JP2009072271A - Needle-like body and method for producing needle-like body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a needle-like body suppressing both of fracture and deformation when force is applied thereto when bringing a micro needle-like body in contact with a skin, applying pressure thereto and puncturing the skin thereby. <P>SOLUTION: This needle-like body is characterized in having a base plate and a projection on the base plate, wherein the projection consists of a structure layer for constituting the external form of the projection, and a reinforcing layer positioned inside the projection and reinforcing the strength of the projection. A low-rigidity material is used for the structure layer for constituting the external form of the projection and a high-rigidity material is used for the reinforcing layer inside the projection to suppress the fracture and deformation of the projection caused by the force applied thereto in the puncture without lowering the puncture performance. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a fine needle-like body. Moreover, it is related with the manufacturing method of a needlelike object suitable for manufacturing the said needlelike object.

  In recent years, as a method for administering a physiologically active substance into a living body, a method of transdermal administration using a fine needle-like body has attracted attention. Perforation of the stratum corneum with high barrier properties using fine needles to form a path for the passage of physiologically active substances enables higher penetration of physiologically active substances compared to general transdermal administration It is. At this time, by designing the fine needle-like body so as not to penetrate the stratum corneum and reach the capillaries and nerves, it is possible to prevent bleeding and pain during use.

  When a fine needle-like body is used for the purpose of transdermal administration, the fine needle-like body penetrates through the stratum corneum, which is a fineness and tip angle sufficient for piercing the skin, and is the outermost layer of the skin, and the nerve. It is desirable to have a length that does not reach the layer. Specifically, the diameter of the needle-like body is about several μm to 100 μm, the tip of the needle-like body is sharp, its angle is 30 degrees or less, and the needle-like shape The length of the body is preferably about several tens of μm to several hundreds of μm.

  As a material constituting a fine needle-like body, even if a damaged needle-like body remains in the body, it is desirable that the material does not adversely affect the human body, such as medical silicone resin, maltose, Biocompatible materials such as polylactic acid and dextran are considered promising (see Patent Document 1).

  Further, as a method for manufacturing the above-described fine needle-like body, a manufacturing method has been proposed in which an original plate of a needle-like body is produced by X-ray lithography, a duplicate plate is made from the original plate, and transfer processing is performed (Patent Document). 2).

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 produced from the original plate, and transfer processing is performed (see Patent Document 3).
Japanese Patent Laid-Open No. 2005-21677 JP 2005-246595 A JP-T-2006-513811

  When a fine needle-shaped body is brought into contact with the skin and the skin is punctured by applying pressure, the fine needle-shaped body is broken / deformed by the applied force. In particular, in the case of a polymer material having biocompatibility and biodegradability that is suitable as a constituent material for a fine needle-like body, a highly rigid material is likely to cause brittle fracture, and the needle-like body is damaged when applied to the skin. Remains in the body. The material with low rigidity suppresses the destruction of the needle-like body when applied to the skin, but on the other hand, the needle-like body is easily deformed because of its deformation, and the skin puncture performance of the needle-like body is significantly reduced. There is.

Therefore, 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 both destruction and deformation when puncturing the skin.

  The invention according to claim 1 of the present invention is a needle-like body having fine protrusions, and includes a substrate, a protrusion on the substrate, and the protrusion includes a structural layer constituting a protrusion outer shape. And a reinforcing layer for reinforcing the strength of the protruding portion located inside the protruding portion.

  The invention according to claim 2 of the present invention is the acicular body according to claim 1, wherein at least the protrusion is made of a polymer having biocompatibility.

  The invention according to claim 3 of the present invention is the acicular body according to claim 1, wherein the structural layer is made of an amorphous polymer.

  The invention according to claim 4 of the present invention is the acicular body according to claim 1, wherein the reinforcing layer is made of a crystalline polymer.

  The invention according to claim 5 of the present invention is the acicular body according to any one of claims 1 to 4, wherein a plurality of fine protrusions are arranged on the substrate.

  Next, the invention according to claim 6 of the present invention is a molding in which a first material layer forming a structural layer and a second material layer forming a reinforcing layer different from the first material layer are laminated. And a step of producing a mold in which the shape of the desired needle-like body is inverted, and a step of transferring and molding the shape of the die onto the molding substrate. It is the manufacturing method of the acicular body in any one of Claims 1-5.

  The invention according to claim 7 of the present invention is the method for producing a needle-like body according to claim 6, further comprising a step for promoting crystallization of the molding material.

  The invention according to claim 8 of the present invention is a needle-like body manufactured by the method according to claim 6 or claim 7.

  In the needle-shaped body of the present invention, the protrusion is composed of a structural layer constituting the outer shape of the protrusion and a reinforcing layer located inside the protrusion to reinforce the strength of the protrusion. And According to the configuration of the present invention, a material having low rigidity is used for the structural layer constituting the outer shape of the protrusion, and a material having high rigidity is used for the reinforcing layer inside the protrusion, so that the puncture performance is not deteriorated. It becomes possible to suppress the destruction / deformation of the protrusion due to the applied force.

  Hereinafter, the needle-shaped body and the method for producing the needle-shaped body of the present invention will be described in detail based on the embodiments.

  The acicular body of the present invention includes a substrate and a protrusion on the substrate, and the protrusion is positioned inside the protrusion to reinforce the strength of the protrusion, and the structural layer that forms the outer shape of the protrusion. And a reinforcing layer.

FIG. 1 is a partial cross-sectional view showing an example of an embodiment of the present invention. Protrusions 2 are arranged on a flat substrate 1, and the outer shape of the protrusions 2 is formed by a structural layer 3, and a reinforcing layer 4 is formed inside the protrusions 2. FIG. 1 shows an example of an embodiment of the present invention, and the shape and arrangement of the protrusions 2, the shape of the substrate 1, the shape of the structural layer 3 and the reinforcing layer 4 are limited to the illustrated forms. It is not a thing. For example, in FIG. 1, the structural layer 3 is present on the substrate 1 in advance, but the structural layer 3 may not be present on the substrate 1. Moreover, although FIG. 1 shows one protrusion formed on the substrate, a plurality of protrusions may be arranged.

  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 applying the acicular body to living body skin, the substrate preferably has biocompatibility. In particular, when the substrate and the protrusion are integrally formed of the same material, the substrate preferably has biocompatibility and biodegradability.

  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 extracting a substance in a living body to the outside of the living body, from the viewpoint of skin puncture performance, the needle-like body has a sharp cone-shaped tip. The root width is several μm to several hundred μm, the length is about several tens μm to several hundred μm, and it is desirable that the needle-like body side wall has no constriction or step.

  The protrusions may be formed on the substrate using a different material from the substrate, or may be integrally formed with the substrate by processing the substrate.

  Moreover, it is preferable that at least the protrusion is formed of a material having biocompatibility. 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. Examples thereof include polymers.

  The structural layer and the reinforcing layer are preferably formed of the polymer having biocompatibility and biodegradability. A material having low rigidity is suitable for the structural layer, and a material having high rigidity is suitable for the reinforcing layer.

  For example, by forming the structural layer with a silicone resin and forming the reinforcing layer with polycarbonate, a protruding portion having a highly rigid reinforcing layer can be produced.

  It is also possible to make a difference between the rigidity of the materials constituting the structural layer and the reinforcing layer by using the difference in the crystallization state of the materials. For example, by forming the structural layer from amorphous polylactic acid and forming the reinforcing layer from crystalline polylactic acid, it is possible to produce a highly rigid reinforcing layer that is a protrusion made of only polylactic acid. it can.

  Next, the manufacturing method of the acicular body of this invention is demonstrated. The method for producing a needle-shaped body of the present invention includes a molding substrate in which a first material layer that forms a structural layer and a second material layer that forms a reinforcing layer different from the first material layer are laminated. A step of producing a mold in which the shape of a desired needle-like body is inverted, and a step of transferring and molding the shape of the die onto the molding substrate.

  First, a molding substrate suitable for the above-described contents is prepared. The first material layer and the second material layer correspond to the structural layer and the reinforcing layer, respectively, in the protrusions of the needle-like body to be manufactured later, and have a rigidity suitable for the structural layer and the reinforcing layer. Select. As the second material layer serving as the reinforcing layer, a material having high rigidity is used. At this time, by adjusting the thickness of the material layer, it is possible to control the form of the structural layer and the reinforcing layer in the protrusion. Here, as described above, the molding substrate having a two-layer structure will be described, but the molding substrate may have a three-layer structure or more.

  Next, the shape of the protrusion is formed on the molding substrate. As a method of forming the shape of the protrusion on the molding substrate, a known manufacturing method may be appropriately used depending on the shape. For example, the mother die may be formed by a microfabrication technique and may be formed by transfer molding using the mother die. Further, for example, a master die may be formed by a microfabrication technique, a replica plate may be produced from the master die, and transfer molding using the replica plate may be performed. When forming the needle-like body by transfer molding, the molding process is performed with the first material layer serving as the structural layer facing the molding plate.

  Here, as the fine processing technique, for example, a lithography method, a wet etching method, a dry etching method, a sand blast method, a laser processing method, a precision machining method, or the like may be used. Further, as the transfer molding method, for example, an injection molding method, an extrusion molding method, an imprint method, a casting method, or the like may be used.

  The protrusion of the needle-like body manufactured by the above-described method is formed of the first material layer that is the structural layer, and has a reinforcing layer region made of a highly rigid material that is the second material layer inside.

  When the needle-shaped body of the present invention is manufactured using the difference in the crystallization state of the resin, a material to be crystallized is used as the second material layer, and the second material layer is crystallized as the first material layer. A molding substrate is manufactured using a material whose crystallization is not accelerated by the process. For example, the molding substrate described above is manufactured using a polylactic acid glycolic acid copolymer as the first material layer and poly-L lactic acid as the second material layer. By producing a needle-like body by the above-mentioned transfer molding using this molding substrate, a needle-like body having a protrusion formed of a polylactic acid glycolic acid copolymer and having a reinforcing layer region made of poly-L-lactic acid inside. can get. By treating this needle-like body at a temperature that promotes the crystallization of poly-L-lactic acid, crystallization of only the poly-L-lactic acid region inside the protrusion is promoted and the rigidity is improved. can get.

  Hereinafter, specific examples of the needle-shaped body and the method for producing the needle-shaped body of the present invention will be described with reference to FIG. Naturally, the manufacturing method of the needle-shaped body of the present invention is not limited to the following examples, and includes other manufacturing methods that can be analogized. Further, the needle-like body of the present invention is not limited to the needle-like body produced in the following examples.

<Production of mold>
First, using precision machining, 100 regular quadrangular pyramidal protrusions (height: 150 μm, bottom surface: 60 μm × 60 μm) were arranged on a single crystal silicon substrate in a 10-row, 10-row grid pattern at 1 mm intervals. A needle-like body was formed. The 100 protrusions were arranged in a square region having a side of about 9 mm.

  Next, a nickel conductive layer having a thickness of 100 nm was formed on the acicular body formed of the silicon substrate by sputtering. This conductive layer becomes a seed layer in the subsequent electrolytic plating. Next, a nickel film having a thickness of 500 μm was formed on the seed layer by electrolytic plating. Next, the silicon substrate is completely removed by wet etching with an aqueous solution of potassium hydroxide having a weight percent concentration of 30% heated to 90 ° C., so that the needle-shaped mold 20 made of nickel shown in FIG. Was made.

<Production of molding substrate>
Next, as shown in FIG. 2B, a second material layer 12 made of a polylactic acid glycolic acid copolymer having a square of about 18 mm on one side and a thickness of about 1.5 mm is prepared. A molding substrate 13 was produced by laminating a first material layer 11 made of poly-L-lactic acid having a square of about 18 mm on one side and a thickness of about 10 μm.

<Needle transfer molding>
Next, as shown in FIG. 2C, needle-like body transfer molding to the molding substrate was performed by a thermal imprint method using the molding substrate 13 and the mold 20. Next, while maintaining the state where the molding substrate 13 and the mold 20 were in contact with each other, heating to 115 ° C. in an oven promoted crystallization of poly-L lactic acid, and then cooled to room temperature.

<Formation of needle-like body>
Next, the mold 20 was peeled from the molding substrate 13 to obtain the needle-like body 5 composed of the substrate 1 and the protrusions 2 shown in FIG. The needle-like body 5 has a square quadrangular pyramid (height: 150 μm, bottom: 60 μm × 60 μm) projections 2 on a square substrate 1 with a side of about 18 mm in a 10-column, 10-row grid pattern at 1 mm intervals. It was produced in a form in which 100 lines were arranged. The 100 protrusions were arranged in a square region having a side of about 9 mm and located in a substantially central region on the square substrate 1 having a side of about 18 mm.

  Next, in order to confirm the state of the material inside the protrusion, the needle-like body produced in the above process was cut on the surface including the protrusion and observed with a polarizing microscope. As a result, light scattering specific to the crystallized polymer was confirmed only in the region inside the protrusion. From this, it was confirmed that crystallization was not promoted in the region including the outer shape of the protrusion, whereas crystallization was promoted in the region inside the protrusion.

  The needle-shaped body of the present invention can be used not only as a needle-shaped body for transdermal administration but also as a fine needle-shaped body used in various fields such as medicine, drug discovery, cosmetics, and MEMS devices.

The schematic sectional drawing which shows one Embodiment of the acicular body of this invention. BRIEF DESCRIPTION OF THE DRAWINGS Schematic explaining one Embodiment of the manufacturing method of the acicular body of this invention in a cross section.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Substrate 2 ... Projection part 3 ... Structural layer 4 ... Reinforcement layer 11 ... 1st material layer 12 ... 2nd material layer 13 ... Substrate 20 for shaping | molding ··Mold

Claims (8)

A needle-like body having fine protrusions,
A substrate,
A protrusion on the substrate;
The protrusion is a structural layer constituting the protrusion outer shape;
A reinforcing layer for reinforcing the strength of the protruding portion located inside the protruding portion;
A needle-like body characterized by comprising:   The acicular body according to claim 1, wherein at least the protrusion is made of a polymer having biocompatibility.   The acicular body according to claim 1, wherein the structural layer is made of an amorphous polymer.   The acicular body according to claim 1, wherein the reinforcing layer is made of a crystalline polymer.   The acicular body according to claim 1, wherein a plurality of fine protrusions are arranged on the substrate. Producing a molding substrate in which a first material layer forming a structural layer and a second material layer forming a reinforcing layer different from the first material layer are laminated;
Producing a mold in which the shape of the desired needle-like body is inverted, and
A step of transferring and molding the shape of the mold onto the molding substrate;
The method for producing a needle-like body according to claim 1, comprising:   The method for producing a needlelike object according to claim 6, further comprising a step for promoting crystallization of the molding material.   A needle-shaped body manufactured by the method according to claim 6 or 7.

Images