Metal micro-needle array flexible paster, percutaneous dosing device and percutaneous dosing paster
Technical field
The present invention relates to medical beauty treatment instrument and medical art, particularly relate to a kind of metal micro-needle array flexible paster, percutaneous dosing device and percutaneous dosing paster.
Background technology
Transdermal delivery system, also known as Transcutaneous Therapeutic System, refers to that medicine enters body circulation by skin through capillary absorbance with certain speed and produces a class preparation of drug effect.Compared with traditional administering mode, percutaneous dosing has many advantages: can produce lasting, constant and controlled blood drug level, the pharmaceutically active that half-life is very short because body intracellular metabolic is rapid is significantly improved, avoid the first pass effect of liver and the interference of gastrointestinal factors, toxic and side effects is dropped to minimum; Have painless, noinvasive or invasive, patient can self-medication, also can interruption of the administration at any time, easy to use.Although percutaneous dosing is very tempting, when the medicine advancing into percutaneous dosing market, the world only has more than 20 to plant, this mainly because the barrier effect of keratodermatitis causes the transdermal penetration rates of most medicine too low, can not meet the needs for the treatment of.The medicine of percutaneous dosing can be subject to many restrictions now, such as molecular weight is less than 500D, fat-solubility, fusing point are less than 150 DEG C, therapeutic dose is less than 20 milligrams/day etc., macromolecule and polar medicine are difficult to realize passive percutaneous dosing.
In order to increase the permeability of skin, people have employed the multiple methods such as chemical enhancers, iontherapy and electroporation.All there is limitation in various degree to transmitted medicine in these methods, some also may can cause larger toxic and side effects.1998, first miniature solid silicon pin array is used for percutaneous dosing field by U.S. Prausnitz teach problem group, find that the percutaneous permeation of biopolymer model drug calcein can be improved 4 orders of magnitude by it, from then on started the tide of microneedle transdermal delivery research in the world.The permeability of medicine can be significantly improved moment in the duct that keratodermatitis and epidermal area produce a large amount of micron dimension size by the pin mode of executing pressing microneedle array, should be applicable in theory to comprise biopharmaceutical macromolecular drug any medicine and not by the restriction of molecular size range, polar drugs, fusing point etc.Because sharp short and small, the medicine-feeding part of micropin does not touch nervous tissue and blood vessel at body surface, therefore pain and bleeding can not be produced; Micropin administration is adopted not need professional to operate, flexible and convenient to use, can interruption of the administration at any time, so be more easily easily accepted by the patient.
With percutaneous dosing in like manner, due to cuticular barrier effect, adopt generally traditional method to use cosmetics and skincare product, most active nutrients are wherein difficult to enter living Epidermis's layer and skin corium, so cosmetic result is not remarkable.If there is by surface application the microneedle array of cosmetics and skincare product to thrust skin, or microneedle array thrust skin after remove and repaste deposited cosmetics and skincare product, all can significantly improve active nutrient and pass through the penetrating power that horny layer enters epidermal area and skin corium cell, thus significantly improve looks improving and the skin nourishing effect.
The material manufacturing micropin has polymer, monocrystal silicon and metal etc.The outstanding problem that existing polymer micro needle exists is that the strength of materials is inadequate, not easily pierces through the fine and close horny layer of skin; Although can batch micro operations monocrystal silicon pin, its easy brittle failure, cost be very high, and silicon does not also belong to conventional medical material; For a long time, people adopt metal to manufacture acupuncture needle or injection needle always, and its safety used is unquestionable.At present, reported some metal micro-needle array structures, it mainly produces microneedle array on same metal substrate, and micropin is vertical with substrate or coplanar.Owing to adopting the microneedle array structure quality of metal substrate harder, and the skin of people is softer, the two is not easily at the laminating position close contact of health, considerable micropin will be caused to be suspended in aerial and skin cannot be thrust, the actual dosage of percutaneous is difficult to accurate control, thus has a strong impact on curative effect generation.In addition, how on very thin short and small micropin, covering medicine as much as possible and to thrust in skin process and can not come off, this is also the key issue that must solve in practicality undoubtedly.
Summary of the invention
(1) technical problem that will solve
The object of the invention is to realize metal micro-needle array plaster to change with the skin shape at laminating position, ensure that all micropins can both thrust skin, improve the comfortableness used;
Another object of the present invention improves metal micro-needle array plaster executes pin convenience in multiple administered area rotation.
(2) technical scheme
In order to solve the problems of the technologies described above, the invention provides a kind of metal micro-needle array flexible paster, described paster comprises flexible substrate, and at least two arrange and the metal micro-needle module being fixed on described flexible substrate surface or being partly embedded in described flexible substrate at a certain distance; Described metal micro-needle module is that edge has the foil protruding micropin, or being fixed on needle stand and edge has the foil protruding micropin, or is fixed on the discrete metal micro-needle on needle stand; Described micropin is vertical with flexible substrate surface, and the needle point of described micropin is outwardly; Described micropin is solid or hollow metal micro-needle.
Wherein, described micropin is 10 microns ~ 1500 microns for the length of the projection thrust, and the external diameter of micropin or width are 10 microns ~ 1000 microns, and the thickness of described foil is 5 microns ~ 800 microns.
Wherein, the needle point end of described micropin have thrust after prevent it from automatically exiting lance pointed structures, described lance pointed structures comprises the card convex protruding micropin sidewall.
Wherein, described needle stand is cuboid or polyhedral, at least fixes described foil or fixing described discrete metal micro-needle in an one side.
Wherein, described micropin has perforation and/or groove, when described micropin has groove, described groove is arranged along the length direction of described micropin.
Wherein, described flexible substrate is polygon or round or disciform lamellar or network structure, or be made up of at least two list structures, the material adopted includes but not limited to by weaving cotton cloth of pure cotton fiber or weaving cotton cloth or non-woven fabrics, rubber, plastics, synthetic leather, paper, the thin slice of metal, filament or fillet of elastic fiber, described flexible substrate can be made up of the one in above-mentioned material or several layered combination forms, and is connected between each layer by adhesive or fixed structure.
Present invention also offers a kind of percutaneous dosing device adopting above-mentioned arbitrary described metal micro-needle array flexible paster, described percutaneous dosing device comprises metal micro-needle array flexible paster and pedestal, described pedestal one end is paster stationary plane, the other end is operating grip, described paster stationary plane is plane or arc-shaped curved surface, described metal micro-needle array flexible paster is permanent or be removably fixed on described paster stationary plane, or described metal micro-needle array flexible patch portion embeds in described paster stationary plane.
Invention further provides a kind of percutaneous dosing paster adopting above-mentioned arbitrary described metal micro-needle array flexible paster, described percutaneous dosing paster comprises metal micro-needle array flexible paster and covers transdermal skin patches thereon, and described transdermal skin patches contains one or more and has treatment, keep healthy or the ingredient of effects of beautification and nourishing face or cosmetics and skincare product.
Wherein, described transdermal skin patches is covered on the micropin that protrudes in metal micro-needle array flexible paster.
Wherein, in the flexible substrate of described metal micro-needle array flexible paster, at least medical adhesive material is had in the surface coverage of its surrounding border area, for described percutaneous dosing paster is pasted onto medicine-feeding part.
(3) beneficial effect
Technique scheme adopts medical material conventional at present and utilizes ripe process technology to manufacture metal micro-needle array flexible paster, because the flexible substrate adopted is easy and skin surface is conformal, ensure that all micropins on it can both thrust skin smoothly, thus significantly improve concordance and the controllability of dosage, and use feel more comfortable, convenient; Metal micro-needle is firm in structure, needle point sharp short and small, be convenient to puncture; Micropin concordance in array is good, during use without pain, lose blood, use the skin of rear Wicresoft can rapid spontaneous recovery, safe and reliable.
Adopt the percutaneous dosing device being core parts with above-mentioned metal micro-needle array flexible paster, just oneself can operate in multiple administered area rotation flexibly and easily with hands and execute pin, metal micro-needle array is removed after thrusting skin very soon, then thrust region surface coating medicament be beneficial to its rapidly diffusion play drug effect, easy to use, pesticide supplying effect is good.
Adopt the percutaneous dosing paster being core parts with above-mentioned metal micro-needle array flexible paster, not only significantly improve drug storage amount placed on it in advance, and greatly can reduce and execute pin process Chinese medicine and come off in external probability, thus select medicine scope, effectively treatment time and the cost performance of transdermal patch can be made to be significantly improved.The paster adopting the present invention to prepare not only can significantly improve the transdermal penetration rate of existing medicine, medicine or cosmetics and skincare product is made to enter epidermal area and skin corium by horny layer rapidly, significantly improve drug effect or looks improving and the skin nourishing effect, the kind being suitable for medicine can also be expanded, develop the percutaneous novel form of more drug and cosmetics.
Accompanying drawing explanation
Fig. 1 is the structural representation that foil that in the embodiment of the present invention 1, edge has a micropin is fixed on a kind of metal micro-needle array flexible paster in needle stand and flexible substrate;
Fig. 2 is the structural representation that metal micro-needle discrete in the embodiment of the present invention 1 is fixed on a kind of metal micro-needle array flexible paster in needle stand and flexible substrate;
Fig. 3 is the structural representation in the embodiment of the present invention 1, micropin and foil all having groove and be fixed on a kind of metal micro-needle array flexible paster on flexible substrate surface;
Fig. 4 is the structural representation that foil that in the embodiment of the present invention 1, edge has a micropin is fixed on a kind of metal micro-needle array flexible paster of strip flexible substrate;
Fig. 5 is the structure sectional view that foil that in the embodiment of the present invention 1, edge has a micropin fixes a kind of metal micro-needle array flexible paster on flexible substrates;
Fig. 6 is the structure sectional view that foil that in the embodiment of the present invention 1, edge has a micropin fixes another kind of metal micro-needle array flexible paster on flexible substrates;
Fig. 7 is the structure sectional view that foil that in the embodiment of the present invention 1, edge has a micropin fixes another kind of metal micro-needle array flexible paster on flexible substrates;
Fig. 8 is the structure sectional view that foil that in the embodiment of the present invention 1, edge has a micropin fixes another kind of metal micro-needle array flexible paster on flexible substrates;
Fig. 9 is the structure sectional view that metal micro-needle discrete in the embodiment of the present invention 1 is fixed on a kind of metal micro-needle array flexible paster in needle stand and flexible substrate;
Figure 10 is a kind of percutaneous dosing device structure sectional view of applied metal microneedle array flexible paster in the embodiment of the present invention 2;
Figure 11 is the another kind of percutaneous dosing device structure sectional view of applied metal microneedle array flexible paster in the embodiment of the present invention 2;
Figure 12 is another percutaneous dosing device structure sectional view of applied metal microneedle array flexible paster in the embodiment of the present invention 2.
Wherein, 1: flexible substrate; 2: micropin; 3: foil; 4: needle stand; 5: needle point; 6: be fixedly connected with layer; 7: hole; 8: groove; 9: pedestal; 10: hands handle; 11: protruding.
Detailed description of the invention
Below in conjunction with drawings and Examples, the specific embodiment of the present invention is described in further detail.Following examples for illustration of the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
Fig. 1-Fig. 9 shows metal micro-needle array flexible paster provided by the present invention, described paster comprises flexible substrate 1, and at least two arrange and the metal micro-needle module being fixed on described flexible substrate 1 surface or being partly embedded in described flexible substrate 1 at a certain distance, described metal micro-needle module is that edge has the foil 3 protruding micropin 2, or to be fixed on needle stand 4 and edge has the foil 3 protruding micropin 2, or the discrete metal micro-needle 2 be fixed on needle stand 4, described micropin 2 is vertical with flexible substrate 1 surface, and the needle point of described micropin 2 is outwardly.By this metal micro-needle array flexible paster, paster can be realized conformal with the surface at dispenser position, ensure that micropin 2 can both thrust dispenser skin simultaneously, improve the effect of dispenser.
The surface that described foil 3 can be parallel to flexible substrate 1 is arranged, also can arrange perpendicular to the surface of flexible substrate 1, according to the set-up mode of foil 3, micropin 2 vertical setting surperficial relative to foil 3 or setting coplanar with foil 3 can be selected, only need finally to realize micropin 2 surperficial and outwardly perpendicular to flexible substrate 1.
In the present embodiment, micropin 2 is solid or hollow metal micro-needle, and both all can realize good pesticide supplying effect.Described micropin 2 is 10 microns ~ 1500 microns for the length of the projection thrust, the external diameter of micropin 2 or width are 10 microns ~ 1000 microns, the thickness of described foil 3 is 5 microns ~ 800 microns, can play the needs that pesticide supplying effect can not injure again dermis of skin in satisfied conventional transcutaneous applications.
The present embodiment metal micro-needle module at least has a foil 3 or a discrete metal micro-needle 2, described foil 3 at least has a micropin 2 protruded in one side edge.Described metal micro-needle module has the microneedle array of at least two micropin 2 compositions protruded carrying out arranging according to setting spacing.
Fig. 1 is the structural representation of a kind of metal micro-needle array flexible paster in the embodiment of the present invention, flexible substrate 1 arranges at a certain distance and is fixed wtih nine metal micro-needle modules, each metal micro-needle module comprises the needle stand 4 of a cuboid, two the side place relative at it is fixed with a foil 3 respectively, the limit place of each foil 3 all has and carries out arranging according to setting spacing and microneedle array that is outwardly and that form perpendicular to two micropins 2 of needle stand 4, micropin 2 is coplanar with the principal plane of foil 3, needle point 5 end of micropin 2 have thrust after prevent it from automatically exiting the lance pointed structures of effect, described lance pointed structures comprises the card convex protruding micropin sidewall.
Be another kind of metal micro-needle array flexible paster in Fig. 2, be that adopting discrete metal micro-needle 2 to instead of limit place has the foil 3 protruding micropin 2 with the main distinction of Fig. 1, the needle point of micropin 2 does not have lance pointed structures in addition.In paster, the size of adjacent metal micropin module and structure can be not quite similar.The shape of needle stand 4 can be varied with making material, is easily fixed thereon by metal.As preferably, needle stand is cuboid or polyhedral, and polymer can be adopted to make, and as adopted the making such as epoxy resin, also can adopt the manufacture such as metal, pottery.Described metal can be the multiple medical metal material such as rustless steel, titanium alloy.Micropin 2 on needle stand 4 or fixing on needle stand 4 of foil 3, can adopt the medical adhesive such as epoxy resin, silicone rubber or special construction to be fixed.
Metal micro-needle array flexible paster and Fig. 1 in Fig. 3,2 the main distinction be flexible substrate 1 arranges at a certain distance and be fixed wtih three metal micro-needle modules on the one hand, each metal micro-needle module has 4 foils 3 protruding micropin 2 by limit place and forms, micropin 2 is vertical with the principal plane of foil 3, and what this foil 3 can adopt epoxy resin adhesive to be formed be fixedly connected with layer 6 is directly fixed in flexible substrate 1 according to a determining deviation; On the other hand, micropin 2 and foil 3 all has groove 8, groove 8 is arranged along the length direction of described micropin 2, the sunk structure that all formed to curving with all or part of region of the both side surface of foil 3 of micropin 2 or micropin 2 specifically, or the sunk structure slotted and formed in a side surface portion region of micropin 2 or micropin 2 and foil 3, the groove structure that micropin 2 has is very beneficial for carrying more medicine and effectively can avoids thrusting skin process Chinese medicine and come off in external.
In Fig. 4, metal micro-needle array flexible paster is that the shape of needle point 5 is different on the one hand from the main distinction of Fig. 3, be that the shape of flexible substrate 1 is different on the other hand, one is the laminated structure of tetragon, and one is made up of four list structures, and flexibility and the permeability of list structure substrate are better.The shape of flexible substrate can be varied with making material, as preferably, it is lamellar or the network structure of polygon or circle or ellipse, or be made up of at least two list structures, the material adopted includes but not limited to by weaving cotton cloth of pure cotton fiber or weaving cotton cloth or non-woven fabrics, rubber, plastics, synthetic leather, paper, the thin slice of metal, filament or fillet of elastic fiber, can to be made up of one wherein or several layered combination forms, to be connected by adhesive or fixed structure between each layer.
Fig. 5 is that in the embodiment of the present invention, limit place has the structure sectional view that the foil 3 protruding micropin 2 is fixed on a kind of metal micro-needle array flexible paster in flexible substrate 1.Wherein, micropin 2 is vertical with the principal plane of foil 3, adopts adhesive foil 3 to be fixed on the upper surface of flexible substrate 1.
In Fig. 6, metal micro-needle array flexible paster and the difference of Fig. 5 are that two of foil 3 relative limit places all have and protrude micropin 2.
In Fig. 7, the difference of metal micro-needle array flexible paster and Fig. 5 is that micropin 2 penetrates the upper surface of flexible substrate 1, adopts adhesive foil 3 to be fixed on the lower surface of flexible substrate 1.
In Fig. 8, the difference of metal micro-needle array flexible paster and Fig. 5 ~ 7 is that flexible substrate is made up of materials at two layers, and foil 3 embeds and is fixed on therebetween, ensures whole paster structure firm stable more.What the upper strata as flexible substrate was selected is silicone rubber elastomeric material, and during use, it is attached on skin, and comfort can be stronger.
In Fig. 9, the main distinction of metal micro-needle array flexible paster and Fig. 5 ~ 8 is that discrete metal micro-needle 2 is fixed in flexible substrate 1 by needle stand 4, and the hole 7 metal micro-needle 2 had for storing more drug, passing hole 7 can be carried more drug and be carried out percutaneous dosing, and medicine can not be caused to come off in external.
Metal micro-needle array flexible paster of the present invention can adopt the processing technique batch micro operations of existing maturation.Such as adopt the conventional methods such as cut, spark cutting, shearing, chemistry or electrochemical corrosion just can process various microneedle configuration in the edge of foil.If make discrete metal micro-needle with solid metal silk or hollow metal capillary tube, adopt conventional grinding and polishing can process multiple common needle point structure, utilize the through hole on hollow needle to can be used for carrying more drug and enter skin.The package technique of existing maturation finally can be adopted to prepare metal micro-needle array flexible paster.
Embodiment 2
Figure 10 and Fig. 9 is the percutaneous dosing device structure sectional view of application provided by the invention above-mentioned metal micro-needle array flexible paster, described percutaneous dosing device comprises metal micro-needle array flexible paster and pedestal 9, described pedestal 9 one end is paster stationary plane, the other end is operation handle 10, described paster stationary plane is plane or arc-shaped curved surface, described metal micro-needle array flexible paster is permanent or be removably fixed on described paster stationary plane, or described metal micro-needle array flexible patch portion embeds in described paster stationary plane.
In Fig. 10, metal micro-needle array flexible paster is fixed on the plane paster stationary plane of pedestal 9 one end, and the needle point structure of micropin 2 is all not identical with aforementioned each figure, is specially out bevelled needle point structure.
In Figure 11, the main distinction of percutaneous dosing device and Figure 10 on the surrounding pedestal 9 of flexible patch, is provided with protruding 11 thrust the degree of depth to limit the maximum of micropin 2, also being equivalent to metal micro-needle array flexible patch portion embeds in described paster stationary plane, and the surrounding of flexible patch remains with the projection that can play barrier effect.
In Figure 12, the main distinction of percutaneous dosing device and Figure 10, Figure 11 is that metal micro-needle array flexible paster is fixed on the arc-shaped surface shape paster stationary plane of pedestal 9 one end, their handle 10 is not identical yet in addition, handle 10 can be set to column or ellipsoid shape or column and combine with ellipsoid shape, and a demand fulfillment is hand-held comfortable.
Pedestal 9 can be the conventional soft and/or hard material such as rubber, plastics, glass, pottery, timber, metal, composite, adopts the manufacture of the maturation process such as injection moulding, machined.Assembling fixed form can adopt multiple maturation methods such as cohering, movable structure is fastening.During percutaneous dosing, remove after first the micropin in above-mentioned percutaneous dosing device can being thrust skin surface, then medicament or cosmetics and skincare product are coated in this skin surface.
Embodiment 3
Embodiments provide a kind of percutaneous dosing paster based on above-mentioned metal micro-needle array flexible paster, it is by metal micro-needle array flexible paster and cover transdermal skin patches thereon and form, and transdermal skin patches wherein contains one or more and has treatment, keep healthy or the ingredient of effects of beautification and nourishing face or cosmetics and skincare product.As preferably, described transdermal skin patches is only covered on the micropin that protrudes in metal micro-needle array flexible paster or on needle point, can not only save valuable medicament like this, and easily control the dose entering skin.Groove on micropin and hole not only can be used for storing more medicine, and can effectively avoid this place's medicine to come off in external problem thrusting in skin process.The multiple conventional physical properties such as dipping, coating, stifling, deposit or chemical method can be adopted on microneedle array even flexible substrate to cover percutaneous administration patch or cosmetic patch.
In use, first the microneedle array on percutaneous dosing paster is all thrust skin, then with common medical adhesive tape, this paster can be fixed.As preferably, can at the medical adhesive material of surface coverage in the region, edge of paster flexible substrate, described percutaneous dosing paster is pasted onto medicine-feeding part, and it is more convenient to use.
The present invention adopts medical material manufacture conventional at present based on percutaneous dosing paster, the Beauty sticking piece of metal micro-needle array flexible paster, medicine or cosmetics and skincare product can be made to enter epidermal area and skin corium by horny layer rapidly by the combination of microneedle array and flexible substrate, thus significantly improve drug effect or looks improving and the skin nourishing effect, and ripe processing technique is utilized to realize the batch micro operations of its low cost, high finished product rate, high duplication; Because the flexible substrate adopted is easily conformal with skin, use and feel more comfortable, facilitate; Microneedle configuration is firm, needle point is sharp, be convenient to puncture; Micropin concordance in array is good, during use without pain, lose blood, use the skin of rear Wicresoft can rapid spontaneous recovery, safe and reliable; The more drug that micropin carries in groove or hole ensure that paster can action time longer; The use amount of chemical enhancers can be avoided or significantly reduce to this paster completely, and not only can significantly improve the transdermal penetration rate of existing medicine, can also expand the kind being suitable for medicine, the percutaneous developing more drug and cosmetics transports product.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the technology of the present invention principle; can also make some improvement and replacement, these improve and replace and also should be considered as protection scope of the present invention.