WO2020119353A1 - 一种软背微针及其制作方法 - Google Patents

一种软背微针及其制作方法 Download PDF

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Publication number
WO2020119353A1
WO2020119353A1 PCT/CN2019/116978 CN2019116978W WO2020119353A1 WO 2020119353 A1 WO2020119353 A1 WO 2020119353A1 CN 2019116978 W CN2019116978 W CN 2019116978W WO 2020119353 A1 WO2020119353 A1 WO 2020119353A1
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Prior art keywords
soft
microneedle
template
raw material
upper plate
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PCT/CN2019/116978
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English (en)
French (fr)
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尹忠
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尹忠
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    • 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
    • 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

Definitions

  • the invention relates to a soft back microneedle and a manufacturing method thereof, belonging to the technical field of medical equipment.
  • Protein and peptide drugs will be degraded and ineffective through the gastrointestinal tract, so they can only be injected. Injectable drug delivery is actually a way for the drug to pass through the biological barrier of the skin with the help of a needle. However, the pain is increased, especially for long-term frequent injections.
  • the non-injection administration of this kind of medicine is a long-cherished long-cherished wish.
  • the non-injection administration of insulin has been studied since 1921 to avoid long-term frequent injections.
  • There have been many non-injectable drug delivery methods of which the two most famous cases are two. The first is Pfizer's inhalant, which took 14 years and cost 2.8 billion US dollars. Two years after listing, it was due to the extremely inaccurate dose into the body. Delisting; The second is that Glaxo's long-term and expensive oral insulin has also been terminated. Therefore, the task of how proteins and peptides hydrophilic drugs enter the body through the biofilm barrier is very difficult.
  • microneedle transdermal drug delivery As a new type of transdermal drug delivery, microneedle transdermal drug delivery combines the advantages of subcutaneous injection drug delivery and transdermal patch drug delivery. It is not only painless and minimally invasive, but also has high drug absorption efficiency. Microneedle transdermal drug delivery is the decomposition of a large needle into a set of short and tiny micro-needles to deliver the drug to the subcutaneous layer without touching the deep nerve vessels, bleeding or pain. It is one of the research fields of non-injection drug delivery. One. With the rapid growth of the types and dosages of protein peptide drugs, microneedle transdermal drug delivery research has gradually become the focus of protein peptide drug delivery.
  • microneedle transdermal drug delivery technology has gained wide attention since its inception.
  • the basic structural form of the microneedle for drug delivery is: on a plate-shaped substrate (such as but not limited to a flat plate, curved plate, etc.) of suitable thickness and appropriate shape (such as but not limited to a circle, square, etc.), a group is erected Various numbers of micro needles.
  • microneedles under the effect of appropriate pressure, use microneedles to open the skin channel, help drugs and other biologically active substances to pass through the skin, and achieve the distribution of biologically active substances such as drugs throughout the body or local skin to achieve treatment or Other beneficial effects have very positive significance.
  • microneedles include metal solid microneedles, metal hollow microneedles, nonmetallic solid microneedles (such as inorganic silicon materials), organic macromolecular material microneedles (such as povidone), etc.
  • metal solid microneedles metal hollow microneedles
  • nonmetallic solid microneedles such as inorganic silicon materials
  • organic macromolecular material microneedles such as povidone
  • the existing ones Micro-needle products and their manufacturing methods have difficulties in mass production and preparation, so that such technologies and products have not seen the case of industrial mass production scale, and due to the limitations of their mass production capacity, the production cost is also high .
  • the following is a comparison of the selection of several microneedle materials and the ultrafine precision manufacturing technology based on the substrate:
  • metal microneedles involves a complicated process of precision machining or precision electroplating film formation, which is difficult to mass-produce at low cost.
  • the metal block For the production of solid metal microneedles, the metal block needs to be processed into 200 microneedles with a height of 1 mm and a minimum diameter of 0.15 mm erected on an area of 3-4 cm 2 (slightly larger than 5 coin).
  • the metal For the production of metal hollow microneedles, the metal needs to be plated on the model layer by layer and then demolded.
  • Such production involves a complicated process of ultra-fine precision machining or electroplating film formation, and due to the rigidity of metal micro-needles and the presence of processing burrs, the foreign body sensation of the metal micro-needles is quite obvious.
  • the melting temperature of the inorganic silicon material is too high, it is difficult to find a suitable high-temperature resistant mold, and the micro-needle is produced by the hot injection process; the inorganic silicon material in the cooled state has high hardness and brittleness, and the machining process of cutting, grinding or lithography is more efficient low.
  • Inorganic silicon material micro-needles also have obvious foreign body sensation due to their rigidity, especially they are very brittle, resulting in a high probability of the tip of the needle breaking into the superficial layer of the skin, resulting in other inconveniences.
  • the concentrated solution of povidone (PVP) is poured into microneedles through the mold, and the microneedles made of PVP material after drying and molding are difficult to demold because of insufficient strength.
  • the mold used in the preparation of povidone microneedles is a template with micropores. Because the micropores are in the form of countersinks, and because the pore diameter of the micropores is very small, in order to prevent the povidone solution from pouring, The obstruction of the air in the micropores cannot sink to the bottom of the micropores.
  • the entire device needs to be placed in a closed container, and the closed container is evacuated, which results in a very troublesome manufacturing process and increased manufacturing costs. Big.
  • microneedle substrate made of these metals and inorganic silicon materials in the prior art is too hard and can only be made relatively small. It can be used locally on the skin. If it is made relatively large and cannot fit the skin, it cannot be used on the human body. Areas with relatively large changes in curved surfaces such as the head and face; and povidone material is very easy to absorb moisture and soften or dissolve. If it absorbs moisture in vitro, the needle softening is difficult to insert into the skin, so its use is greatly restricted.
  • the existing microneedles still have a common shortcoming in shape.
  • the rigidity of the substrate is too strong to match the curvature of the human body surface, which in turn affects the use of larger size microneedles.
  • the purpose of the present invention is to provide a soft-backed microneedle that can be made into a large area and fits the curvature of the skin to solve the problem that the microneedle substrate made of metal and inorganic silicon materials in the prior art has high hardness and polydimensional
  • the invention also provides a manufacturing method of the soft back microneedle.
  • a soft back microneedle includes a base plate and a needle fixed on the bottom of the base plate, the base plate and the needle are integrally molded together, and the base plate and the needle
  • the material is made of thermoplastic material.
  • the thickness of the substrate of this microneedle is set very thin.
  • the thickness of the thermoplastic substrate can be freely curled in a large arc.
  • a soft auxiliary layer is adhered to the smooth surface of the substrate, which not only compensates for the possible lack of mechanical strength after the thickness of the substrate becomes thin, but also makes it easy to demold the negative pressure chuck.
  • the substrate is a flexible flexible board that can be bent, and the needle-shaped structure is large in size and small in size.
  • a soft auxiliary layer is fixedly pasted on the surface of the substrate opposite to the needle.
  • the thickness of the auxiliary layer is 0.1-2 mm.
  • the needle-shaped object has an upper and lower two-stage structure, and the needle-shaped object has a stepped surface between the upper and lower two stages.
  • the density of the needles is 1 to 600 threads/cm 2 .
  • thermoplastic material is polyethylene, polyvinyl chloride, polystyrene, polypropylene, polymethyl methacrylate, copovidone, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl succinate acetate , Polyethylene vinyl acetate, polyvinyl acetate, ethylene copolymers of one or more than two blends or copolymers or block copolymers.
  • the soft back microneedle of the present invention adopts the following technical scheme: a method for manufacturing the soft back microneedle, which includes the following steps: (1) heating and deforming the thermoplastic raw material for preparing the microneedle to a flowing state; (2) preparing the microneedle The bottom plate, soft liner, isolation layer, template and upper plate are placed in order from bottom to top.
  • the upper plate, template, isolation layer, soft liner and bottom plate are all heat-resistant materials, and the isolation layer is breathable Liquid-permeable material, the template is provided with a micro-porous area corresponding to the needle-like objects of the micro-needle, a micro-porous area has a number of micro-holes, the micro-holes are through holes formed in the template, the upper plate Corresponding to the position of the micropore area, there are stepped holes with upper and lower dimensions, so that the stepped holes of the upper plate are correspondingly arranged above the micropore area on the template; (3) Put the raw materials heated in step (1) onto the top In the stepped holes of the plate; (4) Pressurize the raw materials in the stepped holes so that the raw materials are pressed down into the micropores in the micropore area of the template; (5) Flowable raw materials in the stepped holes After cooling and cooling, the raw materials in the stepped holes and the micro-holes are cooled to become solid, and the soft back microneedles are formed
  • the outer surface of the quality auxiliary layer is a smooth surface; (7) A negative pressure suction cup is used to adsorb on the soft auxiliary layer, and the soft auxiliary layer together with the formed soft back microneedles are sucked out from the template to complete demoulding.
  • a method for manufacturing a soft-backed microneedle which includes the following steps: (1) processing the thermoplastic raw material for preparing the microneedle into powder, and weighing the powder raw material with the weight of a single microneedle; (2) preparing the bottom plate of the microneedle , Soft liner, isolation layer, template and upper plate are placed in order from bottom to top, the upper plate, template, isolation layer, soft liner and bottom plate are heat-resistant materials, the isolation layer is breathable and liquid-impermeable Material, the template is provided with a micro-porous area corresponding to the needle-like objects of the micro-needle, a micro-porous area has a number of micro-holes, the micro-holes are through holes opened on the template, the upper plate corresponds to the micro The position of the hole area is provided with a stepped hole of upper and lower size, so that the stepped hole of the upper plate is correspondingly arranged above the micropore area on the template; (3) The powder raw material weighed in step (1) is placed on the upper
  • a method for manufacturing a soft-backed microneedle which includes the following steps: (1) processing the thermoplastic raw material for preparing the microneedle into a solid having the same weight as a single microneedle; (2) preparing the bottom plate of the microneedle and a soft liner , The isolation layer, the template and the upper plate are placed in order from bottom to top.
  • the upper plate, the template, the isolation layer, the soft liner and the bottom plate are all heat-resistant materials, and the isolation layer is a breathable liquid-impermeable material.
  • the template A micro-hole area corresponding to the needle-like objects of the micro-needle is arranged on the micro-hole area. There are several micro-holes in the micro-hole area.
  • the micro-holes are through holes opened on the template, and the corresponding positions of the micro-hole areas on the upper plate There are step holes on the upper and lower sides, so that the step holes on the upper plate are correspondingly arranged above the micropore area on the template; (3)
  • the solid raw material obtained in step (1) is placed in a small section under the step holes on the upper plate; (4) Heat the solid raw material in step (3) until the solid raw material is deformed to a flowing state; (5) Pressurize the raw material in the stepped hole so that the raw material is pressed down into the micropore area of the template (6) Cooling and cooling the flowable raw materials in the stepped holes, the raw materials in the stepped holes and the microholes are cooled to become solid, and the soft back microneedles are formed in the template, and then the upper plate is removed; (7) Paste a soft auxiliary layer on the upper surface of the raw material, the outer surface of the soft auxiliary layer is a smooth surface; (8) Use a negative pressure suction cup to adsorb on the
  • the beneficial effect of the present invention is that when the soft back microneedle of the present invention is manufactured, a fluid thermoplastic raw material is injected into the substrate hole of the substrate template, and the raw material enters the microhole on the needle template downward, because the micropore is Through holes, no need to operate in a vacuum environment, the microneedle raw materials with fluidity will be injected into the micropores, can cooperate with the pressurizing device to pressurize the fluidized microneedle raw materials, can better the air in the micropores Squeeze away, so that the liquid microneedle material is quickly injected into the micropores.
  • the raw material of the microneedle of the invention is a thermoplastic material, which has good fluidity or flexibility after being heated, and can be conveniently solidified and shaped into a specific geometry under the restriction of the template.
  • the ultra-fine and precise size requirements that the microneedles must have are converted to the ultra-fine and precise size requirements for the template, and the requirements for smoothness and no burrs are converted to the same requirements for the template.
  • the soft back microneedle made by the invention is made of thermoplastic material, and the thermoplastic material has the following advantages: First, it is safe and does not cause skin allergies. The second is that the microneedle needles after cooling and forming have suitable hardness and flexibility, which are enough to open the skin and have little or no foreign body sensation. In addition, the thermoplastic materials have a certain degree of swelling in water, and the flexibility after swelling has increased, so the skin feels better after being inserted into the skin to contact body fluids. The third is that the thermoplastic material is insoluble or has very little water solubility or can still maintain sufficient adhesiveness after encountering water. It can be easily pulled out after the end of administration, rather than dissolving in the skin.
  • the thickness of the substrate can be made very thin by controlling the amount used, thereby making the substrate a flexible flexible sheet material that can be bent.
  • a soft auxiliary layer is adhered to the back of the substrate, which not only strengthens the strength of the soft back, but does not affect the softness of the soft back at all.
  • the back of such a soft-backed microneedle has sufficient softness and toughness, and can be tightly adsorbed with the negative pressure suction cup, thereby generating sufficient demoulding pulling force.
  • Such a soft-backed microneedle can be made with a large enough area to meet the requirements of many large-area and large-curve human body parts.
  • the micropores have a two-stage structure, and the prepared microneedles are also a two-stage structure.
  • medicine can be loaded on the lower stage of the microneedles.
  • the micropore has a stepped surface between the upper and lower sections, and the prepared microneedle also has a stepped surface between the upper and lower ends. The stepped surface makes it easier for the microneedle to carry medicine.
  • the compression head presses the thermoplastic material through a heat-resistant gasket
  • the heat-resistant gasket may use a material with a surface property that differs greatly from the thermoplastic material, thereby preventing the compression head from adhering to the thermoplastic material, and the thermoplastic material is stressed Uniform and good product quality.
  • FIG. 1 is a schematic structural view of an embodiment of a soft-backed microneedle of the present invention
  • Figure 2 is an enlarged view of the needle in Figure 1;
  • Embodiment 3 is a flowchart of Embodiment 1 of a method for manufacturing a soft-backed microneedle of the present invention
  • Embodiment 4 is a flowchart of Embodiment 2 of the method for manufacturing a soft-backed microneedle of the present invention
  • Embodiment 3 is a flowchart of Embodiment 3 of a method for manufacturing a soft-backed microneedle of the present invention
  • FIG. 6 is a schematic diagram of an upper plate, a template, an isolation layer, a soft liner and a bottom plate used in the manufacturing method of the soft back microneedle of the present invention.
  • FIG. 7 is a schematic structural view of the upper plate in FIG. 6;
  • FIG. 8 is a schematic structural diagram of the template in FIG. 6.
  • the structure of an embodiment of the soft back microneedle of the present invention is shown in FIGS. 1 to 2.
  • the soft back microneedle of this embodiment includes a substrate 1 and a needle 2 fixed on the bottom of the substrate 1, the substrate 1 and The needle-shaped objects 2 are integrally molded and formed together.
  • the substrate 1 and the needle-shaped objects 2 are made of a thermoplastic material.
  • the substrate 1 is a flexible flexible board that can be bent.
  • the needle-shaped objects 2 are large and small. Structure.
  • the enlarged view of the needle-shaped object 2 is shown in FIG. 2.
  • the needle-shaped object 2 has an upper and lower two-stage structure, and a step surface is provided between the upper and lower two-stage of the needle-shaped object.
  • a soft auxiliary layer 3 is fixedly pasted on the surface of the substrate 1 opposite to the needle 2, and 31 in FIG. 1 represents the adhesive layer 31 between the substrate and the auxiliary layer.
  • the thickness of the auxiliary layer is 0.1-2 mm, and the density of the needle-shaped objects is 1-600 pieces/cm 2 .
  • Thermoplastic materials are polyethylene, polyvinyl chloride, polystyrene, polypropylene, polymethyl methacrylate, copovidone, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl succinate acetate, poly One or more blends or copolymers or block copolymers of ethylene vinyl acetate, polyvinyl acetate, and ethylene copolymers.
  • Thermoplastic materials can be flexibly selected according to actual needs. By using the difference between the hardness and brittleness of different materials and the surface properties, the most suitable purpose can be achieved through the mixed use of one, two or more materials.
  • the soft back microneedles produced in actual production are determined by the density of the needles, the hardness of the thermoplastic material and the thickness of the substrate, so the density of the needles, the thermoplastic material and the substrate The thickness can be flexibly selected according to actual needs.
  • the soft back microneedle of the present invention is made of thermoplastic material, which has the following advantages: First, it is safe and does not cause skin allergies. The second is that the microneedle needles after cooling and forming have suitable hardness and flexibility, which are enough to open the skin and have little or no foreign body sensation. In addition, the thermoplastic materials have a certain degree of swelling in water, and the flexibility after swelling has increased, so the skin feels better after being inserted into the skin to contact body fluids. The third is that the thermoplastic material is insoluble or has very little water solubility or can still maintain sufficient adhesiveness after encountering water. It can be easily pulled out after the end of administration, rather than dissolving in the skin. Moreover, the thermoplastic material can be made into a deformable flexible material, and the manufactured substrate is a flexible flexible board that can be bent. Such microneedles can meet the requirements of many large-area and large-curve human body parts.
  • Embodiment 1 of the manufacturing method of the soft back microneedle is a manufacturing method of the soft back microneedle
  • the manufacturing process of the soft-back microneedle of this embodiment is shown in FIG. 3, and the manufacturing method of the soft-back microneedle of this embodiment includes the following steps: (1) heating and deforming the thermoplastic raw material for preparing the microneedle to a flowing state; (2) As shown in FIG. 6, the bottom plate 8 for preparing the microneedles, the soft pad 7, the isolation layer 6, the template 5 and the upper plate 4 are placed in this order from bottom to top.
  • the upper plate 4, template 5, isolation layer 6 and soft Both the quality pad 7 and the bottom plate 8 are heat-resistant materials, the isolation layer 6 is a gas-permeable and liquid-impermeable material, and the template 5 is provided with a micro-porous area 51 corresponding to the needles of the micro-needles, a micro-porous area There are a number of micro-holes, the micro-holes are through holes opened on the template, and the upper plate 4 is provided with a step hole 41 of upper and lower steps corresponding to the position of the micro-hole area 51, so that the step hole 41 of the upper plate 4 Correspondingly arranged above the micropore area 51 on the template 5; (3) Put the raw material heated in step (1) into the stepped hole of the upper plate; (4) Pressurize the raw material in the stepped hole 41, The raw material is pressed in the stepped hole 41 and enters the micropores of the micropore area 51 of the template; before pressurizing the raw material in the stepped hole, the gasket 9 is placed on the raw
  • Embodiment 2 of the manufacturing method of the soft back microneedle is a manufacturing method of the soft back microneedle
  • the manufacturing process of the soft back microneedles of this embodiment is shown in FIG. 4, and the manufacturing method of the soft back microneedles of this embodiment includes the following steps: (1) The thermoplastic raw material for preparing the microneedles is processed into powder, weighed with a single microneedle Powder materials with equal needle weight; (2) As shown in Figure 6, as shown in Figure 6, the bottom plate 8, soft liner 7, separation layer 6, template 5 and upper plate 4 for preparing microneedles are arranged in order from bottom to top The upper plate 4, the template 5, the isolation layer 6, the soft liner 7 and the bottom plate 8 are all heat-resistant materials.
  • the isolation layer 6 is a gas-permeable and liquid-impermeable material.
  • the needle-like objects of the needle correspond to the micropore area 51, and there are a plurality of micropores in a micropore area.
  • the micropores are through holes formed in the template, and the upper plate 4 is provided with a position corresponding to the micropore area 51.
  • Embodiment 3 of the manufacturing method of the soft back microneedle is a
  • the manufacturing process of the soft-backed microneedles of this embodiment is shown in FIG. 5, and the manufacturing method of the soft-backed microneedles of this embodiment includes the following steps: (1) Processing the thermoplastic raw material for preparing the microneedles to be equal to the weight of a single microneedle (2) As shown in FIG. 6, as shown in FIG. 6, the bottom plate 8 for preparing the microneedles, the soft liner 7, the isolation layer 6, the template 5 and the upper plate 4 are placed in this order from bottom to top.
  • the upper plate 4, the template 5, the isolation layer 6, the soft liner 7 and the bottom plate 8 are all heat-resistant materials, the isolation layer 6 is a gas-permeable and liquid-impermeable material, and the template 5 is provided with needle-shaped needles with microneedles There is a micropore area 51 corresponding to the object, and there are several micropores in one micropore area. The micropores are through holes opened on the template, and the upper plate 4 is provided with positions corresponding to the micropore area 51 in upper and lower sizes.
  • Stepped hole 41 so that the stepped hole 41 of the upper plate 4 is correspondingly arranged above the micropore area 51 on the template 5; (3) Place the solid raw material obtained in step (1) into a small section at the lower part of the stepped hole 41 of the upper plate; (4) Heating the solid raw material in step (3) until the solid raw material is deformed to a flowing state; (5) Pressurizing the raw material in the stepped hole 41 so that the raw material is pressed into the template microscopically in the stepped hole 41 In the micro-holes of the hole area 51; (6) Cooling and cooling the fluidized raw materials in the stepped holes 41, the raw materials in the stepped holes 41 and the micro-holes become solid after cooling and cooling, and the soft back microneedles are formed in the template 5 , Remove the upper plate 4; (7) Paste a soft auxiliary layer 3 on the upper surface of the raw material, the outer surface of the soft auxiliary layer 3 is a smooth surface; (8) Use a negative pressure suction cup to adsorb on the soft auxiliary layer 3,
  • Examples 1, 2, and 3 of the method for manufacturing the soft back microneedle described above before pressurizing the raw material in the stepped hole, a spacer was placed on the raw material, and then the raw material was pressurized through the spacer.
  • the equipment for pressurizing the raw material and the negative pressure chuck for demolding have a simple structural comparison and can be realized using existing equipment, so they are not shown in the drawings.
  • a fluid thermoplastic raw material is injected into the substrate hole of the substrate template, and the raw material enters the microhole on the needle template downward. Since the microhole is a through hole, it does not need to be in a vacuum. Operation under the environment, the microneedle raw materials with fluidity will be injected into the micropores, and the pressurized device can be used to pressurize the fluidized microneedle raw materials, which can better squeeze the air out of the micropores and make the fluidity The raw material of the microneedle is quickly injected into the micropore.
  • the raw material of the microneedle of the invention is a thermoplastic material, which has good fluidity or flexibility after being heated, and can be conveniently solidified and shaped into a specific geometry under the restriction of the template.
  • the ultra-fine and precise size requirements that the microneedles must have are converted to the ultra-fine and precise size requirements for the template, and the requirements for smoothness and no burrs are converted to the same requirements for the template.
  • the microneedles produced by the method of the present invention are thermoplastic material soft back microneedles.
  • the thermoplastic material has the following advantages: First, it is safe and does not cause skin allergies. The second is that the microneedle needles after cooling and forming have suitable hardness and flexibility, which are enough to open the skin and have little or no foreign body sensation. In addition, all thermoplastic materials have a certain degree of water swelling, and the flexibility after swelling has increased, so after inserting into the skin to contact body fluids, the skin feels better. The third is that the thermoplastic material is insoluble or has very little water solubility or can still maintain sufficient adhesiveness after encountering water. It can be easily pulled out after the end of administration, rather than dissolving in the skin. Moreover, the thermoplastic material can be made into a deformable flexible material, and the manufactured substrate is a flexible flexible board that can be bent, so that the microneedles can meet the requirements of many large-area and large-curve human body parts.
  • the pressing mechanism may also be a driving device such as a hydraulic cylinder, a pneumatic cylinder, or a motor, as long as it can drive the pressing head to move down to press the raw material of the microneedle.
  • a driving device such as a hydraulic cylinder, a pneumatic cylinder, or a motor, as long as it can drive the pressing head to move down to press the raw material of the microneedle.
  • the number of microporous areas is also flexibly selected according to actual needs.
  • the number of needles on the soft-backed microneedles and the thickness of the auxiliary layer can be flexibly changed according to actual needs.

Abstract

一种软背微针及其制作方法，软背微针包括基板（1）和固定在基板（1）底部的针状物（2），基板（1）和针状物（2）一体浇注成形在一起，基板（1）和针状物（2）由热塑性材料制成，基板（1）为可弯折的软质柔性板，针状物（2）为上大下小的结构。软背微针为热塑性材质，热塑性材质安全、不引起皮肤过敏，插入皮内接触体液后，皮感较好，且不溶于或水溶度很小或遇水后仍能保持足够的粘接性，给药结束后可以方便地拉出，而不是溶断在皮内。热塑性材料做成可变形的柔性材质，制作成的基板（1）为可弯折的软质柔性板，再黏附上同样柔软的辅助层（3），这样的微针可满足许多大面积和大曲度的人体部位的使用要求。

Description

一种软背微针及其制作方法 技术领域
本发明涉及一种软背微针及其制作方法，属于医疗设备技术领域。
背景技术
蛋白、多肽类药物口服会经过肠胃而被降解失效，故只能注射给药。注射给药其实就是在针头的帮助下，药物通过皮肤这一生物屏障的方式，然而徒增了痛苦，长期频繁注射尤甚。该类药物的非注射给药是由来已久的夙愿，例如从1921年就开始研究胰岛素非注射给药以避免长期的频繁注射。曾出现过很多非注射给药方式，其中最著名案例有二，第一是辉瑞公司的吸入剂，耗时14年，耗资28亿美金，上市两年后，因进入体内剂量的极度不准确而退市；第二是葛兰素公司耗长时耗巨资的口服胰岛素也宣告终止。因此，蛋白、多肽类亲水性药物如何通过生物膜屏障而输入体内的任务十分艰巨。
微针透皮给药作为一种新型透皮给药方式，其集皮下注射给药方式和透皮贴给药的优点于一体，不仅无痛微创，而且药物吸收效率高。微针透皮给药是将一根大针分解成一组短且细小的微型针头将药物递送到皮下潜层，而不触及深层的神经血管，不出血不痛苦，是非注射给药的研究领域之一。随着蛋白多肽药物种类和用量的快速增长，微针透皮给药研究逐渐成为递送蛋白多肽药物的关注点。此外，微针给药时患者可自行给药，方便安全。因此，微针透皮给药技术从开始出现就获得了广泛的关注。给药微针的基本结构形态是：在合适厚度、合适形状(比如但不限于圆形、方形等)的板状基材上(比如但不限于平板、弧形板等)，竖立着一组数量不等的微型针状物。微针的基本使用过程和原理为：在合适压力的作用下，利用微针撑开皮肤通道，帮助药物等生物活性物质穿过皮肤，实现全身或皮肤局部药物等生物活性物质分布，达到治疗或其他有益的效果，具有十分积极的意义。
现有技术的微针有金属实心微针、金属空心微针、非金属材料实心微针(如无机硅材料)、有机大分子材料微针(如聚维酮)等，但是，现有的这些微针制品及其制作方法，都存有量产制备方面的困难，致使此类技术与制品至今未见工业量产规模的案例出现，且因其量产能力的局限，导致制作成本也较高。下面是几种微针材质的选择和基于该基材的超微细精密制作技术的比较：
金属微针的制作涉及精密机械加工或精密电镀成膜的复杂工艺过程，难以低成本规模化量产。金属实心微针的制作，需要将金属块加工成在3-4CM 2(略大于5角硬币)的面积上竖立着200根高1mm、最小直径0.15mm的超微细针状物的微针。金属空心微针的制作，需要在模型上逐层电镀上金属，然后脱模。这样的制作涉及超细微精密机械加工或电镀成 膜的复杂工艺过程，且金属材质的微针因其刚性和加工毛刺的存在，皮肤对金属微针的异物感相当明显。
无机硅材料的熔融温度太高，难以找到合适的耐高温模具，进行热注工艺的微针制作；冷却状态下的无机硅材料硬度高、脆性大，切削、打磨或光刻的加工过程效率较低。无机硅材料微针因其刚性亦有明显异物感，特别是极易脆碎，导致较大概率的出现针尖部分断碎在皮肤浅层内，衍生出其它的不便。
聚维酮(PVP)浓溶液经模具浇注成微针，干燥成型后的PVP材质的微针，因为强度不足，其脱模过程较为困难。聚维酮微针制备过程中使用的模具是带有微孔的模板，由于微孔是沉孔的形式，且由于微孔孔径很小，为了防止浇注聚维酮溶液时，聚维酮溶液受微孔中空气的阻碍无法沉入到微孔底部，在微针制作过程，需要将整个设备放置在密闭容器中，将密闭容器抽真空，这样就导致制作过程就十分麻烦，制作成本就会加大。
现有技术的这些金属、无机硅材料做成的微针基板硬度太大，只能做成比较小，在皮肤局部使用，若做成比较大，不能与皮肤贴合，则就不能使用在人体头部、面部等曲面变化比较大的区域；而聚维酮材料极易吸湿软化或溶解，如在体外吸湿，则针状物软化难以插入皮内，因此使用上就受到了很大的限制。
现有的微针形态上还存在一个共同的缺点，基板的刚性太强，不能与人体表面的曲度相匹配，进而影响较大尺寸微针的使用。
发明内容
本发明的目的在于提供一种可以做成面积较大、贴合皮肤曲度使用的软背微针，用以解决现有技术的金属、无机硅材料做成的微针基板硬度大及聚维酮微针难以插入皮内和不能与人体表面的曲度相匹配的技术问题。同时，本发明还提供一种该软背微针的制作方法。
本发明的软背微针采用如下技术方案：一种软背微针，其包括基板和固定在基板底部的针状物，所述基板和针状物一体浇注成形在一起，所述基板和针状物由热塑性材料制成，这种微针的基板厚度设置的很薄，厚度的热塑性基板可很大的弧度内自由卷曲。热压完成后，在基板的光面，黏附上软质辅助层，既弥补了基板厚度变薄以后可能的机械强度不足，又使得负压吸盘脱模变得十分容易。所述基板为可弯折的软质柔性板，所述针状物为上大下小的结构。
所述基板上与针状物相对的一面上固定粘贴有软质辅助层。
所述辅助层的厚度为0.1-2mm。
所述针状物为上下两段式结构，所述针状物的上下两段之间具有台阶面。
所述针状物的密度为1～600根/cm 2。
所述热塑性材料为聚乙烯、聚氯乙烯、聚苯乙烯、聚丙烯、聚甲基丙烯酸甲酯、共聚维酮、乙基纤维素、羟丙基纤维素、醋酸羟丙基甲基琥珀酸酯、聚乙烯醋酸乙烯酯、聚乙酸乙烯酯、乙烯共聚物中的一种或两种以上的共混物或共聚物或嵌段共聚物。
本发明的软背微针采用如下技术方案：一种软背微针的制作方法，其包括以下步骤：(1)将制备微针的热塑性原料加热变形至流动状态；(2)将制备微针的底板、软质衬垫、隔离层、模板及上板从下至上依次放置，所述上板、模板、隔离层、软质衬垫及底板均为耐热材质，所述隔离层为透气不透液材质，所述模板上设有与微针的针状物对应的微孔区，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板上对应微孔区的位置开设有上大下小的阶梯孔，使上板的阶梯孔对应设置在模板上微孔区的上方；(3)将步骤(1)中加热后的原料置入到上板的阶梯孔内；(4)对阶梯孔内的原料进行加压，使原料在阶梯孔内受压向下进入模板微孔区的微孔内；(5)对阶梯孔内的流动性原料进行冷却降温，阶梯孔内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板；(6)在原料上表面粘贴一层软质辅助层，软质辅助层外表面为光滑表面；(7)使用负压吸盘吸附在软质辅助层上，将软质辅助层连同成型的软背微针从模板中吸出，从而完成脱模。
一种软背微针的制作方法，其包括以下步骤：(1)将制备微针的热塑性原料加工为粉末，称取与单个微针重量相等的粉末原料；(2)将制备微针的底板、软质衬垫、隔离层、模板及上板从下至上依次放置，所述上板、模板、隔离层、软质衬垫及底板均为耐热材质，所述隔离层为透气不透液材质，所述模板上设有与微针的针状物对应的微孔区，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板上对应微孔区的位置开设有上大下小的阶梯孔，使上板的阶梯孔对应设置在模板上微孔区的上方；(3)将步骤(1)中称取的粉末原料放置到上板阶梯孔下部的小段内；(4)对步骤(3)中的粉末原料进行加热直至粉末原料变形至流动状态；(5)对阶梯孔内的原料进行加压，使原料在阶梯孔内受压向下进入模板微孔区的微孔内；(6)对阶梯孔内的流动性原料进行冷却降温，阶梯孔内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板；(7)在原料上表面粘贴一层软质辅助层，软质辅助层外表面为光滑表面；(8)使用负压吸盘吸附在软质辅助层上，将软质辅助层连同成型的软背微针从模板中吸出，从而完成脱模。
一种软背微针的制作方法，其包括以下步骤：(1)将制备微针的热塑性原料加工为与单个微针重量相等的固体；(2)将制备微针的底板、软质衬垫、隔离层、模板及上板从下至上依次放置，所述上板、模板、隔离层、软质衬垫及底板均为耐热材质，所述隔离 层为透气不透液材质，所述模板上设有与微针的针状物对应的微孔区，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板上对应微孔区的位置开设有上大下小的阶梯孔，使上板的阶梯孔对应设置在模板上微孔区的上方；(3)将步骤(1)中得到的固体原料放置到上板阶梯孔下部的小段内；(4)对步骤(3)中的固体原料进行加热直至固体原料变形至流动状态；(5)对阶梯孔内的原料进行加压，使原料在阶梯孔内受压向下进入模板微孔区的微孔内；(6)对阶梯孔内的流动性原料进行冷却降温，阶梯孔内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板；(7)在原料上表面粘贴一层软质辅助层，软质辅助层外表面为光滑表面；(8)使用负压吸盘吸附在软质辅助层上，将软质辅助层连同成型的软背微针从模板中吸出，从而完成脱模。
对阶梯孔内的原料进行加压前，在原料上放置垫片，然后隔着垫片对原料进行加压。
本发明的有益效果是：本发明的软背微针在制作时，将流动性的热塑性原料注入基板模板的基板孔内，原料向下进入针状物模板上的微孔中，由于微孔为通孔，不需要在真空环境下操作，具有流动性的微针原料就会注入微孔内部，可以配合加压装置对流动性微针原料进行加压，能更好的把微孔中的空气挤走，使流动性的微针原料快速的注入微孔内部。本发明微针原材料为热塑性材料，热塑性材料在加热后具有很好的流动性或柔韧性，在模板的限制下可方便的凝固成型为特定的几何体。至此，微针所必须具备的超细微精密尺寸要求就转换为对模板的超微细精密尺寸要求，对光洁和没有毛刺的要求就转换为对模板的同样要求。
本发明制作出的软背微针为热塑性材质，热塑性材质具有以下优点：一是安全、不引起皮肤过敏。二是冷却成形后的微针针状物具有合适的硬度和柔韧度，既足以撑开皮肤又较少有或没有异物感。另外，所述的热塑性材料均有一定的水液溶胀性，且溶胀后的柔韧度有所增加，故插入皮内接触体液后，皮感较好。三是热塑性材质不溶于或水溶度很小或遇水后仍能保持足够的粘接性，给药结束后可以方便地拉出，而不是溶断在皮内。而且，可以通过控制用量的方法，将基板的厚度制作地很薄，进而使得基板成为可弯折的软质柔性板材。同时，为了增强基板的机械强度，再在基板的背面黏附上软质辅助层，既加强了软背的强度，又丝毫不影响软背的柔软度。这样的软背微针的背面具有足够的软韧性和密封性，可以与负压吸盘吸附的很紧，进而产生足够的脱模拉力。这样的软背微针可以制作得面积足够大，借以满足许多大面积和大曲度的人体部位的使用要求。
优选的，微孔为两段式结构，制备出的微针也是两段式结构，使用时可以在微针下段上载药。微孔的上下两段之间具有台阶面，制备出的微针上下两端之间也具有台阶面，台阶面使微针载药更加容易。
优选的，压紧头隔着耐热垫片对热塑性原料加压，耐热垫片可选用表面性质与热塑性原料差异较大的材质，进而防止压紧头粘附热塑性原料，而且热塑性原料受力均匀，产品质量好。
附图说明
图1是本发明软背微针的一种实施例的结构示意图；
图2是图1中针状物的放大图；
图3是本发明软背微针的制作方法实施例1的流程图；
图4是本发明软背微针的制作方法实施例2的流程图；
图5是本发明软背微针的制作方法实施例3的流程图；
图6是本发明软背微针的制作方法所使用的上板、模板、隔离层、软质衬垫及底板的示意图。
图7是图6中上板的结构示意图；
图8是图6中模板的结构示意图。
图中，1-基板，2-针状物，21-台阶面，3-辅助层，31-黏胶层，4-上板，5-模板，6-隔离层，7-软质衬垫，8-底板，9-垫片。
具体实施方式
下面结合附图和具体实施例对本发明进行详细说明。
软背微针的实施例：
本发明软背微针的一种实施例的结构如图1至图2所示，本实施例的软背微针包括基板1和固定在基板1底部的针状物2，所述基板1和针状物2一体浇注成形在一起，所述基板1和针状物2由热塑性材料制成，所述基板1为可弯折的软质柔性板，所述针状物2为上大下小的结构。针状物2的放大图如图2所示，针状物2为上下两段式结构，针状物的上下两段之间具有台阶面。所述基板1上与针状物2相对的一面上固定粘贴有软质辅助层3，图1中31表示基板与辅助层之间的黏胶层31。本实施例中，辅助层的厚度为0.1-2mm，所述针状物的密度为1～600根/cm 2。
热塑性材料为聚乙烯、聚氯乙烯、聚苯乙烯、聚丙烯、聚甲基丙烯酸甲酯、共聚维酮、乙基纤维素、羟丙基纤维素、醋酸羟丙基甲基琥珀酸酯、聚乙烯醋酸乙烯酯、聚乙酸乙烯酯、乙烯共聚物中的一种或两种以上的共混物或共聚物或嵌段共聚物。热塑性材料可以根据实际需要灵活选用，利用不同材料硬度脆度上和表面性质上的区别，通过一种、两种或两种以上材料的混合使用，达成最合适的目的用途。
实际生产制备出的软背微针，软背微针的软硬程度是由针状物的密度和热塑性材质的 硬度以及基板厚度的因素共同决定的，因此针状物的密度和热塑性材质以及基板厚度可根据实际需要灵活选用。
本发明的软背微针为热塑性材质，热塑性材质具有以下优点：一是安全、不引起皮肤过敏。二是冷却成形后的微针针状物具有合适的硬度和柔韧度，既足以撑开皮肤又较少有或没有异物感。另外，所述的热塑性材料均有一定的水液溶胀性，且溶胀后的柔韧度有所增加，故插入皮内接触体液后，皮感较好。三是热塑性材质不溶于或水溶度很小或遇水后仍能保持足够的粘接性，给药结束后可以方便地拉出，而不是溶断在皮内。而且，可以将热塑性材料做成可变形的柔性材质，制作成的基板为可弯折的软质柔性板，这样的微针可以满足许多大面积和大曲度的人体部位的使用要求。
软背微针的制作方法的实施例1：
本实施例软背微针的制作流程如图3所示，本实施例的软背微针的制作方法包括以下步骤：(1)将制备微针的热塑性原料加热变形至流动状态；(2)如图6所示，将制备微针的底板8、软质衬垫7、隔离层6、模板5及上板4从下至上依次放置，所述上板4、模板5、隔离层6、软质衬垫7及底板8均为耐热材质，所述隔离层6为透气不透液材质，所述模板5上设有与微针的针状物对应的微孔区51，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板4上对应微孔区51的位置开设有上大下小的阶梯孔41，使上板4的阶梯孔41对应设置在模板5上微孔区51的上方；(3)将步骤(1)中加热后的原料置入到上板的阶梯孔内；(4)对阶梯孔41内的原料进行加压，使原料在阶梯孔41内受压向下进入模板微孔区51的微孔内；对阶梯孔内的原料进行加压前，在原料上放置垫片9，然后隔着垫片9对原料进行加压。(5)对阶梯孔41内的流动性原料进行冷却降温，阶梯孔41内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板4；(6)在原料上表面粘贴一层软质辅助层3，软质辅助层3外表面为光滑表面；(7)使用负压吸盘吸附在软质辅助层3上，将软质辅助层3连同成型的软背微针从模板中吸出，从而完成脱模。
软背微针的制作方法的实施例2：
本实施例软背微针的制作流程如图4所示，本实施例的软背微针的制作方法包括以下步骤：(1)将制备微针的热塑性原料加工为粉末，称取与单个微针重量相等的粉末原料；(2)如图6所示，如图6所示，将制备微针的底板8、软质衬垫7、隔离层6、模板5及上板4从下至上依次放置，所述上板4、模板5、隔离层6、软质衬垫7及底板8均为耐热材质，所述隔离层6为透气不透液材质，所述模板5上设有与微针的针状物对应的微孔区51，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板4上对应微孔区 51的位置开设有上大下小的阶梯孔41，使上板4的阶梯孔41对应设置在模板5上微孔区51的上方；(3)将步骤(1)中称取的粉末原料放置到上板阶梯孔下部的小段内；(4)对步骤(3)中的粉末原料进行加热直至粉末原料变形至流动状态；(5)对阶梯孔41内的原料进行加压，使原料在阶梯孔41内受压向下进入模板微孔区51的微孔内；对阶梯孔内的原料进行加压前，在原料上放置垫片9，然后隔着垫片9对原料进行加压。(6)对阶梯孔41内的流动性原料进行冷却降温，阶梯孔41内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板；(7)在原料上表面粘贴一层软质辅助层3，软质辅助层3外表面为光滑表面；(8)使用负压吸盘吸附在软质辅助层上，将软质辅助层3连同成型的软背微针从模板5中吸出，从而完成脱模。
软背微针的制作方法的实施例3：
本实施例软背微针的制作流程如图5所示，本实施例软背微针的制作方法，其包括以下步骤：(1)将制备微针的热塑性原料加工为与单个微针重量相等的固体；(2)如图6所示，如图6所示，将制备微针的底板8、软质衬垫7、隔离层6、模板5及上板4从下至上依次放置，所述上板4、模板5、隔离层6、软质衬垫7及底板8均为耐热材质，所述隔离层6为透气不透液材质，所述模板5上设有与微针的针状物对应的微孔区51，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板4上对应微孔区51的位置开设有上大下小的阶梯孔41，使上板4的阶梯孔41对应设置在模板5上微孔区51的上方；(3)将步骤(1)中得到的固体原料放置到上板阶梯孔41下部的小段内；(4)对步骤(3)中的固体原料进行加热直至固体原料变形至流动状态；(5)对阶梯孔41内的原料进行加压，使原料在阶梯孔41内受压向下进入模板微孔区51的微孔内；(6)对阶梯孔41内的流动性原料进行冷却降温，阶梯孔41内和微孔中的原料冷却降温变为固体，软背微针在模板5中成型后，移走上板4；(7)在原料上表面粘贴一层软质辅助层3，软质辅助层3外表面为光滑表面；(8)使用负压吸盘吸附在软质辅助层3上，将软质辅助层3连同成型的软背微针从模板中吸出，从而完成脱模。
上述软背微针的制作方法的实施例1、2、3中，对阶梯孔内的原料进行加压前，在原料上放置垫片，然后隔着垫片对原料进行加压。上述实施例1、2、3中，由于对原料加压的设备和进行脱模的负压吸盘，结构比价简单，利用现有设备可以实现，因此附图中不显示。
本发明的软背微针在制作时，将流动性的热塑性原料注入基板模板的基板孔内，原料向下进入针状物模板上的微孔中，由于微孔为通孔，不需要在真空环境下操作，具有流动性的微针原料就会注入微孔内部，可以配合加压装置对流动性微针原料进行加压，能更好 的把微孔中的空气挤走，使流动性的微针原料快速的注入微孔内部。本发明微针原材料为热塑性材料，热塑性材料在加热后具有很好的流动性或柔韧性，在模板的限制下可方便的凝固成型为特定的几何体。至此，微针所必须具备的超细微精密尺寸要求就转换为对模板的超微细精密尺寸要求，对光洁和没有毛刺的要求就转换为对模板的同样要求。
利用本发明的方法制作出的微针为热塑性材质软背微针，热塑性材质具有以下优点：一是安全、不引起皮肤过敏。二是冷却成形后的微针针状物具有合适的硬度和柔韧度，既足以撑开皮肤又较少有或没有异物感。另外，所有的热塑性材料均有一定的水液溶胀性，且溶胀后的柔韧度有所增加，故插入皮内接触体液后，皮感较好。三是热塑性材质不溶于或水溶度很小或遇水后仍能保持足够的粘接性，给药结束后可以方便地拉出，而不是溶断在皮内。而且，可以将热塑性材料做成可变形的柔性材质，制作成的基板为可弯折的软质柔性板，这样微针可满足许多大面积和大曲度的人体部位的使用要求。
在本发明的其它实施例中，压紧机构还可以液压缸、气压缸或电机等驱动装置，只要是能带动压紧头向下移动压紧微针原料即可。微孔区的数量也是根据实际需要灵活选择的。软背微针上针状物的数量以及辅助层的厚度均是可以根据实际需要灵活改变的。
上述实施例为本发明优选的实施例，以上显示和描述了本发明的基本原理、主要特征和优点。本领域的普通技术人员应该了解，上述实施例不以任何形式限制本发明的保护范围，凡采用等同替换等方式所获得的技术方案，均落于本发明的保护范围内。

Claims (10)

  1. 一种软背微针，其包括基板和固定在基板底部的针状物，其特征在于：所述基板和针状物一体浇注成形在一起，所述基板和针状物由热塑性材料制成，所述基板为可弯折的软质柔性板，所述针状物为上大下小的结构。
  2. 根据权利要求1所述的软背微针，其特征在于：所述基板上与针状物相对的一面上固定粘贴有软质辅助层。
  3. 根据权利要求2所述的软背微针，其特征在于：所述辅助层的厚度为0.1-2mm。
  4. 根据权利要求1所述的软背微针，其特征在于：所述针状物为上下两段式结构，所述针状物的上下两段之间具有台阶面。
  5. 根据权利要求1所述的软背微针，其特征在于：所述针状物的密度为1～600根/cm 2。
  6. 根据权利要求1所述的软背微针，其特征在于：所述热塑性材料为聚乙烯、聚氯乙烯、聚苯乙烯、聚丙烯、聚甲基丙烯酸甲酯、共聚维酮、乙基纤维素、羟丙基纤维素、醋酸羟丙基甲基琥珀酸酯、聚乙烯醋酸乙烯酯、聚乙酸乙烯酯、乙烯共聚物中的一种或两种以上的共混物或共聚物或嵌段共聚物。
  7. 一种软背微针的制作方法，其特征在于，其包括以下步骤：(1)将制备微针的热塑性原料加热变形至流动状态；(2)将制备微针的底板、软质衬垫、隔离层、模板及上板从下至上依次放置，所述上板、模板、隔离层、软质衬垫及底板均为耐热材质，所述隔离层为透气不透液材质，所述模板上设有与微针的针状物对应的微孔区，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板上对应微孔区的位置开设有上大下小的阶梯孔，使上板的阶梯孔对应设置在模板上微孔区的上方；(3)将步骤(1)中加热后的原料置入到上板的阶梯孔内；(4)对阶梯孔内的原料进行加压，使原料在阶梯孔内受压向下进入模板微孔区的微孔内；(5)对阶梯孔内的流动性原料进行冷却降温，阶梯孔内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板；(6)在原料上表面粘贴一层软质辅助层，软质辅助层外表面为光滑表面；(7)使用负压吸盘吸附在软质辅助层上，将软质辅助层连同成型的软背微针从模板中吸出，从而完成脱模。
  8. 一种软背微针的制作方法，其特征在于，其包括以下步骤：(1)将制备微针的热塑性原料加工为粉末，称取与单个微针重量相等的粉末原料；(2)将制备微针的底板、软质衬垫、隔离层、模板及上板从下至上依次放置，所述上板、模板、隔离层、软质衬垫及底板均为耐热材质，所述隔离层为透气不透液材质，所述模板上设有与微针的针状物对应的微孔区，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板上对应微孔区的位置开设有上大下小的阶梯孔，使上板的阶梯孔对应设置在模板 上微孔区的上方；(3)将步骤(1)中称取的粉末原料放置到上板阶梯孔下部的小段内；(4)对步骤(3)中的粉末原料进行加热直至粉末原料变形至流动状态；(5)对阶梯孔内的原料进行加压，使原料在阶梯孔内受压向下进入模板微孔区的微孔内；(6)对阶梯孔内的流动性原料进行冷却降温，阶梯孔内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板；(7)在原料上表面粘贴一层软质辅助层，软质辅助层外表面为光滑表面；(8)使用负压吸盘吸附在软质辅助层上，将软质辅助层连同成型的软背微针从模板中吸出，从而完成脱模。
  9. 一种软背微针的制作方法，其特征在于，其包括以下步骤：(1)将制备微针的热塑性原料加工为与单个微针重量相等的固体；(2)将制备微针的底板、软质衬垫、隔离层、模板及上板从下至上依次放置，所述上板、模板、隔离层、软质衬垫及底板均为耐热材质，所述隔离层为透气不透液材质，所述模板上设有与微针的针状物对应的微孔区，一个微孔区内有若干个微孔，微孔为开设在模板上的通孔，所述上板上对应微孔区的位置开设有上大下小的阶梯孔，使上板的阶梯孔对应设置在模板上微孔区的上方；(3)将步骤(1)中得到的固体原料放置到上板阶梯孔下部的小段内；(4)对步骤(3)中的固体原料进行加热直至固体原料变形至流动状态；(5)对阶梯孔内的原料进行加压，使原料在阶梯孔内受压向下进入模板微孔区的微孔内；(6)对阶梯孔内的流动性原料进行冷却降温，阶梯孔内和微孔中的原料冷却降温变为固体，软背微针在模板中成型后，移走上板；(7)在原料上表面粘贴一层软质辅助层，软质辅助层外表面为光滑表面；(8)使用负压吸盘吸附在软质辅助层上，将软质辅助层连同成型的软背微针从模板中吸出，从而完成脱模。
  10. 根据权利要求7或8或9所述的给药微针的制备方法，其特征在于：对阶梯孔内的原料进行加压前，在原料上放置垫片，然后隔着垫片对原料进行加压。
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