Multi-mode fluid delivery device

Abstract

The present invention relates to a multi-mode fluid delivery device for drugs and vaccines for use in the fields of human clinical care and animal health care. Through the design that multiple needles and multiple holes are matched with the detachable injection head and the needle head piece contained in the detachable injection head, all the advantages of a needle-free injection mode, a micro-needle injection mode and a needle injection mode are combined, the defects of the needle-free injection mode, the micro-needle injection mode and the needle injection mode are eliminated, flexible switching among the needle-free mode, the micro-needle injection mode and the needle injection mode is achieved, and the injection efficiency is improved. The single delivery amount and delivery efficiency of drugs and vaccines are improved while painless and skin injury are avoided, liquid leakage is eliminated, the drugs and vaccines are delivered to one or more target positions with different depths of a human body, the three-dimensional dispersity of the drugs and vaccines at the target positions is controlled, pharmacokinetics is optimized, and the drug delivery efficiency of the drugs and vaccines is improved. Therefore, the contact effect and the bioavailability of the medicine and the vaccine with in-vivo tissues are greatly improved. Related components, systems, and related pharmaceutical and mechanical combinations are also provided.

Description

Technical Field

[0001] The present invention relates to the field of medical devices, and particularly to a multi-mode drug and vaccine delivery device and a combined drug and device product for human clinical medicine and animal health care fields. Background Art

[0002] In the current field of drug and vaccine delivery, needle injection, microneedle injection, and needle-free injection are three main delivery methods. Traditional needle injection is widely used for the delivery of various drugs and vaccines. However, the drugs and vaccines entering the body through needle injection are in an aggregated state, which is not conducive to drug absorption and metabolism. Moreover, needle injection is often accompanied by pain and infection risks for patients, thus causing psychological and physical burdens on patients. For example, needle phobia is the main reason why vaccination cannot be popularized in many countries around the world. The microneedle injection technology, although it can reduce pain and trauma, has limited delivery sites, and its efficiency and applicability are limited when delivering macromolecular drugs or high-dose vaccines. Relatively speaking, needle-free injection technology has greatly improved the dispersion degree of drugs delivered into the body and reduced the risks of pain and infection. However, the application and popularization of pure needle-free injection technology in the fields of clinical medicine and animal health care still face challenges. The main reason is that needle-free injection needs to use high-pressure liquid jets to break the skin, so it greatly limits the area of the delivered liquid jets and the drug dose to be delivered. 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 dispersion mode, needle-free injection pore size design, and the influence of different biological media (such as the epidermis, subcutaneous tissue, and muscle of humans and animals) on drug delivery performance.

[0003] In practical applications, the limitations of needle-free injection technology on the injection pore size and the high requirements for skin fit limit its popularization. This technology is prone to liquid leakage due to the presence of hair, and it is difficult to precisely control the injection position, depth, and dispersion of the liquid medicine. Therefore, although needle-free injection technology has significant advantages in theory, there are still many challenges in actual clinical applications. In addition, the metabolism of drugs and the stimulation of vaccine immunogenicity pose high standards for the three-dimensional dispersion and precise positioning of drugs and vaccines in the body. Existing needle-free injection technology still faces insurmountable difficulties in meeting these requirements. For example, increasing the dispersion degree requires increasing the area of the liquid jet, but the increase in the area of the liquid jet will greatly cause difficulties in breaking the skin, bleeding, and injury.

[0004] A significant gap in current drug delivery technology is how to effectively combine the advantages of needle technology in precise positioning and large-dose delivery, the advantages of needle-free injection technology in high dispersion degree, and the advantages of microneedle injection technology in multi-point delivery to meet the specific needs of different drugs and vaccines. Especially in seeking a solution that can flexibly switch different injection modes according to clinical situations, the existing technology has not been able to provide a satisfactory answer.

[0005] The content described in this background technology is only for facilitating the understanding of the related technologies in the field and is not regarded as an admission of the prior art. Summary of the Invention

[0006] The purpose of the present invention is to provide a multi-mode fluid delivery device, which 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.

[0007] An embodiment of the present invention provides a multi-mode fluid delivery device, including:

[0008] A tube for accommodating 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;

[0009] 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 tube in the second end; and

[0010] A power mechanism, the power mechanism including a piston capable of pushing the fluid provided in the first end of the tube or operably connecting the piston to apply a delivery pressure to the piston for pushing the fluid.

[0011] Some of the other optional features and technical effects of the embodiments of the present invention are described below, and some can be understood by reading this article. Brief Description of the Drawings

[0012] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. The elements shown are not limited by the scale shown in the drawings, and the same or similar reference numerals in the drawings represent the same or similar elements, where:

[0013] Figure 1 A schematic structural diagram showing a multi-mode fluid delivery device according to an embodiment of the present invention;

[0014] Figure 2 A schematic structural diagram showing a multi-mode fluid delivery device according to an embodiment of the present invention;

[0015] Figure 3 A schematic layout diagram of needle members showing a multi-mode fluid delivery device according to an embodiment of the present invention;

[0016] Figure 4 A schematic layout diagram of needle members showing a multi-mode fluid delivery device according to an embodiment of the present invention;

[0017] Figure 5Schematic diagram of the arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0018] Figure 6 Schematic diagram of the arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0019] Figure 7 Schematic diagram of a needle component of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0020] Figure 8 Schematic diagram of a needle component of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0021] Figure 9 Schematic diagram of the linear arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0022] Figure 10 Schematic diagram of the linear arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0023] Figure 11 Schematic diagram of the linear arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0024] Figure 12 Schematic diagram of the linear arrangement of needle components of a multi-mode fluid delivery device according to an implementation of the present invention;

[0025] Figure 13 Schematic diagram of the array arrangement of needle components of a multi-mode fluid delivery device according to an implementation of the present invention;

[0026] Figure 14A Schematic diagram of the arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0027] Figure 14B Schematic diagram of the arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0028] Figure 15 Schematic diagram of the arrangement of needle components with different needle hole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0029] Figure 16 Schematic diagram of the arrangement of needle components with different needle hole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0030] Figure 17 Schematic diagram of the arrangement of needle components with different needle hole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0031] Figure 18 Schematic diagram showing the arrangement of needle tip members with different needle hole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0032] Figure 19 Schematic diagram showing the annular arrangement of needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0033] Figure 20 Schematic diagram showing the annular arrangement of needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0034] Figure 21 Schematic diagram showing the coaxial annular arrangement of multiple groups of needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0035] Figure 22 Schematic diagram showing the coaxial annular arrangement of multiple groups of needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0036] Figure 23 Schematic diagram showing the coaxial annular arrangement of multiple groups of needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0037] Figure 24 Schematic diagram showing the arrangement of the central needle tip member and the peripheral needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0038] Figure 25 Schematic diagram showing the arrangement of the central needle tip member and the peripheral needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0039] Figure 26 Schematic diagram showing the arrangement of the central needle tip member and the peripheral needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0040] Figure 27 Schematic diagram showing the arrangement of the central needle tip member and the peripheral needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0041] Figure 28 Schematic diagram showing the arrangement of the central needle tip member and the peripheral needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0042] Figure 29 Schematic diagram showing the arrangement of the central needle tip member and the peripheral needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0043] Figure 30 Schematic diagram showing the arrangement of the central needle tip member and the peripheral needle tip members of a multi-mode fluid delivery device according to an embodiment of the present invention;

[0044] Figure 31 Schematic diagram of the needle 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;

[0045] Figure 32 Schematic diagram of the needle 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] Figure 33 Schematic diagram of the schematic injection head of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0047] Figure 34 Schematic diagram of the schematic injection head of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0048] Figure 35 Schematic diagram of the schematic needle kit of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0049] Figure 36 Schematic diagram of the schematic needle kit of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0050] Figure 37 Schematic diagram of the schematic needle kit of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0051] Figure 38 Schematic diagram of the needleless cannula of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0052] Figure 39 Schematic diagram of the needleless cannula of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0053] Figure 40 Schematic diagram of the needle arrangement of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0054] Figure 41 Schematic diagram of the structure of the second end of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0055] Figure 42 Schematic diagram of the schematic structure of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0056] Figure 43 Schematic diagram of the structure of the schematic simulation model of the delivery of the multi-mode fluid delivery device according to a specific embodiment of the present invention;

[0057] Figure 44 Schematic diagram of the porous dispersion effect of the delivery of the multi-mode fluid delivery device according to an embodiment of the present invention;

[0058] Figure 45 Schematic diagram showing the porous dispersion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

[0059] Figure 46 Schematic diagram showing the porous dispersion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

[0060] Figure 47 Schematic diagram showing the porous dispersion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

[0061] Figure 48 Schematic diagram showing the arrangement of needle parts delivered by a multi-mode fluid delivery device according to a specific embodiment of the present invention;

[0062] Figure 49 Line graph showing immunological test data delivered by a multi-mode fluid delivery device according to a specific embodiment of the present invention;

[0063] Figure 50 Line graph showing immunological test data delivered by a multi-mode fluid delivery device according to a specific embodiment of the present invention; and

[0064] Figure 51 Line graph showing immunological test data delivered by a multi-mode fluid delivery device according to a specific embodiment of the present invention. Detailed Description of the Invention

[0065] To make the objectives, 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 the accompanying drawings. Herein, the illustrative embodiments of the present invention and their descriptions are used to explain the present invention, but not to limit the present invention.

[0066] As used herein, the term "comprising" and its variants mean open inclusion, that is, "including but not limited to". Unless otherwise stated, the term "or" means "and / or". The term "based on" means "at least partially based 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. There may also be other explicit and implicit definitions below.

[0067] In multiple embodiments of the present invention, as Figure 1 and Figure 2 shown, a multi-mode fluid delivery device is provided, particularly a multi-mode fluid delivery device for drugs and vaccines, which may include a tube 100 for containing fluid, and the tube 100 has a first end 110 and a second end 120. As Figure 1As shown, holes 121 for distributing the fluid within the tube may be provided in the second end 120. As a supplement or alternative, as Figure 2 shown, a self-sealing elastic portion 122 may be provided in the second end 120.

[0068] The multi-mode fluid delivery device may further include an injection head 200 detachably connected to the tube 100, and the injection head 200 includes one or more needle members 210. The one or more needle members 210 are configured to removably dock with the self-sealing elastic portion 122 in the second end 120 or the holes 121 for distributing the fluid 130 within the tube 100.

[0069] The multi-mode fluid delivery device may further include a power mechanism 300, and the power mechanism 300 includes a piston 310 disposed in the first end 110 of the tube 100 that can push the fluid 130 or is operatively connected to the piston 310 to apply a delivery pressure to the piston 310 that pushes the fluid 130.

[0070] In some embodiments of the present invention, as Figure 2 shown, 3 self-sealing elastic portions 122 are provided in the second end 120, and the 3 needle members 210 are configured to removably connect to the self-sealing elastic portions 122 in the second end 120. Specifically, they are configured such that the 3 needle members 210 are inserted into the 3 self-sealing elastic portions 122 provided in the corresponding second end 120.

[0071] In some embodiments of the present invention, the self-sealing elastic portion 122 is formed by filling silicone in the holes 121 for distributing the fluid within the tube provided in the second end 120. The specific composition of the above silicone is not limited herein. Similarly, materials of other suitable types that can be inserted by the plurality of needle members 210 and are different from silicone may be filled in the holes 121, and this is not limited herein.

[0072] In some embodiments of the present invention, as Figure 1 and Figure 2 shown, 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 a delivery pressure to the piston 310. It is also conceivable that in some other embodiments of the present invention, the power mechanism 300 may be integrally integrated with the piston 310.

[0073] 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 use compressed gas, such as compressed nitrogen or compressed carbon dioxide gas for driving, or may use a compressed mechanical spring for driving, or may also be driven by a piezoelectric actuating device, which is not limited herein.

[0074] In some embodiments of the present invention, compared with manual needle injection (the pushing speed of the piston inside the syringe needle is about 0.01 m / s), the piston speed when the piston 310 of the multi-mode fluid delivery device of the present invention pushes 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 when the piston 310 pushes 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.

[0075] In some embodiments of the present invention, compared with manual needle injection (the outlet jet speed of the fluid ejected from the needle is about 2 m / s), the outlet jet speed when the fluid 130 of the multi-mode fluid delivery device of the present invention is pushed away from the plurality of holes 121 in the second end 120 or one or more needle members 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 even more preferably greater than or equal to 150 m / s.

[0076] In some embodiments of the present invention, at least one of the one or more needle members 210 is substantially inserted into a human body or an animal body.

[0077] In some embodiments of the present invention, at least one of the one or more needle members is substantially inserted into a human body or an animal body;

[0078] In some embodiments of the present invention, at least one of the one or more needle members has a pore 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 more preferably in the range of 0.11 mm to 0.50 mm;

[0079] In some embodiments of the present invention, at least one of the self-sealing elastic part 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 more preferably in the range of 0.11 mm to 0.50 mm.

[0080] In some embodiments of the present invention, 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 single hole area of the needle member or hole is 0.0028 - 0.035 mm 2 , preferably 0.0028 - 0.020 mm 2 , more preferably 0.0028 - 0.009 mm 2 , wherein the single hole area of the needle member refers to the single hole area calculated from the inner diameter of the needle of the needle member.

[0081] In an embodiment of the present invention, the multi-mode fluid delivery device of the present invention can deliver a volume (pre-delivery volume) of drug or vaccine of 0.3 mm 3 or more, preferably a volume (pre-delivery volume) of drug or vaccine of 1.0 mm 3 or more, more preferably a volume (pre-delivery volume) of drug or vaccine of 5.0 mm 3 or more; in some embodiments, the volume (pre-delivery volume) of drug or vaccine delivered at one time by the multi-mode fluid delivery device of the present invention can reach 14.0 mm 3 , in a further embodiment, the volume (pre-delivery volume) of drug or vaccine delivered at one time by the multi-mode fluid delivery device of the present invention can reach 46.0 mm 3 .

[0082] In some embodiments of the present invention, the one or more needle members 210 have different adjustable skin insertion depths.

[0083] 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 insert but forms a tight contact with the human or animal skin.

[0084] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that substantially inserts into the inner layer of the human or animal skin.

[0085] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that substantially inserts into the subcutaneous layer of the human or animal.

[0086] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that substantially inserts into the muscle layer of the 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 substantially inserted into an organ of a human or an animal body.

[0088] In some embodiments of the present invention, at least one of the one or more needle members 210 has an adjustable insertion depth.

[0089] In some embodiments of the present invention, the multi-mode fluid delivery device is configured such that the dispersion volume of the fluid 130 in the body is greater than the undelivered volume. Preferably, the dispersion volume of the fluid in the body is more than 1.50 times, 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 the undelivered volume.

[0090] In some embodiments of the present invention, the dispersion volume ratio refers to the ratio of the volume of the dispersion region of the fluid delivered by the multi-mode fluid delivery device in the body to the original volume of the undelivered fluid, that is:

[0091]

[0092] In some other embodiments of the present invention, the dispersion volume ratio may also refer to the ratio of the dispersion volume of the fluid delivered by the multi-mode fluid delivery device according to the embodiments of the present invention in the body to the dispersion volume of the fluid delivered by the artificial needle injection method in the body, that is:

[0093]

[0094] Wherein, the dispersion volume of the delivered fluid can be calculated in various ways, which is not limited herein. 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 an image analysis software can be used to calculate the volume of the dispersion region, such as calculating the envelope of the dispersion region to estimate the volume of the dispersion region.

[0095] It can be understood that when the delivered fluid enters the body through the multi-mode fluid delivery device, due to the dispersion effect of the fluid in the body, the three-dimensional space region of its distribution becomes larger. This dispersion 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.

[0096] It can be understood that those skilled in the art can confirm the corresponding dispersion degrees of the dermis, epidermis, subcutaneous, muscle and human organs in the body of the inoculated subject according to the needle-free delivery inoculated subject under the teaching of the embodiments of the present invention, including but not limited to different types of animals or patients with different physical conditions.

[0097] In some embodiments of the present invention, such as Figures 3 to 6As shown, the needle aperture d of the one or more needle members 210 can be configured such that the fluid jet passing through the one or more needle members 210 has various different in-vivo dispersions, i.e., different dispersion volume ratios, dispersion depths or dispersion 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, and the size of the first needle aperture d1 is configured such that the fluid jet passing through the one or more needle members 210 has different dispersions, preferably different dispersion depths, so that the fluid jet disperses in at least one of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs.

[0098] In some embodiments of the present invention, the outlet jet velocity v of the one or more needle members 210 can be configured such that the fluid jet passing through the one or more needle members 210 has various different in-vivo dispersions, i.e., different dispersion volume ratios, dispersion depths or dispersion breadths; thus, in some embodiments of the present invention, the outlet jet velocities 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 such that the fluid jet passing through the one or more needle members 210 has different dispersions, preferably different dispersion depths, so that the fluid jet disperses in at least one of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs.

[0099] In some embodiments of the present invention, the plurality of needle members includes a first needle member and a second needle member.

[0100] In some embodiments of the present invention, the first needle member has a first skin insertion depth located in one of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs, and the second needle member has a second skin insertion depth located in another of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs. For example, as Figure 7 shown, the skin insertion depths of the one or more needle members 210 can be configured to be unequal, the first needle member 210 has a first skin insertion depth L1, and the second needle member 210' has a second skin insertion depth L2, where L1≠L2.

[0101] In some embodiments of the present invention, the first needle member has a first needle aperture, and the size of the first needle aperture is configured such that the fluid jet passing through the first needle member disperses in at least one of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs; the second needle member has a second needle aperture, and the size of the second needle aperture is configured such that the fluid jet passing through the second needle member disperses in at least another of the dermis layer, epidermis layer, subcutaneous tissue, muscle and human organs. For example, as Figure 8As shown, the first needle member 210 has a first needle aperture diameter d1, and the second needle member 210' has a second needle aperture diameter d2, where d1 ≠ d2.

[0102] In some embodiments of the present invention, the first needle member has a first outlet jet velocity configured such that a fluid jet through the first needle member disperses in at least one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs; the second needle member has a second outlet jet velocity configured such that a fluid jet through the second needle member disperses in at least one other 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.

[0103] In some embodiments of the present invention, the plurality of needle members further includes a third needle member;

[0104] In some embodiments of the present invention, the third needle member has a third skin insertion depth in yet another one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs;

[0105] In some embodiments of the present invention, the third needle member has a third needle aperture diameter sized such that a fluid jet through the third needle member disperses in at least one more of the dermis, epidermis, or subcutaneous tissue among the dermis, epidermis, subcutaneous tissue, muscle, and human organs;

[0106] In some embodiments of the present invention, the third needle member has a third outlet jet velocity configured such that a fluid jet through the third needle member disperses in at least one more of the dermis, epidermis, subcutaneous tissue, muscle, and human organs.

[0107] In some embodiments of the present invention, as Figures 9 to 11 shown, the one or more needle members 210 may be arranged in a straight line.

[0108] In some embodiments of the present invention, the one or more needle members 210 are arranged in a straight line along the diameter or the median line of the injection head 200, and one of the one or more needle members 210 arranged in a straight line along the diameter or the median line of the injection head 200 is located at the center of the injection head 200.

[0109] In one embodiment of the present invention, as Figure 10 shown, there are 3 needle members 210 arranged in a straight line along the diameter (median line) of the injection head 200, including the needle member 210' located at the center of the injection head 200.

[0110] In some embodiments of the present invention, the plurality of needle members 210 arranged in a straight line are equally spaced.

[0111] In one embodiment of the present invention, as Figures 10 to 11 shown, a plurality of needle members 210 are arranged in a straight line along the diameter (center line) of the injection head 200, and the plurality of needle members 210 are equally spaced.

[0112] In some embodiments of the present invention, as Figures 9 to 11 shown, the plurality of needle members 210 arranged in a straight line are mirror-symmetrical with respect to another diameter or center line of the injection head 200 that is different from the straight line.

[0113] In some embodiments of the present invention, the needle members 210 may have multiple groups, and each group of needle members 210 is arranged in a straight line, and each group of needle members 210 is arranged along a diameter or a center line of the injection head 200.

[0114] In one embodiment of the present invention, as Figure 12 shown, three groups of needle members 210, namely group A, group B, and group C, are arranged on the injection head 200 (in Figure 12 and subsequent figures, the needle members 210 of the same group are shown by dashed lines), wherein both group A and group C include 2 needle members 210 arranged in a straight line, and group B includes 3 needle members 210 arranged in a straight line.

[0115] 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 the first and second diameters or center lines perpendicular to each other of the injection head 200, respectively.

[0116] In one embodiment of the present invention, as Figure 13 shown, 4 needle members 210 are arranged in an array on the injection head 200 (the array arrangement relationship of the 4 needle members 210 is shown by perpendicular dashed lines in Figure 13 ), and the 4 needle members 210 are mirror-symmetrical with respect to the first and second diameters (center lines) perpendicular to each other of the injection head 200, respectively.

[0117] In some embodiments of the present invention, the skin insertion depth L' of the needle member 210' located at the center of the injection head 200 is different from the skin insertion depth L of the other needle members 210 of the plurality of needle members 210.

[0118] In one embodiment of the present invention, as Figure 7As shown, there are 3 needle members 210 arranged linearly along the diameter (midline) of the injection head 200, including a needle member 210' located at the 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 the other needle members 210 among the multiple needle members 210. In Figure 7 the configuration shown, L' > L. It can be understood that in other configurations, L' < L can also be configured.

[0119] 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 other groups of needle members 210;

[0120] In one embodiment of the present invention, as Figure 14A shown, there are a total of 2 groups of needle members 210, namely group A and group B, arranged linearly on the injection head 200. Among them, both group A and group B are arranged in a straight line. Among them, the skin insertion depth of the 2 needle members 210' included in group B is L', and the skin insertion depth of the 2 needle members 210 included in group A is L, where L' ≠ L. In Figure 14A the configuration shown, L' < L. It can be understood that in other configurations, L' > L can also be configured.

[0121] In some embodiments of the present invention, the needle aperture d' of the needle member 210' located at the center of the injection head 200 is different from the needle aperture d of the other needle members 210 among the multiple needle members 210.

[0122] In one embodiment of the present invention, as Figure 15 and Figure 16 shown, there are 3 needle members 210 arranged linearly on the injection head 200, including a needle member 210' with a needle aperture of d' located at the center of the injection head 200, and the other two needle members 210 with a needle aperture of d, where d' ≠ d. In Figure 15 the configuration shown, d' < d. In Figure 8 and Figure 16 the configuration shown, d' > d.

[0123] In some embodiments of the present invention, the needle aperture d2 of at least one group of needle members 210 among the multiple groups of needle members 210 is different from the needle aperture d1 of other groups of needle members 210.

[0124] In one embodiment of the present invention, as Figures 17 to 18As shown, there are three groups of needle members 210, namely Group A, Group B, and Group C, arranged on the injection head 200. Among them, both Group A and Group C include 2 needle members 210 arranged in a straight line, while Group B includes 3 needle members 210' arranged in a straight line. Among them, the needle apertures of the 3 needle members 210' included in Group B are d', and the needle apertures of the needle members 210 included in Group A and Group B are d, where d'≠d.

[0125] 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 the other needle members 210 of the plurality of needle members 210.

[0126] In some embodiments of the present invention, the outlet jet velocity v2 of at least one group of the plurality of groups of needle members 210 is different from the outlet jet velocity v1 of the other groups of needle members 210.

[0127] In one embodiment of the present invention, as Figure 17 and Figure 18 shown, there are three groups of needle members 210, namely Group A, Group B, and Group C, arranged on the injection head 200. Among them, both Group A and Group C include 2 needle members 210 arranged in a straight line, while Group B includes 3 needle members 210' arranged in a straight line. Among them, the outlet jet velocity of the 3 needle members 210' included in Group B is v2, and the outlet jet velocity of the needle members 210 included in Group A and Group C is v1, where v2≠v1.

[0128] In some embodiments of the present invention, the plurality of needle members 210 on the injection head 200 are arranged in a circular pattern; the plurality of needle members 210 are arranged in a circular pattern with the center of the injection head 200 as the center.

[0129] In one embodiment of the present invention, as Figure 19 and Figure 20 shown, by way of example, Figure 19 shows that there are 3 needle members 210 arranged on the injection head 200, and the 3 needle members 210 are arranged in a circular pattern with the center O of the injection head 200 as the center, while Figure 20 shows that there are 4 needle members 210 arranged on the injection head 200, and the 4 needle members 210 are arranged in a circular pattern with the circle O of the injection head 200 as the center.

[0130] In some embodiments of the present invention, there are multiple groups of needle members 210, and each group of needle members 210 is arranged in a circular pattern, and the multiple groups of needle members 210 are arranged in a coaxial circular pattern with each other.

[0131] In one embodiment of the present invention, asFigure 21 As shown, there are two groups of needle members 210, namely Group A and Group B, arranged on the injection head 200. Among them, both Group A and Group B are arranged in a circular pattern and are coaxially arranged in a circular pattern with the center O of the injection head 200 as the center of the circle.

[0132] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in a circular pattern has a skin insertion depth L' different from that of the other needle members 210.

[0133] In some embodiments of the present invention, the skin insertion depth of at least one group of the plurality of groups of needle members 210 arranged in a circular pattern is different from the skin insertion depth L of the other groups of needle members 210.

[0134] In one embodiment of the present invention, as Figure 14B and Figure 23 shown, there are two groups of needle members 210, namely Group A and Group B, arranged on the injection head 200. Among them, each of Group A and Group B includes three of the needle members 210. Figure 14B For Figure 23 the cross-sectional view along the axis direction of the tube 100 shown in the configuration, which shows the skin insertion depths of the plurality of needle members 210 arranged in a circular pattern on the injection head. Among them, 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. Figure 14B In the configuration shown in, L' > L; it can be understood that in other configurations, L' < L can also be set.

[0135] In some embodiments of the present invention, the skin insertion depth L of the plurality of groups of needle members 210 arranged coaxially in a circular pattern decreases or increases radially.

[0136] In one embodiment of the present invention, referring again to Figure 14B and Figure 23 , which shows the skin insertion depths of the plurality of needle members 210 arranged in a circular pattern on the injection head. Among them, 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. 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 other configurations, 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.

[0137] In one embodiment of the present invention, referring again to Figure 14B and Figure 23, there are 2 sets of needle members 210, namely Group A and Group B, arranged on the injection head 200. Among them, both Group A and Group B are arranged in a circular pattern and are coaxially arranged in a circular pattern with the center of the injection head 200 as the center. Among them, the skin insertion depth of the 3 needle members 210' included in Group A is L', and the skin insertion depth of the needle members 210 included in Group B is L, where 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 circular pattern with each other, increase radially outward, that is: L' > L; it can be understood that in another configuration, it is also possible to set the skin insertion depths of the needle members 210' of Group A and the needle members 210 of Group B to decrease radially outward, that is: L' < L.

[0138] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in a circular pattern has a needle aperture d' different from that of the other needle members 210;

[0139] In some embodiments of the present invention, the needle aperture d' of at least one set of needle members 210 of the multiple sets of needle members 210 is different from the needle aperture d of the needle members 210 of the other sets;

[0140] In some embodiments of the present invention, the needle apertures d of the multiple sets of needle members 210 arranged coaxially in a circular pattern with each other decrease or increase radially.

[0141] In one embodiment of the present invention, as Figure 14B and Figure 22 and Figure 23 shown, there are 2 sets of needle members 210, namely Group A and Group B, arranged on the injection head 200. Among them, both Group A and Group B are arranged in a circular pattern and are coaxially arranged in a circular pattern with the center (center) of the injection head 200 as the center. Among them, the needle aperture of the 3 needle members 210' included in Group B is d', and the needle aperture of the needle members 210 included in Group A is d, where d'≠d; and in Figure 22 the configuration shown, 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 circular pattern with each other, decrease radially outward, that is: d' > d, while in Figure 23 the configuration shown, 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.

[0142] In some embodiments of the present invention, at least one of the needle members 210 arranged in a circular pattern has an outlet jet velocity v' different from that of the other holes;

[0143] In some embodiments of the present invention, the outlet jet velocity v' of at least one set of needle members 210 of the multiple sets of needle members 210 is different from the outlet jet velocity v of the holes of the other sets;

[0144] In some embodiments of the present invention, the outlet jet velocity v of the multiple groups of needle members 210 arranged coaxially and annularly with each other increases or decreases radially.

[0145] In some embodiments of the present invention, the multiple needle members 210 include a central needle member 210" located at the center or the center of the injection head 200 and multiple peripheral needle members 210 located around the central needle member 210.

[0146] In one embodiment of the present invention, as Figure 24 shown, 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 are arranged on the injection head 200.

[0147] In some embodiments of the present invention, the multiple peripheral needle members 210 are arranged in an annular shape.

[0148] In some embodiments of the present invention, the multiple peripheral needle members 210 are arranged in a coaxial annular shape around the central needle member 210".

[0149] In one embodiment of the present invention, as Figures 24 to 26 shown, a central needle member 210" located at the center (center) of the injection head 200 and multiple peripheral needle members 210 located around the central needle member 210 are arranged on the injection head 200. By way of example, Figure 26 a configuration in which 4 peripheral needle members 210 are arranged on the injection head 200 is shown in.

[0150] In some embodiments of the present invention, there are multiple groups of the peripheral holes 121. Each group of the peripheral needle members 210 is arranged in an annular shape, and the multiple groups of the peripheral needle members 210 are arranged in a coaxial annular shape around the central needle member 210".

[0151] In one embodiment of the present invention, as Figure 27 shown, 6 peripheral needle members 210 are provided on the injection head 200. The 6 peripheral needle members 210 are divided into two groups A and B arranged evenly in a ring shape. Among them, each of the two groups A and B includes 3 peripheral needle members 210, and the two groups of the peripheral needle members 210 are arranged in a coaxial annular shape around the central needle member 210".

[0152] 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 multiple peripheral needle members 210.

[0153] In one embodiment of the present invention, there is provided 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 on the injection head 200, where L" ≠ L. In one configuration, L" < L, and in another configuration, L" > L.

[0154] In some embodiments of the present invention, the skin insertion depth L' of at least one group of the plurality of peripheral needle members 210 is different from the skin insertion depth L of other peripheral needle member groups 210.

[0155] 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 illustrated configurations, L1 > L2, and in another configuration, L1 < L2.

[0156] In some embodiments of the present invention, the skin insertion depths of the plurality of needle members 210 and the central needle member 210" arranged coaxially and annularly with each other decrease or increase radially.

[0157] In one embodiment of the present invention, the skin insertion depth of the one central needle member 210" is L", 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 configuration, the skin insertion depths of the needle members 210 of groups A and B and the central needle member 210" arranged coaxially and annularly with each other decrease radially outward, that is: L" > L1 > L2, and in another configuration, the skin insertion depths of the needle members 210 of groups A and B and the central needle member 210" arranged coaxially and annularly with each other increase radially, that is: L" < L1 < L2.

[0158] In some embodiments of the present invention, the needle aperture d" of the central needle member 210" is different from the needle aperture d of the plurality of peripheral needle members 210.

[0159] In one embodiment of the present invention, as Figures 28 to 29 shown, there is provided a central needle member 210" with a needle aperture of d" and three peripheral needle members 210 with a needle aperture of d on the injection head 200, where d" ≠ d. In the Figure 28 shown configuration, d" < d, and in the Figure 29 shown configuration, d" > d.

[0160] In another embodiment of the present invention, as Figures 30 to 32As shown, on the injection head 200, there is a central needle member 210" with a needle aperture of d" and six peripheral needle members 210 with a needle aperture of d. Among them, d" ≠ d, and the six peripheral needle members 210 are divided into two groups, A and B, which are evenly arranged in a ring. Each of the A and B groups contains three peripheral needle members 210, and the two groups of peripheral needle members 210 are arranged in a coaxial ring around the central needle member 210".

[0161] In some embodiments of the present invention, the needle aperture d1 of at least one group of the multiple groups of peripheral needle members 210 is different from the needle aperture d2 of other groups of peripheral needle members 210.

[0162] In one embodiment of the present invention, as Figure 31 and Figure 32 shown, among them, the three peripheral needle members 210 included in group A have a needle aperture of d1, while the three peripheral needle members 210 included in group B have a needle aperture of d2, and d1 ≠ d2. In the configuration shown in Figure 31 d1 > d2, while in the configuration shown in Figure 32 d1 < d2.

[0163] In some embodiments of the present invention, the needle apertures of the multiple groups of needle members 210 and the central needle member 210" arranged in a coaxial ring increase or decrease radially.

[0164] In one embodiment of the present invention, as Figure 31 and Figure 32 shown, among them, the needle aperture of the one central needle member 210" is d", the three peripheral needle members 210 included in group A have a needle aperture of d1, while the three peripheral needle members 210 included in group B have a needle aperture of d2, and d1 ≠ d2; in the configuration shown in Figure 31 the needle apertures of the A and B groups of needle members 210 and the central needle member 210" arranged in a coaxial ring decrease radially outward, that is: d" > d1 > d2, while in the configuration shown in Figure 32 the needle apertures of the A and B groups of needle members 210 and the central needle member 210" arranged in a coaxial ring increase radially, that is: d" < d1 < d2.

[0165] 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 multiple peripheral needle members 210.

[0166] In some embodiments of the present invention, the outlet jet velocity v1 of at least one group of the multiple groups of peripheral needle members 210 is different from the outlet jet velocity v2 of other peripheral groups of needle members 210.

[0167] In some embodiments of the present invention, the outlet jet velocities of the multiple sets of needle members 210 and the central needle member 210'' that are arranged in coaxial rings with each other increase or decrease radially.

[0168] In some embodiments of the present invention, as Figure 33 and Figure 34 shown, the injection head 200 includes a support portion 220 for supporting the needle member.

[0169] In some embodiments of the present invention, the support portion 220 is configured as a tubular wall extending towards the syringe 100 side; while in some other embodiments of the present invention, the support portion 220 can be an independent component that is independent of the injection head 200 and is used to connect the injection head 200 to the tube 100.

[0170] In some embodiments of the present invention, as Figure 33 and Figure 34 shown, the needle member 210 further includes a first needle head portion 211 located on the side of the support portion 220 facing away from the syringe 100.

[0171] In some embodiments of the present invention, as Figure 33 and Figure 34 shown, the needle member 210 includes a fixed gasket 230 located on the side of the support portion 220 facing the syringe 100, and the fixed gasket 230 is used to fix the needle member 210;

[0172] In some embodiments of the present invention, as Figure 33 and Figure 34 shown, the needle member 210 includes a second needle head portion 212 located on the side of the support portion 220 facing the syringe 100;

[0173] In some embodiments of the present invention, Figure 33 and Figure 34 Alternatively, the needle member 210 does not extend from the side of the support portion 220 facing away from the syringe 100, so that the needle member 210 forms a needleless micropore 213 on the side of the support portion 220 facing away from the syringe 100.

[0174] In some embodiments of the present invention, the needle member 210 further includes an intrusive soft needle removably connected to the hole 210.

[0175] In some embodiments of the present invention, as Figures 35 to 37 shown, the multi-mode fluid delivery device further includes a needle kit 400, and the needle kit 400 includes a needle sleeve 401 for removably surrounding the first needle head portion 211 of the needle member 210.

[0176] In some embodiments of the present invention, as Figures 35 to 37 shown, the height h of the needle sleeve 401 of the needle kit 400 is greater than or equal to the first needle head 211 of the needle head member 210, so as to completely surround the first needle head 211;

[0177] In some embodiments of the present invention, as Figures 35 to 37 shown, optionally, the height h of the needle sleeve 410 of the needle kit 400 is less than the first needle head 211 of the needle head member 210, so as to partially surround the first needle head 211, such that the first needle head 211 protrudes from the front end of the needle sleeve to form an insertion portion 214.

[0178] In some embodiments of the present invention, as Figures 35 to 37 shown, 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, so as to completely surround the first needle head 211 to protect the first needle head 211.

[0179] In some embodiments of the present invention, as Figures 35 to 37 shown, there are multiple needle kits 400, and the multiple needle kits 400 include a first needle kit 410 and a second needle kit 420,

[0180] the first needle kit 410 is configured such that the state of surrounding the first needle head 211 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;

[0181] the second needle kit 420 is configured such that the state of surrounding the first needle head 211 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.

[0182] In some embodiments of the present invention, there are multiple needle kits 400, and the multiple 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;

[0183] the first needle kit 410 is configured such that the first needle head 211 surrounded by it is completely surrounded;

[0184] the second needle kit 420 is configured such that the insertion portion 214 of the first needle head 211 surrounded by it is located in the dermis layer;

[0185] the third needle kit 430 is configured such that the insertion portion 214 of the first needle head 211 surrounded by it is located in the epidermis layer;

[0186] The fourth needle assembly 440 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located subcutaneously;

[0187] The fifth needle assembly 450 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located intramuscularly;

[0188] The sixth needle assembly 460 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located in a human organ.

[0189] In some embodiments of the present invention, the needle sleeve structure can be integrated on the injection head. In some other embodiments of the present invention, the above-mentioned needle sleeve structure can axially move relative to the needle member along the axial direction of the needle member.

[0190] In a further embodiment of the present invention, 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. 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 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 when the needle sleeve portion is retracted, flush with the needle sleeve portion, located in the dermis layer, located in the epidermis layer, located subcutaneously, located intramuscularly, and located in a human organ. In some embodiments of the present invention, 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.

[0191] In an 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. A screwing ring and a first thread portion are provided on the rotating member, and a second thread portion matching the first thread portion is provided on the needle member. 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 axially extend distally, such 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.

[0192] In another embodiment of the present invention, the injection head includes a needle sleeve portion sleeved on the needle member and a rotating member operably connected to the needle member. A screwing ring and a first thread portion are provided on the rotating member, and a second thread portion matching the first thread portion is provided on the needle sleeve 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 axially extend distally, so that the needle sleeve portion sleeved on the needle member covers the top end of the needle member to protect the needle member.

[0193] 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 operably connected to the needle member. A screwing ring and a first thread portion are provided on the rotating member, a second thread portion matching the first thread portion is provided on the needle sleeve portion, and a third thread portion matching the first thread portion is provided on the needle member. 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.

[0194] In an 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 steplessly adjusted through the rotating member, so as to realize the stepless adjustment of the retraction, exposure or exposure length of the needle member relative to the needle sleeve portion.

[0195] In some embodiments of the present invention, the injection head 200 includes a connecting portion 240 for detachably connecting the injection head 200 to the tube 100;

[0196] In some embodiments of the present invention, as Figure 33 and 34 shown, the connecting portion 240 is a threaded connecting portion;

[0197] In some embodiments of the present invention, the connecting portion 240 is a snap connection portion; optionally, the connecting portion 240 is an adhesive connection portion.

[0198] In some embodiments of the present invention, the multi-mode fluid delivery device further includes a locking member for locking the injection head 200 to the tube. The locking member includes a connecting portion for detachably connecting the locking member to the tube;

[0199] In some embodiments of the present invention, the connecting portion is a threaded connecting portion;

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

[0201] In some embodiments of the present invention, the connecting portion is an adhesive connection portion.

[0202] In some embodiments of the present invention, any of the multi-mode fluid delivery devices in the above embodiments of the present invention can also be used in combination with a triple vaccine against feline rhinotracheitis, calicivirus disease, and panleukopenia, wherein the triple vaccine is also known as the feline triple vaccine. Accordingly, the embodiments of the present application also provide corresponding drug-device combination products. In the embodiments of the present invention, the drug-device combination product can include or can be a drug delivery system.

[0203] In the embodiments of the present invention, the feline triple vaccine refers to an inactivated vaccine for preventing common infectious diseases in cats. It can prevent feline rhinotracheitis, feline calicivirus disease, and feline panleukopenia. These three diseases are the most common infectious diseases in cats. When the feline triple vaccine was developed, the dominant epidemic strains of the three infectious diseases in cats were screened from a large number of clinical samples. Therefore, it has the characteristics of good safety, rapid antibody production, long immune duration, and one injection preventing three diseases. It is applicable to cats over 8 weeks old, and generally requires three doses of the basic immunization vaccine at 8 weeks, 12 weeks, and 16 weeks of age. After completing the basic immunization, one booster dose should be administered annually to maintain the immune effect.

[0204] In some embodiments of the present invention, on the injection head 200 of the multi-mode fluid delivery device used in combination with the feline triple vaccine, there are 3 holes 121 arranged in an equally spaced circular pattern around the center of the injection head 200, and the distance between the three holes 121 and the center of the injection head 200 is 1.25 mm ± 20%.

[0205] 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 feline triple vaccine is configured to be 0.12 m / s ± 20%.

[0206] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the feline triple vaccine is configured such that the outlet jet velocity of the feline triple vaccine when it is pushed away from the hole 121 in the injection head 200 by the piston 210 is 150.00 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 such that the dispersion volume of the feline triple vaccine in the body is more than 1.5 times the undelivered volume of the feline triple vaccine.

[0208] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the feline triple vaccine is configured such that the average antibody titer 14 days after the second dose of the feline triple vaccine 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.

[0209] In an embodiment of the present invention, the average antibody titer is an index for measuring the intensity of the immune response and is used to evaluate the antibody level produced by an organism against a specific antigen (such as a virus, a bacterium, or a vaccine). It is expressed as the average of the serum dilution multiples that can neutralize or bind a certain amount of antigen under specific conditions. In other words, the higher the average antibody titer, the stronger the ability of the antibodies produced by the organism to fight against specific pathogens.

[0210] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the feline triple vaccine 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 that of the average antibody titer of the needle injection.

[0211] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the feline triple vaccine is configured such 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 that of the average antibody titer of the needle injection.

[0212] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the feline triple vaccine 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 that of the average antibody titer produced by the needle injection of 100% of the vaccine dose.

[0213] In some embodiments of the present invention, any of the multi-mode fluid delivery devices in the above embodiments of the present invention can also be used in combination with the hepatitis B vaccine. Thus, the embodiments of the present application also provide corresponding drug-device combination products. In an embodiment of the present invention, the drug-device combination product may include or may be a drug delivery system.

[0214] In the embodiments of the present invention, the hepatitis B vaccine refers to a recombinant yeast hepatitis B vaccine (Hansenula anomala) used for preventing hepatitis B (a viral liver disease), which is prepared by purifying the hepatitis B virus surface antigen (HBsAg) expressed by recombinant Hansenula anomala, adding aluminum adjuvant, and the active ingredient is the hepatitis B virus surface antigen. The vaccine is applicable to individuals susceptible to hepatitis B, especially the following: (1) newborns, especially those whose mothers are positive for HBsAg and HBeAg; (2) individuals susceptible to hepatitis B aged 16 and above; (3) medical staff engaged in medical work and laboratory personnel in contact with blood. After vaccination, it can stimulate the immune system to produce protective antibodies, so that the human body has immunity against hepatitis B to achieve the purpose of preventing hepatitis B infection. The conventional immunization site is intramuscular injection in the deltoid muscle of the upper arm. The immunization schedule is 3 doses, administered once each at birth (0 month), 1 - 2 months of age, and 6 - 18 months of age. Newborns are injected with the first dose within 24 hours after birth, and each injection is 1 dose.

[0215] In some embodiments of the present invention, on the injection head 200 of the multi - mode fluid delivery device used in combination with the hepatitis B vaccine, there are 3 holes 121 arranged in an equally - spaced circular pattern around the center of the injection head 200, and the distance between the three holes 121 and the center of the injection head 200 is 1.25 mm ± 20%.

[0216] 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%.

[0217] In some embodiments of the present invention, the multi - mode fluid delivery device used in combination with the hepatitis B vaccine is configured such that the outlet jet velocity of the hepatitis B vaccine when it is pushed away from the holes 121 in the injection head 200 by the piston 210 is 150.00 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 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.

[0219] In some embodiments of the present invention, the multi - mode fluid delivery device used in combination with the hepatitis B vaccine is configured such that the average antibody titer of the hepatitis B vaccine 14 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.

[0220] In some embodiments of the present invention, the multi - mode fluid delivery device used in combination with the hepatitis B vaccine 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.

[0221] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the hepatitis B vaccine is configured such that the average antibody titer 42 days after the second dose is administered with 60% of the 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 intramuscular injection with 100% of the vaccine dose.

[0222] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the hepatitis B vaccine is configured such that the positive expression rate of T lymphocytes 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 intramuscular injection.

[0223] In some embodiments of the present invention, any of the multi-mode fluid delivery devices in the above embodiments of the present invention can also be used in combination with the human pneumococcal vaccine. Accordingly, the embodiments of the present application also provide corresponding drug-device combination products. In the embodiments of the present invention, the drug-device combination product can include or can be a drug delivery system.

[0224] In some embodiments of the present invention, three holes 121 are arranged in an equally spaced circular pattern around the center of the injection head 200 of the multi-mode fluid delivery device used in combination with the human pneumococcal vaccine, and the three holes 121 are 1.25 mm ± 20% away from the center of the injection head 200.

[0225] 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 human pneumococcal vaccine is configured to be 0.14 m / s ± 20%.

[0226] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the human pneumococcal vaccine is configured such that the outlet jet velocity when the human pneumococcal vaccine is pushed away from the hole 121 in the injection head 200 by the piston 210 is 160.00 m / s ± 20%.

[0227] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the human pneumococcal vaccine is configured such that the diffusion volume of the human pneumococcal vaccine in the body is more than 1.5 times the undelivered volume of the human pneumococcal vaccine.

[0228] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the human pneumococcal vaccine is configured such that the average antibody titer 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 intramuscular injection.

[0229] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the human pneumococcal vaccine is configured such that the average antibody titer of the human pneumococcal 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 intramuscular injection.

[0230] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with the human pneumococcal vaccine is configured such that the average antibody titer of the pneumococcal vaccine after 60% of the vaccine dose is injected 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 intramuscular injection of 100% of the vaccine dose.

[0231] In some embodiments of the present invention, any of the multi-mode fluid delivery devices in the above embodiments of the present invention can also be used in combination with GLP-1 polypeptides. Accordingly, the embodiments of the present application also provide corresponding drug-device combination products. In the embodiments of the present invention, the drug-device combination products can include or can be drug delivery systems.

[0232] In some embodiments of the present invention, the injection head 200 of the multi-mode fluid delivery device used in combination with GLP-1 polypeptides is provided with three holes 121, and the three holes 121 are arranged in an equally spaced circular pattern around the center of the injection head 200, and the distance of the three holes from the center is 1.25 mm ± 20%.

[0233] 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 GLP-1 polypeptides is 0.16 m / s ± 20%;

[0234] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with GLP-1 polypeptides is configured such that the outlet jet velocity of the GLP-1 polypeptides when being pushed away from the holes 121 in the injection head 200 by the piston 210 is 170.00 m / s ± 20%.

[0235] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with GLP-1 polypeptides is configured such that the diffusion volume of the GLP-1 polypeptides in vivo is more than 1.5 times the undelivered volume of the GLP-1 polypeptides.

[0236] In some embodiments of the present invention, the GLP-1 polypeptides include semaglutide, and any of the multi-mode fluid delivery devices in the above embodiments of the present invention can be used in combination with semaglutide. Accordingly, the embodiments of the present application also provide corresponding drug-device combination products. In the embodiments of the present invention, the drug-device combination products can include or can be drug delivery systems.

[0237] In some embodiments of the present invention, the semaglutide, also known as somatropin, 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 (with a molecular weight of 4113.58 Da) has excellent hypoglycemic and weight loss effects on diabetic patients, significantly superior to sitagliptin, insulin glargine U100 or extended-release exenatide; it is also superior to its fellow drug liraglutide in terms of weight loss, especially in patients with a BMI ≥ 30. Semaglutide can be administered orally or subcutaneously, such as an oral dosage form of 7 mg / 14 mg once a day or a subcutaneous injection dosage form of 0.5 mg / 1.0 mg once a week. Semaglutide not only shows good efficacy in the treatment of diabetes, but also exhibits significant advantages in weight loss and cardiovascular protection.

[0238] In some embodiments of the present invention, the multi-mode 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 undelivered volume of the semaglutide.

[0239] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with semaglutide is configured such that the effect of the semaglutide on reducing the body weight of humans and animals is consistent with that of needle injection, preferably the weight loss effect is increased by 2% compared to needle injection, more preferably increased by 5%, and still more preferably increased by 10%.

[0240] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with semaglutide is configured such that the body weight reduction endpoint of the semaglutide in the body is consistent with that of needle injection, preferably increased by more than 2%, more preferably increased by more than 5%, and still more preferably increased by more than 10%.

[0241] In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with semaglutide is configured such that the proportion of side effects such as nausea, vomiting, and abdominal distension caused by the semaglutide is consistent with that of needle injection, preferably reduced by more than 5%, more preferably reduced by more than 10%, and still more preferably reduced by more than 20%.

[0242] In some embodiments of the present invention, any of the multi-mode fluid delivery devices in the embodiments of the present invention can also be used in combination with a pharmaceutical preparation. Thus, the embodiments of the present application also provide corresponding drug-device combination products. In the embodiments of the present invention, the drug-device combination products can include or can be a drug delivery system.

[0243] In some embodiments of the present invention, the pharmaceutical preparation is a human rabies vaccine.

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

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

[0246] In some embodiments of the present invention, the pharmaceutical preparation is a hand, foot and mouth disease vaccine for animals.

[0247] In some embodiments of the present invention, the pharmaceutical preparation is a COVID-19 vaccine for humans.

[0248] In some embodiments of the present invention, the pharmaceutical preparation is a hepatitis A vaccine for humans.

[0249] In some embodiments of the present invention, the pharmaceutical preparation is a hemorrhagic fever with renal syndrome vaccine for humans.

[0250] In some embodiments of the present invention, the pharmaceutical preparation is a mumps vaccine for humans.

[0251] In some embodiments of the present invention, the pharmaceutical preparation is an HPV vaccine for humans.

[0252] In some embodiments of the present invention, the pharmaceutical preparation is an anti-tumor chemotherapy drug for humans.

[0253] In some embodiments of the present invention, the pharmaceutical preparation is a nuclear medicine anti-tumor drug for humans.

[0254] In some embodiments of the present invention, the pharmaceutical preparation is an anti-tumor vaccine for humans, including but not limited to polypeptide vaccines, mRNA vaccines, and DNA vaccines.

[0255] In some embodiments of the present invention, the pharmaceutical preparation is a porcine diarrhea bivalent vaccine. In some embodiments of the present invention, the porcine diarrhea bivalent vaccine may include a live bivalent vaccine against transmissible gastroenteritis of swine and porcine epidemic diarrhea (HB08 strain + ZJ08 strain). In some embodiments of the present invention, the porcine diarrhea bivalent vaccine may include an inactivated bivalent vaccine against transmissible gastroenteritis of swine and porcine epidemic diarrhea.

[0256] In some embodiments of the present invention, the pharmaceutical preparation is a porcine reproductive and respiratory syndrome inactivated vaccine. In some embodiments of the present invention, the porcine reproductive and respiratory syndrome inactivated vaccine may include a porcine reproductive and respiratory syndrome inactivated vaccine (CH-1a strain).

[0257] 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 an inactivated vaccine against foot-and-mouth disease serotype O for pigs (strain O / Mya98 / XJ / 2010 + strain O / GX / 09-7). In some embodiments of the present invention, the foot-and-mouth disease vaccine may include a bivalent inactivated vaccine against foot-and-mouth disease serotypes O and A for pigs (strain Re-O / MYA98 / JSCZ / 2013 + strain Re-A / WH / 09). In some embodiments of the present invention, the foot-and-mouth disease vaccine may include an inactivated vaccine against foot-and-mouth disease serotype O (strain OJMS), which can be used for cattle or sheep. In some embodiments of the present invention, the foot-and-mouth disease vaccine may include a bivalent inactivated vaccine against foot-and-mouth disease serotypes O and A (strain O / HB / HK / 99 + strain AF / 72, 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 vaccine against foot-and-mouth disease serotypes O and A (strain O / MYA98 / BY / 2010 + strain Re-A / WH / 09), which can be used for cattle or sheep.

[0258] 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 an inactivated vaccine against bovine viral diarrhea / mucosal disease and infectious bovine rhinotracheitis (strain NMG + strain LY).

[0259] In some embodiments of the present invention, the pharmaceutical preparation is a Pasteurella multocida vaccine. In some embodiments of the present invention, the Pasteurella multocida vaccine may include an inactivated vaccine against bovine Pasteurella multocida.

[0260] In some embodiments of the present invention, the pharmaceutical preparation is an islet.

[0261] In some embodiments of the present invention, the pharmaceutical preparation is a botulinum toxin-based cosmetic drug for medical beauty.

[0262] In some embodiments of the present invention, there is also provided a needleless syringe for a multi-mode fluid delivery device according to any one of the above embodiments of the present invention, including: a tube 100 for accommodating a fluid, the tube 100 having a first end 110 and a second end 120, wherein the first end 110 is configured to be adapted to accommodate a piston 210 for pushing the fluid 130, and the second end 120 has a plurality of holes 121 for dispensing the fluid 130 in the tube.

[0263] In some embodiments of the present invention, as Figures 38 to 39 shown, the second end 120 of the needleless delivery device may further have a tapered section 122 that gradually narrows axially distally from the tube 100, and a hole 124 is provided at an end face 123 of the tapered section 122. The end face 123 is configured to be circular.

[0264] In some embodiments of the present invention, the total fluid delivery area of the plurality of holes of the needleless cannula is 0.009 mm 2 or more, preferably 0.02 mm 2 or more, more preferably 0.053 mm 2 , and more preferably 0.2800 mm 2 or more; the area of a single hole of the holes is 0.0028 - 0.035 mm 2 , preferably 0.0028 - 0.020 mm 2 , more preferably 0.0028 - 0.009 mm 2 .

[0265] In some embodiments of the present invention, the needleless cannula is configured such that the fluid jets passing through the plurality of holes 121 have different in vivo dispersion degrees;

[0266] In some other embodiments of the present invention, the dispersion degree refers to a comprehensive concept describing the distribution characteristics of fluid in vivo. Specifically, the dispersion degree may include, but is not limited to, the dispersion volume ratio, dispersion depth, dispersion center, and edge liquid distribution density of the fluid.

[0267] In some embodiments of the present invention, the aperture diameters of the plurality of holes 121 of the needleless cannula are configured such that the fluid jets passing through the plurality of holes 121 have different in vivo dispersion degrees.

[0268] In some embodiments of the present invention, the plurality of holes 121 of the needleless cannula include a first hole 121;

[0269] In some embodiments of the present invention, the first hole 121 has a first aperture diameter d1, and the size of the first aperture diameter d1 is configured such that the fluid jet passing through the first hole 121 disperses in at least one of the dermis layer, epidermis layer, subcutaneous tissue, muscle, and human organs.

[0270] In some embodiments of the present invention, the plurality of holes 121 of the needleless cannula include a first hole 121 and a second hole 121';

[0271] In some embodiments of the present invention, the first hole 121 has a first aperture diameter d1, and the size of the first aperture diameter d1 is configured such that the fluid jet passing through the first hole 121 disperses in at least one of the dermis layer, epidermis layer, subcutaneous tissue, muscle, and human organs; the second hole 121' has a second aperture diameter d2, and the size of the second aperture diameter d2 is configured such that the fluid jet passing through the second hole 121' disperses in at least another one of the dermis layer, epidermis layer, subcutaneous tissue, muscle, and human organs.

[0272] In some embodiments of the present invention, the plurality of holes 121 of the needleless cannula are arranged in a straight line;

[0273] In some embodiments of the present invention, the plurality of holes 121 are linearly arranged along the diameter or the median line of the second end 120. Preferably, one of the plurality of holes 121 linearly arranged along the diameter or the median line of the second end 120 is located at the center or the center point of the second end 120;

[0274] In some embodiments of the present invention, the plurality of holes 121 linearly arranged are equally spaced;

[0275] In some embodiments of the present invention, the plurality of holes 121 linearly arranged are mirror-symmetrical with respect to the diameter or the median line of the second end 120;

[0276] In some embodiments of the present invention, there are multiple groups of the holes 121, and each group of holes 121 is linearly arranged. Preferably, each group of holes is arranged along a diameter or a median line of the second end 120;

[0277] In some embodiments of the present invention, the plurality of holes 121 are arranged in an array. The plurality of holes 121 arranged in an array are mirror-symmetrical with respect to the first and second diameters or median lines perpendicular to each other of the second end 120 respectively;

[0278] In some embodiments of the present invention, the aperture diameter d of the hole 121 located at the center or the center point of the second end 120 is different from the aperture diameter d' of the other holes 121' of the plurality of holes 121;

[0279] In some embodiments of the present invention, the aperture diameter of at least one group of the plurality of groups of holes 121 is different from the aperture diameter of the other groups of holes.

[0280] In some embodiments of the present invention, the plurality of holes 121 of the needleless syringe barrel are arranged in a ring;

[0281] In some embodiments of the present invention, the plurality of holes 121 are arranged in a ring with the center or the center point of the second end 120 as the center of the circle;

[0282] There are multiple groups of the holes 121, and each group of holes 121 is arranged in a ring. Preferably, the multiple groups of holes 121 are coaxially arranged in a ring with each other;

[0283] In some embodiments of the present invention, at least one of the plurality of holes 121 arranged in a ring has an aperture diameter different from that of the other holes 121;

[0284] In some embodiments of the present invention, the aperture diameter of at least one group of the plurality of groups of holes 121 is different from the aperture diameter of the other groups of holes;

[0285] In some embodiments of the present invention, the aperture diameters of the multiple groups of holes 121 coaxially arranged in a ring with each other increase or decrease radially.

[0286] In some embodiments of the present invention, the plurality of holes of the needleless cannula include a central hole 121" located at the center or the center of the second end 120 and a plurality of peripheral holes 121 located around the central hole;

[0287] In some embodiments of the present invention, the plurality of peripheral holes 121 are arranged in a circular pattern. Preferably, the plurality of peripheral holes 121 are arranged in a coaxial circular pattern around the central hole 121";

[0288] The peripheral holes 121 are provided in multiple groups, and each group of peripheral holes 121 is arranged in a circular pattern. Preferably, the multiple groups of peripheral holes 121 are arranged in a coaxial circular pattern around the central hole 121".

[0289] In some embodiments of the present invention, the aperture d" of the central hole 121" is different from the aperture d of the plurality of peripheral holes 121.

[0290] 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.

[0291] 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;

[0292] Optionally, the needle member 210 includes a first needle head portion 211 located on the first side 221 of the support portion 220;

[0293] Optionally, the needle member 210 includes a fixing gasket 230 located on the first side 221 of the support portion 220, and the fixing gasket 230 is used to fix the needle member 210;

[0294] Optionally, the needle member 210 includes a second needle head portion 212 located on the second side 222 of the support portion 220;

[0295] In some embodiments of the present invention, alternatively, the first needle head portion 211 of the needle member 210 does not extend from the first side 221 of the support portion 220, so that the first side 221 of the support portion 220 forms a needleless micro-hole 213.

[0296] In some embodiments of the present invention, the first needle head portion 211 of the needle member 210 is flat, and the second needle head portion 212 of the needle member 210 is sharp.

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

[0298] In some embodiments of the present invention, the one or more needle members 210 have different adjustable skin insertion depths L;

[0299] 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 insert but forms a tight contact with the human or animal skin.

[0300] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that substantially inserts into the inner layer of the human or animal skin.

[0301] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that substantially inserts into the subcutaneous layer of the human or animal.

[0302] In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that substantially inserts into the muscle layer of the 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 substantially inserts into the internal organs of the human or animal body.

[0304] In some embodiments of the present invention, at least one of the one or more needle members has an adjustable insertion depth.

[0305] It can be understood that in the embodiments of the present invention, the corresponding dermal layer, epidermal layer, subcutaneous layer, muscle, or human organ does not refer to a specific and fixed insertion depth value, nor a specific and fixed insertion depth value range. Those skilled in the art can confirm the insertion depths corresponding to the dermal layer, epidermal layer, subcutaneous layer, muscle, and human organ in the inoculated body according to the inoculated body of needleless delivery, including but not limited to different types of animals or patients with different physical conditions.

[0306] In some embodiments of the present invention, the plurality of needle members 210 includes a first needle member;

[0307] 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, and the size of the first needle aperture d1 is configured such that the fluid jets passing through the one or more needle members 210 have different dispersions, preferably different dispersion depths, so that the fluid jets disperse in at least one of the dermal layer, epidermal layer, subcutaneous layer, muscle, and human organ.

[0308] In some embodiments of the present invention, the plurality of needle members 210 includes a first needle member 210 and a second needle member 210';

[0309] In some embodiments of the present invention, the first needle member 210 has a first skin insertion depth located in one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organs, and the second needle member 210' has a second skin insertion depth located in another of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organs;

[0310] In some embodiments of the present invention, the first needle member 210 has a first needle aperture diameter d, and the size of the first needle aperture diameter d is configured such that the fluid jet passing through the first needle member 210 disperses in at least one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organs; the second needle member 210' has a second needle aperture diameter d', and the size of the second needle aperture diameter d' is configured such that the fluid jet passing through the second needle member 210' disperses in at least another of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organs.

[0311] In some other embodiments of the present invention, preferably, the plurality of needle members further includes a third needle member 210", and preferably, the third needle member 210" has a third skin insertion depth located in yet another of the dermis layer, epidermis layer, subcutaneous layer, muscle, and human organs.

[0312] In some embodiments of the present invention, the plurality of needle members 210 are arranged in a straight line;

[0313] In some embodiments of the present invention, the plurality of needle members 210 are arranged in a straight line along the diameter or the median line of the injection head, and preferably, one of the plurality of needle members 210 arranged in a straight line along the diameter or the median line of the injection head 200 is located at the center of the injection head 200;

[0314] In some embodiments of the present invention, the plurality of needle members 210 arranged in a straight line are equally spaced;

[0315] In some embodiments of the present invention, the plurality of needle members 210 arranged in a straight line are mirror symmetric with respect to the diameter or the median line of the injection head 200;

[0316] In some embodiments of the present invention, the needle members 210 are provided in multiple groups, and each group of needle members 210 is arranged in a straight line, and preferably, each group of needle members 210 is arranged along a diameter or a median line of the injection head;

[0317] The plurality of needle members 210 are arranged in an array, and preferably, the plurality of needle members 210 arranged in an array are mirror symmetric with respect to the first and second diameters or median lines perpendicular to the end face of the injection head 200, respectively.

[0318] In some embodiments of the present invention, the skin insertion depth L” of the needle member 210” located at the center 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;

[0319] Preferably, the skin insertion depth L’ of at least one group of needle members among the multiple groups of needle members 210 is different from the skin insertion depth L of the other groups of needle members 210;

[0320] Preferably, the needle aperture d” of the needle member 210” located at the center of the injection head 200 is different from the needle aperture d of the other needle members 210 of the plurality of needle members 210;

[0321] Preferably, the needle aperture d’ of at least one group of needle members 210’ among the multiple groups of needle members 210 is different from the needle aperture d of the other groups of needle members 210.

[0322] In some embodiments of the present invention, the plurality of needle members 210 are arranged in a circular pattern;

[0323] In some embodiments of the present invention, the plurality of needle members 210 are arranged in a circular pattern with the center of the injection head 200 as the center;

[0324] The needle members 210 have multiple groups, and each group of needle members 210 is arranged in a circular pattern. Preferably, the multiple groups of needle members 210 are arranged in coaxial circular patterns with each other.

[0325] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in a circular pattern has a skin insertion depth L’ different from that of the other needle members 210.

[0326] 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.

[0327] In some embodiments of the present invention, the skin insertion depth L of the multiple groups of needle members 210 arranged in coaxial circular patterns with each other decreases or increases radially.

[0328] In some embodiments of the present invention, at least one of the plurality of needle members 210 arranged in a circular pattern has a needle aperture d’ different from that of the other needle members 210.

[0329] In some embodiments of the present invention, the needle aperture d’ of at least one group of needle members 210’ among the multiple groups of needle members 210 is different from the needle aperture d of the other groups of needle members 210.

[0330] In some embodiments of the present invention, the needle aperture d of the multiple groups of needle members 210 arranged in coaxial circular patterns with each other decreases or increases radially.

[0331] In some embodiments of the present invention, the plurality of needle members 210 includes a central needle member 210" located at the center or the center of the injection head 200 and a plurality of peripheral needle members 210 located around the central needle member 210";

[0332] In some embodiments of the present invention, the plurality of peripheral needle members 210 are arranged in a ring, preferably, the plurality of peripheral needle members 210 are arranged in a coaxial ring around the central needle member 210";

[0333] There are multiple groups of the peripheral needle members, 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".

[0334] 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;

[0335] In some embodiments of the present invention, the skin insertion depth L' of at least one group of peripheral needle members 210' among the multiple groups of peripheral needle members 210 is different from the skin insertion depth L of other peripheral groups of needle members 210;

[0336] 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" arranged in coaxial rings decrease or increase radially;

[0337] Preferably, the needle aperture d" of the central needle member 210" is different from the needle aperture d of the plurality of peripheral needle members 210;

[0338] In some embodiments of the present invention, the needle aperture d' of at least one group of peripheral needle members 210' among the multiple groups of peripheral needle members 210 is different from the needle aperture d of other peripheral groups of needle members 210;

[0339] In some embodiments of the present invention, the needle apertures of the multiple groups of needle members 210 and the central needle member 210" arranged in coaxial rings increase or decrease radially.

[0340] In some embodiments of the present invention, the needle member 210 further includes an interventional soft needle removably connected to the hole.

[0341] In some embodiments of the present invention, there is also provided a needle kit 400 for a multi-mode fluid delivery device, the needle kit 400 includes one or more needle sleeves 401, wherein, the needle sleeve 401 is configured to be adapted to removably surround the first needle head 211 of the needle member 210.

[0342] In some embodiments of the present invention, the height of the needle sleeve 401 is greater than or equal to the first needle head 211 of the needle member 210, so as to completely surround the first needle head 211;

[0343] In some embodiments of the present invention, the height of the needle sleeve 401 of the needle kit is less than the first needle head 211 of the needle member 210, so as to partially surround the first needle head 211, such that the first needle head 211 extends from the front end of the needle sleeve 401 to form an insertion portion 214.

[0344] In some embodiments of the present invention, 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 member, so as to completely surround the first needle head 211 to protect the first needle head 211.

[0345] 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.

[0346] The first needle kit 410 is configured such that the state of surrounding the first needle head 211 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;

[0347] The second needle kit 420 is configured such that the state of surrounding the first needle head 211 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.

[0348] In some embodiments of the present invention, there are more than 400 needle kits. Preferably, the multiple 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;

[0349] The first needle kit 410 is configured such that the first needle head 211 surrounded by it is completely surrounded;

[0350] The second needle kit 420 is configured such that the insertion portion 214 of the first needle head 211 surrounded by it is located in the dermis layer;

[0351] The third needle kit 430 is configured such that the insertion portion 214 of the first needle head 211 surrounded by it is located in the epidermis layer;

[0352] The fourth needle kit 440 is configured such that the insertion portion 214 of the first needle head 211 surrounded by it is located under the skin;

[0353] The fifth needle set 450 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located in the muscle;

[0354] The sixth needle set 460 is configured such that the insertion portion 214 thereof surrounding the first needle head 211 is located in a human organ.

[0355] In some embodiments of the present invention, 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.

[0356] 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 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 when the needle sleeve portion is retracted, flush with the needle sleeve portion, in the dermis layer, in the epidermis layer, in the subcutaneous layer, in the muscle, and in a human organ.

[0357] In some embodiments of the present invention, 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.

[0358] In some embodiments of the present invention, there is also provided the use of the multi-mode fluid delivery device according to any one of the above embodiments of the present invention in the preparation of drugs for human clinical medicine and animal health care for needle-free injection administration.

[0359] In some embodiments of the present invention, the pharmaceutical preparation is a feline triple vaccine.

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

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

[0362] In some embodiments of the present invention, the pharmaceutical preparation is semaglutide.

[0363] In some embodiments of the present invention, the pharmaceutical preparation is a human rabies vaccine.

[0364] In some embodiments of the present invention, the pharmaceutical preparation is an animal rabies vaccine.

[0365] In some embodiments of the present invention, the pharmaceutical preparation is a human meningitis vaccine.

[0366] In some embodiments of the present invention, the pharmaceutical preparation is an animal hand, foot and mouth disease vaccine.

[0367] In some embodiments of the present invention, the pharmaceutical preparation is a COVID-19 vaccine for human use.

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

[0369] In some embodiments of the present invention, the pharmaceutical preparation is a hemorrhagic fever with renal syndrome vaccine for human use.

[0370] In some embodiments of the present invention, the pharmaceutical preparation is a mumps vaccine for human use.

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

[0372] In some embodiments of the present invention, the pharmaceutical preparation is an anti-tumor chemotherapy drug for human use.

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

[0374] In some embodiments of the present invention, the pharmaceutical preparation is an anti-tumor vaccine for human use, including but not limited to polypeptide vaccines, mRNA vaccines, and DNA vaccines.

[0375] In some embodiments of the present invention, the pharmaceutical preparation is a porcine diarrhea bivalent vaccine.

[0376] In some embodiments of the present invention, the pharmaceutical preparation is a porcine reproductive and respiratory syndrome inactivated vaccine.

[0377] In some embodiments of the present invention, the pharmaceutical preparation is a foot-and-mouth disease vaccine.

[0378] In some embodiments of the present invention, the pharmaceutical preparation is a bovine bivalent vaccine.

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

[0380] In some embodiments of the present invention, the pharmaceutical preparation is insulin.

[0381] In some embodiments of the present invention, the pharmaceutical preparation is a botulinum toxin-based cosmetic drug for medical aesthetics.

[0382] In some embodiments of the present invention, a multi-modal pharmaceutical preparation delivery method is further provided, characterized in that:

[0383] Determine the pharmaceutical preparation delivery mode according to the obtained preset information, wherein the delivery mode includes a first delivery mode and a second delivery mode;

[0384] When it is determined to be the first delivery mode, the pharmaceutical preparation is delivered needle - free through a perforated tube, and the first delivery parameters for needle - free delivery are determined according to the preset information, wherein the first delivery parameters include the piston speed of the tube, the aperture diameter of the hole, and the hole jet speed;

[0385] When it is determined to be the second delivery mode, an injection member with one or more needle members is connected to the tube to deliver the pharmaceutical preparation through the injection head with a needle, and the second delivery parameters for the needle - delivery are determined according to the preset information, wherein the second delivery parameters include the insertion depth of the needle member, the aperture diameter, the jet speed, and the piston speed of the tube;

[0386] In the selected delivery mode, the pharmaceutical preparation is delivered according to the determined delivery parameters.

[0387] In some embodiments of the present invention, the preset information includes at least one of inoculum information, inoculation position information, and pharmaceutical preparation information, wherein the inoculation position information includes at least one of inoculation site information, delivery depth information, and delivery dispersion information.

[0388] In some embodiments of the present invention, the dispersion information includes at least one of dispersion volume ratio, dispersion breadth, dispersion depth, dispersion center, and dispersion edge distribution density.

[0389] In some embodiments of the present invention, there are multiple holes, and determining the first delivery parameters for the needle - free delivery according to the preset information includes,

[0390] Determining the number and arrangement mode of the multiple holes on the second end of the tube according to the preset information.

[0391] In some embodiments of the present invention, connecting an injection head with one or more needle members to the tube to deliver the pharmaceutical preparation through the injection member with a needle includes,

[0392] Removably docking one or more needle members of the injection member with corresponding self - sealing elastic parts or holes in the second end of the tube.

[0393] In some embodiments of the present invention, determining the second delivery parameters for the needle - delivery according to the preset information includes,

[0394] Determining the height, number, and arrangement mode of the multiple needle members on the head according to the preset information.

[0395] In some embodiments of the present invention, the method further includes installing a plurality of needle kits on the multiple needle members according to the preset information to adjust the exposed length of the needle members to control the insertion depth of the multiple needle members.

[0396] By configuring the multi-mode fluid delivery device of the embodiments of the present invention, the component parts of the multi-mode fluid delivery device and the related drug-device combination device, and by controlling the flow rate, delivery depth, and dispersion degree of the drug and vaccine jets, at least one of the following problems is solved or improved, or at least one of the following technical effects is achieved:

[0397] (1) The multi-mode fluid delivery device of the embodiments 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 application range and being able to meet the delivery requirements of different types of drugs and vaccines.

[0398] (2) The multi-mode fluid delivery device of the embodiments of the present invention can achieve a significant increase in the delivery volume, including a significant increase in the delivery volume without breaking the skin, and can be widely used for the delivery of drugs and vaccines for human and veterinary use.

[0399] (3) Through porous needle-free delivery, the multi-mode fluid delivery device of the embodiments of the present invention significantly improves the dispersion volume of the delivered substance, especially drugs and vaccines in the body, thereby increasing the contact effect between the delivered drugs and vaccines and the body tissues, and significantly improving the bioavailability of drugs and vaccines.

[0400] (4) By precisely controlling the jet velocity of drugs and vaccines and optimizing the pore size and distribution of the needle-free holes and needles, the multi-mode fluid delivery device of the embodiments of the present invention realizes precise delivery at different depths in the body according to the characteristics of different drugs and vaccines, especially realizes precise delivery of the delivered substance to at least one or more target positions in the dermis, subcutaneous tissue, muscle, or human organ simultaneously.

[0401] (5) By controlling the pore size and arrangement of the multiple holes, the multi-mode fluid delivery device of the embodiments of the present invention realizes different dispersion effects of the delivered substance, especially drugs or vaccines at the delivery position, especially realizes the control of the dispersion volume ratio, dispersion breadth, and dispersion center at the specified position, and realizes specific dispersion effects according to different delivery requirements. Based on the above problems solved and / or effects achieved, the present invention is also used in combination with feline triple vaccine, hepatitis B vaccine, human pneumonia vaccine, GLP-1 polypeptides, especially semaglutide, to achieve further technical effects as recorded in the embodiments of the present invention.

[0402] Example 1

[0403] Now refer to Figure 40 , Figure 41 and Figure 48, which shows one of the structural configurations of the multi-mode fluid delivery device according to an embodiment of the present invention. Specifically, the second end further 120 has a transition section 122 that tapers axially distally from the tube 100. The end face 123 of the transition section 122 is configured to be circular with a diameter of 2.5 mm and is provided with three holes 121 thereon. The three holes 121 are arranged in an equally spaced circular pattern around the center of the end face 123. An angle of 120° is formed between adjacent connecting lines of the three holes and the center (center) of the end face 123. Among them, the aperture diameters of the three holes 121 are uniformly set to d and the distances from the centers of the three holes 121 to the center of the end face 123 are uniformly set to l.

[0404] Now refer to Figure 42 , under the structure of the above multi-mode fluid delivery device, an embodiment of the present invention uses the ANSYS workbench Fluent module as shown in Figure 42 to build a needleless injection dispersion and penetration simulation model. Using the multiphase flow model to simulate the dispersion 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. Among them, the volume of the fluid 130 to be delivered is 0.2 cm3, the viscosity is 1 cp, the calculation method of the needleless injection dispersion and penetration simulation model adopts transient, the multiphase flow model selects the Euler model (Eulerian), the viscosity model selects 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 structure and simulation parameters, the aperture diameter d of the three holes 121 and the distance l from the center of the end face 123 of the three holes 121 are further configured to obtain the following data on the dispersion degree of the porous needleless delivery fluid under different configurations:

[0405] Table 1. Data table of the dispersion degree of the porous needleless delivery fluid

[0406]

[0407] Combined with Table 1 above and Figures 43 to 45 as shown, it shows the dispersion effect achieved by the multi-mode fluid delivery device of an embodiment of the present invention using the multiple holes 121. The present invention realizes different dispersion degrees of the fluid 130 in the body 140, so that the fluid jets of the fluid 130 passing through the multiple holes 121 achieve different dispersion volume ratios, dispersion depths and dispersion breadths in the body 10. Among them, the Figure 43 shows the dispersion effect diagram at d = 0.15 mm and l = 0.65 mm, Figure 44 shows the dispersion effect diagram at d = 0.575 mm and l = 0.65 mm, Figure 45 shows the dispersion effect diagram at d = 1.00 mm and l = 0.65 mm. At the same time, asFigures 43 to 45 As shown, when the multi-mode fluid delivery device according to an embodiment of the present invention delivers fluid into the body, due to the different diffusion volume ratios, diffusion depths, and diffusion breadths of the fluid in the body, the above-mentioned fluid will also have different diffusion centers and diffusion edge densities in 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 some other embodiments of the present invention, the multi-mode fluid delivery device of the present invention with the injection head and the needle member installed is also expected to have a similar diffusion effect as described above.

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

[0409] Example 2

[0410] Now refer to Figure 40 , Figure 41 and Figure 48 , which shows 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 tapers axially distally from the tube 100. The end face 123 of the transition section 122 is configured as a circle with a diameter of 5 mm, and a central hole 121” located at the center (center) of the end face 123 and three peripheral holes 121 located around the periphery of the central hole 121” are provided thereon. The three peripheral holes 121 are arranged in an equally spaced circular pattern around the center of the end face 123. An angle of 120° is formed between the adjacent connecting lines of the three peripheral holes 121 and the center (center) of the end face 123. Among them, the aperture of the central hole 121” is d”, the apertures of the three peripheral holes 121 are uniformly set to d, and d”≠d. The distance from the center of the end face 123 is uniformly set to 1.1 mm.

[0411] Now refer to Figure 42 , in the structure of the above multi-mode fluid delivery device, the embodiment of the present invention adopts as Figure 42The ANSYS workbench Fluent module shown above constructs a needleless injection dispersion and penetration simulation model. Using the multiphase flow model, it simulates the dispersion 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. Among them, the viscosity of the fluid 130 to be delivered is 1 cp. The calculation method of the needleless injection dispersion and penetration simulation model adopts transient state. The multiphase flow model selects the Euler model (Eulerian), the viscous model selects 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 structure and simulation parameters, the aperture d” of the central hole 121” and the aperture d of the 3 peripheral holes 121 are further configured. When the volumes of the delivered fluid are 0.1 cm 3 , 0.2 cm 3 and 0.3 cm 3 respectively, three groups of simulation experiments are carried out on the fluid to obtain the following dispersion degree data of the porous needleless delivered fluid:

[0412] Table 2. Data table of the dispersion degree of the porous needleless delivered fluid in Group 1

[0413]

[0414] Note: The volume of the fluid to be delivered in this group is 0.1 cm 3 .

[0415] Table 3. Data table of the dispersion degree of the porous needleless delivered fluid in Group 2

[0416]

[0417] Note: The volume of the fluid to be delivered in this group is 0.2 cm 3 .

[0418] Table 4. Data table of the dispersion degree of the porous needleless delivered fluid in Group 3

[0419]

[0420] Note: The volume of the fluid to be delivered in this group is 0.3 cm 3 .

[0421] Combined with Tables 2 to 4 above and Figures 46 to 47As shown, the dispersion effect achieved by the multi-mode fluid delivery device of an embodiment of the present invention using a plurality of the holes 121 is shown. By providing the central hole 121" and three peripheral holes 121, the fluid jets of the fluid 130 passing through the plurality of holes achieve a significantly enhanced dispersion effect compared to needle-free delivery in the control group. Specifically, the multi-mode fluid delivery device of the embodiment of the present invention enables the dispersion volume of the delivery fluid 130 in the simulated body 140 to be 2.35 to 3.61 times that before delivery. In the above embodiments of the present invention, the injection head and the needle member thereon are removed from the tube, but in some other embodiments of the present invention, the multi-mode fluid delivery device of the present invention with the injection head and the needle member installed is also expected to have a similar dispersion effect as described above. At the same time, from Table 2 above and Figure 46 it can be seen that in the case of 0.1 cm, the multi-mode fluid delivery device of the present invention achieves a significantly better dispersion breadth than a single hole, and a significantly enhanced dispersion effect is achieved for the delivery fluid. In other words, more sufficient contact between the delivery fluid and the target site in the body is achieved.

[0422] Example 3

[0423] Now refer to Figure 40 , Figure 41 and Figure 48 , which shows one structural configuration of the multi-mode fluid delivery device of the embodiment of the present invention. Specifically, the second end 120 has a transition section 122 that tapers axially distally from the tube 100. The end face 123 of the transition section 122 is configured 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 equally spaced circular pattern around the center of the end face 123. The included angle between the adjacent connecting lines of the three holes and the center (center) of the end face 123 is 120°. Among them, the aperture of the three holes 121 is uniformly set to 0.15 mm and the distance from the center of the end face 123 is uniformly set to 1.1 mm.

[0424] Under the structure of the above multi-mode fluid delivery device, in a specific embodiment of the present invention, a delivery fluid with a viscosity of 1 cp and a volume of 0.2 cm 3 is used for testing, and the displacement change curve of the piston 210 of the multi-mode fluid delivery device of the present invention is obtained, and the movement speed of the piston 210 and the outlet jet speed of the jets ejected from the plurality of holes 121 are obtained as follows:

[0425] Table 5. Data table of piston speed and jet speed

[0426]

[0427] As can be seen from the above table, in a specific embodiment of the multi-mode fluid delivery device of the present invention, it is configured such that the average velocity of the jets ejected from the plurality of holes 121 is greater than 135 m / s, up to 156 m / s. 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 with the injection head and the needle member installed is also expected to have a similar dispersion effect as described above.

[0428] Example 4

[0429] In a specific embodiment of the present invention, the multi-mode fluid delivery device of the present invention is used in combination with a feline triple vaccine, referring to Figure 40 , Figure 41 and Figure 48 , which shows one of the structural configurations of the multi-mode fluid delivery device of the embodiment of the present invention used in combination with the feline triple vaccine. Specifically, the second end 120 has a transition section 122 that axially narrows distally from the tube 100. Wherein, the diameter of the tube is 5 mm, the end face 123 of the transition section 122 is configured as a circle with a diameter of 2.5 mm and is provided with 3 holes 121 thereon. The 3 holes 121 are arranged in an equally spaced circular pattern around the center of the end face 123. An angle of 120° is formed between the adjacent connecting lines of the 3 holes and the center of the end face 123. The measured aperture values of the 3 holes 121 are 0.14 mm to 0.17 mm, and the distance of the 3 holes 121 from the center of the end face 123 is uniformly set to 1.25 mm.

[0430] In the 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 605 strains of inactivated feline rhinotracheitis virus, 255 strains of feline calicivirus, and Cu-4 strains of panleukopenia virus. The R.P. 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 for inoculating healthy cats at 8 weeks of age or older. It can be administered subcutaneously, 1 ml per cat per time. For healthy cats at 8 weeks of age or older, a booster immunization should be carried out 3 to 4 weeks after the first inoculation, with 1 dose. For cats inoculated at less than 12 weeks of age, a booster inoculation of 1 dose should be carried out at 12 to 16 weeks of age to ensure long-lasting immune protection. The feline triple vaccine should be repeatedly inoculated with 1 dose per year to maintain immunity.

[0431] The following is a specific immune evaluation test of the multi-mode fluid delivery device of the present invention. Among them, under the structural configuration of the multi-mode fluid delivery device of the present invention described above, a needle-free injection immune evaluation test for feline vaccines was carried out according to the following test protocol:

[0432] 1. Test materials

[0433] 1.1 Test animals: 27 healthy cats were used as experimental animals. Among them, the 27 cats were all negative for FPV, FHV, and FCV antigens, and the neutralizing antibody titers of 2 / 3 of them were no higher than 1:4 and they had no history of feline triple vaccine immunization.

[0434] 1.2 Delivered vaccine: A triple inactivated vaccine for feline rhinotracheitis, calicivirus disease, and panleukopenia (trade name: Miao San Duo, batch number: E071201A) produced by Zoetis.

[0435] 1.3 Neutralizing antigens for detection: FPV virus solution, FCV virus solution, and FHV virus solution with a virus content of 200 TCID50 / 0.1 ml were selected.

[0436] 1.4 Cells for detection: CRFK cells or F81 cells were used.

[0437] 1.5 Test equipment: A multi-mode fluid delivery device according to the above-mentioned embodiment of the present invention (delivery pressure: 330 N, pore size: 0.14 mm - 0.17 mm); traditional 1 ml syringes with needles, 10 ml syringes, medical cotton swabs, and alcohol cotton.

[0438] 1.6 Test location: Animal hospital.

[0439] 2. Test methods

[0440] 2.1 Animal screening: Nasal swabs (superficial collection is possible), oral swabs, and anal swabs were collected from each of the 37 healthy cats and placed in a centrifuge tube containing 1 ml of PBS; antigen detection was performed according to the methods in Notes 1 - 3; 2 - 3 ml of blood was collected from each healthy cat, the serum was separated, and neutralizing antibody detection was performed.

[0441] 2.2 Animal grouping: After the selected healthy cats entered the test site, they were allowed to adapt to the environment for 7 days, and the cat food was gradually transitioned. Then, according to the gender, age, breed, or antibody data of the healthy cats, they were evenly divided into 3 groups of 7 each, numbered and respectively recorded as test groups 1, 2, and 3; another 6 healthy cats were set as sentinel animals without immunization with the feline triple vaccine and recorded as test group 4.

[0442] 2.3 Preparation before immunization: 2 - 3 days before immunization, the injection sound was played in the test site for 10 - 15 minutes every day, and at the same time, the cats could autonomously contact and smell the odor of the multi-mode fluid delivery device and the electric hair clipper of the present invention. 1 day or 2 hours before injection, the injection site of the test cats was shaved, and the diameter of the shaved area was about 1 cm; 1 - 2 inoculation personnel.

[0443] 2.4 Immunization

[0444] Immunize the aforementioned groups 1, 2, and 3, where:

[0445] Group 1: Immunize using conventional needle injection. Use a disposable 1-ml syringe with a needle hole diameter of 0.45 mm. The immunization dose per time is 1 ml.

[0446] Group 2: Immunize using a three-hole needle-free injection. Use a needle-free syringe with a single-hole injection needle for multi-hole injection. The needle hole diameter is 0.14 mm to 0.17 mm. The immunization dose per time is 1 ml.

[0447] Group 3: Immunize using needle-free multi-hole injection. Use a needle-free syringe with a single-hole injection needle for multi-hole injection. The needle hole diameter is 0.14 mm to 0.17 mm. The immunization dose per time is 0.45 ml.

[0448] Table 6. Immunization Information Table

[0449]

[0450] Note: " / " indicates no operation.

[0451] 2.5. Sample collection:

[0452] On the day of the first immunization and 21 days and 35 days after the first immunization, collect venous blood from each cat according to Table 5 above, separate the serum, and store it at -20°C for further testing. (If the immune response is particularly strong, consider collecting whole blood 1 to 2 weeks after 35 days).

[0453] Table 7. Sample Collection Schedule

[0454]

[0455] 3. Results after immunization

[0456] 3.1. Observation on the day of immunization:

[0457] Conventional injection immunization group (Group 1): The experimental cats were listless and lackluster.

[0458] Needle-free injection immunization groups (Groups 2 and 3): The experimental cats were lively.

[0459] 3.2. Results of neutralizing antibody titer determination

[0460] The neutralizing antibody titer was determined to obtain Tables 7 and 8 below, which show the data tables of the antibody titer determination for each group under the above test conditions:

[0461] Table 8. Data Table of Antibody Titer Determination - 1

[0462]

[0463] Table 9. Data Sheet for Antibody Titer Determination - 2

[0464]

[0465] From the above Table 7 and Table 8, and Figures 49 to 51 it can be seen that in the embodiments of the present invention, when using a multi - mode fluid delivery device including a plurality of holes 121 for the delivery of feline triple vaccine, compared with the traditional needle - based delivery, the following are achieved:

[0466] a. For the needle - free three - hole immunization group using the multi - mode fluid delivery device of the present invention compared with the needle - based equal - dose immunization group, the onset time of antibodies in the needle - free three - hole group using the multi - mode fluid delivery device of the present invention is 1 time faster than that of the needle - based group;

[0467] b. It is found that under the same immunization dose, the antibody produced by the needle - free three - hole immunization using the multi - mode fluid delivery device of the present invention is 25 times higher than that produced by the needle - based conventional immunization group;

[0468] c. For the needle - free three - hole dose - halved group using the multi - mode fluid delivery device of the present invention compared with the needle - based conventional immunization group, the antibody value is 2.4 times higher.

[0469] In the above embodiments of the present invention, the injection head and the needle member thereon are removed from the tube. However, in some other embodiments of the present invention, the multi - mode fluid delivery device of the present invention with the injection head and the needle member installed is also expected to have similar dispersion and immunogenicity effects as described above.

[0470] Example 5

[0471] In a specific embodiment of the present invention, the multi - mode fluid delivery device of the present invention is used in combination with hepatitis B vaccine. Referring to Figure 40 , Figure 41 and Figure 48 , which shows one of the structural configurations of the multi - mode fluid delivery device of the present invention in combination with hepatitis B vaccine. Specifically, the second end 120 has a transition section 122 that axially narrows towards the distal end from the tube 100. Among them, the diameter of the tube is 5 mm, the end face 123 of the transition section 122 is configured as a circle with a diameter of 2.5 mm and is provided with 3 holes 121 thereon. The 3 holes 121 are arranged in an equally - spaced circular pattern around the center of the end face 123. The adjacent connection lines between the 3 holes and the center of the end face 123 form an angle of 120°. Among them, the measured aperture values of the 3 holes 121 are 0.14 mm to 0.17 mm, and the distances of the 3 holes 121 from the center of the end face 123 are uniformly set to 1.25 mm.

[0472] In an embodiment of the present invention, the hepatitis B vaccine refers to a recombinant yeast hepatitis B vaccine (Hansenula polymorpha) used for preventing hepatitis B (a viral liver disease), which is prepared by purifying the hepatitis B virus surface antigen (HBsAg) expressed by recombinant Hansenula polymorpha, adding an aluminum adjuvant, and has the hepatitis B virus surface antigen as the active ingredient. The vaccine is applicable to individuals susceptible to hepatitis B, especially the following: (1) newborns, especially those whose mothers are positive for HBsAg and HBeAg; (2) individuals susceptible to hepatitis B aged 16 and above; (3) medical staff engaged in medical work and laboratory personnel who come into contact with blood. After vaccination, it can stimulate the immune system to produce protective antibodies, thereby enabling the human body to have immunity against hepatitis B to achieve the purpose of preventing hepatitis B infection. The conventional immunization site is intramuscular injection in the deltoid muscle of the upper arm. The immunization schedule is 3 doses, administered once each at birth (0 month), 1 - 2 months of age, and 6 - 18 months of age. Newborns are injected with the first dose within 24 hours after birth, and each injection is 1 dose.

[0473] The following is a specific immunization evaluation test of the multi - mode fluid delivery device of the present invention. Among them, under the structural configuration of the multi - mode fluid delivery device of the present invention described above, the needle - free injection immunization evaluation test of the hepatitis B vaccine was carried out according to the following test protocol:

[0474] 1. Preparation before the test

[0475] 1.1 Test materials: 64 male mice (strain: BALB / c), weighing 17 - 19 g, aged 3 to 4 weeks, were selected and blood was collected after one week of acclimation.

[0476] 1.2 Test equipment: According to the multi - mode fluid delivery device of the above - mentioned embodiment of the present invention, traditional needles, medical cotton swabs, and alcohol cotton.

[0477] 2. Test methods

[0478] 2.1 Animal grouping: The above 64 mice were divided into 8 groups of 8 mice each, including 6 experimental groups and 2 control groups.

[0479] Table 10. Control test grouping table

[0480]

[0481] 2.2 Blood collection plan:

[0482] The mice were immunized according to the D0 / D21 immunization schedule, and blood was collected and serum was separated at D0 / D28 / D35 / D42 after immunization.

[0483] At the start of the experiment: On the morning of the day when the experiment began, use an electric shaver and depilatory cream to shave the hair on the backs and legs of the mice. Before inoculation, use the retro-orbital bleeding method to collect blood from all the mice, with the blood collection volume being 0.2 ml per mouse.

[0484] After one injection: The second injection is given on the 21st day; the second blood collection is carried out on the 28th day, taking 10 mice from one group to collect peripheral blood and 6 mice to collect spleens; the third blood collection of all the mice is carried out on the 35th day; the fourth blood collection is taken from one group on the 42nd day, with 10 mice collecting peripheral blood and 6 mice collecting spleens.

[0485] 2.3 Neutralization experiment

[0486] The micro-method is adopted.

[0487] Use the Karber method to calculate the neutralization endpoint (convert the serum dilution to logarithm), that is, the highest dilution of the serum that can protect 50% of the cells from being infected by the attacking virus of 100 CCID50 is the antibody titer of this serum. The neutralizing antibody titer < 1:4 is negative, and ≥ 1:4 is positive.

[0488] Operating procedure (fixed virus - diluted serum method)

[0489] (1) Inactivate the serum: Inactivate the serum to be tested at 56 °C for 30 minutes

[0490] (2) Dilute the serum: Take the inactivated serum and dilute it on a 96 - well micro - cell plate with serum - free cell culture medium. Start a series of two - fold dilutions from 1:4 (tentatively 1:4, 1:28, 1:56, 1:128, 1:256...), with 50 μL in each well, and 2 - 4 wells for each dilution.

[0491] (3) Neutralize: Add 50 μL of the diluted 200 TCID50 virus solution to each well, and place it in a CO₂ incubator at 37 °C for 2 h for neutralization.

[0492] (4) Add cell suspension: After 2 h of neutralization of the serum and the virus, take out the cell plate, add 0.1 mL / well of cell suspension (it is appropriate to grow into a monolayer in 24 h, generally 1 million - 1.5 million cells per milliliter) to each well, place it in a CO₂ incubator for culture, and judge after 72 h.

[0493] 2.4 Control experiment

[0494] (1) Negative and positive serum controls: Set 2 - 4 wells each. The antibody titers of the negative and positive controls should be valid.

[0495] (2) Virus regression test: Dilute the 200 TCID50 virus solution to 0.1, 1, 10, and 100 TCID50. For each dilution, use 2 - 4 wells, with 50 μL per well; add 50 μL of cell suspension. There should be no cytopathic effect (CPE) at 0.1 TCID50 and complete CPE at 100 TCID50, otherwise the experiment is not valid.

[0496] (3) Cell control: Set up 2 - 4 wells of normal cells without virus and serum as a control. These control cells should maintain good morphology and characteristics.

[0497] 2.5. Result determination and calculation

[0498] Determination can only be carried out when the virus regression test, positive control, negative control, and cell control are all valid. If 100% CPE appears in the test serum wells, it is judged negative; if more than 50% of the cells show protection, it is judged positive; use the Karber method to calculate the results.

[0499] 3. Cellular level detection

[0500] Collect the spleens of mice to measure the content of various T and B cells in mice.

[0501] 3.1. Detection of surface molecular markers of T lymphocytes:

[0502] Use flow cytometry to detect surface molecular markers of T lymphocytes. Place the refrigerated mouse spleen cells in a water bath at 37°C to thaw and prepare a single-cell suspension (1×107 cells / ml). Take 0.1 ml and put it into a falcon tube, add CD3-FITC Ab, CD4-PE Ab, and CD8-PE Ab, place it in the dark at room temperature for 30 min, wash twice with PBS, and add 0.5 ml of PBS and mix. Use CELLQuest functional software to analyze the positive expression rates of the two parameters CD3-FITC, CD4-pe, and CD8-pe of T lymphocytes, and calculate the CD4 / CD8 ratio.

[0503] 3.2. Enzyme-linked immunosorbent assay (ELISA):

[0504] After blood collection, let it stand for 24 hours, collect the supernatant from the ELISPOT plate, and store it at -80°C for enzyme-linked immunosorbent assay (ELISA) detection. Use a Biotek enzyme-linked immunosorbent assay instrument to detect the protein expression level at 450 nm. Divide the absorbance value of each cytokine or chemokine by the absorbance value of the sample before inoculation as the baseline control to obtain the fold change of cytokines and chemokines. Analyze T cells that produce hepatitis B surface antigen-specific IFN-γ, IL-2, and IL-4 through ELISPOT to evaluate the cellular immune response.

[0505] 3.2.1. Contents of the kit:

[0506] PVDF 96-well plate, store at room temperature; 0.1 ml capture antibody, store at 4°C; 0.1 ml biotinylated detection antibody, store at 4°C; 15 ul avidin alkaline phosphatase conjugate, store at 4°C; 0.25 g bovine serum albumin, store at 4°C; 0.25 g non-fat milk, store at 4°C; 11 ml substrate buffer, store at 4°C; 11 ml concentrated PBS (10X), store at room temperature; 11 ml concentrated wash buffer (200x), store at room temperature.

[0507] 3.2.2 Preparation of reagents:

[0508] (1) Dilute 10 ml phosphate buffered saline (PBS, 10X) with 90 ml distilled water;

[0509] (2) Dissolve 0.22 g non-fat milk in 11 ml diluted PBS, final concentration is 2%;

[0510] (3) Dissolve 0.22 g BSA in 22 ml diluted PBS, final concentration is 1%

[0511] (4) Dilute 10 ml concentrated wash buffer (200x) with 1990 ml distilled water;

[0512] (5) Dilute 10 ul avidin alkaline phosphatase with 10 ml PBS-1%, BSA

[0513] (6) Dilute 7 ml alcohol with 3 ml distilled water, final concentration is 70%.

[0514] 3.2.2, Stimulation method:

[0515] Indirect method: First stimulate the cells in a 24-well plate or flask, then place them in the pre-coated wells.

[0516] Dilute PBMC in the culture medium (such as: RPMI 1640 plus 2 mM glutamate and 10% heat-inactivated calf serum), which contains 1 ng / ml PMA and 500 ng / ml ionomycin (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. The incubation time for other stimulants may vary. Based on the amount of cytokine-producing cells, make the best choice according to different situations.

[0517] 3.2.4, Eli-spot operation procedure:

[0518] (1). Incubate the PVDF well plate with 100 ul 70% alcohol for 10 minutes at room temperature.

[0519] (2). Pour off the alcohol and wash 3 times with 100 ul PBS.

[0520] (3). Add 100 μl of capture antibody to 10 ml of PBS, mix, add 100 μl to each well, cover the plate, and incubate overnight at 4°C.

[0521] (4). Pour off the liquid and wash once with 100 μl of PBS.

[0522] (5). Add 100 μl of 2% skim milk PBS (see reagent preparation) to each well, cover the plate, and incubate at room temperature for 2 hours.

[0523] (6). Tap gently over the sink and on absorbent paper, and pour off the liquid.

[0524] (7). Wash three times with 100 μl of PBS for 3 minutes each time.

[0525] (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 pre-stimulated in vitro (indirect Eli-spot). Cover with the standard plastic lid of a 96-well plate and incubate in a 37°C CO2 incubator for a certain period of time (15 - 20 hours). Do not shake or move the plate during this period.

[0526] (9). Tap gently over the sink and on absorbent paper, and pour off the liquid.

[0527] (10). Add 100 μl of wash buffer to each well and incubate at 4°C for 10 minutes.

[0528] (11). Lyse the cells with pre-chilled ice water.

[0529] (12). Wash the wells eight times with 100 μl of wash PBST buffer for 4 minutes each time.

[0530] (13). Dilute 100 μl of detection antibody in 10 ml of PBS-1% BSA, which is the amount for one plate. Add 100 μl of this liquid to each well, cover the plate, and incubate at 37°C for 2 hours.

[0531] (14). Pour off the liquid and wash 5 times with 100 μl of wash buffer.

[0532] (15). Dilute 10 μl of avidin alkaline phosphatase in 10 ml of PBS1% BSA per plate. Add 100 μl of this liquid to each well, cover the plate, and incubate at 37°C for 1 hour.

[0533] 4. Statistical analysis

[0534] Statistical analysis was performed using one-way ANOVA and t-tests (GraphPad Prism 8.0). The differences between groups were considered statistically significant, and the data were expressed as mean ± standard deviation (SD). A p-value < 0.05 was considered statistically significant.

[0535] 5. Final Result

[0536] The multi - mode fluid delivery device of the present invention is configured such that the average antibody titer of the hepatitis B vaccine is more than 1.1 times that of the intramuscular injection 14 days after the second dose is administered;

[0537] The multi - mode fluid delivery device of the present invention is configured such that the average antibody titer of the hepatitis B vaccine is more than 1.5 times that of the intramuscular injection 42 days after the second dose is administered;

[0538] The multi - mode fluid delivery device of the present invention is configured such that the positive expression rate of T lymphocytes of the hepatitis B vaccine is more than 10% higher than that of the intramuscular injection 42 days after the second dose is administered.

[0539] In the above - mentioned 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 with the injection head and the needle member installed also has a similar dispersion effect and immunogenic effect as described above.

[0540] Example 6

[0541] In a specific embodiment of the present invention, the multi - mode fluid delivery device of the present invention is used in combination with GLP - 1 polypeptides, specifically, with semaglutide, with reference to Figure 40 , Figure 41 and Figure 48 , which shows one of the structural configurations of the multi - mode fluid delivery device of the embodiment of the present invention used in combination with semaglutide. Specifically, the second end 120 has a transition section 122 that axially narrows distally from the tube 100. Among them, the diameter of the tube is 5 mm, the end face 123 of the transition section 122 is configured as a circle with a diameter of 2.5 mm and is provided with 3 holes 121 thereon. The 3 holes 121 are arranged in an equally - spaced circular pattern around the center of the end face 123. The adjacent connecting lines between the 3 holes and the center of the end face 123 form an angle of 120°. Among them, the measured pore diameters of the 3 holes 121 are 0.14 mm to 0.17 mm, and the distances of the 3 holes 121 from the center of the end face 123 are uniformly set to 1.25 mm.

[0542] In the embodiment of the present invention, semaglutide, also known as Ozempic, is a second - generation glucagon - like peptide - 1 (GLP - 1) analogue, and its molecular formula is C 187 H 291 N 45 O 59It (molecular weight is 4113.58Da) has excellent hypoglycemic and weight loss effects for diabetic patients, which is significantly better than sitagliptin, insulin glargine U100 or sustained-release exenatide; it is also better than its peer drug liraglutide in weight loss, especially in patients with BMI ≥ 30. Semaglutide can be taken orally or subcutaneously, for example, as an oral dosage form of 7mg / 14mg once a day or a subcutaneous injection of 0.5mg / 1.0mg once a week. Semaglutide not only shows good efficacy in the treatment of diabetes, but also shows significant advantages in weight loss and cardiovascular protection.

[0543] The following is a specific semaglutide rat test of the multi-mode fluid delivery device of the present invention, wherein, under the structural configuration of the aforementioned multi-mode fluid delivery device of the present invention, a semaglutide rat test was conducted using semaglutide of the following structure according to the following experimental scheme:

[0544]

[0545] 1. Test materials

[0546] 1.1. Experimental animals: selection

[0547] Healthy male Wistar rats, aged 6-8 weeks, weighing 200-250 g.

[0548] 1.2. Experimental grouping: The rats were randomly divided into four groups, with 10 rats in each group.

[0549] 1.3. Delivery agent: semaglutide;

[0550] 1.4. Test equipment: a multi-mode fluid delivery device according to the above embodiment of the present invention (delivery pressure: 250N, aperture: 0.14mm-0.17mm); a traditional needle syringe, a medical cotton swab and an alcohol cotton.

[0551] 2. Test operation

[0552] 2.1. Drug administration

[0553] In the needle-free delivery group, the drug was administered using a multi-mode fluid delivery device according to the set parameters, and in the needle delivery group, the drug was administered using a traditional injection method, wherein:

[0554] Group 1: 1x dose with needle, daily*14 days;

[0555] Group 2: No needle 1x dose, daily*14 days;

[0556] Group 3: 10x dose with injection, weekly*2 weeks;

[0557] Group 4: needle-free 10x dose, weekly*2 weeks;

[0558] 2.2. Data collection

[0559] Record the daily changes in the body weight of rats, and monitor blood glucose and insulin levels.

[0560] 3. Result evaluation

[0561] a. Comparison between Group 1 and Group 2: Under the conditions of the same administration dose (1x) and frequency (daily), the total weight loss ratio of Group 2 (needle-free delivery) is 4% greater than that of Group 1 (needle delivery). In addition, the effect duration of Group 2 is longer, and the rebound time is delayed compared to Group 1.

[0562] b. Comparison between Group 3 and Group 4: Under the conditions of a higher dose (10x) and a lower frequency (weekly), the total weight loss ratio of Group 4 (needle-free delivery) is 5.5% greater than that of Group 3 (needle delivery).

[0563] In the above embodiments of the present invention, the injection head and the needle member thereon are removed from the tube. However, in some other embodiments of the present invention, the multi-mode fluid delivery device of the present invention with the injection head and the needle member installed is also expected to have similar diffusion effects and immunogenic effects as described above.

[0564] Example 7

[0565] In a specific embodiment of the present invention, the multi-mode fluid delivery device of the present invention is used in combination with a polypeptide tumor vaccine, referring to Figure 40 , Figure 41 and Figure 48 , which shows one of the structural configurations of the multi-mode fluid delivery device of the present invention in combination with a polypeptide tumor vaccine in the embodiments of the present invention. Specifically, the second end 120 has a transition section 122 that tapers axially distally from the tube 100. Among them, the diameter of the tube is 5 mm, the end face of the transition section 122 is configured as a circle with a diameter of 2.5 mm and is provided with 3 holes 121 thereon. The 3 holes 121 are arranged in an equally spaced circular pattern around the center of the end face 123. The included angle between the adjacent connecting lines of the 3 holes and the center of the end face 123 is 120°. Among them, the measured aperture values of the 3 holes 121 are 0.14 mm to 0.17 mm, and the distances of the 3 holes 121 from the center of the end face 123 are uniformly set to 1.25 mm.

[0566] In the embodiments of the present invention, the polypeptide tumor vaccine is a novel vaccine, which is essentially an immunogen that elicits the formation of effector cell immune responses in vivo. The tumor polypeptide vaccine is an antigen polypeptide eluted from the surface of tumor cells or a related polypeptide obtained from within tumor cells that can enhance the humoral and cellular immune responses against tumors in the immune system. Currently, tumor polypeptide vaccines that are widely studied include vaccines targeting the folate receptor (FR) or developed against the HER2 target.

[0567] The following is a specific polypeptide tumor vaccine rat immunization experiment of the multi-mode fluid delivery device of the present invention. Among them, under the structural configuration of the aforementioned multi-mode fluid delivery device of the present invention, the polypeptide tumor vaccine rat immunization experiment was carried out according to the following experimental protocol:

[0568] 1. Experimental materials

[0569] 1.1 Experimental animals: Sixty healthy male C57BL / 6 mice, 6 - 8 weeks old and weighing 18 - 22 grams, were selected and randomly divided into six experimental groups, namely G1, G2, G3, G4, G5, and G6 (10 mice in each group), using a random number table method.

[0570] 1.2 Experimental equipment: Neoantigen and positive control polypeptide, and the multi-mode fluid delivery device according to the embodiments of the present invention, wherein the pore size is 0.14 - 0.17 mm and the delivery pressure is 160 N.

[0571] 2. Immunization experiment

[0572] 2.1 Experimental setup:

[0573] The immunization experiment was carried out in 3 or 4 rounds according to the grouping in Table 6 below:

[0574] Table 11. Information table of polypeptide tumor vaccine rat immunization experiment

[0575]

[0576] 3. Effect detection

[0577] 3.1 Detection method: After the immunization, mouse spleen cells were taken for 4 rounds of ELISPOT detection of the detection results

[0578] 3.2 Detection results:

[0579] a. After three / four rounds of immunization of the mice, positive signals in the neoantigen group could be detected by the Elispot experiment, but the signals were weak.

[0580] b. There was no statistically significant difference in the average number of spots between the needle-free injection group and the needle injection group.

[0581] c. After the fourth round, the number of spots in each experimental group was less than that after the third round of immunization. Regarding the reduction ratio, the needle-free neoantigen group was 10% less than the needle neoantigen group and 20% less than the positive polypeptide group. It can be seen that the duration of effectiveness of the needle-free plus neoantigen polypeptide vaccine is longer than that of the other two groups.

[0582] In the above embodiments of the present invention, the injection head and the needle member thereon are removed from the tube. However, in some 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 similar dispersion effect and immunogenic effect as described above.

[0583] The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope 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 being 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 being configured to removably dock with the self-sealing elastic part or the hole for dispensing the fluid in the tube 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 operating connection piston to apply a delivery pressure to the piston pushing the fluid.

2. The multi-mode 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, 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 in the second end or the one or more needle members 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, characterized in that, 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 multimodal 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 distributing the 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 - 0.035 mm 2 , preferably 0.0028 - 0.020 mm 2 , more preferably 0.0028 - 0.009 mm 2 .

5. The multi-mode 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 the internal organs 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, wherein, The multi-mode fluid delivery device is configured such that the diffusion volume of the fluid 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 still more preferably more than 3.60 times.

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

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

9. The multi-mode 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, epidermis, subcutaneous layer, muscle, and human organ; Preferably, the third needle member has a third needle aperture sized such that a fluid jet through the third needle member diffuses in at least one more of the dermis, epidermis, or subcutaneous layer of the dermis, epidermis, subcutaneous layer, muscle, and human organ; Preferably, the third needle member has a third exit jet velocity configured such that a fluid jet through the third needle member diffuses in at least one more of the dermis, epidermis, subcutaneous layer, muscle, and human organ.

10. The multimodal 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 median line of the injection head. Preferably, one of the plurality of needle members linearly arranged along the diameter or the median line of the injection head is located at the center or the center of the injection head; Preferably, the plurality of needle members arranged in a line are equally spaced; Preferably, the plurality of needle members arranged in a line are mirror-symmetrical with respect to the diameter or the median line of the injection head; Preferably, there are multiple groups of the needle members, and each group of needle members is arranged in a line. Preferably, each group of needle members is arranged along a diameter or a median 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 median 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 multimodal 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 groups 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, characterized in that, 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 groups of the peripheral needle members, and each group of peripheral needle members is arranged in a ring. Preferably, the multiple groups 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 group of the multiple groups of peripheral needle members is different from the skin insertion depth of the other peripheral groups of needle members; Preferably, the skin insertion depths of the multiple groups 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 group of the multiple groups of peripheral needle members is different from the needle apertures of the other peripheral groups of needle members; Preferably, the needle apertures of the multiple groups 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 group of the multiple groups of peripheral needle members is different from the outlet jet velocities of the other peripheral groups of needle members; Preferably, the outlet jet velocities of the multiple groups of needle members arranged coaxially and annularly with each other and the central needle member decrease or increase radially.

16. The multi-modal 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 microhole 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 intrusive 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 multimodal 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 out from the front end of the needle sleeve to form an insertion portion.

20. The multi-mode 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 tip, so as to completely surround the first needle head to protect the first needle head.

21. The multimodal 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 multi-mode 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 the first needle head surrounded by it is completely surrounded. The second needle kit is configured such that the insertion part of the second needle kit surrounding the first needle head is located in the dermis layer. The third needle kit is configured such that the insertion part of the third needle kit surrounding the first needle head is located in the epidermis layer. The fourth needle kit is configured such that the insertion part of the fourth needle kit surrounding the first needle head is located under the skin. The fifth needle kit is configured such that the insertion part of the fifth needle kit surrounding the first needle head is located in the muscle. The sixth needle kit is configured such that the insertion part of the sixth needle kit surrounding the first needle head 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 tip and a rotating member operatively connected to the needle tip or the needle sleeve portion. The rotating member is configured to adjust the axial positions of the needle tip and the needle sleeve portion by rotation to adjust the exposed length of the needle tip relative to the needle sleeve portion.

24. The delivery device according to claim 23, wherein, The axial positions of the needle tip and the needle sleeve portion are configured to be adjustable between multiple positions so that the exposed length of the needle tip can be adjusted between multiple positions. Preferably, the exposed length of the needle tip can be adjusted between multiple positions of retracting from the needle sleeve portion, being flush with the needle sleeve portion, being 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 tip and the needle sleeve portion are configured to be continuously adjustable so that the exposed length of the needle tip 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 - connecting 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 - connecting portion.

27. A combined product of feline triple vaccine and 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 pharmaceutical device combination product according to claim 27, wherein The second end is provided with three holes, the three holes 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 away from the holes in the second end by the piston is 150.00 m / s ± 20%.

31. The medicament-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 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 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 hepatitis B vaccine drug-device combination product, 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 and medical device combination product according to claim 35, wherein The second end is provided with three holes, the three holes 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 and medical 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 and medical 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 away from the holes in the second end by the piston 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 and medical 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 and medical device combination product according to claim 42, characterized in that, 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 1.25 mm ± 20% away from the center.

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

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

47. The pharmaceutical device combination product according to claim 42, wherein, The multi-mode fluid delivery device is configured such that the average antibody titer of the pneumonia 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 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 1.25 mm ± 20% away from the center.

50. The pharmaceutical and medical device combination product according to claim 48, wherein, The multi-mode fluid delivery device is configured such that the diffusion 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 pharmaceutical and medical 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 pharmaceutical 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 further preferably increased by 10%.

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

54. The pharmaceutical and medical device combination product according to claim 48, characterized in that, 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, it is reduced by more than 5%, more preferably reduced by more than 10%, and further 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 an anti-tumor chemotherapy drug for humans; Optionally, the pharmaceutical preparation is a nuclear medicine treatment 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 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 pore 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, characterized in that, The plurality of holes include a first hole; Preferably, the first hole has a first pore diameter, and the size of the first pore diameter is configured such that the fluid jet through the first hole disperses in at least one of the dermis, epidermis, 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 pore diameter, and the size of the first pore diameter is configured such that the fluid jet through the first hole disperses in at least one of the dermis, epidermis, subcutaneous tissue, muscle, and human organs; the second hole has a second pore diameter, and the size of the second pore diameter is configured such that the fluid jet through the second hole disperses in at least another one of the dermis, epidermis, 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 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, there are multiple groups of the holes, 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, characterized in that, 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 have 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 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 have 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 syringe head according to claim 64, wherein, 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 micropore 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 syringe 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 syringe head according to claim 64, wherein, 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 one more of the dermis, epidermis, or subcutaneous tissue of the dermis, epidermis, subcutaneous tissue, muscle, and human organs.

71. The syringe 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 the 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 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 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, 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 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 depths of the multiple groups of needle members arranged in coaxial circular patterns with respect to each other decrease or increase 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 diameters of the multiple groups of needle members arranged in coaxial circular patterns with respect to each other decrease or increase radially.

75. The injection 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 depths of the multiple groups of needle members and the central needle member arranged in coaxial circular patterns with respect to each other decrease or increase 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 diameters of the multiple groups of needle members and the central needle member arranged in coaxial circular patterns with respect to each other increase or decrease radially.

77. The syringe head according to claim 64, characterized in that, The needle member further includes an intervening soft needle removably connected to the hole.

78. The syringe 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 assembly 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, characterized in that, 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 kit according to claim 80, characterized in that, 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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