JP2018121842A - Method for manufacturing needle-like body - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a needle-like body, which manufactures a needle-like body by creating a transfer plate excellent in durability without using an original plate and using the created transfer plate.SOLUTION: A method for manufacturing a needle-like body in which a protrusion part whose external dimensions are gradually narrowed on one surface of a support substrate is arranged in the form of an array includes: a step for preparing a first metal plate with no through hole, and second metal plates having the same number as stages of the protrusion part, wherein each of the second metal plates includes one through hole of a shape corresponding each of the respective stages of the protrusion part or a plurality of through holes in the form of the same array as the arrangement of the protrusion part; a step for creating a transfer plate with a recessed part of a shape corresponding to the protrusion part by sequentially overlapping and sticking the plurality of second metal plates on the first metal plate in an ascending order of external dimensions of through holes provided in the respective metal plates; and a step for manufacturing a needle-like body by transferring the recessed part formed in the transfer plate to a needle-like body formation material.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a method for manufacturing a needle-shaped body.

  The percutaneous absorption method, which is a method of injecting a delivery product such as a drug from the skin and administering the delivery product into the body, is used as a method capable of easily administering the delivery product without causing pain to the human body. .

  In the field of transdermal administration, a method has been proposed in which a skin is perforated using a pad on which fibers of the order of μm are formed, and a drug or the like is administered into the skin (see Patent Document 1).

  Further, as a method for producing a needle-like body, it has been proposed to prepare an original plate using machining, form a transfer plate from the original plate, and perform transfer processing molding using the transfer plate (Patent Document 2). reference).

  Further, as a method for producing a needle-like body, it has been proposed to prepare an original plate using an etching method, form a transfer plate from the original plate, and perform transfer processing molding using the transfer plate (Patent Document 3). reference). The transfer plate is often made of silicone rubber.

JP-A-48-93192 International Publication No. 2008/013282 International Publication No. 2008/004597

  Since the transfer plate made of silicone rubber is inferior in durability to metal, it is necessary to prepare the transfer plate again after the needle-like body is prepared to some extent. However, the original plate also has a lifetime, and the original plate may be damaged while the transfer plate is manufactured. In this case, the original plate is prepared again.

  An object of this invention is to provide the manufacturing method of the acicular body which produces the transfer plate excellent in durability, without using an original plate, and manufactures an acicular body using the produced transfer plate.

  In order to solve the above-mentioned problems, the present invention provides a method for manufacturing a needle-like body in which projections whose outer dimensions are narrowed in a step-like manner are arranged in an array on one surface of a support substrate. 1 metal plate and the same number of second metal plates as the number of steps of the protrusions, each of the second metal plates having one through hole having a shape corresponding to each step of the protrusions or a protrusion A step of preparing a plurality of second metal plates provided in the same array as the arrangement of the parts, and a plurality of second metal plates on the first metal plate, the outer dimensions of the through holes provided in each of the second metal plates By stacking and laminating in ascending order, forming a transfer plate in which a recess having a shape corresponding to the protrusion is formed, and transferring the recess formed in the transfer plate to the needle-shaped body forming material, A method for producing a needle-like body.

  ADVANTAGE OF THE INVENTION According to this invention, the manufacturing method of the acicular body which manufactures the transfer plate excellent in durability without using an original plate, and manufactures an acicular body using the produced transfer plate is realizable.

FIG. 1 is a perspective view of a needle-like body according to an embodiment of the present invention. FIG. 2 is a top view and a schematic cross-sectional view of a needle-like body according to an embodiment of the present invention. FIG. 3 is a schematic explanatory view of a transfer plate manufacturing method according to an embodiment of the present invention. FIG. 4 is an example of a needle-shaped body manufactured by transferring a recess formed in the transfer plate according to FIG. 3 to a needle-shaped body forming material.

  Embodiments of the present invention will be described in detail with reference to the drawings. First, the structure and material of the needle-shaped body according to the embodiment of the present invention will be described, and then the method for manufacturing the needle-shaped body will be described.

  FIG. 1 shows a perspective view of a needle-like body according to an embodiment of the present invention. FIG. 2 shows a top view and a schematic cross-sectional view of the acicular body according to the embodiment of the present invention. Fig.2 (a) is a top view from the protrusion part side of a needle-shaped object, FIG.2 (b) is a schematic cross section along the cutting | disconnection line II 'of Fig.2 (a). As shown in FIG. 1 and FIGS. 2A and 2B, the needle-like body 1 according to the embodiment of the present invention includes a support substrate 32 and a protrusion 34 having protruding regions 34a to 34c. Refers to a molded body. The shape of the protrusion 34 may be a shape suitable for puncturing the skin, and may be designed as appropriate. Specifically, as the shape of the protruding portion 34, a shape in which the protruding regions 34 a to 34 c are stacked so that the outer dimensions are narrowed stepwise in the direction opposite to the supporting substrate 32 side as shown in FIG. The shape which piled up the protruding area | region of the prism was mentioned so that an external dimension might narrow in a step shape in the direction opposite to the side. In addition, the shape of the projection part 34 may be a cone, a pyramid, a cylinder, a prism, a pencil shape (a body part is a columnar shape, and a tip part is a cone shape). The needle-like body 1 is either (1) one in which only one protrusion 34 is formed on the support substrate 32 or (2) one in which a plurality of protrusions 34 are formed on the support substrate 32. But it ’s okay.

  Further, in the case of the needle-like body 1 in which a plurality of protrusions 34 are formed on the support substrate 32, it is preferable that the protrusions are arranged in an array. Here, the “array shape” indicates a state in which the unit needle-like bodies are arranged two-dimensionally. For example, a pattern such as a lattice arrangement, a close-packed arrangement, a concentric arrangement, or a random pattern It is assumed to include a two-dimensional array pattern.

  In the needle-like body 1, the size of the needle-like protrusion 34 preferably has a thickness and a length suitable for forming a puncture hole in the skin. Specifically, the height H of the protrusion 34 shown in FIG. 2B is preferably in the range of 10 μm to 1000 μm. The height H of the protrusion 34 is a vertical distance from the surface of the support substrate 32 to the tip of the protrusion 34. The height H of the protrusion 34 is preferably determined in consideration of how deep the puncture hole formed when the needle-like body 1 is punctured is formed within the above range.

  In particular, when the puncture hole formed when the needle-like body 1 is punctured is held “in the stratum corneum”, the height H of the protrusion 34 of the needle-like body 1 is, for example, 10 μm or more and 300 μm or less, more preferably 30 μm or more. It is desirable to be in the range of 200 μm or less. In addition, when the puncture hole formed when the needle-like body 1 is punctured is kept at a “length that penetrates the stratum corneum and does not reach the nerve layer”, the height H of the protrusion 34 of the needle-like body 1 is It is desirable that the thickness be in the range of 200 μm to 700 μm, more preferably 200 μm to 500 μm, and still more preferably 200 μm to 300 μm.

  Furthermore, when the puncture hole formed when the needle-like body 1 is punctured is “the length reaching the dermis”, the height H of the protrusion 34 of the needle-like body 1 is in the range of 200 μm or more and 500 μm or less. It is preferable to do. Further, when the puncture hole formed when the needle-like body 1 is punctured is “the length reaching the epidermis”, the height H of the protrusion 34 of the needle-like body 1 is in the range of 200 μm or more and 300 μm or less. It is preferable to do.

  The width D of the protrusion 34 is preferably in the range of 1 μm to 300 μm. The width D of the protrusion 34 is preferably determined in consideration of the depth within the skin at which the puncture hole formed when the needle-like body 1 is punctured is within the above range. The width D of the protrusion 34 is the maximum dimension of the cross section of the protrusion 34 parallel to the support substrate 32. For example, when the protrusion 34 has a shape in which the protruding regions 34a to 34c are overlapped so that the outer dimensions are narrowed in a stepped shape shown in FIG. 1, the diameter of the protruding region 34c is the width D. When the protruding portion 34 has a shape in which protruding regions of regular quadrangular prisms are overlapped so that the external dimensions are narrowed stepwise, a square diagonal line in the protruding region closest to the support substrate 32 of the protruding portion 34 is the width D. . When the protrusion 34 is a cylinder, the diameter of the bottom surface of the protrusion 34 is the width D. When the protrusion 34 is a regular quadrangular prism, a square diagonal line on the bottom surface of the protrusion 34 is the width D.

  The aspect ratio of the protrusion 34 is preferably in the range of 1 to 10. The aspect ratio A is defined by A = H / D using the length H and width D of the protrusion 34.

  The material forming the needle-like body 1 is desirably a thermoplastic resin or a biodegradable polysaccharide. In the case of a thermoplastic resin, for example, polyethylene, polypropylene, polycarbonate, polyacetal, polystyrene, polymethyl methacrylate, cellulose acetate, polyethylene terephthalate, polyurethane, Teflon (registered trademark), polyvinyl chloride, polyvinylidene chloride, ethylene / vinyl acetate A polymer etc. are mentioned. Furthermore, any biodegradable material is preferable, and examples thereof include polylactic acid, polybutylene succinate, polyε-caprolactone, and polyβ-hydroxybutyric acid. Moreover, the mixture of these thermoplastic resins may be sufficient. By using a biodegradable resin, even if the needle-like body 1 breaks in the skin after the needle-like body 1 is punctured into the skin, it is possible to minimize the influence on the human body.

  When the material forming the needle-like body 1 is a biodegradable polysaccharide, for example, dextran, dextrin, pectin, pullulan, chondroitin sulfate, alginate, chitosan, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose And ethyl cellulose. Moreover, the mixture of these biodegradable polysaccharides may be sufficient. By using the biodegradable polysaccharide, the protrusion 34 can be dissolved in the skin after the needle 1 is punctured into the skin. Therefore, when the medicinal component is contained in the needle-like body 1, the delivery product can be quickly introduced into the skin.

  Needle 1 can include a delivery for delivery into the skin. Delivery materials can include pharmacologically active substances and cosmetic compositions. At this time, when a material having a fragrance is used as a delivery product, an odor can be imparted during use, which is preferable for use as a cosmetic product.

  You may select the said pharmacologically active substance suitably according to a use. For example, vaccines such as influenza, painkillers for cancer patients, insulin, biologics, gene therapy drugs, injections, oral preparations, skin preparations, and the like may be used. Since the needle-like body 1 punctures the skin, it can be applied to pharmacologically active substances that require subcutaneous injection, in addition to pharmacologically active substances that are conventionally used for transdermal administration. In particular, vaccines that are injections are suitable for application to children because there is no pain in administration when the needle 1 is used. In addition, with conventional oral administration, it is difficult for children to take an oral formulation, but when the needle 1 is used, it is not necessary to take a drug upon administration, so it is suitable for application to children. .

  In the dissolution type needle-like body in which the punctured needle is eluted into the skin and the delivery product is delivered into the body, the delivery product is contained inside the needle-like body. However, the punctured needle does not elute inside the skin, and the delivered product remains on the support substrate of the needle-like body, resulting in a problem that the medicine is wasted. On the other hand, in the needle-like body 1 according to the present embodiment, the waste of the medicine can be solved by containing the delivery product only in the protrusion.

  The cosmetic composition is a composition used as a cosmetic product and a cosmetic product. For example, moisturizers, colorants, fragrances, and physiologically active substances that exhibit cosmetic effects (improvement effect on wrinkles, acne, pregnancy lines, improvement effect on hair loss, etc.), and the like.

  In addition, when the depth of the puncture hole is kept “in the stratum corneum”, the delivery product can stay in the stratum corneum. Since the stratum corneum is constantly generated by metabolism, the deliverables in the stratum corneum are discharged out of the body over time. That is, the delivered product can be eliminated by washing the skin or peeling the skin.

  In addition, when the depth of the puncture hole is kept at “a length that penetrates the stratum corneum and does not reach the nerve layer”, the delivery product can be delivered to a position deeper than the stratum corneum. Since the puncture hole formed in the stratum corneum is closed over time, the delivery delivered under the stratum corneum is held in the living body while being blocked by the stratum corneum from the outside. For this reason, the delivered product can be reduced for exfoliation due to metabolism of the stratum corneum and washing such as skin care, and can be held for a long time.

  For this reason, when the acicular body 1 according to the present embodiment is used for cosmetic purposes, it can maintain a long-term makeup state. It can be suitably used for delivery of a cosmetic composition at a site where it is desired to maintain the color of the period.

  In addition, the needle-like body 1 according to the present embodiment is preferably used as a prescription (makeup, treatment, etc.) corresponding to skin abnormalities (spotted spots, etc.) caused by a site inside the stratum corneum. it can.

  On the other hand, when administering the delivery article with the needle-like body 1, the delivery article may be applied onto the target skin before or after the needle-like body 1 is punctured into the skin. At this time, the delivery product may be placed on the needle-like body 1 and the delivery product may be applied to the target skin surface.

  Further, the needle-like body 1 according to the present embodiment may include a delivery product on the surface of the protrusion 34.

  Further, in the needle-like body 1 according to the present embodiment, the support substrate 32 may have flexibility. By using a flexible support substrate, it is possible to puncture a flexible object such as a curved surface or biological skin. Moreover, when it has flexibility, the roller which the projection part 34 stood can be formed by making it roll shape.

  Moreover, in the prescription using the needle-shaped body 1 which concerns on this Embodiment, you may use the applicator for fixing the position and direction of insertion.

  Next, the manufacturing method of the acicular body which concerns on embodiment is demonstrated.

  FIG. 3 is a schematic explanatory view of a method for producing a transfer plate according to an embodiment of the present invention, and FIG. 4 is manufactured by transferring a recess formed in the transfer plate according to FIG. 3 to a needle-shaped body forming material. An example of a needle-like body was shown.

  As shown in FIG. 4, the protrusion 34 of the needle-like body 1 manufactured by the manufacturing method according to the present embodiment has a protruding region 34 a whose outer dimensions are narrowed stepwise in the direction opposite to the support substrate 32 side. Thru 34c. When the shape of the protruding portion 34 is the shape, a transfer plate in which a concave portion having the same shape as the protruding portion 34 is easily formed by stacking and bonding a plurality of metal plates having through holes. Further, by increasing the number of metal plates to be bonded, the side surfaces of the recesses formed on the transfer plate can be smoothed. As a result, the transfer plate was used to transfer to the needle-shaped body forming material. The shape of the protrusion of the needle-like body can be a substantially conical shape or a substantially pyramidal shape.

<Process for preparing a metal plate>
First, as shown in FIG. 3A, a cross section when the first metal plate 11 without the through hole 14 and the protruding regions 34 a to 34 c of the protrusion 34 are cut along a plane parallel to the support substrate 32. A plurality of second metal plates 12 having through-holes 14 having the same shape are prepared. The number of the second metal plates 12 is the same as the number of the protrusions 34, that is, the number of the protruding regions 34a to 34c. In the present embodiment, the second metal plate 12 includes three metal plates 12a to 12c. A through hole 14a having an inner diameter corresponding to the projecting region 34a is formed in the second metal plate 12a, and a through hole 14b having an inner diameter corresponding to the projecting region 34b is formed in the second metal plate 12b. A through hole 14c having an inner diameter corresponding to the protruding region 34c is formed in the metal plate 12c, and a concave portion 15 (inverted type) having the same shape as the protruding portion 34 is configured by overlapping these. As the thickness of each of the plurality of second metal plates 12 is smaller, the side surface of the recess 15 corresponding to the protrusion 34 can be made smoother. For example, the thickness of the second metal plate 11 is not less than 0.01 mm and not more than 1 mm. The shape of the through hole 14 is circular when the protruding regions 34a to 34c of the protrusion 34 are cylindrical, and is rectangular when the protruding regions 34a to 34c are quadrangular prisms. In addition, it is also possible to manufacture the projection part 34 of a complicated shape and the projection part 34 of a cone shape or a pyramid shape by combining the shape of various through-holes. Moreover, it is also possible to manufacture the columnar projections 34 and the prismatic projections 34 by making the through holes have the same shape. In addition, since only one protrusion 34 according to the present embodiment is formed on the support substrate 32, the number of the through holes 14 formed in the second metal plate 12 is one. When a plurality of 34 are formed on the support substrate 32, the plurality of through holes 14 are provided in the same array as the arrangement of the protrusions 34.

  A known manufacturing method may be used as the processing method of the through hole 14 as appropriate. At this time, a fine processing technique may be used, for example, a lithography method, a wet etching method, a dry etching method, a laser processing method, a precision machining method, or the like may be used. The material of the first metal plate 11 and the second metal plate 12 may be anything as long as it can be processed. For example, copper, titanium, nickel, aluminum, chromium, gold, magnesium, molybdenum, lead, platinum, Examples include iridium, silver, tantalum, zirconium, tungsten, uranium, vanadium, alloys thereof, stainless steel, steel, carbide, and graphite.

<Process for producing a transfer plate by bonding metal plates>
Next, as shown in FIG. 3B and FIG. 3C, a plurality of second metal plates 12 having through holes 14 are respectively provided on the first metal plate 11 having no through holes. The transfer plate 10 in which the concave portions 15 having the same shape as the protrusions 34 are formed is obtained by stacking and pasting the through holes 14 in order of increasing outer dimensions. As a method of bonding, a known method may be used as appropriate. Note that the second metal plate 12 may be bonded to ceramic or glass instead of the first metal plate 11. Examples of the bonding method include brazing, diffusion bonding, and welding. In particular, when diffusion bonding is used, a large-area metal plate can be bonded with high accuracy. After producing a large-area transfer plate, it may be cut and divided according to the purpose. By doing in this way, it becomes possible to produce a lot of transfer plates efficiently.

<Process of transferring the shape of the concave portion to the needle-shaped body forming material to manufacture the needle-shaped body>
Next, by using the transfer plate 10 shown in FIG. 3C, the concave body 15 is transferred to the above-described needle-shaped body forming material, whereby the needle-shaped body 1 is manufactured. The transfer plate 10 may be subjected to a mold release process in advance. By performing the mold release treatment, the needle-like body 1 can be easily peeled from the transfer plate 10 after the needle-like body is formed. The mold release process may be appropriately performed by a known method.

(1) When the forming material of the needle-like body 1 is a thermoplastic resin, a thermoplastic resin is applied onto the transfer plate 10, heated and melted at a temperature equal to or higher than the melting point of the thermoplastic resin, pressed, and cooled and cured. . These steps may be performed under reduced pressure or under vacuum. By performing the process under reduced pressure or under vacuum, it is possible to quickly form the protrusions 34. The cooling may be performed while being pressed or may be cooled after the press is released. Cooling may be performed by any method such as a contact method or a non-contact method. As described above, the shape of the recess 15 is transferred to the needle-shaped body forming material, and the needle-shaped body 1 can be formed on the transfer plate 10.

(2) When forming material of needle-like body 1 into biodegradable polysaccharide First, the material solution of needle-like body 1 is produced. The solvent is not particularly limited as long as the biodegradable polysaccharide used as the material of the needle-like body 1 is dissolved, and examples thereof include water and alcohol, and a mixed solvent thereof may be used. Next, the produced needle-shaped body material liquid is supplied to the transfer plate 10. As a method for supplying the solution, a known method may be appropriately selected according to the shape and dimensions of the transfer plate 10. For example, as an aqueous solution supply method, a spin coating method, an inkjet method, a method using a dispenser, a casting method, or the like may be used. Further, at the time of filling, the environment around the transfer plate 10 may be under reduced pressure or under vacuum. By performing the process under reduced pressure or under vacuum, it becomes possible to quickly fill the protrusions 34. Next, the needle-shaped body material liquid is dried to remove the solvent. As described above, the shape of the recess 15 is transferred to the needle-shaped body forming material, and the needle-shaped body 1 can be formed on the transfer plate 10.

<Step of peeling the needle-shaped body from the transfer plate>
By peeling the needle-like body 1 from the transfer plate 10, the needle-like body 1 shown in FIG. 4 can be obtained.

  EXAMPLES Hereinafter, although this invention is demonstrated in detail using an Example and a comparative example, this invention is not limited to the following Example.

[Example 1]
One 300 mm × 300 mm copper plate without through holes and 10 300 mm × 300 mm copper plates provided with 560 × 560 through holes every 500 μm were prepared. The through hole was formed by etching. Table 1 shows the thickness of each copper plate and the diameter of each through hole.

  Copper plates No. 1 to 11 were stacked in this order and bonded together by diffusion bonding. The plates obtained by bonding were cut and divided to obtain 49 40 mm × 40 mm transfer plates.

  The transfer plate was subjected to release treatment. Next, under reduced pressure (gauge pressure -0.8 MPa), pellets of low density polyethylene (Nippon Polyethylene, LC600A) were melted at 180 ° C. on the transfer plate, and then pressed with a force of about 0.4 N. Cool to cure. Thereafter, the cured low-density polyethylene was peeled off from the transfer plate under atmospheric pressure to obtain the needle-like body according to Example 1.

[Example 2]
A transfer plate was prepared in the same manner as in Example 1, and the release plate was subjected to a release treatment. Next, under reduced pressure (gauge pressure -0.8 MPa), a 10 wt% aqueous solution of hydroxypropylcellulose (Tokyo Kasei 6-10 mPa · s, 2% in water at 20 ° C) was dropped onto the transfer plate. Next, the transfer plate was placed on a hot plate set at 40 ° C. for 8 hours under atmospheric pressure, and the dripping solution was dried to evaporate water, thereby forming a needle-like body on the transfer plate. Next, the acicular body was peeled from the transfer plate, and the acicular body according to Example 2 was obtained.

  As a result of observing the obtained needle-like bodies according to Examples 1 and 2 with an optical microscope, it was confirmed that a step structure could be formed cleanly up to the tip of the protrusion.

  The acicular body of the present invention can be used in various fields that require fine acicular bodies. For example, it can be expected to be applied as a needle-like body used for MEMS devices, optical members, sample jigs, drug discovery, medical use, cosmetics, cosmetic use, and the like.

DESCRIPTION OF SYMBOLS 1 ... Needle-like body 32 ... Support substrate 34 ... Projection part 34a, 34b, 34c ... Projection-like area | region 10 ... Transfer plate 11 ... 1st metal plate 12, 12a, 12b, 12c ... 2nd metal plate 14, 14a, 14b, 14c ... through hole 15 ... concave portion

Claims (2)

A method of manufacturing a needle-like body in which protrusions whose outer dimensions are narrowed stepwise on one side of a support substrate are arranged in an array,
A first metal plate having no through-hole and a second metal plate having the same number of steps as the protrusions, each of the second metal plates having a shape corresponding to each step of the protrusions Preparing a second metal plate having one through-hole or a plurality of through-holes provided in the same array as the arrangement of the protrusions;
On the first metal plate, a plurality of the second metal plates are overlapped in order from the smallest outer dimension of the through hole provided in each, so that a concave portion having a shape corresponding to the protrusion is formed. Producing a formed transfer plate; and
And a step of manufacturing the needle-like body by transferring the concave portion formed in the transfer plate to the needle-like body forming material.   The method for manufacturing a needle-shaped body according to claim 1, wherein the first metal plate and the plurality of second metal plates are bonded together by diffusion bonding.