Abstract:
A method for measuring an amount of pain involves positioning a needle adjacent a non-human animal which is under anesthesia, inserting the needle at a controlled puncture speed into skin of the non-human animal, and measuring a muscle action potential of a muscle portion of the non-human animal produced by the insertion of the needle. The muscle action potential is measured from insertion start, at which the insertion of the needle into the skin is started, to insertion stop, at which the insertion of the needle into the skin is stopped.

Description:
[0001]    This application is a continuation of U.S. application Ser. No. 14/389,148 filed on Feb. 4, 2015, which is a U.S. national stage application based on International Application No. PCT/JP2013/058263 having an international filing date of Mar. 22, 2013, and claims priority to Japanese Application No. 2012-065373 filed on Mar. 22, 2012, the entire content of all three of which is incorporated herein by reference. 
     
    
     TECHNICAL FIELD 
       [0002]    The present invention relates to an automatic injection device for moving a syringe held in the main body at a high speed to automatically perform puncture/injection. 
       BACKGROUND DISCUSSION 
       [0003]    Presently, as medicaments, use of protein preparations such as molecular targeting drugs, vaccines, and hormonal agents typified by insulin rapidly increases, and a device capable of easy administration of these medicaments is required. These medicaments are a high-molecular protein or peptide and are not absorbed into a body through oral administration. Therefore, administration by a syringe needle into a hypodermis or blood vessel is necessary. 
         [0004]    Administration by a syringe needle, such as hypodermic, intravenous, and intramuscular administrations, is a general administration method presently. However, a drug solution is infused through puncture by the syringe needle and thus this method involves pain when the needle penetrates the skin. Therefore, in some cases, fear of the pain when puncture by a syringe needle is performed and discomfort in infusion of a drug solution is caused in a patient to which the drug solution is administered by using a syringe and the patient refuses the drug treatment or becomes negative about it. This leads to delay in the treatment. In particular, diabetes patients for which insulin injection is necessary and patients with growth deficiency for which growth hormone injection is necessary are frequently children, and the pain and discomfort in injection are also a cause of later “injection phobia” (Needle phobia). 
         [0005]    Therefore, for patients including such child patients, a device that can be easily operated in injection and does not involve pain and allows automatic injection without direct contact with a syringe needle and a syringe is desired. 
         [0006]    To meet this desire, as an automatic injection device that enables a patient to personally administer a drug solution easily, devices that automatically perform puncture and infusion by pressing a syringe and a pusher (plunger) of the syringe by a spring force have been proposed. 
         [0007]    For example, the following device is described in Patent Document 1. The device includes a drive assembly and a syringe assembly mounted to the drive assembly. The drive assembly includes a drive rod, a driver releasably coupled to the drive rod, and a constant force spring that urges the drive rod toward the syringe assembly. In this device, the spring urges the coupled drive rod and driver along the axis line of the device to puncture the skin by a needle of the syringe assembly. Then, the drive rod is decoupled from the driver and the spring continues to urge the drive rod in the axis line direction. Thereby, the drive rod engages with a piston in the syringe assembly and pushes out a medicament therein to automatically perform an injection. 
         [0008]    Furthermore, the following device is described in Patent Document 2. The device includes a housing that is so configured as to internally contain a medicament container. The housing includes a contact part to be applied to an injection site, a needle cover that surrounds a needle disposed to the medicament container and extends by at least the length of the needle, spring means capable of, when being actuated, pushing the needle to make it pass through an end part of the needle cover and operating the medicament container to supply a dose of medicament. The housing further includes first locking means capable of locking the spring means in a pressurized state and first actuating means capable of releasing the spring means for an injection when being manually operated. In this device, by pressing a button, a syringe to which the spring is mounted is actuated and the medicament is automatically injected. 
         [0009]    Moreover, the following device is described in Patent Document 3. The device includes an elongated housing, a container containing a medicament to be infused through a needle, pressurizing means that acts on the container and is capable of, when being actuated, moving the container and the needle for puncture and subsequently expelling the medicament through the needle, and actuating means disposed to actuate the pressurizing means. In this device, the actuating means includes a needle shield disposed slidably relative to the housing and a collapsible holding member connected to an inner end part of the needle shield. Due to this, in the movement of the needle shield, the collapsible holding member collapses when a certain force is applied by the needle shield. Thereby, the further movement of the needle shield actuates the actuating means. Then, the actuating means releases the pressurizing means to initiate infusion of the medicament. 
       PRIOR ART DOCUMENTS 
     Patent Documents 
       [0000]    
       
         Patent Document 1: U.S. Pat. No. 5,478,316 
         Patent Document 2: EP Patent No. 1,349,590 
         Patent Document 3: JP 2010-521260 A 
       
     
       SUMMARY 
       [0013]    The devices described in Patent Documents 1 to 3 are devices with which a series of action of punctuating the skin by a syringe needle and infusing a drug solution and then withdrawing the syringe needle can be automatically performed. However, they do not alleviate pain accompanying the puncture by the syringe needle and the infusion of the drug solution. 
         [0014]    With a device that presses a syringe and a plunger by using a spring to automatically perform puncture and infusion of a drug solution like the devices described in Patent Documents 1 to 3, high-speed puncture based on the repulsive force of the spring is performed and thus an impact on the skin (vibration, feeling of pressure, impact sound, etc.) is made at the time of the puncture, giving anxiety and fear about the injection to the patient. Furthermore, because the puncture and infusion are performed by the same spring, it is difficult to set conditions in detail about the puncture speed, the puncture depth, and the infusion rate of the drug solution depending on the patient and the kind of medicament. 
         [0015]    Furthermore, in the dental field, an electric infusion instrument that automatically infuses a drug solution at a constant speed is used as an instrument to administer anesthetic. However, puncture by a syringe needle is performed by an operator and the puncture is not automatically performed. 
         [0016]    Moreover, to alleviate pain in puncture, a syringe needle whose diameter is set small is developed and is used in a clinical scene. However, in administration of a large amount of medicament and administration of a medicament having a high viscosity, the infusion resistance is high and a long time is taken. 
         [0017]    The automatic injection device disclosed here automatically performs puncture and allows setting of conditions of the puncture according to the thickness of a syringe needle, the puncture depth, and so forth. Furthermore, the automatic injection device reduces pain in puncture and in drug solution infusion and reduces the impact in the puncture to allow alleviation of anxiety and fear of a patient. 
         [0018]    The automatic injection device can automatically perform puncture with very little pain of the puncture at such a puncture speed as to yield almost no pain. 
         [0019]    The automatic injection device performs puncture by causing an advance of a syringe having a distal end at which a syringe needle is disposed. The automatic injection device has a syringe holder that holds the syringe attachably and detachably, a first drive unit that causes the syringe holder holding the syringe to advance to perform puncture by the syringe needle, and a control unit that controls the first drive unit to control a puncture speed. 
         [0020]    Here, it is preferable that the first drive unit includes a first electric motor and a first motion converter that converts rotational motion of the first electric motor to linear motion and causes the syringe holder to advance. 
         [0021]    Furthermore, it is preferable that the thickness of the syringe needle of the syringe is in a range of 18 G to 34 G and the puncture speed in puncture with the syringe needle by the first drive unit satisfies 10 to 500 mm/s. 
         [0022]    In addition, it is preferable to employ the following configuration. Specifically, the syringe has, in addition to the syringe needle, a syringe barrel filled with a drug solution and a plunger for infusing the drug solution in the syringe barrel into a subject from the syringe needle with which puncture is performed. The automatic injection device has a second drive unit that causes the plunger to advance to infuse the drug solution. The control unit controls the second drive unit to infuse the drug solution at a predetermined infusion rate after puncture by the first drive unit. 
         [0023]    Moreover, it is preferable that the second drive unit includes a second electric motor and a second motion converter that converts rotational motion of the second electric motor to linear motion. 
         [0024]    Furthermore, it is preferable that the first drive unit moves the second drive unit and the syringe holder integrally. 
         [0025]    In addition, it is preferable that the control unit controls the infusion rate of the drug solution by the second drive unit to 1 to 1000 μL/s. 
         [0026]    Moreover, it is preferable that the control unit controls the first drive unit so that the puncture depth when the first drive unit causes the syringe holder to advance to perform puncture with the syringe needle is a depth of 1 to 50 mm. 
         [0027]    Furthermore, it is preferable that the control unit controls the first drive unit to cause the syringe holder to retreat and withdraw the syringe needle after elapse of a predetermined stop time after drug solution infusion by the second drive unit. 
         [0028]    In addition, it is preferable that the control unit variably controls a puncture speed in the middle of puncture in the puncture with the syringe needle by the first drive unit. 
         [0029]    In automatically performing puncture, conditions of the puncture can be set according to the thickness of a syringe needle, the puncture depth, and so forth. This reduces pain in the puncture and reduces the impact in the puncture, allowing alleviation of anxiety and fear of a patient. 
         [0030]    Furthermore, according to a preferred mode, the puncture speed in puncture by the first drive unit satisfies 10 to 500 mm/s when the thickness of the syringe needle is in a range of 18 G to 34 G. This can automatically perform puncture with very little pain of the puncture at such a puncture speed as to yield almost no pain. 
         [0031]    Another aspect of the disclosure here involves a method for measuring an amount of pain. The method involves positioning a needle adjacent a non-human animal which is under anesthesia, inserting the needle at a controlled puncture speed into skin of the non-human animal, and measuring a muscle action potential of a muscle portion of the non-human animal produced by the insertion of the needle. The muscle action potential is measured from insertion start, at which the insertion of the needle into the skin is started, to insertion stop, at which the insertion of the needle into the skin is stopped. 
         [0032]    Another aspect involves a method comprising: positioning a needle adjacent a non-human animal which is anesthetized, with the needle being a first-size needle possessing a first outer diameter; inserting the first-size needle at a first controlled puncture speed into the non-human animal through skin of the non-human animal; measuring penetration resistance of the insertion of the first-size needle at the first controlled puncture speed from insertion start, at which the insertion of the first-sized needle into the skin is started, to insertion stop, at which the insertion of the first-size needle into the skin is stopped; measuring an amount of pain during the insertion of the first-size needle at the first controlled puncture speed; and inserting a needle at a second controlled puncture speed into the non-human animal through skin of the non-human animal, with the second controlled puncture speed being different from the first controlled puncture speed, and the needle inserted at the second controlled puncture speed being a first-size needle possessing the first outer diameter. The method also includes: measuring penetration resistance of the insertion of the first-size needle at the second controlled puncture speed from insertion start, at which the insertion of the first-size needle into the skin is started, to insertion stop, at which the insertion of the needle into the skin is stopped; measuring an amount of pain during the insertion of the first-size needle at the second controlled puncture speed; and using results of the measured penetration resistance and the measured amount of pain to select either the first controlled puncture speed or the second controlled puncture speed to reduce pain of the non-human animal resulting from the insertion. 
         [0033]    In accordance with another aspect, a method comprises: positioning a needle adjacent a non-human animal which is anesthetized, the needle being a first-size needle possessing a first outer diameter; inserting the first-size needle at a first controlled puncture speed into the non-human animal through skin of the non-human animal; measuring penetration resistance of the insertion of the first-size needle at the first controlled puncture speed from insertion start, at which the insertion of the first-sized needle into the skin is started, to insertion stop, at which the insertion of the first-size needle into the skin is stopped; measuring an amount of pain during the insertion of the first-size needle at the first controlled puncture speed; and inserting a needle, which is different from the first-size needle, at the first controlled puncture speed into the non-human animal through skin of the non-human animal, wherein the needle which is different from the first-size needle is a second-size needle possessing a second outer diameter different from the first outer diameter. The method additionally includes measuring penetration resistance of the insertion of the second-size needle at the first controlled puncture speed from insertion start, at which the insertion of the second-size needle into the skin is started, to insertion stop, at which the insertion of the second-size needle into the skin is stopped; measuring an amount of pain during the insertion of the second-size needle at the first controlled puncture speed; and using results of the measured penetration resistance and the measured amount of pain to select either the first-size needle or the second-size needle to reduce pain of the non-human animal resulting from the insertion. 
         [0034]    A still further aspect of the disclosure here involves a method comprising: inserting different-size needles, which possess different outer diameters, at different controlled puncture speeds into an anesthetized non-human animal through skin of the anesthetized non-human animal; measuring penetration resistance of the insertion of the different-size needles at the different controlled puncture speeds from insertion start, at which the insertion of each respective different-size needle into the skin is started, to insertion stop, at which the insertion of each respective different-size needle into the skin is stopped; measuring an amount of pain during the insertion of the different-size needles at the different controlled puncture speeds; and using results of the measured penetration resistance and the measured amount of pain to select one of the different-size needles and one of the different controlled puncture speeds to reduce pain of the non-human animal resulting from the insertion. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWING FIGURES 
         [0035]      FIG. 1  is a sectional view conceptually showing one embodiment of an automatic injection device of the present invention. 
           [0036]      FIG. 2  is a front view of the automatic injection device shown in  FIG. 1 . 
           [0037]      FIG. 3  is a sectional view of the automatic injection device in a state in which a syringe is not mounted therein. 
           [0038]      FIG. 4  is a diagram of the automatic injection device shown in  FIG. 1  as seen from a direction “a.” 
           [0039]      FIGS. 5(A) to 5(C)  are diagrams for explaining the operation of the automatic injection device of the present invention. 
           [0040]      FIG. 6  is a perspective view conceptually showing another example of the automatic injection device of the present invention. 
           [0041]      FIG. 7  is a graph representing a result of measurement of the penetration resistance in puncture. 
           [0042]      FIG. 8(A)  is a graph showing the relationship between the puncture speed and the penetration resistance, and  FIG. 8(B)  is a graph showing the relationship between the puncture speed and the electromyography response magnitude. 
           [0043]      FIG. 9(A)  is a graph showing the relationship between the puncture speed and the penetration resistance, and  FIG. 9(B)  is a graph showing the relationship between the puncture speed and the electromyography response magnitude. 
       
    
    
     DETAILED DESCRIPTION 
       [0044]    An automatic injection device according to the present invention will be described in detail below based on a preferred embodiment shown in the accompanying drawings. 
         [0045]      FIG. 1  is a sectional view showing the outline of the automatic injection device according to the present invention and  FIG. 2  is a front view of a state in which a cover  14  of an automatic injection device  10  shown in  FIG. 1  is opened. 
         [0046]    Furthermore,  FIG. 3  is a schematic sectional view of the automatic injection device  10  in a state in which a syringe  70  is removed. 
         [0047]    The syringe  70  mounted in the automatic injection device  10  is a normal syringe having a syringe barrel  72  that is internally filled with a drug solution and has a cylindrical shape, a syringe needle  74  that is disposed at the distal end of the syringe barrel  72  to be inserted into the body of a subject (patient) and expels the drug solution from the distal end, and a plunger  76  for expelling the drug solution in the syringe barrel  72  from the syringe needle  74 . The plunger  76  includes a piston part that is inserted into the syringe barrel  72  from the opposite side to the side of the syringe needle  74  (proximal side) and is slidable in the syringe barrel  72 . 
         [0048]    In the example shown in the diagrams, a flange  72   a  locked into a locking groove  20   b  of a syringe holder  20  to be described later is provided on the proximal side of the syringe barrel  72 . 
         [0049]    Furthermore, a flange  76   a  locked into a locking groove  44   a  of a pressing member  44  to be described later is provided on the proximal side of the plunger  76 . 
         [0050]    Note that the syringe  70  may be filled with a drug solution by an operator or may be a pre-filled syringe filled with a drug solution in advance. 
         [0051]    The automatic injection device  10  is a device that automatically performs injection through mounting of the syringe  70  in a housing  12 . The automatic injection device  10  has the housing  12 , the cover  14 , a first drive unit  16  for performing puncture by the syringe needle  74  of the syringe  70 , a second drive unit  18  for performing infusion of a drug solution by the syringe  70 , the syringe holder  20 , a control unit  22  that controls the first drive unit  16  and the second drive unit  18 , an operation unit  26 , and a battery  28  that supplies the respective units with power. 
         [0052]    The syringe holder  20  is a part that holds the syringe  70  with the longitudinal direction of the syringe  70  set identical to the direction of driving by the first drive unit  16  to be described later. 
         [0053]    As shown in  FIGS. 2 and 3 , the syringe holder  20  has, along the longitudinal direction of the syringe  70 , a recess  20   a  that corresponds to the shape of the syringe barrel  72  of the syringe  70  and has a semicircular shape in section perpendicular to the longitudinal direction. Furthermore, the locking groove  20   b  for locking of the flange  72   a  of the syringe barrel  72  is formed on the proximal side of the recess  20   a  (on the side of the plunger  76 ). 
         [0054]    Note that, in the example shown in the diagrams, the syringe holder  20  is formed monolithically with blocks  34   b  and a base  36  of the first drive unit  16  to be described later. 
         [0055]    The first drive unit  16  is a part for moving the syringe holder  20  on which the syringe  70  is placed toward the syringe needle  74  in the longitudinal direction of the syringe  70  and performing puncture with the syringe needle  74  disposed at the distal end of the syringe  70 . 
         [0056]    Note that, in the following description, the case of moving the syringe holder  20  with the syringe  70  placed thereon toward the syringe needle  74  is defined as an advance and the case of moving the syringe holder  20  toward the plunger  76  is defined as retreat. 
         [0057]    The first drive unit  16  has a first motor  32 , a first motion converter  34 , and the base  36 . 
         [0058]    The first motor  32  is a normal stepping motor that operates according to supplied power and its rotational speed and rotation amount can be controlled. 
         [0059]    The first motor  32  rotates at a predetermined rotational speed by a predetermined rotation amount in such a direction as to cause the syringe holder  20  to advance (hereinafter, defined as the forward direction). Thereafter, after the operation is stopped during a predetermined time, the first motor  32  is controlled by the control unit  22  to be described later to rotate at a predetermined rotational speed by a predetermined rotation amount in such a direction as to cause the syringe holder  20  to retreat (hereinafter, defined as the reverse direction). 
         [0060]    Specifically, when a start button  26   a  of the operation unit  26  is operated, the first motor  32  is first controlled by the control unit  22  to rotate in the forward direction by a predetermined rotation amount at a predetermined rotational speed according to operating conditions of puncture speed and puncture depth that are input by the operation unit  26  and set in advance. After the rotation by the predetermined rotation amount, the operation is temporarily stopped. The second drive unit  18  to be described later operates during the temporary stop of the first motor  32  and therefore the stop state is kept until the completion of the operation of the second drive unit  18 . After the completion of the operation of the second drive unit  18  and the elapse of a predetermined stop time, the first motor  32  is controlled to rotate in the reverse direction by a predetermined rotation amount at a predetermined rotational speed according to a condition of a retreat speed (withdrawal speed) set in advance so that the syringe holder  20  may return to the original position. 
         [0061]    The first motor  32  is connected to a screw shaft  34   a  of the first motion converter  34  and rotates the screw shaft  34   a.    
         [0062]    The first motion converter  34  is a so-called ball screw and is a part for converting the rotational motion of the first motor  32  to linear motion to cause the base  36  of the syringe holder  20  to advance/retreat. 
         [0063]    The first motion converter  34  has the screw shaft  34   a  having a screw groove formed on its circumferential surface, two guide shafts  34   c  symmetrically disposed to sandwich the screw shaft  34   a , and the two blocks  34   b . In the blocks  34   b , a female screw screwed to the screw groove of the screw shaft  34   a  with the intermediary of plural balls is formed and two guide holes into each of which a respective one of the two guide shafts  34   c  is inserted are formed. 
         [0064]    The screw shaft  34   a  is rotatably supported by bearings formed on the housing  12  on both end sides. Furthermore, both end parts of the guide shafts  34   c  are supported by the housing  12 . 
         [0065]    Furthermore, the first motion converter  34  is disposed with the axis of the screw shaft  34   a  set along the longitudinal direction of the syringe  70  (syringe needle  74 ) and thus can move the syringe needle  74  in the puncture direction. 
         [0066]    Moreover, the two blocks  34   b  are disposed at a predetermined interval in the longitudinal direction of the syringe  70 . 
         [0067]    When the first motor  32  rotates, the screw shaft  34   a  connected to the first motor  32  rotates. Upon the rotation of the screw shaft  34   a , the two blocks  34   b  screwed to the screw shaft  34   a  advance/retreat along the axis of the screw shaft  34   a . Here, because the guide shafts  34   c  are inserted into the guide holes of the two blocks  34   b , the two blocks  34   b  make linear motion along the screw shaft  34   a  without rotating around the screw shaft  34   a  when the screw shaft  34   a  rotates. 
         [0068]    The base  36  is fixed to the two blocks  34   b  of the first motion converter  34 . 
         [0069]    Note that, although a ball screw is used as the first motion converter  34  in the example shown in the diagrams, the present invention is not limited thereto and various publicly-known conversion mechanisms between rotational motion and linear motion, such as feed screw mechanism, rack and pinion mechanism, and crank mechanism, may be used. 
         [0070]    Alternatively, a linear motor may be used instead of the first motor  32  and the first motion converter  34 . 
         [0071]    Note that it is preferable to use a ball screw as the first motion converter  34  in that the positional accuracy is high and the controllability is high and in that the friction loss is small and the energy efficiency is high. 
         [0072]    Furthermore, although the configuration in which the first motion converter  34  has the two blocks  34   b  is employed, the configuration is not limited thereto and a configuration in which the first motion converter  34  has one block  34   b  may be employed. By disposing the two blocks  34   b  at a predetermined interval, the base  36  can be prevented from tilting in the front-rear direction and swinging. 
         [0073]    The base  36  is a pedestal on which to place the syringe holder  20  and the second drive unit  18  and is fixed to the blocks  34   b  of the first motion converter  34 . 
         [0074]    Because being fixed to the blocks  34   b  of the first motion converter  34 , the base  36  is made to advance/retreat along the screw shaft  34   a  when the first motor  32  is driven. That is, when the first motor  32  is driven, the syringe holder  20  and the second drive unit  18  are made to integrally advance/retreat. 
         [0075]    Note that the base  36  is formed monolithically with the syringe holder  20  and the blocks  34   b  in the example shown in the diagrams as described above. 
         [0076]    Here, as described above, the first motor  32  is controlled by the control unit  22  to rotate at a predetermined rotational speed by a predetermined rotation amount according to conditions such as puncture speed and puncture depth set in advance by input from the operation unit  26 . Therefore, first, by the rotation of the first motor  32  in the forward direction, the syringe holder  20  linearly moves to a predetermined position at a predetermined advance speed. Thereby, puncture is performed by the syringe needle  74  of the syringe  70  to the set puncture depth at the set puncture speed. 
         [0077]    Next, the base  36  keeps the stop state during the stop of the first motor  32 . Thereafter, by the rotation of the first motor  32  in the reverse direction, the base  36  linearly moves to the original position at a predetermined retreat speed. Thereby, the syringe needle  74  of the syringe  70  is withdrawn at a predetermined withdrawal speed. 
         [0078]    As described above, the conventional automatic injection devices are devices that press a syringe by using the repulsive force of a spring to automatically perform puncture and therefore involve a problem that an impact on the skin (vibration, feeling of pressure, impact sound, etc.) is made at the time of the puncture and anxiety and fear about the injection are given to the patient. Furthermore, because the puncture and infusion are performed by the same spring, there is a problem that it is difficult to set conditions in detail about the puncture speed and the puncture depth according to the thickness of a syringe needle, the kind of medicament, the patient, etc. 
         [0079]    In contrast, in the automatic injection device  10  of the present invention, the first drive unit  16  to drive the syringe holder  20  is configured with the first motor  32  and the first motion converter  34  and the syringe  70  having the syringe needle  74  is held in the syringe holder  20 . In the first drive unit  16 , the first motor  32  rotates according to puncture speed, puncture depth, and so forth set in advance and the syringe holder  20  is made to advance through the first motion converter  34  to perform puncture with the syringe needle  74 . Thus, conditions of the puncture, such as the puncture speed, can be set according to the thickness of the syringe needle, the puncture depth, the patient, and so forth and the puncture can be performed at a proper puncture speed, allowing reduction in pain in the puncture and reduction in the impact in the puncture. This can alleviate anxiety and fear of the patient. 
         [0080]    Furthermore, the first drive unit  16  to perform the puncture is configured independently of the second drive unit  18  to infuse a drug solution. Thus, a proper puncture speed can be set regardless of operating conditions of the second drive unit  18 . 
         [0081]    Here, the advance speed when the first drive unit  16  makes the syringe holder  20  advance to perform the puncture, i.e. the puncture speed, can be appropriately set according to the thickness of the syringe needle  74  and the puncture depth or the sensitivity of the patient, the injection site, and so forth. If a syringe whose thickness of the syringe needle  74  is in a range of 18 G to 34 G is used as the syringe  70 , it is preferable to set the puncture speed in a range of 10 mm/s to 500 mm/s. Furthermore, it is more preferable to set the puncture speed in a range of 25 mm/s to 500 mm/s and it is further preferable to set it in a range of 75 mm/s to 500 mm/s. 
         [0082]    Setting the puncture speed equal to or higher than 10 mm/s can alleviate pain in the puncture and allows the puncture with the patient caused to feel almost no pain. Furthermore, setting the puncture speed equal to or lower than 500 mm/s can reduce impact and recoil at the time of the puncture and reduce anxiety and fear of the patient. 
         [0083]    Furthermore, by setting the puncture speed in a range of 25 mm/s to 500 mm/s, nearly painless puncture can be performed. Moreover, by setting the puncture speed in a range of 75 mm/s to 500 mm/s, painless puncture in which the patient is surely prevented from feeling pain in the puncture can be performed. 
         [0084]    A preferable range of the puncture speed will be described in detail later. 
         [0085]    Furthermore, there is no particular limit to the retreat speed when the first drive unit  16  makes the syringe holder  20  retreat to withdraw the syringe needle  74 , i.e. the withdrawal speed. However, it is preferable to set the withdrawal speed in a range of 1 to 500 mm/s. 
         [0086]    Setting the withdrawal speed to a constant speed in the range of 1 to 500 mm/s is preferable in that the stimulus to pain sensing nerves due to the vibration of the already-inserted needle and friction with the insertion site can be alleviated and pain caused in the withdrawal can be minimized. 
         [0087]    Furthermore, in the present embodiment, as a preferred mode, based on control by the control unit  22 , the first drive unit  16  makes the syringe holder  20  retreat to withdraw the syringe needle  74  after the elapse of a predetermined stop time after the completion of infusion of a drug solution by the second drive unit  18 . If the syringe needle  74  is withdrawn immediately after the infusion of the drug solution, the drug solution does not sufficiently diffuse and possibly the drug solution leaks out. Therefore, it is preferable to withdraw the syringe needle  74  after the elapse of the predetermined stop time from the completion of the infusion of the drug solution. 
         [0088]    In the present embodiment, the stop time to the withdrawal of the syringe needle  74  can also be set through input from the operation unit  26  by an operator. 
         [0089]    In addition, the first drive unit  16  does not only automatically carry out operation for puncture based on an input signal from the start button  26   a  but can cause advance/retreat at a low speed in accordance with operation of the operation unit  26 . That is, an operator can manually make the first drive unit  16  cause advance/retreat by operating the operation unit  26 . This allows the position of the distal end of the syringe needle  74  to be adjusted to a predetermined position after the syringe  70  is set in the syringe holder  20 . 
         [0090]    The second drive unit  18  is a part for pressing the plunger  76  of the syringe  70  in the direction of the syringe needle  74  to make it advance and expelling a drug solution in the syringe barrel  72  from the distal end of the syringe needle  74  based on control by the control unit  22 . 
         [0091]    The second drive unit  18  has a second motor  40 , a second motion converter  42 , and the pressing member  44 . 
         [0092]    The second motor  40  is a normal stepping motor that operates according to supplied power as with the first motor  32 , and its rotational speed and rotation amount can be controlled. 
         [0093]    The second motor  40  is controlled by the control unit  22  to rotate in the forward direction by a predetermined rotation amount at a predetermined speed according to conditions of infusion rate and infusion amount of a drug solution set in advance through input from the operation unit  26  while the first drive unit  16  temporarily stops its operation after carrying out operation of puncture. 
         [0094]    The second motor  40  is connected to a screw shaft  42   a  of the second motion converter  42  and rotates the screw shaft  42   a.    
         [0095]    The second motion converter  42  is a ball screw as with the first motion converter  34 . It is a part that converts rotational motion of the second motor  40  to linear motion and is to cause the plunger  76  locked to the pressing member  44  to advance/retreat. 
         [0096]    Similarly to the first motion converter  34 , the second motion converter  42  has the screw shaft  42   a  having a screw groove formed on its circumferential surface, two guide shafts  42   c  symmetrically disposed to sandwich the screw shaft  42   a , and a block  42   b . In the block  42   b , a female screw screwed to the screw groove of the screw shaft  42   a  with the intermediary of plural balls is formed and two guide holes into each of which a respective one of the two guide shafts  42   c  is inserted are formed. 
         [0097]    The screw shaft  42   a  is rotatably supported by bearings formed on the base  36  on both end sides. Furthermore, both end parts of the guide shafts  42   c  are supported by the base  36 . 
         [0098]    Furthermore, the second motion converter  42  is disposed with the axis of the screw shaft  42   a  set along the longitudinal direction of the syringe  70  and the syringe needle  74 . 
         [0099]    When the second motor  40  rotates based on control from the control unit  22 , the screw shaft  42   a  connected to the second motor  40  rotates. Upon the rotation of the screw shaft  42   a , the block  42   b  screwed to the screw shaft  42   a  advances/retreats along the axis of the screw shaft  42   a . Here, because the guide shafts  42   c  are inserted into the guide holes of the block  42   b , the block  42   b  makes linear motion along the screw shaft  42   a  without rotating around the screw shaft  42   a  when the screw shaft  42   a  rotates. 
         [0100]    The pressing member  44  is fixed to the block  42   b  of the second motion converter  42 . 
         [0101]    Note that another publicly-known motion conversion mechanism may be used as the second motion converter  42  as with the first motion converter  34 . 
         [0102]    The pressing member  44  is a member for pressing the plunger  76  of the syringe  70  to make it advance and is fixed to the block  42   b  of the second motion converter  42 . 
         [0103]    The locking groove  44   a  for locking the flange  76   a  of the plunger  76  is formed in the pressing member  44 . 
         [0104]    Because being fixed to the block  42   b  of the second motion converter  42 , the pressing member  44  is made to advance/retreat along the screw shaft  42   a  when the second motor  40  is driven. 
         [0105]    Here, as described above, the second motor  40  is controlled by the control unit  22  to rotate at a predetermined rotational speed by a predetermined rotation amount according to conditions such as infusion rate and infusion amount set in advance by input from the operation unit  26 . Therefore, by the rotation of the second motor  40  in the forward direction, the pressing member  44  is linearly moved to a predetermined position at a predetermined advance speed. Thereby, the plunger  76  of the syringe  70  is pressed and the set amount of drug solution is expelled from the distal end of the syringe needle  74  at the infusion rate set in advance. 
         [0106]    As above, as a preferred mode of the present invention, the second drive unit  18  for infusing a drug solution is provided independently of the first drive unit  16  for performing puncture. This can set infusion rate and infusion amount regardless of set puncture speed, puncture depth, and so forth. Thus, a drug solution can be infused at the optimum infusion rate and discomfort and so forth accompanying the infusion of the drug solution can be alleviated. Furthermore, the speed of puncture by the first drive unit  16  can be set independently of the second drive unit  18 . Thus, puncture can be performed at the optimum puncture speed, allowing reduction in pain in the puncture and reduction in the impact in the puncture. 
         [0107]    Here, the infusion rate when the second drive unit  18  makes the pressing member  44  advance to infuse a drug solution can be appropriately set according to the thickness of the syringe needle  74  and the puncture depth or the kind of drug solution, the infusion amount, and so forth. It is known that the infusion rate of a drug solution and pain have a correlation and pain is less when the infusion rate is lower. What degree the optimum infusion rate is at in practice differs depending on the kind of infused medicament, the infusion amount, the infusion-target site, and so forth. Nagasawa et al. has made the following report. Specifically, Nagasawa et al. administered a physiological saline to the rat oral mucosa with variation in the infusion rate and measured pain by using electromyography. As a result, the pain was alleviated at a rate of 10 μL/s (Ikuko Nagasawa et al., J. Jpn. Dent. Soc. Anesthesiol., 31:497, 2003). On the other hand, in the case of rapid administration into a blood vessel or hypodermis, the drug solution is infused at a much higher infusion rate in practice. In view of such results, it is preferable to set the infusion rate in a range of 1 to 1000 μL/s. 
         [0108]    Setting the infusion rate of a drug solution in the range of 1 to 1000 μL/s can reduce pain and discomfort accompanying the infusion of the drug solution. 
         [0109]      FIG. 4  is a schematic diagram of the operation unit  26  of the automatic injection device  10  shown in  FIG. 1  as seen from a direction “a.” 
         [0110]    The operation unit  26  is to carry out input operation by an operator. In the example shown in the diagrams, the operation unit  26  has the start button  26   a  to start operation of the automatic injection device  10  and a display unit  26   b  that displays input values and so forth in addition to a cross key for input of operating conditions, an enter button, etc. 
         [0111]    Note that the configuration of the operation unit  26  is not limited thereto and the operation unit  26  may have a trackball or the like or may be formed of a touch panel. 
         [0112]    The operation unit  26  supplies an input signal to the control unit  22  in accordance with input operation. 
         [0113]    In the example shown in the diagrams, the configuration is employed in which the puncture speed, the puncture depth, the size of a mounted syringe, the infusion rate of a drug solution, the infusion amount of the drug solution, and the stop time after drug solution infusion are input from the operation unit  26  as operating conditions. However, the present invention is not limited thereto. 
         [0114]    For example, a configuration in which only the puncture speed is input may be employed and the puncture depth, the infusion rate of a drug solution, the infusion amount of the drug solution, and the stop time after drug solution infusion may be set in advance. 
         [0115]    Furthermore, the present invention is not limited also to the configuration in which the puncture speed is directly input and a configuration may be employed in which at least one of the thickness of the syringe needle  74 , the kind of drug solution, the puncture depth, the infusion amount of the drug solution, and the puncture site is input from the operation unit  26  and the control unit  22  automatically selects the optimum puncture speed according to the input value. 
         [0116]    The control unit  22  controls the respective units of the automatic injection device  10  based on an instruction input from the operation unit  26  by an operator. 
         [0117]    In the present embodiment, the control unit  22  controls the first drive unit  16  according to puncture speed, puncture depth, stop time, and withdrawal speed input and set from the operation unit  26  and controls the second drive unit  18  according to set infusion rate and infusion amount. 
         [0118]    Furthermore, the control unit  22  has a memory to store operating conditions such as the set puncture speed and controls the respective units of the automatic injection device  10  according to the operating conditions stored in the memory. Moreover, if a new operating condition is input from the operation unit  26 , the operating condition stored in the memory is overwritten and the automatic injection device  10  is controlled with the new operating condition. In addition, if no input is made, the control is carried out with the operating conditions already stored in the memory. 
         [0119]    The battery  28  supplies power to the respective units of the automatic injection device  10 , such as the first motor  32 , the second motor  40 , the control unit  22 , and the display unit  26   b.    
         [0120]    As shown in  FIGS. 2 and 3 , the housing  12  is a casing that has a substantially cylindrical shape and houses and supports the first drive unit  16 , the second drive unit  18 , the syringe holder  20 , the control unit  22 , and the battery  28  inside it. 
         [0121]    The first drive unit  16  and the second drive unit  18  are each disposed in the housing  12  with the drive direction (axial direction of the screw shaft ( 34   a ,  42   a )) set identical to the longitudinal direction of the housing  12 . Furthermore, in one end surface of the housing  12 , an insertion hole  12   a  into which the syringe needle  74  is inserted when the syringe  70  is made to advance is formed. Moreover, the part at which the insertion hole  12   a  is formed in the housing  12  serves as an abutting surface  12   b  that abuts against a puncture-target site such as the skin across its outer surface. In administration of a drug solution by the automatic injection device  10 , after the operating conditions are checked, the abutting surface  12   b  is made to abut against a puncture-target site such as the skin and the administration operation is started. Therefore, the length of the part protruding from the insertion hole  12   a  in the distal end of the syringe needle  74  is directly the puncture depth. 
         [0122]    Furthermore, the operation unit  26  is disposed on the end surface of the housing  12  on the opposite side to the abutting surface  12   b.    
         [0123]    Note that the operation unit  26  is disposed with an inclination relative to the abutting surface  12   b  of the housing  12  in the example shown in the diagrams. Disposing the operation unit  26  with an inclination facilitates viewing of the display unit  26   b  of the operation unit  26  when a patient operates the automatic injection device  10 . 
         [0124]    Furthermore, part of the circumferential surface of the housing  12  is opened and the cover  14  is openably/closably disposed at the open part. In the example shown in the diagrams, the housing  12  and the cover  14  are openably/closably connected by a hinge. 
         [0125]    In addition, holding parts  14   a  are formed on the inside surface of the cover  14 . When the cover  14  is closed, the holding parts  14   a  suppress the movement of the syringe barrel  72  of the syringe  70  in directions other than the longitudinal direction of the syringe  70  and prevent the syringe  70  from breaking away from the syringe holder  20 . 
         [0126]    Next, the operation of the automatic injection device  10  will be described. 
         [0127]      FIGS. 5(A) to 5(C)  are schematic sectional views for explaining the operation of the automatic injection device  10 . 
         [0128]    First, the cover  14  is opened and the syringe  70  with the syringe barrel  72  filled with a drug solution is set on the syringe holder  20 , followed by closing of the cover  14  ( FIG. 5(A) ). At this time, if necessary, position adjustment of the syringe holder  20  (distal end of the syringe needle  74 ) is carried out by operating the operation unit  26 . 
         [0129]    Next, the puncture speed, the puncture depth, the infusion rate of the drug solution, and so forth are input and set from the operation unit  26  (stored in the memory). Note that these operating conditions may be set in advance. 
         [0130]    The abutting surface  12   b  in which the insertion hole  12   a  is formed in the automatic injection device  10  is pressed against an injection site of a patient and the start button  26   a  of the operation unit  26  is pushed. Thereupon, based on control by the control unit  22 , first the first drive unit  16  operates according to the set puncture speed and puncture depth to cause the syringe holder  20  and the second drive unit  18  to advance to a predetermined position ( FIG. 5(B) ). Thereby, the syringe needle  74  of the syringe  70  held by the syringe holder  20  protrudes from the insertion hole  12   a  and punctures the injection site of the patient. 
         [0131]    Here, the first drive unit  16  is composed of the first motor  32  and the first motion converter  34  and is so configured that operating conditions can be set. Thus, the puncture can be performed by making the syringe holder  20  advance at the set puncture speed and the puncture can be performed at a proper puncture speed depending on the thickness of the syringe needle, the puncture depth, the patient, and so forth. This reduces pain in the puncture and reduces the impact in the puncture, allowing alleviation of anxiety and fear of the patient. 
         [0132]    Furthermore, because the first drive unit  16  to perform the puncture is configured independently of the second drive unit  18  to infuse the drug solution, a proper puncture speed (puncture condition) can be set regardless of operating conditions of the second drive unit  18 . 
         [0133]    After the puncture operation by the first drive unit  16 , the first drive unit  16  temporarily stops the operation and the second drive unit  18  makes the pressing member  44  advance to infuse a predetermined amount of drug solution at the set infusion rate based on control by the control unit  22  ( FIG. 5(C) ). 
         [0134]    Upon the end of the infusion operation of the drug solution by the second drive unit  18 , after the elapse of a predetermined stop time, the control unit  22  actuates the first drive unit  16  to cause the syringe holder  20  and the second drive unit  18  to retreat to the original position and withdraw the syringe needle  74  from the patient. 
         [0135]    Note that an indication showing the operation end may be displayed on the display unit  26   b  or the completion may be informed by sound after the end of the withdrawal operation of the first drive unit  16 . 
         [0136]    In the above-described manner, the automatic injection device  10  according to the present invention can automatically perform the puncture with the syringe needle  74 , the infusion of a drug solution, and the withdrawal of the syringe needle  74 . 
         [0137]    Here, in the automatic injection device  10  of the example shown in the diagrams, the configuration is employed in which the second drive unit  18  is placed on the base  36  of the first drive unit  16  and moves integrally with the syringe holder  20 . However, the present invention is not limited thereto and a configuration in which the second drive unit  18  is fixed to the housing  12  may be employed. 
         [0138]    When the configuration in which the second drive unit  18  is fixed to the housing  12  is employed, the second drive unit  18  moves the pressing member  44  at the same speed as the advance speed (or retreat speed) of the syringe holder  20  in the movement of the syringe holder  20  by the first drive unit  16  for example. 
         [0139]    Specifically, first, in the puncture operation by the first drive unit  16 , the second drive unit  18  makes the pressing member  44  advance at the same speed as the puncture speed simultaneously with the operation of the first drive unit  16 . Next, the second drive unit  18  makes the pressing member  44  advance to infuse a drug solution at a predetermined infusion rate during the stop of the operation of the first drive unit  16 . After the elapse of a predetermined stop time, in withdrawal operation by the first drive unit  16 , the second drive unit  18  makes the pressing member  44  retreat at the same speed as the withdrawal speed simultaneously with the operation of the first drive unit  16 . 
         [0140]    Alternatively, as another example of the configuration in which the second drive unit  18  is fixed to the housing  12 , a configuration may be employed in which the locking groove  44   a  is not formed in the pressing member  44  and the pressing member  44  only presses the flange  76   a  of the plunger  76  and is not locked. 
         [0141]    In this case, after the syringe holder  20  on which the syringe  70  is placed moves and puncture is performed by the first drive unit  16 , the second drive unit  18  moves the pressing member  44  to the position of the flange  76   a  of the plunger  76  and then makes the pressing member  44  advance to infuse a drug solution at a predetermined infusion rate. Thereafter, the second drive unit  18  makes the pressing member  44  retreat to the original position and then withdrawal operation by the first drive unit  16  is carried out. 
         [0142]    When the configuration in which the second drive unit  18  is fixed to the housing  12  and does not move is employed as above, the mass of the moving object moved by the first drive unit  16  becomes lighter and thus recoil in puncture becomes smaller. Furthermore, the output power of the first motor  32  can be decreased and weight reduction can be achieved by using a small-size motor. 
         [0143]    On the other hand, when the configuration is employed in which the second drive unit  18  is placed on the base  36  of the first drive unit  16  and moves integrally with the syringe holder  20 , control of the operation can be simplified. 
         [0144]    Furthermore, although the configuration in which a drug solution is automatically infused by the second drive unit  18  is employed in the example shown in the diagrams, the present invention is not limited thereto and a configuration in which only puncture operation by the first drive unit  16  is automatically carried out may be employed as a configuration in which the automatic injection device  10  does not have the second drive unit  18 . For example, when a drug solution is applied on the syringe needle  74  to be administered, it is enough to automatically perform only puncture. Alternatively, a configuration in which only puncture is automatically performed and a drug solution is manually infused by an operator may be employed. 
         [0145]    In addition, in the example shown in the diagrams, the configuration is employed in which the cover  14  has the holding parts  14   a  and the holding parts  14   a  hold the syringe  70  to prevent the syringe  70  from breaking away from the syringe holder  20 . However, the configuration is not limited thereto and a configuration in which the syringe holder  20  has a fixing instrument for fixing the syringe  70  may be employed. 
         [0146]    Moreover, in the present embodiment, the configuration is employed in which the first drive unit  16  makes the syringe holder  20  retreat to carry out withdrawal operation of the syringe needle  74  after the elapse of a predetermined stop time after infusion operation of a drug solution by the second drive unit  18 . However, the configuration is not limited thereto and the following configuration may be employed. Specifically, the time from the completion of puncture by the syringe needle  74  through an advance of the syringe holder  20  by the first drive unit  16  is treated as the predetermined stop time and the first drive unit  16  makes the syringe holder  20  retreat to carry out withdrawal operation of the syringe needle  74  after the elapse of the predetermined stop time from the puncture completion. 
         [0147]    Furthermore, the present invention is not limited also to the configuration in which the first drive unit  16  carries out withdrawal operation after the elapse of the predetermined stop time and the following configuration may be employed. Specifically, the infusion pressure relating to drug solution infusion by the second drive unit  18  is measured and the withdrawal operation by the first drive unit  16  is carried out when the infusion pressure has become equal to or lower than a predetermined threshold. 
         [0148]    Specifically, a pressure sensor to measure the pressure applied from the plunger  76  is disposed to the pressing member  44  and the pressure applied to the pressure sensor is measured. Because it takes a certain amount of time for a drug solution infused into a body to diffuse in the body, the pressure applied from the drug solution to the plunger  76  is high immediately after the infusion of the drug solution. As time passes, the drug solution diffuses in the body and the pressure applied from the drug solution to the plunger  76  gradually decreases. Therefore, by carrying out withdrawal operation by the first drive unit  16  when the infusion pressure measured by the pressure sensor has become equal to or lower than a predetermined threshold, the leakage of the drug solution when the syringe needle  74  is withdrawn can be prevented. Furthermore, pressure abnormality occurs if a drug solution is not infused to a predetermined site in a hypodermis, muscle, or blood vessel but accidentally infused into different tissue. Thus, erroneous administration can be forestalled by sensing the abnormality. 
         [0149]    In addition, in the example shown in the diagrams, the distal portion including the insertion hole  12   a , into which the syringe needle  74  is inserted, is monolithically formed in the housing  12 . However, the present invention is not limited thereto and the distal portion including the insertion hole  12   a  may be replaceably configured as a separate member. 
         [0150]    The distal portion of the housing  12  is a part that gets contact with an injection site of a patient and the syringe needle  74  is inserted through it. Thus, there is a possibility that a leaked drug solution and blood by bleeding attach to the distal portion and there is a fear that infection or the like becomes a problem. Therefore, by replaceably configuring the distal portion including the insertion hole  12   a  as a separate member from the housing  12 , the distal portion, which gets contact with an injection site of a patient, can be kept clean and infection or the like can be prevented. 
         [0151]    Moreover, in the above-described embodiment, the configuration is employed in which an operator manually carries out position adjustment of the distal end position of the syringe needle  74  in setting the syringe  70  in the automatic injection device  10  by operating the operation unit  26 . However, the present invention is not limited thereto and a configuration in which the distal end position of the syringe needle  74  is automatically adjusted may be employed. For example, a configuration may be employed in which an optical sensor is disposed at the distal part in the housing  12  to measure the distal end position of the syringe needle  74  and the first drive unit  16  is made to cause advance/retreat to carry out position adjustment according to the measurement result. 
         [0152]    Note that there is no particular limit to the range of the position (distance from the abutting surface  12   b  (insertion hole  12   a ) of the housing  12 ) of the distal end of the syringe needle  74  in the state in which the syringe  70  is set in the automatic injection device  10 . However, it is preferable for the distal end to have a sufficient distance to accelerate the syringe needle  74  to a set puncture speed by the time when the distal end of the syringe needle  74  reaches the skin surface of a patient and puncture is started, according to the performance of the first drive unit  16 , the mass of the syringe holder  20  and the second drive unit  18 , and so forth. 
         [0153]    Furthermore, in the example shown in the diagrams, the configuration is employed in which the first drive unit  16  is controlled by the control unit  22  to perform puncture at a set constant puncture speed. However, the present invention is not limited thereto and the puncture speed may be changed in the middle of puncture. For example, the puncture speed may be variably controlled in such a manner that puncture is performed at a high puncture speed until reaching a skin&#39;s dermis layer and is then performed at a low puncture speed after that. 
         [0154]    In addition, in the case of using such an automatic injection device, the syringe  70  in which the same kind of drug solution is housed is used for one patient basically. Therefore, it is enough that initially operating conditions such as the puncture speed, the puncture depth, the infusion amount of a drug solution, and the stop time are set and there is no need to set the operating conditions in every injection. 
         [0155]    Moreover, a configuration may be employed in which the automatic injection device  10  has a detailed setting mode in which operating conditions such as the puncture speed, the puncture depth, the infusion amount of a drug solution, the infusion rate, and the stop time can be set in detail in making input from the operation unit  26  and a simple setting mode in which only the puncture speed can be set. The following way may be employed. Specifically, when the automatic injection device is used for the first time, a doctor sets the operating conditions in detail in the detailed setting mode. In the subsequent injections, only the puncture speed is set again in the simple setting mode depending on the patient&#39;s preference. Furthermore, the setting of the puncture speed in the simple setting mode is not limited to numerical value input. For example, the puncture speed may be set through choice from puncture speeds set in advance at five stages by an indication of “1” to “5” or the like. 
         [0156]    Furthermore, in the above-described embodiment, the automatic injection device  10  is made to directly abut against a puncture site across the abutting surface  12   b . However, it is enough that the distance between the syringe needle  74  and the puncture site can be identified and a fixing auxiliary instrument to settle the relative positions of the puncture site and the syringe needle  74  may be disposed between the automatic injection device  10  and the puncture site. 
       WORKING EXAMPLES 
       [0157]    Next, the range of a preferred puncture speed will be described in more detail by using working examples. 
         [0158]    The inventors of the present application have found that following facts. Specifically, in puncture by a syringe needle, the penetration resistance decreases depending on the puncture speed. In addition, suppression of the pain response is found in rat electromyography and the pain response evoked by puncture disappears if the puncture speed is higher than a certain puncture speed. Although what kind of behavior causes such an effect in pain sensing nerves of the skin is unclear, due to the high-speed puncture, an action potential would not be generated in the Na ion channel, the Ca ion channel, and so forth to transmit excitement for stimulating nerve terminals that are the pain sensing nerves of the skin. 
         [0159]    Therefore, the inventors of the present application made a puncture device that could perform puncture similar to that by the automatic injection device  10  and measured the relationship among the puncture speed, the penetration resistance, and electromyography by using this puncture device to obtain the range of a preferred puncture speed with which no pain response was evoked. 
         [0160]    In  FIG. 6 , a puncture device  100  is shown. 
         [0161]    The puncture device  100  is an experimental device fabricated to obtain the relationship between the puncture speed and the electromyography response. It is so configured that various syringe needles can be mounted at the tip and the puncture depth, the puncture speed, the withdrawal speed, and so forth can be set. It performs puncture at the set puncture speed. Note that this puncture device  100  has functions similar to those of the device according to the present invention basically. 
         [0162]    The puncture device  100  has the following components: a holder  102  that holds a load cell  112  to which the syringe needle  74  is attached at the tip; a linear actuator  104  that makes the holder  102  advance to perform puncture; an X-table  108   a  and a Z-table  108   b  that are disposed between the holder  102  and the linear actuator  104  and are to adjust the position of the holder  102 ; a controller  110  that controls operation of the linear actuator  104 ; and a base  106  on which to place the linear actuator  104 . 
         [0163]    Here, the linear actuator  104  is composed of a stepping motor and a ball screw. 
         [0164]    In the puncture device  100 , the controller  110  makes the linear actuator  104  advance at a set puncture speed to perform puncture. 
       Working Example 1 
       [0165]    As working example 1, puncture was performed in the plantar regions of rats by using the puncture device  100 . 
         [0166]    The puncture speed of the puncture device  100  was set to 3 mm/s. The puncture depth was set to 3 mm. The stop time was set to two seconds. The withdrawal speed was set to 20 mm/s. 
         [0167]    Furthermore, as the syringe needle  74 , a syringe needle with a thickness of 27 G (27 G Neolus needle φ0.40×19 mm, made by Terumo Corporation) was used. 
         [0168]    In addition, the distance between the tip of the syringe needle  74  before operation start and a puncture site was set to 3 mm. That is, a configuration in which the puncture device  100  made the syringe needle advance by 6 mm was employed. 
         [0169]    Moreover, as the rats of the puncture subject, 7- to 8-week-old SD male rats were purchased from Charles River Laboratories Japan, Inc. and were used for the experiment after an acclimatization period of one week was set. The weights of the animals at the time of the experiment were 273 g to 314 g. 
         [0170]    The rats were anesthetized by inhalation of isoflurane (Escain made by Mylan Inc.). The concentration relative to air in anesthesia induction was set to 4%/Air and the concentration in recording and measurement was set to 1.4 to 1.6%/Air. Furthermore, during the anesthesia, the temperature was heated to 42° C. by a keep-warm mat to keep the body temperature constant. 
         [0171]    Under such conditions, puncture was performed by using the puncture device  100  and the muscle action potential and the penetration resistance were measured. For the measurement, on six rats, each plantar region was punctured total four times with slight offsets of the puncture position. Note that the needle was replaced in each use. 
         [0172]    As the load cell  112 , a micro load cell (RX-1/CPM-N made by Aikoh Engineering Co., Ltd.) was used to measure the penetration resistance. 
         [0173]    Furthermore, as the state of the puncture, how the syringe needle  74  was inserted into the rat plantar skin was observed at a rate of 4000 frames/second by using a high-speed microscope (VW-9000 made by Keyence). 
         [0174]    A marking was made at a position of 3 mm from the tip of the syringe needle  74  so that the position of insertion into the skin could be discriminated. The movement distance of the needle per unit time was measured from high-speed microscope images and the actual puncture speed was calculated. 
         [0175]    In  FIG. 7 , a graph of the penetration resistance measured when puncture with the 27 G needle was performed at a puncture speed of 15 mm/s is shown. Here, in  FIG. 7 , the abscissa is defined as the time [ms] and the ordinate is defined as the resistance value (penetration resistance) [mN]. Furthermore, the time when the tip of the syringe needle  74  got contact with the skin was read from high-speed microscope images and is indicated by a dotted line in  FIG. 7 . Similarly, the time when a jaw portion of the bevel of the syringe needle  74  reached the skin surface was read and is indicated by an arrow y in  FIG. 7 , and the time when the puncture with the syringe needle  74  ended (timing of a puncture depth of 3 mm) was read and is indicated by an arrow z in  FIG. 7 . 
         [0176]    Furthermore, the resistance value at the timing when the puncture with the syringe needle  74  ended (puncture depth was 3 mm) (arrow z) is shown in  FIG. 8(A) . 
         [0177]    Furthermore, for recording of the muscle action potential (hereinafter, referred to also as the electromyography), a needle-shaped bipolar electrode was employed as a recording electrode and an aluminum foil as an earth electrode was attached to the breast skin after dehairing. After amplification by a factor of twenty thousand by a high-sensitivity bioelectric amplifier (ER-1 Extracelular Amplifier made by CYGNUS TECHNOLOGY Inc.), an action potential waveform was displayed on a screen of a personal computer through PowerLab 16/30 (made by ADInstruments). Note that low-pass filter and high-pass filter of the high-sensitivity bioelectric amplifier were set to 3 kHz and 300 Hz, respectively, in order to minimize noise in the potential measurement. 
         [0178]    Furthermore, to facilitate evocation of the paw withdrawal reflex (spinal reflex), the rat was retained with the paw stretched as much as possible. 
         [0179]    Before incision of the thigh skin, to check muscle contraction, a clip-type stimulating electrode (TH207-123 made by Unique Medical) was used to clamp the dorsum and sole of the rat hind paw and pain electrical stimuli (pulse conditions: 40 Hz, 2 ms, 5 mA) were given by an electrostimulator (BSI-950 Biphasic Stimulus Isolator made by Dagan Corporation). 
         [0180]    A line of about 1 cm was drawn at the contracted muscle part and the part was incised. The muscle was exposed and the pain electrical stimuli were given again, and the recording electrode probe was surely indwelled at the contracted muscle part. Thereafter, the pain electrical stimuli were performed again and the anesthetic depth of the rat was fine-tuned from the response strength of the electromyography action potential (maximum amplitude value). 
         [0181]    The muscle action responses evoked by electrical stimuli and pressure stimuli were recorded in a recording device (PowerLab made by ADInstruments) at a sampling interval of 0.1 ms. 
         [0182]    The recorded data was subjected to 30-Hz high-pass digital filter processing in the recording device to remove the influence of body motion caused by the electrical stimuli and pressure stimuli. 
         [0183]    Regarding the recorded data of the muscle action potential, after the data was subjected to full-wave rectification, the position of insertion of the needle into the skin was checked by the high-speed microscope and the range from the point at which the needle tip got contact with the skin (insertion start) to the point at which the needle tip was inserted by 3 mm (insertion stop) was integrated to calculate the electromyography (EMG) response magnitude as Total Power (μV·sec). The value of integral of the action potential was obtained based on a method by Ando et al. (Ando R, et al., Br. J. Anaesth., 95:384, 2005). 
         [0184]    In  FIG. 8(A) , the resistance value when puncture with the 27 G needle was performed at a puncture speed of 3 mm/s is shown. In  FIG. 8(B) , the measured EMG response magnitude (Total Power) is shown. Note that, in  FIG. 8(A) , the average and standard error of the measured resistance value are shown. Similarly, in  FIG. 8(B) , the average and standard error of the measured Total Power are shown. 
         [0185]    Here, although the EMG response magnitude was measured by using rats in the present working example, the human body would also show a tendency similar to that of the rat basically. 
       Working Example 2 
       [0186]    Except for that the puncture speed was changed to 15 mm/s, the penetration resistance and the EMG response magnitude were obtained similarly to working example 1. 
         [0187]    The resistance value at the timing when the puncture with the syringe needle  74  ended (puncture depth was 3 mm) (arrow z) is shown in  FIG. 8(A)  and the EMG response magnitude (Total Power) is shown in  FIG. 8(B) . 
       Working Example 3 
       [0188]    Except for that the puncture speed was changed to 75 mm/s, the penetration resistance and the EMG response magnitude were obtained similarly to working example 1. 
         [0189]    The resistance value at the timing when the puncture with the syringe needle  74  ended (puncture depth was 3 mm) (arrow z) is shown in  FIG. 8(A)  and the EMG response magnitude (Total Power) is shown in  FIG. 8(B) . 
       Working Example 4 
       [0190]    Except for that the thickness of the syringe needle  74  was changed to 31 G (Microfine Plus φ 0.25×5 mm made by Becton, Dickinson and Company), the penetration resistance and the EMG response magnitude were obtained similarly to working example 1. 
         [0191]    The resistance value at the timing when the puncture with the syringe needle  74  ended (puncture depth was 3 mm) (arrow z) is shown in  FIG. 9(A)  and the EMG response magnitude (Total Power) is shown in  FIG. 9(B) . 
       Working Example 5 
       [0192]    Except for that the puncture speed was changed to 15 mm/s, the penetration resistance and the EMG response magnitude were obtained similarly to working example 4. 
         [0193]    The resistance value at the timing when the puncture with the syringe needle  74  ended (puncture depth was 3 mm) (arrow z) is shown in  FIG. 9(A)  and the EMG response magnitude (Total Power) is shown in  FIG. 9(B) . 
       Working Example 6 
       [0194]    Except for that the puncture speed was changed to 75 mm/s, the penetration resistance and the EMG response magnitude were obtained similarly to working example 4. 
         [0195]    The resistance value at the timing when the puncture with the syringe needle  74  ended (puncture depth was 3 mm) (arrow z) is shown in  FIG. 9(A)  and the EMG response magnitude (Total Power) is shown in  FIG. 9(B) . 
         [0196]    As shown in  FIG. 7 , it turns out that the resistance value of the penetration resistance increased as the syringe needle  74  was inserted into the skin to a deeper position and showed the first peak (arrow y) when the jaw portion of the bevel reached the skin. It turns out that, thereafter, the resistance value temporarily decreased and then increased again as the cannula part of the needle went into a deeper position to show the maximum value at the timing of stop of the puncture (puncture depth was 3 mm, arrow z). It turns out that, thereafter, the resistance value remained near a certain value during the stop of the movement of the syringe needle  74  (for two seconds) and rapidly decreased when withdrawal of the syringe needle  74  was started and the resistance value returned to the basal level upon the completion of the withdrawal. 
         [0197]    Furthermore, from  FIGS. 8(A) and 9(A) , it turns out that the resistance value in the puncture was lower with the 31 G syringe needle than with the 27 G needle, i.e. lower when the thickness of the syringe needle was smaller, regardless of the puncture speed. 
         [0198]    Moreover, it turns out that the resistance value in the puncture became lower in proportion to the puncture speed as the puncture speed became higher in both cases of the 27 G and 31 G syringe needles. 
         [0199]    Note that  FIG. 8  shows the resistance value and the EMG response magnitude of 27 G, and  FIG. 9  shows the resistance value and the EMG response magnitude of 31 G. 
         [0200]    Furthermore, from  FIGS. 8(B) and 9(B) , it turns out that the EMG response magnitude with the thickness 31 G of the syringe needle  74  was half or smaller compared with that with the thickness 27 G when the puncture speed was 3 mm/s or 15 mm/s. 
         [0201]    In addition, it turns out that, when the puncture speed was set to 15 mm/s, the EMG response magnitude greatly decreased compared with that when the puncture speed was 3 mm/s in both cases of the thicknesses 31 G and 27 G of the syringe needle  74 . Moreover, when the puncture speed was set to 75 mm/s, the EMG response did not appear at all regardless of the thickness of the syringe needle  74 . 
         [0202]    The measurement values were shown by the average and the standard error when puncture was performed four times on each of the six rats, and a statistical significance test was performed by using one-way analysis of variance (**: p&lt;0.01). 
         [0203]    From the above results, it turns out that, when the thickness of the syringe needle is in a range of 18 G to 34 G, setting the puncture speed equal to or higher than 10 mm/s can greatly decrease the EMG response magnitude and allows puncture with almost no pain felt. Furthermore, it turn out that setting the puncture speed equal to or higher than 25 m/s can make the EMG response almost zero and allows almost painless puncture. Moreover, it turns out that setting the puncture speed equal to or higher than 75 m/s can avoid generation of the EMG response and allows sure painless puncture. 
         [0204]    Although the automatic injection device of the present invention is described in detail above, the present invention is not limited to the above-described embodiment and various kinds of improvements and changes may be made without departing from the scope of the present invention. 
       DESCRIPTION OF REFERENCE SYMBOLS 
       [0000]    
       
           10  Automatic injection device 
           12  Housing 
           12   a  Insertion hole 
           12   b  Abutting surface 
           14  Cover 
           14   a  Holding part 
           16  First drive unit 
           18  Second drive unit 
           20  Syringe holder 
           20   a  Recess 
           20   b  Locking groove 
           22  Control unit 
           26  Operation unit 
           26   a  Start button 
           26   b  Display unit 
           28  Battery 
           32  First motor 
           34  First motion converter 
           34   a ,  42   a  Screw shaft 
           34   b ,  42   b  Block 
           34   c ,  42   c  Guide shaft 
           36  Base 
           40  Second motor 
           42  Second motion converter 
           44  Pressing member 
           70  Syringe 
           72  Syringe barrel 
           72   a ,  76   a  Flange 
           74  Syringe needle 
           76  Plunger 
           100  Puncture device 
           102  Holder 
           104  Linear actuator 
           106  Base 
           108   a  X-table 
           108   b  Z-table 
           110  Controller 
           112  Load cell