CN115025384A - A kind of intelligent microneedle patch for optimizing shading by mathematical simulation and preparation method thereof - Google Patents
A kind of intelligent microneedle patch for optimizing shading by mathematical simulation and preparation method thereofDownload PDFInfo
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- 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
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- 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
- A61M2037/0023—Drug applicators using microneedles
- A—HUMAN NECESSITIES
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- 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
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Abstract
Translated fromChinese
Description
Translated fromChinese技术领域technical field
本发明涉及生物医药技术、数学及工程学技术领域，具体地说是一种数学模拟优化底纹的智能微针贴片及其制备方法。The invention relates to the fields of biomedical technology, mathematics and engineering technology, in particular to an intelligent microneedle patch for optimizing shading by mathematical simulation and a preparation method thereof.
背景技术Background technique
粘膜系统广泛分布于动物体表或体内，其下含有丰富的毛细血管、淋巴管等结构，是药物递送和生物标志物采集的重要靶标位点。目前已有多种用于黏膜部位采样或给药的手段进入临床实践(例如新冠鼻咽拭子，口腔粘膜贴片等)，它们能在粘膜处快速高效采集或递送相应标志物或药物。然而，这类系统作用时间较短，采样或递药效率较低，限制了后续检测和药物治疗效果。因此，发展一种高效、准确的递送或采样技术具有较高的应用价值。The mucosal system is widely distributed on the body surface or in vivo of animals, and contains abundant capillaries, lymphatic vessels and other structures under it, and is an important target site for drug delivery and biomarker collection. At present, a variety of methods for sampling or administering mucosal sites have entered clinical practice (such as nasopharyngeal swabs, oral mucosal patches, etc.), which can quickly and efficiently collect or deliver corresponding markers or drugs at mucosal sites. However, such systems have short duration of action and low sampling or drug delivery efficiency, limiting subsequent detection and drug treatment effects. Therefore, developing an efficient and accurate delivery or sampling technique has high application value.
发明内容SUMMARY OF THE INVENTION
为了增加粘膜处采样和递药的效率，本发明提供一种数学模拟优化底纹的智能微针贴片及其制备方法。该设计受启发于小肠绒毛上皮细胞向外突出以增大表面积的形态的特征，以数学模拟的角度将小肠绒毛上皮细胞模拟为三角函数，设计出三角函数底纹以充分利用微针基底进行采样和给药。与大多数聚焦于微针针体的设计不同，该底纹设计模拟特殊接触面的生物学状态，适用于多种粘膜组织位点，实现高效的采样或递药。In order to increase the efficiency of sampling and drug delivery at the mucosa, the present invention provides an intelligent microneedle patch capable of mathematically simulating and optimizing shading and a preparation method thereof. The design is inspired by the characteristics of the shape of the small intestinal villous epithelial cells that protrude outward to increase the surface area. From the perspective of mathematical simulation, the small intestinal villous epithelial cells are simulated as trigonometric functions, and the trigonometric function shading is designed to make full use of the microneedle base for sampling. and dosing. Unlike most designs that focus on the microneedle body, this shading design simulates the biological state of a special contact surface and is suitable for a variety of mucosal tissue sites for efficient sampling or drug delivery.
本发明的技术方案是：一种数学模拟优化底纹的智能微针贴片，包含微针模具、由交联聚合物制成的采样微针和由非交联聚合物制成的递药微针，其特征在于：微针模具表面带有底纹，底纹上设置有微针，其中底纹方程为符合三角函数、二项式展开函数或正态分布函数，微针包括交联聚合物的采样微针和非交联聚合物的递药微针。The technical scheme of the present invention is: an intelligent microneedle patch for optimizing shading by mathematical simulation, comprising a microneedle mold, a sampling microneedle made of a cross-linked polymer, and a drug delivery micro-needle made of a non-cross-linked polymer The needle is characterized in that: the surface of the microneedle mold is provided with shading, and the shading is provided with microneedles, wherein the shading equation is conformed to a trigonometric function, a binomial expansion function or a normal distribution function, and the microneedle comprises a cross-linked polymer of sampling microneedles and non-crosslinked polymer delivery microneedles.
根据如上所述的一种数学模拟优化底纹的智能微针贴片，其特征在于：其中底纹方程为符合Y＝Asin(2πX/T)的三角函数，其中A为振幅，取值范围为0-1范围，单位为毫米；T为周期，取值范围为0.1-4。According to the above-mentioned intelligent microneedle patch for optimizing shading by mathematical simulation, it is characterized in that: the shading equation is a trigonometric function conforming to Y=Asin(2πX/T), wherein A is the amplitude, and the value range is 0-1 range, the unit is mm; T is the period, the value range is 0.1-4.
根据如上所述的一种数学模拟优化底纹的智能微针贴片，其特征在于：采用非交联羧甲基纤维素钠用于制作递药微针；将非交联羧甲基纤维素钠光交联后成为交联羧甲基纤维素钠，用于制作采样微针。The intelligent microneedle patch for optimizing the shading according to the above-mentioned mathematical simulation is characterized in that: non-cross-linked sodium carboxymethyl cellulose is used to make drug delivery microneedles; After sodium photocrosslinking, it becomes croscarmellose sodium, which is used to make sampling microneedles.
根据如上所述的一种数学模拟优化底纹的智能微针贴片，其特征在于：微针模具底部形状为矩形或圆形。According to the above-mentioned intelligent microneedle patch with optimized shading by mathematical simulation, it is characterized in that the shape of the bottom of the microneedle mold is a rectangle or a circle.
根据如上所述的一种数学模拟优化底纹的智能微针贴片，其特征在于：采样微针、非交联聚合物的递药微针的取值为100-2000，单位为微米；微针底部直径的取值为20-800，单位为微米；微针阵列数量的取值为1-500个。The intelligent microneedle patch for optimizing shading according to the above mathematical simulation is characterized in that: the sampling microneedles and the drug delivery microneedles of non-crosslinked polymer are 100-2000, and the unit is micron; The diameter of the needle bottom is 20-800, and the unit is micron; the number of microneedle arrays is 1-500.
本发明还公开了一种数学模拟优化底纹的智能微针贴片的制备方法，其特征在于：包括以下步骤：The invention also discloses a method for preparing an intelligent microneedle patch for optimizing shading by mathematical simulation, which is characterized by comprising the following steps:
(1)基于仿生结构与数学模拟优化底纹的智能微针PDMS模具的制备：利用3D绘图软件绘制底纹微针模具，其底纹方程符合符合三角函数、二项式展开函数或正态分布函数，利用3D打印技术打印微针模具，以聚二甲氧基硅氧烷倒模，聚二甲氧基硅氧烷加热固化的温度和时间为30-70摄氏度，3-6小时，得到底纹的微针模具；(1) Preparation of intelligent microneedle PDMS mold based on biomimetic structure and mathematical simulation to optimize shading: use 3D drawing software to draw shading microneedle mold, and its shading equation conforms to trigonometric function, binomial expansion function or normal distribution Function, use 3D printing technology to print a microneedle mold, use polydimethoxysiloxane to cast the mold, and the temperature and time of polydimethoxysiloxane heating and curing are 30-70 degrees Celsius, 3-6 hours, and the bottom is obtained. patterned microneedle mold;
(2)交联聚合物溶液的制备：称取非交联聚合物溶解在水中配置成非交联聚合物溶液，聚合物溶液的浓度为1-10％；加入交联剂与引发剂，交联剂浓度为0.5-5％，引发剂浓度为0.01-0.2％；在紫外光下进行光交联反应，紫外光波长为405-450纳米，光交联时间为10-60秒，形成交联聚合物溶液；(2) Preparation of cross-linked polymer solution: Weigh the non-cross-linked polymer and dissolve it in water to prepare a non-cross-linked polymer solution, the concentration of the polymer solution is 1-10%; The concentration of linking agent is 0.5-5%, and the concentration of initiator is 0.01-0.2%; the photo-crosslinking reaction is carried out under ultraviolet light, the wavelength of ultraviolet light is 405-450 nanometers, and the photo-crosslinking time is 10-60 seconds to form cross-linking. polymer solution;
(3)采样微针的制备：将交联聚合物溶液加入底纹微针模具，使用平板离心机离心，烘箱中干燥后，从微针模具上剥离样品；(3) Preparation of sampling microneedles: adding the cross-linked polymer solution to the shading microneedle mold, centrifuging with a flat centrifuge, drying in an oven, and peeling off the sample from the microneedle mold;
(4)递药微针的制备：将非交联聚合物溶液加入底纹微针模具，使用平板离心机离心，烘箱中干燥后，从模具上剥离样品，常温保存。(4) Preparation of drug delivery microneedles: the non-crosslinked polymer solution was added to the shading microneedle mold, centrifuged with a flat centrifuge, dried in an oven, and then peeled off the sample from the mold and stored at room temperature.
根据如上所述的一种数学模拟优化底纹的智能微针贴片的制备方法，其特征在于：根据如上所述的任一项数学模拟优化底纹的智能微针贴片采用如上所述的方法制备。According to a method for preparing a smart microneedle patch for optimizing shading by mathematical simulation as described above, it is characterized in that: the smart microneedle patch for optimizing shading according to any one of the above mathematical simulations adopts the above method of preparation.
根据如上所述的一种数学模拟优化底纹的智能微针贴片的制备方法，其特征在于：步骤3中交联聚合物溶液体积为300-800微升；平板离心的速度和时间为2000-4000转/分钟，5-10分钟；烘箱干燥的温度和时间为35-60摄氏度，2-6小时；步骤4中非交联聚合物溶液的浓度为1-10％；非交联聚合物溶液体积为300-800微升；平板离心的速度和时间为2000-4000转/分钟，5-10分钟，烘箱干燥温度和时间为35-60摄氏度，2-6小时。According to the above-mentioned method for preparing a smart microneedle patch with optimized shading by mathematical simulation, it is characterized in that: in step 3, the volume of the cross-linked polymer solution is 300-800 microliters; the speed and time of plate centrifugation are 2000 microliters. -4000 rpm, 5-10 minutes; oven drying temperature and time at 35-60 degrees Celsius, 2-6 hours; the concentration of non-crosslinked polymer solution in
根据如上所述的一种数学模拟优化底纹的智能微针贴片的制备方法，其特征在于：交联剂为N,N-亚甲基双丙烯酰胺。According to the method for preparing an intelligent microneedle patch with optimized shading by mathematical simulation as described above, it is characterized in that the crosslinking agent is N,N-methylenebisacrylamide.
根据如上所述的一种数学模拟优化底纹的智能微针贴片的制备方法，其特征在于：引发剂为苯基磷酸锂盐。According to the above-mentioned method for preparing a smart microneedle patch for optimizing shading by mathematical simulation, the characteristic is that the initiator is lithium phenyl phosphate.
本发明的有益效果是：该贴片可以高效准确地采集粘膜表面及深层组织液中的生物标志物，并且可以快速简便地将装载药物递送至粘膜表面及深层粘膜组织。本专利提供的底纹微针新颖、高效，其结构符合仿生学与数学演算规律，并且制备方法简单、生物相容性好、重复性好，具有较高的临床转化潜力。The beneficial effects of the present invention are: the patch can efficiently and accurately collect biomarkers in the mucosal surface and deep tissue fluid, and can quickly and easily deliver the loaded drug to the mucosal surface and deep mucosal tissue. The shading microneedle provided by this patent is novel and efficient, its structure conforms to the laws of bionics and mathematical calculus, the preparation method is simple, the biocompatibility is good, the repeatability is good, and it has high clinical transformation potential.
附图说明Description of drawings
图1本发明中仿生结构与数学模拟优化底纹的智能微针模具的照片。Fig. 1 is a photo of the intelligent microneedle mold with bionic structure and mathematical simulation optimized shading in the present invention.
图2本发明中底纹参数的数学计算优化。Fig. 2 Mathematical calculation optimization of shading parameters in the present invention.
图3本发明中高效采样微针和快速递药微针的显微镜照片。Figure 3 is a microscope photo of the high-efficiency sampling microneedle and the rapid drug delivery microneedle in the present invention.
图4本发明中高效采样微针和快速递送微针的扫描电镜照片。Figure 4 is a scanning electron microscope photograph of the high-efficiency sampling microneedle and the rapid delivery microneedle in the present invention.
图5本发明中高效采样微针与传统采样式子效果对比。FIG. 5 is a comparison of the sub-effects of the high-efficiency sampling microneedle in the present invention and the traditional sampling method.
图6本发明中载有抗生素的快速递药微针与常规贴片效果对比。Figure 6. Comparison of the effects of the antibiotic-loaded rapid drug delivery microneedle of the present invention and a conventional patch.
具体实施方式Detailed ways
按照本发明的技术方案，本实施例给出基于仿生结构与数学模拟优化底纹的智能微针贴片制备方法及其抗菌应用，并非对本发明进行限制。According to the technical solution of the present invention, the present embodiment provides a method for preparing an intelligent microneedle patch based on bionic structure and mathematical simulation to optimize shading and its antibacterial application, but does not limit the present invention.
本发明的一种基于仿生结构与数学模拟优化底纹的智能微针贴片及其在粘膜取样和粘膜药物递送中的作用，包含微针模具设计、由交联聚合物制成的采样微针和由非交联聚合物制成的递药微针，微针模具设计中其表面带有底纹，底纹上设置有微针，其中底纹方程为符合基本通式Y＝Asin(2πX/T)的三角函数(包括但不限于三角函数、二项式展开函数、正态分布函数等)，该方程坐标系的X轴的意义为距离原点的水平距离，单位为毫米，Y轴的意义为距离原点的垂直距离，单位为毫米。其中A为振幅，取值范围为0-1范围，单位为毫米；T为周期，取值范围为0.1-4。An intelligent microneedle patch based on biomimetic structure and mathematical simulation to optimize shading and its role in mucosal sampling and mucosal drug delivery of the present invention, including microneedle mold design, sampling microneedle made of cross-linked polymer And the drug delivery microneedle made of non-crosslinked polymer, the surface of the microneedle mold is designed with shading, and the shading is provided with microneedles, wherein the shading equation is consistent with the basic formula Y=Asin(2πX/ T) trigonometric functions (including but not limited to trigonometric functions, binomial expansion functions, normal distribution functions, etc.), the meaning of the X-axis of the equation coordinate system is the horizontal distance from the origin, in millimeters, and the meaning of the Y-axis is the vertical distance from the origin, in millimeters. Where A is the amplitude, the value range is 0-1, the unit is millimeter; T is the period, the value range is 0.1-4.
作为本发明的进一步实施例，微针包括交联聚合物的采样微针和非交联聚合物的递药微针。作为具体实施例，本发明可以采用非交联羧甲基纤维素钠用于制作快速递药微针；将非交联羧甲基纤维素钠光交联后成为交联羧甲基纤维素钠，用于制作高效采样微针。As a further embodiment of the present invention, the microneedles include sampling microneedles of cross-linked polymers and drug delivery microneedles of non-cross-linked polymers. As a specific embodiment, the present invention can use non-cross-linked sodium carboxymethyl cellulose for making rapid drug delivery microneedles; , for making high-efficiency sampling microneedles.
微针模具底部形状可以为矩形、圆形等形状，以交联聚合物的采样微针、非交联聚合物的递药微针的取值为100-2000，单位为微米；微针底部直径的取值为20-800，单位为微米；微针阵列数量的取值为1-500个。本发明利用非交联材料遇水溶解很快的特征，所以能将药物快速释放入组织液；利用交联材料遇水短时间内只溶胀不溶解，所以可以用来组织液采样。这样本发明充分利用不同物质的特性而产生了采样和递药功能。The shape of the bottom of the microneedle mold can be rectangular, circular, etc. The value of the sampling microneedle of cross-linked polymer and the delivery microneedle of non-cross-linked polymer is 100-2000, in microns; the diameter of the bottom of the microneedle is 100-2000. The value of 20-800, the unit is micron; the value of the number of microneedle arrays is 1-500. The present invention utilizes the feature that the non-cross-linked material dissolves quickly in water, so the drug can be rapidly released into the tissue fluid; the cross-linked material only swells and does not dissolve in water in a short time, so it can be used for tissue fluid sampling. In this way, the present invention makes full use of the properties of different substances to generate sampling and drug delivery functions.
本发明还给出了一种微针贴片的其制备方法，包括以下步骤：The present invention also provides a preparation method of the microneedle patch, comprising the following steps:
(1)基于仿生结构与数学模拟优化底纹的智能微针PDMS模具的制备：利用3D绘图软件绘制底纹微针模具，其底纹方程符合基本通式Y＝Asin(2πX/T)的三角函数，利用3D打印技术打印微针模具，以聚二甲氧基硅氧烷(PDMS)倒模，聚二甲氧基硅氧烷加热固化的温度和时间为30-70摄氏度，3-6小时，得到底纹的微针模具。(1) Preparation of intelligent microneedle PDMS mold based on biomimetic structure and mathematical simulation to optimize shading: use 3D drawing software to draw shading microneedle mold, and its shading equation conforms to the basic formula Y=Asin (2πX/T) triangle Function, use 3D printing technology to print microneedle mold, use polydimethoxysiloxane (PDMS) to mold, the temperature and time of polydimethoxysiloxane heating and curing are 30-70 degrees Celsius, 3-6 hours , to obtain the microneedle mold of the shading.
本发明在3D打印最初的阳模时就同时具备底纹和微针，后续只是进行倒模成PDMS阴模，再向其中填充对应材料制备成相应微针，即步骤3和步骤4。The present invention has both shading and microneedles when 3D printing the initial positive mold, and then only performs reverse molding into a PDMS negative mold, and then fills it with corresponding materials to prepare corresponding microneedles, namely
(2)交联聚合物溶液的制备：称取一定量的聚合物溶解在水中配置成聚合物溶液，聚合物溶液的浓度为1-10％。加入交联剂与引发剂，交联剂浓度为0.5-5％，引发剂浓度为0.01-0.2％。在紫外光下进行光交联反应，紫外光波长为405-450纳米，光交联时间为10-60秒，最终形成交联聚合物溶液。(2) Preparation of cross-linked polymer solution: a certain amount of polymer is weighed and dissolved in water to prepare a polymer solution, and the concentration of the polymer solution is 1-10%. A cross-linking agent and an initiator are added, the concentration of the cross-linking agent is 0.5-5%, and the concentration of the initiator is 0.01-0.2%. The photocrosslinking reaction is carried out under ultraviolet light, the wavelength of the ultraviolet light is 405-450 nanometers, and the photocrosslinking time is 10-60 seconds, and finally a crosslinked polymer solution is formed.
(3)高效采样微针的制备：将交联聚合物溶液加入底纹微针模具，使用平板离心机离心，烘箱中干燥后，从微针模具上剥离样品，常温保存。由于交联聚合物遇水短时间(60秒内)只溶胀不溶解，故而能在其溶胀过程中吸取大量组织液，达到高效采样的效果。本步骤中交联聚合物溶液体积为300-800微升；平板离心的速度和时间为2000-4000转/分钟，5-10分钟；烘箱干燥的温度和时间为35-60摄氏度，2-6小时。(3) Preparation of high-efficiency sampling microneedles: The cross-linked polymer solution was added to the shading microneedle mold, centrifuged with a flat centrifuge, dried in an oven, and then peeled off the sample from the microneedle mold, and stored at room temperature. Since the cross-linked polymer only swells and does not dissolve in water for a short time (within 60 seconds), it can absorb a large amount of tissue fluid during the swelling process to achieve the effect of efficient sampling. In this step, the volume of the cross-linked polymer solution is 300-800 microliters; the speed and time of plate centrifugation are 2000-4000 r/min, 5-10 minutes; the temperature and time of drying in the oven are 35-60 degrees Celsius, 2-6 Hour.
(4)快速递药微针的制备：将非交联聚合物溶液加入底纹微针模具，使用平板离心机离心，烘箱中干燥后，从模具上剥离样品，常温保存。由于非交联聚合物遇水能快速溶解，故而能将其中搭载的药物高效的释放入组织液。本步骤中非交联聚合物溶液的浓度为1-10％。非交联聚合物溶液体积为300-800微升。平板离心的速度和时间为2000-4000转/分钟，5-10分钟，烘箱干燥温度和时间为35-60摄氏度，2-6小时。(4) Preparation of rapid drug delivery microneedles: the non-crosslinked polymer solution was added to the shading microneedle mold, centrifuged with a flat centrifuge, dried in an oven, peeled off the sample from the mold, and stored at room temperature. Since the non-cross-linked polymer dissolves rapidly in contact with water, the drug loaded in it can be efficiently released into the tissue fluid. The concentration of the non-crosslinked polymer solution in this step is 1-10%. The volume of the non-crosslinked polymer solution is 300-800 microliters. The plate centrifugation speed and time are 2000-4000 rpm, 5-10 minutes, and the oven drying temperature and time are 35-60 degrees Celsius, 2-6 hours.
本发明的技术方案中所描述的底纹方程包括但不限于三角函数；所使用的聚合物包括但不限于羧甲基纤维素钠(羧甲基纤维素钠为非交联聚合物)；交联剂包括但不限于N,N-亚甲基双丙烯酰胺(Methylene-Bis-Acrylamide,MBA)；引发剂包括但不限于苯基(2,4,6-三甲基苯甲酰基)磷酸锂盐(Lithium phenyl-2,4,6-trimethylbenzoylphosphinate)。The shading equation described in the technical solution of the present invention includes but is not limited to trigonometric functions; the polymers used include but are not limited to sodium carboxymethyl cellulose (sodium carboxymethyl cellulose is a non-crosslinked polymer); Linking agents include but are not limited to N,N-methylenebisacrylamide (Methylene-Bis-Acrylamide, MBA); initiators include but are not limited to phenyl (2,4,6-trimethylbenzoyl) lithium phosphate Salt (Lithium phenyl-2,4,6-trimethylbenzoylphosphinate).
实施例1基于仿生结构与数学模拟优化底纹的智能微针模具的制备Example 1 Preparation of intelligent microneedle mold with optimized shading based on bionic structure and mathematical simulation
如图1所示，利用SolidWorks 2021软件绘制微针模具，贴片为1.5毫米x1.5毫米的正方形，微针排布为7x7阵列，底纹函数表达式为Y＝0.2sin(2πX)，单位为毫米。利用3D打印机打印模具，以95％乙醇清洗，以405纳米的紫外光固化，烘干，加入聚二甲氧基硅氧烷，置于60摄氏度烘箱中加热固化4小时，脱模，即得底纹微针PDMS模具。As shown in Figure 1, use SolidWorks 2021 software to draw a microneedle mold, the patch is a square of 1.5 mm x 1.5 mm, the microneedle is arranged in a 7x7 array, and the shading function expression is Y=0.2sin (2πX), unit to mm. Use a 3D printer to print the mold, clean it with 95% ethanol, cure it with 405 nm UV light, dry it, add polydimethoxysiloxane, heat and cure it in a 60 degree Celsius oven for 4 hours, release the mold, and get the bottom Pattern microneedle PDMS mold.
实施例2底纹参数的数学计算优化
如图2所示，底纹函数的积分长度与采样量和载药量有相关性，利用Matlab软件计算X取值在0～2π时，A的取值在0.1～10和T的取值在0.01π～π时，底纹三角函数的积分长度变化。经过实际优化，确定A的取值为0.2，T的取值为1为较优值。As shown in Figure 2, the integral length of the shading function is related to the sampling amount and the drug loading amount. Using Matlab software to calculate the value of X when the value is 0~2π, the value of A is 0.1~10 and the value of T is between When 0.01π～π, the integral length of the shading trigonometric function changes. After the actual optimization, it is determined that the value of A is 0.2, and the value of T is 1 as a better value.
实施例3交联羧甲基纤维素钠的制备Example 3 Preparation of Croscarmellose Sodium
称取2.5克羧甲基纤维素钠溶解在50毫升水中，向溶液中加入N,N-亚甲基双丙烯酰胺0.5克，苯基(2,4,6-三甲基苯甲酰基)磷酸锂盐0.01克，避光，超声分散。将溶液置于405纳米的紫外光下20秒进行交联反应，得到白色交联羧甲基纤维素钠。Weigh 2.5 g of sodium carboxymethyl cellulose and dissolve it in 50 ml of water, add 0.5 g of N,N-methylenebisacrylamide, phenyl(2,4,6-trimethylbenzoyl)phosphoric acid to the solution Lithium salt 0.01 g, protected from light, dispersed by ultrasonic. The solution was placed under ultraviolet light of 405 nm for 20 seconds to carry out cross-linking reaction to obtain white croscarmellose sodium.
实施例4高效采样微针的制备Example 4 Preparation of high-efficiency sampling microneedles
将500微升交联羧甲基纤维素钠加入到底纹微针PDMS模具中，以水平转子离心机离心(2000转/分钟，离心时间5分钟)，置于烘箱中40摄氏度烘干3小时，从PDMS模具中剥离样品，即得高效采样微针。得到的高效采样微针用扫描电子显微镜观察。Add 500 microliters of croscarmellose sodium to the underlined microneedle PDMS mold, centrifuge with a horizontal rotor centrifuge (2000 rpm,
实施例5快速递药微针的制备Example 5 Preparation of rapid drug delivery microneedles
将500微升5％羧甲基纤维素钠加入到底纹微针PDMS模具中，以水平转子离心机离心(2000转/分钟，离心时间5分钟)，置于烘箱中45摄氏度烘干3小时，从PDMS模具中剥离样品，即得快速递送微针。得到的快速递药微针用扫描电子显微镜观察。Add 500 microliters of 5% sodium carboxymethyl cellulose into the PDMS mold of the shaded microneedle, centrifuge with a horizontal rotor centrifuge (2000 rpm,
实施例6高效采样微针的采样效率测试Example 6 Sampling efficiency test of high-efficiency sampling microneedles
如图3至图6所示，首先吸取大肠埃希菌浓缩液10微升置于5毫升纯水中分散混匀，取200微升稀释液于LB固体培养基上平板涂布，于37摄氏度培养24小时，得到细菌平板。将高效采样微针和普通医用棉签分别置于细菌平板上吸取15秒，取下微针和棉签后分别置于5毫升纯水中充分释放吸收菌液，将菌液梯度稀释至100000倍，各取50微升稀释液分别涂布到LB固体培养基上，于37摄氏度培养24小时，菌落计数对比采样效率。结果证明高效采样微针的采样效率(细菌浓度平均值CFU＝15.7*107)约为普通医用棉签采样效率(细菌浓度平均值CFU＝9.3*106)的12-18倍。As shown in Figure 3 to Figure 6, firstly draw 10 microliters of Escherichia coli concentrated solution and place it in 5 ml of pure water to disperse and mix well, take 200 microliters of diluted solution and spread it on LB solid medium, at 37 degrees Celsius. After culturing for 24 hours, bacterial plates were obtained. Place the high-efficiency sampling microneedle and ordinary medical cotton swab on the bacterial plate and absorb for 15 seconds. After removing the microneedle and cotton swab, place them in 5 ml of pure water to fully release the absorbed bacterial liquid, and dilute the bacterial liquid gradient to 100,000 times. Take 50 microliters of dilutions and spread them on LB solid medium respectively, and cultivate them at 37 degrees Celsius for 24 hours, and count the colonies to compare the sampling efficiency. The results show that the sampling efficiency of high-efficiency sampling microneedles (average bacterial concentration CFU=15.7*107 ) is about 12-18 times that of ordinary medical cotton swabs (average bacterial concentration CFU=9.3*106 ).
实施例7快速递送微针的递送效率测试Example 7 Delivery Efficiency Test of Rapid Delivery Microneedles
如图3至图6所示，首先将盐酸庆大霉素溶解于5％羧甲基纤维素钠溶液中，制备成每毫升含3毫克盐酸庆大霉素的5％羧甲基纤维素钠溶液，此后根据实施例5制备快速递药微针，同法制备不带有微针和底纹的普通贴片作为对照组。吸取大肠埃希菌浓缩液10微升置于5毫升纯水中分散混匀，得大肠埃希菌稀释液，将搭载有庆大霉素的快速递送微针和普通贴片分别置于LB固体培养基上15秒释放药物，取下微针和贴片后分别吸取200微升大肠埃希菌稀释液于LB固体培养基上平板涂布，于37摄氏度培养24小时，统计抑菌圈面积对比递送效率。结果证明快速递送微针的递送效率(抑菌圈平均面积S＝421.603平方毫米)约为普通贴片递送效率(抑菌圈平均面积S＝30.3372平方毫米)的10-15倍。As shown in Figure 3 to Figure 6, firstly, gentamicin hydrochloride was dissolved in 5% sodium carboxymethyl cellulose solution to prepare 5% sodium carboxymethyl cellulose containing 3 mg of gentamicin hydrochloride per milliliter After that, the rapid drug delivery microneedles were prepared according to Example 5, and the ordinary patches without microneedles and shading were prepared by the same method as the control group. Aspirate 10 microliters of Escherichia coli concentrated solution and place it in 5 ml of pure water to disperse and mix to obtain Escherichia coli dilution, and place the rapid delivery microneedle and ordinary patch loaded with gentamicin on LB solids respectively. The drug was released on the medium for 15 seconds. After removing the microneedle and the patch, 200 microliters of Escherichia coli dilution were drawn and spread on the LB solid medium, and incubated at 37 degrees Celsius for 24 hours. The area of inhibition zone was compared. delivery efficiency. The results show that the delivery efficiency of rapid delivery microneedles (average area of inhibition zone S=421.603 square millimeters) is about 10-15 times the delivery efficiency of ordinary patches (average area of inhibition zone S=30.3372 square millimeters).
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| TWI856848B (en)* | 2023-10-19 | 2024-09-21 | 達運精密工業股份有限公司 | Microneedle device |
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| TWI856848B (en)* | 2023-10-19 | 2024-09-21 | 達運精密工業股份有限公司 | Microneedle device |
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