電動無針注射器設計【說明書+CAD+PROE】,說明書+CAD+PROE,電動無針注射器設計【說明書+CAD+PROE】,電動,注射器,設計,說明書,仿單,cad,proe 附錄 Numerical simulation of non-needle syringe and Analysis Zhengrong Cui and Russell J. Mumper Abstract : The CFD Fluent software without the work of the syringe needle to simulate the entire process, the liquid injection pipe pressure and the liquid jet-driven changes of speed. Simulation of the liquid jet in the air in the evolution process, as well as the jet penetrates the skin, the skin layer and subcutaneous layer of the whole process of proliferation. Qualitative numerical results and experimental results. Key words: non-needle syringe; liquid jet; skin; puncture 1 Introduction Needle-free injection device refers to the use of mechanical high-pressure generated by instantaneous asked to promote the Pharmacy (liquid or freeze-dried powder) through a micron-sized nozzles to form a high-speed jet, instead of needles to penetrate the skin into the subcutaneous tissue. No needle injections with no pain, no cross-infection, the advantages of ease of use. Needle-free injection technology to avoid acid, enzyme destruction of drug absorption and stratum corneum skin barrier breakthrough, no first-pass effect, with higher bioavailability, applied to local anesthetics, analgesics, cardiovascular drugs, anti-tumor, anti-hepatitis drug, such as various types of drugs, especially for the acid, enzyme instability of biological macromolecules drugs injection to replace the ordinary local or systemic drug delivery for a wide range of disease prevention and treatment. The rapid absorption of the ordinary injection, high bioavailability, instability in the gastrointestinal tract, significant first-pass effect of the drug is often the only option, but the injection means of delivery will inevitably have to reduce tissue injury in patients with compliance, the use of the inconvenience and there is the risk of cross infection. To this end, a large number of researchers in pharmaceutical preparations into the ways non-injection drug delivery systems of the study, an attempt to resolve the instability of drugs, especially bio-pharmaceutics drugs bottleneck. Syringe without needle, such as by Hingson developed in 1937, the first time in 1941 for the vaccine and the injection of insulin. Since then the needle free syringe research and development and application development by leaps and bounds. Needle-free injection solution to penetrate the skin depth depends on the pinhole diameter and the main exports of the two parameters of jet velocity. These two parameters of the experimental research and theoretical analysis, as well as non-needle syringe Numerical Study of Fluid Dynamics' on the performance of non-needle syringe to improve and optimize the design of great significance. In this paper, CFD Fluent software work on non-needle syringe for the whole process of CFD simulation and experimental results for the new R & D non-needle syringe And provide a basis for performance optimization. Needle-free powder injection system suitable for various types of drugs, such as lidocaine, influenza vaccines, AIDS vaccines, hepatitis B vaccine, insulin, such as a huge market share of the drug has entered or will enter into clinical research, in the near future to the market, very substantial future economic profits, in which the needle-free powder lidocaine injection of the expected sales of up to seven billion U.S. dollars. On the other hand, studies have shown that may be single or repeated use of powder-free syringe needle costs are expected to be sold with the existing pre-filled syringe-type balanced, will further contribute to the promotion and popularization of technology, the development of good potential and market prospects. 2 Calculation of non-needle syringe model Syringe without needle cavity geometry as shown in Figure 1. Syringe without needle injection liquid volume is generally 0.1 ~1.0ml,export jet hole diameter of about 100 ~ 200tLm, export jet velocity of about 100 ~ 200m / s. Flow Reynolds number of 10 ~ 100, can be regarded as laminar flow. Incompressible fluid the continuity equation (A-1) Where, p is the density of liquid; t is time; v for the勃勒operator; V for the velocity vector. Incompressible viscous fluid the Navier-Stokes equation (A-2) Where, p is pressure; v for the flow viscosity coefficient of movement; f for the force per unit volume. Style (A-1), type (A-2) is a viscous incompressible fluid flow the basic equations. Volume force which can not be considered. As a result of Navier-Stokes equations and the nonlinear model of the particularity of the basic analytical solution can not be obtained, numerical simulation is to study non-needle injection fluid an important means of dynamic processes. 3 to solve the border issue and the process of Syringe of liquid on the surface at the entrance to the initial pressure imposed on households pn, jet exports to atmospheric pressure, using finite volume method can be obtained in a syringe exports tn average time v, and then show the continuity equation can be the root entrance Service average. Liquid surface as a result of advanced compression spring to relax, making the drive pressure to reduce liquid. From the entrance can calculate the average speed of Health tn +1 = tn + vt times the value of pressure-driven liquid surface. Needle wall surface and the liquid surface of the frictional resistance is directly proportional to the speed of advance, at all times by a new pressure-driven liquid pn +1, the new moment can be calculated to promote the speed of the liquid jet velocity and export port. Double counting, the syringe can be pressure-driven and export of liquid jet velocity change at any time asked curve. 4 Numerical examples and results analysis Media work for water, injection cavity length L = 28mm, diameter d1 = 5mm, Jet mouth aperture d2 = 152um; liquid density p = 1000kg/m3, sports viscosity v = 1.003mm2 / s. Syringe without needle computational grid as shown in Figure 1, a total of 4500 quadrilateral element, 5566 nodes. Because of a syringe and the outlet side wall of the pressure and pace of change is very large, therefore, the need for adequate grid refinement in order to ensure calculation accuracy. Figure 1. Calculation of non-needle syringe trellis With the solution's advanced compression spring to relax, drive the rapid drop in pressure, liquid to promote the export of jet speed and the speed of a fast decay.Three different flow rate of the drug under the conditions of pressure-driven jet velocity and attenuation export process in Figure 3 shown in Figure 5. Figure 3 in the maximum speed for export 100m / s, Figure 4 the maximum speed for the export of 150m / s, Figure 5 the maximum speed for the export of 200m / s. Due to the volume of liquid is very small, and the jet velocity, and duration is very short, so gravity does not affect the campaign jet. The numericalresults show that: jet in the air line, a thin liquid on the track. Figure 3 .the maximum rate of exports l00m / s at the time of Pressure-driven liquid attenuation curve Figure 4 .the maximum rate of exports of 150m / s at the time of Attenuation export jet velocity curve Figure 5 .the maximum rate of exports of 200m / s at the time of Attenuation export jet velocity curve At v = 100m / s, the drug around the gas jet and a small number of mixed-proliferation; v = 200m / s, the jet with the surrounding gas mixture is almost non-proliferation, a high concentration of liquid, the jet is the only front-end and the air heated collision frictionthere is an obvious phenomenon of the proliferation. 5 liquid jet penetration of the numerical simulation of the skin No experimental results show that injections: injection, the first high-speed jet to penetrate the skin, forming a hole, and then liquid through the holes in the proliferation of the skin. Jet hole in the skin of the phenomenon have been found long ago, but little hole depth research. Liquid jet holes determines the depth of the liquid injection effect and the patient's pain. Experiments show that as the pinhole diameter and jet flow velocity increased, perforation depth will increase accordingly. Drug jet results in the proliferation of skin-penetrating To the literature [7,8] based on the results of the experiment, the use of software for high-speed F1uent fluid jet penetration of the skin to simulate the effect. Calculations, the jet injector for the pinhole diameter d2 = 152um, pinhole air barrier to skin distance is lmm. The thickness of the skin with age, varies in different parts of the body, with an average of about 0.5 ~ 4.0mm. We take the 3mm as the basis for calculating the thickness of the skin. Skin is similar to that of the uniform isotropic permeability porous media (the actual skin is not uniform medium), calculated using a three-dimensional Axisymmetric conditions, only need to calculate an arbitrary angle to the flow profiles. It is divided into three regions: ① pinhole and the air separation between the skin layer; ② skin layer, the porous medium region; ③ human skin muscle tissue as well as porous medium region, but the physical and chemical properties of different skin layers. Porous media due to the resistance of the role of fluid, fluid in a multi-media mobile larvae L, the fluid will gradually lost momentum. Each injection in a dose of 0.07mL, jet exit velocity of 50m / s, 100m / s, 150m / s, 200m / s, the jet of liquid layer on the skin penetration effect of the proliferation of numerical simulation, in Figure 6as shown in Figure8, and with the literature [7,8] of experimental results were compared. (a) numerical results (b) experimental results Figure 6. jet speed of 50m / s when The experimental results show that high-speed jet to penetrate the skin role in penetrating the end of a hole formed, you can approximate a point source is considered. From this point onwards, the proliferation of the surrounding liquid. Numerical results show that the liquid layer on the skin similar to the spread of a spherical pattern, or part spherical. In the jet speed of 50 ~ 100m / s, due to the lower speed liquid jet, liquid does not penetrate the skin layer, Figure 7, shown in Figure 8. (a) numerical results (b) experimental results Figure7 .jet speed of l00m / s, the drug jet results in the proliferation of skin-penetrating Figure 8. jet speed of 150m / s, the drug jet results in the proliferation of skin-penetrating The simulation results with the literature [7,8] the experimental results Broadly in line with the. When the jet exit speed of 150m / s, the jet just penetrate the skin, as a result of penetration in the skin near the bottom, the bottom of the spread of fluid in the skin relatively open. When the jet exit speed of 200m / s, the jet penetration of the skin layer, Most of liquid into the subcutaneous layer. 6 Conclusion In this paper, CFD Fluent software without the work of the syringe needle to simulate the entire process, the liquid injection pipe pressure and export-driven changes of jet velocity, liquid jet in the air in the evolution of the skin depth of jet penetration, drug liquid layer on the skin and subcutaneous tissue layer of the diffusion process. Qualitative numerical results and experimental results are consistent with comparable. 無針注射器數值模擬和工作特性分析 Zhengrong Cui and Russell J. Mumper 摘要：采用CFD Fluent軟件對無針注射器的工作全過程進行數值模擬，得到了注射管內藥液驅動壓強和藥液射流速度的變化規(guī)律。模擬了藥液射流在空氣中的演化過程，以及射流穿透皮膚，在皮膚層和皮下組織層擴散的全過程。數值結果與實驗定性結果一致。 關鍵詞：無針注射器；藥液射流；皮膚；穿刺 1 引言 無針注射是指利用機械裝置產生的瞬問高壓，推動藥劑(液體或凍干粉)經過一個微米級大小的噴嘴，形成高速射流，代替針頭穿透皮膚進入皮下組織。無針注射具有無針痛、無交叉感染、使用方便等優(yōu)點。 無針注射技術可避免酸、酶對藥物的破壞及突破皮膚角質層吸收障礙，無首過效應，具有較高的生物利用度，適用于局麻藥、鎮(zhèn)痛藥、心血管藥物、抗腫瘤、抗肝炎藥物等多種類型的藥物，特別是對酸、酶不穩(wěn)定的生物大分子藥物，可替代普通注射劑局部或全身給藥，用于多種疾病的預防和治療。普通注射劑吸收迅速、生物利用度高，對于在胃腸道不穩(wěn)定、首過效應顯著的藥物往往是唯一的選擇，但注射途徑給藥不可避免產生組織損傷而降低患者順應性，使用不便且存在交叉感染的風險。為此，大量的藥物制劑研究人員投入到非注射途徑給藥系統(tǒng)的研究中，試圖解決不穩(wěn)定藥物，尤其是生物藥物的制劑學瓶頸。 無針注射器是由Hingson等在1937年研制的，1941年首次用于疫苗及胰島素的注射中。此后無針注射器的研究和開發(fā)應用得到長足發(fā)展。無針注射藥液穿透皮膚深度主要取決于針孔直徑和出口射流速度兩個參數。這兩個參數的實驗研究和理論分析以及無針注射器的流體力學數值研究‘們對無針注射器的性能改進和優(yōu)化設計具有重要意義。本文利用CFD Fluent軟件對無針注射器工作全過程進行流體力學計算模擬，并與實驗結果比較，為新型無針注射器的研發(fā)和性能優(yōu)化提供依據。 無針注射適合多種類型的藥物，諸如利多卡因、流感疫苗、艾滋病疫苗、乙型肝炎疫苗、胰島素等市場分額巨大的藥物已進入或將進入臨床研究，在不久的將來可推向市場，未來經濟利潤極其可觀，其中利多卡因無針粉末注射劑的預計市場銷售額可達70億美元。另一方面，目前研究表明，可單次或重復使用的無針粉末注射器的成本可望與現有市售的預填充式注射器持平，將進一步促進此項技術的推廣與普及，具有良好的發(fā)展?jié)摿褪袌銮熬啊? 2 無針注射器的計算模型 無針注射器內腔的幾何結構如圖1所示。無針注射器的注射藥液體積一般為0．1～1.0ml，出口射流孔直徑約為100～200tLm，出口射流速度大約為100～200m/s。流動雷諾數為10～100，可以認為是層流流動。不可壓縮流體的連續(xù)性方程為 (A-1) 式中，p為液體的密度；t為時間；v為那勃勒算子；V為速度矢量。 黏性不可壓縮流體的Navier—Stokes方程為 (A-2) 式中，p為壓強；v為流性的運動黏性系數；f為單位體積力。 式(A-1)、式(A-2)是不可壓縮黏性流體流動的基本方程。其中體積力，可以不考慮。由于Navier—Stokes方程的非線性以及模型的特殊性，解析解基本不可能求得，數值模擬是研究無針注射流體動力學過程的重要手段。 3 邊界問題和求解過程 對注射器入口處的藥液液面施加初始壓強戶pn，射流出口的壓強為大氣壓，利用有限體積法可求得注射器出口處在tn時刻的平均速度v，再根椐連續(xù)性方程可得到入口處平均速度。 由于藥液液面推進，壓縮彈簧放松，使得藥液的驅動壓強減小。由入口平均速度u生可以計算tn+1=tn+vt時刻藥液液面驅動壓強值。 針筒內壁面的摩擦阻力與藥液液面推進速度成正比，由新時刻藥液驅動壓強pn+1，可以計算新時刻的藥液推進速度口和出口射流速度。重復計算，可以得出注射器藥液驅動壓強和出口射流速度隨時問變化的曲線圖。 4 數值算例及結果分析 工作介質為水，注射腔長度L=28mm、直徑d1=5mm，射流口孔徑d2=152um；液體的密度p=1000kg/m3、運動黏度v=1.003mm2/s。無針注射器的計算網格如圖2所示，共有4500個四邊形單元、5566個節(jié)點。由于注射器邊壁和出口處的壓強和速度變化非常大，因此，需對網格進行充分細化，以保證計算精度。 圖2 無針注射器計算網格圖 隨著藥液的推進，壓縮彈簧放松，驅動壓強迅速下降，藥液推進速度和出口射流速度也快速衰減。三組不同射流速度條件下的藥物驅動壓強及出口射流速度衰減過程如圖3～圖5所示。圖3中出口最大速度為lOOm/s，圖4中出口最大速度為150m/s，圖5出口最大速度為200m/s。 圖3 最大出口速度為lOOm/s時的藥液驅動壓強衰減圖 圖4 最大出口速度為l5Om/s時的藥液驅動壓強衰減圖 圖5 最大出口速度為20Om/s時的藥液驅動壓強衰減圖 從圖3～圖5可以看出，壓縮彈簧一旦放松，藥液很快失去驅動力，藥液注射在瞬間完成(毫秒級的注射時間)。藥液注射所施加的初始藥液驅動壓強和注射時間如表1所示。 由于藥液體積量很小，且射流速度大，持續(xù)時間極短，因此重力不影響射流運動。數值結果表明：射流在空中成一直線，藥液集中在一條細長的軌道上。在v=100m/s時，藥物射流與周圍氣體有少量的混合擴散；v=200m/s時，射流與周圍氣體幾乎不擴散混合，藥液集中度很高，只有射流的正前端和空氣激烈碰撞摩擦，有明顯的擴散現象。 5 藥液射流穿透皮膚的數值模擬 無針注射的實驗表明：在注射時，高速射流首先穿透皮膚，形成一個孔洞，隨后藥液通過孔洞在皮膚中擴散。射流在皮膚產生孔洞的現象很早就被發(fā)現，但是對孔洞深度的研究很少。藥液射流孔洞的深度決定了藥液的注射效果和病人的疼痛感。實驗證明，隨著射流針孔直徑和射流速度的增加，穿孔深度會相應加大。藥物射流在皮下穿透擴散結果以文獻[7，8]的實驗結果為依據，利用F1uent流體軟件對高速射流穿透皮膚的效果進行了數值模擬。 計算中，注射器射流針孔的直徑為d2=152um，針孔到皮膚空氣隔離層距離是lmm。皮膚的厚度隨年齡、人體部位不同而異，平均約為0.5～4.0mm。我們取3mm作為計算中的皮膚厚度。近似認為皮膚是各向同性的均勻多孔滲透介質(實際皮膚并非均勻介質)，計算采用了三維軸對稱條件，只需要計算任意角度的一個剖面上的流動即可。 可為三個區(qū)域：①針孔與皮膚之間的空氣隔離層；②皮膚層，為多孔介質區(qū)域；③皮膚下面的人體肌肉組織，也是多孔介質區(qū)域，但理化性質與皮膚層不同。由于多孔介質對流體的阻力作用，流體在多孔介質中流動時，流體的動量會逐漸損失。 在每次注射劑量為0．07mL，射流出射速度分別為50m/s、100m/s、150m/s、200m/s的情況下，對藥液射流在皮膚層穿透擴散的效果進行了數值模擬，如圖6～圖8所示，并與文獻[7，8]中的實驗結果進行了比較。 (a)數值結果 (b)實驗結果 圖6 射流速度為50m/s時, 藥物射流在皮下穿透擴散結果 實驗表明，高速射流對皮膚有穿透作用，在穿透的終點處形成一個孔洞，可以近似認為是一個點源。從這點開始，藥液向四周擴散。數值結果表明，藥液在皮膚層的擴散圖案近似一個球形，或者是部分球形。在射流速度為50～100m/s時，由于藥液射流速度較低，藥液沒有穿透皮膚層，如圖7、圖8所示。 (a)數值結果 (b)實驗結果 圖7 射流速度為lOOm/s時，藥物射流在皮下穿透擴散結果 圖8 射流速度為150m/s時，藥物射流在皮下穿透擴散結果 模擬結果與文獻[7，8]的實驗結果大致符合。當出口處射流速度為150m/s時，射流剛好穿透皮膚，由于穿透點在皮膚的底層附近，流體在皮膚底層擴散得比較開闊。當出口處射流速度為200m/s時，射流穿透了皮膚層，大部分藥液進入皮下組織層。 6 結論 本文采用CFD Fluent軟件對無針注射器的工作全過程進行數值模擬，得到了注射管藥液驅動壓強和出口射流速度的變化規(guī)律、藥液射流在空氣中的演化過程、射流穿透皮膚深度、藥液在皮膚層和皮下組織層的擴散過程。數值結果與實驗定性結果一致，具有可比性。 -45-