CN104069585A - Separable microneedle system and manufacturing method thereof - Google Patents
Separable microneedle system and manufacturing method thereof Download PDFInfo
- Publication number
- CN104069585A CN104069585A CN201410312539.0A CN201410312539A CN104069585A CN 104069585 A CN104069585 A CN 104069585A CN 201410312539 A CN201410312539 A CN 201410312539A CN 104069585 A CN104069585 A CN 104069585A
- Authority
- CN
- China
- Prior art keywords
- micropin
- substrate
- female mold
- microneedle
- binding agent
- 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
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
Abstract
The invention relates to the technical field of the microneedles for the medical cosmetology and in particular relates to a separable microneedle system and a manufacturing method thereof. The separable microneedle system comprises a microneedle and a substrate; the microneedle is detachably fixed on the substrate; when the microneedle penetrates into the skin, the microneedle is separated from the substrate so that the microneedle is remained in the skin. The separable microneedle system has the beneficial effects that the microneedle is made of a biocompatible and degradable material, has enough mechanical strength so as to smoothly pierce the skin and can be remained in the skin for procedural degradation; active substances are stable in activity in the microneedle is made of the biocompatible and degradable material, so that the medicine can be released controllably for a long time in the injection point; the microneedle substrate can be made of a flexible material, the hard microneedle can be separated from the flexible substrate, and after the microneedle penetrates into the skin, the microneedle is removed and the separated microneedle is continuously remained in the skin so that the internal active substances can be controllably dissolved and released.
Description
Technical field
The present invention relates to medical and beauty treatment micropin technical field, particularly a kind of detachable microneedle device and manufacture method thereof.
Background technology
Percutaneous dosing is owing to can avoiding macromolecule to degrade in gastrointestinal tract and easy to use, as being widely used for the effective way of drug delivery.In order to make active ingredient in subcutaneous performance pharmacological action, used the external preparation that comprises active ingredient in the past.As such external preparation, known have liquor, ointment, cream preparation, tape preparation, patch, a paste etc., and by they are coated with partly or are attached, active ingredient percutaneous absorbs, in the desired pharmacological action of subcutaneous performance.Yet there is following shortcoming in above-mentioned coating or the external preparation that attaches form: due to the barriers function of skin, active ingredient can not be absorbed by percutaneous fully, can not bring into play desired pharmacological action.Especially when active ingredient is macromolecular compound, is difficult to percutaneous and absorbs, be difficult to bring into play desired pharmacological action in external preparation.And in use, due to perspiration, cleaning, external pressure etc., active ingredient, before being absorbed by percutaneous, sometimes comes off or disappears.In recent years, be added with the microneedle array of micropin of active ingredient as the technology that solves above-mentioned external preparation shortcoming, be widely studied.For example, the Chinese patent that publication number is 102580232A discloses the mainly scheme as the microneedle array of micropin raw material by fibroin albumen.By micropin being thrust to skin surface and/or keratodermatitis, thus the active ingredient in micropin is supplied to subcutaneous, thereby the micropin thrusting part can be subcutaneous dissolved or be biodegradable disappearance.In addition, micropin is because pin portion is very thin, even thereby thrust skin surface and/or keratodermatitis, also do not produce pain or hemorrhage, and puncture hinders rapid closing, thereby is suitable for as the method to subcutaneous supply active ingredient.This type of microneedle array need to carry out most suitable design according to skin symptom, needs exploitation that various microneedle arrays are provided.The micropin using as external preparation need to synthetically have (1) concurrently and can tolerate the Strong degree that thrusts to skin surface and/or keratodermatitis, (2) and do not thrust to dissolubility in vivo of subcutaneous micropin part or biological degradability etc. for the part thrusting skin surface and/or keratodermatitis does not produce pain or hemorrhage fineness and flexibility and (3).In the past, the substrate of this type of micropin adopts was the material equally hard with micropin, and micropin cannot be separated with substrate, at micropin, thrust after skin, hard substrate must be pressed in skin surface, after waiting for that drug injection completes, just peelable substrate, brings discomfort to user like this.
Summary of the invention
Technical problem to be solved by this invention is: the substrate of existing micropin and micropin are one, at micropin, thrust after skin, hard substrate must be pressed in skin surface, after waiting for that drug injection completes, the peelable substrate of, to user, bring discomfort like this, and the rate of release of wayward medicine and drug loading.
The technical solution adopted for the present invention to solve the technical problems is: a kind of detachable microneedle device, comprise micropin and substrate, and micropin is fixed on substrate separably, and when micropin thrusts after skin, separated micropin and substrate, stay in skin micropin.
Micropin is fixed on substrate separably by binding agent, and binding agent is the binding agent that peelable release binding agent, soluble-type binding agent or structural strength are less than micropin needle structure intensity.
Further limit, peelable release binding agent is peelable release pressure sensitive adhesive; Described soluble-type binding agent is the solubilized viscose glue that albumen or starch are made.
Further limit, the surface that binding agent covers substrate forms tack coat.
Further limit, on the surface of substrate, have needle tray, the bottom of micropin embeds needle tray, between micropin and needle tray, has binding agent, being fixed on substrate separably of the bonding force of micropin by binding agent.
Or, on the surface of substrate, thering is needle tray, the bottom of micropin embeds needle tray, and micropin is fixed on substrate separably by the mechanical bond power between micropin and needle tray.
Or, on the surface of substrate, thering is needle tray, the bottom of micropin embeds needle tray, between micropin and needle tray, has binding agent, and micropin is fixed on substrate separably by the combined effect of the bonding force of the mechanical bond power between micropin and needle tray and binding agent.
Further limit, micropin is haplotype micropin, and needle tray is corresponding with the shape of the bottom of each haplotype micropin.Or micropin is isoplanar microneedle array, needle tray is corresponding with the shape of the micropin base of isoplanar microneedle array, and a plurality of isoplanars microneedle array embeds substrate and forms different plane microneedle array.
Further limit, micropin is made by biodegradable micropin material, adds the active substance of one or more medical treatment or beautifying use in biodegradable micropin material.
Further limit, substrate is made by flexible material.
Further limit, flexible material is bio-compatibility flexible material, bio-compatibility flexible material is hydrogel, polyvinylpyrrolidone/polyvinyl acetate, triethyl citrate, structure edge acid tributyl, trimethyl citrate, and the plasticiser adding in above-mentioned bio-compatibility flexible material is one or more the mixture in glycerol, Oleum Ricini, emulsifying agent T-80, PEG400; Or flexible material is flexible polymer, flexible polymer is one or more the mixture in cellulose, polyester, polypropylene, Merlon, polystyrene, polyethylene, polrvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polydimethylsiloxane, Kynoar, acetate fiber, polyurethane.
Further limit, micropin vertically or is obliquely fixed on substrate.
A manufacture method for detachable microneedle device, has following steps:
1) make micropin female mold;
2) in the micropin groove of micropin female mold, fill up liquid micropin material and solidify;
3) substrate that surface is had to a binding agent is pressed in micropin female mold;
4) make micropin and the base plate bonding in micropin female mold, and together depart from micropin female mold with substrate, obtain detachable microneedle device.
Further limit, step 2 is specially: by micropin female mold by being pressed on the flat board that scribbles liquid micropin material, make to fill up micropin body pre-polymer solution in the micropin groove of micropin female mold, micropin body pre-polymer solution removes flat board after solidifying, and leaves the micropin after solidifying in micropin female mold; Or, directly liquid micropin material is coated in micropin female mold, and then use dull and stereotyped by being pressed in micropin female mold, make to fill up micropin body pre-polymer solution in the micropin groove of micropin female mold, micropin body pre-polymer solution removes flat board after solidifying, and leaves the micropin after solidifying in micropin female mold.
A preparation method for detachable microneedle device, has following steps:
1) make micropin female mold;
2) in the micropin groove of micropin female mold, fill up micropin body pre-polymer solution and solidify;
3) micropin female mold is shifted to flat board above by being pressed in viscosity, make micropin transfer to this viscosity and shift on flat board;
4) utilize this viscosity to shift flat board micropin is transferred in transfer mold, the degree of depth of the micropin groove of this transfer mold is less than the degree of depth of the micropin groove of micropin female mold;
5) micropin in transfer mold is transferred on the substrate that is carved with needle tray, micropin embeds needle tray, and together departs from micropin female mold with substrate, obtains detachable microneedle device.
The invention has the beneficial effects as follows: micropin adopts the degradable micropin material of bio-compatible to make, and has enough mechanical strengths, can pierce through smoothly skin, can stay the degraded of skin internal programization; Active substance can keep activity stabilized in the micropin of the degradable micropin material based on bio-compatible, is conducive to controllably discharge medicine in injection point position director's phase; And micropin substrate can adopt flexible material, hard micropin can be separated with flexible substrate, at micropin, thrusts after skin, peels off substrate, and micropin after separation continues to keep in skin and controllably dissolves and discharge inner active substance.
Accompanying drawing explanation
Below in conjunction with drawings and Examples, the present invention is further described;
Fig. 1 is the micropin delivery process schematic diagram of detachable microneedle device of the present invention;
Fig. 2 is the manufacture process schematic diagram of adhered separable microneedle device of the present invention;
Fig. 3 is the use procedure schematic diagram of adhered separable microneedle device of the present invention;
Fig. 4 is the manufacture process schematic diagram of the separable microneedle device of needle tray formula of the present invention;
Fig. 5 is the use procedure schematic diagram of the separable microneedle device of needle tray formula of the present invention;
Fig. 6 is the manufacture process schematic diagram of the adhered separable microneedle device of many row's assemblings of the present invention;
Fig. 7 is the use procedure schematic diagram of the adhered separable microneedle device of many row's assemblings of the present invention;
In figure, 1. micropin, 2. substrate, 3. binding agent, 4. skin, 5. micropin female mold, 6. flat board, 7. viscosity shift dull and stereotyped, 8. transfer mold, 9. isoplanar microneedle array, the 10. main mould of microneedle array, the micropin material of 11. liquid state.
The specific embodiment
As shown in Figure 1, a detachable microneedle device, comprises micropin 1 and substrate 2, and micropin 1 is fixed on substrate 2 separably, micropin 1 is made by biodegradable micropin material, adds the active substance of one or more medical treatment or beautifying use in biodegradable micropin material.When micropin 1 thrusts after skin 4, separated micropin 1 and substrate 2, stay in skin 4 micropin 1.
Biodegradable micropin material can be selected from fibroin albumen, collagen protein, gelatin, hydrogel, carboxymethyl cellulose, hydroxypropyl emthylcellulose, chondroitin sulfate, glycogen, dextrin, amylose, hyaluronic acid, polylactic-co-glycolic acid, Poly(D,L-lactide-co-glycolide, PVOH ester, polyacrylic acid, polypropylene, Merlon, polystyrene, polyethylene, polrvinyl chloride, ABS plastic (acrylonitrile-butadiene-styrene copolymer), polydimethylsiloxane, Kynoar, acetate fiber, polyester, polyurethane, poly-dioxy ring ethyl ketone, PEG, poly-(lactic acid), polyacrylamide polymer, cycloolefin co-polymer, carboxymethyl chitosan, Poly-L-lactic acid, alginic acid, glucosan, dextran sulfate, hydroxypropyl emthylcellulose, chitin, polyvinylpyrrolidone, lactose, galactose, trehalose, sucrose, maltose, glucosan, glucosides, fructose, chitosan, agarose, Sorbitol, mannitol or xylitol, Dan Baiduotang proteoglycan PG, phosphatidylcholine, polylactide, PGA, hydroxypropyl cellulose, wax, polyester, polyanhydride, polyamide, phosphorus based polymer, poly-(cyanoacrylate), polyurethane, poe, poly-dihydropyran, polyacetals, Biodegradable polymeric, polypeptide, a kind of in carbohydrate or their combination.
The active substance of medical treatment or beautifying use can be medicine or cosmetics molecule, comprise citric acid, protein, peptide, polysaccharide, antigen, immunogen, vaccine, antibody, enzyme, nucleic acid, aptamer, virus, antibacterial, cell, hormone, antibiotic, cancer therapy drug, genetically engineered drug, natural product medicine, Chinese medicine ingredients, nutritional labeling, therapeutic agent, diagnostic agent, and the combination of mentioned reagent.
Detachable microneedle device comprises adhered separable microneedle device and the separable microneedle device of needle tray formula.It is easily more separated with substrate 2 that the separable microneedle device of needle tray formula is compared adhered separable microneedle device, do not need to control bonding force as adhered separable microneedle device, and do not need while departing from moistening.
The structure of adhered separable microneedle device is as follows:
The micropin 1 of adhered separable microneedle device is fixed on substrate 2 separably by binding agent 3, and binding agent 3 is the binding agent that peelable release binding agent, soluble-type binding agent or structural strength are less than micropin needle structure intensity.The surface that binding agent 3 can cover substrate 2 completely forms tack coat, also can be only in the part of the fixed area of micropin 1, exists.
Peelable release binding agent is peelable release pressure sensitive adhesive, as organic silicon pressure-sensitive adhesive, pressure-sensitive acrylate adhesive.Thrust after skin 4, for helping micropin 1 separation, on skin 4 surfaces, coat moisture, the peelable release binding agent of moisture moistening, the bonding force of reduction substrate 2 and micropin 1, then opens substrate 2 binding agent 3 and micropin 1 is departed from.
Soluble-type binding agent is the solubilized viscose glue that albumen or starch are made, the amylan of making as albumen viscose glue and Oryza glutinosa, Semen Tritici aestivi, Semen Maydis, Rhizoma Solani tuber osi.Thrust after skin 4, the moisture that is coated in skin 4 surfaces dissolves soluble-type binding agent, then opens substrate 2 binding agent 3 and micropin 1 are departed from.
While adopting structural strength to be less than the binding agent of micropin needle structure intensity, thrust after skin 4, by translation substrate 2, the micropin 1 that can make vertically or to be obliquely fixed on substrate 2 ruptures in the bonding place with substrate 2, micropin 1 is from substrate 2 separation, stay the active substance that the interior release of skin 4 is wrapped in micropin 1 or spreads upon micropin 1 surface, the micropin 1 being fixed on obliquely on substrate 2 more easily ruptures in bonding place with respect to the micropin 1 being vertically fixed on substrate 2.
On the surface of the substrate 2 of adhered separable microneedle device, also can be designed with needle tray, compare with the separable microneedle device of needle tray formula, between micropin 1 and needle tray, there is no mechanical bond power, the bottom of micropin 1 embeds needle tray, between micropin 1 and needle tray, there is binding agent 3, being fixed on separably on substrate 2 of the bonding force of micropin 1 by binding agent 3.
The structure of the separable microneedle device of needle tray formula is as follows:
On the surface of the substrate 2 of the separable microneedle device of needle tray formula, there is needle tray, the bottom of micropin 1 embeds needle tray, micropin 1 is fixed on substrate 2 separably by the mechanical bond power between micropin 1 and needle tray, the mechanical bond power of micropin 1 and needle tray is less than micropin 1 and thrusts after skin 4, the resistance of 4 pairs of micropins 1 of skin, thrusts after skin 4, opens substrate 2, substrate 2 departs from micropin 1, and micropin 1 is stayed the interior slow dissolving of skin 4 and discharged the medicine in being wrapped in.
Between micropin 1 and needle tray, also can be assisted and be fixed by binding agent, micropin 1 be fixed on substrate 2 separably by the combined effect of the bonding force of the mechanical bond power between micropin 1 and needle tray and binding agent.The combined effect of the mechanical bond power between micropin 1 and needle tray and the bonding force of binding agent is less than micropin 1 and thrusts after skin 4, the resistance of 4 pairs of micropins 1 of skin, thrusts after skin 4, opens substrate 2, substrate 2 departs from micropin 1, and micropin 1 is stayed the interior slow dissolving of skin 4 and discharged the medicine in being wrapped in.
The micropin 1 of adhered separable microneedle device and the separable microneedle device of needle tray formula can be that haplotype micropin can be also isoplanar microneedle array 9, isoplanar microneedle array 9 comprises a plurality of micropin needle bodies and the base that is connected micropin needle body, and micropin needle body and base are in same plane.
As shown in Figure 2, embodiment 1:
The manufacture method of adhered detachable micropin, has following steps:
(1) utilize photoetching process to make the main mould 10 of microneedle array of SU-8 material;
A) with AUTOCAD, draw microneedle array base patterns, make mask plate, the long 300 μ m of micropin base patterns of microneedle array base patterns, wide 200 μ m, the gap 500 μ m between micropin,
B) prepare a slice K9 glass wafer, as substrate of glass, the crome metal (Cr) that sputter one deck 300 nm are thick in substrate of glass;
C) the BP212-37s eurymeric photoresist of spin coating one deck 2 micron thickness subsequently, exposes with the mask plate that step 1) is made, the sodium hydroxide developing liquid developing with 0.5%, and 100 ℃ of after bake 5 min obtain patterned photoresist mask;
D) then use CR-14 corrosive liquid corroding metal chromium (Cr), with acetone, remove photoresist mask subsequently and obtain Cr mask plate, thereby the Cr mask plate that photoetching SU-8 is used is transferred in substrate of glass;
E) SU-8 photoresist is spun in substrate of glass, thickness is 500 μ m;
F) after 90 ℃ of oven dry from the canted exposure of the substrate of glass back side, canted exposure angle is 15 degree, 90 degree are once rotated in every exposure afterwards, canted exposure again after canted exposure four times, is dried, then is used developing liquid developing so altogether, obtains SU-8 microneedle array structure.
(2) make micropin female mold 5;
On the main mould 10 of microneedle array of the SU-8 material preparing, get rid of the mixed liquor that is coated with PDMS performed polymer and cross-linking agent, in the vacuum tank of 90 degree, dry polymerizing curable 30 minutes.Then the main mould 10 of microneedle array of sloughing SU-8 material obtains micropin female mold 5.
(3) in the micropin groove of micropin female mold 5, fill up liquid micropin material 11 and solidify;
On dull and stereotyped 6, get rid of the micropin material 11 that is coated with a kind of liquid state, as contained more than 30% maltose solution of proportion, by micropin female mold 5 by being pressed on the flat board 6 that scribbles liquid micropin material 11, make to fill up micropin body pre-polymer solution in the micropin groove of micropin female mold 5, micropin body pre-polymer solution removes flat board 6 after solidifying, leave the micropin 1 after solidifying in micropin female mold 5; Or, directly liquid micropin material 11 is got rid of and is coated in micropin female mold 5, if proportion is more than 20% silk fibroin protein solution, and then use dull and stereotyped 6 by being pressed in micropin female mold 5, make to fill up micropin body pre-polymer solution in the micropin groove of micropin female mold 5, micropin body pre-polymer solution removes flat board 6 after solidifying, leave the micropin 1 after solidifying in micropin female mold 5.Solidification process can be dried at 20 degree to 90 degree constant-temperature vacuum drying baker.
(4) substrate 2 that surface is had to a tack coat is pressed in micropin female mold 5;
In order to make the micropin 1 in micropin female mold 5 reliably bonding with substrate 2, can apply suitable pressure, and heating simultaneously, make melting after micropin 1 local heat, thereby cooled and solidified is reliably bonding with the binding agent 3 of substrate 2 again, assurance micropin 1 is follow-up can depart from substrate 2.
By the substrate 2 that contains the adhesive layer that the peelable release bonding agent of one deck forms by being pressed in the micropin female mold 5 that is filled with micropin 1.Substrate 2 can adopt bio-compatibility flexible material, bio-compatibility flexible material is hydrogel, polyvinylpyrrolidone/polyvinyl acetate, triethyl citrate (triethyl citrate), structure edge acid tributyl (Tributyl Citrate), trimethyl citrate, and the plasticiser adding in above-mentioned bio-compatibility flexible material is one or more the mixture in glycerol, Oleum Ricini, emulsifying agent T-80, PEG400; Or substrate 2 also can adopt flexible polymer, flexible polymer is one or more the mixture in cellulose, polyester, polypropylene, Merlon, polystyrene, polyethylene, polrvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polydimethylsiloxane, Kynoar, acetate fiber, polyurethane.
(5) make the micropin 1 in micropin female mold 5 bonding with substrate 2, and together depart from micropin female mold 5 with substrate 2, obtain the separable microneedle device of adhered flexibility.
As shown in Figure 3, the using method of above-mentioned adhered separable microneedle device: (1) extruding substrate 2 makes micropin 1 thrust skin 4; (2) thrust after skin 4, be coated in the peelable release binding agent of moisture moistening on skin 4 surfaces, reduce the bonding force of substrate 2 and micropin 1, then open substrate 2 peelable release binding agent and micropin 1 are departed from; (3) micropin 1 is stayed the interior slow dissolving release of skin 4 and is wrapped in interior medicine.
As shown in Figure 4, embodiment 2:
The manufacture method of the separable microneedle device of needle tray formula, has following steps:
(1) make the main mould 10 of microneedle array;
(2) make micropin female mold 5;
(3) in the micropin groove of micropin female mold 5, fill up micropin body pre-polymer solution and solidify;
(4) micropin female mold 5 is shifted on dull and stereotyped 7 by being pressed in viscosity, make micropin 1 transfer to this viscosity and shift on dull and stereotyped 7;
(5) utilize this viscosity to shift dull and stereotyped 7 micropin 1 is transferred in transfer mold 8, the degree of depth of the micropin groove of this transfer mold 8 is less than the degree of depth of the micropin groove of micropin female mold 5;
(6) micropin in transfer mold 81 is transferred on the substrate 2 that is carved with needle tray, micropin 1 embeds needle tray, and together departs from micropin female mold 5 with substrate 2, obtains the flexible detachable microneedle device of needle tray formula.
Manufacturing process (1) to (4) can be with reference to embodiment 1.
The transfer mold with more shallow micropin groove 8 in manufacturing process (5) can be used the step (1) of embodiment 1 and (2) described manufacture method manufacture to form.
In manufacturing process (6), utilize and be laser-ablated in the making needle tray corresponding with the bottom shape of micropin 1 on silica gel (PDMS) surface, using as the substrate 2 that connects micropin 1.
As shown in Figure 5, the using method of the separable microneedle device of needle tray formula: (1) extruding substrate 2 makes micropin 1 thrust skin 4; (2) upwards open substrate 2, due to the adhesion of micropin 1 and the needle tray of substrate 2 a little less than, substrate 2 departs from micropin 1; (3) micropin 1 is stayed the interior slow dissolving release of skin 4 and is wrapped in interior medicine.
As shown in Figure 6, embodiment 3:
The manufacture methods of the adhered separable microneedle device of many row's assemblings: (1) is used resolvability material to be prepared into isoplanar microneedle array 9 as fibroin albumen and maltose material, and the thickness of isoplanar microneedle array 9 is lower than its width; (2) a plurality of isoplanars microneedle array 9 vertically or obliquely embeds the needle tray of substrate 2, and needle tray is corresponding with the shape of the micropin base of isoplanar microneedle array 9, and fixedly obtains different plane microneedle array with bonding agent.
As shown in Figure 7, the using method of the separable microneedle device of adhered many row's assemblings: (1) extruding substrate 2 makes isoplanar microneedle array 9 thrust skin 4; (2) translation substrate 2 makes isoplanar microneedle array 9 rupture in bonding part; (3) post-rift isoplanar microneedle array 9 is stayed the interior slow dissolving release medicine of skin 4.
Claims (16)
1. a detachable microneedle device, comprise micropin (1) and substrate (2), it is characterized in that: it is upper that described micropin (1) is fixed on substrate (2) separably, when micropin (1) thrusts after skin, separated micropin (1) and substrate (2), stay in skin (4) micropin (1).
2. detachable microneedle device according to claim 1, it is characterized in that: it is upper that described micropin (1) is fixed on substrate (2) separably by binding agent (3), and binding agent (3) is the binding agent that peelable release binding agent, soluble-type binding agent or structural strength are less than micropin needle structure intensity.
3. detachable microneedle device according to claim 2, is characterized in that: described peelable release binding agent is peelable release pressure sensitive adhesive; Described soluble-type binding agent is the solubilized viscose glue that albumen or starch are made.
4. according to the detachable microneedle device described in claim 2 or 3, it is characterized in that: the surface that described binding agent (3) covers substrate (2) forms tack coat.
5. detachable microneedle device according to claim 2, it is characterized in that: on the surface of described substrate (2), there is needle tray, the bottom of micropin (1) embeds needle tray, between micropin (1) and needle tray, there is binding agent (3), being fixed on separably on substrate (2) of the bonding force of micropin (1) by binding agent (3).
6. detachable microneedle device according to claim 1, it is characterized in that: on the surface of described substrate (2), there is needle tray, the bottom of micropin (1) embeds needle tray, and micropin (1) is fixed on substrate (2) separably by the mechanical bond power between micropin (1) and needle tray.
7. detachable microneedle device according to claim 1, it is characterized in that: on the surface of described substrate (2), there is needle tray, the bottom of micropin (1) embeds needle tray, between micropin (1) and needle tray, have binding agent (3), micropin (1) is fixed on substrate (2) separably by the combined effect of the bonding force of the mechanical bond power between micropin (1) and needle tray and binding agent (3).
8. according to the detachable microneedle device described in claim 5,6 or 7, it is characterized in that: described micropin (1) is haplotype micropin, and needle tray is corresponding with the shape of the bottom of each haplotype micropin.
9. according to the detachable microneedle device described in claim 5,6 or 7, it is characterized in that: described micropin (1) is isoplanar microneedle array (9), needle tray is corresponding with the shape of the base of isoplanar microneedle array (9), and a plurality of isoplanars microneedle arrays (9) embed substrate (2) and form different plane microneedle array.
10. according to the detachable microneedle device described in claim 1 or 2 or 5 or 7, it is characterized in that: described micropin (1) is made by the degradable micropin material of bio-compatible, in the degradable micropin material of bio-compatible, add the active substance of one or more medical treatment or beautifying use.
11. according to the detachable microneedle device described in claim 1 or 2 or 5 or 7, it is characterized in that: described substrate (2) is made by flexible material.
12. detachable microneedle devices according to claim 11, it is characterized in that: described flexible material is bio-compatibility flexible material, bio-compatibility flexible material is hydrogel, polyvinylpyrrolidone/polyvinyl acetate, triethyl citrate, structure edge acid tributyl, trimethyl citrate, and the plasticiser adding in above-mentioned bio-compatibility flexible material is one or more the mixture in glycerol, Oleum Ricini, emulsifying agent T-80, PEG400;
Or flexible material is flexible polymer, flexible polymer is one or more the mixture in cellulose, polyester, polypropylene, Merlon, polystyrene, polyethylene, polrvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polydimethylsiloxane, Kynoar, acetate fiber, polyurethane.
13. detachable microneedle devices according to claim 1, is characterized in that: described micropin (1) vertically or is obliquely fixed on substrate (2).
The manufacture method of the detachable microneedle device described in 14. 1 kinds of claim 2 or 3 or 4, is characterized in that: have following steps:
1) make micropin female mold (5);
2) in the micropin groove of micropin female mold (5), fill up liquid micropin material (11) and solidify;
3) substrate (2) that surface is had to binding agent (3) is pressed in micropin female mold (5);
4) make the micropin (1) in micropin female mold (5) bonding with substrate (2), and together depart from micropin female mold (5) with substrate (2), obtain detachable microneedle device.
The manufacture method of 15. detachable microneedle devices according to claim 13, is characterized in that: step 2 is specially:
By micropin female mold (5) by being pressed on the flat board (6) that scribbles liquid micropin material (11), make to fill up micropin body pre-polymer solution in the micropin groove of micropin female mold (5), micropin body pre-polymer solution removes flat board (6) after solidifying, and leaves the micropin (1) after solidifying in micropin female mold (5);
Or, directly liquid micropin material (11) is coated in micropin female mold (5), and then use dull and stereotyped (6) by being pressed in micropin female mold (5), make to fill up micropin body pre-polymer solution in the micropin groove of micropin female mold (5), micropin body pre-polymer solution removes flat board (6) after solidifying, and leaves the micropin (1) after solidifying in micropin female mold (5).
The preparation method of the detachable microneedle device described in 16. 1 kinds of claim 5,6 or 7, is characterized in that: have following steps:
1) make micropin female mold (5);
2) in the micropin groove of micropin female mold (5), fill up micropin body pre-polymer solution and solidify;
3) micropin female mold (5) is shifted to dull and stereotyped (7) above by being pressed in viscosity, make micropin (1) transfer to this viscosity and shift on dull and stereotyped (7);
4) utilize this viscosity to shift dull and stereotyped (7) micropin (1) is transferred in transfer mold (8), the degree of depth of the micropin groove of this transfer mold (8) is less than the degree of depth of the micropin groove of micropin female mold (5);
5) micropin (1) in transfer mold (8) is transferred on the substrate (2) that is carved with needle tray, micropin (1) embeds needle tray, and together departs from micropin female mold (5) with substrate (2), obtains detachable microneedle device.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410312539.0A CN104069585B (en) | 2014-07-03 | 2014-07-03 | Detachable microneedle device and its manufacture method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410312539.0A CN104069585B (en) | 2014-07-03 | 2014-07-03 | Detachable microneedle device and its manufacture method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104069585A true CN104069585A (en) | 2014-10-01 |
| CN104069585B CN104069585B (en) | 2017-12-12 |
Family
ID=51591441
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410312539.0A Active CN104069585B (en) | 2014-07-03 | 2014-07-03 | Detachable microneedle device and its manufacture method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104069585B (en) |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104524687A (en) * | 2014-12-31 | 2015-04-22 | 睿金生物科技(苏州）有限公司 | Cosmetology microneedle head and manufacturing method thereof |
| CN105596287A (en) * | 2016-02-04 | 2016-05-25 | 广州新济药业科技有限公司 | Active separation-type soluble microneedle and preparation method thereof |
| WO2016168847A1 (en) * | 2015-04-17 | 2016-10-20 | Georgia Tech Research Corporation | Drug delivery devices having separable microneedles |
| CN106176204A (en) * | 2015-05-08 | 2016-12-07 | 上海拓勤贸易有限公司 | Medicine pin |
| WO2017107417A1 (en) * | 2015-12-24 | 2017-06-29 | 广州新济药业科技有限公司 | Microneedle chip and manufacturing method |
| CN107073251A (en) * | 2014-11-14 | 2017-08-18 | 莱雅公司 | Micropin piece and forming method for reducing wrinkle |
| CN108939280A (en) * | 2018-04-13 | 2018-12-07 | 杭州电子科技大学 | A kind of preparation method of SU8 microneedle array patch |
| CN109045460A (en) * | 2018-08-28 | 2018-12-21 | 杜玉堂 | A kind of microneedle patch and preparation method thereof |
| CN109224191A (en) * | 2018-07-23 | 2019-01-18 | 西安交通大学医学院第附属医院 | A kind of aseptic transfusion port auxiliary implanted device for venous transfusion |
| CN109310854A (en) * | 2016-06-07 | 2019-02-05 | 富士胶片株式会社 | Microneedle array |
| CN109414575A (en) * | 2016-01-22 | 2019-03-01 | 特兰斯德姆公司 | With microneedle array delivery of botulinum |
| CN110496303A (en) * | 2018-05-16 | 2019-11-26 | 富士胶片株式会社 | The manufacturing method of formwork and microneedle array |
| CN110553886A (en) * | 2019-10-15 | 2019-12-10 | 中山大学 | device for extracting and detecting biomarkers in blood by using laser-assisted hydrogel microneedle array and preparation method thereof |
| CN110769812A (en) * | 2017-06-07 | 2020-02-07 | Lts勒曼治疗系统股份公司 | Microneedle system for administering glucagon-like peptide analogs |
| CN111167006A (en) * | 2020-02-11 | 2020-05-19 | 康迈丽德(深圳)生物科技有限公司 | Device for preparing polymer microneedle patch |
| CN111372745A (en) * | 2017-11-24 | 2020-07-03 | 株式会社Lg生活健康 | Method and apparatus for manufacturing microneedle having tip with coating portion |
| CN111494237A (en) * | 2020-04-30 | 2020-08-07 | 重庆福特尔科技有限公司 | Soluble micro-needle patch |
| CN112858430A (en) * | 2021-01-08 | 2021-05-28 | 中山大学 | Sensor for detecting plant active small molecules and preparation method |
| CN113966242A (en) * | 2019-06-07 | 2022-01-21 | 诺和诺德股份有限公司 | Ingestible device with delivery member detachment |
| CN113952609A (en) * | 2020-11-12 | 2022-01-21 | 清华大学 | Hollow metal microneedle array and preparation method thereof, transdermal drug delivery patch and injection needle |
| CN115120863A (en) * | 2022-07-07 | 2022-09-30 | 四川大学 | Microneedle patch and method for producing same |
| US11730937B2 (en) | 2017-10-11 | 2023-08-22 | Georgia Tech Research Corporation | Separable microneedle arrays for sustained release of drug |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100682534B1 (en) * | 2005-10-10 | 2007-02-15 | 한국과학기술원 | Method for manufacturing microneedle array |
| CN101208129A (en) * | 2005-06-27 | 2008-06-25 | 3M创新有限公司 | Microneedle cartridge assembly and method of applying |
| US20080167601A1 (en) * | 2006-08-30 | 2008-07-10 | Franz Laermer | Microneedles to be placed in the skin for the transdermal application of pharhmaceuticals |
| CN101507857A (en) * | 2009-03-27 | 2009-08-19 | 清华大学 | Micro-needle array chip, percutaneous administration device, percutaneous administration patch and preparation method thereof |
| JP2009273772A (en) * | 2008-05-16 | 2009-11-26 | Kyokko Seiko Co Ltd | Microneedle sheet, and method and device for manufacturing the same |
| JP2010233674A (en) * | 2009-03-30 | 2010-10-21 | Fujifilm Corp | Microneedle sheet, its use method and method for producing the same |
| WO2010140760A2 (en) * | 2009-06-02 | 2010-12-09 | Miti Systems Inc. | Flexible microneedle patch system and method for manufacturing the same |
| CN102580232A (en) * | 2012-02-23 | 2012-07-18 | 游学秋 | Silk fibroin micro-needle system, silk fibroin nanometer particle and preparation method thereof |
| CN103170055A (en) * | 2011-12-23 | 2013-06-26 | 罗伯特·博世有限公司 | Microneedle array applicator and method for applying microneedle array |
| CN103263727A (en) * | 2013-05-22 | 2013-08-28 | 清华大学 | Metal microneedle array, percutaneous medicine feeding paster, Dermaroller and microneedle electrode array |
| TW201400140A (en) * | 2012-06-29 | 2014-01-01 | Univ Nat Cheng Kung | Embeddable patch for transdermal drug delivery and method of manufacturing the same |
| CN204352374U (en) * | 2014-07-03 | 2015-05-27 | 台州薇凯生物科技有限公司 | A kind of detachable microneedle device |
-
2014
- 2014-07-03 CN CN201410312539.0A patent/CN104069585B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101208129A (en) * | 2005-06-27 | 2008-06-25 | 3M创新有限公司 | Microneedle cartridge assembly and method of applying |
| KR100682534B1 (en) * | 2005-10-10 | 2007-02-15 | 한국과학기술원 | Method for manufacturing microneedle array |
| US20080167601A1 (en) * | 2006-08-30 | 2008-07-10 | Franz Laermer | Microneedles to be placed in the skin for the transdermal application of pharhmaceuticals |
| JP2009273772A (en) * | 2008-05-16 | 2009-11-26 | Kyokko Seiko Co Ltd | Microneedle sheet, and method and device for manufacturing the same |
| CN101507857A (en) * | 2009-03-27 | 2009-08-19 | 清华大学 | Micro-needle array chip, percutaneous administration device, percutaneous administration patch and preparation method thereof |
| JP2010233674A (en) * | 2009-03-30 | 2010-10-21 | Fujifilm Corp | Microneedle sheet, its use method and method for producing the same |
| WO2010140760A2 (en) * | 2009-06-02 | 2010-12-09 | Miti Systems Inc. | Flexible microneedle patch system and method for manufacturing the same |
| CN103170055A (en) * | 2011-12-23 | 2013-06-26 | 罗伯特·博世有限公司 | Microneedle array applicator and method for applying microneedle array |
| CN102580232A (en) * | 2012-02-23 | 2012-07-18 | 游学秋 | Silk fibroin micro-needle system, silk fibroin nanometer particle and preparation method thereof |
| TW201400140A (en) * | 2012-06-29 | 2014-01-01 | Univ Nat Cheng Kung | Embeddable patch for transdermal drug delivery and method of manufacturing the same |
| CN103263727A (en) * | 2013-05-22 | 2013-08-28 | 清华大学 | Metal microneedle array, percutaneous medicine feeding paster, Dermaroller and microneedle electrode array |
| CN204352374U (en) * | 2014-07-03 | 2015-05-27 | 台州薇凯生物科技有限公司 | A kind of detachable microneedle device |
Cited By (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107073251A (en) * | 2014-11-14 | 2017-08-18 | 莱雅公司 | Micropin piece and forming method for reducing wrinkle |
| US11097086B2 (en) | 2014-11-14 | 2021-08-24 | L'oreal | Micro-needle sheet for reducing wrinkles |
| CN104524687A (en) * | 2014-12-31 | 2015-04-22 | 睿金生物科技(苏州）有限公司 | Cosmetology microneedle head and manufacturing method thereof |
| CN107530534A (en) * | 2015-04-17 | 2018-01-02 | 佐治亚科技研究公司 | Drug delivery device with separable micropin |
| US10940301B2 (en) | 2015-04-17 | 2021-03-09 | Georgia Tech Research Corporation | Drug delivery devices having separable microneedles |
| WO2016168847A1 (en) * | 2015-04-17 | 2016-10-20 | Georgia Tech Research Corporation | Drug delivery devices having separable microneedles |
| EP4205793A1 (en) * | 2015-04-17 | 2023-07-05 | Georgia Tech Research Corporation | Drug delivery devices having separable microneedles |
| CN106176204A (en) * | 2015-05-08 | 2016-12-07 | 上海拓勤贸易有限公司 | Medicine pin |
| CN106176204B (en) * | 2015-05-08 | 2018-06-19 | 上海拓勤贸易有限公司 | Medicine needle |
| WO2017107417A1 (en) * | 2015-12-24 | 2017-06-29 | 广州新济药业科技有限公司 | Microneedle chip and manufacturing method |
| US11452853B2 (en) | 2015-12-24 | 2022-09-27 | Guangzhou Micnano Biotech Co., Ltd | Microneedle chip and manufacturing method thereof |
| CN109414575A (en) * | 2016-01-22 | 2019-03-01 | 特兰斯德姆公司 | With microneedle array delivery of botulinum |
| CN109414575B (en) * | 2016-01-22 | 2021-07-06 | 特兰斯德姆公司 | Delivery of botulinum with microneedle arrays |
| CN105596287B (en) * | 2016-02-04 | 2018-09-18 | 广州新济药业科技有限公司 | Active divergence type solubility micropin and preparation method thereof |
| CN105596287A (en) * | 2016-02-04 | 2016-05-25 | 广州新济药业科技有限公司 | Active separation-type soluble microneedle and preparation method thereof |
| CN109310854A (en) * | 2016-06-07 | 2019-02-05 | 富士胶片株式会社 | Microneedle array |
| CN109310854B (en) * | 2016-06-07 | 2021-09-07 | 富士胶片株式会社 | Microneedle array |
| CN110769812A (en) * | 2017-06-07 | 2020-02-07 | Lts勒曼治疗系统股份公司 | Microneedle system for administering glucagon-like peptide analogs |
| US11730937B2 (en) | 2017-10-11 | 2023-08-22 | Georgia Tech Research Corporation | Separable microneedle arrays for sustained release of drug |
| CN111372745B (en) * | 2017-11-24 | 2021-12-21 | 株式会社Lg生活健康 | Method and apparatus for manufacturing microneedle having tip with coating portion |
| CN111372745A (en) * | 2017-11-24 | 2020-07-03 | 株式会社Lg生活健康 | Method and apparatus for manufacturing microneedle having tip with coating portion |
| US11577064B2 (en) | 2017-11-24 | 2023-02-14 | Lg Household & Health Care Ltd. | Method and device for manufacturing microneedle having coating part on tip thereof |
| CN108939280A (en) * | 2018-04-13 | 2018-12-07 | 杭州电子科技大学 | A kind of preparation method of SU8 microneedle array patch |
| CN110496303B (en) * | 2018-05-16 | 2022-05-13 | 富士胶片株式会社 | Mold shell and method for manufacturing microneedle array |
| CN110496303A (en) * | 2018-05-16 | 2019-11-26 | 富士胶片株式会社 | The manufacturing method of formwork and microneedle array |
| CN109224191A (en) * | 2018-07-23 | 2019-01-18 | 西安交通大学医学院第附属医院 | A kind of aseptic transfusion port auxiliary implanted device for venous transfusion |
| CN109045460B (en) * | 2018-08-28 | 2021-08-03 | 江苏熙美生物科技有限公司 | Microneedle patch and preparation method thereof |
| CN109045460A (en) * | 2018-08-28 | 2018-12-21 | 杜玉堂 | A kind of microneedle patch and preparation method thereof |
| CN113966242A (en) * | 2019-06-07 | 2022-01-21 | 诺和诺德股份有限公司 | Ingestible device with delivery member detachment |
| CN110553886A (en) * | 2019-10-15 | 2019-12-10 | 中山大学 | device for extracting and detecting biomarkers in blood by using laser-assisted hydrogel microneedle array and preparation method thereof |
| CN111167006A (en) * | 2020-02-11 | 2020-05-19 | 康迈丽德(深圳)生物科技有限公司 | Device for preparing polymer microneedle patch |
| CN111494237A (en) * | 2020-04-30 | 2020-08-07 | 重庆福特尔科技有限公司 | Soluble micro-needle patch |
| CN113952609A (en) * | 2020-11-12 | 2022-01-21 | 清华大学 | Hollow metal microneedle array and preparation method thereof, transdermal drug delivery patch and injection needle |
| CN113952609B (en) * | 2020-11-12 | 2023-01-31 | 清华大学 | Hollow metal microneedle array and preparation method thereof, transdermal drug delivery patch and injection needle |
| CN112858430B (en) * | 2021-01-08 | 2021-11-26 | 中山大学 | Sensor for detecting plant active small molecules and preparation method |
| CN112858430A (en) * | 2021-01-08 | 2021-05-28 | 中山大学 | Sensor for detecting plant active small molecules and preparation method |
| CN115120863A (en) * | 2022-07-07 | 2022-09-30 | 四川大学 | Microneedle patch and method for producing same |
| CN115120863B (en) * | 2022-07-07 | 2023-06-13 | 四川大学 | Microneedle patch and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104069585B (en) | 2017-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104069585A (en) | Separable microneedle system and manufacturing method thereof | |
| CN110917176B (en) | Implantable sustained-release microneedle patch and preparation method thereof | |
| CN103501852B (en) | The manufacture method of microstructured bodies | |
| KR101747099B1 (en) | Method of Preparing Micro-Needle Using Biocompatible Polymer | |
| TWI633901B (en) | Medical beauty microneedle patch manufacturing method | |
| CN105073178B (en) | Microarray and its application method for therapeutic agent delivering | |
| JP2019076752A (en) | Micro array for delivery of therapeutic agent, use method and production method | |
| CN110870846A (en) | Rapidly implantable sustained-release microneedle patch and preparation method thereof | |
| EP3544586A1 (en) | Microneedle delivery system and method | |
| TWI629073B (en) | Microneedle patch manufacturing method | |
| CN204352374U (en) | A kind of detachable microneedle device | |
| JP2016511014A5 (en) | ||
| CN105126243B (en) | Microneedle injection bullet and preparation method thereof and microneedle injection equipment | |
| CN107875115B (en) | Sectional separable microneedle and preparation method thereof | |
| EP3148630B1 (en) | A flexible dissolvable patch and its method of fabricating | |
| JP2023540769A (en) | Coated microneedles with multilayer structure, method for preparing the same, and microneedle patch containing the coated microneedles | |
| CN106853271A (en) | The manufacture method of microstructured bodies | |
| KR20190060516A (en) | Micro needle and method of fabricating the same | |
| TWI759712B (en) | Microneedle device and method for making the same | |
| Hwa et al. | Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery | |
| KR102245058B1 (en) | Micro-needle patch containg lidocaine and method for manufacturing the same | |
| WO2015025119A1 (en) | Topical drug patch including microspheres | |
| CN114834066B (en) | Preparation method of composite multilayer microneedle | |
| CN108939284A (en) | It can dissolve microneedle injection device | |
| Park et al. | Research progress on detachable microneedles for advanced applications |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: TAIZHOU WEIKAI BIO-TECHNOLOGY CO., LTD. Free format text: FORMER OWNER: YOU XUEQIU Effective date: 20150228 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 364000 LONGYAN, FUJIAN PROVINCE TO: 318000 TAIZHOU, ZHEJIANG PROVINCE |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20150228 Address after: 318000, No. 201, east section, City Avenue, Jiaojiang District, Zhejiang, Taizhou Applicant after: Wei Kai bio tech Ltd. Taizhou Address before: 364000, room 4, building 37, 105 West Ring Road, Xinluo District, Longyan, Fujian Applicant before: You Xueqiu |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20220818 Address after: Room 805, Rongxin Center, No. 64 Pingshan Nanli, Haicang District, Xiamen City, Fujian Province 361000 Patentee after: Xiamen Weijian Medical Technology Co.,Ltd. Address before: No. 201, East Section of Shifu Avenue, Jiaojiang District, Taizhou City, Zhejiang Province, 318000 Patentee before: Wei Kai bio tech Ltd. Taizhou |
|
| TR01 | Transfer of patent right |