公开(公告)号：US06471903B2

公开(公告)日：2002-10-29

申请号：US09956520

申请日：2001-09-19

申请人： Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

发明人： Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

IPC分类号： B29C3342

CPC分类号： B29C51/082 ,  A61M37/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  B26F1/24 ,  B29C33/0033 ,  B29C33/42 ,  B29C37/0053 ,  B29C45/2628 ,  B29C51/00 ,  B29C2059/023 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055 ,  B81C1/00111 ,  B81C2201/036

摘要： An array of hollow microneedles is constructed of molded plastic, in which a micro-machining technique is used to fabricate the molds used in a plastic microforming process. The molds are detachable and can be re-used. The preferred process for making the plastic arrays of microneedles is a microinjection technique. In the microinjection method, a molten plastic substance is injected between two micro-machined molds that contain microhole and micropillar arrays. Once the desired shape of the microneedle array has been formed, the mold and the plastic material are cooled down. Next, the molds are separated and the plastic microneedle array is detached from the mold structures.

摘要翻译： 中空微针阵列由模制塑料构成，其中使用微加工技术来制造在塑料微成形过程中使用的模具。 模具是可拆卸的，可以重新使用。 用于制造微针的塑料阵列的优选方法是显微注射技术。 在显微注射方法中，将熔融塑料物质注入包含微孔和微柱阵列的两个微加工模具之间。 一旦已经形成所需的微针阵列形状，就将模具和塑料材料冷却下来。 接下来，模具被分离，并且塑料微针阵列与模具结构分离。

公开(公告)号：US06379324B1

公开(公告)日：2002-04-30

申请号：US09328947

申请日：1999-06-09

申请人： Vladimir Gartstein ,  Dragan Danilo Nebrigic ,  Grover David Owens ,  Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov

发明人： Vladimir Gartstein ,  Dragan Danilo Nebrigic ,  Grover David Owens ,  Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov

IPC分类号： A61B1720

CPC分类号： B81C99/0085 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150099 ,  A61B5/150282 ,  A61B5/150389 ,  A61B5/150412 ,  A61B5/150458 ,  A61B5/150969 ,  A61B5/150984 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055

摘要： A first embodiment microneedle array is constructed of silicon and silicon dioxide compounds using MEMS technology and standard microfabrication techniques to create hollow cylindrical individual microneedles. The resulting array of microneedles can penetrate with a small pressure through the stratum corneum of skin to either deliver drugs or to facilitate interstitial fluid sampling through the hollow microneedles into the epidermis. The delivery of drugs and sampling of fluids can be performed by way of passive diffusion (time release), instantaneous injection, or iontophoresis. In a second embodiment, an array of hollow (or solid) microneedles is constructed of plastic or some other type of molded or cast material. An electric field may be used to increase transdermal flow rate, and the microneedles can be effectively combined with the application of an electric field between an anode and cathode attached to the skin which causes a low-level electric current. As a drug delivery system, the microneedle array includes electrodes that apply an electric potential to the skin between the electrode locations. One of the electrode assemblies is filled with an ionized drug, and the charged drug molecules move into the body due to the applied electric potential. As a body-fluid sampling system, the microneedle array also includes electrodes to assist in moving fluid from the body into a receiving chamber, and which further includes a bioelectrochemical sensor to measure the concentration of a particular substance.

摘要翻译： 第一实施例微针阵列由硅和二氧化硅化合物构成，使用MEMS技术和标准微加工技术来制造中空圆柱形单个微针。 所得的微针阵列可以通过皮肤的角质层穿透小的压力，以递送药物或促进通过空心微针进入表皮的间质液取样。 可以通过被动扩散（时间释放），瞬时注射或离子电渗法进行药物的输送和液体取样。 在第二实施例中，中空（或固体）微针的阵列由塑料或其它类型的模制或铸造材料构成。 可以使用电场来增加透皮流速，并且可以将微针与附着在皮肤上的阳极和阴极之间的电场的施加有效地组合，这导致低电平电流。 作为药物递送系统，微针阵列包括在电极位置之间向皮肤施加电位的电极。 电极组件中的一个填充有电离药物，并且带电药物分子由于施加的电位而进入体内。 作为体液采样系统，微针阵列还包括有助于将流体从身体移动到接收室中的电极，并且还包括用于测量特定物质浓度的生物电化学传感器。

公开(公告)号：US06652478B1

公开(公告)日：2003-11-25

申请号：US09580780

申请日：2000-05-26

申请人： Vladimir Gartstein ,  Dragan Danilo Nebrigic ,  Grover David Owens ,  Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Francisco Arias

发明人： Vladimir Gartstein ,  Dragan Danilo Nebrigic ,  Grover David Owens ,  Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Francisco Arias

IPC分类号： A61B1720

CPC分类号： B81C99/0085 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150099 ,  A61B5/150282 ,  A61B5/150389 ,  A61B5/150412 ,  A61B5/150458 ,  A61B5/150969 ,  A61B5/150984 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055

摘要： A hollow microneedle with a substantially sharp edge is provided that includes at least one longitudinal blade at the top surface or tip of the microneedle to aid in penetration of the stratum corneum of skin. In a preferred embodiment, there are two such longitudinal blades that are constructed on opposite surfaces at approximately a 180° angle along the cylindrical side wall of the microneedle. Each edged blade has a cross-section that, when viewed from above the microneedle top, has an isosceles triangle profile. The blade's edge can run the entire length of the microneedle from its very top surface to its bottom surface where it is mounted onto the substrate, or the edge can be discontinued partway down the length of the microneedle. A star-shaped solid microneedle also is provided having at least one blade with a relatively sharp edge to assist in penetrating the stratum corneum of skin. In a preferred embodiment, a three pointed star-shape is used, in which each blade has an isosceles triangular cross-section when viewed from the top of the microneedle. The base of each of the isosceles triangles meets at a center of the microneedle to form the star-shaped structure. At least one hole through the substrate is located near the side surfaces of the pairs of blades of the solid microneedle.

摘要翻译： 提供具有基本锋利边缘的中空微针，其包括在微针的顶表面或尖端处的至少一个纵向刀片，以有助于皮肤角质层的穿透。 在优选实施例中，存在两个这样的纵向叶片，其沿着微针的圆柱形侧壁以大约180°的角度在相对的表面上构造。 每个边缘叶片具有横截面，当从上面观察微针顶部时，其具有等腰三角形轮廓。 刀片的边缘可以将微针的整个长度从其最上表面延伸到其底部表面，在其底部安装到基底上，或者边缘可以在微针的长度上中断。 还提供了星形固体微针，其具有至少一个具有相对锋利边缘的刀片，以有助于穿透皮肤角质层。 在优选实施例中，使用三角星形，其中当从微针的顶部观察时，每个叶片具有等腰三角形横截面。 每个等腰三角形的基部在微针的中心相交，形成星形结构。 穿过基底的至少一个孔位于固体微针的成对叶片的侧表面附近。

公开(公告)号：US06312612B1

公开(公告)日：2001-11-06

申请号：US09328946

申请日：1999-06-09

申请人： Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

发明人： Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

IPC分类号： B81C100

CPC分类号： B29C51/082 ,  A61M37/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  B26F1/24 ,  B29C33/0033 ,  B29C33/42 ,  B29C37/0053 ,  B29C45/2628 ,  B29C51/00 ,  B29C2059/023 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055 ,  B81C1/00111 ,  B81C2201/036

摘要： A microneedle array is constructed of silicon and silicon dioxide compounds using MEMS (i.e., Micro-Electro-Mechanical-Systems) technology and standard microfabrication techniques. The microneedle array may be fabricated from a silicon die which can be etched in a microfabrication process to create hollow cylindrical individual microneedles. The resulting array of microneedles can penetrate with a small pressure through the stratum corneum of skin (including skin of animals, reptiles, or other creatures—typically skin of a living organism) to either deliver drugs or to facilitate interstitial fluid sampling through the hollow microneedles.

摘要翻译： 微针阵列由使用MEMS（即微机电系统）技术和标准微细加工技术的硅和二氧化硅化合物构成。 微针阵列可以由可以在微细加工过程中蚀刻以形成中空圆柱形单个微针的硅晶片制造。 所产生的微针阵列可以通过皮肤角质层（包括动物，爬行动物或其他生物的皮肤，通常是生物体的皮肤）以较小的压力穿透，以递送药物或促进通过空心微针进行间质液取样 。

公开(公告)号：US06256533B1

公开(公告)日：2001-07-03

申请号：US09329025

申请日：1999-06-09

申请人： Vadim Vladimirovich Yuzhakov ,  Faiz Feisal Sherman ,  Grover David Owens ,  Vladimir Gartstein

发明人： Vadim Vladimirovich Yuzhakov ,  Faiz Feisal Sherman ,  Grover David Owens ,  Vladimir Gartstein

IPC分类号： A61N130

CPC分类号： B81C99/0085 ,  A61M5/1723 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  A61M2037/0061 ,  A61N1/30 ,  B81B2201/055

摘要： A microneedle array, constructed of silicon and silicon dioxide compounds or of a molded plastic material, is provided to penetrate the stratum corneum and epidermis layers of skin, but not into the dermis. The microneedles can be used to either dispense a liquid drug, or to sample a body fluid. The delivery of drugs and sampling of fluids can be performed by way of passive diffusion (time release), instantaneous injection, or iontophoresis. A complete closed-loop system can be manufactured including active elements, such as micro-machined pumps, as well as passive elements such as sensors. A “smart patch” can thereby be fabricated that samples body fluids, performs chemistry to decide on the appropriate drug dosage, and then administers the corresponding amount of drug. An electric field may be used to increase transdermal flow rate. Such a system can be made disposable, and can be used with medical devices to dispense drugs by iontophoretic/microneedle enhancement, to sample body fluids (while providing an iontophoretically/microneedle-enhanced body-fluid sensor), and as a closed-loop drug delivery system with fluid sampling feedback using a combination of the other two devices. As a drug dispensing system, the microneedle array includes electrodes that apply an electric potential to the skin between the electrode locations. One of the electrode assemblies is filled with an ionized drug, and the charged drug molecules move into the body due to the applied electric potential. As a body-fluid sampling system, the microneedle array also includes electrodes to assist in moving fluid from the body into a receiving chamber, and which further includes a bioelectrochemical sensor to measure the concentration of a particular substance.

摘要翻译： 提供由硅和二氧化硅化合物或模制塑料材料构成的微针阵列以穿透角质层和皮肤表皮层，但不渗入真皮层。 微针可以用于分配液体药物，或者对体液进行采样。 可以通过被动扩散（时间释放），瞬时注射或离子电渗法进行药物的输送和液体取样。 可以制造完整的闭环系统，包括有源元件，如微加工泵，以及诸如传感器的无源元件。 因此，可以制造“智能贴片”，使样品体液进行化学以确定合适的药物剂量，然后施用相应量的药物。 可以使用电场来增加透皮流速。 这样的系统可以被制成一次性的，并且可以与医疗装置一起使用，通过离子电渗/微针增强来分配药物，以便体液（同时提供离子电渗/微型增强的体液传感器）和作为闭环药物 交付系统采用流体采样反馈，使用其他两个设备的组合。 作为药物分配系统，微针阵列包括在电极位置之间向皮肤施加电位的电极。 电极组件中的一个填充有电离药物，并且带电药物分子由于施加的电位而进入体内。 作为体液采样系统，微针阵列还包括有助于将流体从身体移动到接收室中的电极，并且还包括用于测量特定物质浓度的生物电化学传感器。

公开(公告)号：US07416541B2

公开(公告)日：2008-08-26

申请号：US11121291

申请日：2005-05-03

申请人： Vadim Vladimirovich Yuzhakov ,  Faiz Feisal Sherman ,  Grover David Owens ,  Vladimir Gartstein

发明人： Vadim Vladimirovich Yuzhakov ,  Faiz Feisal Sherman ,  Grover David Owens ,  Vladimir Gartstein

IPC分类号： A61M5/32 ,  A61B17/20 ,  A61B17/32 ,  A61B17/34

CPC分类号： B81C99/0085 ,  A61M5/1723 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  A61M2037/0061 ,  A61N1/30 ,  B81B2201/055

摘要： Improved microneedle arrays are provided having a sufficiently large separation distance between each of the individual microneedles to ensure penetration of the skin while having a sufficiently small separation distance to provide high transdermal transport rates. A very useful range of separation distances between microneedles is in the range of 100-300 microns, and more preferably in the range of 100-200 microns. The outer diameter and microneedle length is also very important, and in combination with the separation distance will be crucial as to whether or not the microneedles will actually penetrate the stratum corneum of skin. For circular microneedles, a useful outer diameter range is from 20-100 microns, and more preferably in the range of 20-50 microns. For circular microneedles that do not have sharp edges, a useful length for use with interstitial fluids is in the range of 50-200 microns, and more preferably in the range of 100-150 microns; for use with other biological fluids, a useful length is in the range of 200 microns-3 mm, and more preferably in the range of 200-400 microns. For circular microneedles having sharp side edges, a useful length for use with interstitial fluids is in the range of 50-200 microns, and more preferably in the range of 80-150 microns; for use with other biological fluids, a useful length is again in the range of 200 microns-3 mm, and more preferably in the range of 200-400 microns. For solid microneedles having a star-shaped profile with sharp edges for its star-shaped blades, a useful length for use with interstitial fluids is in the range of 50-200 microns, and more preferably in the range of 80-150 microns; for use with other biological fluids, a useful length is again in the range of 200 microns-3 mm, and more preferably in the range of 200-400 microns, while the radius of each of its blades is in the range of 10-50 microns, and more preferably in the range of 10-15 microns.

公开(公告)号：US06451240B1

公开(公告)日：2002-09-17

申请号：US09579798

申请日：2000-05-26

申请人： Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

发明人： Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

IPC分类号： B26F124

CPC分类号： B29C51/082 ,  A61M37/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  B26F1/24 ,  B29C33/0033 ,  B29C33/42 ,  B29C37/0053 ,  B29C45/2628 ,  B29C51/00 ,  B29C2059/023 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055 ,  B81C1/00111 ,  B81C2201/036

摘要： A microneedle array is manufactured using a mold preparation procedure that begins by placing an optical mask over a layer of PMMA material, exposing the PMMA material to x-rays, then developing using a photoresist process. The remaining PMMA material is then electroplated with metal. Once the metal has reached an appropriate thickness, it is detached to become a metal mold that is used in a microembossing procedure, in which the metal mold is pressed against a heated layer of plastic material. Once the mold is pressed down to its proper distance, the plastic material is cooled until solidified, and the mold is then detached, thereby leaving behind an array of microneedles.

摘要翻译： 使用模具制备程序制造微针阵列，其通过在PMMA材料层上放置光学掩模开始，将PMMA材料暴露于x射线，然后使用光致抗蚀剂工艺显影。 然后将剩余的PMMA材料用金属电镀。 一旦金属达到适当的厚度，就将其分离成为用于微压制程序的金属模具，其中金属模具被压在加热的塑料材料层上。 一旦将模具按压到适当的距离，塑料材料被冷却直到固化，然后将模具分离，从而留下一组微针。

公开(公告)号：US06931277B1

公开(公告)日：2005-08-16

申请号：US09580819

申请日：2000-05-26

申请人： Vadim Vladimirovich Yuzhakov ,  Faiz Feisal Sherman ,  Grover David Owens ,  Vladimir Garstein

发明人： Vadim Vladimirovich Yuzhakov ,  Faiz Feisal Sherman ,  Grover David Owens ,  Vladimir Garstein

IPC分类号： A61M5/00 ,  A61M5/172 ,  A61M37/00 ,  A61N1/30 ,  A61M5/32

CPC分类号： B81C99/0085 ,  A61M5/1723 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  A61M2037/0061 ,  A61N1/30 ,  B81B2201/055

摘要： Improved microneedle arrays are provided having a sufficiently large separation distance between each of the individual microneedles to ensure penetration of the skin while having a sufficiently small separation distance to provide high transdermal transport rates. A very useful range of separation distances between microneedles is in the range of 100–300 microns, and more preferably in the range of 100–200 microns. The outer diameter and microneedle length is also very important, and in combination with the separation distance will be crucial as to whether or not the microneedles will actually penetrate the stratum corneum of skin. For circular microneedles, a useful outer diameter range is from 20–100 microns, and more preferably in the range of 20–50 microns. For circular microneedles that do not have sharp edges, a useful length for use with interstitial fluids is in the range of 50–200 microns, and more preferably in the range of 100–150 microns; for use with other biological fluids, a useful length is in the range of 200 microns–3 mm, and more preferably in the range of 200–400 microns. For circular microneedles having sharp side edges, a useful length for use with interstitial fluids is in the range of 50–200 microns, and more preferably in the range of 80–150 microns; for use with other biological fluids, a useful length is again in the range of 200 microns–3 mm, and more preferably in the range of 200–400 microns. For solid microneedles having a star-shaped profile with sharp edges for its star-shaped blades, a useful length for use with interstitial fluids is in the range of 50–200 microns, and more preferably in the range of 80–150 microns; for use with other biological fluids, a useful length is again in the range of 200 microns–3 mm, and more preferably in the range of 200–400 microns, while the radius of each of its blades is in the range of 10–50 microns, and more preferably in the range of 10–15 microns.

公开(公告)号：US06591124B2

公开(公告)日：2003-07-08

申请号：US09853442

申请日：2001-05-11

申请人： Faiz Feisal Sherman ,  Francisco Arias ,  Vladimir Gartstein ,  Grover David Owens ,  Milan Marcel Jevtitch ,  Chow Chi Huang

发明人： Faiz Feisal Sherman ,  Francisco Arias ,  Vladimir Gartstein ,  Grover David Owens ,  Milan Marcel Jevtitch ,  Chow Chi Huang

IPC分类号： A61B505

CPC分类号： A61B5/1486 ,  A61B5/14514 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/150022 ,  A61B5/150076 ,  A61B5/150099 ,  A61B5/150221 ,  A61B5/150229 ,  A61B5/150358 ,  A61B5/150389 ,  A61B5/150503 ,  A61B5/150938 ,  A61B5/150969 ,  A61B5/150984 ,  A61B5/15105 ,  A61B5/15113 ,  A61B5/15125 ,  A61B5/15142 ,  A61B5/15153 ,  A61B5/15163 ,  A61B5/15169 ,  A61B5/15171 ,  A61B5/15178 ,  A61B5/15186 ,  A61B5/155 ,  A61B5/157 ,  A61B2560/04 ,  A61B2562/0295 ,  A61M37/0015 ,  A61M2230/201

摘要： A strip-like microneedle device is provided that includes an array of hollow microneedles, a diaphragm pump to extract interstitial fluid from skin, and a sensor that detects the concentration of the fluid. The microneedle device can be interfaced to an external sensor to produce a reading, or can be self-contained. One version uses an attachable/detachable microneedle array as a single-use, disposable unit. The device is portable, and is used by placing one finger on the microneedle array, and actuating the diaphragm pump with another finger, thereby obtaining the fluid sample. Solid coated or transparent microneedles could instead be used as an in-situ sensor, with either electrodes or an optical sensor.

公开(公告)号：US06565532B1

公开(公告)日：2003-05-20

申请号：US09614321

申请日：2000-07-12

申请人： Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

发明人： Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

IPC分类号： A61M3700

CPC分类号： B81C99/0085 ,  A45D34/04 ,  A45D2200/1018 ,  A45D2200/1045 ,  A61M37/0015 ,  A61M37/0076 ,  A61M2037/003 ,  A61M2037/0053 ,  A61N1/30 ,  B29C51/00 ,  B81B2201/055

摘要： An array of microneedles is provided to apply semi-permanent or permanent markings to skin, or to apply semi-permanent subcutaneous makeup or other cosmetic compounds to skin. The microneedles can apply identifications or other tattoo-like graphics, and will not enter into the dermal layer of the skin so that the application procedure is painless. The microneedle array is also useful for delivering specific compounds or actives into the skin, such as cosmetic compounds or nutrients, or various skin structure modifiers that can be delivered subcutaneously without having to visit a cosmetic surgery clinic.

摘要翻译： 提供一系列微针，以将半永久性或永久性标记施用于皮肤，或将半永久性皮下化妆或其他化妆品化合物施用于皮肤。 微针可以应用标识或其他纹身图形，并且不会进入皮肤的真皮层，使得应用程序是无痛的。 微针阵列还可用于将特定的化合物或活性物质递送到皮肤中，例如化妆品化合物或营养物，或可以皮下递送而不必访问整容手术诊所的各种皮肤结构修饰剂。