JP4888011B2 - Needle-like body and manufacturing method thereof - Google Patents

Description

  The present invention relates to a method for producing a fine needle for use in medicine and drug discovery such as a drug delivery system (DDS).

  In recent years, in the field of medicine and drug discovery, the development of fine needles as painless needles without pain has been promoted.

  This fine acicular body physically penetrates the stratum corneum existing in the outermost layer of the skin, which is the biggest barrier for the transdermal administration of drugs, and the penetration of the drug solution into the skin Can be realized.

  There are two methods for using fine needles, one used alone and the other used in an array. In general, what is used as a single unit is often used for blood collection and the like, and the central part of the needle-like body is hollow. On the other hand, what is arranged and used in an array is often used for injecting transdermal preparations, etc., in which a drug is applied to a chip in which needles are arranged in an array, and decomposed in vivo Various forms have been developed, such as making needles of such a material and containing a drug therein.

In the fields of medicine and drug discovery, the influence on the human body cannot be ignored. For this reason, as mentioned above, in the use used for a human body, the needle-like body using the material which has a low influence on a human body is desired. Biomaterials such as medical silicone resins, maltose, polylactic acid, and dextran are promising as materials that have a low impact on the human body. (Patent Document 1)
When creating a fine needle-shaped body, there are a type in which the needle-shaped body is directly manufactured and a type in which a plate is first made and a product is manufactured through a transfer process.

  As shown in Patent Document 2, as a method for producing a needle-shaped plate, there is a method in which a multistage structure is produced using a photolithography technique and a soft lithography technique to produce a needle-shaped plate. Are listed. According to this publication, in order to produce a plate with a sharp tip, first, a shape that is pulled out into a small cylinder is produced by the first resist patterning step, and the same resist is applied from above the structure. A shape that is formed in a cylinder slightly larger than the first pattern is formed at the same position as the patterning position, and a desired structure is formed by repeating this.

  However, in this method, it is necessary to repeat the resist patterning process several times to create the needle-like structure, and it is necessary to perform setting of application conditions and alignment with the underlayer at the time of exposure, Yield is poor and not suitable for mass production. Further, since the needle shape is formed by superimposing the rectangular patterns, the sharpness of the tip cannot be obtained. Furthermore, since the shape in which the rectangles are overlapped cannot obtain a smooth shape, it is caught at the time of puncturing.

The patent literature is as follows.
Japanese Patent Laying-Open No. 2005-21677 (see paragraph number 0005) Japanese Patent Laying-Open No. 2004-526581 (see paragraph 0007)

  Therefore, the technical problem to be solved by the present invention is to provide a method for producing a fine needle-like body and a needle-like body which are suitable for mass production and have a sharp tip, a thick base and high strength.

  This invention is made | formed in view of said technical subject, Comprising: The manufacturing method of an acicular body and an acicular body are provided with the following structures.

  As described above, as a material for the painless needle used in the DDS, it is desirable to use a biocompatible material that does not affect even if it remains in the body. At this time, in order to mass-produce painless needles made of a biocompatible material, a method of performing transfer processing molding using a plate is effective.

  The plate mold manufacturing method includes various methods such as a method using a machining technique such as cutting and grinding, a method using a fine processing technique such as a lithography technique and an etching technique, and a method using a casting technique such as injection molding and extrusion molding. Is mentioned.

  Among them, the lithography technique and the etching technique that have been used in the semiconductor manufacturing process can be said to be fine and processing methods for mass production.

Therefore, the method for producing a needle-like body of the present invention according to claim 1 includes a step of applying a positive photoresist on a substrate in the method for producing a fine needle-like body, and an opening in the positive photoresist. Performing a patterning process using a mask having a portion, forming a filling layer on the positive photoresist subjected to the patterning process,
And a step of peeling the filler layer, a mask having the openings have a micro lens for condensing the transmitted light that has passed through the open mouth to the positive photoresist, patterning process using the mask This is a method for producing a needle-like body, characterized in that an inverted conical plate-shaped structure is produced in the positive photoresist by performing the above .

  Moreover, the manufacturing method of the acicular body of this invention which concerns on Claim 2 uses a biocompatible resin for the said filling layer, It is a manufacturing method of the acicular body of Claim 1 characterized by the above-mentioned.

  Moreover, the manufacturing method of the acicular body of this invention which concerns on Claim 3 is an acicular body manufactured by the manufacturing method of the acicular body in any one of Claim 1 or 2.

  In general, when a needle-like body is used for a transdermal preparation or the like, the main purpose is to penetrate the stratum corneum which is the outermost skin layer as described above.

  The thickness of the stratum corneum varies slightly depending on the part of the human body, but is about 20 μm on average. That is, in order to penetrate the stratum corneum and infiltrate the chemical solution, a needle having a thickness of at least 20 μm is required. Therefore, in the manufacturing method of the present invention, it is necessary to form a resist having a thickness of 20 μm or more.

  However, it is not difficult to apply the resist having a thickness of 20 μm. For example, when SU-8 (manufactured by Microchem) is used, it is possible to apply a thickness of about 20 μm to 200 μm.

  Further, in the above configuration, by arranging a convex microlens on the back surface of the exposure portion of the mask, incident light at the time of exposure can be condensed and exposed in an inverted conical shape.

  Furthermore, the size can be changed by changing the diameter of the lens, and the apex angle of the cone can be made variable by changing the curvature of the lens.

  In the present invention, when a resist is exposed by using a mask in which convex lens-shaped microlenses are arranged at predetermined positions, incident light at the time of exposure can be condensed to form a structure that forms a needle-shaped plate. At this time, since a large number of needle-like bodies can be collectively formed in a large area in one step, mass production can be performed at low cost.

Further, the shape of the plate is an inverted conical shape, and the needle-like body transferred therefrom has a further effect that a highly tapered needle-like body having a forward tapered shape can be formed from the tip to the root. (Figure 3)
Furthermore, the method for manufacturing a needle-shaped body of the present invention is characterized in that transfer processing molding is performed using a biocompatible material. By transferring onto a biocompatible material (medical silicone resin, maltose, polylactic acid, dextran, carbohydrate, etc.), it becomes possible to produce a needle-like body using a material with a low load on the living body. If a biocompatible material is used, even if a fine needle-like body is broken and left in the body, there is an effect that it is harmless.

  Hereinafter, the manufacturing method of the fine acicular body of this invention is demonstrated in detail in order of a process, referring FIG. 1 (a)-(f).

(1) The process of apply | coating a resist to a base material The resist 11 is apply | coated to the surface of the base material 10 like FIG.1 (b). For the base material, for example, silicon glass or the like can be used. However, it is apparent from the configuration of the present invention that the resist-coated surface is not limited to this as long as it is smooth. For example, a positive resist is used as the resist, and a coating process is performed by a spin coating method, for example. Further, by baking the resist-coated substrate, excess solvent is volatilized and removed. The baking process is generally set to about 1 hour for a resist having a thickness of 100 μm. In addition, when the desired thickness is not reached by a single coating process, the coating process is performed until the desired thickness is achieved by the repeated coating process in which the coating process and the baking process are repeated.

(2) Step of performing exposure processing and development processing using a mask in which a portion where an acicular body is to be formed becomes an opening in the coated resist Next, the resist after the coating processing is finished as shown in FIG. A mask 12 is arranged on the attached substrate 10a and an exposure process is performed. At this time, the mask 12 is disposed at a position facing the resist, and has a microlens that condenses the light passing through the opening on the resist at a position corresponding to the opening of the mask 12.

  Furthermore, an inverted conical structure as shown in FIG. 1D is obtained by performing development processing.

(3) Step of forming and peeling the filling layer on the plate mold Next, the filling layer is formed and peeled on the plate made in an inverted conical shape as shown in FIGS. Form the body. For example, an imprint method is used for forming and peeling the filling layer.

  For the filling layer, it is desirable to use a biocompatible material that is harmless even when it remains in the body, such as polylactic acid.

  Hereinafter, specific examples will be shown to describe the present invention in more detail.

In FIG. 1A, a silicon wafer used for semiconductor manufacturing or the like was prepared as a base material 10 on which a resist was applied.

  Next, a resist 11 was applied to the surface of the prepared silicon wafer. A positive resist was used as the resist, and it was applied to a thickness of 250 μm by performing an overcoating process by spin coating.

  Further, the resist-coated silicon wafer after the coating treatment was baked at 110 ° C. for 3 hours to completely remove excess solvent.

  Next, as shown in FIG. 1C, an exposure process (exposure source: ultraviolet rays (365 μm)) is performed using a mask 12 with microlenses in which microlenses are arranged at a predetermined interval (interval between lenses; 250 μm). Thereafter, development processing is performed with a developer corresponding to the positive resist to thereby form an inverted conical plate type structure as shown in FIG. 1D (interval between needles; 250 μm, height; 250 μm, tip angle; 20 °) was successfully produced.

  Using the same plate as in Example 1, the needle-shaped body was duplicated by the imprint method. Here, polylactic acid, which is a biocompatible material, was used. Thereby, the acicular body made of polylactic acid could be integrally formed into a conical shape as shown in FIG.

It is a schematic sectional drawing for demonstrating the manufacturing process of a plate mold over time. (A) The perspective view which looked at the mask from the surface on the front side, (b) The perspective view which looked at the mask from the surface on the back side. It is a figure showing the acicular body when a transfer process is performed based on the said plate type | mold.

Explanation of symbols

10, 10a: base material 11: resist 12, 20: mask 13: incident light 14, 21: lens 15: inverted conical shape 16: filling layer 17, 31: acicular body 30: transfer base material

Claims (3)

In the method for producing fine needles,
Applying a positive photoresist on the substrate;
Performing a patterning process on the positive photoresist using a mask having an opening;
Forming a filling layer in the positive photoresist subjected to the patterning process;
Peeling the filler layer,
Mask having the openings have a micro lens for condensing the transmitted light that has passed through the open mouth to the positive photoresist, inverted cone in the positive photoresist by patterning process using the mask A method for producing a needle-like body, comprising producing a plate-shaped structure having a shape .   The method for producing a needle-shaped body according to claim 1, wherein a biocompatible resin is used for the filling layer.   An acicular body manufactured by the method for manufacturing an acicular body according to claim 1.

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