JP5995127B2 - Drug injection device - Google Patents

Description

The present invention relates to a drug injection device .

  Conventionally, CED (Convection-enhanced delivery) has been developed as a method for injecting a drug into the brain of a patient. CED is a method of administering a drug at a high concentration and in a wide range to the brain region by continuously injecting a drug into a brain cell gap from a needle for injection placed in the brain. According to CED, since a drug can be injected by bypassing the blood brain barrier, a drug can be efficiently delivered into the brain.

Using this conventional CED, an experiment of drug injection is performed by the present inventors. In this experiment, when 300 μL of 4% Evans blue dye (4% Evans blue dye) was injected into the brain of a cynomolgus monkey (Macaca fuscicularis) as a drug in a predetermined injection pattern over 140 minutes, It has been confirmed that the drug has spread in a region of 700 mm ³ (for example, see Non-Patent Document 1).

  However, in the conventional CED, since the drug is micro-injected at an injection rate of about 1 to 5 μL / min, it usually takes several days to administer the necessary amount. Thus, a method has been developed to improve the drug injection efficiency by applying ultrasonic vibration to the brain surface when injecting a drug with CED (for example, see Non-Patent Document 2). In addition, an ultrasonic vibrator is attached to the base of the needle that injects the drug with the CED, and the ultrasonic vibrator is vibrated on the surface of the brain, and the ultrasonic vibration is also transmitted to the needle disposed in the brain. An apparatus for improving the above has been developed (for example, see Non-Patent Document 3 or Patent Document 1).

  In addition, although it has been reported that it is effective to give an ultrasonic vibration of 80 to 180 kHz for drug delivery in the brain, an experiment is actually performed only with an ultrasonic vibration of 1.34 MHz. The authenticity is unknown (see, for example, Non-Patent Document 4).

Sugiyama S., et al., “Safety and feasibility of convection-enhanced delivery of nimustine hydrochloride co-infused with free gadolinium for real-time monitoring in the primate brain”, Neurological Research, 2012, 34 (6), 581-7 Liu Y., et al., “Ultrasound-Enhanced Drug Transport and Distribution in the Brain”, AAPS PharmSciTech, September 2010, Vol.11, No.3, p.1005-1017 Lewis G.K.Jr., et al., “Ultrasound-assisted convection-enhanced delivery to the brain in vivo with a novel transducer cannula assembly”, J Neurosurg, December 2012, Volume 117, p.1128-1140 Mitragotri S., et al., “Healing sound: the use of ultrasound in drug delivery and other therapeutic applications”, Nature Reviews, March 2005, Volume 4, p.255-260

International Publication WO2011 / 109735

  The method of applying ultrasonic vibration to the brain surface described in Non-Patent Document 2 is effective for lesions in the vicinity of the brain surface, but a brain such as a malignant brain tumor or a neurodegenerative disease such as Parkinson's disease. However, there is a problem that the improvement of the drug injection efficiency by the ultrasonic vibration can hardly be expected for the lesion that requires the drug injection into the deep part. In addition, in the device that transmits ultrasonic vibration to the needle for injecting a medicine described in Non-Patent Document 3 and Patent Document 1, when transmitting through a hollow needle, ultrasonic vibration such as a decrease in sound pressure or a frequency change is generated. Since the characteristics change, it is considered that improvement in drug injection efficiency by needle vibration is hardly obtained. For this reason, only the effect of ultrasonic vibration on the brain surface can be obtained, and as in Non-Patent Document 2, the improvement of drug injection efficiency by ultrasonic vibration is almost impossible for lesions that require drug injection into the deep part of the brain. There was a problem that could not be expected. In addition to the drug injection into the brain, it is considered that the same problem exists in the drug injection into other parenchymal organs.

The present invention has been made paying attention to such a problem, and can improve the drug injection efficiency in the deep part of the real organ such as the brain, and the lesion that requires the drug injection into the deep part of the real organ such as the brain. An object of the present invention is to provide a drug injecting device capable of enhancing the therapeutic effect on the patient.

To achieve the above object, a drug injection device according to the present invention is a drug injection device for injecting a drug into a patient's parenchymal organ, and is provided with an inner end provided to be inserted into the parenchymal organ. has a There elongated insertion body fulfilling, and generating ultrasonic vibrations, and the insert to the ultrasonic vibration applying ultrasonic generator, a tube capable of discharging said agent to said solid organ from the tip, the The distal end portion of the insert inserted into the parenchymal organ is ultrasonically vibrated in the vicinity of the injection position of the drug, so that the parenchymal organ is vibrated to spread the drug inside the parenchymal organ. It is characterized by that.

Related to the present invention, the drug injection method is a drug infusion method of injecting the drug into the patient's real organ, while injecting the drug into the solid organ, the tip portion of the elongated insert body interior is enriched substantially It is characterized by being inserted into an organ and ultrasonically vibrated.

Related to the present invention, the drug injection method can be preferably performed by the drug infusion device according to the present invention. The drug injecting apparatus according to the present invention and the drug injecting method according to the present invention spread the drug injected into the substantial organ within the substantial organ by ultrasonically vibrating the insert having the tip inserted into the substantial organ. be able to. At this time, the insertion body is not hollow like an injection needle, and the inside of the insertion body is clogged and filled, so that the sound pressure does not decrease and the frequency does not change, and it is an effective characteristic for drug transmission The ultrasonic vibration can be transmitted to the tip of the insert as it is. For this reason, the medicine can be effectively spread over a wide range, and the medicine injection efficiency can be increased.

  In particular, by ultrasonically vibrating the distal end portion of the insertion body in the vicinity of the injection position of the drug, the drug can be more effectively spread over a wide range, and the drug injection efficiency can be further increased. Even in a deep part of a parenchymal organ such as the brain, the drug injection efficiency can be increased by inserting the tip of the insert into the site and injecting the drug while vibrating ultrasonically. For this reason, the therapeutic effect with respect to the lesion | pathological-change which requires chemical | medical agent injection | pouring to the deep part of real organs, such as a brain, can be heightened.

  The parenchymal organs include, for example, the central nervous system such as the cerebrum, cerebellum, and brain stem, the endocrine glands such as the pituitary gland, the thyroid gland, the adrenal gland, the salivary glands such as the parotid gland and the hypothalamus, the digestive organs such as the pancreas, the liver, and the kidneys. Urogenital organs such as gonads such as ovaries and testes, immune organs such as thymus, spleen, and lymph nodes, skeletal and motor organs such as bones and muscles, and sensory organs such as eyeballs. The ultrasonic vibration may be generated in any configuration, but it is preferable that the frequency and amplitude can be controlled by using a piezoelectric element or the like.

  The insert need only have a solid interior rather than being hollow, and may have any cross-sectional shape such as a circle, an ellipse, or a polygon. Moreover, you may comprise the shape which has an unevenness | corrugation in a cross section. The insert may have a sharp tip or may be rounded so that it can be easily inserted into a substantial organ. The outer diameter of the insert is preferably 200 μm to 1 mm so as to be approximately the same thickness as a general injection needle. The insert preferably has a length of about several centimeters to 20 centimeters so that the tip can be inserted at any depth in the target parenchymal organ. Further, a plurality of inserts having different lengths may be prepared and used depending on the insertion depth.

In the pharmaceutical injection device according to the present invention, it is preferable that the distal end portion of the insert is ultrasonically vibrated at 200 to 700 kHz. Related to the present invention, the drug infusion process is preferably ultrasonically vibrating the tip portion of the insert in 200～700KHz. In this case, in particular, the drug injection efficiency can be increased.

  In the pharmaceutical injection device according to the present invention, the ultrasonic wave generation unit connects the vibrator and the insert so that the vibrator vibrates ultrasonically and the ultrasonic vibration of the vibrator is transmitted to the insert. It is preferable to have a vibration transmitting member formed so that the outer diameter gradually decreases from one end portion in contact with the vibrator toward the other end portion in contact with the insert. In this case, the vibration transmission member can efficiently transmit the ultrasonic vibration of the vibrator to the insertion body, and the energy efficiency is good. The vibration transmitting member is preferably made of a cone whose bottom surface is in contact with the vibrator and whose tip is connected to the insertion body, for example. Note that the vibration transmitting member may have other shapes and configurations as long as ultrasonic vibrations can be efficiently transmitted and input to the insert.

  In the drug injection device according to the present invention, the insert may have a groove along the length direction at least on a side surface of the distal end portion, and the distal end portion of the tube may be inserted into the groove. In this case, the distal end portion of the insertion body and the distal end portion of the tube can be integrated, and the tube can be inserted into the substantial organ simultaneously with the insertion body. In addition, by aligning the tip opening of the tube that discharges the drug with the position of the tip of the insert, the tip of the insert can be ultrasonically vibrated in the vicinity of the injection position of the drug, and the drug injection efficiency can be improved. Can be increased.

Further, the drug injection device according to the present invention is a drug injection device for injecting a drug into a patient's real organ, and is a long and thin elongated insert provided to be inserted into the real organ. And an ultrasonic generator that generates ultrasonic vibrations and applies the ultrasonic vibrations to the insert, and the insert is provided on a side surface so as to extend to the tip along the length direction. And a covering material covering the upper part of the groove so that the groove opens at the tip, the drug can be passed through the groove , and the drug can be discharged from the opening at the tip of the groove to the parenchymal organ . The distal end portion of the insert inserted into the parenchymal organ is ultrasonically vibrated in the vicinity of the injection position of the drug, thereby vibrating the parenchymal organ and spreading the drug inside the parenchymal organ. It may be. Also in this case, the site for injecting the drug can be inserted into the parenchymal organ simultaneously with the insert. In addition, the tip of the insert can be ultrasonically vibrated in the immediate vicinity of the drug injection position, and the drug injection efficiency can be further increased. Compared with the case where the tube is inserted into the groove, the thickness of the tube can be omitted, and the cross-sectional area of the flow path through which the drug flows can be increased. For this reason, it is advantageous when reducing the diameter of the insert. The covering material is preferably made of a thin film, may have a sheet shape, may be attached so as to cover only the upper part of the groove, has a cylindrical shape, and an insert is inserted therein. May be attached.

ADVANTAGE OF THE INVENTION According to this invention, the chemical | medical agent injection apparatus which can improve the chemical | medical agent injection | pouring efficiency in the deep part of real organs, such as a brain, and can improve the therapeutic effect with respect to the lesion | pathological-requirement which requires the chemical | medical agent injection | pouring to the deep part of real organs, such as a brain. Can be provided.

It is (a) side view of the chemical injection device of an embodiment of the invention, (b) sectional view of an insert and a tube, and (c) sectional view of an insert showing a modification. (A) a graph showing frequency characteristics at the tip of the insert when ultrasonic vibration is applied, (b) applied voltage and sound pressure at a resonance frequency of 250 to 300 kHz of the insert shown in FIG. (C) is a graph which shows the relationship between the applied voltage and the sound pressure in the resonance frequency 520-540 kHz of an insertion body. When (A) ultrasonic vibration is not applied to the test of drug injection into the rat brain by the drug injection device shown in FIG. 1, (B) frequency 252 kHz, applied voltage 30 V, (C) frequency 252 kHz, applied voltage 60 V, (D) Microscopic photograph (20 times) in the brain of a rat when an ultrasonic vibration having a frequency of 532 kHz and an applied voltage of 30 V and (E) a frequency of 532 kHz and an applied voltage of 60 V is applied. It is a graph which shows the spread of the chemical | medical agent with respect to different ultrasonic vibration of the injection | pouring test of the chemical | medical agent in the rat brain by the chemical | medical agent injection apparatus shown in FIG. In the test of drug injection into the rat brain by the drug injection device shown in FIG. 1, (A) when no ultrasonic vibration is applied, (B) MRI when ultrasonic vibration with a frequency of 260 kHz and an applied voltage of 60 V is applied. It is a graph which shows the result of having measured the area of the range of an image and (C) different signal strength. It is a top view which shows the injection | pouring position of the chemical | medical agent of the injection | pouring test of the chemical | medical agent in the brain of the cynomolgus monkey by the chemical | medical agent injection apparatus shown in FIG. It is a graph which shows the breadth of a chemical | medical agent when an insertion body and a tube are inserted separately of the injection | pouring test of the chemical | medical agent in the rat brain by the chemical | medical agent injection apparatus shown in FIG. At the tip of (a) a 15 cm long insert of the drug injection device shown in FIG. 1, (b) a 4 cm long insert, (c) a 15 cm long hollow needle when ultrasonic vibration is applied It is a graph which shows the frequency characteristic. (A) Insert the 15 cm long insert of the drug injection device shown in FIG. 1, (b) Insert a 15 cm long hollow needle into an agarose gel and apply ultrasonic vibration to the frequency characteristics at the tip. It is a graph to show.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
1 to 9 show a drug injection device according to an embodiment of the present invention and a drug injection method according to the embodiment of the present invention .
As shown in FIGS. 1 (a) and 1 (b), a drug injection device 10 is a drug injection device 10 for injecting a drug into a substantial organ of a patient, and includes an insert 11, an ultrasonic generator 12, and a tube. 13.

  As shown in FIG. 1A, the insert 11 has an elongated rod shape so that the distal end portion 11a can be inserted into a substantial organ. As shown in FIG. 1 (b), the insert 11 has a substantially circular cross-sectional shape, and the inside is not hollow like an injection needle but is solid. The insert 11 has a groove 11b on the side surface that extends along the length direction from the tip 11a to the other end.

  As shown in FIG. 1A, the ultrasonic wave generation unit 12 includes a vibrator 21 made of a piezoelectric element and a vibration transmission member 22 having a conical shape. The vibrator 21 is configured to vibrate ultrasonically so that the frequency and amplitude can be controlled. The vibration transmitting member 22 has the vibrator 21 attached to the bottom surface 22a and the other end of the insert 11 attached to the tip 22b to connect the vibrator 21 and the insert 11. The vibration transmission member 22 has an outer diameter that gradually decreases from the bottom surface 22 a toward the tip 22 b, so that the ultrasonic vibration of the vibrator 21 can be efficiently transmitted to the insert 11. The vibration transmitting member 22 may have other shapes and configurations as long as the ultrasonic vibration can be efficiently transmitted and input to the insert.

  As shown in FIGS. 1 (a) and 1 (b), the tube 13 is configured such that a medicine can be discharged from the opening at the tip, and the tip is inserted into the groove 11 b of the insert 11. The tube 13 is attached with the opening at the tip aligned with the position of the tip 11 a of the insert 11.

  In the specific example shown in FIGS. 1A and 1B, the insert 11 has an outer diameter of 600 to 650 μm and a depth of the groove 11b of 200 μm. Moreover, there are two types of inserts 11 having a length of 4 cm and 15 cm, and the inserts 11 can be used in accordance with the insertion depth.

The drug injection method according to the embodiment of the present invention can be preferably implemented by the drug injection device 10. The drug infusion method of the embodiment of the present invention, first, a desired site in a patient's real organ, inserting the distal end portion 11a of the insert 11. At this time, since the tube 13 is inserted into the groove 11b of the insert 11, the tube 13 can be inserted into the substantial organ simultaneously with the insert 11. At that site, the tip 11 a of the insert 11 is vibrated ultrasonically by the ultrasonic generator 12 while injecting a drug from the opening at the tip of the tube 13. Thereby, a chemical | medical agent can be inject | poured into the desired site | part of a parenchymal organ, and the chemical | medical agent can be spread inside a parenchymal organ.

In the drug injection device 10 according to the embodiment of the present invention and the drug injection method according to the embodiment of the present invention , the insert 11 is not hollow like an injection needle, and the inside of the insert 11 is clogged and enriched. The ultrasonic vibration can be transmitted to the distal end portion 11a of the insertion body 11 with the characteristics effective for drug transmission. For this reason, the medicine can be effectively spread over a wide range, and the medicine injection efficiency can be increased. In addition, since the distal end portion 11a of the insert 11 is ultrasonically vibrated near the injection position of the drug, the drug can be more effectively spread over a wide range, and the drug injection efficiency can be further increased.

In the drug injection device 10 according to the embodiment of the present invention and the drug injection method according to the embodiment of the present invention, the distal end portion 11a of the insertion body 11 is inserted into the site even in the deep part of the substantial organ, and ultrasonic vibration is performed. The drug injection efficiency can be increased by injecting the drug while making it happen. For this reason, the therapeutic effect with respect to the lesion which needs the chemical | medical agent injection | pouring to the deep part of a parenchymal organ can be heightened. Further, by inserting and using the insert 11 having a different length according to the depth of the site where the drug is injected, efficient drug injection can be performed.

  In addition, as shown in FIG.1 (c), the chemical | medical agent injection apparatus 10 has the coating | covering material 31 which covers the upper direction of the groove | channel 11b so that the groove | channel 11b may open at the front end instead of the tube 13, and a chemical | medical agent is provided in the groove | channel 11b. The medicine may be ejected from the opening at the tip of the groove 11b to the substantial organ. The covering material 31 is made of a thin film, has a cylindrical shape, and is attached with the insert 11 inserted therein. In this case, at the same time as the insertion body 11, the part into which the medicine is injected can be inserted into the substantial organ. Further, the distal end portion 11a of the insert 11 can be ultrasonically vibrated in the immediate vicinity of the drug injection position, and the drug injection efficiency can be further increased. Compared with the case where the tube 13 is inserted into the groove, the thickness of the tube 13 can be omitted, and the cross-sectional area of the flow path for the drug can be increased. For this reason, it is advantageous when the diameter of the insert 11 is reduced.

  1 (a) and 1 (b), an insertion body 11 having a length of 4 cm is used and insertion is performed while changing the frequency of ultrasonic vibration generated by the vibrator 21 from about 100 kHz to 800 kHz. The vibration at the tip of the body 11 was measured. FIG. 2A shows the relationship between the vibration frequency and the sound pressure at the tip of the insert 11 obtained by the measurement. As shown to Fig.2 (a), it was confirmed that the resonant frequency of the front-end | tip of the insertion body 11 is 250-300 kHz and 520-540 kHz.

  Next, the relationship between the voltage applied to the vibrator 21 and the sound pressure at the tip of the insert 11 at resonance frequencies of 250 to 300 kHz and 520 to 540 kHz was examined, and the results are shown in FIGS. c). As shown in FIGS. 2B and 2C, it was confirmed that the sound pressure increased in proportion to the applied voltage. It was also confirmed that the sound pressure at an applied voltage of 60 V at 250 to 300 kHz was substantially equal to the sound pressure at an applied voltage of 30 V at 520 to 540 kHz.

  With respect to the drug injection device 10 shown in FIGS. 1 (a) and 1 (b), a drug injection test into a rat brain was performed using an insert 11 having a length of 15 cm. In the test, 4% Evans blue dye (4% Evans blue dye) was used as a drug, and the tip of the insert 11 was vibrated ultrasonically while injecting 10 μL of the drug into the brain of the rat. The spread of was measured visually. Further, as the ultrasonic vibration, five kinds of vibrations of applied voltage 13V, 30V, and 60V were applied at a frequency of 252 kHz, a frequency of applied voltage 30 V and 60 V, and a frequency of 524 kHz.

  An example of the observation results of drug spread in the rat brain is shown in FIG. 3, and the results of six tests for each of the different ultrasonic vibrations are shown in Table 1. The average value (Mean) and standard of the test are shown in Table 1. A graph showing the deviation (SD) is shown in FIG. For comparison, a test was also conducted on the spread of the drug when no ultrasonic vibration was applied, and the results are also shown ("Control" in FIG. 3, Table 1, and FIG. 4). 4A and 4B, Tukey's multiple comparison test is performed on each data by one-way analysis of variance (One-way ANOVA). Further, in FIG. 4C, Student's t test (Unpaired student's t-test) of two samples is performed.

  As shown in FIG. 3, Table 1, and FIGS. 4 (A) and 4 (B), it was confirmed that by applying ultrasonic vibration, the drug spreads compared to the case where ultrasonic vibration was not applied. Further, as shown in FIG. 4A, when the ultrasonic vibration is 252 kHz, the spread of the drug increases as the applied voltage increases. However, as shown in FIG. When the vibration was 524 kHz, it was confirmed that the spread of the drug hardly changed even when the applied voltage was increased. Further, as shown in FIG. 4C, when the sound pressure is almost the same, the frequency is 252 kHz, the applied voltage is 60 V, and the frequency is 524 kHz, and the applied voltage is 13 V, the former is the drug. It was confirmed that the spread of From this, it can be said that the spread of the medicine can be increased by applying ultrasonic vibration having a small frequency at the same sound pressure.

  Next, using a 5 mM Gd-DTPA contrast agent as a drug, and applying ultrasonic vibration as a vibration with a frequency of 260 kHz and an applied voltage of 60 V, the spread of the drug in the rat brain is measured by MRI. Observed. For comparison, the spread of the drug when no ultrasonic vibration was applied was also observed (“Control”). An example of these test results is shown in FIGS. 5 (A) and 5 (B). The range of the signal intensity of the contrast agent is 10% or more, 20% or more, 30% or more, 40% or more as the spread of the drug. The result of automatic measurement from the image is shown in FIG. For comparison, the results with 4% Evans blue dye (4% EBD) shown in FIG. 4 are also shown in FIG. In FIG. 5C, Student's t test (Unpaired student's t-test) of two samples is performed.

  As shown in FIGS. 5A to 5C, it was confirmed that by applying ultrasonic vibration, the drug spreads compared to the case where ultrasonic vibration is not applied. It was also confirmed that the spread of the drug can be measured from the MRI image and can be applied clinically.

  With respect to the drug injection device 10 shown in FIGS. 1 (a) and (b), a drug injection test into the brain of a cynomolgus monkey (Macaca fuscicularis) was performed using an insert 11 having a length of 15 cm. In the test, 4% Evans blue dye (4% Evans blue dye) was used as a drug, and the injection pattern was the same as that of Non-Patent Document 1, and injection was performed at four locations shown in FIG. Went. Specific injection patterns include 0.2 μL / min for 10 minutes, 0.5 μL / min for 10 minutes, 0.8 μL / min for 10 minutes, 1.0 μL / min for 10 minutes, 1.5 μL / min. 300 μL was injected over 140 minutes in the order of 10 minutes, 2.0 μL / minute for 10 minutes, and 3.0 μL / minute for 80 minutes. Further, the injection position in FIG. 6 is a position shifted by 1 cm forward, backward, left and right from the center position of the head (the position of the star in the figure).

  Further, as the ultrasonic vibration, two kinds of vibrations having a frequency of 263 kHz and an applied voltage of 60 V, and a frequency of 551 kHz and an applied voltage of 60 V were given. Table 2 shows the measurement results for the case where the spread of the drug is measured visually from the MRI image and the case where the range where the MRI signal intensity is 10% or more is automatically measured. The measurement is performed 3 to 4 times for each vibration, and the average value (Mean) and the standard deviation (SD) are obtained.

In Non-Patent Document 1, as a result of performing a similar test without applying ultrasonic vibration, it has been confirmed that the drug has spread to an area of 300 to 700 mm ³ in the brain. On the other hand, as shown in Table 2, it was confirmed that by applying ultrasonic vibration, the drug spread in a region of 800 to 1400 mm ³ in the brain. From this, it can be said that the medicine can be spread over a wide range by ultrasonic vibration, and the medicine injection efficiency can be increased. In addition, from Table 2, it was confirmed that the spread of the drug can be increased when the frequency of the ultrasonic vibration is small with the same applied voltage.

  As the drug injection device 10, an insert 11 having a length of 15 cm is used, and the tube 13 is not inserted into the groove 11 b of the insert 11, but is inserted in close proximity to the brain of the rat, and a drug injection test is performed. It was. In the test, 4% Evans blue dye (4% Evans blue dye) was used as a drug, and the tip of the insert 11 was vibrated ultrasonically while injecting 10 μL of the drug into the brain of the rat. The spread of was measured visually. As ultrasonic vibration, vibration with a frequency of 532 kHz and an applied voltage of 30 V was applied.

  The measurement was performed five times, the measurement results are shown in Table 3, and the mean value (Mean) and standard deviation (SD) are shown in a graph in FIG. For comparison, the measurement of the spread of the drug when no ultrasonic vibration was applied was also performed nine times, and the results are also shown (Table 3, “Control” in FIG. 7). In FIG. 7, Student's t test (Unpaired student's t-test) of two samples is performed.

  As shown in Table 3 and FIG. 7, even if the insert 11 and the tube 13 are not integrated, the distal end portion 11a of the insert 11 is ultrasonically vibrated in the vicinity of the injection position of the drug, thereby effectively It was confirmed that it can be spread over a wide range and drug injection efficiency can be increased.

  Ultrasonic vibration was applied to the 15 cm long and 4 cm inserts 11 of the drug injection device 10 and the 15 cm long hollow needle similar to that used in Non-Patent Document 3 and Patent Document 1. The vibration at the tip was measured. In the measurement, the applied voltage was set to 30 V, and the frequency of ultrasonic vibration was changed in the range of about 100 kHz to 800 kHz. The measurement results are shown in FIG. Note that the inserted body 11 and the hollow needle used have an outer diameter of 600 to 650 μm and have substantially the same outer diameter.

  As shown in FIGS. 8 (a) and 8 (b), the 15 cm insert 11 has a high sound pressure at 200 kHz to 700 kHz, and the 4 cm insert 11 has a sound pressure of 200 kHz to 800 kHz, particularly 500 kHz to 700 kHz. It was confirmed that it would be higher. On the other hand, as shown in FIG. 8 (c), it was confirmed that with a hollow needle, the sound pressure does not increase below 700 kHz, and the sound pressure increases when the frequency is higher than 700 kHz. Thus, it can be said that the insert 11 which is filled and filled is easier to transmit ultrasonic vibrations having a lower frequency than the hollow needle. For this reason, from the results of Example 2 and Example 3, it can be said that the insert 11 can spread the medicine over a wide range compared to the hollow needle, and the medicine injection efficiency is high.

  Next, in order to investigate the frequency characteristics with respect to the ultrasonic vibration in the brain, the insert 11 having a length of 15 cm and the hollow having a length of 15 cm of the drug injection device 10 are placed in an agarose gel having substantially the same density as the tissue in the brain. A needle was inserted and the same measurement was performed. The measurement results are shown in FIG. As shown in FIG. 9A, it was confirmed that the sound pressure was increased at 200 kHz to 800 kHz in the 15 cm insert 11. On the other hand, as shown in FIG. 9B, in the hollow needle, although the sound pressure is slightly high in the vicinity of 300 kHz and in the vicinity of 800 kHz, it was confirmed that the sound pressure is generally low. Therefore, when used in the brain, the insert 11 that is filled and filled is easier to transmit ultrasonic vibration than the hollow needle, can spread the medicine in a wide range, and has high drug injection efficiency. It can be said. From the results of FIGS. 8 and 9, it is considered that the hollow needle has a decrease in sound pressure and a change in frequency.

Since the drug injection device according to the present invention and the drug injection method according to the present invention can enhance the therapeutic effect on a lesion that requires drug injection into the deep part of a parenchymal organ such as the brain, an effective drug distribution in the brain can be obtained. It is effective when used for the treatment of diseases for which therapeutic effects are expected to be improved, such as brain tumors, neurodegenerative diseases such as Parkinson's disease, congenital metabolic disorders such as Gaucher's disease, and epilepsy. . Further, as one of the therapeutic methods expected to improve the therapeutic effect by obtaining an effective drug distribution in the brain, there is gene therapy, the drug injection device according to the present invention and the drug injection related to the present invention The method can also be expected to be the basis for the development of effective gene therapy.

DESCRIPTION OF SYMBOLS 10 Drug injection apparatus 11 Insert 11a Tip part 11b Groove 12 Ultrasonic wave generation part 21 Vibrator 22 Vibration transmission member 22a Bottom face 22b Tip 13 Tube

Claims (5)

A drug injection device for injecting a drug into a patient's real organ,
A long and thin insert that is provided so that the tip can be inserted into the parenchymal organ,
An ultrasonic generator that generates ultrasonic vibrations and applies the ultrasonic vibrations to the insert;
A tube capable of discharging the drug from the tip to the parenchymal organ ;
The distal end portion of the insert inserted into the parenchymal organ is ultrasonically vibrated in the vicinity of the injection position of the drug, so that the parenchymal organ is vibrated to spread the drug inside the parenchymal organ. drug infusion device, characterized in that there. The insert has a groove along the length direction at least on a side surface of the distal end portion,
The drug injection device according to claim 1, wherein a tip of the tube is inserted into the groove. A drug injection device for injecting a drug into a patient's real organ,
A long and thin insert that is provided so that the tip can be inserted into the parenchymal organ,
An ultrasonic generator that generates ultrasonic vibration and applies the ultrasonic vibration to the insert,
The insert has a groove provided on the side surface so as to extend to the tip portion along the length direction, and a covering material that covers the groove so that the groove opens at the tip.
The drug can be passed through the groove , and the drug can be discharged into the parenchymal organ from an opening at the tip of the groove, and the distal end of the insert inserted into the parenchymal organ is placed in the vicinity of the injection position of the drug. A drug injection device configured to vibrate the parenchymal organ and to spread the drug within the parenchymal organ by sonic vibration .   The ultrasonic wave generation unit connects the vibrator and the insert to transmit the ultrasonic vibration of the vibrator to the insert and transmits the ultrasonic vibration of the vibrator to the insert, and from one end in contact with the vibrator. The drug injection device according to any one of claims 1 to 3, further comprising a vibration transmission member formed so that an outer diameter gradually decreases toward the other end contacting the insert. . The drug injection device according to any one of claims 1 to 4, wherein the distal end portion of the insert is ultrasonically vibrated at 200 to 700 kHz.