JP6060547B2 - Manufacturing method of needle-shaped body - Google Patents

Manufacturing method of needle-shaped body Download PDF

Info

Publication number
JP6060547B2
JP6060547B2 JP2012166020A JP2012166020A JP6060547B2 JP 6060547 B2 JP6060547 B2 JP 6060547B2 JP 2012166020 A JP2012166020 A JP 2012166020A JP 2012166020 A JP2012166020 A JP 2012166020A JP 6060547 B2 JP6060547 B2 JP 6060547B2
Authority
JP
Japan
Prior art keywords
needle
protrusion
original plate
shaped
plate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2012166020A
Other languages
Japanese (ja)
Other versions
JP2014023699A (en
Inventor
大蔵 植村
大蔵 植村
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Toppan Inc
Original Assignee
Toppan Inc
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
Application filed by Toppan Inc filed Critical Toppan Inc
Priority to JP2012166020A priority Critical patent/JP6060547B2/en
Publication of JP2014023699A publication Critical patent/JP2014023699A/en
Application granted granted Critical
Publication of JP6060547B2 publication Critical patent/JP6060547B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046Solid microneedles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M37/00Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053Methods for producing microneedles

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Description

本発明は、針状体の製造方法に関する。   The present invention relates to a method for manufacturing a needle-shaped body.

皮膚上から薬剤などの送達物を浸透させ体内に送達物を投与する方法である経皮吸収法は、人体に痛みを与えることなく簡便に送達物を投与することが出来る方法として用いられている。また、経皮投与の分野で、μmオーダーの微細な針状体(マイクロニードル)を用いて皮膚を穿孔し、皮膚内に薬剤を投与する方法が提案されている(特許文献1参照)。   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 of perforating the skin using a fine needle (microneedle) on the order of μm and administering a drug into the skin has been proposed (see Patent Document 1).

この際に用いる微細な針状体の形状は、皮膚を穿孔するための十分な細さと先端角、および皮下に薬液を浸透させるための十分な長さを有していることが必要とされ、直径は数μmから数百μm(具体的には、例えば、1μm〜300μm程度)、長さは、具体的には数十μmから数百μm(具体的には、例えば、20μm〜1000μm程度)のものが望ましいとされている。   The shape of the fine needle-like body used at this time is required to have a sufficient fineness and tip angle for piercing the skin and a sufficient length for allowing the drug solution to penetrate subcutaneously, The diameter is several μm to several hundred μm (specifically, for example, about 1 μm to 300 μm), and the length is specifically several tens of μm to several hundred μm (specifically, for example, about 20 μm to 1000 μm). Is desirable.

また、針状体を構成する材料としては、仮に破損した針状体が体内に残留した場合でも、人体に悪影響を及ぼさない材料であることが望ましく、このような材料としてはキチン・キトサン等の生体適合材料が好適である(特許文献2参照)。   In addition, the material constituting the acicular body is preferably a material that does not adversely affect the human body even if the damaged acicular body remains in the body, such as chitin and chitosan. A biocompatible material is suitable (see Patent Document 2).

また、上述した針状体の製造方法として、切削加工を用いて原版を作成し、複製版を形成し、転写加工成型を行なうことが提案されている(特許文献3参照)。   In addition, as a method for manufacturing the needle-like body described above, it has been proposed to create an original plate using cutting, form a duplicate plate, and perform transfer processing molding (see Patent Document 3).

特開昭48−93192号公報JP-A-48-93192 国際公開第2008/020632号パンフレットInternational Publication No. 2008/020632 Pamphlet 国際公開第2008/013282号パンフレットInternational Publication No. 2008/013282 Pamphlet

皮膚を穿刺する針状体は、穿刺後、皮膚から剥がれないことが求められる仕様を要求されることがある。   The needle-like body that punctures the skin may be required to have a specification that is required not to peel from the skin after puncturing.

そこで、本発明は、上述の課題を解決するためになされたものであり、穿刺後、皮膚から剥がれることを抑制できる針状体を製造する針状体の製造方法を提供することを目的とする。   Then, this invention is made | formed in order to solve the above-mentioned subject, and it aims at providing the manufacturing method of the acicular body which manufactures the acicular body which can suppress peeling from skin after puncture. .

上記課題を解決するために請求項1に係る発明としては、基材の一方の面に針状の突起部を備える針状体の製造方法であって、基材の一方の面に針状の突起部を備える針状体原版を作製する針状体原版作製工程と、前記針状体原版の突起部形成面にマイクロカプセル分散液を塗布し、前記針状体原版の突起部形成面にマイクロカプセルを配置し、前記針状体原版の突起部表面に微小突起を形成する微小突起形成工程と、該微小突起が形成された針状体原版から複製版を作製する複製版作製工程と、該複製版に針状体形成材料を充填し該針状体形成材料を剥離することにより、基材の一方の面に針状の突起部を備え、かつ、突起部表面に微小突起を備える針状体と作製する転写成形工程とを備えることを特徴とする針状体の製造方法とした。
また、請求項2に係る発明としては、前記針状体原版の突起部形成面にマイクロカプセルを配置する前に、前記針状体原版の突起部形成面表面を改質する表面改質工程を備えることを特徴とする請求項1記載の針状体の製造方法とした。

In order to solve the above-mentioned problem, the invention according to claim 1 is a method of manufacturing a needle-like body having a needle-like protrusion on one surface of a base material, and the needle-like surface is provided on one side of the base material. A needle-shaped original plate preparation step for preparing a needle-shaped original plate provided with a protrusion, a microcapsule dispersion is applied to the protrusion-forming surface of the needle-shaped original plate , and a micro-capsule dispersion is applied to the protrusion-forming surface of the needle-shaped original Arranging a capsule, forming a microprojection on the surface of the projection of the needle-shaped original plate, forming a microplate from the needle-shaped original plate on which the microprotrusion is formed, and producing a replica plate, By filling the replica plate with the needle-shaped body forming material and peeling the needle-shaped body forming material, the needle-shaped body is provided with a needle-like projection on one surface of the base material, and the projection surface has a micro-projection. The needle-shaped body manufacturing method is characterized by comprising a body and a transfer molding step to be manufactured.
Further, the invention according to claim 2 includes a surface modification step for modifying the surface of the projection of the needle-shaped body original plate before arranging the microcapsule on the surface of the projection of the needle-shaped body original plate. The needle-shaped body manufacturing method according to claim 1, wherein the needle-shaped body manufacturing method is provided.

本発明の針状体の製造方法は、針状体原版の表面に対し濡れ性が高いマイクロカプセルを塗布する。これにより、針状体原版の表面上で、マイクロカプセルが粒状に留まり、針状体の表面に微小突起を多量に形成することができる。そして、マイクロカプセルが粒上に配置された針状体原版を複製して針状体を作製することにより、形成された微小突起部位を有する形状が、針状体を皮膚に穿刺するとき皮膚内に係留され、穿刺後針状体が皮膚から剥がれることを抑制できる。   In the method for producing a needle-shaped body of the present invention, a microcapsule having high wettability is applied to the surface of a needle-shaped body original plate. As a result, the microcapsules remain in a granular shape on the surface of the needle-shaped body original plate, and a large amount of microprojections can be formed on the surface of the needle-shaped body. Then, the needle-shaped body original plate in which the microcapsules are arranged on the grains is duplicated to produce a needle-shaped body, so that the shape having the formed micro-projection site is formed in the skin when the needle-shaped body is punctured into the skin. The needle-like body can be prevented from being peeled from the skin after puncturing.

図1は本発明の針状体の斜視図である。FIG. 1 is a perspective view of a needle-shaped body of the present invention. 図2は本発明の針状体の突起部の拡大斜視図である。FIG. 2 is an enlarged perspective view of the protrusion of the needle-shaped body of the present invention. 図3は本発明の針状体の突起部の模式断面図をである。FIG. 3 is a schematic cross-sectional view of the protrusion of the needle-shaped body of the present invention. 図4は本発明の針状体の製造方法の模式断面図(説明図)である。FIG. 4 is a schematic cross-sectional view (explanatory drawing) of the method for producing a needle-shaped body of the present invention. 図5は本発明の針状体の製造方法の模式断面図(説明図)である。FIG. 5 is a schematic cross-sectional view (explanatory drawing) of the method for manufacturing a needle-shaped body of the present invention.

本発明の針状体について説明する。
図1の本発明の針状体の斜視図を示した。本発明の針状体1は、基材11上に針状の突起部12を備える。本発明の針状体1は、基材11に1つの突起部を具備してもよく、また基材11に複数の突起部を具備してもよい。複数の突起部を具備する場合には、アレイ状に突起部を具備してよい。ここで、「アレイ状」とは、図1に示すように、各突起部が並んでいる状態を示すものであり、例えば、格子配列、最密充填配列、同心円状に配列、ランダムに配列などのパターンを含む。
The acicular body of the present invention will be described.
The perspective view of the needlelike object of the present invention of Drawing 1 was shown. The needle-like body 1 of the present invention includes a needle-like protrusion 12 on a base material 11. In the needle-like body 1 of the present invention, the base 11 may have one protrusion, and the base 11 may have a plurality of protrusions. When a plurality of protrusions are provided, the protrusions may be provided in an array. Here, the “array shape” indicates a state in which the protrusions are arranged as shown in FIG. 1, for example, a lattice arrangement, a close-packed arrangement, a concentric arrangement, a random arrangement, etc. Including patterns.

針状体の突起部の形状は、錐体形状であることが好ましい。具体的には、円錐、角錐といった錐体形状が例示される。また錐体形状と、円柱、角柱といった柱状形状を組み合わせた鉛筆形状(胴体部が柱体形状であり、先端部が錐体形状のもの)等の形状も選択することができる。また、針状体の針状部の形状としては、円錐台形形状、角錐台形形状を選択することもできる。また、針状体の針状部の形状としては、柱体形状を選択することもできる。   The shape of the protrusion of the needle-like body is preferably a cone shape. Specifically, cone shapes such as a cone and a pyramid are exemplified. In addition, a pencil shape in which a cone shape and a columnar shape such as a cylinder or a prism are combined (the body portion is a column shape and the tip portion is a cone shape) can be selected. Further, as the shape of the needle-like portion of the needle-like body, a truncated cone shape or a truncated pyramid shape can be selected. In addition, as the shape of the needle-like portion of the needle-like body, a columnar shape can be selected.

図2に本発明の針状体の突起部の拡大斜視図を示した。本発明の針状体の突起部12は表面に微小突起13を備える。突起部表面に微小突起を備えることにより、針状体を皮膚に穿刺するとき皮膚内に係留され、穿刺後針状体が皮膚から剥がれることを抑制できる。また、突起部表面に微小突起を多量に備える針状体は、針状体表面に医薬品等の送達物を設けた場合に、多量の送達物を突起部表面に保持することが可能となる。   FIG. 2 shows an enlarged perspective view of the protrusion of the needle-like body of the present invention. The projection 12 of the needle-like body of the present invention has a microprojection 13 on the surface. By providing the microprojections on the surface of the projecting portion, it is possible to suppress the needle-like body from being moored in the skin when the needle-like body is punctured into the skin and peeling off from the skin after the puncture. In addition, a needle-like body having a large amount of microprojections on the surface of the protrusion can hold a large amount of delivery on the surface of the protrusion when a delivery product such as a medicine is provided on the surface of the needle-like body.

図3に本発明の針状体の突起部の模式断面図を示した。本発明の針状体にあっては、突起部12の寸法は皮膚に穿刺孔を形成するのに適した細さと長さを有することが好ましい。具体的には、図3に示す針状部の高さHは10μm以上1000μm以下の範囲内であることが好ましい。突起部の高さHは、基材11から突起部12の先端部までの距離である。突起部の高さHは、前記範囲内で針状体を穿刺した際に形成される穿刺孔を皮膚内のどのくらいの深さまで形成するかを考慮して決定することが好ましい。   FIG. 3 shows a schematic cross-sectional view of the protrusion of the needle-shaped body of the present invention. In the needle-like body of the present invention, it is preferable that the dimensions of the protrusion 12 have a thickness and a length suitable for forming a puncture hole in the skin. Specifically, the height H of the needle-like portion shown in FIG. 3 is preferably in the range of 10 μm or more and 1000 μm or less. The height H of the protrusion is a distance from the base material 11 to the tip of the protrusion 12. The height H of the protrusion is preferably determined in consideration of how deep the puncture hole formed when the needle-like body is punctured within the above range is formed in the skin.

特に、針状体を穿刺した際に形成される穿刺孔を「角質層内」に留める場合、針状体の突起部の高さHは10μm以上300μm以下、より好ましくは30μm以上200μm以下の範囲内にすることが望ましい。   In particular, when the puncture hole formed when the needle-like body is punctured is held in “in the stratum corneum”, the height H of the protrusion of the needle-like body is in the range of 10 μm to 300 μm, more preferably 30 μm to 200 μm. It is desirable to be inside.

また、針状体を穿刺した際に形成される穿刺孔を「角質層を貫通し、かつ神経層へ到達しない長さ」に留める場合、針状体の突起部の高さHは200μm以上700μm以下、より好ましくは200μm以上500μm以下、さらに好ましくは200μm以上300μm以下の範囲内にすることが望ましい。   Further, when the puncture hole formed when the needle-like body is punctured is kept to “the length that penetrates the stratum corneum and does not reach the nerve layer”, the height H of the protrusion of the needle-like body is 200 μm or more and 700 μm. In the following, it is more preferable that the thickness be in the range of 200 μm to 500 μm, and more preferably 200 μm to 300 μm.

さらに、針状体を穿刺した際に形成される穿刺孔を「穿刺孔が真皮に到達する長さ」とする場合、針状体の突起部部の高さHは200μm以上500μm以下の範囲内とすることが好ましい。また、針状体を穿刺した際に形成される穿刺孔を「穿刺孔が表皮に到達する長さ」の場合、針状体の突起部の高さHは200μm以上300μm以下の範囲内とすることが好ましい。   Further, when the puncture hole formed when the needle-like body is punctured is “the length that the puncture hole reaches the dermis”, the height H of the protrusion of the needle-like body is in the range of 200 μm to 500 μm. It is preferable that When the puncture hole formed when the needle-like body is punctured is “the length that the puncture hole reaches the epidermis”, the height H of the projection of the needle-like body is in the range of 200 μm or more and 300 μm or less. It is preferable.

また、針状部の幅Dは、1μm以上300μm以下の範囲内であることが好ましい。針状部の幅Dは、前記範囲内で針状体を穿刺した際に形成される穿刺孔を皮膚内のどのくらいの深さまで形成するか等を考慮して決定することが好ましい。突起部の幅Dは、突起部を基板面と平行に投影した際の基体と接している針状部の長さのうち最大の長さである。例えば、針状部が円錐形状である場合、針状部と基体と接している面の円の直径が幅Dとなる。針状部が正四角錐である場合、突起部と基体と接している面の正方形の対角線が幅Dとなる。   Moreover, it is preferable that the width | variety D of a needle-shaped part exists in the range of 1 micrometer or more and 300 micrometers or less. The width D of the needle-like portion is preferably determined in consideration of the depth of the puncture hole formed when the needle-like body is punctured within the above range. The width D of the protrusion is the maximum length among the lengths of the needle-shaped portions in contact with the base when the protrusion is projected in parallel with the substrate surface. For example, when the needle-like part has a conical shape, the diameter of the circle of the surface in contact with the needle-like part and the base body is the width D. When the needle-like part is a regular quadrangular pyramid, the square diagonal line of the surface in contact with the protrusion and the base is the width D.

また、針状部のアスペクト比Aは1以上10以下の範囲内であることが好ましい。アスペクト比Aとは、突起部の長さHと幅Dを用い、A=H/Dにより定義される。   In addition, the aspect ratio A of the needle-shaped part is preferably in the range of 1 or more and 10 or less. The aspect ratio A is defined by A = H / D using the length H and width D of the protrusion.

また、針状体が複数の突起部を備える場合、各突起部の高さは、同一であっても良いし、同一でなくとも良い。各突起部の長さが異なる場合、例えば、(1)アレイ状の外周のみ高い突起部とした場合には、曲面に対し、好適に接触することができるといった効果を奏する。また、(2)アレイ状の外周のみ低い突起部とすることで、破損しやすい外周部のマイクロニードルの機械的強度を補強することができるといった効果を奏する。また、各突起部の距離であるピッチ寸法は仕様に応じて適宜設計および決定して良い。   Further, when the needle-like body includes a plurality of protrusions, the heights of the protrusions may or may not be the same. When the lengths of the protrusions are different, for example, (1) when the protrusions are high only on the outer periphery of the array, there is an effect that the curved surface can be suitably contacted. In addition, (2) by providing a low protrusion only on the outer periphery of the array, there is an effect that the mechanical strength of the microneedles on the outer periphery that is easily damaged can be reinforced. Further, the pitch dimension, which is the distance between the protrusions, may be appropriately designed and determined according to the specifications.

また、針状体の形状が、基材に複数の突起部が林立した形状の場合、微小突起は、突起部間の基材部位にも形成される。このとき基材上の微小突起は、針状体全体の表面積を増大させることになり、医薬品などの送達物によっては底面上にある送達物も針状体側面を通じて針状体先端部分に伝わることから、送達物の保持量および有効使用効率を上げることが可能となる。   In addition, when the shape of the needle-like body is a shape in which a plurality of protrusions are erected on the base material, the fine protrusions are also formed on the base material portion between the protrusions. At this time, the microprotrusions on the base material increase the surface area of the entire needle-like body, and depending on the delivery product such as pharmaceuticals, the delivery product on the bottom surface is also transmitted to the tip of the needle-like body through the side surface of the needle-like body. Therefore, it is possible to increase the amount of the delivered product and the effective use efficiency.

なお、図3では、基材と接した面を底面とし垂直方向を頂点とした形状の錐形の錐体である針状の突起部が連なるアレイ構造であり、基板と突起部底面は一体成形されている。図3では、基材11と突起部12が一体成形された針状体1の一例を示したが、基材と突起部は別種の材料より構成されていても良い。   In addition, in FIG. 3, it is an array structure in which the needle-shaped projection part which is a cone-shaped cone of the shape which made the surface which touched the base material the bottom face, and made the perpendicular | vertical direction apex, and a board | substrate and a protrusion bottom face are integrally molded. Has been. Although FIG. 3 shows an example of the needle-like body 1 in which the base material 11 and the protrusion 12 are integrally formed, the base material and the protrusion may be made of different types of materials.

次に、本発明の針状体の製造方法について説明する。図4及び図5に本発明の針状体の製造方法の模式断面図(説明図)を示した。   Next, the manufacturing method of the acicular body of this invention is demonstrated. 4 and 5 show schematic cross-sectional views (descriptive drawings) of the method for producing the needle-shaped body of the present invention.

本発明の針状体の製造方法は、基材の一方の面に針状の突起部を備える針状体原版を作製する針状体原版作製工程と、前記針状体原版の突起部形成面にマイクロカプセルを配置し、前記針状体原版の突起部表面に微小突起を形成する微小突起形成工程と、該微小突起が形成された針状体原版から複製版を作製する複製版作製工程と、該複製版に針状体形成材料を充填し該針状体形成材料を剥離することにより、基材の一方の面に針状の突起部を備え、かつ、突起部表面に微小突起を備える針状体と作製する転写成形工程とを備えることを特徴とする。   The needle-shaped body manufacturing method of the present invention includes a needle-shaped body original plate preparation step for manufacturing a needle-shaped body original plate having a needle-shaped protrusion on one surface of a substrate, and a protrusion-forming surface of the needle-shaped body original plate A micro-projection forming step for forming a micro-projection on the surface of the projection of the needle-shaped body original plate, and a replica plate-preparing step for preparing a duplicate plate from the needle-shaped original plate on which the micro-projections are formed; The replica plate is filled with a needle-like body forming material and the needle-like body forming material is peeled off, whereby a needle-like protrusion is provided on one surface of the substrate, and a minute protrusion is provided on the surface of the protrusion. It comprises a needle-shaped body and a transfer molding process to be produced.

[針状体原版形成工程]
まず、基材の一方の面に針状の突起部を備える針状体原版21を作製する(図4(a))。針状体原版の作製方法としては、適宜公知の微細加工技術を用いた針状体原版製造方法を用いておこなうことができる。例えば、(1)板状の基板に対し、研削加工や切削加工など微細機械加工を用いた針状体原版製造方法、(2)リソグラフィ法やエッチング法など微細加工技術を用いた針状体原版製造方法などが挙げられる。針状体原版の作成するための板状の基板材料は、加工方法に応じて適宜選択することができる。例えば、カーボン、セラミックス、シリコン、石英、金属、樹脂などの基板材料を用いても良い。
[Needle body forming process]
First, the acicular body original plate 21 having acicular protrusions on one surface of the substrate is produced (FIG. 4A). As a method for producing the needle-shaped body precursor, a needle-shaped body precursor manufacturing method using a known fine processing technique can be used as appropriate. For example, (1) a needle-shaped original plate manufacturing method using fine machining such as grinding or cutting on a plate-shaped substrate, and (2) a needle-shaped original plate using a fine processing technique such as a lithography method or an etching method. Examples include production methods. The plate-shaped substrate material for producing the needle-shaped body original plate can be appropriately selected according to the processing method. For example, substrate materials such as carbon, ceramics, silicon, quartz, metal, and resin may be used.

[表面改質工程]
針状体原版の突起部形成面にマイクロカプセルを配置する前には、針状体原版の突起部形成面表面を改質する表面改質工程が設けられることが好ましい(図4(b))。表面改質工程は任意工程であるが、表面改質により表面改質層22を設けることにより、後述するマイクロカプセル分散液を用いて状体原版の突起部形成面にマイクロカプセルを配置する際に、流動性のあるマイクロカプセルを濡れ性の高い針状体原版表面上で凝集させることができる。
[Surface modification process]
Before the microcapsules are arranged on the protrusion-forming surface of the needle-shaped body original plate, it is preferable to provide a surface modification step for modifying the surface of the needle-shaped body original plate on which the protrusion-forming portion is formed (FIG. 4B). . Although the surface modification step is an optional step, by providing the surface modification layer 22 by surface modification, when the microcapsules are disposed on the projection forming surface of the substrate precursor using the microcapsule dispersion described later. The fluid microcapsules can be agglomerated on the surface of the needle-shaped original plate having high wettability.

表面改質方法としては、(1)プラズマ表面改質法、(2)オゾンガスを用いた表面改質法、(3)マイクロカプセルに対し濡れ性の高い表面改質層を前記針状体原版に形成する方法、(4)微細加工技術により針状体表面にサブミクロンオーダーの微細な凹凸を形成する方法などを用いることができる。   As the surface modification method, (1) plasma surface modification method, (2) surface modification method using ozone gas, and (3) a surface modification layer having high wettability with respect to microcapsules is formed on the original needle body. A method of forming, (4) a method of forming fine irregularities of submicron order on the surface of the needle-like body by a fine processing technique, and the like can be used.

表面改質層を前記針状体原版に形成する場合、表面改質層は、親水性を示し、前記微小突起部は、水系のマイクロカプセル分散液としても良い。微小突起部が水系のマイクロカプセル分散液であるとき、表面改質層が親水性を示すことで、針状体原版表面を、マイクロカプセルに対し、濡れ性が高い表面とすることが出来る。   When the surface modified layer is formed on the acicular body original plate, the surface modified layer may be hydrophilic, and the microprojection may be an aqueous microcapsule dispersion. When the microprojection is a water-based microcapsule dispersion, the surface modified layer exhibits hydrophilicity, whereby the surface of the acicular body original plate can be made highly wettable with respect to the microcapsules.

表面改質層となる材料を前記針状体原版に塗布する場合、表面改質層の塗布方法としては、適宜公知の三次元形状に適した塗布方法を用いて良い。塗布方法としては、具体的には、例えば、ディップコート法、スプレーコート法、ポッティングコート法、などが挙げられる。特に、ディップコート法は、針状体原版の表面の表面改質層の流動性を確保することが出来、好適に、針状体全面に塗布を行なうことができる。なお、表面改質層となる塗布材料としては、ポリエチレングリコール、ポリビニルアルコールを使用することができる。   In the case of applying the material to be the surface modification layer to the needle body original plate, as a method for applying the surface modification layer, a known application method suitable for a three-dimensional shape may be used. Specific examples of the coating method include a dip coating method, a spray coating method, and a potting coating method. In particular, the dip coating method can ensure the fluidity of the surface modification layer on the surface of the needle-like body original plate, and can preferably be applied to the entire surface of the needle-like body. In addition, as a coating material used as a surface modification layer, polyethylene glycol and polyvinyl alcohol can be used.

[微小突起部形成工程]
次に、針状体原版の突起部形成面に微小突起部となるマイクロカプセルを配置する。ただし本発明におけるマイクロカプセル(microcapsule)とは、マイクロメートルサイズの微小な容器のことを指す。すなわち、それを球とみなしたとき、径がマイクロメートル領域にあるカプセルのことである。
[Microprojection forming process]
Next, a microcapsule that becomes a minute protrusion is disposed on the protrusion-forming surface of the needle-shaped body original plate. However, the microcapsule in the present invention refers to a micro container having a micrometer size. That is, a capsule whose diameter is in the micrometer region when it is considered as a sphere.

マイクロカプセルの製法は多数存在し、大別すると化学反応を利用する化学的方法、物理化学的変化を利用する物理化学的方法及び物理的ないし機械的操作を主に利用する物理的方法に分類できる。   There are many methods for producing microcapsules, which can be broadly classified into chemical methods using chemical reactions, physicochemical methods using physicochemical changes, and physical methods mainly using physical or mechanical operations. .

マイクロカプセル利用例は多種多様であるが、利用されている機能の面から整理してみると以下のようになる。例えば、カプセル内の材料である芯物質を外部環境から保害する機能を利用したものには、感圧型複写紙、圧力測定シート、感圧型接着剤、液晶表示材料などがあり、また芯物質の外部環境への放出速度を調節する機能を利用したものには持続放出性医薬品、持効性農薬などがあり、更に人工細胞、人工臓器などへの利用は両方の機能を同時に果たしている。   There are many examples of using microcapsules, but the following is a summary of the functions used. For example, there are pressure-sensitive copying paper, pressure measurement sheets, pressure-sensitive adhesives, liquid crystal display materials, etc. that use the function to protect the core material, which is the material in the capsule, from the external environment. Examples of products that use the function of regulating the release rate to the environment include sustained-release pharmaceuticals and sustained-release agrochemicals. Furthermore, their use in artificial cells and artificial organs fulfills both functions simultaneously.

マイクロカプセルの壁膜をつくっている材料は、主として天然及び合成高分子であるが、高分子でなければならない必然性はなく、ワックス類や無機化合物も壁材料として利用することが可能である。   The material forming the wall film of the microcapsule is mainly natural and synthetic polymers, but there is no necessity to be a polymer, and waxes and inorganic compounds can also be used as the wall material.

マイクロカプセルは、前記針状体原版の表面に対し濡れ性が高く、前記針状体原版の表面上で粒状に留まる。濡れ性の高い表面にマイクロカプセルを塗布した場合、マイクロカプセルが均一に塗り広がりやすくなる。本発明は上記知見を利用するものである。なお、本発明の針状体の製造方法で使用するマイクロカプセルの平均粒子径は、針状体原版の側面積や形状にもよるが、0.5〜100μmの範囲内であることが望ましい。なお、平均粒子径は、当該マイクロカプセル20個の最大径を光学顕微鏡もしくは電子顕微鏡で測定し、その平均値として求めることができる。また、形成される複数の微小突起は、各微小突起同士が規則性なくランダム配列されることになる。   The microcapsule has high wettability with respect to the surface of the acicular body original plate, and remains in a granular form on the surface of the acicular body original plate. When a microcapsule is applied to a highly wettable surface, the microcapsule is easily spread uniformly. The present invention utilizes the above knowledge. In addition, although the average particle diameter of the microcapsule used with the manufacturing method of the acicular body of this invention is based also on the side area and shape of an acicular body original plate, it is desirable to exist in the range of 0.5-100 micrometers. The average particle diameter can be obtained as an average value obtained by measuring the maximum diameter of the 20 microcapsules with an optical microscope or an electron microscope. In addition, the plurality of microprotrusions that are formed are randomly arranged with no regularity between the microprotrusions.

針状体原版の突起部形成面に微小突起となるマイクロカプセルを配置するにあっては、マイクロカプセル分散液を用意し、マイクロカプセル分散液23を針状体原版の突起部形成面に塗布し(図4(c))、乾燥をおこなうことにより形成することができる(図4(d))。   In arranging the microcapsules to be microprojections on the projection forming surface of the needle-shaped original plate, prepare a microcapsule dispersion and apply the microcapsule dispersion 23 to the projection forming surface of the needle-shaped original plate. (FIG. 4C) and can be formed by drying (FIG. 4D).

マイクロカプセル分散液を針状体原版に塗布する場合、マイクロカプセル分散液の塗布方法としては、適宜公知の三次元形状に適した塗布方法を用いて良い。   When the microcapsule dispersion is applied to the needle plate precursor, a known application method suitable for a three-dimensional shape may be used as the method for applying the microcapsule dispersion.

塗布方法としては、具体的には、例えば、ディップコート法、スプレーコート法、ポッティングコート法、などが挙げられる。特に、ディップコート法は、針状体原版の表面のマイクロカプセルの流動性を確保することができ、好適に、針状体全面に塗布をおこなうことができる。   Specific examples of the coating method include a dip coating method, a spray coating method, and a potting coating method. In particular, the dip coating method can ensure the fluidity of the microcapsules on the surface of the needle-shaped body original plate, and can preferably be applied to the entire surface of the needle-shaped body.

また、マイクロカプセル分散液には、ポリビニルアルコール(PVA)溶液やポリエチレングリコール(PEG)溶液といった各種水溶性合成樹脂や、フェノール樹脂(PF)溶液やエポキシ樹脂(EP)溶液といった各種樹脂含有有機溶剤溶液などを使用してもよい。   The microcapsule dispersion includes various water-soluble synthetic resins such as polyvinyl alcohol (PVA) solution and polyethylene glycol (PEG) solution, and various resin-containing organic solvent solutions such as phenol resin (PF) solution and epoxy resin (EP) solution. Etc. may be used.

また、マイクロカプセル分散液23を塗布後、針状体上のマイクロカプセル分散液を加熱乾燥してもよい。加熱処理により、マイクロカプセルの溶媒を揮発させ、流動性のあるマイクロカプセルを濡れ性の高い針状体原版表面上で凝集させることができる。   Further, after applying the microcapsule dispersion liquid 23, the microcapsule dispersion liquid on the needle-like body may be dried by heating. By the heat treatment, the solvent of the microcapsules can be volatilized, and the microcapsules having fluidity can be agglomerated on the surface of the acicular original plate having high wettability.

以上により、突起部表面にマイクロカプセルが配置された、微小突起24を備える針状体原版が作製される。   As described above, an acicular body original plate having microprojections 24 in which microcapsules are arranged on the surface of the projection is produced.

[複製版作製工程]
次に、針状体原版から複製版25が作製される(図5(e)、図5(f))
複製版25は、針状体原版の形状に対応した凹版となる。
針状体原版から複製版を作製し、複製版を用いて転写成型をおこなうことにより、マイクロカプセルに求められる特性に縛られず、所望する針状体形成材料からなる各微小突起部同士が規則性なくランダム配列された形状の針状体を製造することができる。
また、同一の複製版から、複数の各微少突起部同士が規則性なくランダム配列されている針状体を製造することができることから、生産コストを低くし、生産性を高めることが可能となる。
[Copying plate making process]
Next, a duplicate plate 25 is produced from the needle-shaped body original plate (FIGS. 5E and 5F).
The duplicate plate 25 is an intaglio plate corresponding to the shape of the acicular body original plate.
By making a duplicate plate from the needle plate precursor and performing transfer molding using the replica plate, the microprojections made of the desired needle-like body forming material are regular without being restricted by the characteristics required of the microcapsule. A needle-like body having a randomly arranged shape can be produced.
In addition, since a needle-like body in which a plurality of minute protrusions are randomly arranged without regularity can be manufactured from the same duplicate plate, the production cost can be reduced and the productivity can be increased. .

複製版25の材質としては、複製版として機能するだけの形状追従性、後述する転写加工成形における転写性、耐久性及び離型性を考慮した材質を選択することができる。   The material of the duplicate plate 25 can be selected in consideration of the shape following ability to function as the duplicate plate, the transfer property in the transfer processing molding described later, the durability, and the release property.

また、複製版の作製方法としては、複製版の材質に応じて、適宜公知の形状転写方法を用いてよい。例えば、(1)複製版の材質としてニッケルを用いた場合、電鋳めっき法、PVD法、など(2)複製版の材質として熱硬化性樹脂(例えば、エポキシ樹脂、シリコーン樹脂など)用いた場合、針状体原版に溶融した樹脂を流入し、樹脂を硬化し、樹脂を原版から剥離する、などの方法を用いても良い。
このとき、複製版と針状体原版を剥離する方法としては、例えば、(1)物理的な剥離力による剥離、(2)選択的エッチング法、などを用いることができる。
Further, as a method for producing a duplicate plate, a known shape transfer method may be appropriately used depending on the material of the duplicate plate. For example, (1) When nickel is used as the material of the duplicate plate, electroforming plating method, PVD method, etc. (2) When a thermosetting resin (eg, epoxy resin, silicone resin, etc.) is used as the material of the duplicate plate Alternatively, a method may be used in which a molten resin is allowed to flow into the needle-shaped body original plate, the resin is cured, and the resin is peeled off from the original plate.
At this time, for example, (1) peeling by physical peeling force, (2) selective etching, and the like can be used as a method for peeling the duplicated plate and the acicular body original plate.

[転写成形工程]
次に、得られた複製版25に針状体形成材料26を充填し(図5(g))、該針状体形成材料を剥離することにより基材の一方の面に針状の突起部を備え、かつ、突起部表面に微小突起を備える針状体26が作製される(図5(h))。
[Transfer molding process]
Next, the obtained replica plate 25 is filled with the needle-like body forming material 26 (FIG. 5G), and the needle-like body-forming material is peeled off, whereby a needle-like protrusion is formed on one surface of the substrate. And a needle-like body 26 having minute protrusions on the surface of the protrusion (FIG. 5 (h)).

また、複製版を用いた転写成型工程を行なう場合、針状体形成材料は生体適合材料であることが好ましい。生体適合材料を用いて作製することで、穿刺時に折れや欠けなどの問題が生じたとしても、人体に悪影響を与えることを抑制することが出来る。特に、本発明の針状体は、微小突起部が皮膚に係留することから、体内に残留しやすく、生体適合性材料を用いることの効果は多大である。   Moreover, when performing the transfer molding process using a replication plate, it is preferable that the acicular body forming material is a biocompatible material. By using a biocompatible material, even if problems such as breakage or chipping occur at the time of puncture, adverse effects on the human body can be suppressed. In particular, the needle-shaped body of the present invention is likely to remain in the body because the microprojections are anchored to the skin, and the effect of using a biocompatible material is great.

複製版に針状体形成材料を充填する方法としては、適宜公知の充填方法を用いて良い。充填方法としては、例えば、インプリント法、ホットエンボス法、射出成形法、押出成形法、キャスティング法などが挙げられる。   As a method of filling the replica plate with the needle-shaped body forming material, a known filling method may be used as appropriate. Examples of the filling method include an imprint method, a hot embossing method, an injection molding method, an extrusion molding method, and a casting method.

なお、針状体を形成する針状体形成材料として生体適合性材料としては、医療用シリコーン、ポリ乳酸、ポリグリコール酸、ポリカーボネート等の樹脂などを挙げられる。これらの材料を用いた場合には、樹脂を溶融することにより、複製版に針状体形成材料が充填され、冷却することにより針状体が形成される。   Examples of the biocompatible material as the needle-shaped body forming material for forming the needle-shaped body include medical silicone, resins such as polylactic acid, polyglycolic acid, and polycarbonate. When these materials are used, the replica is filled with the needle-shaped body forming material by melting the resin, and the needle-shaped body is formed by cooling.

また、針状体を形成する針状体形成材料として生体適合性材料としては、アルギン酸塩、カードラン、キチン、キトサン、グルコマンナン、ポリリンゴ酸、ヒアルロン酸、コラーゲン、コラーゲンペプチド、ヒドロキシプロピルセルロース、ゼラチンなどの水溶性高分子を挙げることができる。これらの材料を用いた場合には、水等の溶媒に材料を溶解または分散し材料を液体化して複製版に充填され、加熱等により溶媒を除去することにより針状体が形成される。   In addition, the biocompatible material as the needle-forming material for forming the needle-shaped body includes alginate, curdlan, chitin, chitosan, glucomannan, polymalic acid, hyaluronic acid, collagen, collagen peptide, hydroxypropylcellulose, gelatin And water-soluble polymers such as When these materials are used, the needle-shaped body is formed by dissolving or dispersing the material in a solvent such as water, liquefying the material, filling the duplicate plate, and removing the solvent by heating or the like.

また、複製版と針状体形成材料の剥離性を向上させるために、針状体形成材料の充填前に、複製版の表面上に離型効果を増すための離型層を形成してもよい。離型層としては、例えば広く知られているフッ素系の樹脂を用いることができる。また、離型層の形成方法としては、PVD法、CVD法、スピンコート法、ディップコート法等の薄膜形成手法を好適に用いることができる。   Further, in order to improve the peelability of the replica plate and the needle-shaped body forming material, a release layer for increasing the mold release effect may be formed on the surface of the replica plate before filling the needle-shaped body forming material. Good. As the release layer, for example, a widely known fluorine-based resin can be used. Moreover, as a formation method of a mold release layer, thin film formation methods, such as PVD method, CVD method, a spin coat method, a dip coat method, can be used suitably.

複製版と針状体原版を剥離する方法としては、例えば物理的な剥離力による剥離を用いることができる。   As a method for peeling the duplicated plate and the acicular body original plate, for example, peeling by physical peeling force can be used.

以上より、本発明を実施することができる。なお、本発明の針状体の製造方法は上記実施の形態に限定されず、各工程において類推することのできる他の公知の方法も含むものとする。   As described above, the present invention can be implemented. In addition, the manufacturing method of the acicular body of this invention is not limited to the said embodiment, The other well-known method which can be guessed in each process shall also be included.

以下実施例について説明する。   Examples will be described below.

<実施例1>
まず、基板に微細機械加工を用いて、針状体原版21を作成した。
針状体原版21を作成する基板材料として、5mm厚さのカーボン板を用意した。また、微細機械加工として、ボール半径0.01mmの二枚刃のボールエンドミルを用いた。XYZ軸を持つNC制御フライス盤に、切削工具として上記のボールエンドミルを取り付け、工具を針状体の中心から外周方向へ公転させるにつれ切り込み量を増やすことで、円錐型の突起部が形成されるように加工を行った。
ボールエンドミルの設定条件は、回転数を50000rpm、送り速度を0.1mm/sとした。また、加工によって形成される円錐底面の直径は280μm、ピッチを500μm、加工深さを450μmに設計した。また、針状体の無い部分は450μmの深さで均一に切削することで突起部頂点が基材上で最も高くなる構造とした。
<Example 1>
First, the acicular body original plate 21 was prepared by using micromachining on the substrate.
A carbon plate having a thickness of 5 mm was prepared as a substrate material for producing the needle-shaped body original plate 21. Further, as fine machining, a two-blade ball end mill having a ball radius of 0.01 mm was used. The above-mentioned ball end mill is attached as a cutting tool to an NC control milling machine having an XYZ axis, and a conical projection is formed by increasing the cutting amount as the tool revolves from the center of the needle-like body to the outer peripheral direction. Was processed.
The setting conditions of the ball end mill were a rotational speed of 50000 rpm and a feed rate of 0.1 mm / s. The diameter of the bottom surface of the cone formed by machining was designed to be 280 μm, the pitch was 500 μm, and the machining depth was 450 μm. In addition, the portion without the needle-like body was cut uniformly at a depth of 450 μm, so that the protrusion vertex was highest on the substrate.

上述のように作製した針状体原版を走査型電子顕微鏡で観察した。その結果、根元幅280μm、高さ445μmであり、先端角が35°の円錐状の針状体原版21が作製できたことを確認した。   The needle-shaped body original plate produced as described above was observed with a scanning electron microscope. As a result, it was confirmed that a conical acicular original plate 21 having a root width of 280 μm and a height of 445 μm and a tip angle of 35 ° could be produced.

次に、針状体原版21の表面上に、表面改質層22を形成した(図3(b))。
このとき、表面改質層22は、酸素プラズマ処理によって、酸化皮膜を形成した。上記表面改質層22の水に対する接触角を計測したところ20°を示した。よって、針状体原版21の表面が親水性を示すことが確認された。
Next, the surface modification layer 22 was formed on the surface of the needle-shaped body original plate 21 (FIG. 3B).
At this time, the surface modification layer 22 formed an oxide film by oxygen plasma treatment. When the contact angle of the surface modified layer 22 to water was measured, it was 20 °. Therefore, it was confirmed that the surface of the acicular body original plate 21 shows hydrophilicity.

次に、表面改質層22が形成された針状体原版21に、マイクロカプセル分散液23を塗布した(図4(c))。
このとき、液状の低沸点炭化水素を熱可塑性高分子殻(シェル)で包み込んだマイクロカプセルの分散液(マツモトマイクロスフェアー:松本油脂製薬株式会社製)を用いた。
また、塗布方法として、ディップコート法を用い、引き上げ速度は100mm/minと設定した。また、マイクロカプセル7は針状体原版5上に粒状に留まり、その粒径は3μm〜10μmであり、平均粒子径は6μmであった。
Next, the microcapsule dispersion liquid 23 was applied to the acicular body original plate 21 on which the surface modification layer 22 was formed (FIG. 4C).
At this time, a microcapsule dispersion (Matsumoto Microsphere: manufactured by Matsumoto Yushi Seiyaku Co., Ltd.) in which liquid low-boiling hydrocarbons were wrapped in a thermoplastic polymer shell (shell) was used.
Further, as a coating method, a dip coating method was used, and the lifting speed was set to 100 mm / min. Further, the microcapsules 7 remained in a granular form on the needle-shaped body original plate 5, and the particle diameter thereof was 3 μm to 10 μm, and the average particle diameter was 6 μm.

次に、マイクロカプセル分散液23が塗布された針状体原版の加熱処理を行い、室温により自然冷却した(図4(d))。加熱処理は、クリーンオーブンを用い、100℃にて1時間おこなった。以上により、微小突起24を備える針状体原版を作製した。   Next, the needle-shaped body original plate coated with the microcapsule dispersion liquid 23 was subjected to heat treatment and naturally cooled at room temperature (FIG. 4D). The heat treatment was performed at 100 ° C. for 1 hour using a clean oven. As described above, an acicular body original plate provided with the fine protrusions 24 was produced.

作製した針状体を走査型電子顕微鏡で観察したところ、針状体側面に、幅と高さが3μm〜10μm程度の微小突起部が、無数に形成されているのが観察され、微小突起24を備えた針状体を作製できたことが確認された。   When the produced acicular body was observed with a scanning electron microscope, an infinite number of microprojections having a width and a height of about 3 μm to 10 μm were observed on the side surface of the acicular body. It was confirmed that a needle-like body provided with

次に、複数の微小突起24が形成された針状体原版21を原版として、複製版9を作製し、転写加工成型を行なった。図5を用いて具体的に説明を行なう。   Next, the replica plate 9 was produced using the needle-like body original plate 21 on which the plurality of minute protrusions 24 were formed as an original plate, and was subjected to transfer processing molding. This will be specifically described with reference to FIG.

針状体原版21に複製版材料25として、エポキシ樹脂で充填し、クリーンオーブンを用い、100℃にて1時間熱硬化処理をおこなった(図5(e))。   The acicular body original plate 21 was filled with an epoxy resin as a replica plate material 25, and was subjected to thermosetting treatment at 100 ° C. for 1 hour using a clean oven (FIG. 5E).

次に、針状体原版21と硬化した複製版材料25とを剥離し、エポキシ樹脂からなる複製版25を作製した(図5(f))。   Next, the acicular body original plate 21 and the cured duplication plate material 25 were peeled off to produce a duplication plate 25 made of an epoxy resin (FIG. 5 (f)).

次に、複製版25に対し、インプリント法を用いて針状体形成材料26の充填をおこなった(図5(g))。このとき、針状体形成材料26として、生体適合材料であるポリグリコール酸を用いた。   Next, the replica plate 25 was filled with the needle-shaped body forming material 26 by using an imprint method (FIG. 5G). At this time, polyglycolic acid, which is a biocompatible material, was used as the needle-like body forming material 26.

次に、複製版25と針状体形成材料26とを剥離し、針状体形成材料10からなる本発明の針状体26を製造した(図4(g))。   Next, the duplicate plate 25 and the needle-shaped body forming material 26 were peeled off to produce the needle-shaped body 26 of the present invention made of the needle-shaped body forming material 10 (FIG. 4G).

針状体形成材料16からなる本発明の針状体1を走査型電子顕微鏡で観察したところ、根元直径280μm、高さ445μmであり、先端角が35°の円錐形状に加えて、幅と高さが2〜5μm程度の微小突起が無数に形成されていることが確認された。   When the needle-like body 1 of the present invention made of the needle-like body-forming material 16 was observed with a scanning electron microscope, it had a root diameter of 280 μm, a height of 445 μm, a tip angle of 35 °, and a width and height. It was confirmed that an infinite number of minute protrusions having a length of about 2 to 5 μm were formed.

<比較例1>
マイクロカプセル配置工程をおこなわなかった以外は<実施例1>の針状体の製造方法と同様にして、表面に微小突起を備えない針状体を作製した。
<Comparative Example 1>
Except for not performing the microcapsule placement step, a needle-like body having no microprotrusions on the surface was produced in the same manner as in the method for producing a needle-like body of <Example 1>.

得られた<実施例1>の針状体と<比較例1>の針状体の突起部を人工皮膚に穿刺後、当該針状体の引き抜き容易か否かを確認したところ、<比較例1>の針状体と比べ<実施例1>の針状体は引き抜き難く、皮膚から剥がれることを抑制できることが確認された。   After the obtained needle-like body of <Example 1> and the protrusion of the needle-like body of <Comparative Example 1> were punctured into the artificial skin, it was confirmed whether or not the needle-like body was easily pulled out. It was confirmed that the needle-like body of <Example 1> was less likely to be pulled out than the needle-like body of 1> and could be prevented from peeling off from the skin.

本発明の針状体の製造方法は、医療のみならず、微細な針状体を必要とする様々な分野に適用可能であり、例えばMEMSデバイス、光学部材、創薬、化粧品、美容用途などに用いる微細な針状体の製造方法としても有用である。   The method for producing a needle-shaped body of the present invention can be applied not only to medical treatment but also to various fields that require a fine needle-shaped body, such as MEMS devices, optical members, drug discovery, cosmetics, and cosmetic applications. It is also useful as a method for producing fine needles to be used.

1 針状体
11 基材
12 突起部
13 微小突起
21 針状体原版
22 表面改質層
23 マイクロカプセル分散液
24 微小突起
25 複製版
26 針状体形成材料/針状体
DESCRIPTION OF SYMBOLS 1 Acicular body 11 Base material 12 Protrusion part 13 Microprotrusion 21 Acicular body original plate 22 Surface modification layer 23 Microcapsule dispersion liquid 24 Microprotrusion 25 Duplicate plate 26 Acicular body formation material / acicular body

Claims (2)

基材の一方の面に針状の突起部を備える針状体の製造方法であって、
基材の一方の面に針状の突起部を備える針状体原版を作製する針状体原版作製工程と、
前記針状体原版の突起部形成面にマイクロカプセル分散液を塗布し、前記針状体原版の突起部形成面にマイクロカプセルを配置し、前記針状体原版の突起部表面に微小突起を形成する微小突起形成工程と、
該微小突起が形成された針状体原版から複製版を作製する複製版作製工程と、
該複製版に針状体形成材料を充填し該針状体形成材料を剥離することにより、基材の一方の面に針状の突起部を備え、かつ、突起部表面に微小突起を備える針状体と作製する転写成形工程と
を備えることを特徴とする針状体の製造方法。
A method for producing a needle-like body having a needle-like protrusion on one surface of a substrate,
A needle-shaped original plate preparation step for preparing a needle-shaped original plate provided with a needle-like protrusion on one surface of the substrate;
A microcapsule dispersion is applied to the protrusion-forming surface of the needle-shaped original plate, the microcapsules are arranged on the protrusion-forming surface of the needle-shaped original plate, and minute protrusions are formed on the surface of the needle-shaped original plate. Microprojection forming process,
A replica plate making step of preparing a replica plate from the needle-shaped body original plate on which the microprojections are formed;
A needle provided with a needle-like protrusion on one surface of the substrate and a micro-protrusion on the surface of the protrusion by filling the replica plate with the needle-like member-forming material and peeling the needle-like member-forming material. A method for producing a needle-like body, comprising: a shaped body and a transfer molding step for producing the shaped body.
前記針状体原版の突起部形成面にマイクロカプセルを配置する前に、前記針状体原版の突起部形成面表面を改質する表面改質工程を備えることを特徴とする請求項1記載の針状体の製造方法。   The surface modification process of modifying the surface of the protrusion-forming surface of the needle-shaped body precursor plate before arranging the microcapsules on the surface of the needle-shaped body original plate. A method for producing a needle-like body.
JP2012166020A 2012-07-26 2012-07-26 Manufacturing method of needle-shaped body Active JP6060547B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2012166020A JP6060547B2 (en) 2012-07-26 2012-07-26 Manufacturing method of needle-shaped body

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2012166020A JP6060547B2 (en) 2012-07-26 2012-07-26 Manufacturing method of needle-shaped body

Publications (2)

Publication Number Publication Date
JP2014023699A JP2014023699A (en) 2014-02-06
JP6060547B2 true JP6060547B2 (en) 2017-01-18

Family

ID=50197944

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2012166020A Active JP6060547B2 (en) 2012-07-26 2012-07-26 Manufacturing method of needle-shaped body

Country Status (1)

Country Link
JP (1) JP6060547B2 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6753167B2 (en) * 2016-06-24 2020-09-09 凸版印刷株式会社 Sponge spicule
JP6809013B2 (en) * 2016-07-20 2021-01-06 凸版印刷株式会社 Transdermal administration device

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009207733A (en) * 2008-03-05 2009-09-17 Toppan Printing Co Ltd Needle-like member
JP2010194003A (en) * 2009-02-24 2010-09-09 Toppan Printing Co Ltd Needle-shaped body device and method of manufacturing needle-shaped body device

Also Published As

Publication number Publication date
JP2014023699A (en) 2014-02-06

Similar Documents

Publication Publication Date Title
US10682504B2 (en) Microneedle and method for manufacturing microneedle
WO2014077244A1 (en) Transdermal absorption sheet, and manufacturing method for same
JP6565906B2 (en) Needle-like body manufacturing method and needle-like body
US10799691B2 (en) Needle assembly for transdermal administration and method of producing the same
WO2014073531A1 (en) Needle-like structure and method for manufacturing same
JP2008237673A (en) Needle shape body and its manufacturing method
JP7020399B2 (en) Transdermal administration device
JP6060547B2 (en) Manufacturing method of needle-shaped body
Babu et al. Unravelling the role of microneedles in drug delivery: Principle, perspectives, and practices
EP3111985B1 (en) Hollow needle-shaped body manufacturing method and hollow needle-shaped body
JP5173331B2 (en) Needle-shaped body chip and manufacturing method thereof
JP6003339B2 (en) Needle-shaped body manufacturing apparatus and needle-shaped body manufacturing method
JP6255759B2 (en) Micro needle
JP2013111104A (en) Method for manufacturing microneedle device
JP2014023697A (en) Needle-like body package
JP6476799B2 (en) Method of manufacturing needle-like body
EP3363491B1 (en) Administration instrument
CN110251824B (en) Flexible microneedle patch for transdermal drug delivery and manufacturing method thereof
CN114828936A (en) Method for manufacturing microneedle array
JP5034777B2 (en) Method for producing needle-like body, manufacturing method and needle-like body
JP2018175240A (en) Micro needle
JP2016106757A (en) Stylet, and stylet manufacturing method
JP6268733B2 (en) Manufacturing method of needle-shaped body
BAO et al. Fabrication of Dissolvable Microneedles by utilizing 3D-printed PMMA Microstamp for Transdermal Drug Delivery
JP5593355B2 (en) Needle-like body and method for producing needle-like body

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20150623

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20160517

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160617

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20161115

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20161128

R150 Certificate of patent or registration of utility model

Ref document number: 6060547

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250