Multi-mode fluid delivery device

Abstract

The present invention relates to a multi-mode fluid delivery solution for delivering drugs and vaccines in the fields of human clinical care and animal health care, including a multi-mode fluid delivery device, a related component thereof, a system, and a related drug and device combination product. Through the design of multiple holes and a detachable injection head and syringe needle members contained therein, the multi-mode fluid delivery device allows flexible switching among a needle-free injection mode, a microneedle injection mode, and a needle injection mode, and can control the flow rate of the jet flow of the drug and the vaccine, the dispersion degree of the drug and the vaccine in vivo, the number of holes and the syringe needle members, and the size and distribution of the holes. Through the different injection modes, the present invention significantly improves the single-dose delivery amount of the drug and the vaccine without damaging the skin, greatly increases the delivery efficiency relative to existing needle-free injection and microneedle injection modes, makes the dispersion degree of the drug in vivo far higher than that of existing needle injection mode, and thus possesses broader application prospects. The present invention can precisely deliver the drug and the vaccine to one or more target sites of different depths in or under the skin, in the muscles, or in human organs by means of a high-speed jet flow or the syringe needle members, and thus enhance the dispersion effect at the target sites. The present invention can also accurately control the three-dimensional dispersion degree of the drug and the vaccine at the target sites, and therefore greatly improves the contact effect of the drug and the vaccine with tissues and the bioavailability of the drug and the vaccine. The multi-mode fluid delivery solution of the present invention exhibits a significantly improved drug absorption effect, good efficacy, and a significantly enhanced vaccine response effect in drug and device combination use with 3-in-1 vaccines for cats, human hepatitis B vaccines, human pneumonia vaccines, human tumor vaccines, and semaglutide.

Description

Multimodal fluid delivery device

[0001] This application claims priority to Chinese patent application No. 202311790592.7 filed on December 22, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0002] The present invention relates to the field of medical devices, and in particular to a multimodal drug and vaccine delivery device and a drug-device combination product for use in the fields of human clinical medicine and animal health care. Background Art

[0003] In the current field of drug and vaccine delivery, needle, microneedle and needle-free injection are the three main delivery methods. Traditional needle injection is widely used for the delivery of various drugs and vaccines, but the drugs and vaccines that enter the body through needle injection are in an aggregated state, which is not conducive to drug absorption and metabolism. In addition, needle injection is often accompanied by pain and infection risks for patients, which puts a psychological and physical burden on patients. For example, needle phobia is the main reason why vaccination is not popular in many countries around the world. Although microneedle injection technology can reduce pain and trauma, its delivery site is limited, and its efficiency and applicability are limited when delivering large molecule drugs or high-dose vaccines. Relatively speaking, needle-free injection technology greatly improves the diffusion of drugs after delivery into the body and reduces the risk of pain and infection. However, the application and popularization of simple needle-free injection technology in clinical and animal health fields still face challenges. The main reason is that needle-free injection requires the use of high-pressure liquid jets to break the skin, which greatly limits the area of ​​the delivered liquid jet and the delivered drug dose. In addition, there is insufficient scientific research on the penetration and precise delivery performance of needle-free injection, especially in terms of jet flow rate, drug chemical properties, drug diffusion mode, needle-free injection aperture design, and the impact of different biological media (such as the epidermis, subcutaneous tissue, and muscle of humans and animals) on drug delivery performance.

[0004] In actual applications, the popularity of needle-free injection technology is limited by its limitations on the injection aperture and its high requirements for skin adhesion. This technology is prone to drug leakage due to the presence of hair, and it is difficult to accurately control the injection position, depth and diffusion of the drug. Therefore, although needle-free injection technology has significant advantages in theory, it still faces many challenges in actual clinical applications. In addition, the stimulation of drug metabolism and vaccine immunogenicity places high standards on the three-dimensional diffusion and precise positioning of drugs and vaccines in the body. Existing needle-free injection technology still faces unsolvable difficulties in meeting these requirements. For example, increasing the diffusion requires increasing the area of ​​the liquid jet, but the increase in the area of ​​the liquid jet will greatly cause skin breaking difficulties, bleeding and damage.

[0005] A significant gap in current drug delivery technology is how to effectively combine the advantages of needle-based technology for precise targeting and high-dose delivery, the high diffusion efficiency of needle-free injection, and the multi-point delivery capabilities of microneedle injection to meet the specific needs of different drugs and vaccines. In particular, existing technologies have yet to provide a satisfactory solution for flexibly switching between different injection modes based on clinical circumstances.

[0006] The content of this background technology description is only for facilitating understanding of the relevant technology in this field and is not regarded as an admission of the prior art.

[0007] Summary of the Invention

[0008] The purpose of the present invention is to provide a multimodal fluid delivery device that combines the advantages of needle-free delivery, needle delivery, and microneedle delivery to solve the problems existing in the above three delivery methods, thereby improving the stability, accuracy and bioavailability of the delivery system.

[0009] An embodiment of the present invention provides a multi-mode fluid delivery device, comprising:

[0010] a tube for containing a fluid, the tube having a first end and a second end, the second end being provided with a self-sealing elastic portion or a hole for dispensing the fluid in the tube;

[0011] an injection head detachably connected to the tube, the injection head comprising one or more needle members configured to removably interface with the self-sealing elastic portion in the second end or the hole for dispensing fluid in the tube; and

[0012] A power mechanism includes a piston disposed in the first end of the tube and capable of pushing the fluid or is operatively connected to the piston to apply delivery pressure to the piston pushing the fluid.

[0013] Other optional features and technical effects of the embodiments of the present invention are partially described below, and partially can be understood by reading this document. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. The elements shown are not limited to the scale shown in the drawings. The same or similar reference numerals in the drawings represent the same or similar elements, wherein:

[0015] FIG1 shows a schematic structural diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0016] FIG2 shows a schematic structural diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0017] FIG3 shows a schematic needle arrangement diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0018] FIG4 shows a schematic needle arrangement diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0019] FIG5 shows a schematic needle arrangement diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0020] FIG6 shows a schematic needle arrangement diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0021] FIG7 shows a schematic diagram of a needle member of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0022] FIG8 shows a schematic diagram of a needle member of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0023] FIG9 shows a schematic diagram of a linear arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0024] FIG10 is a schematic diagram showing a linear arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0025] FIG11 is a schematic diagram showing a linear arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0026] FIG12 shows a schematic diagram of a linear arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0027] FIG13 shows a schematic diagram of an array arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0028] FIG14A shows a schematic diagram of a needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0029] FIG14B shows a schematic diagram of a needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0030] FIG15 is a schematic diagram showing an arrangement of needle members with different needle hole diameters in a multi-mode fluid delivery device according to an embodiment of the present invention;

[0031] FIG16 is a schematic diagram showing an arrangement of needle members with different needle hole diameters in a multi-mode fluid delivery device according to an embodiment of the present invention;

[0032] FIG17 is a schematic diagram showing an arrangement of needle members with different needle hole diameters in a multi-mode fluid delivery device according to an embodiment of the present invention;

[0033] FIG18 is a schematic diagram showing an arrangement of needle members with different needle hole diameters in a multi-mode fluid delivery device according to an embodiment of the present invention;

[0034] FIG19 shows a schematic diagram of a circular arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0035] FIG20 shows a schematic diagram of a circular arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0036] FIG21 shows a schematic diagram of a coaxial annular arrangement of multiple needle groups of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0037] FIG22 shows a schematic diagram of a coaxial annular arrangement of multiple needle groups of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0038] FIG23 is a schematic diagram showing a coaxial ring of multiple sets of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0039] 24 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle member of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0040] FIG25 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle members of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0041] FIG26 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle member of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0042] FIG27 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle member of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0043] FIG28 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle member of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0044] FIG29 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle members of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0045] FIG30 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle member of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0046] 31 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle members of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0047] 32 shows a schematic diagram of the arrangement of the central needle member and the peripheral needle members of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0048] FIG33 shows a schematic diagram of an injection head of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0049] FIG34 shows a schematic diagram of an injection head of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0050] FIG35 shows a schematic diagram of a needle kit of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0051] FIG36 shows a schematic diagram of a needle assembly of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0052] FIG37 shows a schematic diagram of a needle assembly of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0053] FIG38 shows a schematic diagram of a needle-free needle cannula of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0054] FIG39 shows a schematic diagram of a needle-free needle cannula of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0055] FIG40 shows a schematic diagram of a needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0056] FIG41 shows a schematic diagram of the second end structure of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0057] FIG42 shows a schematic structural diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0058] FIG43 shows a schematic simulation model structure diagram of a multi-mode fluid delivery device according to a specific embodiment of the present invention;

[0059] FIG44 is a schematic diagram showing the porous diffusion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

[0060] FIG45 is a schematic diagram showing the porous diffusion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

[0061] FIG46 is a schematic diagram showing the porous diffusion effect delivered by the multi-mode fluid delivery device according to an embodiment of the present invention;

[0062] FIG47 is a schematic diagram showing the porous diffusion effect delivered by the multi-mode fluid delivery device according to an embodiment of the present invention;

[0063] FIG39 is a schematic diagram showing the porous diffusion effect delivered by the multi-mode fluid delivery device according to an embodiment of the present invention;

[0064] FIG48 shows a schematic diagram of the arrangement of needles for a multi-mode fluid delivery device according to an embodiment of the present invention;

[0065] FIG49 is a line graph showing immunological test data delivered by a multi-mode fluid delivery device according to one embodiment of the present invention;

[0066] FIG50 shows a line graph of immunological test data delivered by a multi-mode fluid delivery device according to one embodiment of the present invention; and

[0067] 51 is a line graph showing immunological assay data delivered by a multimodal fluid delivery device according to one embodiment of the present invention. DETAILED DESCRIPTION

[0068] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below in conjunction with specific embodiments and accompanying drawings. Here, the exemplary embodiments of the present invention and their descriptions are used to explain the present invention, but are not intended to limit the present invention.

[0069] As used herein, the term "including" and its variations represent open inclusion, i.e., "including but not limited to." Unless otherwise stated, the term "or" means "and / or." The term "based on" means "based at least in part on." The terms "an example embodiment" and "an embodiment" mean "at least one example embodiment." The term "another embodiment" means "at least one additional embodiment." The terms "first," "second," etc. may refer to different or the same objects. Other explicit and implicit definitions may also be included below.

[0070] In various embodiments of the present invention, as shown in Figures 1 and 2, a multimodal fluid delivery device is provided, particularly a multimodal fluid delivery device for drugs and vaccines, which may include a tube 100 for containing a fluid, wherein the tube 100 has a first end 110 and a second end 120. As shown in Figure 1, the second end 120 may be provided with a hole 121 for distributing the fluid in the tube. Additionally or alternatively, as shown in Figure 2, the second end 120 may be provided with a self-sealing elastic portion 122.

[0071] The multi-mode fluid delivery device may further include an injection head 200 detachably connected to the tube 100, the injection head 200 including one or more needle members 210. The one or more needle members 210 are configured to removably interface with the self-sealing elastic portion 122 in the second end 120 or the hole 121 for dispensing the fluid 130 in the tube 100.

[0072] The multi-mode fluid delivery device may further include a power mechanism 300 including a piston 310 disposed in the first end 110 of the tube 100 capable of pushing the fluid 130 or operatively connected to the piston 310 to apply delivery pressure to the piston 310 pushing the fluid 130 .

[0073] In some embodiments of the present invention, as shown in Figure 2, three self-closing elastic portions 122 are provided in the second end 120, and the three needle members 210 are configured to be removably connected to the self-closing elastic portion 122 in the second end 120. Specifically, the three needle members 210 are configured so that the three needle members 210 are inserted into the corresponding three self-closing elastic portions 122 provided in the second end 120.

[0074] In some embodiments of the present invention, the self-sealing elastic portion 122 is formed by filling the hole 121 for distributing the fluid in the tube provided in the second end 120 with silicone. There is no limitation on the specific composition of the silicone. Similarly, the hole 121 may be filled with a material other than silicone that is suitable for being inserted by the multiple needle members 210, and there is no limitation on this.

[0075] In some embodiments of the present invention, as shown in Figures 1 and 2, the piston 310 may be provided as an independent component, and the power mechanism 300 is configured to be operatively connected to the piston 310 to apply delivery pressure to the piston 310. It is also conceivable that in other embodiments of the present invention, the power mechanism 300 may be integrally integrated with the piston 310.

[0076] In some embodiments of the present invention, the driving mode of the power mechanism 300 may include any one of compressed gas driving, spring driving, electromagnetic driving, or a combination of the above driving modes. For example, in some embodiments, the power mechanism 300 may be driven by compressed gas, such as compressed nitrogen or compressed carbon dioxide gas, or may be driven by a compressed mechanical spring, or may be driven by a piezoelectric actuator, which is not limited here.

[0077] In some embodiments of the present invention, compared to manual needle injection (the pushing speed of the piston inside the needle tube is about 0.01 m / s), the piston speed of the piston 310 of the multi-mode fluid delivery device of the present invention when pushing the fluid 130 in the tube 100 is greater than or equal to 10 times the piston speed of manual needle injection. The piston speed of the piston 310 when pushing the fluid 130 is 0.05 m / s to 0.50 m / s, preferably 0.09 m / s to 0.25 m / s, and more preferably 0.14 to 0.20 m / s.

[0078] In some embodiments of the present invention, compared to manual needle injection (the outlet jet velocity of the fluid ejected from the needle is about 2 m / s), the outlet jet velocity of the fluid 130 of the multi-mode fluid delivery device of the embodiments of the present invention when being pushed away from the multiple holes 121 in the second end 120 or the one or more needle parts 210 of the injection head 200 by the piston 310 is greater than or equal to 10 m / s, preferably greater than or equal to 50 m / s, more preferably greater than or equal to 100 m / s, and more preferably greater than or equal to 150 m / s.

[0079] In some embodiments of the present invention, at least one of the one or more needle members 210 is substantially inserted into the human or animal body.

[0080] In some embodiments of the present invention, at least one of the one or more needle members is substantially inserted into a human or animal body;

[0081] In some embodiments of the present invention, at least one of the one or more needle members has a hole diameter in the range of 0.06 mm to 1.50 mm, further preferably in the range of 0.11 mm to 1.00 mm, and even more preferably in the range of 0.11 mm to 0.50 mm;

[0082] In some embodiments of the present invention, at least one of the self-sealing elastic portion or the hole for distributing the fluid in the tube has a diameter in the range of 0.06 mm to 1.50 mm, further preferably in the range of 0.11 mm to 1.00 mm, and even more preferably in the range of 0.11 mm to 0.50 mm.

[0083] In some embodiments of the present invention, the total fluid delivery area of ​​the plurality of needle members or the plurality of holes for distributing the fluid in the tube is 0.009 mm 2 Above, preferably 0.020mm 2 More than, more preferably 0.053mm 2 More than, more preferably 0.28mm 2 The needle or hole has a single hole area of ​​0.0028 to 0.035 mm 2 , preferably 0.0028~0.020mm 2 , more preferably 0.0028 to 0.009 mm 2 , wherein the single hole area of ​​the needle part refers to the single hole area calculated from the inner diameter of the needle part.

[0084] In an embodiment of the present invention, the multi-mode fluid delivery device of the present invention can deliver 0.3mm 3 The volume of the drug or vaccine (pre-delivery volume) is preferably 1.0 mm 3More than the volume (pre-delivery volume) of the drug or vaccine, more preferably 5.0mm 3 In some embodiments, the volume of drugs or vaccines delivered by the multi-mode fluid delivery device of the present invention at one time (volume before delivery) can reach 14.0 mm 3 In a further embodiment, the volume of medicine or vaccine delivered by the multi-mode fluid delivery device of the present invention at one time (volume before delivery) can reach 46.0 mm 3 .

[0085] In some embodiments of the present invention, the one or more needle members 210 have different adjustable skin insertion depths.

[0086] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that does not substantially penetrate the skin but forms close contact with the skin of a human or animal.

[0087] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that is substantially sufficient to penetrate the inner layer of human or animal skin.

[0088] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the subcutaneous layer of a human or animal.

[0089] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the muscle layer of a human or animal.

[0090] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth sufficient to be inserted into an organ in a human or animal body.

[0091] In some embodiments of the present invention, at least one of the one or more needle members 210 has an adjustable insertion depth.

[0092] In some embodiments of the present invention, the multimodal fluid delivery device is configured such that the diffusion volume of the fluid 130 in the body is greater than the undelivered volume. Preferably, the diffusion volume of the fluid in the body is more than 1.50 times the undelivered volume, preferably more than 1.80 times, further preferably more than 2.40 times, more preferably more than 3.00 times, and even more preferably more than 3.60 times.

[0093] In some embodiments of the present invention, the diffusion volume ratio refers to the ratio of the diffusion area volume of the fluid delivered by the multi-mode fluid delivery device in the body to the original volume of the fluid not delivered, that is:

[0094] In other embodiments of the present invention, the diffusion volume ratio may also refer to the ratio of the diffusion volume of the fluid delivered by the multi-mode fluid delivery device of the present invention to the diffusion volume of the fluid delivered by artificial needle injection, that is:

[0095] The diffusion volume of the delivery fluid can be calculated in a variety of ways, which are not limited here. For example, in some embodiments of the present invention, a fluorescent marker can be added to the drug or vaccine in advance, and then scanned by medical imaging technology and image analysis software can be used to calculate the volume of the diffusion area. For example, the envelope diagram of the diffusion area can be calculated to estimate the volume of the diffusion area.

[0096] It is understandable that when the delivery fluid enters the body through the multimodal fluid delivery device, the three-dimensional spatial area of ​​its distribution becomes larger due to the diffusion of the fluid in the body. This diffusion process will increase the surface area of ​​contact between the fluid, especially the drug or vaccine, and the tissues in the body, thereby improving the bioavailability and efficacy of the drug.

[0097] It is understandable that those skilled in the art can, under the guidance of the embodiments of the present invention, confirm the corresponding diffusion degrees of the dermis, epidermis, subcutaneous layer, muscle and human organs in the body of the inoculated object according to the needle-free delivery inoculated object, including but not limited to different types of animals or patients with different physical conditions.

[0098] In some embodiments of the present invention, as shown in Figures 3 to 6, the needle aperture d of the one or more needle members 210 can be configured so that the fluid jet passing through the one or more needle members 210 has a variety of different in vivo diffusion degrees, that is, different diffusion volume ratios, diffusion depths or diffusion breadths; thus, in some embodiments of the present invention, the needle apertures of the one or more needle members 210 can be equal and have a first needle aperture d1, the size of the first needle aperture d1 is configured so that the fluid jet passing through the one or more needle members 210 has different diffusion degrees, preferably, different diffusion depths, so that the fluid jet diffuses in at least one of the dermis, epidermis, subcutaneous layer, muscle and human organs.

[0099] In some embodiments of the present invention, the outlet jet velocity v of the one or more needle members 210 can be configured so that the fluid jet passing through the one or more needle members 210 has a plurality of different in vivo diffusion degrees, that is, different diffusion volume ratios, diffusion depths or diffusion breadths; thus, in some embodiments of the present invention, the outlet jet velocity v of the one or more needle members 210 can be equal and have a first outlet jet velocity v1, and the size of the first outlet jet velocity v1 is configured so that the fluid jet passing through the one or more needle members 210 has different diffusion degrees, preferably, different diffusion depths, so that the fluid jet diffuses in at least one of the dermis, epidermis, subcutaneous layer, muscle and human organs.

[0100] In some embodiments of the present invention, the plurality of needle members include a first needle member and a second needle member.

[0101] In some embodiments of the present invention, the first needle member has a first skin insertion depth located in one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs, and the second needle member has a second skin insertion depth located in another of the dermis, epidermis, subcutaneous tissue, muscle, and human organs. For example, as shown in FIG7 , the skin insertion depths of the one or more needle members 210 can be configured to be unequal, with the first needle member 210 having a first skin insertion depth L1 and the second needle member 210′ ​​having a second skin insertion depth L2, where L1≠L2.

[0102] In some embodiments of the present invention, the first needle member has a first needle aperture, the size of which is configured such that the fluid jet passing through the first needle member diffuses into at least one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs; and the second needle member has a second needle aperture, the size of which is configured such that the fluid jet passing through the second needle member diffuses into at least another of the dermis, epidermis, subcutaneous tissue, muscle, and human organs. For example, as shown in FIG8 , the first needle member 210 has a first needle aperture d1, and the second needle member 210′ ​​has a second needle aperture d2, where d1 ≠ d2.

[0103] In some embodiments of the present invention, the first needle member has a first outlet jet velocity, and the first outlet jet velocity is configured to cause the fluid jet passing through the first needle member to diffuse in at least one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs; the second needle member has a second outlet jet velocity, and the second outlet jet velocity is configured to cause the fluid jet passing through the second needle member to diffuse in at least another of the dermis, epidermis, subcutaneous tissue, muscle, and human organs. For example, the first needle member 210 may have a first outlet jet velocity v1, and the second needle member 210' may have a second outlet jet velocity v2, where v1≠v2.

[0104] In some embodiments of the present invention, the plurality of needle members further comprises a third needle member;

[0105] In some embodiments of the present invention, the third needle member has a third skin insertion depth located in the dermis, epidermis, subcutaneous tissue, muscle, and human organs;

[0106] In some embodiments of the present invention, the third needle member has a third needle aperture, and the size of the third needle aperture is configured to allow the fluid jet passing through the third needle member to diffuse in at least one of the dermis, epidermis, subcutaneous tissue, muscle, and dermis, epidermis, or subcutaneous tissue of a human organ;

[0107] In some embodiments of the present invention, the third needle member has a third outlet jet velocity, and the third outlet jet velocity is configured to allow the fluid jet passing through the third needle member to diffuse in at least one of the dermis, epidermis, subcutaneous tissue, muscle and human organs.

[0108] In some embodiments of the present invention, as shown in FIG. 9 to FIG. 11 , the one or more needle members 210 may be arranged along a straight line.

[0109] In some embodiments of the present invention, the one or more needle members 210 are arranged in a straight line along the diameter or midline of the injection head 200, and one of the one or more needle members 210 arranged in a straight line along the diameter or midline of the injection head 200 is located at the center of the circle or center of the injection head 200.

[0110] In one embodiment of the present invention, as shown in FIG. 10 , three needle members 210 are arranged in a straight line along the diameter (center line) of the injection head 200 , including a needle member 210 ′ located at the center (center) of the injection head 200 .

[0111] In some embodiments of the present invention, the plurality of needle members 210 arranged along a straight line are arranged at equal intervals.

[0112] In one embodiment of the present invention, as shown in FIG. 10 and FIG. 11 , a plurality of needle members 210 are arranged in a straight line along the diameter (center line) of the injection head 200 , wherein the plurality of needle members 210 are arranged at equal intervals.

[0113] In some embodiments of the present invention, as shown in FIG. 9 to FIG. 11 , the plurality of needle members 210 arranged along a straight line are mirror-symmetrical with respect to another diameter or center line of the injection head 200 different from the straight line.

[0114] In some embodiments of the present invention, the needle members 210 may be in multiple groups, and the needle members 210 of each group are arranged along a straight line, and the needle members 210 of each group are arranged along a diameter or a center line of the injection head 200 .

[0115] In one embodiment of the present invention, as shown in FIG12 , the injection head 200 is provided with three groups of needle members 210, namely, Group A, Group B and Group C (in FIG12 and subsequent figures, the needle members 210 of the same group are indicated by dotted lines), wherein Group A and Group C each include two needle members 210 arranged in a straight line, and Group B includes three needle members 210 arranged in a straight line.

[0116] In some embodiments of the present invention, the plurality of needle members 210 are arranged in an array; the plurality of needle members 210 arranged in an array are mirror-symmetrical with respect to first and second perpendicular diameters or center lines of the injection head 200 .

[0117] In one embodiment of the present invention, as shown in FIG13 , the injection head 200 is provided with four needle members 210 arranged in an array (the array arrangement relationship of the four needle members 210 is shown by mutually perpendicular dotted lines in FIG13 ), and the four needle members 210 are mirror-symmetrical with respect to the mutually perpendicular first and second diameters (center lines) of the injection head 200.

[0118] In some embodiments of the present invention, the skin insertion depth L′ of the needle member 210 ′ located at the center or centre of the injection head 200 is different from the skin insertion depths L of the other needle members 210 of the plurality of needle members 210 .

[0119] In one embodiment of the present invention, as shown in Figure 7, three needle members 210 are arranged in a straight line along the diameter (center line) of the injection head 200 on the injection head 200, including a needle member 210' located at the center (center) of the injection head 200. The skin insertion depth L' of the needle member 210' is different from the skin insertion depth L of other needle members 210 of the multiple needle members 210. In the configuration shown in Figure 7, L'>L. It can be understood that in other configurations, L'<L can also be configured.

[0120] In some embodiments of the present invention, the skin insertion depth L' of at least one group of needle members 210' among the multiple groups of needle members 210 is different from the skin insertion depth L of the other groups of needle members 210;

[0121] In one embodiment of the present invention, as shown in FIG14A , two groups of needle members 210, namely Group A and Group B, are arranged in a straight line on the injection head 200, wherein Group A and Group B are arranged in a straight line, wherein the skin insertion depth of the two needle members 210' included in Group B is L', and the skin insertion depth of the two needle members 210 included in Group A is L, wherein L'≠L. In the configuration shown in FIG14A , L'<L. It can be understood that in other configurations, L'>L can also be configured.

[0122] In some embodiments of the present invention, the needle hole diameter d′ of the needle member 210 ′ located at the center or centre of the injection head 200 is different from the needle hole diameters d of the other needle members 210 of the plurality of needle members 210 .

[0123] In one embodiment of the present invention, as shown in Figures 15 and 16, the injection head 200 is provided with three needle members 210 arranged in a straight line, including a needle member 210' with a needle aperture of d' located at the center or center of the injection head 200, and the remaining two needle members 210 with a needle aperture of d, wherein d'≠d, in the configuration shown in Figure 15, d'<d, and in the configurations shown in Figures 8 and 16, d'>d.

[0124] In some embodiments of the present invention, the needle hole diameter d2 of at least one group of needle members 210 among the multiple groups of needle members 210 is different from the needle hole diameters d1 of the other groups of needle members 210 .

[0125] In one embodiment of the present invention, as shown in Figures 17 and 18, three groups of needle members 210, namely Group A, Group B and Group C, are arranged on the injection head 200, wherein Group A and Group C each include two needle members 210 arranged along a straight line, and Group B includes three needle members 210' arranged along a straight line, wherein the needle aperture of the three needle members 210' included in Group B is d', and the needle aperture of the needle members 210 included in Group A and Group B is d, wherein d'≠d.

[0126] In some embodiments of the present invention, the outlet jet velocity v′ of the needle member 210 ′ located at the center of the injection head 200 is different from the outlet jet velocity v of other needle members 210 of the plurality of needle members 210 .

[0127] In some embodiments of the present invention, the outlet jet velocity v2 of at least one group of needle members 210 among the multiple groups of needle members 210 is different from the outlet jet velocity v1 of the other groups of needle members 210 .

[0128] In one embodiment of the present invention, as shown in Figures 17 and 18, three groups of needle members 210, namely Group A, Group B and Group C, are arranged on the injection head 200, wherein Group A and Group C each include two needle members 210 arranged along a straight line, and Group B includes three needle members 210' arranged along a straight line, wherein the outlet jet velocity v2 of the three needle members 210' included in Group B, and the outlet jet velocity v1 of the needle members 210 included in Group A and Group C, wherein v2≠v1.

[0129] In some embodiments of the present invention, the multiple needle members 210 on the injection head 200 are arranged in a ring; the multiple needle members 210 are arranged in a ring with the center of the injection head 200 as the center.

[0130] In one embodiment of the present invention, as shown in Figures 19 and 20, as an example, Figure 19 shows that three needle parts 210 are arranged on the injection head 200, and the three needle parts 210 are arranged in a ring with the center O of the injection head 200 as the center, while Figure 20 shows that four needle parts 210 are arranged on the injection head 200, and the four needle parts 210 are arranged in a ring with the circle O of the injection head 200 as the center.

[0131] In some embodiments of the present invention, the needle members 210 are provided in multiple groups, each group of needle members 210 is arranged in a ring shape, and the multiple groups of needle members 210 are coaxially arranged in a ring shape.

[0132] In one embodiment of the present invention, as shown in FIG21 , two groups of needle components 210, Group A and Group B, are arranged on the injection head 200, wherein Group A and Group B are arranged in a circular shape and are coaxially arranged in a circular shape with the center O of the injection head 200 as the center.

[0133] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in an annular manner has a skin insertion depth L′ different from that of the other needle members 210 .

[0134] In some embodiments of the present invention, the skin insertion depth L of at least one group of the plurality of groups of needle members 210 arranged in an annular manner is different from the skin insertion depth L of the other groups of needle members 210 .

[0135] In one embodiment of the present invention, as shown in Figures 14B and 23, two groups of needle members 210, Group A and Group B, are arranged on the injection head 200, wherein Group A and Group B each include three needle members 210. Figure 14B is a cross-sectional view of the configuration shown in Figure 23 along the axial direction of the tube 100, which shows the skin insertion depth of the multiple needle members 210 arranged in a ring on the injection head, wherein the skin insertion depth of the three needle members 210 included in Group A is L', and the skin insertion depth of the three needle members 210 included in Group B is L, and L'≠L. In the configuration shown in Figure 14B, L'>L; it can be understood that in other configurations, L'<L can also be set.

[0136] In some embodiments of the present invention, the skin insertion depths L of the multiple groups of needle members 210 coaxially arranged in an annular manner decrease or increase radially.

[0137] In one embodiment of the present invention, referring again to Figures 14B and 23, which show the skin insertion depths of the multiple needle members 210 arranged in a ring on the injection head, wherein the skin insertion depth of the three needle members 210 included in Group A is L', and the skin insertion depth of the three needle members 210 included in Group B is L, and the skin insertion depth L of the needle members 210 in Group A and Group B increases radially outward, that is, L'>L; it can be understood that in another configuration, the skin insertion depth L of the needle members 210 in Group A and Group B can also be set to decrease radially outward, that is, L'<L.

[0138] In one embodiment of the present invention, referring again to Figures 14B and 23, two groups of needle members 210, Group A and Group B, are arranged on the injection head 200, wherein the Group A and the Group B are arranged in a ring and coaxially in a ring with the center of the injection head 200 as the center, wherein the skin insertion depth of the three needle members 210' included in the Group A is L', and the skin insertion depth of the needle members 210 included in the Group B is L, wherein L'≠L; and in one configuration, the skin insertion depths of the needle members 210' of Group A and the needle members 210 of Group B, which are coaxially arranged in a ring with each other, increase radially outward, that is: L'>L; it can be understood that in another configuration, the skin insertion depths of the needle members 210' of Group A and the needle members 210 of Group B can also be set to decrease radially outward, that is: L'<L.

[0139] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in an annular manner has a needle hole diameter d' different from that of the other needle members 210;

[0140] In some embodiments of the present invention, the needle hole diameter d' of at least one group of needle members 210 of the plurality of groups of needle members 210 is different from the needle hole diameters d of the other groups of needle members 210;

[0141] In some embodiments of the present invention, the needle apertures d of the multiple groups of needle members 210 coaxially arranged in an annular manner decrease or increase in the radial direction.

[0142] In one embodiment of the present invention, as shown in Figure 14B and Figures 22 and 23, two groups of needle members 210, namely Group A and Group B, are arranged on the injection head 200, wherein the Group A and the Group B are arranged in a ring and are coaxially arranged in a ring with the center (center) of the injection head 200 as the center, wherein the needle aperture of the three needle members 210' included in the Group B is d', and the needle aperture of the needle member 210 included in the Group A is d, wherein d'≠d; and in the configuration shown in Figure 22, the needle apertures of the needle members 210 of Group A and the needle members 210' of Group B, which are coaxially arranged in a ring, decrease radially outward, that is: d'>d, while in the configuration shown in Figure 23, the needle apertures of the needle members 210 of Group A and the needle members 210' of Group B increase radially outward, that is: d'<d.

[0143] In some embodiments of the present invention, at least one of the annularly arranged needle members 210 has an outlet jet velocity v' different from that of the other holes;

[0144] In some embodiments of the present invention, the outlet jet velocity v' of at least one group of needle members 210 of the plurality of groups of needle members 210 is different from the outlet jet velocity v of the other groups of holes;

[0145] In some embodiments of the present invention, the outlet jet velocities v of the multiple groups of needle members 210 coaxially arranged in an annular manner increase or decrease radially.

[0146] In some embodiments of the present invention, the plurality of needle members 210 include a central needle member 210 ″ located at the center of the injection head 200 and a plurality of peripheral needle members 210 located around the central needle member 210 .

[0147] In one embodiment of the present invention, as shown in FIG. 24 , the injection head 200 is provided with a central needle member 210 ″ located at the center (center) of the injection head 200 and two peripheral needle members 210 located around the central needle member 210 .

[0148] In some embodiments of the present invention, the plurality of peripheral needle members 210 are arranged in a ring.

[0149] In some embodiments of the present invention, the plurality of peripheral needle members 210 are arranged in a coaxial ring around the central needle member 210 ″.

[0150] In one embodiment of the present invention, as shown in Figures 24 to 26, the injection head 200 is provided with a central needle member 210" located at the center (center) of the injection head 200 and a plurality of peripheral needle members 210 located around the central needle member 210. As an example, Figure 26 shows a configuration in which four peripheral needle members 210 are arranged on the injection head 200.

[0151] In some embodiments of the present invention, the peripheral holes 121 have multiple groups, each group of peripheral needle members 210 is arranged in a ring, and the multiple groups of peripheral needle members 210 are coaxially arranged in a ring around the central needle member 210".

[0152] In one embodiment of the present invention, as shown in FIG27 , the injection head 200 is provided with six peripheral needle members 210 . The six peripheral needle members 210 are divided into two groups A and B that are evenly arranged in a ring shape. Groups A and B each contain three peripheral needle members 210 , and the two groups of peripheral needle members 210 are coaxially arranged in a ring around the central needle member 210 .

[0153] In some embodiments of the present invention, the skin insertion depth L″ of the central needle member 210 ″ is different from the skin insertion depths of the plurality of peripheral needle members 210 .

[0154] In one embodiment of the present invention, the injection head 200 is provided with a central needle member 210" with a skin insertion depth of L" and three peripheral needle members 210 with a skin insertion depth of L, wherein L"≠L, in one configuration L"<L, and in another configuration L">L.

[0155] In some embodiments of the present invention, the skin insertion depth L′ of at least one group of peripheral needle members 210 among the plurality of groups of peripheral needle members 210 is different from the skin insertion depth L of the other groups of peripheral needle members 210 .

[0156] In one embodiment of the present invention, the skin insertion depth of the three peripheral needle members 210 included in group A is L1, and the skin insertion depth of the three peripheral needle members 210 included in group B is L2, and L1≠L2, in one of the configurations shown, L1>L2, and in the other configuration, L1<L2.

[0157] In some embodiments of the present invention, the skin insertion depths of the multiple groups of needle members 210 and the central needle member 210 ″ coaxially arranged in an annular manner decrease or increase radially.

[0158] In one embodiment of the present invention, the skin insertion depth of the central needle member 210" is L", the skin insertion depth of the three peripheral needle members 210 included in the group A is L1, and the skin insertion depth of the three peripheral needle members 210 included in the group B is L2, and L1≠L2; in one configuration, the skin insertion depths of the needle members 210 of the A and B groups and the central needle member 210" coaxially arranged in a ring decrease radially outward, that is: L">L1>L2, and in another configuration, the skin insertion depths of the needle members 210 of the A and B groups and the central needle member 210" coaxially arranged in a ring increase radially, that is: L"<L1<L2.

[0159] In some embodiments of the present invention, the needle hole diameter d″ of the central needle member 210 ″ is different from the needle hole diameters d of the plurality of peripheral needle members 210 .

[0160] In one embodiment of the present invention, as shown in Figures 28 and 29, the injection head 200 is provided with a central needle member 210" with a needle aperture of d" and three peripheral needle members 210 with a needle aperture of d, wherein d"≠d, in the configuration shown in Figure 28, d"<d, and in the configuration shown in Figure 29, d">d.

[0161] In another embodiment of the present invention, as shown in Figures 30 to 32, the injection head 200 is provided with a central needle member 210" with a needle aperture d" and 6 peripheral needle members 210 with a needle aperture d, wherein d"≠d, and the 6 peripheral needle members 210 are divided into two groups A and B that are evenly arranged in a ring shape, wherein the two groups A and B each contain 3 peripheral needle members 210, and the two groups of peripheral needle members 210 are coaxially arranged in a ring around the central needle member 210".

[0162] In some embodiments of the present invention, the needle aperture diameter d1 of at least one group of peripheral needle members 210 among the plurality of groups of peripheral needle members 210 is different from the needle aperture diameter d2 of the other groups of peripheral needle members 210 .

[0163] In one embodiment of the present invention, as shown in Figures 31 and 32, the needle aperture of the three peripheral needle parts 210 included in group A is d1, and the needle aperture of the three peripheral needle parts 210 included in group B is d2, and d1≠d2, in the configuration shown in Figure 31, d1>d2, and in the configuration shown in Figure 32, d1<d2.

[0164] In some embodiments of the present invention, the needle apertures of the multiple groups of needle members 210 and the central needle member 210 ″ coaxially arranged in an annular manner increase or decrease in radial direction.

[0165] In one embodiment of the present invention, as shown in Figures 31 and 32, the needle aperture of the one central needle piece 210" is d", the needle aperture of the three peripheral needle pieces 210 included in group A is d1, and the needle aperture of the three peripheral needle pieces 210 included in group B is d2, and d1≠d2; in the configuration shown in Figure 31, the needle apertures of the needle pieces 210 of groups A and B, which are coaxially arranged in a ring, and the central needle piece 210" decrease radially outward, that is: d">d1>d2, while in the configuration shown in Figure 32, the needle apertures of groups A and B, which are coaxially arranged in a ring, and the central needle piece 210" increase radially, that is: d"<d1<d2.

[0166] In some embodiments of the present invention, the outlet jet velocity v″ of the central needle member 210 ″ is different from the outlet jet velocity v of the plurality of peripheral needle members 210 .

[0167] In some embodiments of the present invention, the outlet jet velocity v1 of at least one group of peripheral needle members 210 among the plurality of groups of peripheral needle members 210 is different from the outlet jet velocity v2 of the other groups of peripheral needle members 210 .

[0168] In some embodiments of the present invention, the outlet jet velocities of the multiple groups of needle members 210 and the central needle member 210 ″ that are coaxially annularly arranged with each other increase or decrease radially.

[0169] In some embodiments of the present invention, as shown in FIG. 33 and FIG. 34 , the injection head 200 includes a supporting portion 220 for supporting the needle member.

[0170] In some embodiments of the present invention, the support portion 220 is configured as a tubular wall extending toward one side of the needle tube 100; while in other embodiments of the present invention, the support portion 220 may be an independent component independent of the injection head 200 and used to connect the injection head 200 to the tube 100.

[0171] In some embodiments of the present invention, as shown in FIG. 33 and FIG. 34 , the needle member 210 further includes a first needle portion 211 located on a side of the support portion 220 facing away from the needle tube 100 .

[0172] In some embodiments of the present invention, as shown in FIG33 and FIG34 , the needle member 210 includes a fixing pad 230 located on the side of the support portion 220 facing the needle tube 100 , and the fixing pad 230 is used to fix the needle member 210 ;

[0173] In some embodiments of the present invention, as shown in FIG33 and FIG34 , the needle member 210 includes a second needle portion 212 located on a side of the support portion 220 facing the needle tube 100;

[0174] In some embodiments of the present invention, alternatively to Figures 33 and 34, the needle member 210 does not extend from the side of the support portion 220 facing away from the needle tube 100, so that the needle member 210 forms a needle-free microhole 213 on the side of the support portion 220 facing away from the needle tube 100.

[0175] In some embodiments of the present invention, the needle member 210 further comprises an interventional soft needle removably connected to the hole 210 .

[0176] In some embodiments of the present invention, as shown in FIG. 35 to FIG. 37 , the multi-mode fluid delivery device further includes a needle kit 400 , wherein the needle kit 400 includes a needle sleeve 401 for removably surrounding the first needle portion 211 of the needle member 210 .

[0177] In some embodiments of the present invention, as shown in FIG35 to FIG37 , the height h of the needle sleeve 401 of the needle kit 400 is greater than or equal to the first needle portion 211 of the needle member 210 , thereby completely surrounding the first needle portion 211 ;

[0178] In some embodiments of the present invention, as shown in Figures 35 to 37, optionally, the height h of the needle sleeve 410 of the needle kit 400 is smaller than the first needle head 211 of the needle member 210, thereby partially surrounding the first needle head 211, so that the first needle head 211 extends from the front end of the needle sleeve to form an insertion portion 214.

[0179] In some embodiments of the present invention, as shown in Figures 35 to 37, the needle kit 400 includes a first needle kit 410, and the height of the needle sleeve 401 of the first needle kit 410 is greater than the first needle head 211 of the needle head member, thereby completely surrounding the first needle head 211 to protect the first needle head 211.

[0180] In some embodiments of the present invention, as shown in FIG. 35 to FIG. 37 , the needle kit 400 is multiple, and the multiple needle kits 400 include a first needle kit 410 and a second needle kit 420 .

[0181] The first needle kit 410 is configured so that the first needle head 211 is partially surrounded, and the insertion portion is located in the dermis, the epidermis, the subcutaneous layer, the muscle, or the human organ.

[0182] The second needle kit 420 is configured such that the first needle head 211 is partially surrounded and the insertion portion is located in the dermis, the epidermis, the subcutaneous layer, the muscle, or the human organ.

[0183] In some embodiments of the present invention, there are multiple needle kits 400, including a first needle kit 410, a second needle kit 420, a third needle kit 430, a fourth needle kit 440, a fifth needle kit 450 and a sixth needle kit 460;

[0184] The first needle kit 410 is configured so that it completely surrounds the first needle head 211;

[0185] The second needle kit 420 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located in the dermis;

[0186] The third needle set 430 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located in the epidermis;

[0187] The fourth needle set 440 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located subcutaneously;

[0188] The fifth needle set 450 is configured so that the insertion portion 214 thereof surrounding the first needle head 211 is located in the muscle;

[0189] The sixth needle kit 460 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is positioned in a human organ.

[0190] In some embodiments of the present invention, the needle guard structure may be integrated on the injection head. In other embodiments of the present invention, the needle guard structure may be axially movable relative to the needle member along the axial direction of the needle member.

[0191] In a further embodiment of the present invention, the injection head further comprises a needle sheath portion sleeved over the needle member and a rotating member operatively connected to the needle member or the needle sheath portion, the rotating member being configured to adjust the axial position of the needle member and the needle sheath portion by rotation to adjust the exposed length of the needle member relative to the needle sheath portion. In some embodiments of the present invention, the axial position of the needle member and the needle sheath portion is configured to be adjustable between multiple positions so that the exposed length of the needle member can be adjusted between multiple positions. Preferably, the exposed length of the needle member can be adjusted between multiple positions including the needle sheath portion being retracted, being flush with the needle sheath portion, being located in the dermis, being located in the epidermis, being located subcutaneously, being located in the muscle, and being located in a human organ. In some embodiments of the present invention, the axial position of the needle member and the needle sheath portion is configured to be continuously adjustable so that the exposed length of the needle member can be continuously adjusted.

[0192] In one embodiment of the present invention, the injection head includes a needle sleeve portion sleeved on the needle member and a rotating member operatively connected to the needle member, the rotating member is provided with a screwing ring and a first threaded portion, and the needle member is provided with a second threaded portion matching the first threaded portion. The rotating member can adjust the axial position of the needle member by rotating the screwing ring. For example, in one case, the clockwise rotation of the screwing ring can drive the needle member to extend axially toward the distal end, so that the needle member extends out of the needle sleeve portion sleeved on the needle member to form an exposed portion or adjust the length of the exposed portion.

[0193] In another embodiment of the present invention, the injection head includes a needle sleeve portion sleeved on the needle member and a rotating member operatively connected to the needle member, the rotating member is provided with a screwing ring and a first threaded portion, and the needle sleeve portion is provided with a second threaded portion matching the first threaded portion. The rotating member can adjust the axial position of the needle sleeve portion by rotating the screwing ring. For example, in one case, clockwise rotation of the screwing ring can drive the needle sleeve portion to extend axially toward the distal end, so that the needle sleeve portion sleeved on the needle member covers the top end of the needle member to protect the needle member.

[0194] In a further embodiment of the present invention, the injection head includes a needle sleeve portion sleeved on the needle member and a rotating member operatively connected to the needle member, the rotating member is provided with a screwing ring and a first threaded portion, the needle sleeve portion is provided with a second threaded portion matching the first threaded portion, and the needle member is provided with a third threaded portion matching the first threaded portion, and the rotating member can adjust the relative axial position of the needle member and the needle sleeve portion sleeved on the needle member by rotating the screwing ring.

[0195] In the embodiment of the present invention, the relative axial position of the needle member and the needle sleeve portion sleeved on the needle member can be infinitely adjusted by the rotating member, so as to achieve infinite adjustment of the retraction, exposure or exposure length of the needle member relative to the needle sleeve portion.

[0196] In some embodiments of the present invention, the injection head 200 includes a connection portion 240 for detachably connecting the injection head 200 to the tube 100;

[0197] In some embodiments of the present invention, as shown in Figures 33 and 34, the connection portion 240 is a threaded connection portion;

[0198] In some embodiments of the present invention, the connecting portion 240 is a clamping portion; optionally, the connecting portion 240 is an adhesive portion.

[0199] In some embodiments of the present invention, the multi-mode fluid delivery device further comprises a locking member for locking the injection head 200 to the tube, wherein the locking member comprises a connecting portion for detachably connecting the locking member to the tube;

[0200] In some embodiments of the present invention, the connection portion is a threaded connection portion;

[0201] In some embodiments of the present invention, the connecting portion is a clamping portion;

[0202] In some embodiments of the present invention, the connecting portion is an adhesive portion.

[0203] In some embodiments of the present invention, any of the multimodal fluid delivery devices described above can also be used in combination with a triple vaccine for feline rhinotracheitis, calicivirus disease, and panleukopenia, wherein the triple vaccine is also referred to as a feline triple vaccine. Thus, embodiments of the present application also provide corresponding drug-device combination products. In embodiments of the present invention, the drug-device combination product can include or be a drug delivery system.

[0204] In an embodiment of the present invention, the cat triple vaccine refers to an inactivated vaccine for preventing common infectious diseases of cats, which can prevent feline rhinotracheitis, feline calicivirus disease and feline panleukopenia. These three diseases are the most common infectious diseases of cats. When the cat triple vaccine is developed, it is based on the dominant epidemic strains of the three infectious diseases of cats screened from a large number of clinical samples. Therefore, it has good safety, rapid antibody production, long immune duration, and one-shot prevention of three diseases. It is suitable for cats over 8 weeks of age, and generally requires three shots of basic immunization at 8 weeks, 12 weeks, and 16 weeks of age. After completing basic immunization, a booster shot should be inoculated every year to maintain the immune effect.

[0205] In some embodiments of the present invention, the injection head 200 of the multimodal fluid delivery device used in combination with the feline triple vaccine is provided with three holes 121 arranged in a circular pattern at equal intervals around the center of the injection head 200, and the three holes 121 are 1.25 mm ± 20% away from the center of the injection head 200.

[0206] In some embodiments of the present invention, the pushing speed of the piston 210 of the multi-mode fluid delivery device used in combination with a feline triple vaccine is configured to be 0.12 m / s±20%.

[0207] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the feline triple vaccine is configured so that the outlet jet velocity of the feline triple vaccine when pushed away from the hole 121 in the injection head 200 by the piston 210 is 150.00 m / s±20%.

[0208] In some embodiments of the present invention, a multimodal fluid delivery device used in combination with a feline triple vaccine is configured such that the diffusion volume of the feline triple vaccine in vivo is more than 1.5 times the undelivered volume of the feline triple vaccine.

[0209] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with the feline triple vaccine is configured so that the average antibody titer of the feline triple vaccine 14 days after the second dose is more than 1.2 times, preferably more than 2.0 times, and more preferably more than 4.8 times the average antibody titer of needle injection.

[0210] In the present embodiments, the average antibody titer is a measure of the strength of an immune response, used to assess the level of antibodies produced by an organism against a specific antigen (such as a virus, bacteria, or vaccine). It is expressed as the average of the serum dilutions that can neutralize or bind to a certain amount of antigen under specific conditions. In other words, a higher average antibody titer indicates a stronger ability of the antibodies produced by the organism to fight a specific pathogen.

[0211] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with the feline triple vaccine is configured so that the average antibody titer of the feline triple vaccine 30 days after the second dose is more than 1.2 times, preferably more than 2.0 times, and more preferably more than 3.7 times the average antibody titer of needle injection.

[0212] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with the feline triple vaccine is configured so that the average antibody titer of the feline triple vaccine 60 days after the second dose is more than 1.2 times, preferably more than 2.0 times, and more preferably more than 6.3 times the average antibody titer of needle injection.

[0213] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with a feline triple vaccine is configured so that the average antibody titer of the feline triple vaccine 60 days after the second dose of 60% vaccine dose is more than 1.1 times, preferably more than 1.5 times, and more preferably more than 2.0 times the average antibody titer produced by injection of 100% vaccine dose by needle.

[0214] In some embodiments of the present invention, any of the multimodal fluid delivery devices described above can also be used in combination with a hepatitis B vaccine. Thus, embodiments of the present application also provide corresponding drug-device combination products. In embodiments of the present invention, the drug-device combination product can include or be a drug delivery system.

[0215] In the embodiments of the present invention, the hepatitis B vaccine refers to a recombinant yeast vaccine (Hansenula) for preventing hepatitis B (a viral liver disease). It is prepared by purifying the hepatitis B virus surface antigen (HBsAg) expressed by recombinant Hansenula and adding an aluminum adjuvant. The active ingredient is the hepatitis B virus surface antigen. The vaccine is suitable for people susceptible to hepatitis B, especially the following people: (1) newborns, especially those whose mothers are HBsAg or HBeAg positive, (2) people susceptible to hepatitis B aged 16 years and above, and (3) medical staff engaged in medical work and laboratory personnel who come into contact with blood. After vaccination, the immune system can be stimulated to produce protective antibodies, thereby giving the human body immunity to prevent hepatitis B, thereby achieving the purpose of preventing hepatitis B infection. The conventional immunization site is the deltoid muscle of the upper arm. The immunization program is 3 injections, one at birth (0 months), one at 1-2 months of age, and one at 6-18 months of age. Newborns are given the first injection within 24 hours after birth, and each injection is one dose.

[0216] In some embodiments of the present invention, the injection head 200 of the multimodal fluid delivery device used in combination with the hepatitis B vaccine is provided with three holes 121 arranged in a circular pattern at equal intervals around the center of the injection head 200, and the three holes 121 are 1.25 mm ± 20% away from the center of the injection head 200.

[0217] In some embodiments of the present invention, the pushing speed of the piston 210 of the multi-mode fluid delivery device used in combination with the hepatitis B vaccine is configured to be 0.12 m / s±20%.

[0218] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the hepatitis B vaccine is configured so that the outlet jet velocity of the hepatitis B vaccine when pushed away from the hole 121 in the injection head 200 by the piston 210 is 150.00 m / s±20%.

[0219] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with a hepatitis B vaccine is configured such that the diffusion volume of the hepatitis B vaccine in the body is more than 1.5 times the non-delivered volume of the hepatitis B vaccine.

[0220] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with the hepatitis B vaccine is configured so that the average antibody titer of the hepatitis B vaccine 14 days after the second dose is more than 1.1 times the average antibody titer of needle injection, preferably more than 1.5 times, and more preferably more than 2.0 times.

[0221] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with the hepatitis B vaccine is configured so that the average antibody titer of the hepatitis B vaccine 42 days after the second dose is more than 1.1 times the average antibody titer of needle injection, preferably more than 1.5 times, and more preferably more than 2.0 times.

[0222] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with the hepatitis B vaccine is configured so that the average antibody titer of the hepatitis B vaccine 42 days after the second dose of 60% vaccine dose is more than 1.1 times, preferably more than 1.3 times, and more preferably more than 1.5 times the average antibody titer produced by injection of 100% vaccine dose by needle.

[0223] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with the hepatitis B vaccine is configured so that the T lymphocyte positive expression rate of the hepatitis B vaccine 42 days after the second dose is higher than that of needle injection by more than 10%, preferably more than 20% higher, and more preferably more than 50% higher.

[0224] In some embodiments of the present invention, any of the multimodal fluid delivery devices described above can also be used in combination with a human pneumonia vaccine. Thus, embodiments of the present application also provide corresponding drug-device combination products. In embodiments of the present invention, the drug-device combination product can include or be a drug delivery system.

[0225] In some embodiments of the present invention, the injection head 200 of the multimodal fluid delivery device used in combination with a human pneumonia vaccine is provided with three holes 121 arranged in a circular pattern at equal intervals around the center of the injection head 200, and the three holes 121 are 1.25 mm ± 20% away from the center of the injection head 200.

[0226] In some embodiments of the present invention, the pushing speed of the piston 210 of the multi-mode fluid delivery device used in combination with a pneumonia vaccine for humans is configured to be 0.14 m / s±20%.

[0227] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with a pneumonia vaccine for humans is configured so that the exit jet velocity of the pneumonia vaccine for humans when pushed away from the hole 121 in the injection head 200 by the piston 210 is 160.00 m / s±20%.

[0228] In some embodiments of the present invention, a multimodal fluid delivery device used in combination with a human pneumonia vaccine is configured such that the diffusion volume of the human pneumonia vaccine in vivo is more than 1.5 times the undelivered volume of the human pneumonia vaccine.

[0229] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with a pneumonia vaccine for humans is configured so that the average antibody titer of the pneumonia vaccine for humans after vaccination is 1.1 times or more, preferably 1.5 times or more, and even more preferably 2.0 times or more, higher than the average antibody titer of needle injection.

[0230] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with a pneumonia vaccine for humans is configured so that the average antibody titer of the pneumonia vaccine for humans 42 days after the second dose is 1.1 times or more, preferably 1.5 times or more, and even more preferably 2.0 times or more of the average antibody titer after needle injection.

[0231] In some embodiments of the present invention, a multimodal fluid delivery device used in combination with a pneumonia vaccine for humans is configured such that the average antibody titer of the pneumonia vaccine after 60% vaccine dose injection is 1.1 times or more, preferably 1.3 times or more, and even more preferably 1.5 times or more, the average antibody titer produced by 100% vaccine dose injection.

[0232] In some embodiments of the present invention, any of the multimodal fluid delivery devices described above can also be used in combination with a GLP-1 polypeptide. Thus, embodiments of the present application also provide corresponding drug-device combination products. In embodiments of the present invention, the drug-device combination product can include or be a drug delivery system.

[0233] In some embodiments of the present invention, the injection head 200 of the multimodal fluid delivery device used in combination with GLP-1 polypeptides is provided with three holes 121, which are arranged in a circular pattern with equal intervals around the center of the injection head 200, and the three holes are 1.25 mm ± 20% away from the center.

[0234] In some embodiments of the present invention, the pushing speed of the piston 210 of the multimodal fluid delivery device used in combination with a GLP-1 polypeptide is 0.16 m / s ± 20%;

[0235] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with a GLP-1 polypeptide is configured such that the outlet jet velocity of the GLP-1 polypeptide when pushed away from the hole 121 in the injection head 200 by the piston 210 is 170.00 m / s±20%.

[0236] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with a GLP-1 polypeptide is configured such that the diffusion volume of the GLP-1 polypeptide in vivo is greater than 1.5 times the volume of the GLP-1 polypeptide not delivered.

[0237] In some embodiments of the present invention, the GLP-1 polypeptide includes semaglutide, and any of the multimodal fluid delivery devices described in the embodiments of the present invention can be used in combination with semaglutide. Thus, embodiments of the present application also provide corresponding drug-device combination products. In embodiments of the present invention, the drug-device combination product can include or be a drug delivery system.

[0238] In some embodiments of the present invention, the semaglutide (Simeigelutai), also known as semaglutide, is a second-generation glucagon-like peptide-1 (GLP-1) analogue with a molecular formula of C 187 H 291 N 45 O 59 It (molecular weight of 4113.58Da) has excellent blood sugar lowering and weight loss effects in diabetic patients, significantly better than sitagliptin, insulin glargine U100 or extended-release exenatide; it is also better than its peer liraglutide in weight loss, especially in patients with BMI ≥ 30. Semaglutide can be taken orally or subcutaneously, for example, as a 7mg / 14mg oral dosage form once daily or a 0.5mg / 1.0mg subcutaneous injection once weekly. Semaglutide not only shows good efficacy in the treatment of diabetes, but also shows significant advantages in weight loss and cardiovascular protection.

[0239] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with semaglutide is configured such that the diffusion volume of the semaglutide in the body is more than 1.5 times the non-delivered volume of the semaglutide.

[0240] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with semaglutide is configured so that the weight loss effect of semaglutide on humans and animals is consistent with that of needle injection, preferably the weight loss effect is increased by 2%, further preferably by 5%, and even more preferably by 10% compared with needle injection.

[0241] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with semaglutide is configured so that the weight loss endpoint of semaglutide in vivo is consistent with that of needle injection, preferably increased by more than 2%, more preferably increased by more than 5%, and even more preferably increased by more than 10%.

[0242] In some embodiments of the present invention, the multimodal fluid delivery device used in combination with semaglutide is configured so that the ratio of side effects such as nausea, vomiting, and abdominal distension caused by semaglutide is consistent with that caused by needle injection, preferably reduced by more than 5%, further preferably reduced by more than 10%, and even more preferably reduced by more than 20%.

[0243] In some embodiments of the present invention, any of the multimodal fluid delivery devices described herein may also be used in combination with a pharmaceutical formulation. Thus, embodiments of the present application also provide corresponding drug-device combination products. In embodiments of the present invention, the drug-device combination product may include or may be a drug delivery system.

[0244] In some embodiments of the present invention, the pharmaceutical preparation is a rabies vaccine for human use.

[0245] In some embodiments of the present invention, the pharmaceutical preparation is a rabies vaccine for animals.

[0246] In some embodiments of the present invention, the pharmaceutical preparation is a meningitis vaccine for human use.

[0247] In some embodiments of the present invention, the pharmaceutical preparation is a hand, foot and mouth disease vaccine for animals.

[0248] In some embodiments of the present invention, the pharmaceutical preparation is a new coronavirus vaccine for human use.

[0249] In some embodiments of the present invention, the pharmaceutical preparation is a hepatitis A vaccine for human use.

[0250] In some embodiments of the present invention, the pharmaceutical preparation is a vaccine for hemorrhagic fever with renal syndrome for humans.

[0251] In some embodiments of the present invention, the pharmaceutical preparation is a mumps vaccine for human use.

[0252] In some embodiments of the present invention, the pharmaceutical preparation is an HPV vaccine for humans.

[0253] In some embodiments of the present invention, the pharmaceutical preparation is a tumor chemotherapy drug for human use.

[0254] In some embodiments of the present invention, the pharmaceutical preparation is a nuclear medicine for treating tumors in humans.

[0255] In some embodiments of the present invention, the pharmaceutical preparation is a human tumor vaccine, including but not limited to polypeptide vaccines, mRNA vaccines, and DNA vaccines.

[0256] In some embodiments of the present invention, the pharmaceutical preparation is a combined porcine diarrhea vaccine. In some embodiments of the present invention, the combined porcine diarrhea vaccine may include a combined live vaccine for porcine transmissible gastroenteritis and porcine epidemic diarrhea (HB08 strain + ZJ08 strain). In some embodiments of the present invention, the combined porcine diarrhea vaccine may include a combined inactivated vaccine for porcine transmissible gastroenteritis and porcine epidemic diarrhea.

[0257] In some embodiments of the present invention, the pharmaceutical preparation is an inactivated blue ear vaccine. In some embodiments of the present invention, the inactivated blue ear vaccine may include an inactivated porcine reproductive and respiratory syndrome vaccine (CH-1a strain).

[0258] In some embodiments of the present invention, the pharmaceutical preparation is a foot-and-mouth disease vaccine. In some embodiments of the present invention, the foot-and-mouth disease vaccine can be used for pigs, cattle or sheep. In some embodiments of the present invention, the foot-and-mouth disease vaccine may include swine foot-and-mouth disease O type inactivated vaccine (O / Mya98 / XJ / 2010 strain + O / GX / 09-7 strain). In some embodiments of the present invention, the foot-and-mouth disease vaccine may include swine foot-and-mouth disease O type, A type bivalent inactivated vaccine (Re-O / MYA98 / JSCZ / 2013 strain + Re-A / WH / 09 strain). In some embodiments of the present invention, the foot-and-mouth disease vaccine may include foot-and-mouth disease O type inactivated vaccine (OJMS strain), which can be used for cattle or sheep. In some embodiments of the present invention, the foot-and-mouth disease vaccine may include foot-and-mouth disease O type, A type bivalent inactivated vaccine (O / HB / HK / 99 strain + AF / 72 strain, suspension culture), which can be used for cattle. In some embodiments of the present invention, the foot-and-mouth disease vaccine may include a bivalent inactivated foot-and-mouth disease type O and type A vaccine (O / MYA98 / BY / 2010 strain + Re-A / WH / 09 strain), which can be used for cattle or sheep.

[0259] In some embodiments of the present invention, the pharmaceutical preparation is a bovine bivalent vaccine. In some embodiments of the present invention, the bovine bivalent vaccine may include a bovine viral diarrhea / mucosal disease and infectious rhinotracheitis bivalent inactivated vaccine (NMG strain + LY strain).

[0260] In some embodiments of the present invention, the pharmaceutical preparation is a Pasteurella vaccine. In some embodiments of the present invention, the Pasteurella vaccine may include an inactivated bovine Pasteurella multocida vaccine.

[0261] In some embodiments of the present invention, the pharmaceutical preparation is pancreatic islets.

[0262] In some embodiments of the present invention, the pharmaceutical preparation is a botulinum toxin cosmetic drug used for medical cosmetology.

[0263] In some embodiments of the present invention, a needle-free needle tube for a multi-mode fluid delivery device according to any of the above embodiments of the present invention is also provided, comprising: a tube 100 for containing fluid, the tube 100 having a first end 110 and a second end 120, wherein the first end 110 is configured to accommodate a piston 210 for pushing the fluid 130, and the second end 120 has a plurality of holes 121 for distributing the fluid 130 in the tube.

[0264] In some embodiments of the present invention, as shown in Figures 38 and 39, the second end 120 of the needle-free delivery device may further have a narrowing section 122 that gradually narrows axially from the tube 100 toward the distal end, and a hole 124 is provided on the end surface 123 of the narrowing section 122. The end surface 123 is configured to be circular.

[0265] In some embodiments of the present invention, the total fluid delivery area of ​​the plurality of holes of the needle-free needle tube is 0.009 mm 2 Above, preferably 0.02mm 2 More than, more preferably 0.053mm 2 , more preferably 0.2800 mm 2 The single hole area of ​​the hole is 0.0028~0.035mm 2 , preferably 0.0028~0.020mm 2 , more preferably 0.0028 to 0.009 mm 2 .

[0266] In some embodiments of the present invention, the needle-free needle tube is configured such that the fluid jets passing through the plurality of holes 121 have different in vivo diffusion degrees;

[0267] In other embodiments of the present invention, the diffusivity refers to a comprehensive concept that describes the distribution characteristics of fluid in the body. Specifically, the diffusivity may include but is not limited to the fluid's diffusion volume ratio, diffusion depth, diffusion center, and edge liquid distribution density.

[0268] In some embodiments of the present invention, the apertures of the plurality of holes 121 of the needle-free needle tube are configured such that the fluid jets passing through the plurality of holes 121 have different in vivo diffusion degrees.

[0269] In some embodiments of the present invention, the plurality of holes 121 of the needle-free needle tube includes a first hole 121;

[0270] In some embodiments of the present invention, the first hole 121 has a first pore size d1, and the size of the first pore size d1 is configured to allow the fluid jet passing through the first hole 121 to diffuse in at least one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs.

[0271] In some embodiments of the present invention, the plurality of holes 121 of the needle-free needle tube include a first hole 121 and a second hole 121 ′;

[0272] In some embodiments of the present invention, the first hole 121 has a first aperture d1, and the size of the first aperture d1 is configured so that the fluid jet passing through the first hole 121 diffuses in at least one of the dermis, epidermis, subcutaneous layer, muscle and human organs; the second hole 121' has a second aperture d2, and the size of the second aperture d2 is configured so that the fluid jet passing through the second hole 121' diffuses in at least another one of the dermis, epidermis, subcutaneous layer, muscle and human organs.

[0273] In some embodiments of the present invention, the plurality of holes 121 of the needle-free needle tube are arranged along a straight line;

[0274] In some embodiments of the present invention, the plurality of holes 121 are arranged in a straight line along the diameter or midline of the second end 120. Preferably, one of the plurality of holes 121 arranged in a straight line along the diameter or midline of the second end 120 is located at the center or centre of the second end 120.

[0275] In some embodiments of the present invention, the plurality of holes 121 arranged along a straight line are arranged at equal intervals;

[0276] In some embodiments of the present invention, the plurality of holes 121 arranged along a straight line are mirror-symmetrical with respect to the diameter or the midline of the second end 120;

[0277] In some embodiments of the present invention, the holes 121 are arranged in multiple groups, and each group of holes 121 is arranged along a straight line. Preferably, each group of holes is arranged along a diameter or a center line of the second end 120;

[0278] In some embodiments of the present invention, the plurality of holes 121 are arranged in an array, and the plurality of holes 121 arranged in the array are mirror-symmetrical with respect to the first and second diameters or the center line perpendicular to each other of the second end 120;

[0279] In some embodiments of the present invention, the aperture d of the hole 121 located at the center or centre of the second end 120 is different from the apertures d′ of the other holes 121 ′ of the plurality of holes 121 ;

[0280] In some embodiments of the present invention, the pore size of at least one group of holes 121 among the multiple groups of holes 121 is different from the pore sizes of the other groups of holes.

[0281] In some embodiments of the present invention, the plurality of holes 121 of the needle-free needle tube are arranged in a ring shape;

[0282] In some embodiments of the present invention, the plurality of holes 121 are arranged in a ring with the center or centre of the second end 120 as the centre;

[0283] The holes 121 are arranged in a plurality of groups, and each group of holes 121 is arranged in a circular shape. Preferably, the plurality of groups of holes 121 are arranged in a coaxial circular shape.

[0284] In some embodiments of the present invention, at least one of the plurality of holes 121 arranged in an annular manner has a different pore size from the other holes 121;

[0285] In some embodiments of the present invention, the aperture of at least one group of holes 121 of the plurality of groups of holes 121 is different from the apertures of the other groups of holes;

[0286] In some embodiments of the present invention, the diameters of the multiple groups of holes 121 coaxially arranged in an annular manner increase or decrease radially.

[0287] In some embodiments of the present invention, the plurality of holes of the needle-free needle tube include a central hole 121 ″ located at the center or center of the second end 120 and a plurality of peripheral holes 121 located around the central hole;

[0288] In some embodiments of the present invention, the plurality of peripheral holes 121 are arranged in a ring shape. Preferably, the plurality of peripheral holes 121 are arranged in a coaxial ring shape around the central hole 121 ″.

[0289] The peripheral holes 121 are arranged in a plurality of groups, and each group of peripheral holes 121 is arranged in a ring shape. Preferably, the plurality of groups of peripheral holes 121 are arranged in a coaxial ring shape around the central hole 121 ″.

[0290] In some embodiments of the present invention, the diameter d″ of the central hole 121 ″ is different from the diameter d of the plurality of peripheral holes 121 .

[0291] In some embodiments of the present invention, an injection head 200 for a multi-mode fluid delivery device is further provided. The injection head 200 includes one or more needle members 210 and a support portion 220 for supporting the needle members 210 .

[0292] In some embodiments of the present invention, the support portion 220 has a first side 221 and a second side 222 opposite to the first side 221 ;

[0293] Optionally, the needle member 210 includes a first needle portion 211 located on the first side 221 of the support portion 220;

[0294] Optionally, the needle member 210 includes a fixing pad 230 located on the first side 221 of the support portion 220 , and the fixing pad 230 is used to fix the needle member 210 ;

[0295] Optionally, the needle member 210 includes a second needle portion 212 located on the second side 222 of the support portion 220;

[0296] In some embodiments of the present invention, alternatively, the first needle portion 211 of the needle member 210 does not extend from the first side 221 of the support portion 220 , so that a needle-free micropore 213 is formed on the first side 221 of the support portion 220 .

[0297] In some embodiments of the present invention, the first needle portion 211 of the needle member 210 is flat, and the second needle portion 212 of the needle member 210 is sharp.

[0298] In some embodiments of the present invention, the first needle portion 211 and the second needle portion 212 of the needle member 210 are both sharp.

[0299] In some embodiments of the present invention, the one or more needle members 210 have different adjustable skin insertion depths L;

[0300] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that does not substantially penetrate the skin but forms close contact with the skin of a human or animal.

[0301] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that is substantially sufficient to penetrate the inner layer of human or animal skin.

[0302] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the subcutaneous layer of a human or animal.

[0303] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the muscle layer of a human or animal.

[0304] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth sufficient to be inserted into an organ in a human or animal body.

[0305] In some embodiments of the present invention, at least one of the one or more needle members has an adjustable insertion depth.

[0306] It can be understood that in the embodiments of the present invention, the dermis, epidermis, subcutaneous layer, muscle or human organ do not correspond to a certain exact and fixed insertion depth value, nor to a certain exact and fixed insertion depth value range. Those skilled in the art can confirm the corresponding insertion depths of the dermis, epidermis, subcutaneous layer, muscle and human organ in the body of the inoculated object based on the needle-free delivery object, including but not limited to different types of animals or patients with different physical conditions.

[0307] In some embodiments of the present invention, the plurality of needle members 210 include a first needle member;

[0308] In some embodiments of the present invention, the needle apertures of the one or more needle members 210 may be equal and have a first needle aperture d1, the size of which is configured such that the fluid jet passing through the one or more needle members 210 has different diffusion degrees, preferably, different diffusion depths, so that the fluid jet diffuses in at least one of the dermis, epidermis, subcutaneous tissue, muscle and human organs.

[0309] In some embodiments of the present invention, the plurality of needle members 210 include a first needle member 210 and a second needle member 210 ′;

[0310] In some embodiments of the present invention, the first needle member 210 has a first skin insertion depth located in one of the dermis, epidermis, subcutaneous layer, muscle, and human organs, and the second needle member 210' has a second skin insertion depth located in another of the dermis, epidermis, subcutaneous layer, muscle, and human organs;

[0311] In some embodiments of the present invention, the first needle member 210 has a first needle aperture d, and the size of the first needle aperture d is configured so that the fluid jet passing through the first needle member 210 diffuses in at least one of the dermis, epidermis, subcutaneous tissue, muscle and human organs; the second needle member 210' has a second needle aperture d', and the size of the second needle aperture d' is configured so that the fluid jet passing through the second needle member 210' diffuses in at least another one of the dermis, epidermis, subcutaneous tissue, muscle and human organs.

[0312] In other embodiments of the present invention, preferably, the plurality of needle members further include a third needle member 210", preferably, the third needle member 210" has a third skin insertion depth located in the dermis, epidermis, subcutaneous layer, muscle and human organs.

[0313] In some embodiments of the present invention, the plurality of needle members 210 are arranged along a straight line;

[0314] In some embodiments of the present invention, the plurality of needle members 210 are arranged in a straight line along the diameter or midline of the injection head. Preferably, one of the plurality of needle members 210 arranged in a straight line along the diameter or midline of the injection head 200 is located at the center or centre of the injection head 200.

[0315] In some embodiments of the present invention, the plurality of needle members 210 arranged along a straight line are arranged at equal intervals;

[0316] In some embodiments of the present invention, the plurality of needles 210 arranged along a straight line are mirror-symmetrical with respect to the diameter or center line of the injection head 200;

[0317] In some embodiments of the present invention, the needle members 210 are provided in multiple groups, and the needle members 210 of each group are arranged along a straight line. Preferably, the needle members 210 of each group are arranged along a diameter or a center line of the injection head.

[0318] The plurality of needle members 210 are arranged in an array. Preferably, the plurality of needle members 210 arranged in an array are mirror-symmetrical with respect to first and second diameters or center lines perpendicular to each other on the end face of the injection head 200 .

[0319] In some embodiments of the present invention, the skin insertion depth L″ of the needle member 210″ located at the center or centre of the injection head 200 is different from the skin insertion depth L of the other needle members of the plurality of needle members 210;

[0320] Preferably, the skin insertion depth L' of at least one group of needle members in the plurality of groups of needle members 210 is different from the skin insertion depth L of the other groups of needle members 210;

[0321] Preferably, the needle hole diameter d'' of the needle member 210'' located at the center or centre of the injection head 200 is different from the needle hole diameters d'' of the other needle members 210 of the plurality of needle members 210;

[0322] Preferably, the needle hole diameter d' of at least one group of needle members 210' in the plurality of groups of needle members 210 is different from the needle hole diameters d of the other groups of needle members.

[0323] In some embodiments of the present invention, the plurality of needle members 210 are arranged in a ring;

[0324] In some embodiments of the present invention, the plurality of needle members 210 are arranged in a ring with the center or centre of the injection head 200 as the centre;

[0325] The needle members 210 are arranged in multiple groups, and each group of needle members 210 is arranged in a ring. Preferably, the multiple groups of needle members 210 are arranged coaxially in a ring.

[0326] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in an annular manner has a skin insertion depth L′ different from that of the other needle members 210 .

[0327] In some embodiments of the present invention, the skin insertion depth L' of at least one group of needle members 210' among the multiple groups of needle members 210 is different from the skin insertion depths L of the other groups of needle members.

[0328] In some embodiments of the present invention, the skin insertion depths L of the multiple groups of needle members 210 coaxially arranged in an annular manner decrease or increase radially.

[0329] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in an annular manner has a needle hole diameter d′ different from that of the other needle members 210 .

[0330] In some embodiments of the present invention, the needle hole diameter d′ of at least one group of needle members 210 ′ among the multiple groups of needle members 210 is different from the needle hole diameters d of the other groups of needle members 210 .

[0331] In some embodiments of the present invention, the needle apertures d of the multiple groups of needle members 210 coaxially arranged in an annular manner decrease or increase in the radial direction.

[0332] In some embodiments of the present invention, the plurality of needle members 210 include a central needle member 210 ″ located at the center or center of the injection head 200 and a plurality of peripheral needle members 210 located around the central needle member 210 ″;

[0333] In some embodiments of the present invention, the plurality of peripheral needle members 210 are arranged in a ring shape. Preferably, the plurality of peripheral needle members 210 are arranged in a coaxial ring shape around the central needle member 210 ″.

[0334] The peripheral needle members include multiple groups, and each group of peripheral needle members 210 is arranged in a ring. Preferably, the multiple groups of peripheral needle members 210 are arranged in a coaxial ring around the central needle member 210".

[0335] In some embodiments of the present invention, the skin insertion depth L″ of the central needle member 210 ″ is different from the skin insertion depth L of the plurality of peripheral needle members 210 ;

[0336] In some embodiments of the present invention, the skin insertion depth L' of at least one group of peripheral needle members 210' of the plurality of groups of peripheral needle members 210 is different from the skin insertion depth L of the other peripheral groups of needle members 210;

[0337] In some embodiments of the present invention, the skin insertion depths of the multiple groups of needle members 210 and the central needle member 210 ″ coaxially arranged in an annular manner decrease or increase radially;

[0338] Preferably, the needle hole diameter d'' of the central needle member 210'' is different from the needle hole diameters d'' of the plurality of peripheral needle members 210;

[0339] In some embodiments of the present invention, the needle aperture diameter d' of at least one group of peripheral needle members 210' of the plurality of groups of peripheral needle members 210 is different from the needle aperture diameters d of the other peripheral groups of needle members 210;

[0340] In some embodiments of the present invention, the needle apertures of the multiple groups of needle members 210 and the central needle member 210 ″ coaxially arranged in an annular manner increase or decrease in radial direction.

[0341] In some embodiments of the present invention, the needle member 210 further comprises an interventional soft needle removably connected to the hole.

[0342] In some embodiments of the present invention, a needle kit 400 for a multi-mode fluid delivery device is further provided. The needle kit 400 includes one or more needle sleeves 401 , wherein the needle sleeves 401 are configured to removably surround the first needle portion 211 of the needle member 210 .

[0343] In some embodiments of the present invention, the height of the needle sleeve 401 is greater than or equal to the first needle portion 211 of the needle member 210 , thereby completely surrounding the first needle portion 211 ;

[0344] In some embodiments of the present invention, the height of the needle sleeve 401 of the needle kit is smaller than the first needle head 211 of the needle member 210 , thereby partially surrounding the first needle head 211 , so that the first needle head 211 extends from the front end of the needle sleeve 401 to form an insertion portion 214 .

[0345] In some embodiments of the present invention, the needle kit 400 includes a first needle kit 410 , wherein the needle sleeve 401 of the first needle kit 410 is higher than the first needle head 211 of the needle member, thereby completely surrounding the first needle head 211 to protect the first needle head 211 .

[0346] In some embodiments of the present invention, there are multiple needle kits 400. Preferably, the multiple needle kits 400 include a first needle kit 410 and a second needle kit 420.

[0347] The first needle kit 410 is configured so that the first needle head 211 is partially surrounded, and the insertion portion is located in the dermis, the epidermis, the subcutaneous layer, the muscle, or the human organ.

[0348] The second needle kit 420 is configured such that the first needle head 211 is partially surrounded and the insertion portion is located in the dermis, the epidermis, the subcutaneous layer, the muscle, or the human organ.

[0349] In some embodiments of the present invention, the needle kits are more than 400, preferably, the plurality of needle kits include a first needle kit 410, a second needle kit 420, a third needle kit 430, a fourth needle kit 440, a fifth needle kit 450 and a sixth needle kit 460;

[0350] The first needle kit 410 is configured so that it completely surrounds the first needle head 211;

[0351] The second needle kit 420 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located in the dermis;

[0352] The third needle set 430 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located in the epidermis;

[0353] The fourth needle set 440 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located subcutaneously;

[0354] The fifth needle set 450 is configured so that the insertion portion 214 thereof surrounding the first needle head 211 is located in the muscle;

[0355] The sixth needle kit 460 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is positioned in a human organ.

[0356] In some embodiments of the present invention, the injection head further comprises a needle sleeve portion sleeved on the needle member and a rotating member operatively connected to the needle member or the needle sleeve portion, wherein the rotating member is configured to adjust the axial position of the needle member and the needle sleeve portion by rotation to adjust the exposed length of the needle member relative to the needle sleeve portion.

[0357] In some embodiments of the present invention, the axial positions of the needle member and the needle sleeve portion are configured to be adjustable between multiple positions so that the exposed length of the needle member can be adjusted between multiple positions. Preferably, the exposed length of the needle member can be adjusted between the positions of the needle sleeve portion retracted, flush with the needle sleeve portion, located in the dermis, located in the epidermis, located under the skin, located in the muscle, and located in the human organ.

[0358] In some embodiments of the present invention, the axial positions of the needle member and the needle hub are configured to be continuously adjustable so that the exposed length of the needle member can be continuously adjusted.

[0359] In some embodiments of the present invention, there is also provided use of the multi-mode fluid delivery device according to any one of the above embodiments of the present invention in the preparation of human clinical medical and animal health drugs for needle-free injection administration.

[0360] In some embodiments of the present invention, the pharmaceutical preparation is a feline triple vaccine.

[0361] In some embodiments of the present invention, the pharmaceutical preparation is a hepatitis B vaccine.

[0362] In some embodiments of the present invention, the pharmaceutical preparation is a pneumonia vaccine for human use.

[0363] In some embodiments of the present invention, the pharmaceutical preparation is semaglutide.

[0364] In some embodiments of the present invention, the pharmaceutical preparation is a rabies vaccine for human use.

[0365] In some embodiments of the present invention, the pharmaceutical preparation is a rabies vaccine for animals.

[0366] In some embodiments of the present invention, the pharmaceutical preparation is a meningitis vaccine for human use.

[0367] In some embodiments of the present invention, the pharmaceutical preparation is a hand, foot and mouth disease vaccine for animals.

[0368] In some embodiments of the present invention, the pharmaceutical preparation is a new coronavirus vaccine for human use.

[0369] In some embodiments of the present invention, the pharmaceutical preparation is a hepatitis A vaccine for human use.

[0370] In some embodiments of the present invention, the pharmaceutical preparation is a vaccine for hemorrhagic fever with renal syndrome for humans.

[0371] In some embodiments of the present invention, the pharmaceutical preparation is a mumps vaccine for human use.

[0372] In some embodiments of the present invention, the pharmaceutical preparation is an HPV vaccine for humans.

[0373] In some embodiments of the present invention, the pharmaceutical preparation is a tumor chemotherapy drug for human use.

[0374] In some embodiments of the present invention, the pharmaceutical preparation is a nuclear medicine for treating tumors in humans.

[0375] In some embodiments of the present invention, the pharmaceutical preparation is a human tumor vaccine, including but not limited to polypeptide vaccines, mRNA vaccines, and DNA vaccines.

[0376] In some embodiments of the present invention, the pharmaceutical preparation is a pig diarrhea bivalent vaccine.

[0377] In some embodiments of the present invention, the pharmaceutical preparation is an inactivated blue ear vaccine.

[0378] In some embodiments of the present invention, the pharmaceutical preparation is a foot-and-mouth disease vaccine.

[0379] In some embodiments of the present invention, the pharmaceutical preparation is a bovine bivalent vaccine.

[0380] In some embodiments of the present invention, the pharmaceutical preparation is a Pasteurella vaccine.

[0381] In some embodiments of the present invention, the pharmaceutical preparation is insulin.

[0382] In some embodiments of the present invention, the pharmaceutical preparation is a botulinum toxin cosmetic drug used for medical cosmetology.

[0383] In some embodiments of the present invention, a multimodal drug preparation delivery method is further provided, characterized in that:

[0384] Determining a drug preparation delivery mode according to the acquired preset information, wherein the delivery mode includes a first delivery mode and a second delivery mode;

[0385] When the first delivery mode is determined, the drug preparation is delivered needle-free through a tube with a hole, and first delivery parameters of the needle-free delivery are determined according to the preset information, wherein the first delivery parameters include a piston speed of the tube, an aperture of the hole, and a jet velocity of the hole;

[0386] When the second delivery mode is determined, an injection member with one or more needle members is connected to a tube to deliver the drug preparation through the injection head with a needle, and second delivery parameters of the needle delivery are determined according to the preset information, wherein the second delivery parameters include the insertion depth, aperture, and jet velocity of the needle member and the piston speed of the tube;

[0387] Under the selected delivery mode, the pharmaceutical formulation is delivered according to determined delivery parameters.

[0388] In some embodiments of the present invention, the preset information includes at least one of inoculum information, inoculation position information, and drug preparation information, wherein the inoculation position information includes at least one of inoculation site information, delivery depth information, and delivery diffusion information.

[0389] In some embodiments of the present invention, the diffusion information includes at least one of diffusion volume ratio, diffusion breadth, diffusion depth, diffusion center and diffusion edge distribution density.

[0390] In some embodiments of the present invention, there are multiple holes, and determining the first delivery parameter of the needle-free delivery according to the preset information includes:

[0391] The number and arrangement of the plurality of holes on the second end of the tube are determined according to the preset information.

[0392] In some embodiments of the present invention, the step of connecting an injection head with one or more needle members to a tube to deliver the drug formulation through the injection member comprises:

[0393] One or more needle members of the injection member are removably docked with corresponding self-closing resilient portions or holes in the second end of the tube.

[0394] In some embodiments of the present invention, determining the second delivery parameter of the needle delivery according to the preset information includes:

[0395] The height, quantity and arrangement of the multiple needle members on the head are determined according to the preset information.

[0396] In some embodiments of the present invention, the method further comprises installing a plurality of needle kits on the plurality of needle members according to the preset information to adjust the exposed lengths of the needle members to control the insertion depths of the plurality of needle members.

[0397] The multimodal fluid delivery device of the present invention solves or improves at least one of the following problems or achieves at least one of the following technical effects by configuring the multimodal fluid delivery device of the present invention, its components, and related drug-device combination devices, and by controlling the flow rate, delivery depth, and dispersion of the drug and vaccine jets:

[0398] (1) The multimodal fluid delivery device of the embodiment of the present invention is not limited to a single delivery mode, but combines three modes: needle-free injection, microneedle injection, and needle injection, comprehensively providing a wider range of applications and being able to meet the delivery needs of different types of drugs and vaccines.

[0399] (2) The multimodal fluid delivery device of the embodiment of the present invention can achieve a significant increase in the delivery volume, including achieving a significant increase in the delivery volume without breaking the skin, and can be widely used in the delivery of drugs and vaccines for human and veterinary use.

[0400] (3) The multimodal fluid delivery device of the embodiment of the present invention significantly improves the diffusion volume of the delivered substances, especially drugs and vaccines, in the body through multi-porous needle-free delivery, thereby increasing the contact effect between the delivered drugs and vaccines and the tissues in the body, and significantly improving the bioavailability of drugs and vaccines.

[0401] (4) The multimodal fluid delivery device of the embodiment of the present invention achieves precise delivery of drugs and vaccines at different depths in the body according to the characteristics of different drugs and vaccines by precisely controlling the jet velocity of drugs and vaccines and optimizing the size and distribution of the pinholes and needles. In particular, it achieves precise delivery of the delivery substance to at least one or more target locations within the skin, subcutaneous tissue, muscle or human organs at the same time.

[0402] (5) The multimodal fluid delivery device of the embodiment of the present invention achieves different diffusion effects of the delivered substance, especially drugs or vaccines, at the delivery location by controlling the pore size and arrangement of the multiple holes, especially achieving control of the diffusion volume ratio, diffusion width and diffusion center at a specified location, and achieving specific diffusion effects according to different delivery requirements. Based on the above-mentioned problems solved and / or effects achieved, the present invention is also used in combination with cat triple vaccine, hepatitis B vaccine, human pneumonia vaccine, GLP-1 peptide, especially semaglutide, to achieve further technical effects as described in the embodiments of the present invention.

[0403] Example 1

[0404] Now refer to Figures 40, 41 and 48, which show one structural configuration of the multi-mode fluid delivery device according to an embodiment of the present invention. Specifically, the second end 120 further has a transition section 122 that narrows axially from the tube 100 to the distal end, and the end surface 123 of the transition section 122 is constructed as a circle with a diameter of 2.5 mm and is provided with three holes 121 thereon. The three holes 121 are arranged in a ring shape at equal intervals around the center of the end surface 123, and an angle of 120° is formed between adjacent connecting lines of the three holes and the center (center) of the end surface 123. The apertures of the three holes 121 are uniformly set to d and the distances from the center of the end surface 123 are uniformly set to l.

[0405] Referring now to FIG. 42 , under the structure of the multimodal fluid delivery device described above, an embodiment of the present invention utilizes the ANSYS Workbench Fluent module shown in FIG. 42 to construct a needle-free injection diffusion and penetration simulation model. A multiphase flow model is employed to simulate the diffusion of fluid 130 contained in tube 100 within body 140 when a delivery pressure of 400 N is applied by power mechanism 200 to fluid 130. The volume of fluid 130 to be delivered is 0.2 cm 3 and its viscosity is 1 cp. The needle-free injection diffusion and penetration simulation model utilizes a transient calculation method, an Eulerian model for the multiphase flow model, a K-epsilon Realizable model for the viscosity model, and a porous medium model 140. Hybrid initialization is employed for initialization. Based on the above structure and simulation parameters, the pore diameters d of the three pores 121 and the distance l between the centers of the end faces 123 of the three pores 121 are further configured. The following porous needle-free fluid diffusion data for different configurations are obtained:

[0406] Table 1. Fluid diffusion data for porous needle-free delivery

[0407] Table 1 and Figures 43 to 45 illustrate the diffusion effect achieved by a multi-mode fluid delivery device according to one embodiment of the present invention using multiple holes 121. The present invention achieves different diffusion degrees of fluid 130 within a body 140, such that the fluid jets of fluid 130 passing through the multiple holes 121 achieve different diffusion volume ratios, diffusion depths, and diffusion widths within the body 10. Figure 43 shows the diffusion effect at d = 0.15 mm, l = 0.65 mm, Figure 44 shows the diffusion effect at d = 0.575 mm, l = 0.65 mm, and Figure 45 shows the diffusion effect at d = 1.00 mm, l = 0.65 mm. Furthermore, as shown in Figures 43 to 45, when the multi-mode fluid delivery device according to the present embodiment delivers fluid into a body, the different diffusion volume ratios, diffusion depths, and diffusion widths of the fluid within the body result in different diffusion center and diffusion edge densities within the body. In the above embodiments of the present invention, the injection head and the needle member thereon are removed from the tube, but in other embodiments of the present invention, the multi-mode fluid delivery device of the present invention equipped with the injection head and the needle member is also expected to have a diffusion effect similar to that described above.

[0408] Compared with the needle-free delivery of the control group, the porous multimodal fluid delivery device of the embodiment of the present invention makes the diffusion volume of the delivery fluid 130 in the simulated body 140 2.09 to 2.77 times that before delivery, achieving a better diffusion effect for the delivery fluid. In other words, it achieves more sufficient contact between the delivery fluid and the target site in the body.

[0409] Example 2

[0410] Reference is now made to Figures 40, 41 and 48, which illustrate one structural configuration of a multi-mode fluid delivery device according to an embodiment of the present invention. Specifically, the second end 120 has a transition section 122 that narrows axially from the tube 100 toward the distal end. The end surface 123 of the transition section 122 is constructed as a circle with a diameter of 5 mm and is provided with a central hole 121" located at the center (center) of the end surface 123 and three peripheral holes 121 located around the central hole 121". The three peripheral holes 121 are arranged in a circular manner at equal intervals around the center (center) of the end surface 123. The three peripheral holes 121 form an angle of 120° with adjacent lines connecting the three peripheral holes 121 and the center (center) of the end surface 123. The diameter of the central hole 121 is d", and the diameters of the three peripheral holes 121 are uniformly set to d, and d"≠d, and the distances from the center (center) of the end surface 123 are uniformly set to 1.1 mm.

[0411] Referring now to FIG42 , under the structure of the above-mentioned multi-mode fluid delivery device, an embodiment of the present invention uses the ANSYS workbench Fluent module shown in FIG42 to build a needle-free injection diffusion penetration simulation model. A multiphase flow model is used to simulate the diffusion of the fluid 130 in the body 140 when the power mechanism 200 applies a delivery pressure of 400 N to the fluid 130 contained in the tube 100. The viscosity of the fluid 130 to be delivered is 1 cp. The calculation method of the needle-free injection diffusion penetration simulation model adopts transient, the multiphase flow model adopts the Eulerian model, the viscosity model adopts the K-epsilon Realizable model, the body 140 model is set as a porous medium, and the initialization method adopts hybrid initialization. Under the above-mentioned structure and simulation parameters, the aperture d" of the central hole 121" and the aperture d of the three peripheral holes 121 are further configured. The delivery fluid volume adopts 0.1 cm 3 , 0.2cm 3 and 0.3cm 3 , three sets of simulated experimental fluids were conducted to obtain the following porous needle-free delivery fluid diffusivity data:

[0412] Table 2. Group 1 - Porous Needle-Free Delivery Fluid Diffusion Data Note: The volume of fluid to be delivered in this group is 0.1 cm 3 .

[0413] Table 3. Group 2 - Porous Needle-Free Delivery Fluid Diffusion Data Note: The volume of fluid to be delivered in this group is 0.2 cm 3 .

[0414] Table 4. Group 3 - Porous Needle-Free Delivery Fluid Diffusion Data Note: The volume of fluid to be delivered in this group is 0.3 cm 3 .

[0415] Combined with Tables 2 to 4 and Figures 46 to 47, the diffusion effect achieved by the multi-mode fluid delivery device of one embodiment of the present invention using the multiple holes 121 is shown. The arrangement of the central hole 121" and the three peripheral holes 121 enables the fluid jet of the fluid 130 passing through the multiple holes to achieve a significantly enhanced diffusion effect compared to the needle-free delivery of the control group. Specifically, the multi-mode fluid delivery device of the embodiment of the present invention enables the diffusion volume of the delivered fluid 130 in the simulated body 140 to be 2.35 times to 3.61 times that before delivery. In the above embodiments, the injection head and the needle member thereon were removed from the tube. However, in other embodiments of the present invention, the multimodal fluid delivery device of the present invention, equipped with the injection head and the needle member, is also expected to achieve similar diffusion effects as described above. Furthermore, as shown in Table 2 and FIG. 46 , at 0.1 cm, the multimodal fluid delivery device of the present invention achieves a diffusion width significantly superior to that of a single aperture, achieving a significantly enhanced diffusion effect for the delivered fluid. In other words, it achieves more complete contact between the delivered fluid and the target site in the body.

[0416] Example 3

[0417] Now refer to Figures 40, 41 and 48, which show one structural configuration of the multi-mode fluid delivery device according to an embodiment of the present invention. Specifically, the second end 120 has a transition section 122 that narrows axially from the tube 100 to the distal end. The end face 123 of the transition section 122 is constructed as a circle with a diameter of 2.5 mm and is provided with three holes 121. The three holes 121 are arranged in a circular shape at equal intervals around the center of the end face 123, and an angle of 120° is formed between adjacent connecting lines of the three holes and the center (center) of the end face 123. The apertures of the three holes 121 are uniformly set to 0.15 mm and the distances from the center of the end face 123 are uniformly set to 1.1 mm.

[0418] Under the structure of the multi-mode fluid delivery device, a specific embodiment of the present invention adopts a viscosity of 1 cp and a volume of 0.2 cm 3 The delivery fluid was tested to obtain the displacement change curve of the piston 210 of the multi-mode fluid delivery device of the present invention, and the movement speed of the piston 210 and the outlet jet speed of the jets ejected from the multiple holes 121 were obtained accordingly as follows:

[0419] Table 5. Piston speed and jet speed data

[0420] As can be seen from the table above, in one specific embodiment, the multi-mode fluid delivery device of the present invention is configured such that the average velocity of the jets emitted from the plurality of holes 121 is greater than 135 m / s, and can reach a maximum of 156 m / s. In the above embodiments of the present invention, the injection head and the needle member thereon are removed from the tube. However, in other embodiments of the present invention, the multi-mode fluid delivery device of the present invention, when equipped with the injection head and the needle member, is also expected to achieve a similar diffusion effect as described above.

[0421] Example 4

[0422] In a specific embodiment of the present invention, the multimodal fluid delivery device of the present invention is used in combination with a feline triple vaccine. Referring to Figures 40, 41 and 48, one structural configuration of the multimodal fluid delivery device of the embodiment of the present invention used in combination with a feline triple vaccine is shown. Specifically, the second end 120 has a transition section 122 that narrows axially from the tube 100 to the distal end, wherein the diameter of the tube is 5 mm, and the end face 123 of the transition section 122 is constructed as a circle with a diameter of 2.5 mm and is provided with three holes 121 thereon. The three holes 121 are arranged in an annular manner at equal intervals around the center of the end face 123, and an angle of 120° is formed between adjacent lines connecting the three holes and the center of the end face 123, wherein the pore diameter measurement value of the three holes 121 is 0.14 mm to 0.17 mm, and the distance between the three holes 121 and the center of the end face 123 is uniformly set to 1.25 mm.

[0423] In an embodiment of the present invention, the feline triple vaccine is a triple inactivated vaccine for preventing feline rhinotracheitis, calicivirus disease, and panleukopenia. Each dose of the feline triple vaccine contains inactivated feline rhinotracheitis virus 605 strain, feline calicivirus 255 strain, and panleukopenia virus Cu-4 strain, and the RP value of each component should not be less than 1.0 to ensure the immunogenicity and efficacy of the feline triple vaccine. The feline triple vaccine is only used to vaccinate healthy cats aged 8 weeks or above, and can be injected subcutaneously, 1 ml per head per time; for healthy cats aged 8 weeks or above, booster immunization should be performed 3 to 4 weeks after the first vaccination, with 1 dose vaccinated; for cats vaccinated under 12 weeks of age, 1 dose should be boosted at 12 to 16 weeks of age to ensure lasting immune protection. The feline triple vaccine should be repeated with 1 dose per year to maintain immunity.

[0424] The following is a specific immune evaluation test of the multi-mode fluid delivery device of the present invention. In this test, a needle-free immune evaluation test of a cat vaccine was conducted according to the following test protocol under the structural configuration of the multi-mode fluid delivery device of the present invention:

[0425] 1. Test materials

[0426] 1.1. Experimental Animals: 27 healthy cats were used as experimental animals, all of which were negative for FPV, FHV, and FCV antigens, with two-thirds of the three neutralizing antibody titers being no higher than 1:4 and no history of feline triple vaccine immunization.

[0427] 1.2. Delivery vaccine: Feline rhinotracheitis, calicivirus disease, and panleukopenia triple inactivated vaccine produced by Zoetis (trade name: Feline Triple, batch number: E071201A).

[0428] 1.3. Neutralizing antigen for detection: FPV virus solution, FCV virus solution and FHV virus solution with a virus content of 200TCID50 / 0.1ml were selected.

[0429] 1.4. Cells used for detection: CRFK cells or F81 cells were used.

[0430] 1.5. Test equipment: a multi-mode fluid delivery device according to the above embodiment of the present invention (delivery pressure: 330 N, aperture: 0.14 mm to 0.17 mm); a conventional 1 ml syringe with a needle, a 10 ml syringe, a medical cotton swab, and an alcohol cotton pad.

[0431] 1.6. Experimental location: Animal hospital.

[0432] 2. Test methods

[0433] 2.1. Animal Screening: From each of the 37 healthy cats, a nasal swab (superficial collection is permitted), an oral swab, and anal swab were collected and placed in a centrifuge tube containing 1 ml of PBS. Antigen testing was performed according to the methods in Notes 1 to 3. 2 to 3 ml of blood was collected from each healthy cat, and the serum was separated for neutralizing antibody testing.

[0434] 2.2 Animal Grouping: The healthy cats selected were allowed to acclimate to the environment for 7 days after entering the experimental site, and were gradually transitioned to cat food. They were then divided into 3 groups based on their sex, age, breed, or antibody data, with 7 cats in each group. These groups were numbered and recorded as experimental groups 1, 2, and 3. Six healthy cats that were not immunized with the feline triple vaccine were set up as sentinel animals and recorded as experimental group 4.

[0435] 2.3. Pre-immunization Preparation: 2-3 days prior to immunization, the injection sound was played in a loop for 10-15 minutes daily at the testing site. Cats were allowed to voluntarily contact and sniff the multi-modal fluid delivery device and electric shaver of the present invention. One day or two hours prior to immunization, the injection site of the test cats was shaved, approximately 1 cm in diameter. One to two people were assigned to perform the immunization.

[0436] 2.4 Immunity

[0437] The aforementioned groups 1, 2, and 3 were immunized, wherein:

[0438] Group 1: Immunization was performed using a conventional needle injection with a disposable 1 ml syringe with a needle hole diameter of 0.45 mm; the dose for each immunization was 1 ml.

[0439] Group 2: Immunization was performed using a three-hole needle-free injection, a needle-free syringe, a single-hole injection needle, and multi-hole injection. The needle hole diameter was 0.14mm to 0.17mm; the dose for each immunization was 1ml.

[0440] Group 3: Immunization was performed using needle-free multi-hole injection, using a needle-free syringe, a single-hole injection needle, and multi-hole injection, with a needle hole diameter of 0.14mm to 0.17mm; the dose for each immunization was 0.45ml.

[0441] Table 6. Immunization information table Note: “ / ” means no operation.

[0442] 2.5. Sample collection:

[0443] On the day of the first vaccination and 21 and 35 days after the first vaccination, venous blood was collected from each cat according to Table 5 above. The serum was separated and stored at -20°C for testing. (If the immune response is particularly strong, consider collecting whole blood 1-2 weeks after 35 days).

[0444] Table 7. Sample collection schedule

[0445] 3. Results after immunization

[0446] 3.1. Observation on the day of immunization:

[0447] Conventional injection immunization group (Group 1): The experimental cats were listless and listless;

[0448] In the needle-free immunization groups (Groups 2 and 3), the experimental cats were lively and energetic.

[0449] 3.2 Neutralizing Antibody Titer Determination Results

[0450] Neutralizing antibody titer determination was performed to obtain the following Tables 7 and 8, which show the antibody titer determination data of each group under the above experimental conditions:

[0451] Table 8. Antibody titer determination data table-1

[0452] Table 9. Antibody titer determination data table-2

[0453] As can be seen from Tables 7 and 8 and Figures 49 to 51, the use of a multimodal fluid delivery device comprising a plurality of holes 121 for delivering a feline triple vaccine in the embodiments of the present invention achieves the following compared to conventional needle delivery:

[0454] a. The needle-free three-hole immunization group using the multimodal fluid delivery device of the present invention was compared to the needle-immunized group with the same dose. The needle-free three-hole antibody onset time using the multimodal fluid delivery device of the present invention was 1 times faster than that of the needle-immunized group;

[0455] b. Found that under the same immune dose, the use of the multi-mode fluid delivery device of the present invention, three-hole needle-free immunization produces antibodies 25 times higher than the conventional needle immunization group;

[0456] c. The antibody value produced by the needle-free three-hole half-dose group using the multi-mode fluid delivery device of the present invention was 2.4 times higher than that of the conventional immunization group with a needle.

[0457] In the above embodiments of the present invention, the injection head and the needle part thereon are removed from the tube, but in other embodiments of the present invention, the multimodal fluid delivery device of the present invention equipped with the injection head and the needle part is also expected to have similar diffusion and immunogenic effects as described above.

[0458] Example 5

[0459] In a specific embodiment of the present invention, the multimodal fluid delivery device of the present invention is used in combination with a hepatitis B vaccine. Referring to Figures 40, 41 and 48, one structural configuration of the multimodal fluid delivery device of an embodiment of the present invention used in combination with a hepatitis B vaccine is shown. Specifically, the second end 120 has a transition section 122 that narrows axially from the tube 100 to the distal end, wherein the diameter of the tube is 5 mm, and the end face 123 of the transition section 122 is constructed as a circle with a diameter of 2.5 mm and is provided with three holes 121 thereon. The three holes 121 are arranged in a ring at equal intervals around the center of the end face 123, and an angle of 120° is formed between adjacent lines connecting the three holes and the center of the end face 123, wherein the aperture measurement value of the three holes 121 is 0.14 mm to 0.17 mm, and the distance between the three holes 121 and the center of the end face 123 is uniformly set to 1.25 mm.

[0460] In the embodiments of the present invention, the hepatitis B vaccine refers to a recombinant yeast vaccine (Hansenula) for preventing hepatitis B (a viral liver disease). It is prepared by purifying the hepatitis B virus surface antigen (HBsAg) expressed by recombinant Hansenula and adding an aluminum adjuvant. The active ingredient is the hepatitis B virus surface antigen. The vaccine is suitable for people susceptible to hepatitis B, especially the following people: (1) newborns, especially those whose mothers are HBsAg or HBeAg positive, (2) people susceptible to hepatitis B aged 16 years and above, and (3) medical staff engaged in medical work and laboratory personnel who come into contact with blood. After vaccination, the immune system can be stimulated to produce protective antibodies, thereby giving the human body immunity to prevent hepatitis B, thereby achieving the purpose of preventing hepatitis B infection. The conventional immunization site is the deltoid muscle of the upper arm. The immunization program is 3 injections, one at birth (0 months), one at 1-2 months of age, and one at 6-18 months of age. Newborns are given the first injection within 24 hours after birth, and each injection is one dose.

[0461] The following is a specific immunological evaluation test of the multimodal fluid delivery device of the present invention. Under the structural configuration of the multimodal fluid delivery device of the present invention, a hepatitis B vaccine needle-free injection immunological evaluation test was conducted according to the following experimental protocol:

[0462] 1. Preparation before the test

[0463] 1.1. Experimental Materials: 64 male mice (BALB / c strain), weighing 17-19 g and aged 3 to 4 weeks, were selected and blood was collected after one week of acclimatization.

[0464] 1.2. Test equipment: The multi-mode fluid delivery device according to the above embodiment of the present invention traditionally includes a needle, a medical cotton swab, and an alcohol cotton pad.

[0465] 2. Test methods

[0466] 2.1. Animal grouping: The 64 mice were divided into 8 groups of 8 mice each, including 6 experimental groups and 2 control groups.

[0467] Table 10. Control trial group table

[0468] 2.2 Blood collection plan:

[0469] Mice were immunized according to the D0 / D21 immunization schedule, and blood was collected and serum was separated on D0 / D28 / D35 / D42 after immunization.

[0470] At the beginning of the experiment: On the morning of the experiment, shave the hair on the back and legs of the mice with an electric razor and depilatory cream. Before inoculation, blood was collected from all mice using the retroorbital bleeding method, with a blood volume of 0.2 ml per mouse.

[0471] After one vaccination: the second vaccination was performed on the 21st day; the second blood collection was performed on the 28th day, with peripheral blood collected from a group of 10 mice and spleen collected from six mice; the third blood collection was performed on all mice on the 35th day; the fourth blood collection was performed on the 42nd day, with peripheral blood collected from a group of 10 mice and spleen collected from six mice.

[0472] 2.3 Neutralization experiment

[0473] Use micro-method.

[0474] Neutralization endpoint was calculated using the Karber method (serum dilution converted to logarithms). The highest serum dilution that protected 50% of cells from infection with 100 CCID50 of the challenge virus was defined as the serum antibody titer. A neutralizing antibody titer of <1:4 was considered negative, and ≥1:4 was considered positive.

[0475] Operating Procedure (Fixed Virus Dilution Serum Method)

[0476] (1) Inactivation of serum: Inactivate the serum to be tested at 56°C for 30 minutes

[0477] (2) Dilute serum: Take inactivated serum and dilute it with serum-free cell culture medium on a 96-well microplate. Make a series of serial dilutions starting from 1:4, tentatively (1:4, 1:28, 1:56, 1:128, 1:256...). The content of each well is 50 μL, and 2 to 4 wells are used for each dilution.

[0478] (3) Neutralization: Add 50 μL of diluted 200 TCID50 virus solution to each well and place in a CO2 incubator at 37°C for 2 h.

[0479] (4) Add cell suspension: After 2 hours of serum and virus neutralization, remove the cell plate and add 0.1 mL / well cell suspension to each well (it is best to allow the monolayer to grow for 24 hours, generally 1 million to 1.5 million cells per mL), place in a CO2 incubator for culture, and make a judgment after 72 hours.

[0480] 2.4 Control Experiment

[0481] (1) Negative and positive serum controls: 2 to 4 wells are set up for each. The titer of the negative and positive control antibodies should be established.

[0482] (2) Virus regression test: Dilute the 200 TCID50 virus solution into 0.1, 1, 10, and 100 TCID50 dilutions, and add 50 μL of each dilution to 2 to 4 wells. Add 50 μL of cell suspension. 0.1 TCID50 results in no pathological changes, while 100 TCID50 results in complete pathological changes. Otherwise, the experiment is invalid.

[0483] (3) Cell control: Set up 2 to 4 wells of normal cell control without virus and serum. The control cells should maintain good morphology and characteristics.

[0484] 2.5. Result determination and calculation

[0485] Only when the virus regression test, positive, negative, and cell controls are all established can the test be judged. 100% CPE in the serum wells tested is considered negative, and more than 50% of the cells are protected as positive. The results are calculated using the Karber method.

[0486] 3. Cell level detection

[0487] The spleens of mice were collected to determine the contents of various T and B cells in mice.

[0488] 3.1. Detection of T lymphocyte surface molecular markers:

[0489] Flow cytometry was used to detect T lymphocyte surface markers. Refrigerated mouse spleen cells were thawed in a water bath at 37°C to prepare a single-cell suspension (1 × 107 cells / ml). 0.1 ml was transferred to a falcon tube and CD3-FITC Ab, CD4-PE Ab, and CD8-PE Ab were added. The tubes were placed in a dark place at room temperature for 30 minutes, washed twice with PBS, and mixed with 0.5 ml of PBS. The positive expression rates of CD3-FITC, CD4-PE, and CD8-PE on T lymphocytes were analyzed using CELLQuest software, and the CD4 / CD8 ratio was calculated.

[0490] 3.2 Enzyme-linked immunosorbent assay:

[0491] After blood collection, the supernatant was collected from the ELISPOT plate and stored at -80°C for 24 hours prior to enzyme-linked immunosorbent assay (ELISA). Protein expression levels were measured at 450 nm using a Biotek enzyme-linked immunosorbent assay (ELISA). The absorbance of each cytokine or chemokine was divided by the absorbance of the pre-vaccination sample as a baseline control to calculate the fold change in cytokine and chemokine expression. Cellular immune responses were assessed by ELISPOT analysis of T cells producing hepatitis B surface antigen-specific IFN-γ, IL-2, and IL-4.

[0492] 3.2.1. Kit Contents:

[0493] PVDF 96-well plate, stored at room temperature; 0.1 ml capture antibody, stored at 4°C; 0.1 ml biotin-labeled detection antibody, stored at 4°C; 15 ul avidin alkaline phosphatase label, stored at 4°C; 0.25 g bovine serum albumin, stored at 4°C; 0.25 g skim milk, stored at 4°C; 11 ml substrate buffer, stored at 4°C; 11 ml concentrated PBS (10X), stored at room temperature; 11 ml concentrated wash buffer (200x), stored at room temperature.

[0494] 3.2.2 Preparation of reagents:

[0495] (1) Dilute 10 ml of phosphate buffered saline (PBS, 10X) with 90 ml of distilled water;

[0496] (2) Dissolve 0.22 g skim milk in 11 ml diluted PBS to a final concentration of 2%;

[0497] (3) 0.22g BSA was dissolved in 22ml diluted PBS to a final concentration of 1%

[0498] (4) Dilute 10 ml of concentrated washing solution (200x) with 1990 ml of distilled water;

[0499] (5) Dilute 10ul of avidin alkaline phosphatase with 10ml of PBS-1%, BSA

[0500] (6) Dilute 7 ml of alcohol with 3 ml of distilled water to a final concentration of 70%.

[0501] 3.2.2, Stimulation method:

[0502] Indirect method: Cells are first stimulated in a 24-well plate or flask and then placed into the coated wells.

[0503] Dilute PBMCs in culture medium (e.g., RPMI 1640 with 2 mM glutamate and 10% heat-inactivated calf serum) containing 1 ng / ml PMA and 500 ng / ml chloramphenicol (Sigma, Saint Louis, MO). Add 2.104 to 5.104 cells to the antibody-coated PVDF wells and incubate in an incubator for 10-15 hours. Incubation times may vary with other stimulants and should be optimized based on the abundance of cytokine-producing cells.

[0504] 3.2.4 Eli-spot operation process:

[0505] (1) Incubate the PVDF plate with 100ul of 70% alcohol at room temperature for 10 minutes.

[0506] (2) Pour off the alcohol and wash three times with 100ul PBS.

[0507] (3) Add 100ul of capture antibody to 10ml of PBS, mix, add 100ul to each well, cover the plate, and incubate at 4°C overnight.

[0508] (4) Pour off the liquid and wash once with 100ul PBS.

[0509] (5) Add 100ul of 2% skim milk PBS (see reagent preparation) to each well, cover the plate, and incubate at room temperature for 2 hours.

[0510] (6) Tap gently over the sink and onto absorbent paper to remove the liquid.

[0511] (7) Wash three times with 100ul PBS, three minutes each time.

[0512] (8) Add 100 μl of cell suspension (containing an appropriate amount of cells and the corresponding concentration of stimulant) to each well. The cells can be stimulated in vitro (indirect Eli-spot). Cover the well with a standard 96-well plastic plate cover and incubate in a 37°C CO2 incubator for a specified period of time (15-20 hours). Do not shake or move the well plate during this period.

[0513] (9) Tap gently over the sink and onto absorbent paper to remove the liquid.

[0514] (10) Add 100 μl of washing buffer to each well and incubate at 4°C for 10 minutes.

[0515] (11) Use pre-chilled ice water to break the cells.

[0516] (12) Wash the wells eight times with 100ul of PBST buffer for four minutes each time.

[0517] (13) Dilute 100 μl of detection antibody in 10 ml of PBS-1% BSA. This is the amount for one plate. Add 100 μl of this solution to each well, cover the plate, and incubate at 37°C for 2 hours.

[0518] (14) Pour off the liquid and wash five times with 100ul washing buffer.

[0519] (15) Dilute 10 μl of avidin alkaline phosphatase in 10 ml of PBS 1% BSA per plate. Add 100 μl of this solution to each well, cover the plate, and incubate at 37°C for 1 hour.

[0520] 4. Statistical analysis

[0521] Statistical analysis: One-way analysis of variance and t-test (GraphPad Prism 8.0) were used to analyze the statistically significant differences between the groups. Data are expressed as mean ± standard deviation (SD). A p value < 0.05 was considered statistically significant.

[0522] 5. Final Result

[0523] The multi-mode fluid delivery device of the present invention is configured so that the average antibody titer of the hepatitis B vaccine 14 days after the second dose is more than 1.1 times the average antibody titer of the needle injection;

[0524] The multi-mode fluid delivery device of the present invention is configured so that the average antibody titer of the hepatitis B vaccine 42 days after the second dose is more than 1.5 times the average antibody titer of the needle injection;

[0525] The multi-mode fluid delivery device of the present invention is configured so that the T lymphocyte positive expression rate of the hepatitis B vaccine 42 days after the second dose is higher than that of needle injection by more than 10%.

[0526] In the above embodiments of the present invention, the injection head and the needle part thereon are removed from the tube, but in other embodiments of the present invention, the multimodal fluid delivery device of the present invention equipped with the injection head and the needle part is also expected to have similar diffusion effects and immunogenic effects as described above.

[0527] Example 6

[0528] In a specific embodiment of the present invention, the multimodal fluid delivery device of the present invention is used in combination with a GLP-1 polypeptide, specifically, semaglutide. Referring to Figures 40, 41 and 48, one structural configuration of the multimodal fluid delivery device of an embodiment of the present invention used in combination with semaglutide is shown. Specifically, the second end 120 has a transition section 122 that narrows axially from the tube 100 to the distal end, wherein the diameter of the tube is 5 mm, and the end face 123 of the transition section 122 is constructed as a circle with a diameter of 2.5 mm and is provided with three holes 121 thereon. The three holes 121 are arranged in an annular shape at equal intervals around the center of the end face 123, and an angle of 120° is formed between adjacent connecting lines of the three holes and the center of the end face 123, wherein the pore diameter measurement value of the three holes 121 is 0.14 mm to 0.17 mm, and the distance between the three holes 121 and the center of the end face 123 is uniformly set to 1.25 mm.

[0529] In the embodiment of the present invention, the semaglutide (Simeigelutai), also known as semaglutide, is a second-generation glucagon-like peptide-1 (GLP-1) analogue, and its molecular formula is C 187 H 291 N 45 O 59 It (molecular weight of 4113.58Da) has excellent blood sugar lowering and weight loss effects in diabetic patients, significantly better than sitagliptin, insulin glargine U100 or extended-release exenatide; it is also better than its peer liraglutide in weight loss, especially in patients with BMI ≥ 30. Semaglutide can be taken orally or subcutaneously, for example, as a 7mg / 14mg oral dosage form once daily or a 0.5mg / 1.0mg subcutaneous injection once weekly. Semaglutide not only shows good efficacy in the treatment of diabetes, but also shows significant advantages in weight loss and cardiovascular protection.

[0530] The following is a specific semaglutide rat test using the multimodal fluid delivery device of the present invention. Under the structural configuration of the aforementioned multimodal fluid delivery device of the present invention, the semaglutide rat test was conducted using semaglutide with the following structure according to the following experimental protocol:

[0531] 1. Test materials

[0532] 1.1. Experimental Animals: Selection

[0533] Healthy male Wistar rats, aged 6-8 weeks, weighing 200-250 g.

[0534] 1.2. Experimental Grouping: The rats were randomly divided into four groups, with 10 rats in each group.

[0535] 1.3. Delivery agent: semaglutide;

[0536] 1.4. Test equipment: a multi-mode fluid delivery device according to the above embodiment of the present invention (delivery pressure: 250 N, aperture: 0.14 mm to 0.17 mm); a traditional needle syringe, a medical cotton swab, and an alcohol cotton pad.

[0537] 2. Test operation

[0538] 2.1. Drug Administration

[0539] In the needle-free delivery group, drugs were administered using a multimodal fluid delivery device according to set parameters, and in the needle delivery group, drugs were administered using traditional injections, where:

[0540] Group 1: 1x dose with injection, daily for 14 days;

[0541] Group 2: No needle, 1x dose, daily for 14 days;

[0542] Group 3: 10x dose with injection, weekly*2 weeks;

[0543] Group 4: needle-free 10x dose, weekly*2 weeks;

[0544] 2.2 Data Collection

[0545] The body weight changes, blood glucose and insulin levels of the rats were recorded daily.

[0546] 3. Result evaluation

[0547] Comparison between Group 1 and Group 2: Under the same dosing conditions (1x) and frequency (daily), Group 2 (needle-free delivery) achieved a 4% greater overall weight loss than Group 1 (needle-delivered delivery). Furthermore, the effects of Group 2 lasted longer, with a delayed rebound effect compared to Group 1.

[0548] b. Comparison between Group 3 and Group 4: Under the conditions of higher dose (10x) and lower frequency (weekly), the total weight loss rate of Group 4 (no needle delivery) was 5.5% greater than that of Group 3 (with needle delivery).

[0549] In the above embodiments of the present invention, the injection head and the needle part thereon are removed from the tube, but in other embodiments of the present invention, the multimodal fluid delivery device of the present invention equipped with the injection head and the needle part is also expected to have similar diffusion effects and immunogenic effects as described above.

[0550] Example 7

[0551] In a specific embodiment of the present invention, the multimodal fluid delivery device of the present invention is used in combination with a polypeptide tumor vaccine. Referring to Figures 40, 41 and 48, one structural configuration of the multimodal fluid delivery device of the embodiment of the present invention used in combination with a polypeptide tumor vaccine is shown. Specifically, the second end 120 has a transition section 122 that narrows axially from the tube 100 to the distal end, wherein the diameter of the tube is 5 mm, and the end face of the transition section 122 is constructed as a circle with a diameter of 2.5 mm and is provided with three holes 121 thereon. The three holes 121 are arranged in a circular shape at equal intervals around the center of the end face 123, and an angle of 120° is formed between adjacent lines connecting the three holes and the center of the end face 123, wherein the pore diameter measurement value of the three holes 121 is 0.14 mm to 0.17 mm, and the distance between the three holes 121 and the center of the end face 123 is uniformly set to 1.25 mm.

[0552] In the embodiments of the present invention, the polypeptide tumor vaccine is a new type of vaccine, which is essentially an immunogen that induces an effector cell immune response in the body. The tumor polypeptide vaccine is an antigen polypeptide eluted from the surface of tumor cells or a related polypeptide obtained from tumor cells that can enhance the body's anti-tumor humoral immunity and cellular immunity after immunization. Currently, the most widely studied tumor polypeptide vaccines include vaccines targeting folate receptors (FR) or HER2 targets.

[0553] The following is a specific polypeptide tumor vaccine rat immunization test using the multimodal fluid delivery device of the present invention. The polypeptide tumor vaccine rat immunization test was conducted using the multimodal fluid delivery device of the present invention according to the following experimental protocol:

[0554] 1. Test materials

[0555] 1.1 Experimental Animals: Sixty healthy male C57BL / 6 mice, aged 6-8 weeks and weighing 18-22 g, were randomly divided into six experimental groups (G1, G2, G3, G4, G5, and G6) (10 mice in each group).

[0556] 1.2. Test equipment: neoantigen and positive control peptide, and a multimodal fluid delivery device according to an embodiment of the present invention, wherein the pore size is 0.14-0.17 mm and the delivery pressure is 160N.

[0557] 2. Immunity test

[0558] 2.1 Experimental arrangement:

[0559] Three or four rounds of immune tests were performed in groups according to Table 6 below:

[0560] Table 11. Information of the peptide tumor vaccine rat immunization test

[0561] 3. Effect detection

[0562] 3.1. Detection method: After immunization, spleen cells from mice were taken for 4 rounds of ELISPOT detection.

[0563] 3.2 Test results:

[0564] a. After three / four rounds of immunization, positive signals of the new antigen group can be detected by Elispot assay, but the signals are weak.

[0565] b. There was no statistical difference in the number of parity spots between the needle-free injection group and the needle-injection group.

[0566] c. After the fourth round of immunization, the number of spots in each experimental group was lower than in the third round. Regarding the reduction ratio, the needle-free neoantigen group had 10% fewer spots than the needle-treated neoantigen group and 20% fewer spots than the positive peptide group. This indicates that the effectiveness of the needle-free plus neoantigen peptide vaccine lasts longer than the other two groups.

[0567] In the above embodiments of the present invention, the injection head and the needle part thereon are removed from the tube, but in other embodiments of the present invention, the multimodal fluid delivery device of the present invention equipped with the injection head and the needle part is also expected to have similar diffusion effects and immunogenic effects as described above.

[0568] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A multi-mode fluid delivery device, characterized in that, Comprising: A tube for containing fluid, the tube having a first end and a second end, and a self-sealing elastic part or a hole for dispensing the fluid in the tube is provided in the second end; An injection head detachably connected to the tube, the injection head including one or more needle members, and the one or more needle members are configured to removably dock with the self-sealing elastic part or the hole for dispensing the fluid in the second end; And A power mechanism, the power mechanism including a piston capable of pushing the fluid provided in the first end of the tube or an operationally connected piston to apply a delivery pressure to the piston that pushes the fluid.

2. The multimode fluid delivery device according to claim 1, wherein, The power mechanism is any one of a compressed gas drive, a spring drive, an electromagnetic drive or a combination of the above drive modes; The pushing speed of the piston of the multi-mode fluid delivery device is 0.05 - 0.50 m / s, preferably 0.09 - 0.25 m / s, and more preferably 0.14 - 0.25 m / s; The multi-mode fluid delivery device is configured such that the outlet jet velocity when the fluid is pushed away from the hole or the one or more needle members in the second end by the piston is greater than or equal to 10 m / s, preferably greater than or equal to 50 m / s, further preferably greater than or equal to 100 m / s, and more preferably greater than or equal to 150 m / s.

3. The multimodal fluid delivery device according to claim 1 or 2, wherein, At least one of the one or more needle members is substantially inserted into the human body or an animal body; Preferably, at least one of the one or more needle members has a pore diameter in the range of 0.06 mm - 1.50 mm, further preferably in the range of 0.11 mm - 1.00 mm, and more preferably in the range of 0.11 mm - 0.50 mm; Preferably, at least one of the self-sealing elastic part or the hole for dispensing the fluid in the tube has a diameter in the range of 0.06 mm - 1.50 mm, further preferably in the range of 0.11 mm - 1.00 mm, and more preferably in the range of 0.11 mm - 0.50 mm.

4. The multi-mode fluid delivery device according to claim 1 or 2, characterized in that, The total fluid delivery area of the plurality of needle members or the plurality of holes for dispensing fluid in the tube is 0.009 mm 2 or more, preferably 0.020 mm 2 or more, more preferably 0.053 mm 2 or more, more preferably 0.28 mm 2 or more; the area of a single hole of the needle member or the hole is 0.0028 to 0.035 mm 2 , preferably 0.0028 to 0.020 mm 2 , more preferably 0.0028 to 0.009 mm 2 .

5. The multimodal fluid delivery device according to claim 1 or 2, characterized in that, The one or more needle members have different adjustable skin insertion depths; Preferably, at least one of the one or more needle members has an insertion depth that does not substantially insert but forms a tight contact with the human or animal skin; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into the inner layer of the human or animal skin; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into the subcutaneous layer of the human or animal; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into the muscle layer of the human or animal; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into an internal organ of the human or animal body; Preferably, at least one of the one or more needle members has an adjustable insertion depth.

6. The multi-mode fluid delivery device according to claim 1 or 2, characterized in that The multi-mode fluid delivery device is configured such that the diffused volume of the fluid in the body is greater than the undelivered volume, preferably the diffused volume of the fluid in the body is more than 1.50 times the undelivered volume, preferably more than 1.80 times, further preferably more than 2.40 times, more preferably more than 3.00 times, and still more preferably more than 3.60 times.

7. The multimodal fluid delivery device according to claim 1 or 2, wherein, The plurality of needle members includes a first needle member; Preferably, the first needle member has a first skin insertion depth located in one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; Preferably, the first needle member has a first needle aperture sized such that the fluid jet through the first needle member diffuses in at least one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; Preferably, the first needle member has a first exit jet velocity configured such that the fluid jet through the first needle member diffuses in at least one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ.

8. The multimodal fluid delivery device according to claim 1 or 2, characterized in that, The plurality of needle members includes a first needle member and a second needle member; Preferably, the first needle member has a first skin insertion depth located in one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ, and the second needle member has a second skin insertion depth located in another of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; Preferably, the first needle member has a first needle aperture sized such that the fluid jet through the first needle member diffuses in at least one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; the second needle member has a second needle aperture sized such that the fluid jet through the second needle member diffuses in at least another of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; Preferably, the first needle member has a first exit jet velocity configured such that the fluid jet through the first needle member diffuses in at least one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; the second needle member has a second exit jet velocity configured such that the fluid jet through the second needle member diffuses in at least another of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ.

9. The multi-modal fluid delivery device according to claim 8, wherein, The plurality of needle members further includes a third needle member; Preferably, the third needle member has a third skin insertion depth located in yet another of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; Preferably, the third needle member has a third needle aperture sized such that the fluid jet through the third needle member diffuses in at least one more of the dermis layer, epidermis layer, or subcutaneous layer of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ; Preferably, the third needle member has a third exit jet velocity configured such that the fluid jet through the third needle member diffuses in at least one more of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organ.

10. The multi-mode fluid delivery device according to claim 1 or 2, characterized in that, The plurality of needle members are arranged in a straight line; Preferably, the plurality of needle members are linearly arranged along the diameter or the center line of the injection head. Preferably, one of the plurality of needle members linearly arranged along the diameter or the center line of the injection head is located at the center or the center of the injection head; Preferably, the plurality of needle members linearly arranged are equally spaced; Preferably, the plurality of needle members linearly arranged are mirror-symmetrical with respect to the diameter or the center line of the injection head; Preferably, there are multiple groups of the needle members, and each group of needle members is linearly arranged. Preferably, each group of needle members is arranged along a diameter or a center line of the injection head; The plurality of needle members are arranged in an array. Preferably, the plurality of needle members arranged in an array are mirror-symmetrical with respect to the first and second diameters or center lines perpendicular to each other of the injection head respectively.

11. The multi-mode fluid delivery device according to claim 10, wherein the skin insertion depth of the needle member located at the center or the center of the injection head is different from the skin insertion depths of the other needle members of the plurality of needle members; Preferably, the skin insertion depth of at least one group of needle members among the multiple groups of needle members is different from the skin insertion depths of the other groups of needle members; Preferably, the needle aperture of the needle member located at the center or the center of the injection head is different from the needle apertures of the other needle members of the plurality of needle members; Preferably, the needle aperture of at least one group of needle members among the multiple groups of needle members is different from the needle apertures of the other groups of needle members; Preferably, the outlet jet velocity of the needle member located at the center or the center of the injection head is different from the outlet jet velocities of the other needle members of the plurality of needle members; Preferably, the outlet jet velocity of at least one group of needle members among the multiple groups of needle members is different from the outlet jet velocities of the other groups of needle members.

12. The multi-modal fluid delivery device according to claim 1 or 2, characterized in that, The plurality of needle members are arranged in a ring; Preferably, the plurality of needle members are arranged in a ring with the center or the center of the injection head as the center; There are multiple groups of the needle members, and each group of needle members is arranged in a ring. Preferably, the multiple groups of needle members are arranged coaxially in a ring with each other.

13. The multi-mode fluid delivery device according to claim 12, wherein at least one of the plurality of needle members arranged in a ring has a skin insertion depth different from that of the other needle members; Preferably, the skin insertion depth of at least one group of needle members among the multiple groups of needle members is different from the skin insertion depths of the other groups of needle members; Preferably, the skin insertion depths of the multiple groups of needle members arranged coaxially in a ring with each other decrease or increase radially; Preferably, at least one of the plurality of needle members arranged in a ring has a needle aperture different from that of the other needle members; Preferably, the needle aperture of at least one group of needle members among the multiple groups of needle members is different from the needle apertures of the other groups of needle members; Preferably, the needle apertures of the multiple groups of needle members arranged coaxially in a ring with each other decrease or increase radially; Preferably, at least one of the plurality of needle members arranged in a ring has an outlet jet velocity different from that of the other needle members; Preferably, the outlet jet velocity of at least one group of needle members among the multiple groups of needle members is different from the outlet jet velocities of the other groups of needle members; Preferably, the outlet jet velocities of the multiple sets of needle members arranged coaxially and annularly with each other decrease or increase radially.

14. The multimodal fluid delivery device according to claim 1 or 2, wherein, The multiple needle members include a central needle member located at the center or the center of the injection head and a plurality of peripheral needle members located around the central needle member; Preferably, the plurality of peripheral needle members are arranged in a ring, and preferably, the plurality of peripheral needle members are arranged coaxially and annularly around the central needle member; There are multiple sets of the peripheral needle members, and each set of peripheral needle members is arranged in a ring. Preferably, the multiple sets of peripheral needle members are arranged coaxially and annularly around the central needle member.

15. The multi-mode fluid delivery device according to claim 14, wherein the skin insertion depth of the central needle member is different from the skin insertion depth of the plurality of peripheral needle members; Preferably, the skin insertion depth of at least one set of the multiple sets of peripheral needle members is different from the skin insertion depth of the other peripheral sets of needle members; Preferably, the skin insertion depths of the multiple sets of needle members arranged coaxially and annularly with each other and the central needle member decrease or increase radially; Preferably, the needle aperture of the central needle member is different from the needle apertures of the plurality of peripheral needle members; Preferably, the needle aperture of at least one set of the multiple sets of peripheral needle members is different from the needle apertures of the other peripheral sets of needle members; Preferably, the needle apertures of the multiple sets of needle members arranged coaxially and annularly with each other and the central needle member increase or decrease radially; Preferably, the outlet jet velocity of the central needle member is different from the outlet jet velocities of the plurality of peripheral needle members; Preferably, the outlet jet velocity of at least one set of the multiple sets of peripheral needle members is different from the outlet jet velocities of the other peripheral sets of needle members; Preferably, the outlet jet velocities of the multiple sets of needle members arranged coaxially and annularly with each other and the central needle member decrease or increase radially.

16. The multi-mode fluid delivery device according to any one of claims 1 to 15, characterized in that, The injection head includes a support portion for supporting the needle member; Preferably, the needle member further includes a first needle head portion located on the side of the support portion facing away from the tube; Preferably, the needle member includes a fixed gasket located on the side of the support portion facing the tube, and the fixed gasket is used to fix the needle member; Preferably, the needle member includes a second needle head portion located on the side of the support portion facing the tube; Alternatively, the needle member does not extend from the side of the support portion facing away from the tube, so that a needleless micro-hole is formed on the side of the support portion facing away from the needle tube.

17. The multi-mode fluid delivery device according to claim 16, wherein, The needle member includes an intervening soft needle removably connected to the hole of the tube.

18. The multimodal fluid delivery device according to claim 16, wherein The multi-mode fluid delivery device further includes a needle kit, and the needle kit includes a needle sleeve for removably surrounding the first needle head portion of the needle member.

19. The multi-mode fluid delivery device according to claim 18, wherein The height of the needle sleeve of the needle kit is greater than or equal to the first needle head portion of the needle member, so as to completely surround the first needle head portion; Optionally, the height of the needle sleeve of the needle kit is less than the first needle head portion of the needle member, so as to partially surround the first needle head portion, such that the first needle head portion extends from the front end of the needle sleeve to form an insertion portion.

20. The multimodal fluid delivery device according to claim 19, wherein The needle kit includes a first needle kit, and the height of the needle sleeve of the first needle kit is greater than the first needle head of the needle member, so as to completely surround the first needle head to protect the first needle head.

21. The multi-mode fluid delivery device according to claim 19, wherein There are multiple needle kits. Preferably, the multiple needle kits include a first needle kit and a second needle kit. The first needle kit is configured such that when it surrounds the first needle head, it can be in one of the states of being partially surrounded, with the insertion part located in the dermis layer, in the epidermis layer, under the skin, in the muscle, or in a human organ. The second needle kit is configured such that when it surrounds the first needle head, it can be in another of the states of being partially surrounded, with the insertion part located in the dermis layer, in the epidermis layer, under the skin, in the muscle, or in a human organ.

22. The multimodal fluid delivery device according to claim 18, wherein There are multiple needle kits. Preferably, the multiple needle kits include a first needle kit, a second needle kit, a third needle kit, a fourth needle kit, a fifth needle kit, and a sixth needle kit. The first needle kit is configured such that when it surrounds the first needle head, the first needle head is completely surrounded. The second needle kit is configured such that when it surrounds the first needle head, the insertion part is located in the dermis layer. The third needle kit is configured such that when it surrounds the first needle head, the insertion part is located in the epidermis layer. The fourth needle kit is configured such that when it surrounds the first needle head, the insertion part is located under the skin. The fifth needle kit is configured such that when it surrounds the first needle head, the insertion part is located in the muscle. The sixth needle kit is configured such that when it surrounds the first needle head, the insertion part is located in a human organ.

23. The multimodal fluid delivery device according to claim 16, wherein, The injection head further includes a needle sleeve portion sleeved on the needle member and a rotating member operatively connected to the needle member or the needle sleeve portion. The rotating member is configured to adjust the axial positions of the needle member and the needle sleeve portion by rotation to adjust the exposed length of the needle member relative to the needle sleeve portion.

24. The delivery device according to claim 23, wherein The axial positions of the needle member and the needle sleeve portion are configured to be adjustable between multiple positions such that the exposed length of the needle member can be adjusted between multiple positions. Preferably, the exposed length of the needle member can be adjusted between multiple positions including retracted from the needle sleeve portion, flush with the needle sleeve portion, located in the dermis layer, in the epidermis layer, under the skin, in the muscle, and in a human organ. Preferably, the axial positions of the needle member and the needle sleeve portion are configured to be continuously adjustable such that the exposed length of the needle member can be continuously adjusted.

25. The multimodal fluid delivery device according to any one of claims 1 to 24, characterized in that, The injection head includes a connecting portion for detachably connecting the injection head to the tube. Preferably, the connecting portion is a threaded connecting portion. Optionally, the connecting portion is a snap - connecting portion. Optionally, the connecting portion is an adhesive - bonding portion.

26. The multimode fluid device according to any one of claims 1 to 24, characterized in that, The multi - mode fluid delivery device further includes a locking member for locking the injection head to the tube. The locking member includes a connecting portion for detachably connecting the locking member to the tube. Preferably, the connecting portion is a threaded connecting portion. Optionally, the connecting portion is a snap - connecting portion. Optionally, the connecting portion is an adhesive - bonding portion.

27. A combined product of a feline triple vaccine and a medical device, characterized in that, It includes a multi - mode fluid delivery device and a feline triple vaccine, wherein the multi - mode fluid delivery device is the multi - mode fluid delivery device according to any one of claims 1 to 26.

28. The medicament-device combination product according to claim 27, wherein The second end is provided with three holes, which are arranged in an equally spaced circular pattern around the center of the second end. The aperture diameters of the three holes are 0.10 mm to 0.17 mm, and the three holes are at a distance of 1.25 mm ± 20% from the center.

29. The pharmaceutical and medical device combination product according to claim 27, wherein, The pushing speed of the piston of the multi-mode fluid delivery device is 0.12 m / s ± 20%.

30. The pharmaceutical device combination product according to claim 27, wherein, The multi-mode fluid delivery device is configured such that the outlet jet velocity when the feline triple vaccine is pushed by the piston away from the holes in the second end is 150.00 m / s ± 20%.

31. The pharmaceutical device combination product according to claim 27, wherein The multi-mode fluid delivery device is configured such that the diffusion volume of the feline triple vaccine in the body is more than 1.5 times the undelivered volume of the feline triple vaccine.

32. The pharmaceutical and medical device combination product according to claim 27, wherein The multi-mode fluid delivery device is configured such that the average antibody titer of the feline triple vaccine 14 days after the second dose is more than 1.2 times, preferably more than 2.0 times, and more preferably more than 4.8 times the average antibody titer of needle injection.

33. The pharmaceutical and medical device combination product according to claim 27, wherein, The multi-mode fluid delivery device is configured such that the average antibody titer of the feline triple vaccine 30 days after the second dose is more than 1.2 times, preferably more than 2.0 times, and more preferably more than 3.7 times the average antibody titer of needle injection.

34. The pharmaceutical device combination product according to claim 27, wherein The multi-mode fluid delivery device is configured such that the average antibody titer of the feline triple vaccine 60 days after the second dose of 60% of the vaccine dose is more than 1.1 times, preferably more than 1.5 times, and more preferably more than 2.0 times the average antibody titer produced by 100% of the vaccine dose of needle injection.

35. A combined product of a hepatitis B vaccine and a medical device, characterized in that, Comprising a multi-mode fluid delivery device and a hepatitis B vaccine, wherein the multi-mode fluid delivery device is the multi-mode fluid delivery device according to any one of claims 1 to 26.

36. The pharmaceutical device combination product according to claim 35, wherein, The second end is provided with three holes, which are arranged in an equally spaced circular pattern around the center of the second end. The aperture diameters of the three holes are 0.10 mm to 0.17 mm, and the three holes are at a distance of 1.25 mm ± 20% from the center.

37. The pharmaceutical device combination product according to claim 35, wherein, The pushing speed of the piston of the multi-mode fluid delivery device is 0.12 m / s ± 20%.

38. The pharmaceutical device combination product according to claim 35, wherein The multi-mode fluid delivery device is configured such that the outlet jet velocity when the hepatitis B vaccine is pushed by the piston away from the holes in the second end is 150.00 m / s ± 20%.

39. The pharmaceutical device combination product according to claim 35, wherein, The multi-mode fluid delivery device is configured such that the diffusion volume of the hepatitis B vaccine in the body is more than 1.5 times the undelivered volume of the hepatitis B vaccine.

40. The pharmaceutical device combination product according to claim 35, wherein, The multi-mode fluid delivery device is configured such that the average antibody titer of the hepatitis B vaccine 42 days after the second dose is more than 1.1 times, preferably more than 1.5 times, and more preferably more than 2.0 times the average antibody titer of needle injection.

41. The pharmaceutical device combination product according to claim 35, wherein, The multi-mode fluid delivery device is configured such that the positive expression rate of T lymphocytes of the hepatitis B vaccine 42 days after the second dose is more than 10% higher, preferably more than 20% higher, and more preferably more than 50% higher than that of needle injection.

42. A combined product of a human pneumonia vaccine and a medical device, characterized in that, Comprising a multi-mode fluid delivery device and a human pneumococcal vaccine, wherein the multi-mode fluid delivery device is the multi-mode fluid delivery device according to any one of claims 1 to 26.

43. The pharmaceutical device combination product according to claim 42, wherein The second end is provided with three holes, which are arranged in an equally spaced circular pattern around the center of the second end. The aperture diameters of the three holes are 0.10 mm to 0.17 mm, and the three holes are at a distance of 1.25 mm ± 20% from the center.

44. The drug-device combination product according to claim 42, wherein The pushing speed of the piston of the multi-mode fluid delivery device is 0.14 m / s ± 20%.

45. The pharmaceutical and medical device combination product according to claim 42, wherein, The multi-mode fluid delivery device is configured such that the exit jet velocity when the human pneumococcal vaccine is pushed away from the holes in the second end by the piston is 160.00 m / s ± 20%.

46. The pharmaceutical and medical device combination product according to claim 42, wherein, The multi-mode fluid delivery device is configured such that the dispersion volume of the human pneumococcal vaccine in the body is more than 1.5 times the undelivered volume of the human pneumococcal vaccine.

47. The pharmaceutical and medical device combination product according to claim 42, wherein, The multi-mode fluid delivery device is configured such that the average antibody titer of the pneumococcal vaccine 42 days after vaccination is more than 1.1 times, preferably more than 1.5 times, and more preferably more than 2.0 times the average antibody titer of needle injection.

48. A GLP-1 polypeptide drug-device combination product, characterized in that, Comprising a multi-mode fluid delivery device and a GLP-1 polypeptide, wherein the multi-mode fluid delivery device is the multi-mode fluid delivery device according to any one of claims 1 to 26.

49. The pharmaceutical and medical device combination product according to claim 48, wherein, The second end is provided with three holes, which are arranged in an equally spaced circular pattern around the center of the second end. The aperture diameters of the three holes are 0.10 mm to 0.17 mm, and the three holes are at a distance of 1.25 mm ± 20% from the center.

50. The pharmaceutical device combination product according to claim 48, wherein The multi-mode fluid delivery device is configured such that the dispersion volume of the GLP-1 polypeptide in the body is more than 1.5 times the undelivered volume of the GLP-1 polypeptide.

51. The medicament-device combination product according to claim 48, wherein The pushing speed of the piston of the multi-mode fluid delivery device is 0.16 m / s ± 20%; The multi-mode fluid delivery device is configured such that the exit jet velocity when the GLP-1 polypeptide is pushed away from the holes in the second end by the piston is 160.00 m / s ± 20%.

52. The drug-device combination product according to claim 48, wherein, The multi-mode fluid delivery device is configured such that the effect of the GLP-1 polypeptide on reducing the body weight of humans and animals is the same as that of needle injection, preferably the weight reduction effect is increased by 2% compared to needle injection, more preferably increased by 5%, and even more preferably increased by 10%.

53. The pharmaceutical and medical device combination product according to claim 48, wherein, The multi-mode fluid delivery device is configured such that the body weight reduction endpoint of the GLP-1 polypeptide in the body is the same as that of needle injection, preferably increased by more than 2%, more preferably increased by more than 5%, and even more preferably increased by more than 10%.

54. The pharmaceutical and medical device combination product according to claim 48, wherein The multi-mode fluid delivery device is configured such that the proportion of side effects such as nausea, vomiting, and abdominal distension caused by the GLP-1 polypeptide is the same as that of needle injection, preferably reduced by more than 5%, more preferably reduced by more than 10%, and even more preferably reduced by more than 20%.

55. A drug-device combination product, characterized in that, Comprising a multi-mode fluid delivery device and a pharmaceutical preparation, the multi-mode fluid delivery device is the multi-mode fluid delivery device according to any one of claims 1 to 26.

56. The pharmaceutical device combination product according to claim 55, wherein Optionally, the pharmaceutical preparation is a human rabies vaccine; Optionally, the pharmaceutical preparation is an animal rabies vaccine; Optionally, the pharmaceutical preparation is a human meningitis vaccine; Optionally, the pharmaceutical preparation is a hand, foot and mouth disease vaccine for animals; Optionally, the pharmaceutical preparation is a COVID-19 vaccine for humans; Optionally, the pharmaceutical preparation is a hepatitis A vaccine for humans; Optionally, the pharmaceutical preparation is a hemorrhagic fever with renal syndrome vaccine for humans; Optionally, the pharmaceutical preparation is a mumps vaccine for humans; Optionally, the pharmaceutical preparation is an HPV vaccine for humans; Optionally, the pharmaceutical preparation is a chemotherapeutic drug for human tumors; Optionally, the pharmaceutical preparation is a nuclear medicine therapeutic drug for human tumors; Optionally, the pharmaceutical preparation is a human tumor vaccine, including but not limited to polypeptide vaccines, mRNA vaccines, DNA vaccines; Optionally, the pharmaceutical preparation is a porcine diarrhea bivalent vaccine; Optionally, the pharmaceutical preparation is a porcine reproductive and respiratory syndrome inactivated vaccine; Optionally, the pharmaceutical preparation is a foot-and-mouth disease vaccine; Optionally, the pharmaceutical preparation is a bovine bivalent vaccine; Optionally, the pharmaceutical preparation is a Pasteurella multocida vaccine; Optionally, the pharmaceutical preparation is insulin; Optionally, the pharmaceutical preparation is a botulinum toxin-based cosmetic drug for medical aesthetics.

57. A tube for a multi-mode fluid delivery device, characterized in that the tube has a first end and a second end, wherein the first end is configured to accommodate a piston for pushing the fluid in the tube, and a self-sealing elastic part or a plurality of holes for dispensing the fluid in the tube are provided in the second end.

58. The tube according to claim 57, wherein, The tube is configured such that the fluid jets through the plurality of holes have different in-vivo dispersions; Preferably, the aperture diameters of the plurality of holes of the tube are configured such that the fluid jets through the plurality of holes have different in-vivo dispersions.

59. The tube according to claim 57, wherein, The plurality of holes include a first hole; Preferably, the first hole has a first aperture diameter, and the size of the first aperture diameter is configured such that the fluid jet through the first hole disperses in at least one of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs.

60. The tube according to claim 57, wherein, The plurality of holes include a first hole and a second hole; Preferably, the first hole has a first aperture diameter, and the size of the first aperture diameter is configured such that the fluid jet through the first hole disperses in at least one of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs; the second hole has a second aperture diameter, and the size of the second aperture diameter is configured such that the fluid jet through the second hole disperses in at least one other of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs.

61. The tube according to claim 57, wherein, The plurality of holes are arranged in a straight line; Preferably, the plurality of holes are arranged in a straight line along the diameter or the midline of the second end. Preferably, one of the plurality of holes arranged in a straight line along the diameter or the midline of the second end is located at the center or the center point of the second end; Preferably, the plurality of holes arranged in a straight line are equally spaced; Preferably, the plurality of holes arranged in a straight line are mirror-symmetrical with respect to the diameter or the midline of the second end; Preferably, the holes are provided in multiple groups, and each group of holes is arranged in a straight line. Preferably, each group of holes is arranged along a diameter or a midline of the second end; Preferably, the plurality of holes are arranged in an array, and the plurality of holes arranged in an array are mirror-symmetrical with respect to the first and second diameters or midlines perpendicular to each other of the second end respectively; Preferably, the aperture of the hole located at the center of the second end is different from the apertures of the other holes among the plurality of holes; Preferably, the aperture of at least one group of holes among the multiple groups of holes is different from the apertures of the other groups of holes.

62. The tube according to claim 57, wherein, The plurality of holes are arranged in a ring; Preferably, the plurality of holes are arranged in a ring with the center of the second end as the center; The holes are in multiple groups, and each group of holes is arranged in a ring. Preferably, the multiple groups of holes are arranged in coaxial rings with each other; Preferably, at least one of the plurality of holes arranged in a ring has an aperture different from that of the other holes; Preferably, the aperture of at least one group of holes among the multiple groups of holes is different from the apertures of the other groups of holes; Preferably, the apertures of the multiple groups of holes arranged in coaxial rings increase or decrease radially.

63. The tube according to claim 57, characterized in that, The plurality of holes include a central hole located at the center of the second end and a plurality of peripheral holes located around the central hole; Preferably, the plurality of peripheral holes are arranged in a ring. Preferably, the plurality of peripheral holes are arranged in coaxial rings around the central hole; The peripheral holes are in multiple groups, and each group of peripheral holes is arranged in a ring. Preferably, the multiple groups of peripheral holes are arranged in coaxial rings around the central hole; Preferably, the aperture of the central hole is different from the apertures of the plurality of peripheral holes.

64. An injection head for a multi-mode fluid delivery device, characterized in that, The injection head includes one or more needle members and a support portion for supporting the needle members.

65. The injection head according to claim 64, characterized in that, The support portion has a first side and a second side opposite to the first side; Optionally, the needle member includes a first needle head portion located on the first side of the support portion; Optionally, the needle member includes a fixing gasket located on the second side of the support portion, and the fixing gasket is used to fix the needle member; Optionally, the needle member includes a second needle head portion located on the second side of the support portion; Alternatively, the second needle head portion of the needle member does not extend from the second side of the support portion, so that a needleless micro-hole is formed on the second side of the support portion.

66. The injection head according to claim 64, wherein Optionally, the first needle head portion of the needle member is sharp, and the second needle head portion of the needle member is flat; Optionally, both the first needle head portion and the second needle head portion of the needle member are sharp.

67. The injection head according to claim 64, characterized in that, The one or more needle members have different adjustable skin insertion depths; Preferably, at least one of the one or more needle members has an insertion depth that does not substantially insert but forms a tight contact with the human or animal skin; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into the inner layer of the human or animal skin; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into the subcutaneous layer of the human or animal; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into the muscle layer of the human or animal; Preferably, at least one of the one or more needle members has an insertion depth that substantially inserts into the internal organs of the human or animal; Preferably, at least one of the one or more needle members has an adjustable insertion depth.

68. The injection head according to claim 64, characterized in that, The plurality of needle members include a first needle member; Preferably, the first needle member has a first needle aperture sized such that a fluid jet through the first needle member is dispersed in one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs.

69. The injection head according to claim 64, characterized in that, The plurality of needle members includes a first needle member and a second needle member; Preferably, the first needle member has a first skin insertion depth in one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs, and the second needle member has a second skin insertion depth in another of the dermis, epidermis, subcutaneous tissue, muscle, and human organs; Preferably, the first needle member has a first needle aperture sized such that a fluid jet through the first needle member is dispersed in at least one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs; the second needle member has a second needle aperture sized such that a fluid jet through the second needle member is dispersed in at least another of the dermis, epidermis, subcutaneous tissue, muscle, and human organs.

70. The injection head according to claim 69, characterized in that, The plurality of needle members further includes a third needle member; Preferably, the third needle member has a third skin insertion depth in yet another of the dermis, epidermis, subcutaneous tissue, muscle, and human organs; Preferably, the third needle member has a third needle aperture sized such that a fluid jet through the third needle member is dispersed in at least yet another of the dermis, epidermis, or subcutaneous tissue of the dermis, epidermis, subcutaneous tissue, muscle, and human organs.

71. The injection head according to claim 64, characterized in that, The plurality of needle members are arranged in a straight line; Preferably, the plurality of needle members are arranged in a straight line along the diameter or the center line of the injection head. Preferably, one of the plurality of needle members arranged in a straight line along the diameter or the center line of the injection head is located at the center or the center point of the injection head; Preferably, the plurality of needle members arranged in a straight line are equally spaced; Preferably, the plurality of needle members arranged in a straight line are mirror-symmetrical with respect to the diameter or the center line of the injection head; Preferably, there are multiple groups of needle members, and each group of needle members is arranged in a straight line. Preferably, each group of needle members is arranged along a diameter or a center line of the injection head; The plurality of needle members are arranged in an array. Preferably, the plurality of needle members arranged in an array are mirror-symmetrical with respect to the first and second diameters or center lines perpendicular to the end face of the injection head, respectively.

72. The injection head according to claim 71, wherein the skin insertion depth of the needle member located at the center or the center point of the injection head is different from the skin insertion depths of the other needle members of the plurality of needle members; Preferably, the skin insertion depth of at least one group of needle members among the multiple groups of needle members is different from the skin insertion depths of the other groups of needle members; Preferably, the needle aperture of the needle member located at the center or the center point of the injection head is different from the needle apertures of the other needle members of the plurality of needle members; Preferably, the needle aperture of at least one group of needle members among the multiple groups of needle members is different from the needle apertures of the other groups of needle members.

73. The syringe head according to claim 64, wherein, The plurality of needle members are arranged in a ring; Preferably, the plurality of needle members are arranged in a ring with the center or the center point of the injection head as the center; The needle members are provided in multiple groups, and each group of needle members is arranged in a circular pattern. Preferably, the multiple groups of needle members are arranged in coaxial circular patterns with respect to each other.

74. The injection head according to claim 73, wherein at least one of the needle members arranged in a circular pattern has a skin insertion depth different from that of the other needle members; preferably, the skin insertion depth of at least one group of the multiple groups of needle members is different from that of the other groups of needle members; preferably, the skin insertion depth of the multiple groups of needle members arranged in coaxial circular patterns with respect to each other decreases or increases radially; preferably, at least one of the needle members arranged in a circular pattern has a needle aperture diameter different from that of the other needle members; preferably, the needle aperture diameter of at least one group of the multiple groups of needle members is different from that of the other groups of needle members; preferably, the needle aperture diameter of the multiple groups of needle members arranged in coaxial circular patterns with respect to each other decreases or increases radially.

75. The syringe head according to claim 64, wherein, The multiple needle members include a central needle member located at the center of the injection head and a plurality of peripheral needle members located around the central needle member; preferably, the plurality of peripheral needle members are arranged in a circular pattern, and preferably, the plurality of peripheral needle members are arranged in a coaxial circular pattern around the central needle member; The peripheral needle members are provided in multiple groups, and each group of peripheral needle members is arranged in a circular pattern. Preferably, the multiple groups of peripheral needle members are arranged in a coaxial circular pattern around the central needle member.

76. The injection head according to claim 75, wherein the skin insertion depth of the central needle member is different from that of the plurality of peripheral needle members; preferably, the skin insertion depth of at least one group of the multiple groups of peripheral needle members is different from that of the other groups of peripheral needle members; preferably, the skin insertion depth of the multiple groups of needle members and the central needle member arranged in coaxial circular patterns with respect to each other decreases or increases radially; preferably, the needle aperture diameter of the central needle member is different from that of the plurality of peripheral needle members; preferably, the needle aperture diameter of at least one group of the multiple groups of peripheral needle members is different from that of the other groups of peripheral needle members; preferably, the needle aperture diameter of the multiple groups of needle members and the central needle member arranged in coaxial circular patterns with respect to each other increases or decreases radially.

77. The injection head according to claim 64, wherein, The needle member further includes an interventional soft needle removably connected to the hole.

78. The injection head according to claim 64, characterized in that, The injection head further includes a needle sleeve portion sleeved on the needle member and a rotating member operatively connected to the needle member or the needle sleeve portion. The rotating member is configured to adjust the axial positions of the needle member and the needle sleeve portion by rotation to adjust the exposed length of the needle member relative to the needle sleeve portion.

79. The syringe head according to claim 78, characterized in that, The axial positions of the needle member and the needle sleeve portion are configured to be adjustable between multiple positions such that the exposed length of the needle member is adjustable between multiple positions. Preferably, the exposed length of the needle member is adjustable between multiple positions including retracted from the needle sleeve portion, flush with the needle sleeve portion, located in the dermis layer, located in the epidermis layer, located in the subcutaneous layer, located in the muscle, and located in a human organ; Preferably, the axial positions of the needle member and the needle sleeve portion are configured to be continuously adjustable such that the exposed length of the needle member is continuously adjustable.

80. A needle kit for a multi-mode fluid delivery device, characterized in that the needle kit includes one or more needle sleeves, wherein the needle sleeve is configured to removably surround the first needle head portion of the needle member.

81. The needle kit according to claim 80, wherein, The height of the needle sleeve is greater than or equal to the first needle head portion of the needle member, so as to completely surround the first needle head portion; Optionally, the height of the needle sleeve of the needle kit is less than the first needle head portion of the needle member, so as to partially surround the first needle head portion, such that the first needle head portion extends from the front end of the needle sleeve to form an insertion portion.

82. The needle kit according to claim 80, characterized in that, The needle kit includes a first needle kit, and the height of the needle sleeve of the first needle kit is greater than the first needle head portion of the needle member, so as to completely surround the first needle head portion to protect the first needle head portion.

83. The needle kit according to claim 80, wherein, There are multiple needle kits. Preferably, the multiple needle kits include a first needle kit and a second needle kit. The first needle kit is configured such that the state of surrounding the first needle head portion includes one of being partially surrounded, the insertion portion being located in the dermis layer, in the epidermis layer, under the skin, in the muscle, or in a human organ. The second needle kit is configured such that the state of surrounding the first needle head portion includes another one of being partially surrounded, the insertion portion being located in the dermis layer, in the epidermis layer, under the skin, in the muscle, or in a human organ.

84. The needle assembly according to claim 80, wherein, There are multiple needle kits. Preferably, the multiple needle kits include a first needle kit, a second needle kit, a third needle kit, a fourth needle kit, a fifth needle kit, and a sixth needle kit. The first needle kit is configured such that the first needle head portion surrounded by it is completely surrounded. The second needle kit is configured such that the insertion portion of the first needle head portion surrounded by it is located in the dermis layer. The third needle kit is configured such that the insertion portion of the first needle head portion surrounded by it is located in the epidermis layer. The fourth needle kit is configured such that the insertion portion of the first needle head portion surrounded by it is located under the skin. The fifth needle kit is configured such that the insertion portion of the first needle head portion surrounded by it is located in the muscle. The sixth needle kit is configured such that the insertion portion of the first needle head portion surrounded by it is located in a human organ.

85. Use of the multi-mode fluid delivery device according to any one of claims 1 to 26 in the preparation of human clinical medical and animal health care pharmaceutical preparations for multi-mode fluid delivery administration.

86. The use according to claim 85, characterized in that Optionally, the pharmaceutical preparation is a feline triple vaccine; Optionally, the pharmaceutical preparation is a hepatitis B vaccine; Optionally, the pharmaceutical preparation is a human pneumonia vaccine; Optionally, the pharmaceutical preparation is semaglutide; Optionally, the pharmaceutical preparation is a human rabies vaccine; Optionally, the pharmaceutical preparation is an animal rabies vaccine; Optionally, the pharmaceutical preparation is a human meningitis vaccine; Optionally, the pharmaceutical preparation is an animal hand, foot and mouth disease vaccine; Optionally, the pharmaceutical preparation is a human COVID-19 vaccine; Optionally, the pharmaceutical preparation is a human hepatitis A vaccine; Optionally, the pharmaceutical preparation is a human hemorrhagic fever with renal syndrome vaccine; Optionally, the pharmaceutical preparation is a mumps vaccine for human use; Optionally, the pharmaceutical preparation is a human papillomavirus (HPV) vaccine; Optionally, the pharmaceutical preparation is a chemotherapeutic drug for human tumors; Optionally, the pharmaceutical preparation is a nuclear medicine therapeutic drug for human tumors; Optionally, the pharmaceutical preparation is a human tumor vaccine, including but not limited to polypeptide vaccines, mRNA vaccines, and DNA vaccines; Optionally, the pharmaceutical preparation is a porcine diarrhea bivalent vaccine; Optionally, the pharmaceutical preparation is a porcine reproductive and respiratory syndrome (PRRS) inactivated vaccine; Optionally, the pharmaceutical preparation is a foot-and-mouth disease vaccine; Optionally, the pharmaceutical preparation is a bovine bivalent vaccine; Optionally, the pharmaceutical preparation is a Pasteurella multocida vaccine; Optionally, the pharmaceutical preparation is insulin; Optionally, the pharmaceutical preparation is a botulinum toxin-based cosmetic drug for medical aesthetics.

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