Needleless syringe

Abstract

To provide a low-invasive medicine injection method capable of achieving an effect equivalent to that of a conventional injection by a patient himself / herself.SOLUTION: A needleless syringe 1 includes: a substrate 11; a conductive layer 12 arranged on the substrate 11; an insulation layer 13 arranged so as to be stacked on the conductive layer 12, for arranging a medicine particle to be injected on a surface opposite to the conductive layer 12; and a voltage application part 14. The conductive layer 12 and the insulation layer 13 are formed with a bridge part 20 having a narrow width including a region in which the medicine particle is arranged. When the sum of a heat of fusion and heat of evaporation of the conductive layer 12 is e0, the voltage application part 14 applies a voltage equal to or higher than e0 and equal to or less than 1.5 e0 to the bridge part 20 of the conductive layer 12.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to needleless injectors. [Background technology]

[0002] One known method for gene transfer into animal or plant cells is the particle bombardment method, in which nanoparticles coated with drugs or DNA are ejected at high speed to penetrate target cells (see, for example, Non-Patent Document 1). [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] V. Vasil et al, “Herbicide Resistant Fertile Transgenic Wheat Plants Obtained by Microprojectile Bombardment of Regenable Embryogenic Callus,” Nat. Biotechnol. 10, pp.667-674 (1994). Summary of the Invention [Problem to be solved by the invention]

[0004] From the perspectives of curbing rising medical costs, appropriately allocating medical resources in the event of an outbreak or disaster, and securing treatment options in extreme medical environments such as remote islands and outer space, there is an increasing need for self-medication, which allows patients to treat and care for themselves without having to go to a medical institution.

[0005] The technology described in Non-Patent Document 1 can be one solution to the above problem. The particle acceleration here is based on the high-speed plastic deformation phenomenon of the membrane surface caused by shock waves generated in a small, self-rupturing shock tube. However, the particle injection speed achievable with this method is limited to about 300 m / s, taking operational safety into consideration. This is not sufficient to achieve drug administration to patients with the same effect as a regular injection.

[0006] The present disclosure has been made in light of these circumstances, and its purpose is to provide a minimally invasive drug injection technique that allows patients to achieve the same effect as conventional injections by themselves. [Means for solving the problem]

[0007] To solve the above problems, one embodiment of the needleless syringe of the present invention includes a substrate, a conductive layer disposed on the substrate, an insulating layer disposed on the conductive layer and for disposing drug particles to be injected on the surface opposite the conductive layer, and a voltage application unit. The conductive layer has a bridge portion formed in a portion corresponding to a lower portion of the insulating layer where the drug particles are disposed. When the sum of the heat of fusion and heat of vaporization per unit mass of the conductive layer is e0, the voltage application unit applies a voltage corresponding to e0 or more and 1.5e0 or less to the bridge portion of the conductive layer.

[0008] In some embodiments of the needle-free injector, both the conductive layer and the insulating layer may have bridges formed therein.

[0009] Another aspect of the present invention is also a needle-free syringe. This needle-free syringe includes a substrate, a conductive layer disposed on the substrate, an insulating layer disposed on top of the conductive layer and for disposing drug particles to be injected on the surface opposite the conductive layer, and a voltage application unit including a capacitor and a switch for turning on and off the discharge of the capacitor. The conductive layer, insulating layer, and voltage application unit are integrated with one another.

[0010] Any combination of the above components, and conversion of the present disclosure into a method, device, system, recording medium, computer program, etc., are also valid aspects of the present disclosure. [Effects of the Invention]

[0011] According to the present disclosure, it is possible to provide a minimally invasive needleless syringe that allows patients to achieve the same effect as a conventional injection by themselves. [Brief explanation of the drawings]

[0012] [Figure 1] 1 is a schematic diagram of a needleless syringe according to a first embodiment. [Figure 2] 1 is a micrograph taken from above showing drug particles arranged in the region near the bridge portion of the insulating layer. [Figure 3] 2 is a schematic diagram showing the operation of the needleless syringe of FIG. 1. [Figure 4] 1 is a schematic diagram of the experimental system and measurement circuit of the demonstration experiment. [Figure 5] 10 is a graph showing the relationship between the energy due to a voltage applied to a bridge portion of a conductive layer and each component of stress applied to an insulating layer. [Figure 6] 10 is a graph showing the relationship between the impact load applied to the insulating layer after deformation and the change in height of the insulating layer after deformation. [Figure 7] 10 is a graph showing the relationship between the energy density applied to the bridge portion and the maximum surface velocity of the insulating layer. [Figure 8] 10 is a graph showing the change over time in the input power to the bridge portion and the surface velocity of the insulating layer. [Figure 9] This is a photograph taken from the side with a high-speed camera showing the deformation of the insulating layer. [Figure 10] 1 is a graph showing the relationship between the depth of gold particles reaching into human skin and the injection speed when gold particles with a diameter of 10 μm are injected toward the skin. [Figure 11]Figure 11(a) is a photograph of a "human skin gel" that uses a multilayer structure of silicone and urethane to simulate human skin. Figure 11(b) is a photograph of tungsten particles with a median diameter of 10 μm being injected into the human skin gel of Figure 12(a) at a speed of 2.8 km / s using a needleless syringe according to the present disclosure. [Figure 12] FIG. 10 is a schematic diagram of a needleless syringe according to a second embodiment. [Figure 13] FIG. 10 is a schematic diagram of a needleless syringe according to a modified example. DETAILED DESCRIPTION OF THE INVENTION

[0013] Preferred embodiments will be described below with reference to the drawings. The same or equivalent components, parts, and processes shown in each drawing will be designated by the same reference numerals, and redundant descriptions will be omitted where appropriate. Furthermore, the embodiments are merely examples and do not limit the invention, and all features and combinations thereof described in the embodiments are not necessarily essential to the invention.

[0014] In addition, the dimensions (thickness, length, width, etc.) of each component shown in the drawings may be enlarged or reduced as appropriate for ease of understanding. Furthermore, the dimensions of multiple components do not necessarily represent their relative sizes, and even if a component A is depicted as being thicker than another component B in the drawings, it is possible that component A is thinner than component B.

[0015] [First embodiment] Example 1 FIG. 1 is a schematic diagram of a needle-free syringe 1 according to a first embodiment. In FIG. 1, the x-axis and y-axis are defined in a horizontal plane, and the z-axis is defined in a vertical direction (the same applies hereinafter unless otherwise noted). FIG. 1 shows the needle-free syringe 1 placed on a horizontal surface. The needle-free syringe 1 includes a substrate 11, a conductive layer 12 disposed on the substrate 11, an insulating layer 13 disposed on top of the conductive layer 12 and on the surface opposite the conductive layer 12 for disposing drug particles to be injected, and a voltage application unit 14. The conductive layer 12 and the insulating layer 13 are provided with narrow bridge portions 20, each including an area where drug particles are to be disposed, formed such that their cross-sectional area decreases rapidly on the conductive layer 12 and the insulating layer 13. When the sum of the heat of fusion and heat of vaporization per unit mass of the conductive layer is defined as e0, the voltage application unit 14 applies a voltage corresponding to e0 or more and 1.5e0 or less to the bridge portion of the conductive layer 12.

[0016] The substrate 11 may be, for example, an FR-4 substrate having a thickness of about 1 mm to 2 mm, but is not limited to this.

[0017] The conductive layer 12 may be, for example, a metal plate such as copper having a thickness of about several tens of micrometers, but is not limited to this.

[0018] Insulating layer 13 may be, for example, a polyimide plate with a thickness of about several tens of μm, but is not limited to this. As will be described later, drug particles to be injected are placed on the surface of insulating layer 13 opposite to conductive layer 12.

[0019] The conductive layer 12 and the insulating layer 13 have narrow (and therefore small area) bridge portions 20 formed near the centers of these layers in the x-axis and y-axis directions. The drug particles are arranged near the bridge portions 20 of the insulating layer 13.

[0020] The surface of the substrate 11 on the conductive layer side may have adhesive properties to biological tissue such as skin. Alternatively, an adhesive film having adhesive properties to biological tissue may be sandwiched and disposed between the conductive layer 12 and the insulating layer 13.

[0021] The voltage application units 14 are provided, for example, on both ends of the conductive layer 12 in the x-axis direction, and apply a voltage to the conductive layer 12 by, for example, pulse discharging a capacitor.

[0022] Next, we will explain the operation of the needle-free syringe 1. Drug particles to be injected are placed on the surface of the insulating layer 13 opposite the conductive layer 12. The needle-free syringe 1 is attached to the patient, for example, with the insulating layer 13 in contact with the skin.

[0023] Figure 2 is a micrograph taken from above showing drug particles arranged in the area near the bridge portion 20 of the insulating layer 13. In this example, the bridge portion 20 is formed as a 0.2 mm x 0.2 mm square. The drug particles are arranged in an area of ​​0.77 mm x 1.35 mm centered on this bridge portion.

[0024] In this state, electrical energy, for example, precharged in a capacitor, is instantaneously supplied to the voltage application unit 14 via a thyristor circuit. A current then flows through the conductive layer 12, and its current density rapidly increases at the narrow bridge portion 20. If the applied voltage is equal to or greater than the sum of the heat of fusion and heat of vaporization per unit mass of the conductive layer, the conductive layer 12 instantly melts and vaporizes due to Joule heating (hereinafter referred to as ablation). This generates a blast wave (shock wave) due to an explosion in the closed space between the substrate 11 and the insulating layer 13. This blast wave and high-pressure gas push the insulating layer 13 upward. As a result, particles arranged on the surface of the insulating layer 13 are ejected toward the patient's skin at a speed equivalent to the plastic deformation rate of the insulating layer 13. The ejected drug particles penetrate the patient's body a distance determined by the tensile strength and mass density of the target cells and then stop within the cells. Figure 3 shows a schematic diagram of the above-described operation.

[0025] A blast wave is a shock wave formed by the successive integration of compression waves. Blast waves are characterized by a significant increase in pressure and temperature in an extremely small space, approximately one ten-thousandth the size of a human hair. Conventionally, blast waves generated using pulsed current have been used primarily as detonators for rocket separation bolts. In contrast, the technology disclosed here is based on a new perspective: utilizing blast waves generated by pulsed current in the medical field, such as for self-medication.

[0026] The key to this technology is determining the value of the voltage applied by the voltage application unit 14 to the bridge portion 20 of the conductive layer 12. In other words, if the applied voltage is too weak, ablation will not occur. Conversely, if the applied voltage is too strong, the insulating layer 13 will rupture, making it impossible to eject drug particles in the desired direction. After extensive research and experimentation, the inventors have found that, when the sum of the heat of fusion and heat of vaporization per unit mass of the conductive layer 12 is e0, the desired results can be obtained by applying a voltage from the voltage application unit 14 to the bridge portion 20 of the conductive layer 12 that corresponds to e0 or more and 1.5e0 or less.

[0027] (Demonstration experiment) The inventors conducted an experiment to demonstrate the effectiveness of the technology disclosed herein. Figure 4 shows a schematic diagram of the experimental system and measurement circuit. The substrate 11 is a 1.6 mm thick FR4 board. The conductive layer 12 is a 9 μm thick copper conductive layer rolled onto the substrate 11. The insulating layer 13 is a 25 μm thick polyimide layer. The bridge portion 20 is a square with a length and width of 0.2 mm. In this experiment, the deformation velocity history of the insulating layer surface was measured using a photonic Doppler velocimetry (hereinafter referred to as PDV). In velocity measurement using PDV, the time resolution is determined by the sampling frequency of the second oscilloscope. In this experiment, a sampling frequency of 50 GHz and an analog frequency band of 6 GHz were used to ensure a high time resolution of less than 5 ns.In addition, the pulse current history flowing through the bridge section 20 and the voltage history at both ends of the bridge section 20 were measured using a Rogowski coil and a high-voltage probe, respectively, and the operating power during particle emission was calculated.

[0028] 5 to 11 show the experimental results. Fig. 5 is a graph showing the relationship between the energy e due to the voltage applied to the bridge portion 20 of the conductive layer 12 and the stress applied to the insulating layer 13. Specifically, each component of the stress, namely, Bending normal stress component

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[0029] FIG. 6 shows the relationship between the impact load i applied to the insulating layer 13 after deformation and the change in height δ of the insulating layer 13 after deformation. c 10 is a graph showing the relationship between the width and the thickness of the bridge portion 20. The width of the bridge portion 20 is changed to 0.3 mm and 0.4 mm, and the thickness is changed to 25 μm and 50 μm, and experiments are carried out for each of these.

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[0030] As described above, it has been demonstrated that when the voltage application unit 14 applies a voltage corresponding to e0 or more and 1.5e0 or less to the bridge portion 20 of the conductive layer 12, drug particles can be ejected without the insulating layer 13 rupturing.

[0031] Figure 7 is a graph showing the relationship between the energy density applied to the bridge portion and the maximum surface velocity of the insulating layer 13. An energy density of 15.5 MJ / kg corresponds to e = 1.5e0. Figure 7 shows that the insulating layer 13 ruptured at an energy density of 15.5 MJ / kg.

[0032] FIG. 8 shows the input power P b 1 is a graph showing the change over time in the surface velocity u of the insulating layer 13 and the surface velocity u of the insulating layer 13. The surface velocity of the insulating layer 13 shows actual measurements and their 6th-order polynomial approximations. The horizontal axis represents time in nanoseconds. The left vertical axis represents power in megawatts. The right vertical axis represents velocity in kilometers per second. When a voltage is applied at time t=0, an explosion occurs in the closed space between the substrate 11 and the insulating layer 13 approximately 80 nanoseconds later. The insulating layer 13 then rapidly deforms. The surface velocity u of the insulating layer 13 reaches its maximum at t=300 nanoseconds. The maximum value of u is approximately 2.9 kilometers per second.

[0033] 9 is a photograph taken from the side with a high-speed camera, showing the deformation of insulating layer 13. The time interval between frames is 10 ns.

[0034] Figure 10 is a graph showing the relationship between the depth of penetration into human skin and the injection speed of gold particles with a diameter of 10 μm. As shown in the figure, when the injection speed is 2 km / s or higher, the gold particles reach the subcutaneous tissue below the dermis.

[0035] As mentioned above, the ejection speed based on a conventional small shock tube with a natural membrane rupture method was approximately 300 m / s. Referring to FIG. 10, this corresponds to the penetration distance from the epidermis to the dermis in a human. In contrast, the technology disclosed herein achieves an ejection speed of approximately 2.9 km / s, nearly 10 times faster than this. This corresponds to the penetration distance to the subcutaneous tissue in a human, and was not possible to achieve with conventional technology.

[0036] Figure 11(a) is a photograph of a "human skin gel" that mimics human skin using a multilayer structure of silicone and urethane. Figure 11(b) is a photograph of tungsten particles with a median diameter of 10 μm being injected into the human skin gel of Figure 12(a) at a speed of 2.8 km / s using a needleless syringe according to the present disclosure.

[0037] In this skin gel, the first layer of urethane (density 1.1 g / cm 3 , depth 0 mm to 0.05 mm) simulates the stratum corneum, and the second layer of silicone (density 1.08 g / cm 3 , depth 0.05 mm to 0.3 mm) simulates the epidermis layer, and the third layer of silicone (density 0.97 g / cm 3 , depth 0.3 mm to 1.7 mm) simulates the dermis layer, and the fourth layer of silicone (density 0.95 g / cm 3 , depth 1.7mm to 4.0mm) simulates the subcutaneous tissue layer.

[0038] As shown in Figure 11(b), the tungsten particles penetrated to a depth of approximately 2 mm, which corresponds to the human subcutaneous tissue layer.

[0039] As described above, according to the present embodiment, it is possible to provide a minimally invasive needleless syringe that allows patients to achieve the same effect as a conventional injection by themselves.

[0040] Example 2 In the above-described embodiment, the conductive layer 12 and the insulating layer 13 have substantially the same shape, and the bridge portion 20 is formed in both the conductive layer 12 and the insulating layer 13. However, the embodiment is not limited to this. For example, in the configuration of Figure 1, the bridge portion 20 may be formed in the conductive layer 12 in a portion corresponding to the lower portion of the region in the insulating layer 13 where the drug particles are to be placed, and the bridge portion 20 may not be formed in the insulating layer 13.

[0041] This modification also provides the same effects as the above-described embodiment.

[0042] [Second embodiment] Fig. 12 is a schematic diagram of a needle-free syringe 2 according to a second embodiment. The needle-free syringe 2 includes a substrate 11, a conductive layer 12 disposed on the substrate 11, an insulating layer 13 disposed on top of the conductive layer 12 and for disposing drug particles to be injected on the surface opposite the conductive layer 12, and a voltage application unit 14 including a capacitor 15 and a switch 16 for turning on and off the discharge of the capacitor 15. The conductive layer 12, the insulating layer 13, and the voltage application unit 14 are integrated with one another. Fig. 12 also shows a battery 17 for charging the capacitor 15.

[0043] The configuration of the substrate 11, the conductive layer 12 and the insulating layer 13 may be the same as that of the needleless syringe 1 of FIG.

[0044] The conductive layer 12 and the insulating layer 13 may be formed on the substrate 11 integrally with the voltage application unit 14. In this case, the conductive layer 12 and the insulating layer 13 may be removable from the patient's skin together with the voltage application unit 14.

[0045] Alternatively, the conductive layer 12 and the insulating layer 13 may be formed to be detachable from the voltage application unit 14. In this case, the conductive layer 12 and the insulating layer 13 may be detachable from the patient's skin independently of the voltage application unit 14.

[0046] The battery 17 may be formed integrally with the capacitor 15. Alternatively, the battery 17 may be formed so as to be detachable from the capacitor 15.

[0047] According to this embodiment, it is possible to provide a compact and detachable needleless syringe equipped with a voltage application unit including a capacitor and a switch.

[0048] In this embodiment, when the sum of the heat of fusion and the heat of vaporization per unit mass of the conductive layer 12 is e0, the voltage application unit 14 may apply a voltage corresponding to e0 or more and 1.5e0 or less to the bridge portion of the conductive layer 12.

[0049] According to this embodiment, it is possible to provide a minimally invasive, compact and removable needleless syringe that allows patients to achieve the same effect as a conventional injection themselves.

[0050] The present invention has been described above based on the embodiments. These embodiments are merely examples, and it will be understood by those skilled in the art that various modifications are possible in the combination of the respective components and treatment processes, and that such modifications are also within the scope of the present invention.

[0051] Figure 13 is a schematic diagram of a needle-free syringe 3 according to a modified example. The needle-free syringe 3 is formed by connecting four needle-free syringe units 19 in the x-axis direction and two in the y-axis direction, each unit consisting of the conductive layer 12 and insulating layer 13 of the needle-free syringe 1 in Figure 1. The conductive layer 12 may be formed on the substrate 11 by, for example, inkjet printing.

[0052] This modified example has a configuration in which multiple bridge sections (blast wave sources) are provided within a single injector. This configuration enables the injection of medicine over a wide area that is not possible with conventional syringes, and is therefore expected to be applied as a new treatment for skin diseases and arthritis.

[0053] Any combination of the above-described embodiments and modifications is also useful as an embodiment of the present disclosure. A new embodiment resulting from the combination has the combined effects of the combined embodiments and modifications.

[0054] The embodiments have been described above. When understanding the abstract technical ideas of the embodiments, the technical ideas should not be interpreted as being limited to the contents of the embodiments. The above-described embodiments and variations are merely illustrative examples, and many design changes, such as changes, additions, and deletions of components, are possible. In the embodiments, the contents in which such design changes are possible are emphasized by adding the notation "embodiment." However, design changes are also permitted even in contents not so notated. [Industrial Applicability]

[0055] The needle-free syringe of the present disclosure can be widely used in the medical field, including self-medication, the agricultural field using methods such as DNA transfer into plant cells, and the drug discovery field. [Explanation of symbols]

[0056] 1. Needleless syringe, 2. Needleless syringes, 3. Needleless syringe, 11··Substrate, 12··Conductive layer, 13··Insulating layer, 14. Voltage application unit, 15··Capacitor, 16··switch, 19··Needleless syringe unit, 20··Bridge section.

Claims

1. A needleless syringe comprising: a substrate; a conductive layer disposed on the substrate; an insulating layer disposed on the conductive layer and for disposing drug particles to be injected on a surface opposite to the conductive layer; and a voltage application unit, a bridge portion is formed in the conductive layer at a portion corresponding to a lower portion of the insulating layer in which the drug particles are arranged; The sum of the heat of fusion and the heat of vaporization per unit mass of the conductive layer is e ０ When the voltage application unit is set to the bridge portion of the conductive layer, ０ 1.5e or more ０ A needleless syringe characterized by applying a voltage corresponding to the following:

2. 2. The needleless syringe according to claim 1, wherein the bridge portion is formed on both the conductive layer and the insulating layer.

3. A needleless syringe comprising: a substrate; a conductive layer disposed on the substrate; an insulating layer disposed on top of the conductive layer and for disposing drug particles to be injected on a surface opposite to the conductive layer; and a voltage application unit including a capacitor and a switch for turning on and off the discharge of the capacitor, The needleless syringe is characterized in that the conductive layer, the insulating layer, and the voltage application section are integrated with one another.

4. The sum of the heat of fusion and the heat of vaporization per unit mass of the conductive layer is e ０ When the voltage application unit is set to the bridge portion of the conductive layer, ０ 1.5e or more ０ 4. The needleless syringe of claim 3, wherein a voltage corresponding to:

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