JP6405916B2 - Injection device - Google Patents

Description

  The present invention relates to providing a microneedle device injection device for transdermal administration of a vaccine or the like.

  As a method by which a delivery product can be easily administered without causing pain to the human body, there is a transdermal absorption method in which a liquid such as a drug is permeated through the skin and the delivery product is administered into the body. This is a method of puncturing the skin using fine microneedles on the order of μm, and administering a body injection liquid into the skin, and is called a microneedle. (See Patent Document 1).

  The shape of the fine microneedles used at this time must have a sufficient fineness and tip angle for piercing the skin, and a sufficient length for allowing the infusion fluid to penetrate into the skin. Is done. For this reason, the diameter of the needle-shaped body is several tens to several hundreds of micrometers, the length penetrates the stratum corneum, which is the outermost layer of the skin, and does not reach the nerve layer, specifically, several hundreds of micrometers to several It is desirable to be about mm.

  In addition, the material constituting the microneedle is desirably a material that does not adversely affect the human body even if the microneedle remains in the body, and a biocompatible material such as polylactic acid is proposed as such a material. (See Patent Document 2).

  Microneedles include solid types and hollow types. Solid molds are classified into coating molds and dissolution molds. For coating molds, for example, a coating method by dipping has been proposed (see Patent Document 3).

  In the dissolution mold, for example, a method of dropping a biocompatible water-soluble material solution onto a mold and drying it has been proposed (see Patent Document 4).

  The hollow microneedle is a small-sized injection needle for injecting an in-vivo injection liquid represented by a conventional needle and syringe into an in-vivo injection liquid typified by a vaccine or the like.

  The administration method using hollow needles can use the liquid dosage form as in the case of the current injection, can increase the infusion liquid dosage, and can precisely control the infusion liquid dosage. There is an advantage such as.

  Skill is required to insert the injection needle into the subcutaneous tissue of a living body without causing as much pain or bleeding as possible. Moreover, the injection needle has a high possibility of causing various infectious diseases by being reused. In addition, it puts the workers at the waste disposal facility at risk and is highly likely to cause various infections in people who are injured by the discarded needles.

  Therefore, in recent years, a multi-needle device in which a plurality of micron-like needle-like bodies are formed on a plate-like support has been used in place of a conventional injection needle.

  It is formed on the plate-like support by creating the length of a plurality of micron-order needle-like members formed on the plate-like support within the thickness range of the intradermal tissue. Even if a plurality of micron-order needle-like bodies are pressed against the surface of the living body skin, the plurality of needle-like bodies can be punctured into the skin tissue of the living body without causing pain or bleeding.

  Intradermal tissues are rich in antigen-presenting cells, and when in vivo fluids that act on these antigen-presenting cells are injected into the body's intradermal tissues, the amount of such intracorporeal fluids used is conventionally reduced. There are things that can be reduced.

  When such a multi-needle device is used, a plurality of needle-like bodies of the multi-needle device are punctured into a part of the skin of a living body to be injected with the in-body injecting liquid, and the in-body injecting liquid becomes the skin of the living body It is injected into the internal tissue.

  For example, a pad base for transdermal administration has been proposed in which a large number of fine needles are erected on the side of the skin of a base material applied to the skin (Patent Document 5). The tip of various microneedles is cut horizontally, and a bottomed hole is formed to hold in-vivo infused liquid from this horizontal cut surface to the vicinity of various base ends of the microneedles.

  A part responsible for transdermal administration of the in-vivo infusion liquid in such a pad base, which is referred to as a transdermal dosage pad, is produced in large quantities at low cost by a transfer molding method such as injection molding, imprinting or casting. It is therefore disposable, reducing the risk of infection from reuse. In addition, many microneedles are short, their tips are cut horizontally, and formed on the pad base at a high density, so there is little possibility of hurting people when discarded.

  However, this conventional transdermal dosing pad base is designed to take a relatively long administration time, and injects a precise desired amount of in-vivo fluid into the intradermal tissue in a short time. Not suitable for.

  In addition, a structure designed to be able to inject into a living body's intradermal tissue in a short time using a multi-needle device to inject a predetermined amount is disclosed (Patent Document 6).

  In this case, the multi-needle device is attached to the other end of the leaf spring that is fixed to the back surface of the substrate and extends along the back surface of the substrate. That is, the multi-needle device is held in a state where it is elastically bent to a position away from the back surface of the base end. At one end of the leaf spring, a medicine cartridge storing a body injection liquid as a predetermined amount of body injection liquid is disposed.

  After bringing the surface of the substrate into contact with the region where the in-vivo injection liquid is to be injected on the surface of the living body skin, the multi-needle-like body is pierced into the region by the elastic force of the leaf spring. At the same time, the in-body injection liquid in the drug cartridge is supplied to the multi-needle device, and the in-body injection liquid is injected into the intradermal tissue in the region of the living body skin.

Patent No. 4276691 Patent No. 5267910 Patent No. 5049268 JP2014-4077 JP-A-2005-21677 Special table 2013-500773

  However, this hollow microneedle array has a complicated structure and requires a special dedicated drug cartridge. Furthermore, it is difficult to change the amount of in-vivo infusion liquid stored in advance in the in-body infusion liquid cartridge. However, the thickness of the skin usually differs depending on the animal species, race, age, site, etc., and even when such an auxiliary device is used, depending on the thickness of the skin when administered with a hollow needle-shaped body. In some cases, the injection depth is not appropriate, and the infusion fluid leaks into the skin surface or subcutaneous tissue. Therefore, by selecting the puncture injection conditions according to the thickness of the skin and administering the infusion fluid to an appropriate depth within the skin, the infusion fluid does not leak into the skin surface or subcutaneous tissue, Although a certain amount of in-vivo infusion fluid can be accurately administered, such a method has not been proposed as an appropriate method when using a microneedle.

  This invention is made | formed in view of such a subject, Comprising: It is providing the injection device which can inject | pour in-body injection | pouring liquid into the place of the appropriate depth with respect to skin.

  An injection device according to a first invention of the present application includes a microneedle device including a protrusion on one surface of a substrate, the microneedle device including the substrate and a microneedle penetrating the protrusion, and a support. An injection mechanism characterized by having an adjustment mechanism capable of adjusting the protrusion height of the protrusion from the body surface to a predetermined height, for example, 0.1 mm to 3.0 mm, or 3 to 10 for the dial. It is an instrument.

  An injection device according to a second invention of the present application is an injection device in which the adjustment mechanism is a screw mechanism.

  An injection device according to a third invention of the present application is an injection device in which the support is composed of a syringe capable of discharging an internal liquid and a cylindrical body formed so as to surround the microneedle device.

  An injection device according to a fourth invention of the present application is an injection device further comprising a holder for connecting the syringe and the microneedle and capable of discharging the liquid discharged from the syringe from the protrusion of the microneedle device. is there.

  An injection device according to a fifth invention of the present application is the injection device in which the cylindrical body is connected to the holder by a screw mechanism.

  The injection device of the present invention enables the protrusion height of the protrusion to be adjusted at a level of 3 or more and 10 or less, so that the protrusion of the protrusion becomes an injection depth with respect to the skin even if the user has no special skill. The depth can be adjusted.

  Moreover, in 2nd invention, the protrusion height of a projection part can be easily adjusted by employ | adopting a screw mechanism as an adjustment mechanism.

  In the third invention, it becomes easy to change the amount of the in-vivo infusion liquid stored in advance in the in-body infusion liquid cartridge.

  In the fourth invention, a special syringe can be used as it is without requiring a special dedicated in-vivo infusion cartridge.

In the fifth invention, the protrusion height of the protrusion can be freely set regardless of the amount of in-body injection liquid.

It is a schematic sectional drawing which shows an example of the cross section of one Example of the injection device of this invention. It is a disassembled schematic perspective view which shows the relationship between the holder of one Example of the injection device of FIG. 1, a screw mechanism, and a cylindrical body. It is sectional drawing which shows the relationship between the holder and microneedle device of one Example of the injection device of FIG. It is a disassembled schematic perspective view which shows the relationship between the holder and microneedle device of one Example of the injection device of FIG. It is a perspective view which shows the screw mechanism of one Example of the injection device of FIG.

  Hereinafter, an embodiment of the injection device and the method of using the injection device in the present embodiment will be described with reference to FIGS. 1 and 2. Moreover, as a matter of course, the injection device of the present invention is not limited to the following embodiment, and includes other manufacturing methods that can be inferred from known materials in each step.

  An injection device according to an embodiment of the present invention will be described below as an injection device including a microneedle device 10, a syringe 20, a holder 30, a cylindrical body 40, and a screw mechanism 50.

  Further, the injection device includes a microneedle device 10 provided with a microneedle provided on one surface on which a plurality of protrusions are formed and on another surface located on the opposite side of the one surface from the protrusions. It is designed to be injected into the skin. In this embodiment, the microneedle device 10 has a disk shape having a predetermined diameter.

  Into the internal space of the outer cylinder 20a of the conventional syringe 20 through the through-hole of the injection needle mounting projection 20b, a desired amount of the body injection liquid 20c (for example, the body to be injected into the intradermal layer of a living body including a human being) Injection liquid or vaccine) is inhaled and retained. The conventional syringe 20 is easily available at a low cost. The outer cylinder 20a of the conventional syringe 20 is substantially transparent so that the amount of the in-vivo infused liquid 20c held inside can be visually recognized from the outside, and a scale that clearly indicates the amount is attached to the outer surface of the outer cylinder 20a. Therefore, by using the conventional syringe 20, the amount of the in-body injection liquid 20c retained in the inner space of the outer tube 20a of the conventional syringe 20 can be easily and precisely changed.

  As shown in FIG. 2, the injection needle attachment protrusion 20b of the outer cylinder 20a of the syringe 20 holding the desired amount of in-vivo injection liquid 20c is formed in the injection needle attachment protrusion connection hole 41a of the fixed tubular body 40 of the injection device. In addition, it is detachably connected in a liquid-tight manner. Thereafter, the plunger 20d of the syringe 20 is slightly pushed, and a small amount of in-body injection liquid 70 in the outer cylinder 20a of the syringe 20 passes through the through-hole of the injection needle mounting protrusion 20b of the outer cylinder 20a, and the syringe 30 The area where the through hole 31b of the support portion 31 and the microneedle device 10 are liquid-tight by the structure sandwiching the O-ring 33, and the microneedle which is a plurality of through-holes of the microneedle device 10 Meet.

Next, as shown in FIG. 3, the skin contact region 42 on the one end side of the cylindrical body 40 from which the protruding portion of the microneedle device 10 protrudes on the outer surface of the holder 30 of the injection device includes a person. The skin tissue of the living body is pressed against the surface of the region (intradermal injection region) into which the infusion liquid 70 is injected, and a plurality of microneedles of the microneedle device 10 is inserted into the intradermal injection region. During this time, in the intradermal injection region of the skin tissue, the portion surrounded by the skin contact region on the outer surface of the holder 30 of the injection device is relieved of the pressing force by the skin contact region, and a plurality of micros of the microneedle device 10 The needle is inserted deeper.

  Next, as shown in FIG. 1 (B), when the plunger 20d of the syringe 20 is further pushed by a predetermined distance, the remaining desired amount of the in-vivo infusion fluid 70 in the outer cylinder 20a of the syringe 20 becomes the outer cylinder 20a. The through hole of the injection needle mounting protrusion 20b, the opening 31b of the syringe support 31 and the area where the microneedle device 10 is liquid-tight by the structure sandwiching the O-ring 33, and the micro The microneedles that are a plurality of through holes of the needle device 10 are injected into the portion surrounded by the skin contact region on the outer surface of the holder 30 of the injection device in the intradermal injection region of the skin tissue. In the portion, since the pressing force by the skin contact region on the outer surface of the holder 30 of the injection device is relaxed, the in-body injection liquid 70 from the through holes of the plurality of microneedles 10 is injected into the skin tissue. It is easily injected into the intradermal injection area without leaking out of the surface of the area.

  In addition, the outer cylinder 20a of the conventional syringe 20 is substantially transparent so that the amount of the in-vivo injecting liquid 70 held inside can be visually recognized from the outside, and the scale clearly shows the amount on the outer surface of the outer cylinder 20a. Is attached. Therefore, when the injection device of this embodiment is used in combination with the conventional syringe 20, a precise desired amount of the desired infusion liquid 70 can be injected into the intradermal tissue in a short time. Hereinafter, each member will be described in detail.

<Microneedle device 10>
The microneedle device 10 has a plurality of hollow microneedles having a protrusion 12 at the tip and a through hole 11 through which the in-vivo injection liquid can be discharged from the tip of the protrusion. In producing the microneedle device 10 having the hollow microneedle, a non-through hole is first formed in the substrate. Here, various known techniques such as wet etching, dry etching, laser processing, and machining can be used for the step of forming the non-through hole. Next, an etching mask is formed on the substrate on the surface opposite to the surface where the non-through holes are formed. Here, the etching mask includes an arc shape in a part or all of the outer shape of the bottom surface portion, and has a shape in which the thickness continuously increases from the peripheral edge portion to the central portion.

  Further, in the step of forming the etching mask, the etching mask and the previously formed non-through hole are aligned. Next, a structure having needle-like through holes 11 is formed on the substrate by performing an etching process using the etching mask. At this time, in the microneedle device 10, the previously formed non-through hole may be passed through or may be left unpenetrated. Next, by forming an upper slope on the structure, a microneedle device 10 having a plurality of microneedles having through holes 11 is obtained.

  The substrate material may be any material that can be processed by wet etching, dry etching, and the like, and examples thereof include metals such as titanium, aluminum, and stainless steel, synthetic resins such as polycarbonate, polystyrene, acrylic resin, and fluororesin, and silicon. .

  In the microneedle device 10, a structure having at least a plurality of microneedles is formed of a biocompatible material, and preferably the entire microneedle device 10 including the plurality of microneedles is integrally formed of a biocompatible material. Has been. As biocompatible materials, for example, metal materials such as stainless steel, titanium and manganese, medical silicone, resin materials such as polyglycolic acid and polycarbonate, and inorganic materials such as silicon are known.

When the entire microneedle device 10 including a plurality of microneedles is integrally formed with a biocompatible material, conventional molding techniques such as injection molding, extrusion molding, imprinting, hot embossing, and casting are employed. I can do it. For various types of microneedles, the conventional surface of the microneedle device 10 and the various outer surfaces of the plurality of microneedles are formed by a conventional micro-drilling processing technique such as microdrilling or laser processing. Through holes are formed along the center line of various microneedles. The through hole may be concentric with the center line of various microneedles or may not be concentric.

  The various overall shapes of the plurality of microneedles can be, for example, a polygonal pyramid including a cone, a triangular pyramid, and a quadrangular pyramid, a cylinder, or a polygonal column, and the height of the microneedle from the one surface is that of a living body including a human being. It is set within the thickness range of the intradermal tissue.

<Syringe 20>
The syringe provided with the outer cylinder 20a and the plunger 20d can apply the instrument generally used. As shown in FIG. 1A, the outer cylinder 10 has a substantially cylindrical shape as a whole, and a circulation port for sucking or discharging liquid into the outer cylinder 20a is formed on the distal end side. As long as the insertion opening into which the plunger 20d can be inserted is formed on the proximal end side.

<Holder 30>
The holder 30 includes a syringe support part 31, a microneedle device support part 32, and an O-ring 33. The syringe support 31 includes an opening 31a having a female screw, an opening 31b for connecting a syringe, and a male screw protrusion 31c.

  The opening 31b to which the syringe is connected has a tapered shape conforming to the luer lock standard because the injection needle mounting protrusion 20b of the outer cylinder 20a of the conventional syringe 20 is connected in a liquid-tight detachable state. preferable.

  The male screw protrusion 31c is screwed with the female screw 32a of the microneedle device support 32, and the microneedle device 10 is detachably fixed with the O-ring 33 interposed therebetween, thereby forming a liquid-tight structure. The liquid-tight structure is provided by an annular liquid-tight member, for example, an O-ring, sandwiched between the holder 30 and the microneedle device 10. In this embodiment, the portion in contact with the infusion liquid 70 needs to be covered with or formed of a substance that does not alter the infusion liquid 70 or a substance that is not altered by the infusion liquid 70.

<Tubular body 40>
The cylindrical body 40 includes a cylindrical body lid 41 and a cylindrical body main body 42. Moreover, the injection device of this application is assembled in the order shown in FIG. That is, the screw body 50 and the cylindrical body lid 41 are assembled in this order with respect to the cylindrical body main body 42.

  The cylindrical body lid 41 includes an opening 41 a slightly larger than the outer diameter of the syringe 20 and an opening 41 b having an inner diameter slightly larger than the outer diameter of the convex portion 50 b for supporting the screw mechanism 50.

  The shape of the cylindrical body 40 is not particularly limited, but a cylindrical shape is desirable because it is used for the hand. More preferably, an elliptical column shape is desirable so that it can be easily grasped. Also, a grip shape may be used so that the hand does not slip.

Although the cylindrical body 40 is not specifically limited regarding a material, For example, polylactic acid, polyvinyl chloride, polyethylene, polypropylene, cyclic polyolefin, polystyrene, poly- (4-methylpentene-1), polycarbonate, an acrylic resin, acrylonitrile butadiene -Resins such as styrene copolymers, polyesters such as polyethylene terephthalate, polyethylene naphthalate, butadiene-styrene copolymers, polyamides (for example, nylon 6, nylon 6,6, nylon 6,10, nylon 12) may be used. . The tubular body 40 is preferably transparent or translucent in order to ensure the visibility of the internal syringe.

<Screw mechanism 50>
FIG. 5 is a perspective view of a screw mechanism 50 related to the present invention. The screw mechanism 50 is provided on the microneedle holder supporting cylindrical body, and has a fixing portion in which a through hole is formed, a screw groove member in which a screw hole is formed and fixed in the through hole, and a screw hole of the screw groove member. And a holder support cylindrical body provided with the inserted screw shaft 50a. An adjustment dial is provided at the upper end of the screw shaft.

  The opening 31a having the female screw of the holder is screwed with the male screw portion 50a of the screw mechanism for adjusting the microneedle puncture depth, and the needle height of the microneedle device 10 to which the syringe 20 and the holder 30 are coupled is determined by the screw mechanism. 50 is adjusted.

  In the present invention, a convex portion is formed at a predetermined level in the groove portion where the male screw and the female screw are screwed together, and the protruding height of the protruding portion can be adjusted at a level of 3 to 10. . That is, the instrument user can adjust the puncture depth at a predetermined level, and adjustment is easy at the time of use.

  On the other hand, if the protrusion height can be freely adjusted between users, it is necessary to adjust the height with a scale or the like at the time of use. Therefore, it is possible to set the needle height freely, but it takes time to set.

  In the present invention, it is further preferable that the height of the protrusion can be adjusted to a level of 4 or more and 7 or less.

  The main body is formed of a resin material in order to reduce the weight of the entire instrument and reduce manufacturing costs. The adjustment dial has an adjustment scale. For this reason, the rotation angle of the adjustment dial can be easily determined from the adjustment scale. Therefore, the protruding height of the microneedle can be easily determined from the appearance by the position of the adjustment scale. The adjustment dial is preferably an index type.

  Examples of index type adjustment dials include the following.

[Example 1 (displays the needle height (projection height of the protrusion from the support surface))]
First level: 0.2 mm
Second level: 0.4mm
Third level: 0.6mm
4th level: 0.8mm
5th level: 1.0 mm
6th level: 1.2mm
7th level: 1.4mm
[Example 2 (Displaying age appropriate for needle height)]
1st level: Target age 1-3 years 2nd level: Target age 4-6 years 3rd level: Target age 7-9 years 4th level: Target age 10-12 years 5th level: Target age 13-18 years Sixth level: Target age 19-59 years Seventh level: Target age 60 years and over [Example 3 (displays target (age / sex) suitable for needle height)]
1st level: Women 7 to 20 years 2nd level: Women 21 to 59 years 3rd level: Women 60 years and older 4th level: Men 7 to 20 years 5th level: Men 21 to 59 years 6th level: 60 men Over age [Example 4 (display the puncture site)]
1st level: face 2nd level: arms 3rd level: back of hand 4th level: feet The above are examples 1 to 4.

  In the injection device of the present invention, it is preferable that the protrusion height of the protrusion of the microneedle device from the support surface is adjusted within a range of 0.1 mm to 3.0 mm.

  In the injection device of the present invention, it is preferable that the protrusion height of the protrusion of the microneedle device from the support surface is adjusted within a range of 0.01 mm to 0.8 mm per dial. . In other words, in the injection device of the present invention, the protrusion height of the protrusion of the microneedle device from the support surface changes within a range of 0.01 mm or more and 0.8 mm or less when the dial is turned. Is preferred.

  As described above, the puncture depth of the microneedle can be adjusted according to the state of the limb to be punctured, and at the site of use, it is possible to administer the intracorporeal infusion fluid transcutaneously without pain by a simple pressing operation. The applicability in clinical practice is extremely large. In addition to medical treatment, it can be used in various fields that require fine microneedles. For example, as a method for producing fine microneedles used for MEMS devices, optical members, drug discovery, cosmetics, cosmetic applications, etc. Useful.

DESCRIPTION OF SYMBOLS 10 Microneedle device 11 Through-hole 12 Protrusion part 20 Syringe 20a Outer cylinder 20b Injection needle attachment protrusion 20d Plunger 30 Holder 31 Syringe support part 31a Opening part 31b Opening part 31c Male screw protrusion part 32 Microneedle device support part 32a Male screw 33 O-ring 40 Tubular body 41 Tubular body lid 41a Opening 42 Tubular body body 50 Screw mechanism 50b Convex part 70 Intrabody injection liquid

Claims (5)

Providing a protrusion on one surface of the substrate, a microneedle device having a microneedle penetrating the substrate and the protrusion, and a support,
Wherein the protruding height of the protrusions from the support surface have a adjustable adjustment mechanism at a predetermined height, and,
The adjusting mechanism is a screw mechanism;
The support comprises a syringe capable of discharging an internal liquid and a cylindrical body formed so as to surround the microneedle device,
A holder capable of connecting the syringe and the microneedle and discharging the liquid discharged from the syringe from the microneedle device protrusion;
The cylindrical body is connected to the holder by a screw mechanism,
The adjustment mechanism is capable of adjusting the protrusion height of the protrusion from the surface of the support at a level of 3 to 10, and the adjustment mechanism includes an index type adjustment dial. Instruments. The injection device according to claim 1, wherein the index type adjustment dial displays the height of the protruding portion from the support surface. The infusion device according to claim 1, wherein the index type adjustment dial displays an age suitable for use. The infusion device according to claim 1, wherein the index type adjustment dial displays an age and sex suitable for use. The injection device according to claim 1, wherein the index type adjustment dial displays a puncture site suitable for use.

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