Injector, and injection method of injecting a solution containing a biomolecule to an injection target using the injector

Abstract

To provide an injector in which the ratio of a biological molecule that functions in an injection target to the injected biological molecule is large when a solution containing a biological molecule is injected into the injection target, and a method of injecting a solution containing a biological molecule into an injection target using the above-described injector, the problem can be solved by an injector that does not perform injection via a given structure when the injection target has the given structure inserted therein, but injects a solution containing a biological molecule from an injector main body into the injection target, the injector including a housing portion that houses the solution containing the biological molecule, and a nozzle portion having a discharge port through which the solution containing the biological molecule that has been pressurized flows and is discharged toward the injection target, and satisfies a given condition.

Description

[0001] This application is a divisional application of the application filed on February 8, 2019, with application number 201980012482.3 and entitled "Injector and Injection Method for Injecting a Solution Containing Biomolecules into an Injection Object Using the Injector". Technical Field

[0002] This invention relates to an injector and an injection method for injecting a solution containing biomolecules into an injection target using the injector. Background Technology

[0003] As injectors for injecting drugs into living organisms, in addition to needle-based injectors that inject with a needle and needleless injectors that inject without a needle, there are also liquid delivery tubes that have a needle and a drive source to deliver the drug to the target.

[0004] Needle-free injectors sometimes employ a configuration that uses pressurized gas, a spring, or electromagnetic force to apply pressure to a chamber containing the injection solution, thereby ejecting the injection component. For example, a configuration has been developed where multiple nozzle holes are formed inside the injector body, and pistons that are driven during ejection are arranged corresponding to each nozzle hole (Patent Document 1). This configuration allows for simultaneous ejection of the injection solution from multiple nozzle holes, achieving uniform injection to the target. Furthermore, by injecting a plasmid containing the luciferase gene into rats, highly efficient cell transduction was achieved.

[0005] Furthermore, pressurized gas can be used as a power source for the ejection of the injection liquid in a needle-free injector. For example, a pressurization method has been demonstrated in which a large pressure is applied momentarily at the initial stage of ejection, followed by a gradual reduction of the pressure over a period of 40 to 50 milliseconds (Patent Document 2).

[0006] However, when a solution containing biomolecules is injected into an injectable object using an injector, there are no reports of conditions necessary for ejecting the solution containing biomolecules from the injector in order to increase the proportion of biomolecules that function in the injectable object relative to the injected biomolecules.

[0007] Existing technical documents

[0008] Patent documents

[0009] Patent Document 1: Japanese Patent Application Publication No. 2004-358234

[0010] Patent Document 2: U.S. Patent Application Publication No. 2005 / 0010168 Summary of the Invention

[0011] The problem that the invention aims to solve

[0012] The present invention was made in this context, and the objective is to provide an injector in which the proportion of functional biomolecules in the injectable object is large relative to the injected biomolecules when a solution containing biomolecules is injected into the injectable object, and a method for injecting a solution containing biomolecules into the injectable object using the above-described injector.

[0013] Methods for solving problems

[0014] The inventors have conducted in-depth research on injectors containing solutions comprising biomolecules, focusing on the change in ejection pressure of the solution comprising biomolecules ejected from the injector per unit time from the start of ejection to a given time, as well as the ejection pressure of the solution comprising biomolecules from the start of ejection to the given time. As a result, they discovered that the injector described below can solve the aforementioned problems, thus completing the present invention. The present invention is as follows.

[0015] [1] An injector that injects a solution containing biomolecules from an injector body into an injection object without injecting through the given structure into the injection object, wherein the injector comprises: a receiving portion for containing the solution containing biomolecules, and a nozzle portion having an ejection outlet for flowing through and ejecting the pressurized solution containing biomolecules into the injection object, wherein the ejection pressure rate, which is the change in ejection pressure of the solution containing biomolecules per unit time, from the start of ejection of the solution containing biomolecules up to 0.20 milliseconds, is 7.0 × 10⁻⁶. 3 The pressure of the solution containing biomolecules is greater than 25 MPa / second, and from the start of the ejection of the solution containing biomolecules to 4.0 milliseconds, the ejection pressure of the solution containing biomolecules is less than 25 MPa.

[0016] [2] According to the injector described in [1], the injection pressure rate, which is the change in injection pressure per unit time of the solution containing biomolecules from the start of injection of the above-mentioned solution containing biomolecules up to 0.20 milliseconds, is 2.3 × 10⁻⁶. 4 MPa / second or higher.

[0017] [3] According to the injector described in [1] or [2], the time from the start of the drop of the first peak ejection pressure of the solution containing biomolecules to the moment when the ejection pressure reaches the lowest value immediately following the first peak ejection pressure is 6.0 milliseconds or less in the first drop of the ejection pressure of the solution containing biomolecules.

[0018] [4] A method of injecting a solution containing biomolecules into an injection object using any one of the injectors described in [1] to [3].

[0019] The effects of the invention

[0020] According to the present invention, an injector in which the proportion of biomolecules that function in the injectable object is large relative to the injected biomolecules when a solution containing biomolecules is injected into the injectable object, and a method for injecting a solution containing biomolecules into the injectable object using the above-described injector, are provided. Attached Figure Description

[0021] Figure 1 This is a diagram illustrating the schematic structure of an injector in one embodiment of the first invention of the present invention.

[0022] Figure 2 This is a graph showing the ejection pressure of the filled water over time in one embodiment of the first invention.

[0023] Figure 3 This is a graph showing the ejection pressure of the filled water over time in one embodiment of the first invention.

[0024] Figure 4 This is a coordinate graph illustrating a second embodiment of the present invention, showing the value obtained by dividing the expression level (luminescence intensity) of the gene after injecting a plasmid DNA solution containing the gene into a rat by the amount of plasmid DNA solution injected.

[0025] Figure 5 This is a coordinate graph illustrating a second embodiment of the present invention, showing the value obtained by dividing the expression level (luminescence intensity) of the gene by the amount of plasmid DNA solution injected into the pig after injecting the gene-containing plasmid DNA solution.

[0026] Symbol Explanation

[0027] 1・・・・Instrument

[0028] 2・・・・Outer shell

[0029] 3・・・・Syringe section

[0030] 4...plunger

[0031] 5... Piston

[0032] 6... Syringe body

[0033] 7・・・・Drive Section

[0034] 8...buttons

[0035] 9・・・・Batteries

[0036] 10・・・・Injector Assembly

[0037] 31・・・・ Nozzle Section

[0038] 31a...ejection outlet

[0039] 32・・・・ Filling Chamber

[0040] 71...Igniter Detailed Implementation

[0041] The present invention includes an injector (first invention) and a method for injecting a solution containing biomolecules into an injection target using the aforementioned injector (second invention).

[0042] <First Invention>

[0043] The first invention is an injector that injects a solution containing biomolecules from the injector body into the injection target without injecting through the given structure inserted into the injection target. The injector includes a container for holding the solution containing biomolecules and a nozzle for ejecting the pressurized solution into the injection target. From the start of ejection of the solution containing biomolecules until 0.20 milliseconds, the ejection pressure rate, representing the change in ejection pressure of the solution containing biomolecules per unit time, is 7.0 × 10⁻⁶. 3 The pressure of the solution containing biomolecules is greater than 25 MPa / second, and from the start of the ejection of the solution containing biomolecules to 4.0 milliseconds, the ejection pressure of the solution containing biomolecules is less than 25 MPa.

[0044] For the injector of the first invention, the injection pressure rate, which is the change in injection pressure per unit time of the solution containing biomolecules from the start of injection of the solution to 0.20 milliseconds, is set to 7.0 × 10⁻⁶. 3 The solution contains biomolecules at a pressure of MPa / second or higher, and the ejection pressure of the solution containing biomolecules from the start of ejection of the solution containing biomolecules to 4.0 milliseconds is less than 25 MPa. When the solution containing biomolecules is injected into the injection target, the proportion of biomolecules that function in the injection target relative to the injected biomolecules can be increased.

[0045] Specifically, the ejection pressure of the biomolecule-containing solution from the start of ejection to 0.20 milliseconds is set to 7.0 × 10⁻⁶. 3At pressures exceeding MPa / s, significant deformation of the injected object can be expected. Furthermore, by keeping the ejection pressure of the biomolecule-containing solution below 25 MPa from the start of ejection to 4.0 ms, excessive damage to the injected object can be avoided. As a result, when the biomolecule-containing solution is injected into the injected object, the proportion of functional biomolecules in the injected object relative to the injected biomolecules can be increased.

[0046] At this time, the ejection pressure velocity of the solution containing biomolecules from the start of ejection to 0.20 milliseconds is preferably 2.3 × 10⁻⁶. 4 MPa / s or higher, more preferably 3.4 × 10 MPa / s. 4 MPa / s or higher, more preferably 6.8 × 10 MPa / s. 4 Above MPa / s. Furthermore, there is no specific upper limit; for example, 7.5 × 10⁻⁶ could be cited. 4 Below MPa / second.

[0047] Furthermore, the ejection pressure of the solution containing biomolecules from the start of ejection of the above-mentioned solution containing biomolecules up to 4.0 milliseconds is preferably 20 MPa or less, and is generally greater than 0 MPa. From the viewpoint of having an output capability sufficient to deliver the solution containing biomolecules to the injection target, it is preferably 1.5 MPa or more, more preferably 5.0 MPa or more, further preferably 7.0 MPa or more, and even more preferably 15 MPa or more.

[0048] Furthermore, in the first drop region of the ejection pressure of the solution containing biomolecules, the time from the start of the drop of the first peak ejection pressure of the solution containing biomolecules to the moment when the ejection pressure reaches the lowest value immediately following the first peak ejection pressure is usually greater than 0 milliseconds and usually less than 6.0 milliseconds. Therefore, when the solution containing biomolecules is injected into the injection target, the proportion of biomolecules that function in the injection target relative to the injected biomolecules can be increased.

[0049] Here, the first peak ejection pressure refers to the ejection pressure at the earliest moment when the ejection pressure of the solution containing biomolecules reaches its peak value after the ejection of the solution begins. Furthermore, the first decrease region of the ejection pressure of the solution containing biomolecules refers to the area where the ejection pressure decreases from the first peak ejection pressure until it reaches the lowest value immediately following the first peak ejection pressure.

[0050] Specifically, by setting the time to less than 6.0 milliseconds, it is expected that a sufficient amount of solution containing biomolecules can be delivered using rapidly changing fluid flow without excessive penetration of the injection target. As a result, when the aforementioned solution containing biomolecules is injected into the injection target, the proportion of biomolecules that function in the injection target relative to the injected biomolecules can be increased.

[0051] At this time, the time is preferably less than 4.1 milliseconds, more preferably less than 1.0 milliseconds, further preferably less than 0.95 milliseconds, even more preferably less than 0.80 milliseconds, and particularly preferably less than 0.40 milliseconds. In addition, it is generally greater than 0, and preferably greater than 0.30 milliseconds.

[0052] In the first invention, the biomolecule injected into the injection target is not particularly limited to any substance that functions in the injection target upon injection. Furthermore, the biomolecule can be a natural or synthetic substance. Examples include: nucleic acids or derivatives thereof; nucleosides, nucleotides, or derivatives thereof; amino acids, peptides, proteins, or derivatives thereof; lipids or derivatives thereof; metal ions; low-molecular-weight compounds or derivatives thereof; antibiotics; vitamins or derivatives thereof, etc. If it is a nucleic acid, it can be DNA or RNA, and it can also contain genes. In the embodiments described later, free plasmid DNA containing a luciferase gene was used as the biomolecule, and this luciferase gene was used as a reporter gene.

[0053] For biomolecules injected into the target, as long as the biomolecules exist stably and do not cause damage or other adverse effects to the target, they can be in a free form or in a form fixed on a carrier such as nanoparticles, and can be modified, including by solvents. There are no particular limitations on the implementation method.

[0054] When DNA contains a gene, examples include designing an expression cassette or expression vector containing the gene in a specific form. Alternatively, the gene can be configured under the control of a promoter suitable for the type of DNA to be injected and the injection site. That is, known genetic engineering methods can be used in any manner. In the embodiments described later, a mammalian expression vector, pGL3 control vector (manufactured by Promega), was used as the expression vector. This plasmid vector is well-known and readily available to those skilled in the art. Subcloning of the expression vector and recombinant vector can be performed according to known methods.

[0055] (Functions of biomolecules)

[0056] As an example where the proportion of the biomolecule that functions in the injected object is large relative to the amount of biomolecule injected into the injected object, one could cite the case where DNA, as a biomolecule, contains a gene, and the expression level of that gene is high relative to the amount of DNA injected into the injected object. As a confirmation method, for example, as described in the embodiments below, after injecting a DNA solution into the injected object, a cylindrical tissue with a desired radius is collected centered on the injection port of the DNA solution, a sample is prepared using known biological methods, and confirmation is made by measuring the expression level of the gene. Appropriate known methods can be used depending on the type of gene, for example, in the case of a luciferase gene, an example could be given where the luminescence level is measured using luciferin as a substrate.

[0057] In the injector of the first invention, "front end side" refers to the side with an outlet from which a solution containing biomolecules is ejected from the injector, and "base end side" refers to the side of the injector opposite to the front end side. These expressions do not limit the specific location or position.

[0058] The injector of the first invention is an injector that injects a solution containing biomolecules into the injection object from the injector body without inserting a given structure into the injection object. For example, in cases where the distance from the injector body to the injection object is large, the injector may include a structure to guide the solution containing biomolecules from the injector body to the injection object; for example, it may include a given structure such as a liquid guide tube. Therefore, the injector of the first invention may optionally include or not include such a given structure, but when the given structure is included, the injector does not inject the solution containing biomolecules into the injection object with the given structure inserted into the injection object.

[0059] In the injector of the first invention, the drive unit for pressurizing the solution containing biomolecules is not particularly limited. Pressurization can be achieved, for example, by the pressure generated when the pressure of a compressed gas is released, or by the pressure generated by the combustion of gunpowder ignited by an ignition device. Alternatively, pressurization can be performed using electromagnetic force, for example, by using a linear electromagnetic actuator. Preferably, at least the pressure generated by the combustion of gunpowder ignited by an ignition device is used; furthermore, it can be used in combination with any one or both of the other two pressurization methods described above.

[0060] When pressurization is achieved by using pressure generated by the combustion of gunpowder ignited by an ignition device, the gunpowder can be, for example, any one of the following: 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), aluminum and iron oxide (AFO), or a combination of several of these. A characteristic of these gunpowders is that their combustion products are gaseous even at high temperatures, but do not contain gaseous components at room temperature; therefore, the combustion products condense immediately after ignition.

[0061] In addition, when the energy generated by the gas generator is used as the ejection energy, various gas generators used in single-base smokeless gunpowder, gas generators for airbags, and gas generators for seat belt pretensioners can also be used as gas generators.

[0062] In the injector of the first invention, the filling chamber is not initially filled with a solution containing biomolecules, but rather the solution is drawn into the filling chamber via a nozzle having an injection outlet. Thus, by employing a configuration that requires filling the filling chamber, any desired solution containing biomolecules can be injected into the recipient. Therefore, in the injector of the first invention, the syringe portion is configured to be detachable.

[0063] Hereinafter, an example of an injector according to one embodiment of the first invention will be described with reference to the accompanying drawings. It should be noted that the configuration of the following embodiment is merely an example, and the first invention is not limited to this configuration. It should be noted that the terms "front end side" and "base end side" are used to indicate the relative positional relationship of the syringe 1 along its length. The "front end side" refers to the position near the front end of the syringe 1 (described later), i.e., near the injection port 31a, and the "base end side" refers to the direction opposite to the "front end side" along the length of the syringe 1, i.e., the direction towards the drive section 7. Furthermore, this example uses the combustion energy of gunpowder ignited by an ignition device as the ejection energy and a DNA solution as the solution containing biomolecules, but the first invention is not limited to this.

[0064] (Structure of syringe 1)

[0065] Figure 1This is a schematic diagram showing the structure of syringe 1, and also a cross-sectional view of syringe 1 along its length. Syringe 1 is constructed by mounting syringe assembly 10 to housing (syringe housing) 2. Syringe assembly 10 is obtained by assembling a sub-assembly consisting of a syringe barrel 3 and a plunger 4, and a sub-assembly consisting of a syringe body 6, a piston 5, and a drive unit 7 into one unit.

[0066] As described above, the syringe assembly 10 is configured to be freely detachable from the housing 2. The filling chamber 32 formed between the syringe barrel 3 and the plunger 4 within the syringe assembly 10 is filled with DNA solution, and the syringe assembly 10 is a disposable unit used after each injection of DNA solution. On the other hand, the housing 2 side includes a battery 9, which supplies power to the igniter 71 included in the drive unit 7 of the syringe assembly 10. Power is supplied from the battery 9 via wiring between the electrodes on the housing 2 side and the electrodes on the drive unit 7 side of the syringe assembly 10 by the user pressing the button 8 provided on the housing 2. It should be noted that the shape and position of the electrodes on the housing 2 side and the drive unit 7 side of the syringe assembly 10 are designed so that they automatically contact each other when the syringe assembly 10 is installed on the housing 2. Furthermore, the housing 2 is a reusable unit as long as the battery 9 retains enough power to supply the drive unit 7. It should be noted that in the housing 2, if the battery 9 is depleted, the housing 2 can be used by simply replacing the battery 9.

[0067] in addition, Figure 1 Although no additional gunpowder components are specifically configured inside the syringe body 6 shown, a gas generating agent that generates gas by combustion of the combustion products produced by the gunpowder in the igniter 71 can be configured inside the igniter 71 and the through hole of the syringe body 6 in order to adjust the pressure change of the injection fluid applied through the piston 5. The structure of configuring the gas generating agent inside the igniter 71 is known technology, as disclosed in International Publication No. 01-031282 and Japanese Patent Application Publication No. 2003-25950. Furthermore, as an example of a gas generating agent, a single-base smokeless gunpowder comprising 98% by mass of nitrocellulose, 0.8% by mass of diphenylamine, and 1.2% by mass of potassium sulfate can be cited. Additionally, various gas generating agents used in airbag gas generators and seatbelt pretensioner gas generators can also be used. By adjusting the size, shape, and especially the surface shape of the gas generator disposed within the through-hole, the combustion end time of the gas generator can be changed, thereby allowing for a desired change in the pressure applied to the DNA solution, i.e., a change that enables the DNA solution to be appropriately injected into the injection target. In the first invention, the gas generator or the like, used as needed, is also included in the drive unit 7.

[0068] (Injection object)

[0069] The injection target in the first invention can be any object among cells, cell sheets, tissues, organs, organ systems, individuals (organs), etc., without limitation. Furthermore, as the injection target, for a higher level, a lower level contained within it can also be used. That is, for example, when a tissue is used as the injection target, the cells contained in that tissue can be used as the injection target, or the intercellular matrix contained in that tissue can be used as the injection target, or both can be used as the injection target.

[0070] As a preferred injection target, the aforementioned injection targets derived from mammals can be cited as examples. More preferably, it is the skin of a mammalian individual (organism), and even more preferably, it is one or more tissues selected from the intradermal, subcutaneous, and dermo-muscular regions within the skin. In this case, a method can be employed to inject a solution containing biomolecules from an injector onto the skin surface of the mammalian individual (organism) and then inject it from the skin surface into one or more tissues selected from the intradermal, subcutaneous, and dermo-muscular regions within the skin.

[0071] Furthermore, the system that injects a solution containing biomolecules from an injector into the target body can be any system, primarily an in vitro system, an in vivo system, or an ex vivo system.

[0072] Furthermore, there are no specific restrictions on whether a mammal can be included; examples include: humans, mice, rats, guinea pigs, hamsters, cows, goats, sheep, pigs, monkeys, dogs, and cats. Additionally, depending on the recipient, other mammalian methods besides humans can also be cited.

[0073] <Second Invention>

[0074] The second invention is a method for injecting a solution containing biomolecules into an injection target using the injector of the first invention.

[0075] The description of the injector, the injection target, and the solution containing biomolecules in the second invention of the present invention is based on the description of the first invention described above.

[0076] Example

[0077] The present invention will be described in more detail below through embodiments, but the present invention is not limited to the following embodiments as long as it does not depart from its spirit.

[0078] (Evaluation of the injector's injection pressure)

[0079] [Example 1-1]

[0080] Towards Figure 1The injector shown (nozzle diameter: 0.1 mm) was filled with 100 μL of water, and the injection pressure in the injector after injection was evaluated from the pressurization of the water using the combustion of the ignition propellant. 55 mg of zirconium-containing and potassium perchlorate-containing propellant (ZPP) was used as the propellant, and 40 mg of single-base smokeless propellant (hereinafter, sometimes referred to as "GG") was used as the gas generator.

[0081] The injection pressure is measured in the manner described in Japanese Patent Application Publication No. 2005-21640. The injection force is distributed and applied to a diaphragm of a force sensor located downstream of the nozzle. The output from the force sensor is acquired by a data acquisition and display device using a detection amplifier. The output is displayed and stored in the form of injection force (N) per hour. The injection force (N) is then divided by the area of ​​the nozzle orifice for calculation.

[0082] [Examples 1-2]

[0083] Except for the use of 35 mg of ZPP, the procedure was the same as in Example 1-1.

[0084] [Examples 1-3]

[0085] Except for the use of 15 mg of ZPP, the procedure was the same as in Example 1-1.

[0086] [Examples 1-4]

[0087] Except for the use of 25 mg of ZPP, the procedure was the same as in Example 1-1.

[0088] Figure 2 This is a graph showing the ejection pressure of water over time in each embodiment. Additionally, Figure 3 It is Figure 2 The image is obtained by magnifying the initial 0.20 ms plot. Additionally, the parameters are shown in Table 1.

[0089]

[0090] (Evaluation using gene expression in rats)

[0091] [Example 2-1]

[0092] Fill the injector used in Examples 1-1 above with 30 μL of a solution of plasmid pGL3-controlvector (promega) containing the luciferase gene (solvent: endotoxin-free TE buffer, final concentration: 1.0 mg / mL) and inject it into the skin of the back of a female SD rat (10 weeks old).

[0093] A 5-fold dilution of Luciferase assay system (Promega) "Cell Culture Lysis × 5" was prepared and added to a 2 mL microvolume tube containing 1.5 mL of the solution. Tissue samples, approximately 1 cm square, were cut from the injection site, extending from the intradermal to the dermomuscular region (i.e., intradermal, subcutaneous, and dermomuscular), and added to the solution. Using dissecting scissors, the tissue was finely diced in the solution (approximately 2 minutes, about 100 cuts) into particles smaller than 2 mm square. The mixture was then stirred for 10 seconds using a vortex mixer or ultrasonic cleaner. Next, the microvolume tube was frozen at -80°C or in dry ice for approximately 15 minutes. After confirming freezing, the tube was thawed at room temperature for approximately 20 minutes. This freezing and thawing process was repeated three times to promote cell destruction. The sample was then centrifuged (4°C, 2000 rpm, 5 min) to obtain the supernatant.

[0094] The luciferase assay was performed using a Lumitester C100 (manufactured by Kikkoman Biochemifa). First, the Luciferase Assay Substrate of the Luciferase assay system was brought to room temperature and opened. 10 mL of Luciferase Assay Buffer, also brought to room temperature, was added. The mixture was gently vortexed without foaming to confirm dissolution. 100 μL of this solution was added to a Lumitester tube, followed by 20 μL of the serum sample to be tested. Multiple pipetting was performed to ensure homogeneity. The sample was then placed in the Lumitester assay chamber within approximately 20 seconds for measurement, and the luminescence intensity was obtained. This luminescence intensity is correlated with the expression level of the luciferase gene.

[0095] [Example 2-2]

[0096] Except for using the injector used in Examples 1-2 above, the operation is the same as in Example 2-1.

[0097] [Examples 2-3]

[0098] Except for using the injector used in Examples 1-3 above, the operation is the same as in Example 2-1.

[0099] [Examples 2-4]

[0100] Except for using the injector used in Examples 1-4 above, the operation is the same as in Example 2-1.

[0101] Figure 4This is a graph showing the values ​​obtained by dividing the expression level (luminescence intensity) of the luciferase gene by the amount of plasmid DNA injected in each embodiment. The horizontal line in the graph represents the average value.

[0102] (Evaluation using pig gene expression)

[0103] [Example 3-1]

[0104] The injector used in Examples 1-1 was filled with 100 μL of a solution of plasmid pGL3-controlvector (promega) containing the luciferase gene (solvent: endotoxin-free TE buffer, final concentration: 1 mg / mL), and injected into the skin of the abdomen of a female hog (3 months old, weighing about 65 kg). After 24 hours of feeding, the intradermal tissue was used as the sample for luciferase assay. Otherwise, the procedure was the same as in Examples 2-1.

[0105] Figure 5 This is a graph showing the values ​​obtained by dividing the expression level (luminescence intensity) of the luciferase gene by the amount of plasmid DNA injected, as in Example 3-1. The horizontal lines in the graph represent the average values.

Claims

1. An injector, which injects a solution containing biomolecules into the object of injection without inserting a given structure into the object. The injector has the following features: A container for holding a solution containing biomolecules, and It has a nozzle portion that allows the pressurized solution containing biomolecules to flow through and be ejected towards the injection target. The ejection pressure rate from the start of ejection of the solution containing biomolecules to 0.20 milliseconds is 7.0 × 10⁻⁶. 3 The pressure is greater than MPa / second, and the ejection pressure of the biomolecule-containing solution from the start of ejection of the solution to 4.0 milliseconds is less than 25 MPa, wherein the ejection pressure rate is the change in ejection pressure of the biomolecule-containing solution per unit time.

2. The injector according to claim 1, wherein, The ejection pressure rate from the start of ejection of the solution containing biomolecules to 0.20 milliseconds is 2.3 × 10⁻⁶. 4 The ejection pressure rate is above MPa / second, where the ejection pressure rate is the change in ejection pressure per unit time of the solution containing biomolecules.

3. The injector according to claim 1, wherein, In the first drop region of the ejection pressure of the solution containing biomolecules, the time from the start of the drop of the first peak ejection pressure of the solution containing biomolecules to the moment when the ejection pressure reaches the lowest value immediately following the first peak ejection pressure is less than 6.0 milliseconds.

4. The injector according to claim 2, wherein, In the first drop region of the ejection pressure of the solution containing biomolecules, the time from the start of the drop of the first peak ejection pressure of the solution containing biomolecules to the moment when the ejection pressure reaches the lowest value immediately following the first peak ejection pressure is less than 6.0 milliseconds.

5. A method for injecting a solution containing biomolecules into an injection object other than an individual animal using the injector of claim 1.

6. A method for injecting a solution containing biomolecules into an injection object other than an animal individual using the injector of claim 2.

7. A method for injecting a solution containing biomolecules into an injection subject other than an animal individual using the injector of claim 3.

8. A method for injecting a solution containing biomolecules into an injection subject other than an animal individual using the injector of claim 4.

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