CN103386164B - Method and device for carrying medicine by solid microneedle array device - Google Patents
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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Abstract
本发明涉及实心微针阵列器件载药的方法及装置。本发明是利用药物溶液与凹槽底板的粘附力和微米尺度的薄液层弱化毛细现象，从而实现实心微针阵列器件上的微针的针尖准确、均匀、经济的载药。所述实心微针阵列器件载药的方法是依靠实心微针阵列器件自身的重力，将实心微针阵列器件上的微针的针尖置于厚度为微米尺度的药物溶液的薄液层之中，使药物溶液吸附在微针的针尖上，从而实现实心微针阵列器件的载药。本发明的装置是根据实心微针阵列器件载药的方法的原理设计出来的一种手动及一种自动化的实心微针阵列器件载药的装置，薄液层的形成、实心微针阵列器件的放置和切换可实现自动化，避免了人工操作带来的误差，使得载药过程具有均一性。
The invention relates to a method and a device for loading medicine on a solid microneedle array device. The invention utilizes the adhesion force between the drug solution and the bottom plate of the groove and the micron-scale thin liquid layer to weaken the capillary phenomenon, so as to realize accurate, uniform and economical drug loading on the tip of the microneedle on the solid microneedle array device. The drug-loading method of the solid microneedle array device is to place the tip of the microneedle on the solid microneedle array device in the thin liquid layer of the drug solution with a thickness of micron scale by relying on the gravity of the solid microneedle array device itself, The drug solution is adsorbed on the tip of the microneedle, so as to realize the drug loading of the solid microneedle array device. The device of the present invention is a manual and an automatic solid microneedle array device drug loading device designed according to the principle of the method of solid microneedle array device drug loading, the formation of thin liquid layer, the solid microneedle array device The placement and switching can be automated, avoiding errors caused by manual operations, and making the drug loading process uniform.
Description
技术领域 technical field
本发明涉及实心微针阵列器件载药的方法及实心微针阵列器件载药的装置，具体的说，是利用药物溶液与凹槽底板的粘附力和微米尺度的薄液层弱化毛细现象，从而实现实心微针阵列器件上的微针的针尖准确、均匀、经济的载药。The invention relates to a drug-loading method for a solid microneedle array device and a drug-loading device for a solid microneedle array device. Specifically, it uses the adhesion force between the drug solution and the bottom plate of the groove and the micron-scale thin liquid layer to weaken the capillary phenomenon, Therefore, accurate, uniform and economical drug loading of the needle tip of the microneedle on the solid microneedle array device is realized.
背景技术 Background technique
经皮给药方式受到角质层的阻碍作用，导致可以用于经皮给药的药物受到很大的限制。为了克服角质层的阻碍作用，目前有很多方法，可以分为主动方式和被动方式两大类。在各种主动方式中，实心微针阵列器件具有使用简单、无需外界能源等优点，因此显得更有吸引力。基于实心微针阵列器件的药物给药主要有四种模式。其中最有应用前景的给药模式为：药物吸附在实心微针阵列器件上的微针的针尖上形成药膜再穿刺皮肤（简称：实心微针阵列器件载药），吸附在实心微针阵列器件的上的微针的针尖上的药物溶解在皮肤内。载药的实心微针阵列器件可以制成贴片，所以能够实现患者自我给药。而且，药物吸附在实心微针阵列器件上的微针的针尖上是固态的，在这种状态下，即使是常温条件下也能保持较长时间的稳定性。在这样的背景下，有不少科学家研究实心微针阵列器件的载药方法。实心微针阵列器件的载药的难点在于如何弱化毛细现象，而使药物不会污染实心微针阵列器件的基底。The way of transdermal drug delivery is hindered by the stratum corneum, so the drugs that can be used for transdermal drug delivery are greatly limited. In order to overcome the hindering effect of the stratum corneum, there are many methods at present, which can be divided into two categories: active methods and passive methods. Among various active methods, the solid microneedle array device has the advantages of simple use and no need for external energy, so it is more attractive. There are four main modes of drug delivery based on solid microneedle array devices. Among them, the most promising drug delivery mode is: the drug is adsorbed on the tip of the microneedle on the solid microneedle array device to form a drug film and then punctures the skin (abbreviation: solid microneedle array device loaded with drug), adsorbed on the solid microneedle array The drug on the tips of the microneedles on the device dissolves in the skin. The drug-loaded solid microneedle array device can be made into a patch, so it can realize self-administration by patients. Moreover, the drug adsorbed on the tip of the microneedle on the solid microneedle array device is solid, and in this state, it can maintain stability for a long time even under normal temperature conditions. In this context, many scientists have studied the drug loading method of solid microneedle array devices. The difficulty in drug loading of the solid microneedle array device is how to weaken the capillary phenomenon so that the drug will not contaminate the substrate of the solid microneedle array device.
目前，已报道的实心微针阵列器件的载药方法：Harvinder S.Gill等（Coatedmicroneedles for transdermal delivery，Journal of Controlled Release 117(2007)227–237）、Oshiyuki Matsudo等(Microneedle device,Pub.No.:US2010/0221314A1Pub.Date:Sep.22010)和Alexander K.Andrianov等（Methods and systems forcoating a microneedle with a dosage of a biologically active compound,Pub.No:US 2009/0017210A1）发明的微孔法，即制作与实心微针阵列器件上的微针相匹配的微孔阵列，通过往微孔内注入药物溶液或用压力将药物溶液压入微孔内，然后使实心微针阵列器件上的微针插入微孔的载药方法，该方法需要准确定位每根实心微针阵列器件上的微针与每个微孔的位置，在微米尺度下操作的精确度要求高，容易使实心微针阵列器件上的微针受到损害。BIRCHALJames等（AEROSOL COATING OF MICRONEEDLES，International ApplicationNo.:PCT/GB2008/004205）发明的气雾法，即在密闭空腔内形成药物气雾，维持高温，把实心微针阵列器件置于其中进行吸附，该方法温度高容易造成蛋白类药物失活，而且十分浪费药物。Xianfeng Chen等（Dry-coatedmicroprojection array patches for targeted delivery of immunotherapeutics to theskin，Journal of Controlled Release 139(2009)212–220）和McGrath Marie G.等（Determination of parameters for successful spray coating of siliconmicroneedle arrays，Int J Pharm.2011Aug 30;415(1-2):140-9.）发明的喷射法，采用气枪把药物溶液喷射到实心微针阵列器件上的微针的针尖上，药物溶液在针尖上不仅不均匀，而且容易造成药物的浪费。Peter R.Johnson等（Maskingmethod for coating a microneedle array,US Patent Pub.No：US2008/0102192）发明的掩膜法，即在微针器件实心微针阵列器件的基底上先覆盖一层掩膜，再加入药物溶液，使药物吸附于实心微针阵列器件上的微针的针尖上，该方法耗时长，易造成药物浪费。Choi等(Method of contact coating a microneedlearray,US Patent Pub.No：US2011/8057842）发明的沾涂法，即采用沾取药物的塑料薄片在实心微针阵列器件上的微针的针尖上进行拖动，该方法容易使实心微针阵列器件上的微针的针尖受到损害，而且载药不均匀。Michel J NCormier等（Method and apparatus for coating skin piercing microprojections.ALZA February 2005:US 6855372）发明的滚轮法，即通过滚轮从药物溶液池中带出溶液，通过刮片控制滚轮上的药物溶液层的厚度，使实心微针阵列器件上的微针的针尖接触该药物溶液层，该方法需要精密的控制实心微针阵列器件上的微针的针尖与药物溶液层的接触，否则容易使实心微针阵列器件上的微针的针尖受到损害。目前开发的实心微针阵列器件的载药方法有诸多缺陷，限制了载药实心微针阵列器件给药方式的发展，开发一种新的载药方法意义重大。At present, the drug-loading method of the reported solid microneedle array device: Harvinder S.Gill et al. :US2010/0221314A1Pub.Date:Sep.22010) and Alexander K.Andrianov et al. (Methods and systems forcoating a microneedle with a dosage of a biologically active compound, Pub.No:US 2009/0017210A1) invented the microporous method, namely the production The microhole array matched with the microneedle on the solid microneedle array device, by injecting the drug solution into the microhole or pressing the drug solution into the microhole with pressure, and then inserting the microneedle on the solid microneedle array device into the microhole The drug-loading method of the hole, this method needs to accurately locate the position of each microneedle and each micropore on the solid microneedle array device, and the accuracy of the operation at the micron scale is high, and it is easy to make the microneedle array device on the solid microneedle array device The microneedles are damaged. The aerosol method invented by BIRCHALJames et al. (AEROSOL COATING OF MICRONEDLES, International Application No.: PCT/GB2008/004205) is to form a drug aerosol in a closed cavity, maintain a high temperature, and place a solid microneedle array device in it for adsorption. The high temperature of this method is likely to cause the inactivation of protein drugs, and it is a waste of drugs. Xianfeng Chen等（Dry-coatedmicroprojection array patches for targeted delivery of immunotherapeutics to theskin，Journal of Controlled Release 139(2009)212–220）和McGrath Marie G.等（Determination of parameters for successful spray coating of siliconmicroneedle arrays，Int J Pharm .2011Aug 30;415(1-2):140-9.) Invented spraying method, the drug solution is sprayed onto the needle tip of the microneedle on the solid microneedle array device by using an air gun, the drug solution is not only uneven on the needle tip, And it is easy to cause the waste of medicine. The masking method invented by Peter R.Johnson et al. (Maskingmethod for coating a microneedle array, US Patent Pub.No: US2008/0102192), that is to cover a layer of mask on the substrate of the solid microneedle array device of the microneedle device, and then Adding the drug solution to make the drug adsorb on the tip of the microneedle on the solid microneedle array device takes a long time and easily causes drug waste. Choi et al. (Method of contact coating a microneedlearray, US Patent Pub.No: US2011/8057842) invented the dip coating method, that is, the plastic sheet dipped in medicine is dragged on the tip of the microneedle on the solid microneedle array device , this method easily damages the tip of the microneedle on the solid microneedle array device, and the drug loading is uneven. The roller method invented by Michel J NCormier et al. (Method and apparatus for coating skin piercing microprojections. ALZA February 2005: US 6855372), that is, the solution is taken out from the drug solution pool by the roller, and the thickness of the drug solution layer on the roller is controlled by the scraper , making the tip of the microneedle on the solid microneedle array device contact the drug solution layer, this method requires precise control of the contact between the tip of the microneedle on the solid microneedle array device and the drug solution layer, otherwise it is easy to make the solid microneedle array The tips of the microneedles on the device were damaged. The currently developed drug-loading methods for solid microneedle array devices have many defects, which limit the development of drug-loading methods for solid microneedle array devices. It is of great significance to develop a new drug-loading method.
发明内容 Contents of the invention
本发明的目的之一是为了克服现有的实心微针阵列器件载药的方法的限制（如：需要精确控制，容易使药物失活，载药不均匀，造成药物浪费等），提供一种实心微针阵列器件载药的方法。One of the purposes of the present invention is to overcome the limitations of the existing methods of loading drugs on solid microneedle array devices (such as: need for precise control, easy to inactivate drugs, uneven drug loading, resulting in waste of drugs, etc.), to provide a A method for loading drugs into solid microneedle array devices.
本发明的目的之二是提供一种适用于实心微针阵列器件载药的方法的简单的手动实心微针阵列器件载药的装置（如图1所示），使实心微针阵列器件载药的过程变得简便、准确、经济。The second object of the present invention is to provide a simple manual drug-loading device for solid microneedle array devices (as shown in Figure 1), which is suitable for the method of loading solid microneedle array devices, so that the solid microneedle array devices are loaded with drugs The process becomes simple, accurate and economical.
本发明的目的之三是提供一种适用于实心微针阵列器件载药的方法的自动化实心微针阵列器件载药的装置（如图2所示），实现上述实心微针阵列器件载药方法的自动化。The third object of the present invention is to provide an automatic solid microneedle array device drug loading device (as shown in Figure 2) suitable for the method of solid microneedle array device drug loading, to realize the above solid microneedle array device drug loading method automation.
本发明的实心微针阵列器件载药的方法是依靠实心微针阵列器件自身的重力，将实心微针阵列器件上的微针置于厚度为微米尺度的药物溶液的薄液层之中，且所述的实心微针阵列器件上的微针的针尖的长度高于所述的药物溶液的薄液层的厚度，使药物溶液吸附在实心微针阵列器件上的微针的针尖上，从而实现实心微针阵列器件的载药。The drug-loading method of the solid microneedle array device of the present invention is to place the microneedles on the solid microneedle array device in the thin liquid layer of the drug solution with a thickness of micron scale by relying on the gravity of the solid microneedle array device itself, and The length of the tip of the microneedle on the solid microneedle array device is higher than the thickness of the thin liquid layer of the drug solution, so that the drug solution is adsorbed on the tip of the microneedle on the solid microneedle array device, thereby realizing Drug loading of solid microneedle array devices.
所述的微米尺度优选为75μm～500μm。The micron scale is preferably 75 μm to 500 μm.
为了能够更好的实现本发明的方法，本发明提供了一种适用于上述方法的手动实心微针阵列器件载药的装置（如图1所示），该手动实心微针阵列器件载药的装置包括凹槽底板和框式刮板。In order to better realize the method of the present invention, the present invention provides a drug-loading device for a manual solid microneedle array device suitable for the above method (as shown in Figure 1), the drug-loaded device for the manual solid microneedle array device The device includes a grooved bottom plate and a frame scraper.
所述的框式刮板安装于所述的凹槽底板之上，所述的框式刮板和所述的凹槽底板的凹槽共同形成一个储液池。The frame-type scraper is installed on the groove bottom plate, and the frame-type scraper and the groove of the groove bottom plate together form a liquid storage pool.
所述的储液池用于存储药物溶液。The liquid reservoir is used for storing the medicine solution.
所述的凹槽的深度为微米尺度。所述的微米尺度优选为75μm～500μm。The depth of the groove is in the micron scale. The micron scale is preferably 75 μm to 500 μm.
利用上述本发明的手动实心微针阵列器件载药的装置实现实心微针阵列器件载药的方法为：将药物溶液置于由所述的框式刮板和所述的凹槽底板的凹槽共同形成的储液池中，使所述的框式刮板与所述的凹槽底板做相对运动，在所述的凹槽底板的凹槽中形成一层厚度与所述的凹槽底板的凹槽的深度相同的厚度为微米尺度的药物溶液的薄液层，依靠实心微针阵列器件自身的重力，将实心微针阵列器件上的微针的针尖置于由所述的药物溶液形成的薄液层之中（一般实心微针阵列器件上的微针的针尖在药物溶液中停留的时间要短，例如1秒左右），且所述的针尖的长度高于所述的薄液层的厚度，使所述的药物溶液吸附在所述的实心微针阵列器件上的微针的针尖上，由于针尖的长度高于薄液层的厚度，溶液不会污染微针阵列的基底，从而实现实心微针阵列器件的载药。The method for realizing the drug loading of the solid microneedle array device by using the device for loading the drug in the manual solid microneedle array device of the present invention is as follows: placing the drug solution in the groove formed by the frame-type scraper and the groove bottom plate In the liquid storage pool formed together, the frame-type scraper and the groove bottom plate are relatively moved to form a layer in the groove of the groove bottom plate whose thickness is the same as that of the groove bottom plate. The depth of the groove is the same as the thickness of the thin liquid layer of the micron-scale drug solution, relying on the self-gravity of the solid microneedle array device, the needle tip of the microneedle on the solid microneedle array device is placed on the surface formed by the drug solution In the thin liquid layer (generally, the tip of the microneedle on the solid microneedle array device stays in the drug solution for a short time, such as about 1 second), and the length of the tip is higher than that of the thin liquid layer. thickness, so that the drug solution is adsorbed on the tip of the microneedle on the solid microneedle array device, because the length of the tip is higher than the thickness of the thin liquid layer, the solution will not contaminate the substrate of the microneedle array, thereby achieving Drug loading of solid microneedle array devices.
为了能够更好的实现本发明的方法，本发明还提供了一种适用于上述方法的自动化实心微针阵列器件载药的装置（如图2所示），该自动化实心微针阵列器件载药的装置包括凹槽底板、框式刮板、实心微针阵列器件、实心微针阵列器件固定圆盘、实心微针阵列器件固定帽、转动盘、第一步进电机、第二步进电机、第三步进电机、数字控制面板和恒温恒湿箱。In order to better realize the method of the present invention, the present invention also provides a drug-loading device for an automated solid microneedle array device suitable for the above method (as shown in Figure 2), the drug-loaded automated solid microneedle array device The device includes a grooved bottom plate, a frame scraper, a solid microneedle array device, a solid microneedle array device fixing disc, a solid microneedle array device fixing cap, a rotating disc, a first stepping motor, a second stepping motor, The third stepper motor, digital control panel and constant temperature and humidity box.
在所述的恒温恒湿箱内，所述的凹槽底板1固定于所述的恒温恒湿箱的箱底上，所述的框式刮板安装于所述的凹槽底板之上，所述的框式刮板和所述的凹槽底板的凹槽共同形成一个储液池；所述的框式刮板上安装有旋转螺杆，安装在恒温恒湿箱内的所述的第一步进电机的电机转轴为一旋转螺杆，所述的框式刮板上的旋转螺杆与所述的第一步进电机上的旋转螺杆通过旋转螺杆上的旋转螺纹相连接；所述的实心微针阵列器件固定圆盘为一中心有孔，且外边缘带有齿轮的圆盘，所述的实心微针阵列器件固定圆盘通过中心孔表面上的旋转螺纹与安装在一固定于恒温恒湿箱的箱底上的旋转螺杆上的旋转螺纹相连接，且所述的实心微针阵列器件固定圆盘位于所述的凹槽底板的斜上方；所述的实心微针阵列器件固定帽安装在所述的实心微针阵列器件上，所述的实心微针阵列器件固定帽悬挂于所述的实心微针阵列器件固定圆盘上；安装在恒温恒湿箱内的所述的第二步进电机的电机转轴为一旋转螺杆，该旋转螺杆上的旋转螺纹与所述的实心微针阵列器件固定圆盘的外边缘带有的齿轮相连接；安装在恒温恒湿箱内的所述的第三步进电机的电机转轴为一旋转螺杆，该旋转螺杆上的旋转螺纹与外边缘带有齿轮的转动盘的齿轮相连接。In the constant temperature and humidity box, the groove bottom plate 1 is fixed on the bottom of the constant temperature and humidity box, the frame scraper is installed on the groove bottom plate, the The frame-type scraper and the groove of the groove bottom plate together form a liquid storage pool; the frame-type scraper is equipped with a rotating screw, and the first step installed in the constant temperature and humidity box The motor shaft of the motor is a rotating screw, and the rotating screw on the frame-type scraper is connected with the rotating screw on the first stepping motor through the rotating threads on the rotating screw; the solid microneedle array The device fixing disk is a disk with a hole in the center and gears on the outer edge. The solid microneedle array device fixing disk is installed on a device fixed in a constant temperature and humidity box through the rotating thread on the surface of the center hole. The rotating threads on the rotating screw on the bottom of the box are connected, and the solid microneedle array device fixing disc is located obliquely above the groove bottom plate; the solid microneedle array device fixing cap is installed on the On the solid microneedle array device, the solid microneedle array device fixing cap is suspended on the solid microneedle array device fixing disc; the motor of the second stepping motor installed in the constant temperature and humidity box The rotating shaft is a rotating screw, and the rotating thread on the rotating screw is connected with the gear on the outer edge of the fixed disk of the solid microneedle array device; the third stepper installed in the constant temperature and humidity box The motor shaft of the motor is a rotating screw, and the rotating thread on the rotating screw is connected with the gear of the rotating disk with gears on the outer edge.
所述的第二步进电机、第三步进电机可固定在一金属板上，该金属板固定在所述的恒温恒湿箱的箱壁上；所述的恒温恒湿箱外安装有用于所述的第一步进电机、所述的第二步进电机和所述的第三步进电机进行工作状态控制的所述的数字控制面板。Described second stepping motor, the 3rd stepping motor can be fixed on a metal plate, and this metal plate is fixed on the box wall of described constant temperature and humidity box; The digital control panel for controlling the working state of the first stepping motor, the second stepping motor and the third stepping motor.
所述的储液池用于存储药物溶液。The liquid reservoir is used for storing the medicine solution.
所述的凹槽的深度为微米尺度。所述的微米尺度优选为75μm～500μm。The depth of the groove is in the micron scale. The micron scale is preferably 75 μm to 500 μm.
利用上述本发明的自动化实心微针阵列器件载药实现实心微针阵列器件载药的方法为：将一一对应连接在多个（根据需要一般设计为10个左右）实心微针阵列器件固定帽上的多个（根据需要一般设计为10支左右）实心微针阵列器件悬挂于实心微针阵列器件固定圆盘上；在所述的实心微针阵列器件固定圆盘上安装上所述的多个实心微针阵列器件，将药物溶液置于由框式刮板和凹槽底板的凹槽共同形成的储液池中，关上恒温恒湿箱的箱体门后，接通电源，调节所需的温度和湿度，通过数字控制面板，调出载药程序，点击自动运行进行自动化实心微针阵列器件的载药；通过第一步进电机带动所述的框式刮板向左或右进行运动到最左端或最右端，然后返回到初始位置，在所述的凹槽底板的凹槽中形成一层厚度与所述的凹槽底板的凹槽的深度相同的厚度为微米尺度的药物溶液的薄液层；通过第二步进电机带动所述的实心微针阵列器件固定圆盘做向下运动，让正对着所述的薄液层上方的所述的实心微针阵列器件缓慢下降到所述的薄液层上，依靠实心微针阵列器件自身的重力，将第一支实心微针阵列器件上的微针的针尖置于由所述的药物溶液形成的薄液层之中（一般实心微针阵列器件上的微针的针尖在药物溶液中停留1秒左右），使所述的药物溶液吸附在所述的第一支实心微针阵列器件上的微针的针尖上，从而实现第一支实心微针阵列器件的载药；然后再通过第二步进电机带动所述的实心微针阵列器件固定圆盘做向上运动回到初始位置，并使转动盘的齿轮与实心微针阵列器件固定圆盘的齿轮相连接；通过第三步进电机带动转动盘，使所述的实心微针阵列器件固定圆盘做顺时针或逆时针旋转（转动盘的齿轮与实心微针阵列器件固定圆盘的齿轮相连接，从而实现第三步进电机对实心微针阵列器件固定圆盘的控制），使下一支所述的实心微针阵列器件位于所述的薄液层上方，实现所述的实心微针阵列器件之间的切换；然后重复开始进行自动化实心微针阵列器件的载药操作，直至使安装在所述的实心微针阵列器件固定圆盘上的所述的实心微针阵列器件都载药完成为止。该装置能够通过所述的第一步进电机、所述的第二步进电机和所述的第三步进电机及程序实现实心微针阵列器件的载药，提高载药的精密度与准确度，并能够实现批量载药。The method of using the above-mentioned automatic solid microneedle array device drug loading of the present invention to realize the drug loading of the solid microneedle array device is: connect one-to-one correspondence to multiple (generally designed to be about 10 according to needs) solid microneedle array device fixing caps A plurality of solid microneedle array devices (generally designed to be about 10 according to needs) on the solid microneedle array device are suspended on the fixed disk of the solid microneedle array device; A solid microneedle array device, put the drug solution in the liquid reservoir formed by the frame scraper and the groove of the groove bottom plate, close the door of the constant temperature and humidity box, turn on the power, adjust the required temperature and humidity, through the digital control panel, call out the drug loading program, click on the automatic operation to carry out the drug loading of the automated solid microneedle array device; drive the frame scraper to move left or right through the first stepping motor to the leftmost or rightmost, and then return to the initial position, forming a layer of drug solution with the same thickness as the depth of the groove of the groove bottom plate in the groove of the groove bottom plate thin liquid layer; drive the solid microneedle array device fixed disc to move downward through the second stepping motor, so that the solid microneedle array device facing above the thin liquid layer slowly descends to On the thin liquid layer, by relying on the gravity of the solid microneedle array device itself, the needlepoints of the microneedles on the first solid microneedle array device are placed in the thin liquid layer formed by the drug solution (generally The tip of the microneedle on the solid microneedle array device stays in the drug solution for about 1 second), so that the drug solution is adsorbed on the tip of the microneedle on the first solid microneedle array device, thereby realizing The drug loading of the first solid microneedle array device; then the second stepping motor drives the fixed disc of the solid microneedle array device to move upwards and return to the initial position, and the gear of the rotating disc and the solid microneedle The gears of the fixed disk of the array device are connected; the rotating disk is driven by the third stepping motor, so that the fixed disk of the solid microneedle array device is rotated clockwise or counterclockwise (the gear of the rotating disk and the solid microneedle array device The gears of the fixed disk are connected to each other, so as to realize the control of the third stepper motor on the fixed disk of the solid microneedle array device), so that the next solid microneedle array device is located above the thin liquid layer, realizing Switch between the solid microneedle array devices; then repeat the drug-loading operation of the automated solid microneedle array device until the solid microneedle array device installed on the fixed disc of the solid microneedle array device Needle array devices are loaded with drugs. The device can realize the drug loading of the solid microneedle array device through the first stepping motor, the second stepping motor and the third stepping motor and the program, improving the precision and accuracy of drug loading. degree, and can achieve bulk drug loading.
所述的第一步进电机、所述的第二步进电机和所述的第三步进电机的工作状态的控制，是通过所述的数字控制面板发出的指令进行控制。The control of the working states of the first stepping motor, the second stepping motor and the third stepping motor is controlled by instructions sent by the digital control panel.
所述的针尖的长度高于所述的薄液层的厚度。The length of the needle tip is higher than the thickness of the thin liquid layer.
所述的薄液层的厚度为微米尺度。所述的微米尺度优选为75μm～500μm。The thickness of the thin liquid layer is on the scale of microns. The micron scale is preferably 75 μm to 500 μm.
其中，所述的实心微针阵列器件固定帽的形状可以是帽型的、片状型或柱状型，可以方便地连接在所述的实心微针阵列器件的支持体部位的上部，与实心微针阵列器件的支持体之间方便拆卸，当所述的实心微针阵列器件依靠自身的重力使实心微针阵列器件上的微针的针尖置于薄液层之中时，实心微针阵列器件固定帽能够被实心微针阵列器件顶起，实现实心微针阵列器件依靠自身的重力使实心微针阵列器件上的微针的针尖竖直垂放于薄液层之中。Wherein, the shape of the solid microneedle array device fixing cap can be cap-shaped, sheet-like or columnar, and can be easily connected to the upper part of the support body of the solid microneedle array device, and the solid microneedle array device The supports of the needle array device are convenient to disassemble. When the solid microneedle array device relies on its own gravity to place the needle tips of the microneedles on the solid microneedle array device in the thin liquid layer, the solid microneedle array device The fixed cap can be lifted up by the solid microneedle array device, so that the solid microneedle array device relies on its own gravity to vertically place the tips of the microneedles on the solid microneedle array device in the thin liquid layer.
其中，所述的实心微针阵列器件固定圆盘与所述的实心微针阵列器件固定帽的结合，可以实现所述的实心微针阵列器件的固定，并且所述的实心微针阵列器件上的微针的针尖在浸入薄液层时，把所述的实心微针阵列器件固定帽向上顶起，可以实现所述的实心微针阵列器件竖直依靠自身的重力放置。Wherein, the combination of the solid microneedle array device fixing disk and the solid microneedle array device fixing cap can realize the fixing of the solid microneedle array device, and the solid microneedle array device When the tip of the microneedle is immersed in the thin liquid layer, the fixed cap of the solid microneedle array device is lifted up, so that the solid microneedle array device can be placed vertically by its own gravity.
其中，所述的转动盘与所述的实心微针阵列器件固定圆盘的结合可以实现所述的实心微针阵列器件之间的位置切换。实心微针阵列器件固定盘用于固定实心微针阵列器件，实心微针阵列器件的支持体在穿过所述的实心微针阵列器件固定圆盘上用于悬挂实心微针阵列器件所开的孔后，再与实心微针阵列器件固定帽结合，使所述的实心微针阵列器件在孔中能够自由上下运动，转动盘带动实心微针阵列器件固定盘实现实心微针阵列器件位置之间的切换。Wherein, the combination of the rotating disk and the fixed disk of the solid microneedle array device can realize position switching among the solid microneedle array devices. The solid microneedle array device fixing plate is used to fix the solid microneedle array device, and the support body of the solid microneedle array device is used to hang the solid microneedle array device through the solid microneedle array device fixing disc. After the hole, it is combined with the solid microneedle array device fixing cap, so that the solid microneedle array device can move up and down freely in the hole, and the rotating disk drives the solid microneedle array device fixing plate to realize the position between the positions of the solid microneedle array device. switch.
其中，所述的步进电机为3台，分别实现各自的功能：实现所述的框式刮板与所述的凹槽底板的左右运动，形成薄液层；实现所述的实心微针阵列器件的自上而下，自下而上的浸入薄液层的动作；实现不同实心微针阵列器件之间的位置切换。Wherein, there are 3 stepping motors, which respectively realize their respective functions: realize the left and right movement of the frame scraper and the groove bottom plate to form a thin liquid layer; realize the solid microneedle array The top-down and bottom-up immersion action of the device in the thin liquid layer; realize the position switching between different solid microneedle array devices.
其中，所述的数字控制面板控制3台步进电机，实现各种所述的实心微针阵列器件的载药参数（框式刮板的运行速度、载药次数、实心微针阵列器件上的微针的针尖在药物溶液中的停留时间、循环次数等），实现全自动程序管理。Wherein, the digital control panel controls 3 stepping motors to realize various drug loading parameters of the solid microneedle array device (the running speed of the frame scraper, the number of times of drug loading, and the drug loading parameters on the solid microneedle array device). The residence time of the needle tip of the microneedle in the drug solution, the number of cycles, etc.), to realize fully automatic program management.
其中，所述的恒温恒湿箱控制整个体系的温度湿度。所述的恒温恒湿箱内的温度在4～37℃可调，湿度在50%～95%可调。Wherein, the constant temperature and humidity chamber controls the temperature and humidity of the whole system. The temperature in the constant temperature and humidity chamber can be adjusted at 4-37°C, and the humidity can be adjusted at 50%-95%.
所述的凹槽的表面需要一定的亲水性，由此所述的凹槽底板的材质选自普通玻璃、铝、锌、表面经亲水性处理的不锈钢和表面经亲水性处理的铜等中的一种（所述的亲水性处理，可在室温下，将不锈钢或铜放入亲水化试剂（由1体积质量浓度为36%的HCl水溶液、1体积质量浓度为0.5%的乙二胺四乙酸（EDTA）水溶液和2体积质量浓度为30%的H2O2组成，且以HCl水溶液的体积单位为准）中处理一分钟），或选自表面被上述材质中的一种修饰的材质。所述的框式刮板的材质可以是玻璃、不锈钢或聚四氟乙烯。The surface of the groove needs a certain degree of hydrophilicity, so the material of the bottom plate of the groove is selected from ordinary glass, aluminum, zinc, stainless steel with a hydrophilic surface and copper with a hydrophilic surface. etc. (the described hydrophilic treatment can be at room temperature, put stainless steel or copper into the hydrophilizing reagent (by 1 volume mass concentration of 36% HCl aqueous solution, 1 volume mass concentration of 0.5% Ethylenediaminetetraacetic acid (EDTA) aqueous solution and H 2 O 2 with a volume concentration of 30% and treated for one minute in the volume unit of HCl aqueous solution), or selected from the surface covered by one of the above materials A modified material. The material of the frame scraper can be glass, stainless steel or polytetrafluoroethylene.
所述的实心微针阵列器件作为载药的对象，实心微针阵列器件的截面形状可是圆锥形或多面锥形。所述的实心微针阵列器件上的微针的材质选自单晶硅、钛、不锈钢和高分子材料（所述的高分子材料选自聚乳酸、聚羟基乙酸、聚乙烯、聚乙烯醇、聚碳酸酯、聚丙烯酰胺、聚丙烯和尼龙中的一种）中的一种。所述的实心微针阵列器件上的微针的针尖的长度在100～1000微米之间；所述的实心微针阵列器件上的微针的针尖的直径在100纳米～10微米之间；所述的实心微针阵列器件上的微针的针尖的锥角是20～60度。The solid microneedle array device is used as the drug-loading object, and the cross-sectional shape of the solid microneedle array device can be conical or polyhedral. The material of the microneedles on the solid microneedle array device is selected from monocrystalline silicon, titanium, stainless steel and polymer materials (the polymer materials are selected from polylactic acid, polyglycolic acid, polyethylene, polyvinyl alcohol, One of polycarbonate, polyacrylamide, polypropylene and nylon). The length of the tips of the microneedles on the solid microneedle array device is between 100 and 1000 microns; the diameter of the tips of the microneedles on the solid microneedle array device is between 100 nanometers and 10 microns; The cone angle of the tip of the microneedle on the solid microneedle array device is 20-60 degrees.
所述的药物溶液需要能够与凹槽底板形成均匀的薄液层，并有一定的粘附力，从而实现弱化毛细现象，避免药物溶液污染实心微针阵列器件的基底，进行均匀载药的目的。所以，所述的药物溶液的配方中应包括药物（包括所有适用于微针载药的药物）和含有增稠剂的水溶液。所述的增稠剂，具有增稠性和成膜性，增稠性是为了提高实心微针阵列器件上的微针的针尖与药物的结合能力，从而提高载药量，成膜性是为了使药物溶液形成的薄液层均匀，从而提高载药的均匀性，与此同时，增强药物溶液与凹槽底板的粘附力，能够弱化毛细现象，避免药物溶液污染实心微针阵列器件的基底，实现实心微针阵列器件上的微针的针尖载药，节省药物。框式刮板与凹槽底板做相对(或左右)运动，形成一层厚度与凹槽底板的凹槽的深度相同的薄液层，该薄液层的厚度为微米尺度，能够进一步弱化毛细现象，从而避免药物溶液污染实心微针阵列器件的基底，并且节省药物。然后实心微针阵列器件依靠自身的重力，将实心微针阵列器件上的微针的针尖置于药物溶液的薄液层之中，使药物溶液吸附在实心微针阵列器件上的微针的针尖上，从而实现实心微针阵列器件的载药。The drug solution needs to be able to form a uniform thin liquid layer with the bottom plate of the groove, and have a certain adhesion force, so as to achieve the purpose of weakening the capillary phenomenon, preventing the drug solution from polluting the substrate of the solid microneedle array device, and carrying out the purpose of uniform drug loading . Therefore, the formulation of the drug solution should include drugs (including all drugs suitable for microneedle drug loading) and an aqueous solution containing a thickener. The thickener has thickening and film-forming properties. The thickening property is to improve the binding ability of the needle tip of the microneedle on the solid microneedle array device and the drug, thereby increasing the drug loading. The film-forming property is for Make the thin liquid layer formed by the drug solution uniform, thereby improving the uniformity of drug loading, and at the same time, enhance the adhesion between the drug solution and the bottom plate of the groove, which can weaken the capillary phenomenon and prevent the drug solution from polluting the substrate of the solid microneedle array device , to realize drug loading on the tip of the microneedle on the solid microneedle array device, and save the drug. The frame scraper moves relative (or left and right) to the groove bottom plate to form a thin liquid layer with the same thickness as the groove depth of the groove bottom plate. The thickness of the thin liquid layer is on the scale of microns, which can further weaken the capillary phenomenon , so as to prevent the drug solution from polluting the substrate of the solid microneedle array device and save the drug. Then the solid microneedle array device relies on its own gravity to place the needlepoints of the microneedles on the solid microneedle array device in the thin liquid layer of the drug solution, so that the drug solution is adsorbed on the needlepoints of the microneedles on the solid microneedle array device , so as to realize the drug loading of the solid microneedle array device.
根据不同的载药量要求，所述的药物溶液的组成为药物和含有增稠剂的水溶液。According to different drug loading requirements, the composition of the drug solution is a drug and an aqueous solution containing a thickener.
所述的药物溶液中的药物的浓度优选范围为0.1%～50%（w/v），更优选范围为0.5%～5%（w/v）。The concentration of the drug in the drug solution preferably ranges from 0.1% to 50% (w/v), more preferably ranges from 0.5% to 5% (w/v).
所述的药物溶液中的增稠剂的浓度优选范围为0.1%～50%（w/v），更优选范围为1%～10%（w/v）。The concentration of the thickener in the drug solution preferably ranges from 0.1% to 50% (w/v), more preferably ranges from 1% to 10% (w/v).
所述的增稠剂选自海藻酸钠、明胶、透明质酸、羧甲基纤维素钠、羟丙基甲基纤维素、羟乙基纤维素、羟丙基纤维素、卡波姆、聚丙烯酰胺、聚乙烯醇、聚乙烯吡咯烷酮、淀粉、黄原胶、聚丙烯酸、阿拉伯树胶和壳聚糖等中的一种或几种。Described thickener is selected from sodium alginate, gelatin, hyaluronic acid, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carbomer, poly One or more of acrylamide, polyvinyl alcohol, polyvinylpyrrolidone, starch, xanthan gum, polyacrylic acid, gum arabic and chitosan.
本发明的方法中，实心微针阵列器件是依靠自身的重力，将实心微针阵列器件上的微针的针尖置于药物溶液的薄液层的表面是十分有意义的，克服了背景技术中提到的国际上目前使用的载药方法需要精确控制的缺点。如本发明的方法无需将实心微针阵列器件上的微针准确地对准相应的微孔进行载药的过程，所以不需要精确控制，整个过程在室温下进行，不会因为高温对药物活性造成影响。In the method of the present invention, the solid microneedle array device relies on its own gravity, and it is very meaningful to place the needlepoints of the microneedles on the solid microneedle array device on the surface of the thin liquid layer of the drug solution, which overcomes the problems in the background technology. The mentioned shortcomings of the currently used drug loading methods internationally require precise control. For example, the method of the present invention does not require the process of accurately aligning the microneedles on the solid microneedle array device with the corresponding micropores for drug loading, so precise control is not required, and the entire process is carried out at room temperature, which will not affect the drug activity due to high temperature. make an impact.
本发明的装置是根据实心微针阵列器件载药的方法的原理设计出来的，薄液层的形成、实心微针阵列器件的放置和切换可实现自动化，避免了人工操作带来的误差，使得载药过程具有均一性。同时增添了恒温恒湿箱，可以控制箱体的温度和湿度，能够有效保持蛋白类药物的活性。实现自动化后，各种参数：如凹槽底板的凹槽的深度、框式刮板的运行速度、框式刮板的停留时间、载药次数、实心微针阵列器件上的微针的针尖在药物溶液中的停留时间、循环次数实现调控，各种参数的结合可以实现实心微针阵列器件上的微针的针尖的载药的深度、载药膜厚及载药量的可调控。The device of the present invention is designed according to the principle of the method of loading solid microneedle array devices. The formation of the thin liquid layer, the placement and switching of the solid microneedle array devices can be automated, and errors caused by manual operations are avoided. The drug loading process is uniform. At the same time, a constant temperature and humidity box is added, which can control the temperature and humidity of the box, and can effectively maintain the activity of protein drugs. After the automation is realized, various parameters such as the depth of the groove of the groove bottom plate, the running speed of the frame scraper, the residence time of the frame scraper, the number of times of drug loading, and the needle tip of the microneedle on the solid microneedle array device The residence time and number of cycles in the drug solution can be regulated, and the combination of various parameters can realize the controllable drug-loading depth, drug-loading film thickness and drug-loading amount of the tip of the microneedle on the solid microneedle array device.
本发明的实心微针阵列器件载药的方法是将实心微针阵列器件依靠重力置于薄液层之上进行载药的一种方法。本发明的方法原理与上述背景技术中提到的载药方法完全不同，是通过微米尺度的薄液层和药物溶液与凹槽底板的凹槽之间的粘附力来弱化毛细现象，该方法不需要精确控制（如在背景技术中提到的需要把微针准确地对准相应的微孔进行载药，这个过程需要精确控制，而本发明的方法不涉及微针对准微孔的过程，所以不需要精确控制），不会使药物失活，载药均匀，能够实现实心微针阵列器件载药过程不污染实心微针阵列器件的基底，从而节省药物与准确定量。The drug loading method of the solid microneedle array device of the present invention is a method of placing the solid microneedle array device on the thin liquid layer by gravity for drug loading. The principle of the method of the present invention is completely different from the drug-loading method mentioned in the above-mentioned background technology. It is to weaken the capillary phenomenon through the adhesion between the micron-scale thin liquid layer and the drug solution and the groove of the bottom plate of the groove. Precise control is not required (as mentioned in the background art, it is necessary to accurately align the microneedles to the corresponding micropores for drug loading, this process requires precise control, and the method of the present invention does not involve the process of aligning the microneedles to the micropores, Therefore, precise control is not required), the drug will not be inactivated, and the drug loading is uniform, so that the drug loading process of the solid microneedle array device does not pollute the substrate of the solid microneedle array device, thereby saving drugs and accurate quantification.
本发明的实心微针阵列器件载药的装置是根据实心微针阵列器件载药的方法的原理设计出来，实现了全自动化（利用三个步进电机和程序实现的操作），进一步优化了手动载药带来的人为误差，使得实心微针阵列器件的载药过程更加精确，准确，经济，简便。The drug loading device of the solid microneedle array device of the present invention is designed according to the principle of the drug loading method of the solid microneedle array device, which realizes full automation (operation realized by using three stepping motors and programs), and further optimizes manual operation. The human error caused by the drug loading makes the drug loading process of the solid microneedle array device more precise, accurate, economical and convenient.
附图说明 Description of drawings
图1.本发明的一种手动的实心微针阵列器件载药的装置的示意图；其中：图1a为俯视图；图1b为左视图。Fig. 1. A schematic diagram of a device for loading a manual solid microneedle array device of the present invention; wherein: Fig. 1a is a top view; Fig. 1b is a left view.
图2.本发明的一种自动化的实心微针阵列器件载药的装置的示意图。Fig. 2. A schematic diagram of an automated solid microneedle array device drug-loading device of the present invention.
附图标记reference sign
1.凹槽底板 2.凹槽 3.框式刮板1. Groove bottom plate 2. Groove 3. Frame scraper
4.储液池 5.薄液层 6.实心微针阵列器件4. Reservoir 5. Thin liquid layer 6. Solid microneedle array device
7.载药前的实心微针阵列器件 8.载药后的实心微针阵列器件7. Solid microneedle array device before drug loading 8. Solid microneedle array device after drug loading
9.实心微针阵列器件固定圆盘 10.实心微针阵列器件固定帽9. Solid microneedle array device fixing disc 10. Solid microneedle array device fixing cap
11.转动盘 12.第一步进电机 13.第二步进电机11. Turning disc 12. The first stepping motor 13. The second stepping motor
14.第三步进电机 15.数字控制面板 16.恒温恒湿箱14. The third stepper motor 15. Digital control panel 16. Constant temperature and humidity box
具体实施方式 Detailed ways
以下将结合附图和实施例对本发明做进一步的说明，本发明的实施例仅用来说明本发明的技术方案，并非限定本发明。The present invention will be further described below in conjunction with the accompanying drawings and embodiments. The embodiments of the present invention are only used to illustrate the technical solution of the present invention, not to limit the present invention.
实施例1.Example 1.
请参见图1（采用手动的方式进行实心微针阵列器件的载药），手动实心微针阵列器件载药的装置包括采用普通玻璃制作的凹槽底板1和采用型号为304的不锈钢制作的框式刮板3；所述的框式刮板3安装于所述的凹槽底板1之上，所述的框式刮板3和所述的凹槽底板1的凹槽2共同形成一个储液池4。凹槽2的深度为75μm，宽度为10mm，长度为30mm。框式刮板3为正方形框，边长为10mm，高度为10mm。Please refer to Figure 1 (the drug loading of the solid microneedle array device is performed manually), the device for manually loading the solid microneedle array device includes a grooved bottom plate 1 made of ordinary glass and a frame made of 304 stainless steel Type scraper 3; the frame scraper 3 is installed on the groove bottom plate 1, and the frame scraper 3 and the groove 2 of the groove bottom plate 1 together form a liquid storage pool4. Groove 2 has a depth of 75 μm, a width of 10 mm, and a length of 30 mm. The frame scraper 3 is a square frame with a side length of 10 mm and a height of 10 mm.
所用实心微针阵列器件6上的微针的材质采用的是单晶硅材料，阵列为6×6，阵列面积为0.25cm2，由36支微针组成，每支微针的长度为100μm，针尖的直径为100nm，针尖的最大锥角为20°。实心微针阵列器件的背部粘附于柱状基底上作为实心微针阵列器件的支持体形成实心微针阵列器件，便于取放。The material of the microneedles on the solid microneedle array device 6 used is monocrystalline silicon material, the array size is 6×6, the array area is 0.25cm 2 , it is composed of 36 microneedles, and the length of each microneedle is 100 μm. The diameter of the tip is 100 nm, and the maximum cone angle of the tip is 20°. The back of the solid microneedle array device is adhered to the columnar substrate as a support for the solid microneedle array device to form a solid microneedle array device, which is convenient for taking and placing.
药物溶液中以含有羟丙基甲基纤维素的水溶液作为增稠剂，药物溶液中羟丙基甲基纤维素的浓度为1%（w/v）；药物溶液中以荧光素钠作为模型药物，药物溶液中荧光素钠的浓度为3%（w/v）。In the drug solution, an aqueous solution containing hydroxypropyl methylcellulose is used as a thickener, and the concentration of hydroxypropyl methylcellulose in the drug solution is 1% (w/v); in the drug solution, sodium fluorescein is used as a model drug , the concentration of sodium fluorescein in the drug solution was 3% (w/v).
利用上述手动实心微针阵列器件载药的装置进行实心微针阵列器件载药：将药物溶液置于由所述的框式刮板3和所述的凹槽底板1的凹槽2共同形成的储液池4中，使所述的框式刮板与所述的凹槽底板做相对运动，在所述的凹槽底板1的凹槽2中形成一层厚度与所述的凹槽底板的凹槽的深度相同的药物溶液的薄液层5，依靠实心微针阵列器件自身的重力，将载药前的实心微针阵列器件7的每支微针的针尖置于由所述的药物溶液形成的薄液层之中，停留1秒，使所述的药物溶液吸附在所述的实心微针阵列器件的每支微针的针尖上，得到载药后的实心微针阵列器件8，从而实现实心微针阵列器件的载药。Use the above-mentioned device for loading the solid microneedle array device to carry out the drug loading of the solid microneedle array device: place the drug solution in the groove 2 jointly formed by the frame scraper 3 and the groove bottom plate 1 In the liquid storage tank 4, the frame scraper and the groove bottom plate are relatively moved to form a layer in the groove 2 of the groove bottom plate 1 whose thickness is the same as that of the groove bottom plate. The thin liquid layer 5 of the drug solution with the same depth of the groove relies on the gravity of the solid microneedle array device itself, and the needle tip of each microneedle of the solid microneedle array device 7 before loading is placed on the drug solution In the formed thin liquid layer, stay for 1 second, so that the drug solution is adsorbed on the tip of each microneedle of the solid microneedle array device to obtain the drug-loaded solid microneedle array device 8, thereby Realize the drug loading of solid microneedle array devices.
实施例2Example 2
请参见图1（采用手动的方式进行实心微针阵列器件的载药），手动实心微针阵列器件载药的装置包括采用铝板制作的凹槽底板1和采用聚四氟乙烯制作的框式刮板3；所述的框式刮板3安装于所述的凹槽底板1之上，所述的框式刮板3和所述的凹槽底板1的凹槽2共同形成一个储液池4。凹槽2的深度为300μm，宽度为14mm，长度为30mm。框式刮板3为正方形框，边长为14mm，高度为10mm。Please refer to Figure 1 (the drug loading of the solid microneedle array device is performed manually), the device for manually loading the solid microneedle array device includes a grooved bottom plate 1 made of an aluminum plate and a frame-type scraper made of polytetrafluoroethylene. Plate 3; the frame-type scraper 3 is installed on the groove bottom plate 1, and the frame-type scraper 3 and the groove 2 of the groove bottom plate 1 together form a liquid storage pool 4 . Groove 2 has a depth of 300 μm, a width of 14 mm, and a length of 30 mm. The frame scraper 3 is a square frame with a side length of 14 mm and a height of 10 mm.
所用实心微针阵列器件6上的微针的材质采用的是高分子聚乳酸材料，阵列为9×9，阵列面积为0.64cm2，由81支微针组成，每支微针的长度为500μm，针尖的直径为200nm，针尖的最大锥角为26°。实心微针阵列器件的背部粘附于柱状基底上作为实心微针阵列器件的支持体形成实心微针阵列器件，便于取放。The material of the microneedles on the used solid microneedle array device 6 is polymer polylactic acid material, the array size is 9×9, the array area is 0.64cm 2 , it is composed of 81 microneedles, and the length of each microneedle is 500 μm , the diameter of the tip is 200 nm, and the maximum cone angle of the tip is 26°. The back of the solid microneedle array device is adhered to the columnar substrate as a support for the solid microneedle array device to form a solid microneedle array device, which is convenient for taking and placing.
药物溶液中以含有羟丙基甲基纤维素的水溶液作为增稠剂，药物溶液中羟丙基甲基纤维素的浓度为5%（w/v）；药物溶液中以荧光素钠作为模型药物，药物溶液中荧光素钠的浓度为0.1%（w/v）。In the drug solution, an aqueous solution containing hydroxypropyl methylcellulose is used as a thickener, and the concentration of hydroxypropyl methylcellulose in the drug solution is 5% (w/v); in the drug solution, sodium fluorescein is used as a model drug , the concentration of sodium fluorescein in the drug solution was 0.1% (w/v).
利用上述手动实心微针阵列器件载药的装置进行实心微针阵列器件载药：将药物溶液置于由所述的框式刮板3和所述的凹槽底板1的凹槽2共同形成的储液池4中，使所述的框式刮板与所述的凹槽底板做相对运动，在所述的凹槽底板1的凹槽2中形成一层厚度与所述的凹槽底板的凹槽的深度相同的药物溶液的薄液层5，依靠实心微针阵列器件自身的重力，将载药前的实心微针阵列器件7的每支微针的针尖置于由所述的药物溶液形成的薄液层之中，停留1秒，使所述的药物溶液吸附在所述的实心微针阵列器件的每支微针的针尖上，得到载药后的实心微针阵列器件8，从而实现实心微针阵列器件的载药。Use the above-mentioned device for loading the solid microneedle array device to carry out the drug loading of the solid microneedle array device: place the drug solution in the groove 2 jointly formed by the frame scraper 3 and the groove bottom plate 1 In the liquid storage tank 4, the frame scraper and the groove bottom plate are relatively moved to form a layer in the groove 2 of the groove bottom plate 1 whose thickness is the same as that of the groove bottom plate. The thin liquid layer 5 of the drug solution with the same depth of the groove relies on the gravity of the solid microneedle array device itself, and the needle tip of each microneedle of the solid microneedle array device 7 before loading is placed on the drug solution In the formed thin liquid layer, stay for 1 second, so that the drug solution is adsorbed on the tip of each microneedle of the solid microneedle array device to obtain the drug-loaded solid microneedle array device 8, thereby Realize the drug loading of solid microneedle array devices.
实施例3.Example 3.
请参见图1（采用手动的方式进行实心微针阵列器件的载药），手动实心微针阵列器件载药的装置包括采用不锈钢板制作的凹槽底板1和采用型号为304的不锈钢制作的框式刮板3；所述的框式刮板3安装于所述的凹槽底板1之上，所述的框式刮板3和所述的凹槽底板1的凹槽2共同形成一个储液池4。凹槽2的深度为500μm，宽度为14mm，长度为30mm。凹槽的表面经亲水性处理（以HCl水溶液的体积单位为准，在室温下，将不锈钢放入由1体积质量浓度为36%的HCl水溶液、1体积质量浓度为0.5%的EDTA水溶液和2体积质量浓度为30%的H2O2组成的亲水化试剂中处理一分钟）。框式刮板3为正方形框，边长为14mm，高度为10mm。Please refer to Figure 1 (the drug loading of the solid microneedle array device is performed manually), the device for manually loading the solid microneedle array device includes a groove bottom plate 1 made of stainless steel plate and a frame made of 304 stainless steel Type scraper 3; the frame scraper 3 is installed on the groove bottom plate 1, and the frame scraper 3 and the groove 2 of the groove bottom plate 1 together form a liquid storage pool4. Groove 2 has a depth of 500 μm, a width of 14 mm, and a length of 30 mm. The surface of the groove is treated with hydrophilicity (according to the volume unit of HCl aqueous solution. 2 in a hydrophilizing reagent composed of 30% H 2 O 2 by volume and mass concentration for one minute). The frame scraper 3 is a square frame with a side length of 14 mm and a height of 10 mm.
所用实心微针阵列器件6上的微针的材质采用的是不锈钢材料，阵列为9×9，阵列面积为0.64cm2，由81支微针组成，每支微针的长度为1000μm，针尖的直径为10μm，针尖的最大锥角为60°。实心微针阵列器件的背部粘附于柱状基底上作为实心微针阵列器件的支持体形成实心微针阵列器件，便于取放。The material of the microneedles on the solid microneedle array device 6 used is stainless steel, the array size is 9×9, the array area is 0.64cm 2 , and it is composed of 81 microneedles, the length of each microneedle is 1000 μm, and the length of the needle tip is The diameter is 10 μm, and the maximum cone angle of the tip is 60°. The back of the solid microneedle array device is adhered to the columnar substrate as a support for the solid microneedle array device to form a solid microneedle array device, which is convenient for taking and placing.
药物溶液中以含有聚乙烯吡咯烷酮的水溶液作为增稠剂，药物溶液中聚乙烯吡咯烷酮的浓度为50%（w/v）；药物溶液中以荧光素钠作为模型药物，药物溶液中荧光素钠的浓度为5%（w/v）。In the drug solution, an aqueous solution containing polyvinylpyrrolidone is used as a thickener, and the concentration of polyvinylpyrrolidone in the drug solution is 50% (w/v); in the drug solution, sodium fluorescein is used as a model drug, and the concentration of sodium fluorescein in the drug solution is The concentration is 5% (w/v).
利用上述手动实心微针阵列器件载药的装置进行实心微针阵列器件载药：将药物溶液置于由所述的框式刮板3和所述的凹槽底板1的凹槽2共同形成的储液池4中，使所述的框式刮板与所述的凹槽底板做相对运动，在所述的凹槽底板1的凹槽2中形成一层厚度与所述的凹槽底板的凹槽的深度相同的药物溶液的薄液层5，依靠实心微针阵列器件自身的重力，将载药前的实心微针阵列器件7的每支微针的针尖置于由所述的药物溶液形成的薄液层之中，停留1秒，使所述的药物溶液吸附在所述的实心微针阵列器件的每支微针的针尖上，得到载药后的实心微针阵列器件8，从而实现实心微针阵列器件的载药。Carry out drug loading on solid microneedle array devices using the above-mentioned device for loading drugs on manual solid microneedle array devices: place the drug solution in the groove 2 jointly formed by the frame scraper 3 and the groove bottom plate 1 In the liquid storage tank 4, the frame-type scraper and the groove bottom plate are made to move relative to each other, and a layer of thickness equal to that of the groove bottom plate is formed in the groove 2 of the groove bottom plate 1. The thin liquid layer 5 of the drug solution having the same depth as the groove relies on the self-gravity of the solid microneedle array device to place the needle tip of each microneedle of the solid microneedle array device 7 before loading on the drug solution. In the formed thin liquid layer, stay for 1 second, so that the drug solution is adsorbed on the tip of each microneedle of the solid microneedle array device, to obtain the drug-loaded solid microneedle array device 8, thereby Realize the drug loading of solid microneedle array devices.
实施例4.Example 4.
请参见图2（采用自动化的方式进行实心微针阵列器件的载药），自动化实心微针阵列器件载药的装置包括凹槽底板1、框式刮板3、实心微针阵列器件6、实心微针阵列器件固定圆盘9、实心微针阵列器件固定帽10、转动盘11、第一步进电机12、第二步进电机13、第三步进电机14、数字控制面板15和恒温恒湿箱16。Please refer to Figure 2 (the drug loading of the solid microneedle array device is carried out in an automated way), the device for automatic drug loading of the solid microneedle array device includes a groove bottom plate 1, a frame scraper 3, a solid microneedle array device 6, a solid Microneedle array device fixing disc 9, solid microneedle array device fixing cap 10, rotating disk 11, first stepping motor 12, second stepping motor 13, third stepping motor 14, digital control panel 15 and constant temperature constant wet box 16.
在所述的恒温恒湿箱16内，所述的凹槽底板1固定于所述的恒温恒湿箱16的箱底上，所述的框式刮板3安装于所述的凹槽底板1之上，所述的框式刮板3和所述的凹槽底板1的凹槽2共同形成一个储液池4；所述的框式刮板3上安装有旋转螺杆，安装在恒温恒湿箱16内的所述的第一步进电机12的电机转轴为一旋转螺杆，所述的框式刮板3上的旋转螺杆与所述的第一步进电机12上的旋转螺杆通过旋转螺杆上的旋转螺纹相连接；所述的实心微针阵列器件固定圆盘9为一中心有孔，且外边缘带有齿轮的圆盘，所述的实心微针阵列器件固定圆盘9通过中心孔表面上的旋转螺纹与安装在一固定于恒温恒湿箱的箱底上的旋转螺杆上的旋转螺纹相连接，且所述的实心微针阵列器件固定圆盘9位于所述的凹槽底板1的斜上方；所述的实心微针阵列器件固定帽10安装在所述的实心微针阵列器件6上，所述的实心微针阵列器件固定帽10悬挂于所述的实心微针阵列器件固定圆盘上；安装在恒温恒湿箱16内的所述的第二步进电机13的电机转轴为一旋转螺杆，该旋转螺杆上的旋转螺纹与所述的实心微针阵列器件固定圆盘9的外边缘带有的齿轮相连接；安装在恒温恒湿箱16内的所述的第三步进电机14的电机转轴为一旋转螺杆，该旋转螺杆上的旋转螺纹与外边缘带有齿轮的转动盘11的齿轮相连接。In the constant temperature and humidity box 16, the groove bottom plate 1 is fixed on the bottom of the constant temperature and humidity box 16, and the frame scraper 3 is installed on the groove bottom plate 1 Above, the frame-type scraper 3 and the groove 2 of the groove bottom plate 1 jointly form a liquid storage pool 4; the frame-type scraper 3 is equipped with a rotating screw, installed in a constant temperature and humidity box The motor shaft of the first stepping motor 12 in 16 is a rotating screw, and the rotating screw on the frame scraper 3 and the rotating screw on the first stepping motor 12 pass through the rotating screw. The rotating thread of the solid microneedle array device is connected; the solid microneedle array device fixing disc 9 is a disc with a hole in the center and a gear on the outer edge, and the solid microneedle array device fixing disc 9 passes through the surface of the center hole The rotating thread on the top is connected with the rotating thread on a rotating screw fixed on the bottom of the constant temperature and humidity box, and the fixed disk 9 of the solid microneedle array device is located on the slope of the bottom plate 1 of the groove. Above: the solid microneedle array device fixing cap 10 is installed on the solid microneedle array device 6, and the solid microneedle array device fixing cap 10 is suspended from the solid microneedle array device fixing disc On the top; the motor shaft of the second stepping motor 13 installed in the constant temperature and humidity box 16 is a rotating screw, and the rotating thread on the rotating screw is connected with the outer surface of the fixed disk 9 of the solid microneedle array device. The gear on the edge is connected; the motor shaft of the third stepping motor 14 installed in the constant temperature and humidity box 16 is a rotating screw, and the rotating thread on the rotating screw is connected with the rotating disk with gears on the outer edge. 11 gears are connected.
所述的第二步进电机13、第三步进电机14可固定在一金属板上，该金属板固定在所述的恒温恒湿箱16的箱壁上；所述的恒温恒湿箱16外安装有用于所述的第一步进电机12、所述的第二步进电机13和所述的第三步进电机14进行工作状态控制的所述的数字控制面板15。Described second stepping motor 13, the 3rd stepping motor 14 can be fixed on a metal plate, and this metal plate is fixed on the case wall of described constant temperature and humidity box 16; Described constant temperature and humidity box 16 The digital control panel 15 for controlling the working state of the first stepper motor 12 , the second stepper motor 13 and the third stepper motor 14 is installed outside.
所述的凹槽底板1和所述的框式刮板3均采用不锈钢板制作。Both the groove bottom plate 1 and the frame scraper 3 are made of stainless steel plates.
所述的凹槽2的深度为100μm，宽度为10mm，长度为30mm。凹槽的表面经亲水性处理（以HCl水溶液的体积单位为准，在室温下，将不锈钢放入由1体积质量浓度为36%的HCl水溶液、1体积质量浓度为0.5%的EDTA水溶液和2体积质量浓度为30%的H2O2组成的亲水化试剂中处理一分钟）。框式刮板3为正方形框，边长为10mm，高度为10mm。The groove 2 has a depth of 100 μm, a width of 10 mm, and a length of 30 mm. The surface of the groove is treated with hydrophilicity (according to the volume unit of HCl aqueous solution. 2 in a hydrophilizing reagent composed of 30% H 2 O 2 by volume and mass concentration for one minute). The frame scraper 3 is a square frame with a side length of 10 mm and a height of 10 mm.
所用实心微针阵列器件6上的微针的材质采用的是单晶硅材料，阵列为6×6，阵列面积为0.25cm2，由36支微针组成，每支微针的长度为260μm，针尖的直径为2μm，针尖的最大锥角为26°。实心微针阵列器件的背部粘附于柱状基底上作为实心微针阵列器件的支持体形成实心微针阵列器件，便于取放。The material of the microneedles on the solid microneedle array device 6 used is monocrystalline silicon material, the array size is 6×6, the array area is 0.25cm 2 , it is composed of 36 microneedles, and the length of each microneedle is 260 μm. The diameter of the needle tip is 2 μm, and the maximum cone angle of the needle tip is 26°. The back of the solid microneedle array device is adhered to the columnar substrate as a support for the solid microneedle array device to form a solid microneedle array device, which is convenient for taking and placing.
药物溶液中以含有羧甲基纤维素钠的水溶液作为增稠剂，药物溶液中羧甲基纤维素钠的浓度为1%（w/v）；药物溶液中以左旋肉碱作为模型药物，药物溶液中左旋肉碱的浓度为50%（w/v）。In the drug solution, an aqueous solution containing sodium carboxymethyl cellulose is used as a thickener, and the concentration of sodium carboxymethyl cellulose in the drug solution is 1% (w/v); in the drug solution, L-carnitine is used as a model drug, and the drug The concentration of L-carnitine in the solution was 50% (w/v).
利用上述自动化实心微针阵列器件载药的装置实现实心微针阵列器件载药的方法为：将一一对应连接在10个实心微针阵列器件固定帽10上的10支实心微针阵列器件6悬挂于实心微针阵列器件固定圆盘上；在所述的实心微针阵列器件固定圆盘9上安装上所述的10个实心微针阵列器件6，将药物溶液置于由框式刮板3和凹槽底板1的凹槽2共同形成的储液池4中，关上恒温恒湿箱16的箱体门后，接通电源，调节所需的温度和湿度，通过数字控制面板15，调出载药程序，点击自动运行进行自动化实心微针阵列器件的载药；通过第一步进电机12带动所述的框式刮板3向左或右进行运动到最左端或最右端，然后返回到初始位置，在所述的凹槽底板1的凹槽2中形成一层厚度与所述的凹槽底板的凹槽的深度相同的药物溶液的薄液层5；通过第二步进电机13带动所述的实心微针阵列器件固定圆盘做向下运动，让正对着所述的薄液层上方的所述的实心微针阵列器件缓慢下降到所述的薄液层上，依靠实心微针阵列器件自身的重力，将第一支实心微针阵列器件的针尖置于由所述的药物溶液形成的薄液层之中停留1秒，使所述的药物溶液吸附在所述的第一支实心微针阵列器件的针尖上，从而实现第一支实心微针阵列器件的载药；然后再通过第二步进电机带动所述的实心微针阵列器件固定圆盘做向上运动回到初始位置，并使转动盘11的齿轮与实心微针阵列器件固定圆盘9的齿轮相连接；通过第三步进电机14带动转动盘11，使所述的实心微针阵列器件固定圆盘做顺时针或逆时针旋转（转动盘11的齿轮与实心微针阵列器件固定圆盘9的齿轮相连接，从而实现第三步进电机14对实心微针阵列器件固定圆盘的控制），使下一支所述的实心微针阵列器件位于所述的薄液层上方，实现所述的实心微针阵列器件之间的切换；然后重复开始进行自动化实心微针阵列器件的载药操作，直至使安装在所述的实心微针阵列器件固定圆盘上的10支所述的实心微针阵列器件都载药完成为止。该装置能够通过所述的第一步进电机12、所述的第二步进电机13和所述的第三步进电机14及程序实现实心微针阵列器件的载药，提高载药的精密度与准确度，并能够实现批量载药。The method of realizing the drug loading of the solid microneedle array device by using the above-mentioned automatic solid microneedle array device drug loading device is as follows: connect 10 solid microneedle array devices 6 on the 10 solid microneedle array device fixing caps 10 one by one Suspended on the solid microneedle array device fixed disk; on the solid microneedle array device fixed disk 9, the 10 solid microneedle array devices 6 described above are installed, and the drug solution is placed on the frame-type scraper 3 and the groove 2 of the groove bottom plate 1 form the liquid reservoir 4 together, after closing the cabinet door of the constant temperature and humidity box 16, turn on the power, adjust the required temperature and humidity, and adjust the temperature and humidity through the digital control panel 15. Exit the drug loading program, click Auto Run to load the drug of the automated solid microneedle array device; drive the frame scraper 3 to the left or right through the first stepping motor 12 to move to the leftmost or rightmost end, and then return To initial position, in the groove 2 of described groove bottom plate 1, form the thin liquid layer 5 of the drug solution identical with the depth of the groove of described groove bottom plate; Drive the fixed disc of the solid microneedle array device to move downward, so that the solid microneedle array device facing above the thin liquid layer slowly descends to the thin liquid layer, relying on the solid Due to the gravity of the microneedle array device itself, the needle tip of the first solid microneedle array device is placed in the thin liquid layer formed by the drug solution for 1 second, so that the drug solution is adsorbed on the first solid microneedle array device. on the needle tip of a solid microneedle array device, so as to realize the drug loading of the first solid microneedle array device; initial position, and the gear of the rotating disk 11 is connected with the gear of the fixed disk 9 of the solid microneedle array device; the rotating disk 11 is driven by the third stepping motor 14, so that the fixed disk of the solid microneedle array device is made Rotate clockwise or counterclockwise (the gear of the rotating disk 11 is connected with the gear of the fixed disk 9 of the solid microneedle array device, thereby realizing the control of the third stepping motor 14 on the fixed disk of the solid microneedle array device), so that the next One of the solid microneedle array devices is located above the thin liquid layer to realize switching between the solid microneedle array devices; then repeat the drug loading operation of the automated solid microneedle array device until the The 10 solid microneedle array devices installed on the fixed disk of the solid microneedle array device are all loaded with medicine. The device can realize the drug loading of the solid microneedle array device through the first stepping motor 12, the second stepping motor 13 and the third stepping motor 14 and the program, and improve the precision of drug loading. Accuracy and accuracy, and can achieve batch drug loading.
所述的第一步进电机12、所述的第二步进电机13和所述的第三步进电机14的工作状态的控制，是通过所述的数字控制面板15发出的指令进行控制。The control of the working states of the first stepping motor 12 , the second stepping motor 13 and the third stepping motor 14 is controlled by instructions sent by the digital control panel 15 .
实施例5.Example 5.
采用自动化的方式进行实心微针阵列器件的载药，自动化实心微针阵列器件载药的装置基本同实施例4，不同之处是：所述的凹槽底板1和所述的框式刮板3均采用锌板制作。所述的凹槽2的深度为75μm，宽度为14mm，长度为30mm。框式刮板3为正方形框，边长为14mm，高度为10mm。所用实心微针阵列器件6上的微针的材质采用的是单晶硅材料，阵列为11×11，阵列面积为1cm2，由121支微针组成，每支微针的长度为150μm，针尖的直径为2μm，针尖的最大锥角为38°。实心微针阵列器件的背部粘附于柱状基底上作为实心微针阵列器件的支持体形成实心微针阵列器件，便于取放。The drug loading of the solid microneedle array device is carried out in an automated manner, and the drug loading device of the automated solid microneedle array device is basically the same as that of Example 4, the difference is: the groove bottom plate 1 and the frame scraper 3 are made of zinc plate. The groove 2 has a depth of 75 μm, a width of 14 mm, and a length of 30 mm. The frame scraper 3 is a square frame with a side length of 14 mm and a height of 10 mm. The material of the microneedles on the used solid microneedle array device 6 is monocrystalline silicon material, the array size is 11×11, the array area is 1cm 2 , and it is composed of 121 microneedles, the length of each microneedle is 150 μm, and the needle tip The diameter of the needle is 2 μm, and the maximum cone angle of the needle tip is 38°. The back of the solid microneedle array device is adhered to the columnar substrate as a support for the solid microneedle array device to form a solid microneedle array device, which is convenient for taking and placing.
药物溶液中以含有羧甲基纤维素钠的水溶液作为增稠剂，药物溶液中羧甲基纤维素钠的浓度为4%（w/v）；药物溶液中以干扰素作为模型药物，药物溶液中干扰素的浓度为1%（w/v）。In the drug solution, an aqueous solution containing sodium carboxymethyl cellulose is used as a thickener, and the concentration of sodium carboxymethyl cellulose in the drug solution is 4% (w/v); in the drug solution, interferon is used as a model drug, and the drug solution The concentration of interferon in the medium was 1% (w/v).
利用上述自动化实心微针阵列器件载药的装置实现实心微针阵列器件载药的方法同实施例4。The method of realizing the drug loading of the solid microneedle array device by using the above-mentioned automatic drug loading device for the solid microneedle array device is the same as that in Example 4.
实施例6.Example 6.
采用自动化的方式进行实心微针阵列器件的载药，自动化实心微针阵列器件载药的装置基本同实施例4，不同之处是：所述的凹槽2的深度为500μm，宽度为14mm，长度为30mm。框式刮板3为正方形框，边长为14mm，高度为10mm。所用实心微针阵列器件6上的微针的材质采用的是聚乳酸材料，阵列为9×9，阵列面积为0.64cm2，由81支微针组成，每支微针的长度为1000μm，针尖的直径为2μm，针尖的最大锥角为38°。实心微针阵列器件的背部粘附于柱状基底上作为实心微针阵列器件的支持体形成实心微针阵列器件，便于取放。The drug loading of the solid microneedle array device is carried out in an automated manner, and the drug loading device of the automated solid microneedle array device is basically the same as that of Example 4, except that the groove 2 has a depth of 500 μm and a width of 14 mm. The length is 30mm. The frame scraper 3 is a square frame with a side length of 14 mm and a height of 10 mm. The material of the microneedles on the used solid microneedle array device 6 is polylactic acid material, the array size is 9×9, the array area is 0.64cm 2 , it is composed of 81 microneedles, the length of each microneedle is 1000 μm, and the needle tip The diameter of the needle is 2 μm, and the maximum cone angle of the needle tip is 38°. The back of the solid microneedle array device is adhered to the columnar substrate as a support for the solid microneedle array device to form a solid microneedle array device, which is convenient for taking and placing.
药物溶液中以含有海藻酸钠的水溶液作为增稠剂，药物溶液中海藻酸钠的浓度为10%（w/v）；药物溶液中以核黄素作为模型药物，药物溶液中核黄素的浓度为3%（w/v）。In the drug solution, an aqueous solution containing sodium alginate is used as a thickener, and the concentration of sodium alginate in the drug solution is 10% (w/v); in the drug solution, riboflavin is used as a model drug, and the concentration of riboflavin in the drug solution is 3% (w/v).
利用上述自动化实心微针阵列器件载药的装置实现实心微针阵列器件载药的方法同实施例4。The method of realizing the drug loading of the solid microneedle array device by using the above-mentioned automatic drug loading device for the solid microneedle array device is the same as that in Example 4.
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Effective date of registration: 20181227 Address after: Room 1103, Building No. 22, Tianrong Street, Daxing Biomedical Industry Base, Zhongguancun Science and Technology Park, Daxing District, Beijing 102600 Patentee after: ZHONGKE WEIZHEN (BEIJING) TECHNOLOGY Co.,Ltd. Address before: No. 29 East Zhongguancun Road, Haidian District, Beijing 100190 Patentee before: Technical Institute of Physics and Chemistry Chinese Academy of Sciences |