JP4985025B2 - Microneedle chip assembly, microneedle chip, medical instrument, microneedle chip assembly manufacturing method, and microneedle chip manufacturing method - Google Patents

Description

  The present invention relates to a microneedle chip assembly used in a medical instrument for puncturing skin, a method for manufacturing a microneedle chip assembly, and a microneedle chip obtained by cutting the microneedle chip assembly.

  The whole human body is covered with skin. The skin is divided into an epidermis, dermis and subcutaneous tissue from the surface in a three-layer structure. The epidermis is on the outermost side of the skin and is very thin, averaging 200 μm thick. The dermis is a thick layer that lies beneath the epidermis and consists mainly of a nipple layer and a reticular layer of fiber cells. The papillary layer is the dermis that has engulfed the epidermis, where the capillaries, lymph vessels, and peripheral nerve endings are located, and the reticular layer has capillaries, lymph vessels, nerves, sebaceous glands, sweat glands, and other appendages, It plays an important role in the skin. The subcutaneous tissue is the foundation of the skin and has subcutaneous fat. It is responsible for protecting the body, maintaining body temperature and storing energy.

  The epidermis is a human protective barrier and consists of stratum corneum, granule layer, spiny layer and basal layer. The basal layer is a cell layer in contact with the dermis, arranged in a wavy shape, and epidermal cells are born. In the upper layer of the basal layer, there is a spiny layer that occupies most of the epidermis, and lymph and tissue fluids flow and nutrients are replenished. In the upper layer, a granular layer is located and functions to protect the human body from acid and alkali. Further, a stratum corneum is present at the uppermost part (outermost part) of the epidermis, and protects the living body from contamination such as gonococci and poisons as the forefront of the protective barrier.

  These layers are not separate cell layers, but are connected in time series and are responsible for skin metabolism. Cells divide in the basal layer and basal cells are born. This basal cell moves to the skin surface while protecting the living body while changing its size, shape and function with spiny cells, granule cells, and keratinocytes as time passes, and finally it becomes red and dandruff, and the skin surface Peel off. A keratinocyte is a dead cell, and protects the living body as a hard layer without metabolic capacity.

  Through the human epidermis having the above-mentioned protection system, active ingredients of pharmaceuticals and cosmetics are delivered, and body fluids for examination are widely collected, and in the case of steep, subcutaneous injection method, intramuscular injection method, or Intravenous injection is performed. As a slow delivery method, a patch method such as a poultice is applied. At this time, the patch method requires a formulation in which the active ingredient reaches the body fluid (blood) through the skin (epidermal) barrier. For example, when the active ingredient has a high molecular weight, it is difficult to penetrate the skin barrier. is there.

  There has been a demand for a method in which an active ingredient that is difficult to penetrate the skin barrier is injected subcutaneously while efficiently relieving pain and fear at the time of use. In accordance with this requirement, a chip having a plurality of fine needles called microneedles on the surface has been developed. For example, a patch using a microneedle chip having a special structure has been developed for the purpose of delivering a pharmaceutical composition (see, for example, Patent Document 1).

  When a microneedle is used for the purpose of transdermal administration, the microneedle is thin enough to pierce the skin, penetrates the tip corner, the stratum corneum that is the outermost layer of the skin, and 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 is several tens of μm. To about several hundred μm. Further, in the case of using a microneedle for the purpose of collecting body fluid for examination, a needle-like body having a height of at least 350 μm or more is required due to the above-described skin configuration.

  In addition, when a medical device that penetrates the skin and pushes into the body is damaged and a part of the microneedle remains in the body, the residue is harmless and is gradually decomposed in the body and further discharged outside the body. As described above, it is desirable to use a biocompatible material for medical use from which impurities are removed as much as possible (see, for example, Non-Patent Documents 1 to 3 and Patent Document 2).

  As the biocompatible material, medical silicone resin, polyester, polylactic acid, polyglycolic acid, ascorbic acid, maltose, dextran, and the like are known. These polymers are used alone, in blends, or in polymer compositions. Any of these polymers is a biodegradable polymer for medical use from which impurities are completely removed, and is an expensive material.

  Moreover, as a microneedle for medication such as insulin, a medical instrument has been proposed in which a circular microneedle tip is attached using an applicator (see, for example, Non-Patent Documents 1 to 4).

Further, as a method of manufacturing a microneedle chip, a manufacturing method has been proposed in which a microneedle chip original plate is prepared by machining, a replica plate is formed from the original plate, and transfer processing is performed (see, for example, Patent Document 3). .
JP-T-2004-516868 JP 2005-021677 A JP-T-2006-513811 Jung-Hwan Park, Mark G. et al. Allen, and Mark R. Prausnitz, “Polymer Microneedles for Controlled-Release Drug Delivery”, Pharmaceutical Research, Vol. 23, no. 5 (2006), 1008-1019. Sobrasua E.I. M.M. Ibim, Archel M .; A. Ambrosio, Michael S. Kwon, Saadiq F.M. El-Amin, Harry R .; Allcock, Cato T .; Laurecin, "Novel Polyphosphazene / Poly (lactide-co-glycolide) blends: miscibility and degradation studies", Biomaterials, 18 (1997), 1565-1569. Giovanni Vozzi, Christopher Flaim, Artiahluwalia, Sangereta Bhatia, “Fabrication of PLGA scaffolding using soft lithography 33” A. J. et al. Nijenhuis, E .; Colste, D.C. W. Grijpma, A.M. J. et al. Pennings, “High molecular weight poly (L-latide) and poly (ethyl oxide) blends: thermal charactarization and physical properties, 58, 49, Vol.

  A microneedle chip used for a medical instrument for puncturing the skin is desired to be easily handled in a manufacturing / storage / transportation process without damaging the microneedle part, which is a fine structure part. Yes.

  Accordingly, the present invention has been made to solve the above-described problems, and an object thereof is to provide a microneedle chip assembly that can be easily handled.

The present invention according to claim 1 is a microneedle chip assembly used in a medical instrument for puncturing the skin, comprising a plurality of microneedles for puncturing the skin, and a regular hexagonal pedestal that supports the microneedles. A microneedle tip assembly comprising a plurality of microneedle tips arranged in a row.

The present invention according to claim 2 is a microneedle chip assembly used in a medical instrument for puncturing the skin, comprising a plurality of microneedles for puncturing the skin and a circular pedestal for supporting the microneedles. A microneedle chip assembly comprising a microneedle chip, wherein a plurality of the microneedle chips are arranged .

A third aspect of the present invention is the microneedle chip assembly according to the first or second aspect, wherein when a plurality of microneedle chips are arranged, one microneedle chip is another six microneedles. A microneedle chip assembly, which is arranged so as to be in contact with a needle chip .

The present invention according to claim 4 is a microneedle chip assembly used in a medical instrument for puncturing the skin, comprising a plurality of microneedles for puncturing the skin and a pedestal for supporting the microneedles. comprising a chip, the microneedle chip is a microneedle chip line connecting the plurality of microneedles microneedles positioned in the outermost portion is arranged to be circular, and the microneedle chip arrayed A microneedle chip assembly characterized by having been made .

The present invention according to claim 5 is a microneedle chip assembly used in a medical instrument for puncturing the skin, comprising a plurality of microneedles that puncture the skin and a pedestal that supports the microneedles. comprising a chip, the microneedle chip is a microneedle chip intersection angle of a line connecting a plurality of microneedles located outermost are arranged so as to be smaller polygons than 180 degrees greater than 90 degrees, And it is the microneedle chip | tip aggregate | assembly characterized by arranging the said microneedle chip | tip in multiple numbers .

A sixth aspect of the present invention is the microneedle chip assembly according to any one of the first to fifth aspects, wherein the microneedle chip is a microneedle and a pedestal formed of the same material. A microneedle chip assembly, which is a needle chip .

A seventh aspect of the present invention is the microneedle chip assembly according to any one of the first to sixth aspects, wherein at least the microneedles are made of a biocompatible resin. This is a microneedle chip assembly .

The present invention according to claim 8 is the microneedle chip assembly according to any one of claims 1 to 7, wherein the microneedle chip is arranged at a position corresponding to the outermost edge portion of the base. A microneedle chip assembly, characterized in that the microneedle chip is not a microneedle chip .

The present invention described in claim 9 is a microneedle chip obtained by cutting the microneedle chip assembly according to any one of claims 1 to 7 .

The present invention according to claim 10 is a medical instrument using the microneedle chip assembly according to any one of claims 1 to 9 .

The present invention according to claim 11 is a microneedle chip assembly manufacturing method used for a medical instrument for puncturing the skin, comprising a step of forming a microneedle chip, and a step of arranging the microneedle chip, The microneedle chip includes a microneedle chip including a plurality of microneedles that puncture the skin and a regular hexagonal pedestal that supports the microneedles, and a plurality of the microneedle chips arranged in a row. A method for producing a microneedle chip assembly, which is a needle chip assembly .

The present invention according to claim 12 is a microneedle chip assembly manufacturing method used for a medical instrument for puncturing the skin, comprising a step of forming a microneedle chip, and a step of arranging the microneedle chip, The microneedle chip comprises a microneedle chip comprising a plurality of microneedles for puncturing the skin and a circular pedestal for supporting the microneedles, and a plurality of the microneedle chips arranged. A method of manufacturing a microneedle chip assembly, which is a chip assembly .

A thirteenth aspect of the present invention is a method for producing a microneedle chip assembly for use in a medical instrument for puncturing the skin, comprising the steps of forming a microneedle chip and arranging the microneedle chips. In addition, the microneedle tip includes a microneedle tip including a plurality of microneedles that puncture the skin and a pedestal that supports the microneedles, and the microneedle tip is located at the outermost position. A microneedle chip which is a microneedle chip arranged so that a line connecting a plurality of microneedles is circular, and a microneedle chip assembly in which a plurality of the microneedle chips are arranged It is an assembly manufacturing method .

The present invention according to claim 14 is a microneedle chip assembly manufacturing method used for a medical instrument for puncturing the skin, comprising a step of forming a microneedle chip, and a step of arranging the microneedle chip, In addition, the microneedle chip includes a microneedle chip that includes a plurality of microneedles that puncture the skin and a pedestal that supports the microneedle, and the microneedle chip includes a plurality of microneedle chips that are located on the outermost side. A microneedle chip arranged so that the intersection angle of lines connecting the microneedles is a polygon larger than 90 degrees and smaller than 180 degrees, and a microneedle chip assembly in which a plurality of the microneedle chips are arranged in the microneedle chip assembly manufacturing method characterized by certain That.

A fifteenth aspect of the present invention is a method for manufacturing a microneedle chip assembly, wherein the microneedle chip assembly according to any one of the tenth to fourteenth aspects is used as a prototype, and transfer processing is performed.

The present invention described in claim 16 is a microneedle chip manufacturing method comprising cutting the microneedle assembly manufactured by the microneedle chip assembly manufacturing method according to claim 15 .

  The microneedle chip assembly of the present invention is characterized in that a plurality of microneedle chips are arranged. According to the configuration of the present invention, by arranging a plurality of microneedle chips, the microneedle chips can be manufactured / stored / transported in a sheet shape / tape shape. For this reason, it can suppress that a microneedle chip | tip is damaged by contact with microneedle chip | tips at the time of manufacture / storage / transportation by setting it as a sheet | seat shape / tape shape. In addition, it is possible to reduce the need for managing fine microneedle tips individually, and to reduce the management / storage effort.

Hereinafter, the microneedle chip assembly of the present invention will be described.
The microneedle chip assembly of the present invention,
A plurality of microneedles that puncture the skin;
A pedestal for supporting the microneedle;
Comprising a microneedle tip comprising
A microneedle chip assembly in which a plurality of the microneedle chips are arranged.

The microneedle chip assembly of the present invention is characterized in that a plurality of microneedle chips are arranged. According to the configuration of the present invention, by arranging a plurality of microneedle chips, the microneedle chips can be manufactured / stored / transported in a sheet shape / tape shape. For this reason, it can suppress that a microneedle chip | tip is damaged by contact with microneedle chip | tips at the time of manufacture / storage / transportation by setting it as a sheet | seat shape / tape shape. In addition, it is possible to reduce the need for managing fine microneedle tips individually, and to reduce the management / storage effort.
FIG. 1 shows an example of the microneedle chip assembly of the present invention when the pedestal is filled with a regular hexagonal microneedle chip.

  Moreover, about the microneedle chip | tip aggregate | assembly, the arrangement | sequence of a microneedle chip should just be arranged in a plane without a microneedle chip | tip overlapping. For example, a lattice arrangement or a close packed arrangement may be used.

  In the microneedle chip assembly of the present invention, when a plurality of microneedle chips are arranged, it is preferable that one microneedle chip is arranged so as to be in contact with the other six microneedle chips. Here, “arrangement so that one microneedle tip is in contact with the other six microneedle tips” means an arrangement in which one microneedle tip can be in contact with the other six microneedle tips. For example, in the microneedle chip assembly, the microneedle chips arranged on the outer edge or the like do not necessarily have to be in contact with the six microneedle chips.

  By arranging one microneedle tip in contact with the other six microneedle tips, it will be arranged in a close-packed arrangement, and the area of the microneedle tip that occupies the sheet / tape-shaped microneedle tip assembly The ratio of can be improved. Therefore, in the microneedle chip assembly, the microneedle integration rate per area of the microneedle chip assembly can be improved.

FIG. 2 shows an example of the microneedle chip assembly of the present invention in each case when (a) circular chips are arranged in a close-packed arrangement and (b) circular chips are arranged in a grid. In FIG. 2, for example, when the radius of a circular chip is 1 cm, in the case of a lattice arrangement, the occupied area is 4 cm ² for arranging one chip. For placement, the occupied area is about 3.46 cm ² . For this reason, in the microneedle chip assembly, the integration of the microneedle chips is advantageous by about 13% compared to the lattice arrangement by using the close-packed arrangement.

  In particular, when the pedestal of the microneedle tip is a regular hexagon, it can be arranged in a close-packed arrangement with a single pedestal shape and a plane filling rate of 100%. Further, when the base of the microneedle tip is a regular hexagon, the microneedle assembly has a honeycomb structure, and therefore the mechanical strength of the microneedle assembly itself in a sheet shape / tape shape can be reinforced ( FIG. 3).

Hereinafter, the microneedle chip constituting the microneedle chip assembly of the present invention will be described.
The microneedle chip constituting the microneedle chip assembly of the present invention includes a plurality of microneedles that puncture the skin and a pedestal that supports the microneedles (FIG. 4).

The microneedle is provided for puncturing the skin.
When a microneedle is used for the purpose of transdermal administration, the microneedle is thin enough to pierce the skin and has a length that does not reach the nerve layer and penetrate the tip corner, the stratum corneum, which is the outermost layer of the skin. 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 is from several tens of μm. It is desirable to be about several hundred μm.
In addition, when using a microneedle for the purpose of collecting body fluid for examination, a needle-like body having a height of at least 350 μm or more is desirable because of the structure of the skin.

Moreover, it is preferable that at least the microneedle is made of a biocompatible resin. Thereby, even if the medical instrument that penetrates the skin and pushes into the body is broken and a part of the microneedle remains in the body, the residue is harmless and gradually decomposed in the body, Furthermore, it is discharged outside the body.
Examples of the biocompatible material include medical silicone resin, polyester, polylactic acid (poly L lactic acid / poly D lactic acid), polyglycolic acid, ascorbic acid, maltose, dextran polyester, polybutylene succinate, polycaprolactone, polymalic acid, poly Examples include amino acids. These polymers can be used alone, blended, or in polymer composition. More preferably, poly L lactic acid, poly D lactic acid, polyglycolic acid and the like alone, a blend, or a polymer composition may be mentioned.

  The arrangement of the microneedles is not particularly limited, and may be, for example, a concentric arrangement, a lattice arrangement, or a close-packed arrangement. Here, a close-packed arrangement is particularly preferable. By using the close-packed arrangement, the accumulation rate of microneedles per area can be improved. Here, the “closest packing arrangement” refers to an arrangement in which the other six microneedles are arranged at an equal distance with respect to one microneedle.

In addition, regarding the arrangement of the microneedles, it is preferable that the microneedles are not arranged at a position corresponding to the outermost edge portion of the pedestal described later.
Thereby, when cutting along the arrangement of the microneedle tips, since the microneedle is not present at a position corresponding to the cutting portion, it is possible to prevent the microneedle from being damaged at the time of cutting. In addition, since the microneedle is not arranged at the position corresponding to the outermost edge of the pedestal in the chip cut along the arrangement of the microneedle chips, the microneedle on the outer edge of the pedestal, which is easily damaged during handling, is a concern. There is no need to do.

  Since the microneedles are not arranged at the outermost edge portion of the microneedle chip base, a pattern in which the microneedles do not exist at a constant period is formed in the microneedle chip assembly. Since this pattern repeats at regular intervals in the microneedle chip assembly, it can be used as an alignment mark or the like used for the formation position or positioning of a sprocket hole used for roll conveyance in a subsequent process.

In addition, with respect to the arrangement of the microneedles, the line connecting the plurality of microneedles located at the outermost part is arranged so as to have a circular shape or a polygonal shape having an intersection angle greater than 90 degrees and smaller than 180 degrees. It is preferable.
Regardless of the shape of the pedestal, which will be described later, by arranging the microneedles as described above, when cutting along the microneedle chip arrangement, breakage during handling (including when puncturing the skin and using it) It is possible to suppress breakage of the microneedles arranged at the outermost end portion (position corresponding to the corner of a line connecting a plurality of microneedles located at the outermost portion). In particular, a circular shape is preferable because a line connecting a plurality of microneedles located at the outermost portion does not form a corner.

  Moreover, about the arrangement | sequence of a microneedle, the microneedle may be arrange | positioned to the position corresponded to the outermost edge part of the base mentioned later. In this case, when a plurality of pedestals are arranged, the microneedle integration rate can be improved in the microneedle chip assembly.

  The pedestal is provided to support the above-described microneedle. The pedestal is not particularly limited as long as it has sufficient mechanical strength to support the microneedles. Moreover, even if it forms from the same material as a microneedle, you may form from a material different from a microneedle. Moreover, it is preferable that it is a low irritation | stimulation material with respect to a biological body. Moreover, it is preferable to have flexibility so that the surface can be uniformly pressed against the curved surface.

  Moreover, it is preferable that the microneedle and the base are made of the same material. By using the same material for the microneedle and the pedestal, both can be integrally formed.

The shape of the pedestal may be polygonal or circular.
When the pedestal shape is circular, there is no corner that is stressed during handling for each microneedle chip, so that the mechanical strength is improved. When the pedestal shape is circular, the plane filling rate is not 100%, and there is a gap between the pedestal and the pedestal. Since this gap is repeated at a constant period in the microneedle chip assembly, it can be used as a sprocket hole used for roll conveyance, an alignment mark used for positioning, or the like in a subsequent process.

  When the pedestal shape is a polygon, the pedestal shape is preferably a combination of graphic shapes that can be plane-filled. Here, “planar filling” refers to an operation of filling a plane with polygons without gaps.

  At this time, among the polygons, all the triangles and trapezoids (including parallelograms and rectangles) can fill the plane with one kind, and thus are suitable as pedestal shapes. In addition, in regular polygons, regular triangles (collecting six at one point), squares (collecting four at one point), regular hexagons (collecting three at one point) are regular polygons that can fill the plane with one kind, It is suitable as a pedestal shape.

In plane filling with two or more types of figures, for example, “one square, two regular octagons”, “one regular triangle, two regular dodecagons”, “two regular triangles, two regular hexagons (alternate) ", 1 regular triangle, 2 squares, 1 regular hexagon (in order 3, 4, 6, 4)", 1 square, 1 regular hexagon, 1 regular dodecagon, 1 "regular triangle "4 pieces, regular hexagon 1 piece", "regular triangle 3 pieces, square 2 pieces (in order 3,3,4,3,4)", "regular triangle 3 pieces, square 2 pieces (in order 3, 3, 3) , 4, 4) ", etc., but the pedestal shape of the present invention is not limited to these combinations.
Further, the Penrose tile may be used in the form of two-sided rhombuses (“rhombus with acute 72 ° and obtuse angle 108 °”, “rhombus with acute 36 ° and obtuse angle 144 °)”.

  Among the polygons described above, a regular hexagonal pedestal is particularly preferable. By making it a regular hexagon, when plane filling is performed, the arrangement of the pedestals becomes the closest packing arrangement (FIG. 3). Further, when the base of the microneedle tip is a regular hexagon, the microneedle assembly has a honeycomb structure, and therefore the mechanical strength of the microneedle assembly itself in a sheet shape / tape shape can be reinforced ( FIG. 1).

FIG. 5 shows an example of the microneedle chip of the present invention.
In FIG.
(A) The pedestal has a circular shape, and the microneedles are arranged concentrically (the line connecting the plurality of microneedles located at the outermost part is circular),
(B) The pedestal has a regular hexagonal shape, and the microneedles are arranged concentrically (the line connecting the plurality of microneedles located at the outermost part is circular),
(C) The pedestal has a regular hexagonal shape, and the arrangement of microneedles is a close-packed arrangement (the line connecting a plurality of microneedles located at the outermost part is a regular hexagonal shape)
(D) The pedestal has a regular hexagonal shape, and the arrangement of microneedles is a close-packed arrangement (the line connecting a plurality of microneedles located at the outermost part is a regular dodecagonal shape).
It is.
When the shape of the pedestal is different from the graphic shape of the line connecting the plurality of microneedles located at the outermost part, at least a part of the position corresponding to the outermost edge of the pedestal is not arranged with the microneedles. For this reason, in the microneedle chip assembly, portions where the microneedles do not exist are formed in a pattern in a constant cycle. Since this pattern repeats at regular intervals in the microneedle chip assembly, it can be used as an alignment mark or the like used for the formation position or positioning of a sprocket hole used for roll conveyance in a subsequent process.

  Further, the microneedle assembly may be appropriately cut and used according to the specification / design of the medical instrument to be used. At this time, cutting may be performed along the arrangement of the microneedle tips or may be performed without being attached to the arrangement of the microneedle tips.

  In particular, when cutting without being stuck to the arrangement of the microneedle tips, it is possible to flexibly cope with the specifications / design of the medical device, and it is possible to manufacture a tip having a size / shape suitable for the administration site.

Hereinafter, the method for producing the microneedle assembly of the present invention will be described.
The microneedle chip assembly manufacturing method of the present invention,
Forming a microneedle tip; and
Arranging the microneedle tips;
It is provided with.

For the step of forming the microneedle tip, a microneedle tip manufacturing method using a known fine processing technique may be used as appropriate.
At this time, as a 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.
Also, a micro-needle chip may be manufactured by producing a prototype by the fine processing technique and performing transfer processing molding using the prototype and a molding material. As the transfer processing molding, a known transfer processing molding method may be used as appropriate. For example, an injection molding method, an extrusion molding method, an imprint method, a casting method, or the like can be suitably used. In particular, when forming a microneedle chip with a single-shaped pedestal, a microneedle chip with a single-shaped pedestal is formed in large quantities on the same replicated plate by making a replicated plate with high mechanical strength. This is preferable because it is possible.

The step of arranging the microneedle tips may be arranged so as to fill a plane as appropriate in accordance with the shape of the pedestal of the microneedle tips.
After the arrangement, it is desirable to fix the pedestals so that the arrangement is not disturbed.

  From the above, the microneedle assembly manufacturing method of the present invention can be carried out.

  Moreover, it is preferable to perform transfer processing molding using the microneedle chip assembly manufactured by the above-described manufacturing method as a prototype. By performing transfer processing molding, it is possible to manufacture a microneedle chip assembly by selecting a material without being stuck with the processing characteristics for molding the microneedle chip. For this reason, for example, biocompatible materials such as medical silicone resin, polyester, polylactic acid (poly L lactic acid / poly D lactic acid), polyglycolic acid, ascorbic acid, maltose, dextran polyester, polybutylene succinate, polycaprolactone, By using polymalic acid, polyamino acid or the like, a microneedle chip assembly applicable to a living body can be formed. If a biocompatible material is used, even if the microneedle is broken and left in the body, there is an effect that it is harmless.

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.
Since a microneedle chip assembly can be produced in a large amount with the same replica plate by making a replica plate with high mechanical strength, the production cost can be reduced and the productivity can be increased.

  In addition, when forming a replica plate in transfer processing molding, a microneedle chip assembly may be used as a prototype, or a microneedle chip assembly may be used as a prototype to form a replica plate as a microneedle chip assembly. May be.

  In particular, since the microneedle chip assembly of the present invention has a sheet shape / tape shape, it is continuously manufactured roll-to-roll, for example, by forming a replica plate into a roll shape in transfer processing molding. I can do it.

  Further, the manufactured microneedle assembly may be appropriately cut and used according to the specification / design of the medical instrument to be used. At this time, cutting may be performed along the arrangement of the microneedle tips or may be performed without being attached to the arrangement of the microneedle tips.

  In particular, when cutting without being stuck to the arrangement of the microneedle tips, it is possible to flexibly cope with the specifications / design of the medical device, and it is possible to manufacture a tip having a size / shape suitable for the administration site.

<Example 1>
Microneedle tip (microneedle array: closest packing array, shape of line connecting a plurality of microneedles located at the outermost part: regular hexagon, number of microneedles: 500, pedestal area: 2.0 cm ² , pedestal shape : Regular hexagonal shape) and a flat mold having a shape in which 25 microneedle chips are arranged in a close-packed arrangement was prepared and heated to 180 ° C.
Next, separately prepared poly L lactic acid (molecular weight 20 kDa) is printed on a flat metal mold and defoamed, and then the poly L lactic acid layer is 0.5 mm with a 170 ° C. hot roll. Flattened.
Next, the flat mold and poly L lactic acid were cooled to 30 ° C., and the poly L lactic acid film formed from the flat mold was peeled off to obtain a microneedle chip assembly made of tape-shaped poly L lactic acid.
Next, the microneedle chip assembly was cut along the array of microneedle chips to obtain a microneedle chip made of poly-L lactic acid.

<Example 2>
Similar to Example 1, a microneedle chip assembly made of tape-shaped poly-L-lactic acid was produced, and the microneedle chip assembly was cut along the array of microneedle chips.
However, the arranged microneedle tips are microneedle tips (microneedle arrangement: closest packing arrangement, shape of line connecting a plurality of microneedles located at the outermost part: circular shape, number of microneedles: 490, pedestal Area: 1.8 cm ² , pedestal shape: circular shape (radius: 0.76 cm)).

<Example 3>
Similar to Example 1, a microneedle chip assembly made of tape-shaped poly-L-lactic acid was produced, and the microneedle chip assembly was cut along the array of microneedle chips.
However, the arrayed microneedle tip is a microneedle tip (microneedle array: closest packing array, shape of line connecting plural outermost microneedles: regular pentagon, number of microneedles: 485, pedestal Area: 1.8 cm ² , pedestal shape: circular shape (radius: 0.76 cm)).

<Example 4>
Similar to Example 1, a microneedle chip assembly made of tape-shaped poly-L-lactic acid was produced, and the microneedle chip assembly was cut along the array of microneedle chips.
However, the arranged microneedle tips are microneedle tips (microneedle arrangement: closest packing arrangement, line shape connecting a plurality of microneedles located at the outermost part: square, number of microneedles: 529, pedestal Area: 2.3 cm ² , pedestal shape: square shape (one side: 1.52 cm)), and the arrangement of the microneedle tips was a lattice arrangement.

<Example 5>
Similar to Example 1, a microneedle chip assembly made of tape-shaped poly-L-lactic acid was produced, and the microneedle chip assembly was cut along the array of microneedle chips.
However, the arranged microneedle tips are microneedle tips (microneedle arrangement: closest packing arrangement, shape of line connecting a plurality of microneedles located at the outermost part: circular shape, number of microneedles: 490, pedestal Area: 1.8 cm ² , pedestal shape: circular shape (radius: 0.76 cm)), and the arrangement of the microneedle tips was a lattice arrangement.

<Evaluation 1>
In the microneedle chip assemblies manufactured in Example 2 and Example 5, the sheet area occupied by one arranged chip was compared.

  From Table 1, the sheet area per the number of arranged chips was reduced by making the arrangement of the microneedle chips the closest packing arrangement. This indicates that the number of microneedle tips arranged per sheet area is higher in the close-packed arrangement. Therefore, when cutting the microneedle tips for each arrangement, more microneedle tips can be obtained from the same area when the closest packing arrangement is used.

<Evaluation 2>
The strength evaluation was performed on the microneedle tip made of poly-L lactic acid produced in Example 1, Example 2, Example 3, and Example 4. For the evaluation, compression test evaluation was performed using Tensilon universal testing machine RTF-2350 manufactured by A & D Co., Ltd.

<Evaluation method>
A silicone rubber sheet 10 (rubber hardness 30) having a thickness of about 1 mm and a polyvinylidene chloride film 9 having a thickness of about 15 μm were adhered and stacked in this order on the test stand, and the microneedle chip 8 was placed on the polyvinylidene chloride film. A 3 kg load was applied at a displacement of 10 mm / min with a Tensilon universal testing machine. A compression test was performed on 10 microneedle tips each having various shapes, and the microneedle breakage after the test was confirmed with an optical microscope, and the number of microneedle tips having no abnormality was counted. Table 2 shows the strength evaluation results of the microneedle tip.

From Table 2, it was confirmed that the shape of the line connecting the plurality of microneedles located at the outermost part is easily broken. At this time, the damaged microneedle was a microneedle located in a square corner.
Further, when the shape of the line connecting the plurality of microneedles located at the outermost part was a circular / polygonal shape, no breakage of the corner was confirmed.

It is a figure which shows an example of the microneedle chip | tip aggregate | assembly of this invention. It is a figure which shows an example of the arrangement | sequence of a microneedle chip | tip in the microneedle chip | tip aggregate | assembly of this invention. It is a figure which shows an example of the arrangement | sequence of a microneedle chip | tip in the microneedle chip | tip aggregate | assembly of this invention. It is sectional drawing of the microneedle chip | tip of this invention. It is a figure which shows an example of the microneedle chip | tip of this invention. It is the schematic which shows the microneedle strength test in an Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Microneedle chip assembly 2 ... Microneedle chip 3 ... Microneedle 4 ... Base 5 ... Load cell side compression plate 6 ... Microneedle chip 7 ... Polyvinylidene chloride film 8 ... Silicone rubber sheet 9 ...... Tester side compression plate

Claims (16)

A microneedle chip assembly used in a medical instrument for puncturing the skin,
A plurality of microneedles that puncture the skin;
A microneedle chip having a regular hexagonal pedestal for supporting the microneedle,
A microneedle chip assembly in which a plurality of the microneedle chips are arranged. A microneedle chip assembly used in a medical instrument for puncturing the skin,
A plurality of microneedles that puncture the skin;
A circular pedestal for supporting the microneedle;
With a microneedle tip with
Arranging a plurality of the microneedle tips
A microneedle chip assembly characterized by the above. The microneedle chip assembly according to claim 1 or 2,
When multiple microneedle tips are arranged, one microneedle tip should be placed in contact with the other six microneedle tips
A microneedle chip assembly characterized by the above. A microneedle chip assembly used in a medical instrument for puncturing the skin,
A plurality of microneedles that puncture the skin;
A pedestal for supporting the microneedle;
With a microneedle tip with
The microneedle tip is a microneedle tip arranged so that a line connecting a plurality of microneedles on the outermost part of the microneedle is circular, and a plurality of the microneedle tips are arranged.
A microneedle chip assembly characterized by the above. A microneedle chip assembly used in a medical instrument for puncturing the skin,
A plurality of microneedles that puncture the skin;
A pedestal for supporting the microneedle;
With a microneedle tip with
The microneedle tip is a microneedle tip arranged so that an intersection angle of lines connecting a plurality of microneedles located at the outermost portion is a polygon larger than 90 degrees and smaller than 180 degrees, and Arranging multiple needle tips
A microneedle chip assembly characterized by the above. The microneedle chip assembly according to any one of claims 1 to 5,
The microneedle tip is a microneedle tip that is made of the same material as the microneedle and pedestal.
A microneedle chip assembly characterized by the above. The microneedle chip assembly according to any one of claims 1 to 6,
Regarding the microneedle chip, at least the microneedle is made of a biocompatible resin.
A microneedle chip assembly characterized by the above. The microneedle chip assembly according to any one of claims 1 to 7,
The microneedle tip is a microneedle tip in which the microneedle is not disposed at a position corresponding to the outermost edge of the pedestal.
A microneedle chip assembly characterized by the above. A microneedle chip obtained by cutting the microneedle chip assembly according to claim 1. A medical instrument using the microneedle chip assembly according to any one of claims 1 to 9. A method for producing a microneedle chip assembly for use in a medical instrument for puncturing the skin,
Forming a microneedle tip; and
And arranging the microneedle tips, and
The microneedle tip comprises a microneedle tip comprising a plurality of microneedles that puncture the skin and a regular hexagonal pedestal that supports the microneedles, and a plurality of the microneedle tips are arranged. Is an aggregate
A method for producing a microneedle chip assembly. A method for producing a microneedle chip assembly for use in a medical instrument for puncturing the skin,
Forming a microneedle tip; and
And arranging the microneedle tips, and
The microneedle chip assembly includes a microneedle chip having a plurality of microneedles for puncturing the skin and a circular pedestal for supporting the microneedle, and a microneedle chip assembly in which a plurality of the microneedle chips are arranged Body
A method for producing a microneedle chip assembly. A method for producing a microneedle chip assembly for use in a medical instrument for puncturing the skin,
Forming a microneedle tip; and
And arranging the microneedle tips, and
The microneedle tip includes a microneedle tip provided with a plurality of microneedles that puncture the skin and a pedestal that supports the microneedle, and the microneedle tip includes a plurality of microneedles located on the outermost side. A microneedle chip arranged so that a line connecting the microneedles is circular, and a microneedle chip assembly in which a plurality of the microneedle chips are arranged
A method for producing a microneedle chip assembly. A method for producing a microneedle chip assembly for use in a medical instrument for puncturing the skin,
Forming a microneedle tip; and
And arranging the microneedle tips, and
The microneedle tip comprises a microneedle tip provided with a plurality of microneedles for puncturing the skin and a pedestal for supporting the microneedle, and the microneedle tip is a plurality of microneedles located at the outermost part. A microneedle tip arranged so that the intersection angle of lines connecting the two is a polygon larger than 90 degrees and smaller than 180 degrees, and a microneedle chip assembly in which a plurality of the microneedle chips are arranged
A method for producing a microneedle chip assembly. A method for producing a microneedle chip assembly, wherein the microneedle chip assembly according to any one of claims 10 to 14 is used as a prototype, and transfer processing is performed. A microneedle chip manufacturing method comprising cutting a microneedle assembly manufactured by the microneedle chip assembly manufacturing method according to claim 15.