CN118566453B - Microfluidic drug analysis system simulating in-vivo dynamic circulation - Google Patents
Microfluidic drug analysis system simulating in-vivo dynamic circulation Download PDFInfo
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Abstract
本发明公开一种模拟体内动态循环的微流控药物分析系统，包括，药物分析装置和用于实时监测的显微图像分析设备，药物分析装置包括：液体池、第一毛细管微通道、蠕动泵、分流聚流型微通道模块、第二毛细管微通道、药物注入口、培养槽型微通道模块、第三毛细管微通道、三通阀门、第四毛细管微通道；分流聚流型微通道模块和培养槽型微通道模块连接显微图像分析设备。采用本发明的技术方案，可以进行细胞或组织的体外在线培养、实时观测、随时取样分析，有效补充药物和药物载体评价过程中的空白和不足，推动给药和释放分析过程的进行。
The present invention discloses a microfluidic drug analysis system for simulating dynamic circulation in vivo, including a drug analysis device and a microscopic image analysis device for real-time monitoring, wherein the drug analysis device includes: a liquid pool, a first capillary microchannel, a peristaltic pump, a flow-dividing and converging microchannel module, a second capillary microchannel, a drug injection port, a culture trough microchannel module, a third capillary microchannel, a three-way valve, and a fourth capillary microchannel; the flow-dividing and converging microchannel module and the culture trough microchannel module are connected to the microscopic image analysis device. The technical solution of the present invention can be used to carry out in vitro online culture, real-time observation, and sampling and analysis of cells or tissues at any time, effectively supplement the gaps and deficiencies in the evaluation process of drugs and drug carriers, and promote the drug administration and release analysis process.
Description
技术领域Technical Field
本发明属于微流控技术领域，特别是涉及一种模拟体内动态循环的微流控药物分析系统。The invention belongs to the field of microfluidic technology, and in particular relates to a microfluidic drug analysis system for simulating dynamic circulation in vivo.
背景技术Background Art
近年来，随着药物开发合成技术和药物载体递送技术的发展，越来越多的新药物和新载体涌入市场。为了明晰药物的作用机制、代谢动力学、毒副作用等特征，保证使用安全性，这些药物和载体需要经过一系列的实验分析和检测评价。其中，注射给药通常比口服给药、粘膜给药、透皮给药和吸入给药的检测评价更加严格。In recent years, with the development of drug development synthesis technology and drug carrier delivery technology, more and more new drugs and new carriers have flooded into the market. In order to clarify the mechanism of action, metabolic dynamics, toxicity and side effects of drugs and ensure their safety, these drugs and carriers need to undergo a series of experimental analysis and testing evaluation. Among them, injection is usually more stringent than oral administration, mucosal administration, transdermal administration and inhalation administration.
在分析评价的过程中，药物释放行为和动力学特征是最重要的指标之一。目前，主要采用的研究分析方式主要有体外静态试验、体外动态试验、动物试验、临床试验等。其中，体外静态、动态试验通常是在容器中盛放模拟体液或真实体液，在无搅拌和有搅拌的情况下进行分析，仿真度和可靠性差；动物试验、临床试验通常需要对受试目标直接注入药物来进行测试，成本高、代价大。两者之间存在着显著的差异和割裂，给药物释放分析的快速推动造成了很大困难。In the process of analysis and evaluation, drug release behavior and kinetic characteristics are one of the most important indicators. At present, the main research and analysis methods used are in vitro static tests, in vitro dynamic tests, animal tests, clinical trials, etc. Among them, in vitro static and dynamic tests usually contain simulated body fluids or real body fluids in containers, and analyze them without or with stirring, with poor simulation and reliability; animal tests and clinical trials usually require direct injection of drugs into the test subjects for testing, which is costly and expensive. There are significant differences and divisions between the two, which has caused great difficulties for the rapid promotion of drug release analysis.
随着微流控技术的进步，可以设计仿生系统来实现对药物更有效的分析评价。例如，构建模拟体内肾癌细胞及其转移环境的仿生微流控芯片，克服动物试验实用性低的问题（CN202210927875）；通过生物3D打印建立具有肿瘤微环境的微流控模型，进行肿瘤扩散模拟和药物筛选（Advanced Materials，DOI: 10.1002/adma.201806899）；以及设计人体器官芯片的微流控系统，进行对投药剂量和投药速度的精确控制（CN202210810808）。这些方法针对各自的目标均能取得较好的效果，但难以普适应用于其他组织和细胞的给药评价。此外，在现有的微流控系统中，鲜见考虑到体内动态循环所带来的复杂流体特性对药物输运，特别是对药物载体有效率的影响。同时，这些系统也通常缺乏连接一般仪器的端口，不易于进行实时观测、取样分析。这些都是将微流控技术广泛应用于药物分析评价中所亟待解决的关键问题。With the advancement of microfluidic technology, bionic systems can be designed to achieve more effective analysis and evaluation of drugs. For example, a bionic microfluidic chip that simulates renal cancer cells and their metastatic environment in vivo is constructed to overcome the problem of low practicality of animal experiments (CN202210927875); a microfluidic model with a tumor microenvironment is established through biological 3D printing to simulate tumor diffusion and drug screening (Advanced Materials, DOI: 10.1002/adma.201806899); and a microfluidic system for human organ chips is designed to accurately control the dosage and speed of drug administration (CN202210810808). These methods can achieve good results for their respective goals, but it is difficult to be universally applied to the evaluation of drug administration in other tissues and cells. In addition, in existing microfluidic systems, it is rare to consider the effects of complex fluid properties brought about by dynamic circulation in the body on drug transport, especially on the efficiency of drug carriers. At the same time, these systems usually lack ports for connecting general instruments, which is not easy to conduct real-time observation and sampling analysis. These are the key issues that need to be solved urgently in order to widely apply microfluidic technology in drug analysis and evaluation.
发明内容Summary of the invention
本发明要解决的技术问题是，提供一种模拟体内动态循环的药物分析系统，可以进行细胞或组织的体外在线培养、实时观测、随时取样分析，有效补充药物和药物载体评价过程中的空白和不足，推动给药和释放分析过程的进行。The technical problem to be solved by the present invention is to provide a drug analysis system that simulates the dynamic circulation in the body, which can carry out online culture of cells or tissues in vitro, real-time observation, and sampling and analysis at any time, effectively supplement the gaps and deficiencies in the evaluation process of drugs and drug carriers, and promote the drug administration and release analysis process.
为了实现上述目的，本发明采用如下的技术方案是：In order to achieve the above object, the present invention adopts the following technical solution:
一种模拟体内动态循环的微流控药物分析系统，包括，药物分析装置和用于实时监测的显微图像分析设备，药物分析装置包括：液体池、第一毛细管微通道、蠕动泵、分流聚流型微通道模块、第二毛细管微通道、药物注入口、培养槽型微通道模块、第三毛细管微通道、三通阀门、第四毛细管微通道；其中，液体池与蠕动泵通过第一毛细管微通道相连；蠕动泵与分流聚流型微通道模块的入口通过第二毛细管微通道相连，第二毛细管微通道上安装有药物注入口；分流聚流型微通道模块的出口与培养槽型微通道模块的入口通过第三毛细管微通道相连；培养槽型微通道模块出口与液体池通过第四毛细管微通道相连，形成循环回路；分流聚流型微通道模块和培养槽型微通道模块连接显微图像分析设备，进行循环过程中的取样分析。A microfluidic drug analysis system for simulating dynamic circulation in vivo comprises a drug analysis device and a microscopic image analysis device for real-time monitoring, wherein the drug analysis device comprises: a liquid pool, a first capillary microchannel, a peristaltic pump, a flow-dividing and converging microchannel module, a second capillary microchannel, a drug injection port, a culture trough type microchannel module, a third capillary microchannel, a three-way valve, and a fourth capillary microchannel; wherein the liquid pool is connected to the peristaltic pump through the first capillary microchannel; the peristaltic pump is connected to the inlet of the flow-dividing and converging microchannel module through the second capillary microchannel, and the second capillary microchannel is provided with a drug injection port; the outlet of the flow-dividing and converging microchannel module is connected to the inlet of the culture trough type microchannel module through the third capillary microchannel; the outlet of the culture trough type microchannel module is connected to the liquid pool through the fourth capillary microchannel to form a circulation loop; the flow-dividing and converging microchannel module and the culture trough type microchannel module are connected to the microscopic image analysis device to perform sampling and analysis during the circulation process.
作为优选，分流聚流型微通道模块从入口通道开始分流，分流以1通道单次分成2-16通道为1级，进行1-8级分流，每级分流微通道的管径相应变小；分流后再汇集聚流，聚流以2-16通道单次汇聚成1通道为1级，经过1-8级聚流，每级聚流微通道的管径相应变大，最终到达出口。Preferably, the flow-dividing and converging microchannel module starts to divert from the inlet channel, with 1 channel being divided into 2-16 channels at a time as 1 level, and 1-8 levels of diversion are performed, and the diameter of each level of diversion microchannel becomes smaller accordingly; after diversion, the flow is converged and concentrated, with 2-16 channels being converged into 1 channel at a time as 1 level, and after 1-8 levels of concentration, the diameter of each level of concentration microchannel becomes larger accordingly, and finally reaches the outlet.
作为优选，液体池装载的液体为人体血液、人造血液及生理盐水的其中的一种。Preferably, the liquid loaded in the liquid pool is one of human blood, artificial blood and physiological saline.
作为优选，在第一毛细管微通道、第二毛细管微通道、第三毛细管微通道、第四毛细管微通道上设有三通阀门。Preferably, three-way valves are provided on the first capillary microchannel, the second capillary microchannel, the third capillary microchannel and the fourth capillary microchannel.
作为优选，所述药物注入口连接有注射器、吊瓶、进样蠕动泵中其中的一种，用于待测药物的注入。Preferably, the drug injection port is connected to one of a syringe, a hanging bottle, and a sampling peristaltic pump for injecting the drug to be tested.
作为优选，分流聚流型微通道模块的数量为1-8个，采用串联或并联的连接方式。Preferably, the number of flow-dividing and converging microchannel modules is 1-8, and they are connected in series or in parallel.
作为优选，培养槽型微通道模块的数量为1-16个，采用串联或并联的连接方式。Preferably, the number of culture trough-type microchannel modules is 1-16, and they are connected in series or in parallel.
作为优选，显微图像分析设备为生物显微镜、金相显微镜、倒置荧光显微镜、激光共聚焦扫描显微镜、双目体式显微镜、相差显微镜、暗视野显微镜其中的一种。Preferably, the microscopic image analysis device is one of a biological microscope, a metallographic microscope, an inverted fluorescence microscope, a laser confocal scanning microscope, a binocular stereo microscope, a phase contrast microscope, and a dark field microscope.
作为优选，循环过程中的取样分析为红外光谱分析、拉曼光谱分析、紫外-可见光谱分析、元素分析、粒径分析、电子显微镜分析其中一种。Preferably, the sampling analysis during the circulation process is one of infrared spectroscopy analysis, Raman spectroscopy analysis, UV-visible spectroscopy analysis, elemental analysis, particle size analysis, and electron microscopy analysis.
与现有技术相比，本发明具有如下技术果：Compared with the prior art, the present invention has the following technical results:
（1）通过分流聚流型微通道模块，可以模拟液体动态循环过程中分流、聚流、剪切、湍动的复杂流道和流态，能够随意进行并联、串联，便于改进、更新，能够更真实的测试分析药物、药物载体所受到的影像。(1) Through the flow-dividing and converging microchannel module, the complex flow channels and flow states of flow diversion, converging, shearing and turbulence in the dynamic circulation process of liquid can be simulated. It can be connected in parallel or in series at will, which is convenient for improvement and updating, and can more realistically test and analyze the effects of drugs and drug carriers.
（2）通过培养槽型微通道模块，可以进行待检测细胞或组织的体外在线培养-分析，能够随意进行并联、串联，便于改进、更新，能够进一步提高系统及微环境的仿真度。(2) Through the culture trough-type microchannel module, the cells or tissues to be tested can be cultured and analyzed online in vitro. They can be connected in parallel or in series at will, which is convenient for improvement and updating, and can further improve the simulation degree of the system and microenvironment.
（3）本发明通过分流聚流型微通道模块和培养槽型微通道模块连接显微图像分析设备，实时观测液体、组织细胞、药物和药物载体的动态特征和结合过程；通过设置三通阀门和取样口，可以随时取样分析。(3) The present invention connects the microscopic image analysis equipment through the flow-dividing and converging microchannel module and the culture tank microchannel module to observe the dynamic characteristics and binding process of liquid, tissue cells, drugs and drug carriers in real time; by setting a three-way valve and a sampling port, sampling and analysis can be carried out at any time.
（4）本发明与体外动态、静态试验相比仿真性好、可靠性高，与动物试验、临床试验相比成本低、代价小，可以有效补充药物和药物载体评价过程中的空白和不足，推动给药和释放分析过程的进行。(4) Compared with in vitro dynamic and static tests, the present invention has better simulation and higher reliability. Compared with animal tests and clinical trials, it has lower cost and lower price. It can effectively supplement the gaps and deficiencies in the evaluation process of drugs and drug carriers and promote the drug administration and release analysis process.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据提供的附图获得其他的附图。In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.
图1是本发明实施例模拟体内动态循环的微流控药物分析系统的结构结构图；1 is a structural diagram of a microfluidic drug analysis system for simulating dynamic circulation in vivo according to an embodiment of the present invention;
图2为静态系统-胶囊1释放图；Figure 2 is a static system - capsule 1 release diagram;
图3为静态系统-胶囊2释放图；Figure 3 is a static system - capsule 2 release diagram;
图4为动态系统-胶囊1释放图；Fig. 4 is a dynamic system-capsule 1 release diagram;
图5为动态系统-胶囊2释放图；Figure 5 is a dynamic system - capsule 2 release diagram;
图6为循环系统-胶囊1释放图；Fig. 6 is a diagram of the release of the circulatory system-capsule 1;
图7为循环系统-胶囊2释放图；FIG7 is a diagram of the release of the circulatory system-capsule 2;
图8为静态系统线性拟合图；Figure 8 is a linear fitting diagram of a static system;
图9为动态系统线性拟合图；Figure 9 is a linear fitting diagram of the dynamic system;
图10为循环系统线性拟合图；Figure 10 is a linear fitting diagram of the circulation system;
图11为静态系统线性拟合局部放大图；Figure 11 is a partial enlarged view of the linear fitting of the static system;
图12为动态系统线性拟合局部放大图；Figure 12 is a partial enlarged view of the linear fitting of the dynamic system;
图13为循环系统线性拟合局部放大图；FIG13 is a partial enlarged view of the linear fitting of the circulation system;
图14为标准曲线示意图；Figure 14 is a schematic diagram of a standard curve;
其中，1.液体池，2.蠕动泵，3.分流聚流型微通道模块，4.培养槽型微通道模块，5.药物注入口，6.显微图像分析设备，7-1.第一毛细管微通道，7-2.第二毛细管微通道，7-3.第三毛细管微通道，7-4.第四毛细管微通道，8.三通阀门。Among them, 1. liquid pool, 2. peristaltic pump, 3. flow diversion and convergence type microchannel module, 4. culture trough type microchannel module, 5. drug injection port, 6. microscopic image analysis equipment, 7-1. first capillary microchannel, 7-2. second capillary microchannel, 7-3. third capillary microchannel, 7-4. fourth capillary microchannel, 8. three-way valve.
具体实施方式DETAILED DESCRIPTION
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图和具体实施方式对本发明作进一步详细的说明。In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.
实施例1：Embodiment 1:
如图1所示，本发明实施例提供一种模拟体内动态循环的微流控药物分析系统，包括，药物分析装置和用于实时监测的显微图像分析设备6，药物分析装置包括：液体池1、第一毛细管微通道7-1、蠕动泵2、分流聚流型微通道模块3、第二毛细管微通道7-2、药物注入口5、培养槽型微通道模块4、第三毛细管微通道7-3、三通阀门8、第四毛细管微通道7-4；分流聚流型微通道模块3和培养槽型微通道模块4连接显微图像分析设备6。液体池1装载的液体为人体血液、人造血液及生理盐水的其中的一种。As shown in Fig. 1, an embodiment of the present invention provides a microfluidic drug analysis system for simulating dynamic circulation in vivo, including a drug analysis device and a microscopic image analysis device 6 for real-time monitoring, wherein the drug analysis device includes: a liquid pool 1, a first capillary microchannel 7-1, a peristaltic pump 2, a flow-dividing and converging microchannel module 3, a second capillary microchannel 7-2, a drug injection port 5, a culture trough microchannel module 4, a third capillary microchannel 7-3, a three-way valve 8, and a fourth capillary microchannel 7-4; the flow-dividing and converging microchannel module 3 and the culture trough microchannel module 4 are connected to the microscopic image analysis device 6. The liquid loaded in the liquid pool 1 is one of human blood, artificial blood and physiological saline.
作为本发明实施例的一种实施方式，液体池1与蠕动泵2通过第一毛细管微通道7-1相连，以实现液体的输送；蠕动泵2与分流聚流型微通道模块3的入口通过第二毛细管微通道7-2相连，第二毛细管微通道7-2上安装有药物注入口5，以便于待测药物的注入；分流聚流型微通道模块3的出口又与培养槽型微通道模块4的入口通过第三毛细管微通道7-3相连；培养槽型微通道模块4出口与液体池1最终再通过第四毛细管微通道7-4相连，形成循环回路；分流聚流型微通道模块3从入口通道开始分流，分流以1通道单次分成2-16通道为1级，进行1-8级分流，每级分流微通道的管径相应变小；分流后再汇集聚流，聚流以2-16通道单次汇聚成1通道为1级，经过1-8级聚流，每级聚流微通道的管径相应变大，最终到达出口，该分流聚流型微通道模块能够模拟体内动态循环过程中的复杂流道和流态；培养槽型微通道模块4内包含小型开口培养槽，培养槽数量为1-16个，通过微通道串联或并联连接，最终与入口和出口相连，该培养槽型微通道模块能够进行待检测细胞或组织的培养，进一步提高系统及微环境的仿真度，并根据培养槽数量实施平行对比分析；在循环和分析过程中，开口培养槽结构应通过透明材料密封。分流聚流型微通道模块和培养槽型微通道模块连接显微图像分析设备，进行循环过程中的取样分析，实现离线测试分析和观察。循环过程中的取样分析为红外光谱分析、拉曼光谱分析、紫外-可见光谱分析、元素分析、粒径分析、电子显微镜分析中的其中一种或多种。As an implementation mode of an embodiment of the present invention, the liquid pool 1 is connected to the peristaltic pump 2 through the first capillary microchannel 7-1 to realize liquid transportation; the peristaltic pump 2 is connected to the inlet of the diversion and convergence type microchannel module 3 through the second capillary microchannel 7-2, and the second capillary microchannel 7-2 is equipped with a drug injection port 5 to facilitate the injection of the drug to be tested; the outlet of the diversion and convergence type microchannel module 3 is connected to the inlet of the culture trough type microchannel module 4 through the third capillary microchannel 7-3; the outlet of the culture trough type microchannel module 4 is finally connected to the liquid pool 1 through the fourth capillary microchannel 7-4 to form a circulation loop; the diversion and convergence type microchannel module 3 starts to divert from the inlet channel, and the diversion is divided into 2-16 channels as 1 level with 1 channel at a time, and 1-8 levels are performed. The diameter of each level of shunting microchannel becomes smaller accordingly; after shunting, the flow is gathered and concentrated, and the concentration is 2-16 channels that converge into 1 channel at a time as 1 level. After 1-8 levels of concentration, the diameter of each level of concentration microchannel becomes larger accordingly, and finally reaches the outlet. The shunting and converging type microchannel module can simulate the complex flow channels and flow states in the dynamic circulation process in the body; the culture trough type microchannel module 4 contains small open culture troughs, the number of which is 1-16, which are connected in series or in parallel through microchannels and finally connected to the inlet and outlet. The culture trough type microchannel module can culture the cells or tissues to be tested, further improve the simulation degree of the system and microenvironment, and implement parallel comparative analysis according to the number of culture troughs; during the circulation and analysis process, the open culture trough structure should be sealed with transparent materials. The shunting and converging type microchannel module and the culture trough type microchannel module are connected to the microscopic image analysis equipment to perform sampling and analysis during the circulation process, and realize offline test analysis and observation. The sampling analysis during the circulation process is one or more of infrared spectroscopy analysis, Raman spectroscopy analysis, UV-visible spectroscopy analysis, elemental analysis, particle size analysis, and electron microscope analysis.
进一步地，在所述毛细管微通道7-1、7-2、7-3、7-4上设有三通阀门8，用于以便于取样。Furthermore, three-way valves 8 are provided on the capillary microchannels 7-1, 7-2, 7-3, and 7-4 to facilitate sampling.
进一步地，所述药物注入口5连接注射器、吊瓶、进样蠕动泵的其中一种，以便于待测药物的注入。Furthermore, the drug injection port 5 is connected to one of a syringe, a hanging bottle, and a sampling peristaltic pump to facilitate the injection of the drug to be tested.
分流聚流型微通道模块3的数量为1-8个，采用串联或并联的连接方式，以增加流体复杂性或实施平行对比分析。培养槽型微通道模块4的数量为1-16个，采用串联或并联的连接方式，以实施复杂系统实验或平行对比分析。显微图像分析设备6为生物显微镜、金相显微镜、倒置荧光显微镜、激光共聚焦扫描显微镜、双目体式显微镜、相差显微镜、暗视野显微镜的其中的一种，实时观察分流聚流型微通道模块3和培养槽型微通道模块4的状态。The number of the flow-dividing and converging microchannel modules 3 is 1-8, and they are connected in series or in parallel to increase the complexity of the fluid or to implement parallel comparative analysis. The number of the culture tank type microchannel modules 4 is 1-16, and they are connected in series or in parallel to implement complex system experiments or parallel comparative analysis. The microscopic image analysis device 6 is one of a biological microscope, a metallographic microscope, an inverted fluorescence microscope, a laser confocal scanning microscope, a binocular stereo microscope, a phase contrast microscope, and a dark field microscope, and observes the status of the flow-dividing and converging microchannel modules 3 and the culture tank type microchannel modules 4 in real time.
实验对比：Experimental comparison:
将含有茶树油的胶囊（25.9μm和21.9μm）注射进入三个系统，分别为静态系统用j表示、动态系统用d表示、循环系统用x表示，第四列数据是每间隔一小时分别取样测得静态、动态、循环系统的茶树油吸光度的值，267nm为茶树油最大吸收峰所对应的波长，代表着化合物在紫外可见光谱中的特征吸收，如表1、表2所示。Capsules (25.9 μm and 21.9 μm) containing tea tree oil were injected into three systems, which were represented by j for the static system, d for the dynamic system, and x for the circulatory system. The fourth column of data is the absorbance values of the tea tree oil in the static, dynamic, and circulatory systems measured at one-hour intervals. 267 nm is the wavelength corresponding to the maximum absorption peak of tea tree oil, which represents the characteristic absorption of the compound in the UV-visible spectrum, as shown in Tables 1 and 2.
表1Table 1
表2Table 2
通过对比大小不同的两个胶囊（25.9μm和21.9μm）可以看出在不同系统中它们到达释放极限的时间一样。By comparing two capsules of different sizes (25.9 μm and 21.9 μm), it can be seen that the time to reach the release limit is the same in different systems.
静态系统j、动态系统d、循环系统x，静态系统系统是直接把微胶囊放进烧杯中观察胶囊释放，动态系统是在烧杯加以磁子在烧杯中搅拌观察胶囊释放，循环系统是本发明实施例的内容。Static system j, dynamic system d, circulation system x. The static system is to directly put the microcapsules into the beaker to observe the release of the capsules. The dynamic system is to stir the beaker with a magnet to observe the release of the capsules. The circulation system is the content of the embodiment of the present invention.
如图2-7所示，这些数据是每间隔一小时分别取样测得静态、动态、循环系统的茶树油吸光度的值，然后再由这个吸光度的值带入到标准曲线里求浓度，标准曲线如图14所示，然后分别绘制了浓度时间曲线，为了直观地看出三个系统之间胶囊释放的区别，把所有的起始点都固定在了同一个点。如图8-10所示， 三个系统两个胶囊释放即将达到释放极限的线性拟合图。如图11-13所示，三个系统两个胶囊释放即将达到释放极限的线性拟合图的局部放大图。As shown in Figure 2-7, these data are the absorbance values of tea tree oil in the static, dynamic and circulating systems measured by sampling at intervals of one hour, and then the absorbance values are brought into the standard curve to calculate the concentration. The standard curve is shown in Figure 14. Then the concentration-time curves are drawn respectively. In order to intuitively see the difference in capsule release between the three systems, all the starting points are fixed at the same point. As shown in Figure 8-10, the linear fitting graphs of the release of two capsules in the three systems are about to reach the release limit. As shown in Figure 11-13, the partial enlarged graphs of the linear fitting graphs of the release of two capsules in the three systems are about to reach the release limit.
通过测量浓度来观察多久到达胶囊的释放极限，可以看出随着时间的增长，浓度也不断增大，直到浓度数值增长幅度变小或趋于不变即达到释放极限，静态释放的浓度变化随着时间的推移缓慢增加，直至11 h达到极限；动态释放的浓度变化是在短时间内快速上升，在5 h达到极限；循环释放则更快，仅为3h，分别是静态释放的27.3%和动态释放的60%，通过三组对比实验说明了该循环系统的优越性。By measuring the concentration to observe how long it takes to reach the release limit of the capsule, it can be seen that the concentration continues to increase with time until the concentration value growth rate becomes smaller or tends to remain unchanged, that is, the release limit is reached. The concentration change of static release increases slowly with the passage of time until it reaches the limit in 11 hours; the concentration change of dynamic release rises rapidly in a short period of time and reaches the limit in 5 hours; the cyclic release is faster, only 3 hours, which is 27.3% of the static release and 60% of the dynamic release respectively. The superiority of the cyclic release is demonstrated through three sets of comparative experiments.
以上所述的实施例仅是对本发明优选方式进行的描述，并非对本发明的范围进行限定，在不脱离本发明设计精神的前提下，本领域普通技术人员对本发明的技术方案做出的各种变形和改进，均应落入本发明权利要求书确定的保护范围内。The embodiments described above are only descriptions of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.
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