JP2017121315A - Method and apparatus for manufacturing stylet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method and an apparatus for manufacturing a stylet in which the punching of the stylet and the holding/conveying of the stylet can be performed together, and chips of a punching plate in the punching are not produced.SOLUTION: A method for manufacturing a stylet includes: a step of holding a stylet sheet with a stylet part formed on the sheet serving as a support substrate by a stylet sheet holding mechanism; a punching blade setting step of making an upper part punching blade face a lower part punching blade across the stylet sheet; a step of bringing a space formed by the upper part punching blade and the stylet sheet into a negative pressure state; a step of punching the stylet sheet by bringing the upper part punching blade into contact with the lower part punching blade; a step of holding and conveying the stylet punched from the stylet sheet by the upper part punching blade while keeping the space into the negative pressure state; and a step of releasing the negative pressure state and releasing the holding of the stylet.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a method and an apparatus for manufacturing a needle-shaped body, and more particularly to a method and an apparatus for manufacturing a needle-shaped body including a fine needle that is punctured by being attached to the skin.

  The percutaneous absorption method in which a delivery product such as a drug is permeated through the skin and the delivery product is administered into the body is used as a method for simply administering the delivery product without causing pain to the human body.

  In the field of percutaneous administration by the percutaneous absorption method, there has been proposed a method of puncturing the skin using a needle-like body on which a needle having a size of μm is formed, and administering a drug or the like into the skin (patent) Reference 1).

  As a method for producing a needle-like body, a method is proposed in which an original plate is produced by machining, an intaglio plate (transfer plate) is formed from the original plate, and transfer processing molding is performed using the intaglio plate (Patent Document 2). reference). There has also been proposed a method in which an original plate is produced using an etching method, an intaglio plate is formed from the original plate, and transfer processing molding is performed using the intaglio plate (see Patent Document 3).

  The material constituting the acicular body needs to be a material that does not adversely affect the human body even if the damaged acicular body remains in the body. For this reason, biocompatible materials such as chitin and chitosan have been proposed as needle-shaped body materials (see Patent Document 4).

JP 2007-130030 A International Publication No. 2008/013282 International Publication No. 2008/004597 International Publication No. 2008/020632

  A needle-like body using a biocompatible material made of a water-soluble polymer can be dissolved inside the skin after puncturing the skin. Therefore, in addition to the water-soluble polymer, a delivery object intended for delivery into the skin is included to make a needle, and after the needle is punctured into the skin, the water-soluble polymer dissolves so that the delivery substance is absorbed into the skin. Can be delivered to.

  As a method for producing needle-shaped bodies with water-soluble polymer materials, a water-soluble polymer material solution is cast on an intaglio and then dried (sometimes freeze-dried), and the material is first solidified by solidifying the material. There is a method of forming a body (hereinafter referred to as a needle-like body sheet) (in some cases, heating is performed at a desired temperature in order to speed up drying).

  The formed acicular sheet is held at both ends by a suction pad or a chuck and is peeled vertically from the intaglio.

  The peeled needle-shaped body sheet is mounted on the work table with the needle-side surface of the needle-shaped body facing upward, and is desired (product size) using a blade or the like while taking care not to damage the needle section. Punched into shape and size.

  When the needle-shaped body sheet is punched into a desired shape and size, if punched before peeling from the intaglio, the needle portion will not be damaged, but the intaglio may be damaged. The intaglio cannot be damaged because it needs to be used repeatedly in consideration of manufacturing costs and the like.

  As shown in FIG. 6, when the needle-like body 11 is placed on the punching plate 35 and punched on the punching plate 35 during punching, chips 36 of the punching plate 35 are generated and mixed into the needle-like body 11. The human body may be affected.

  The needle-shaped body after punching is held with the surface on the side of the needle part facing up, and is transported to a subsequent process such as adhesive sticking, but falls during transportation without damaging the needle part during transportation. It is necessary to keep it so that it will not happen.

  In view of the above circumstances, the present invention can perform both the punching of the needle-like body and the holding / conveying of the needle-like body without damaging the needle portion, and generates chips on the punching plate at the time of punching. It aims at providing the manufacturing method and manufacturing apparatus of a needle-shaped object which are not made to do.

In order to achieve the above object, the invention described in claim 1 is a method of manufacturing a needle-like body comprising a support substrate and a plurality of needle portions provided on the support substrate,
A step of holding a needle-like body sheet in which a needle part is formed on a sheet serving as a support substrate by a needle-like body sheet holding mechanism;
A punching blade setting step in which the upper punching blade and the lower punching blade are opposed to each other across the needle-shaped body sheet;
A step of bringing the space formed by the upper punching blade and the acicular sheet into a negative pressure state;
A step of punching the acicular sheet by bringing the upper punching blade and the lower punching blade into contact with each other;
Holding and conveying the needle-like body punched from the needle-like body sheet with the upper punching blade while the space is in a negative pressure state;
Releasing the negative pressure state and releasing the holding of the acicular body;
This is a method for manufacturing a needle-like body.

  According to a second aspect of the present invention, the upper punching blade and the lower punching blade have a single-blade structure in which a surface in contact with a side surface of the needle-like body is vertical. This is a method for manufacturing a body.

  According to a third aspect of the present invention, the degree of vacuum when the spaces are in a substantially constant negative pressure state in each of the above steps is in the range of -80.0 to -13.0 kPa as gauge pressure. The needle-shaped body manufacturing method according to claim 1 or 2, characterized in that it is characterized.

  The invention according to claim 4 is characterized in that the flow rate of the compressed air when injecting the compressed air into the space to release the negative pressure state is in the range of 40 to 130 L / min. It is set as the manufacturing method of the acicular body in any one of claim | item 1 -3.

  The invention described in claim 5 is the method for manufacturing a needle-shaped body according to any one of claims 1 to 4, characterized in that the injection of the compressed air is performed through a flow rate control mechanism. .

Invention of Claim 6 is a manufacturing apparatus of the acicular body provided with the support substrate and the some needle part provided on the said support substrate,
A mechanism for holding a needle-like body sheet having a needle portion formed on a sheet serving as a support substrate by a needle-like body sheet holding mechanism;
A punching blade set mechanism that causes the upper punching blade and the lower punching blade to face each other across the needle-like sheet,
A mechanism in which the space formed by the upper punching blade and the acicular sheet is in a negative pressure state;
A mechanism for punching the acicular sheet by bringing the upper punching blade and the lower punching blade into contact with each other;
A mechanism for holding and transporting the needle-like body punched from the needle-like body sheet while the space is in a negative pressure state by an upper punching blade;
A mechanism for releasing the negative pressure state and releasing the holding of the needle-like body;
The needle-shaped body manufacturing apparatus is characterized by comprising:

  According to the manufacturing method and manufacturing apparatus of the needle-shaped body of the present invention, the punching plate is used without damaging the needle portion by including the upper punching blade, the lower punching blade, and the needle-shaped sheet holding mechanism. Therefore, the acicular body sheet can be punched out and conveyed without generating chips, thereby producing the acicular body.

The schematic cross section which shows a part of manufacturing process of an acicular body sheet | seat. The schematic cross section which shows a part of manufacturing process of the acicular body by the manufacturing method and manufacturing apparatus of this invention. The schematic cross section which shows a part of manufacturing process of the acicular body by the manufacturing method and manufacturing apparatus of this invention. The perspective view which shows the acicular body which is a product of this invention. (A) Schematic plan view of FIG. 4 (b) Schematic sectional view of FIG. The schematic cross section which shows the punching method of the conventional acicular body sheet | seat.

  The needle-like body 1 manufactured by the manufacturing method of the present invention includes a support substrate 10 and a needle portion 20 formed on the support substrate 10 as shown in FIG. The shape and material of the needle-shaped body 1 manufactured by the manufacturing method of the present invention will be described in detail later.

  In the needle-like body 1, the support substrate 10 is preferably made of the same material as the needle portion 20. By forming the support substrate 10 and the needle portion 20 with the same material, the support substrate 10 and the needle portion 20 can be integrally formed as a needle-like body sheet. The needle-like body 1 is obtained by punching a needle-like body sheet into a desired shape and size.

  Hereinafter, according to the embodiment of the present invention, a manufacturing method and a manufacturing apparatus of the needle-like body 1 obtained by integrally forming the support substrate 10 and the needle portion 20 with the same material are shown in the order of steps in FIGS. This will be described with reference to FIG. In the description, the same components are denoted by the same reference numerals. In addition, in the drawings used in the following description, in order to make the features easy to understand, the portions that become the features may be shown in an enlarged manner, and the dimensional ratios of the respective components are not always the same as the actual ones. .

(Preparation of intaglio)
First, an original plate (not shown) for determining the shape of the needle portion is prepared, and an intaglio plate 30 in which the shape of the original plate is inverted is prepared. The original plate can be produced by a known method according to the shape of the needle part, and a fine processing technique may be used. Examples of the fine processing technique include a lithography method, a wet etching method, a dry etching method, a sand blasting method, a laser processing method, and a precision machining method. A known shape transfer method can be used to produce the intaglio 30 from the original. For example, Ni electroforming, transfer molding using molten resin, and the like can be mentioned. By the above procedure, the intaglio plate 30 having the concave portions 30a corresponding to the respective needle portions is produced (FIG. 1A).

(Preparation of needle-shaped body sheet)
Separately, a needle-shaped sheet forming composition (solution) containing a needle-shaped body material and a delivery product is prepared. The fluidity of the needle-shaped sheet forming composition is preferably set so that the amount of the solute and the like can be appropriately adjusted so that the recess 30a of the intaglio 30 can be suitably filled.

  Next, the composition 20a for forming an acicular sheet is cast on the intaglio plate 30. The casting method is such that the composition 20a for forming the acicular body sheet is poured into the intaglio 30 under reduced pressure, or the composition 20a for forming the acicular body sheet 20a is applied to the intaglio 30 under normal pressure, and the pressure roll P is applied from above the solution. Is pressed to the bottom of the concave portion serving as the needle tip (FIG. 1B), and the sheet thickness on the intaglio plate 30 (the portion corresponding to the support substrate) is uniformly formed.

  Next, the needle-shaped sheet-forming composition 20a cast and formed with a portion corresponding to the support substrate is dried and solidified. The drying method is preferably heat drying at a desired temperature in order to increase the drying speed.

  Next, the acicular body sheet 1 a formed by solidifying the acicular body sheet-forming composition 20 a is peeled off from the intaglio plate 30. In the peeling method, both ends are held by a suction pad or a chuck, and the needle part 20 is peeled vertically so as not to be damaged.

(Installation, punching, and transporting to the needle body manufacturing equipment)
Next, the needle-shaped body sheet 1a is installed on the needle-shaped body sheet holding mechanism 45 of the needle-shaped body manufacturing apparatus 40 of the present invention (see FIG. 2A) so that the surface of the needle-shaped body sheet 1a is on the upper side.

  Next, after the upper punching blade 50a and the lower punching blade 50b of the needle-like body manufacturing apparatus 40 are moved to desired positions on the needle-like body sheet 1a, they are sucked from the intake port 60, and the upper punching blade 50a and the needle The space formed by the sheet-like sheet 1a is set to the negative pressure space 70, and the upper punching blade 50a and the lower punching blade 50b are slightly abutted against the needle-like sheet 1a. (FIG. 2 (a)).

  When the negative pressure space 70 is set, depending on the weight of the needle-like body sheet 1a, the negative pressure state cannot be maintained, and the needle-like body sheet 1a may be twisted to break the needle portion. In this case, for example, by installing the stopper 51 inside the upper punching blade 50a, the warpage of the acicular sheet 1a can be suppressed (FIG. 2B). The installation position of the stopper 51 is preferably a position where the bottom surface of the stopper 51 is in close contact with the surface of the support substrate portion of the needle-like body sheet when the upper punching blade 50a is lowered during the punching described later. In the following FIG. 3, a structure in which the stopper 51 is installed is shown.

  Next, while raising the degree of vacuum of the negative pressure space 70, the upper punching blade 50a is lowered and further abutted against the needle-like body sheet 1a, and the lower punching blade 50b is further abutted, and the needle-like body sheet 1a is punched. A shaped body is produced (FIG. 3A). In order to hold the needle-like body 1 after punching, the upper punching blade 50a has a single-blade structure in which the surface in contact with the side surface of the needle-like body 1 is vertical, and the lower punching blade 50b has a similar single-blade structure. ing.

  Next, when the lower punching blade 50b is lowered from the punching position and the upper punching blade 50a, the needle-like body 1 and the stopper 51 are provided, the needle-like body is maintained while maintaining the space formed by the stopper 51 in a negative pressure state. 1 is separated from the original needle-like body sheet and transported to a desired position for subsequent processes such as adhesive sticking (FIG. 3B).

When the negative pressure space 70 is made by the needle-shaped body manufacturing apparatus 40, if the suction force is too large, the needle-shaped body sheet 1a.
May cause damage to the needle. For this reason, the degree of vacuum in the negative pressure space 70 varies from the state in which the upper punching blade 50a is slightly abutted against the needle-shaped body sheet 1a (FIG. 2 (a)) to the state during conveyance (FIG. 3 (b)). When the process is in a substantially constant negative pressure state, the gauge pressure is preferably in the range of −80.0 to −13 kPa. More preferably, the gauge pressure is in the range of −38.5 to −13 kPa. In addition, a preferable range includes the range of the both ends.

  After conveying the needle-like body 1 to a desired position, before or after the post-process such as adhesive application, the negative pressure state is released by injecting compressed air or the like from the intake port 60 and pressurizing the needle-like body 1. Is released, and the manufacturing process ends.

  The flow rate of the compressed air or the like when injecting compressed air or the like into the negative pressure space 70 is in the range of 40 to 130 L / min so that the needle-like body 1 is not blown away when the negative pressure state is released. It is preferable. More preferably, it is the range of 40-55 L / min. In addition, a preferable range includes the range of the both ends. Moreover, it is preferable to inject compressed air or the like through a flow rate control mechanism.

  The acicular body 1 produced by the above method becomes a acicular body that can be affixed to the skin or the like when an adhesive is affixed around it. The pressure-sensitive adhesive is preferably made of a material suitable for skin application, and more preferably capable of withstanding the sterilization process.

  As described above, according to the needle-like body manufacturing method and manufacturing apparatus of the present invention, in the punching / conveying step, the upper punching blade and the lower punching blade punch the needle-like body sheet into a desired shape and size. The upper punching blade plays a role of holding and transporting the punched needle-like body. By providing such an upper punching blade, a lower punching blade, and a needle-like body sheet holding mechanism, the needle-like body does not break without generating a chip without damaging the needle portion and no punching plate. Can be manufactured.

(In the case of multiple impositions)
In the above description, the original plate, the intaglio plate, and the production of the acicular sheet are all assumed to be single-sided, but these may be multi-sided. A single-sided original plate may be used for producing the multi-sided intaglio plate, or a multi-sided original plate may be used. Similarly, a single-sided intaglio may be used for producing a multi-faced needle-like body sheet, or a multifaceted intaglio may be used.

  When the method and apparatus for producing the needle-shaped body of the present invention are applied to a multi-faced needle-like body sheet, a desired (product size) is obtained for each side of the multi-faced needle-like body sheet by the production method of the present invention. (1) The shape and size are punched to produce a needle-shaped body.

(Needle shape)
FIG. 4 shows a perspective view of the needle-like body 1 manufactured by the manufacturing method and manufacturing apparatus of the present invention. The needle-like body 1 includes a needle portion 20 on a support substrate 10.

  In the needle-like body 1, the needle portion 20 punctures the skin. In the needle-like body 1, the needle portion 20 may be in a shape suitable for puncturing the skin. The needle part 20 has shapes, such as a cone, a pyramid, a cylinder, a prism, and a pencil shape (a trunk | drum is a pillar shape and a front-end | tip part is a cone shape) etc., for example. Further, the needle portion 20 may be either (1) a form in which one needle is present on the support substrate 10 or (2) a form in which a plurality of needles are formed on the support substrate 10. When a plurality of needle parts 20 stands on the support substrate 10, the needle parts are preferably arranged in an array. Here, the “array shape” indicates a state in which the unit needle portions are arranged. For example, a lattice arrangement, a close-packed arrangement, a concentric arrangement, a random arrangement, and the like are included.

  In the usage form of the needle-like body, an applicator for fixing the insertion position and direction of the needle-like body can be attached. The needle-like body may be provided with a hole in the needle portion. The hole may be a hole penetrating to the back surface of the support substrate or a non-through hole. Moreover, you may provide a hole in a support substrate. In this case as well, the hole may be a through hole reaching the back surface of the support substrate or a non-through hole.

  5A is a plan view of the needle-shaped body 1 shown in FIG. 4 as viewed from above, and FIG. 5B is a cross-sectional view of the needle-shaped body 1 taken along the line II ′ in FIG. It is.

  In the needle-like body 1, it is preferable that the size of the needle portion 20 has a thickness and a length suitable for forming a puncture hole in the skin. Specifically, the height H of the needle portion 20 shown in FIG. 5B is preferably in the range of 10 μm or more and 1000 μm or less. The height H of the needle part is a distance from the support substrate 10 to the tip of the needle part 20.

  The height H of the needle portion is preferably determined in consideration of how deep the puncture hole formed when the needle portion is punctured within the above range is formed in the skin. In particular, when the puncture hole formed when the needle part is punctured is held in “the stratum corneum”, the height H of the needle part is, for example, not less than 10 μm and not more than 300 μm, more preferably not less than 30 μm and not more than 200 μm. Is desirable.

  In addition, when the puncture hole formed when the needle is punctured is “length that penetrates the stratum corneum and does not reach the nerve layer”, the height H of the needle is 200 μm or more and 700 μm or less, more preferably It is desirable that the thickness be in the range of 200 μm to 500 μm, more preferably 200 μm to 300 μm.

  Furthermore, when the puncture hole formed when the needle part is punctured is “the length that the puncture hole reaches the dermis”, the height H of the needle part is preferably in the range of 200 μm to 500 μm. Further, when the puncture hole formed when the needle portion is punctured is “the length that the puncture hole reaches the epidermis”, the height H of the needle portion is preferably in the range of 200 μm to 300 μm.

  The width D of the needle part is preferably in the range of 1 μm to 300 μm. The width D of the needle portion is preferably determined in consideration of the extent to which the puncture hole formed when the needle portion is punctured within the above range is formed in the skin.

  The width D of the needle portion is the maximum length of the lengths of the needle portions that are in contact with the support substrate when the needle portion is projected in parallel with the support substrate surface. For example, when the needle portion is conical, the diameter of the circle on the surface in contact with the needle portion and the support substrate is the width D. When the needle portion is a regular quadrangular pyramid, the square diagonal line of the surface in contact with the needle portion and the support substrate is the width D. Further, when the needle part is a cylinder, the diameter of the circle of the surface in contact with the needle part and the support substrate is the width D. When the needle portion is a regular quadrangular prism, the square diagonal line of the surface in contact with the needle portion and the support substrate is the width D.

  The aspect ratio is preferably in the range of 1 to 10. The aspect ratio A is defined by A = H / D using the length H and width D of the needle portion. When the needle part has a tip angle like a cone shape and penetrates the stratum corneum, the tip angle θ of the needle part is preferably 5 ° or more and 30 ° or less, and is preferably in the range of 10 ° or more and 20 ° or less. More desirable. The tip angle θ indicates the maximum angle (vertical angle) when the needle portion is projected perpendicularly to the support substrate surface.

(Needle material)
Next, the acicular body sheet forming composition 20a produced by the production method and production apparatus of the present invention will be described.

  The composition for forming an acicular sheet is preferably composed of a water-soluble polymer or a polysaccharide. For example, water-soluble polymers and polysaccharides include chitosan, chitosan succinamide, hydroxypropylcellulose (HPC), carboxymethylcellulose (CMC), sodium chondroitin sulfate, curdlan, trehalose, sucrose, gelatin, collagen, pullulan, pectin, alginic acid. Salt, starch, methylcellulose, hydroxypropylmethylcellulose (HPMC), polyvinyl alcohol (PVA), polyacrylic acid polymer, polyacrylamide (PAM), polyethylene oxide (PEO), etc. can be used, but are not limited to this. is not. Further, these materials may be mixed.

  Especially, it is preferable to select from chitosan, chitosan succinamide, hydroxypropyl cellulose, carboxymethyl cellulose, sodium chondroitin sulfate, curdlan, trehalose, sucrose, gelatin, collagen, pullulan, pectin, and alginate. The reason is that it is biologically safe. Note that these materials may be mixed.

  The material is not particularly limited as long as it can be dissolved or dispersed in a solvent to be a liquid material.

  The delivery product contained in order to deliver the composition for forming an acicular sheet into the skin can include a pharmacologically active substance and a cosmetic delivery product. At this time, when a material having a fragrance is used as a delivery product, an odor can be imparted during use, which is preferable for use as a cosmetic product.

  The pharmacologically active substance may be appropriately selected depending on the application. For example, it may be a vaccine such as influenza, an anti-pain drug for cancer patients, insulin, a biologic, a gene therapy drug, an injection, an oral preparation, a preparation for skin application, and the like. Since the needle-like body punctures the skin, it can be applied to pharmacologically active substances that require subcutaneous injection, in addition to pharmacologically active substances that are conventionally used for transdermal administration. In particular, vaccines that are injections are suitable for application to children because there is no pain in administration when needles are used. In addition, it is difficult for children to take an oral agent by conventional oral administration, but when a needle-shaped body is used, it is not necessary to drink a drug at the time of administration, so it is suitable for application to children.

  The cosmetic delivery product is a composition used as a cosmetic product and a cosmetic product. For example, moisturizers, colorants, fragrances, and physiologically active substances that exhibit cosmetic effects (improvement effect on wrinkles, acne, pregnancy lines, improvement effect on hair loss, etc.), and the like.

1, 11 Needle-like body 1a Needle-like body sheet 10 Support substrate 20 Needle portion 20a Composition for forming needle-like body sheet 30 Intaglio 30a Recess 35 Punching plate 36 Chip 40 Needle-like body manufacturing apparatus 45 Needle-like body sheet holding mechanism 50a Upper punching blade 50b Lower punching blade 51 Stopper 60 Inlet 70 Negative pressure space P Pressure roll

Claims (6)

A method for producing a needle-like body comprising a support substrate and a plurality of needle portions provided on the support substrate,
A step of holding a needle-like body sheet in which a needle part is formed on a sheet serving as a support substrate by a needle-like body sheet holding mechanism;
A punching blade setting step in which the upper punching blade and the lower punching blade are opposed to each other across the needle-shaped body sheet;
A step of bringing the space formed by the upper punching blade and the acicular sheet into a negative pressure state;
A step of punching the acicular sheet by bringing the upper punching blade and the lower punching blade into contact with each other;
Holding and conveying the needle-like body punched from the needle-like body sheet with the upper punching blade while the space is in a negative pressure state;
Releasing the negative pressure state and releasing the holding of the acicular body;
A method for producing a needle-like body, comprising:   2. The method for manufacturing a needle-shaped body according to claim 1, wherein the upper punching blade and the lower punching blade have a single-edged structure in which a surface in contact with a side surface of the needle-shaped body is vertical.   The degree of vacuum when the space is in a substantially constant negative pressure state in each of the steps is in a range of -80.0 to -13.0 kPa as a gauge pressure, or A method for producing the needle-shaped body according to 2.   The flow rate of the compressed air when injecting compressed air into the space to release the negative pressure state is in a range of 40 to 130 L / min, according to any one of claims 1 to 3. Manufacturing method of needle-shaped body.   The method for manufacturing a needlelike object according to any one of claims 1 to 4, wherein the injection of the compressed air is performed through a flow rate control mechanism. An apparatus for manufacturing a needle-like body comprising a support substrate and a plurality of needle portions provided on the support substrate,
A mechanism for holding a needle-like body sheet having a needle portion formed on a sheet serving as a support substrate by a needle-like body sheet holding mechanism;
A punching blade set mechanism that causes the upper punching blade and the lower punching blade to face each other across the needle-like sheet,
A mechanism in which the space formed by the upper punching blade and the acicular sheet is in a negative pressure state;
A mechanism for punching the acicular sheet by bringing the upper punching blade and the lower punching blade into contact with each other;
A mechanism for holding and transporting the needle-like body punched from the needle-like body sheet while the space is in a negative pressure state by an upper punching blade;
A mechanism for releasing the negative pressure state and releasing the holding of the needle-like body;
An apparatus for producing a needle-like body, comprising: