Device assembly for needleless syringe

Abstract

To provide a technology for injecting at least an injection object substance intracutaneously.SOLUTION: A device assembly for needleless syringe intracutaneously injects an injection object substance not via an injection needle, in which an energy value of gas generated when an igniter and a gas generating agent the device assembly are combusted, is within a prescribed range.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present disclosure relates to a device assembly for a needleless injection device. [Background technology]

[0002] A syringe is an example of a device for administering a medicinal liquid to a target region of a living body, etc. However, in recent years, needle-free syringes, which do not have a needle, have been developed for reasons of ease of use, hygiene, etc. Generally, needle-free syringes are configured to eject a medicinal liquid pressurized by a driving source such as compressed gas or a spring toward the target region, and then administer the medicinal liquid into the target region using the kinetic energy of the medicinal liquid. The use of gunpowder combustion as an alternative driving source is also being considered. As such, needle-free syringes are highly convenient for users because they do not have a mechanical component (e.g., a syringe needle) that directly contacts the interior of the target region. However, due to the absence of such a mechanical component, it has not always been easy to administer the medicinal liquid to a desired location within the target region.

[0003] A technology has been reported in which a needleless syringe is used to deliver a medicinal solution to a desired depth in a living body's skin structure (Patent Document 1). Specifically, with regard to the pressurization for injecting the injection solution, in order to form a through-path in the injection target area, pressure is controlled by performing two modes: a first pressurization mode in which the pressure is increased to a first peak pressure and then the pressure on the injection solution is decreased to a standby pressure; and a second pressurization mode in which the injection solution at the standby pressure is pressurized and the pressure on the injection solution is increased to a second peak pressure to inject a predetermined amount. By performing such pressurization control, the behavior of the injection solution within the target area is controlled. Furthermore, a technology has been reported for a needleless syringe that injects an injection target substance into a target area without using an injection needle, in which the depth to which the injected injection target substance reaches in the target area can be precisely adjusted (Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2012-61269 [Patent Document 2] Japanese Patent Application Publication No. 2019-5406 Summary of the Invention [Problem to be solved by the invention]

[0005] The object of the present disclosure is to provide at least a technique for intradermally injecting an injection target substance. [Means for solving the problem]

[0006] In order to solve the above problems, the inventors focused on the amount of energy of the gas generated when an ignition charge and a gas generating agent provided in a needleless syringe device assembly that injects an injection target substance into the skin without using a syringe needle, and as a result, the inventors newly discovered that by setting the energy parameter within a predetermined range, the injected injection target substance can be injected into the skin.

[0007] Specifically, the present disclosure provides, as an embodiment, A needleless syringe device assembly for injecting an injection target substance intradermally without using an injection needle, an encapsulation part for encapsulating the injection target substance; an igniter containing an ignition charge and a combustion chamber into which combustion products generated by the combustion of the ignition charge flow; a drive unit having a gas generating agent disposed in a chamber and ignited by the combustion products to generate gas; a pressurizing unit that applies pressure to the injection objective substance enclosed in the enclosing unit when the driving unit is driven; an injection port through which the injection objective substance pressurized by the pressurizing unit is injected into a target area; Equipped with the gas generating agent is formed so that its burning speed is slower than the burning speed of the ignition charge and its burning duration is longer than the burning duration of the ignition charge; The pressure applying unit is the injection target substance is pressurized so that the injection pressure of the injection target substance, which is defined as the pressure of the injection target substance ejected from the ejection port, rises to a first peak pressure after pressurization starts, then drops to a pressure lower than the first peak pressure, and then rises again to a second peak pressure; The drive unit is The igniter is activated to make the injection pressure of the injection target substance reach the first peak pressure by the pressure of the combustion gas of the ignition charge, and the injection pressure of the injection target substance reach the second peak pressure by the pressure of the combustion gas of the gas generating agent that is burned subsequently to the ignition charge, the ignition charge is specified so that, when burned, it generates combustion gas having a gas amount n1 (mol) and a temperature T1 (K), and the energy value of the combustion gas from the ignition charge, expressed as n1 × T1 (mol K), is 1.0 mol K or more and 2.7 mol K or less; The gas generating agent is specified so that, upon combustion, it generates combustion gas having a gas amount n2 (mol) and a temperature T2 (K), and the energy value of the combustion gas from the gas generating agent, expressed as n2 × T2 (mol K), is 3.7 mol K or more and 9.2 mol K or less. A needle-free injection device assembly can be provided.

[0008] In the needle-free syringe device assembly, the ignition charge may be any one of a gunpowder containing zirconium and potassium perchlorate, a gunpowder containing zirconium, tungsten, and potassium perchlorate, a gunpowder containing titanium hydride and potassium perchlorate, and a gunpowder containing titanium and potassium perchlorate, or a gunpowder containing a combination of two or more of these. The gas generating agent of the needle-free injection device assembly may be any one of single-base, double-base, and triple-base gas generating agents containing nitrocellulose, or a gas generating agent containing a combination of two or more of these.

[0009] The present disclosure can provide a needle-free injector including the above-described needle-free injector device assembly and a control unit to which the needle-free injector device assembly is attached and which generates an activation signal to the igniter. The present disclosure can also provide a method for injecting a target substance intradermally using the needleless injector. [Effects of the Invention]

[0010] Patent Document 2 discloses a technique for accurately adjusting the depth of an injected injection objective substance in a target area, but does not mention the conditions for intradermal injection. In contrast, the present disclosure can provide at least a technique for intradermal injection of an injection objective substance. There are many benefits to being able to inject the target substance into the skin. For example, the skin contains dendritic cells (Langerhans cells) that recognize and phagocytose antigens, transmit information to T cells, etc., and activate lymphocytes. Therefore, for example, to deliver a vaccine into the skin, This allows for a more effective antigen-antibody reaction to be induced. Furthermore, pigment cells that function to protect against the effects of ultraviolet rays irradiated from the external environment are contained within the skin, and therefore, for example, by delivering a specific substance for whitening to the skin, it is possible to carry out a so-called whitening treatment. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a diagram showing a schematic configuration of a syringe driven by an ignition charge. [Figure 2A] 2 is a diagram showing a schematic configuration of a first subassembly that constitutes a device assembly incorporated into the syringe shown in FIG. 1. FIG. [Figure 2B] 2 is a diagram showing a schematic configuration of a second subassembly that constitutes a device assembly incorporated into the syringe shown in FIG. 1. FIG. [Figure 3] 2 is a diagram showing the change in injection pressure of the injection liquid injected by the syringe shown in FIG. 1. FIG. [Figure 4] FIG. 1 is a diagram illustrating the structure of the skin. DETAILED DESCRIPTION OF THE INVENTION

[0012] The configurations and combinations thereof in each embodiment are merely examples, and additions, omissions, substitutions, and other modifications of the configurations are possible as appropriate without departing from the spirit of the present invention. The present disclosure is not limited by the embodiments, but is limited only by the scope of the claims. Furthermore, each aspect disclosed in this specification can be combined with any other feature disclosed in this specification.

[0013] In the present disclosure, "the injection target substance has reached the intradermal area" refers to the eventual intradermal arrival of the injection target substance, which can be determined by the formation of blisters (a state in which the skin surface is swollen due to the injection solution) at the injection site after injection. If blisters are not formed after injection, this indicates, for example, that most of the injection solution has been delivered subcutaneously or to the muscle, and in this case, it is not considered that "the injection target substance has reached the intradermal area." Furthermore, for example, as described below, if the injection target substance reaches the intradermal area or a location deeper than the intradermal area, but is pushed back to the skin surface or stratum corneum due to the recovery (elasticity) of the skin, and the injection target substance ultimately does not reach the intradermal area, it is not considered that "the injection target substance has reached the intradermal area."

[0014] One embodiment of the present disclosure comprises: A needleless syringe device assembly for injecting an injection target substance intradermally without using an injection needle, an encapsulation part for encapsulating the injection target substance; a drive unit including an igniter containing an ignition charge and a gas generating agent disposed in a combustion chamber into which combustion products generated by combustion of the ignition charge flow, the gas generating agent being ignited by the combustion products to generate gas; a pressurizing unit that applies pressure to the injection objective substance enclosed in the enclosing unit when the driving unit is driven; an injection port through which the injection objective substance pressurized by the pressurizing unit is injected into a target area; Equipped with. The gas generating agent is formed so that its burning speed is slower than that of the ignition charge and its burning duration is longer than that of the ignition charge. Furthermore, the pressure applying unit the injection target substance is pressurized so that the injection pressure of the injection target substance, which is defined as the pressure of the injection target substance ejected from the ejection port, rises to a first peak pressure after pressurization starts, then drops to a pressure lower than the first peak pressure, and then rises again to a second peak pressure; The drive unit is The igniter is activated to cause the pressure of the combustion gas from the ignition charge to increase the injection pressure of the injection target substance to the first peak pressure, and the pressure of the combustion gas from the gas generating agent, which is subsequently burned after the ignition charge, is added to cause the injection pressure of the injection target substance to increase to the second peak pressure. Furthermore, the ignition charge is specified so that, when burned, it generates combustion gas with a gas amount n1 (mol) and a temperature T1 (K), and the energy value of the combustion gas from the ignition charge, expressed as n1 × T1 (mol K), is 1.0 mol K or more and 2.7 mol K or less; The gas generating agent is specified so that, upon combustion, it generates combustion gas with a gas amount n2 (mol) and a temperature T2 (K), and the energy value of the combustion gas from the gas generating agent, expressed as n2 × T2 (mol·K), is between 3.7 mol·K and 9.2 mol·K.

[0015] For both ignition charges and gas generants, the energy of each gas is calculated by multiplying the amount of gas generated (n) and the gas temperature (T) by the gas constant (R), yielding nRT. Here, as the gas temperature increases, R becomes the gas constant for an ideal gas and remains a constant value. Therefore, nT without R is an alternative value for energy that characterizes the energy value, but in this disclosure it will be referred to as the energy value (or simply energy).

[0016] The device assembly for a needle-free syringe according to this embodiment can be configured as a cartridge configured to be detachable from a housing of a needle-free syringe according to another embodiment described below. The housing includes a battery that supplies power to an igniter included in a drive unit of the device assembly. The housing is a control unit that can be used repeatedly as long as there is power remaining in the battery that can be supplied to the drive unit. These details are referred to in the description of the needle-free syringe according to another embodiment described below. In other words, a needle-free syringe according to another embodiment described below is configured to include the needle-free syringe device assembly according to this embodiment and the control unit to which the needle-free syringe device assembly is attached and which generates an activation signal to the igniter. Furthermore, the needle-free syringe device assembly in the needle-free syringe can be detachably attached to the control unit, and the syringe device assembly can be configured as a cartridge that is disposable each time an injection target substance is injected intradermally.

[0017] Another embodiment of the present disclosure is a needle-free injector including a needle-free injector device assembly and a control unit to which the needle-free injector device assembly is attached, the control unit generating an activation signal to the igniter. That is, the needleless syringe according to the present disclosure is A needleless syringe that injects an injection target substance into the skin without using an injection needle, a needleless injection device assembly; a control unit to which the needle-free injector device assembly is attached, the control unit generating an activation signal to the igniter; Equipped with The needleless injection device assembly includes: an encapsulation part for encapsulating the injection target substance; a drive unit including an igniter containing an ignition charge and a gas generating agent disposed in a combustion chamber into which combustion products generated by combustion of the ignition charge flow, the gas generating agent being ignited by the combustion products to generate gas; a pressurizing unit that applies pressure to the injection objective substance enclosed in the enclosing unit when the driving unit is driven; an injection port through which the injection objective substance pressurized by the pressurizing unit is injected into a target area; Equipped with the gas generating agent is formed so that its burning speed is slower than the burning speed of the ignition charge and its burning duration is longer than the burning duration of the ignition charge; The pressure applying unit is the injection target substance is pressurized so that the injection pressure of the injection target substance, which is defined as the pressure of the injection target substance ejected from the ejection port, rises to a first peak pressure after pressurization starts, then drops to a pressure lower than the first peak pressure, and then rises again to a second peak pressure; The drive unit is The igniter is activated to make the injection pressure of the injection target substance reach the first peak pressure by the pressure of the combustion gas of the ignition charge, and the injection pressure of the injection target substance reach the second peak pressure by the pressure of the combustion gas of the gas generating agent that is burned subsequently to the ignition charge, the ignition charge is specified so that, when burned, it generates combustion gas having a gas amount n1 (mol) and a temperature T1 (K), and the energy value of the combustion gas from the ignition charge, expressed as n1 × T1 (mol K), is 1.0 mol K or more and 2.7 mol K or less; The gas generating agent is specified so that, upon combustion, it generates combustion gas with a gas amount n2 (mol) and a temperature T2 (K), and the energy value of the combustion gas from the gas generating agent, expressed as n2 × T2 (mol·K), is between 3.7 mol·K and 9.2 mol·K.

[0018] In the needle-free syringe according to this embodiment, the pressurizing unit applies pressure to the injection target substance enclosed in the enclosing unit in order to inject the injection target substance into a target area. In the needle-free syringe according to this embodiment, the energy used for the pressurization is the combustion energy of the ignition charge ignited by the activation of the igniter (the energy of the combustion gas of the ignition charge) and the combustion energy of the gas generating agent ignited by the combustion gas of the ignition charge (the energy of the combustion gas of the gas generating agent).

[0019] Examples of the injection target substance injected by the needleless syringe according to this embodiment include a substance containing a component expected to be effective intradermally or a component expected to exert a predetermined function intradermally. Therefore, as long as injection is possible with at least the energy required for pressurization, the physical form of the injection target substance may be dissolved in a liquid, or may simply be mixed without being dissolved in the liquid. For example, the predetermined substance to be delivered may be a vaccine for antibody enhancement, a protein for cosmetic purposes, or cultured cells for hair regeneration. These substances are incorporated into a liquid medium to form the injection target substance, enabling injection. Preferably, the medium does not inhibit the efficacy or function of the predetermined substance when injected intradermally. Alternatively, the medium may be a medium that exerts the efficacy or function by interacting with the predetermined substance when injected intradermally.

[0020] The injection pressure of the injection target substance formed by pressurization by the pressurizing unit rises to a first peak pressure after pressurization begins, then drops to a pressure lower than the first peak pressure, and then rises again to a second peak pressure. This first peak pressure is primarily the characteristic pressure required when the initially injected target substance punctures and penetrates the target area and enters its interior, while the subsequent second peak pressure is the characteristic pressure required to deliver most of the target substance intradermally. The injection pressure is defined as the pressure of the injection objective substance injected from the injection port, and is the pressure applied to the injection objective substance immediately after being injected from the injection port, i.e., in the vicinity of the injection port, and is the pressure required for the injection objective substance to be injected from the injection port.

[0021] The area of ​​the injection port of the needle-free syringe according to this embodiment is the same as that of the injection port of a normal needle-free syringe. For example, 0.0046 mm 2 More than 0.0095mm 2 It is less than 0.0028mm. 2 It may be 0.023 mm or more. 2 It may be the following: The diameter of the nozzle of the needle-free syringe according to this embodiment may be the same as the diameter of the nozzle of a typical needle-free syringe. For example, it may be 0.09 mm or more and 0.11 mm or less. It may also be 0.06 mm or more and 0.17 mm or less.

[0022] In a needleless syringe that achieves an injection pressure that transitions through the two peak pressures, the magnitude of the energy n1 × T1 (mol K) (related to the magnitude of the first peak pressure) and the magnitude of the energy n2 × T2 (mol K) (related to the magnitude of the second peak pressure) predominantly determine whether the injected substance reaches the skin.

[0023] The needle-free syringe according to this embodiment includes an igniter containing an ignition charge, and a gas generating agent that is disposed in a combustion chamber into which combustion products (flame and combustion gas) generated by combustion of the ignition charge flow, and that generates combustion products (flame and combustion gas) by being ignited by the combustion products of the ignition charge. The ignition charge is preferably a gunpowder containing zirconium and potassium perchlorate (ZPP), a gunpowder containing zirconium, tungsten, and potassium perchlorate (ZWPP), a gunpowder containing titanium hydride and potassium perchlorate (THPP), a gunpowder containing titanium and potassium perchlorate (TiPP), a gunpowder that can be used as an ignition charge for a gas generator, or a gunpowder containing a combination of two or more of these gunpowder.

[0024] The gas generating agent is formed so that its burning speed is slower than that of the ignition charge and its burning duration is longer than that of the ignition charge. The burning speed is expressed by the time it takes for the gas generating agent to start burning at one end under a predetermined pressure and for the burning to reach the opposite end (a predetermined burning distance), and the burning duration is expressed by the time from the start of combustion to the end of combustion.

[0025] Examples of gas generating agents include those containing nitrocellulose as a main component, which are ignited by combustion products generated by the combustion of the ignition charge to generate gas. It is also possible to use single-base smokeless powder and various gas generating agents used in gas generators for airbags and gas generators for seatbelt pretensioners. Examples of suitable powders include aluminum potassium perchlorate (APP), aluminum bismuth oxide (ABO), aluminum molybdenum oxide (AMO), aluminum copper oxide (ACO), aluminum iron oxide (AFO), single-base smokeless powders such as those listed as M1, M6, and M10 in Interior Ballistics of Guns, Progress in Astronautics and Aeronautics, Martin Summerfield, Series Editor-in-Chief, Volume 66, double-base powders such as those listed as M2, triple-base powders such as those listed as M30 and M31, and mixtures containing combinations of these.

[0026] The pressurizing unit activates the igniter to make the injection pressure of the injection target substance reach the first peak pressure by the pressure of the combustion gas of the ignition charge, and also makes the injection pressure of the injection target substance reach the second peak pressure by adding the pressure of the combustion gas of the gas generating agent that is burned subsequently to the ignition charge. By burning the ignition charge and the gas generating agent in conjunction in this way, it is possible to pressurize the injection target substance by the pressurizing unit described above.

[0027] A feature of the above ignition charge is that the injection pressure drops quickly once it reaches the first peak pressure. After that, the gas generating agent burns, causing the injection pressure to reach the second peak pressure relatively slowly. In this way, the ignition charge is mainly responsible for forming the initial pressure transition of the injection pressure, and the gas generating agent is responsible for forming the subsequent injection pressure transition, thereby facilitating the delivery of the injected substance into the skin. This can be preferably done.

[0028] In the needle-free syringe according to this embodiment, as described above, the igniter is activated to cause the injection pressure of the injection target substance to reach the first peak pressure by the pressure of the combustion gas of the ignition charge. The first peak pressure is a characteristic pressure required when the initially injected injection target substance punctures and penetrates the target area and enters the interior thereof. Therefore, in order to deliver the injection target substance intradermally, the value of the energy n1×T1 (mol·K), which is related to the first peak pressure, is set within a predetermined range. Furthermore, in the needle-free syringe according to this embodiment, as described above, the pressure of the combustion gas from the ignition charge is added to the pressure of the combustion gas from the gas generating agent, which is burned following the ignition charge, causing the injection pressure of the injection target substance to reach the second peak pressure. The second peak pressure is a characteristic pressure required to deliver most of the injection target substance intradermally. Therefore, in order to deliver the injection target substance intradermally, the value of the energy n2 × T2 (mol K), which is related to the second peak pressure, is set within a predetermined range.

[0029] The sum of the energy n1 × T1 (mol·K) and the energy n2 × T2 (mol·K) is not particularly limited as long as it allows the injection target substance to be delivered intradermally, and is preferably 4.6 mol·K or more and 11.8 mol·K or less. Also, for example, 4.8mol·K, 5.0mol·K, 5.2mol·K, 5.4mol·K, 5.6mol·K, 5.8mol·K, 5.9mol·K, 6.0mol·K, 6.1mol·K, 6.2mol·K, 6.3mol·K, 6.4mol·K, 6.6mol·K, 6.7mol·K, 6.8mol·K, 6.9 mol K, 7.0 mol K, 7.1 mol K, 7.2 mol K, 7.4 mol K, 7.5 mol K, 7.6 mol K, 7.7 mol K, 7.8 mol K, 7.9 mol K, 8.0 mol K, 8.2 mol K, 8.3 mol K, 8.4 mol K, 8.5 mol K, 8.6 mol K, 8.8 mo The upper or lower limit may be any one of 1·K, 8.9mol·K, 9.0mol·K, 9.1mol·K, 9.2mol·K, 9.3mol·K, 9.4mol·K, 9.5mol·K, 9.6mol·K, 9.7mol·K, 9.8mol·K, 9.9mol·K, 10.0mol·K, 10.1mol·K, 10.2mol·K, 10.3mol·K, 10.4mol·K, 10.5mol·K, 10.6mol·K, 10.7mol·K, 10.8mol·K, 10.9mol·K, 11.0mol·K, 11.1mol·K, 11.2mol·K, 11.3mol·K, 11.4mol·K, and 11.6mol·K.

[0030] The energy required to deliver an injection target substance intradermally has the following relationship between the energy n1×T1 (mol·K) and the energy n2×T2 (mol·K): For example, the energy of the combustion gas generated by the combustion of the ignition charge is largely influenced by the gas temperature and less by the number of moles of gas. In other words, the gas temperature rises rapidly during combustion and tends to drop after combustion, resulting in a sudden (non-sustained) supply of energy from the ignition charge. Therefore, the energy of the combustion gas generated by the combustion of the ignition charge is primarily used to perforate the skin and partially deliver the injection target substance into the skin. On the other hand, the energy of the combustion gas generated by the combustion of the gas generant is more heavily influenced by the number of moles of gas and less affected by the temperature drop. Furthermore, the sustained supply of this energy is thought to deliver the injection target substance so that it diffuses over a wide area within the skin. Therefore, even if the energy of the combustion gas generated by the combustion of the ignition charge is relatively small and the injection target substance is not sufficiently delivered into the skin initially, as long as a perforation is achieved, it is speculated that the energy of the combustion gas generated by the gas generant may have a complementary effect. In other words, it is speculated that the energy of the combustion gas from the gas generant acts to widely diffuse the injection target substance initially injected to a predetermined depth corresponding to the depth within the skin. Specifically, when the energy n1 × T1 (mol·K) is in the range of 1.0 mol·K to 2.7 mol·K, and the energy n2 × T2 (mol·K) exceeds 9.2 mol·K, it is estimated that the injection target substance will ultimately pass through the skin and be delivered to the dermis. Therefore, when the energy n1 × T1 (mol·K) is in the range of 1.0 mol·K to 2.7 mol·K, it is preferable that the energy n2 × T2 (mol·K) be set to 9.2 mol·K or less. In this way, the energy n1×T1 (mol·K) and the energy n2×T2 (mol·K) work together to deliver the injection target substance intradermally.

[0031] Furthermore, when the energy n2×T2 (mol·K) is less than 3.7 mol·K, even if the energy n1×T1 (mol·K) is within the range of 1.0 mol·K or more and 2.7 mol·K or less, it is presumed that the injection objective substance will not be able to reach the intradermal space with the energy n1×T1 (mol·K) and that the injection objective substance will not be able to reach the intradermal space with the energy n2×T2 (mol·K) either. Alternatively, even if the injection objective substance can reach the intradermal space with the energy n1×T1 (mol·K), the injection objective substance will be pushed back from the intradermal space to the skin surface or stratum corneum due to the recovery (elasticity) of the skin during the time when the injection pressure decreases after reaching the first peak pressure to a pressure lower than the first peak pressure, and that the injection objective substance will not be able to reach the intradermal space again with the energy n2×T2 (mol·K). Therefore, when the energy n1×T1 (mol·K) is in the range of 1.0 mol·K or more and 2.7 mol·K or less, the energy n2×T2 (mol·K) is preferably set to 3.7 mol·K or more.

[0032] Furthermore, when the energy n1×T1 (mol·K) is less than 1.0 mol·K, even if the energy n2×T2 (mol·K) is within the range of 3.7 mol·K or more and 9.2 mol·K or less, the injection objective substance cannot perforate or penetrate the target area or enter its interior with the energy n1×T1 (mol·K), and furthermore, the injection objective substance cannot perforate or penetrate the target area or enter its interior with the energy n2×T2 (mol·K), so it is presumed that the injection objective substance cannot be delivered intradermally. Therefore, when the energy n2×T2 (mol·K) is within the range of 3.7 mol·K or more and 9.2 mol·K or less, it is preferable that the energy n1×T1 (mol·K) be set to 1.0 mol·K or more.

[0033] Furthermore, when the energy n1×T1 (mol·K) exceeds 2.7 mol·K, even if the energy n2×T2 (mol·K) is within the range of 3.7 mol·K to 9.2 mol·K, it is presumed that the injection objective substance will be delivered deep into the skin by the first peak pressure, and ultimately the injection objective substance will diffuse deeper than intradermal. Therefore, when the energy n2×T2 (mol·K) is within the range of 3.7 mol·K to 9.2 mol·K, it is preferable to set the energy n1×T1 (mol·K) to 2.7 mol·K or less.

[0034] Furthermore, the energy n1×T1 (mol·K) may be, for example, any of 1.1 mol·K, 1.3 mol·K, 1.5 mol·K, 1.7 mol·K, 1.9 mol·K, 2.1 mol·K, 2.3 mol·K, and 2.5 mol·K, and may be set as an upper or lower limit value. Furthermore, the energy n2×T2 (mol·K) may be, for example, any of 4.3 mol·K, 4.9 mol·K, 5.5 mol·K, 6.1 mol·K, 6.7 mol·K, 7.3 mol·K, 7.9 mol·K, and 8.5 mol·K, and may be set as an upper or lower limit.

[0035] The energy n1 × T1 (mol·K) is calculated using the method described in JP-A-2010-269969 and The amount of ignition charge can be converted using n1 and T1 obtained by simulation using NEWPEP disclosed in Table 2001-515009. The energy n2 × T2 (mol·K) is described in "Explosives and Ammunition Technology Handbook, 2012 Revised Edition, Published by the Defense Technology Association" and "Interior Ballistics of Guns, Progress in Astronautics and Aeronautics, Martin Summerfield, Series Editor-in-Chief, Volume 66." The information provided allows conversion to and from the amount of gas generating agent.

[0036] The phrase "the injection target substance reaches the intradermal space" refers to, for example, as in the examples described below, when the injection target substance is injected onto the skin surface with a sample number N=5 or more, and the proportion of the number of times the injection target substance reaches the intradermal space relative to the number of injections under those conditions is 60% or more, with a higher proportion being preferable, and in order of increasing preference, these are 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, and 100%.

[0037] A needleless syringe (hereinafter simply referred to as "syringe") 1 according to one embodiment of the present disclosure will be described below with reference to the drawings. The syringe 1 is a needleless syringe that uses the combustion energy of gunpowder to inject an injection solution corresponding to the injection target substance of the present application into a target area, i.e., a device that injects an injection solution intradermally without using an injection needle. The syringe 1 will be described below.

[0038] The configurations of the following embodiments are merely examples, and the present invention is not limited to the configurations of these embodiments. In these examples, the terms "tip side" and "base side" are used to describe the relative positional relationship in the longitudinal direction of the syringe 1. The "tip side" refers to a position closer to the tip of the syringe 1, which will be described later, i.e., closer to the injection port 31a, and the "base side" refers to the direction opposite to the "tip side" in the longitudinal direction of the syringe 1, i.e., the direction toward the drive unit 70.

[0039] <Configuration of Syringe 1> FIG. 1 is a diagram showing a schematic configuration of a syringe 1 and is also a cross-sectional view of the syringe 1 taken along its longitudinal direction. The syringe 1 is configured by attaching to a housing 2 a device assembly 10, which is an integral assembly of a subassembly 10A (see FIG. 2A below) consisting of a syringe section 3 and a plunger 4, which will be described later, and a subassembly 10B (see FIG. 2B below) consisting of a syringe body 6, a piston 5, and a drive section 70. In the following description of this disclosure, the injection solution delivered into the skin by the syringe 1 is formed by incorporating a predetermined substance, which exerts an expected efficacy or function within the skin, into a liquid medium. In the injection solution, the predetermined substance may be dissolved in the liquid medium, or may simply be mixed without being dissolved.

[0040] Examples of the predetermined substance contained in the injection solution include biomolecules that can be injected intradermally. There are no particular limitations on the biomolecules, as long as they are physiologically active within the skin upon injection. Furthermore, the biomolecules may be natural or artificially synthesized. Examples include nucleic acids or their derivatives; nucleosides, nucleotides, or their derivatives; amino acids, peptides, proteins, or their derivatives; lipids or their derivatives; metal ions; low-molecular-weight compounds or their derivatives; antibiotics; and vitamins or their derivatives. Nucleic acids may be DNA or RNA, and may contain genes or may be in the form of vaccines. Further examples of biomolecules include low-molecular-weight drugs, inorganic substances such as metal particles for thermotherapy or radiotherapy, and various substances with pharmacological or therapeutic effects, including carriers. The liquid medium for the injection solution may be any substance suitable for delivering these biomolecules to the skin, regardless of whether it is aqueous or oily. Furthermore, the viscosity of the liquid medium is not particularly limited as long as the predetermined substance can be injected using the syringe 1.

[0041] The device assembly 10 is configured to be detachable from the housing 2. A filling chamber 32 (see FIG. 2A ) formed between the syringe portion 3 and plunger 4 included in the device assembly 10 is filled with an injection solution. The device assembly 10 can be configured as a unit, i.e., a cartridge, that is replaced each time an injection solution is to be injected. Meanwhile, the housing 2 is configured as a control unit that controls the injection of the injection solution by the device assembly 10, and the housing 2 includes a battery 9 that supplies power to an igniter 71 included in a drive unit 70 of the device assembly 10. When a user presses a button 8 provided on the housing 2, power is supplied from the battery 9 via wiring between an electrode on the housing 2 side and an electrode on the initiator 7 side of the drive unit 70 of the device assembly 10. The shapes and positions of the electrodes on the housing 2 side and the electrode on the initiator 7 side of the drive unit 70 of the device assembly 10 are designed so that they automatically come into contact when the device assembly 10 is attached to the housing 2. The housing 2 is a control unit that can be used repeatedly as long as there is power remaining in the battery 9 that can be supplied to the initiator 7 of the drive unit 70. When the battery 9 of the housing 2 runs out of power, the battery 9 alone may be replaced and the housing 2 may continue to be used, or the battery 9 may be recharged and used repeatedly.

[0042] 2A and 2B, the configurations of subassemblies 10A and 10B, and the detailed configurations of syringe section 3, plunger 4, piston 5, syringe body 6, and drive section 70 included in both subassemblies will be described. Syringe section 3 has nozzle section 31 including filling chamber 32, which is a space capable of containing an injection solution, and plunger 4 is disposed in subassembly 10A so as to be slidable within filling chamber 32.

[0043] For example, known materials such as nylon 6-12, polyarylate, polybutylene terephthalate, polyphenylene sulfide, or liquid crystal polymer can be used for the body 30 of the syringe portion 3. Furthermore, these resins may contain fillers such as glass fiber or glass filler, and polybutylene terephthalate may contain 20 to 80% by mass of glass fiber, polyphenylene sulfide may contain 20 to 80% by mass of glass fiber, and liquid crystal polymer may contain 20 to 80% by mass of mineral.

[0044] The plunger 4 is disposed in a filling chamber 32 formed inside the body 30 so as to be slidable toward the nozzle portion 31 (toward the tip side), and the space formed between the plunger 4 and the body 30 of the syringe portion 3 is the space in which the injection solution 320 is sealed. In this embodiment, the filling chamber 32 in which the injection solution 320 is sealed corresponds to the "sealing portion." Here, as the plunger 4 slides within the filling chamber 32, the injection solution 320 contained in the filling chamber 32 is pressed and injected from the injection port 31a provided on the tip side of the nozzle portion 31. For this reason, the plunger 4 is formed of a material that allows smooth sliding within the filling chamber 32 and prevents the injection solution 320 from leaking from the plunger 4 side. Specific examples of the material that can be used for the plunger 4 include butyl rubber and silicone rubber. Further examples include styrene elastomers, hydrogenated styrene elastomers, and mixtures thereof with polyolefins such as polyethylene, polypropylene, polybutene, and α-olefin copolymers, oils such as liquid parabens and process oil, and powdered inorganic materials such as talc, cast, and mica. Furthermore, polyvinyl chloride elastomers, olefin elastomers, polyester elastomers, polyamide elastomers, polyurethane elastomers, various rubber materials (especially vulcanized ones) such as natural rubber, isoprene rubber, chloroprene rubber, nitrile-butadiene rubber, and styrene-butadiene rubber, and mixtures thereof, can also be used as the material for plunger 4. Furthermore, in order to ensure and adjust the sliding properties between plunger 4 and syringe portion 3, the surface of plunger 4 and the surface of filling chamber 32 of syringe portion 3 can be coated with various substances. The surface can be coated or treated with other materials such as PTFE (polytetrafluoroethylene), silicone oil, diamond-like carbon, and nanodiamond.

[0045] As shown in FIG. 2A , the plunger 4 has a head 41 and a body 42, which are connected by a neck 43 having a diameter smaller than the diameters of the head 41 and the body 42. The diameter of the neck 43 is reduced in this manner to provide a space for accommodating an O-ring, which serves as a sealing member. The contour of the distal end of the head 41 roughly matches the contour of the inner wall surface of the nozzle 31. This minimizes the gap formed between the plunger 4 and the inner wall surface of the nozzle 31 when the plunger 4 slides toward the nozzle 31 during injection of the injection solution and reaches the innermost position in the filling chamber 32. This prevents the injection solution 320 from remaining in the filling chamber 32 and being wasted. However, the shape of the plunger 4 is not limited to a specific shape as long as the desired effect can be achieved in the syringe of this embodiment.

[0046] Furthermore, plunger 4 is provided with a rod portion 44 that extends further in the proximal direction from the end face on the proximal side of barrel portion 42. This rod portion 44 has a diameter that is sufficiently smaller than barrel portion 42, but has a diameter that allows a user to grasp rod portion 44 and move it within filling chamber 32. Furthermore, the length of rod portion 44 is determined so that even when plunger 4 is at the innermost position of filling chamber 32 of syringe portion 3, rod portion 44 protrudes from the end face on the proximal side of syringe portion 3, allowing a user to grasp rod portion 44.

[0047] Returning now to the description of the syringe unit 3, the inner diameter of the flow path provided in the nozzle unit 31 on the syringe unit 3 side is formed smaller than the inner diameter of the filling chamber 32. With this configuration, the highly pressurized injection solution 320 is ejected to the outside from the ejection port 31a of the flow path. Therefore, an annular shield unit 31b is provided on the tip side of the syringe unit 3 near the nozzle unit 31 so as to surround the ejection port 31a. When the ejection port 31a is pressed against a target area such as human skin to eject the injection solution, the shield unit 31b can shield the ejected injection solution from scattering around the area. Furthermore, by slightly indenting the skin when the ejection port is pressed against the skin surface, the contact between the ejection port and the skin can be improved, thereby suppressing the scattering of the injection solution. Therefore, as shown in FIG. 2A, the tip of the nozzle unit 31, where the ejection port 31a is located, may protrude slightly in the injection direction beyond the end face of the shield unit 31b.

[0048] Furthermore, a threaded portion 33a is formed on neck portion 33 located on the base end side of syringe portion 3 for connecting syringe body 6 on the subassembly 10B side, which will be described later, to syringe portion 3. The diameter of neck portion 33 is set smaller than the diameter of body 30.

[0049] Next, subassembly 10B including piston 5, syringe body 6, and drive unit 70 will be described with reference to FIG. 2B . Piston 5 is pressurized by combustion products generated by igniter 71 of drive unit 70 and slides within through-hole 64 formed within body 60 of syringe body 6. A coupling recess 61 is formed on the distal end side of syringe body 6 relative to through-hole 64. This coupling recess 61 is a portion that couples with neck 33 of syringe unit 3, and a threaded portion 62a that threadably engages with threaded portion 33a provided on neck 33 is formed on a side wall surface 62 of coupling recess 61. Through-hole 64 and coupling recess 61 are connected by a communicating portion 63, the diameter of which is set smaller than the diameter of through-hole 64. A drive unit recess 65 is formed on the proximal end side of syringe body 6 relative to through-hole 64. The initiator 7 of the drive unit 70 is to be placed in this drive unit recess 65.

[0050] Piston 5 is made of metal and has first body 51 and second body 52. ​​Piston 5 is disposed in through-hole 64 so that first body 51 faces coupling recess 61 and second body 52 faces drive recess 65. Piston 5 slides within through-hole 64 while first body 51 and second body 52 face the inner wall surface of through-hole 64 of syringe body 6. First body 51 and second body 52 are connected by a connecting portion that is thinner than the diameter of each body. An O-ring or the like is disposed in the resulting space between both bodies to enhance adhesion to the inner wall surface of through-hole 64. Piston 5 may also be made of resin. In this case, metal may also be used in combination with resin in portions that require heat resistance and pressure resistance.

[0051] Here, a pressing column 53 having a diameter smaller than that of the first body 51 and smaller than that of the communicating portion 63 of the syringe body 6 is provided on the end surface on the tip side of the first body 51. The pressing column 53 has an accommodating hole 54 that opens on the end surface on the tip side, has a diameter equal to or greater than that of the rod portion 44, and is deeper than the length of the rod portion 44. Therefore, when the piston 5 is pressurized by the combustion gas of the igniter 71, the pressing column 53 can transmit the combustion energy to the end surface on the base side of the body 42 of the plunger 4 via the end surface on the tip side. The shape of the piston 5 is not limited to the shape shown in FIG. 2B . In this embodiment, the plunger 4 and the piston 5 constitute a "pressurizing portion."

[0052] Next, the drive unit 70 will be described. The drive unit 70 includes an initiator 7 and a gas generating agent 80, and the initiator 7 includes an igniter 71 and a body 72. The drive unit 70 has a cylindrical body 72 that includes an igniter 71 containing an ignition charge that burns the ignition charge to generate energy for ejection. The initiator 7 of the drive unit 70 is disposed in the drive unit recess 65, as described above, so that combustion energy from the igniter 71 can be transmitted to the second body portion 52 of the piston 5. More specifically, the body 72 of the drive unit 70 may be formed by fixing an injection-molded resin to a metal collar. A known injection molding method can be used for this injection molding. The resin material for the body 72 of the drive unit 70 is the same as that for the body 30 of the syringe unit 3.

[0053] Here, the energy of the combustion gas generated when the ignition charge used in the igniter 71 burns provides the energy required for the syringe 1 to perforate the target area with the injection liquid and to inject the injection liquid to a predetermined depth within the target area. Preferable ignition charges include zirconium and potassium perchlorate (ZPP), zirconium, tungsten, and potassium perchlorate (ZWPP), titanium hydride and potassium perchlorate (THPP), titanium and potassium perchlorate (TiPP), and other explosives that can be used as ignition charges in gas generators, or explosives containing a combination of these explosives. Other explosives may also be used as ignition charges as long as they are capable of properly injecting the injection liquid.

[0054] In addition to the ignition charge, the syringe 1 uses a gas generant 80 to adjust the pressure transition applied to the injection liquid via the piston 5. The gas generant 80 is ignited and burned by combustion products (flame and combustion gases) of the ignition charge in the igniter 71, thereby generating combustion gas. In the present disclosure, the gas generant 80 constitutes part of the drive unit 70 and is disposed in a location where it can be exposed to combustion products from the igniter 71, as shown in FIGS. 1 and 2B, for example. Alternatively, the gas generant 80 may be disposed within the igniter 71, as disclosed in International Publication No. 01-031282 and Japanese Patent Application Laid-Open No. 2003-25950. An example of a gas generant is a single-base smokeless powder containing 98% by mass of nitrocellulose, 1.0% by mass of diphenylamine, and 1.0% by mass of potassium sulfate. Various gas generants used in gas generators for airbags and gas generators for seatbelt pretensioners may also be used. When placed in the through-hole 64, the gas generating agent By adjusting the dimensions, size, shape, and especially the surface shape, it is possible to change the time until the combustion of the gas generating agent is completed, thereby adjusting the pressure transition applied to the injection liquid and making the injection pressure transition as desired.

[0055] The injection solution 320 is filled into the subassembly 10A by inserting the plunger 4 to the innermost position, immersing the injection port 31a in a container filled with the injection solution, and then, while maintaining this state, pulling the plunger 4 back to the opening side of the filling chamber 32, i.e., the base end side of the syringe portion 3. At this time, the plunger 4 is pulled out until the base end face of the barrel portion 42 of the plunger 4 reaches a position where it projects slightly beyond the base end face of the syringe portion 3.

[0056] In the subassembly 10B, the piston 5 is first inserted from the base end side of the syringe 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. The piston 5 is then positioned so that the tip end face of the piston 5, i.e., the tip end face of the pressing column portion 53 where the accommodating hole 54 opens, protrudes a predetermined amount from the bottom face of the coupling recess 61 (a plane perpendicular to the side wall surface 62). The piston 5 can be positioned using any known technique, such as setting a positioning mark in the through-hole 64 or using a positioning jig. Then, the gas generating agent 80 is placed in the through-hole 64, and the initiator 7 of the drive unit 70 is attached to the drive unit recess 65. The fixing force of the piston 5 in the through-hole 64 is set to a level that allows the piston 5 to slide smoothly within the through-hole 64 depending on the pressure received from the combustion products of the igniter 71 of the drive unit 70, and is set to a level that is sufficient to resist the force received by the piston 5 from the plunger 4 when the subassembly 10A is attached to the subassembly 10B, and prevents the position of the piston 5 from fluctuating.

[0057] Subassembly 10A configured in this manner is attached to subassembly 10B by threading threads 33a and 62a together, thereby forming device assembly 10. As the two components are joined together, rod portion 44 of plunger 4 enters and is housed in accommodation hole 54 provided in pressing column portion 53 of piston 5, and eventually the tip end face of pressing column portion 53 comes into contact with the base end face of barrel portion 42 of plunger 4. Note that accommodation hole 54 is large enough to house rod portion 44, so in this contact state, the inner wall surface at the back of accommodation hole 54 (particularly the bottom surface of accommodation hole 54) does not come into contact with the base end of rod portion 44, and therefore rod portion 44 does not receive a load from piston 5. When the piston 5 is further advanced to the final screwing position, the piston 5 is fixed in position in the through-hole 64 by sufficient friction as described above, and therefore the pressing column portion 53 pushes the plunger 4 toward the injection port 31a, positioning the plunger 4 within the syringe portion 3. A portion of the injection solution 320 according to the amount of the plunger 4 pushed out is discharged from the injection port 31a.

[0058] When the plunger 4 is positioned at the final position in this manner, the formation of the device assembly 10 is completed. In this device assembly 10, the piston 5 is positioned at a predetermined position relative to the syringe body 6, and the position of the plunger 4 in the filling chamber 32 of the syringe part 3 is finally determined mechanically using the piston 5 as a reference. Since the final position of the plunger 4 is a position that is uniquely determined in the device assembly 10, it is possible to set the amount of injection solution 320 finally contained in the filling chamber 32 to a predetermined amount.

[0059] The device assembly 10 is attached to the housing 2, and when the user presses the button 8 while the injection port 31a is in contact with the target area, the injection liquid 320 is pressurized via the piston 5 and plunger 4, and the injection is performed, so that the injection liquid 320 is injected into the target area.

[0060] FIG. 3 shows the change in pressure of the injection solution ejected from the ejection port 31a (hereinafter simply referred to as "injection pressure") as the drive unit 70 of the syringe 1 ejects the injection solution. The horizontal axis of FIG. 3 represents elapsed time, and the vertical axis represents the injection pressure. The injection pressure can be measured using conventional techniques. For example, the injection force may be measured using the method described in Japanese Patent Application Laid-Open No. 2005-21640. Specifically, the injection force is distributed across the diaphragm of a load cell located downstream of the nozzle. The output from the load cell is then collected by a data collection device via a detection amplifier and stored as the injection force (N) per unit time. The injection pressure is calculated by dividing the thus measured injection force by the area of ​​the ejection port 31a of the syringe 1. The example shown in Figure 3 shows the transition of injection pressure obtained by using ZPP (containing zirconium and potassium perchlorate) as the ignition charge in the igniter 71 in the drive unit 70 and placing a gas generating agent in the through-hole 64.

[0061] The injection pressure transition shown in FIG. 3 is the transition of the injection pressure from the start of combustion until the injection pressure is almost completely eliminated, with the point of time when the button 8 of the drive unit 70 is pressed as the origin. The rise of the injection pressure is slightly shifted from the origin because it takes a certain amount of time for the injection liquid to be pressurized and ejected from the injection port 31a as a result of the combustion of the ignition charge and the resulting combustion energy propelling the piston 5. Here, in the syringe 1, as described above, the ignition charge in the igniter 71 first burns, followed by the combustion of the gas generant 80, resulting in two peak pressures P1 and P2 appearing in the transition of the injection pressure in a manner that roughly corresponds to the respective combustion events. That is, due to the combustion of the ignition charge, which has a relatively fast combustion rate, a first peak pressure P1 appears, which forms a steep pressure transition at the beginning of the transition of the injection pressure. The timing at which this first peak pressure P1 appears is referred to as first timing T1. When the ignition charge burns, the gas generating agent is exposed to the combustion products produced thereby, thereby initiating combustion of the gas generating agent 80. However, since the ignition charge is gaseous at high temperatures but does not contain any gaseous components at room temperature, the injection pressure drops immediately after the first timing T1 has passed. On the other hand, since the combustion rate of the gas generating agent 80 is slower than that of the ignition charge, even when combustion of the gas generating agent 80 begins, the increase in injection pressure is relatively gradual compared to the process leading to the first peak pressure, and the second peak pressure P2 is reached at the second timing T2, which is delayed from the first timing T1. After the second peak pressure P2 has passed, the injection pressure decreases, and the point at which the injection pressure becomes approximately zero is defined as the pressurization end timing Tf.

[0062] In this way, syringe 1 can also be described as a device that pressurizes the injection solution to generate the injection pressure shown in Figure 3. The injection solution to which this injection pressure is applied physically acts on the target area, perforating and penetrating the target area and penetrating into the interior, thereby achieving intradermal injection of the injection solution. Here, examples of targets for syringe 1 include the skin structures of living organisms such as humans and livestock. Figure 4 shows a schematic diagram of the anatomical structure of human skin. Human skin is layered from the surface of the skin toward the depth direction, consisting of the epidermis, dermis, subcutaneous tissue, and muscle tissue. The epidermis can be further divided into layers: the stratum corneum and intradermal layer. Each layer of the skin structure differs in the main cells and tissue characteristics that make up the tissue.

[0063] Specifically, the stratum corneum is primarily composed of keratinocytes and, because it is located on the outermost surface of the skin, functions as a barrier layer. The stratum corneum is generally about 0.01–0.015 mm thick, and keratinocytes protect the human surface. Therefore, it requires a relatively high level of strength to provide a certain degree of physical barrier between the external environment and the human body. The stratum corneum and the dermis form the epidermis, which is generally about 0.1–0.2 mm thick. The dermis is also home to a complex network of blood vessels and capillaries on the skin, sweat glands for regulating body temperature, hair roots (including scalp hair), and associated sebaceous glands. The dermis is the layer that connects the epidermis to the human body (subcutaneous tissue and muscle tissue), and is composed of fibroblasts and collagen. Therefore, the condition of the dermis plays a major role in the development of wrinkles and hair loss caused by a lack of collagen and elastin.

[0064] The target area into which the injection objective substance is injected by the needle-free syringe according to this embodiment and the intradermal area into which the injection objective substance is injected are preferably the target area of ​​a mammal and the intradermal area into which the injection objective substance is injected, respectively. They may also be in vitro systems, in vivo systems, or ex vivo systems. That is, the target area and the intradermal area into which the injection objective substance is injected may be in a state where they exist in an individual (living body), or may not exist in an individual (living body). The latter may be, for example, a state where they have been extracted or separated from an individual (living body). The latter may also be a form excluding the target area that exists in an individual (living body) and the intradermal area into which the injection objective substance is injected. The mammals include humans and non-human mammals. Humans include healthy individuals and individuals (patients) suffering from diseases, etc. The non-human mammals include, for example, pigs, cows, goats, sheep, monkeys, dogs, cats, rats, mice, hamsters, and guinea pigs. The target area into which the injection objective substance is injected by the needleless syringe according to this embodiment and the intradermal area into which the injection objective substance is injected may be the skin surface and intradermal area of ​​a skin model, respectively. The skin model and the stem cells may be derived from mammals, and preferred embodiments of the mammals are as described above.

[0065] Another embodiment of the present disclosure is a method for injecting an injection target substance intradermally using the needleless syringe. The target area into which the injection objective substance is injected by the needle-free syringe and the intradermal form into which the injection objective substance is injected are the same as those previously described. Therefore, this embodiment may be, for example, a method of injecting an injection objective substance intradermally using the needle-free syringe (excluding the intradermal form in an individual (living body)), a method of injecting an injection objective substance intradermally (excluding the intradermal form in humans) using the needle-free syringe, or a method of injecting an injection objective substance intradermally into a mammal (excluding humans) using the needle-free syringe. [Example]

[0066] The following examples are provided, but none of the examples should be construed as limiting.

[0067] The experimental conditions and results of an injection experiment conducted using the syringe 1 according to the present disclosure are shown below. The following experimental conditions were set with the aim of delivering the injection solution into the pig's skin. Note that pig's skin is widely used as a model of human skin in various tests, so the results of this experiment can also be applied to cases where human skin is the target.

[0068] <Experimental conditions> (Regarding syringe 1) The initiator 20's ignition charge 22 was a ZPP (zirconium-potassium perchlorate) mixture that generates gas with the energy values ​​listed on the vertical axis of Table 1, and the gas generant 30 was a single-base smokeless powder (M10) that generates gas with the energy values ​​listed on the horizontal axis of Table 1. From Interior Ballistics of Guns, Progress in Astronautics and Aeronautics, Martin Summerfield, Series Editor-in-Chief, Volume 66, the values ​​used for n1 of ZPP were 0.94 (mol / 100g) and T1 = 4048 (K), rounded to the nearest tenth. Also, from NEWPEP, the value for n2 of M10 was 4.07 (mol / 100g). g), T2 = 3,000 (K) and round it off to the first decimal place. did. The value in each cell of Table 1 is the sum of the energy value of the gas generated when the ZPP mixture is burned, listed on the vertical axis, and the energy value of the gas generated when the gas generant 30 is burned, listed on the horizontal axis. However, this sum is calculated by adding the energy value of the gas generated when the ZPP mixture is burned, listed on the vertical axis, and the energy value of the gas generated when the gas generant 30 is burned, listed on the horizontal axis, taking into account two decimal places, and then rounding it off to one decimal place. Therefore, if this sum differs from the value obtained by simply adding the values ​​on the vertical axis and the horizontal axis in Table 1, the value in each cell will be treated as a normal sum. The diameter of the nozzle 4 is 0.1 mm, and one nozzle 4 is disposed in the syringe portion 3. The component ratio of single-base smokeless powder, for example, M10 as expressed in Interior Ballistics of Guns, Progress in Astronautics and Aeronautics, Martin Summerfield Series Editor-in-Chief, Volume 66, is as follows: Nitrocellulose: 98.0% by weight Diphenylamine: 1.0% by weight Potassium sulfate: 1.0% by weight Graphite (external component): trace amount

[0069] (Regarding injection subjects) In this example, the target area was the skin surface of the pig's abdomen. Specifically, the injection target area was the skin surface from the mid-abdomen to the flank of a pig (SPF piglet, LWD, female, weighing approximately 50 kg). The pig was anesthetized immediately before the experiment, and was placed on its back on a bed with its limbs immobilized. In this state, the nozzle part 31 of the syringe 1 was pressed as perpendicularly as possible against the skin surface, and then a load of 500 to 1500 g·f was applied to press the nozzle part 31 onto the skin surface, and the switch was pressed to inject the injection liquid. When the skin of a slaughtered pig is used as the injection target area, either refrigerated pig skin or frozen and then thawed pig skin may be used, and the pressure applied to syringe 1 is 500 to 1500 g·f.

[0070] (Injection) To make it easier to grasp the diffusion state of the injection solution after injection, a colored aqueous solution (methylene blue) was used, and the injection volume (ejection volume) was set to 100 μL.

[0071] <Experimental Results> The experimental results are shown in Table 2. In Table 2, cells marked with "A" were evaluated using a sample number of N = 5 or more, and indicate cases where the percentage of times the injected substance reached the skin relative to the number of injections under the experimental conditions was 60% or more.

[0072] [Table 1]

[0073] [Table 2] [Explanation of symbols]

[0074] REFERENCE SIGNS LIST 1 syringe, 2 housing, 3 syringe portion, 4 plunger, 5 piston, 6 syringe body, 7 initiator, 70 drive portion, 8 button, 9 battery, 10 device assembly, 10A, 10B subassembly, 30 body, 31 nozzle portion, 31a injection port, 31b shield portion, 32 filling chamber, 33 neck portion, 33a Threaded portion, 41...head portion, 42...body portion, 43...neck portion, 44...rod portion, 51...first body portion, 52...second body portion, 53...pressure column portion, 54...accommodating hole, 60...body, 61...connecting recess portion, 62...side wall surface, 62a...threaded portion, 63...communicating portion, 64...through hole, 65...recess portion for driving portion, 71...igniter, 72...body, 80...gas generating agent, 320...injection liquid

Claims

[Claim 1] A needleless syringe device assembly for injecting an injection target substance intradermally without using an injection needle, an encapsulation part for encapsulating the injection target substance; a drive unit including an igniter containing an ignition charge and a gas generating agent disposed in a combustion chamber into which combustion products generated by combustion of the ignition charge flow, the gas generating agent being ignited by the combustion products to generate gas; a pressurizing unit that applies pressure to the injection objective substance enclosed in the enclosing unit when the driving unit is driven; an injection port through which the injection objective substance pressurized by the pressurizing unit is injected into a target area; Equipped with the gas generating agent is formed so that its burning speed is slower than the burning speed of the ignition charge and its burning duration is longer than the burning duration of the ignition charge; The pressure applying unit is the injection target substance is pressurized so that an injection pressure of the injection target substance, which is defined as a pressure of the injection target substance ejected from the ejection port, rises to a first peak pressure after pressurization starts, then drops to a pressure lower than the first peak pressure, and thereafter rises again to a second peak pressure; The drive unit is The igniter is activated to make the injection pressure of the injection target substance reach the first peak pressure by the pressure of the combustion gas of the ignition charge, and the injection pressure of the injection target substance reach the second peak pressure by the pressure of the combustion gas of the gas generating agent that is burned subsequently to the ignition charge, the ignition charge is specified so that, when burned, it generates combustion gas having a gas amount n1 (mol) and a temperature T1 (K), and the energy value of the combustion gas from the ignition charge, expressed as n1 × T1 (mol K), is 1.0 mol K or more and 2.5 mol K or less; The gas generating agent is specified so that, upon combustion, it generates combustion gas having a gas amount n2 (mol) and a temperature T2 (K), and the energy value of the combustion gas from the gas generating agent, expressed as n2 x T2 (mol K), is 4.9 mol K or more and 8.5 mol K or less. Device assembly for needleless syringe.

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