CN108325063B - Device with electric stimulation micro needle point array structure - Google Patents
Device with electric stimulation micro needle point array structure Download PDFInfo
- Publication number
- CN108325063B CN108325063B CN201711400311.7A CN201711400311A CN108325063B CN 108325063 B CN108325063 B CN 108325063B CN 201711400311 A CN201711400311 A CN 201711400311A CN 108325063 B CN108325063 B CN 108325063B
- Authority
- CN
- China
- Prior art keywords
- electric
- micro
- stimulation
- electric stimulation
- stimulation unit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000000638 stimulation Effects 0.000 title claims abstract description 91
- 125000006850 spacer group Chemical group 0.000 claims description 26
- 239000002184 metal Substances 0.000 claims description 15
- 238000009413 insulation Methods 0.000 claims description 6
- 239000003814 drug Substances 0.000 abstract description 13
- 238000004520 electroporation Methods 0.000 abstract description 10
- 238000001890 transfection Methods 0.000 abstract description 9
- 108090000623 proteins and genes Proteins 0.000 abstract description 8
- 230000003796 beauty Effects 0.000 abstract description 5
- 238000007920 subcutaneous administration Methods 0.000 abstract description 5
- 238000002512 chemotherapy Methods 0.000 abstract description 3
- 230000036560 skin regeneration Effects 0.000 abstract description 2
- 238000012377 drug delivery Methods 0.000 description 11
- 229940079593 drug Drugs 0.000 description 9
- 230000000694 effects Effects 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 108010054624 red fluorescent protein Proteins 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/328—Applying electric currents by contact electrodes alternating or intermittent currents for improving the appearance of the skin, e.g. facial toning or wrinkle treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
- A61N1/36014—External stimulators, e.g. with patch electrodes
- A61N1/36017—External stimulators, e.g. with patch electrodes with leads or electrodes penetrating the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M2037/0007—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0023—Drug applicators using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/05—General characteristics of the apparatus combined with other kinds of therapy
- A61M2205/054—General characteristics of the apparatus combined with other kinds of therapy with electrotherapy
Abstract
The application provides a device with an electro-stimulation micro-needle point array structure, wherein: the electric stimulation micro-needle point array structure comprises a mounting frame, a plurality of electric stimulation units regularly arranged on the mounting frame, and a plurality of insulating spacing parts for spacing adjacent electric stimulation units; a supply circuit for transmitting electric stimulation signals to each electric stimulation unit; any one electrical stimulation unit has opposite electric polarity to the adjacent electrical stimulation unit; each electric stimulation unit is provided with uniformly distributed micro-needle points. By combining appropriate electrical stimulation, skin regeneration can be stimulated more rapidly, and simultaneously, the delivery efficiency of subcutaneous gene medicine can be accelerated. Can be applied to the fields of beauty medicine, electroporation transfection, electric chemotherapy and the like.
Description
Technical Field
The application relates to the technical field of medical auxiliary drug delivery instruments and medical beauty instruments, in particular to a gene drug therapy auxiliary tool and a beauty auxiliary tool, and particularly relates to a device with an electric stimulation micro-needle point array structure.
Background
The major technical barrier to effective vaccination via DNA vaccines or the treatment of diseases with certain functional gene drugs is the need for drug delivery across the cell membrane. Whereas the current drug delivery by injection of DNA drugs into muscle tissue or subcutaneous tissue is very inefficient, which results in very weak immune responses of these genetic drugs in large mammals, greatly reducing the utility of these drugs.
A number of different strategies have been used to facilitate the delivery of these genetic drugs into the interior of cells, with cells that effectively deliver the drug to skin tissue receiving more attention in the clinic. Because skin is the largest organ of the human body, is the most accessible and easily monitored compared to other tissues, and has very high immunological competence, various surgical procedures on skin can be resumed in a very fast time. The strong protective ability of the skin to the body severely limits the effectiveness of various gene drugs delivered to the skin tissue.
For efficient drug delivery or gene delivery in skin tissue, various physical, chemical or biological methods have been developed, including gene gun, liposome vector and viral vector methods have been widely used, but some of these methods are too expensive, some are too expensive, and even some methods are not bio-safe, may cause other serious genetic variation, and cannot be applied to human body.
The method of electroporation using electrical stimulation is considered as a physical method of gene drug delivery with high efficiency and high biosafety. The method is to apply a short electrical pulse to the skin or other tissue, so that the cell membrane in the target area generates an aqueous pathway, thereby allowing certain macromolecules (DNA, etc.) to penetrate the cell membrane into the cell interior, and effective drug delivery is completed.
In order to achieve electroporation of organ cells, a certain threshold value of electric field strength needs to be met, and often the threshold values are relatively high, so that electric damage to a target organ is easily caused. Currently, to reduce damage to the underlying skin, most electroporation electrode assemblies employ a single microneedle to form an array of closely spaced electrodes so that sufficient electric field strength can be achieved at low voltages.
For example, chinese patent application (application number 201180011473.6) discloses a minimally invasive electroporation device comprising a plurality of micro-needles arranged in an array. The device performs effective, near pain-free dermal delivery of gene drugs by controlling the length and spacing of the microneedles. There is another hand-held device (chinese patent application No. 201280029914. X) that also achieves subcutaneous electroporation by an array of microneedles that invade the skin. However, these devices are all assembled independently with a single microneedle, which limits the size of the entire electrode array, resulting in drug delivery in a small area, which limits certain application scenarios requiring larger doses of drug delivery.
Disclosure of Invention
In view of the above, the present application aims to provide a device with an electrical stimulation micro-needle tip array structure, which can more rapidly stimulate skin regeneration by matching with appropriate electrical stimulation, and can also accelerate the delivery efficiency of subcutaneous gene drugs. Can be applied to the fields of beauty medicine, electroporation transfection, electric chemotherapy and the like.
In order to achieve the above purpose, the technical scheme adopted by the application is as follows:
a device with an electro-stimulated microneedle array structure, wherein:
the electric stimulation micro-needle point array structure comprises a mounting frame, a plurality of electric stimulation units regularly arranged on the mounting frame, and a plurality of insulating spacing parts for spacing adjacent electric stimulation units;
a supply circuit for transmitting electric stimulation signals to each electric stimulation unit;
any one electrical stimulation unit has opposite electric polarity to the adjacent electrical stimulation unit; each electric stimulation unit is provided with uniformly distributed micro-needle points.
Further, the electric stimulation signal is pulse voltage, the pulse is square wave or exponential wave, the voltage intensity is 3V-70V, the pulse width is 0.1-100ms, and the pulse interval is 0.5-10s.
Further, the material of the electric stimulation unit is biocompatible metal.
Further, the electric stimulation unit and the insulation spacer are both sheet-shaped, and the thickness of the electric stimulation unit is 50-200 mu m; the length of the micro needle points is 1mm to 3mm; the protruding insulating spacers have a length of 0.5mm to 2mm.
Further, the mounting frame is formed on a handle, one end of the mounting frame is provided with a handle head part serving as the mounting frame, the other end of the mounting frame is provided with a handle tail part, and the handle head part is provided with a groove part for mounting the stimulation unit; the tail part of the handle is provided with an electric plug for receiving an electric stimulation signal.
Further, the electric plug is connected and fixed with two columnar connectors of the electric stimulation unit which respectively penetrate through the groove part and are electrically connected with different electric polarities through wires inside the handle.
Further, the electric stimulation unit is rectangular sheet-shaped, the micro needle points are uniformly distributed on one side of the electric stimulation unit, and the tips of the micro needle points are positioned on or approximately positioned on the same plane; the insulating spacer is rectangular sheet-shaped.
Further, the insulating spacer is formed with two through holes through which the columnar joints pass, and the electro-stimulation unit is formed with a single through hole through which one of the columnar joints passes according to different electric polarities.
Further, the electric stimulation unit is in a round shape or a round-like sheet shape, and the micro needle points are uniformly distributed on the circumference side of the electric stimulation unit; the tips of the micro needle points are positioned on or approximately positioned on the same cylinder or cylinder-like curved surface; the insulation interval is in a round or round-like sheet shape;
the groove part is provided with a rotating shaft which penetrates through and is fixedly connected with each electric stimulation unit and the insulating spacing part.
Further, the electric plug is connected with the sliding electric ring electrically connected with each electric stimulation unit through a metal connecting wire inside the handle.
By adopting the technical scheme, the electric stimulation unit with the micro needle point is in an electric interconnection structure: the electric stimulation units and the insulating spacing parts are mutually arranged at intervals, so that the electric polarities of two adjacent electric stimulation units are opposite, the electric stimulation of low voltage can be completed within a small distance, and the electric damage to the skin is reduced to the minimum. Therefore, the microneedle array is utilized to electrically stimulate the skin, so that the skin can be quickly subjected to cosmetic regeneration or subcutaneous drug administration efficiency is increased, the core function of the microneedle massage device is optimized, the using effect of the product is improved, breakthrough progress is achieved, and the microneedle massage device has higher popularization value.
Drawings
FIG. 1 is an enlarged schematic view of a portion of a body structure and a microneedle array of an apparatus with an electro-stimulation microneedle array structure according to an embodiment of the present application.
FIG. 2 is an enlarged schematic view of a portion of the body structure and an electrical plug from another perspective of an apparatus with an electrical stimulation micro-needle array structure according to an embodiment of the application.
FIG. 3 is an exploded view of an apparatus with an electro-stimulated micro-needle array structure in accordance with one embodiment of the present application.
FIG. 4 is a schematic diagram of an electro-stimulation unit in an apparatus with an electro-stimulation micro-needle array structure according to an embodiment of the present application.
FIG. 5 is a schematic diagram of the structure of an insulating spacer in an apparatus with an electro-stimulation micro-needle array structure according to an embodiment of the present application.
FIG. 6 is an enlarged schematic view of a portion of a body structure and a microneedle array of an apparatus with an electro-stimulation microneedle array structure according to another embodiment of the present application.
FIG. 7 is an enlarged schematic view of a portion of a body structure and a tail electrical plug from another perspective of a device with an electrical stimulation micro-needle tip array structure in accordance with another embodiment of the application.
FIG. 8 is an exploded view of a device with an electro-stimulated micro-needle array structure in accordance with another embodiment of the present application.
FIG. 9 is a schematic diagram of the structure of an electro-stimulation unit in a preferred implementation of the device with an electro-stimulation micro-needle tip array structure in another embodiment of the application.
FIG. 10 is an exploded view of a portion of the structure of a preferred implementation of a device with an electro-stimulated microneedle array structure in accordance with another embodiment of the present application.
FIG. 11 is a schematic diagram of the structure of an electro-stimulation unit in another preferred implementation of the device with an electro-stimulation micro-needle tip array structure in another embodiment of the application.
FIG. 12 is a schematic view of the structure of an insulating spacer in another preferred implementation of the device with an electro-stimulation micro-needle tip array structure in another embodiment of the application.
FIG. 13 is an exploded view of a portion of the structure of another preferred implementation of a device with an electro-stimulated microneedle array structure in accordance with another embodiment of the present application.
FIG. 14 is a schematic diagram showing the effect of red fluorescent protein plasmid transfection on mouse skin when an animal experiment is performed with a device having an array structure of electrically stimulated micro-tips according to another embodiment of the present application.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application.
In a basic embodiment, a device with an electro-stimulation micro-needle tip array structure is provided, wherein:
the electric stimulation micro-needle point array structure comprises a mounting frame, a plurality of electric stimulation units regularly arranged on the mounting frame, and a plurality of insulating spacing parts for spacing adjacent electric stimulation units; the power supply circuit is used for transmitting electric stimulation signals to each electric stimulation unit; any one electrical stimulation unit has opposite electric polarity to the adjacent electrical stimulation unit; each electric stimulation unit is provided with uniformly distributed micro-needle points. Thus, the electrical stimulation unit with the micro-needle points is in an electrical interconnection structure: the electric stimulation units and the insulating spacing parts are mutually arranged at intervals, so that the electric polarities of two adjacent electric stimulation units are opposite, the electric stimulation of low voltage can be completed within a small distance, and the electric damage to the skin is reduced to the minimum.
The electric stimulation signal is pulse voltage, the pulse is square wave or exponential wave, the voltage intensity is 10V-70V, the pulse width is 0.1-100ms, and the pulse interval is 0.5-10s. The number of therapeutic pulses may be selected from the range of 3-20 times, depending on the needs.
In all embodiments of the application, the microneedle tips are sheet-like with triangular or triangularly-like profiles having a width to length ratio of 1:3 to 1:10.
The mounting frame is formed on a handle, one end of the mounting frame is provided with a handle head part serving as the mounting frame, the other end of the mounting frame is provided with a handle tail part, and the handle head part is provided with a groove part provided with a stimulation unit; the tail part of the handle is provided with an electric plug for receiving the electric stimulation signal.
According to a different implementation, in an embodiment, the electrical plug is connected by wires inside the handle to two cylindrical joints fixed in the slot, respectively penetrating and electrically connecting the electrical stimulation units of different electrical polarities.
The electric stimulation unit is rectangular sheet-shaped, the micro needle points are uniformly distributed on one side of the electric stimulation unit, and the tips of the micro needle points are positioned on or approximately positioned on the same plane; the insulating spacer is rectangular sheet-shaped.
The insulating spacer is formed with two through holes through which the columnar joints pass, and the electric stimulation unit is formed with a single through hole through which one of the columnar joints passes respectively according to different electric polarities.
With reference to fig. 1 to 5, in the present embodiment, the device is implemented as a planar tip stimulator comprising two parts of a handle and a needle (an assembly of an electrical stimulation unit, an insulating spacer and a cylindrical joint).
Wherein, the handle includes: a handle body 101 having a handle needle tip mounting head 102 formed at one end and a handle tail 103 formed at the other end, and having a groove portion for mounting a needle 110; a handle needle tip pocket 104 is provided to close the open end of the slot.
Needle 110 includes: a plurality of pins 111 as electrical stimulation units and spacers 121 as insulating spacers are arranged at intervals.
The handle tail 103 is provided with: the electrical plug 105, which is used to receive the electrical stimulation signal, has electrical plug contacts 131a and 131b, respectively, connected to the columnar joints 132a and 132b of the handle head by metal wires inside the handle, which will be used to energize the microneedle array. Referring to fig. 3, a broken line represents an electrical connection, and two metal sheets arbitrarily spaced apart from each other are respectively connected to the positive electrode and the negative electrode. Part of the disk needle may be shielded by the septum and the depth of penetration of the needle tip into the skin is controlled by the length of the needle tip exposed to the outside.
Needle 110 is electrically interconnected: the plurality of spacers 121 and the needles 111 are arranged at intervals, two adjacent spacers of the interface 113 of the needle 111 are respectively arranged at the electric interfaces 132a and 132b of the head of the handle, so that the opposite electric polarities of the two adjacent needles are realized, the low-voltage electric stimulation can be completed within a small distance, and the electric damage to the skin is minimized. Specifically, the "small distance" is achieved by the septum thickness ranging from 0.5 to 2mm and the needle thickness ranging from 50 to 200 μm.
Handle needle tip hub 104 is inserted into receptacle 106 of the handle head via plug 107, the locations of which may be interchanged in some embodiments.
Referring to fig. 4 and 5, the shape of the needle 111 is as follows: having an array of needle tips 112 and electrical receptacles 113. The needle point is triangle-shaped, and wherein triangle-shaped bottom length is 0.3mm to 1mm, and length is 1mm to 3mm, and the spacer blocks the back, and the exposed needle point length of coming out is 0.5mm to 2mm inequality, and according to the skin thickness difference of using the position, it is better to adopt the needle point effect of corresponding length. The shape of the spacer 121 is as shown in the figure: including a double sided via 122 that allows electrical interconnect lines to pass through.
In another embodiment, the foregoing embodiment is modified, specifically, in this embodiment, the electrical stimulation unit is in a shape of a circle or a quasi-circle, and the micro needle points are uniformly distributed on the circumferential side of the electrical stimulation unit; the tips of the micro needle points are positioned on or approximately positioned on the same cylinder or cylinder-like curved surface; the insulation interval is round or round-like sheet; the groove part is provided with a rotating shaft which penetrates through and is fixedly connected with each electric stimulation unit and the insulating spacing part. The electric plug is connected with the sliding electric ring which is electrically connected with each electric stimulation unit through a metal connecting wire inside the handle.
With reference to fig. 6 to 13, in the present embodiment, the implementation of the device comprises a roller-type needle tip stimulator of two parts, namely a handle and a roller needle (an assembly of an electrical stimulation unit, an insulating spacer and an electrical connection structure).
Specifically, the handle includes: handle body 201, handle tip placement head 202, handle tail 203, handle tip pocket 204.
Needle 210 includes: a disk needle 220 as an electrical stimulation unit, and a spacer 230 as an insulating spacer. The needle point formed by the disc needle is triangular, wherein the side length of the bottom of the triangle is 0.3mm to 1mm, the length is 1mm to 3mm, the exposed needle point length is 0.5mm to 2mm and is different after the spacer is blocked, and the needle point effect of adopting the corresponding length is better according to the different skin thicknesses of the using parts.
Handle tail 203 specifically includes: the electrical plug 205 is used for receiving electrical signals, and the electrical plug contacts 231a and 231b are respectively connected to the sliding electrical ring 232 of the handle head 204 connected with the roller through metal wires inside the handle, and are used for powering the microneedle array. In connection with fig. 8, the dashed lines represent the internal electrical connections, with any two adjacent pins connected to the positive and negative electrodes, respectively.
An electrical interconnection structure: the spacers 230 and the needles 220 are arranged at intervals, the electrical polarities of two adjacent needles are opposite through internal electrical interconnection, and the electrical contacts 241 and 251 on the two sides of the needles are connected with the electrical ring 232 of the head of the handle to realize low-voltage electrical stimulation within a small distance, so that the electrical damage to the skin is minimized.
To make inter-chip insulation, two preferred implementations can be used in this embodiment:
a preferred implementation of the circular disc needle 220 a:
the wires will be connected to the corresponding metal disc pins through holes in the disc pins. The needles 220a include a plurality of micro needle points and through holes 221a for electrical connection, are disposed on the shaft 250a in the shape of 221a, a plurality of needles 220a and spacers 230a are alternately arranged on the shaft, and the through holes 221a of adjacent needles are alternately installed in the fixing grooves 252a of the shaft 250a, and are connected to the metal shafts 251a and 241a of the shafts 250a and 240a by wires or metal rods, as shown in fig. 10.
Another preferred implementation of circular disk needle 220 b:
the disc needle 220b includes a plurality of micro needle points and large through holes 221a and small through holes 222b for electrical connection, the small through holes 222b are used for electrical signals connected with wires or metal rods, and the large through holes provide enough space for the wires or metal rods inside to pass through and provide good insulation. The wires will be connected to the corresponding metal disc pins through small holes in the disc pins, while the large holes allow the wires to pass through, keeping the disc pins insulated from the wires passing through the large holes. The plurality of needles 220b and the spacer 230b are mounted on the rotating shaft in the mounting manner shown in fig. 13, and are connected to the metal shafts 251b and 241b of the shafts 250b and 240b by wires or metal rods.
In summary, embodiments of the present application depict devices for electrically stimulating skin using microneedle arrays through different implementations, which can achieve the goals of skin cosmetic or increasing subcutaneous drug delivery efficiency. Can be applied to the fields of beauty medicine, electroporation transfection, electric chemotherapy and the like.
The table plotted in fig. 14 shows the effect of performing a red fluorescent protein plasmid transfection experiment on mouse skin.
The experimental procedure was as follows: firstly, injecting red fluorescent protein plasmid into the skin of a mouse, attaching the application to a target region, lightly penetrating the skin of the mouse, and then stimulating the region by 10 short pulses (10 ms, 1s interval) with different voltage intensities to carry out electroporation transfection.
The efficiency of electroporation transfection is judged by the amount of the red fluorescent protein on the target site of the mouse, and the graph shows that the transfection effect is obviously enhanced by adding the electric stimulation, particularly, the peak is reached at the 50V intensity, and the damage caused by the further enhancement of the voltage is increased, so that the transfection rate is reduced. Compared with other commercial electrotransfection devices, the electric stimulation administration efficiency of the application is higher. Further observations were made of mice from each group, the skin lesions of the skin areas of mice stimulated with electricity using the present application were significantly reduced and were able to recover within days.
In addition, as the device provided by the embodiments of the application can support flexible adjustment of the action area of the micro-needle tip array, the drug delivery can be performed in a large enough area, and the requirements of certain application scenes requiring larger dosage of drug delivery are met.
It will be apparent that the described embodiments are only some, but not all, embodiments of the application. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application. The features and advantages of the present application will be described in detail below with reference to the attached drawing figures.
Claims (5)
1. A device with an electrical stimulation micro-needle point array structure is characterized in that,
the electric stimulation micro-needle point array structure comprises a mounting frame, a plurality of electric stimulation units regularly arranged on the mounting frame, and a plurality of insulating spacing parts for spacing adjacent electric stimulation units;
a supply circuit for transmitting electric stimulation signals to each electric stimulation unit;
any one electrical stimulation unit has opposite electric polarity to the adjacent electrical stimulation unit; each electric stimulation unit is provided with uniformly distributed micro needle points;
the electric stimulation unit and the insulation spacer are both sheet-shaped, and the length of the micro needle point is 1mm to 3mm; the protruding insulating spacers have a length of 0.5mm to 2mm;
the mounting frame is formed on a handle, one end of the mounting frame is provided with a handle head serving as the mounting frame, the other end of the mounting frame is provided with a handle tail, and the handle head is provided with a groove part for mounting the electric stimulation unit; the tail part of the handle is provided with an electric plug for receiving an electric stimulation signal;
the electric plug is connected and fixed to two columnar connectors of the electric stimulation unit which respectively penetrate through the groove part and are electrically connected with different electric polarities through wires inside the handle;
the insulating spacer is provided with two through holes for the columnar joints to pass through, and the electric stimulation unit is provided with a single through hole for one of the columnar joints to pass through according to different electric polarities.
2. The device with an electro-stimulation micro-needle tip array structure according to claim 1, wherein the electro-stimulation signal is a pulse voltage, the pulse is a square wave or an exponential wave, the voltage intensity is 3V-100V, the pulse width is 0.1-100ms, and the pulse interval is 0.1-10s.
3. The device with an electro-stimulation micro-needle tip array structure of claim 1, wherein the electro-stimulation unit is made of biocompatible metal.
4. The device with an electro-stimulation micro-needle tip array structure of claim 1, wherein the electro-stimulation unit has a thickness of 50-200 μm.
5. The device with the electric stimulation micro-needle point array structure according to claim 1, wherein the electric stimulation unit is in a rectangular sheet shape, the micro-needle points are uniformly distributed on one side of the electric stimulation unit, and the tips of the micro-needle points are positioned on or approximately positioned on the same plane; the insulating spacer is rectangular sheet-shaped.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711400311.7A CN108325063B (en) | 2017-12-22 | 2017-12-22 | Device with electric stimulation micro needle point array structure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711400311.7A CN108325063B (en) | 2017-12-22 | 2017-12-22 | Device with electric stimulation micro needle point array structure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108325063A CN108325063A (en) | 2018-07-27 |
| CN108325063B true CN108325063B (en) | 2023-12-15 |
Family
ID=62923323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711400311.7A Active CN108325063B (en) | 2017-12-22 | 2017-12-22 | Device with electric stimulation micro needle point array structure |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108325063B (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI702038B (en) * | 2018-09-10 | 2020-08-21 | 微采視像科技股份有限公司 | System for facilitating hair growth |
| JP2022509497A (en) * | 2018-10-26 | 2022-01-20 | カイトペン コーポレイション | Devices, systems, and kits for electroporation, and how to use them. |
| CN109350842A (en) * | 2018-11-02 | 2019-02-19 | 清华大学 | Promote the idler wheel for seeping pen and its sheet metal, rush seep pen |
| CN109893756B (en) * | 2019-03-28 | 2023-02-28 | 中国科学院微电子研究所 | Self-power-generation type electrical stimulation physiotherapy device |
| CN111073814B (en) * | 2019-12-12 | 2021-08-06 | 北京大学 | Microneedle electrode array device and control method thereof |
| US20220032049A1 (en) * | 2020-06-30 | 2022-02-03 | Industrial Technology Research Institute | Microneedle electroporation device |
| CN113350684A (en) * | 2021-06-02 | 2021-09-07 | 张彧 | Electric micro-needle roller type skin physiotherapy instrument and control method thereof |
| CN114305432A (en) * | 2021-12-31 | 2022-04-12 | 武汉衷华脑机融合科技发展有限公司 | Microneedle based on integrated circuit chip |
| CN114343655A (en) * | 2021-12-31 | 2022-04-15 | 武汉衷华脑机融合科技发展有限公司 | Micro-needle |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080161747A1 (en) * | 2006-12-20 | 2008-07-03 | Justin Lee | Electrically conductive microneedle roller |
| JP2010253199A (en) * | 2009-04-28 | 2010-11-11 | Toppan Forms Co Ltd | Device for electroporation |
| KR20100124481A (en) * | 2009-05-19 | 2010-11-29 | 박신규 | Massage roller for stimulating skin using micro-current |
| CN102143778A (en) * | 2008-09-03 | 2011-08-03 | 迪特斯实验室株式会社 | Skin stimulator |
| CN102176877A (en) * | 2008-08-06 | 2011-09-07 | 罗琮柱 | Method, system, and apparatus for dermalogical treatment |
| KR20130043298A (en) * | 2011-10-20 | 2013-04-30 | 김기태 | Skin care device for radio frequency electric treatment |
| CN104434302A (en) * | 2014-12-19 | 2015-03-25 | 重庆德马光电技术有限公司 | Radio frequency output device |
| CN105833425A (en) * | 2016-06-08 | 2016-08-10 | 深圳半岛医疗有限公司 | Micro needle assembly and micro needle treatment head |
| CN106344363A (en) * | 2015-07-16 | 2017-01-25 | 韩国哈贝任医学美容仪器有限公司 | Roller-type cosmetic device |
| CN107206234A (en) * | 2014-07-24 | 2017-09-26 | 希纳普斯提姆有限公司 | For the apparatus and method for being delivered to bodily tissue will to be stimulated |
| CN208626415U (en) * | 2017-12-22 | 2019-03-22 | 北京大学 | Device with electro photoluminescence micro needlepoint array structure |
-
2017
- 2017-12-22 CN CN201711400311.7A patent/CN108325063B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080161747A1 (en) * | 2006-12-20 | 2008-07-03 | Justin Lee | Electrically conductive microneedle roller |
| CN102176877A (en) * | 2008-08-06 | 2011-09-07 | 罗琮柱 | Method, system, and apparatus for dermalogical treatment |
| CN102143778A (en) * | 2008-09-03 | 2011-08-03 | 迪特斯实验室株式会社 | Skin stimulator |
| JP2010253199A (en) * | 2009-04-28 | 2010-11-11 | Toppan Forms Co Ltd | Device for electroporation |
| KR20100124481A (en) * | 2009-05-19 | 2010-11-29 | 박신규 | Massage roller for stimulating skin using micro-current |
| KR20130043298A (en) * | 2011-10-20 | 2013-04-30 | 김기태 | Skin care device for radio frequency electric treatment |
| CN107206234A (en) * | 2014-07-24 | 2017-09-26 | 希纳普斯提姆有限公司 | For the apparatus and method for being delivered to bodily tissue will to be stimulated |
| CN104434302A (en) * | 2014-12-19 | 2015-03-25 | 重庆德马光电技术有限公司 | Radio frequency output device |
| CN106344363A (en) * | 2015-07-16 | 2017-01-25 | 韩国哈贝任医学美容仪器有限公司 | Roller-type cosmetic device |
| CN105833425A (en) * | 2016-06-08 | 2016-08-10 | 深圳半岛医疗有限公司 | Micro needle assembly and micro needle treatment head |
| CN208626415U (en) * | 2017-12-22 | 2019-03-22 | 北京大学 | Device with electro photoluminescence micro needlepoint array structure |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108325063A (en) | 2018-07-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108325063B (en) | Device with electric stimulation micro needle point array structure | |
| US11331479B2 (en) | Device and method for single-needle in vivo electroporation | |
| Heller et al. | Electrically mediated delivery of plasmid DNA to the skin, using a multielectrode array | |
| JP4499295B2 (en) | Delivery of macromolecules into cells | |
| Gothelf et al. | What you always needed to know about electroporation based DNA vaccines | |
| JP5197006B2 (en) | Devices that move molecules to cells using electrical force | |
| US20130197425A1 (en) | Current cage for reduction of a non-target tissue exposure to electric fields in electroporation based treatment | |
| US8455228B2 (en) | Method to facilitate directed delivery and electroporation using a charged stream | |
| Kardos et al. | Contactless magneto-permeabilization for intracellular plasmid DNA delivery in-vivo | |
| US11951307B2 (en) | Targeted remote electrostimulation by interference of bipolar nanosecond pulses | |
| JP2005518904A (en) | Clinical syringe with electrical stimulation aspect | |
| CN1187145A (en) | Method of treatment using electroporation mediated delivery of drugs and genes | |
| US20070016125A1 (en) | Painless electroporating apparatus | |
| US20210353939A1 (en) | Multiple Tissue Layer Electroporation Applicator and Device | |
| US6937890B2 (en) | Nonpenetrating electroporation device | |
| CN208626415U (en) | Device with electro photoluminescence micro needlepoint array structure | |
| EP3347087B1 (en) | Electrostimulation device | |
| Hui et al. | Enhancing transdermal drug delivery with electroporation | |
| Huang et al. | Microneedle roller electrode array (M-REA): A new tool for in vivo low-voltage electric gene delivery | |
| Li et al. | High-density microneedle array (hidma): an in vivo electroporation method for low-voltage gene delivery | |
| Gonzalez et al. | Electroporation of the Skin | |
| WO2023224829A1 (en) | Intracellular treatment device and methods of use thereof | |
| Jaroszeski et al. | Nonpenetrating electroporation device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20201224 Address after: 315800 Room 405, office building 31, Meishan Avenue business center, Beilun District, Ningbo City, Zhejiang Province Applicant after: Analysis mang (Ningbo) biological microsystem Co.,Ltd. Address before: 100871, Peking University, 5 the Summer Palace Road, Beijing, Haidian District Applicant before: Peking University |
|
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20230828 Address after: Room 508, No. 16 Chuangyan Street (Building 2), Kexin Industrial Park, Guangzhou, Guangdong Province, 510700 Applicant after: Guangzhou Ximang Medical Technology Co.,Ltd. Address before: 315800 Room 405, office building 31, Meishan Avenue business center, Beilun District, Ningbo City, Zhejiang Province Applicant before: Analysis mang (Ningbo) biological microsystem Co.,Ltd. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |