CN101254326A - Preparation of micro-needle array injection syringe - Google Patents

Abstract

The invention discloses a method for preparing a micro-needle array syringe, and belongs to the field of biomedical apparatus. The method takes a micron and sub-micron solid micro-needle array as a template, and uses the imprinting and pulling modes for preparing the hollow high-quality polymer micro-needle array syringe with adjustable length. The preparation method has the advantages of cheap price, no need of complicated devices and technologies, mass rapid production, etc. The technology is applicable to the industrial production, the micro-needle array syringe with high-quality and cheap-price can be industrially produced, so the expensive transdermal drug delivery technology in the biomedical field can go to the mass market by the low cost of the micro-needle array syringe.

Description

Translated fromChinese

微针阵列注射器的制备方法Preparation method of microneedle array syringe

技术领域technical field

本发明涉及一种纳米和微米微结构材料的制备方法，特别是一种微针阵列注射器的制备方法。The invention relates to a preparation method of nanometer and micron microstructure materials, in particular to a preparation method of a microneedle array injector.

背景技术Background technique

随着新型药物的出现、对人体舒适度和药物可控释放的更高要求，近年来一种新的给药途径----透皮给药开始进入临床应用。透皮给药是指突破皮肤表面角质层阻碍作用的皮肤表面给药方式，药物由皮肤吸收进入全身血液循环并达到有效血药浓度实现疾病治疗或预防。透皮给药的优势很明显：克服了口服给药对胃肠道的刺激以及肝脏、胃肠道的首过作用效应；克服了其对皮肤伤害引起疼痛的缺点；克服了经皮给药速率慢的缺点。同时不会给皮肤造成创伤，特别是不会带来疼痛感，因此可以改善病人的适应性；释药平稳，可长时间维持恒定的有效血药浓度，避免峰谷现象，减少药物的毒副作用，可长时间给药以提高疗效；安全性高，出现副作用时可随时终止给药。With the emergence of new drugs and higher requirements for human comfort and controlled release of drugs, a new route of drug delivery - transdermal drug delivery has begun to enter clinical application in recent years. Transdermal drug delivery refers to a skin surface drug delivery method that breaks through the barrier effect of the stratum corneum on the skin surface. Drugs are absorbed from the skin into the blood circulation of the whole body and reach effective blood drug concentrations to achieve disease treatment or prevention. The advantages of transdermal administration are obvious: it overcomes the stimulation of oral administration to the gastrointestinal tract and the first-pass effect of the liver and gastrointestinal tract; it overcomes the disadvantage of causing pain to the skin; it overcomes the speed of transdermal administration The downside of being slow. At the same time, it will not cause trauma to the skin, especially it will not cause pain, so it can improve the patient's adaptability; the drug release is stable, and it can maintain a constant effective blood drug concentration for a long time, avoiding the peak and valley phenomenon, and reducing the toxic and side effects of the drug. , it can be administered for a long time to improve the curative effect; it has high safety, and the administration can be terminated at any time when side effects occur.

透皮给药的关键是如何使药物突破皮肤角质层。由于空心微针阵列透皮给药对药物几乎没有限制，并且在普通透皮给药优点的基础上，具有自己独特的优势：可以传输高分子、超分子甚至微粒药物；可任意控制药物的传输速率；对所传输的药物无特殊要求；可长时间连续恒定速率给药；可双向液体交换，不仅可透过皮肤角质层给药，也可抽取组织液。因此除可用作常规无痛给药外，在一些特殊的领域更具优势，如胰岛素的长期给药、现代生物科技合成的高分子蛋白质的输运、药物微胶囊的人体介入、预防疫苗接种等等。对需要长期稳定给药的人群和打针怕疼的儿童尤其适用，具有很大的市场潜力。The key to transdermal drug delivery is how to make the drug break through the stratum corneum of the skin. Because the hollow microneedle array transdermal drug delivery has almost no restrictions on drugs, and on the basis of the advantages of ordinary transdermal drug delivery, it has its own unique advantages: it can transport polymer, supramolecular and even particle drugs; the delivery of drugs can be controlled arbitrarily Speed; no special requirements for the drug to be transported; long-term continuous administration at a constant rate; two-way liquid exchange, not only can be administered through the stratum corneum of the skin, but also can extract interstitial fluid. Therefore, in addition to being used for routine painless administration, it has advantages in some special fields, such as long-term administration of insulin, transport of high molecular protein synthesized by modern biotechnology, human intervention of drug microcapsules, and preventive vaccination. etc. It is especially suitable for people who need long-term stable drug administration and children who are afraid of pain from injections, and has great market potential.

目前实心微针的制备方法多采用依靠半导体微加工技术直接制备，如反应离子束刻蚀(RIE)、聚焦离子束刻蚀(FIB)等，但实心微针的成本可以通过微铸造等方法大规模复制而降低。空心微针的性能远超实心微针，但其制备却困难得多。目前空心微针也主要依靠三维微细加工技术(LIGA)、反应离子束刻蚀(RIE)、感应耦合等离子刻蚀(ICP)等微加工技术直接制备，但难以象实心微针一样大规模复制，制造成本居高不下。而且，为了预防感染、玷污等，注射器通常需要一次性使用，其使用成本也很高昂。因此，空心微针阵列给药方式迄今没有进入普通大众消费人群，目前仅在一些特殊行业应用，如美容业等。另外，目前制备的空心微针阵列所选用的材料基本为硅等适合微加工的半导体材料。这些材料的典型特点是硬而脆，极细的微针容易在皮肤内折断。考虑到力学要求，结合生物相容性，高分子无疑是较好的微针阵列材料。At present, solid microneedles are mostly prepared directly by semiconductor micromachining techniques, such as reactive ion beam etching (RIE), focused ion beam etching (FIB), etc., but the cost of solid microneedles can be greatly reduced by microcasting and other methods. Reduced by scale replication. The performance of hollow microneedles far exceeds that of solid microneedles, but their preparation is much more difficult. At present, hollow microneedles are mainly prepared directly by microfabrication techniques such as three-dimensional microfabrication technology (LIGA), reactive ion beam etching (RIE), inductively coupled plasma etching (ICP), but it is difficult to reproduce them on a large scale like solid microneedles. Manufacturing costs remain high. Moreover, in order to prevent infection, contamination, etc., the syringe is usually required to be used only once, and its use cost is also very high. Therefore, the hollow microneedle array drug delivery method has not entered the general public consumer group so far, and is currently only used in some special industries, such as the beauty industry. In addition, the materials selected for the currently prepared hollow microneedle arrays are basically silicon and other semiconductor materials suitable for microprocessing. These materials are typically hard and brittle, with extremely fine microneedles breaking easily within the skin. Considering the mechanical requirements and biocompatibility, polymers are undoubtedly better materials for microneedle arrays.

为了使集成诸多优点的空心微针阵列透皮给药方式走近大众，其成本必须降到普通医用一次性注射器的成本之下。因此，需要开发适合于企业批量生产的新的制备技术，获得廉价、实用的空心微针阵列注射器。In order to make the hollow microneedle array transdermal drug delivery method integrating many advantages approach the public, its cost must be reduced below the cost of ordinary medical disposable syringes. Therefore, it is necessary to develop a new preparation technology suitable for mass production in enterprises to obtain cheap and practical hollow microneedle array syringes.

发明内容Contents of the invention

发明目的：本发明的目的是提供一种工艺简单、适合于工业化生产的微米和亚微米微针阵列注射器的制备方法。Purpose of the invention: The purpose of the present invention is to provide a method for preparing micron and submicron microneedle array syringes with simple process and suitable for industrial production.

技术方案：本发明通过两种方法制备所述的微针阵列注射器。Technical solution: the present invention prepares the microneedle array syringe through two methods.

第一种方法包括以下步骤：The first method involves the following steps:

(1)对聚合物I进行表面功能化处理，在表面获得1nm～500μm厚度的膜层；(1) Carry out surface functionalization treatment to polymer I, and obtain a film layer with a thickness of 1 nm to 500 μm on the surface;

(2)在聚合物I表面制备10～500μm厚度的聚合物材料II；(2) preparing polymer material II with a thickness of 10-500 μm on the surface of polymer I;

(3)利用加温或溶剂处理聚合物材料I和II；(3) Treat polymer materials I and II with heating or solvent;

(4)调控压入速率及深度将实心微针阵列利用辊子滚压或直接压入聚合物材料I和II；(4) Regulate the pressing speed and depth to roll the solid microneedle arrays into the polymer materials I and II with rollers or directly;

(5)剥离微针，去除聚合物II后，即得聚合物I的空心微针阵列；(5) peeling off the microneedles and removing polymer II to obtain a hollow microneedle array of polymer I;

(6)将空心微针阵列制成贴片式或针筒式微针阵列注射器。(6) Make the hollow microneedle array into a patch-type or syringe-type microneedle array injector.

第二种方法包括以下步骤：The second method involves the following steps:

(7)对聚合物I进行表面功能化处理，在表面获得1nm～500μm厚度的膜层；(7) Carrying out surface functionalization treatment to the polymer I, obtaining a film layer with a thickness of 1 nm to 500 μm on the surface;

(8)在聚合物I表面制备10～500μm厚度的聚合物材料II；(8) preparing polymer material II with a thickness of 10-500 μm on the surface of polymer I;

(9)利用加温或溶剂处理聚合物材料I和II；(9) treating polymer materials I and II by heating or solvent;

(10)在一定温度或溶剂处理条件下将实心微针阵列以合适速率压入聚合物材料I和II；(10) Pressing the solid microneedle array into polymer materials I and II at a suitable rate under certain temperature or solvent treatment conditions;

(11)在一定温度或溶剂环境下以合适速率提拉微针；(11) Pulling the microneedle at an appropriate rate under a certain temperature or solvent environment;

(12)取出微针，去除聚合物II后，即得聚合物I的空心微针阵列；(12) Take out the microneedles and remove the polymer II to obtain the hollow microneedle array of the polymer I;

(13)将空心微针阵列制成贴片式或针筒式微针阵列注射器。(13) Make the hollow microneedle array into a patch type or syringe type microneedle array injector.

在步骤(1)和(7)中，所说的聚合物I为天然高分子材料，或合成高分子材料，或者以上材料的组合；聚合物II为天然高分子材料，或合成高分子材料，或者以上材料的组合；所说的表面功能化处理的方法为涂覆，或溅射，或化学镀，或电镀，或PVD，或CVD，或以上方法任意组合；所用材料为金属、无机物或有机物及其任意组合。In steps (1) and (7), said polymer I is a natural polymer material, or a synthetic polymer material, or a combination of the above materials; polymer II is a natural polymer material, or a synthetic polymer material, Or a combination of the above materials; the method of surface functionalization treatment is coating, or sputtering, or electroless plating, or electroplating, or PVD, or CVD, or any combination of the above methods; the materials used are metal, inorganic or Organic matter and any combination thereof.

在步骤(2)和(8)中，所说的聚合物II为天然高分子材料，或合成高分子材料，或者以上材料的组合；所说在聚合物I表面制备聚合物II的方法为旋涂，或拉膜，或贴膜，或喷涂，或以上方法任意组合。In steps (2) and (8), said polymer II is a natural polymer material, or a synthetic polymer material, or a combination of the above materials; said method for preparing polymer II on the surface of polymer I is spin Coating, or pulling film, or sticking film, or spraying, or any combination of the above methods.

在步骤(3)和(9)中，所说的温度为高于被处理聚合物软化点的温度0～100℃，时间为0.1min～24h；溶剂为CHCl₃、CHCl₂、丙酮、甲苯、苯、四氢呋喃等溶剂或其任意组合，处理时间为0.1min～12h。In steps (3) and (9), the temperature is 0-100°C higher than the softening point of the treated polymer, and the time is 0.1min-24h; the solvent is CHCl₃ , CHCl₂ , acetone, toluene, Solvents such as benzene, tetrahydrofuran or any combination thereof, the treatment time is 0.1min to 12h.

在步骤(4)中，所说的压入速率为0.01～100cm/s；压入深度为1～2000μm。In step (4), the indentation rate is 0.01-100 cm/s; the indentation depth is 1-2000 μm.

在步骤(10)、(11)中，所说的温度为30～200℃，时间为0.1min～24h；溶剂为CHCl₃、CHCl₂、丙酮、甲苯、苯、四氢呋喃等溶剂中的一种或几种，处理时间为0.1min～12h；所说的提拉速率为0.01cm/s～100m/s；提拉高度为10μm～1cm。In steps (10) and (11), the temperature is 30-200°C, and the time is 0.1min-24h; the solvent is one of CHCl₃ , CHCl₂ , acetone, toluene, benzene, tetrahydrofuran, etc. or Several types, the treatment time is 0.1min~12h; the said pulling rate is 0.01cm/s~100m/s; the pulling height is 10μm~1cm.

有益效果：本发明与现有技术相比，具有以下突出优点：Beneficial effect: compared with the prior art, the present invention has the following outstanding advantages:

1、极大地降低了微针阵列注射器的制备成本。1. The preparation cost of the microneedle array syringe is greatly reduced.

2、不需微加工等昂贵复杂技术和设备。2. No need for expensive and complex techniques and equipment such as micromachining.

3、工艺简单，对场地环境无特别要求。3. The process is simple and there is no special requirement for the site environment.

4、操作简单，制备周期短。4. Simple operation and short preparation period.

5、适合于工业化生产。5. Suitable for industrial production.

附图说明Description of drawings

附图是本发明的制备过程的示意图。其中(a)-(d)表示方法1的制备过程：(a)实心微针阵列压入聚合物基体；(b)压入后实心微针表面形成聚合物包层；(c)去除实心微针阵列形成聚合物空心微针阵列；(d)获得空心微针阵列注射器。(e)-(h)表示方法2的制备过程：(e)实心微针阵列压入聚合物基体；(f)提拉实心微针形成聚合物管状结构；(g)去除实心微针阵列形成聚合物空心微针阵列；(h)获得空心微针阵列注射器。Accompanying drawing is the schematic diagram of the preparation process of the present invention. Among them, (a)-(d) represent the preparation process of method 1: (a) the solid microneedle array is pressed into the polymer matrix; (b) the polymer cladding is formed on the surface of the solid microneedle after pressing in; (c) the solid microneedle array is removed. The needle array forms a polymer hollow microneedle array; (d) obtains a hollow microneedle array syringe. (e)-(h) represent the preparation process of method 2: (e) the solid microneedle array is pressed into the polymer matrix; (f) the solid microneedle is pulled to form a polymer tubular structure; (g) the solid microneedle array is removed to form Polymer hollow microneedle array; (h) obtaining a hollow microneedle array syringe.

具体实施方式Detailed ways

本发明所述的一种微针阵列注射器的工业化制备方法，包括聚合物材料表面处理工艺与参数的确定；压印与提拉参数的确定；微针阵列针头与注射器结合参数的确定等。The industrial preparation method of a microneedle array syringe according to the present invention includes the determination of the polymer material surface treatment process and parameters; the determination of embossing and pulling parameters; the determination of the combination parameters of the microneedle array needle and the syringe, etc.

实施例1：在PMMA表面旋涂50微米厚度的石蜡层作为功能化膜层，然后再贴附400μm厚度的PMMA，置于100℃烘箱中热处理30min，然后以50cm/s的速率将二氧化硅实心微针压入，深度为700μm，冷却，将微针拔出，然后将上下两层PMMA剥离，即得PMMA的空心微针阵列。然后将微针阵列粘结在一次性注射器端部，即形成针筒式微针阵列注射器。Example 1: Spin-coat a 50-micron-thick paraffin layer on the PMMA surface as a functional film layer, then attach 400-micron-thick PMMA, place it in a 100°C oven for heat treatment for 30min, and then place the silicon dioxide at a rate of 50cm/s The solid microneedles are pressed in to a depth of 700 μm, cooled, the microneedles are pulled out, and then the upper and lower layers of PMMA are peeled off to obtain a PMMA hollow microneedle array. Then, the microneedle array is bonded to the end of the disposable syringe to form a syringe type microneedle array syringe.

实施例2：在PMMA表面旋涂50微米厚度的石蜡层作为功能化膜层，然后再旋涂300μm厚度的聚苯乙烯，在CHCl₃蒸汽中处理20min，然后以30cm/s的速率将二氧化硅实心微针压入，深度为600μm，冷却，将实心微针拔出，然后将上下两层聚合物剥离，即得聚苯乙烯的空心微针阵列。然后将微针阵列粘结在一次性注射器端部，即形成针筒式微针阵列注射器。Embodiment 2: spin-coat the paraffin layer of 50 micron thickness on PMMA surface as the functional film layer, then spin-coat the polystyrene of 300 μm thickness, in CHCl₃ process 20min in vapor, then with the speed of 30cm/s the carbon dioxide Silicon solid microneedles were pressed in to a depth of 600 μm, cooled, the solid microneedles were pulled out, and then the upper and lower layers of polymer were peeled off to obtain a polystyrene hollow microneedle array. Then, the microneedle array is bonded to the end of the disposable syringe to form a syringe type microneedle array syringe.

实施例3：在PDMS表面溅射100纳米厚度的金层作为功能化膜层，然后再旋涂300μm厚度的PMMA，置于90℃烘箱中热处理20min，然后以0.1cm/s的速率将硅实心微针压入，深度为600μm，冷却，将实心微针拔出，然后将上下两层聚合物剥离，即得聚苯乙烯的空心微针阵列。然后将微针阵列热熔在一次性注射器端部，即形成针筒式微针阵列注射器。Embodiment 3: A gold layer with a thickness of 100 nanometers is sputtered on the PDMS surface as a functional film layer, and then PMMA with a thickness of 300 μm is spin-coated, placed in a 90° C. The microneedles are pressed in to a depth of 600 μm, cooled, the solid microneedles are pulled out, and then the upper and lower layers of polymer are peeled off to obtain a polystyrene hollow microneedle array. Then the microneedle array is thermally fused on the end of the disposable syringe to form a syringe type microneedle array syringe.

实施例4：在PDMS表面旋涂5微米厚度的聚乙烯醇作为功能化膜层，然后再旋涂200μm厚度的PMMA，置于140℃烘箱中热处理20min，然后以1cm/s的速率将二氧化硅实心微针压入，深度为400μm，接着以10m/s的速率将二氧化硅实心微针提拉300μm，冷却，将微针拔出，然后将其置于水中使上下两层PMMA剥离，即得PMMA的空心微针阵列。然后将微针阵列粘结在一次性注射器端部，即形成针筒式微针阵列注射器。Example 4: Spin-coat polyvinyl alcohol with a thickness of 5 microns on the surface of PDMS as a functional film layer, then spin-coat PMMA with a thickness of 200 μm, place it in a 140°C oven for heat treatment for 20min, and then oxidize the polyvinyl alcohol at a rate of 1cm/s. The silicon solid microneedle is pressed in with a depth of 400 μm, then the silicon dioxide solid microneedle is pulled 300 μm at a rate of 10 m/s, cooled, the microneedle is pulled out, and then placed in water to peel off the upper and lower layers of PMMA, That is, the hollow microneedle array of PMMA is obtained. Then, the microneedle array is bonded to the end of the disposable syringe to form a syringe type microneedle array syringe.

实施例5：在PDMS表面旋涂5微米厚度的聚乙烯醇作为功能化膜层，然后再旋涂300μm厚度的聚苯乙烯，置于CHCl₂蒸汽中处理20min，然后以30cm/s的速率将二氧化硅实心微针压入，深度为600μm，接着以50m/s的速率将二氧化硅实心微针提拉500μm，冷却，将实心微针拔出，然后将上下两层聚合物剥离，即得聚苯乙烯的空心微针阵列。然后将微针阵列封装在聚合物薄膜上，即形成贴片式微针阵列注射器。Embodiment 5: Spin-coat polyvinyl alcohol with a thickness of 5 microns on the surface of PDMS as a functionalized film layer, then spin-coat polystyrene with a thickness of 300 μm, place_CHCl in vapor and process it for 20min, then with a speed of 30cm/s The silicon dioxide solid microneedle is pressed in with a depth of 600 μm, then the silicon dioxide solid microneedle is pulled 500 μm at a rate of 50 m/s, cooled, the solid microneedle is pulled out, and then the upper and lower layers of polymer are peeled off, that is A polystyrene hollow microneedle array was obtained. Then the microneedle array is packaged on the polymer film, that is, a patch type microneedle array injector is formed.

实施例6：在PDMS表面溅射100纳米厚度的金层作为功能化膜层，然后再旋涂300μm厚度的PMMA，置于90℃烘箱中热处理20min，然后以0.1cm/s的速率将硅实心微针压入，深度为500μm，接着以10m/s的速率将二氧化硅实心微针提拉1000μm，冷却，将实心微针拔出，然后将上下两层聚合物剥离，即得聚苯乙烯的空心微针阵列。然后将微针阵列封装在聚合物薄膜上，即形成贴片式微针阵列注射器。Embodiment 6: A gold layer with a thickness of 100 nanometers is sputtered on the surface of PDMS as a functional film layer, and then PMMA with a thickness of 300 μm is spin-coated, placed in a 90° C. The microneedle is pressed in with a depth of 500 μm, then the silica solid microneedle is pulled 1000 μm at a rate of 10 m/s, cooled, the solid microneedle is pulled out, and then the upper and lower layers of polymer are peeled off to obtain polystyrene hollow microneedle arrays. Then the microneedle array is packaged on the polymer film, that is, a patch type microneedle array injector is formed.

实施例7：在PMMA表面旋涂10微米厚度的石蜡层作为功能化膜层，然后再旋涂300μm厚度的PMMA，置于130℃烘箱中热处理30min，然后以50cm/s的速率将附着二氧化硅实心微针的辊子滚动压过，冷却后将上下两层PMMA剥离，即得PMMA的空心微针阵列。然后将微针阵列粘结在一次性注射器端部，即形成针筒式微针阵列注射器。Example 7: Spin-coat a 10-micron-thick paraffin layer on the PMMA surface as a functional film layer, then spin-coat PMMA with a thickness of 300 μm, place it in a 130°C oven for heat treatment for 30min, and then adhere to the carbon dioxide at a rate of 50cm/s. A roller of silicon solid microneedles is rolled and pressed, and after cooling, the upper and lower layers of PMMA are peeled off to obtain a PMMA hollow microneedle array. Then, the microneedle array is bonded to the end of the disposable syringe to form a syringe type microneedle array syringe.

实施例8：在PMMA表面旋涂50微米厚度的石蜡层作为功能化膜层，然后再旋涂300μm厚度的聚苯乙烯，在甲苯和丙酮(体积比1∶1)混合蒸汽中处理30min，然后以30cm/s的速率将附着金属实心微针的辊子滚动压过，冷却后将上下两层聚合物剥离，即得聚苯乙烯的空心微针阵列。然后将微针阵列封装在聚合物薄膜上，即形成贴片式微针阵列注射器。Embodiment 8: spin-coat the paraffin layer of 50 micron thickness on the PMMA surface as functional film layer, then spin-coat the polystyrene of 300 μm thickness, process 30min in toluene and acetone (volume ratio 1: 1) mixed steam, then At a speed of 30cm/s, the roller with metal solid microneedles is rolled over, and after cooling, the upper and lower layers of polymer are peeled off to obtain a polystyrene hollow microneedle array. Then the microneedle array is packaged on the polymer film to form a patch type microneedle array injector.

实施例9：基本步骤同于实施例1，所不同的是贴附PMMA的厚度为200um。Embodiment 9: The basic steps are the same as in Embodiment 1, except that the thickness of the attached PMMA is 200um.

实施例10：基本步骤同于实施例1，所不同的是压入深度为500um。Embodiment 10: The basic steps are the same as in Embodiment 1, except that the indentation depth is 500um.

实施例11：基本步骤同于实施例1，所不同的是压入速率为50cm/s。Embodiment 11: The basic steps are the same as in Embodiment 1, except that the indentation speed is 50 cm/s.

实施例12：基本步骤同于实施例1，所不同的是热处理温度为140℃。Example 12: The basic steps are the same as in Example 1, except that the heat treatment temperature is 140°C.

Claims (8)

1, a kind of preparation method of micro-needle array injection syringe is characterized in that this method may further comprise the steps:

(1) polymeric material I is carried out surface-functionalized processing, obtain the rete of 1nm～500 μ m thickness on the surface;

(2) at the polymeric material II of polymer I surface preparation 10～500 μ m thickness;

(3) utilize temperature or solvent processing polymeric material I and II;

(4) regulation and control are pressed into speed and the degree of depth is utilized the solid microneedles array roller roll extrusion or directly is pressed into polymeric material I and II;

(5) peel off micropin, behind the removal polymer II, promptly get the empty micropin array of polymer I;

(6) make empty micropin array SMD or the syringe-type micro-needle array injection syringe;

Described polymeric material I, polymeric material II are natural macromolecular materials, or synthesized polymer material, perhaps the combination of above material;

In the step (3), said temperature is 0～100 ℃ of the temperature that is higher than processed polymer softening point, and the time is 0.1min～24h; Solvent is CHCl₃, CHCl₂, in the acetone, toluene, benzene, oxolane any one or a few, the processing time is 0.1min～12h;

In the step (4), the said speed that is pressed into is 0.01～100cm/s; Compression distance is 1～2000 μ m.

2, the preparation method of a kind of micro-needle array injection syringe according to claim 1, it is characterized in that in step (1), the method of said surface-functionalized processing is for applying, or sputter, or chemical plating, or electroplate, or PVD, or CVD, or above method combination in any, material therefor is metal, inorganic matter or Organic substance and combination in any thereof.

3, the preparation method of a kind of micro-needle array injection syringe according to claim 1 is characterized in that in step (2), and said method at polymer I surface preparation polymer II is spin coating, or membrane, or pad pasting, or spraying, or above method combination in any.

4, the preparation method of a kind of micro-needle array injection syringe according to claim 1 is characterized in that in step (6) method that said empty micropin array is made hollow micro-needle array injection syringe is a hot melt, or bonding, or its combination in any.

5, a kind of preparation method of micro-needle array injection syringe is characterized in that this method may further comprise the steps:

(1) polymer I is carried out surface-functionalized processing, obtain the rete of 1nm～500 μ m thickness on the surface;

(2) at the polymeric material II of polymer I surface preparation 10～500 μ m thickness;

(3) utilize temperature or solvent processing polymeric material I and II;

(4) under uniform temperature or solvent processing condition, the solid microneedles array is pressed into polymeric material I and II with appropriate speed;

(5) under uniform temperature or solvent environment, lift micropin with appropriate speed;

(6) take out micropin, behind the removal polymer II, promptly get the empty micropin array of polymer I;

(7) make empty micropin array SMD or the syringe-type micro-needle array injection syringe;

Described polymeric material I, polymeric material II are natural macromolecular materials, or synthesized polymer material, perhaps the combination of above material;

In the step (3), said temperature is 0～100 ℃ of the temperature that is higher than processed polymer softening point, and the time is 0.1min～24h; Solvent is CHCl₃, CHCl₂, in the acetone, toluene, benzene, oxolane any one or a few, the processing time is 0.1min～12h;

In step (4), (5), said temperature is 30～200 ℃, and the time is 0.1min～24h; Solvent is CHCl₃, CHCl₂, in the acetone, toluene, benzene, oxolane any one or a few, the processing time is 0.1min～12h; The said rate of pulling is 0.01cm/s～100m/s; Lifting highly is 10 μ m～1cm.

6, the preparation method of a kind of micro-needle array injection syringe according to claim 5, it is characterized in that in step (1), the method of said surface-functionalized processing is for applying, or sputter, or chemical plating, or electroplate, or PVD, or CVD, or above method combination in any, material therefor is metal, inorganic matter or Organic substance and combination in any thereof.

7, the preparation method of a kind of micro-needle array injection syringe according to claim 5 is characterized in that in step (2), and said method at polymer I surface preparation polymer II is spin coating, or membrane, or pad pasting, or spraying, or above method combination in any.

8, the preparation method of a kind of micro-needle array injection syringe according to claim 5 is characterized in that in step (7) method that said empty micropin array is made hollow micro-needle array injection syringe is a hot melt, or bonding, or its combination in any.

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