CN110025883A - Metal drug storage microneedle patch and preparation method thereof - Google Patents

Metal drug storage microneedle patch and preparation method thereof Download PDF

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Publication number
CN110025883A
CN110025883A CN201910419607.6A CN201910419607A CN110025883A CN 110025883 A CN110025883 A CN 110025883A CN 201910419607 A CN201910419607 A CN 201910419607A CN 110025883 A CN110025883 A CN 110025883A
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CN
China
Prior art keywords
metal
drug storage
microneedle
micropin
film
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CN201910419607.6A
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Chinese (zh)
Inventor
赵科研
杨淑艳
郭文平
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Wuxi Yuanxu Biotechnology Co Ltd
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Wuxi Yuanxu Biotechnology Co Ltd
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Priority to CN201910419607.6A priority Critical patent/CN110025883A/en
Publication of CN110025883A publication Critical patent/CN110025883A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • 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
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/04—Coating on selected surface areas, e.g. using masks
    • C23C14/042—Coating on selected surface areas, e.g. using masks using masks
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/06—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
    • C23C14/14—Metallic material, boron or silicon
    • C23C14/16—Metallic material, boron or silicon on metallic substrates or on substrates of boron or silicon
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/06—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
    • C23C14/14—Metallic material, boron or silicon
    • C23C14/16—Metallic material, boron or silicon on metallic substrates or on substrates of boron or silicon
    • C23C14/165—Metallic material, boron or silicon on metallic substrates or on substrates of boron or silicon by cathodic sputtering
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/22—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
    • C23C14/24—Vacuum evaporation
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
    • C23C14/22—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
    • C23C14/34—Sputtering
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
    • C23C16/04—Coating on selected surface areas, e.g. using masks
    • C23C16/042—Coating on selected surface areas, e.g. using masks using masks
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C16/00—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes
    • C23C16/44—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes characterised by the method of coating
    • C23C16/455—Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes characterised by the method of coating characterised by the method used for introducing gases into reaction chamber or for modifying gas flows in reaction chamber
    • C23C16/45523—Pulsed gas flow or change of composition over time
    • C23C16/45525—Atomic layer deposition [ALD]
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C18/00—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating
    • C23C18/16—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating by reduction or substitution, e.g. electroless plating
    • C23C18/1601—Process or apparatus
    • C23C18/1603—Process or apparatus coating on selected surface areas
    • C23C18/1605—Process or apparatus coating on selected surface areas by masking
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C18/00—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating
    • C23C18/16—Chemical coating by decomposition of either liquid compounds or solutions of the coating forming compounds, without leaving reaction products of surface material in the coating; Contact plating by reduction or substitution, e.g. electroless plating
    • C23C18/31—Coating with metals
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D5/00—Electroplating characterised by the process; Pretreatment or after-treatment of workpieces
    • C25D5/02—Electroplating of selected surface areas
    • C25D5/022—Electroplating of selected surface areas using masking means
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D7/00—Electroplating characterised by the article coated
    • C25D7/12—Semiconductors
    • 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
    • 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

Abstract

The invention belongs to biological medicine and micrometer-nanometer processing technology fields, more particularly to metal drug storage microneedle patch, including metal drug storage microneedle array and patch pedestal, metal drug storage microneedle array is arranged in the glue surface of patch pedestal, metal drug storage microneedle array is an integral molding structure, metal drug storage microneedle array includes metal base, metal base upwardly extends to form multiple taper micropins, it is upward that taper microneedle array is distributed in metal base, taper micropin is hollow structure, and top offers pin hole, it is filled out inside taper micropin equipped with drug, the orthographic projection of metal drug storage microneedle array is in the glue surface of patch pedestal.The present invention also provides the preparation method of metal drug storage microneedle patch, metal drug storage microneedle patch provided by the invention is cheap, the simple process of its preparation, is suitable for mass production, and needle point is sharp, hardness is larger, is easy to pierce through skin and not easy to break.

Description

Metal drug storage microneedle patch and preparation method thereof
Technical field
The invention belongs to biological medicine and micrometer-nanometer processing technology field more particularly to metal drug storage microneedle patch and its preparations Method.
Background technique
Transdermal delivery system is also known as Transcutaneous Therapeutic System, refers to that drug is inhaled by skin through capillary with certain rate Take in a kind of preparation that drug effect is generated into body circulation.Compared with traditional administration mode, percutaneous dosing is had many advantages: can be produced Raw lasting, constant and controllable blood concentration, make because metabolism in vivo rapidly due to half-life period very short pharmaceutical activity obviously mentions Height avoids the first pass effect of liver and the interference of gastrointestinal factors, toxic side effect is minimized；With painless and noninvasive or Minimal invasive, patient can self-medication, it is easy to use, can interruption of the administration at any time, patient compliance is higher equal to become all new Most fast one of the novel form of growth rate in dosage form.
Micropin technology remarkably promotes various kinds of drug molecule and includes since it can directly destroy the obstacle of keratoderma The Transdermal absorption of protein and peptide and drug-carrying nanometer particle etc. is will to inject that be blended in integrated one with transdermal patch advantage fine New medicine-feeding technology, and become most promising cutaneous penetration new technology.Microneedles in Transdermal Drug Delivery System has painless, micro- The advantages that wound, safe and efficient, easy to carry, patient can voluntarily use.For therapeutic effect, micropin should enough " big ", To provide drug or preparation of small particle enters the channel of skin；But simultaneously again enough " small ", to avoid patient pain and To the fear of syringe needle.
Four kinds are summarized as according to administration mode micropin: 1, forming corresponding hole on the skin using solid or hollow micropin, Then medicine is sticked on therapentic part, the micropin being administered with this method is called patch needle；2, it is wrapped up on solid microneedles surface The micropin being administered in this way in patient body is injected into after drug to be commonly referred to as being coated micropin；3, drug is wrapped in Inside micropin, micropin is then penetrated into sufferer percutaneous drug delivery, the micropin with this administration mode is packaging medicine micropin；4, lead to It crosses empty micropin and carrys out microinfusion administration, this micropin is referred to as microinjection mode, micropin is administered.
I has been filed in patent application document (a kind of metal micro-needle of CN106730309A- and preparation method thereof) to monocrystalline The production method and feature of silicon micropin describe in detail, but because of its material characteristics, monocrystalline silicon is more crisp, and the micropin of preparation is easily broken It splits, more important is micropins to use as intervening equipment, and exists after the micropin piercing skin of monocrystalline silicon preparation and cause skin mistake The risk of the bodies such as quick, inflammation rejection.Meanwhile wrapping up material used in micropin is mostly polymer, but polymer micro needle intensity compared with Difference, processing technology are complicated.
Summary of the invention
In view of the above shortcomings of the prior art, the present invention provides metal drug storage microneedle patch, in order to solve single Crystal silicon micropin is solid construction, can not be wrapped up drug, and there are sensitization risks, and can not guarantee that needle body is sharply painless While take into account toughness；Wrapping up material used in micropin in the prior art simultaneously is mostly polymer, and polymer micro needle intensity is poor The technical issues of.The present invention also provides the preparation method of metal drug storage microneedle patch, purpose in order to solve to use polymer for The technical problem of the processing technology complexity of material preparation package micropin.
The present invention provides metal drug storage microneedle patch, specific technical solution is as follows:
Metal drug storage microneedle patch, including metal drug storage microneedle array and patch pedestal, the metal drug storage microneedle array It is arranged in the glue surface of the patch pedestal,
The metal drug storage microneedle array is an integral molding structure, and the metal drug storage microneedle array includes metal base, The metal base upwardly extends to form multiple taper micropins, and it is upward that the taper microneedle array is distributed in the metal base, The taper micropin is hollow structure, and top offers pin hole, fills out inside the taper micropin equipped with drug,
The orthographic projection of the metal drug storage microneedle array is in the glue surface of the patch pedestal.
In some embodiments, the centrum angle of the taper micropin is 60-80 degree.
In some embodiments, the diameter of the pin hole is 10-100 μm.
In some embodiments, the spacing between the taper micropin is 300-500 μm.
In some embodiments, the height perpendicular to the metal base of the taper micropin is 100-300 μm.
The present invention also provides the preparation methods of metal drug storage microneedle patch, are used to prepare above-mentioned metal drug storage microneedle patch The method of piece, includes the following steps:
S1 selects the monocrystalline silicon of single-sided polishing as silicon chip, cleans by substrate, by high-temperature thermal oxidation, in silicon substrate On piece forms the two-sided protective film of silicon body, and using photoetching, pattern transfer and wet etching obtain silicon micropin substrate；
S2 plates hypo-allergenic metal film, the metal on the surface of the silicon micropin substrate obtained in step sl and needle body Film with a thickness of 1-100 μm；
Hypo-allergenic metal film point in S3, step S2 includes needle tip metal film and gluing portion metal film, in the gluing Portion's metal film smear a layer photoresist, the photoresist with a thickness of 1-7 μm, be put into nitrohydrochloric acid, corrode the needle tip Metal film exposes silicon layer；
S4, removal photoresist utilize silicon etch solution, corrode the silicon micropin substrate at the back side, obtain metal drug storage micropin battle array Column；
S5, the drug storage that metal drug storage microneedle array in step S4 is added in active pharmaceutical ingredients is intracavitary, encloses medical to viscous Glue-line cuts into qualified size, obtains gold drug storage microneedle patch.
In some embodiments, in step S2, the method for the plated film is vapour deposition method, sputtering method, atomic vapor deposition Method, galvanoplastic or in-situ chemical reaction method.
In some embodiments, in step S2, the hypo-allergenic metal film is golden film, silverskin, platinum film, titanium film or palladium Film.
In some embodiments, in step S4, the silicon etch solution is the mixed liquor of KOH, IPA and H2O.
The invention has the following advantages: the present invention manufactures metal drug storage micropin by matrix of monocrystalline silicon micropin, medicine Object storage is provided with micropore to inside metal micro-needle at the top of micropin, and microneedle array is made, then enclose it is medical to adhesive-layer, i.e., It is prepared into metal drug storage microneedle patch.
Detailed description of the invention
Fig. 1 is metal drug storage microneedle patch structural schematic diagram of the invention；
Fig. 2 is the step flow chart of the preparation method of metal drug storage microneedle patch of the invention；
Fig. 3 is the scanning electron microscope (SEM) photograph of metal drug storage microneedle array of the invention.
Specific embodiment
To make the objectives, technical solutions, and advantages of the present invention clearer, below in conjunction with specific embodiment, and reference Attached drawing, the present invention is described in more detail.
The present invention provides metal drug storage microneedle patch, specific technical solution is as follows:
Metal drug storage microneedle patch, including metal drug storage microneedle array 1 and patch pedestal 2, metal drug storage microneedle array 1 are set It sets in the glue surface 21 of patch pedestal 2, metal drug storage microneedle array 1 is an integral molding structure, and metal drug storage microneedle array 1 includes Metal base 11, metal base 11 upwardly extend to form multiple taper micropins 12, and 12 array distribution of taper micropin is in metal base 11 upwards, and taper micropin 12 is hollow structure, and top offers pin hole 13, is filled out inside taper micropin 12 equipped with drug, metal The orthographic projection of drug storage microneedle array 1 is in the glue surface 21 of patch pedestal 2.The drug stored in metal drug storage microneedle array 1 can be with For medicinal herb components drug, vaccine, beautifying drug etc., metal drug storage microneedle patch is pasted on the skin, metal drug storage microneedle array 1 Puncture skin, wherein the drug of storage is released through skin through needle passing hole 13 and enters body circulation through capillary absorbance.
Further, the centrum angle of taper micropin 12 is 60-80 degree.Centrum angle is that 60-80 degree can guarantee sharply Object tingling sensation, while guaranteeing to be not easily broken.The centrum angle of taper micropin 12 is 72 degree in the present embodiment.
Further, the diameter of pin hole 13 is 10-100 μm.In this way, guaranteeing that pin hole 13 is not easily susceptible to pollute, while can also To be used for drug release, the diameter of the pin hole 13 in the present embodiment is 50 μm.
Further, the spacing between taper micropin 12 is 300-500 μm.Between taper micropin 12 in the present embodiment Spacing is 400 μm.
Further, the height perpendicular to metal base 11 of taper micropin 12 is 100-300 μm.Cone in the present embodiment The height perpendicular to metal base 11 of shape micropin 12 is 200 μm.
The present invention also provides the preparation methods of metal drug storage microneedle patch, are used to prepare above-mentioned metal drug storage microneedle patch The method of piece, includes the following steps:
S1 selects the monocrystalline silicon of single-sided polishing as silicon chip, cleans by substrate, by high-temperature thermal oxidation, in silicon substrate On piece forms the two-sided protective film of silicon body, and using photoetching, pattern transfer and wet etching obtain silicon micropin substrate；
S2 plates hypo-allergenic metal film on the surface of the silicon micropin substrate obtained in step sl and needle body, metal film With a thickness of 1-100 μm；
Hypo-allergenic metal film point in S3, step S2 includes needle tip metal film and gluing portion metal film, in gluing portion gold Belong to film smear a layer photoresist, photoresist with a thickness of 1-7 μm, be put into nitrohydrochloric acid, corrode needle tip metal film, expose silicon Layer；
S4, removal photoresist utilize silicon etch solution, corrode the silicon micropin substrate at the back side, obtain metal drug storage microneedle array 1；
S5, the drug storage that metal drug storage microneedle array 1 in step S4 is added in active pharmaceutical ingredients is intracavitary, encloses medical to viscous Glue-line cuts into qualified size, obtains gold drug storage microneedle patch.
Further, in step S2, the method for plated film is vapour deposition method, sputtering method, atomic vapor deposition method, galvanoplastic or original Position chemical reaction method.Film plating process in the present embodiment is vapour deposition method.
Further, in step S2, hypo-allergenic metal film is golden film, silverskin, platinum film, titanium film or palladium film.In the present embodiment The hypo-allergenic metal film selected is golden film.
In the present embodiment, in step S4, the mixed liquor of silicon etch solution KOH, IPA and H2O.
The simple process that metal drug storage microneedle patch provided by the invention is cheap, it is prepared, is suitable for mass production, And needle point is sharp, hardness is larger, is easy to pierce through skin and not easy to break.It is such as good with bio-compatibility, hypo-allergenic gold, titanium Equal metals are the good material for manufacturing micropin.The present invention manufactures metal drug storage micropin by matrix of monocrystalline silicon micropin, drug It stores inside metal micro-needle, micropore is provided at the top of micropin, microneedle array is made, then enclose medical to adhesive-layer, that is, make For at metal drug storage microneedle patch.
Above-mentioned preferable possible embodiments only of the invention, are not limitations of the present invention, the present invention is also not limited to above-mentioned Citing, those skilled in the art, within the essential scope of the present invention, made variations, modifications, additions or substitutions, Also it should belong to protection scope of the present invention.

Claims (9)

1. metal drug storage microneedle patch, which is characterized in that including metal drug storage microneedle array and patch pedestal, the metal drug storage Microneedle array is arranged in the glue surface of the patch pedestal,
The metal drug storage microneedle array is an integral molding structure, and the metal drug storage microneedle array includes metal base, described Metal base upwardly extends to form multiple taper micropins, and it is upward that the taper microneedle array is distributed in the metal base, described Taper micropin is hollow structure, and top offers pin hole, fills out inside the taper micropin equipped with drug,
The orthographic projection of the metal drug storage microneedle array is in the glue surface of the patch pedestal.
2. metal drug storage microneedle patch according to claim 1, which is characterized in that the centrum angle of the taper micropin is 60-80 degree.
3. metal drug storage microneedle patch according to claim 1, which is characterized in that the diameter of the pin hole is 10-100 μ m。
4. metal drug storage microneedle patch according to claim 1, which is characterized in that the spacing between the taper micropin is 300-500μm。
5. metal drug storage microneedle patch according to claim 1, which is characterized in that the taper micropin perpendicular to described The height of metal base is 100-300 μm.
6. the preparation method of metal drug storage microneedle patch is used to prepare the described in any item metal drug storage micropins of claim 1-4 The method of patch, which comprises the steps of:
S1 selects the monocrystalline silicon of single-sided polishing as silicon chip, cleans by substrate, by high-temperature thermal oxidation, on a silicon substrate The two-sided protective film of silicon body is formed, using photoetching, pattern transfer and wet etching obtain silicon micropin substrate；
S2 plates hypo-allergenic metal film on the surface of the silicon micropin substrate obtained in step sl and needle body, the metal film With a thickness of 1-100 μm；
Hypo-allergenic metal film point in S3, step S2 includes needle tip metal film and gluing portion metal film, in the gluing portion gold Belong to film smear a layer photoresist, the photoresist with a thickness of 1-7 μm, be put into nitrohydrochloric acid, corrode the needle tip metal Film exposes silicon layer；
S4, removal photoresist utilize silicon etch solution, corrode the silicon micropin substrate at the back side, obtain metal drug storage microneedle array；
S5, the drug storage that metal drug storage microneedle array in step S4 is added in active pharmaceutical ingredients is intracavitary, enclose it is medical to adhesive-layer, Qualified size is cut into, gold drug storage microneedle patch is obtained.
7. the preparation method of metal drug storage microneedle patch according to claim 6, which is characterized in that described in step S2 The method of plated film is vapour deposition method, sputtering method, atomic vapor deposition method, galvanoplastic or in-situ chemical reaction method.
8. the preparation method of metal drug storage microneedle patch according to claim 6, which is characterized in that described in step S2 Hypo-allergenic metal film is golden film, silverskin, platinum film, titanium film or palladium film.
9. the preparation method of metal drug storage microneedle patch according to claim 6, which is characterized in that described in step S4 Silicon etch solution is the mixed liquor of KOH, IPA and H2O.
CN201910419607.6A 2019-05-20 2019-05-20 Metal drug storage microneedle patch and preparation method thereof Pending CN110025883A (en)

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