JP2005087521A - Liquid medicine injector - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liquid medicine injector puncturing a needle into the skin while reducing a pain, preventing the needle from coming off from the skin, and percutaneously injecting a sufficient amount of the liquid medicine into the skin. <P>SOLUTION: This liquid medicine injector 1 is provided with a container 11, a retainer body 12 for retaining the container 11, a plurality of hollow needles 20 communicated with the container 11, penetrating through the retainer body 12 and projecting outward from the retainer body 12, a pushing element 13 providing a driving force for percutaneously injecting the liquid medicine in the container 11 into the skin via the needle 20, and an adhesive layer 30 formed on the end face 124 of the retainer body 12 being contactable with the skin and containing an adhesive. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a chemical solution injection device, and more particularly, to a chemical solution injection device for transdermally injecting a chemical solution from the surface of a human or animal skin through a needle.

  In recent years, production of high molecular weight pharmaceuticals represented by insulin, growth hormone, interferon, calcitonin and the like has increased due to advances in biotechnology. Since these are protein preparations, many of them are decomposed in the gastrointestinal tract when they are taken like conventional pharmaceuticals. Therefore, it is necessary to avoid degradation in the gastrointestinal tract in order to obtain an effective amount of a high molecular weight pharmaceutical product. For this reason, when administering a high molecular weight pharmaceutical, it is necessary to rely on subcutaneous injection or intramuscular injection which is parenteral administration. However, the patient's fear of injection is persistent, and there is a strong demand for means for reducing pain caused by needle puncture at the time of injection. Especially for those who need to repeatedly administer insulin every day, such as diabetic patients, the pain caused by needle puncture at the time of injection is a serious problem.

  The skin generally consists of a stratum corneum consisting of a dead epidermal cell layer, a live epidermal cell layer, a dermis layer, and a subcutaneous adipose tissue layer, and this skin is in contact with the muscle layer via the fascia. The most commonly used injection is subcutaneous injection, and this injection method involves administering a drug solution into the subcutaneous adipose tissue through the stratum corneum, the living epidermal cell layer, and the dermis layer. However, since the dermis layer and subcutaneous adipose tissue layer have abundant free nerve endings and blood vessels that accept pain stimuli, the needle tip damages the nerves and damages the blood vessels. It stimulates production and causes pain. The simplest way to reduce pain from needle puncture is to minimize damage to nerves and blood vessels. Specifically, it is effective to make the needle thinner and shorter. Insulin self-injection needles have become thinner and shorter over time, and recently, needles with an outer diameter of 0.25 mm (31 G needle) and a length of 5 mm have appeared. However, patient satisfaction has not yet been fully achieved with respect to puncture pain.

  If the needle is made thinner in this way, the puncture pain is reduced. However, if the needle is made thinner, the waist of the needle body becomes weak, so that the needle is easily bent and difficult to stab, and the resistance of the drug solution flowing through the needle increases, making it difficult to push out the drug solution. For this reason, a uniform needle thinner than the 31G needle has not been realized for insulin.

  In order to solve this problem, in recent years, needles have been proposed in which the outer diameter is thin at the tip and thicker from the tip to the base, and the inner diameter is changed accordingly (see Patent Documents 1 and 2). This simultaneously solves the problems of the weakness of the thin needle and the increase in flow resistance. However, as shown in Patent Document 2, the proposed needle is mainly a single needle having a total length of 5 mm or more, and is intended for subcutaneous injection. That is, Patent Documents 1 and 2 do not present a technique for administering a drug solution into the skin reliably and easily while reducing puncture pain.

  On the other hand, if the needle length is shortened, a new problem arises. Unlike the subcutaneous adipose tissue layer, the epidermis and dermis layer of the skin are dense and hard. For this reason, when a chemical solution is administered to the epidermis or dermis layer, a large amount cannot be administered with one needle. In general, in the case of intradermal administration between the epidermis and the dermis layer of the skin or into the dermis layer, 0.1 ml is injected for tuberculin reaction test, and 0.02 ml for drug hypersensitivity tests such as allergen test and antibiotics. Is done. However, when 0.1 ml or more of drug solution is injected into the skin, the skin swells up due to the limitation of the drug solution storage capacity based on the narrow cell space and the absorption of the drug solution into the living body through blood vessels Eventually, the drug solution leaks from the needle piercing in the skin. Thus, the current intradermal administration has a limitation on the dose of the drug solution. In addition, in order to position the needle tip in the skin, there are generally technical difficulties such as having to pierce a long needle substantially parallel to the skin.

  In order to solve this problem, recently, a transdermal system for administering a drug by applying a plurality of hollow needles with a maximum length of 1 mm (especially 1 to 500 μm) vertically to the skin surface and applying an electric field has been proposed. (See Patent Document 3). However, the skin has elasticity and, as described above, the cells of the epidermis and dermis tend to be dented without being pierced to a certain distance even if the needle is pressed because the cells are dense and hard. For this reason, the plurality of needles in the system described in the above document are expected to be less likely to pierce the skin because of the short length and the point of contact with the skin is not a point. Moreover, since the needle is short, it is easy to come off even if it is stabbed. That is, there is a risk that many of the administered drug solution may leak without entering the living body. In addition, since the plurality of needles of the above system are manufactured integrally by a micro region processing method such as photolithography, there is a problem that it is technically difficult to manufacture.

In addition, there has been proposed an injection device provided with means for creating a vacuum in order to fix the device to the skin during the injection of a chemical solution (see Patent Document 4). However, this injection device is configured such that the action of injecting the chemical solution and the effect of fixing the device to the skin are exerted by the action of the user pressing the plunger mechanism. It is difficult to reliably maintain the sticking to. For this reason, if even one of the plurality of needles is detached from the skin, there is a risk that the chemical solution leaks from the detached needle having a low flow resistance.
JP 2002-159576 A JP 2002-291844 A Japanese National Patent Publication No. 10-510175 Japanese National Patent Publication No. 8-508901

  The present invention has been made to solve the above-described problems, and an object of the present invention is to puncture a needle into the skin while reducing pain, and to prevent the needle from coming off the skin, and a sufficient amount. It is an object of the present invention to provide a drug solution injection device capable of transdermally injecting a drug solution into the skin.

  The object of the present invention is achieved by the following means.

  (1) a container capable of storing a chemical solution, a holding body for holding the container, and a plurality of hollow needles communicating with the inside of the container and penetrating through the holding body and projecting outward from the holding body , A drug solution driving means for providing a driving force for injecting the drug solution in the container percutaneously into the skin through the needle, and an adhesive formed on the end surface of the holder that can contact the skin And a pressure-sensitive adhesive layer.

(2) A container having a sealing member made of an elastic material for sealing a distal end opening to which a driving force for supplying a driving force for transdermally injecting a drug into the skin can be attached. A holding body for holding the container and a cutting edge for penetrating the sealing member so as to be able to communicate with the inside of the container are formed on the proximal end side, and penetrates the holding body to the outside from the holding body. A plurality of hollow needles projecting, and an adhesive layer made of an adhesive formed on an end surface of the holder that can contact the skin,
A chemical injection device characterized by comprising:

  (3) The outer diameter of the distal end of the needle is 0.1 mm or more and 0.25 mm or less, and the outer diameter of the proximal end of the needle is larger than the outer diameter of the distal end (1) Or the chemical injection device as described in (2).

  (4) The liquid injection device according to (3), wherein the needle outer diameter has a portion where the outer diameter gradually increases from the distal end toward the proximal end.

  (5) The needle includes a base from a base end to a position corresponding to an end surface of the holding body, and a puncturing portion that protrudes from the end surface of the holding body and is a portion that can be punctured into a living body. The chemical liquid injector according to any one of (1) to (4) above, wherein the total length of the liquid is 1 mm or more and 2.5 mm or less.

  (6) The said chemical | medical solution injection apparatus as described in said (1) characterized by the said container having a filling port for filling the chemical | medical solution in the said container.

  (7) The container is filled with a chemical solution in advance, and the chemical solution is sealed by the sealing member and a gasket that is inserted into the container and movable by the chemical solution driving means. The chemical injection device according to (2).

  (8) The chemical liquid drive means is connected to a gasket inserted into the container and can be pushed by a user, a leaf spring for pressing the chemical liquid in the container, and a coil for pressing the gasket The above, characterized in that it has any one of a spring, a mechanism using a balloon made of an elastic material, an electric pump, a mechanism using iontophoresis drive, and a mechanism using volume expansion of a superabsorbent substance ( The chemical liquid injector according to any one of 1) to (7).

  (9) The chemical injection device according to any one of (1) to (8), wherein the adhesive layer is formed on an outer peripheral portion of an end surface of the holding body.

  (10) The chemical solution injection according to any one of (1) to (8), wherein the adhesive layer is formed in a region near the protruding portion of the needle on the end surface of the holding body. apparatus.

  According to the chemical injection device of the present invention, by using a plurality of needles, it is possible to puncture the skin while reducing the pain and reducing pain, and it is possible to prevent the needle from coming off the skin. Therefore, a sufficient amount of a drug solution such as a polymer drug that is difficult to administer orally, for example, can be reliably and easily injected into the skin percutaneously.

  Embodiments of the present invention will be described below with reference to the drawings.

  1A and 1B are diagrams showing a chemical liquid injector according to a first embodiment of the present invention, in which FIG. 1A is a schematic cross-sectional view, and FIG. 1B is a bottom view with a cap removed. FIG. 2 is a schematic enlarged view of the needle shown in FIG.

  As shown in FIG. 1, the chemical liquid injector 1 according to this embodiment includes a main body 10 and a needle 20.

  The main body 10 has a container 11 that can store a chemical solution, a holding body 12 for holding the container 11, and a driving force for transdermally injecting the chemical solution in the container 11 into the skin through the needle 20. And a pusher 13 as a chemical liquid drive means to be provided.

  In this specification, intradermal refers to the dermis layer, and includes the site between the epidermal cell layer and the dermis layer of the skin. In addition, although the chemical | medical solution injection device 1 of this embodiment is intended for intradermal administration of a chemical | medical solution, the apparatus which may inject | pour a chemical | medical solution into other site | parts, such as subcutaneously, as a result is also included.

  The container 11 has a substantially cylindrical shape, and has an internal space 111 into which the pusher 13 is inserted so as to be able to reciprocate in the axial direction of the container 11. An opening 112 for inserting the pusher 13 into the internal space 111 is formed on the side of the container 11 opposite to the holding body 12 (upper side in the figure).

  Further, the container 11 has a filling port 113 for filling the internal space 111 of the container 11 with a chemical solution. A valve 42 that can open and close the flow path is attached to the filling port 113 via a tube 41. A chemical liquid supply device such as a syringe (not shown) for supplying the chemical liquid can be connected to the valve 42.

  On the side near the tip of the holding body 12, a wing 122 that can contact the skin is provided. By providing the wing part 122, the chemical liquid injector 1 can be stably supported on the skin. However, in the present embodiment, the wing portion can be omitted. Although the wing | blade part 122 is exhibiting the elliptical plate shape as FIG. 1 (B) shows, if it is a substantially flat plate shape, it can take arbitrary shapes. Moreover, the area | region of the protrusion location of the needle | hook 20 in the end surface of the holding body 12, specifically the center end surface 123 is exhibiting the plane, and can contact | abut to skin.

  In the present embodiment, the container 11 and the holding body 12 are preferably integrally formed. However, it is also possible to form the container 11 and the holding body 12 as separate members and fix the holding body 12 to the end of the container 11 by means such as adhesion or welding.

  An adhesive layer 30 containing an adhesive is formed on the end surface of the holder 12 that can contact the skin. In FIG. 1, the adhesive layer 30 is formed on the outer peripheral portion of the end surface of the holding body 12, specifically on the end surface 124 of the wing portion 122. However, the adhesive layer 30 may be formed on the central end surface 123, or may be formed on both the end surface 124 of the wing part 122 and the central end surface 123. By forming the adhesive layer 30 on the central end face 123, the vicinity of the protruding portion of the needle 20 can be firmly adhered to the skin, and by forming the adhesive layer 30 on the end face 124 of the wing 122, the chemical solution can be injected. The holding body 12 of the device 1 can be firmly fixed on the skin. Thereby, it can prevent that a needle | hook remove | deviates from skin at the time of injection | pouring of a chemical | medical solution, for example. A release sheet (not shown) is affixed to the outer surface of the adhesive layer 30 and is peeled off during use.

  As the pressure-sensitive adhesive of the pressure-sensitive adhesive layer 30, any general pressure-sensitive adhesive can be used. For example, a natural rubber pressure-sensitive adhesive or an acrylic pressure-sensitive adhesive can be used. The adhesive layer may contain a target substance other than the adhesive, such as a substance for cooling the skin.

  A gasket 131 that is inserted into the container 11 and is in close contact with the inner wall is attached to the tip of the pusher 13. When the pusher 13 is pushed by the user and moves toward the holding body 12, the gasket 131 seals the chemical liquid so that it does not leak backward, and serves to push the chemical liquid forward.

  The gasket 131 is manufactured by a molding process using a material such as butyl rubber, silicon rubber, or elastomer. The container 11, the holding body 12, and the pusher 13 are manufactured by molding using a material such as plastic or glass such as polypropylene or polyethylene. The container 11 and the holding body 12 are preferably transparent plastic.

  The needle 20 communicates with the internal space 111 in the container 11 and penetrates the holding body 12 and protrudes outward from the central end surface 123. The needle 20 has a hollow shape, and a plurality of needles 20 are provided. In FIG. 1B, five needles 20 are shown. If the number of needles is plural, the dose of the drug solution can be effectively increased. Therefore, the range of 2 to 100 needles is preferable, and in view of the reliability of needle puncture and the manufacturing cost, 2 to 10 The book range is more preferred.

As shown in FIG. 2, the outer diameter _{D 1} of the tip of the needle 20 is 0.1mm or more and 0.25mm or less, the outer diameter _{D 2} of the proximal end of the needle 20, than the outer diameter _{D 1} of the tip It is set large (the needle having such a shape is also called “different diameter needle”). Therefore, not only is the puncture pain reduced by making the tip of the needle thinner, but also the strength of the needle for puncturing the skin is ensured and the increase in flow resistance is prevented by making the base end thicker. Is possible. Further, there is an advantage that the needle 20 can be prevented from falling off from the holding body 12 toward the distal end side.

The needle 20 includes a base portion 21 from a base end to a position corresponding to the central bottom surface 123 of the holding body 12, and a puncture portion 22 that protrudes from the central bottom surface 123 of the holding body 12 and is a portion that can be punctured in a living body. The It may be configured such that part of the thick portion having an outer diameter D ₂ protrudes outward from the central bottom surface 123 of the holding member 12.

  Here, the thickness of the stratum corneum of the skin generally varies depending on the individual, sex, age, body part, and living environment and is not constant, but is usually 10 to 30 μm in the human arm. Moreover, the thickness of the living epidermal cell layer is not constant due to various factors, but is usually 30 to 100 μm in the upper arm of a person. Also, the thickness of the dermis layer is not constant, but is usually 1 to 3 mm.

  Therefore, when attempting intradermal administration, the length of the portion of the needle 20 that is punctured into the skin is preferably in the range of 0.04 to 2.5 mm, more preferably 0.5 to 2.0 mm. As a result, the portion of the needle 20 that protrudes from the central bottom surface 123 of the holding body 12, that is, the total length L of the puncture portion 22 (the total length including the portion that does not enter the skin) is the puncture portion 22 due to the flexibility of the skin. In consideration of the fact that it may not be completely pushed down to the root of the diameter, it is preferably 0.1 to 3 mm, more preferably 1 to 2.5 mm.

  Further, the puncture portion 22 of the needle 20 has a main inclined surface 23 in which a blade surface is formed by being obliquely cut at the first grinding angle and a blade by being obliquely cut at the second grinding angle. It has a pair of front-end | tip inclination surface 24 in which the surface was formed. Thereby, the tip of the needle 20 has a point shape that is easy to puncture the skin.

  As shown in FIG. 3, the outer diameter of the needle may gradually increase from the distal end toward the proximal end. The needle 20a shown in FIG. 3 has an advantage that the strength is higher than that of the needle 20 shown in FIG. 2 and the change in flow path resistance is smooth. On the other hand, the needle 20 shown in FIG. 2 is easier to manufacture than the needle 20a shown in FIG.

The needle 20a shown in FIG. 3 also includes a base portion 21a and a puncture portion 22a. The outer diameter D _{1 of the} tip and the total length L of the puncture portion 22 are the same as those of the needle 20 shown in FIG. Note that the outer diameter may gradually increase from the distal end to the proximal end in a part of the longitudinal direction of the needle, not over the entire length of the needle.

  The needle 20 is generally manufactured using, for example, plastic processing using stainless steel. However, it is also possible to manufacture the needle 20 from other metals such as titanium or materials such as plastic. Adherence of the needle 20 to the main body 10 is achieved by, for example, insert molding or adhesion.

  Moreover, it is preferable that the chemical injection device 1 is provided with a cap 60 for protecting the tip of the needle 20. Thereby, it can prevent that the front-end | tip of the needle | hook 20 is bent accidentally, and it can be made not to give fear to a patient. The cap 60 is attached to the holding body 12 by a method such as screwing or fitting.

  The usage method of the chemical injection device 1 configured as described above will be described.

  First, with the cap 60 attached to the chemical solution injection device 1, the valve 42 connected to the container 11 is opened, and the chemical solution is filled into the container 11 using a chemical solution supply device such as a syringe connected to the valve 42. To do. After filling with the chemical solution, the cap 60 is removed, and the air in the container 11 is removed with the tip of the needle 20 facing upward.

  Then, the chemical liquid injector 1 is adhered to the injection site of the skin by the adhesive layer 30 formed on the end surface 124 of the wing part 122. Therefore, it is possible to prevent the needle 20 from coming off the skin. After confirming that the holding body 12 is firmly adhered to the skin, the pusher 13 is pushed to inject the chemical solution in the container 11 into the skin.

  The drug solution used in the drug solution injector 1 is a solution, gel, or suspension containing a drug. The drugs that can be used are not substantially limited as long as they are other than drugs that are not suitable for transdermal administration.

  Major drugs include, for example, antibacterial drugs, antiviral drugs, vaccines, antitumor drugs, immunosuppressive drugs, steroid drugs, anti-inflammatory drugs, antirheumatic drugs, arthritis drugs, antihistamine drugs, antiallergic drugs, diabetes treatment Drugs, hormones, bone / calcium metabolizers, vitamins, blood products, hematopoietics, antithrombotics, antihyperlipidemics, antiarrhythmics, vasodilators, prostaglandins, calcium antagonists, ACE inhibitors, β-blocker, antihypertensive, diuretic, xanthine derivative, β agonist, anti-asthma, antitussive, expectorant, anticholinergic, antidiarrheal, gastrointestinal, antiulcer, laxative, hypnotic, sedative, antipyretic , Cold medicine, antiepileptic drug, antipsychotic drug, antidepressant drug, anxiolytic drug, central nervous stimulant, parasympathomimetic drug, sympathomimetic drug, antiemetic, central stimulant drug, antiparkinsonian drug, muscle relaxant , Antispasmodics, anesthesia Drugs, antipruritics, anti-migraine drugs, diagnostic drugs, oligonucleotides, gene drugs and the like. However, the drug is preferably a protein, peptide, polysaccharide, oligonucleotide, DNA, or the like that does not show an effect or is attenuated by oral administration, specifically, insulin, growth hormone, interferon, It is a high molecular weight pharmaceutical such as calcitonin.

  Thus, according to the chemical injection device of the first embodiment, by using a plurality of needles, it is possible to puncture the skin while reducing the pain by reducing the needles and to prevent the needles from coming off the skin. it can. Therefore, a sufficient amount of a drug solution such as a polymer drug that is difficult to administer orally, for example, can be reliably and easily injected into the skin percutaneously.

  4A and 4B are diagrams showing a chemical liquid injector according to a second embodiment of the present invention, in which FIG. 4A is a schematic cross-sectional view, and FIG. 4B is a bottom view with a cap removed. FIG. 5 is a schematic enlarged view of the needle shown in FIG. Hereinafter, a description will be given focusing on differences from the first embodiment. In addition, the same code | symbol is used for the member which has a function which is common in 1st Embodiment.

  The chemical injection device 1a according to the second embodiment includes a holding body 12a for holding the container 11a to which the container 11a can be attached. That is, the container 11a can be detachably connected to the holding body 12. In the present embodiment, the container 11a is inserted from the opening 112 of the holding body 12a and attached to the holding body 12a.

  The container 11a is provided with a pusher 13 as a chemical solution driving means for providing a driving force for injecting the chemical solution into the skin percutaneously. The container 11a is used for sealing the tip opening 114. A sealing member 115 made of an elastic material is provided. A gasket 131 attached to the tip of the pusher 13 is inserted into the container 11a and is in close contact with the inner wall. The container 11a is preferably made of glass, but may be made of plastic.

  As shown in FIG. 5, a blade edge 25 for penetrating the sealing member 115 is formed on the proximal end side of the needle 20b so as to communicate with the inside of the container 11a. The blade edge 25 is formed by, for example, cutting the base end side of the needle 20b obliquely at a predetermined grinding angle. The needle 20b has the same configuration as the needle 20 except that the cutting edge 25 is formed, and the proximal end side is formed thick. For this reason, the strength when penetrating the sealing member 115 is ensured. Note that the cutting edge 25 may be formed on the proximal end side with respect to the needle whose outer diameter gradually increases from the distal end toward the proximal end as shown in FIG.

  Further, the center end surface 123a of the holding body 12 is formed in a convex shape toward the tip side. Therefore, since the center end surface 123a is an area where the needle 20 protrudes outward, it is easy to maintain a state in which the plurality of needles 20 are evenly stuck in the skin and stuck. The convex shape of the central end surface 123a is not limited to a substantially conical shape as shown in FIG. 4, and may be a part of a spherical shape, for example. However, the central end surface 123a may be a flat surface. Needless to say, the central end surface 123 in the chemical injection device 1 of the first embodiment may also be formed in a convex shape toward the distal end side.

  When using the chemical injection device 1a configured as described above, a container 11a in which a chemical is preliminarily filled between the gasket 131 and the sealing member 115 is mounted on the holding body 12a. At this time, the cutting edge 25 of the needle 20b erected on the holding body 12a passes through the sealing member 115, and the needle 20b communicates with the inside of the container 11a. When air remains in the container 11a, the pusher 13 is pushed with the tip of the needle 20 facing upward, and the air in the container 11a is released.

  And the chemical | medical solution injection device 1a is adhered to the injection site of the skin by the adhesive layer 30 formed on the end surface 124 of the wing part 122. Therefore, it is possible to prevent the needle 20 from coming off the skin. After confirming that the holding body 12a is firmly adhered to the skin, the pusher 13 is pushed to inject the chemical solution in the container 11a into the skin.

  Thus, also by the chemical | medical solution injection apparatus of 2nd Embodiment, it is possible to acquire the effect similar to said 1st Embodiment. In addition, the container 11a can be replaced with another one for the one holding body 12a.

  Next, an experiment related to intradermal administration of a chemical solution was performed, which will be described below.

<Experiment 1>
An experiment was conducted to confirm whether the blood kinetics when insulin was administered intradermally was equivalent to the conventional subcutaneous administration.

(Method)
Male rats (Crj: Wister, 11 weeks old) were used. Under anesthesia, a catheter was placed in the carotid artery and the drug solution administration site was shaved. After fasting overnight, it was used for the experiment. The rats were divided into two groups, and insulin was administered subcutaneously to one group of rats and intradermally to the other group of rats under unanesthetized restraint. A syringe for insulin (Myjector; manufactured by Terumo Corporation) with a 29G needle (outer diameter 0.33 mm) was used for injection. The dose of insulin (Humarin R injection; manufactured by Shionogi & Co., Ltd.) was 0.5 U / kg, and was used after diluting with physiological saline so that the dose volume was about 20 μl. After administration of insulin, blood was collected from the carotid artery 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours, and the amount of each insulin was measured using an enzyme immunoassay. It measured with the kit for a measurement (Gurazyme Insulin-EIA TEST; Wako Pure Chemical Industries Ltd. make).

(result)
The result of Experiment 1 is shown in FIG. As shown in the figure, when 0.5 U / kg of insulin was administered intradermally, the blood insulin concentration was maximized between 5 minutes and 15 minutes, and blood dynamics lasting 1 hour were obtained (in FIG. 6). Dashed line). This is almost the same as the result of subcutaneous injection (solid line in FIG. 6), and it was found that the same medicinal effect as subcutaneous administration can be obtained even by intradermal administration. In addition, the point in a figure shows an average value, and the length of the vertical line extended from a point shows a standard deviation.

<Experiment 2>
Next, it was examined how much volume could be administered intradermally with one or three needles.

(Method)
About 10 kg pigs were used. Under anesthesia, the flank was shaved, and a different diameter needle attached to the tip of the tube was punctured to a depth of 1.0 mm to 1.2 mm perpendicular to the porcine flank. After fixing the puncture site, the other end of the tube is connected to a 10 ml syringe containing physiological saline, and physiological saline is continuously injected into the skin of the pig using a syringe pump (STC-531; manufactured by Terumo Corporation). did. There were four doses per unit time: 0.05 ml, 0.15 ml, 0.5 ml, and 5 ml per hour. The tube was provided with a side branch, and a comocardio continuous cardiac output monitor (CO-203; manufactured by Terumo Corporation) was connected to the side branch so that the injection pressure could be continuously measured. Leakage from the skin was judged with the naked eye by mixing blue ink into physiological saline. In addition, when the pump injection pressure was not stabilized and increased abnormally, the experiment was terminated at that time. The observation time was 1 hour when one needle was used and 30 minutes when three needles were used. In this experiment, a stainless steel different diameter needle having a total length of 12 mm and an outer diameter of the distal end of 0.18 mm (inner diameter 0.08 mm) and an outer diameter of the tube side (base end) of 0.35 mm (inner diameter 0.25 mm) was used. Using. In addition, at the tip of the needle, a main inclined surface having a blade surface formed by cutting obliquely at the first grinding angle and a pair of tips having a blade surface formed by cutting obliquely at the second grinding angle An inclined surface was provided.

(result)
The result of Experiment 2 is shown in FIG. As shown in the figure, when the dosage was 0.15 ml or less per hour with one needle, physiological saline could be administered relatively stably. However, at a dose of 0.5 ml / hr, the injection pressure increased and the skin was slightly swollen after 1 hour. Furthermore, at a dose of 5 ml / hr, administration became impossible after injection of 0.1-0.2 ml. As shown by the experimental result of 5 ml / hr, it was found that about 0.1 to 0.2 ml can be administered intradermally in a single administration. Furthermore, as shown by the experimental results with three needles, it was found that increasing the number of needles could increase the dose.

  From the results of the above experiments 1 and 2, it can be seen that a desired medicinal effect can be obtained by transdermally injecting a chemical solution into the skin using the chemical solution injection device of the present invention.

  The present invention is not limited to the above-described embodiments, and various modifications can be made within the scope of the claims.

  For example, in the above-described embodiment, the case where the pusher is used as the chemical solution driving means for providing the driving force for transdermally injecting the chemical solution in the container into the skin through the needle has been described. The chemical solution driving means of the invention is not limited to such a case. For example, a leaf spring for pressing the chemical solution in the container may be used. In this case, by pressing the convex surface of the leaf spring arranged in a convex shape, the force when the leaf spring becomes convex in the opposite direction to the initial is used. Further, a coil spring for pressing the gasket in the container may be used. Further, a mechanism using a balloon made of an elastic material may be used. In this case, the force when the balloon that has been inflated after being filled with the chemical solution is contracted is used. In addition, an electric pump capable of delivering a chemical solution may be used. Further, a mechanism using iontophoresis driving may be used. In this case, the ionic drug is transdermally introduced into the living body by electric repulsion or attractive force. Further, a mechanism using the volume expansion of the highly water-absorbing substance may be used. In this case, the chemical solution is delivered by a force accompanying a physical change called volume expansion.

It is a figure which shows the chemical | medical solution injection device which concerns on 1st Embodiment of this invention, Comprising: (A) is a schematic sectional drawing, (B) is a bottom view of the state which removed the cap. It is a schematic enlarged view of the needle | hook shown by FIG. It is a schematic enlarged view which shows the other example of a needle | hook. It is a figure which shows the chemical | medical solution injection device which concerns on 2nd Embodiment of this invention, Comprising: (A) is a schematic sectional drawing, (B) is a bottom view of the state which removed the cap. FIG. 5 is a schematic enlarged view of the needle shown in FIG. 4. It is a graph which shows the blood insulin concentration in the case of intradermal administration and subcutaneous administration. It is a figure which shows the experimental result for confirming the volume which can be intradermally administered with one or three needles.

Explanation of symbols

1, 1a chemical injection device,
10 body,
11, 11a container,
111 internal space,
113 filling port,
114 tip opening,
115 sealing member,
12, 12a holder,
122 wings,
123, 123a center end face,
124 end face,
13 Pusher,
131 gasket,
20, 20a, 20b needle,
21, 21a base,
22, 22a Puncture part,
25 cutting edge,
30 adhesive layer,
60 caps,
D1, D2 needle outer diameter,
L Total length of puncture site.

Claims (10)

A container that can contain a chemical solution;
A holding body for holding the container;
A plurality of hollow needles communicating with the inside of the container and penetrating through the holding body and projecting outward from the holding body;
A drug solution driving means for providing a driving force for transdermally injecting the drug solution in the container into the skin through the needle;
An adhesive layer made of an adhesive formed on an end surface of the holder that can contact the skin;
A chemical injection device characterized by comprising: A container having a sealing member made of an elastic material for sealing a tip opening, to which a driving force for providing a driving force for transdermally injecting the drug solution into the skin, is attached. A holding body for holding
A plurality of hollow needles formed on the base end side to penetrate the sealing member so as to communicate with the inside of the container, and projecting outward from the holding body through the holding body;
An adhesive layer made of an adhesive formed on an end surface of the holder that can contact the skin;
A chemical injection device characterized by comprising: The outer diameter of the tip of the needle is 0.1 mm or more and 0.25 mm or less,
3. The drug solution injector according to claim 1, wherein an outer diameter of a proximal end of the needle is larger than an outer diameter of a distal end.   The drug solution injection device according to claim 3, wherein the needle outer diameter has a portion in which the outer diameter gradually increases from the distal end toward the proximal end. The needle comprises a base from a base end to a position corresponding to the end face of the holding body, and a puncture part that protrudes from the end face of the holding body and is a part that can be punctured into a living body,
The total length of the said puncture part is 1 mm or more and 2.5 mm or less, The chemical injection device as described in any one of Claims 1-4 characterized by the above-mentioned.   The chemical solution injection device according to claim 1, wherein the container has a filling port for filling the chemical solution in the container.   3. The chemical solution is filled in the container in advance, and the chemical solution is sealed by the sealing member and a gasket that is inserted into the container and movable by the chemical solution driving means. The chemical injection device according to the description.   The chemical liquid driving means is connected to a gasket inserted into the container and can be pushed by a user, a leaf spring for pressing the chemical liquid in the container, a coil spring for pressing the gasket, and an elasticity 8. A mechanism using a balloon made of a material, an electric pump, a mechanism using iontophoresis driving, and a mechanism using volume expansion of a highly water-absorbing substance. The chemical injection device according to any one of the above.   The chemical liquid injector according to any one of claims 1 to 8, wherein the adhesive layer is formed on an outer peripheral portion of an end surface of the holding body.   The drug solution injection device according to claim 1, wherein the adhesive layer is formed in a region in the vicinity of a protruding portion of the needle on an end surface of the holding body.

Images