WO2017115869A1 - 射出装置 - Google Patents
射出装置 Download PDFInfo
- Publication number
- WO2017115869A1 WO2017115869A1 PCT/JP2016/089194 JP2016089194W WO2017115869A1 WO 2017115869 A1 WO2017115869 A1 WO 2017115869A1 JP 2016089194 W JP2016089194 W JP 2016089194W WO 2017115869 A1 WO2017115869 A1 WO 2017115869A1
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- WIPO (PCT)
- Prior art keywords
- injection
- pressure
- liquid
- energy
- vibration
- Prior art date
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/30—Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/24—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic
- A61M5/2422—Ampoule syringes, i.e. syringes with needle for use in combination with replaceable ampoules or carpules, e.g. automatic using emptying means to expel or eject media, e.g. pistons, deformation of the ampoule, or telescoping of the ampoule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/42—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for desensitising skin, for protruding skin to facilitate piercing, or for locating point where body is to be pierced
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/48—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for varying, regulating, indicating or limiting injection pressure
- A61M5/482—Varying injection pressure, e.g. by varying speed of injection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/48—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for varying, regulating, indicating or limiting injection pressure
- A61M5/484—Regulating injection pressure
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
- G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
- G16H20/17—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H40/00—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
- G16H40/60—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
- G16H40/63—ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
Definitions
- the present invention relates to an injection device for injecting an injection liquid containing a predetermined substance into a target region, and particularly to a technique for injecting a high-speed energy to the target region by applying high speed energy to the injection liquid.
- a syringe can be exemplified as a device for administering a drug solution to a target region such as a living body, but in recent years, a needleless syringe without an injection needle has been developed from the viewpoint of ease of handling and hygiene.
- a drug solution pressurized by a driving source such as a compressed gas or a spring is ejected toward a target region, and the drug solution is administered into the target region using the kinetic energy of the drug solution.
- a driving source such as a compressed gas or a spring
- a needleless syringe does not have a mechanical configuration (that is, an injection needle) that directly contacts the inside of the target region, convenience for the user is high.
- a mechanical configuration that is, an injection needle
- Patent Document 1 discloses a technique in which a drug solution is sent to a desired depth of a skin structure of a living body by a needleless syringe. Specifically, with regard to pressurization for injection of an injection solution, in order to form a penetration path in the injection target region, after increasing the pressure to the first peak pressure, the pressure on the injection solution is increased to a standby pressure. A first pressurizing mode for lowering and a second pressurizing the injection solution at the standby pressure to increase the pressure to the injection solution to the second peak pressure to inject a predetermined injection amount Pressure control for performing the pressure mode is performed. By performing such pressurization control, the behavior of the injection solution in the target region is controlled.
- an injection device for injecting various chemical solutions including a needleless syringe, a spring, compressed gas, explosives, and the like have been used as drive sources for the injection.
- the chemical solution is injected into the target region by pressurizing the chemical solution, and the kinetic energy of the chemical solution is used to be injected into the target region. Therefore, when the target region is viewed microscopically, an excessive load is applied to the constituent of the target region (for example, the tissue or cell if the target region is a living body or the like), the constituent is destroyed, and its function is There is a risk of damage.
- the influence on the target area caused by the injection is regarded as invasiveness to the target area, and is not sufficiently considered in the injection apparatus according to the prior art.
- a suitable injection solution is ejected by controlling the pressure applied to the injection solution by explosive combustion separately in two pressurization modes.
- the injection solution is pressurized at the first peak pressure at the initial stage of injection in order to reach the desired depth
- the injection solution is considered in consideration of the invasiveness to the target region.
- the conventional injection device other than the needleless syringe according to Patent Document 1 there is no disclosure of the injection control that sufficiently considers the invasiveness to the target region.
- an object of the present invention is to provide a technique capable of reducing the invasiveness to a target area at the time of injection in an injection apparatus for injecting an injection liquid containing a predetermined substance to the target area.
- the present invention is intended to solve the above-mentioned problems from the aspect of a technique of injecting a high-speed energy to an injection liquid and injecting the target region of treatment (hereinafter also referred to as “high-speed energy treatment technique”).
- high-speed energy treatment technique In order to treat a target region, it is important to ensure that a predetermined substance reaches the target region and to reduce invasiveness as much as possible in the process of reaching the target region.
- the coexistence has not been realized so far, but due to the diligent efforts of the inventors of the present application, attention is paid to the pressure transition of the injection liquid in the initial stage of injection, and the high-speed energy to the injection liquid is determined.
- high-speed energy There is a possibility of various treatment technologies using high-speed energy, which is a new technology that can achieve both low invasiveness and more reliable arrival of the injection liquid to the target area through pressurization control by application. It was suggested.
- the present invention is an injection device for injecting an injection liquid containing a predetermined substance into a target region, the storage unit storing the injection liquid, a drive unit for applying injection energy, and the drive unit.
- a pressurizing unit that pressurizes the ejection liquid accommodated in the accommodating unit, and an ejection unit that ejects the ejection liquid pressurized by the pressurizing unit from the ejection port to the target region. And comprising.
- the vibration in the pressure transition reaches a converged state within a predetermined period from the rise of the pressure.
- the pressure reaches the peak value at a predetermined increase speed, or the vibration within the predetermined period is vibration at a frequency belonging to a predetermined frequency range.
- the drive unit is configured to generate ejection energy that is used to eject the ejection liquid to the target region.
- the injection energy may be generated chemically, and an example of the injection energy may be combustion energy generated by an oxidation reaction of a high energy substance such as explosive or explosive.
- the emission energy may be generated electrically, and an example of the emission energy may be energy generated by electric power input such as a piezoelectric element or an electromagnetic actuator.
- the generation of the injection energy may be physically generated, and examples of the injection energy include elastic energy by an elastic body and internal energy of a compressed object such as compressed gas. Good.
- the energy generated by the drive unit according to the present invention may be any energy as long as it enables the ejection liquid to be ejected in the ejection device.
- the injection energy may be a composite energy in which internal energy such as combustion energy, electric power, and elastic energy is appropriately combined.
- examples of the high energy substance include explosives containing zirconium and potassium perchlorate, explosives containing titanium hydride and potassium perchlorate, and titanium and perchlorine.
- Gunpowder containing potassium acid, powder containing aluminum and potassium perchlorate, powder containing aluminum and bismuth oxide, powder containing aluminum and molybdenum oxide, powder containing aluminum and copper oxide, powder containing aluminum and iron oxide It may be a single explosive or an explosive composed of a plurality of combinations thereof.
- these high energy substances even if the combustion product is a gas at a high temperature, it does not contain a gas component at room temperature. When it is used for the injection of, efficient injection to a shallower part of the target region becomes possible.
- examples of the predetermined substance contained in the injection liquid include a substance that includes a component that is expected to be effective in the target region and a component that is expected to exhibit a predetermined function in the target region. it can. Therefore, the physical form of the predetermined substance in the injection liquid may exist in a state dissolved in the liquid, or at least without being dissolved in the liquid, as long as injection with the injection energy by the drive unit is possible. It may be simply mixed.
- the predetermined substances to be delivered include vaccines for enhancing antibodies, proteins for cosmetics, cultured cells for hair regeneration, etc., which are included in a liquid medium so that they can be injected.
- an injection liquid is formed.
- region is preferable.
- a medium that exhibits the above-mentioned effects and functions by acting together with a predetermined substance in a state where it is injected into the target region may be used.
- the pressure transition of the injection liquid at the injection port corresponding to the application of the injection energy that is, the transition of the pressure applied to the injection liquid injected by the injection energy (hereinafter referred to as “injection”).
- the pressure transition is referred to as a transition that can reduce damage to the target area at the time of injection.
- the pressure of the injection liquid at the injection port is a pressure applied to the injection liquid immediately after being injected from the injection port, that is, in the vicinity of the injection port, and is a pressure for the injection liquid to be injected from the injection port. .
- the present invention relates to the ejection liquid when the ejection liquid is ejected from the ejection device toward the target area. Focusing on the kinetic energy possessed by, the term “pressure of the injected liquid at the injection port” and the term “pressure transition” are used. Therefore, when there is a predetermined correlation between the separation distance from the injection port and the pressure drop due to the separation distance, the pressure transition of the injection liquid at the position of the separation distance is the “injection port” according to the present invention. It can be considered that it reflects the “pressure transition of the injected liquid at“.
- This injection pressure transition is a pressure transition in the initial stage of injection starting from the application of injection energy. Therefore, the ejected liquid ejected by the transition of the ejection pressure passes through the process of entering the target area from the outside, and exerts some mechanical action on the target area. Therefore, the formation of this injection pressure transition is extremely important from the viewpoint of reducing damage to the target area during injection.
- the inventors of the present application through their own experiments, etc., in this injection pressure transition, the pressure vibration reaches a convergence state within a predetermined period from the rise of pressure, and at that time, in the vibration within the predetermined period,
- the pressure reaches a peak value at a predetermined increase rate, or the vibration within the predetermined period is a vibration at a frequency belonging to a predetermined frequency range, so that damage to the target region is greatly increased.
- the vibration element said here comprises a part of pressure vibration included in injection pressure transition.
- the injection liquid can reach the target area, and at that time, the invasiveness to the target area can be reduced.
- a predetermined substance when a predetermined substance is to be introduced into a cell, by controlling the pressure oscillation as described above, a temporary opening of the cell membrane can be generated, and the predetermined substance can be efficiently introduced into the cell. That is, the inventor of the present application can achieve both the low invasiveness and the more reliable arrival of the injection liquid to the target region by giving the above-described vibration characteristics to the injection pressure transition using high-speed energy. The possibility of the method is derived.
- the predetermined increase speed and the predetermined frequency range are parameters related to vibrations that enable the less invasive injection found by the inventors of the present application.
- the predetermined increase speed and the predetermined frequency range can be appropriately set according to a specific structure of the target region (for example, specific cells of a living body) and physical characteristics (elastic force).
- the predetermined increase speed is a speed that reaches the pressure of 10 MPa or more, which is the peak value, within 0.5 msec from the rise.
- the predetermined frequency range is 500 to 10,000 Hz.
- the period is preferably within 2 msec from the rise time, and more preferably within 1.5 msec from the rise time.
- the total amplitude of the other vibration elements included in the vibration within the predetermined period is 15 MPa or less.
- other vibration elements other than the first vibration element penetrating the surface layer of the target area it is possible to reduce the invasiveness to the target area by preventing the total amplitude from being excessively increased in this way. It becomes.
- the gas generating agent that generates a predetermined gas by combustion and exposed to the combustion product generated by the combustion of the high energy substance.
- the injection liquid is further pressurized by the energy generated by the combustion of the gas generating agent in the vicinity of the time when the predetermined period has elapsed from the rise of the pressure of the injection liquid.
- the gas generating agent is used for single-base smokeless gunpowder, gas generators for airbags and gas generators for seat belt pretensioners. It is also possible to use various gas generating agents.
- the injection liquid When the injection liquid is pressurized using the gas generating agent as described above, it is preferably performed in the vicinity of the time when a predetermined period has elapsed from the start-up, that is, the time when the pressure of the injection liquid is almost converged.
- the injection liquid is further discharged by combustion of the gas generating agent from the state in which the injection liquid is fed while reducing the invasiveness to the target region by burning of the high energy substance. Will be sent. Since the gas generating agent has a relatively slow combustion rate, the pressure transition of the injection liquid during the combustion of the gas generating agent is gradually increased as compared with the combustion of the high energy substance. Therefore, it is possible to send more ejected liquid into the target area while maintaining a state in which the invasiveness to the target area is reduced.
- the second injection energy is used.
- the peak value in the pressure transition of the injection liquid may be equal to or greater than the peak value in the pressure transition excluding the first vibration element in the pressure transition of the injection liquid due to the first ejection energy.
- the combustion rate of the gas generating agent is relatively slow.
- the target region is It can withstand the load at that time and is not easily damaged.
- the peak value in the pressure transition at the time of combustion of the gas generating agent becomes high, it becomes possible to efficiently and quickly send the injection liquid into the target region.
- the above-described ejection device may be a device that ejects the ejection liquid from the ejection port to the target area without using an introduction unit.
- the injection device may be a cell processing device that introduces a predetermined substance into a living body cell to be injected, and is also applied to a living tissue or organ while performing the processing. It may be a device capable of injecting cells.
- the injection apparatus may be an apparatus that injects a medical solution or the like via a catheter portion to a target region of a living body.
- an injection apparatus for injecting an injection liquid containing a predetermined substance into a target area, invasiveness to the target area at the time of injection can be reduced.
- the injection device 1 is a device that injects an injection liquid into a target region as described below, and the injection operation of the injection liquid corresponds to the injection operation of the injection device according to the present invention. Therefore, the ejection liquid corresponds to the ejection liquid according to the present invention.
- the structure of the following embodiment is an illustration and this invention is not limited to the structure of this embodiment.
- “front end side” and “base end side” are used as terms representing the relative positional relationship in the longitudinal direction of the injection apparatus 1.
- the “front end side” represents a position closer to the distal end of the injection apparatus 1 to be described later, that is, a position closer to the injection port 31 a, and the “base end side” is the opposite side of the “front end side” in the longitudinal direction of the injection apparatus 1.
- the direction, that is, the direction on the drive unit 7 side is shown.
- FIG. 1 is a diagram showing a schematic configuration of the injection apparatus 1, and is also a cross-sectional view of the injection apparatus 1 along its longitudinal direction.
- the injection device 1 includes a sub-assembly including a later-described syringe unit 3 and a plunger 4 (see FIG. 2A described later) 10A, an injection device body 6, a piston 5, and a drive unit 7.
- the device assembly 10 is integrally assembled with a three-dimensional body (see FIG. 2B described later) 10B.
- the injection liquid injected into the target area by the injection device 1 is formed by containing a predetermined substance that exhibits the efficacy and function expected in the target area in the liquid medium. Has been.
- the predetermined substance may be in a state of being dissolved in a liquid as a medium, or may be in a state of being simply mixed without being dissolved.
- Examples of the predetermined substance contained in the injection liquid include not only drugs and pharmaceuticals that can be injected in a target region that is a living body, but also biologically derived substances and substances that emit a desired physiological activity.
- DNA, RNA, nucleic acid, antibody, cell, etc. are exemplified.
- Substances that exhibit physiological activity include various low molecular weight drugs, inorganic substances such as metal particles for thermotherapy and radiotherapy, and various pharmacology including carriers that serve as carriers. -Substances that have a therapeutic effect.
- the liquid that is the medium of the injection liquid may be any material that is suitable for injecting these predetermined substances into the target region, and may be water-based or oil-based.
- the viscosity of the liquid as the medium is not particularly limited.
- the target area that is an injection target of the injection liquid is an area where the predetermined substance is to be injected, such as a living body cell or tissue (skin etc.), an organ organ (eyeball, heart, liver etc.). It can be illustrated.
- the structure of the living body as the target region in a state of being separated from the living body.
- the injection of the predetermined substance to the target area (tissue or organ) ex-vivo and the injection of the predetermined substance to the target area (cultured cell or cultured tissue) in-vitro are also included in the category of the injection apparatus according to the present invention. include.
- the device assembly 10 is configured to be detachable from the housing 2.
- the ejection liquid is accommodated in the accommodation chamber 32 (see FIG. 2A) formed between the syringe unit 3 and the plunger 4 included in the apparatus assembly 10, and the apparatus assembly 10 is configured to eject the ejection liquid. It is a unit that is exchanged every time.
- a battery 9 that supplies power to an igniter 71 included in the drive unit 7 of the device assembly 10 is included on the housing 2 side.
- the power supply from the battery 9 is performed by the user pressing the button 8 provided on the housing 2, so that the electrode on the housing 2 side and the electrode on the drive unit 7 side of the device assembly 10 are connected via wiring. Will be done between.
- the electrode on the housing 2 side and the electrode on the drive unit 7 side of the device assembly 10 are designed such that the shape and position of both electrodes are automatically contacted when the device assembly 10 is attached to the housing 2.
- the housing 2 is a unit that can be used repeatedly as long as the electric power that can be supplied to the drive unit 7 remains in the battery 9. In the housing 2, when the battery 9 has run out of power, only the battery 9 may be replaced and the housing 2 may continue to be used.
- the syringe unit 3 includes a nozzle unit 31 including a storage chamber 32 that is a space that can store an ejection liquid, and the plunger 4 is disposed so as to be slidable in the storage chamber 32 in the subassembly 10A. Is done.
- the body 30 of the syringe unit 3 may be made of, for example, known nylon 6-12, polyarylate, polybutylene terephthalate, polyphenylene sulfide, or liquid crystal polymer. These resins may contain a filler such as glass fiber or glass filler. In polybutylene terephthalate, 20 to 80% by mass of glass fiber, and in polyphenylene sulfide, 20 to 80% by mass of glass fiber, The liquid crystal polymer may contain 20 to 80% by mass of mineral.
- the plunger 4 is arrange
- the formed space is a space in which the ejection liquid 320 is accommodated.
- the plunger 4 slides in the storage chamber 32, the injection liquid 320 stored in the storage chamber 32 is pressed and injected from the injection port 31 a provided on the distal end side of the nozzle portion 31. become. Therefore, the plunger 4 is formed of a material that slides smoothly in the storage chamber 32 and does not leak the ejected liquid 320 from the plunger 4 side.
- the plunger 4 for example, butyl rubber or silicon rubber can be adopted. Furthermore, styrene elastomers, hydrogenated styrene elastomers, polyolefins such as polyethylene, polypropylene, polybutene, and ⁇ -olefin copolymers, oils such as para, process oil, and powders such as talc, cast, mica, etc. The thing which mixed the inorganic substance is mention
- various rubber materials such as polyvinyl chloride elastomers, olefin elastomers, polyester elastomers, polyamide elastomers, polyurethane elastomers, natural rubber, isoprene rubber, chloroprene rubber, nitrile-butadiene rubber, styrene-butadiene rubber (especially added) Sulfurized ones) and mixtures thereof can be used as the material of the plunger 4.
- the surface of the plunger 4 and the surface of the storage chamber 32 of the syringe unit 3 may be coated and surface-treated with various substances.
- PTFE polytetrafluoroethylene
- silicon oil diamond-like carbon, nanodiamond, etc.
- the vibration element thereof may be controlled.
- the plunger 4 has a head portion 41 and a trunk portion 42, and the two are connected by a neck portion 43 having a diameter smaller than the diameter of the head portion 41 and the trunk portion 42. Can be.
- the reason why the diameter of the neck portion 43 is reduced in this way is to form an accommodation space for an O-ring that becomes a seal member.
- the contour on the tip side of the head 41 has a shape that substantially matches the contour of the inner wall surface of the nozzle portion 31. Accordingly, when the ejected liquid is ejected, the plunger 4 slides toward the nozzle portion 31, and when reaching the innermost position located in the innermost position in the storage chamber 32, between the plunger 4 and the inner wall surface of the nozzle portion 31.
- the gap formed in the container can be made as small as possible, and the ejection liquid 320 can be prevented from remaining in the storage chamber 32 and being wasted.
- the shape of the plunger 4 is not limited to a specific shape as long as a desired effect is obtained in the injection device of the present invention.
- one or a plurality of protrusions can be provided in the body part 42 to adjust the contact area between the plunger 4 and the storage chamber 32 to adjust the slidability between the plunger 4 and the syringe part 3.
- the slidability can also be adjusted by changing the shape of this, and thereby the injection pressure transition and its vibration element described later may be controlled.
- the plunger 4 is provided with a rod portion 44 extending from the end surface on the base end side of the body portion 42 in the direction of the base end side.
- the rod portion 44 is sufficiently small in diameter as compared to the body portion 42, but has a diameter that allows the user to grip the rod portion 44 and move the inside of the storage chamber 32. Further, even when the plunger 4 is at the innermost position of the storage chamber 32 of the syringe part 3, the rod part 44 protrudes from the end face on the proximal end side of the syringe part 3 so that the user can grip the rod part 44.
- the length of the part 44 is determined.
- the inner diameter of the flow path provided in the nozzle part 31 on the syringe part 3 side is formed smaller than the inner diameter of the storage chamber 32.
- the injection part 31a when the injection port 31a is pressed against the surface layer of the injection target region such as human skin and the injection liquid is injected, the injection part may be shielded by the shield part 31b so that the injected injection liquid does not scatter around it. it can.
- the skin when the injection port is pressed against the skin, the skin is recessed to some extent, so that the contact between the injection port and the skin can be improved, and scattering of the injection liquid can be suppressed. Therefore, as shown in FIG. 2A, the tip of the nozzle part 31 where the injection port 31a is located may protrude slightly from the end face of the shield part 31b in the injection direction of the injection liquid.
- a threaded portion 33 a for connecting the injection device main body 6 and the syringe portion 3 on the sub-assembly 10B side described later is formed on the neck portion 33 located on the proximal end side of the syringe portion 3.
- the diameter of the neck 33 is set smaller than the diameter of the body 30.
- the piston 5 is configured to be pressurized by a combustion product generated by the igniter 71 of the drive unit 7 and slide in a through hole 64 formed in the body 60 of the injection device body 6.
- the injection device body 6 is formed with a coupling recess 61 on the tip side with the through hole 64 as a reference.
- the coupling recess 61 is a portion that couples with the neck portion 33 of the syringe portion 3, and a screw portion 62 a that engages with the screw portion 33 a provided on the neck portion 33 is formed on the side wall surface 62 of the coupling recess 61.
- the through hole 64 and the coupling recess 61 are connected by the communication part 63, and the diameter of the communication part 63 is set smaller than the diameter of the through hole 64.
- the injection device main body 6 is formed with a driving portion recess 65 on the proximal end side with respect to the through hole 64.
- the drive unit 7 is disposed in the drive unit recess 65.
- the piston 5 is made of metal and has a first body 51 and a second body 52.
- the piston 5 is disposed in the through hole 64 such that the first body 51 faces the coupling recess 61 and the second body 52 faces the drive part recess 65.
- the piston 5 slides in the through hole 64 while the first body 51 and the second body 52 are opposed to the inner wall surface of the through hole 64 of the injection apparatus body 6.
- the first body portion 51 and the second body portion 52 are connected by a connecting portion that is thinner than the diameter of each body portion, and the space between both body portions formed as a result is a through hole 64.
- an O-ring or the like is disposed.
- the piston 5 may be made of resin, and in that case, a metal may be used in combination in a portion where heat resistance and pressure resistance are required.
- a pressing column portion 53 having a diameter smaller than that of the first body portion 51 and smaller than the diameter of the communication portion 63 of the injection device main body 6 is provided on the end surface on the distal end side of the first body portion 51. It has been.
- the pressing column portion 53 is provided with an accommodation hole 54 that opens to the end surface on the distal end side thereof, whose diameter is equal to or larger than the diameter of the rod portion 44, and whose depth is deeper than the length of the rod portion 44. . Therefore, the pressing column 53 has its combustion energy transferred to the base end side end face of the body 42 of the plunger 4 when the piston 5 is pressurized by the combustion product of the igniter 71 via the end face on the front end side. Can be communicated to.
- the shape of the piston 5 is not limited to the shape shown in FIG. 2B.
- the drive unit 7 has a body 72 formed in a cylindrical shape, and includes an igniter 71 that is an electric igniter that burns an igniting agent to generate energy for injection.
- the driving energy is disposed in the driving unit recess 65 so that the combustion energy is transmitted to the second body 52 of the piston 5.
- the body 72 of the drive unit 7 may be a resin in which an injection molded resin is fixed to a metal collar. A known method can be used for the injection molding.
- the resin material of the body 72 of the drive unit 7 is formed of the same resin material as that of the body 30 of the syringe unit 3.
- the igniter used in the igniter 71 corresponds to the high energy substance according to the present invention.
- the combustion energy of the said igniting agent is equivalent to the injection energy which concerns on this invention, Therefore
- generation of combustion energy, ie, combustion of an igniting agent, corresponds to provision of injection energy.
- the igniting agent is preferably an explosive containing zirconium and potassium perchlorate (ZPP), an explosive containing titanium hydride and potassium perchlorate (THPP), an explosive containing titanium and potassium perchlorate (TiPP).
- no gas generating agent is disposed as an additional explosive component, but an igniter is used in order to adjust the pressure transition applied to the injection liquid via the piston 5. It is also possible to arrange a gas generating agent or the like that burns with combustion products generated by the explosive combustion in 71 to generate gas.
- the location is, for example, a location that can be exposed to combustion products from the igniter 71, as shown by the dotted line in FIG. 2B.
- the gas generating agent disposed in the igniter 71 is a known technique as disclosed in International Publication No. 01-031282, Japanese Patent Application Laid-Open No. 2003-25950, and the like.
- the gas generating agent a single base smokeless gunpowder composed of 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine and 1.2% by mass of potassium sulfate can be mentioned. It is also possible to use various gas generating agents that are used in gas generators for airbags and gas generators for seat belt pretensioners. It is possible to change the combustion completion time of the gas generating agent by adjusting the size, size and shape of the gas generating agent when disposed in the through hole 64, in particular, the surface shape. The transition of pressure applied to the injection liquid can be adjusted, and the injection pressure can be set as a desired transition. In the present invention, a gas generating agent used as necessary is also included in the drive unit 7.
- the filling of the injection liquid 320 in the sub-assembly 10A is performed by immersing the injection port 31a in a container filled with the injection liquid while the plunger 4 is inserted to the innermost position and maintaining the state. Is carried out by pulling back to the opening side of the storage chamber 32, that is, to the proximal end side of the syringe unit 3. At this time, the plunger 4 is pulled out until the end surface on the proximal end side of the body portion 42 of the plunger 4 slightly protrudes from the end surface on the proximal end side of the syringe portion 3.
- the piston 5 is inserted from the base end side of the injection apparatus main body 6 shown in FIG. 2B. At this time, the piston 5 is inserted into the through hole 64 so that the pressing column portion 53 faces the coupling recess 61 side.
- the end surface on the front end side of the piston 5, that is, the end surface on the front end side of the pressing column portion 53 in which the accommodation hole 54 opens, is in a state of protruding a predetermined amount from the bottom surface (surface orthogonal to the side wall surface 62) of the coupling recess 61.
- a known technique such as setting a positioning mark in the through hole 64 or using a positioning jig may be used as appropriate.
- the drive part 7 is attached to the recessed part 65 for drive parts.
- the fixing force in the through-hole 64 of the piston 5 is such that the piston 5 can slide in the through-hole 64 sufficiently smoothly depending on the pressure received from the combustion product by the igniter 71 of the drive unit 7, and
- the piston 5 is sufficiently resistant to the force that the piston 5 receives from the plunger 4 when the subassembly 10A is attached to the subassembly 10B, so that the position of the piston 5 does not fluctuate.
- the device assembly 10 is formed by attaching the sub-assembly 10A configured as described above to the sub-assembly 10B by screwing the screw portions 33a and 62a. At this time, as the coupling of the two proceeds, the rod portion 44 of the plunger 4 enters and is accommodated in the accommodation hole 54 provided in the pressing column portion 53 of the piston 5. The end surface on the distal end side of the pressing column portion 53 comes into contact with the end surface on the proximal end side of the body portion 42 of the plunger 4. Since the accommodation hole 54 is large enough to accommodate the rod portion 44, the inner wall surface behind the accommodation hole 54 (particularly, the bottom surface of the accommodation hole 54) is the rod portion in this contact state.
- the rod portion 44 is not in contact with the end portion on the base end side, and therefore the rod portion 44 does not receive a load from the piston 5 side.
- the piston 5 is fixed to the through-hole 64 with sufficient frictional force as described above, so that the plunger 4 is moved toward the injection port 31a by the pressing column 53.
- the plunger 4 is pushed in such a way that the plunger 4 is positioned in the syringe unit 3. A part of the ejection liquid 320 corresponding to the pushing amount of the plunger 4 is discharged from the ejection port 31a.
- the formation of the device assembly 10 is completed.
- the piston 5 is positioned at a predetermined position with respect to the injection device main body 6, and the position of the plunger 4 in the storage chamber 32 of the syringe unit 3 is mechanically based on the piston 5.
- the final position of the plunger 4 is a position uniquely determined in the apparatus assembly 10, the amount of the ejected liquid 320 finally stored in the storage chamber 32 is set to a predetermined amount. It becomes possible.
- the device assembly 10 is attached to the housing 2 and the user presses the button 8 in a state where the injection port 31a is in contact with the target region, whereby the injection liquid 320 is connected via the piston 5 and the plunger 4. Is pressurized, its injection is executed, and the injection liquid 320 is injected into the target area.
- examples of the target region of the injection apparatus 1 include a skin structure of a living body such as a human being or a domestic animal.
- FIG. 3 schematically shows the anatomical structure of human skin.
- the human skin is composed of the epidermis, dermis, subcutaneous tissue / muscle tissue in layers from the skin surface side to the depth direction, and the epidermis can be distinguished into the stratum corneum, intradermal and layered.
- Each layer of the skin structure is different also in the main cells constituting the tissue and the characteristics of the tissue.
- the stratum corneum is mainly composed of keratinocytes and has a function as a barrier layer because it is located on the outermost surface side of the skin.
- the stratum corneum has a thickness of about 0.01 to 0.015 mm, and protects human surface by keratinocytes. For this reason, a relatively high strength is also required to physically shield the external environment and the human body to some extent.
- the skin is composed of dendritic cells (Langerhans cells) and pigment cells (melanocytes), and the epidermis is formed by the stratum corneum and the skin.
- the thickness of the epidermis is generally 0.1- It is about 2 mm.
- Dendritic cells in the skin are thought to be involved in antigen / antibody reactions. This is because the antigen-antibody reaction that activates the lymphocytes that recognize dendritic cells and play a role in foreign body attack is easily induced by taking up the antigen.
- pigment cells in the skin have a function of preventing the influence of ultraviolet rays irradiated from the external environment.
- blood vessels and capillaries on the skin are intricately spread in the dermis, and sweat glands for adjusting body temperature, hair roots of body hair (including hair) and sebaceous glands associated therewith also exist in the dermis. .
- the dermis is a layer that connects the human body (subcutaneous tissue / muscle tissue) and the epidermis and includes fibroblasts and collagen cells. Therefore, the state of the dermis is largely involved in the generation of wrinkles and hair loss due to so-called lack of collagen or elastin.
- the human skin structure is generally formed in a layered manner, and inherent anatomical functions are exhibited by the cells / tissues mainly contained in each layer. This means that when medical treatment or the like is performed on the skin, it is desirable to inject a substance for treatment to the location (depth) of the skin structure according to the treatment purpose. . For example, since dendritic cells exist in the skin, a more effective antigen-antibody reaction can be expected by injecting the vaccine here. Furthermore, since pigment cells are present in the skin, it is required to inject a predetermined whitening substance into the skin even when a so-called whitening cosmetic treatment is performed.
- fibroblasts and collagen cells exist in the dermis, proteins, enzymes, vitamins, amino acids, minerals, sugars, nucleic acids, various growth factors (epithelial cells and fibroblasts) are used to remove skin wrinkles. ) Etc., an effective beauty treatment effect is expected.
- stem cell injection method in which dermal papilla cells, epidermal stem cells, etc. are self-cultured and autotransplanted into the scalp, and several growth factors and nutrients extracted from stem cells are placed near the dermis. It is said that injection is preferable.
- the predetermined substance to be ejected according to the purpose of treatment and the position (depth) in the skin structure where it is desirable to be ejected individually correspond to each other, but the substance at the intended arrival position It is not easy to deliver. Even if the predetermined substance can reach the intended arrival position, if the cells in the vicinity of the arrival position are destroyed by the injection liquid containing the predetermined substance, the desired effect of the predetermined substance is sufficiently obtained. You can't expect. Furthermore, if the injection liquid exerts some load on the tissues and cells through which the injection liquid has passed in the process up to the arrival position, it causes damage, destruction, etc. It is recognized by the user as pain or the like, and gives discomfort.
- the injection liquid when there is no structure (introduction part) that guides the injection liquid to the inside of the target region from the device that performs injection of the injection liquid to the target region, such as the injection device 1, the injection liquid is in the target region.
- a certain amount of energy is applied to the injection liquid so as to be able to enter the inside (in the case of the present invention, the energy is combustion energy by the igniter 71). Therefore, since the injection liquid is given a relatively high energy and is ejected toward the target area, it tends to exert an unnecessary mechanical action on the target area components (for example, cells), and the target liquid
- the invasiveness is not necessarily low. In the prior art, the injection of the injection liquid in which the invasiveness with respect to the target region is sufficiently considered is not performed as described above, and therefore, the efficacy by the predetermined substance cannot be sufficiently extracted.
- the minimally invasiveness with respect to the target region is achieved by, for example, injecting the injection liquid so as not to damage the function of the organ or tissue of the living body at the time of injection, or suppressing the damage of the function as much as possible. It is defined as ejecting the ejected liquid.
- injecting a liquid when a living cell is used as a target region, the injection liquid is injected so as not to cause unnecessary cell death, or the injection is performed while suppressing unnecessary cell death as much as possible. It is defined as injecting a liquid.
- the injection by the combustion energy generated in the drive unit 7 is performed so that the pressure transition of the injection liquid injected from the injection apparatus 1 shows a low invasiveness with respect to the target region.
- a configuration for adjusting the pressure of the liquid was adopted. Details will be described below.
- FIG. 4 shows the transition of the pressure of the ejection liquid ejected from the ejection port 31a (hereinafter simply referred to as “injection pressure”) when ejection of the ejection liquid is performed by driving the drive unit 7 in the ejection apparatus 1.
- FIG. 4 The horizontal axis in FIG. 4 represents elapsed time in milliseconds, and the vertical axis represents injection pressure in MPa.
- the injection pressure can be measured using conventional techniques. For example, in the measurement of the radiation output, as in the measurement method described in Japanese Patent Application Laid-Open No. 2005-21640, the injection force is distributed and applied to the diaphragm of the load cell arranged downstream of the nozzle.
- the output may be measured by a method in which the output is collected by a data acquisition device via a detection amplifier and stored as a time-dependent emission power (N).
- the injection pressure is calculated by dividing the radiant power measured in this way by the area (nozzle area) of the injection port 31a of the injection apparatus 1.
- ZPP including zirconium and potassium perchlorate
- a gas generating agent is disposed in the through hole 64. It is a transition of the obtained injection pressure.
- the upper part (a) of FIG. 4 shows the transition of the injection pressure in the period from the start of combustion to about 40 milliseconds from the time when the button 8 is pressed by the drive unit 7 as the origin.
- (B) is an enlarged display of the injection pressure transition in the initial period (a period until about 10 milliseconds have elapsed from the origin) in the pressure transition shown in the upper stage (a).
- the rise of the injection pressure is not at the origin but in the vicinity of 5 milliseconds, because the igniting agent burns and the piston 5 is propelled by the combustion energy to pressurize the injection liquid and inject from the injection port 31a. This is because it takes a certain amount of time to complete.
- a plurality of pressure vibration elements S1 to S4 exist during a predetermined period ⁇ t until about 2 milliseconds elapse from the rising timing T0. After the elapse of the predetermined period ⁇ t, the pressure vibration is almost converged.
- the pressure vibration in the pressure vibration, one cycle in which the injection pressure rises / falls is handled as one pressure vibration element.
- a pressure vibration element S1 (hereinafter referred to as “first vibration element S1”) is first generated.
- the first vibration element S1 is a change in injection pressure during a period from when the peak value Px1 (about 45 MPa) is reached once to the next minimum value after the injection pressure (about 0 Pa) at the rising timing T0.
- the fluctuation range (peak to peak) of the injection pressure during the period is defined as the total amplitude of the first vibration element S1, and specifically, the total amplitude of the first vibration element S1 is about 45 MPa.
- the second vibration element S2, the third vibration element S3, and the fourth vibration element S4 follow the first vibration element S1.
- the second vibration element S2 is a change in injection pressure during a period from when the peak value Px2 (about 37 MPa) is reached to the next minimum value from the end timing of the first vibration element S1.
- the fluctuation range (peak to peak) of the injection pressure during the period is defined as the total amplitude of the second vibration element S2, and specifically, the total amplitude of the second vibration element S2 is about 10 MPa.
- the third vibration element S3 and the fourth vibration element S4 the period for defining each vibration element and the total amplitude of each vibration element are the same as those of the second vibration element S2, and the detailed description thereof is omitted.
- the total amplitude of the third vibration element S3 and the total amplitude of the fourth vibration element S4 decrease with time. That is, in the predetermined period ⁇ t, the pressure transition is a damped vibration with the passage of time, and the vibration is almost converged after the predetermined period ⁇ t has elapsed.
- the period of pressure oscillation in the predetermined period ⁇ t is about 0.5 milliseconds, and from the peak value of the second vibration element S2 and the peak value of the third vibration element S3.
- the calculated period is about 0.5 milliseconds.
- the pressure fluctuation in the predetermined period ⁇ t is mainly caused by the combustion of the igniter in the igniter 71.
- combustion of the gas generating agent in the through hole 64 is started by the combustion product of the igniting agent, and the combustion energy further starts to act on the injection liquid.
- the injection pressure increases again after the elapse of the predetermined period ⁇ t, and reaches the peak value Py at a timing of approximately 18 milliseconds. After that, the injection pressure gradually decreases with time. Since the burning rate of the gas generating agent is lower than the burning rate of the igniting agent, the rate of increase of the injection pressure accompanying the burning of the gas generating agent is also relatively low.
- the injection of the skin structure shown in FIG. 3 onto the epidermis shows how the injection liquid acts on the components in the target region and exhibits minimal invasiveness by the injection pressure showing such transition characteristics. Will be described as an example.
- Various joining means exist in the basal cells of the basal layer of the epidermis.
- the epidermis and the dermis are closely joined by the epidermis basement membrane structure, and the part in contact with both is the epidermis basement membrane.
- a transparent zone is formed between the cell membrane of the basal cell and the basement plate, and the hemidesmosome is greatly involved in the junction between the basal cell and the basement membrane.
- desmosomes and gap junctions are involved in the junction between adjacent basal cells.
- the desmosome has a structure called an adhesion plate inside the cell membrane and a structure that penetrates the cell membrane and takes charge of adhesion between cells.
- the gap junction is formed by connexin, and thereby has a structure in which adjacent cells are joined with a gap of 2 to 3 nm. These joining means prevent dissociation between the epidermis and the dermis and retain moisture in the skin structure.
- the cells themselves are surrounded by the cell membrane, and there are various types of joining means between the cells. Therefore, in order to show minimally invasiveness to cells etc. when the skin structure is the target area for injection liquid injection, unnecessary mechanics to the cell membrane while suitably resisting the bonding force between cells by the bonding means It is considered important to control the injection pressure so as to avoid the negative effect. And it is thought that the technical idea regarding such injection pressure can be similarly applied to a target region in a living body other than the skin structure.
- the first vibration element S1 having the highest peak pressure is first generated within the predetermined period ⁇ t, and then the second, third, and fourth vibration elements S2 to S4. Will arrive sequentially.
- the total amplitude of each vibration element decreases in order, and the pressure vibration attenuates.
- the injection pressure transition in the predetermined period ⁇ t is pressure oscillation at a frequency of about 2000 Hz.
- the inventor of the present application has disclosed that an injection liquid between cells without exerting an unnecessary mechanical action on a cell membrane at the time of injection if the transition of the injection pressure in the predetermined period ⁇ t is a pressure oscillation particularly at a frequency in the range of 500 to 10000 Hz. It has been found that the diffusion of the liquid is promoted and the ejected liquid can reach the target region suitably.
- the total amplitudes of the other vibration elements S2 to S4 excluding the first vibration element S1 are not more than the reference total amplitude value (for example, 15 MPa). Preferably it is. As a result, unnecessary mechanical action on the cell membrane due to excessive increase of the total amplitude can be avoided.
- the inventor of the present application pays attention to the increasing speed to the peak value of the first vibration element S1 as compared with the second, third, and fourth vibration elements S2 to S4 in the pressure transition showing the damped vibration within the predetermined period ⁇ t. did. That is, when the injection pressure reaches a pressure of 10 MPa or more (the peak value of the first vibration element S1) within 0.5 msec from the rising time, it does not exert unnecessary mechanical action on the cell membrane at the time of injection, and moves between cells. It has been found that the diffusion of the injection liquid is promoted so that the injection liquid can suitably reach the target area.
- the injection pressure oscillates damped and the first peak value of the first vibration element S1 in the vibration of the injection pressure. Achieving both the arrival of the injection liquid to the target area and the minimally invasiveness to the target area by the relatively high increase speed or the vibration frequency at the time of the injection being a value belonging to a certain frequency range. It becomes possible.
- the combustion of the gas generating agent is started by the combustion product of the igniting agent.
- the injection pressure of the injection liquid in which the pressure vibration has almost converged rises again and reaches the peak value Py.
- the introduction of a minimally invasive substance into the cell by adopting at least one of the above two requirements in the transition of the injection pressure Is achieved. That is, the peak value of the first vibration element that is the first vibration element in the pressure vibration group within the predetermined period ⁇ t is made steep, or the frequency of the pressure vibration group is set to the predetermined frequency range. It has been found by the inventors of the present application that the substance can be reliably delivered to the cell and the introduction of the substance into the cell in a less invasive manner can be promoted by setting the frequency to belong to.
- the frequency range relating to the pressure increase speed in the first vibration element or the vibration of the injection pressure transition in the predetermined period ⁇ t that realizes such a minimally invasive injection depends on the target region to be injected. May be appropriately changed.
- the target region is an organ of the liver or heart
- the minimally invasiveness can suppress the influence on the blood vessel in the organ as much as possible, and the tissue that does not constitute the blood vessel in the organ. It becomes possible to inject a predetermined substance.
- injection with minimal invasiveness is extremely useful. Therefore, the pressure increase rate and frequency range described above are determined so that minimally invasiveness to the blood vessels in the organ can be realized.
- the horizontal axis of FIG. 5 represents elapsed time in milliseconds, and the vertical axis represents pressure in MPa.
- a line L1 in the drawing represents a change in pressure in the through hole 64 in the injection device 1
- a line L2 represents a change in pressure of the injection liquid 320 accommodated in the accommodation chamber 32.
- L3 is the injection pressure of the injection liquid 320.
- the transition of the injection pressure represented by L3 is obtained by using the injection power obtained according to the above-described known measurement method (for example, the measurement method described in Japanese Patent Application Laid-Open No.
- the value of the injection port 31a of the injection device 1 It can be obtained by dividing by the area (nozzle area).
- the pressure value is displayed with 50% of the original value superimposed on other pressure changes (lines L ⁇ b> 1 and L ⁇ b> 2).
- the pressure in the through hole 64 is measured by installing a pressure sensor in a pressure measurement port provided so as to be connected to the through hole 64, and the injection liquid pressure in the storage chamber 32 is connected to the storage chamber 32. It is measured by installing a pressure sensor in the pressure measurement port provided in the.
- the igniter in the igniter 71 burns, so that the pressure in the through hole 64 rises sharply.
- the piston 5 pushes the plunger 4 so that the ejected liquid is pressurized via the plunger 4.
- the pressure of the injected liquid in the storage chamber 32 due to the pressurization rises at a time slightly earlier than the rise time of the injection pressure, as indicated by a line L2, but is approximately the same as or higher than the rise of the injection pressure.
- the subsequent pressure vibrations are damped vibrations with substantially the same period and substantially constant frequency as the injection pressure transitions. That is, in the example shown in FIG. 5, the injection pressure transition has converged in a predetermined period ⁇ t of about 1.5 milliseconds.
- a predetermined substance injected into the target area by the injection device 1 is a substance that changes its physical properties by being pressurized in a liquid medium
- the substance introduction efficiency into the target region can be increased using the change reaction.
- Japanese Patent Application Laid-Open No. 2003-261777 discloses a technique in which a fine hydrogel is formed when a water-soluble natural product capable of hydrogen bonding with polyvinyl alcohol is placed under high pressure. Under high pressure, the hydroxyl group, amino group, and carboxylic acid group of natural products are bonded to form a micro hydrogen bond aggregate, which may change the three-dimensional structure of the molecule and make it easier to permeate the membrane. .
- the substance after reaction can be introduce
- the vibration experiment the ejection liquid is ejected in a state where the ejection port 31a of the ejection apparatus 1 is arranged immediately above the polyacrylamide gel imitating the target region.
- the vertical vibration (vibration along the injection direction of the injection liquid) of the polyacrylamide gel was imaged with a camera and visualized by performing image processing, thereby detecting displacement due to the vibration.
- FIG. 6 shows, as a comparative example of the vibration experiment, the pressure transition of the injection solution injected by a spring-driven needleless syringe (hereinafter referred to as “spring-driven syringe”) using the elastic force of the spring as the driving source ( (Injection pressure transition) is represented by a line L12.
- spring-driven syringe the pressure transition of the injection solution injected by a spring-driven needleless syringe (hereinafter referred to as “spring-driven syringe”) using the elastic force of the spring as the driving source (Injection pressure transition) is represented by a line L12.
- the injection pressure transition by the spring-driven syringe will be briefly described.
- a spring (elastic body) disposed inside a main body is compressed, and the elastic energy accumulated therein is transmitted to the injection solution, thereby injecting the injection solution. Since the spring released from the compressed state is repeatedly expanded and contracted due to inertia, the vibration of the spring is greatly reflected in the injection pressure as shown in FIG. Specifically, it can be recognized that the vibration of the relatively large pressure amplitude continues until the time when the peak value due to the combustion of the gas generant is reached in the injection device 1 (about 18 milliseconds). .
- the amplitude (total amplitude) changes irregularly in the pressure oscillation that continues for a long period from the pressure rising timing.
- the amplitude of pressure vibration increases with time in the range of 7.5 to 9 milliseconds on the horizontal axis. Therefore, in the spring-driven syringe, the change in the amplitude of the pressure vibration such as the damped vibration that appears in the injection device 1 cannot be found.
- the injection device 1 according to the present invention when comparing the injection device 1 according to the present invention with a spring-driven syringe as a comparative example, in the injection device 1, the pressure vibration at the initial stage of injection reaches a convergence state in a very short period such as the predetermined period ⁇ t. In a spring-driven syringe, pressure oscillation continues for a relatively long time. Further, in the pressure vibration related to the injection device 1, the pressure amplitude decreases with time in the predetermined period ⁇ t, whereas in the spring-driven syringe, the pressure vibration eventually converges, but in the process, the pressure amplitude Increase or decrease irregularly. Thus, it can be understood that the injection device 1 according to the present invention and the spring-driven syringe according to the comparative example show completely different characteristics with respect to the transition of the injection pressure.
- the horizontal axis of FIG. 7 represents elapsed time in milliseconds, and the vertical axis represents gel displacement.
- the displacement is in units of the number of pixels on the screen in image processing. Therefore, the amplitude in the vibration waveform represented by the line L13 in FIG. 7 means the displacement amount (vibration amplitude) of the gel at the time of injection of the injection apparatus 1, and similarly the amplitude in the vibration waveform represented by the line L14. Means the displacement amount (vibration amplitude) of the gel at the time of injection of the spring-driven syringe.
- the injection pressures of the injection device 1 and the spring-driven syringe are approximately the same, but the displacement transition of the line L13 and the displacement transition of the line L14 are changed.
- the amount of gel displacement is greater for the spring-driven syringe than for the injection device 1.
- the displacement amount of the injection device 1 is substantially constant, whereas the displacement amount of the spring-driven syringe varies greatly.
- the injection solution ejected by the spring-driven syringe may enter the target area and then be greatly displaced within the target area, resulting in unnecessary mechanical action on the target area. ing.
- the displacement amount inside the target liquid can be suppressed to be small, thereby avoiding unnecessary mechanical action on the target area. It suggests that you can.
- the structure of the polyacrylamide gel is different from that of living tissue and cells, the injection device 1 has a very low mechanical action on the target region as shown in FIG. 7, so that it is suitable for injection into a living subject. It can be fully expected that
- the experimental condition and experimental result are shown below.
- the following experimental conditions are that the inflammatory reaction (erythema and scab of the erythema and crusts) at each elapsed time (24 hours, 48 hours, 72 hours) when the inflammatory substance is injected into the skin, which is the skin tissue of a rabbit body.
- the purpose is to confirm the presence or absence of formation and edema.
- injection of the injection solution in the needle syringe was performed under a constant pressurization rate.
- Table 1 shows the experimental results regarding the rabbit living body.
- the injection device 1 As can be understood from the comparison of the above table, according to the injection device 1, the inflammatory reaction in the intradermal cells due to the inflammatory substance contained in the injection liquid is effectively suppressed as compared with the comparative example. This is considered to indicate that inflammatory substances can be injected and diffused into the skin without being invaded by the skin cells. As described above, according to the present invention, it is possible to realize injection that suppresses invasiveness to cells and diffuses an injection liquid over a wide range of skin tissue.
- the experimental conditions and the experimental results are shown below.
- the following experimental conditions are intended to inject the MRI contrast medium onto the porcine abdominal skin tissue and to confirm the state of entry of the MRI contrast agent in the porcine abdominal skin tissue with the captured image by the MRI apparatus. To do.
- the contrast agent Magnevist manufactured by Bayer Yakuhin Co., Ltd. was diluted to obtain an injection liquid and an injection liquid.
- the injection amount is 100 ⁇ l.
- FIG. 8 shows, as an MRI image, the state of entry of injection liquid or the like when injection or the like is performed on the porcine abdominal skin tissue by each device. Note that the magnification of each MRI image is the same.
- (1) in FIG. 8 is an MRI image by the injection of the injection apparatus 1.
- (2) in FIG. 8 is an MRI image by injection with a needled syringe according to a comparative example
- (3) in FIG. 8 is an MRI image by injection with a spring-driven syringe according to a comparative example.
- the injection liquid enters the skin tissue from the incident position (the process of entering from the incident side to the back side in the image).
- the contrast of the portion through which the injection liquid has passed is clearly stronger in the relatively shallow portion (the portion up to about 10 mm in depth) than in the case of the needled syringe and the spring-driven syringe. Yes.
- the contrast agent contained in the ejected liquid diffuses in the vicinity of the flow path in the shallow region after entering the skin tissue, and as a result is further diluted to about 0.1 mmol / kg. Yes.
- the injection liquid wets between the cells and diffuses into the tissue so as to enter the cells, and a minimally invasive injection is realized. Inferred.
- the injection solution stays in a liquid pool state at a relatively shallow site, and the skin as in the case of the injection device 1. It cannot be said that it is widely spread within the organization.
- the contrast due to the contrast agent at the shallow portion from the incident position is greatly reduced as compared with the case of the injection apparatus 1 and the flow path diameter is narrowed.
- the diffusion diameter in the vicinity of the flow path in the relatively shallow portion is about 2.2 mm, and the injection device 1 having a different injection pressure is used.
- the diffusion diameter was increased to about 4.4 mm.
- the diffusion diameter in the vicinity of the flow path in the relatively shallow region is about 1.3 mm.
- the injection solution that has entered the skin tissue penetrates the target region, and it has not been possible to achieve an appropriate injection depth.
- the flow velocity of the injected injection liquid and the like is substantially the same, and the nozzle diameter is also the same.
- the diffusion of the injection solution is not promoted, and it is assumed that most of the injection solution enters the back side as it is. It can also be seen that the injection device 1 can adjust the degree of diffusion of the injection liquid in a relatively shallow region by changing the injection conditions.
- Such a clear difference between the injection device 1, a needled syringe and a spring-driven syringe is considered to depend on whether or not there is a change in the injection pressure of the injection liquid characteristic of the present invention described above. That is, the injection liquid injected by the injection apparatus 1 enters the porcine abdominal skin tissue with the pressure transition shown in FIG. 4 so that the invasiveness to the cells is suppressed and the tissue can be diffused over a wide range. It can be understood that it has been injected.
- FIG. 9 shows a micrograph of the rat skin tissue section where the injection experiment was performed by the injection apparatus 1, and the lower part (2) of the part where the injection was performed by the needle syringe.
- a photomicrograph of a rat skin tissue section is shown. The magnifications of both micrographs are the same, and the injection target corresponding to each micrograph is a different individual.
- the ink collection is shown surrounded by a solid line, but this display shows a part of the collection representatively and does not represent all the ink collection.
- the ink which is the injection liquid is in a state of being widely diffused in the skin tissue.
- the ink since the ink is gathered in a very small amount and diffused into the skin tissue, it can be easily grasped that a suitable diffusion of the ejected liquid is realized.
- the ink does not reach the vicinity of the muscle tissue or the boundary between the muscle tissue and the skin tissue and is widely diffused in a very shallow region in the skin tissue.
- the injection result by the needled syringe shown in the lower stage (2) is seen, the injected ink is retained near the boundary between the skin tissue and the muscular tissue, and a large liquid pool is formed. Also, some of the ink has reached the inside of the muscle tissue. From this, it can be understood that with a needled syringe, the ink can not be suitably diffused in the skin tissue, and it is not easy to keep the ink in the relatively shallow skin tissue.
- Such a clear difference between the injection device 1 and the needled syringe is considered to depend on whether or not there is a change in the injection pressure of the injection liquid characteristic of the present invention described above. That is, the injection liquid injected by the injection apparatus 1 enters the rat skin tissue with the pressure transition shown in FIG. 4, thereby suppressing the invasiveness to the cells and injecting so that the tissue can diffuse over a wide range. I can understand that.
- the injection apparatus 1 of the present invention can be suitably used for introducing biological substances such as genes.
- biological substances such as genes.
- for regenerative medicine for humans it becomes possible to seed cultured cells, stem cells, and the like on cells to be ejected and scaffold tissues / scaffolds.
- seed cultured cells, stem cells, and the like on cells to be ejected and scaffold tissues / scaffolds.
- cells that can be appropriately determined by those skilled in the art depending on the site to be transplanted and the purpose of recellularization such as endothelial cells, endothelial precursor cells, bone marrow cells, prebones Blast cells, chondrocytes, fibroblasts, skin cells, muscle cells, liver cells, kidney cells, intestinal cells, stem cells, and any other cells considered in the field of regenerative medicine can be ejected by the ejection device 1. is there.
- the injection device 1 according to the present invention can also be used for delivery of DNA or the like to cells, scaffold tissue, scaffolds, etc. as described in JP-T-2007-525192.
- the use of the injection device 1 according to the present invention is more preferable than the case where delivery is performed using a needle because the influence on the cells, scaffold tissue, scaffold, etc. itself can be suppressed.
- the injection device 1 when delivering various genes, tumor suppressor cells, lipid envelopes or the like directly to a target tissue, or injecting an antigen gene to enhance immunity against a pathogen, the injection device 1 according to the present invention provides Preferably used.
- various disease treatment fields fields described in JP 2008-508881, JP 2010-503616, etc.
- immunomedical fields fields described in JP 2005-523679, etc.
- the injection device 1 can be used, and the field in which the injection device 1 can be used is not intentionally limited.
- the injection liquid is injected using the igniting agent or the combination of the igniting agent and the gas generating agent as the power source, and the injection pressure is changed as shown in FIG. Achieves low invasive injection into the area.
- the transition of the injection pressure of the injection liquid is extremely important. In other words, as long as the above-described characteristic injection pressure transition of the present invention can be realized, the type of the driving source for injecting the injection liquid is not limited.
- piezoelectric actuators such as piezo elements
- electrical actuators such as ultrasonic waves
- pneumatic actuators such as compressed gas
- hydraulic actuators that utilize pressure due to boiling and expansion of liquids by lasers, etc.
- the injection pressure transition of the injection liquid which is a characteristic of the present invention, is a damped oscillation in a predetermined period ⁇ t with a steep rise in pressure as described above.
- a gas layer such as air or an inert gas may be included in the injection liquid as long as there is no problem in the injection to the target region.
- the piston 5 is employed as a configuration for transmitting the combustion energy of the ignition agent to the injection liquid (hereinafter also referred to as “transmission configuration”), but instead of this configuration, a diaphragm is used.
- Energy may be transmitted by a mechanical element such as a ram or a ram.
- a film-like form made of an elastic material or a plate-like form made of a metal material can be employed as the diaphragm.
- the diaphragm is adopted as the transmission configuration, it is possible to distinguish between a combustion space where the ignition powder is burned by the diaphragm and an arrangement space where the injection liquid is arranged.
- the injection liquid is stored in the storage chamber 32 formed in the body 30 of the syringe unit 3.
- the material of the body 30 include glass, resin, metal, and the like.
- the combustion energy generated by the combustion of the igniting agent is transmitted to the injection liquid in the storage chamber 32 through the piston 5
- the formation of the injection pressure transition of the injection liquid characteristic of the present invention is mainly performed by the plunger. It is considered that pressurization via 4 contributes, but the transition may be formed by the vibration of the piston 5 receiving the combustion energy being transmitted to the injection liquid through the body 30. Therefore, the material of the body 30 may be determined from such a viewpoint.
- a pressurizing structure in which the injection liquid is ejected from the body 30 of the syringe unit 3 by pressing the plunger 4 via the piston 5.
- Other pressurizing structures may be employed as long as the characteristic injection liquid transition of the injection liquid is realized.
- the injection liquid is stored in a flexible container that is deformed by external pressure, and the container is deformed when the container is pressurized by the injection energy from the driving unit 7.
- a pressurized structure in which the injection liquid is injected outside is also useful.
- an injection apparatus to which the present invention can be applied it is also desirable to refer to an injection apparatus having a form different from the above-described embodiments.
- the present invention can be suitably applied to an apparatus used in the field of cell processing.
- an introduction device for introducing a biological substance such as a gene into a cell it is possible to form an introduction device for introducing a biological substance such as a gene into a cell.
- the biological substance to be introduced is included in the liquid, and the liquid is pressurized and injected into the target cell.
- the injection pressure of this liquid becomes the above-mentioned characteristic injection pressure transition of the present invention, a minimally invasive substance introduction into cells is realized.
- the substance introduction the substance may be introduced into cells simultaneously from a plurality of routes.
- a catheter device As another method of the injection device to which the present invention can be applied, a catheter device can be mentioned.
- the catheter device is a device that has a catheter portion that can enter a living body and injects a desired drug solution or the like from the distal end portion of the catheter device.
- the present invention can be applied to the configuration of the chemical solution ejection from the distal end portion of the catheter portion. That is, when the medical solution is ejected from the distal end portion in a state where the catheter portion has entered the inside of the living body, the injection pressure of the chemical solution is controlled to become the above-described characteristic injection pressure transition of the present invention.
- a minimally invasive chemical solution ejection can be realized for a predetermined region of a target region (for example, an internal organ such as the heart or liver) from which the chemical solution is ejected.
- the chemical solution is injected in the form of continuous droplets, that is, in a state of being pulsed at high speed. May be.
- the chemical liquid can be injected in the form of a finer aerosol, and therefore, a less invasive chemical liquid injection can be realized.
- Such pulsing of the chemical solution can be achieved by rapidly expanding and contracting the whole or part of the reservoir containing the chemical solution.
- the expansion and contraction of the reservoir are repeated so that the transition of the injection pressure of the injected chemical solution becomes the characteristic injection pressure transition of the present invention described above.
- the expansion and contraction of the reservoir may be repeated by a mechanical configuration capable of transmitting or amplifying the pulse vibration together with the pulse vibration generation device that generates vibration electrically.
Abstract
Description
ここで、図1は、射出装置1の概略構成を示す図であり、射出装置1のその長手方向に沿った断面図でもある。射出装置1は、後述するシリンジ部3とプランジャ4とで構成されるサブ組立体(後述の図2Aを参照)10Aと、射出装置本体6とピストン5と駆動部7とで構成されるサブ組立体(後述の図2Bを参照)10Bとが一体に組み立てられた装置組立体10が、ハウジング2に取り付けられることで構成される。なお、本願の以降の記載においては、射出装置1により対象領域に射出される射出液体は、当該対象領域で期待される効能や機能を発揮する所定物質が液体の媒体に含有されることで形成されている。その射出液体において、所定物質は媒体である液体に溶解した状態となっていてもよく、また、溶解されずに単に混合された状態となっていてもよい。
ここで、射出装置1の対象領域の例として、ヒトや家畜等の生体の皮膚構造体が挙げられる。図3にはヒトの皮膚の解剖学的な構造を概略的に示す。ヒトの皮膚は、皮膚表面側から深さ方向に向かって、表皮、真皮、皮下組織・筋肉組織と層状に構成され、更に表皮は角層、皮内と層状に区別することができる。皮膚構造体の各層は、その組織を構成する主な細胞等や組織の特徴も異なる。
<実験条件>
(射出対象について)
Std:JW/CSK 雄性 16週齢 毛刈り済み・スムーススキン確認済みのものを使用した。
(射出液体及び注射液について)
下記の炎症性物質の水溶液を射出液体及び注射液とした。
炎症性物質:酢酸、蒸留水にて所定の濃度に希釈、射出量100μl
以下の表1及び表2に、実験結果を示す。なお、紅斑及び痂皮の形成、浮腫の形成のそれぞれに関する、表中の実験結果を表す数値の定義については、以下の通りである。
(紅斑及び痂皮の形成について)
0・・・紅斑なし
1・・・非常に軽度な紅斑(かろうじて視認できる紅斑)
2・・・軽度の紅斑(はっきりと視認可能な紅斑)
3・・・中度ないし高度の紅斑
4・・・高度の紅斑から痂皮の形成まで
(浮腫の形成について)
0・・・浮腫なし
1・・・非常に軽度な浮腫(かろうじて視認できる浮腫)
2・・・軽度の浮腫(はっきりと膨隆による縁を視認可能な浮腫)
3・・・中度の浮腫(約1mmの膨隆)
4・・・高度の浮腫(1mm以上の膨隆と曝露範囲を超えた広がり)
<実験条件>
(射出装置1について)
流速:202m/s(射出圧で約40MPa相当)
ノズル径:φ0.17mm
(比較例の有針注射器について)
有針注射器における注射液の注射は、一定の加圧速度の下、実行された。
注射針:27G
(比較例のバネ駆動注射器について)
流速:205m/s(射出圧で約40MPa相当)
ノズル径:φ0.17mm
(射出対象について)
ブタ皮膚組織 雌性 3ケ月齢(約50kg)腹部より採取
(射出液体及び注射液について)
バイエル薬品株式会社製の造影剤マグネビストを希釈し、射出液体及び注射液とした。なお、MRI装置による撮像において、射出液体等における造影剤の濃度が更に希釈されたとき、MRI画像でのコントラストがピークとなる。また、射出量は、100μlである。
図8に、各装置によってブタ腹部皮膚組織に対して射出等が行われた際の、射出液体等の進入の様子をMRI画像で示す。なお、各MRI画像の倍率は同じである。図8の(1)は、射出装置1の射出によるMRI画像である。図8の(2)は、比較例に係る有針注射器の注射によるMRI画像であり、図8の(3)は、比較例に係るバネ駆動注射器の注射によるMRI画像である。各MRI画像から理解できるように、射出装置1による射出を行った場合、射出液体がその入射位置から皮膚組織内を進入していく過程(画像中の入射側から奥側へ進入していく過程)のうち、比較的浅い部位(深さが10mm前後までの部位)において、射出液体が通過した部位のコントラストが、有針注射器の場合及びバネ駆動注射器の場合と比べて、明らかに強くなっている。これは、射出液体に含まれる造影剤が、皮膚組織への入射後にその浅い部位の流路近傍で拡散しその結果更に0.1mmol/kg程度に希釈された状態となっていることを意味している。そして、その拡散において、皮膚組織の体積変化は認められなかったため、射出液体は細胞間を湿潤するとともに、細胞内にも入り込むように組織内に拡散し、低侵襲の射出が実現されていると推察される。
<実験条件>
(射出装置1について)
射出圧:10.9MPa
ノズル径:φ0.11mm
(比較例の有針注射器について)
有針注射器における射出液体の注射は、一定の加圧速度の下、実行された。
注射針:27G
(射出対象について)
10週齢雄のSDラット皮膚組織
(射出液体について)
射出液体は墨汁であり、射出量は、10μlである。
図9の上段(1)に、射出装置1により射出実験が行われた箇所の、ラット皮膚組織切片の顕微鏡写真が示され、下段(2)に有針注射器により注射が行われた箇所の、ラット皮膚組織切片の顕微鏡写真が示されている。両顕微鏡写真の倍率は同じであり、また、各顕微鏡写真に対応する射出対象は、それぞれ異なる個体である。なお、図中では墨汁の集まりを実線で囲って表示しているが、この表示は一部の集まりを代表的に示したものであり、全ての墨汁の集まりを表したものではない。ここで、射出装置1による射出結果を見ると、射出液体である墨汁が、皮膚組織内に広く拡散している状態であることが分かる。この状態において、墨汁は極めて少量の集まりとなって皮膚組織内に拡散していることからも、射出液体の好適な拡散が実現されていることが容易に把握できる。また、墨汁は、筋肉組織や、筋肉組織と皮膚組織の境界近傍には到達しておらず、皮膚組織内の極めて浅い部位で広く拡散していることが理解できる。一方、下段(2)に示す有針注射器による注射結果を見ると、注射された墨汁が、皮膚組織と筋肉組織との境界近傍に滞留し大きな液溜りが形成されている。また、一部の墨汁は、筋肉組織の内部にまで到達している。このことから、有針注射器では、皮膚組織内で墨汁を好適に拡散させることはできず、また、比較的浅い皮膚組織内に墨汁を留め置くことも容易ではないことが理解できる。
本発明の射出装置1は遺伝子等の生物由来物質の導入にも好適に利用できる。例えば、ヒトに対する再生医療のために、射出対象となる細胞や足場組織・スキャフォールドに培養細胞、幹細胞等を播種することが可能となる。例えば、特開2008-206477号公報に示すように、移植される部位及び再細胞化の目的に応じて当業者が適宜決定し得る細胞、例えば、内皮細胞、内皮前駆細胞、骨髄細胞、前骨芽細胞、軟骨細胞、繊維芽細胞、皮膚細胞、筋肉細胞、肝臓細胞、腎臓細胞、腸管細胞、幹細胞、その他再生医療の分野で考慮されるあらゆる細胞を、射出装置1により射出することが可能である。
上述までの実施形態においては、点火薬、又は点火薬とガス発生剤の組合せを動力源として、射出液体の射出を行い、その射出圧を図4に示すような圧力推移とすることで、対象領域への侵襲性の低い射出を実現している。このような低侵襲性の射出を実現するためには、上記説明の通り、射出液体の射出圧の推移が極めて重要である。換言すれば、上述した本願発明の特徴的な射出圧推移を実現可能である限りにおいては、射出液体を射出する駆動源の種類は問われない。例えば、ピエゾ素子等の圧電的アクチュエータ、超音波等の電気的アクチュエータ、圧縮ガス等の空圧的アクチュエータ、レーザーによる液体の煮沸膨張による圧力を利用した液圧的アクチュエータ等が、射出液体の加圧のための駆動源として利用できる。
2・・・・ハウジング
3・・・・シリンジ部
4・・・・プランジャ
5・・・・ピストン
6・・・・射出装置本体
7・・・・駆動部
8・・・・ボタン
9・・・・バッテリ
10・・・・装置組立体
10A、10B・・・・サブ組立体
31・・・・ノズル部
32・・・・収容室
44・・・・ロッド部
53・・・・押圧柱部
54・・・・収容孔
64・・・・貫通孔
71・・・・点火器
Claims (10)
- 所定物質を含む射出液体を対象領域に射出する射出装置であって、
前記射出液体を収容する収容部と、
射出エネルギーを付与する駆動部と、
前記駆動部での射出エネルギーにより、前記収容部に収容されている前記射出液体を加圧する加圧部と、
前記加圧部によって加圧された前記射出液体を前記対象領域に対して射出口より射出する射出部と、
を備え、
前記射出口での前記射出液体の圧力推移において、圧力の立ち上り時からの所定期間内に該圧力推移における振動が収束状態を迎え、
前記所定期間内の振動における最初の第1振動要素では圧力が所定の増加速度でそのピーク値まで到達し、又は、該所定期間内の振動は所定周波数範囲に属する周波数での振動である、
射出装置。 - 前記所定の増加速度は、前記立ち上がり時から0.5msec以内に、前記ピーク値である10MPa以上の圧力に至る速度である、
請求項1に記載の射出装置。 - 前記所定周波数範囲は、500~10000Hzである、
請求項1又は請求項2に記載の射出装置。 - 前記駆動部は、少なくとも高エネルギー物質を含み、該高エネルギー物質を燃焼させることで前記射出エネルギーを生成する、
請求項1から請求項3の何れか1項に記載の射出装置。 - 前記所定期間内の振動における前記第1振動要素を除く他の振動要素の全振幅は、15MPa以下である、
請求項1から請求項4の何れか1項に記載の射出装置。 - 前記所定期間は、前記立ち上がり時から2msec以内の期間である、
請求項1から請求項5の何れか1項に記載の射出装置。 - 前記所定期間は、前記立ち上がり時から1.5msec以内の期間である、
請求項6に記載の射出装置。 - 燃焼により所定ガスを生成するガス発生剤であって、前記高エネルギー物質の燃焼によって発生する燃焼生成物に晒される位置に配置されるガス発生剤を、更に備え、
前記射出液体の圧力の前記立ち上り時から前記所定期間が経過した時期の近傍で、更に、前記ガス発生剤の燃焼で生じるエネルギーにより前記射出液体が加圧される、
請求項4に記載の射出装置。 - 前記射出エネルギーを第1射出エネルギーとし、
前記ガス発生剤の燃焼で生じるエネルギーを第2射出エネルギーとし、
前記第2射出エネルギーによる前記射出液体の圧力推移におけるピーク値は、前記第1射出エネルギーによる該射出液体の圧力推移のうち前記第1振動要素を除く圧力推移におけるピーク値以上である、
請求項8に記載の射出装置。 - 前記射出装置は、導入部を介することなく、前記射出液体を前記射出口から前記対象領域に射出する装置である、
請求項1から請求項9の何れか1項に記載の射出装置。
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US16/022,487 US20180333538A1 (en) | 2015-12-28 | 2018-06-28 | Injection apparatus |
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Also Published As
Publication number | Publication date |
---|---|
JP6954521B2 (ja) | 2021-10-27 |
EP3398635B1 (en) | 2021-12-08 |
IL260338B (en) | 2022-03-01 |
CN108430545A (zh) | 2018-08-21 |
IL260338A (en) | 2018-12-31 |
JPWO2017115869A1 (ja) | 2018-11-01 |
EP3398635A4 (en) | 2019-08-28 |
EP3398635A1 (en) | 2018-11-07 |
US20180333538A1 (en) | 2018-11-22 |
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