WO2016060020A1 - Procédé de fabrication d'une fine protubérance creuse - Google Patents

Procédé de fabrication d'une fine protubérance creuse Download PDF

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Publication number
WO2016060020A1
WO2016060020A1 PCT/JP2015/078372 JP2015078372W WO2016060020A1 WO 2016060020 A1 WO2016060020 A1 WO 2016060020A1 JP 2015078372 W JP2015078372 W JP 2015078372W WO 2016060020 A1 WO2016060020 A1 WO 2016060020A1
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WO
WIPO (PCT)
Prior art keywords
base sheet
protrusion
convex
fine hollow
projection
Prior art date
Application number
PCT/JP2015/078372
Other languages
English (en)
Japanese (ja)
Inventor
貴利 新津
小林　英男
智志 上野
良輔 真鍋
Original Assignee
花王株式会社
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from JP2015176375A external-priority patent/JP6064012B1/ja
Priority claimed from JP2015176377A external-priority patent/JP6586329B2/ja
Priority claimed from JP2015176376A external-priority patent/JP6126658B2/ja
Application filed by 花王株式会社 filed Critical 花王株式会社
Priority to KR1020177010103A priority Critical patent/KR102021212B1/ko
Priority to US15/519,440 priority patent/US10632653B2/en
Priority to CN201580056329.2A priority patent/CN107073249B/zh
Publication of WO2016060020A1 publication Critical patent/WO2016060020A1/fr

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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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C59/00—Surface shaping of articles, e.g. embossing; Apparatus therefor
    • B29C59/02—Surface shaping of articles, e.g. embossing; Apparatus therefor by mechanical means, e.g. pressing

Definitions

  • the present invention relates to a method for producing a fine hollow projection having a hollow inside.
  • the present invention relates to a method for producing a fine hollow projection having a through hole.
  • microneedles in particular, can expand the options for the agent disposed in the hollow portion.
  • microneedles include a self-dissolving type in which the needle itself is made of a soluble agent and a coating type in which the needle surface is coated with the agent.
  • the supply amount (retention amount) of the agent depends on the shape of the needle.
  • the hollow mold has an advantage that a large amount of agent can be supplied without depending on the needle shape.
  • the microneedle can be manufactured by, for example, a manufacturing method disclosed in Patent Document 1 or 2. Since the manufacturing method described in Patent Document 1 arranges a resin body on an elastic body, and heats the resin body from the back side of the elastic body, a fine nozzle is made to penetrate the resin body to manufacture a fine nozzle. There is no need to use a mold including fine concave portions in which the outer shape of the concave and convex portions is inverted. Therefore, it is said that the disposable fine nozzle made from resin can be manufactured.
  • Patent Document 2 states that a hollow microneedle array can be manufactured using a pre-formed mold.
  • Patent Document 3 discloses a method of manufacturing a microneedle by bridging a base sheet into a rod-shaped convex shape, and then heating the entire base sheet to deform it into a rod-shaped convex shape. Has been.
  • the supply of agents using microneedles has attracted attention in the medical field or beauty field.
  • the microneedle By puncturing the shallow layer of the skin, the microneedle can obtain the same performance as the supply of the agent by a syringe without pain.
  • a microneedle having a through hole is effective because it allows a wider range of options for the agent disposed inside the microneedle.
  • the microneedle having a through hole is used particularly in the medical field or the beauty field, the accuracy of the height of the microneedle or the precision of the through hole is required.
  • the microneedle having a through-hole can be manufactured by, for example, a manufacturing method disclosed in Patent Documents 1 to 3.
  • a resin body is arranged on an elastic body, and while the resin body is heated from the back side of the elastic body, a fine needle is passed through the resin body, and the elastic body and the fine needle are interposed between the elastic body and the fine needle.
  • a method for producing a fine nozzle by pouring a resin body is described.
  • Patent Document 2 uses a mold with a plurality of pre-formed recesses and a mold with a plurality of pre-formed protrusions, and inserts each protrusion into each recess, A method for producing a hollow microneedle array by molding is described.
  • Patent Document 4 a fine microneedle having a fine through hole is manufactured by forming a through hole by a short pulse laser method in a fine microneedle replicated on a substrate by a thermal imprint method. A method is described.
  • Patent Document 1 since the manufacturing method of the fine nozzle described in Patent Document 1 is heated from the back side of the elastic body using a hot plate or the like to warm the entire resin body arranged on the elastic body, It takes time to warm up and it is difficult to improve productivity. Moreover, since it is necessary to warm the whole resin body arrange
  • Patent Document 2 the manufacturing method of the fine through-hole molded product described in Patent Document 2 leads to an increase in cost because the mold for molding is expensive, and the degree of freedom of the shape of the microneedle and the material that can be selected is high. Low.
  • Patent Document 1 since the manufacturing method described in Patent Document 1 is heated from the back surface side of the elastic body using a hot plate or the like to warm the entire resin body arranged on the elastic body, It takes time and it is difficult to mass-produce fine nozzles at low cost. Patent Document 1 does not describe anything about the viewpoint of adjusting the height of the microneedle and the viewpoint of adjusting the size of the through hole formed in the microneedle.
  • Patent Document 2 leads to an increase in cost because the mold for molding is expensive, and the degree of freedom of materials that can be selected as the shape of the microneedle to be manufactured and the raw material of the microneedle is also increased. Low and it is difficult to mass-produce hollow microneedle arrays at low cost.
  • Patent Document 2 does not describe anything about the viewpoint of adjusting the height of the microneedle and the viewpoint of adjusting the size of the through hole formed in the microneedle.
  • Patent Document 4 since the through hole of the microneedle is formed by using a post-processed short pulse laser method, the manufacturing method described in Patent Document 4 has a large equipment burden and reduces the fine microneedle having the through hole. It is difficult to mass-produce at cost. Moreover, since the through-hole of the microneedle is formed using the short pulse laser method in the manufacturing method described in Patent Document 4, the previously formed micro-needle is damaged and has a through-hole. It is difficult to produce fine microneedles with high quality. Patent Document 4 does not describe anything about the viewpoint of adjusting the height of the microneedle and the viewpoint of adjusting the size of the through hole formed in the microneedle.
  • the present invention (first invention) relates to a method for producing a fine hollow projection having a hollow inside.
  • a convex portion provided with a heating means is brought into contact from one surface side of a base sheet formed with a thermoplastic resin, and the corresponding contact portion in the base sheet
  • This invention relates to the manufacturing method of the fine hollow protrusion which has a through-hole.
  • a projection forming step for forming the projection a convex portion having a heating means is brought into contact with one surface of a base material sheet formed including a thermoplastic resin.
  • the protruding portion is stabbed into the base sheet while softening the corresponding contact portion in the base sheet by heat, and protrudes from the other surface of the base sheet, and the front end on the other side of the base sheet
  • the protrusion is cooled while the convex part is inserted inside. That a cooling step, after the cooling step, and a, and release steps of forming a fine hollow projections having the through hole from the inside of the protruding portion by far the convex portion.
  • the present invention (third invention) relates to a method for producing fine hollow protrusions.
  • a convex portion provided with a heating means is brought into contact from one side of a base sheet formed with a thermoplastic resin, and the corresponding contact portion in the base sheet A protrusion that pierces the base sheet toward the other surface of the base sheet while softening the substrate with heat and forms a protrusion protruding from the other surface of the base sheet A forming step, a cooling step of cooling the protruding portion in a state where the protruding portion is stabbed inside the protruding portion, and after the cooling step, the protruding portion is removed from the inside of the protruding portion to form a fine hollow And a release step for forming a protrusion.
  • the protruding portion forming step uses a receiving member that is spaced apart from the other surface of the base sheet, and in the protruding portion forming step, the convex portion comes into contact with the receiving member and contacts the protruding portion. A through hole is formed.
  • FIG. 1 is a schematic perspective view of an example of a fine hollow projection produced by the method for producing a fine hollow projection of the present invention (first invention).
  • 2 is a cross-sectional view taken along line II-II shown in FIG.
  • FIG. 3 is an explanatory view showing a method for measuring the tip diameter of the hollow projection.
  • FIG. 4 is a diagram showing an overall configuration of the first embodiment of the manufacturing apparatus for manufacturing the fine hollow projection shown in FIG. 1.
  • FIG. 5 is an explanatory diagram showing a method for measuring the tip angle of the convex portion.
  • 6 (a) to 6 (d) are diagrams illustrating a process of manufacturing a fine hollow protrusion using the manufacturing apparatus shown in FIG.
  • FIG. 7A to 7D are diagrams illustrating a process of manufacturing a fine hollow protrusion using the manufacturing apparatus of the second embodiment.
  • FIG. 8 is a schematic perspective view of another example of the fine hollow projection produced by the method for producing a fine hollow projection of the present invention (first invention).
  • FIG. 9 is a diagram showing an overall configuration of a manufacturing apparatus according to a preferred embodiment for manufacturing the fine hollow projection shown in FIG. 8 (corresponding to FIG. 4).
  • FIG. 10 is a diagram showing an overall configuration of a manufacturing apparatus according to another preferred embodiment for manufacturing the fine hollow projection shown in FIG. 8 (corresponding to FIG. 4).
  • FIG. 11 is a schematic perspective view of an example of a fine hollow projection in which projections having through holes are arranged in an array produced by the method for producing a fine hollow projection having a through hole of the present invention (second invention).
  • FIG. FIG. 12 is a perspective view of a fine hollow protrusion focusing on one protrusion shown in FIG. 13 is a cross-sectional view taken along line III-III shown in FIG.
  • FIG. 14 is a diagram showing an overall configuration of the first embodiment of the manufacturing apparatus for manufacturing the fine hollow projection shown in FIG. 11.
  • FIG. 15 is an explanatory diagram showing a method of measuring the convex tip diameter and tip angle of the convex part.
  • 16 (a) to 16 (e) are diagrams illustrating a process of manufacturing a fine hollow protrusion having a through hole using the manufacturing apparatus shown in FIG. 17 (a) to 17 (e) are diagrams illustrating a process of manufacturing a fine hollow projection having a through hole using the manufacturing apparatus of the second embodiment.
  • 18 is a diagram showing an overall configuration of a manufacturing apparatus of another preferred embodiment for manufacturing the fine hollow projection shown in FIG. 11 (corresponding to FIG. 14).
  • FIG. 19 is a schematic perspective view of an example of the fine hollow protrusions that are produced by the method for producing fine hollow protrusions of the present invention (third invention) and that have protrusions having through holes arranged in an array.
  • FIG. 20 is a perspective view of a fine hollow protrusion focusing on one protrusion shown in FIG. 21 is a cross-sectional view taken along line III-III shown in FIG.
  • FIG. 22 is a diagram showing an overall configuration of the first embodiment of the manufacturing apparatus for manufacturing the fine hollow projection shown in FIG.
  • FIG. 23 is an explanatory diagram showing a method of measuring the convex tip diameter and tip angle of the convex part.
  • FIG. 24 is a perspective view of the receiving member included in the manufacturing apparatus shown in FIG.
  • FIG. 25 (a) to 25 (e) are diagrams illustrating a process of manufacturing a fine hollow projection having a through hole using the manufacturing apparatus shown in FIG.
  • FIG. 26 is an enlarged cross-sectional view of a main part in the state shown in FIG.
  • FIG. 27 is a diagram showing an overall configuration of a second embodiment of the manufacturing apparatus for manufacturing the fine hollow projection shown in FIG.
  • FIG. 30 is a perspective view of the receiving member provided in the manufacturing apparatus of another embodiment for manufacturing the fine hollow projection shown in FIG. 19 as viewed from the base sheet side.
  • FIG. 31 is a perspective view of an opening plate used in the manufacturing apparatus of another preferred embodiment for manufacturing the fine hollow projection shown in FIG.
  • FIG. 1 shows a fine hollow protrusion 1 according to an embodiment manufactured by the method of manufacturing a fine hollow protrusion according to the first embodiment.
  • the fine hollow protrusion 1 has a sheet-like base portion 2 and one conical protrusion portion 3 standing on the upper surface of the base portion 2.
  • the fine hollow projection 1 has a hollow interior. Specifically, a hollow space is formed extending through the base portion 2 and into the inside of the protrusion 3.
  • the space inside the protrusion 3 is formed in a conical shape corresponding to the outer shape of the protrusion 3.
  • the projection part 3 is a cone shape in the fine hollow protrusion 1, in addition to a cone shape, a truncated cone shape, a column shape, a prism shape, a pyramid shape, a truncated pyramid shape, etc. may be sufficient. .
  • the tip is inserted into the stratum corneum at the shallowest point and deeply into the dermis, preferably 0.01 mm or more, More preferably, it is 0.02 mm or more, preferably 10 mm or less, more preferably 5 mm or less, specifically preferably 0.01 mm or more and 10 mm or less, more preferably 0.02 mm or more. 5 mm or less.
  • the protrusion 3 has an average thickness T1 of preferably 0.005 mm or more, more preferably 0.01 mm or more, and preferably 1.0 mm or less, more preferably 0.5 mm or less.
  • the base 2 has a thickness T2 of preferably 0.01 mm or more, more preferably 0.02 mm or more, and preferably 1.0 mm or less, more preferably 0.7 mm or less. Is preferably 0.01 mm or more and 1.0 mm or less, more preferably 0.02 mm or more and 0.7 mm or less.
  • the tip diameter of the fine hollow projection 1 is preferably 0.001 mm or more, more preferably 0.005 mm or more, and preferably 0.5 mm or less, more preferably 0.3 mm or less. Specifically, it is preferably 0.001 mm to 0.5 mm, and more preferably 0.005 mm to 0.3 mm.
  • the tip diameter of the fine hollow projection 1 is measured as follows.
  • the tip of the hollow protrusion 1 is observed like a SEM image shown in FIG. 3 in a state where the tip is enlarged by a predetermined magnification using a scanning electron microscope (SEM) or a microscope.
  • SEM scanning electron microscope
  • the imaginary straight line ILa is extended along the straight line portion on one side 1a of the both sides 1a and 1b
  • the imaginary straight line ILb is extended along the straight line portion on the other side 1b.
  • a location where the one side 1a is separated from the virtual straight line ILa is obtained as the first distal point 1a1
  • a location where the other side 1b is separated from the virtual straight line ILb is obtained as the second distal point 1b1.
  • the length L of the straight line connecting the first tip point 1a1 and the second tip point 1b1 thus determined is measured using a scanning electron microscope (SEM) or a microscope, and the measured length of the straight line is measured. Is the tip diameter of the fine hollow projection 1.
  • FIG. 4 shows the overall configuration of a manufacturing apparatus 100A according to the first embodiment used for carrying out the manufacturing method according to the first embodiment.
  • the fine hollow protrusion 1 is very small, but for convenience of explanation, the fine hollow protrusion 1 is drawn very large in FIG.
  • a manufacturing apparatus 100A according to the first embodiment shown in FIG. 4 has a protruding portion forming portion 10 that forms the protruding portion 3 on the base sheet 2A from the upstream side to the downstream side, a cooling portion 20, and a convex portion 11 described later.
  • a release portion 30 a cutting portion 40 for cutting into each fine hollow projection 1, and a re-pitch portion 50 for adjusting the interval between the fine hollow projections 1.
  • the direction in which the base sheet 2A is transported is the Y direction
  • the direction orthogonal to the transport direction and the width direction of the transported base sheet 2A are transported in the X direction.
  • the convex part 11 is a member provided with a convex mold 110 that is a part that pierces the substrate sheet.
  • the convex part 11 has the convex mold 110 on the disk-shaped base part. It has a structure.
  • the present invention is not limited to this, and it may be a convex part composed only of the convex mold 110, or may be a convex part 11 in which a plurality of convex molds 110 are arranged on a table-like support as in the embodiment described later. There may be.
  • the protruding portion forming portion 10 includes a convex portion 11 having heating means (not shown).
  • no heating means is provided other than the heating means (not shown) of the convex portion 11.
  • “no heating means other than the heating means of the convex portion 11” not only refers to the case of excluding other heating means, but also below the softening temperature of the base sheet 2A, Or the case where a means for heating below the glass transition temperature is provided is included. However, it is preferable not to include any other heating means.
  • the heating means (not shown) of the convex portion 11 is a heater device in the manufacturing apparatus 100A of the first embodiment.
  • the belt-like base sheet 2A is fed out from the raw roll of the base sheet 2A formed by including the thermoplastic resin, and is conveyed in the Y direction. And the convex part 11 is made to contact
  • the base material sheet 2A is stabbed and the protrusion part 3 which protrudes from the other surface 2U side of the base material sheet 2A is formed (protrusion part formation process).
  • the convex portion 11 has a shape having a conical portion with a sharp tip corresponding to the outer shape of the conical protrusion 3 of the fine hollow protrusion 1 to be manufactured.
  • the convex portion 11 is disposed with its tip facing upward, and is movable at least up and down in the thickness direction (Z direction). More specifically, in the manufacturing apparatus 100A of the first embodiment, the convex portion 11 is movable up and down in the thickness direction (Z direction) by an electric actuator (not shown), and is in the transport direction (Y direction). ) In parallel with the base sheet 2A. Control of the operation of the convex part 11 is controlled by a control means (not shown) provided in the manufacturing apparatus 100A of the first embodiment.
  • the manufacturing apparatus 100 ⁇ / b> A is an apparatus having the so-called box motion type projection forming unit 10 that draws an endless track. Control of heating of the heating means (not shown) of the convex portion 11 is also controlled by a control means (not shown) provided in the manufacturing apparatus 100A of the first embodiment.
  • the base sheet 2A is a sheet that becomes the base portion 2 of the fine hollow protrusion 1 to be manufactured, and is formed including a thermoplastic resin.
  • the thermoplastic resin include poly fatty acid ester, polycarbonate, polypropylene, polyethylene, polyester, polyamide, polyamideimide, polyetheretherketone, polyetherimide, polystyrene, polyethylene terephthalate, polyvinyl chloride, nylon resin, acrylic resin, etc.
  • poly fatty acid esters are preferably used.
  • Specific examples of the polyfatty acid ester include polylactic acid, polyglycolic acid, and combinations thereof.
  • the base sheet 2A may be formed of a mixture containing hyaluronic acid, collagen, starch, cellulose and the like in addition to the thermoplastic resin.
  • the thickness of the base material sheet 2A is equal to the thickness T2 of the base portion 2 of the fine hollow protrusion 1 to be manufactured.
  • the shape on the front end side of the convex portion 11 only needs to be a shape corresponding to the outer shape of the protrusion 3 of the fine hollow protrusion 1 to be manufactured.
  • the convex mold 110 of the convex mold part 11 is formed such that its height H2 is the same as or slightly higher than the height H1 of the fine hollow projection 1 to be manufactured, preferably 0.01 mm or more, more preferably 0. 0.02 mm or more, preferably 30 mm or less, more preferably 20 mm or less, specifically preferably 0.01 mm or more and 30 mm or less, more preferably 0.02 mm or more and 20 mm or less.
  • the convex mold 110 of the convex mold part 11 has a tip diameter D1 (see FIG.
  • the tip diameter D1 of the convex mold 110 of the convex mold part 11 is measured as follows.
  • the convex mold 110 of the convex mold section 11 has a root diameter D2 of preferably 0.1 mm or more, more preferably 0.2 mm or more, and preferably 5 mm or less, more preferably 3 mm or less.
  • the convex mold 110 of the convex mold section 11 has a tip angle ⁇ of preferably 1 degree or more, and more preferably 5 degrees or more, from the viewpoint that sufficient strength is easily obtained.
  • the tip angle ⁇ is preferably 60 degrees or less, more preferably 45 degrees or less from the viewpoint of obtaining the protrusion 3 having an appropriate angle, and specifically, preferably 1 degree or more and 60 degrees or less. More preferably, it is 5 degrees or more and 45 degrees or less.
  • the tip angle ⁇ of the convex portion 11 is measured as follows.
  • a location where the one side 11a is separated from the virtual straight line ILc is obtained as the first distal point 11a1
  • a location where the other side 11b is separated from the virtual straight line ILd is obtained as the second distal point 11b1.
  • the length D1 of the straight line connecting the first tip point 11a1 and the second tip point 11b1 thus determined is measured using a scanning electron microscope (SEM) or a microscope, and the measured length of the straight line is measured. Is the tip diameter of the convex mold 110.
  • the angle formed between the virtual straight line ILc and the virtual straight line ILd is measured using a scanning electron microscope (SEM) or a microscope, and the measured angle is determined as the tip angle ⁇ of the convex mold 110 of the convex portion 11.
  • the convex part 11 is formed of a high-strength material that is difficult to break.
  • Examples of the material of the convex part 11 include metals such as steel, stainless steel, aluminum, aluminum alloy, nickel, nickel alloy, cobalt, cobalt alloy, copper, copper alloy, beryllium copper, and beryllium copper alloy, or ceramic. .
  • the protruding portion forming portion 10 is a support member 12 that supports the base sheet 2A when the protruding portion 11 is pierced into the base sheet 2A as shown in FIG. have.
  • the support member 12 is disposed on the other surface 2U side of the base sheet 2A, and serves to make the sheet base material 2A difficult to bend when the convex portion 11 is inserted from the one surface 2D side.
  • the support member 12 is arrange
  • the material constituting the support member 12 may be the same material as that of the convex portion 11, or may be formed of a synthetic resin or the like.
  • the projection is formed on the other surface 2U side (upper surface side) of the strip-shaped base sheet 2A that is fed from the raw roll and conveyed in the Y direction.
  • the paired support members 12 and 12 support both side portions along the conveyance direction (Y direction) of the base sheet 2A.
  • the convex portion 11 is brought into contact with the surface 2D side (lower surface side).
  • the other surface 2U side (upper surface side) corresponding to the contact portion TP of the base sheet 2A with which the convex portion 11 is contacted is for forming a protrusion.
  • the convex part 11 in the contact portion TP, the convex part 11 is heated by the heater device, and heat is generated in the contact portion TP, so that the contact portion is formed. Softens TP. Then, while softening the contact portion TP, as shown in FIG. 6B, the convex portion 11 is moved from the one surface 2D side (lower surface side) to the other surface 2U side (upper surface side) as shown in FIG. It raises and stabs into the base material sheet 2A, and the protrusion part 3 which protrudes from the other surface 2U side (upper surface side) of the base material sheet 2A is formed.
  • the heating temperature of the base sheet 2A by the convex part 11 is preferably equal to or higher than the glass transition temperature of the base sheet 2A used and lower than the melting temperature, and in particular, melted above the softening temperature. It is preferable that the temperature is lower than the temperature. More specifically, the heating temperature is preferably 30 ° C. or higher, more preferably 40 ° C. or higher, and preferably 300 ° C. or lower, more preferably 250 ° C. or lower. It is not less than 300 ° C and more preferably not less than 40 ° C and not more than 250 ° C.
  • the said heating temperature is applied as a temperature range of the part of the base material sheet 2A which contacted the convex mold 110, also when heating the base material sheet 2A using an ultrasonic vibration apparatus in 1st Embodiment.
  • the glass transition temperature (Tg) is measured by the following method, and the softening temperature is measured according to JIS K-7196 “Softening temperature test method by thermomechanical analysis of thermoplastic film and sheet”. .
  • the “glass transition temperature (Tg) of the base sheet” means the glass transition temperature (Tg) of the constituent resin of the base sheet, and when there are a plurality of types of the constituent resins, the plurality of types of glass transitions.
  • the heating temperature of the base sheet by the heating means is preferably at least the lowest glass transition temperature (Tg) among the plurality of glass transition temperatures (Tg), More preferably, the glass transition temperature (Tg) is higher than the highest glass transition temperature (Tg).
  • the "softening temperature of the base sheet” is also the same as the glass transition temperature (Tg), that is, when there are a plurality of types of constituent resins of the base sheet, when the plurality of types of softening temperatures are different from each other,
  • the heating temperature of the base sheet by the heating means is preferably at least the lowest softening temperature among the plurality of softening temperatures, and more preferably at least the highest softening temperature among the plurality of softening temperatures.
  • the heating temperature of the base sheet by the heating means is preferably less than the lowest melting point among the plurality of melting points. .
  • Tg glass transition temperature
  • the amount of heat is measured using a DSC measuring instrument to determine the glass transition temperature.
  • the measuring instrument uses a differential scanning calorimeter (Diamond DSC) manufactured by Perkin Elmer. 10 mg of a test piece is collected from the base sheet. The measurement conditions are that 20 ° C. is isothermal for 5 minutes, and then the temperature is increased from 20 ° C. to 320 ° C. at a rate of 5 ° C./min to obtain a DSC curve of the horizontal axis temperature and the vertical axis calorific value. And glass transition temperature Tg is calculated
  • the insertion speed at which the convex portion 11 is inserted into the base sheet 2A is excessively softened by heating the resin excessively, and if it is too fast, the heat softening becomes insufficient, so that the convex portion 11 can be efficiently formed. Therefore, it is preferably 0.1 mm / second or more, more preferably 1 mm / second or more, and preferably 1000 mm / second or less, more preferably 800 mm / second or less, and specifically preferably 0 mm / second or less. It is 1 mm / second or more and 1000 mm / second or less, more preferably 1 mm / second or more and 800 mm / second or less.
  • the heating time of the convex part 11 is stopped and the softening time, which is the time until the convex part 11 is transported to the next process (cooling process) in a state where the convex part 11 is stuck inside the protrusion 3, is too long.
  • the softening time which is the time until the convex part 11 is transported to the next process (cooling process) in a state where the convex part 11 is stuck inside the protrusion 3.
  • it is preferably 0 seconds or longer, more preferably 0.1 seconds or longer, and preferably 10 seconds or shorter, more preferably 5 seconds or shorter.
  • the insertion height of the convex portion 11 that pierces the base sheet 2 ⁇ / b> A is preferably 0.01 mm or more, more preferably 0.02 mm or more, and preferably Is not more than 10 mm, more preferably not more than 5 mm, specifically preferably not less than 0.01 mm and not more than 10 mm, more preferably not less than 0.02 mm and not more than 5 mm.
  • the insertion height means that the apex of the convex portion 11 and the other surface 2U (upper surface) of the base sheet 2A in the state where the convex portion 11 is most inserted into the base sheet 2A. Means the distance between.
  • the piercing height in the protruding portion forming step means that the protruding portion 11 is deeply inserted in the protruding portion forming step and the protruding portion 11 comes out from the other surface 2U of the base sheet 2A. It is the distance from the other surface 2U to the apex of the convex portion 11 measured in the vertical direction.
  • the cooling unit 20 is installed downstream of the protrusion forming unit 10.
  • the cooling unit 20 includes a cold air blowing device 21.
  • the cold air blowing device 21 covers the entire other surface 2U side (upper surface side) and one surface 2D side (lower surface side) of the belt-shaped base sheet 2A being conveyed.
  • the belt-shaped base sheet 2A is conveyed in the conveyance direction (Y direction).
  • an air blowing port 22 for blowing cold air is provided on the other surface 2U side (upper surface side) of the base sheet 2 ⁇ / b> A. It is designed to cool by spraying. Control of the cooling temperature and cooling time of the cold air blower 21 is also controlled by a control means (not shown) provided in the manufacturing apparatus 100A of the first embodiment.
  • the protruding portion 11 is inserted into the inside of the protruding portion 3 in the tunnel of the cold air blowing device 21 using the box motion type protruding portion forming portion 10.
  • the substrate sheet 2A is conveyed in parallel with the conveyance direction (Y direction), and is arranged on the other surface 2U side (upper surface side) of the substrate sheet 2A in the tunnel as shown in FIG. Cooling air is blown from the blower opening 22, and cooling is performed while the protruding portion 11 is stuck inside the protrusion 3.
  • the heating of the convex portion 11 by the heater device may be continued or stopped.
  • the cooling part 20 installed downstream of the protrusion part forming part 10 may be natural cooling. It is preferable to perform positive cooling, and it is preferable to provide the cold air blowing device 21.
  • the temperature of the cold air to be blown is preferably ⁇ 50 ° C. or higher, more preferably ⁇ 40 ° C. or higher, and preferably 26 ° C. or lower, more preferably 10 ° C. or lower, from the viewpoint of forming the convex portion 11. Specifically, it is preferably ⁇ 50 ° C. or higher and 26 ° C. or lower, and more preferably ⁇ 40 ° C. or higher and 10 ° C. or lower.
  • the cooling time for cooling by blowing cold air is preferably 0.01 seconds or more, more preferably 0.5 seconds or more, and preferably 60 seconds or less, from the viewpoint of compatibility between moldability and processing time. More preferably, it is 30 seconds or less, specifically, preferably 0.01 seconds or more and 60 seconds or less, more preferably 0.5 seconds or more and 30 seconds or less.
  • a release unit 30 is installed downstream of the cooling unit 20.
  • the convex portion 11 is removed from the inside of the projection 3 to form the precursor 1 ⁇ / b> A of the fine hollow projection 1.
  • the release process of the first embodiment as shown in FIG. 6 (d), using the box motion type projection forming part 10, from one surface 2D side (lower surface side) of the base sheet 2 ⁇ / b> A.
  • a cutting unit 40 is installed downstream of the release unit 30.
  • the cutting part 40 includes a cutter part 41 having a cutter blade at the tip and an anvil part 42.
  • the cutter blade of the cutter unit 41 is formed wider than the entire width (length in the X direction) of the belt-shaped fine hollow projection precursor 1A.
  • the belt-shaped fine hollow projection precursor 1A is transported between the pair of cutter parts 41 and the anvil part 42 and is adjacent to the transport direction (Y direction).
  • the fine hollow protrusion 1 of a single wafer is continuously manufactured by cutting with a cutter blade of the cutter part 41 between the protrusions 3 and 3.
  • the cutting of the precursor 1A of the band-shaped fine hollow protrusions only needs to be performed so as to extend in the width direction of each fine hollow protrusion 1, and can be performed linearly across the width direction of each fine hollow protrusion 1, for example. . Or it can cut so that a cutting line may draw a curve. In any case, it is preferable to employ a cutting pattern that does not cause trimming by cutting.
  • a re-pitch part 50 is installed downstream of the cutting part 40 as shown in FIG.
  • the re-pitch portion 50 includes a plurality of rollers 51 that are arranged so that their rotation axes are parallel to each other, and an endless conveyance belt 52 that is spanned between the rollers 51. have.
  • a suction box 53 is provided inside the conveyor belt 52.
  • the conveyor belt 52 is provided with a plurality of through holes (not shown) for sucking air from the outside to the inside of the circuit track by starting the suction box 53.
  • the conveyance speed of the conveyance belt 52 is faster than the conveyance speed of the base sheet 2 ⁇ / b> A up to the cutting unit 40.
  • the heating elements 2 of each leaf are continuously placed on the conveying belt 52 while being sucked by the suction box 53 through a through hole (not shown), and the conveying direction ( In the Y direction), the distance between the fine hollow protrusions 1 and 1 adjacent to each other in the front and rear directions is increased, and the fine hollow protrusions 1 are rearranged at a predetermined distance.
  • the fine hollow projection 1 is manufactured by only a simple process. Therefore, the cost increase can be suppressed, and the fine hollow projection 1 can be manufactured efficiently and continuously.
  • the manufacturing apparatus 100A uses the control means (not shown) to operate the convex portion 11, the heating condition of the heating means (not shown) provided in the convex portion 11, the cold air blowing
  • the cooling temperature and cooling time of the device 21 are controlled. Therefore, the amount of insertion of the convex portion 11 into the base sheet 2A can be easily changed by controlling the insertion height of the convex portion 11 in the protrusion forming step, for example, by a control means (not shown).
  • the protrusion height H1 of the fine hollow protrusion 1 to be manufactured can be controlled.
  • the fine The thickness T1 and the like of the protrusion 3 constituting the hollow protrusion 1 can be freely controlled.
  • the shape of the fine hollow projection 1 can be freely controlled by controlling at least one of the insertion speed of the convex portion 11 into the base sheet 2A, the shape of the convex portion 11 and the cooling condition in the cooling step. can do.
  • a pair of support members 12 and 12 arranged on the other surface 2U side (upper surface side) of the base sheet 2A is used. Supports both side portions along the conveyance direction (Y direction) of the material sheet 2A, and floats between the pair of support members 12 and 12 in the base sheet 2A (non-supported by the pair of support members 12 and 12)
  • the protruding portion 11 is brought into contact with one surface 2D side (lower surface side) of the central portion in the support state, and the contact portion TP is softened by heat to form the protruding portion 3.
  • the recessed part etc. which fit in the convex-shaped part 11 for forming a protrusion part are unnecessary, a cost increase can be suppressed and the protrusion part 3 with which the fine hollow protrusion 1 manufactured is manufactured efficiently Can be formed with high accuracy.
  • the heating means (not shown) of the convex portion 11 is a heater device, but in the second embodiment used in the second embodiment.
  • an ultrasonic vibration device is used instead.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device as in the manufacturing apparatus 100A of the second embodiment, as shown in FIG.
  • the convex part 11 is ultrasonically vibrated by the vibration device to generate heat due to friction at the contact part TP to soften the contact part TP.
  • the convex part 11 is moved from the one surface 2D side (lower surface side) to the other surface 2U side (upper surface side) as shown in FIG. It raises and stabs into the base material sheet 2A, and the protrusion part 3 which protrudes from the other surface 2U side (upper surface side) of the base material sheet 2A is formed.
  • the protruding portion 3 protrudes to the set height, the rising of the protruding portion 11 is stopped, and the protruding portion 11 is transported to the next process while being stuck in the protruding portion 3.
  • the ultrasonic vibration of the convex portion 11 by the wave vibration device is performed from immediately before the convex portion 11 comes into contact with the base sheet 2A to immediately before reaching the cooling portion 20 in the next step (cooling step).
  • the frequency is preferably 10 kHz or more, more preferably 15 kHz or more, and preferably 50 kHz or less from the viewpoint of formation of the convex part 11, More preferably, it is 40 kHz or less, specifically, preferably 10 kHz or more and 50 kHz or less, more preferably 15 kHz or more and 40 kHz or less.
  • the amplitude is preferably 1 ⁇ m or more, more preferably 5 ⁇ m or more, and preferably 60 ⁇ m or less from the viewpoint of forming the convex portion 11. Yes, more preferably 50 ⁇ m or less, specifically preferably 1 ⁇ m or more and 60 ⁇ m or less, and more preferably 5 ⁇ m or more and 50 ⁇ m or less.
  • the cooling unit 20 is provided with the cold air blowing device 21 in order to positively cool, but the heating unit (not shown) of the convex portion 11 is provided. Since it is an ultrasonic vibration device, it is not always necessary to provide the cold air blowing device 21, and cooling can also be performed by cutting the vibration of the ultrasonic vibration device. In this respect, it is preferable to use ultrasonic vibration as a heating means because it simplifies the apparatus and facilitates the production of fine hollow projections at high speed. Further, in the portion of the base sheet 2A that is not in contact with the convex portion 11, heat is more difficult to be transmitted, and since cooling is efficiently performed by turning off the application of ultrasonic vibration, deformation other than the molded portion occurs. There is an advantage that it is difficult.
  • FIG. 11 shows a perspective view of a microneedle array 1M as a fine hollow protrusion 1 according to an embodiment manufactured by the method of manufacturing the fine hollow protrusion 1 of the first embodiment.
  • the microneedle array 1M of this embodiment has a sheet-like base portion 2 and a plurality of protrusions 3.
  • the number of the protrusions 3, the arrangement of the protrusions 3, and the shape of the protrusions 3 are not particularly limited, but the microneedle array 1M of the present embodiment is preferably provided on the upper surface of the sheet-like base 2.
  • Nine frustoconical protrusions 3 are arranged in an array (matrix).
  • Nine protrusions 3 arranged in an array (matrix) form three rows in the Y direction, which is a direction (longitudinal direction of the base sheet 2A) for transporting a base sheet 2A described later, and are orthogonal to the transport direction. It is arranged in three rows in the X direction, which is the horizontal direction of the direction and the substrate sheet 2A to be conveyed.
  • FIG. 12 is a perspective view of the microneedle array 1M focusing on one of the protrusions 3 in the array (matrix) shape of the microneedle array 1M.
  • FIG. FIG. 3 is a sectional view taken along line III-
  • the microneedle array 1M has a through hole 3h as shown in FIG.
  • a space extending from the base portion 2 to the through hole 3 h is formed inside each projection portion 3.
  • a through-hole 3h is formed at the tip of each.
  • the space inside each protrusion 3 is formed in a shape corresponding to the outer shape of the protrusion 3 in the microneedle array 1M.
  • the space corresponding to the outer shape of the frustoconical protrusion 3 is formed. It is formed in a truncated cone shape.
  • the projection part 3 is truncated cone shape in this embodiment, cylindrical shape, prismatic shape, truncated pyramid shape, etc. may be sufficient other than a truncated cone shape.
  • Each protrusion 3 of the microneedle array 1M has a protrusion height H1 of preferably 0.01 mm or more, more preferably 0.1 mm because the protrusion height H1 penetrates the stratum corneum at the shallowest point and deeply into the dermis. It is 02 mm or more, preferably 10 mm or less, more preferably 5 mm or less, specifically preferably 0.01 mm or more and 10 mm or less, and more preferably 0.02 mm or more and 5 mm or less.
  • Each protrusion 3 has an average thickness T1 of preferably 0.005 mm or more, more preferably 0.01 mm or more, and preferably 1.0 mm or less, more preferably 0.5 mm or less, Specifically, it is preferably 0.005 mm or more and 1.0 mm or less, and more preferably 0.01 mm or more and 0.5 mm or less.
  • the base 2 has a thickness T2 of preferably 0.01 mm or more, more preferably 0.02 mm or more, and preferably 1.0 mm or less, more preferably 0.7 mm or less. Is preferably 0.01 mm or more and 1.0 mm or less, more preferably 0.02 mm or more and 0.7 mm or less.
  • the tip diameter L of each protrusion 3 of the microneedle array 1M is preferably 1 ⁇ m or more, more preferably 5 ⁇ m or more, and preferably 500 ⁇ m or less, more preferably 300 ⁇ m or less. Specifically, it is preferably 1 ⁇ m or more and 500 ⁇ m or less, and more preferably 5 ⁇ m or more and 300 ⁇ m or less.
  • the tip diameter L of the fine hollow projection 1 is the length at the widest position at the tip of the projection 3. Within this range, there is almost no pain when the microneedle array 1M is inserted into the skin.
  • the fine hollow projection 1 includes a through hole 3 h located at the tip of each projection 3, and a base side through hole 2 h located on the lower surface of the base 2 corresponding to each projection 3. have.
  • the through hole 3h and the base side through hole 2h are formed concentrically.
  • the opening area S1 is good properly is 0.7 [mu] m 2 or more, more preferably 20 [mu] m 2 or more, and preferably not 200000Myuemu 2 or less, still more preferably 70000Myuemu 2 or less, particularly specifically, the preferably at 0.7 [mu] m 2 or more 200000Myuemu 2 or less, still more preferably 20 [mu] m 2 or more 70000Myuemu 2 or less.
  • the opening area S2 of the base side through hole 2h is preferably 0.007 mm 2 or more, more preferably 0.03 mm 2 or more, and preferably 20 mm 2 or less, more preferably 7 mm 2 or less. in and, specifically, preferably at 0.007 mm 2 or more 20 mm 2 or less, more preferably at 0.03 mm 2 or more 7 mm 2 or less.
  • the nine protrusions 3 arranged in an array (matrix) on the upper surface of the sheet-like base 2 have a uniform center distance in the vertical direction (Y direction) and a center distance in the horizontal direction (X direction). Is preferably uniform, and the center-to-center distance in the vertical direction (Y direction) and the center-to-center distance in the horizontal direction (X direction) are preferably the same distance.
  • the center-to-center distance in the longitudinal direction (Y direction) of the protrusion 3 is preferably 0.01 mm or more, more preferably 0.05 mm or more, and preferably 10 mm or less, more preferably 5 mm.
  • the distance between the centers of the protrusions 3 in the lateral direction (X direction) is preferably 0.01 mm or more, more preferably 0.05 mm or more, and preferably 10 mm or less, more preferably 5 mm or less.
  • it is preferably 0.01 mm or more and 10 mm or less, and more preferably 0.05 mm or more and 5 mm or less.
  • FIG. 14 shows the overall configuration of a manufacturing apparatus 100B according to the first embodiment used for carrying out the manufacturing method according to the first embodiment.
  • each protrusion 3 of the microneedle array 1M is very small, but for convenience of explanation, each protrusion 3 of the microneedle array 1M is drawn very large in FIG. .
  • the manufacturing apparatus 100B has a protrusion precursor forming portion 10A and a base sheet 2A that form a hollow protrusion precursor 3b on the base sheet 2A from the upstream side toward the downstream side.
  • the protrusion extending portion 10B for forming the protrusion 3 on the surface, the cooling portion 20, the release portion 30 for extracting the convex portion 11 described later, the cutting portion 40 for cutting each microneedle array 1M, and the interval between the microneedle arrays 1M are adjusted.
  • a re-pitch portion 50 is provided.
  • the manufacturing apparatus 100B includes a protruding portion forming portion 10 that forms the protruding portion 3 including a protruding portion precursor forming portion 10A and a protruding portion 10B.
  • the protruding portion The process from the protrusion precursor forming process using the precursor forming part 10A to the protrusion extending process using the protrusion extending part 10B is referred to as a protrusion forming process.
  • the direction in which the base sheet 2A is transported is the Y direction
  • the direction orthogonal to the transport direction and the lateral direction of the transported base sheet 2A are transported in the X direction.
  • the thickness direction of the base material sheet 2 ⁇ / b> A will be described as the Z direction.
  • the protrusion precursor forming part 10 ⁇ / b> A and the protrusion extending part 10 ⁇ / b> B included in the protrusion forming part 10 include a convex part 11 having a heating means (not shown).
  • the convex part 11 has a convex mold 110 corresponding to the number and arrangement of the protrusions 3 of the microneedle array 1M to be manufactured, and the substantially outer shape of each protrusion 3, and in the manufacturing apparatus 100B of the first embodiment.
  • the amount of heat applied from the convex portion 11 to the base sheet 2A by the projection extending portion 10B is changed from the convex portion 11 to the base sheet by the projection precursor forming portion 10A. It is larger than the amount of heat given to 2A.
  • the amount of heat given to the base sheet 2A means the amount of heat per unit insertion height given to the base sheet 2A.
  • the condition that the amount of heat given from the convex portion 11 to the base sheet 2A at the protrusion extension portion 10B is larger than the amount of heat given from the convex portion 11 to the base sheet 2A at the projection portion precursor forming portion 10A.
  • the insertion speed of the protrusion extending portion 10B is slower than the insertion speed of the protrusion precursor forming portion 10A.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device, the ultrasonic frequency of the convex portion 11 of the protrusion extending portion 10B is higher than that of the protrusion precursor forming portion 10A.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device
  • the amplitude of the sound wave is larger than the amplitude of the ultrasonic wave of the convex portion 11 of the protrusion precursor forming portion 10A.
  • the heating means (not shown) of the convex portion 11 is a heater
  • the heater temperature of the convex portion 11 of the protrusion extension portion 10B is higher than that of the protrusion precursor forming portion 10A. It means that at least one condition of being higher than the heater temperature of the part 11 is satisfied.
  • a heating means other than the heating means (not shown) of the convex-shaped part 11 is not provided.
  • “no heating means other than the heating means of the convex portion 11” not only refers to the case of excluding other heating means, but also below the softening temperature of the base sheet 2A, Or the case where a means for heating below the glass transition temperature is provided is included. However, it is preferable not to include any other heating means.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device.
  • the belt-like base sheet 2A is fed out from the raw roll of the base sheet 2A formed by including the thermoplastic resin, and is conveyed in the Y direction.
  • the convex portion 11 is brought into contact with one surface 2D of the belt-like base material sheet 2A being conveyed in the Y direction, and the contact portion TP in the base material sheet 2A is softened by heat while the convex portion 11 is used as a base.
  • a hollow projection precursor 3b having a through hole 3h penetrating the material sheet 2A and projecting from the other surface 2U of the base material sheet 2A and penetrating at the tip of the other surface 2U side of the base material sheet 2A is formed (projection portion).
  • the conical convex mold 110 having nine sharp tips is arranged on the convex portion 11 with the tips facing upward, and the convex portion 11 is movable up and down at least in the thickness direction (Z direction).
  • the convex portion 11 can be moved up and down in the thickness direction (Z direction) by an electric actuator (not shown), and the conveyance direction (Y Direction) and can run parallel to the base sheet 2A.
  • Control of the operation (electric actuator) of the convex portion 11 is controlled by a control means (not shown) provided in the manufacturing apparatus 100B of the first embodiment.
  • the manufacturing apparatus 100B of the first embodiment is an apparatus having the so-called box motion type convex portion 11 that draws an endless track.
  • Control of heating of the heating means (not shown) of the convex portion 11 is also controlled by a control means (not shown) provided in the manufacturing apparatus 100B of the first embodiment.
  • the base material sheet 2A is a sheet that becomes the base portion 2 of the microneedle array 1M to be manufactured, and is formed including a thermoplastic resin.
  • the thermoplastic resin include poly fatty acid ester, polycarbonate, polypropylene, polyethylene, polyester, polyamide, polyamideimide, polyetheretherketone, polyetherimide, polystyrene, polyethylene terephthalate, polyvinyl chloride, nylon resin, acrylic resin, etc.
  • poly fatty acid esters are preferably used.
  • Specific examples of the polyfatty acid ester include polylactic acid, polyglycolic acid, and combinations thereof.
  • the base sheet 2A may be formed of a mixture containing hyaluronic acid, collagen, starch, cellulose and the like in addition to the thermoplastic resin.
  • the thickness of the base sheet 2A is equal to the thickness T2 of the base portion 2 of the microneedle array 1M to be manufactured.
  • the convex mold 110 of the convex mold part 11 has a sharper outer shape than the outer shape of the protrusion 3 of the microneedle array 1M.
  • the convex mold 110 of the convex mold section 11 is formed such that its height H2 (see FIG. 14) is higher than the height H1 of the microneedle array 1M to be manufactured, preferably 0.01 mm or more, more preferably Is 0.02 mm or more, preferably 30 mm or less, more preferably 20 mm or less, specifically preferably 0.01 mm or more and 30 mm or less, more preferably 0.02 mm or more and 20 mm or less. It is.
  • the convex mold 110 of the convex mold part 11 has a tip diameter D1 (see FIG.
  • the tip diameter D1 of the convex mold 110 of the convex mold part 11 is measured as follows.
  • the convex mold 110 of the convex mold part 11 has a root diameter D2 (see FIG.
  • the convex mold 110 of the convex mold section 11 has a tip angle ⁇ (see FIG. 15) of preferably 1 degree or more, more preferably 5 degrees or more, from the viewpoint that sufficient strength is easily obtained.
  • the tip angle ⁇ is preferably 60 degrees or less, more preferably 45 degrees or less from the viewpoint of obtaining the protrusion 3 having an appropriate angle, and specifically, preferably 1 degree or more and 60 degrees or less. More preferably, it is 5 degrees or more and 45 degrees or less.
  • the tip angle ⁇ of the convex mold 110 of the convex mold part 11 is measured as follows.
  • a location where one side 11a is separated from the virtual straight line ILa is obtained as a first distal point 11a1
  • a location where the other side 11b is separated from the virtual straight line ILb is obtained as a second distal point 11b1.
  • the length D1 of the straight line connecting the first tip point 11a1 and the second tip point 11b1 thus determined is measured using a scanning electron microscope (SEM) or a microscope, and the measured length of the straight line is measured. Is the tip diameter of the convex mold 110.
  • the angle formed between the virtual straight line ILa and the virtual straight line ILb is measured using a scanning electron microscope (SEM) or a microscope, and the measured angle is determined as the tip angle ⁇ of the convex mold 110 of the convex portion 11.
  • the convex part 11 is formed of a high-strength material that is difficult to break.
  • Examples of the material of the convex part 11 include metals such as steel, stainless steel, aluminum, aluminum alloy, nickel, nickel alloy, cobalt, cobalt alloy, copper, copper alloy, beryllium copper, and beryllium copper alloy, or ceramic. .
  • the protrusion precursor forming part 10A supports the base sheet 2A when the protruding part 11 is pierced into the base sheet 2A as shown in FIG.
  • a member 12 is provided.
  • the support member 12 is disposed on the other surface 2U side of the base sheet 2A, and plays a role of making the sheet base 2A difficult to bend when the convex portion 11 is inserted from the one surface 2D.
  • the support member 12 is arrange
  • Each support member 12 extends from the protrusion part precursor forming part 10 ⁇ / b> A to the position where the release part 30 ends through the protrusion extension part 10 ⁇ / b> B and the cooling part 20.
  • the material for forming the support member 12 may be the same material as that of the convex portion 11, or may be formed of a synthetic resin or the like.
  • the pair of support members 12, 12 arranged on the both sides support both side portions along the conveyance direction (Y direction) of the base sheet 2 ⁇ / b> A. Then, using the box motion type convex portion 11, the portion of the base sheet 2A that is not supported by the support member 12, that is, one surface of the central region between the pair of support members 12 and 12 in the base sheet 2A The tip part of each convex mold 110 of the convex part 11 is brought into contact with 2D (lower surface).
  • the other surface 2U (upper surface) corresponding to the contact portion TP of the base sheet 2A with which the convex molds 110 of the convex mold part 11 are in contact with the protrusions.
  • the convex portion 11 for formation There is no concave portion or the like that fits into the convex portion 11 for formation, and it is in a floating state.
  • the convex portion 11 is ultrasonically vibrated by an ultrasonic vibration device, and heat due to friction is applied to the contact portion TP.
  • the contact portion TP is softened by being generated.
  • the convex portion 11 is raised toward the upper surface and the tip of the convex mold 110 is pierced into the base sheet 2A.
  • a hollow projection part precursor 3b having the following is formed.
  • the vibration frequency (hereinafter referred to as frequency) of the projection part 11 with respect to the ultrasonic vibration by the ultrasonic vibration device is a projection part precursor 3b having a through hole 3h.
  • the amplitude thereof is preferably 1 ⁇ m or more, more preferably 5 ⁇ m or more, from the viewpoint of the formation of the projection precursor 3b having the through hole 3h. And it is 60 micrometers or less preferably, More preferably, it is 50 micrometers or less, Specifically, Preferably they are 1 micrometer or more and 60 micrometers or less, More preferably, they are 5 micrometers or more and 50 micrometers or less.
  • the frequency and amplitude of the ultrasonic vibration of the convex portion 11 may be adjusted in the above-described range in the protrusion precursor forming step.
  • the resin is excessively softened and the size of the through hole 3h is increased. However, if it is too fast, the softening becomes insufficient and the through hole 3h is not formed. Therefore, from the viewpoint of efficiently forming the projection precursor 3b having the through hole 3h, it is preferably 0.1 mm / second or more, more preferably 1 mm / second. And preferably 1000 mm / second or less, more preferably 800 mm / second or less, specifically preferably 0.1 mm / second or more and 1000 mm / second or less, more preferably 1 mm / second or less. It is 2 seconds or more and 800 mm / seconds or less.
  • the insertion height of the convex part 11 to be inserted into the base sheet 2A is from the viewpoint of efficiently forming the protrusion precursor 3b having the through hole 3h.
  • it is 0.001 mm or more, more preferably 0.01 mm or more, and preferably 2 mm or less, more preferably 1 mm or less, specifically preferably 0.001 mm or more and 2 mm or less, More preferably, it is 0.01 mm or more and 1 mm or less.
  • the insertion height refers to the apex of the convex mold 110 of the convex part 11 and the base sheet 2A in the state where the convex mold 110 of the convex part 11 is inserted into the base sheet 2A. It means the distance between the surface 2U. Therefore, the insertion height in the protrusion precursor forming step refers to the state in which the convex mold 110 is inserted deepest in the protrusion precursor forming step and the convex mold 110 comes out from the other surface 2U of the base sheet 2A. The distance from the other surface 2U to the top of the convex 110 measured in the vertical direction.
  • a protruding portion extending portion 10B is installed on the downstream side of the protruding portion precursor forming portion 10A.
  • the contact portion TP in the base sheet 2A is softened by heat while the protruding portion 11 is inserted into the protruding portion precursor 3b.
  • the convex part 11 is further stabbed into the base sheet 2A to form a protrusion 3 that protrudes a longer distance from the other surface 2U of the base sheet 2A (projection extension step).
  • the box motion type convex portion 11 is further moved upward in the thickness direction (Z direction) by an electric actuator (not shown), and each projection portion precursor is moved.
  • each convex part 11 in the base sheet 2A is ultrasonically vibrated by the ultrasonic vibration device, and the abutting part TP is obtained.
  • the convex mold 110 of the convex mold section 11 is further pierced into the base sheet 2A while generating heat due to friction and further softening, thereby forming the protrusion 3 that further protrudes from the other surface 2U of the base sheet 2A.
  • the array-shaped protrusions 3 in which the convex part 110 of the convex part 11 is inserted are parallel to the conveyance direction (Y direction) of the base sheet 2A. Move to.
  • the frequency and amplitude of the ultrasonic vibration of the convex part 11 by the ultrasonic vibration device are respectively higher than those in the protrusion precursor forming process. It is the same as the frequency and amplitude of the sonic vibration.
  • the opening area of the through-hole 3h of the protrusion 3 formed in the protrusion extension process is an area equal to or larger than the opening area S1 of the through-hole 3h of the protrusion precursor 3b formed in the protrusion precursor formation process. However, it is preferably the same area as the opening area S1.
  • the insertion speed for piercing the convex portion 11 into the base sheet 2A is pierced, and the piercing speed for inserting the convex portion 11 into the base sheet 2A in the protrusion precursor forming step. It is slower than the input speed.
  • the insertion speed for piercing the convex portion 11 into the base sheet 2A is excessively soft, the resin is excessively softened, and the size of the through hole 3h is greatly changed. If the speed is too fast, the softening becomes insufficient and the height of the protrusion 3 tends to be insufficient.
  • the protrusion 3 having the through-hole 3h it is preferably 0.1 mm / second or more, more preferably 1 mm / second. And preferably 1000 mm / second or less, more preferably 800 mm / second or less, specifically preferably 0.1 mm / second or more and 1000 mm / second or less, more preferably 1 mm / second or less. It is 2 seconds or more and 800 mm / seconds or less.
  • each contact portion TP in the base sheet 2A will be excessively softened. From the viewpoint of compensating for the softening shortage, it is preferably 0 seconds or more, and more preferably Is 0.1 second or longer, and preferably 10 seconds or shorter, more preferably 5 seconds or shorter, specifically preferably 0 seconds or longer and 10 seconds or shorter, and more preferably 0.1 seconds or shorter. 2 seconds or more.
  • the insertion height of the convex part 11 inserted into the base sheet 2A is preferably 0.01 mm from the viewpoint of efficiently forming the protrusion 3 having the through hole 3h. More preferably, it is 0.02 mm or more, and preferably 10 mm or less, more preferably 5 mm or less, specifically preferably 0.01 mm or more and 10 mm or less, more preferably 0.00. It is 02 mm or more and 5 mm or less.
  • the conditions of the heating means (not shown) provided in the convex part 11 in the protrusion precursor forming process and the heating means (not provided) in the convex part 11 in the protrusion extension process are the same as the conditions in FIG. It is slower than the speed of stabbing.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device, but the ultrasonic wave of the convex portion 11 included in the protrusion extending portion 10B.
  • the frequency and amplitude of the vibration are the same as the frequency and amplitude of the ultrasonic vibration of the convex portion 11 included in the projection precursor forming portion 10A, and the conditions (b) and (c) are not satisfied.
  • the insertion speed in the protrusion extension process is slower than the insertion speed in the protrusion precursor formation process. And satisfies the condition (a). For this reason, the amount of heat given from the convex portion 11 to the base sheet 2A in the projection extension step is larger than the amount of heat given from the convex portion 11 to the base sheet 2A in the projection portion precursor forming step.
  • the box motion type convex-shaped part 11 since the box motion type convex-shaped part 11 is used, regarding the insertion speed of the convex-shaped part 11 to the base material sheet 2A, from a protrusion part precursor formation process.
  • the insertion speed is continuously slowing down the protrusion extension process. That is, the insertion speed gradually decreases. Therefore, in the first embodiment, the amount of heat per unit insertion height given from the convex portion 11 to the base sheet 2A in the protrusion precursor forming step and the base portion from the convex portion 11 in the protrusion extension step.
  • the amount of heat per unit insertion height given to the material sheet 2A continuously changes from the latter stage of the projection precursor forming process to the first stage of the projection extension process.
  • the amount of heat per unit insertion height is a value obtained by dividing the total amount of heat applied to the base sheet 2A by the moving distance of the convex portion 11 in each step. For example, in the protrusion precursor forming step, the total amount of heat given to the base sheet 2A from the time when the convex portion 11 contacts the base sheet 2A to the end of the step is the total movement distance of the step. It is the value divided.
  • the cooling unit 20 is disposed downstream of the protrusion forming process, specifically downstream of the protrusion extending part 10B of the protrusion forming process. is set up.
  • the cooling unit 20 includes a cold air blowing device 21.
  • the protruding portion 3 is cooled using the cold air blower 21 while the protruding portion 11 is stuck inside the protruding portion 3 (cooling step).
  • the cold air blowing device 21 covers the entire other surface 2U side (upper surface side) and one surface 2D side (lower surface side) of the belt-shaped base sheet 2A being conveyed.
  • the belt-shaped base sheet 2A is conveyed in the conveyance direction (Y direction).
  • an air blowing port 22 for blowing cold air is provided on the other surface 2 U side (upper surface side) of the base sheet 2 ⁇ / b> A. It is designed to cool by spraying.
  • the cooling temperature and cooling time of the cold air blower 21 are also controlled by a control means (not shown) provided in the manufacturing apparatus 100B of the first embodiment.
  • the convex part 110 of the convex part 11 is placed in the protrusion 3 in the tunnel of the cold air blower 21.
  • the sheet In the state of being stabbed into the interior of the sheet, the sheet is conveyed in parallel with the conveyance direction (Y direction) of the base sheet 2A, and as shown in FIG. Cool air is blown from the blower opening 22 arranged on the upper surface side, and the protrusion 110 is cooled while the protrusion 110 of the protrusion 11 is inserted into the protrusion 3.
  • the ultrasonic vibration by the ultrasonic device of the convex portion 11 may be in a continuous state or stopped, but from the viewpoint of keeping the shape of the protrusion 3 constant without excessive deformation. It is preferable to be stopped.
  • the temperature of the cold air to be blown is preferably ⁇ 50 ° C. or higher, more preferably ⁇ 40 ° C. or higher, and preferably 26 ° C. or lower, more preferably, from the viewpoint of forming the protrusion 3 having the through hole 3h. It is 10 ° C. or lower, specifically, preferably ⁇ 50 ° C. or higher and 26 ° C. or lower, and more preferably ⁇ 40 ° C. or higher and 10 ° C. or lower.
  • the cooling time for cooling by blowing cold air is preferably 0.01 seconds or more, more preferably 0.5 seconds or more, and preferably 60 seconds or less, from the viewpoint of compatibility between moldability and processing time. More preferably, it is 30 seconds or less, specifically, preferably 0.01 seconds or more and 60 seconds or less, more preferably 0.5 seconds or more and 30 seconds or less.
  • the release unit 30 is installed downstream of the cooling unit 20.
  • the convex portion 11 is removed from the protrusion 3 to form the precursor 1A of the microneedle array 1M (release step).
  • the convex portion is formed from one surface 2D (lower surface) of the base sheet 2A.
  • a precursor 1A of a band-shaped fine hollow protrusion is formed to be a microneedle array 1M in which the protrusions 3 are arranged in an array.
  • a cutting unit 40 is installed downstream of the release unit 30.
  • the cutting unit 40 includes a cutter unit 41 having a cutter blade at the tip and an anvil unit 42.
  • the cutter blade of the cutter unit 41 is formed wider than the entire width (length in the X direction) of the belt-shaped fine hollow projection precursor 1A.
  • the belt-shaped fine hollow projection precursor 1A is transported between the pair of cutter parts 41 and the anvil part 42 and is adjacent to the transport direction (Y direction).
  • a single-sided microneedle array 1M in which protrusions 3 having through holes 3h are arranged in an array is continuously cut between the array-like protrusions 3 and 3 with a cutter blade of the cutter part 41.
  • the cutting of the strip-shaped fine hollow projection precursor 1A may be performed so as to extend in the lateral direction of each microneedle array 1M, and for example, can be performed linearly across the lateral direction of each microneedle array 1M. Or it can cut so that a cutting line may draw a curve. In any case, it is preferable to employ a cutting pattern that does not cause trimming by cutting.
  • the re-pitch part 50 is installed downstream of the cutting part 40.
  • the re-pitch unit 50 includes a plurality of rollers 51 that are arranged so that the rotation axes thereof are parallel to each other, and an endless conveyance belt 52 that is spanned between the rollers 51. have.
  • a suction box 53 is provided inside the conveyor belt 52.
  • the conveyor belt 52 is provided with a plurality of through holes (not shown) for sucking air from the outside to the inside of the circuit track by starting the suction box 53.
  • the conveyance speed of the conveyance belt 52 is faster than the conveyance speed of the base sheet 2 ⁇ / b> A up to the cutting unit 40.
  • the microneedle array 1M for each leaf is continuously placed on the transport belt 52 while being sucked by the suction box 53 through a through hole (not shown), and is transported in the transport direction.
  • the distance between the microneedle arrays 1M and 1M adjacent to each other in the front-and-rear direction is widened and rearranged at a predetermined distance to manufacture the microneedle array 1M as the fine hollow projection 1.
  • the protrusion precursor 3b having the through holes 3h As described above, according to the manufacturing method of the first embodiment for manufacturing the microneedle array 1M having the through holes 3h using the manufacturing apparatus 100B of the first embodiment, the protrusion precursor 3b having the through holes 3h.
  • the microneedle array 1M having the through-holes 3h can be manufactured with a simple process, and the cost can be reduced. Moreover, according to the manufacturing method of the first embodiment, the microneedle array 1M having the through holes 3h continuously and efficiently can be stably mass-produced.
  • “microneedle array having through-holes” means “microneedle array having microneedles that are protrusions having through-holes”.
  • the amount of heat given from the convex portion 11 to the base sheet 2A in the projection extension step is changed from the convex portion 11 to the base sheet 2A in the projection portion precursor forming step. Since it is larger than the amount of heat to be applied, the microneedle array 1M having a high quality through-hole 3h with higher accuracy of the height of the protrusion 3 and the size of the through-hole 3h of the protrusion 3 can be manufactured. . More specifically, since the amount of heat given to the base material sheet 2A is small in the protrusion part precursor forming step, it is a condition that the front end part is more easily opened than the base material sheet 2A is stretched.
  • the size of the through hole 3h at the tip is easy to control.
  • the amount of heat given to the base sheet 2A is large, and therefore the hole-formed protrusion precursor 3b is easily extended. Therefore, it becomes easy to design the height of the protrusion 3 while maintaining a good shape while suppressing damage to the shape of the through hole 3h.
  • the frequency and amplitude conditions of the ultrasonic vibration by the ultrasonic vibration device included in the convex portion 11 in the protrusion precursor forming step that is, the conditions of the heating means
  • the conditions of the frequency and amplitude of ultrasonic vibration (that is, the condition of the heating means) by the ultrasonic vibration device provided in the convex portion 11 in the protrusion extending step are the same.
  • the speed at which the convex part 11 is further stabbed into the base sheet 2A in the protrusion extension process is slower than the speed at which the convex part 11 is stabbed into the base sheet 2A in the protrusion precursor forming process.
  • the amount of heat given from the convex part 11 to the base material sheet 2A in the protrusion extension step is larger than the amount of heat given from the convex part 11 to the base material sheet 2A in the protrusion part precursor forming step. In this way, the rate at which the convex portion 11 is pierced into the base sheet 2A is changed, and the amount of heat given from the convex portion 11 to the base sheet 2A in the projection extension step is determined in the projection precursor formation step. Since the amount of heat applied from the convex portion 11 to the base sheet 2A is larger, it is easier to control the accuracy of the height of the protrusion 3 provided in the microneedle array 1M and the size of the through hole 3h of the protrusion 3.
  • the microneedle array 1M having the high-quality through-holes 3h can be further manufactured. Moreover, according to the manufacturing method of 1st Embodiment, since the total calorie
  • the projection from the projection precursor forming step using the box motion type convex portion 11 is performed.
  • the insertion speed is continuously reduced.
  • the amount of heat given from the convex part 11 to the base sheet 2A in the protrusion part precursor forming step and the amount of heat given from the convex part 11 to the base sheet 2A in the protrusion extension step are the protrusion part precursor. It changes continuously from the formation process to the protrusion extension process. Therefore, it is easier to control the accuracy of the height of the protrusion 3 provided in the microneedle array 1M and the size of the through hole 3h of the protrusion 3.
  • the ultrasonic vibration device is used as the heating means (not shown) of the convex portion 11, it is not always necessary to provide the cold air blower 21, and the ultrasonic vibration device. It is possible to cool by simply turning off the vibration.
  • the microneedle array 1M having the through holes 3h can be manufactured at a high speed with simplification of the apparatus.
  • heat is more difficult to be transmitted, and since cooling is efficiently performed by turning off the ultrasonic vibration, deformation other than the molded portion occurs. It is difficult to manufacture the microneedle array 1M with high accuracy.
  • the protrusion forming unit 10 of the manufacturing apparatus 100B is configured to control the operation of the convex part 11 and the heating means (not shown) of the convex part 11 by the control means (not shown).
  • the heating conditions, the cooling temperature of the cold air blower 21 and the cooling time are controlled. Therefore, by controlling the insertion height of the convex portion 11 in the protrusion extension process, for example, by the control means (not shown), the insertion amount of the convex portion 11 into the base sheet 2A can be easily changed.
  • the protrusion height H1 of the manufactured microneedle array 1M can be controlled.
  • the conditions of the heating means (not shown) of the convex part 11, the softening time of the contact part TP of the base sheet 2A, the insertion speed of the convex part 11 into the base sheet 2A, and the shape of the convex part 11 If at least one of these is controlled, the thickness T1 and the like of the protrusions 3 constituting the microneedle array 1M can be freely controlled, and the shape of the microneedle array 1M having the through holes 3h can be freely controlled. be able to.
  • the shape of the microneedle array 1M can be freely controlled by controlling at least one of the cooling conditions in the process.
  • a pair of support members 12 and 12 disposed on the other surface 2U side (upper surface side) of the base sheet 2A is used.
  • the projecting portion 11 is brought into contact with one surface 2D (lower surface) on the opposite side of the surface, and the contact portion TP is softened to form the projection 3.
  • the recessed part etc. which fit in the convex part 11 for forming the protrusion part 3 are unnecessary, cost increase can be suppressed, and the protrusion part 3 with which the microneedle array 1M to be manufactured is provided can be efficiently used. Can be formed with high accuracy.
  • the present invention (second invention) will be described based on the second embodiment with reference to FIG.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device, but in the second embodiment used in the second embodiment.
  • the manufacturing apparatus 100B uses a heater device instead.
  • the heating means (not shown) of the convex portion 11 is a heater device as in the manufacturing apparatus 100B of the second embodiment, as shown in FIG.
  • the convex part 11 is heated by the apparatus, heat is generated in the contact part TP, and the contact part TP is softened.
  • the projection part precursor formation process of a 2nd embodiment as shown in FIG.17 (b)
  • the convex portion 11 is raised toward the upper surface and the tip of the convex mold 110 is pierced into the base sheet 2A.
  • a hollow projection part precursor 3b having the following is formed.
  • the heating temperature of the base sheet 2A by the convex part 11 is the glass transition temperature of the base sheet 2A used from the viewpoint of the formation of the projection part precursor 3b. It is preferable that the temperature is higher than or equal to (Tg) and lower than the melting temperature, and more preferably higher than or equal to the softening temperature of the resin and lower than the melting temperature. More specifically, the heating temperature is preferably 30 ° C. or higher, more preferably 40 ° C. or higher, and preferably 300 ° C. or lower, more preferably 250 ° C. or lower. It is not less than 300 ° C and more preferably not less than 40 ° C and not more than 250 ° C.
  • the said heating temperature is applied as a temperature range of the part of the base material sheet 2A which contacted the convex mold 110, also when heating the base material sheet 2A using an ultrasonic vibration apparatus in 1st Embodiment. .
  • the “glass transition temperature (Tg) of the base sheet” means the glass transition temperature (Tg) of the constituent resin of the base sheet, and when there are a plurality of types of the constituent resins, the plurality of types of glass transitions.
  • the heating temperature of the base sheet by the heating means is preferably at least the lowest glass transition temperature (Tg) among the plurality of glass transition temperatures (Tg), More preferably, the glass transition temperature (Tg) is higher than the highest glass transition temperature (Tg).
  • the "softening temperature of the base sheet” is also the same as the glass transition temperature (Tg), that is, when there are a plurality of types of constituent resins of the base sheet, when the plurality of types of softening temperatures are different from each other,
  • the heating temperature of the base sheet by the heating means is preferably at least the lowest softening temperature among the plurality of softening temperatures, and more preferably at least the highest softening temperature among the plurality of softening temperatures.
  • the heating temperature of the base sheet by the heating means is preferably less than the lowest melting point among the plurality of melting points. .
  • Tg glass transition point
  • the amount of heat is measured using a DSC measuring machine to determine the glass transition temperature.
  • the measuring instrument uses a differential scanning calorimeter (Diamond DSC) manufactured by Perkin Elmer. 10 mg of a test piece is collected from the base sheet. The measurement conditions are that 20 ° C. is isothermal for 5 minutes, and then the temperature is increased from 20 ° C. to 320 ° C. at a rate of 5 ° C./min to obtain a DSC curve of the horizontal axis temperature and the vertical axis calorific value. And glass transition temperature Tg is calculated
  • the convex part 11 is moved at the same temperature as the protrusion precursor formation process by the heater device.
  • the convex portion 11 is further raised from one surface 2D (lower surface) of the base sheet 2A toward the other surface 2U (upper surface) while heating and generating heat at the contact portion TP to soften the contact portion TP.
  • the tip portion of the convex mold 110 is further stabbed into the base sheet 2A to form a protrusion 3 having a through hole 3h that further protrudes from the other surface 2U (upper surface) of the base sheet 2A.
  • the insertion speed for inserting the convex portion 11 into the base sheet 2A is pierced into the base sheet 2A in the protruding portion precursor forming step. It is slower than the speed of insertion.
  • the heating means (not shown) of the convex part 11 is a heater, but the heater temperature and the convex part of the convex part 11 of the protrusion extension part 10B.
  • the heater temperature of the convex portion 11 of the precursor forming portion 10A is the same temperature and does not satisfy the condition (d).
  • the insertion speed in the protrusion extension step is slower than the insertion speed in the protrusion precursor formation step. And satisfies the condition (a). For this reason, the amount of heat given from the convex portion 11 to the base sheet 2A in the projection extension step is larger than the amount of heat given from the convex portion 11 to the base sheet 2A in the projection portion precursor forming step.
  • the other surface 2U side (upper surface side) of the base sheet 2A in the tunnel. Cooling air is blown from the air outlet 22 arranged in the air-cooling port 22, and the protrusion 3 is cooled while the protrusion 110 of the protrusion 11 is inserted into the protrusion 3.
  • the heating of the convex portion 11 by the heater device may be continued or stopped.
  • the cooling unit 20 installed downstream of the protrusion forming unit 10 is natural. Although cooling may be sufficient, it is preferable to provide the cold air blower 21 and perform positive cooling.
  • the convex portion 11 is lowered from one surface 2D (lower surface) of the base sheet 2A. Then, from the state in which the convex mold 110 of the convex mold section 11 is inserted into each projection section 3, the convex mold 110 of the convex mold section 11 is pulled out, and the projection section having a through hole 3h and having a hollow inside.
  • a precursor 1A of a band-shaped fine hollow projection that becomes a microneedle array 1M in which 3 is arranged in an array is formed.
  • the single-sided microneedle array 1M in which the projections 3 having the through holes 3h are arranged in an array by cutting with the cutter blade of the cutter unit 41. are continuously arranged and rearranged in the re-pitch portion 50 to produce the microneedle array 1M.
  • the heating condition (condition of the heating means) by the heating heater device provided in the convex portion 11 in the protrusion precursor forming process, and the protrusion extending process are the same.
  • the speed at which the convex part 11 is further stabbed into the base sheet 2A in the protrusion extension process is slower than the speed at which the convex part 11 is stabbed into the base sheet 2A in the protrusion precursor forming process.
  • the amount of heat given from the convex part 11 to the base material sheet 2A in the protrusion extension step is larger than the amount of heat given from the convex part 11 to the base material sheet 2A in the protrusion part precursor forming step. In this way, the rate at which the convex portion 11 is pierced into the base sheet 2A is changed, and the amount of heat given from the convex portion 11 to the base sheet 2A in the projection extension step is determined in the projection precursor formation step. Since the amount of heat applied from the convex portion 11 to the base sheet 2A is larger, it is easier to control the accuracy of the height of the protrusion 3 provided in the microneedle array 1M and the size of the through hole 3h of the protrusion 3. The microneedle array 1M having the high-quality through-holes 3h can be further manufactured.
  • heat due to the heating of the convex portion 11 is efficiently transmitted to the abutting portion TP, and the surrounding portion becomes an environment where only the desired heating can be applied. 3 is less likely to occur, the substrate sheet 2A is less likely to be distorted, and the substrate sheet 2A is easily continuously conveyed.
  • the manufacturing method of this invention is a manufacturing method of the fine hollow protrusion which has a through-hole.
  • FIG. 19 shows a perspective view of a microneedle array 1M as a fine hollow protrusion of one embodiment manufactured by the method of manufacturing the fine hollow protrusion 1 of the first embodiment.
  • the microneedle array 1M of this embodiment has a sheet-like base portion 2 and a plurality of protrusions 3.
  • the number of the protrusions 3, the arrangement of the protrusions 3, and the shape of the protrusions 3 are not particularly limited, but the microneedle array 1M of the present embodiment is preferably provided on the upper surface of the sheet-like base 2.
  • Nine frustoconical protrusions 3 are arranged in an array (matrix).
  • Nine protrusions 3 arranged in an array (matrix) form three rows in the Y direction, which is a direction (longitudinal direction of the base sheet 2A) for transporting a base sheet 2A described later, and are orthogonal to the transport direction. It is arranged in three rows in the X direction, which is the horizontal direction of the direction and the substrate sheet 2A to be conveyed.
  • FIG. 20 is a perspective view of the microneedle array 1M focusing on one of the protrusions 3 in the array (matrix) shape of the microneedle array 1M, and FIG. FIG. 3 is a sectional view taken along line III-III.
  • the microneedle array 1M has a through hole 3h as shown in FIG.
  • a space extending from the base portion 2 to the through hole 3h is formed inside each protrusion 3, and each protrusion 3 A through-hole 3h is formed at the tip of each.
  • the space inside each protrusion 3 is formed in a shape corresponding to the outer shape of the protrusion 3 in the microneedle array 1M.
  • the space corresponding to the outer shape of the frustoconical protrusion 3 is formed. It is formed in a truncated cone shape.
  • the projection part 3 is truncated cone shape in this embodiment, cylindrical shape, prismatic shape, truncated pyramid shape, etc. may be sufficient other than a truncated cone shape.
  • Each protrusion 3 of the microneedle array 1M has a protrusion height H1 of preferably 0.01 mm or more, more preferably 0.1 mm because the protrusion height H1 penetrates the stratum corneum at the shallowest point and deeply into the dermis. It is 02 mm or more, preferably 10 mm or less, more preferably 5 mm or less, specifically preferably 0.01 mm or more and 10 mm or less, and more preferably 0.02 mm or more and 5 mm or less.
  • Each protrusion 3 has an average thickness T1 of preferably 0.005 mm or more, more preferably 0.01 mm or more, and preferably 1.0 mm or less, more preferably 0.5 mm or less, Specifically, it is preferably 0.005 mm or more and 1.0 mm or less, and more preferably 0.01 mm or more and 0.5 mm or less.
  • the base 2 has a thickness T2 of preferably 0.01 mm or more, more preferably 0.02 mm or more, and preferably 1.0 mm or less, more preferably 0.7 mm or less. Is preferably 0.01 mm or more and 1.0 mm or less, more preferably 0.02 mm or more and 0.7 mm or less.
  • the tip diameter L of each protrusion 3 of the microneedle array 1M is preferably 1 ⁇ m or more, more preferably 5 ⁇ m or more, and preferably 500 ⁇ m or less, more preferably 300 ⁇ m or less. Specifically, it is preferably 1 ⁇ m or more and 500 ⁇ m or less, and more preferably 5 ⁇ m or more and 300 ⁇ m or less.
  • the tip diameter L of the fine hollow projection 1 is the length at the widest position at the tip of the projection 3. Within this range, there is almost no pain when the microneedle array 1M is inserted into the skin.
  • the fine hollow protrusion 1 includes a through hole 3 h located at the tip of each protrusion 3, and a base side through hole 2 h located on the lower surface of the base 2 corresponding to each protrusion 3. have.
  • the through hole 3h and the base side through hole 2h are formed concentrically.
  • the opening area S1 is good properly is 0.7 [mu] m 2 or more, more preferably 20 [mu] m 2 or more, and preferably not 200000Myuemu 2 or less, still more preferably 70000Myuemu 2 or less, particularly specifically, the preferably at 0.7 [mu] m 2 or more 200000Myuemu 2 or less, still more preferably 20 [mu] m 2 or more 70000Myuemu 2 or less.
  • the opening area S2 of the base side through hole 2h is preferably 0.007 mm 2 or more, more preferably 0.03 mm 2 or more, and preferably 20 mm 2 or less, more preferably 7 mm 2 or less. in and, specifically, preferably at 0.007 mm 2 or more 20 mm 2 or less, more preferably at 0.03 mm 2 or more 7 mm 2 or less.
  • the nine protrusions 3 arranged in an array (matrix) on the upper surface of the sheet-like base 2 have a uniform center distance in the vertical direction (Y direction) and a center distance in the horizontal direction (X direction). Is preferably uniform, and the center-to-center distance in the vertical direction (Y direction) and the center-to-center distance in the horizontal direction (X direction) are preferably the same distance.
  • the center-to-center distance in the longitudinal direction (Y direction) of the protrusion 3 is preferably 0.01 mm or more, more preferably 0.05 mm or more, and preferably 10 mm or less, more preferably 5 mm.
  • the distance between the centers of the protrusions 3 in the lateral direction (X direction) is preferably 0.01 mm or more, more preferably 0.05 mm or more, and preferably 10 mm or less, more preferably 5 mm or less.
  • it is preferably 0.01 mm or more and 10 mm or less, and more preferably 0.05 mm or more and 5 mm or less.
  • FIG. 22 shows the overall configuration of a manufacturing apparatus 100C according to the first embodiment used for carrying out the manufacturing method according to the first embodiment.
  • each protrusion 3 of the microneedle array 1M is very small, but for convenience of explanation, each protrusion 3 of the microneedle array 1M is drawn very large in FIG. .
  • the manufacturing apparatus 100C has, from the upstream side toward the downstream side, a protrusion part forming part 10 that forms the protrusion part 3 on the base sheet 2A, a cooling part 20, and a convex part 11 described later.
  • a release portion 30 a cutting portion 40 for cutting each microneedle array 1M, and a re-pitch portion 50 for adjusting the interval between the microneedle arrays 1M.
  • the direction in which the base sheet 2A is transported is the Y direction
  • the direction orthogonal to the transport direction and the lateral direction of the transported base sheet 2A are transported in the X direction.
  • the thickness direction of the base material sheet 2 ⁇ / b> A will be described as the Z direction.
  • the protruding portion forming portion 10 includes a convex portion 11 having a heating means (not shown).
  • the convex part 11 has a convex part 110 corresponding to the number and arrangement of the protruding parts 3 of the microneedle array 1M to be manufactured and the substantially outer shape of each protruding part 3, and in the manufacturing apparatus 100C of the first embodiment.
  • a heating means other than the heating means (not shown) of the convex-shaped part 11 is not provided.
  • heating means other than the heating means of the convex portion 11 not only refers to the case of excluding other heating means, but also below the softening temperature of the base sheet 2A, Or the case where a means for heating below the glass transition temperature is provided is included. However, it is preferable not to include any other heating means.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device.
  • the belt-like base sheet 2A is fed out from the raw roll of the base sheet 2A formed by including the thermoplastic resin, and is conveyed in the Y direction.
  • the convex part 11 is contact
  • the protruding portion 11 is pierced into the base sheet 2A toward the other surface 2U, and the protrusion 3 protruding from the other surface 2U side of the base sheet 2A is formed (projection forming step).
  • the receiving member 13 disposed on the other surface 2U side of the base sheet 2A with a space from the other surface 2U is used.
  • the convex portion 11 comes into contact with the receiving member 13, and the through hole 3 h is formed in the protruding portion 3.
  • a part of the base sheet 2A stretched by the convex portion 11 contacts the receiving member 13, and the base sheet 2A is in contact with the convex portion 11. It is in a state of being sandwiched between the receiving member 13.
  • the convex portion 11 is pushed into the base sheet 2A until it penetrates the base sheet 2A, and the convex portion 11 protrudes from the other surface 2U side of the base sheet 2A and penetrates to the other surface 2U side of the base sheet 2A.
  • a protrusion 3 having a through hole 3h is formed.
  • the conical convex mold 110 having nine sharp tips is arranged on the convex portion 11 with the tips facing upward.
  • the portion 11 is movable up and down at least in the thickness direction (Z direction). More preferably, in the manufacturing apparatus 100C of the first embodiment, the convex portion 11 can be moved up and down in the thickness direction (Z direction) by an electric actuator (not shown), and the conveyance direction (Y Direction) and can run parallel to the base sheet 2A. Control of the operation of the convex portion 11 is controlled by a control means (not shown) provided in the manufacturing apparatus 100C of the first embodiment.
  • the manufacturing apparatus 100 ⁇ / b> C of the first embodiment is an apparatus having the so-called box motion type convex portion 11 that draws an endless track. Control of heating of the heating means (not shown) of the convex portion 11 is also controlled by a control means (not shown) provided in the manufacturing apparatus 100C of the first embodiment.
  • the base material sheet 2A is a sheet that becomes the base portion 2 of the microneedle array 1M to be manufactured, and is formed including a thermoplastic resin.
  • the thermoplastic resin include poly fatty acid ester, polycarbonate, polypropylene, polyethylene, polyester, polyamide, polyamideimide, polyetheretherketone, polyetherimide, polystyrene, polyethylene terephthalate, polyvinyl chloride, nylon resin, acrylic resin, etc.
  • poly fatty acid esters are preferably used.
  • Specific examples of the polyfatty acid ester include polylactic acid, polyglycolic acid, and combinations thereof.
  • the base sheet 2A may be formed of a mixture containing hyaluronic acid, collagen, starch, cellulose and the like in addition to the thermoplastic resin.
  • the thickness of the base sheet 2A is equal to the thickness T2 of the base portion 2 of the microneedle array 1M to be manufactured.
  • the convex mold 110 of the convex mold part 11 has a sharper outer shape than the outer shape of the protrusion 3 of the microneedle array 1M.
  • the convex mold 110 of the convex mold section 11 is formed such that its height H2 (see FIG. 22) is higher than the height H1 of the microneedle array 1M to be manufactured, preferably 0.01 mm or more, more preferably Is 0.02 mm or more, preferably 30 mm or less, more preferably 20 mm or less, specifically preferably 0.01 mm or more and 30 mm or less, more preferably 0.02 mm or more and 20 mm or less. It is.
  • the convex mold 110 of the convex mold part 11 has a tip diameter D1 (see FIG.
  • the tip diameter D1 of the convex mold 110 of the convex mold part 11 is measured as follows.
  • the convex mold 110 of the convex mold section 11 has a root diameter D2 (see FIG.
  • the convex mold 110 of the convex mold section 11 has a tip angle ⁇ (see FIG. 23) of preferably 1 degree or more, more preferably 5 degrees or more, from the viewpoint that sufficient strength is easily obtained.
  • the tip angle ⁇ is preferably 60 degrees or less, more preferably 45 degrees or less from the viewpoint of obtaining the protrusion 3 having an appropriate angle, and specifically, preferably 1 degree or more and 60 degrees or less. More preferably, it is 5 degrees or more and 45 degrees or less.
  • the tip angle ⁇ of the convex mold 110 of the convex mold part 11 is measured as follows.
  • a location where one side 11a is separated from the virtual straight line ILa is obtained as a first distal point 11a1
  • a location where the other side 11b is separated from the virtual straight line ILb is obtained as a second distal point 11b1.
  • the length D1 of the straight line connecting the first tip point 11a1 and the second tip point 11b1 thus determined is measured using a scanning electron microscope (SEM) or a microscope, and the measured length of the straight line is measured. Is the tip diameter of the convex mold 110.
  • the angle formed between the virtual straight line ILa and the virtual straight line ILb is measured using a scanning electron microscope (SEM) or a microscope, and the measured angle is determined as the tip angle ⁇ of the convex mold 110 of the convex portion 11.
  • the convex part 11 is formed of a high-strength material that is difficult to break.
  • Examples of the material of the convex part 11 include metals such as steel, stainless steel, aluminum, aluminum alloy, nickel, nickel alloy, cobalt, cobalt alloy, copper, copper alloy, beryllium copper, and beryllium copper alloy, or ceramic. .
  • the receiving member 13 used in the manufacturing method of the fine hollow projection of the present invention is arranged on the other surface 2U side of the base sheet 2A with a space from the base sheet 2A.
  • the length of the plate-shaped receiving member 13 in the Y direction is substantially the same as the length of the convex portion 11 in the Y direction
  • the length in the X direction is substantially the same as the length of the convex portion 11 in the X direction. The same.
  • such a plate-shaped receiving member 13 is a box motion type convex shape with the base material sheet 2A being conveyed in the Y direction interposed therebetween, as shown in FIG.
  • An endless trajectory is drawn by the box motion type so as to perform the operation of the unit 11 and the operation of the target.
  • the box motion type receiving member 13 is arranged at a distance from the other surface 2U of the base sheet 2A in the thickness direction (Z direction) with an interval therebetween, and the base sheet 2A in the transport direction (Y direction). Parallel running is possible.
  • the movement speed of the receiving member 13 in the conveyance direction (Y direction) corresponds to the movement speed of the convex portion 11 in the conveyance direction (Y direction), and is provided in the manufacturing apparatus 100C of the first embodiment. It is controlled by control means (not shown).
  • the receiving member 13 only needs to be harder than the hardness of the base sheet 2A when the convex portion 11 is inserted into the base sheet 2A and comes into contact with the receiving member 13, an elastic member such as rubber, You may form from the same material as the material of synthetic resin or the convex part 11, etc. In addition, it is preferable from the viewpoint of the ease of processing that the hardness of the material of the receiving member 13 is higher than the hardness of the softened base sheet 2A when the base sheet 2A is heated to the softening temperature or higher.
  • the interval between the receiving member 13 and the base sheet 2A coincides with the protruding height H1 of the protruding portion 3 of the manufactured microneedle array 1M, and according to the protruding height H1 of the protruding portion 3 to be manufactured, It can be changed by a control means (not shown) provided in the manufacturing apparatus 100C of the first embodiment.
  • the receiving member 13 has a recess 131 in the manufacturing apparatus 100 ⁇ / b> C of the first embodiment, and preferably has the recess 131 in a portion in contact with the convex portion 11.
  • the shape of the opening peripheral edge 131a of the recess 131 matches the shape of the outer periphery 11c (see FIG. 23) at the position in contact with the receiving member 13 on the peripheral wall 11W of the convex portion 11.
  • the manufacturing apparatus 100 ⁇ / b> C of the first embodiment has nine concave portions 131 corresponding to the nine convex molds 110.
  • the shape of the opening periphery 131a of the recess 131 is the contour shape of the recess 131 when the recess 131 formed on the surface of the receiving member 13 on the base sheet 2A side is viewed from the base sheet 2A side.
  • the shape of the outer periphery 11 c of the convex portion 11 is the contour of the convex die 110 when the convex die 110 is viewed in cross section at a position in contact with the receiving member 13 on the peripheral wall 11 W of the convex die 110 of the convex die portion 11.
  • each convex mold 110 is conical, the shape of each outer periphery 11c is circular, and the shape of the opening peripheral edge 131a of each recess 131 is also circular. If the shape of the convex mold 110 is a pyramid shape, the shape of the outer periphery 11c is a rectangular shape, and the shape of the opening peripheral edge 131a of the concave portion 131 is also a rectangular shape.
  • each recess 131 of the receiving member 13 only the shape of the opening peripheral edge 131 a is required to coincide with the shape of the outer periphery 11 c of each convex portion 11, and the shape inside the receiving member 13 is particularly limited rather than the opening peripheral edge 131 a.
  • the manufacturing apparatus 100C of the first embodiment as shown in FIG. 24, it is formed in a columnar shape.
  • the protruding portion forming portion 10 is a support member 12 that supports the base sheet 2A when the protruding portion 11 is pierced into the base sheet 2A as shown in FIG. have.
  • the support member 12 is disposed on the other surface 2U side of the base sheet 2A, and plays a role of making the sheet base material 2A difficult to bend when the convex portion 11 is inserted from the one surface 2D side.
  • the support member 12 is arrange
  • Each support member 12 extends from the protrusion forming part 10 to the position where the release part 30 ends through the cooling part 20.
  • the material for forming the support member 12 may be the same material as that of the convex portion 11, or may be formed of a synthetic resin or the like.
  • the protruding portion forming step of the first embodiment is arranged on the other surface 2U side (upper surface side) of the belt-shaped base sheet 2A that is fed from the raw roll and conveyed in the Y direction.
  • the paired support members 12 and 12 support both side portions along the conveyance direction (Y direction) of the base sheet 2A. Then, using the box motion type convex portion 11, the portion of the base sheet 2A that is not supported by the support member 12, that is, one surface of the central region between the pair of support members 12 and 12 in the base sheet 2A The tip of each convex mold 110 of the convex mold part 11 is brought into contact with the 2D side (lower surface side).
  • the convex portion 11 is ultrasonically vibrated by an ultrasonic vibration device, and heat due to friction is applied to the contact portion TP.
  • the contact portion TP is softened by being generated.
  • the convex part 11 is raised toward the side (upper surface side), and the tip of the convex part 110 is pierced into the base sheet 2A.
  • FIG. 25C shows an enlarged cross-sectional view of the main part of FIG.
  • the box motion type convex portion 11 is moved upward in the thickness direction (Z direction) by an electric actuator (not shown).
  • Each convex mold 110 of the portion 11 is pierced into the base sheet 2A, and the protrusion 3 protruding from the other surface 2U side of the base sheet 2A is formed. And the convex part 11 is further moved upward in the thickness direction (Z direction) by an electric actuator (not shown), and as shown in FIG. 26, the tip of each convex mold 110 of the convex part 11 is moved to the receiving member. 13 is pierced to the inside of a cylindrical recess 131 formed on the surface of the base material sheet 2A.
  • the base sheet 12 is brought into contact with the opening peripheral edge 131a of the recess 131, and further or simultaneously, the peripheral wall 11W of the convex portion 11 is brought into contact with the outer periphery 11c of the peripheral wall 11W, so that the convex portion 11 is brought into contact with the base sheet.
  • Penetrate 2A As described above, in the manufacturing apparatus 100C according to the first embodiment, the convex portion 110 of the convex portion 11 and the concave portion 131 of the receiving member 13 project from the other surface 2U side of the base sheet 2A and the base sheet 2A. Protrusions 3 having through holes 3h penetrating on the other surface 2U side are formed in an array.
  • the arrayed protruding portions 3 in which the convex portions 110 of the convex portion 11 are inserted are parallel to the conveyance direction (Y direction) of the base sheet 2A. Moving.
  • the ultrasonic vibration by the ultrasonic vibration device of the convex portion 11 is preferably 10 kHz or more in terms of the frequency from the viewpoint of forming the protrusion 3 having the through hole 3h. More preferably, it is 15 kHz or more, and preferably 50 kHz or less, more preferably 40 kHz or less, specifically preferably 10 kHz or more and 50 kHz or less, more preferably 15 kHz or more and 40 kHz or less.
  • the amplitude thereof is preferably 1 ⁇ m or more, more preferably 5 ⁇ m or more, from the viewpoint of forming the protrusion 3 having the through hole 3h, and Preferably it is 60 micrometers or less, More preferably, it is 50 micrometers or less, Specifically, Preferably they are 1 micrometer or more and 60 micrometers or less, More preferably, they are 5 micrometers or more and 50 micrometers or less.
  • the frequency and amplitude of the ultrasonic vibration of the convex portion 11 may be adjusted in the above-described range in the protrusion forming step.
  • the insertion speed for piercing the convex portion 11 into the base sheet 2A is preferably 0 from the viewpoint of efficiently forming the projection 3 having the through hole 3h.
  • 1 mm / second or more more preferably 1 mm / second or more, and preferably 1000 mm / second or less, more preferably 800 mm / second or less, and specifically 0.1 mm / second or more. It is 1000 mm / second or less, More preferably, it is 1 mm / second or more and 800 mm / second or less.
  • the insertion height of the convex portion 11 to be inserted into the base sheet 2A is determined from the viewpoint of efficiently forming the through hole 3h of the protruding portion 3 and the receiving member 13. It is higher than the distance between the base sheet 2A, that is, the protrusion height H1 of the protrusion 3 of the microneedle array 1M to be manufactured, preferably 0.01 mm or more, more preferably 0.02 mm or more, and Preferably it is 10 mm or less, More preferably, it is 5 mm or less, Specifically, Preferably it is 0.01 mm or more and 10 mm or less, More preferably, it is 0.02 mm or more and 5 mm or less.
  • the insertion height means that in the state where the convex mold 110 of the convex mold portion 11 is most inserted into the base sheet 2A, the apex of the convex mold 110 of the convex mold section 11 and the base sheet 2A. It means the distance between the other surface 2U (upper surface). Therefore, the insertion height in the protruding portion forming step refers to the other surface in a state where the protruding die 110 is deeply inserted in the protruding portion forming step and the protruding die 110 comes out from the other surface 2U of the base sheet 2A. This is the distance from 2U to the peak of the convex 110 measured in the vertical direction.
  • each contact portion TP in the base sheet 2A will be excessively softened, but from the viewpoint of compensating for insufficient softening, it is preferably 0 seconds or more, and further Preferably it is 0.1 second or more, and preferably 10 seconds or less, more preferably 5 seconds or less, specifically preferably 0 seconds or more and 10 seconds or less, more preferably 0. It is 1 second or more and 5 seconds or less.
  • the cooling unit 20 is installed downstream of the protrusion forming unit 10.
  • the cooling unit 20 includes a cold air blowing device 21.
  • the protruding portion 3 is cooled using the cold air blower 21 while the protruding portion 11 is stabbed inside the protruding portion 3 (cooling step).
  • the cold air blowing device 21 covers the entire other surface 2U side (upper surface side) and one surface 2D side (lower surface side) of the belt-shaped base sheet 2A being conveyed.
  • the belt-shaped base sheet 2A is conveyed in the conveyance direction (Y direction).
  • a blower port 22 for blowing cold air is provided between the other surface 2U side (upper surface side) of the base sheet 2A and the receiving member 13. And it cools by blowing cold air from the blower opening 22.
  • Control of the cooling temperature and cooling time of the cold air blower 21 is also controlled by a control means (not shown) provided in the manufacturing apparatus 100C of the first embodiment.
  • the convex mold 110 of the convex mold 11 is placed in the projection 3 by using the box motion type convex mold 11 in the tunnel of the cold air blower 21.
  • the substrate sheet 2A is conveyed in parallel to the conveyance direction (Y direction) of the substrate sheet 2A, and as shown in FIG. Cool air is blown from the air outlet 22 arranged on the side), and the protrusion 110 is cooled while the protrusion 110 of the protrusion 11 is stuck inside the protrusion 3.
  • the ultrasonic vibration by the ultrasonic device of the convex portion 11 may be in a continuous state or stopped, but from the viewpoint of keeping the opening area of the through hole 3h of the protrusion 3 constant. It is preferable to be stopped.
  • the temperature of the cold air to be blown is preferably ⁇ 50 ° C. or higher, more preferably ⁇ 40 ° C. or higher, and preferably 26 ° C. or lower, more preferably, from the viewpoint of forming the protrusion 3 having the through hole 3h. It is 10 ° C. or lower, specifically, preferably ⁇ 50 ° C. or higher and 26 ° C. or lower, and more preferably ⁇ 40 ° C. or higher and 10 ° C. or lower.
  • the cooling time for cooling by blowing cold air is preferably 0.01 seconds or more, more preferably 0.5 seconds or more, and preferably 60 seconds or less, from the viewpoint of compatibility between moldability and processing time. More preferably, it is 30 seconds or less, specifically, preferably 0.01 seconds or more and 60 seconds or less, more preferably 0.5 seconds or more and 30 seconds or less.
  • a release unit 30 is installed downstream of the cooling unit 20.
  • the convex portion 11 is removed from the protrusion 3 to form the precursor 1A of the microneedle array 1M (release step).
  • the convex portion 11 of the base sheet 2A is protruded from the one surface 2D side (lower surface side) using the box motion type convex portion 11.
  • the convex mold 110 of the convex mold part 11 is pulled out to have a through hole 3h and the inside A precursor 1A of a band-shaped fine hollow protrusion is formed which becomes a microneedle array 1M in which hollow protrusions 3 are arranged in an array.
  • a cutting unit 40 is installed downstream of the release unit 30.
  • the cutting unit 40 includes a cutter unit 41 having a cutter blade at the tip and an anvil unit 42.
  • the cutter blade of the cutter unit 41 is formed wider than the entire width (length in the X direction) of the belt-shaped fine hollow projection precursor 1A.
  • the belt-shaped fine hollow projection precursor 1A is transported between the pair of cutter parts 41 and the anvil part 42 and is adjacent to the transport direction (Y direction).
  • a single-sided microneedle array 1M in which protrusions 3 having through holes 3h are arranged in an array is continuously cut between the array-like protrusions 3 and 3 with a cutter blade of the cutter part 41.
  • the cutting of the strip-shaped fine hollow projection precursor 1A may be performed so as to extend in the lateral direction of each microneedle array 1M, and for example, can be performed linearly across the lateral direction of each microneedle array 1M. Or it can cut so that a cutting line may draw a curve. In any case, it is preferable to employ a cutting pattern that does not cause trimming by cutting.
  • the re-pitch part 50 is installed downstream of the cutting part 40.
  • the re-pitch unit 50 includes a plurality of rollers 51 that are arranged so that their rotation axes are parallel to each other, and an endless conveyance belt 52 that is spanned between the rollers 51. have.
  • a suction box 53 is provided inside the conveyor belt 52.
  • the conveyor belt 52 is provided with a plurality of through holes (not shown) for sucking air from the outside to the inside of the circuit track by starting the suction box 53.
  • the conveyance speed of the conveyance belt 52 is faster than the conveyance speed of the base sheet 2 ⁇ / b> A up to the cutting unit 40.
  • the microneedle array 1M for each leaf is continuously placed on the transport belt 52 while being sucked by the suction box 53 through a through hole (not shown), and is transported in the transport direction.
  • the distance between the microneedle arrays 1M and 1M adjacent to each other in the front-and-rear direction is widened and rearranged at a predetermined distance to manufacture the microneedle array 1M as the fine hollow projection 1.
  • the convex portion 11 including the ultrasonic device. And a receiving member 13 arranged at a distance from the base sheet 2A, and a part of the convex portion 11 is in contact with the receiving member 13 on the tip side from the base and penetrates the base sheet 2A. Until then, the convex part 11 is pierced into the base sheet 2A, so that the height accuracy of the projection 3 of the fine hollow projection is high, and the size of the through hole 3h is high and the high quality through hole 3h. Can be manufactured.
  • the microneedle array 1M having the through-holes 3h can be manufactured with a simple process, and the cost can be reduced. Moreover, according to the manufacturing method of the first embodiment, the microneedle array 1M having the through holes 3h continuously and efficiently can be stably mass-produced.
  • “microneedle array having through-holes” means “microneedle array having microneedles that are protrusions having through-holes”.
  • the receiving member 13 to be used has the recess 131 in the portion that contacts the convex portion 11, as shown in FIG. It corresponds to the shape of the outer periphery 11c in the peripheral wall 11W of the convex portion 11.
  • the tip of each convex mold 110 of the convex mold part 11 is pierced into the cylindrical concave part 131 of the receiving member 13.
  • the peripheral wall 11W of the convex portion 11 is brought into contact with the opening peripheral edge 131a of the concave portion 131 at the outer periphery 11c of the peripheral wall 11W and penetrates through the base sheet 2A.
  • the through hole 3h is formed in this way, the accuracy of the size of the through hole 3h is further increased, and a microneedle array 1M having a further high quality through hole 3h can be manufactured.
  • the tip of the conical convex mold 110 does not contact the receiving member 13, the durability of the convex mold 110 is improved and the number of replacements is reduced, so that the cost can be reduced.
  • the ultrasonic vibration device is used as the heating means (not shown) of the convex portion 11, it is not always necessary to provide the cold air blower 21, and the ultrasonic vibration device. It is possible to cool by simply turning off the vibration.
  • the microneedle array 1M having the through holes 3h can be manufactured at a high speed with simplification of the apparatus.
  • heat is more difficult to be transmitted, and since cooling is efficiently performed by turning off the ultrasonic vibration, deformation other than the molded portion occurs. It is difficult to manufacture the microneedle array 1M with high accuracy.
  • the ultrasonic vibration device is used only at the contact portion TP of the base sheet 2A with which the convex portion 11 is in contact. Since the convex part 11B is vibrated and the contact part TP is softened, the microneedle array 1M having the through holes 3h can be manufactured continuously and efficiently with energy saving.
  • the manufacturing apparatus 100C has the microneedle array 1M to be manufactured because the interval between the receiving member 13 and the base sheet 2A can be adjusted by a control means (not shown).
  • the protrusion height H1 of the protrusion 3 can be easily adjusted and changed.
  • the material of the receiving member 13 is a material that can be easily processed, the size of the through hole 3h can be easily changed by adjusting the size of the opening peripheral edge 131a of the recess 131.
  • the shape of the microneedle array 1M having the through holes 3h can be freely controlled.
  • the manufacturing apparatus 100C uses the control means (not shown) to operate the convex portion 11 and the heating means (not shown) of the convex portion 11 in the protrusion forming portion 10.
  • the heating conditions, the softening time of the contact part TP of the base sheet 2A, and the insertion speed of the convex part 11 into the base sheet 2A can be adjusted.
  • the cooling temperature and the cooling time of the cold air blower 21 in the cooling unit 20 are controlled by a control means (not shown). Therefore, the thickness T1 of the microneedle array 1M to be manufactured can be controlled by controlling the insertion speed of the convex portion 11 in the protrusion forming step, for example, by a control means (not shown).
  • the insertion height of the convex part 11 in a protrusion part formation process is controlled, the insertion amount to the base material sheet 2A of the convex part 11 can be changed easily, and the protrusion of the microneedle array 1M manufactured The height H1 can be controlled.
  • the conditions of the heating means provided in the convex part 11, the insertion height of the convex part 11 into the base sheet 2A, the softening time of the contact part TP of the base sheet 2A, the convex If at least one of the insertion speed of the mold part 11 into the base sheet 2A, the cooling conditions in the cooling process, and the shape of the convex mold part 11 is controlled, the thickness T1 of the protrusions 3 constituting the microneedle array 1M, etc. Can be freely controlled, and the shape of the microneedle array 1M having the through holes 3h can be freely controlled.
  • a pair of support members 12 and 12 arranged on the other surface 2U side (upper surface side) of the base sheet 2A is used.
  • the convex part 11 is brought into contact with the surface 2D side (lower surface side) opposite to the side, and the contact part TP is softened to form the protruding part 3.
  • the recessed part etc. which fit in the convex part 11 for forming the protrusion part 3 are unnecessary, cost increase can be suppressed, and the protrusion part 3 with which the microneedle array 1M to be manufactured is provided can be efficiently used. Can be formed with high accuracy.
  • the present invention (third invention) will be described with reference to FIGS. 27 to 29 based on the second embodiment.
  • the heating means (not shown) of the convex portion 11 is an ultrasonic vibration device, but the second embodiment used in the second embodiment.
  • a heater device is used instead.
  • the manufacturing apparatus 100D according to the second embodiment forms a protrusion 3 on the base sheet 2A from the upstream side toward the downstream side, similarly to the manufacturing apparatus 100C according to the first embodiment.
  • a part forming part 10, a cooling part 20, a release part 30, a cutting part 40 and a re-pitch part 50 are provided.
  • nine frustoconical convex molds 110B have their tips 110t on the convex mold parts 11B of the protrusion forming part 10. It is arranged upward.
  • the convex mold 110B has a truncated cone shape, but may have a truncated pyramid shape.
  • each convex mold 110B of the convex mold part 11B has a truncated cone shape, and the tip 110t is a circular plane.
  • the area of this circular plane coincides with the opening area S1 of the through hole 3h located at the tip of each protrusion 3 included in the manufactured microneedle array 1M.
  • the box motion type receiving member 13B of the protruding portion forming portion 10 has a flat surface 13f that is in contact with the convex portion 11B.
  • the convex portion 11B is pierced into the base sheet 2A until the tip 110t of the convex portion 11B comes into contact with the flat surface 13f of the receiving member 13B and penetrates the base sheet 2A. It has come to go.
  • a second embodiment using the manufacturing apparatus 100D of the second embodiment will be described with reference to FIG.
  • the heating means (not shown) of the convex portion 11B is a heater device as in the manufacturing apparatus 100D of the second embodiment, as shown in FIG.
  • the convex part 11B is heated by the apparatus, and heat is generated in the contact part TP to soften the contact part TP.
  • softening each contact part TP it is the other surface 2U from the one surface 2D side (lower surface side) of the base material sheet 2A.
  • the convex part 11B is raised toward the side (upper surface side) and the convex mold 110B is stabbed into the base sheet 2A.
  • the circular shape of the tip 110 t of each convex portion 11 ⁇ / b> B of the convex portion 11 is formed on the flat surface 13 f of the receiving member 13.
  • the convex part 11 is stabbed into the base material sheet 2A until the flat surface comes into contact and penetrates the base material sheet 2A.
  • the box motion type convex portion 11 is moved upward in the thickness direction (Z direction) by an electric actuator (not shown), and the convex portion 11 has a truncated cone shape.
  • Each convex mold 110 is stabbed into the base material sheet 2A, and the projection part 3 which protrudes from the other surface 2U side of the base material sheet 2A is formed. Then, the convex part 11 is further moved upward in the thickness direction (Z direction) by an electric actuator (not shown), and the flat surface of the tip 110 t of each convex part 110 of the convex part 11 is set to the flat surface of the receiving member 13. 13f is made to contact, and the convex part 11 is penetrated to the base material sheet 2A.
  • the heating temperature of the base sheet 2A by the convex portion 11B is equal to or higher than the glass transition temperature (Tg) of the base sheet 2A used from the viewpoint of forming the protrusion 3. It is preferable that the temperature is lower than the melting temperature, and it is more preferable that the temperature is higher than the softening temperature and lower than the melting temperature. More specifically, the heating temperature is preferably 30 ° C. or higher, more preferably 40 ° C. or higher, and preferably 300 ° C. or lower, more preferably 250 ° C. or lower. It is not less than 300 ° C and more preferably not less than 40 ° C and not more than 250 ° C.
  • the said heating temperature is applied as a temperature range of the part of the base material sheet 2A which contacted the convex mold 110, also when heating the base material sheet 2A using an ultrasonic vibration apparatus in 1st Embodiment.
  • the glass transition temperature (Tg) is measured by the following method, and the softening temperature is measured according to JIS K-7196 “Softening temperature test method by thermomechanical analysis of thermoplastic film and sheet”. .
  • the “glass transition temperature (Tg) of the base sheet” means the glass transition temperature (Tg) of the constituent resin of the base sheet, and when there are a plurality of types of the constituent resins, the plurality of types of glass transitions.
  • the heating temperature of the base sheet by the heating means is preferably at least the lowest glass transition temperature (Tg) among the plurality of glass transition temperatures (Tg), More preferably, the glass transition temperature (Tg) is higher than the highest glass transition temperature (Tg).
  • the "softening temperature of the base sheet” is also the same as the glass transition temperature (Tg), that is, when there are a plurality of types of constituent resins of the base sheet, when the plurality of types of softening temperatures are different from each other,
  • the heating temperature of the base sheet by the heating means is preferably at least the lowest softening temperature among the plurality of softening temperatures, and more preferably at least the highest softening temperature among the plurality of softening temperatures.
  • the heating temperature of the base sheet by the heating means is preferably less than the lowest melting point among the plurality of melting points. .
  • Tg glass transition temperature
  • the amount of heat is measured using a DSC measuring instrument to determine the glass transition temperature.
  • the measuring instrument uses a differential scanning calorimeter (Diamond DSC) manufactured by Perkin Elmer. 10 mg of a test piece is collected from the base sheet. The measurement conditions are that 20 ° C. is isothermal for 5 minutes, and then the temperature is increased from 20 ° C. to 320 ° C. at a rate of 5 ° C./min to obtain a DSC curve of the horizontal axis temperature and the vertical axis calorific value. And glass transition temperature Tg is calculated
  • the cooling unit 20 installed downstream of the protrusion forming unit 10 is natural. Although cooling may be sufficient, it is preferable to provide the cold air blower 21 and perform positive cooling.
  • the convex portion 11 is formed from the one surface 2D side (lower surface side) of the base sheet 2A.
  • the protrusion 110 of the protrusion 11 is removed from the state in which the protrusion 110 of the protrusion 11 is stabbed inside each protrusion 3, and the protrusion having the through hole 3h and having a hollow inside is provided.
  • a band-shaped fine hollow projection precursor 1A that forms a microneedle array 1M in which the portions 3 are arranged in an array is formed.
  • the single-sided microneedle array 1M in which the projections 3 having the through holes 3h are arranged in an array by cutting with the cutter blade of the cutter unit 41. are continuously arranged and rearranged in the re-pitch portion 50 to produce the microneedle array 1M.
  • the convex portion 11B is based on the flat surface 13f of the receiving member 13B until the tip 110t of the convex portion 11B comes into contact with the base sheet 2A.
  • the microneedle array 1M in which the protrusions 3 having the through holes 3h are arranged in an array is continuously manufactured by piercing the material sheet 2A. Therefore, the opening area S1 of the through hole 3h located at the tip of each protrusion 3 in the microneedle array 1M to be manufactured can be controlled only by changing the circular size of the tip 110t of each convex mold 110B.
  • the control means (not shown) can easily adjust and change the protrusion height H1 of the protrusion 3 by adjusting the distance between the receiving member 13 and the base sheet 2A, and has a high-quality through-hole 3h.
  • the microneedle array 1M can be manufactured.
  • heat due to the heating of the convex portion 11B is efficiently transmitted to the contact portion TP, and the surrounding portion becomes an environment where only the desired heating can be applied. 3 is less likely to occur, the substrate sheet 2A is less likely to be distorted, and the substrate sheet 2A is easily continuously conveyed.
  • the present invention has been described based on preferred embodiments thereof, but the present invention (first invention to third invention) is not limited to the above embodiments, and can be changed as appropriate. It is.
  • the manufactured fine hollow projection 1 has one projection 3 on the upper surface of the sheet-like base 2, but a plurality of projections 3 are arranged in an array as shown in FIG. You may have.
  • having the protrusions 3 in the form of an array means having a plurality of protrusions 3 on the upper surface of the sheet-like base 2, and in particular, the plurality of protrusions 3 are It is preferable that the upper surface of the sheet-like base portion 2 is arranged in a matrix having a plurality of rows and a plurality of columns.
  • the protruding portion forming section 10 includes a protruding portion 11 having a plurality of protruding molds 110 corresponding to the number and arrangement of the protruding portions 3 and the outer shape of each protruding portion 3. ing.
  • the fine hollow protrusion 1 having a plurality of protrusions 3 may be manufactured by inserting one convex portion 11 into the base sheet 2A a plurality of times.
  • the manufacturing apparatus 100A shown in FIG. 9 the same number is attached
  • a projection forming unit 10 that can move only in the thickness direction (Z direction) is used instead of the box motion type projection forming unit 10 that draws an endless track.
  • the projection can be formed.
  • the manufacturing apparatus 100A of the first embodiment or the second embodiment of the present invention has a base material when the convex part 11 is pierced into the base material sheet 2A.
  • the manufacturing apparatus 100A has a pair of plate-like support members 12 and 12 that support the sheet 2A, a pair of plate-like members are provided as long as they support the base sheet 2A by being arranged on the other surface 2U side of the base sheet 2A.
  • Other than the support members 12, 12 may be used.
  • a punching plate 12A which is an example of an opening plate having an opening 121 at a position corresponding to the contact portion TP, as shown in FIG.
  • the opening plate is a plate having an opening part into which the convex mold 110 of the convex part 11 can be inserted.
  • the opening is a through hole, but it may be non-through.
  • it can be said that the part which opposes the opening part of 2 A of base materials is not supported by the opening plate.
  • the protruding portion forming section 10 includes a protruding portion 11 having a plurality of protruding molds 110 corresponding to the number and arrangement of the protruding portions 3 and the outer shape of each protruding portion 3. I am doing so.
  • the opening plate 12A is arranged so as to be in contact with the other surface 2U side of the base sheet 2A.
  • the same number is attached
  • the base sheet 2A is sandwiched between the convex portion 11 and the opening plate 12A.
  • the opening plate 12 ⁇ / b> A is provided with one through-hole 121 at a position corresponding to the contact portion TP of one convex mold 110 of the convex mold part 11 in the base sheet 2.
  • one through-hole 121 may be arranged at a position corresponding to the contact portion TP of the plurality of convex molds 110.
  • the through-hole 121 is formed in a circular shape in the manufacturing apparatus 100A shown in FIG. 10, although the shape of the opening plate 12A is not particularly limited when the opening plate 12A is viewed from the upper surface side.
  • the shape of the opening plate 12A is not particularly limited, but is formed in a plate shape in the manufacturing apparatus 100A shown in FIG.
  • the length of the plate-shaped opening plate 12A in the Y direction is substantially the same as the length of the convex portion 11 in the Y direction
  • the length of the X direction is substantially the same as the length of the convex portion 11 in the X direction. The same.
  • such a plate-shaped opening plate 12A sandwiches the base sheet 2A conveyed in the Y direction, and the operation of the box motion type convex portion 11 and the target operation. It is designed to draw an endless track with a box motion formula.
  • the box motion type opening plate 12A is arranged adjacent to the upper surface in the thickness direction (Z direction) from the other surface 2U of the base sheet 2A, and runs parallel to the base sheet 2A in the transport direction (Y direction). It is possible.
  • the movement speed of the opening plate 12A in the conveyance direction (Y direction) corresponds to the movement speed of the convex portion 11 in the conveyance direction (Y direction), and the control provided in the manufacturing apparatus 100A shown in FIG. It is controlled by means (not shown).
  • the convex portion 11 pierces the base sheet 2A upward from below.
  • the positional relationship between the convex portion and the support member with respect to the base sheet and the insertion direction are not limited to this, and fine hollow protrusions may be formed from the top to the bottom.
  • the frequency and amplitude of the ultrasonic vibration of the convex portion 11 of the protrusion extending portion 10B and the protrusion are the same and do not satisfy the conditions (b) and (c), but the insertion speed in the protrusion extension process Is slower than the insertion speed in the projection precursor forming step, satisfies the condition (a), and as a result, the amount of heat given from the convex portion 11 to the base sheet 2A in the projection extension step is It is larger than the amount of heat given from the convex portion 11 to the base sheet 2A in the precursor forming step.
  • the heater temperature of the convex portion 11 of the protrusion extending portion 10B and the heater temperature of the convex portion 11 of the protrusion precursor forming portion 10A are as follows. Although it is the same temperature and does not satisfy the condition (d), the insertion speed in the protrusion extension step is slower than the insertion speed in the protrusion precursor formation step, and satisfies the condition (a), As a result, the amount of heat given from the convex part 11 to the base material sheet 2A in the protrusion extension step is larger than the amount of heat given from the convex part 11 to the base material sheet 2A in the protrusion part precursor forming step.
  • the conditions of the heating means included in the convex portion 11 in the protrusion precursor forming step and the conditions of the heating means included in the convex portion 11 in the protrusion extension step are the same.
  • the speed at which the convex portion 11 is further pierced into the base sheet 2A in the protrusion extension step is slower than the speed at which the convex portion 11 is pierced into the base sheet 2A in the protrusion precursor forming step. It is a manufacturing method.
  • the speed at which the convex part 11 is stabbed into the base sheet 2A in the protrusion precursor forming step and the speed at which the convex part 11 is further stabbed into the base sheet 2A in the protrusion extension step are the same.
  • the amount of heat applied to the base sheet 2A under the conditions of the heating means provided in the convex part 11 in the protrusion extension step is the base sheet 2A under the conditions of the heating means provided in the convex part 11 in the protrusion precursor forming step.
  • the manufacturing method may be larger than the amount of heat applied to.
  • the frequency or amplitude of the ultrasonic vibration of the convex portion 11 included in the protrusion extending portion 10B is higher than the convex shape included in the protrusion precursor forming portion 10A.
  • the amount of heat applied to the base sheet 2A from the convex part 11 in the protrusion extension process is larger than the frequency or amplitude of the ultrasonic vibration of the part 11 and satisfies the condition (b) or (c). It may be larger than the amount of heat given from the convex part 11 to the base sheet 2A in the protrusion precursor forming step.
  • the heater temperature of the convex portion 11 of the protrusion extension portion 10B is higher than the heater temperature of the convex portion 11 of the protrusion precursor forming portion 10A, As a result, the amount of heat given from the convex portion 11 to the base material sheet 2A in the projection extension step is equivalent to the amount of heat given from the convex portion 11 to the base material sheet 2A in the projection portion precursor forming step. May be larger. Further, all of the conditions (a), (b), (c), and (d) may be satisfied.
  • the microneedle array 1M as the fine hollow protrusion 1 manufactured by the method for manufacturing the fine hollow protrusion of the first embodiment and the second embodiment of the present invention (second invention) is a sheet-like base.
  • the nine frustoconical protrusions 3 are arranged in an array (matrix) on the upper surface of the part 2, one protrusion 3 may be provided.
  • the microneedle array 1M manufactured by the method of manufacturing the fine hollow protrusions of the first embodiment and the second embodiment includes a through-hole 3h located at the tip of the protrusion 3 and a base-side through-hole located at the lower surface. 2h is formed in a concentric shape, but may not be a concentric shape.
  • the box motion type convex portion 11 that draws an endless track is used, but the upper and lower sides in the thickness direction (Z direction).
  • the amount of heat given from the convex portion 11 to the base sheet 2A in the projection precursor forming step and the convex portion 11 to the base sheet 2A in the projection extension step The microneedle array 1M may be manufactured by changing the amount of heat applied in a stepwise manner from the protrusion precursor forming process to the protrusion extension process.
  • the manufacturing apparatus 100B of the first embodiment or the second embodiment of the present invention (second invention), as shown in FIG.
  • a pair of plate-like support members 12 and 12 that support the sheet 2A
  • a pair of plate-like members are provided as long as they support the base sheet 2A by being arranged on the other surface 2U side of the base sheet 2A.
  • Other than the support members 12, 12 may be used.
  • a punching plate 12 A which is an example of an opening plate having an opening 121 at a position corresponding to the contact portion TP, as shown in FIG.
  • the opening plate is a plate having an opening part into which the convex mold 110 of the convex part 11 can be inserted.
  • the opening is a through hole, but it may be non-through.
  • it can be said that the part which opposes the opening part of 2 A of base materials is not supported by the opening plate.
  • the protruding portion forming unit 10 includes a protruding portion 11 having a plurality of protruding molds 110 corresponding to the number and arrangement of the protruding portions 3 and the outer shape of each protruding portion 3. I am doing so.
  • the opening plate 12A is arranged so that the other surface 2U side of the base sheet 2A is in contact with each other.
  • the same number is attached
  • the base material sheet 2A is sandwiched between the convex portion 11 and the opening plate 12A.
  • the opening plate 12 ⁇ / b> A is provided with one through-hole 121 at a position corresponding to the contact portion TP of one convex mold 110 of the convex mold part 11 in the base sheet 2.
  • one through-hole 121 may be arranged at a position corresponding to the contact portion TP of the plurality of convex molds 110.
  • the through-hole 121 is formed in a circular shape in the manufacturing apparatus 100B shown in FIG. 18, although the shape is not particularly limited when the opening plate 12A is viewed from the upper surface side.
  • the shape of the opening plate 12A is not particularly limited, but is formed in a plate shape in the manufacturing apparatus 100B shown in FIG.
  • the length of the plate-shaped opening plate 12A in the Y direction is substantially the same as the length of the convex portion 11 in the Y direction
  • the length of the X direction is substantially the same as the length of the convex portion 11 in the X direction.
  • such a plate-shaped opening plate 12 ⁇ / b> A sandwiches the base material sheet 2 ⁇ / b> A conveyed in the Y direction, and the operation of the box motion type convex portion 11 and the target operation. It is designed to draw an endless track with a box motion formula.
  • the box motion type opening plate 12A is arranged adjacent to the upper surface in the thickness direction (Z direction) from the other surface 2U of the base sheet 2A, and runs parallel to the base sheet 2A in the transport direction (Y direction). It is possible.
  • the movement speed of the opening plate 12A in the conveyance direction (Y direction) corresponds to the movement speed of the convex portion 11 in the conveyance direction (Y direction), and the control provided in the manufacturing apparatus 100B shown in FIG. It is controlled by means (not shown).
  • the convex portion 11 pierces the base sheet 2A from below to above.
  • the positional relationship between the convex portion and the support member with respect to the base sheet and the insertion direction are not limited to this, and the microneedle array 1M may be formed from the top to the bottom.
  • the receiving member 13 having a recess 131 formed in a columnar shape is provided.
  • Each conical recess 131 shown in FIG. 30 has a shape corresponding to the tip of the conical convex mold 110 included in the convex portion 11 shown in FIG. The shape coincides with the shape of the outer periphery 11c of the convex mold 110 (see FIG. 23).
  • the cylindrical recessed part 131 with which the receiving member 13 shown in FIG. 24 is a bottomed shape the shape penetrated may be sufficient.
  • the microneedle array 1M as the fine hollow projection 1 manufactured by the method for producing the fine hollow projection of the first embodiment and the second embodiment of the present invention (third invention) is a sheet-like base.
  • the nine frustoconical protrusions 3 are arranged in an array (matrix) on the upper surface of the part 2, one protrusion 3 may be provided.
  • the microneedle array 1M manufactured by the method of manufacturing the fine hollow protrusions of the first embodiment and the second embodiment includes a through-hole 3h located at the tip of the protrusion 3 and a base-side through-hole located at the lower surface. 2h is formed in a concentric shape, but may not be a concentric shape.
  • the box motion type convex portion 11 that draws an endless track is used, but the upper and lower sides in the thickness direction (Z direction).
  • the microneedle array 1M may be manufactured by using the convex portion 11 that can move only to the center.
  • the manufacturing apparatus 100C of the first embodiment or the manufacturing apparatus 100D of the second embodiment of the present invention pierces the convex part 11 into the base sheet 2A as shown in FIG. If it has a pair of plate-like support members 12 and 12 that support the base sheet 2A, the base sheet 2A is provided on the other surface 2U side to support the base sheet 2A.
  • the pair of plate-like support members 12, 12 may be used.
  • a punching plate 12A which is an example of an opening plate having an opening 121 at a position corresponding to the contact portion TP, as shown in FIG.
  • the opening plate is a plate having an opening part into which the convex mold 110 of the convex part 11 can be inserted.
  • the opening is a through hole, but it may be non-through.
  • it can be said that the part which opposes the opening part of 2 A of base materials is not supported by the opening plate.
  • the punching plate 12A shown in FIG. 31 is used instead of the support member 12, the opening plate 12A is provided on the other surface 2U of the base sheet 2A. Arranged so that they touch each other.
  • the punching plate 12A shown in FIG. 31 when used instead of the support member 12, the base sheet 2A is sandwiched between the convex portion 11 and the opening plate 12A. It will be in the state.
  • one through hole 121 is arranged at a position corresponding to the contact portion TP of one convex mold 110 of the convex mold part 11 in the base sheet 2.
  • One through hole 121 may be arranged at a position corresponding to the contact portion TP of the convex mold 110.
  • the through hole 121 is not particularly limited in shape when the opening plate 12A is viewed from the upper surface side, but is formed in a circular shape in the punching plate 12A shown in FIG.
  • the shape of the opening plate 12A is not particularly limited, but the punching plate 12A shown in FIG. 31 is formed in a plate shape.
  • the length of the plate-shaped opening plate 12A in the Y direction is substantially the same as the length of the convex portion 11 in the Y direction
  • the length of the X direction is substantially the same as the length of the convex portion 11 in the X direction. The same.
  • such a plate-shaped opening plate 12A has a box motion type convex shape sandwiching the base material sheet 2A conveyed in the Y direction. An endless trajectory is drawn by the box motion type so as to perform the operation of the unit 11 and the operation of the target.
  • the box motion type opening plate 12A is arranged adjacent to the upper surface in the thickness direction (Z direction) from the other surface 2U of the base sheet 2A, and runs parallel to the base sheet 2A in the transport direction (Y direction). It is possible.
  • the movement speed of the opening plate 12A in the conveyance direction (Y direction) corresponds to the movement speed of the convex portion 11 in the conveyance direction (Y direction), and is provided in the manufacturing apparatus 100C or the manufacturing apparatus 100D. It is controlled by means (not shown).
  • the opening plate 12A When manufacturing a fine hollow protrusion using the opening plate 12A shown in FIG. 31, it is preferable to arrange the opening plate 12A between the base sheet 2A and the receiving member 13.
  • the manufacturing apparatus 100C of the said 1st Embodiment of this invention (3rd invention), or the manufacturing apparatus 100D of 2nd Embodiment as shown in FIG.
  • the positional relationship between the convex portion and the support member with respect to the base sheet and the insertion direction are not limited to this, and the microneedle array 1M may be formed from the top to the bottom. .
  • the present invention further discloses the following method for producing fine hollow protrusions.
  • the projecting portion forming step is performed using a support member that supports the base sheet when the convex portion is stabbed into the base sheet, and the support member is disposed on the other surface side of the base sheet.
  • ⁇ 3> The manufacturing method of the fine hollow protrusion of said ⁇ 2> using the opening plate which has an opening part which can insert the convex in the said convex part as said support member.
  • ⁇ 4> The manufacturing method of the fine hollow projection according to ⁇ 3>, wherein the opening plate includes a plurality of the openings.
  • ⁇ 5> The manufacturing method of the fine hollow protrusion as described in said ⁇ 3> or ⁇ 4> in which one said convex type is inserted with respect to one said opening part of the said opening plate.
  • ⁇ 6> The method for producing a fine hollow protrusion according to ⁇ 3> or ⁇ 4>, wherein the plurality of convex molds are inserted into the opening of the opening plate.
  • ⁇ 7> The heating condition of the convex part in the protrusion forming step, the softening time of the contact part of the base sheet, the insertion speed of the convex part into the base sheet, and the cooling condition in the cooling step.
  • a band-shaped substrate sheet is used as the substrate sheet, and the fine hollow protrusions are continuously formed on the other surface side of the band-shaped substrate sheet.
  • the manufacturing method of the fine hollow protrusion of description is described.
  • the heating temperature of the base sheet by heating the convex mold part is the fine hollow projection according to any one of ⁇ 1> to ⁇ 8>, which is not lower than the glass transition temperature and lower than the melting temperature of the base sheet.
  • Production method. ⁇ 10> The method for producing a fine hollow projection according to any one of the above items ⁇ 1> to ⁇ 9>, wherein the heating temperature of the base sheet by heating the convex portion is not lower than the softening temperature and lower than the melting temperature of the base sheet.
  • Said heating temperature is 30 degreeC or more and 300 degrees C or less, The manufacturing method of the fine hollow protrusion of said ⁇ 9> or ⁇ 10> description.
  • ⁇ 12> The method for producing a fine hollow protrusion according to any one of ⁇ 1> to ⁇ 11>, wherein the heating means provided in the convex portion is a heater device.
  • the heating means provided in the convex part is an ultrasonic vibration device, and the ultrasonic vibration device is used to ultrasonically vibrate the convex part and generate heat due to friction at the contact part to soften the corresponding contact part.
  • ⁇ 14> The method for producing a fine hollow projection according to ⁇ 13>, wherein the frequency of the ultrasonic vibration is 10 kHz to 50 kHz, and more preferably 15 kHz to 40 kHz.
  • ⁇ 15> The method for producing a fine hollow projection according to ⁇ 13> or ⁇ 14>, wherein the amplitude of the ultrasonic vibration is 1 ⁇ m or more and 60 ⁇ m or less, more preferably 5 ⁇ m or more and 50 ⁇ m or less.
  • ⁇ 16> The method for producing a fine hollow projection according to any one of ⁇ 1> to ⁇ 15>, wherein no heating means other than the heating means for the convex part is provided in the protrusion forming step.
  • a temperature equal to or higher than the softening temperature of the base sheet is applied only to the portion of the base sheet in which the convex portion is inserted and a region in the vicinity thereof, and a temperature rise is expected in other regions of the base sheet.
  • ⁇ 18> The fine hollow projection according to any one of ⁇ 1> to ⁇ 17>, wherein the height of the convex portion is the same as or slightly higher than the height of the produced fine hollow projection.
  • ⁇ 19> The fine hollow protrusion according to any one of ⁇ 1> to ⁇ 18>, wherein the height of the convex portion is 0.01 mm to 30 mm, and more preferably 0.02 mm to 20 mm. Manufacturing method.
  • the convex portion has a tip diameter of not less than 0.001 mm and not more than 1 mm, more preferably not less than 0.005 mm and not more than 0.5 mm, according to any one of ⁇ 1> to ⁇ 19>.
  • Manufacturing method of fine hollow protrusion ⁇ 21> The fine hollow protrusion according to any one of ⁇ 1> to ⁇ 20>, wherein the convex portion has a root diameter of 0.1 mm to 5 mm, more preferably 0.2 mm to 3 mm.
  • Manufacturing method. ⁇ 22> The micro hollow according to any one of ⁇ 1> to ⁇ 21>, wherein the convex portion has a tip angle of 1 degree to 60 degrees, more preferably 5 degrees to 45 degrees.
  • Protrusion manufacturing method ⁇ 23> The method for producing a fine hollow projection according to any one of ⁇ 1> to ⁇ 22>, wherein, in the cooling step, cooling is performed by a cold air blower in a state where a protruding portion is stabbed inside the protruding portion. . ⁇ 24> The method for producing a fine hollow projection according to ⁇ 23>, wherein the temperature of the cold air is ⁇ 50 ° C. or higher and 26 ° C. or lower, preferably ⁇ 40 ° C. or higher and 10 ° C. or lower.
  • ⁇ 25> The method for producing fine hollow protrusions according to ⁇ 23> or ⁇ 24>, wherein the cooling time for cooling by blowing the cold air is 0 second to 60 seconds, and more preferably 0.5 seconds to 30 seconds. .
  • ⁇ 26> The method for producing a fine hollow projection according to any one of ⁇ 1> to ⁇ 25>, wherein in the cooling step, natural cooling is performed without performing cooling by a cold air blower.
  • the protruding portion has a plurality of protruding portions that form a plurality of protruding portions by being inserted into different positions of the base sheet.
  • ⁇ 30> The method for producing a fine hollow protrusion according to ⁇ 29>, wherein the fine hollow protrusion is a microneedle array in which a plurality of the protrusions are arranged on a base sheet.
  • a convex portion having a heating means is brought into contact with one surface of a base material sheet formed including a thermoplastic resin, and the corresponding contact portion in the base material sheet is softened by heat.
  • the convex part is stabbed into the base sheet, and a hollow projection precursor having a through hole penetrating from the other end of the base sheet is formed while projecting from the other face of the base sheet.
  • a protrusion precursor forming step In a state where the convex part is stabbed inside the protrusion precursor, the convex part is further stabbed into the base sheet while the contact portion of the base sheet is softened by heat, A method for producing a fine hollow protrusion according to any one of ⁇ 1> to ⁇ 30>, further comprising a protrusion extending step of forming a protrusion that further protrudes from the other surface of the base sheet.
  • a method for producing a fine hollow projection having a through-hole As a projection forming step for forming the projection, a convex portion provided with a heating means is brought into contact with one surface of a base material sheet containing a thermoplastic resin, and the corresponding contact portion in the base material sheet is heated.
  • a release step of removing the convex portion from the inside of the protrusion to form a fine hollow protrusion having the through hole has a through hole, ⁇ 1> to ⁇ 30>
  • the amount of heat given from the convex part to the base sheet in the projection extension step is larger than the amount of heat given from the convex part to the base sheet in the projection precursor formation step, ⁇ 31> or ⁇ 32>
  • the manufacturing method of the fine hollow protrusion which has a through-hole as described in 32>.
  • ⁇ 34> The amount of heat per unit insertion height given from the convex part to the base sheet in the projection precursor forming step and the unit insertion given from the convex part to the base sheet in the projection extension step
  • the amount of heat per height is a fine hollow projection having a through hole according to any one of ⁇ 31> to ⁇ 33>, which continuously changes from the projection precursor forming step to the projection extension step. Manufacturing method.
  • the protrusion forming step the conditions of the heating means provided in the convex part, the insertion height of the convex part into the base sheet, the softening time of the contact portion of the base sheet, the convex
  • the shape of the fine hollow projection having the through hole is controlled by controlling at least one of the insertion speed of the mold portion into the base sheet and the shape of the convex mold portion.
  • the manufacturing method of the fine hollow protrusion which has a through-hole as described in any one of>.
  • the shape of the fine hollow protrusion having the through hole is controlled by controlling the insertion speed of the convex portion into the base material sheet. Manufacturing method of fine hollow protrusion.
  • the condition of the heating means provided in the convex portion and the condition of the heating means provided in the convex portion in the projection extension step are the same, and in the projection extension step
  • the piercing speed for further piercing the convex part into the base sheet is slower than the piercing speed for piercing the convex part into the base sheet in the protrusion precursor forming step, ⁇ 31
  • the heating means provided in the convex part is an ultrasonic vibration device, and the ultrasonic vibration device is used to ultrasonically vibrate the convex part and generate heat due to friction at the contact part to soften the corresponding contact part.
  • ⁇ 41> The method for producing a fine hollow projection having a through hole according to ⁇ 39> or ⁇ 40>, wherein the amplitude of the ultrasonic vibration is 1 ⁇ m or more and 60 ⁇ m or less, more preferably 5 ⁇ m or more and 50 ⁇ m or less.
  • ⁇ 42> The penetration according to any one of ⁇ 31> to ⁇ 38>, wherein the heating means provided in the convex portion is a heater, and the convex portion is heated by a heater device to soften the contact portion.
  • the protrusion precursor forming step and the protrusion extension step are performed using the convex portion having a plurality of convex shapes to form a plurality of fine hollow protrusions having the through holes in an array, ⁇ 31 A method for producing a fine hollow projection having a through hole according to any one of> to ⁇ 42>.
  • the projecting portion forming step is performed using a support member that supports the base sheet when the convex portion is stabbed into the base sheet, and the support member is disposed on the other surface side of the base sheet. Any one of ⁇ 31> to ⁇ 43>, wherein the protruding portion is formed by contacting the convex portion from one surface of the portion of the base sheet that is not supported by the support member.
  • the manufacturing method of the fine hollow protrusion which has a through-hole of description.
  • the method for producing a fine hollow projection according to ⁇ 44>, wherein an opening plate having an opening into which the protrusion in the protrusion can be inserted is used as the support member.
  • ⁇ 48> The method for producing a fine hollow protrusion according to any one of ⁇ 44> to ⁇ 46>, wherein the plurality of convex molds are inserted into the opening of the opening plate.
  • ⁇ 49> ⁇ 31> to ⁇ 48>, wherein a strip-shaped substrate sheet is used as the substrate sheet, and the fine hollow protrusions are continuously formed on the other surface of the strip-shaped substrate sheet.
  • ⁇ 50> The fine hollow having the through hole according to any one of ⁇ 31> to ⁇ 49>, wherein the heating temperature of the base sheet by heating the convex portion is not less than the glass transition temperature of the base sheet and less than the melting temperature.
  • ⁇ 51> The fine hollow projection having the through hole according to any one of ⁇ 31> to ⁇ 49>, wherein the heating temperature of the base sheet by heating the convex portion is not less than the softening temperature of the base sheet and lower than the melting temperature.
  • the said heating temperature is a manufacturing method of the fine hollow protrusion which has a through-hole as described in ⁇ 50> or ⁇ 51> which is 30 degreeC or more and 300 degrees C or less.
  • ⁇ 53> The method for producing a fine hollow protrusion having a through hole according to any one of ⁇ 31> to ⁇ 52>, wherein no heating means is provided other than the heating means for the convex portion in the protrusion forming step.
  • ⁇ 54> A temperature equal to or higher than the softening temperature of the base sheet is applied only to the portion of the base sheet in which the convex portion is inserted and the region in the vicinity thereof, and in the other regions of the base sheet, the trend increases.
  • ⁇ 55> The fine hollow having a through hole according to any one of ⁇ 31> to ⁇ 54>, wherein the height of the convex portion is the same as or slightly higher than the height of the fine hollow protrusion to be produced. Protrusion manufacturing method.
  • the height of the convex part is 0.01 mm or more and 30 mm or less, more preferably 0.02 mm or more and 20 mm or less, and the fine part having a through hole according to any one of ⁇ 31> to ⁇ 55> Manufacturing method of hollow protrusion.
  • the convex portion has a tip diameter of 0.001 mm to 1 mm, and more preferably 0.005 mm to 0.5 mm, in any one of ⁇ 31> to ⁇ 56>.
  • the convex portion has a through hole according to any one of ⁇ 31> to ⁇ 57>, wherein a root diameter is 0.1 mm to 5 mm, and more preferably 0.2 mm to 3 mm. Manufacturing method of fine hollow protrusion.
  • the convex portion has the through hole according to any one of ⁇ 31> to ⁇ 58>, in which a tip end angle is not less than 1 degree and not more than 60 degrees, more preferably not less than 5 degrees and not more than 45 degrees.
  • the manufacturing method of the fine hollow protrusion which has.
  • ⁇ 60> The method for producing a fine hollow protrusion according to any one of ⁇ 31> to ⁇ 59>, wherein in the cooling step, cooling is performed by a cold air blower in a state where a protrusion is inserted into the protrusion.
  • ⁇ 61> The method for producing a fine hollow projection having a through-hole according to ⁇ 60>, wherein the temperature of the cold air is ⁇ 50 ° C. or higher and 26 ° C. or lower, preferably ⁇ 40 ° C. or higher and 10 ° C. or lower.
  • ⁇ 62> The fine hollow projection having the through hole according to ⁇ 60> or ⁇ 61>, wherein the cooling time for cooling by blowing the cold air is 0 second to 60 seconds, more preferably 0.5 seconds to 30 seconds.
  • ⁇ 63> The method for producing a fine hollow projection having a through hole according to any one of ⁇ 31> to ⁇ 62>, wherein in the cooling step, natural cooling is performed without cooling by a cold air blower.
  • ⁇ 64> The method for producing a fine hollow protrusion having a through hole according to any one of ⁇ 31> to ⁇ 63>, wherein the protrusion is a microneedle.
  • a method for producing fine hollow projections wherein a convex part having a heating means is brought into contact with one surface side of a base sheet formed by including a thermoplastic resin, and a corresponding contact portion in the base sheet is Protruding part forming the protruding part protruding from the other surface side of the base sheet by piercing the base sheet toward the other side of the base sheet while being softened by heat
  • a release step for forming an object wherein the protrusion forming step uses a receiving member disposed at a distance from the other surface of the base sheet, and in the protruding portion forming step, the receiving member A through-hole is formed in the protrusion by contacting the convex part.
  • the receiving member has a concave portion, and the opening peripheral shape of the concave portion coincides with the outer peripheral shape at a position in contact with the receiving member on the peripheral wall of the convex portion, and in the protrusion forming step,
  • Protrusion manufacturing method ⁇ 67> The method for producing a fine hollow protrusion according to ⁇ 66>, wherein a tip of the convex portion does not contact the receiving member.
  • the receiving member has a flat surface in contact with the convex portion, and in the protrusion forming step, the tip of the convex portion comes into contact with the flat surface of the receiving member, and the base sheet.
  • the heating means provided in the convex part is an ultrasonic vibration device, and the ultrasonic vibration device is used to ultrasonically vibrate the convex part and generate heat due to friction at the contact part to soften the corresponding contact part.
  • ⁇ 71> The method for producing a fine hollow projection according to ⁇ 70>, wherein the frequency of the ultrasonic vibration is 10 kHz or more and 50 kHz or less, and more preferably 15 kHz or more and 40 kHz or less.
  • ⁇ 72> The method for producing a fine hollow projection according to ⁇ 70> or ⁇ 71>, wherein the amplitude of the ultrasonic vibration is 1 ⁇ m or more and 60 ⁇ m or less, more preferably 5 ⁇ m or more and 50 ⁇ m or less.
  • ⁇ 73> The fine unit according to any one of ⁇ 65> to ⁇ 69>, wherein the heating means provided in the convex portion is a heater, and the convex portion is heated by a heater device to soften the contact portion.
  • the protruding portion forming step is performed using the protruding portion having a plurality of protruding shapes to form a plurality of the fine hollow protrusions in an array. The manufacturing method of the fine hollow protrusion of description.
  • the projecting portion forming step is performed using a support member that supports the base sheet when the convex portion is stabbed into the base sheet, and the support member is disposed on the other surface side of the base sheet. Any one of ⁇ 65> to ⁇ 74>, wherein the protruding portion is formed by contacting the convex portion from one side of the portion of the base sheet that is not supported by the support member.
  • the manufacturing method of the fine hollow protrusion which has a through-hole as described in any one of.
  • ⁇ 77> The manufacturing method of the fine hollow protrusion according to ⁇ 76>, wherein the opening plate includes a plurality of the openings.
  • ⁇ 78> The method for producing a fine hollow projection according to ⁇ 76> or ⁇ 77>, wherein one convex mold is inserted into one opening of the opening plate.
  • ⁇ 79> The method for producing a fine hollow projection according to ⁇ 76> or ⁇ 77>, wherein the plurality of convex molds are inserted into the opening of the opening plate.
  • ⁇ 80> ⁇ 65> to ⁇ 79>, wherein a strip-shaped substrate sheet is used as the substrate sheet, and the fine hollow protrusions are continuously formed on the other surface side of the strip-shaped substrate sheet. Manufacturing method of fine hollow protrusions.
  • ⁇ 81> The manufacturing temperature of the fine hollow projection according to any one of ⁇ 65> to ⁇ 80>, wherein the heating temperature of the base sheet by heating the convex part is not less than the glass transition temperature of the base sheet and less than the melting temperature.
  • Method. ⁇ 82> The method for producing a fine hollow projection according to any one of ⁇ 65> to ⁇ 81>, wherein the heating temperature of the base sheet by heating the convex mold part is not lower than the softening temperature and lower than the melting temperature of the base sheet. .
  • the said heating temperature is a manufacturing method of the fine hollow protrusion of ⁇ 81> or ⁇ 82> description which is 30 degreeC or more and 300 degrees C or less.
  • ⁇ 84> The method for producing a fine hollow projection according to any one of ⁇ 65> to ⁇ 83>, wherein no heating means other than the heating means for the convex part is provided in the protrusion forming step.
  • a temperature equal to or higher than the softening temperature of the base sheet is applied only to the portion of the base sheet in which the convex portion is inserted and a region in the vicinity thereof, and a temperature rise is expected in other regions of the base sheet.
  • ⁇ 86> The production of the fine hollow projection according to any one of ⁇ 65> to ⁇ 85>, wherein the height of the convex portion is the same as or slightly higher than the height of the fine hollow projection to be produced.
  • Method. ⁇ 87> The height of the convex portion is 0.01 mm or more and 30 mm or less, more preferably 0.02 mm or more and 20 mm or less, and the fine hollow projection according to any one of ⁇ 65> to ⁇ 86> Production method.
  • ⁇ 88> The fine-shaped portion according to any one of ⁇ 65> to ⁇ 87>, wherein the convex portion has a tip diameter of 0.001 mm to 1 mm, more preferably 0.005 mm to 0.5 mm. Manufacturing method of hollow protrusion.
  • ⁇ 89> The fine hollow protrusion according to any one of ⁇ 65> to ⁇ 88>, wherein the convex portion has a root diameter of 0.1 mm to 5 mm, more preferably 0.2 mm to 3 mm.
  • Manufacturing method. ⁇ 90> The fine hollow protrusion according to any one of ⁇ 65> to ⁇ 89>, wherein the convex portion has a tip angle of 1 to 60 degrees, more preferably 5 to 45 degrees.
  • Manufacturing method. ⁇ 91> The method for producing a fine hollow projection according to any one of ⁇ 65> to ⁇ 90>, wherein, in the cooling step, cooling is performed by a cold air blower in a state where a convex portion is stabbed inside the projection.
  • ⁇ 92> The method for producing fine hollow projections according to ⁇ 91>, wherein the temperature of the cold air is ⁇ 50 ° C. or higher and 26 ° C. or lower, preferably ⁇ 40 ° C. or higher and 10 ° C. or lower.
  • ⁇ 93> The method for producing fine hollow projections according to ⁇ 91> or ⁇ 92>, wherein a cooling time for blowing the cold air to cool is 0 second to 60 seconds, and more preferably 0.5 seconds to 30 seconds.
  • ⁇ 94> The method for producing a fine hollow projection according to any one of ⁇ 65> to ⁇ 90>, wherein in the cooling step, natural cooling is performed without performing cooling by a cold air blower.
  • ⁇ 95> Any one of ⁇ 65> to ⁇ 94> having a plurality of protrusions, wherein the protrusions form a plurality of protrusions by inserting the convex part into different positions of the base sheet in the protrusion forming step.
  • ⁇ 96> The method for producing a member hollow protrusion according to any one of ⁇ 65> to ⁇ 95>, wherein the protrusion is a microneedle.
  • ⁇ 97> The method for producing a fine hollow protrusion according to ⁇ 96>, wherein the fine hollow protrusion is a microneedle array in which a plurality of the protrusions are arranged on a base sheet.
  • the convex part 11 is made of SUS304, which is made of stainless steel, and has a conical tip.
  • the convex part 11 had a height (taper part height) H2 of 2.5 mm, a tip diameter D1 of 15 ⁇ m, and a root diameter D2 of 0.5 mm.
  • Base Material Sheet 2A As the base material sheet 2A, a strip-like sheet having a thickness of 0.3 mm formed of polylactic acid (PLA) was prepared.
  • PLA polylactic acid
  • Example 1A A fine hollow projection 1 was produced according to the procedure shown in FIG. Specifically, the heating means of the convex portion 11 was a heater device. As the manufacturing conditions, as shown in Table 1, the heating temperature is 140 ° C., the insertion height is 1.0 mm, the insertion speed is 1 mm / second, the softening time is 10 seconds, cooling Time was 10 seconds.
  • Example 2A A fine hollow projection 1 was produced according to the procedure shown in FIG. Specifically, the heating means of the convex part 11 was an ultrasonic vibration device. As shown in Table 1, the manufacturing conditions are as follows: the frequency of ultrasonic vibration is 20 kHz, the amplitude of ultrasonic vibration is 40 ⁇ m, the insertion height is 1.0 mm, and the insertion speed is 10 mm / second. The softening time was 0.5 seconds and the cooling time was 2 seconds.
  • the fine hollow protrusions of Examples 1A to 2A had good shape accuracy. Therefore, according to the production method for producing the fine hollow projections of Examples 1A to 2A, it can be expected that the fine hollow projections having good shape accuracy can be produced efficiently and continuously.
  • the convex mold part 11 had one conical convex mold 110.
  • the convex mold 110 has a height (taper height) H2 of 2.5 mm, a tip diameter D1 of 15 ⁇ m, a root diameter D2 of 0.5 mm, and a tip angle of 11 degrees. there were.
  • base sheet 2A As base sheet 2A, a strip-shaped sheet having a thickness of 0.3 mm formed of polylactic acid (PLA; Tg 55.8 ° C.) was prepared.
  • PLA polylactic acid
  • Example 1B A microneedle array 1M as a fine hollow protrusion 1 was manufactured according to the procedure shown in FIG. Specifically, the heating means of the convex part 11 was an ultrasonic vibration device. As shown in Table 2, the manufacturing conditions are the same in both the protrusion precursor forming part 10A and the protrusion extension part 10B, and the frequency of ultrasonic vibration is common at 20 kHz, and the amplitude of ultrasonic vibration is common at 40 ⁇ m. there were. Further, in the protrusion precursor forming portion 10A, the insertion height was 0.1 mm, and the insertion speed was 30 mm / second.
  • the insertion height was 1.0 mm and the insertion speed was 5 mm / second.
  • the insertion speed in the protrusion extension part 10B was slower than the insertion speed in the protrusion precursor forming part 10A.
  • the softening time was 0.5 seconds and the cooling time was 1 second.
  • the fine hollow projection of Example 1B was manufactured under the above manufacturing conditions.
  • the temperature of the base material sheet at the time of insertion was 85 degreeC, and the base material sheet was softened.
  • Comparative Example 1B A fine hollow protrusion of Comparative Example 1B was manufactured under the same manufacturing conditions as Example 1B, except that the protrusion speed was 5 mm / second in the protrusion precursor forming part 10A.
  • Example 1B As is clear from the results shown in Table 2, the fine hollow protrusions of Example 1B have through holes formed in the protrusions as compared to the fine hollow protrusions of Comparative Example 1B. The accuracy of the size of the through hole was good. The reason why such a result was obtained is that, in the protrusion precursor forming portion 10A, the insertion of Example 1B was compared to the setting of 0.1 mm where the insertion height conditions of Example 1B and Comparative Example 1B were the same.
  • the protrusion precursor 3b having the through hole 3h is This is probably because the through hole 3h could not be formed in Comparative Example 1B. That is, in the manufacturing process of the fine hollow protrusion of Comparative Example 1B, it is considered that the through hole was not formed in the protrusion because the protrusion precursor formation process was not performed. Therefore, according to the manufacturing method for manufacturing the fine hollow projection of Example 1B, it is possible to efficiently and continuously manufacture the fine hollow projection with good accuracy in the height of the projection and the size of the through hole. I can expect.
  • the convex mold part 11 had one conical convex mold 110.
  • the convex mold 110 has a height (taper height) H2 of 2.5 mm, a tip diameter D1 of 15 ⁇ m, a root diameter D2 of 0.5 mm, and a tip angle of 11 degrees. there were.
  • base sheet 2A As base sheet 2A, a strip-shaped sheet having a thickness of 0.3 mm formed of polylactic acid (PLA; Tg 55.8 ° C.) was prepared.
  • PLA polylactic acid
  • Example 1C According to the procedure shown in FIG. 25, a microneedle array 1M as a fine hollow protrusion 1 was manufactured. Specifically, the heating means of the convex part 11 was an ultrasonic vibration device. In addition, as the receiving member 13, a material made of a synthetic resin made of polyacetal was prepared. The receiving member 13 had one conical recess 131. The shape of the opening periphery 131a of the recess 131 coincided with the shape of the outer periphery 11c at a position where the convex mold 110 of the convex portion 11 contacts the receiving member 13 on the peripheral wall 11W. That is, the diameter at the opening peripheral edge 131a and the diameter at the contact position of the convex mold 110 were the same.
  • the position of the convex mold 110 at the contact position is a portion between the tip portion and the root portion.
  • the frequency of ultrasonic vibration was 20 kHz, and the amplitude of ultrasonic vibration was 40 ⁇ m.
  • the insertion height was 0.5 mm, and the insertion speed was 10 mm / second.
  • the softening time was 0.5 seconds and the cooling time was 1 second.
  • the fine hollow protrusion of Example 1C was manufactured.
  • the temperature of the base material sheet at the time of insertion was 85 degreeC, and the base material sheet was softened.
  • Comparative Example 1C A fine hollow projection of Comparative Example 1C was produced under the same production conditions as Example 1C, except that a receiving member having a through-hole was used. The diameter of the recess 131 at the opening periphery was larger than the root diameter D2 of the convex mold 110.
  • the fine hollow protrusions of Example 1C are formed with through holes as compared with the fine hollow protrusions of Comparative Example 1C.
  • the size accuracy was good. Therefore, according to the manufacturing method for manufacturing the fine hollow projection of Example 1C, it is possible to efficiently and continuously manufacture the fine hollow projection with good accuracy in the height of the protrusion and the size of the through hole. I can expect.
  • a fine hollow projection having a high-quality through-hole having a high accuracy in the height of the fine hollow projection and the size of the through-hole can be stably produced at low cost. Can be mass-produced.

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Abstract

La présente invention concerne un procédé de fabrication d'une fine protubérance creuse (1) comprend une étape de formation d'une partie saillante visant à mettre une partie convexe (11) dotée d'un moyen de chauffage en contact avec une face avant (2D) d'une feuille de substrat (2) formée à partir d'une résine thermoplastique, et, tout en ramollissant avec de la chaleur une partie de contact (TP) dans la feuille de substrat (2), à faire pénétrer dans la feuille de substrat (2) la partie convexe (11) et à former une partie saillante (3) qui fait saillie depuis une autre face (2U) de la feuille de substrat (2). Le procédé comprend en outre une étape de refroidissement visant à refroidir la partie saillante (3), la partie convexe (11) pénétrant dans la partie interne de la partie saillante (3). Le procédé comprend en outre une étape de libération visant, après l'étape de refroidissement, à retirer la partie convexe (11) de la partie interne de la partie en saillante (3) et à former une fine protubérance creuse (1).
PCT/JP2015/078372 2014-10-17 2015-10-06 Procédé de fabrication d'une fine protubérance creuse WO2016060020A1 (fr)

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KR1020177010103A KR102021212B1 (ko) 2014-10-17 2015-10-06 미세 중공 돌기물의 제조 방법
US15/519,440 US10632653B2 (en) 2014-10-17 2015-10-06 Fine hollow protrusion manufacturing method
CN201580056329.2A CN107073249B (zh) 2014-10-17 2015-10-06 微细中空突起物的制造方法

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JP2015176375A JP6064012B1 (ja) 2014-10-17 2015-09-08 微細中空突起物の製造方法
JP2015176377A JP6586329B2 (ja) 2015-08-17 2015-09-08 微細中空突起物の製造方法
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JP2015176376A JP6126658B2 (ja) 2015-08-17 2015-09-08 微細中空突起物の製造方法
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WO2018211421A1 (fr) * 2017-05-19 2018-11-22 Sabic Global Technologies B.V. Procédés et systèmes de production de réseaux de micro-aiguilles polymères par estampage ultrasonore, et réseaux de micro-aiguilles résultants
CN110709128A (zh) * 2017-06-07 2020-01-17 花王株式会社 微细突起单元的制造方法和微细突起单元
CN111526918A (zh) * 2017-12-26 2020-08-11 三岛光产株式会社 微针阵列

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US20050178760A1 (en) * 2004-02-17 2005-08-18 Eng-Pi Chang Method of making microneedles
JP2006518675A (ja) * 2003-02-24 2006-08-17 コリウム インターナショナル， インコーポレイテッド 貫通孔を備えた複数のマイクロエレメントを有するマイクロ構造物の製造方法
WO2008093679A1 (fr) * 2007-01-29 2008-08-07 Medrx Co., Ltd. Procédé de fabrication d'une micro-aiguille d'une substance thermosensible
JP2010068840A (ja) * 2008-09-16 2010-04-02 Toppan Printing Co Ltd 針状体および針状体製造方法

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JPH01110929A (ja) * 1987-10-26 1989-04-27 Mitsubishi Plastics Ind Ltd プラスチックシートの折り曲げ方法
JP2003501162A (ja) * 1999-06-09 2003-01-14 ザ プロクター アンド ギャンブル カンパニー 皮内用ミクロ針アレイ装置
JP2006518675A (ja) * 2003-02-24 2006-08-17 コリウム インターナショナル， インコーポレイテッド 貫通孔を備えた複数のマイクロエレメントを有するマイクロ構造物の製造方法
US20050178760A1 (en) * 2004-02-17 2005-08-18 Eng-Pi Chang Method of making microneedles
WO2008093679A1 (fr) * 2007-01-29 2008-08-07 Medrx Co., Ltd. Procédé de fabrication d'une micro-aiguille d'une substance thermosensible
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WO2018211421A1 (fr) * 2017-05-19 2018-11-22 Sabic Global Technologies B.V. Procédés et systèmes de production de réseaux de micro-aiguilles polymères par estampage ultrasonore, et réseaux de micro-aiguilles résultants
CN110709128A (zh) * 2017-06-07 2020-01-17 花王株式会社 微细突起单元的制造方法和微细突起单元
CN110709128B (zh) * 2017-06-07 2022-02-25 花王株式会社 微细突起单元的制造方法和微细突起单元
CN111526918A (zh) * 2017-12-26 2020-08-11 三岛光产株式会社 微针阵列
US11801372B2 (en) 2017-12-26 2023-10-31 Mishima Kosan Co., Ltd. Microneedle array

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