JP5205016B2 - Needle-like body, needle-like body manufacturing method - Google Patents

Needle-like body, needle-like body manufacturing method Download PDF

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JP5205016B2
JP5205016B2 JP2007228647A JP2007228647A JP5205016B2 JP 5205016 B2 JP5205016 B2 JP 5205016B2 JP 2007228647 A JP2007228647 A JP 2007228647A JP 2007228647 A JP2007228647 A JP 2007228647A JP 5205016 B2 JP5205016 B2 JP 5205016B2
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substrate
needle
protrusions
protrusion
manufacturing
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JP2009060930A (en
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雅弘 上野
賢洋 兒玉
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Hisamitsu Pharmaceutical Co Inc
Toppan Inc
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Toppan Inc
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    • 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
    • A61M2037/0053Methods for producing microneedles

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
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Description

本発明は、微細な構造体である針状体に関する。   The present invention relates to a needle-like body that is a fine structure.

皮膚上から薬剤を浸透させ体内に薬剤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薬剤を投与することが出来る方法として用いられているが、薬剤の種類によっては経皮吸収法で投与が困難な薬剤が存在する。これらの薬剤を効率よく体内に吸収させる方法として、ミクロンオーダーの微細な針状体を用いて皮膚を穿孔し、皮膚内に直接薬剤を投与する方法が注目されている。この方法によれば、投薬用の特別な機器を用いることなく、簡便に薬剤を皮下投薬することが可能となる(特許文献1参照)。   The percutaneous absorption method, which is a method of infiltrating a drug from the skin and administering the drug into the body, is used as a method that can be easily administered without causing pain to the human body. There are drugs that are difficult to administer by transdermal absorption. As a method of efficiently absorbing these drugs into the body, a method of perforating the skin using micron-order fine needles and administering the drug directly into the skin has attracted attention. According to this method, it is possible to easily administer a drug subcutaneously without using a special medication device (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、突起部の直径は数μmから数百μm、突起部の長さは皮膚の最外層である角質層を貫通し、かつ神経層へ到達しない長さ、具体的には数十μmから数百μm程度のものであること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 of the protrusion is several μm to several hundred μm, and the length of the protrusion is a length that penetrates the stratum corneum, which is the outermost layer of the skin, and does not reach the nerve layer, specifically several tens μm to several hundred μm. It is said that it is desirable to have a degree.

より具体的には、最外皮層である角質層を貫通することが求められる。角質層の厚さは人体の部位によっても若干異なるが、平均して20μm程度である。また、角質層の下にはおよそ200μmから350μm程度の厚さの表皮が存在し、さらにその下層には毛細血管が張りめぐる真皮層が存在する。このため、角質層を貫通させ薬液を浸透させるためには少なくとも20μm以上の針が必要となる。また、採血を目的とする針状体を製造する場合には、上記の皮膚の構成から少なくとも350μm以上の高さの突起部が必要となる。   More specifically, it is required to penetrate the stratum corneum that is the outermost skin layer. The thickness of the stratum corneum varies slightly depending on the part of the human body, but is about 20 μm on average. In addition, an epidermis having a thickness of about 200 μm to 350 μm exists under the stratum corneum, and further, a dermis layer in which capillaries are stretched exists under the epidermis. For this reason, in order to penetrate the stratum corneum and allow the chemical solution to penetrate, a needle of at least 20 μm or more is required. Further, when producing a needle-like body for the purpose of blood collection, a protrusion having a height of at least 350 μm or more is required due to the structure of the skin.

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必要であり、この材料としては医療用シリコーン樹脂や、マルトース、ポリ乳酸、デキストラン等の生体適合樹脂が有望視されている(特許文献2参照)。   In addition, the material constituting the needle-like body must be a material that does not adversely affect the human body even if the damaged needle-like body remains in the body, such as a medical silicone resin or Biocompatible resins such as maltose, polylactic acid, and dextran are considered promising (see Patent Document 2).

このような微細構造を低コストかつ大量に製造するためには、射出成形法、インプリント法、キャスティング法等に代表される転写成形法が有効であるが、いずれの方法においても成形を行うためには所望の形状を凹凸反転させた原型が必要であり、突起部のようなアスペクト比(構造体の幅に対する高さ、もしくは深さの比率)が高く、先端部の先鋭化が必要である構造体を形成するためには、その製造工程が非常に複雑となる。   In order to produce such a fine structure at low cost and in large quantities, a transfer molding method represented by an injection molding method, an imprinting method, a casting method, etc. is effective. Requires a prototype in which the desired shape is inverted, has a high aspect ratio (height or depth ratio to the width of the structure) like a projection, and requires sharpening of the tip. In order to form the structure, the manufacturing process becomes very complicated.

例えば、微細な針状体を製造する方法として、X線リソグラフィにより突起部の原版を作製し、原版から複製版を作り、転写成形加工を行う製造方法が提案されている(特許文献3参照)。   For example, as a method for producing a fine needle-like body, a production method has been proposed in which a projection original plate is produced by X-ray lithography, a duplicate plate is produced from the original plate, and transfer molding is performed (see Patent Document 3). .

また、機械加工により針状体の原版を作製し、原版から複製版を作り、転写成形加工を行う製造方法が提案されている(特許文献4参照)。
米国特許第6,183,434号明細書 特開2005−21677号公報 特開2005−246595号公報 特表2006−513811号公報
In addition, a manufacturing method has been proposed in which an original plate of needle-like bodies is produced by machining, a duplicate plate is made from the original plate, and transfer molding is performed (see Patent Document 4).
US Pat. No. 6,183,434 Japanese Patent Laid-Open No. 2005-21677 JP 2005-246595 A JP-T-2006-513811

針状体に薬液を塗布する際、薬液が突起部が形成されたアレイ領域外に流出することがある。このため、厳密に薬液塗布量を決定する事が出来ず、処方に沿った薬液の投与が困難となるという問題がある。   When a chemical solution is applied to the needle-like body, the chemical solution may flow out of the array area where the protrusions are formed. For this reason, there is a problem that it is difficult to precisely determine the amount of the chemical solution applied and it becomes difficult to administer the chemical solution according to the prescription.

そこで、本発明は、上述の問題を解決するためになされたものであり、針状体が形成されたアレイ領域外に薬液が過剰に流出することを抑制できる針状体を提供することを目的とする。   Accordingly, the present invention has been made to solve the above-described problems, and an object thereof is to provide a needle-like body that can suppress an excessive outflow of a chemical solution outside the array region where the needle-like body is formed. And

請求項1に記載の本発明は、基板と、前記基板上に設けた複数の突起部と、を備え、前記基板は基板端部から基板中央部に向かって次第に深さが深くなる窪みを有し、前記突起部は前記窪みの部位に形成されており、かつ、前記複数の突起部のそれぞれ突起部の最先端部が同一平面に位置し、前記複数の突起部が外周部から中央部にかけてアスペクト比が段階的に大きくなることを特徴とする針状体である。 The present invention according to claim 1 includes a substrate and a plurality of protrusions provided on the substrate, and the substrate has a recess that gradually increases in depth from the substrate end toward the center of the substrate. The protrusions are formed in the recesses , and the most distal portions of the protrusions are located on the same plane, and the protrusions extend from the outer periphery to the center. The needle-like body is characterized in that the aspect ratio increases stepwise .

請求項に記載の本発明は、請求項1に記載の針状体であって、少なくとも、突起部は生体適合材料よりなることを特徴とする針状体である。 The present invention described in claim 2 is the needle-shaped body according to claim 1 , wherein at least the protrusion is made of a biocompatible material.

請求項に記載の本発明は、基板に複数の突起部を形成する工程と、前記複数の突起部同士の間に溝を形成することにより基板に窪みを形成する工程と、を備え、前記溝は、基板端部から基板中央部に向かって次第に深さが深くなる溝であり、かつ、前記複数の突起部のそれぞれ突起部の最先端部が同一平面に位置し、前記複数の突起部が外周部から中央部にかけてアスペクト比が段階的に大きくなることを特徴とする針状体製造方法である。 The present invention described in claim 3 includes a step of forming a plurality of protrusions on the substrate, and a step of forming a recess in the substrate by forming a groove between the plurality of protrusions. The groove is a groove that gradually increases in depth from the substrate end toward the center of the substrate , and the most prominent portions of the plurality of protrusions are located on the same plane, and the plurality of protrusions Is a method for producing a needle-like body, wherein the aspect ratio gradually increases from the outer peripheral part to the central part .

請求項に記載の本発明は、請求項に記載の突起部製造方法であって、ダイシングブレードを用いて、複数の突起部同士の間に溝を形成することを特徴とする針状体製造方法である。 The present invention described in claim 4 is the method for manufacturing a protrusion according to claim 3 , wherein a groove is formed between the plurality of protrusions using a dicing blade. It is a manufacturing method.

請求項に記載の本発明は、請求項またはのいずれかに記載の突起部の製造方法で作製した突起部を母型とし、転写成形加工を行うことを特徴とする針状体製造方法である。 According to a fifth aspect of the present invention, there is provided a needle-shaped body manufactured by performing transfer molding using the protrusion produced by the method for producing a protrusion according to any of claims 3 or 4 as a mother die. Is the method.

本発明の針状体は、基板に窪みを有し、突起部が窪みの部位に形成されていることを特徴とする。
本発明の構成によれば、基板端部から基板中央部に向かって次第に深さが深くなる窪みにより、窪み内に薬液を留めることが出来、突起部が形成されたアレイ領域内に薬液を留めることが出来る。
よって、突起部が形成されたアレイ領域外に薬液が過剰に流出することを抑制できる突起部を提供することが可能となる。
The needle-shaped body of the present invention is characterized in that the substrate has a recess and the protrusion is formed at the recess.
According to the configuration of the present invention, the chemical solution can be retained in the recess by the recess that gradually becomes deeper from the substrate end toward the center of the substrate, and the chemical solution is retained in the array region in which the protrusion is formed. I can do it.
Therefore, it is possible to provide a protrusion that can suppress excessive outflow of the chemical solution outside the array region where the protrusion is formed.

以下、本発明の針状体について説明を行う。
本発明の針状体は、
基板と、
前記基板上に設けた複数の突起部と、を備え、
前記基板は基板端部から基板中央部に向かって次第に深さが深くなる窪みを有し、
前記突起部は前記窪みの部位に形成されている。
Hereinafter, the acicular body of the present invention will be described.
The needle-shaped body of the present invention is
A substrate,
A plurality of protrusions provided on the substrate,
The substrate has a recess that gradually becomes deeper from the end of the substrate toward the center of the substrate,
The protrusion is formed at the recess.

<基板>
基板は突起部を保持するのに充分な機械特性を備えていれば、特に制限は無い。例えば、金属や無機材料、有機材料などを用いて良い。
針状体を生体皮膚に対して適用する場合、基板は生体適合性と生分解性を有していることが好ましい。生体適合性と生分解性を有する材料としては、例えば、ポリ乳酸、ポリグリコール酸、ポリ乳酸グリコール酸共重合体、ポリクエン酸、ポリリンゴ酸、ポリアミノ酸、マルトース、デキストランなどが挙げられる。特に、基板と突起部とを同一の材料により一体成形する場合、基板は生体適合性と生分解性を有していることが好ましい。
<Board>
The substrate is not particularly limited as long as it has sufficient mechanical properties to hold the protrusion. For example, a metal, an inorganic material, an organic material, or the like may be used.
When the acicular body is applied to living skin, the substrate preferably has biocompatibility and biodegradability. Examples of the material having biocompatibility and biodegradability include polylactic acid, polyglycolic acid, polylactic acid glycolic acid copolymer, polycitric acid, polymalic acid, polyamino acid, maltose, and dextran. In particular, when the substrate and the protrusion are integrally formed of the same material, the substrate preferably has biocompatibility and biodegradability.

また、本発明の基板は、前記基板は基板端部から基板中央部に向かって次第に深さが深くなる窪みを備える。基板端部から基板中央部に向かって次第に深さが深くなる窪みにより、窪み内に薬液を留めることが出来る。   Moreover, the board | substrate of this invention is equipped with the hollow from which the said board | substrate becomes deep gradually toward the board | substrate center part from the board | substrate edge part. The chemical solution can be retained in the recess by the recess gradually increasing in depth from the substrate end toward the center of the substrate.

<突起部>
突起部は、基板の窪みが形成された部位に複数設ける。突起部は、用途によりその形状を自由に設計してよい。例えば、生理活性物質の経皮吸収を促進する目的や、経皮的に生体内の物質を生体外へ取り出す目的の場合、皮膚穿刺性能の観点からは、針状体の先端が先鋭な概錐形状であって、根元幅は数μmから数100μm、長さは数十μmから数百μm程度であることが望ましい。
<Protrusions>
A plurality of protrusions are provided at the site where the depression of the substrate is formed. The shape of the protrusion may be freely designed depending on the application. For example, in the case of the purpose of promoting percutaneous absorption of a physiologically active substance or the purpose of percutaneously removing a substance in a living body from the living body, from the viewpoint of skin puncture performance, the tip of the needle-like body has a sharp cone. It is desirable for the shape to have a root width of several μm to several hundred μm and a length of several tens μm to several hundred μm.

また、突起部は基板と別種の材料を用いて基板に形成したり、基板を加工することにより基板と一体成形したり、しても良い。   Further, the protrusion may be formed on the substrate using a material different from that of the substrate, or may be integrally formed with the substrate by processing the substrate.

また、複数の突起部について、それぞれ突起部の最先端部が同一平面に位置することが好ましい。
本発明の針状体では、1)基板端部から基板中央部に向かって次第に深さが深くなる窪みを有し、2)突起部は前記窪みの部位に形成されている、ため、3)突起部の最先端部が同一平面に位置する場合、必然的に、基板端部の突起部のアスペクト比は、基板中央部のアスペクト比よりも小さくなる(例えば、図2(e)を参照)。
本発明の発明者は鋭意検討の結果、a)針状体を皮膚へ穿刺する場合、皮膚の伸縮性により、配列したアレイの外周部の突起部に応力が集中しやすいため、外周部に位置する突起部ほど変形しやすいこと、b)突起部のアスペクト比が小さいほど、外部からの応力に対して変形が少ないこと、を見出した。
よって、1)基板端部から基板中央部に向かって次第に深さが深くなる窪みを有し、2)突起部は前記窪みの部位に形成され、3)突起部の最先端部が同一平面に位置すること、により、A)突起部は先端部が同一平面内に存在するため、皮膚への穿刺時にそれぞれの突起部に均等に圧力がかかり、各突起部への負荷を低減する事が出来る、B)外周部に位置する突起部のアスペクト比を小さくすることにより、皮膚への穿刺時に皮膚の伸縮性によるアレイ領域外周部の突起部の破損を抑制することが出来る、という効果を同時に奏するという格段の効果を示す。
Moreover, it is preferable that the foremost portion of each of the plurality of protrusions is located on the same plane.
In the needle-like body of the present invention, 1) a recess having a depth that gradually increases from the end of the substrate toward the center of the substrate, and 2) the protruding portion is formed at a portion of the recess. When the foremost portion of the protrusion is located on the same plane, the aspect ratio of the protrusion at the edge of the substrate is inevitably smaller than the aspect ratio of the center of the substrate (see, for example, FIG. 2E). .
As a result of intensive studies, the inventor of the present invention a) When the needle-like body is punctured into the skin, the stress tends to concentrate on the protrusions on the outer periphery of the array array due to the elasticity of the skin. It has been found that the protruding portion is more easily deformed, and b) the smaller the aspect ratio of the protruding portion, the less the deformation with respect to external stress.
Therefore, 1) there is a recess that gradually increases in depth from the substrate end toward the center of the substrate, 2) the protrusion is formed at the position of the recess, and 3) the most advanced portion of the protrusion is on the same plane. By being positioned, A) Since the tip of the protrusion is in the same plane, pressure is evenly applied to each protrusion when puncturing the skin, and the load on each protrusion can be reduced. B) By simultaneously reducing the aspect ratio of the protrusions located on the outer periphery, it is possible to simultaneously suppress the damage to the protrusions on the outer periphery of the array region due to the elasticity of the skin when puncturing the skin. This shows a remarkable effect.

また、少なくとも、突起部は生体適合材料よりなることが好ましい。生体適合性を備えた材料を用いることにより、生体皮膚への適用時に針状体が破損して、その一部が生体内に取り残されても、生体への影響を低減することが出来る。生体適合性を備えた材料としては、例えば、ポリ乳酸、ポリグリコール酸、ポリ乳酸グリコール酸共重合体、ポリクエン酸、ポリリンゴ酸、ポリアミノ酸、マルトース、デキストランなどの生体適合性と生分解性を有する有機高分子などが挙げられる。   Moreover, it is preferable that at least the protrusion is made of a biocompatible material. By using a material having biocompatibility, even if the needle-like body is damaged when applied to living body skin and a part of the needle-like body is left in the living body, the influence on the living body can be reduced. Examples of the material having biocompatibility have biocompatibility and biodegradability such as polylactic acid, polyglycolic acid, polylactic acid glycolic acid copolymer, polycitric acid, polymalic acid, polyamino acid, maltose, and dextran. Organic polymer etc. are mentioned.

以下、本発明の針状体の製造に適した針状体製造方法の一例について具体的に、図1を用いながら説明を行う。
本発明の針状体製造方法は、
基板に複数の突起部を形成する工程と、
前記複数の突起部同士の間に、基板端部から基板中央部に向かって次第に深さが深くなる溝を、形成することにより基板に窪みを形成する工程と、を備える。
Hereinafter, an example of the needle-shaped body manufacturing method suitable for manufacturing the needle-shaped body of the present invention will be described in detail with reference to FIG.
The needle-shaped body manufacturing method of the present invention comprises:
Forming a plurality of protrusions on the substrate;
Forming a recess in the substrate by forming a groove that gradually increases in depth from the substrate end to the center of the substrate between the plurality of protrusions.

<基板上に突起部を形成する工程(図1(a))>
基板10上に、アレイ状に突起部11を形成する。突起部の形成方法は、微細加工方法を用いて、仕様に応じて形成して良い。ここで、微細加工方法としては、例えば、微細機械加工、エッチング加工、リソグラフィ加工などを用いても良い。
<Process for Forming Protrusions on Substrate (FIG. 1A)>
Projections 11 are formed in an array on the substrate 10. As a method for forming the protrusion, a fine processing method may be used according to the specifications. Here, as a fine processing method, for example, fine mechanical processing, etching processing, lithography processing, or the like may be used.

<複数の突起部同士の間に溝を形成することにより基板に窪みを形成する工程(図1(b)〜1(c))>
次に、突起部アレイ領域において、複数の突起部同士の間に窪み13を形成する。このとき、形成する溝は、基板端部から基板中央部に向かって次第に深さが深くなるように加工する。溝の加工方法としては、形成した突起部の寸法に応じて精度良く加工できる微細加工方法であれば良い。
<Process for forming a depression in a substrate by forming a groove between a plurality of protrusions (FIGS. 1 (b) to 1 (c))>
Next, in the protrusion array region, the depression 13 is formed between the plurality of protrusions. At this time, the groove to be formed is processed so that the depth gradually increases from the substrate end toward the center of the substrate. As a processing method of the groove, any micro-processing method that can be processed with high accuracy according to the dimension of the formed protrusion may be used.

また、特に、ダイシングブレードを用いて、複数の突起部同士の間に溝を形成することが好ましい。図1(b)に示すようにダイシングブレード12の様な高速で回転する刃を基板面に押し当てて、溝を形成することにより、ダイシングブレードの円弧の曲率を利用する事によって、基板端部から基板中央部に向かって次第に深さが深くなる溝を好適に形成することが出来る。
このとき、ダイシングブレードを押し当てる方向は、1方向のみに限らず、図1(c)の様に、形成した突起部の配列に応じて同様の処理を複数回施す事によって、基板端部から基板中央部に向かって次第に深さが深くなる窪みを有した針状体17を形成することが出来る。
In particular, it is preferable to form a groove between the plurality of protrusions using a dicing blade. As shown in FIG. 1B, the edge of the substrate is formed by utilizing the curvature of the arc of the dicing blade by pressing a blade rotating at a high speed such as the dicing blade 12 against the substrate surface to form a groove. Thus, it is possible to suitably form a groove that gradually becomes deeper toward the center of the substrate.
At this time, the direction in which the dicing blade is pressed is not limited to only one direction, and as shown in FIG. A needle-like body 17 having a recess that gradually becomes deeper toward the center of the substrate can be formed.

以上より、本発明の針状体の製造方法を実施することが出来る。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をも含むものとする。   As mentioned above, the manufacturing method of the acicular body of this 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 estimated in each process shall also be included.

また、本発明の針状体製造方法で作製した針状体を母型とし、転写成形加工を行うことが好ましい。一体成形された機械的強度の高い複製版を作製することにより、同一の複製版で多量の針状体を製造することが出来るため、生産コストを低くし、生産性を高めることが可能となる。また、転写材料は微細加工に対する加工特性を考慮することなく選択することが出来るため、特に、生体適合性材料により形成された針状体を好適に製造することが出来る。   Moreover, it is preferable to perform transfer molding processing using the needle-shaped body produced by the method for producing a needle-shaped body of the present invention as a matrix. By producing a replica plate with high mechanical strength that is integrally molded, a large amount of needle-like bodies can be manufactured with the same replica plate, which makes it possible to reduce production costs and increase productivity. . In addition, since the transfer material can be selected without considering the processing characteristics for microfabrication, in particular, a needle-like body made of a biocompatible material can be suitably manufactured.

以下、具体的に図2を用いながら転写成形加工の実施の一例について説明を行う。   Hereinafter, an example of the transfer molding process will be described with reference to FIG.

<針状体から複製版を作製する工程(図2(a)〜(c))>
まず、針状体17に充填層14を形成し、充填層14を針状体17から剥離する事で凹型の複製版15を形成する。
<The process of producing a replica from a needle-like body (FIGS. 2A to 2C)>
First, the filling layer 14 is formed on the needle-like body 17, and the filling layer 14 is peeled from the needle-like body 17, thereby forming the concave replication plate 15.

このとき、充填層の材料としては、特に制限されず、複製版として機能するだけの形状追従性、後述する転写成形加工における転写性、耐久性および離型性を考慮した材質を選択することが出来る。例えば、充填層としてニッケル、熱硬化性のシリコーン樹脂などを用いても良い。ニッケルを選択した場合、充填層の形成方法としては、メッキ法、PVD法、CVD法などが挙げられる。   At this time, the material of the filling layer is not particularly limited, and it is possible to select a material that takes into account the shape following ability to function as a duplicate plate, transferability in transfer molding processing described later, durability, and releasability. I can do it. For example, nickel, a thermosetting silicone resin, or the like may be used as the filling layer. When nickel is selected, examples of the method for forming the filling layer include plating, PVD, and CVD.

また、充填層と針状体の剥離方法としては、物理的な剥離力による剥離または選択性エッチング法などを用いることが出来る。   Moreover, as a peeling method of a filling layer and an acicular body, peeling by a physical peeling force or a selective etching method can be used.

<複製版を用いた転写成形加工(図2(d)〜(e))>
次に、複製版15に突起部材料16を充填する。
突起部材料は特に制限されないが、生体適合性材料である医療用シリコーン樹脂や、マルトース、ポリ乳酸、デキストラン、糖質等を用いることで、生体に適用可能な突起部を形成出来る。生体適合性材料を用いれば、微細な突起部が折れて、体内に取り残された場合も、無害であるという効果を奏する。
また、突起部材料の充填方法についての制限は無いが、生産性の観点から、インプリント法、ホットエンボス法、射出成形法、押し出し成形法およびキャスティング法を好適に用いることが出来る。
<Transfer Molding Process Using Duplicated Plate (FIGS. 2D to 2E)>
Next, the projection plate material 16 is filled in the duplicate plate 15.
The protrusion material is not particularly limited, but a protrusion applicable to a living body can be formed by using a medical silicone resin which is a biocompatible material, maltose, polylactic acid, dextran, carbohydrate, or the like. If a biocompatible material is used, even if a fine protrusion is broken and left in the body, there is an effect that it is harmless.
Moreover, although there is no restriction | limiting about the filling method of protrusion part material, from a viewpoint of productivity, the imprint method, the hot embossing method, the injection molding method, the extrusion molding method, and the casting method can be used suitably.

次に、突起部材料を複製版から離型し、転写成形された針状体を得る。
このとき、複製版の剥離性を向上させるために、突起部材料の充填前に、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(図示せず)。
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出来る。
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。
Next, the protrusion material is released from the duplicate plate to obtain a transfer-molded needle-like body.
At this time, in order to improve the peelability of the duplicated plate, a release layer for increasing the mold release effect may be formed on the surface of the duplicated plate before filling the protrusion material (not shown).
As the release layer, for example, a well-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.

<実施例1>
まず、基板として、厚さ725μmのシリコン基板を用意した。
<Example 1>
First, a silicon substrate having a thickness of 725 μm was prepared as a substrate.

次に、80°の傾斜を持つダイジングブレードを用い、シリコン基板を碁盤目状に研削加工を行った。このとき、加工によって形成される突起部の高さを100μmとなるように研削加工を行った。   Next, the silicon substrate was ground into a grid using a dicing blade having an inclination of 80 °. At this time, grinding was performed so that the height of the protrusion formed by the machining was 100 μm.

次に、アレイ領域の突起部同士の間に、研削深さが233μmとなるように90°の角度を持つダイシングブレードを基板面に対して垂直に押し当てた。さらに、一度押し当てたダイシングブレードと垂直方向の向きにも同様の処理を行った。   Next, a dicing blade having an angle of 90 ° was pressed perpendicularly to the substrate surface so that the grinding depth was 233 μm between the protrusions in the array region. Further, the same processing was performed on the dicing blade that had been pressed once in the direction perpendicular to the dicing blade.

以上より、外周の4隅に位置する突起部の根元径が35μm、高さが100μm、また、中央部に位置する突起部の根元系が35μm、高さが333μmであり、外周部から中央部にかけてアスペクト比が段階的に大きくなる針状体を製造出来た。   From the above, the root diameter of the protrusions located at the four corners of the outer periphery is 35 μm, the height is 100 μm, the root system of the protrusion located at the center is 35 μm, and the height is 333 μm. As a result, a needle-like body having an aspect ratio gradually increasing was produced.

<実施例2>
実施例1で作製した突起部を版型とし、転写成形加工を行った。
まず、突起部に充填層としてニッケルを電鋳法で形成した。メッキ浴にはスルファミン酸ニッケル溶液を用いた。60%スルファミン酸溶液を用い、浴温は45℃として5時間のメッキ処理により充填層を形成した。
次に、版型であるシリコンの針状体に、25%KOH溶液を用いて80℃で4時間溶解処理を施し、複製版を作製した。
<Example 2>
The protrusion produced in Example 1 was used as a plate, and transfer molding was performed.
First, nickel was formed by electroforming as a filling layer on the protrusion. A nickel sulfamate solution was used for the plating bath. A 60% sulfamic acid solution was used, the bath temperature was 45 ° C., and a filling layer was formed by plating for 5 hours.
Next, the silicon needle-like body, which is a plate mold, was subjected to a dissolution treatment at 80 ° C. for 4 hours using a 25% KOH solution to prepare a duplicate plate.

次に、複製版に対し、インプリント法を用いて針状体の作製を行った。
充填する突起部材料として、生体適合性材料であるポリ乳酸を用いた。
Next, a needle-shaped body was produced on the duplicated plate using an imprint method.
Polylactic acid, which is a biocompatible material, was used as the projection material to be filled.

以上より、生体適合性材料であるポリ乳酸から成る針状体を形成する事が出来た。   From the above, a needle-like body made of polylactic acid, which is a biocompatible material, could be formed.

本発明の針状体の製造方法は、医療のみならず、微細な突起部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、創薬、化粧品などに用いる微細な突起部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 fine projections. For example, the production of fine projections used in MEMS devices, drug discovery, cosmetics, and the like. It is also useful as a method.

本発明の針状体の製造工程を経時的に説明するための概略斜視図である。It is a schematic perspective view for demonstrating the manufacturing process of the acicular body of this invention with time. 本発明の針状体の転写工程を示す概略断面図である。It is a schematic sectional drawing which shows the transfer process of the acicular body of this invention.

符号の説明Explanation of symbols

10……基板
11……突起部
12……ダイシングブレード
13……窪み
14……充填層
15……複製版
16……突起部材料
17……針状体
DESCRIPTION OF SYMBOLS 10 ... Board | substrate 11 ... Protruding part 12 ... Dicing blade 13 ... Indentation 14 ... Filling layer 15 ... Duplicating plate 16 ... Protruding part material 17 ... Acicular body

Claims (5)

基板と、
前記基板上に設けた複数の突起部と、を備え、
前記基板は基板端部から基板中央部に向かって次第に深さが深くなる窪みを有し、
前記突起部は前記窪みの部位に形成されており、かつ、
前記複数の突起部のそれぞれ突起部の最先端部が同一平面に位置し、
前記複数の突起部が外周部から中央部にかけてアスペクト比が段階的に大きくなること
を特徴とする針状体。
A substrate,
A plurality of protrusions provided on the substrate,
The substrate has a recess that gradually becomes deeper from the end of the substrate toward the center of the substrate,
The protrusion is formed at the indentation , and
Each of the plurality of protrusions is located on the same plane as the most distal portion of the protrusion,
An acicular body characterized in that the plurality of protrusions gradually increase in aspect ratio from the outer peripheral part to the central part .
請求項1に記載の針状体であって、
少なくとも、突起部は生体適合材料よりなること
を特徴とする針状体。
The acicular body according to claim 1 ,
At least the protrusion is made of a biocompatible material.
基板に複数の突起部を形成する工程と、
前記複数の突起部同士の間に溝を形成することにより基板に窪みを形成する工程と、を備え、
前記溝は、基板端部から基板中央部に向かって次第に深さが深くなる溝であり、かつ、
前記複数の突起部のそれぞれ突起部の最先端部が同一平面に位置し、
前記複数の突起部が外周部から中央部にかけてアスペクト比が段階的に大きくなること
を特徴とする針状体製造方法。
Forming a plurality of protrusions on the substrate;
Forming a recess in the substrate by forming a groove between the plurality of protrusions, and
The groove is a groove that gradually becomes deeper from the edge of the substrate toward the center of the substrate , and
Each of the plurality of protrusions is located on the same plane as the most distal portion of the protrusion,
The method for manufacturing a needle-like body, wherein the aspect ratio of the plurality of protrusions gradually increases from the outer peripheral part to the central part .
請求項に記載の針状体製造方法であって、
ダイシングブレードを用いて、複数の突起部同士の間に溝を形成すること
を特徴とする針状体製造方法。
It is a needle-shaped object manufacturing method according to claim 3 ,
A method for producing a needle-like body, wherein a groove is formed between a plurality of protrusions using a dicing blade.
請求項またはのいずれかに記載の針状体の製造方法で作製した針状体を母型とし、転写成形加工を行うこと
を特徴とする針状体製造方法。
A needle-shaped object manufacturing method, wherein the needle-shaped object manufactured by the method for manufacturing a needle-shaped object according to any one of claims 3 and 4 is used as a matrix, and transfer molding is performed.
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