Injector, method for forming void using said injector, and method for reducing interstitial liquid accumulated in object

Abstract

At least the following is provided. That is, an injector capable of forming a void in an object is provided. The problem is solved by an injector for injecting a liquid and a gas into an object from an injector body without injecting through a predetermined structure in a state in which the predetermined structure is inserted into the object, the injector comprising: a housing part that houses the liquid and the gas; a nozzle part that communicates with the housing part and has an ejection port for ejecting the liquid and the gas toward the object; and a pressure part that pressurizes the liquid and the gas housed in the housing part during operation to eject the liquid and the gas from the ejection port toward the object, wherein the ratio of the volume of the gas to the total of the volume of the liquid and the gas is more than 60% and 80% or less.

Description

Injector, method for forming a void using said injector, and method for reducing interstitial fluid accumulation in a subject

[0001] The present disclosure relates to an injector and a method for using the injector to create a void and reduce interstitial fluid accumulation in a subject.

[0002] Injectors for injecting a medicinal liquid into an injection target include needle-equipped syringes that inject using a syringe needle, needleless syringes that inject without using a syringe needle, etc. In addition, catheters equipped with a syringe needle and a driving source, multi-hole syringes, etc. are also used to transport a medicinal liquid to an injection target.

[0003] Among these, needle-free syringes sometimes employ a configuration in which pressure is applied to a chamber containing the injection solution using pressurized gas, a spring, or electromagnetic force to eject the injection component. For example, one configuration employs multiple nozzle holes formed inside the syringe body, with pistons corresponding to each nozzle hole being driven during injection (Patent Document 1). This configuration simultaneously ejects the injection solution from multiple nozzle holes, achieving uniform injection into the subject. Furthermore, a plasmid containing a luciferase gene was injected into rats, achieving highly efficient cell transfer. Another type of needle-free syringe utilizes pressurized gas as the injection power source for the injection solution. For example, one type employs a pressurization configuration in which a large amount of pressure is applied instantaneously at the beginning of injection, followed by a gradual reduction in the pressure over 40 to 50 msec (Patent Document 2).

[0004] On the other hand, a method of injecting a drug solution by mixing air into it is known. For example, when azacitidine, a drug for treating myelodysplastic syndrome, is administered subcutaneously using a needle syringe in the usual manner without mixing air, side effects that cause discomfort to the patient, such as redness at the injection site, pain at the injection site, and bruising at the injection site, have been reported. In contrast, it has been reported that administration with air prevents contact between the epithelium and the drug solution, thereby reducing side effects (Non-Patent Document 1). Another known method involves injecting a solution containing a biomolecule and a specific gas into an injection target. It has been disclosed that this method increases the proportion of biomolecules that function in the injection target (Patent Document 3).

[0005] Lymphedema is a type of interstitial edema. It develops due to stagnation of lymphatic flow, primarily caused by cancer treatment, and typically occurs in the hands and feet. Current treatments for lymphedema include complex treatments that combine compression therapy, exercise therapy, lifestyle guidance, skin care, and lymphatic drainage, as well as surgical treatments that eliminate lymphatic congestion through lymphaticovenous anastomosis.

[0006] Patent Document 1: JP 2004-358234 A, US Patent Application Publication No. 2005 / 0010168, International Publication No. 2022 / 149550

[0007] Can. Oncol. Nurs. J., 22(4):222-34, 2012

[0008] The present disclosure addresses at least the following objectives: to provide an injector capable of forming a void in a subject; to provide a novel method for forming a void; and to provide a novel method for reducing interstitial fluid.

[0009] The present inventors have conducted extensive research to solve the above problems and have found that the above problems can be solved by using a specific injector.

[0010] That is, the gist of the present disclosure is as follows. [1] An injector that injects a liquid and a gas into a target from an injector body without performing injection through a predetermined structure inserted into the target, comprising: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an ejection port for ejecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section to eject the liquid and the gas from the ejection port toward the target, wherein the ratio of the volume of the gas to the total volume of the liquid and the gas is more than 60% and not more than 80%. [2] The injector according to [1], wherein the gas is air. [3] The injector according to [1] or [2], wherein injecting into the target is injection into the target by jet injection. [4] The injector according to any one of [1] to [3], wherein the injection speed of the liquid and the gas exceeds 83.3 μL / s. [5] The injector according to any one of [1] to [4], wherein the liquid contains a biofunctional substance. [6] The injector according to [5], wherein the biofunctional substance is one or more selected from the group consisting of nucleic acids, peptides, proteins, and low molecular weight compounds. [7] An injector for reducing interstitial fluid accumulated in a subject, the injector injecting a liquid and a gas into the subject from an injector body without performing injection through a predetermined structure inserted into the subject, the injector comprising: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an ejection port for ejecting the liquid and the gas toward the subject; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby ejecting the liquid and the gas from the ejection port toward the subject. [8] The injector according to [7], wherein the ratio of the volume of the gas to the total volume of the liquid and the gas is 30% or more and 80% or less. [9] The injector according to [7] or [8], wherein the gas is air.

[10] The injector according to any one of [7] to [9], wherein injecting into the subject is injecting into the subject by jet injection.

[11] The injector according to any one of [7] to

[10] , wherein the injection speed of the liquid and the gas exceeds 83.3 μL / s.

[12] The injector according to any one of [7] to

[11] , wherein the liquid contains a biofunctional substance.

[13] The injector according to

[12] , wherein the biofunctional substance is one or more selected from the group consisting of nucleic acids, peptides, proteins, and low molecular weight compounds.

[14] A method for forming a void using a syringe, the syringe being an injector that injects a liquid and a gas into a target from a syringe body without performing injection through a predetermined structure inserted into the target, the injector comprising: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an outlet for injecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby injecting the liquid and the gas from the outlet toward the target; the formation method comprising the steps of: storing the liquid and the gas in the storage section; pressurizing the liquid and the gas stored in the storage section; and injecting the liquid and the gas into the target, wherein the viscoelastic modulus at 25°C of the injection point of the target is 47% or more and 82% or less.

[15] The method for forming a void according to

[14] , wherein the injecting step involves injecting into the target by jet injection.

[16] The method for forming a void according to

[14] or

[15] , wherein the ratio of the volume of the gas to the total volume of the liquid and the gas is 30% or more and 80% or less.

[17] The method for forming a void according to any of

[14] to

[16] , wherein the gas is air.

[18] The method for forming a void according to any of

[14] to

[17] , wherein the injection speed of the liquid and the gas exceeds 83.3 μL / s.

[19] The method for forming a void according to any of

[14] to

[18] , wherein the relaxation time of the injection site of the target when viscoelasticity is measured at 25°C is 0.89 ms or more and 4.39 ms or less.

[20] A method for reducing interstitial fluid accumulated in a subject using an injector, the injector injecting a liquid and a gas into the subject from an injector body without performing injection through a predetermined structure inserted into the subject, the injector comprising: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an ejection port for ejecting the liquid and the gas toward the subject; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby ejecting the liquid and the gas from the ejection port toward the subject; the reduction method comprising the steps of: storing the liquid and the gas in the storage section; pressurizing the liquid and the gas stored in the storage section; and injecting the liquid and the gas into the subject.

[21] The method according to

[20] , wherein the subject is a mammal other than a human.

[22] The method according to

[20] or

[21] , wherein the injecting step involves injecting into the subject by jet injection.

[23] The method according to any one of

[20] to

[22] , wherein the ratio of the volume of the gas to the total volume of the liquid and the gas is 30% or more and 80% or less.

[24] The method according to any one of

[20] to

[23] , wherein the gas is air.

[25] The method according to any one of

[20] to

[24] , wherein the injection speed of the liquid and the gas exceeds 83.3 μL / s.

[26] The method according to any one of

[20] to

[25] , wherein the liquid contains a biofunctional substance.

[27] The method according to

[26] , wherein the biofunctional substance is one or more selected from the group consisting of nucleic acids, peptides, proteins, and low-molecular-weight compounds.

[28] The method according to any one of

[20] to

[27] , further comprising the step of injecting a solution or cells containing a biofunctional substance into the void formed by the injecting step.

[0011] The present disclosure may at least provide the effect of forming a void in a predetermined object, and may also provide a novel method for reducing interstitial fluid.

[0012] 1 is a diagram showing a schematic configuration of an injector according to an embodiment of the present disclosure. Fig. 1 is a stereomicroscope image of a tissue section from Test Example 1 (photograph substitute for drawing). Fig. 2 is a stereomicroscope image of a tissue section from Test Example 2 (photograph substitute for drawing). Fig. 3 is a stereomicroscope image of a tissue section from Test Example 3 (photograph substitute for drawing). Fig. 4 is a stereomicroscope image of a tissue section from Test Example 4 (photograph substitute for drawing). Fig. 5 is a graph showing the relative values ​​of tail diameters 21 and 28 days after skin peeling. Fig. 6 is a stereomicroscope image after injecting liquid and gas into konjac jelly at a gas ratio of 50% (photograph substitute for drawing). Fig. 7 is a stereomicroscope image after injecting liquid and gas into konjac jelly at a gas ratio of 60% (photograph substitute for drawing). Fig. 8 is a stereomicroscope image after injecting liquid and gas into konjac jelly at a gas ratio of 80% (photograph substitute for drawing). 1 shows an image (photograph) of a 0.7% agarose gel after injecting a liquid and gas at an 80% gas ratio into 0.7% agarose gel. 2 shows an image (photograph) of a 0.5% agarose gel after injecting a liquid and gas at an 80% gas ratio into 0.5% agarose gel. 3 shows an image (photograph) of a marshmallow after injecting a liquid and gas at a 50% gas ratio into 0.7% agarose gel. 4 shows an image (photograph) of a marshmallow after injecting a liquid and gas at a 60% gas ratio into 0.5% agarose gel. 5 shows an image (photograph) of a marshmallow after injecting a liquid and gas at an 80% gas ratio into 0.7% agarose gel. 6 shows an image (photograph) of a marshmallow after injecting a liquid and gas at an 80% gas ratio into 0.5% agarose gel. 7 shows an image (photograph) of a pig abdomen after injecting a liquid and gas at a 50% gas ratio into 0.5% agarose gel.

[0013] Each configuration and combination thereof in each embodiment is merely an example, and additions, omissions, substitutions, and other modifications of configurations are possible as appropriate within the scope of the present disclosure. The present disclosure is not limited by the embodiments, but 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. Furthermore, a numerical range expressed using "to" means a range that includes the numerical values ​​before and after "to" as the lower and upper limits, and "A to B" means greater than or equal to A and less than or equal to B.

[0014] The present disclosure includes an invention of an injector (first embodiment), an invention of an injector for reducing interstitial fluid accumulated in a subject (second embodiment), an invention of a method for forming a void using an injector (third embodiment), an invention of a method for reducing interstitial fluid accumulated in a subject using an injector (fourth embodiment), and a method for reducing interstitial fluid accumulated in a subject (fifth embodiment).

[0015] <First embodiment> A first embodiment of the present disclosure is an injector that injects a liquid and a gas into a target from an injector body without performing injection through a predetermined structure with the predetermined structure inserted into the target, the injector comprising: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an ejection port for ejecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby ejecting the liquid and the gas from the ejection port toward the target.

[0016] In this embodiment, the liquid and the gas are present in the container, and the liquid is injected into the target while the gas dissolves in the liquid as pressure is applied. After injection into the target, it is presumed that a portion of the gas dissolved in the liquid returns to a gas state as pressure is reduced, generating countless microscopic bubbles, and the shearing action of the bubbles can form multiple voids in the target. The voids typically have a maximum diameter of approximately 10 μm to approximately 1000 μm, but larger voids can also be formed by multiple voids connecting together. The formation of voids can be confirmed using a stereomicroscope or the like. The voids can be used, for example, as a flow path or reservoir for any liquid or gas.

[0017] [Liquid] In this embodiment, the liquid contained in the container may be, for example, water, and preferably a liquid isotonic with the animal's bodily fluids. Specifically, physiological saline, Ringer's solution, lactate Ringer's solution, acetate Ringer's solution, bicarbonate Ringer's solution, etc., can be suitably used. These can be prepared by known methods, and commercially available products can also be used. The liquid that can be injected by the injector of this embodiment may contain, as necessary, conventional additives such as biofunctional substances, buffers, isotonicity agents, pH adjusters, antioxidants, thickeners, stabilizers, humectants, emulsifiers, binders, and oils and fats. However, even if the liquid does not contain these additives, it is possible to form voids in a specified target and reduce interstitial fluid.

[0018] The biofunctional substance is not particularly limited as long as it exerts physiological activity in a subject. The biofunctional substance may be one type or multiple types. The biofunctional substance may be a natural product or an artificially synthesized product.

[0019] The biofunctional substance is preferably one or more selected from the group consisting of nucleic acids, peptides, proteins, and low molecular weight compounds.

[0020] Examples of nucleic acids include DNA, RNA, and PNA. The nucleic acid may be a nucleic acid containing a portion that encodes a protein, or a nucleic acid that does not contain a portion that encodes a protein (non-coding nucleic acid).

[0021] Examples of peptides and proteins include antigens (i.e., those that induce the production of antibodies against the peptide or protein), antibodies, peptide vaccines, protein vaccines, peptide hormones, protein hormones, growth factors, cytokines, blood coagulation factors, serum albumin, digestive enzymes, anti-inflammatory peptides, and anti-inflammatory proteins. Extracellular matrices can also be used as proteins. Extracellular matrices are non-cellular components that make up the human body and are expected to contribute to maintaining voids as a scaffold for cells. Examples of extracellular matrices include collagen, fibronectin, and laminin.

[0022] A low molecular weight compound generally refers to a compound having a molecular weight of 2000 or less, but is not limited to this and includes compounds that are considered to be low molecular weight compounds in the art. Preferred ranges for the molecular weight of low molecular weight compounds include, for example, 50 or more and 100 or more. Other preferred ranges include 2000 or less and 1000 or less. That is, examples include 50 to 2000, 50 to 1000, and 100 to 2000.

[0023] In the present disclosure, physiological activity refers to an effect on a specific physiological regulatory function of a living organism. Evaluation indicators for physiological activity can be appropriately set depending on the purpose and may be either qualitative or quantitative, with quantitative indicators being preferred. For example, specific mRNA levels, protein levels, cytokine levels, antibody titers, cell counts of specific cell types, etc. can be used as indicators. These quantitative indicators can be quantified by methods known in the art.

[0024] In particular, when the biologically functional substance is a nucleic acid containing a portion encoding a protein, the amount of the protein encoded by the nucleic acid can be quantified and used as an evaluation index for physiological activity. Alternatively, the activity of the protein may be quantitatively evaluated. For example, when the protein is luciferase, the physiological activity can be evaluated by measuring the intensity of bioluminescence.

[0025] When the biofunctional substance is a nucleic acid, the nucleic acid may be incorporated into a viral vector or carried on lipid nanoparticles and contained in the liquid, but viral vectors or lipid nanoparticles may not be used. When viral vectors or lipid nanoparticles are not used, the possibility of inducing side reactions such as anaphylaxis in the subject can be reduced.

[0026] The content of the biofunctional substance relative to the total amount of the liquid can be appropriately set based on the type of the biofunctional substance, the subject, the physiological activity exhibited by the biofunctional substance in the subject into which the biofunctional substance is injected, etc.

[0027] Examples of buffers that can be used include buffers using phosphate (e.g., phosphate buffer, phosphate buffered saline (PBS) (which may be PBS(+) or PBS(-)), Dulbecco's phosphate buffered saline (D-PBS), citrate-phosphate buffer, citrate-phosphate buffered saline, etc.), citrate buffer, trishydroxymethylaminomethane-HCl buffer (tris-hydrochloric acid buffer), acetate buffer, GOOD buffer (e.g., HEPES-NaOH buffer, etc.), amino acid buffer (e.g., glycine-hydrochloric acid buffer, glycine-NaOH buffer, glycylglycine-KOH buffer, etc.), imidazole buffer, etc. Among these, buffers using phosphate are preferred from the viewpoint of versatility.

[0028] Examples of the isotonicity agent include ionic isotonicity agents and nonionic isotonicity agents. Examples of the ionic isotonicity agents include salts such as sodium chloride, potassium chloride, calcium chloride, and magnesium chloride. Examples of the nonionic isotonicity agents include glycerin, propylene glycol, polyethylene glycol, glucose, sorbitol, mannitol, trehalose, maltose, and sucrose. Among these, sodium chloride is preferred from the viewpoint of versatility.

[0029] Examples of pH adjusters include hydrochloric acid, phosphoric acid, citric acid, acetic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, and sodium hydrogen carbonate.

[0030] Examples of antioxidants include ascorbic acid, sodium sulfite, butylhydroxyanisole, butylhydroxytoluene, propyl gallate, and tocopherol.

[0031] Thickeners include alginic acid, polyethylene glycol, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and the like.

[0032] Examples of fats and oils include sesame oil, soybean oil, rapeseed oil, and olive oil. Glycerin, which is a constituent of fats and oils, can also be used. These fats and oils are expected to remain in the formed voids and contribute to maintaining the voids.

[0033] [Gas] In this embodiment, the gas contained in the container is not particularly limited, but air can be exemplified. The air may be any commonly used air, and its composition is not particularly limited. For example, a mixed gas of approximately 80% nitrogen and approximately 20% oxygen can be exemplified. Examples of the gas include nitrogen, oxygen, ozone, carbon dioxide, hydrogen, and carbon monoxide, and a mixed gas of any two or more of these. In a preferred embodiment, the gas does not contain microorganisms or the like, or, even if it does contain microorganisms or the like, the microorganisms have been killed.

[0034] The ratio of the volume of the gas to the total volume of the liquid and the gas is not particularly limited, but is preferably 30% or more, more preferably more than 60%. Also, it is preferably less than 100%, more preferably 80% or less. That is, preferred ranges for the volume ratio of the gas include 30% or more and less than 100%, 30% or more and 80% or less, and more than 60% and 80% or less. When the volume of the gas is within this range, multiple voids are likely to form in the target.

[0035] [Target] The target that can be injected using the injector according to this embodiment may be a living or non-living object. The target in this embodiment may be, for example, one or more selected from the group consisting of cells, cell sheets, cell masses, tissues, organs (skin, organs, etc.), organ systems, individuals (living organisms), etc. Furthermore, the target may be one or more selected from the group consisting of tissues, organs (skin, organs, etc.), organ systems, individuals (living organisms), etc. The target may be any of an in vitro system, an in vivo system, an ex vivo system, etc. The cell mass may be a cell mass obtained by three-dimensional culture, and the organ (skin, organ, etc.) may be an organoid.

[0036] Furthermore, when injected into the subject, it may be injected into a lower layer contained therein. That is, for example, when an individual (living body) is the subject, it may be injected into a tissue contained in the individual (living body), or into a cell contained in the individual (living body), or it may be injected into both. Furthermore, when a tissue is the subject, it may be injected into a cell contained in the tissue, or into the extracellular matrix contained in the tissue, or it may be injected into both.

[0037] Furthermore, when the subject in this embodiment is one or more selected from the group consisting of cells, cell sheets, cell clumps, tissues, organs (skin, organs, etc.), and organ systems, it may be one or more selected from the group consisting of cells, cell sheets, cell clumps, tissues, organs (skin, organs, etc.), and organ systems in a state where they are present in an individual (living organism), or it may be one or more selected from the group consisting of cells, cell sheets, cell clumps, tissues, organs (skin, organs, etc.), and organ systems in a state where they are not present in an individual (living organism) (for example, a state where they have been extracted or separated from an individual (living organism) or a state where they have been produced outside an individual (living organism)).

[0038] Furthermore, the subject in this embodiment may be one or more selected from the group consisting of cells, cell sheets, cell masses, tissues, organs (skin, internal organs, etc.), and organ systems derived from stem cells such as iPS cells (induced pluripotent stem cells), and these may be in a state that exists in an individual (living organism) or in a state that does not exist in an individual (living organism) (for example, in a state that has been extracted or separated from an individual (living organism), or in a state that has been produced outside an individual (living organism)).

[0039] The individual (living body) is preferably a mammalian individual (living body). The mammal is not particularly limited, but includes humans and non-human mammals. Non-human mammals include mice, rats, guinea pigs, hamsters, cows, goats, sheep, pigs, monkeys, dogs, cats, etc.

[0040] The organ may be one or more selected from the group consisting of a joint cavity, an eyeball, skin, a muscle, a bone, a cartilage, a bone marrow, a ligament, a brain, a spinal cord, a lung, a liver, a heart, a kidney, a pancreas, a gallbladder, a digestive tract, a urinary bladder, a reproductive organ, a lymph node, a lymphatic network, and a blood vessel, and a tumor occurring in any one of these. Reproductive organs include the testes and ovaries.

[0041] Furthermore, regardless of whether the subject of this embodiment is any of the above, when injection is performed into a cell, injection may be performed into the cytoplasm of the cell, injection may be performed into the cell nucleus of the cell, or injection may be performed into both the cytoplasm and the cell nucleus of the cell.

[0042] Furthermore, the target of this embodiment is not particularly limited, but is preferably one or more selected from the group consisting of the intradermal space, subcutaneous space, and underlying muscle layer in the skin of an individual mammal (living body). In this case, a method can be employed in which the liquid and the gas are injected into the skin by ejecting them from an injector toward the skin surface, thereby injecting them into one or more selected from the group consisting of the intradermal space, subcutaneous space, and underlying muscle layer in the skin.

[0043] In particular, the target of this embodiment is preferably a site in the skin of a mammalian individual (living body) where interstitial edema is occurring. When a liquid and a gas are injected into the site of interstitial edema using the injector of this embodiment, multiple voids are formed. It is believed that these voids become flow paths for interstitial fluid, reducing the amount of interstitial fluid that has accumulated locally.

[0044] The viscoelastic modulus of the target injection site at 25°C is preferably 47% or more and 82% or less. The viscoelastic modulus is a value obtained by the following formula, and indicates the ratio of the viscous element to the elastic element of the target: Viscoelastic modulus = (viscous strain amount) / (viscous strain amount + elastic strain amount) An ideal elastic body has a viscoelastic modulus of 0%, and an ideal viscous body has a viscoelastic modulus of 100%. The viscoelastic modulus of the target at 25°C is more preferably 47% or more and 71% or less.

[0045] The relaxation time of the injection site of the target, when measured for viscoelasticity at 25°C, is preferably 0.89 ms or more and 4.39 ms or less, more preferably 0.89 ms or more and 3.11 ms or less. The relaxation time is the time constant of the stress relaxation behavior of a viscoelastic body, and is an index that represents the vibration frequency characteristics of a viscoelastic substance. It is a value that can be calculated using the following formula: Relaxation time = (viscosity data) / (elasticity data). The viscoelastic modulus and relaxation time can be measured according to the instruction manual for a Vesmeter (for biological measurement, E-100HS, WAVECYBER CORP.). Specifically, at room temperature (25°C), the probe of the Vesmeter is placed vertically from above on the target, and the same location is measured 4 to 35 times, and the average value can be used as the measured value.

[0046] [Injector] As described above, the injector according to this embodiment includes a storage section that stores a liquid and a gas, a nozzle section that communicates with the storage section and has an outlet for injecting the liquid and the gas toward the target, and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby injecting the liquid and the gas from the outlet toward the target; and the liquid and the gas are injected into the target by being ejected from the outlet of the nozzle section.

[0047] The injector according to this embodiment injects the liquid and the gas into the target from the injector body without injecting the liquid and the gas through a predetermined structure inserted into the target. The injector according to this embodiment may include a predetermined structure, such as a catheter, that guides the liquid and the gas from the injector body to the target, for example, when the distance from the injector body to the target is large. Therefore, the injector according to this embodiment may or may not include such a predetermined structure.

[0048] In the injector according to this embodiment, the energy applied by the pressurizing unit to pressurize the liquid and gas can be applied in the form of energy application using known pressurizing techniques. One example of the applied energy may be chemically generated energy, such as combustion energy generated by the oxidation reaction of gunpowder or explosives. Alternatively, the energy for pressurization may be electrically generated, such as energy generated by a piezoelectric element or an electromagnetic actuator driven by input power. Still another example of the energy for pressurization may be physically generated, such as elastic energy generated by an elastic body or internal energy of a compressed object such as compressed gas. In other words, the energy for pressurization may be any energy that enables the injector to eject the liquid. Furthermore, the energy for pressurization may be a composite energy that appropriately combines internal energies such as combustion energy, electrical energy, and elastic energy.

[0049] In view of the above, the pressurizing unit may apply pressure by utilizing the pressure generated by the combustion of explosives ignited by an ignition device, or by utilizing the pressure generated when compressed gas is released. Furthermore, the pressurizing unit may apply pressure by utilizing the biasing force of a compression spring, or by utilizing electromagnetic force, for example, by utilizing a linear electromagnetic actuator. The pressurizing unit is preferably one that at least utilizes the pressure generated by the combustion of explosives ignited by an ignition device, and may also be used in combination with any of the other pressurizing modes described above.

[0050] When the pressurizing unit utilizes the pressure generated by the combustion of explosives, the explosives may be, for example, any one of the following explosives: zirconium and potassium perchlorate (ZPP), titanium hydride and potassium perchlorate (THPP), titanium and potassium perchlorate (TiPP), aluminum and potassium perchlorate (APP), aluminum and bismuth oxide (ABO), aluminum and molybdenum oxide (AMO), aluminum and copper oxide (ACO), and aluminum and iron oxide (AFO), or a combination of these explosives. A feature of these explosives is that their combustion products are gaseous at high temperatures but do not contain gaseous components at room temperature, so that the combustion products condense immediately after ignition.

[0051] Furthermore, when the pressurizing unit uses energy generated by combustion of a gas generating agent as ejection energy, it is also possible to use, as the gas generating agent, a single-base smokeless powder (GG) or various gas generating agents used in gas generators for airbags and gas generators for seatbelt pretensioners. An example of a single-base smokeless powder is a single-base smokeless powder containing 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine, and 1.2% by mass of potassium sulfate.

[0052] Below, referring to the drawings, a syringe 1 (needleless syringe) will be described as an example of the syringe of this embodiment. Note that the following configuration is an example and is not limited thereto. Note that 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, i.e., closer to the ejection port 31a, which will be described later, 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 7. Furthermore, this example is an example in which combustion energy of gunpowder ignited by an ignition device is used as ejection energy for pressurization, but the present disclosure is not limited thereto.

[0053] 1 is a diagram showing a schematic configuration of syringe 1, and is also a cross-sectional view taken along the longitudinal direction of syringe 1. Syringe 1 is configured by attaching to a housing (syringe housing) 2 a syringe assembly 10 in which a sub-assembly consisting of a syringe portion 3 and a plunger 4 and a sub-assembly consisting of a syringe body 6, a piston 5, and a drive portion 7 are integrally assembled.

[0054] As described above, the syringe assembly 10 is configured to be detachable from the housing 2. The storage compartment 32 formed between the syringe portion 3 and plunger 4 included in the syringe assembly 10 is filled with a liquid and a gas, and the syringe assembly 10 is a unit that is disposable after each injection of the liquid and the gas. The storage compartment 32 may comprise a first storage compartment for storing the gas and a second storage compartment for storing the liquid. The housing 2 includes a battery 9 that supplies power to an igniter 71 included in the drive unit 7 of the syringe 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 drive unit 7 side of the syringe assembly 10. The shapes and positions of the electrodes on the housing 2 side and the electrode on the drive unit 7 side of the syringe assembly 10 are designed so that they automatically come into contact when the syringe assembly 10 is attached to the housing 2. The housing 2 is a unit that can be used repeatedly as long as the battery 9 has enough power to supply to the drive unit 7. When the battery 9 of the housing 2 runs out of power, it is possible to continue using the housing 2 by replacing only the battery 9.

[0055] Next, details of the syringe assembly 10 will be described. First, a subassembly including the syringe portion 3 and the plunger 4 will be described. The syringe portion 3 has a storage portion 32 formed therein, which is a space capable of storing the liquid and the gas. More specifically, as shown in FIG. 1 , the plunger 4 is slidably disposed along the inner wall surface of the syringe portion 3 extending in the axial direction, and the storage portion 32 is defined by the inner wall surface of the syringe portion 3 and the plunger 4. The syringe portion 3 also has a nozzle portion 31 communicating with the storage portion 32, and an ejection port 31a is formed at the tip end of the nozzle portion 31. The cross-sectional area of ​​the nozzle portion 31 gradually decreases from the storage portion 32 side toward the ejection port 31a side, and the nozzle portion 31 serves as a flow path for guiding the liquid and gas stored in the storage portion 32 to the ejection port 31a. In the example shown in FIG. 1 , the shape of the tip end of the plunger 4 generally matches the shape of the nozzle portion 31.

[0056] Next, a subassembly including the syringe body 6, the piston 5, and the drive unit 7 will be described. The piston 5 is made of, for example, metal and is configured to slide through a through-hole formed inside the syringe body 6 by being pressurized by combustion products (combustion gas) generated by an igniter 71 of the drive unit 7. The syringe body 6 is a generally cylindrical member, and the piston 5 is slidably housed along its inner wall surface extending in the axial direction. The piston 5 may be made of resin, and in this case, metal may be used in combination in parts requiring heat resistance and pressure resistance. As shown in FIG. 1 , the piston 5 is integrally connected to the plunger 4.

[0057] Next, the drive unit 7 will be described. As shown in FIG. 1 , the drive unit 7 is fixed to the base end side with respect to the through-hole in the syringe body 6. The drive unit 7 has an igniter 71, which is an electric igniter. The igniter 71 is disposed so as to face the inside of the through-hole in the syringe body 6, and an ignition charge is accommodated therein. As the ignition charge, various types of explosives can be used, as described above. The ignition charge can also be accommodated in an explosive cup formed of an appropriate thin-walled metal, for example.

[0058] In the syringe 1 configured as described above, the volume of the gas contained in the containing portion 32 is adjusted to be, for example, 30% or more and 80% or less of the volume of the containing portion 32.

[0059] Next, the operation of the syringe 1 configured as described above will be described. As shown in FIG. 1 , with the syringe assembly 10 attached to the housing 2, liquid and gas can be drawn through the ejection port 31a of the nozzle portion 31. This allows the liquid and gas to be filled into the storage portion 32. From this state, for example, when the user presses the button 8 provided on the housing 2 while the ejection port 31a of the syringe 1 is abutted against a target, this triggers the supply of operating power from the battery 9 to the igniter 71 of the drive unit 7, activating the igniter 71. When the igniter 71 is activated, the ignition charge is ignited and burns, generating combustion products (such as a flame and combustion gas). As a result, for example, the powder cup of the igniter 71 is split open, and the combustion gas of the ignition charge is released into the through-hole in the syringe body 6. This causes a sudden increase in pressure within the through-hole of the syringe body 6, pressing the piston 5 toward the tip of the syringe body 6, causing the piston 5 to slide toward the tip along the inner wall surface of the through-hole in the syringe body 6. As described above, the plunger 4 is integrally connected to the piston 5, and therefore the plunger 4 also slides along the inner wall surface of the syringe portion 3 in conjunction with the piston 5. That is, when the plunger 4 is pushed toward the nozzle portion 31 located at the tip side of the syringe portion 3, the volume of the storage portion 32 containing the liquid and gas decreases, causing it to be suddenly pressurized. As a result, the liquid and gas filled in the storage portion 32 are forced into the nozzle portion 31 and ejected at high pressure from the ejection port 31a. This allows the liquid and gas to be injected into the target.

[0060] Although no additional explosive components are disposed within the syringe body 6 shown in FIG. 1 , a gas generating agent or the like that burns with combustion products produced by explosive combustion in the igniter 71 to generate gas may be disposed within the igniter 71 or the through-hole of the syringe body 6 in order to adjust the pressure transition applied to the liquid and the gas via the piston 5. The configuration of disposing a gas generating agent within the igniter 71 is a well-known technique, as disclosed in International Publication No. 01-031282 and Japanese Patent Application Laid-Open No. 2003-25950. An example of a gas generating agent is a single-base smokeless powder containing 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine, and 1.2% by mass of potassium sulfate. Various gas generating agents used in gas generators for airbags and seatbelt pretensioners may also be used. By adjusting the dimensions, size, shape, and particularly the surface shape, of the gas generating agent when disposed within the through-hole, the combustion completion time of the gas generating agent can be changed. This allows the pressure transition applied to the liquid and the gas to be a desired transition, i.e., a transition that allows the liquid and the gas to reach the target appropriately. In this embodiment, the driving unit 7 also includes a gas generating agent that is used as needed. In this embodiment, the plunger 4 and the piston 5 constitute a "pressurizing unit."

[0061] In this embodiment, injecting a liquid and a gas into a target using an injector may refer to injection into the target by jet injection. Here, in the present disclosure, "jet injection" refers to an injection in which a liquid and a gas are ejected from an injection port toward a target, thereby forming a through-hole that penetrates the boundary between the inside and outside of the target, and generating a high-pressure ultra-microfluidic stream through which the liquid and the gas can be injected into the target. For example, if the target is a mammalian individual (living body), this refers to an injection in which a high-pressure ultra-microfluidic stream is generated that can penetrate, for example, the skin of the mammalian individual (living body).

[0062] The syringe according to this embodiment can inject the liquid and the gas at an injection speed typically exceeding 83.3 μL / s. The injection speed is preferably 200 μL / s or higher, more preferably 250 μL / s or higher, even more preferably 300 μL / s or higher, even more preferably 350 μL / s or higher, even more preferably 400 μL / s or higher, and most preferably 500 μL / s or higher. There is no particular upper limit, but an example is 5000 μL / s or lower. That is, preferred ranges of the injection speed include more than 83.3 μL / s and not more than 5000 μL / s, 200 μL / s or more and not more than 5000 μL / s, 250 μL / s or more and not more than 5000 μL / s, 300 μL / s or more and not more than 5000 μL / s, 350 μL / s or more and not more than 5000 μL / s, 400 μL / s or more and not more than 5000 μL / s, and 500 μL / s or more and not more than 5000 μL / s. When the injection speed is within the above range, injection into the subject can be easily performed as a jet injection.

[0063] In the present disclosure, the injection speed is the speed of the liquid as it is ejected from the ejection port, and can be calculated, for example, by dividing the ejected volume by the time required from the start to the end of ejection. The time required from the start to the end of ejection can be measured, for example, by capturing images of the liquid being ejected from the ejection port using an imaging device such as a high-speed camera. The injection speed can be set within the above range by adjusting the injection energy depending on the shape and material of the nozzle, as well as the volume and viscosity of the liquid, etc.

[0064] The amount of the liquid injected into the subject is determined based on the volume of the storage unit and the volume of the gas stored in the storage unit. Examples of the amount of the liquid injected into the subject include 10 μL or more, 50 μL or more, or 100 μL or more. Examples of other amounts include 50 mL or less, 10 mL or less, and 5 mL or less. Examples of other amounts include 10 μL to 50 mL, 50 μL to 10 mL, and 100 μL to 5 mL.

[0065] The time required to inject the liquid into the target is not particularly limited as long as it is a time that allows the injected amount of liquid to be injected at the injection speed, and examples thereof include 0.001 seconds or more, 0.005 seconds or more, or 0.01 seconds or more. Other examples include 100 seconds or less, 50 seconds or less, and 10 seconds or less. That is, examples include 0.001 to 100 seconds, 0.005 to 50 seconds, and 0.01 to 10 seconds.

[0066] <Second embodiment> A second embodiment of the present disclosure is an injector for reducing interstitial fluid accumulated in a target, which injects a liquid and a gas into the target from an injector body without performing injection through a predetermined structure while the predetermined structure is inserted into the target, and comprises: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an ejection port for ejecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby ejecting the liquid and the gas from the ejection port toward the target.

[0067] When a lymphatic vessel is partially resected or damaged during surgery for cancer treatment, the flow of lymph (also called interstitial fluid) is impeded, resulting in localized accumulation, which can lead to interstitial edema. This condition is called lymphedema. When a liquid and a gas are injected into an area where interstitial edema is occurring using the injector of this embodiment, multiple voids are created. These voids are thought to serve as flow paths for the interstitial fluid, reducing the locally accumulated interstitial fluid. In this way, the injector of this embodiment can be used as an injector for reducing interstitial fluid accumulated in a subject. Furthermore, when the interstitial fluid is derived from lymphatic vessels, it can also be used as an injector for treating lymphedema.

[0068] The liquid, gas, target, and injector in this embodiment are the same as those in the first embodiment. When the liquid contains a biofunctional substance, collagen is preferred as the biofunctional substance.

[0069] <Third embodiment> A third embodiment of the present disclosure is a method for forming a void using a syringe, wherein the syringe is an syringe that injects a liquid and a gas into a target from a syringe body without performing injection through a predetermined structure with the predetermined structure inserted into the target, and includes: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an outlet for injecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby injecting the liquid and the gas from the outlet toward the target; and the formation method includes: a step of storing the liquid and the gas in the storage section; a step of pressurizing the liquid and the gas stored in the storage section; and a step of injecting the liquid and the gas into the target, wherein the viscoelastic modulus of the target at 25°C is 47% or more and 82% or less. This is a method for forming voids using a syringe.

[0070] The liquid, gas, target, and injector in this embodiment are the same as those in the first embodiment.

[0071] The process of storing the liquid and the gas in the storage section is not particularly limited, but may be a process of storing the liquid and the gas in the storage section by sucking them from outside the injector through the injection port of the nozzle section.

[0072] The energy application by the pressurizing unit in the step of pressurizing the liquid and the gas contained in the container unit can be in the form of energy application by a known pressurizing technique. Specifically, the description of the injector of the first embodiment is cited.

[0073] The step of injecting the liquid and the gas into the target may, for example, be carried out by bringing the injection port into contact with the target and ejecting the liquid and the gas through a nozzle portion using ejection energy generated by a step of pressurizing the liquid and the gas.

[0074] The steps of storing the liquid and the gas in the storage unit, pressurizing the liquid and the gas stored in the storage unit, and injecting the liquid and the gas into the target may be performed once or multiple times. Furthermore, when the injecting step is performed multiple times, the injection sites on the target may be the same or different.

[0075] <Fourth embodiment> A fourth embodiment of the present disclosure is a method for reducing interstitial fluid accumulated in a target using an injector, wherein the injector is an injector that injects a liquid and a gas into the target from an injector body without performing injection through a predetermined structure while the predetermined structure is inserted into the target, and comprises: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an outlet for injecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby injecting the liquid and the gas from the outlet toward the target; and the reduction method is a method for reducing interstitial fluid accumulated in a target using an injector, comprising the steps of: storing the liquid and the gas in the storage section; pressurizing the liquid and the gas stored in the storage section; and injecting the liquid and the gas into the target. When the interstitial fluid is derived from lymphatic vessels, the method according to this embodiment may be a method for treating lymphedema.

[0076] The liquid, gas, target, and injector in this embodiment are the same as those in the first embodiment.

[0077] The explanation of the third embodiment is applied to the process of storing the liquid and the gas in the storage section, the process of pressurizing the liquid and the gas stored in the storage section, and the process of injecting the liquid and the gas into the target.

[0078] The reduction method according to this embodiment may further include a step of injecting a solution or cells containing a biofunctional substance into the void formed by the injecting step. By using the void formed by the injecting step as a reservoir for the solution or cells containing the biofunctional substance, the solution or the like can be locally distributed and retained.

[0079] The solution containing the biofunctional substance may be one in which the biofunctional substance that can be used in the first embodiment is dissolved (in the present disclosure, this includes suspension and emulsification) in a liquid that can be used in the first embodiment. When the liquid contains a biofunctional substance, the biofunctional substance contained in the liquid and the biofunctional substance contained in the solution may be the same or different.

[0080] The cells used in the step of injecting a solution or cells containing a biologically functional substance may be cells extracted from a living organism, or may be cultured cells derived from stem cells such as iPS cells (induced pluripotent stem cells). The cells may also be in the form of a cell sheet, cell cluster, or the like. The cell cluster may be a cell cluster obtained by three-dimensional culture.

[0081] The step of injecting the solution containing the biofunctional substance or the cells may be performed using the injector described above or another injector, such as, but not limited to, an injector consisting of a syringe, a plunger, and an injection needle.

[0082] The step of injecting the solution containing the biofunctional substance or the cells into the void formed by the injecting step may be carried out once or multiple times.

[0083] Fifth Embodiment A fifth embodiment of the present disclosure is a method for reducing interstitial fluid accumulation in a subject in need of treatment, the method comprising injecting a composition comprising a liquid and a gas into an injection site in the subject. In this embodiment, the injection can be performed using a needleless syringe. Alternatively, the injection can be performed using the injector in the first embodiment.

[0084] In this embodiment, the liquid may be pressurized, and the method according to this embodiment may further include pressurizing the liquid and the gas in an injector.

[0085] The liquid, gas, target, and injector in this embodiment are the same as those in the first embodiment.

[0086] The present disclosure will be specifically described below with reference to examples, but the present disclosure is not limited to the aspects of the following examples.

[0087] [Experiment 1: Creation of intradermal spaces in rats or pigs] (Subjects for administration) Rats: SD rats, female, 8 weeks old, were used. After anesthetizing and shaving, the animals were laid down with their flanks facing upwards, and were held in place for administration to the flanks. Pig: SPF domestic pigs were used. After anesthetizing and shaving, the animals were laid down with their flanks facing upwards, and were administered the compound in the abdominal or groin area.

[0088] (Method of filling and administering liquid and gas) A syringe having the structure shown in Figure 1 was used. PBS (Nacalai Tesque, 14249-95) solution was sucked up through the nozzle of the syringe in the syringe's housing. Thereafter, the plunger was further pulled up without sucking up the PBS solution, and normal laboratory air was filled. The volumes of liquid and gas sucked up are shown in Table 1. After confirming that air was present on the plunger side and the PBS solution was present on the tip side of the nozzle, the solution was administered to the subject.

[0089]

[0090] After administration, the animals were euthanized by exsanguination under anesthesia. Skin was collected from the administration site and fixed in 10% neutral buffered formaldehyde (Nacalai Tesque, 37152-51) for 1 to 3 nights. The skin was then washed twice with PBS and immersed in fresh PBS. The skin was removed from the PBS and immersed in ethanol for dehydration and defatting. Substitution with xylene and paraffin was then performed. The tissue was embedded in paraffin and thinly sectioned. The obtained sections were deparaffinized using xylene and ethanol. Hematoxylin staining was performed, followed by washing with water, eosin staining, and decolorization with ethanol. Dehydration with ethanol was performed. After substitution with xylene, the sections were mounted on glass slides using mounting medium. Microscopic observation was then performed. Images of the sections were captured using a Keyence all-in-one fluorescence microscope (BZ-X710).

[0091] As shown in Figures 2 to 5, it was confirmed by image observation that voids were formed throughout the entire dermis layer.

[0092] [Experiment 2: Administration to rat tail edema] Rats were anesthetized, and a full-thickness strip of skin 10 mm from the base of the tail was removed in a 5 mm longitudinal direction and excised. The lymphatic vessels and veins on the caudal side of the removed area were then cauterized with an electric scalpel. The treated rats were kept until the formation of edema was confirmed. Liquid and gas were administered to four sites at 90-degree intervals around the site of skin removal. The volumes of liquid and gas were 30 μL and 20 μL, respectively (gas ratio 40%). 28 days after administration, the rats were euthanized and samples were taken.

[0093] On days 21, 22, and 23 after the tail skin detachment, lactated Ringer's solution (LRS), lactated Ringer's solution containing 5% glycerin (glycerin), lactated Ringer's solution containing 5% sesame oil (sesame), or collagen solution containing 5% sesame oil (ColSes) was injected. The collagen solution was prepared by mixing Nippon Ham's porcine skin atelocollagen solution (1% concentration), 10x Minimum Essential Medium (MEM), and reconstitution buffer (2.2 g sodium bicarbonate and 4.77 g HEPES dissolved in 100 mL of 0.05 N aqueous NaOH) in an 8:1:1 ratio. The diameter at the distal 5 mm was compared between days 21 and 28 after skin detachment. The results are shown in Figure 6. The tail diameters of all injected groups were significantly smaller than those of the uninjected group (Cont). The error bars indicate standard deviation. The number of samples was 9 for Cont, 9 for Glycerin, 6 for LRS, 6 for Sesami, and 6 for ColSes.

[0094] When 30 μL each of lactated Ringer's solution, glycerin, sesame oil, and collagen was mixed with 20 μL of air and injected, it was suggested that lymphedema improved.

[0095] [Experiment 3: Formation of voids in various administration subjects] (Administration subjects) Mice: Female Bulb / c mice, 8 weeks old, were used. After anesthesia and shaving, the animals were placed facing up and restrained for administration or measurement in the flank. Pigs: SPF domestic pigs were used. After anesthesia and shaving, the animals were placed facing up and for administration or measurement in the abdominal or groin region. Alternatively, after shaving, the animals were placed face down and for administration or measurement in the back. Abdominal administration or measurement was either performed under normal conditions or with air introduced into the abdominal cavity to stretch the skin. In tables and figures, the former is indicated as "(without air)" and the latter as "(with air)." Konjac jelly: Konnyaku Hatake (registered trademark), Mannan Life. When measuring physical properties, a sheet of Prowipe (Daioh Paper Co., Ltd.) was placed on the konjac jelly, and measurements were taken on top of it. Agarose gel (0.5%, 0.7%, or 1%): Agarose (Agarose ME (medium electroosmosis) Classic Type 100G, Nacalai Tesque, 01158-56) was added to PBS to achieve the above concentration, heated in a microwave oven, and then allowed to stand at 4°C. Marshmallow: White marshmallow (Eiwa Co., Ltd.) was administered.

[0096] (Method of measuring physical properties) Measurements were made according to the instruction manual for Vesmeter (for biological measurement, E-100HS, WAVECYBER CORP.). Specifically, at room temperature (25°C), the probe of the Vesmeter was placed vertically on the object to be measured from above, and the same location was measured 4 to 35 times, and the average value was taken as the measured value.

[0097] (Liquid and Gas Filling and Administration Method) A syringe having the structure shown in Figure 1 was used. A predetermined amount of D-PBS(-) (Nacalai Tesque, 14249-24) solution containing 1% malachite green (Malachite Green Oxalate, manufactured by Nacalai Tesque, 21015-12) was drawn up from the nozzle of the syringe's housing. The plunger was then raised to the 100 μL mark without drawing up any solution, and ordinary laboratory air was filled. This set the volumetric ratio of air in the housing to 30-80%. After confirming that air was present on the plunger side and the D-PBS solution was present on the tip side of the nozzle, the syringe was administered to the recipient.

[0098] (Observations after administration of liquid and gas) The konjac jelly was sliced ​​approximately 7 mm across the administration site and observed under a microscope. The agarose gel was prepared and administered in a 50 mL centrifuge tube and visually observed from outside the tube. The marshmallow was split lengthwise using the center of administration as a marker and visually observed. Mice and pigs were sliced ​​in the same manner as in Experiment 1 and observed under a microscope. Observed images of each subject are shown in Figures 7 to 15.

[0099] The formation of voids was evaluated according to the following criteria: A: Multiple voids were formed in the object. In konjac jelly, agarose, and marshmallow, this refers to a state in which multiple bubble-like voids are observed within the malachite green color. B: One large void was formed in the object. In konjac jelly, agarose, and marshmallow, this refers to a state in which one void is observed within the malachite green color. C: No void was formed. Table 2 shows the gas ratio, hardness measured by a Vesmeter, elasticity, viscosity coefficient, viscoelastic modulus, and relaxation time, as well as the evaluation of void formation. Multiple pig inguinal regions were measured, and the results are designated and identified as pig inguinal region 1 and pig inguinal region 2, respectively.

[0100]

[0101] As shown in Table 2, voids were formed in the samples having a viscoelastic modulus of 47% or more and 82% or less at 25° C. and a relaxation time of 0.89 ms or more and 4.39 ms or less.

Claims

1. An injector which injects a liquid and a gas into a target from an injector body without injecting through a specified structure with the specified structure inserted into the target, comprising: a storage section which stores the liquid and the gas; a nozzle section which communicates with the storage section and has an ejection outlet for ejecting the liquid and the gas toward the target; and a pressurizing section which, when activated, pressurizes the liquid and the gas stored in the storage section, thereby ejecting the liquid and the gas from the ejection outlet toward the target, wherein the ratio of the volume of the gas to the total volume of the liquid and the gas is more than 60% and not more than 80%.

2. The injector of claim 1, wherein said gas is air.

3. The injector of claim 1 or 2, wherein injecting into the subject comprises injecting into the subject by jet injection.

4. The injector of claim 1 or 2, wherein the injection rate of the liquid and the gas exceeds 83.3 μL / s.

5. The injector according to claim 1 or 2, wherein the liquid contains a biologically functional substance.

6. The injector according to claim 5, wherein the biofunctional substance is one or more selected from the group consisting of nucleic acids, peptides, proteins, and low molecular weight compounds.

7. An injector for reducing interstitial fluid accumulated in a target, which injects liquid and gas into the target from an injector body without injecting through a specified structure while the specified structure is inserted into the target, comprising: a container for containing the liquid and the gas; a nozzle section communicating with the container and having an ejection outlet for ejecting the liquid and the gas toward the target; and a pressurizing section which, when activated, pressurizes the liquid and the gas contained in the container, thereby ejecting the liquid and the gas from the ejection outlet toward the target.

8. The injector according to claim 7, wherein the ratio of the volume of said gas to the total volume of said liquid and said gas is 30% or more and 80% or less.

9. An injector according to claim 7 or 8, wherein the gas is air.

10. The injector of claim 7 or 8, wherein injecting into the subject comprises injecting into the subject by jet injection.

11. The injector of claim 7 or 8, wherein the injection rate of the liquid and the gas exceeds 83.3 μL / s.

12. The injector according to claim 7 or 8, wherein the liquid contains a biologically functional substance.

13. The injector according to claim 12, wherein the biofunctional substance is at least one selected from the group consisting of nucleic acids, peptides, proteins, and low molecular weight compounds.

14. A method for forming a void using a syringe, the syringe being an injector that injects a liquid and a gas into a target from a syringe body without injecting through a specified structure with the specified structure inserted into the target, the injector comprising: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an outlet for injecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby injecting the liquid and the gas toward the target from the outlet; the forming method comprising the steps of: storing the liquid and the gas in the storage section; pressurizing the liquid and the gas stored in the storage section; and injecting the liquid and the gas into the target, the viscoelasticity of the injection point of the target being 47% or more and 82% or less at 25°C.

15. The method for forming a void according to claim 14, wherein the step of injecting comprises injecting into the subject by jet injection.

16. A method for forming a void according to claim 14 or 15, wherein the ratio of the volume of the gas to the total volume of the liquid and the gas is 30% or more and 80% or less.

17. The method for forming a gap according to claim 14 or 15, wherein the gas is air.

18. The method for forming a gap according to claim 14 or 15, wherein the injection speed of the liquid and the gas exceeds 83.3 μL / s.

19. A method for forming a void as described in claim 14 or 15, wherein the relaxation time of the injection site of the target when subjected to viscoelasticity measurement at 25°C is 0.89 ms or more and 4.39 ms or less.

20. A method for reducing interstitial fluid accumulated in a target using an injector, the injector being an injector that injects liquid and gas into the target from an injector body without injecting through a specific structure while the specific structure is inserted into the target, the injector comprising: a storage section that stores the liquid and the gas; a nozzle section that communicates with the storage section and has an ejection outlet for ejecting the liquid and the gas toward the target; and a pressurizing section that, when activated, pressurizes the liquid and the gas stored in the storage section, thereby ejecting the liquid and the gas from the ejection outlet toward the target; the reduction method comprising the steps of: storing the liquid and the gas in the storage section; pressurizing the liquid and the gas stored in the storage section; and injecting the liquid and the gas into the target.

21. The method of claim 20, wherein the subject is a mammal other than a human.

22. The method of claim 20 or 21, wherein in the step of injecting, the subject is injected by jet injection.

23. The method according to claim 20 or 21, wherein the ratio of the volume of the gas to the total volume of the liquid and the gas is 30% or more and 80% or less.

24. The method of claim 20 or 21, wherein the gas is air.

25. The method of claim 20 or 21, wherein the liquid and gas have an injection rate of greater than 83.3 μL / s.

26. The method according to claim 20 or 21, wherein the liquid contains a biologically functional substance.

27. The method according to claim 26, wherein the biofunctional substance is one or more selected from the group consisting of nucleic acids, peptides, proteins, and low molecular weight compounds.

28. The method according to claim 20 or 21, further comprising the step of injecting a solution or cells containing a biologically functional substance into the gap formed by the injecting step.

Images