JP6232978B2 - Needle-like body manufacturing method and manufacturing apparatus - Google Patents

Description

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

  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 for efficiently absorbing these drugs into the body, a method of perforating the skin using micron-sized fine needles (microneedles) and administering the drug directly into the skin has attracted attention. According to this method, a drug can be easily administered subcutaneously without using a conventional injection device (see Patent Document 1).

  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 penetrating the drug solution under the skin. Several μm to several hundred μm, the length penetrates the stratum corneum, which is the outermost layer of the skin, and does not reach the nerve layer, specifically, a cone-shaped one having a diameter of several tens μm to several hundred μm (cone Body).

  More specifically, the acicular body is required to penetrate the stratum corneum that is the outermost skin layer. The thickness of the stratum corneum varies slightly depending on the site, 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. Further, a dermis layer in which capillaries are stretched exists below 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 needle-like body having a needle height of at least 350 μm or more is required due to the above-described skin structure.

  In addition, the material constituting the acicular body must be a material that does not adversely affect the human body even if the damaged acicular 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).

In addition, as a mechanism for administration into the body, a mechanism in which the drug is administered by applying the drug on the surface of the needle and puncturing the needle, or a needle-shaped body having a hollow needle or a pore for passing the drug solution is used. A mechanism has been proposed in which a drug is administered from the substrate surface (see Patent Document 3).
Furthermore, as a method for improving the productivity of the needle-shaped body, a method of manufacturing using a metal intaglio has been proposed (see Patent Document 4).

US Pat. No. 6,183,434 Japanese Patent Laid-Open No. 2005-21677 JP 2001-309777 A Japanese Patent No. 4779084

However, when the needle-like body is peeled from the metal intaglio, the needle-like body and the intaglio are in close contact with each other, and peeling may be difficult.
The present invention has been made to solve the above-described problems, and provides a manufacturing method and a manufacturing apparatus that improve the peelability of a needle-shaped body from a metal intaglio and improve the productivity of the needle-shaped body. For the purpose.

  A method for manufacturing a needle-like body according to one aspect of the present invention is a method for manufacturing a needle-like body having a needle-like portion on one surface of a substrate, and in order to achieve the above object, an intaglio forming step, A body forming process and a peeling process are provided. In the intaglio forming step, an intaglio is provided that includes a metal recess corresponding to the needle-like portion and a resin layer made of a resin material on the outer periphery of the metal recess. In the needle-shaped body molding step, the needle-shaped body molding material is supplied to the concave portions of the intaglio, and the needle-shaped body molding material is solidified in a state of covering at least a part of the surface of the resin layer to mold the needle-shaped body. . A biocompatible material is preferably used as the needle-shaped body material. In the peeling step, the exposed portion of the resin layer is pressed and deformed with a peeling jig, and the needle-like body is peeled from the intaglio by inserting the peeling jig between the resin layer and the needle-like body.

  According to one aspect of the present invention, when the solidified needle-like body molding material is peeled from the metal recess, the peelability from the metal recess can be improved.

It is the schematic of a groove forming process. It is the schematic of an acicular body original plate shaping | molding process. It is the schematic of a packed bed shaping | molding process. It is the schematic of a metal plate preparation process. It is the schematic of an intaglio production process. It is the schematic of an acicular body molding material supply process. It is the schematic of an acicular body formation process. It is the schematic of a peeling process. It is the schematic of an acicular body molded product.

  Hereinafter, the needle-shaped object manufacturing method according to the embodiment of the present invention will be described. In the needle-shaped body manufacturing method according to the present embodiment, an intaglio molding step for molding an intaglio including a metal recess and a resin layer, and a needle-shaped body is formed by supplying and solidifying a needle-shaped body molding material to the intaglio. And a peeling step of peeling the needle-like body from the intaglio by inserting a peeling jig between the resin layer and the needle-like body.

<Intaglio molding process>
First, an intaglio plate having a metal recess and a resin layer is formed. As a method for forming the intaglio, an intaglio manufacturing method using a known fine processing technique may be used as appropriate. It is also possible to form an intaglio by forming a needle-shaped body original plate by a known method, filling the needle-shaped body original plate with a filling material, and peeling the filling material from the needle-shaped body original plate.

As a method for producing the needle-shaped body original plate, for example, (1) a needle-shaped body manufacturing method using fine machining such as grinding or cutting on the substrate, and (2) a micro-processing technique such as lithography or etching. Examples of the method for producing the needle-shaped body used include (3) a method for transfer-molding the needle-shaped body original plate produced by the above-described known method.
The filling material for the acicular body original plate is not particularly limited, but a material can be selected in consideration of shape followability sufficient to function as a plate, transferability in transfer processing molding described later, plate durability, and peelability. In particular, when considering plate durability, a metal material such as nickel or copper can be selected. When filling the metal material, it is desirable to select an electroforming method from the viewpoint of shape followability with the needle-shaped body original plate.

  A resin material is supplied to the outer peripheral portion of the manufactured intaglio surface and solidified to form a resin layer. As a supply location, the outer side is better than the needle-like part, and the inner side is better than the end part of the needle-like body substrate. Although it does not specifically limit about the thickness of a resin layer, A preferable thickness can be selected when shape | molding an acicular body. When it is desired to smooth the substrate of the acicular body original plate, it is desirable that the surface of the intaglio plate including the resin material is smooth. The resin material is not particularly limited, and a highly flexible silicone resin or epoxy resin is desirable.

<Needle body forming process>
Next, the needle-shaped body molding material is supplied to the intaglio and solidified to mold the needle-shaped body. Here, the intaglio is filled with a polymer material as the needle-shaped body molding material. The polymer material is not particularly limited, but a needle-like body applicable to a living body can be formed by using a medical silicone resin that is a biocompatible material, maltose, polylactic acid, dextran, carbohydrate, or the like. If a biocompatible material is used, even if the needle-shaped body is broken and left in the body, there is an effect that it is harmless. For the purpose of forming a needle-like body, a thermoplastic polymer material such as an epoxy resin, a polyamide resin, or a phenol resin may be used. Moreover, although the filling method of a polymeric material is not limited, the imprint method, the hot embossing method, the injection molding method, the extrusion molding method, and the casting method can be used suitably.

  In this embodiment, the needle-shaped body molding material is in a state of covering at least a part of the surface of the resin layer. For example, when filling the polymer material that is a needle-shaped molding material, or when the filled polymer material is pushed into the intaglio, the outer edge of the polymer material is at least on the surface of the resin layer. Cover part. The covered state is not limited to the contact / contact state, but may be a state where there is a gap or a state where another layer is sandwiched therebetween.

<Peeling process>
Next, the acicular body is peeled from the intaglio to obtain a shaped acicular body. As a peeling method, a physical peeling method can be considered. Specifically, it is considered that a peeling claw produced by processing stainless steel equivalent to SUS304 or SUS440C, die steel equivalent to SKD11, high speed steel equivalent to SKH51, etc. is hooked on the needle-like body and pulled in the peeling direction. It is done. Moreover, the location where the peeling claw contacts the needle-like body is not particularly limited, and may be the side surface of the needle-like body substrate, the substrate surface, or the back surface.

  In this embodiment, when the needle-shaped body is peeled from the intaglio, the resin material is pressed (or pressed) with a peeling claw and deformed, and the peeling claw is inserted between the polymer material and the resin material, The needle-like body is peeled from the intaglio. At this time, if necessary, the needle-like body may be peeled from the intaglio by inserting the peeling claw and then pulling in the peeling direction.

<Peeling layer molding process>
Although not essential, in order to improve the peelability of the intaglio, a release layer for increasing the release effect is formed on the surface of the intaglio after the intaglio is formed and before filling with the polymer material that is a needle-like material. It may be molded. That is, after the intaglio forming process is completed, the release layer forming process is performed before the start of the needle-shaped object forming process. However, actually, the release layer forming step may be performed as a part of the intaglio forming step or the needle-like member forming step.

Gas phase treatment and liquid phase treatment can be selected as a method for forming the release layer. Examples of the gas phase treatment include coating with titanium nitride, DLC (Diamond-like Carbon), or a fluororesin, and a fluororesin coating is desirable. The fluororesin coating is generally called a Teflon (registered trademark) coating. Examples of the liquid phase treatment include chromium plating and electroless plating containing PTFE (polytetrafluoroethylene), and preferably electroless plating containing PTFE.
The above is the outline of the method for manufacturing the needle-shaped body according to the present embodiment, but the present invention is not limited to the example described above, and other methods applicable in each step may be used.

Hereinafter, an example of this embodiment will be described with reference to FIGS.
First, a square with a side of 50 mm, a thickness of 2 mm, and a silicone substrate 101 were prepared, and while grinding blades were rotated, the substrate 101 was ground to a surface depth of 300 μm, as shown in FIG. A groove 102 having a length of 50 mm was formed. The width of the upper opening of the groove 102 was about 418 μm and the depth was 300 μm. In this embodiment, the angle formed by the surface of the substrate 101 and the side wall surface of the groove 102 is 110 °.

  A desired number of grooves 102 were formed. In this example, a total of four grooves were produced. Three convex portions were formed by the four groove forming steps. Further, the substrate 101 having the three convex portions formed by the four groove forming steps formed on the surface thereof was rotated by 90 °, and grinding was performed under the same conditions as those of the four groove forming steps. As a result, the needle body original plate 103 in which the portions remaining without being ground were arranged in an array of 3 columns and 3 rows was obtained. The needle-shaped original plate obtained at this time was a quadrangular pyramid as shown in FIG. 2, the tip angle was 40 °, the height was 300 μm, and the width of one side of the bottom surface was about 231 μm.

Next, transfer processing molding was performed on the produced needle body original plate 103. First, nickel was filled by an electroforming method as a filling layer on the needle body original plate 103. A nickel sulfamate solution was used for the plating bath. Using a 60% sulfamic acid solution and a bath temperature of 45 ° C., a filling layer 104 was formed by plating for 12 hours as shown in FIG.
Next, the acicular body original plate 103 which is a plate mold was subjected to dissolution treatment at 80 ° C. for 4 hours using a 25% KOH (potassium hydroxide) solution, and a metal plate 105 was produced as shown in FIG. A concave portion is formed on the surface of the metal plate 105. The shape of the concave portion of the metal plate 105 corresponds to the shape of the convex portion of the needle body original plate 103.

  Next, a silicone resin is supplied as a resin material to the outer peripheral portion of the metal plate 105 so that the end of the metal plate 105 is flush with the concave surface of the metal plate 105, and the temperature is increased to 100 ° C. using a clean oven. The resin layer 106 was formed by performing a thermosetting treatment for 1 hour. As a result, an intaglio 107 in which the metal plate 105 and the resin layer 106 were integrally formed was produced as shown in FIG. On the surface of the intaglio plate 107, the same concave portion as the metal plate 105 is formed at the center. A resin layer 106 made of a resin material is formed on the outer peripheral portion at the same height as the concave surface of the metal plate 105.

  Next, the needle-shaped body molding material 108 was supplied to the concave portion of the intaglio 107. As the needle-shaped body molding material 108, polyglycolic acid, which is a biocompatible material, was used. Thereby, as shown in FIG. 6, the needle-shaped molding material 108 using a biocompatible material was supplied to the concave surface of the intaglio 107. Here, the needle-shaped body molding material 108 covers at least a part of the surface of the resin layer 106 that is a resin portion of the intaglio 107. A portion of the surface of the resin layer 106 that is exposed even after being coated exists.

Next, the needle-like body molding material 108 was pushed into the concave portion of the intaglio plate 107 by using a hot press method, and the needle-like body molding material 108 was cooled to mold the needle-like body 109. After the polyglycolic acid, which is the needle-shaped molding material 108, was sufficiently cooled in the recesses and on the surface of the recesses of the intaglio plate 107, as shown in FIG.
In actuality, even if the needle-shaped molding material 108 does not cover at least part of the surface of the resin layer 106, the needle-shaped body 109 covers at least part of the surface of the resin layer 106 after hot pressing. It only has to be in a state of being.

  Finally, in order to peel off the needle-like body 109 from the intaglio plate 107, it was peeled off with a peeling claw 110 produced by processing SUS304. As shown in FIG. 8, the peeling claw 110 presses the exposed portion of the resin layer 106, which is a resin portion of the intaglio 107, and inserts the claw portion into the gap between the resin layer 106 and the acicular body 109 generated thereby, The needle-like body 109 was peeled from the intaglio 107 by being hooked on the needle-like body 109 and pulling in the direction of peeling the needle-like body 109.

  The shape of the needle-shaped body 109 was confirmed with a scanning electron microscope. As shown in FIG. 9, the needle-shaped body 109 was made of polyglycolic acid and had a tip angle of 40 °, a height of 298 μm, and a width of one side of the bottom of about 230 μm. It was confirmed that the body 109 was produced.

  The method for manufacturing a needle-like body according to the present embodiment can be applied not only to medical treatment but also to various fields that require a fine needle-like body. For example, a MEMS (Micro Electro Mechanical Systems) device, an optical member, a creation It is also useful as a method for producing fine needles for use in medicine, cosmetics, cosmetics and the like.

DESCRIPTION OF SYMBOLS 101 ... Substrate 102 ... Groove 103 ... Acicular body original plate 104 ... Filling layer 105 ... Metal plate 106 ... Resin layer 107 ... Intaglio 108 ... Acicular body molding material 109 ... Acicular body 110 ... Peeling nail

Claims (9)

A method of manufacturing a needle-like body having a needle-like portion on one surface of a substrate,
An intaglio forming step of forming an intaglio plate comprising a metal recess corresponding to the needle-like portion and a resin layer made of a resin material on the outer periphery of the recess;
Needle-shaped body molding is performed by supplying a needle-shaped body molding material to the concave portion of the intaglio and solidifying the needle-shaped body molding material while covering at least a part of the surface of the resin layer. Process,
The exposed portion of the resin layer is pressed and deformed with a peeling jig provided with a peeling claw, and the peeling claw is inserted between the resin layer and the needle-like body and hooked on the needle-like body, and the peeling claw And a peeling step of peeling the needle-like body from the intaglio by pulling in the direction of peeling the needle-like body. The method of manufacturing a needle-shaped body according to claim 1, wherein a surface of the peeling claw that contacts the needle-shaped body is inclined. The needle-like body according to claim 2, wherein in the peeling step, the inclined surface of the peeling claw is brought into contact with the needle-like body between the resin layer and the needle-like body. Manufacturing method. The method for producing a needle-like body according to any one of claims 1 to 3, wherein a biocompatible material is used as the needle-like body material. In the needle-shaped body molding step, the needle-shaped body molding material is supplied to the intaglio and the needle-shaped body molding material covers at least a part of the surface of the resin layer using a hot press method. The method for manufacturing a needle-like body according to any one of claims 1 to 4, wherein Said release jig, stainless steel, die steel, or the separation claw fabricated by processing one of the high-speed steel claim 1, wherein the obtaining Bei according to any one of claims 5 A method for producing a needle-like body. After molding of the intaglio, before supplying the needle-shaped body molding material to the recesses of the intaglio, the electroless material contains fluororesin coating by vapor phase treatment or PTFE (polytetrafluoroethylene) by liquid phase treatment The method for producing a needlelike object according to any one of claims 1 to 6 , further comprising a release layer forming step of performing plating and forming a release layer on the surface of the intaglio. An apparatus for manufacturing a needle-like body having a needle-like portion on one surface of a substrate,
An intaglio forming apparatus for forming an intaglio plate comprising a metal recess corresponding to the needle-like portion and a resin layer made of a resin material on an outer peripheral portion of the recess;
Needle-shaped body molding is performed by supplying a needle-shaped body molding material to the concave portion of the intaglio and solidifying the needle-shaped body molding material while covering at least a part of the surface of the resin layer. Equipment,
The exposed portion of the resin layer is pressed and deformed with a peeling jig provided with a peeling claw, and the peeling claw is inserted between the resin layer and the needle-like body and hooked on the needle-like body, and the peeling claw And a peeling device for peeling the needle-like body from the intaglio by pulling the needle-like body in the peeling direction . The apparatus for manufacturing a needle-shaped body according to claim 8, wherein a surface of the peeling claw in contact with the needle-shaped body is inclined.

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