced by the fine particle molding device according to an embodiment of the present invention.
第8圖：本發明一實施例的微粒成型裝置設有一集收槽之組合剖視圖。 FIG. 8 is a cross-sectional view of a particle forming apparatus provided with a collecting and collecting tank according to an embodiment of the present invention.
第9圖：本發明一實施例微粒噴頭的延伸管之局部放大剖視圖。 FIG. 9 is a partially enlarged cross-sectional view of an extension pipe of a particle sprayer according to an embodiment of the present invention.
第10圖：本發明另一實施例微粒噴頭的延伸管之局部放大剖視圖。 FIG. 10 is a partially enlarged cross-sectional view of an extension pipe of a particle sprayer according to another embodiment of the present invention.
第11圖：本發明另一實施例的微粒成型裝置之組合剖視圖。 FIG. 11 is a cross-sectional view of a particle molding device according to another embodiment of the present invention.
第12圖：經本發明一實施例的微粒成型裝置所製得含藥物活性成分的微粒成品示意圖。 FIG. 12 is a schematic diagram of a microparticle finished product containing a pharmaceutically active ingredient prepared by a microparticle molding device according to an embodiment of the present invention.
第13圖：經本發明一實施例的微粒成型裝置所製得含空氣微泡的微粒成品示意圖。 FIG. 13 is a schematic diagram of a microparticle finished product containing air microbubbles produced by a microparticle molding device according to an embodiment of the present invention.
為讓本發明之上述及其他目的、特徵及優點能更明顯易懂， 下文特舉本發明之較佳實施例，並配合所附圖式，作詳細說明如下： 請參照第2及3圖所示，係本發明一實施例的微粒噴頭，包含一噴頭本體1，該噴頭本體1內部具有一流道11，該流道11之一端連接數個延伸管12，各該延伸管12遠離該流道11之一端形成一流出口121，且各該延伸管12之流出口121係間隔設置。該數個延伸管12可以平行設置，且各該延伸管12之流出口121較佳位於同一平面上。 In order to make the above and other objects, features, and advantages of the present invention more comprehensible, The preferred embodiments of the present invention are described below in detail, in conjunction with the accompanying drawings, as follows: Please refer to FIG. 2 and FIG. 3, which is a particulate shower head according to an embodiment of the present invention, which includes a shower head body 1, which has a first channel 11 inside, and one end of the flow channel 11 is connected to a plurality of extension tubes 12, each One end of the extension pipe 12 away from the flow channel 11 forms a first-stage outlet 121, and the flow outlets 121 of the extension pipes 12 are arranged at intervals. The plurality of extension tubes 12 may be disposed in parallel, and the outflow ports 121 of the extension tubes 12 are preferably located on the same plane.
該流道11可供注入一油相流體F1，使該油相流體F1沿該流道11流動，並且經由各該延伸管12之流出口121流出該噴頭本體1。其中，雖然該油相流體F1仍會在各該流出口121的位置承受表面張力，惟各該延伸管12於流出口121外周並無足夠的表面積供油相流體F1附著，因此油相流體F1不易在各該流出口121的位置聚積。 The flow channel 11 can be used to inject an oil-phase fluid F1 so that the oil-phase fluid F1 flows along the flow channel 11 and flows out of the shower head body 1 through the flow outlet 121 of each extension tube 12. Among them, although the oil-phase fluid F1 still receives surface tension at the position of each of the outflow ports 121, each extension tube 12 does not have sufficient surface area on the periphery of the outflow port 121 for the oil-phase fluid F1 to adhere, so the oil-phase fluid F1 It is difficult to accumulate at the positions of the respective outflow ports 121.
請參照第4圖所示，本發明實施例的微粒噴頭實際使用時，可應用於一微粒成形裝置中，該微粒成形裝置包含一容槽2、一流體剪切裝置3及一溫度控制系統4。該噴頭本體1之延伸管12係伸入該容槽2內部。該流體剪切裝置3設置於該容槽2，該流體剪切裝置3可以包含一攪拌裝置31或一超音波產生器32，或同時包含該攪拌裝置31及該超音波產生器32。在本實施例中，該流體剪切裝置3同時具有該攪拌裝置31及該超音波產生器32。該攪拌裝置31設置於該容槽2內部，該超音波產生器32可以結合於該容槽2外壁，該容槽2設置於該溫度控制系統4中。 Please refer to FIG. 4. In actual use, the particle sprayer according to the embodiment of the present invention can be applied to a particle forming device. The particle forming device includes a tank 2, a fluid shearing device 3, and a temperature control system 4. . The extension tube 12 of the shower head body 1 extends into the inside of the receiving tank 2. The fluid shearing device 3 is disposed in the tank 2. The fluid shearing device 3 may include a stirring device 31 or an ultrasonic generator 32, or both the stirring device 31 and the ultrasonic generator 32. In this embodiment, the fluid shearing device 3 has both the stirring device 31 and the ultrasonic generator 32. The stirring device 31 is disposed inside the tank 2, and the ultrasonic generator 32 may be coupled to the outer wall of the tank 2, and the tank 2 is disposed in the temperature control system 4.
更詳言之，該容槽2可供裝載一水相流體F2，因此該容槽2具有一液面高度21，該液面高度21即該容槽2裝載該水相流體F2時的液面所在位置。該噴頭本體1之延伸管12係伸入該容槽2內部，使各該延伸管12之流出口121位於該液面高度21與該容槽2的一底面22之間；換言之，該流出口121將位於該水相流體F2中。該流體剪切裝置3用以使裝載於該容槽2之水相流體F2產生擾動。其中，該攪拌裝置31可受馬達帶動 旋轉，進而驅動該水相流體F2流動。該超音波產生器32能夠產生高頻率振動，舉例而言，該超音波產生器32可由壓電材料以及能夠產生高頻電能之電源組成，所述壓電材料可以將該高頻電能轉變為高頻率振動，並且進一步經由該容槽2外壁將高頻率振動傳遞至該水相流體F2，使該水相流體F2產生振動。該溫度控制系統4可以對該水相流體F2進行溫度控制，以保持該水相流體F2於一預定溫度。 In more detail, the tank 2 can be used for loading an aqueous phase fluid F2. Therefore, the tank 2 has a liquid surface height 21, which is the liquid level when the tank 2 is loaded with the aqueous phase fluid F2. location. The extension tube 12 of the nozzle body 1 extends into the inside of the tank 2 so that the outlet 121 of each extension tube 12 is located between the liquid level 21 and a bottom surface 22 of the tank 2; in other words, the outlet 121 will be located in the aqueous phase fluid F2. The fluid shearing device 3 is used for disturbing the water-phase fluid F2 loaded in the tank 2. The stirring device 31 can be driven by a motor. The rotation causes the water-phase fluid F2 to flow. The ultrasonic generator 32 is capable of generating high-frequency vibrations. For example, the ultrasonic generator 32 may be composed of a piezoelectric material and a power source capable of generating high-frequency electrical energy, and the piezoelectric material may convert the high-frequency electrical energy into high-frequency electrical energy. Frequency vibration, and further transmit high-frequency vibration to the water-phase fluid F2 through the outer wall of the tank 2 to cause the water-phase fluid F2 to vibrate. The temperature control system 4 can perform temperature control on the aqueous phase fluid F2 to maintain the aqueous phase fluid F2 at a predetermined temperature.
其中，該油相流體F1係將聚合物加熱至玻璃轉移溫度(glass transition temperature；以下簡稱Tg點溫度)或者加入少量有機溶劑(例如：乙酸乙酯、二氯甲烷…等)製成。所述聚合物可以是可生物降解高分子材料，包括脂肪族聚酯、脂肪族-芳香族聚酯共聚物、聚乳酸-脂肪族聚酯共聚物、聚己內酯、聚麩胺酸、聚羥基羧酸酯或聚乳酸。更詳細而言，脂肪族聚酯可為聚甘醇酸、聚丁二酸丁二胺或聚乙烯丁二酸酯。脂肪族-芳香族聚酯共聚物可為聚對苯二甲酸乙二醇酯-聚氧乙烯。聚乳酸-脂肪族聚酯共聚物可為聚乳酸聚甘醇酸。然而，本發明並不以此為限，亦可使用其他可用作藥物微載體的可生物降解高分子材料作為所述聚合物。在本實施例中，所述聚合物較佳例如是聚己內酯、聚乳酸或聚乳酸聚甘醇酸，其中聚己內酯具有良好的生物相容性與混溶性，且基於Tg點溫度較低而在生物體內具有良好的分子流動性，對於低分子量的藥物活性成分呈現優異的滲透性。 The oil phase fluid F1 is prepared by heating a polymer to a glass transition temperature (hereinafter referred to as Tg point temperature) or adding a small amount of an organic solvent (for example, ethyl acetate, dichloromethane, etc.). The polymer may be a biodegradable polymer material, including aliphatic polyester, aliphatic-aromatic polyester copolymer, polylactic acid-aliphatic polyester copolymer, polycaprolactone, polyglutamic acid, poly Hydroxycarboxylic acid ester or polylactic acid. In more detail, the aliphatic polyester may be polyglycolic acid, polysuccinic acid succinate, or polyethylene succinate. The aliphatic-aromatic polyester copolymer may be polyethylene terephthalate-polyoxyethylene. The polylactic acid-aliphatic polyester copolymer may be polylactic acid and polyglycolic acid. However, the present invention is not limited to this, and other biodegradable polymer materials that can be used as a drug microcarrier can also be used as the polymer. In this embodiment, the polymer is preferably, for example, polycaprolactone, polylactic acid, or polylactic acid polyglycolic acid, wherein the polycaprolactone has good biocompatibility and miscibility, and is based on the Tg point temperature It is low and has good molecular fluidity in the body, and exhibits excellent permeability for low molecular weight pharmaceutically active ingredients.
請一併參照第4及5圖所示，本發明一實施例之微粒成形方法可利用該微粒成形裝置執行。該實施例之微粒成形方法係以該容槽2裝載該水相流體F2；啟動該溫度控制系統4以保持該水相流體F2於一預定溫度，該預定溫度等於或低於該油相流體F1之Tg點溫度。在本實施例中，該水相流體F2可以選用濃度1~15%的聚乙烯醇(polyvinyl acetate,PVA)溶液，惟不以此為限。將該噴頭本體1之延伸管12伸入該容槽2內部，並於 該噴頭本體1之流道11中通入該油相流體F1，使該油相流體F1經由各該延伸管12之流出口121流出該噴頭本體1，以產生連續油相流體F1；帶動該攪拌裝置31旋轉及啟動該超音波產生器32。其中，較佳對該流道11加壓，使該油相流體F1能夠以一定的流速通過該流道11，進而經由各該流出口121連續地被打入該水相流體F2中，以產生所述連續油相流體F1。 Please refer to FIG. 4 and FIG. 5 together. The particle forming method according to an embodiment of the present invention can be performed by using the particle forming apparatus. The particle forming method of this embodiment is to load the water-phase fluid F2 in the tank 2; start the temperature control system 4 to keep the water-phase fluid F2 at a predetermined temperature, and the predetermined temperature is equal to or lower than the oil-phase fluid F1. Tg point temperature. In this embodiment, the aqueous phase fluid F2 may be a polyvinyl acetate (PVA) solution having a concentration of 1 to 15%, but is not limited thereto. Extend the extension tube 12 of the shower head body 1 into the inside of the receiving tank 2 and The oil-phase fluid F1 is passed into the flow channel 11 of the showerhead body 1, and the oil-phase fluid F1 flows out of the showerhead body 1 through the outlet 121 of each of the extension tubes 12 to generate a continuous oil-phase fluid F1; driving the stirring The device 31 rotates and activates the ultrasonic generator 32. Among them, it is preferable to pressurize the flow channel 11 so that the oil phase fluid F1 can pass through the flow channel 11 at a certain flow rate, and then be continuously driven into the water phase fluid F2 through each of the outflow ports 121 to generate The continuous oil phase fluid F1.
該攪拌裝置31能夠驅動該水相流體F2流動，以利用該水相流體F2流動時的剪切力打斷流出該噴頭本體1的油相流體F1，使該油相流體F1形成微液滴。或者，該超音波產生器32能夠使該水相流體F2產生振動，以打斷由各流出口121流出的連續油相流體F1，使該油相流體F1形成微液滴。此時，裝載於該容槽2之中的水相流體F2即可包覆於該微液滴的外層(即，〝乳化現象〞)，以輔助該微液滴固化定型，而可以於該容槽2中形成如第6圖所示之微粒半成品S，該微粒半成品S包含由該油相流體F1所形成之內層S1，以及由該水相流體F2所形成之外層S2。 The stirring device 31 can drive the water-phase fluid F2 to flow, so as to interrupt the oil-phase fluid F1 flowing out of the shower head body 1 by the shearing force when the water-phase fluid F2 flows, so that the oil-phase fluid F1 forms micro-droplets. Alternatively, the ultrasonic generator 32 can cause the water-phase fluid F2 to vibrate, so as to interrupt the continuous oil-phase fluid F1 flowing out from each of the outflow ports 121, and form the oil-phase fluid F1 into micro-droplets. At this time, the aqueous phase fluid F2 loaded in the container 2 can cover the outer layer of the microdroplet (ie, an "emulsification phenomenon") to assist the microdroplet to solidify and set, and can be used in the container. The microparticle semi-finished product S shown in FIG. 6 is formed in the tank 2, and the microparticle semi-finished product S includes an inner layer S1 formed by the oil-phase fluid F1 and an outer layer S2 formed by the water-phase fluid F2.
接著，收集該微粒半成品S並去除該水相流體F2所形成之外層S2，使該油相流體F1所形成之內層S1成形為微粒成品M(如第7圖所示)。舉例而言，將該微粒半成品S以乾燥法(例如：熱風乾燥)處理，以蒸發該外層S2；或者，利用水溶液對該微粒半成品S進行洗滌，以除去該外層S2，均可成形僅由該油相流體F1所形成之微粒成品M。詳言之，工者可利用該容槽2收集該微粒半成品S；或者，請參照第4及8圖所示，在本實施例中，該容槽2可設有一入口管23及一出口管24，該入口管23及該出口管24係貫穿該容槽2外壁，且該出口管24較佳設置於鄰近該底面22的位置，該微粒成形裝置可另設有一集收槽5，該集收槽5連通該容槽2之出口管24。藉此，該容槽2中的水相流體F2連帶該微粒半成品S係經由該出口管24流向該集收槽5，使工者可利用該集收槽5收集該微粒半成品S。另一方面，該入口管23可供注入該水相流體F2，以保持該容槽 2中的水相流體F2具有該液面高度21，進而確保各該延伸管12之流出口121位於該水相流體F2中。 Next, the particulate semi-finished product S is collected and the outer layer S2 formed by the aqueous phase fluid F2 is removed, and the inner layer S1 formed by the oil-phase fluid F1 is formed into a particulate finished product M (as shown in FIG. 7). For example, the particulate semi-finished product S is processed by a drying method (for example, hot air drying) to evaporate the outer layer S2; or the particulate semi-finished product S is washed with an aqueous solution to remove the outer layer S2, which can be formed only by the The fine particle product M formed by the oil phase fluid F1. In detail, the worker can use the tank 2 to collect the particulate semi-finished product S; or, as shown in FIGS. 4 and 8, in this embodiment, the tank 2 can be provided with an inlet pipe 23 and an outlet pipe 24. The inlet pipe 23 and the outlet pipe 24 run through the outer wall of the receiving tank 2, and the outlet pipe 24 is preferably disposed adjacent to the bottom surface 22. The particle forming device may be further provided with a collecting tank 5. The receiving tank 5 communicates with the outlet pipe 24 of the receiving tank 2. Accordingly, the aqueous phase fluid F2 in the tank 2 and the particulate semi-finished product S flow to the collecting tank 5 through the outlet pipe 24, so that workers can use the collecting tank 5 to collect the particulate semi-finished product S. On the other hand, the inlet pipe 23 can be used to inject the aqueous phase fluid F2 to maintain the tank. The water-phase fluid F2 in 2 has the liquid surface height 21, thereby ensuring that the outflow ports 121 of the extension pipes 12 are located in the water-phase fluid F2.
相較前述習知微粒噴頭9仰賴表面張力作用於各開口92位置聚積形成液滴，導致所生產之微粒的粒徑分布較為分散。本發明實施例的微粒噴頭、微粒成形裝置及微粒成形方法能夠藉由該噴頭本體1產生連續油相流體F1，並且利用該水相流體F2的剪切力或振動打斷所述連續油相流體F1，進而成形微粒成品M。由於各該延伸管12於流出口121外周並無足夠的表面積供油相流體F1附著，因此油相流體F1不易在各該流出口121的位置聚積，使得所成形之微粒成品M的粒徑分布集中，具有提升微粒均一性之功效。 Compared with the conventional particle spray head 9 described above, the surface tension acts on the positions of the openings 92 to accumulate and form droplets, resulting in a dispersed particle size distribution of the particles produced. The particle spray head, the particle forming device and the particle forming method according to the embodiments of the present invention can generate a continuous oil phase fluid F1 through the nozzle body 1 and interrupt the continuous oil phase fluid by using the shear force or vibration of the water phase fluid F2. F1, and further, a fine particle product M is formed. Since each of the extension tubes 12 does not have sufficient surface area on the periphery of the outflow port 121 for the oil phase fluid F1 to adhere, the oil phase fluid F1 is not easy to accumulate at the position of each of the outflow ports 121, so that the particle size distribution of the formed particulate product M Concentrated, has the effect of improving the uniformity of particles.
再者，本發明實施例的微粒成形裝置及微粒成形方法係利用該水相流體F2的剪切力或振動打斷所述連續油相流體F1，因此透過調整該攪拌裝置31的轉速以控制該水相流體F2的剪切力；或者透過調整該超音波產生器32的頻率與振福以控制該水相流體F2的振動，即可精確控制所成形之微粒成品M的粒徑。舉例而言，若該流道11中所通入的油相流體F1黏度較高時，可以透過提升該攪拌裝置31的轉速或該超音波產生器32的振福，使該水相流體F2產生的剪切力加大，確保該水相流體F2能夠有效打斷連續的油相流體F1，避免所成形之微粒成品M的粒徑受該油相流體F1的黏度影響，進而精確控制所成形之微粒成品M的粒徑。據此，相較前述習知微粒噴頭9所生產之微粒的粒徑難以控制且無法用以生產高黏度油相溶液的微粒，本發明實施例的微粒噴頭、微粒成形裝置及微粒成形方法能夠提升微粒粒徑的控制精確度，且可適用於高黏度(例如：高分子材料黏度>9wt%)的油相流體F1，具有提升適用範圍之功效。 Furthermore, the particle forming apparatus and the particle forming method according to the embodiment of the present invention interrupt the continuous oil phase fluid F1 by using the shear force or vibration of the water phase fluid F2, so the rotation speed of the stirring device 31 is adjusted to control the The shearing force of the aqueous phase fluid F2; or by adjusting the frequency and vibration of the ultrasonic generator 32 to control the vibration of the aqueous phase fluid F2, the particle size of the formed fine particle product M can be precisely controlled. For example, if the viscosity of the oil-phase fluid F1 flowing in the flow channel 11 is high, the water-phase fluid F2 can be generated by increasing the rotation speed of the stirring device 31 or the vibration of the ultrasonic generator 32. The increased shear force ensures that the water-phase fluid F2 can effectively interrupt the continuous oil-phase fluid F1, and avoids that the particle size of the formed fine particle M is affected by the viscosity of the oil-phase fluid F1, so as to precisely control the formed fluid. Particle size of the fine particle finished product M. According to this, compared with the particle diameter of the particles produced by the conventional particle nozzle 9 described above, which is difficult to control and cannot be used to produce particles of a high viscosity oil phase solution, the particle nozzle, the particle forming device and the particle forming method of the embodiment of the present invention can be improved. The particle size is controlled accurately, and can be applied to oil phase fluid F1 with high viscosity (for example, polymer material viscosity> 9wt%), which has the effect of improving the applicable range.
再者，本發明實施例的微粒噴頭、微粒成形裝置及微粒成形方法藉由使該油相流體F1經由各該延伸管12之流出口121流出該噴頭本 體1，該油相流體F1能夠以一定的流速通過該流道11與各該延伸管12，以產生連續油相流體F1，進而成形微粒成品M。相較前述習知微粒噴頭9形成液滴並使液滴脫離的過程冗長，本發明實施例的微粒噴頭、微粒成形裝置及微粒成形方法能夠讓該油相流體F1較快地流出該噴頭本體1，以縮減該微粒成形方法的製程時間，具有提升微粒生產效率之功效。 Furthermore, the particle spray head, the particle forming device, and the particle forming method according to the embodiments of the present invention flow the oil phase fluid F1 through the outlet 121 of each of the extension tubes 12 out of the nozzle head. In the body 1, the oil phase fluid F1 can pass through the flow channel 11 and each of the extension tubes 12 at a certain flow rate to generate a continuous oil phase fluid F1, and then a fine particle product M is formed. Compared with the conventional process of forming droplets and detaching the droplets from the conventional particulate spray head 9, the particulate spray head, the particulate forming device, and the particulate forming method of the embodiment of the present invention can make the oil phase fluid F1 flow out of the spray head body 1 faster. In order to reduce the processing time of the particle forming method, it has the effect of improving the production efficiency of particles.
除此之外，藉由該攪拌裝置31驅動該水相流體F2流動，或者藉由該超音波產生器32驅使該水相流體F2振動，能夠避免該油相流體F1所形成的微液滴於該水相流體F2中團聚。據此，本發明實施例的微粒成形裝置及微粒成形方法能夠確保所述微液滴個別為水相流體F2包覆定型，具有提升微粒的生產良率之功效。 In addition, the water-phase fluid F2 is driven to flow by the stirring device 31, or the water-phase fluid F2 is driven to vibrate by the ultrasonic generator 32, so that the micro-droplets formed by the oil-phase fluid F1 can be avoided. This aqueous phase fluid F2 is agglomerated. According to this, the microparticle forming device and the microparticle forming method of the embodiments of the present invention can ensure that the microdroplets are individually coated and shaped by the aqueous phase fluid F2, and have the effect of improving the production yield of microparticles.
據由上述技術概念，以下詳細列舉本發明實施例的微粒噴頭、微粒成形裝置及微粒成形方法的特點並逐一說明：請參照第9圖所示，各該延伸管12之流出口121具有一口徑D1，且各該延伸管12之管壁具有一厚度D2。該厚度D2較佳小於該口徑D1，以縮減各該延伸管12於流出口121外周的表面積，使該油相流體F1不易在各該流出口121的位置聚積，進而有效降低表面張力對所成形之微粒成品M粒徑的影響。 According to the above technical concept, the characteristics of the particle sprayer, the particle forming device and the particle forming method according to the embodiments of the present invention are enumerated below and explained one by one: Please refer to FIG. 9, and the outlet 121 of each extension tube 12 has a diameter. D1, and the wall of each extension tube 12 has a thickness D2. The thickness D2 is preferably smaller than the diameter D1, so as to reduce the surface area of each extension tube 12 on the outer periphery of the outflow opening 121, so that the oil-phase fluid F1 is not easy to accumulate at the position of each outflow opening 121, thereby effectively reducing surface tension on the formed The effect of the particle size of the fine particle M.
在本實施例中，各該延伸管12具有該流出口121之一端可以形成平口端。惟，請參照第10圖所示，在本發明部分實施例中，各該延伸管12具有該流出口121之一端亦可形成斜口端，藉由使該各該延伸管12成斜口端，可以在該油相流體F1經由各該流出口121流出時，進一步縮減該油相流體F1與各該延伸管12的接觸面積，確實防止該油相流體F1在各該流出口121聚積，以更有效地降低表面張力對所成形之微粒成品M粒徑的影響。 In this embodiment, one end of each of the extension tubes 12 having the outflow port 121 may form a flat mouth end. However, referring to FIG. 10, in some embodiments of the present invention, each of the extension tubes 12 may have an inclined end at one end of the outflow port 121, and each of the extension tubes 12 may be an inclined end. When the oil-phase fluid F1 flows out through each of the outflow ports 121, the contact area between the oil-phase fluid F1 and each of the extension tubes 12 can be further reduced, and the oil-phase fluid F1 can be prevented from accumulating at each of the outflow ports 121, so that The effect of surface tension on the particle size of the formed fine particle M is more effectively reduced.
此外，在本發明部分實施例中，各該延伸管12具有該流出 口121之一端可設有一層疏水性材料。所述疏水性材料可為SiO2或TiO2，惟不以此為限。該層疏水性材料能夠以(但不限於)鍍覆之方式形成於各該延伸管12具有該流出口121之一端，藉由在各該延伸管12之流出口121設置該層疏水性材料，可以讓該油相流體F1經由各該流出口121流出時接觸該層疏水性材料，使該油相流體F1不易附著在各該延伸管12上，確實防止該油相流體F1在各該流出口121聚積，以更有效地降低表面張力對所成形之微粒成品M粒徑的影響。 In addition, in some embodiments of the present invention, a layer of hydrophobic material may be provided on one end of each extension tube 12 having the outflow port 121. The hydrophobic material may be SiO 2 or TiO 2 , but is not limited thereto. The layer of hydrophobic material can be formed (but not limited to) by plating on one end of each of the extension tubes 12 having the outflow port 121. By providing the layer of hydrophobic material on the outflow port 121 of each of the extension tubes 12, The oil-phase fluid F1 can be allowed to contact the layer of hydrophobic material when flowing out through each of the outflow ports 121, so that the oil-phase fluid F1 is not easily attached to each of the extension pipes 12, and the oil-phase fluid F1 is surely prevented from being at each of the outflow ports 121 accumulates to more effectively reduce the effect of surface tension on the M particle size of the finished particulate product.
值得注意的是，該口徑D1將決定經由各該流出口121流出之連續油相流體F1的流量，進而控制所成形之微粒成品M的粒徑。據此，該口徑D1係對應所欲生產之微粒成品M的粒徑設計。舉例而言，若欲生產粒徑為100μm的微粒成品M，則該口徑D1可以設計為100μm左右；相對地，若欲生產粒徑為5μm以下的微粒成品M，則該口徑D1可以設計為5μm左右。詳言之，若欲製造粒徑比該口徑D1更小之微粒成品M，可藉由調整該油相流體F1之流速、該攪拌裝置31的轉速或該超音波產生器32的頻率來達成，據此本發明實施例並不限於生產粒徑與該口徑D1相同之的微粒成品M，更可製造粒徑比該口徑D1更小之微粒成品M，故此處示例之微粒成品M的粒徑雖為微米等級，惟根據本發明亦可使微粒成品M的粒徑達到奈米等級。 It is worth noting that the caliber D1 will determine the flow rate of the continuous oil phase fluid F1 flowing out through each of the outflow ports 121, and then control the particle size of the formed particulate product M. According to this, the caliber D1 is designed corresponding to the particle size of the fine particle product M to be produced. For example, if you want to produce a fine particle M with a particle size of 100 μm, the diameter D1 can be designed to be about 100 μm. In contrast, if you want to produce a fine particle M with a particle size of 5 μm or less, the diameter D1 can be designed to be 5 μm about. Specifically, if it is desired to produce a fine particle product M having a smaller particle diameter than the caliber D1, it can be achieved by adjusting the flow rate of the oil-phase fluid F1, the rotation speed of the stirring device 31, or the frequency of the ultrasonic generator 32. Accordingly, the embodiment of the present invention is not limited to the production of fine particle products M having the same particle diameter as the diameter D1, and it is also possible to manufacture fine particle products M having a particle diameter smaller than the diameter D1. It is a micrometer grade, but according to the present invention, the particle size of the fine particle finished product M can also reach a nanometer grade.
請參照第2及3圖所示，本發明實施例的微粒噴頭之噴頭本體1可以包含一模仁1a及一座體1b，該模仁1a係可拆裝地結合於該座體1b。舉例而言，該模仁1a可以設有一組裝部13，該模仁1a由該組裝部13可拆裝地結合於該座體1b。在本實施例當中，該組裝部13可以為一鎖孔，使一鎖固元件14能夠穿過該組裝部13並將該模仁1a鎖固於該座體1b。該流道11係貫通該模仁1a及該座體1b，且各該延伸管12係設置於該模仁1a。本發明實施例的微粒噴頭藉由設置可拆裝地結合於該座體1b之模 仁1a以構成該噴頭本體1，僅需替換具有不同口徑D1之流出口12的模仁1a，即可以該微粒成形裝置生產不同粒徑的微粒成品M，具有提升微粒噴頭的實用性功效。 Please refer to FIG. 2 and FIG. 3, the nozzle body 1 of the particle sprayer according to the embodiment of the present invention may include a mold core 1a and a base body 1b, and the mold core 1a is detachably coupled to the base body 1b. For example, the mold core 1 a may be provided with an assembly portion 13, and the mold core 1 a is detachably coupled to the base body 1 b by the assembly portion 13. In this embodiment, the assembling portion 13 may be a locking hole, so that a locking element 14 can pass through the assembling portion 13 and lock the mold core 1a to the base body 1b. The flow channel 11 passes through the mold core 1a and the base body 1b, and each extension tube 12 is disposed on the mold core 1a. The particle sprayer according to the embodiment of the present invention is provided with a mold detachably coupled to the base body 1b. The kernel 1a constitutes the nozzle body 1. Only the mold kernel 1a having the outlet 12 with a different diameter D1 needs to be replaced, that is, the particle forming device can produce particle finished products M with different particle diameters, which has the practical effect of improving the particle nozzle.
此外，該噴頭本體1之各延伸管12間具有一最小間距D3，該最小間距D3較佳大於該口徑D1，以避免由相鄰之延伸管12所流出的連續油相流體F1產生混合現象。 In addition, there is a minimum distance D3 between the extension tubes 12 of the nozzle body 1, and the minimum distance D3 is preferably larger than the diameter D1 to avoid the mixing phenomenon of the continuous oil phase fluid F1 flowing from the adjacent extension tubes 12.
如前所述，本發明實施例之微粒成形方法可對該流道11加壓，使該油相流體F1能夠以一定的流速通過該流道11，進而經由各該流出口121連續地被打入該水相流體F2中。因此，請參照第4圖所示，在本實施例中，該噴頭本體1由該容槽2的一水平上方位置伸入該微粒成形裝置之容槽2；或者，請參照第11圖所示，在本發明部分實施例中，該噴頭本體1亦由該容槽2的一水平下方位置伸入該容槽2；同理；在本發明其他實施例中，該噴頭本體1亦可由與該容槽2水平的位置伸入該容槽2。換言之，本發明並不加以限制該噴頭本體1與該容槽2的相對位置，僅需將該噴頭本體1之延伸管12伸入該容槽2內部，並使各該延伸管12之流出口121位於該液面高度21與該容槽2的底面22之間，即可將該油相流體F1打入該水相流體F2中。 As described above, the particle forming method of the embodiment of the present invention can pressurize the flow channel 11 so that the oil-phase fluid F1 can pass through the flow channel 11 at a certain flow rate, and then be continuously blown through each of the flow outlets 121. Into this aqueous phase fluid F2. Therefore, please refer to FIG. 4. In this embodiment, the shower head body 1 protrudes from a level above the receptacle 2 into the receptacle 2 of the particle forming device; or, refer to FIG. 11. In some embodiments of the present invention, the sprinkler body 1 also extends into the containing groove 2 from a level below the containing groove 2; the same is true; in other embodiments of the present invention, the sprinkler body 1 may also The cuvette 2 extends into the cuvette 2 in a horizontal position. In other words, the present invention does not limit the relative position of the shower head body 1 and the cuvette 2. It only needs to extend the extension tube 12 of the shower head body 1 into the cistern 2 and make the outlets of each of the extension tubes 12. 121 is located between the liquid surface height 21 and the bottom surface 22 of the tank 2, and the oil phase fluid F1 can be driven into the water phase fluid F2.
再者，請參照第4圖所示，在本實施例中，該溫度控制系統4可以為一加熱線圈，且該溫度控制系統4係結合於該容槽2外壁。藉此，該溫度控制系統4可以經由該容槽2外壁對該水相流體F2進行加熱，以保持該水相流體F2於該預定溫度。或者，如第11圖所示，在本發明部分實施例中，該溫度控制系統4可以為一恆溫箱，且該容槽2可以設置於該溫度控制系統4內部。藉此，該溫度控制系統4同樣能夠保持該水相流體F2於該預定溫度。 Furthermore, please refer to FIG. 4. In this embodiment, the temperature control system 4 may be a heating coil, and the temperature control system 4 is coupled to the outer wall of the tank 2. Thereby, the temperature control system 4 can heat the aqueous phase fluid F2 through the outer wall of the tank 2 to keep the aqueous phase fluid F2 at the predetermined temperature. Alternatively, as shown in FIG. 11, in some embodiments of the present invention, the temperature control system 4 may be a thermostat, and the tank 2 may be disposed inside the temperature control system 4. Thereby, the temperature control system 4 can also maintain the water-phase fluid F2 at the predetermined temperature.
其中，本發明實施例之微粒成形方法係藉由啟動該溫度控制 系統4以保持該水相流體F2於該預定溫度，使得該油相流體F1形成微液滴時，該水相流體F2之溫度能夠輔助該微液滴固化定型。然而，如前所述，該油相流體F1可透過將聚合物加入少量有機溶劑製成，故在部分情況下，該油相流體F1所形成之微液滴能否固化定型與該水相流體F2之溫度未成顯著相關，因此在本發明部分實施例之微粒成形方法中，亦可選擇不啟動該溫度控制系統4。 Among them, the particle forming method of the embodiment of the present invention is performed by activating the temperature control. The system 4 maintains the water-phase fluid F2 at the predetermined temperature, so that when the oil-phase fluid F1 forms micro-droplets, the temperature of the water-phase fluid F2 can assist in curing and setting of the micro-droplets. However, as mentioned above, the oil-phase fluid F1 can be made by adding a small amount of organic solvent to the polymer, so in some cases, can the micro-droplets formed by the oil-phase fluid F1 be solidified and shaped with the water-phase fluid The temperature of F2 is not significantly related, so in the particle forming method of some embodiments of the present invention, it is also possible to choose not to activate the temperature control system 4.
此外，工者亦可以藉由改變該油相流體F1的組成，以成形如第12圖所示之微粒成品M，該微粒成品M包含一藥物活性成分M1。詳言之，如前所述，該油相流體F1可以是可生物降解高分子材料，藉由乳化法使該油相流體F1混參有該藥物活性成分M1，即可使該微粒成品M包含該藥物活性成分M1。藉此，當該微粒成品M投予一生物體時，即可以藉由該生物可降解高分子材料的包覆，達成緩慢釋放該藥物活性成分M1的效果。再者，藉由在該油相流體F1中混參氣體，可以成形如第13圖所示之微粒成品M，該微粒成品M包含數個空氣微泡M2，可提升該微粒成品M的藥物釋放效果，或者利用該數個空氣微泡M2作為微粒孔隙供細菌附著，進而達成提高細菌附著數目之功效。 In addition, the worker can also change the composition of the oil-phase fluid F1 to form a fine particle product M as shown in FIG. 12. The fine particle product M includes a pharmaceutically active ingredient M1. In detail, as described above, the oil phase fluid F1 may be a biodegradable polymer material, and the oil phase fluid F1 is mixed with the drug active ingredient M1 by an emulsification method, so that the fine particle product M contains The pharmaceutical active ingredient M1. Therefore, when the fine particle finished product M is administered to an organism, the effect of slowly releasing the active pharmaceutical ingredient M1 can be achieved by coating the biodegradable polymer material. Furthermore, by mixing the reference gas in the oil-phase fluid F1, a fine particle product M shown in FIG. 13 can be formed, and the fine particle product M includes several air microbubbles M2, which can enhance the drug release of the fine particle product M. Effect, or use the plurality of air microbubbles M2 as the pores of the particles for bacteria to attach, thereby achieving the effect of increasing the number of bacteria attached.
綜上所述，本發明實施例的微粒成形裝置及微粒成形方法能夠藉由該噴頭本體1產生連續油相流體F1，並且藉由該流體剪切裝置3使裝載於該容槽2之水相流體F2產生擾動，以利用該水相流體F2的剪切力或振動打斷所述連續油相流體F1，進而成形微粒成品M。該噴頭本體1設有數個延伸管12，以防止油相流體F1在各該流出口121的位置聚積，使得所成形之微粒成品M的粒徑分布集中，確實具有提升微粒均一性功效。 In summary, the particle forming device and the particle forming method of the embodiment of the present invention can generate a continuous oil phase fluid F1 through the nozzle body 1, and the water phase loaded in the tank 2 through the fluid shearing device 3. The fluid F2 generates a disturbance to interrupt the continuous oil-phase fluid F1 by using the shearing force or vibration of the aqueous-phase fluid F2 to form a fine particle product M. The nozzle body 1 is provided with a plurality of extension tubes 12 to prevent the oil phase fluid F1 from accumulating at the positions of the outflow ports 121, so that the particle size distribution of the formed particle finished product M is concentrated, and indeed has the effect of improving the uniformity of the particles.
再者，本發明實施例的微粒成形裝置及微粒成形方法係利用該水相流體F2的剪切力或振動打斷所述連續油相流體F1，因此透過調整該攪拌裝置31的轉速以控制該水相流體F2的剪切力；或者透過調整該超 音波產生器32的頻率與振福以控制該水相流體F2的振動，即可精確控制所成形之微粒成品M的粒徑，並且適用於生產高黏度油相流體F1的微粒，確實具有提升微粒粒徑的控制精確度及微粒成形裝置與方法的適用範圍功效。 Furthermore, the particle forming apparatus and the particle forming method according to the embodiment of the present invention interrupt the continuous oil phase fluid F1 by using the shear force or vibration of the water phase fluid F2, so the rotation speed of the stirring device 31 is adjusted to control the The shear force of the aqueous phase fluid F2; or by adjusting the The frequency and vibration of the sonic generator 32 to control the vibration of the aqueous phase fluid F2 can accurately control the particle size of the formed fine particle M, and it is suitable for the production of high viscosity oil phase fluid F1. The accuracy of particle size control and the effectiveness of the applicable range of the particle forming device and method.
此外，本發明實施例的微粒成形裝置及微粒成形方法能夠讓該油相流體F1以連續形式較快地流出該噴頭本體1，進而縮減該微粒成形方法的製程時間，確實具有提升微粒生產效率之功效。又，該微粒成形裝置及微粒成形方法藉由該攪拌裝置31驅動該水相流體F2流動，或者藉由該超音波產生器32驅使該水相流體F2振動，能夠避免該油相流體F1所形成的微液滴於該水相流體F2中團聚，確保所述微液滴個別為水相流體F2包覆定型，具有提升微粒的生產良率之功效。 In addition, the particle forming device and the particle forming method of the embodiment of the present invention can allow the oil phase fluid F1 to flow out of the nozzle body 1 in a continuous form relatively quickly, thereby reducing the processing time of the particle forming method, and indeed has the effect of improving the particle production efficiency. efficacy. In addition, the particle forming device and the particle forming method drive the water-phase fluid F2 to flow through the stirring device 31, or drive the water-phase fluid F2 to vibrate by the ultrasonic generator 32, thereby preventing formation of the oil-phase fluid F1. The micro-droplets are agglomerated in the water-phase fluid F2 to ensure that the micro-droplets are individually coated and shaped by the water-phase fluid F2, which has the effect of improving the production yield of the particles.
雖然本發明已利用上述較佳實施例揭示，然其並非用以限定本發明，任何熟習此技藝者在不脫離本發明之精神和範圍之內，相對上述實施例進行各種更動與修改仍屬本發明所保護之技術範疇，因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。 Although the present invention has been disclosed using the above-mentioned preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various changes and modifications to the above embodiments without departing from the spirit and scope of the present invention. The technical scope protected by the invention, so the scope of protection of the present invention shall be determined by the scope of the appended patent application.
Claims (13)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW106124957A TWI660789B (en) | 2016-10-25 | 2016-10-25 | Particle forming apparatus with the nozzle and particle forming method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW106124957A TWI660789B (en) | 2016-10-25 | 2016-10-25 | Particle forming apparatus with the nozzle and particle forming method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201815482A TW201815482A (en) | 2018-05-01 |
| TWI660789B true TWI660789B (en) | 2019-06-01 |
Family
ID=62949217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW106124957A TWI660789B (en) | 2016-10-25 | 2016-10-25 | Particle forming apparatus with the nozzle and particle forming method |
Country Status (1)
| Country | Link |
|---|---|
| TW (1) | TWI660789B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2601731Y (en) * | 2003-01-20 | 2004-02-04 | 上海理工大学 | Muti-functional Sprayer head for supercritical fluid preparing particle |
| CN2764486Y (en) * | 2005-03-11 | 2006-03-15 | 中国人民解放军第二军医大学 | Assemblable atomization sprayer for preparing particle from supercritical fluid |
| WO2009054343A1 (en) * | 2007-10-22 | 2009-04-30 | Hitachi Chemical Company, Ltd. | Method of forming copper wiring pattern and copper oxide particle dispersion for use in the same |
| CN102814497A (en) * | 2012-08-31 | 2012-12-12 | 北京科技大学 | Method and device for spray forming of high-speed solid phase particles |
| CN103521128A (en) * | 2013-11-06 | 2014-01-22 | 上海纳米技术及应用国家工程研究中心有限公司 | Device for preparing superfine particles through supercritical fluid |
| CN205235997U (en) * | 2015-12-15 | 2016-05-18 | 浙江大学 | One -component multicomponent liquid drop preparation facilities based on integrated microchannel |
-
2016
- 2016-10-25 TW TW106124957A patent/TWI660789B/en active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN2601731Y (en) * | 2003-01-20 | 2004-02-04 | 上海理工大学 | Muti-functional Sprayer head for supercritical fluid preparing particle |
| CN2764486Y (en) * | 2005-03-11 | 2006-03-15 | 中国人民解放军第二军医大学 | Assemblable atomization sprayer for preparing particle from supercritical fluid |
| WO2009054343A1 (en) * | 2007-10-22 | 2009-04-30 | Hitachi Chemical Company, Ltd. | Method of forming copper wiring pattern and copper oxide particle dispersion for use in the same |
| CN102814497A (en) * | 2012-08-31 | 2012-12-12 | 北京科技大学 | Method and device for spray forming of high-speed solid phase particles |
| CN103521128A (en) * | 2013-11-06 | 2014-01-22 | 上海纳米技术及应用国家工程研究中心有限公司 | Device for preparing superfine particles through supercritical fluid |
| CN205235997U (en) * | 2015-12-15 | 2016-05-18 | 浙江大学 | One -component multicomponent liquid drop preparation facilities based on integrated microchannel |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201815482A (en) | 2018-05-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2419115C (en) | Microparticles, and method and apparatus for forming same | |
| Chong et al. | Advances in fabricating double-emulsion droplets and their biomedical applications | |
| Liu et al. | On the spray drying of uniform functional microparticles | |
| Tran et al. | Why and how to prepare biodegradable, monodispersed, polymeric microparticles in the field of pharmacy? | |
| TWI643680B (en) | Nozzle | |
| Jones | Air suspension coating for multiparticulates | |
| KR101640272B1 (en) | Method for producing polymers and reactor for carrying out said method | |
| Spyropoulos et al. | Advances in membrane emulsification. Part A: recent developments in processing aspects and microstructural design approaches | |
| US11850852B2 (en) | Process and device for in-air production of single droplets, compound droplets, and shape-controlled (compound) particles or fibers | |
| CN102211008A (en) | Detachable T-shaped microchannel device and method for preparing monodisperse polymer microspheres by same | |
| Gunduz et al. | A device for the fabrication of multifunctional particles from microbubble suspensions | |
| US10137090B2 (en) | Nozzle, apparatus, and method for producing microparticles | |
| TWI660789B (en) | Particle forming apparatus with the nozzle and particle forming method | |
| CN209791507U (en) | Rotary disc device for producing microdroplets of liquid material and apparatus for producing microspheres | |
| Rezvanpour et al. | Enhancement of particle collection efficiency in electrohydrodynamic atomization process for pharmaceutical particle fabrication | |
| TWI621481B (en) | Nozzle, particle forming apparatus with the nozzle and particle forming method | |
| Dormer et al. | Monodispersed microencapsulation technology | |
| CN108608600B (en) | Particle forming device and particle forming method thereof | |
| JPH05220374A (en) | Production of particulate material | |
| Dormer et al. | Monodispersed microencapsulation technologies | |
| CN109772240B (en) | Turntable device for generating microdroplets from liquid material and apparatus for manufacturing microspheres | |
| Demont et al. | 6 Encapsulation via Spinning Disk Technology | |
| Jones | Coating processes and equipment | |
| JP2002058982A (en) | Conical fluidized bed granulating method with air dispersing device of vortex type orifice and apparatus |