WO2010048757A1 - Method for preparation of rack with micro-blind holes on the surface carrying gene material - Google Patents
Method for preparation of rack with micro-blind holes on the surface carrying gene material Download PDFInfo
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- WO2010048757A1 WO2010048757A1 PCT/CN2008/072887 CN2008072887W WO2010048757A1 WO 2010048757 A1 WO2010048757 A1 WO 2010048757A1 CN 2008072887 W CN2008072887 W CN 2008072887W WO 2010048757 A1 WO2010048757 A1 WO 2010048757A1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
- B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
- B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
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Abstract
Method for preparation of rack with micro-blind holes on the surface carrying gene material is characterized by dissolving gene material to be carried under normal temperature, adding proper amount of protective agent for gene activity, spraying the gene solution by ultrasonic atomization, pressurized and spraying apparatus. Gene material enters into the micro-blind holes and is painted on the surface of the rack. The present invention provides the rack with micro-blind holes on the surface carrying gene material. The rack can be used to exert endothelialization function of gene fast, and improves curative effect in clinic application. First, dissolve gene material to be carried by the rack under normal temperature, add proper amount of protective agent for gene activity to make sure the gene effecting normally. Second, spray the gene solution by ultrasonic atomization, pressurized and spraying apparatus to make sure the gene material attaching to the surface of rack with micro-blind holes. Consequently, control of carrying quantity of gene material is achieved, and the repeatable accuracy is high.
Description
说明书 微盲孔支架承载基因物质的制备方法 技术领域 Description Method for preparing micro-blind hole-supporting genetic material
[1] 本发明涉及医疗器械装置及其承载基因物质的制备方法， 属于生物医学材料和 生物化学等领域。 除涉及微盲孔支架 （其制备方法见"金属支架表面微盲孔载药 层的制作方法 "专利号： ZL200610109422.8; ) 的外表涂覆基因物质一裸质粒 的制备外， 还包括基因物质的溶解及保护的方法， 特别是微盲孔支架承载基因 物质裸质粒的制备方法。 [1] The present invention relates to a medical device device and a method for preparing the same for carrying a genetic material, and belongs to the fields of biomedical materials and biochemistry. In addition to the micro-blind-hole scaffolds (for the preparation method, see "Manufacturing method of micro-blind hole drug-loading layer on metal scaffold surface" patent number: ZL200610109422.8; ), the preparation of the surface-coated genetic material-naked plasmid, including genetic material The method for dissolving and protecting, in particular, the method for preparing a naked plasmid carrying a microbone in a micro-blind-hole scaffold.
背景技术 Background technique
[2] 医疗器械中的心血管支架介入治疗成形术， 已经成为当前医学领域应用越来越 广泛的方法。 但单纯心血管支架植入术面临着一个严峻的挑战， 即术后的生物 相容性问题和组织再生问题； 为解决上述问题， 研究人员试验在心血管支架表 面携带某种药物， 包括生物活性物质， 以使得更有利于临床的治疗效果。 因此 人们使用高分子聚合物作为承载过渡层， 涂覆在心血管支架表面； 然后使其与 药物等目的物结合， 通过界面释放以达到治疗的作用。 但几年过去了， 高分子 聚合物作为载体的药物支架， 被植入人体后脱落的不良反应吋有发生， 尤其是 高分子聚合物在血液中的离散移动， 会给患者造成新的远端血栓等。 而表面带 有微盲孔的心血管支架， 它不仅可以直接装载药物和基因等粒子， 而且自身的 生物相容性较好， 使得血管内皮细胞能快速地完成内皮化过程， 可以起到很好 的治疗作用。 [2] Cardiovascular stenting in medical devices has become an increasingly widely used method in the medical field. However, simple cardiovascular stenting presents a serious challenge, namely postoperative biocompatibility and tissue regeneration. To solve the above problems, the researchers tested carrying a drug, including bioactive substances, on the surface of the cardiovascular stent. In order to make it more conducive to clinical therapeutic effects. Therefore, high-molecular polymers are used as a bearing transition layer, which is coated on the surface of the cardiovascular stent; then it is combined with a drug and the like, and released through the interface to achieve therapeutic effects. However, a few years have passed, the drug carrier of high molecular weight polymer as a carrier, the adverse reaction of detachment after being implanted into the human body has occurred, especially the discrete movement of the polymer in the blood, which will cause a new distal end to the patient. Thrombosis, etc. The cardiovascular stent with micro-blind holes on the surface can not only directly load particles such as drugs and genes, but also has good biocompatibility, so that vascular endothelial cells can quickly complete the endothelialization process, which can be very good. Therapeutic effect.
[3] 在分子生物学飞速发展的今天， 人们可以方便的获得各种基因物质， 包括 DNA [3] In today's rapid development of molecular biology, people can easily access a variety of genetic material, including DNA.
、 RNA等。 这些物质已经在临床上得到了广泛的应用， 其显示的疗效和安全性 也是令人瞩目的。 将含有某种具有临床意义的活性分子的编码基因物质， 涂覆 到微盲孔血管支架表面； 在植入人体后， 其所携带的基因物质可以进入植入部 位的血管内皮细胞并表达出相应的分子活性， 从而达到预期的治疗目的。 目前 所应用的涂覆方法， 一般为浸泡法； 即将微盲孔血管支架在基因物质溶液中进 行浸泡， 从而使基因物质粘附到支架表面。 但这种方法存在着诸多的弊端， 如
溶液无法完全有效地进入支架的微盲孔内； 单枚支架表面的基因物质携带量无 法精确控制； 操作过程重复精确度差， 无法规模化加工等。 本发明则为解决以 上问题， 提供了一种新的方法。 , RNA, etc. These substances have been widely used clinically, and their efficacy and safety are also remarkable. The genetically encoded gene containing a clinically meaningful active molecule is applied to the surface of the micro-blind vascular stent; after implantation into the human body, the genetic material carried by the human can enter the vascular endothelial cells at the implantation site and express corresponding The molecular activity is thus achieved for the intended therapeutic purpose. The coating method currently applied is generally a soaking method; that is, the micro-blind-hole vascular stent is immersed in a solution of the genetic material to adhere the genetic material to the surface of the stent. But this method has many drawbacks, such as The solution cannot enter the micro-blind hole of the stent completely and effectively; the carrying amount of the genetic material on the surface of the single stent cannot be precisely controlled; the accuracy of the repeated repetition of the operation process cannot be scaled up. The present invention provides a new method for solving the above problems.
对发明的公开 Disclosure of invention
技术解决方案 Technical solution
[4] 为了解决基因物质涂层微盲孔支架制备过程中存在的各种问题， 本发明提供了 一种微盲孔支架承载基因物质的制备方法， 釆用超声微雾化加压射流涂层方法 ， 能够使基因物质顺利地进入微盲孔内及支架表面， 精确地控制每枚微盲孔血 管支架所携带的基因物质的量。 [4] In order to solve various problems in the preparation process of the micro-blind hole scaffold for the genetic material coating, the present invention provides a method for preparing a micro-blind hole scaffold carrying a genetic material, and the ultrasonic micro-atomizing pressurized jet coating is used. The method enables the genetic material to smoothly enter the micro-blind hole and the surface of the stent, and precisely controls the amount of the genetic material carried by each micro-blind hole vascular stent.
[5] 本发明为解决其技术问题所釆用的技术方案是： 首先， 将目标基因物质一裸 质粒， 用不会破坏其生物活性的超纯水、 糖类进行溶解， 再在溶液中加入对人 体无害的维生素5、 维生素 C作为保护剂； 从而使基因物质一裸质粒涂层支架 能够顺利到达靶血管。 其次， 应用超声波使溶液雾化， 超声波强度 0.8， 药物流 量 0.025ml/min， 支架推进速度 0.1cm/s， 支架旋转速度 250r/min， 惰性气体压力 lp sio 经辅助计算机程序控制下进行高速喷涂后， 使单枚支架的基因物质一裸质 粒携带量在 120-150μβ范围之内， 精确可调， 重复精度高， 可以实现规模化加工 [5] The technical solution adopted by the present invention to solve the technical problem is as follows: First, the target gene substance is a naked plasmid, which is dissolved by ultrapure water or sugar which does not destroy its biological activity, and then added to the solution. Vitamin 5 and vitamin C, which are harmless to the human body, act as a protective agent; thus, the naked-plasmid coated stent of the genetic material can reach the target blood vessel smoothly. Secondly, the solution is atomized by ultrasonic wave, the ultrasonic intensity is 0.8, the drug flow rate is 0.025ml/min, the support speed of the support is 0.1cm/s, the rotation speed of the support is 250r/min, and the inert gas pressure lp sio is controlled by the auxiliary computer program after high-speed spraying. , the genetic material of a single scaffold can be carried within the range of 120-150μ β , which can be accurately adjusted, with high repeatability, and can realize large-scale processing.
[6] 微盲孔支架承载基因物质的制备方法， 其特征在于在常温下溶解被承载的基因 物质， 并适量加入基因活性保护剂； 使用超声微雾化加压喷涂设备进行喷涂， 使基因物质进入到微盲孔内部并涂覆到支架表面。 [6] A method for preparing a micro-blind-hole-supporting genetic material, which is characterized in that a gene substance to be carried is dissolved at a normal temperature, and a gene-active protective agent is added in an appropriate amount; and ultrasonic micro-atomizing pressure spraying equipment is used for spraying to make a genetic substance Enter the inside of the micro-blind hole and apply it to the surface of the holder.
[7] 所述具体特征如下： 微盲孔支架材质包括金属和非金属； 可以是医用不锈钢、 钛镍合金、 钴铬合金及高分子材料。 微盲孔支架包括球囊扩张型支架和自膨胀 型支架， 含用其它方法输送和扩张的金属和非金属支架； 可以是应用球囊导管 进行支架的输送和扩张。 微盲孔支架包括激光雕刻支架、 编织支架以及其它方 法加工的植入人体的心血管支架。 [7] The specific features are as follows: The material of the micro-blind hole bracket includes metal and non-metal; it can be medical stainless steel, titanium-nickel alloy, cobalt-chromium alloy and polymer material. The micro-blind-aperture stent includes a balloon-expandable stent and a self-expanding stent, including metal and non-metallic stents that are otherwise delivered and expanded; the balloon catheter can be used for delivery and expansion of the stent. Micro-blind hole supports include laser-engraved stents, braided stents, and other methods of implanting cardiovascular stents implanted into the human body.
承载的基因物质是裸质粒； 包括真核细胞和原核细胞来源的裸质粒， 也包括非 细胞来源的裸质粒； 可以是非病毒载体的裸质粒 DNA和质粒脂质体。 裸质粒包 括抗性质粒、 降解质粒、 侵入性质粒； 它是一种寓于宿主细胞中染色体外裸露
的双链 DNA。 所加入基因活性保护剂， 可以是溶液、 糖类、 维生素类。 可以单 独使用， 也可以混合使用， 浓度在 1.0%_10%之间。 其溶液可以是超纯水； 也可 以是任何一种无害液体，其中可加入一种糖， 也可以加入多种糖。 糖类包括单糖 或多糖； 可以是葡萄糖、 蔗糖。 在喷涂基因物质吋可以单次单层， 也可以多次 多层。 The hosted genetic material is a naked plasmid; a naked plasmid derived from eukaryotic cells and prokaryotic cells, and a naked plasmid derived from a non-cell source; a naked plasmid DNA and a plasmid liposome which may be non-viral vectors. The naked plasmid includes a resistance plasmid, a degradation plasmid, an invasive plasmid; it is an extrachromosomal exposure in a host cell. Double-stranded DNA. The gene activity protective agent to be added may be a solution, a saccharide or a vitamin. They may be used singly or in combination, and the concentration is between 1.0% and 10%. The solution may be ultrapure water; it may be any harmless liquid in which a sugar may be added or a plurality of sugars may be added. The sugars include monosaccharides or polysaccharides; they may be glucose or sucrose. In the spraying of genetic material, it can be a single layer, or multiple layers.
[8] 微盲孔支架表面布满微孔， 如果将支架直接浸入基因物质溶液， 则微盲孔表面 即刻被液体覆盖， 由于液体张力的作用， 使微盲孔内的空气无法排出， 从而造 成溶液无法进入微盲孔内； 如图 7所示。 [8] The surface of the micro-blind hole bracket is covered with micro-pores. If the stent is directly immersed in the solution of the genetic material, the surface of the micro-blind hole is immediately covered by the liquid, and the air in the micro-blind hole cannot be discharged due to the liquid tension, thereby causing The solution could not enter the micro-blind hole; as shown in Figure 7.
[9] 另外， 如果基因物质具有较好的水溶性， 单纯将其涂覆的支架表面， 在植入的 过程中相当部分的基因物质将会在到达靶病变部位前被血液溶解。 利用本发明 提供的方法， 在基因物质溶液中加入对人体无害的溶液、 糖类、 维生素类等保 护物质， 干燥后会为基因物质提供一种保护层。 虽然保护剂在血液中也可以溶 解， 但其溶解速度并不是很快， 完全可以使支架上携带的基因物质安全到达病 变部位。 将加入了溶液或糖类或维生素类的基因物质溶液进行超声波震荡， 使 其产生直径在微米级的小液滴 （范围 18-48μηι) ， 这些液滴在惰性气体 （氮气或 氦气 [9] In addition, if the genetic material has good water solubility, the surface of the stent that is simply coated, a considerable portion of the genetic material will be dissolved by the blood before reaching the target lesion. By using the method provided by the present invention, a protective substance such as a solution, a saccharide or a vitamin which is harmless to the human body is added to the solution of the genetic substance, and after drying, a protective layer is provided for the genetic substance. Although the protective agent can be dissolved in the blood, its dissolution rate is not so fast, and the genetic material carried on the stent can be safely reached to the diseased site. The solution of the genetic material added with the solution or the saccharide or vitamin is ultrasonically oscillated to produce small droplets (range 18-48 μηι) having a diameter of micrometers, and the droplets are in an inert gas (nitrogen or helium).
) 施加的压力推动下快速射向旋转的微盲孔支架， 便可顺利进入微盲孔内前尺 寸迅速变小。 在此过程中， 支架的旋转非常重要， 因为在旋转过程中， 小液滴 与支架表面存在一种剪切力， 而这种剪切力是使小液滴进入微盲孔不可或缺的 因素。 The applied pressure pushes the fast-moving micro-blind hole holder, and the front size can be quickly reduced when it enters the micro-blind hole smoothly. During this process, the rotation of the stent is very important because during the rotation, there is a shearing force between the droplets and the surface of the stent, and this shearing force is an indispensable factor for the droplets to enter the micro-blind hole. .
[10] 微盲孔血管支架载物原理： [10] Micro blind hole vascular stent loading principle:
[11] 1、 超声雾化粒径大小。 由图 3中可知超声雾化粒径大小为 25— 120μηι。 [11] 1. Ultrasonic atomization particle size. It can be seen from Fig. 3 that the ultrasonic atomization particle size is 25 - 120 μηι.
[12] 2、 支架表面液膜厚度。 支架筋宽和壁厚约为 0.1mm, 薄液膜在支架筋的每个 面上形成如图 6所示的球冠形液滴。 液滴半径 r可以通过 Kalvin公式计算 [12] 2. The thickness of the liquid film on the surface of the stent. The stent rib width and wall thickness are about 0.1 mm, and the thin liquid film forms spherical crown droplets as shown in Fig. 6 on each side of the stent rib. The droplet radius r can be calculated by the Kalvin formula
[13] 应用 Young方程可以计算出润湿角 Θ [13] The Young equation can be used to calculate the wetting angle Θ
[14] 由图 4可知， 根据半径 r和润湿角 Θ可以计算出球冠形液滴的高度， 即液膜厚度 。 另一方面， 液体的表面张力是决定液体能否在金属表面铺展幵的重要因素， 表面张力越小， 接触角越小， 则越易铺展， 有助于液体的发挥。 但表面张力过
小， 会导致液体的流失。 [14] As can be seen from Fig. 4, the height of the spherical crown droplet, that is, the liquid film thickness, can be calculated from the radius r and the wetting angle Θ. On the other hand, the surface tension of the liquid is an important factor determining whether the liquid can spread on the surface of the metal. The smaller the surface tension, the smaller the contact angle, the easier it is to spread and contribute to the liquid. But the surface tension has passed Small, it will lead to the loss of liquid.
[15] 3、 载物原理。 超声喷涂机将溶解了基因物质雾化成直径为 18 - 48μηι的小液滴[15] 3, the principle of loading. The ultrasonic sprayer atomizes the dissolved genetic material into small droplets with a diameter of 18 - 48μηι
， 每个小液滴中含有基因物质与溶剂分子， 每一个基因物质均被众多溶剂分子 包围， 当液滴喷在支架表面吋， 基因物质分子可以分散进入微孔， 如图 5所示。 Each droplet contains genetic material and solvent molecules. Each genetic material is surrounded by a plurality of solvent molecules. When the droplets are sprayed on the surface of the stent, the molecular material molecules can be dispersed into the micropores, as shown in FIG.
[16] 支架表面引入微盲孔的主要目的是载物， 主要通过三个方面来实现： 一、 微盲 孔本身直接装载一部分基因物质； 二、 增加了支架表面的粗糙度； 三、 提高了 支架表面的自由能。 在喷涂过程中， 小液滴不断落在支架表面， 由于微盲孔支 架的表面能较大， 基因物质容易被吸附， 在支架表面形成了一层薄液膜， 其薄 液膜的厚度取决于液体的表面张力， [16] The main purpose of introducing micro-blind holes on the surface of the stent is to carry the cargo mainly by three aspects: 1. The micro-blind hole itself directly loads a part of the genetic material; 2. The roughness of the surface of the stent is increased; Free energy of the surface of the stent. During the spraying process, small droplets continuously land on the surface of the stent. Due to the large surface energy of the micro-blind hole holder, the genetic material is easily adsorbed, and a thin liquid film is formed on the surface of the stent, and the thickness of the thin liquid film depends on Surface tension of the liquid,
液体表面张力的变化、 支架各部位表面自由能的不同， 液体内部会出现液体流 动从新分布，基因物质均匀分布在孔外的支架表面； 形成了如图 6所示的状况。 The change of the surface tension of the liquid and the free energy of the surface of each part of the stent, the liquid flow will be newly distributed inside the liquid, and the genetic material is evenly distributed on the surface of the stent outside the hole; the condition shown in Fig. 6 is formed.
[17] 4、 动量冲量原理的应用。 每个液滴在抵达支架表面吋有一定速度 V， 据动量定 理： Δηιν = F At则 F= Δηιν/Δΐ [17] 4. The application of the momentum impulse principle. Each droplet has a certain velocity V after reaching the surface of the stent. According to the momentum: Δηιν = F At then F = Δηιν/Δΐ
[18] 液膜具有表面张力 σ，产生一收缩力 F σ :F σ = oL [18] The liquid film has a surface tension σ, which produces a contraction force F σ : F σ = oL
[19] 如 〉 F σ， 则液滴可以克服表面张力进入微盲孔内。 [19] If 〉 F σ, the droplet can overcome the surface tension into the micro-blind hole.
有益效果 Beneficial effect
[20] 本发明的有益效果是， 通过计算机程序控制， 可以将基因物质有效地、 精确的 涂覆到微盲孔支架表面。 自动化程度高， 重复性好， 可规模化加工。 [20] The beneficial effects of the present invention are that the genetic material can be effectively and accurately applied to the surface of the micro-blind hole holder by computer program control. High degree of automation, good repeatability, and large-scale processing.
附图说明 DRAWINGS
[21] 图 1、 图 2是喷涂机 （DES_2000) 结构示意图； 图 3超声雾化粒径分布； 图 4润 湿角 Θ; 图 5基因物质和溶剂混合液小液滴； 图 6 [21] Figure 1 and Figure 2 are schematic diagrams of the spraying machine (DES_2000); Figure 3: Ultrasonic atomization particle size distribution; Figure 4: Wet angle Θ; Figure 5: Small droplets of genetic material and solvent mixture;
载物过程中支架表面； 图 7微盲孔支架壁面上的液滴。 其中， 超声波高频震荡发 生器 1、 溅射喷嘴接头 2、 喷嘴 3 The surface of the stent during the loading process; Figure 7 The droplets on the wall of the micro-blind hole stent. Among them, ultrasonic high frequency oscillation generator 1, sputtering nozzle joint 2, nozzle 3
、 微盲孔支架 4、 支架夹具 5、 支架推进器 6、 涂层溶液池接头 7、 涂层溶液池 8、 溶液高压推进器。 , micro blind hole bracket 4, bracket fixture 5, bracket thruster 6, coating solution pool joints 7, coating solution pool 8, solution high pressure propeller.
本发明的实施方式 Embodiments of the invention
[22] 1、 单层喷涂法 [22] 1. Single layer spraying method
[23] 用超纯水配制 2mg/ml的裸质粒 DNA, 充分溶解后加入蔗糖， 使溶液中蔗糖浓
度达到 1.1% ; 将配制好的溶液装入涂层溶液池 8， 用四氟乙烯软管连接喷嘴接头 2与涂层溶液池接头 7 ; 将微盲孔支架 4安装在支架夹具 5上； 启动喷涂系统， 对 超声波发生器 1的功率、 支架推进器 6的推进速度、 涂层溶液推进器 9的推进速度 进行设定， 使微盲血管孔支架 4从喷嘴 3下往返一次便达到预期的基因物质载量 [23] Prepare 2mg/ml of naked plasmid DNA in ultrapure water, fully dissolve and add sucrose to make the solution sucrose rich The degree is up to 1.1%; the prepared solution is charged into the coating solution tank 8, and the nozzle joint 2 and the coating solution tank joint 7 are connected by a tetrafluoroethylene hose; the micro blind hole bracket 4 is mounted on the bracket fixture 5; The spraying system sets the power of the ultrasonic generator 1, the advancing speed of the stent pusher 6, and the advancing speed of the coating solution propeller 9, so that the micro-blind vascular hole holder 4 is reciprocated from the nozzle 3 to reach the desired gene. Material load
[24] 2、 多层喷涂法 [24] 2 , multi-layer spraying method
[25] 用超纯水配制 2mg/ml的基因物质溶液， 充分溶解后加入蔗糖， 使溶液中蔗糖浓 度达到 1.1% ; 将配好的溶液装入涂层溶液池 8， 用四氟乙烯软管连接喷嘴接头 2 与涂层溶液池接头 7 ; 将微盲孔血管支架 4安装在支架夹具 5上； 启动喷涂系统， 对超声波发生器 1的功率、 支架推进器 6的推进速度、 涂层溶液推进器 9的推进速 度进行设定， 使微盲孔支架 4从喷嘴 3下往返多次方可达到预期的基因物质载量 。 重复喷涂应在微盲孔支架 4自然干燥后进行。
[25] Prepare a 2mg/ml solution of the genetic material in ultrapure water, dissolve it thoroughly, and add sucrose to make the sucrose concentration in the solution reach 1.1%. Put the prepared solution into the coating solution tank 8 and use a tetrafluoroethylene hose. Connecting the nozzle joint 2 and the coating solution pool joint 7; mounting the micro-blind hole blood vessel support 4 on the bracket clamp 5; starting the spraying system, the power of the ultrasonic generator 1, the advancement speed of the stent pusher 6, and the coating solution advancement The advancement speed of the device 9 is set such that the micro-blind hole holder 4 is reciprocated from the nozzle 3 multiple times to achieve the desired genetic material load. Repeated spraying should be performed after the micro-blind hole holder 4 is naturally dried.
Claims
1、 微盲孔支架承载基因物质的制备方法， 其特征在于在常温下溶解被承载 的基因物质， 并适量加入基因活性保护剂； 使用超声微雾化加压喷涂设备 进行喷涂， 使基因物质进入到微盲孔内部并涂覆到支架表面。 1. A method for preparing a micro-blind hole-supporting genetic material, which is characterized in that a gene substance to be carried is dissolved at a normal temperature, and a gene-active protective agent is added in an appropriate amount; and the ultrasonic micro-atomizing pressure spraying device is used for spraying to make the genetic substance enter Inside the micro blind hole and apply to the surface of the stent.
2、 根据权利 1所述的微盲孔支架承载基因物质的制备方法， 其特征在于微 盲孔支架材质包括金属和非金属； 可以是医用不锈钢、 钛镍合金、 钴铬合 金及高分子材料。 2. The method for preparing a micro-blind hole-supporting genetic material according to claim 1, wherein the micro-blind hole support material comprises metal and non-metal; and may be medical stainless steel, titanium-nickel alloy, cobalt-chromium alloy and polymer material.
3、 根据权利 1或 2所述的微盲孔支架承载基因物质的制备方法， 其特征在于 微盲孔支架包括球囊扩张型支架和自膨胀型支架， 含用其它方法输送和扩 张的金属和非金属支架； 可以是应用球囊导管进行支架的输送和扩张。 3. The method for preparing a micro-blind hole-supporting genetic material according to claim 1 or 2, wherein the micro-blind-hole support comprises a balloon-expandable stent and a self-expanding stent, and the metal and the metal which are transported and expanded by other methods. Non-metallic stents; may be the use of balloon catheters for the delivery and expansion of the stent.
4、 根据权利 1或 2所述的微盲孔支架承载基因物质的制备方法， 其特征在于 微盲孔支架包括激光雕刻支架、 编织支架以及其它方法加工的植入人体的 心血管支架。 4. The method for preparing a micro-blind hole-supporting genetic material according to claim 1 or 2, wherein the micro-blind hole support comprises a laser-engraved stent, a braided stent, and a cardiovascular stent implanted in the human body by other methods.
5、 根据权利 1所述的微盲孔支架承载基因物质的制备方法， 其特征在于基 因物质是裸质粒； 包括真核细胞和原核细胞来源的裸质粒， 也包括非细胞 来源的裸质粒； 可以是非病毒载体的裸质粒 DNA和质粒脂质体。 它是一种 寓于宿主细胞中染色体外裸露的双链 DNA, 包括抗性质粒、 降解质粒、 侵 入性质粒。 The method for preparing a micro-blind hole-supporting genetic material according to claim 1, wherein the genetic material is a naked plasmid; and comprises a naked plasmid derived from a eukaryotic cell and a prokaryotic cell, and a naked plasmid derived from a non-cell source; Non-viral vectors are naked plasmid DNA and plasmid liposomes. It is a double-stranded DNA that is exposed extrachromosomally in a host cell, including a resistance plasmid, a degradation plasmid, and an invasive plasmid.
6、 根据权利 1所述的微盲孔支架承载基因物质的制备方法， 其特征在于适 量加入基因活性保护剂； 可以是溶液、 糖类、 维生素类。 The method for preparing a micro-blind hole-supporting genetic material according to claim 1, characterized in that a gene-active protective agent is added in an appropriate amount; and the solution may be a solution, a saccharide or a vitamin.
7、 根据权利 1或 6所述的微盲孔支架承载基因物质的制备方法， 其特征在于 溶液可以是超纯水； 也可以是任何一种无害液体； 溶液中的糖类， 可以是 单糖或多糖； 维生素类可以是维生素 E或维生素^ 7. The method for preparing a micro-blind hole-supporting genetic material according to claim 1 or 6, wherein the solution may be ultrapure water; or any harmless liquid; the sugar in the solution may be a single Sugar or polysaccharide; vitamins can be vitamin E or vitamins ^
8、 根据权利 1或 8. According to right 1 or
7所述的微盲孔支架承载基因物质的制备方法， 其特征在于基因活性保护剂 可以单独使用， 也可以混合使用， 浓度在 1.0— 10%之间。 The method for preparing a micro-blind hole-supporting genetic material is characterized in that the gene-active protective agent can be used alone or in combination, and the concentration is between 1.0 and 10%.
9、 根据权利 1所述的微盲孔支架承载基因物质的制备方法， 其特征在于在 喷涂基因物质吋可以单次单层， 也可以多次多层。
9. The method for preparing a micro-blind hole-supporting genetic material according to claim 1, wherein the spraying of the genetic material is performed in a single layer or in multiple layers.
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| Application Number | Priority Date | Filing Date | Title |
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| PCT/CN2008/072887 WO2010048757A1 (en) | 2008-10-31 | 2008-10-31 | Method for preparation of rack with micro-blind holes on the surface carrying gene material |
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| PCT/CN2008/072887 WO2010048757A1 (en) | 2008-10-31 | 2008-10-31 | Method for preparation of rack with micro-blind holes on the surface carrying gene material |
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