CN103386164A - Method and device for carrying medicines through solid micro-needle array device - Google Patents
Method and device for carrying medicines through solid micro-needle array device Download PDFInfo
- Publication number
- CN103386164A CN103386164A CN2012101405453A CN201210140545A CN103386164A CN 103386164 A CN103386164 A CN 103386164A CN 2012101405453 A CN2012101405453 A CN 2012101405453A CN 201210140545 A CN201210140545 A CN 201210140545A CN 103386164 A CN103386164 A CN 103386164A
- Authority
- CN
- China
- Prior art keywords
- array device
- solid microneedles
- microneedles array
- medicine carrying
- micropin
- 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.)
- Granted
Links
Images
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
- 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
- A61M2037/0046—Solid 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
- 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
- A61M2037/0053—Methods for producing microneedles
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
The invention relates to a method and a device for carrying medicines through a solid micro-needle array device. The capillary phenomenon is weakened by utilizing an adhesive force of a medicine solution and a groove base plate, and a thin liquid layer of micrometer scale, so that the accurate, uniform and economic medicine carrying through a needle point of a micro needle on the solid micro-needle array device is realized. The method for carrying the medicines through the solid micro-needle array device is as follows: the needle point of the micro needle on the solid micro-needle array device is arranged in the thin liquid layer of the medicine solution of which the thickness is micrometer scale according to the own gravity of the solid micro-needle array device, so that the medicine solution is adsorbed on the needle point of the micro needle, thereforeby the medicine carrying of the solid micro-needle array device is realized. The device provided by the invention is a manual and automatic device for carrying the medicines through the solid micro-needle array device, which is designed according to a principle of the method for carrying the medicines through the solid micro-needle array device; and the automation of the formation of the thin liquid layer, and the arrangement and switching of the solid micro-needle array device can be realized, so that the errors brought by manual operation areis avoided, and the medicine carrying process is uniform.
Description
Technical field
The present invention relates to the method for solid microneedles array device medicine carrying and the device of solid microneedles array device medicine carrying, specifically, be to utilize the adhesion of drug solution and groove base plate and the thin liquid layer of micro-meter scale to weaken capillarity, thereby realize accurate, even, the economic medicine carrying of needle point of the micropin on the solid microneedles array device.
Background technology
The percutaneous dosing mode is subject to cuticular inhibition, and the medicine that causes being used for percutaneous dosing is very restricted.In order to overcome cuticular inhibition, a lot of methods are arranged at present, can be divided into active mode and the large class of passive mode two.In various active modes, the solid microneedles array device has advantages such as using simply, need not outside resources, and more attractive therefore seems.Drug administration based on the solid microneedles array device mainly contains four kinds of patterns.Wherein have most the mode of administration of application prospect to be: Drug absorbability form on the needle point of the micropin on the solid microneedles array device medicine film again skin puncture (be called for short: solid microneedles array device medicine carrying), be adsorbed on medicine dissolution on the needle point of upper micropin of solid microneedles array device in skin.The solid microneedles array device of medicine carrying can be made paster, so can realize patient's automedication.And Drug absorbability is solid-state on the needle point of the micropin on the solid microneedles array device, in this state, even also can keep the stability of long period under normal temperature condition.Under such background, there are many scientists to study the medicine-carrying method of solid microneedles array device.The difficult point of the medicine carrying of solid microneedles array device is how to weaken capillarity, and makes medicine can not pollute the substrate of solid microneedles array device.
at present, the medicine-carrying method of the solid microneedles array device of having reported: (the Coated microneedles for transdermal delivery such as Harvinder S.Gill, Journal of Controlled Release 117 (2007) 227 – 237), (the Microneedle device such as Oshiyuki Matsudo, Pub.No.:US2010/0221314A1Pub.Date:Sep.22010) and (the Methods and systems for coating a microneedle with a dosage of a biologically active compound such as Alexander K.Andrianov, Pub.No:US 2009/0017210A1) MP method of invention, namely make with the solid microneedles array device on the microwell array that is complementary of micropin, by injection of medicine solution in micropore or with pressure, drug solution is pressed in micropore, then make the medicine-carrying method of the micropin insertion micropore on the solid microneedles array device, micropin on the every solid microneedles array device in the accurate location of the method needs and the position of each micropore, the degree of accuracy that operates under micro-meter scale requires high, micropin on the solid microneedles array device is suffered damage.(the AEROSOL COATING OF MICRONEEDLES such as BIRCHAL James, International Application No.:PCT/GB2008/004205) aeroponics of invention, namely form pharmaceutical aerosol in closed cavity, keep high temperature, the solid microneedles array device is placed in one and adsorbs, the method temperature height easily causes the protein medicaments inactivation, and extremely wastes medicine.(the Dry-coated microprojection array patches for targeted delivery of immunotherapeutics to the skin such as Xianfeng Chen, Journal of Controlled Release 139 (2009) 212 – 220) and (Determination of parameters for successful spray coating of silicon microneedle arrays, the Int J Pharm.2011Aug 30 such as McGrath Marie G.; 415 (1-2): the 140-9.) spurt method of invention, adopt air gun drug solution to be ejected on the needle point of the micropin on the solid microneedles array device, drug solution is not only inhomogeneous on needle point, and easily causes the waste of medicine.(the Masking method for coating a microneedle array such as Peter R.Johnson, US Patent Pub.No:US2008/0102192) mask method of invention, namely first cover one deck mask in the substrate of micropin device solid microneedles array device, add again drug solution, make Drug absorbability on the needle point of the micropin on the solid microneedles array device, the method length consuming time, easily cause drug waste.(the Method of contact coating a microneedle array such as Choi, US Patent Pub.No:US2011/8057842) invention is stained with the method for being coated with, namely adopt the plastic tab that picks medicine to drag on the needle point of the micropin on the solid microneedles array device, the method easily makes the needle point of the micropin on the solid microneedles array device suffer damage, and medicine carrying is inhomogeneous.the roller method of the invention such as Michel J NCormier (Method and apparatus for coating skin piercing microprojections.ALZA February 2005:US 6855372), namely by roller, take solution out of from the drug solution pond, control the thickness of the drug solution layer on roller by scraping blade, make the needle point of the micropin on the solid microneedles array device contact this drug solution layer, the method needs the needle point of micropin and contacting of drug solution layer on accurate control solid microneedles array device, otherwise the needle point of the micropin on the solid microneedles array device is suffered damage.The medicine-carrying method of the solid microneedles array device of exploitation has many defects at present, has limited the development of medicine carrying solid microneedles array device administering mode, develops a kind of new medicine-carrying method significant.
Summary of the invention
One of purpose of the present invention is (as: need to accurately control for the restriction of the method that overcomes existing solid microneedles array device medicine carrying, easily make drug inactivation, medicine carrying is inhomogeneous, causes drug waste etc.), a kind of method of solid microneedles array device medicine carrying is provided.
Two of purpose of the present invention is to provide a kind of simple manually device (as shown in Figure 1) of solid microneedles array device medicine carrying that is applicable to the method for solid microneedles array device medicine carrying, makes the process of solid microneedles array device medicine carrying become easy, accurate, economical.
Three of purpose of the present invention is to provide a kind of device (as shown in Figure 2) of automatization's solid microneedles array device medicine carrying of the method that is applicable to solid microneedles array device medicine carrying, the automatization that realizes above-mentioned solid microneedles array device medicine-carrying method.
The method of solid microneedles array device medicine carrying of the present invention is the gravity that relies on solid microneedles array device self, micropin on the solid microneedles array device is placed among the thin liquid layer of drug solution that thickness is micro-meter scale, and the length of the needle point of the micropin on described solid microneedles array device is higher than the thickness of the thin liquid layer of described drug solution, drug solution is adsorbed on the needle point of the micropin on the solid microneedles array device, thereby realizes the medicine carrying of solid microneedles array device.
Described micro-meter scale is preferably 75 μ m～500 μ m.
In order better to realize method of the present invention, the invention provides a kind of device (as shown in Figure 1) that is applicable to the manual solid microneedles array device medicine carrying of said method, the device of this manual solid microneedles array device medicine carrying comprises groove base plate and frame scraper plate.
Described frame scraper plate is installed on described groove base plate, liquid storage tank of the common formation of the groove of described frame scraper plate and described groove base plate.
Described liquid storage tank is used for the storage drug solution.
The degree of depth of described groove is micro-meter scale.Described micro-meter scale is preferably 75 μ m～500 μ m.
utilize the device of the manual solid microneedles array device medicine carrying of the invention described above to realize that the method for solid microneedles array device medicine carrying is: drug solution is placed in by the common liquid storage tank that forms of the groove of described frame scraper plate and described groove base plate, described frame scraper plate and described groove base plate are done relative motion, forming a layer thickness thickness identical with the degree of depth of the groove of described groove base plate in the groove of described groove base plate is the thin liquid layer of the drug solution of micro-meter scale, rely on the gravity of solid microneedles array device self, among the needle point of the micropin on the solid microneedles array device being placed in the thin liquid layer that is formed by described drug solution, (needle point of the micropin on general solid microneedles array device is short in the time that drug solution stops, for example about 1 second), and the length of described needle point is higher than the thickness of described thin liquid layer, described drug solution is adsorbed on the needle point of the micropin on described solid microneedles array device, due to the length of the needle point thickness higher than thin liquid layer, solution can not pollute the substrate of microneedle array, thereby realize the medicine carrying of solid microneedles array device.
In order better to realize method of the present invention, the present invention also provides a kind of device (as shown in Figure 2) that is applicable to automatization's solid microneedles array device medicine carrying of said method, and the device of this automatization's solid microneedles array device medicine carrying comprises groove base plate, frame scraper plate, solid microneedles array device, solid microneedles array device fixed disc, solid microneedles array device locking cap, rolling disc, the first motor, the second motor, the 3rd motor, digital control panel and climatic chamber.
In described climatic chamber, on described groove base plate 1 is fixed at the bottom of the case of described climatic chamber, described frame scraper plate is installed on described groove base plate, liquid storage tank of the common formation of the groove of described frame scraper plate and described groove base plate; On described frame scraper plate, rotary screw is installed, the machine shaft that is arranged on described the first motor in climatic chamber is a rotary screw, and the rotary screw on described frame scraper plate is connected by the rotation screw thread on rotary screw with the rotary screw on described the first motor; Described solid microneedles array device fixed disc is that a center is porose, and the cogged disk of outward flange band, described solid microneedles array device fixed disc is connected with the rotation screw thread on being arranged on a rotary screw on being fixed at the bottom of the case of climatic chamber by the lip-deep rotation screw thread of centre bore, and described solid microneedles array device fixed disc is positioned at the oblique upper of described groove base plate; Described solid microneedles array device locking cap is arranged on described solid microneedles array device, and described solid microneedles array device locking cap hangs on described solid microneedles array device fixed disc; The machine shaft that is arranged on described the second motor in climatic chamber is a rotary screw, the outward flange of the rotation screw thread on this rotary screw and described solid microneedles array device fixed disc with gear be connected; The machine shaft that is arranged on described the 3rd motor in climatic chamber is a rotary screw, and the rotation screw thread on this rotary screw is connected with the gear of the cogged rolling disc of outward flange band.
Described the second motor, the 3rd motor can be fixed on a metallic plate, and this metallic plate is fixed on the tank wall of described climatic chamber; Described climatic chamber is equipped with the described digital control panel that carries out working state control for described the first motor, described the second motor and described the 3rd motor outward.
Described liquid storage tank is used for the storage drug solution.
The degree of depth of described groove is micro-meter scale.Described micro-meter scale is preferably 75 μ m～500 μ m.
utilize automatization's solid microneedles array device medicine carrying of the invention described above to realize that the method for solid microneedles array device medicine carrying is: a plurality of (generally being designed to as required 10 left and right) the solid microneedles array device that will connect one to one on a plurality of (generally being designed to as required 10 left and right) solid microneedles array device locking cap hangs on solid microneedles array device fixed disc, install described a plurality of solid microneedles array device on described solid microneedles array device fixed disc, drug solution is placed in by the common liquid storage tank that forms of the groove of frame scraper plate and groove base plate, after shutting the cabinet door of climatic chamber, switch on power, regulate required temperature and humidity, by digital control panel, access the medicine carrying program, click operation automatically and carry out the medicine carrying of automatization's solid microneedles array device, by the first described frame scraper plate of stepping driven by motor left or the right side move to high order end or low order end, then turn back to initial position, forming a layer thickness thickness identical with the degree of depth of the groove of described groove base plate in the groove of described groove base plate is the thin liquid layer of the drug solution of micro-meter scale, do and move downward by the second described solid microneedles array device of stepping driven by motor fixed disc, allow the described solid microneedles array device slow decreasing that faces described thin liquid layer top to described thin liquid layer, rely on the gravity of solid microneedles array device self, the needle point of the micropin on first solid microneedles array device is placed in (needle point of the micropin on general solid microneedles array device stopped about 1 second at drug solution) among the thin liquid layer that is formed by described drug solution, described drug solution is adsorbed on the needle point of the micropin on described first solid microneedles array device, thereby realize the medicine carrying of first solid microneedles array device, and then do to move upward by the second described solid microneedles array device of stepping driven by motor fixed disc and get back to initial position, and the gear of rolling disc is connected with the gear of solid microneedles array device fixed disc, drive rolling disc by the 3rd motor, make described solid microneedles array device fixed disc do clockwise or be rotated counterclockwise that (gear of rolling disc is connected with the gear of solid microneedles array device fixed disc, thereby realize the control of the 3rd motor to solid microneedles array device fixed disc), make next described solid microneedles array device be positioned at described thin liquid layer top, realize the switching between described solid microneedles array device, then repeat to start to carry out the medicine carrying operation of automatization's solid microneedles array device, until make the described solid microneedles array device that is arranged on described solid microneedles array device fixed disc all medicine carrying complete.This device can be realized by described the first motor, described the second motor and described the 3rd motor and program the medicine carrying of solid microneedles array device, improves precision and the accuracy of medicine carrying, and can realize medicine carrying in batches.
The control of the duty of described the first motor, described the second motor and described the 3rd motor is to control by the instruction that described digital control panel sends.
The length of described needle point is higher than the thickness of described thin liquid layer.
The thickness of described thin liquid layer is micro-meter scale.Described micro-meter scale is preferably 75 μ m～500 μ m.
wherein, the shape of described solid microneedles array device locking cap can be shape for hat, sheet type or column type, can be connected to easily the top at the support position of described solid microneedles array device, and for convenience detach between the support of solid microneedles array device, when described solid microneedles array device relies on the gravity of self to make the needle point of the micropin on the solid microneedles array device be placed among thin liquid layer, solid microneedles array device locking cap can be by solid microneedles array device jack-up, realize that the solid microneedles array device relies on the gravity of self to make the vertical lowering of needle point of the micropin on the solid microneedles array device among thin liquid layer.
Wherein, the combination of described solid microneedles array device fixed disc and described solid microneedles array device locking cap, can realize the fixing of described solid microneedles array device, and the needle point of the micropin on described solid microneedles array device is when immersing thin liquid layer,, the described solid microneedles array device locking cap jack-up that makes progress, can realize that described solid microneedles array device vertically relies on the gravity of self to place.
Wherein, the combination of described rolling disc and described solid microneedles array device fixed disc can realize the position switching between described solid microneedles array device.Solid microneedles array device fixed disk is used for fixedly solid microneedles array device, the support of solid microneedles array device is after passing the hole of opening for suspension solid microneedles array device on described solid microneedles array device fixed disc, be combined with solid microneedles array device locking cap again, described solid microneedles array device can freely be moved up and down in hole, rolling disc drive solid microneedles array device fixed disk is realized the switching between solid microneedles array device position.
Wherein, described motor is 3, realizes respectively function separately: realize the side-to-side movement of described frame scraper plate and described groove base plate, form thin liquid layer; Realize described solid microneedles array device from top to bottom, the action of the thin liquid layer of immersion from bottom to top; Realize the position switching between different solid microneedles array devices.
Wherein, described digital control panel is controlled 3 motors, realize the loading parameter (time of staying of the needle point of the micropin on the speed of service of frame scraper plate, medicine carrying number of times, solid microneedles array device in drug solution, cycle-index etc.) of various described solid microneedles array devices, realize full-automatic program management.
Wherein, described climatic chamber is controlled the temperature humidity of whole system.Temperature in described climatic chamber 4～37 ℃ adjustable, humidity is adjustable 50%～95%.
The surface of described groove needs certain hydrophilic, the material of described groove base plate is selected from a kind of (the described hydrophilic processing in simple glass, aluminum, zinc, surperficial rustless steel through the hydrophilic processing and surperficial copper through the hydrophilic processing etc. thus, can be at room temperature, it (is that 0.5% ethylenediaminetetraacetic acid (EDTA) aqueous solution and 2 volume mass concentration are 30% H by 1 volume mass concentration be 36% HCl aqueous solution, 1 volume mass concentration that rustless steel or copper are put into hydrophiling reagent
2O
2Form, and with the volume unit of HCl aqueous solution, be as the criterion) the middle processing one minute), or be selected from surface by the material of a kind of modification in above-mentioned material.The material of described frame scraper plate can be glass, rustless steel or politef.
Described solid microneedles array device is as the object of medicine carrying, and the cross sectional shape of solid microneedles array device is conical or polyhedral cone shaped.The material of the micropin on described solid microneedles array device is selected from a kind of in monocrystal silicon, titanium, rustless steel and macromolecular material (described macromolecular material be selected from polylactic acid, polyglycolic acid, polyethylene, polyvinyl alcohol, Merlon, polyacrylamide, polypropylene and nylon a kind of).The length of the needle point of the micropin on described solid microneedles array device is between 100～1000 microns; The diameter of the needle point of the micropin on described solid microneedles array device is between 100 nanometers～10 micron; The cone angle of the needle point of the micropin on described solid microneedles array device is 20～60 degree.
Described drug solution needs and can form uniform thin liquid layer with the groove base plate, and certain adhesion is arranged, thereby realizes weakening capillarity, avoids the substrate of drug solution pollution solid microneedles array device, carries out the purpose of even medicine carrying.So, should comprise medicine (comprising that all are applicable to the medicine of micropin medicine carrying) in the formula of described drug solution and contain the aqueous solution of thickening agent.Described thickening agent, have thickening property and film property, thickening property is the binding ability for the needle point that improves the micropin on the solid microneedles array device and medicine, thereby raising drug loading, film property be for the thin liquid layer that drug solution is formed even, thereby improve the uniformity of medicine carrying, meanwhile, strengthen the adhesion of drug solution and groove base plate, can weaken capillarity, avoid the substrate of drug solution pollution solid microneedles array device, realize the needle point medicine carrying of the micropin on the solid microneedles array device, save medicine.The frame scraper plate is done relative (or left and right) motion with the groove base plate, form a layer thickness thin liquid layer identical with the degree of depth of the groove of groove base plate, the thickness of this thin liquid layer is micro-meter scale, can further weaken capillarity, thereby the substrate of avoiding drug solution to pollute the solid microneedles array device, and save medicine.Then the solid microneedles array device relies on the gravity of self, the needle point of the micropin on the solid microneedles array device is placed among the thin liquid layer of drug solution, drug solution is adsorbed on the needle point of the micropin on the solid microneedles array device, thereby realizes the medicine carrying of solid microneedles array device.
According to different drug loading requirements, the consisting of medicine and contain the aqueous solution of thickening agent of described drug solution.
The concentration preferable range of the medicine in described drug solution is 0.1%～50%(w/v), and more preferably scope is 0.5%～5%(w/v).
The concentration preferable range of the thickening agent in described drug solution is 0.1%～50%(w/v), and more preferably scope is 1%～10%(w/v).
Described thickening agent is selected from one or more in sodium alginate, gelatin, hyaluronic acid, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carbomer, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, starch, xanthan gum, polyacrylic acid, Radix Acaciae senegalis and chitosan etc.
In method of the present invention, the solid microneedles array device is the gravity that relies on self, the surface that the needle point of the micropin on the solid microneedles array device is placed in the thin liquid layer of drug solution is very significant, and having overcome the medicine-carrying method that uses at present in the world of mentioning in the background technology needs the shortcoming of accurately controlling.Need not that as method of the present invention micropin on the solid microneedles array device is aimed at corresponding micropore exactly and carry out the process of medicine carrying, so do not need accurate control, whole process is at room temperature carried out, and can not impact pharmaceutically active because of high temperature.
Device of the present invention is according to the principle design of the method for solid microneedles array device medicine carrying out, the placement of the formation of thin liquid layer, solid microneedles array device and switching can realize automatization, the error of having avoided manually-operated to bring, make the medicine carrying process have homogeneity.Increase simultaneously climatic chamber, can control the temperature and humidity of casing, can effectively keep the activity of protein medicaments.After realizing automatization, various parameters: the time of staying, the cycle-index of needle point in drug solution as the micropin on time of staying of the speed of service of the degree of depth of the groove of groove base plate, frame scraper plate, frame scraper plate, medicine carrying number of times, solid microneedles array device realizes regulation and control, and the combination of various parameters can realize the regulating and controlling of the degree of depth, medicine carrying thickness and drug loading of medicine carrying of the needle point of the micropin on the solid microneedles array device.
The method of solid microneedles array device medicine carrying of the present invention is to rely on gravity to be placed on thin liquid layer a kind of method of carrying out medicine carrying the solid microneedles array device.the medicine-carrying method of mentioning in Method And Principle of the present invention and above-mentioned background technology is fully different, that adhesion between the groove of thin liquid layer by micro-meter scale and drug solution and groove base plate weakens capillarity, the method does not need accurate control (as what mention in background technology, need to aim at exactly corresponding micropore to micropin and carry out medicine carrying, this process need is accurately controlled, and method of the present invention does not relate to the process of micropin aligning micropore, so do not need accurate control), can not make drug inactivation, medicine carrying is even, can realize the substrate that solid microneedles array device medicine carrying process is not polluted the solid microneedles array device, thereby save medicine and accurate quantitative analysis.
The device of solid microneedles array device medicine carrying of the present invention is according to the principle design of the method for solid microneedles array device medicine carrying out, realized full-automatic (operation that utilizes three motors and program to realize), further optimized the personal error that manual medicine carrying brings, make the medicine carrying process of solid microneedles array device more accurate, accurately, economy is easy.
Description of drawings
Fig. 1. the schematic diagram of the device of a kind of manual solid microneedles array device medicine carrying of the present invention; Wherein: Fig. 1 a is top view; Fig. 1 b is left view.
Fig. 2. the schematic diagram of the device of the solid microneedles array device medicine carrying of a kind of automatization of the present invention.
Reference numeral
1. groove base plate 2. groove 3. frame scraper plates
4. thin liquid layer 6. solid microneedles array devices of liquid storage tank 5.
7. the solid microneedles array device after solid microneedles array device 8. medicine carryings before medicine carrying
9. solid microneedles array device fixed disc 10. solid microneedles array device locking caps
11. rolling disc 12. first motor 13. second motors
14. the 3rd digital control panel 16. climatic chambers of motor 15.
The specific embodiment
The present invention is described further below with reference to drawings and Examples, and embodiments of the invention only are used for technical scheme of the present invention is described, and non-limiting the present invention.
See also Fig. 1 (adopting manual mode to carry out the medicine carrying of solid microneedles array device), manually the device of solid microneedles array device medicine carrying comprises that adopting the groove base plate 1 that simple glass makes and adopting model is the frame scraper plate 3 that 304 rustless steel is made; Described frame scraper plate 3 is installed on described groove base plate 1, liquid storage tank 4 of groove 2 common formation of described frame scraper plate 3 and described groove base plate 1.The degree of depth of groove 2 is 75 μ m, and width is 10mm, and length is 30mm.Frame scraper plate 3 is square-shaped frame, and the length of side is 10mm, is highly 10mm.
What the material of the micropin on solid microneedles array device 6 used adopted is single crystal silicon material, and array is 6 * 6, and array area is 0.25cm
2, being formed by 36 micropins, the length of every micropin is 100 μ m, and the diameter of needle point is 100nm, and the maximum cone angle of needle point is 20 °.The back of solid microneedles array device adheres to the support as the solid microneedles array device on cylindrical substrate and forms the solid microneedles array device, is convenient to pick and place.
Use in drug solution contain hydroxypropyl emthylcellulose aqueous solution as thickening agent, in drug solution, the concentration of hydroxypropyl emthylcellulose is 1%(w/v); Fluorescein sodium use in drug solution as model drug, and in drug solution, the concentration of fluorescein sodium is 3%(w/v).
utilize the device of above-mentioned manual solid microneedles array device medicine carrying to carry out solid microneedles array device medicine carrying: drug solution is placed in the liquid storage tank 4 that the groove 2 by described frame scraper plate 3 and described groove base plate 1 forms jointly, described frame scraper plate and described groove base plate are done relative motion, form the thin liquid layer 5 of a layer thickness drug solution identical with the degree of depth of the groove of described groove base plate in the groove 2 of described groove base plate 1, rely on the gravity of solid microneedles array device self, the needle point of every micropin of the solid microneedles array device 7 before medicine carrying is placed among the thin liquid layer that is formed by described drug solution, stopped 1 second, described drug solution is adsorbed on the needle point of every micropin of described solid microneedles array device, obtain the solid microneedles array device 8 after medicine carrying, thereby realize the medicine carrying of solid microneedles array device.
Embodiment 2
See also Fig. 1 (adopting manual mode to carry out the medicine carrying of solid microneedles array device), manually the device of solid microneedles array device medicine carrying comprises the groove base plate 1 that adopts the aluminium sheet making and the frame scraper plate 3 that adopts politef to make; Described frame scraper plate 3 is installed on described groove base plate 1, liquid storage tank 4 of groove 2 common formation of described frame scraper plate 3 and described groove base plate 1.The degree of depth of groove 2 is 300 μ m, and width is 14mm, and length is 30mm.Frame scraper plate 3 is square-shaped frame, and the length of side is 14mm, is highly 10mm.
What the material of the micropin on solid microneedles array device 6 used adopted is the polyphosphazene polymer lactate material, and array is 9 * 9, and array area is 0.64cm
2, being formed by 81 micropins, the length of every micropin is 500 μ m, and the diameter of needle point is 200nm, and the maximum cone angle of needle point is 26 °.The back of solid microneedles array device adheres to the support as the solid microneedles array device on cylindrical substrate and forms the solid microneedles array device, is convenient to pick and place.
Use in drug solution contain hydroxypropyl emthylcellulose aqueous solution as thickening agent, in drug solution, the concentration of hydroxypropyl emthylcellulose is 5%(w/v); Fluorescein sodium use in drug solution as model drug, and in drug solution, the concentration of fluorescein sodium is 0.1%(w/v).
utilize the device of above-mentioned manual solid microneedles array device medicine carrying to carry out solid microneedles array device medicine carrying: drug solution is placed in the liquid storage tank 4 that the groove 2 by described frame scraper plate 3 and described groove base plate 1 forms jointly, described frame scraper plate and described groove base plate are done relative motion, form the thin liquid layer 5 of a layer thickness drug solution identical with the degree of depth of the groove of described groove base plate in the groove 2 of described groove base plate 1, rely on the gravity of solid microneedles array device self, the needle point of every micropin of the solid microneedles array device 7 before medicine carrying is placed among the thin liquid layer that is formed by described drug solution, stopped 1 second, described drug solution is adsorbed on the needle point of every micropin of described solid microneedles array device, obtain the solid microneedles array device 8 after medicine carrying, thereby realize the medicine carrying of solid microneedles array device.
See also Fig. 1 (adopting manual mode to carry out the medicine carrying of solid microneedles array device), manually the device of solid microneedles array device medicine carrying comprises that adopting the groove base plate 1 that corrosion resistant plate makes and adopting model is the frame scraper plate 3 that 304 rustless steel is made; Described frame scraper plate 3 is installed on described groove base plate 1, liquid storage tank 4 of groove 2 common formation of described frame scraper plate 3 and described groove base plate 1.The degree of depth of groove 2 is 500 μ m, and width is 14mm, and length is 30mm.The surface of groove processes through hydrophilic that (volume unit with the HCl aqueous solution is as the criterion, and at room temperature, with rustless steel HCl aqueous solution, 1 volume mass concentration that to put into by 1 volume mass concentration be 36%, is that 0.5% EDTA aqueous solution and 2 volume mass concentration are 30% H
2O
2Processed one minute in the hydrophiling reagent that forms).Frame scraper plate 3 is square-shaped frame, and the length of side is 14mm, is highly 10mm.
What the material of the micropin on solid microneedles array device 6 used adopted is stainless steel material, and array is 9 * 9, and array area is 0.64cm
2, being formed by 81 micropins, the length of every micropin is 1000 μ m, and the diameter of needle point is 10 μ m, and the maximum cone angle of needle point is 60 °.The back of solid microneedles array device adheres to the support as the solid microneedles array device on cylindrical substrate and forms the solid microneedles array device, is convenient to pick and place.
Use in drug solution contain polyvinylpyrrolidone aqueous solution as thickening agent, in drug solution, the concentration of polyvinylpyrrolidone is 50%(w/v); Fluorescein sodium use in drug solution as model drug, and in drug solution, the concentration of fluorescein sodium is 5%(w/v).
utilize the device of above-mentioned manual solid microneedles array device medicine carrying to carry out solid microneedles array device medicine carrying: drug solution is placed in the liquid storage tank 4 that the groove 2 by described frame scraper plate 3 and described groove base plate 1 forms jointly, described frame scraper plate and described groove base plate are done relative motion, form the thin liquid layer 5 of a layer thickness drug solution identical with the degree of depth of the groove of described groove base plate in the groove 2 of described groove base plate 1, rely on the gravity of solid microneedles array device self, the needle point of every micropin of the solid microneedles array device 7 before medicine carrying is placed among the thin liquid layer that is formed by described drug solution, stopped 1 second, described drug solution is adsorbed on the needle point of every micropin of described solid microneedles array device, obtain the solid microneedles array device 8 after medicine carrying, thereby realize the medicine carrying of solid microneedles array device.
See also Fig. 2 (mode of employing automatization is carried out the medicine carrying of solid microneedles array device), the device of automatization's solid microneedles array device medicine carrying comprises groove base plate 1, frame scraper plate 3, solid microneedles array device 6, solid microneedles array device fixed disc 9, solid microneedles array device locking cap 10, rolling disc 11, the first motor 12, the second motor 13, the 3rd motor 14, digital control panel 15 and climatic chamber 16.
In described climatic chamber 16, on described groove base plate 1 is fixed at the bottom of the case of described climatic chamber 16, described frame scraper plate 3 is installed on described groove base plate 1, liquid storage tank 4 of groove 2 common formation of described frame scraper plate 3 and described groove base plate 1; On described frame scraper plate 3, rotary screw is installed, the machine shaft that is arranged on described the first motor 12 in climatic chamber 16 is a rotary screw, and the rotary screw on described frame scraper plate 3 is connected by the rotation screw thread on rotary screw with the rotary screw on described the first motor 12; Described solid microneedles array device fixed disc 9 is that a center is porose, and the cogged disk of outward flange band, described solid microneedles array device fixed disc 9 is connected with the rotation screw thread on being arranged on a rotary screw on being fixed at the bottom of the case of climatic chamber by the lip-deep rotation screw thread of centre bore, and described solid microneedles array device fixed disc 9 is positioned at the oblique upper of described groove base plate 1; Described solid microneedles array device locking cap 10 is arranged on described solid microneedles array device 6, and described solid microneedles array device locking cap 10 hangs on described solid microneedles array device fixed disc; The machine shaft that is arranged on described the second motor 13 in climatic chamber 16 is a rotary screw, the outward flange of the rotation screw thread on this rotary screw and described solid microneedles array device fixed disc 9 with gear be connected; The machine shaft that is arranged on described the 3rd motor 14 in climatic chamber 16 is a rotary screw, and the rotation screw thread on this rotary screw is connected with the gear of the cogged rolling disc 11 of outward flange band.
Described the second motor 13, the 3rd motor 14 can be fixed on a metallic plate, and this metallic plate is fixed on the tank wall of described climatic chamber 16; The outer described digital control panel 15 that carries out working state control for described the first motor 12, described the second motor 13 and described the 3rd motor 14 that is equipped with of described climatic chamber 16.
Described groove base plate 1 and described frame scraper plate 3 all adopt corrosion resistant plate to make.
The degree of depth of described groove 2 is 100 μ m, and width is 10mm, and length is 30mm.The surface of groove processes through hydrophilic that (volume unit with the HCl aqueous solution is as the criterion, and at room temperature, with rustless steel HCl aqueous solution, 1 volume mass concentration that to put into by 1 volume mass concentration be 36%, is that 0.5% EDTA aqueous solution and 2 volume mass concentration are 30% H
2O
2Processed one minute in the hydrophiling reagent that forms).Frame scraper plate 3 is square-shaped frame, and the length of side is 10mm, is highly 10mm.
What the material of the micropin on solid microneedles array device 6 used adopted is single crystal silicon material, and array is 6 * 6, and array area is 0.25cm
2, being formed by 36 micropins, the length of every micropin is 260 μ m, and the diameter of needle point is 2 μ m, and the maximum cone angle of needle point is 26 °.The back of solid microneedles array device adheres to the support as the solid microneedles array device on cylindrical substrate and forms the solid microneedles array device, is convenient to pick and place.
Use in drug solution contain sodium carboxymethyl cellulose aqueous solution as thickening agent, in drug solution, the concentration of sodium carboxymethyl cellulose is 1%(w/v); L-carnitine use in drug solution as model drug, and in drug solution, the concentration of L-carnitine is 50%(w/v).
Utilize the device of above-mentioned automatization solid microneedles array device medicine carrying to realize that the method for solid microneedles array device medicine carrying is: 10 solid microneedles array devices 6 that will connect one to one on 10 solid microneedles array device locking caps 10 hang on solid microneedles array device fixed disc; Install described 10 solid microneedles array devices 6 on described solid microneedles array device fixed disc 9, drug solution is placed in the liquid storage tank 4 that the groove 2 by frame scraper plate 3 and groove base plate 1 forms jointly, after shutting the cabinet door of climatic chamber 16, switch on power, regulate required temperature and humidity, by digital control panel 15, access the medicine carrying program, click operation automatically and carry out the medicine carrying of automatization's solid microneedles array device; Drive described frame scraper plates 3 left or the right side moves to high order end or low order end by the first motor 12, then turn back to initial position, form the thin liquid layer 5 of a layer thickness drug solution identical with the degree of depth of the groove of described groove base plate in the groove 2 of described groove base plate 1; Do and move downward by the second motor 13 described solid microneedles array device fixed discs of drive, allow the described solid microneedles array device slow decreasing that faces described thin liquid layer top to described thin liquid layer, rely on the gravity of solid microneedles array device self, stopped 1 second among the needle point of first solid microneedles array device being placed in the thin liquid layer that is formed by described drug solution, described drug solution is adsorbed on the needle point of described first solid microneedles array device, thereby realizes the medicine carrying of first solid microneedles array device; And then do to move upward by the second described solid microneedles array device of stepping driven by motor fixed disc and get back to initial position, and the gear of rolling disc 11 is connected with the gear of solid microneedles array device fixed disc 9; Drive rolling disc 11 by the 3rd motor 14, make described solid microneedles array device fixed disc do clockwise or be rotated counterclockwise that (gear of rolling disc 11 is connected with the gear of solid microneedles array device fixed disc 9, thereby realize the control of 14 pairs of solid microneedles array device fixed discs of the 3rd motor), make next described solid microneedles array device be positioned at described thin liquid layer top, realize the switching between described solid microneedles array device; Then repeat to start to carry out the medicine carrying operation of automatization's solid microneedles array device, until make 10 described solid microneedles array devices being arranged on described solid microneedles array device fixed disc all medicine carrying complete.This device can be realized by described the first motor 12, described the second motor 13 and described the 3rd motor 14 and program the medicine carrying of solid microneedles array device, improves precision and the accuracy of medicine carrying, and can realize medicine carrying in batches.
The control of the duty of described the first motor 12, described the second motor 13 and described the 3rd motor 14 is to control by the instruction that described digital control panel 15 sends.
The mode of employing automatization is carried out the medicine carrying of solid microneedles array device, and the device of automatization's solid microneedles array device medicine carrying is substantially with embodiment 4, and difference is: described groove base plate 1 and described frame scraper plate 3 all adopt zine plate to make.The degree of depth of described groove 2 is 75 μ m, and width is 14mm, and length is 30mm.Frame scraper plate 3 is square-shaped frame, and the length of side is 14mm, is highly 10mm.What the material of the micropin on solid microneedles array device 6 used adopted is single crystal silicon material, and array is 11 * 11, and array area is 1cm
2, being formed by 121 micropins, the length of every micropin is 150 μ m, and the diameter of needle point is 2 μ m, and the maximum cone angle of needle point is 38 °.The back of solid microneedles array device adheres to the support as the solid microneedles array device on cylindrical substrate and forms the solid microneedles array device, is convenient to pick and place.
Use in drug solution contain sodium carboxymethyl cellulose aqueous solution as thickening agent, in drug solution, the concentration of sodium carboxymethyl cellulose is 4%(w/v); Interferon use in drug solution as model drug, and in drug solution, the concentration of interferon is 1%(w/v).
Utilize the device of above-mentioned automatization solid microneedles array device medicine carrying to realize that the method for solid microneedles array device medicine carrying is with embodiment 4.
The mode of employing automatization is carried out the medicine carrying of solid microneedles array device, and the device of automatization's solid microneedles array device medicine carrying is substantially with embodiment 4, and difference is: the degree of depth of described groove 2 is 500 μ m, and width is 14mm, and length is 30mm.Frame scraper plate 3 is square-shaped frame, and the length of side is 14mm, is highly 10mm.What the material of the micropin on solid microneedles array device 6 used adopted is poly-lactic acid material, and array is 9 * 9, and array area is 0.64cm
2, being formed by 81 micropins, the length of every micropin is 1000 μ m, and the diameter of needle point is 2 μ m, and the maximum cone angle of needle point is 38 °.The back of solid microneedles array device adheres to the support as the solid microneedles array device on cylindrical substrate and forms the solid microneedles array device, is convenient to pick and place.
Use in drug solution contain sodium alginate aqueous solution as thickening agent, in drug solution, the concentration of sodium alginate is 10%(w/v); Riboflavin use in drug solution as model drug, and in drug solution, the concentration of riboflavin is 3%(w/v).
Utilize the device of above-mentioned automatization solid microneedles array device medicine carrying to realize that the method for solid microneedles array device medicine carrying is with embodiment 4.
Claims (16)
1. the method for a solid microneedles array device medicine carrying, it is characterized in that: the method for described solid microneedles array device medicine carrying is the gravity that relies on solid microneedles array device self, the needle point of the micropin on the solid microneedles array device is placed among the thin liquid layer of drug solution that thickness is micro-meter scale, and the length of the needle point of the micropin on described solid microneedles array device is higher than the thickness of the thin liquid layer of described drug solution, drug solution is adsorbed on the needle point of the micropin on the solid microneedles array device, realizes the medicine carrying of solid microneedles array device.
2. the method for solid microneedles array device medicine carrying according to claim 1, it is characterized in that: described micro-meter scale is 75 μ m～500 μ m.
3. the device of the manual solid microneedles array device medicine carrying of a method that realizes solid microneedles array device medicine carrying, it is characterized in that: the device of described manual solid microneedles array device medicine carrying comprises groove base plate and frame scraper plate;
Described frame scraper plate is installed on described groove base plate, liquid storage tank of the common formation of the groove of described frame scraper plate and described groove base plate;
The degree of depth of described groove is micro-meter scale.
4. a device that utilizes manual solid microneedles array device medicine carrying claimed in claim 3 is realized the method for solid microneedles array device medicine carrying, it is characterized in that: drug solution is placed in by the common liquid storage tank that forms of the groove of frame scraper plate and groove base plate, described frame scraper plate and described groove base plate are done relative motion, forming a layer thickness thickness identical with the degree of depth of the groove of described groove base plate in the groove of described groove base plate is the thin liquid layer of the drug solution of micro-meter scale, rely on the gravity of solid microneedles array device self, the needle point of the micropin on the solid microneedles array device is placed among the thin liquid layer that is formed by described drug solution, and the length of the needle point of the micropin on described solid microneedles array device is higher than the thickness of described thin liquid layer, described drug solution is adsorbed on the needle point of the micropin on described solid microneedles array device, realize the medicine carrying of solid microneedles array device.
5. the device of automatization's solid microneedles array device medicine carrying of a method that realizes solid microneedles array device medicine carrying, it is characterized in that: the device of described automatization solid microneedles array device medicine carrying comprises groove base plate, frame scraper plate, solid microneedles array device, solid microneedles array device fixed disc, solid microneedles array device locking cap, rolling disc, the first motor, the second motor, the 3rd motor, digital control panel and climatic chamber;
In described climatic chamber, on described groove base plate is fixed at the bottom of the case of described climatic chamber, described frame scraper plate is installed on described groove base plate, liquid storage tank of the common formation of the groove of described frame scraper plate and described groove base plate; On described frame scraper plate, rotary screw is installed, the machine shaft that is arranged on described the first motor in climatic chamber is a rotary screw, and the rotary screw on described frame scraper plate is connected by the rotation screw thread on rotary screw with the rotary screw on described the first motor; Described solid microneedles array device fixed disc is that a center is porose, and the cogged disk of outward flange band, described solid microneedles array device fixed disc is connected with the rotation screw thread on being arranged on a rotary screw on being fixed at the bottom of the case of climatic chamber by the lip-deep rotation screw thread of centre bore, and described solid microneedles array device fixed disc is positioned at the oblique upper of described groove base plate; Described solid microneedles array device locking cap is arranged on described solid microneedles array device, and described solid microneedles array device locking cap hangs on described solid microneedles array device fixed disc; The machine shaft that is arranged on described the second motor in climatic chamber is a rotary screw, the outward flange of the rotation screw thread on this rotary screw and described solid microneedles array device fixed disc with gear be connected; The machine shaft that is arranged on described the 3rd motor in climatic chamber is a rotary screw, and the rotation screw thread on this rotary screw is connected with the gear of the cogged rolling disc of outward flange band;
Described climatic chamber is equipped with the described digital control panel that carries out working state control for described the first motor, described the second motor and described the 3rd motor outward;
The degree of depth of described groove is micro-meter scale.
6. a device that utilizes automatization claimed in claim 5 solid microneedles array device medicine carrying is realized the method for solid microneedles array device medicine carrying, it is characterized in that: a plurality of solid microneedles array devices that will connect one to one on a plurality of solid microneedles array device locking caps hang on solid microneedles array device fixed disc, install described a plurality of solid microneedles array device on described solid microneedles array device fixed disc, drug solution is placed in by the common liquid storage tank that forms of the groove of frame scraper plate and groove base plate, after shutting the cabinet door of climatic chamber, switch on power, regulate required temperature and humidity, by digital control panel, access the medicine carrying program, click operation automatically and carry out the medicine carrying of automatization's solid microneedles array device, by the first described frame scraper plate of stepping driven by motor left or the right side move to high order end or low order end, then turn back to initial position, forming a layer thickness thickness identical with the degree of depth of the groove of described groove base plate in the groove of described groove base plate is the thin liquid layer of the drug solution of micro-meter scale, do and move downward by the second described solid microneedles array device of stepping driven by motor fixed disc, allow the described solid microneedles array device slow decreasing that faces described thin liquid layer top to described thin liquid layer, rely on the gravity of solid microneedles array device self, the needle point of the micropin on first solid microneedles array device is placed among the thin liquid layer that is formed by described drug solution, described drug solution is adsorbed on the needle point of the micropin on described first solid microneedles array device, thereby realize the medicine carrying of first solid microneedles array device, and then do to move upward by the second described solid microneedles array device of stepping driven by motor fixed disc and get back to initial position, and the gear of rolling disc is connected with the gear of solid microneedles array device fixed disc, drive rolling disc by the 3rd motor, make described solid microneedles array device fixed disc do clockwise or be rotated counterclockwise, make next described solid microneedles array device be positioned at described thin liquid layer top, realize the switching between described solid microneedles array device, then repeat to start to carry out the medicine carrying operation of automatization's solid microneedles array device, until make the described solid microneedles array device that is arranged on described solid microneedles array device fixed disc all medicine carrying complete,
The length of the needle point of the micropin on described solid microneedles array device is higher than the thickness of described thin liquid layer;
The control of the duty of described the first motor, described the second motor and described the 3rd motor is to control by the instruction that described digital control panel sends.
7. according to claim 3 or 5 described devices, it is characterized in that: described micro-meter scale is 75 μ m～500 μ m.
8. according to claim 3 or 5 described devices, it is characterized in that: the material of described groove base plate be selected from simple glass, aluminum, zinc, surface through rustless steel that hydrophilic is processed and surface a kind of in the copper that hydrophilic is processed, or be selected from surface by the material of a kind of modification in above-mentioned material; The material of described frame scraper plate is glass, rustless steel or politef.
9. according to claim 3 or 5 described devices, it is characterized in that: the length of the needle point of the micropin on described solid microneedles array device is between 100～1000 microns; The diameter of the needle point of the micropin on described solid microneedles array device is between 100 nanometers～10 micron; The cone angle of the needle point of the micropin on described solid microneedles array device is 20～60 degree; The material of the micropin on described solid microneedles array device is selected from a kind of in monocrystal silicon, titanium, rustless steel and macromolecular material.
10. device according to claim 9 is characterized in that: described macromolecular material is selected from a kind of in polylactic acid, polyglycolic acid, polyethylene, polyvinyl alcohol, Merlon, polyacrylamide, polypropylene and nylon.
11. according to claim 1,4 or 6 described methods is characterized in that: the length of the needle point of the micropin on described solid microneedles array device is between 100～1000 microns; The diameter of the needle point of the micropin on described solid microneedles array device is between 100 nanometers～10 micron; The cone angle of the needle point of the micropin on described solid microneedles array device is 20～60 degree; The material of the micropin on described solid microneedles array device is selected from a kind of in monocrystal silicon, titanium, rustless steel and macromolecular material.
12. method according to claim 11 is characterized in that: described macromolecular material is selected from a kind of in polylactic acid, polyglycolic acid, polyethylene, polyvinyl alcohol, Merlon, polyacrylamide, polypropylene and nylon.
13. according to claim 1,4 or 6 described methods is characterized in that: the consisting of medicine and contain the aqueous solution of thickening agent of described drug solution;
Described thickening agent is selected from one or more in sodium alginate, gelatin, hyaluronic acid, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carbomer, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, starch, xanthan gum, polyacrylic acid, Radix Acaciae senegalis and chitosan.
14. method according to claim 13 is characterized in that: the concentration of the medicine in described drug solution is 0.1%～50%(w/v), and the concentration of thickening agent is 0.1%～50%(w/v).
15. method according to claim 14 is characterized in that: the concentration of the medicine in described drug solution is 0.5%～5%(w/v).
16. method according to claim 14 is characterized in that: the concentration of the thickening agent in described drug solution is 1%～10%(w/v).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210140545.3A CN103386164B (en) | 2012-05-08 | 2012-05-08 | The method of solid array of microneedles device medicine carrying and device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210140545.3A CN103386164B (en) | 2012-05-08 | 2012-05-08 | The method of solid array of microneedles device medicine carrying and device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103386164A true CN103386164A (en) | 2013-11-13 |
| CN103386164B CN103386164B (en) | 2015-11-04 |
Family
ID=49530696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210140545.3A Active CN103386164B (en) | 2012-05-08 | 2012-05-08 | The method of solid array of microneedles device medicine carrying and device |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103386164B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104888343A (en) * | 2015-05-07 | 2015-09-09 | 北京化工大学 | Macromolecule solid micro needle and batched preparing method thereof |
| CN106691516A (en) * | 2017-03-06 | 2017-05-24 | 桂林市威诺敦医疗器械有限公司 | Skin test instrument with humidity detection function |
| CN110947085A (en) * | 2018-09-27 | 2020-04-03 | 中科微针（北京）科技有限公司 | Method for accelerating forming and instant drug delivery of polyvinyl alcohol soluble microneedle and prepared microneedle |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3470011A (en) * | 1967-02-07 | 1969-09-30 | American Cyanamid Co | Process for applying liquid biologicals to applicators for intracutaneous injection |
| CN101076409B (en) * | 2004-11-18 | 2011-11-23 | 3M创新有限公司 | Method of contact coating a microneedle array |
-
2012
- 2012-05-08 CN CN201210140545.3A patent/CN103386164B/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104888343A (en) * | 2015-05-07 | 2015-09-09 | 北京化工大学 | Macromolecule solid micro needle and batched preparing method thereof |
| CN106691516A (en) * | 2017-03-06 | 2017-05-24 | 桂林市威诺敦医疗器械有限公司 | Skin test instrument with humidity detection function |
| CN106691516B (en) * | 2017-03-06 | 2023-05-05 | 桂林市威诺敦医疗器械有限公司 | Skin tester with humidity detection function |
| CN110947085A (en) * | 2018-09-27 | 2020-04-03 | 中科微针（北京）科技有限公司 | Method for accelerating forming and instant drug delivery of polyvinyl alcohol soluble microneedle and prepared microneedle |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103386164B (en) | 2015-11-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2612005C (en) | Coated microstructures and method of manufacture thereof | |
| US11772305B2 (en) | Production method of mold having recessed pattern in recessed step portion | |
| US11007678B2 (en) | Production method of mold, manufacturing method of pattern sheet, production method of electroform, and production method of mold using electroform | |
| CN107405478B (en) | Method for producing percutaneous absorption sheet | |
| CN103386164B (en) | The method of solid array of microneedles device medicine carrying and device | |
| EP3416620B1 (en) | Method to print microneedle patches rapidly | |
| TW201628586A (en) | Microneedle patch, method for manufacturing same, and apparatus for manufacturing microneedle array | |
| WO2014156455A1 (en) | Cell culturing tool | |
| EP3456505B1 (en) | Method for fabricating mold having recessed pattern and method for producing patterned sheet | |
| TW202135886A (en) | Method for dispensing an aqueous chemical species to a surface | |
| US20210023355A1 (en) | Method of producing microneedle array, microneedle array, and microneedle array unit | |
| CN106853271B (en) | Method for producing microstructure | |
| ES2346707T3 (en) | DEVICE AND PROCEDURE TO COVER UNIFORMLY SUBSTRATES. | |
| JP2013043034A (en) | Method for manufacturing microneedle device | |
| US20210121674A1 (en) | Japanese encephalitis vaccine-containing microneedle array | |
| EP3646919A1 (en) | Manufacturing method of plate precursor having needle-like protrusion, and manufacturing method of microneedle array | |
| CN110251824B (en) | Flexible microneedle patch for transdermal drug delivery and manufacturing method thereof | |
| US20180147399A1 (en) | Method of producing transdermal absorption sheet for medical use | |
| US20130209660A1 (en) | Micro-needle coating method | |
| EP3778169B1 (en) | Method for manufacturing mold having concave pedestal pattern and method for manufacturing pattern sheet | |
| CN219517547U (en) | Novel inclined microneedle structure | |
| US20210378951A1 (en) | Microneedle array and method of producing microneedle array | |
| JP2013043035A (en) | Method for manufacturing microneedle device | |
| JP6537072B2 (en) | Mold and pattern sheet manufacturing method | |
| TW201306890A (en) | Microneedle device and manufacturing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20181227 Address after: Room 1103, Building No. 22, Tianrong Street, Daxing Biomedical Industry Base, Zhongguancun Science and Technology Park, Daxing District, Beijing 102600 Patentee after: Zhongke Microneedle (Beijing) Technology Co., Ltd. Address before: No. 29 East Zhongguancun Road, Haidian District, Beijing 100190 Patentee before: Technical Institute of Physics and Chemistry, CAS |
|
| TR01 | Transfer of patent right |