JP4978243B2 - Needle-like body and method for producing needle-like body - Google Patents

Needle-like body and method for producing needle-like body Download PDF

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JP4978243B2
JP4978243B2 JP2007055450A JP2007055450A JP4978243B2 JP 4978243 B2 JP4978243 B2 JP 4978243B2 JP 2007055450 A JP2007055450 A JP 2007055450A JP 2007055450 A JP2007055450 A JP 2007055450A JP 4978243 B2 JP4978243 B2 JP 4978243B2
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needle
photocurable resin
resin solution
manufacturing
exposure light
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JP2008212458A (en
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大輔 井ノ口
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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

Description

本発明は、針状体および該針状体の製造方法に関するものである。   The present invention relates to a needle-shaped body and a method for producing the needle-shaped body.

薬剤を経皮的に投与する方法として、注射針による皮膚真皮層への穿刺、皮膚表面への薬剤/軟膏剤の塗布、貼付型経皮投与製剤の使用が挙げられる。
真皮層には、神経細胞が含まれるので注射針の真皮層への穿刺は疼痛を伴い、また塗布剤や貼付型経皮投与製剤では、経皮投与可能な薬剤は少ないという問題点がある。経皮投与可能な薬剤が少ない理由は、角質層の不透過性による。角質層は厚さ10〜30μmの層状構造をなし、種々の物質の体内への侵入、及び種々の物質の体内からの漏出を防ぐバリアとなり、そのため薬剤が角質層下へ透過することが困難となっている。
Examples of the method of transdermally administering the drug include puncture of the skin dermis layer with an injection needle, application of the drug / ointment to the skin surface, and use of a patch type transdermal preparation.
Since the dermis layer contains nerve cells, there is a problem that puncture of the dermis layer of an injection needle is accompanied by pain, and there are few drugs that can be administered transdermally in coating agents and patch-type transdermal preparations. The reason why there are few drugs that can be administered transdermally is due to the impermeability of the stratum corneum. The stratum corneum has a layered structure with a thickness of 10 to 30 μm, and serves as a barrier that prevents various substances from entering the body and leakage of various substances from the body, so that it is difficult for the drug to penetrate below the stratum corneum. It has become.

経皮的に薬剤の透過性を向上させるためのデバイスの形態として、痛みを伴わない無痛針としてマイクロニードルの開発が進められている。経皮投与の目的で微細な針状体を用いる場合、微細な針状体は、皮膚を穿孔するための十分な細さ、および先端角、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、を有していることが望ましく、具体的には、針状体の直径は数μmから100μm程度、針状体の先端角度は30°以下、針状体の長さは数十μmから数百μm程度、であることが望ましいとされている。   As a form of device for improving the permeability of a drug percutaneously, a microneedle has been developed as a painless needle without pain. When using fine needles for the purpose of transdermal administration, the fine needles are fine enough to pierce the skin and penetrate the stratum corneum, the tip corner, the outermost layer of the skin, and It is desirable to have a length that does not reach the nerve layer. Specifically, the diameter of the needle-like body is about several μm to 100 μm, the tip angle of the needle-like body is 30 ° or less, and the length of the needle-like body The thickness is preferably about several tens of μm to several hundreds of μm.

また、体内への薬剤の供給や体内からの血液/体液の採取に用いられることを目的とする医療用マイクロニードルとして、アレイ状に配置した貫通口の無いマイクロニードルのニードルアレイ面に、あらかじめ薬剤を塗布し、ニードルアレイ面を皮膚に押し付けることにより、薬剤がニードル表面と皮膚の間を浸透するタイプが提案されている。(特許文献1、非特許文献1)   In addition, as medical microneedles intended to be used for supply of drugs to the body and collection of blood / fluid from the body, the drugs are preliminarily placed on the needle array surface of microneedles without through holes arranged in an array. A type in which the drug penetrates between the surface of the needle and the skin by applying a sachet and pressing the needle array surface against the skin has been proposed. (Patent Document 1, Non-Patent Document 1)

また、マイクロニードルの内部に貫通口を形成し、薬剤の供給や体内からの血液/体液の採取が貫通口を通して行われるタイプが提案されている。(特許文献2、非特許文献2)   In addition, there has been proposed a type in which a through-hole is formed inside the microneedle, and a medicine is supplied and blood / body fluid is collected from the body through the through-hole. (Patent Document 2, Non-Patent Document 2)

また、薬剤の浸透性を向上させるためにマイクロニードル表面及び/または、マイクロニードルが形成された基板に溝を形成し、流体経路を設けたタイプが提案されている。(特許文献3、特許文献4)   In order to improve the drug permeability, a type in which a groove is formed on a surface of a microneedle and / or a substrate on which the microneedle is formed to provide a fluid path has been proposed. (Patent Document 3, Patent Document 4)

また、上述した微細な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、材料としては医療用シリコン樹脂や、マルトース、ポリ乳酸、デキストラン等の生体適合性材料が有望視されている。(特許文献5)   In addition, the material constituting the fine needle-shaped body is preferably a material that does not adversely affect the human body even if the damaged needle-shaped body remains in the body. Biocompatible materials such as maltose, polylactic acid, and dextran are considered promising. (Patent Document 5)

一方、3次元モデルを造型するための方法として、光硬化性樹脂の液面にレーザー光を照射させ、3次元モデルを形成する光造型方法が知られている。(特許文献6)
特開2004−114552号公報 特開2002−369816号公報 特表2005−501615号公報 特表2005−514179号公報 特開2005−021677号公報 特開平9−226010号公報 Jung-Hwan Parket al. Journal of Controlled Release 104(2005) 51-66, Biodegradable polymer microneedles : Fabrication, mechanics and transdermal drug delivery Shyh-Chyi Kuoet al. Tamkang Journal of Science and Engineering,Vol. 7, No. 2, pp. 95-98A(2004), Novel Polymer MicroneedleArrays and PDMS Micromolding Technique
On the other hand, as a method for molding a three-dimensional model, a photo-molding method for forming a three-dimensional model by irradiating a liquid surface of a photocurable resin with laser light is known. (Patent Document 6)
JP 2004-114552 A JP 2002-369816 A JP-T-2005-501615 JP-T-2005-514179 JP 2005-021677 A JP-A-9-222010 Jung-Hwan Parket al. Journal of Controlled Release 104 (2005) 51-66, Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery Shyh-Chyi Kuoet al. Tamkang Journal of Science and Engineering, Vol. 7, No. 2, pp. 95-98A (2004), Novel Polymer MicroneedleArrays and PDMS Micromolding Technique

微細な針状体について、薬剤を効率よく皮膚内に浸透させるために、針状体内部に空孔や、針状体側面に溝を設けることが知られているが、従来の製造方法は、針の作製後に放電加工やレーザー加工等により貫通口を形成したり、リソグラフィプロセスによる基板両面のパターニングを行ったりするため、所望する形状の針状体を得るためには厳密なアライメントが必要であった。   For fine needle-like bodies, in order to efficiently penetrate the drug into the skin, it is known to provide holes inside the needle-like bodies and grooves on the side surfaces of the needle-like bodies. After forming the needle, through holes are formed by electric discharge machining, laser machining, etc., and patterning is performed on both sides of the substrate by a lithography process. To obtain a needle-like body with a desired shape, strict alignment is required. It was.

また、光造型方法を用いて微細な構造体を形成する場合、分割部位同士の間の光硬化性樹脂が硬化することにより、所望する形状が損なわれるという問題があった。例えば、針状体内部に空孔や、針状体側面に溝などを設けた複雑な形状の針状体の場合、空孔や溝の内部に残留した光硬化性樹脂により、該空孔や該溝が埋められてしまうという問題があった。   Moreover, when forming a fine structure using the photomolding method, there existed a problem that the desired shape was impaired when the photocurable resin between division parts hardens | cured. For example, in the case of a needle-shaped body having a complicated shape in which a hole is formed inside the needle-shaped body or a groove is provided on the side surface of the needle-shaped body, the hole or There was a problem that the groove was filled.

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、特に、針状体内部に空孔や、針状体側面に溝などを設けた複雑な形状の針状体を好適に製造することが出来る針状体製造方法を提供することを目的とする。   Therefore, the present invention has been made to solve the above-described problems, and in particular, a needle-shaped body having a complicated shape in which a hole is formed inside the needle-shaped body or a groove is provided on the side surface of the needle-shaped body is preferable. It aims at providing the needle-shaped object manufacturing method which can be manufactured in this.

請求項1に記載の本発明は、底面に対して垂直な方向に貫通孔を有する微細な針状体の製造方法において、針状体の形状データを、針状体を底面に対して垂直な面で複数の針状体分割部位に分割する形状データ分割工程と、前記分割した形状データに基いて、光造型装置を用いて光硬化性樹脂溶液を露光し、針状体分割部位を形成する分割部位形成工程と、前記光硬化性樹脂溶液の外で、前記針状体分割部位を接合する接合工程と、を備え、かつ、前記接合工程において前記貫通孔の側壁が接合され貫通孔が形成されることを特徴とする針状体製造方法である。
なお、本明細書において、「針状体」とは、製造される一本の針のみならず、針が規則的に整列された構造体(例えば、アレイ状に配列された構造体)をも含むものとして定義する。
According to the first aspect of the present invention, in the method of manufacturing a fine needle-like body having a through-hole in a direction perpendicular to the bottom surface, the shape data of the needle-like body is obtained by using the needle-like body perpendicular to the bottom surface. A shape data dividing step for dividing the surface into a plurality of needle-like body divided portions, and a photocurable resin solution is exposed using a photo-molding device based on the divided shape data to form needle-like body divided portions. A split part forming step and a joining step of joining the needle-like body split part outside the photocurable resin solution , and in the joining step, side walls of the through holes are joined to form through holes. This is a method for manufacturing a needle-shaped body.
In this specification, the “needle-like body” includes not only a single needle to be manufactured but also a structure in which needles are regularly arranged (for example, a structure arranged in an array). Define as including.

請求項2に記載の本発明は、請求項1に記載の針状体製造方法であって、形状データ分割工程は、さらに針状体を底面に対して平行な面で複数の針状体分割部位に分割する工程であ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 2 is the needle-shaped body manufacturing method according to claim 1, wherein the shape data dividing step further divides the needle-shaped body into a plurality of needle-shaped bodies on a plane parallel to the bottom surface. A method for producing a needle-like body, characterized by being a step of dividing into parts.

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針状体製造方法であって、光造型装置を用いて光硬化性樹脂溶液を露光するとき、複数本の露光光線を用いることを特徴とする針状体製造方法である。 A third aspect of the present invention is the needle-shaped body manufacturing method according to the first or second aspect , wherein a plurality of exposures are performed when the photocurable resin solution is exposed using an optical molding apparatus. A method for producing a needle-like body, characterized by using light rays.

請求項に記載の本発明は、請求項に記載の針状体製造方法であって、複数本の露光光線は、アレイ状に整列された複数本の露光光線であ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 needle-shaped body manufacturing method according to claim 3 , wherein the plurality of exposure light beams are a plurality of exposure light beams arranged in an array. It is a needle-shaped object manufacturing method.

請求項に記載の本発明は、請求項1からのいずれかに記載の針状体製造方法で作製した針状体を原型とし、転写加工成形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 processing molding using the needle-shaped body manufactured by the method for manufacturing a needle-shaped body according to any one of the first to fourth aspects as a prototype. Is the method.

請求項に記載の本発明は、請求項1からのいずれかに記載の針状体製造方法により製造された針状体である。 The present invention described in claim 6 is a needle-like body manufactured by the needle-like body manufacturing method according to any one of claims 1 to 5 .

本発明の針状体製造方法は、光造型装置を用いて光硬化性樹脂溶液を露光することで針状体分割部位を形成し、該光硬化性樹脂溶液の外で、該針状体分割部位を接合することを特徴とする。光硬化性樹脂溶液の外で、針状体分割部位を接合するため、接合に際して、分割部位周囲の光硬化性樹脂により形状が損なわれることを抑制することが可能となる。   The needle-shaped body manufacturing method of the present invention forms a needle-shaped body divided portion by exposing a photocurable resin solution using an optical molding apparatus, and the needle-shaped body is divided outside the photocurable resin solution. It is characterized by joining parts. Since the needle-like body divided parts are joined outside the photocurable resin solution, it is possible to prevent the shape from being damaged by the photocurable resin around the divided parts at the time of joining.

以下、本発明の針状体製造方法について説明を行う。
図1は、本発明に係る針状体の作製方法における手順の一例を示す工程図である。
また、本発明は、これに限定することなく例えば図2や図3に示す手順をとることもできる。
Hereinafter, the needle-shaped object manufacturing method of the present invention will be described.
FIG. 1 is a process diagram showing an example of a procedure in a method for producing a needle-like body according to the present invention.
Further, the present invention is not limited to this, and for example, the procedure shown in FIGS. 2 and 3 can be taken.

図1(a)において先ず針状体の設計データ1のデータ処理を行い、底面に対して並行にスライスしたデータ2を作成する。
このとき、針状体をスライスした時の一層あたりの厚さは0.4μm〜100μm、好ましくは1μm〜20μm程度が望ましい。
In FIG. 1A, first, data processing of the needle-shaped design data 1 is performed, and data 2 sliced in parallel with respect to the bottom surface is created.
At this time, the thickness per layer when the acicular body is sliced is 0.4 μm to 100 μm, preferably about 1 μm to 20 μm.

また、図2や図3に示すように、前期データ処理により針状体を放射状に分割したデータ3や針状体を放射状に分割したデータ3を作成し、さらに底面に対して平行にスライスしたデータ4を作成しても良い。   Further, as shown in FIG. 2 and FIG. 3, data 3 obtained by dividing the needle-like body radially by data processing in the previous period and data 3 obtained by radially dividing the needle-like body are created and further sliced parallel to the bottom surface. Data 4 may be created.

次に、データ処理された針状体の形状データ2〜4を基に光造型装置を用いて針状体分割部位の作製を行う。
該光造型装置は、データを基に光硬化性樹脂溶液に露光光を照射、集光することにより任意の構造物を作製することができる。
Next, a needle-shaped body divided portion is prepared using an optical molding apparatus based on the shape data 2 to 4 of the needle-processed data.
The optical molding apparatus can produce an arbitrary structure by irradiating and condensing exposure light to a photocurable resin solution based on data.

光造型装置による針状体分割部位の作製は、データ処理の分割方法により異なり図1に示すように、針状体を底面に対し並行にスライスしたデータ2を用い、光造型装置を用いて光硬化性樹脂溶液に露光光を集光し、底面の層から硬化させ、露光光を集光する高さを変更することにより順次(第一層5、第二層6、第三層7、第四層8)、針状体の先端まで積層させる方法をとることができる。(図1(b)〜(f))   The production of the needle-shaped body dividing part by the optical molding apparatus differs depending on the data processing division method, and as shown in FIG. 1, the data 2 obtained by slicing the needle-shaped body in parallel with the bottom surface is used. The exposure light is condensed on the curable resin solution, cured from the bottom layer, and sequentially changed by changing the height at which the exposure light is condensed (first layer 5, second layer 6, third layer 7, first Four layers 8), a method of laminating to the tip of the acicular body can be taken. (FIGS. 1B to 1F)

光造型装置は、光学系レンズや微細針構造物を作製するステージの高さを制御することにより、露光光を集光する高さを変更することができる。
このとき、積層する総数は特に限定されないが、総数が多いほど針状体の側壁を滑らかに形成することができ、総数が少ないほど作製時間を短縮することができる。
The optical molding apparatus can change the height at which the exposure light is collected by controlling the height of the stage for producing the optical system lens and the fine needle structure.
At this time, the total number of layers to be stacked is not particularly limited, but the side wall of the needle-like body can be formed more smoothly as the total number is larger, and the production time can be shortened as the total number is smaller.

また、図2に示すように、針状体を放射状に分割したデータ3を作成後、更に底面に対して並行にスライスしたデータ4作成し、データ4を用い、光造型装置を用いて光硬化性樹脂溶液に露光光を集光し針状体を放射状に分割したブロック毎に、底面に対して並行にスライスした部位を底面の層から硬化させ、順次(第一層5、第二層6、第三層7、第四層8)、各ブロックの先端まで積層させた後、光硬化性樹脂溶液の外で各ブロック(ブロック10〜13)を接合させる方法をとることができる。   In addition, as shown in FIG. 2, after creating data 3 obtained by radially dividing the needle-like body, data 4 is further sliced parallel to the bottom surface, and data 4 is used and photocured using an optical molding apparatus. For each block in which the exposure light is condensed on the photosensitive resin solution and the needle-like body is radially divided, the portions sliced in parallel to the bottom surface are cured from the bottom layer, and sequentially (first layer 5, second layer 6). , The third layer 7, the fourth layer 8), and after laminating to the tip of each block, a method of joining each block (blocks 10 to 13) outside the photocurable resin solution can be taken.

該ブロックを接合させる方法は、特に限定されないが、通常、熱融着、接着剤や粘着剤による接着が適している。
該ブロックを光硬化性樹脂溶液の外で接合させることにより、中空部を有する針状体等を作製するとき、中空部への光硬化性樹脂溶液の残存を防ぐことができ、確実に中空部を形成することができる。
The method for joining the blocks is not particularly limited, but usually heat fusion, adhesion with an adhesive or a pressure-sensitive adhesive is suitable.
By joining the block outside the photocurable resin solution, when producing a needle-like body having a hollow portion, the photocurable resin solution can be prevented from remaining in the hollow portion, and the hollow portion can be surely formed. Can be formed.

また、図3に示すように、針状体を放射状に分割したデータ3を用いて、光造型装置を用いて光硬化性樹脂溶液に露光光を集光し、針状体を放射状に分割したブロック毎に各ブロック(ブロック10〜13)の外周部(底面14、側壁15〜18)を選択的に硬化させた後、光硬化性樹脂溶液の外で露光機を用いて一括露光光19の照射を行うことにより各ブロック内部の光硬化性樹脂溶液を硬化させると同時に該ブロックを接合させる方法をとることができる。   Further, as shown in FIG. 3, using the data 3 obtained by radially dividing the needle-like body, the exposure light is condensed on the photocurable resin solution using the photo-molding device, and the needle-like body is radially divided. After selectively curing the outer peripheral portion (the bottom surface 14 and the side walls 15 to 18) of each block (blocks 10 to 13) for each block, the collective exposure light 19 is exposed outside the photocurable resin solution using an exposure machine. By irradiating, it is possible to cure the photocurable resin solution inside each block and simultaneously join the blocks.

露光機は、通常のコンタクトアライナーや両面プリンタ等を用いることができ、光源波長は光硬化性樹脂溶液が感光する波長を用いることができる。   As the exposure machine, a normal contact aligner, a double-sided printer, or the like can be used, and the wavelength at which the photocurable resin solution is exposed can be used as the light source wavelength.

光硬化性樹脂溶液の外で一括露光することにより各ブロック内部の光硬化性樹脂溶液を硬化させると同時に該ブロックを接合させるため、各ブロックの接合面に光硬化性樹脂が付着していることが望ましい。   In order to cure the photocurable resin solution inside each block by simultaneous exposure outside the photocurable resin solution, and to bond the block at the same time, the photocurable resin must adhere to the joint surface of each block Is desirable.

図3に示す方法を用いると、光硬化性樹脂溶液の外で一括露光することにより該ブロックを接合させると同時に各ブロック内部の光硬化性樹脂溶液を硬化させることにより、中空部を有する針状体等の作製時に、中空部への光硬化性樹脂溶液の残存を防ぐことができ、確実に中空部を形成することができ、且つ光造型装置の使用を該ブロックの外周部に限定することができるためスループットを大幅に向上することができる。   When the method shown in FIG. 3 is used, the blocks are joined by batch exposure outside the photocurable resin solution, and at the same time, the photocurable resin solution inside each block is cured to form a needle-like shape having a hollow portion. It is possible to prevent the photocurable resin solution from remaining in the hollow part during the production of the body, etc., to reliably form the hollow part, and to limit the use of the optical molding apparatus to the outer peripheral part of the block Therefore, the throughput can be greatly improved.

光硬化性樹脂溶液としては、ラジカル重合反応で硬化するウレタンアクリレート系、エポキシアクリレート系、エステルアクリレート系等やカチオン重合反応で硬化するエポキシ系、ビニルエーテル系、オキセタン系等の光重合性オリゴマー、反応性希釈剤及び光重合開始剤が配合されたものを用いることができ、これらに必要に応じて光重合助剤、添加剤、着色剤などを配合することもできる。   Photocurable resin solutions include urethane acrylates, epoxy acrylates, ester acrylates, etc. that cure by radical polymerization reactions, epoxy polymers that cure by cationic polymerization reactions, vinyl ethers, oxetanes, and other photopolymerizable oligomers. What mixed the diluent and the photoinitiator can be used, and a photopolymerization assistant, an additive, a coloring agent, etc. can also be mix | blended with these as needed.

このとき、光硬化性樹脂として、寸法精度の観点からカチオン重合反応で硬化する樹脂を用いることが好ましく、更に人体への安全性や高速重合の必要性から脂環族エポキシ化合物を用いることが望ましい。
このため、例えば、具体的に、オキセタン化合物を用いることにより寸法精度と強靭性を両立することができる。
At this time, it is preferable to use a resin that is cured by a cationic polymerization reaction from the viewpoint of dimensional accuracy, and it is preferable to use an alicyclic epoxy compound from the viewpoint of safety to the human body and the need for high-speed polymerization. .
For this reason, for example, by specifically using an oxetane compound, it is possible to achieve both dimensional accuracy and toughness.

光造型装置の光源としては、ルビーレーザーやYAGレーザー等の固体レーザー、色素レーザー等の液体レーザー、He−CdレーザーやArレーザー、He−Neレーザー等のガスレーザー、InGaAsP系、GaAlAs系、GaAlInP系、GaN系等の半導体レーザーを用いることができ、さらに分解能を数百nm以下まで向上することができるためフェムト秒レーザーやエバネッセント光を用いることが望ましい。   As a light source of the optical molding apparatus, a solid laser such as a ruby laser or a YAG laser, a liquid laser such as a dye laser, a gas laser such as a He—Cd laser, an Ar laser, or a He—Ne laser, an InGaAsP system, a GaAlAs system, a GaAlInP system It is desirable to use a femtosecond laser or evanescent light because a semiconductor laser such as GaN can be used and the resolution can be improved to several hundred nm or less.

また、光造型装置を用いて光硬化性樹脂溶液を露光するとき、複数本の露光光線を用いることが好ましい。露光光線を複数本とすることで、スループットを向上することが出来る。を露光光線を複数本とする方法としては、露光光源が多数配置された光造型装置を用いて複数本の露光光線を用いる方法、光造型装置の露光光源から放射される露光光線をスプリッター等の光線を分岐させることのできる光学素子を用いて複数本に分岐させる方法、等が挙げられる。   Moreover, when exposing a photocurable resin solution using a photomolding apparatus, it is preferable to use a plurality of exposure light beams. By using a plurality of exposure light beams, the throughput can be improved. The method of using a plurality of exposure light beams includes a method of using a plurality of exposure light beams using a photo-molding apparatus in which a large number of exposure light sources are arranged, and a method such as a splitter that converts the exposure light beams emitted from the exposure light source of the light molding apparatus Examples include a method of branching into a plurality of beams using an optical element that can split a light beam.

特に、複数本の露光光線をアレイ状に整列させた場合、アレイ状に配列された針状体を製造することが出来る。このとき、露光光線の間隔によりアレイのピッチを制御することが出来る。 In particular, when a plurality of exposure light beams are arranged in an array, needle-like bodies arranged in an array can be manufactured. At this time, the pitch of the array can be controlled by the interval of the exposure light beam.

以上の工程により針状体9を作製することができる。   The needle-like body 9 can be produced by the above process.

また、上述した針状体製造方法で作製した針状体を原型とし、転写加工成形を行うことが好ましい。転写加工成形を行うことで、原型を成形するための加工特性に頓着することなく、材料を選択し針状体を製造することが出来る。このため、例えば、生体適合性材料である医療用シリコン樹脂や、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、生体に適用可能な針状体を形成出来る。生体適合性材料を用いれば、微細な針状体が折れて、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。   In addition, it is preferable to perform transfer processing molding using the needle-shaped body produced by the above-described needle-shaped body manufacturing method as a prototype. By performing transfer processing molding, it is possible to select a material and manufacture a needle-like body without being stuck to the processing characteristics for molding the original pattern. Therefore, for example, by using a medical silicone resin that is a biocompatible material, maltose, polylactic acid, dextran, carbohydrate, or the like, a needle-like body applicable to a living body can be formed. If a biocompatible material is used, even if a fine needle is broken and left in the body, there is an effect that it is harmless.

このとき、転写加工成形としては、公知の転写加工成形法を適宜選択して用いて良い。例えば、Ni電鋳法などにより、複製版を作り、複製版を用いたインプリント法、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などを行っても良い。
機械的強度が高く、多面付けされた複製版を作ることにより、同一の複製版で多量かつ大画面に、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。
At this time, as transfer processing molding, a known transfer processing molding method may be appropriately selected and used. For example, a duplicate plate may be made by Ni electroforming or the like, and an imprint method using the duplicate plate, a hot embossing method, an injection molding method, an extrusion molding method, or a casting method may be performed.
By making a duplicated plate with high mechanical strength and multiple impositions, needles can be produced in large quantities and on a large screen with the same duplicated plate, thus reducing production costs and increasing productivity. Is possible.

また、作製した針状体9に任意の材料を成膜しても良い。任意の材料を成膜することにより使用に適した特性を得ることができる。例えば、針状体9に成膜する任意の材料がCu、Al、Feやステンレス合金等の金属である場合、針状体9の強度を向上させることが可能であり、且つ生体適合性チタン等の生体適合性金属を用いると生体への穿刺時に生体への刺激を低減することができる。また、同様な理由からポリ乳酸樹脂等の生体適合性樹脂を成膜しても良い。   Further, an arbitrary material may be formed on the produced needle-like body 9. Properties suitable for use can be obtained by depositing an arbitrary material. For example, when an arbitrary material to be deposited on the needle-like body 9 is a metal such as Cu, Al, Fe or stainless alloy, the strength of the needle-like body 9 can be improved, and biocompatible titanium or the like When the biocompatible metal is used, it is possible to reduce irritation to the living body when puncturing the living body. For the same reason, a biocompatible resin such as polylactic acid resin may be formed.

以下、本発明の針状体製造方法の実施の一例について、具体的に説明を行う。当然のことながら、本発明の針状体製造方法は下記実施例に限定されるものではない。   Hereinafter, an example of implementation of the needle-shaped body manufacturing method of the present invention will be specifically described. As a matter of course, the needle-shaped body manufacturing method of the present invention is not limited to the following examples.

<実施例1>
まず、三次元CADを用いてコンピュータ上で、直径5μmの貫通孔を有する高さ300μm、底面巾105μmの角錐状の針状体を設計し、針状体の形状データを作成した。
<Example 1>
First, a pyramidal needle-like body having a height of 300 μm and a bottom width of 105 μm having a through-hole having a diameter of 5 μm was designed on a computer using three-dimensional CAD, and the shape data of the needle-like body was created.

次に、フェムト秒レーザーを光源に持つ光造型装置を用いて、該光造型装置内での配置や積層方向(立法、倒立、横転など)を決定し、針状体の形状データを、底面に対して平行な面で、3μmピッチの等間隔にスライスした針状体分割部位の形状データを作成した。   Next, using an optical molding apparatus having a femtosecond laser as a light source, the arrangement and stacking direction (legislation, inversion, rollover, etc.) in the optical molding apparatus are determined, and the shape data of the needle-like body is displayed on the bottom surface. On the other hand, the shape data of the needle-like body divided parts sliced at equal intervals of 3 μm on a plane parallel to the surface was created.

次に、前記針状体分割部位の形状データを基に前記光造型装置とオキセタン系光硬化性樹脂溶液を用いて、底面より前記光硬化性樹脂溶液を露光光でスキャンした。被照射部分の樹脂溶液が硬化し、針状体分割部位の形状データに対応する針状体分割部位が形成された。この工程を繰り返して、針状体の先端まで針状体分割部位を順次積層した。   Next, the photocurable resin solution was scanned with exposure light from the bottom using the photomolding device and an oxetane-based photocurable resin solution based on the shape data of the needle-like body division site. The resin solution of the irradiated portion was cured, and a needle-like body divided portion corresponding to the shape data of the needle-like body divided portion was formed. This process was repeated, and the needle-like body division sites were sequentially stacked up to the tip of the needle-like body.

次に、積層された針状体分割部位をオキセタン系光硬化性樹脂溶液から取り出し、露光機を用いて一括露光を行い、前記針状体分割部位を接合した。
以上より、針状体を製造することが出来た。
Next, the laminated acicular body divided parts were taken out from the oxetane-based photocurable resin solution and subjected to batch exposure using an exposure machine to join the acicular body divided parts.
From the above, a needle-like body could be manufactured.

<実施例2>
実施例1で製造された針状体を母型とし、転写加工成形を行った。
まず、実施例1で製造された針状体を母型とし、電解メッキ法によりニッケル複製版を作製した。このとき、シード層としては蒸着により作製したニッケル層30nmを用い、電解メッキ時のメッキ液にはスルファミン酸ニッケル溶液を用いた。また、メッキ浴のpHは4.7、メッキ浴槽温度50℃とし、膜厚400μmまでニッケルを成膜した。
<Example 2>
The needle-shaped body manufactured in Example 1 was used as a mother mold, and transfer processing molding was performed.
First, the acicular body manufactured in Example 1 was used as a mother mold, and a nickel replica was produced by electrolytic plating. At this time, a nickel layer 30 nm formed by vapor deposition was used as a seed layer, and a nickel sulfamate solution was used as a plating solution at the time of electrolytic plating. Moreover, the pH of the plating bath was 4.7, the temperature of the plating bath was 50 ° C., and nickel was deposited to a film thickness of 400 μm.

次に、ニッケルの成膜後、母型として使用したシリコン及びレジストを90℃、25wt%濃度の水酸化カリウム水溶液により溶解除去し、シリコン原版の凹凸反転パターンを有するニッケル複製版を完成させた。   Next, after the nickel film was formed, the silicon and resist used as the mother mold were dissolved and removed with a potassium hydroxide aqueous solution at 90 ° C. and a concentration of 25 wt% to complete a nickel replica plate having an uneven pattern of the silicon original plate.

次に、170℃の加熱により軟化させたPLAに上記のニッケル複製版を用いて熱プレス成型した。このとき、ニッケル複製版のPLAへの押し込み圧力は15MPa、保持時間は1分とし、保持時間経過後にPLA及びニッケル複製版を室温まで冷却したのちに、ニッケル複製版を剥離した。   Next, hot press molding was performed on the PLA softened by heating at 170 ° C. using the above nickel replica. At this time, the indentation pressure of the nickel replica plate to PLA was 15 MPa, the holding time was 1 minute. After the holding time had elapsed, the PLA and nickel replica plate were cooled to room temperature, and then the nickel replica plate was peeled off.

以上より、生体適合性樹脂で構成された本発明の針状体を製造することが出来た。   From the above, the needle-like body of the present invention composed of a biocompatible resin could be manufactured.

本発明の針状体製造方法について手順の一例を示す工程図である。It is process drawing which shows an example of a procedure about the acicular body manufacturing method of this invention. 本発明の針状体製造方法について手順の一例を示す工程図である。It is process drawing which shows an example of a procedure about the acicular body manufacturing method of this invention. 本発明の針状体製造方法について手順の一例を示す工程図である。It is process drawing which shows an example of a procedure about the acicular body manufacturing method of this invention.

符号の説明Explanation of symbols

1・・・針状体の形状データ
2・・・針状体スライスデータ
3・・・針状体放射状分割データ
4・・・針状体放射状分割スライスデータ
5・・・第一層
6・・・第二層
7・・・第三層
8・・・第四層
9・・・光硬化性樹脂からなる針状体
10・・・第一放射状分割ブロック
11・・・第二放射状分割ブロック
12・・・第三放射状分割ブロック
13・・・第四放射状分割ブロック
14・・・放射状分割ブロックにおける底面
15・・・放射状分割ブロックにおける第一側壁
16・・・放射状分割ブロックにおける第二側壁
17・・・放射状分割ブロックにおける第三側壁
18・・・放射状分割ブロックにおける第四側壁
19・・・一括露光光
DESCRIPTION OF SYMBOLS 1 ... Shape data 2 of a needle-like body ... Needle-like body slice data 3 ... Needle-like body radial division data 4 ... Needle-like body radial division slice data 5 ... First layer 6 ... Second layer 7 ... third layer 8 ... fourth layer 9 ... needle 10 made of photo-curable resin ... first radial divided block 11 ... second radial divided block 12 ... third radial division block 13 ... fourth radial division block 14 ... bottom face 15 in the radial division block ... first side wall 16 in the radial division block ... second side wall 17 in the radial division block ..Third side wall 18 in radial division block ... Fourth side wall 19 in radial division block ... Batch exposure light

Claims (6)

底面に対して垂直な方向に貫通孔を有する微細な針状体の製造方法において、
針状体の形状データを、針状体を底面に対して垂直な面で複数の針状体分割部位に分割する形状データ分割工程と、
前記分割した形状データに基いて、光造型装置を用いて光硬化性樹脂溶液を露光し、針状体分割部位を形成する分割部位形成工程と、
前記光硬化性樹脂溶液の外で、前記針状体分割部位を接合する接合工程と、
を備え、かつ、
前記接合工程において前記貫通孔の側壁が接合され貫通孔が形成されること
を特徴とする針状体製造方法。
In the method of manufacturing a fine needle-like body having a through hole in a direction perpendicular to the bottom surface ,
A shape data dividing step of dividing the needle-like body shape data into a plurality of needle-like body dividing portions in a plane perpendicular to the bottom surface ;
Based on the divided shape data, a photocurable resin solution is exposed using an optical molding apparatus, and a divided part forming step for forming a needle-like body divided part; and
Outside the photocurable resin solution, a joining step for joining the acicular body divided parts,
Equipped with, and,
The needle-like body manufacturing method , wherein in the joining step, side walls of the through holes are joined to form a through hole .
請求項1に記載の針状体製造方法であって、
形状データ分割工程は、さらに針状体を底面に対して平行な面で複数の針状体分割部位に分割する工程であること
を特徴とする針状体製造方法。
The needle-shaped body manufacturing method according to claim 1,
The shape data dividing step is a step of further dividing the needle-like body into a plurality of needle-like body division portions in a plane parallel to the bottom surface.
請求項またはのいずれかに記載の針状体製造方法であって、
光造型装置を用いて光硬化性樹脂溶液を露光するとき、複数本の露光光線を用いることを特徴とする針状体製造方法。
It is a needle-shaped object manufacturing method in any one of Claim 1 or 2 ,
A method for producing a needle-like body, wherein a plurality of exposure light beams are used when a photocurable resin solution is exposed using an optical molding apparatus.
請求項に記載の針状体製造方法であって、
複数本の露光光線は、アレイ状に整列された複数本の露光光線であ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 ,
The method for producing a needle-like body, wherein the plurality of exposure light beams are a plurality of exposure light beams arranged in an array.
請求項1からのいずれかに記載の針状体製造方法で作製した針状体を原型とし、転写加工成形を行うこと
を特徴とする針状体製造方法。
5. A method for producing a needle-like body, wherein the needle-like body produced by the method for producing a needle-like body according to any one of claims 1 to 4 is used as a prototype, and transfer processing is performed.
請求項1からのいずれかに記載の針状体製造方法により製造された針状体。 The needlelike object manufactured by the needlelike object manufacturing method according to any one of claims 1 to 5 .
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