A needleless transdermal administration device

Abstract

This invention provides a needle-free transdermal drug delivery device, relating to the field of biomedical engineering technology. The device includes: a drug liquid reservoir; a refrigerant supply reservoir; and a drug delivery reservoir, comprising: a drug delivery chamber and a negative pressure chamber. The drug delivery chamber contains an array of multiple drug delivery microchannels and multiple refrigerant microchannels. Each drug delivery microchannel is a tree-like microchannel with a multi-level diversion structure, used to progressively divide liquid drug into microdroplets. The refrigerant microchannels are connected to the refrigerant supply reservoir and are used to freeze the microdroplets within the drug delivery microchannels to form micro-ice columns. The negative pressure chamber is used to contact the surface of human skin to form a sealed space. A vacuum chamber provides a negative pressure source to the negative pressure chamber to drive the micro-ice columns within the drug delivery chamber to detach from the drug delivery microchannels and penetrate the skin. This invention utilizes microfluidics technology to achieve precise drug segmentation, realizing needle-free, painless, and highly active transdermal drug delivery.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology, and in particular to a needle-free transdermal drug delivery device. Background Technology

[0002] Transdermal drug delivery, as an important route for delivering active ingredients to specific layers of the skin to achieve therapeutic purposes, has continuously evolved to pursue ideal drug delivery effects. An ideal drug delivery technology should possess advantages such as precise and minute single-dose delivery, uniform subcutaneous drug distribution, painless or minimally painful delivery, controllable delivery depth, ease of operation, and low risk of infection. However, existing drug delivery technologies still have significant limitations in these aspects, making it difficult to fully meet the needs of clinical practice and patients.

[0003] Current transdermal drug delivery technologies can be mainly divided into needle-based injection, needle-free liquid jet injection, and the emerging cryo-microneedling technology. Needle-based injection techniques, including single-needle and multi-needle mesotherapy, while technically mature and with controllable depth, have inherent drawbacks that cannot be ignored. The mechanical puncture of the skin by the needle not only stimulates pain nerve endings, causing pain and psychological fear in patients and reducing treatment compliance, but also damages the skin barrier, leading to risks of bleeding, infection, and scarring. Furthermore, the drug tends to accumulate in focal clumps around the needle tract, resulting in uneven distribution, and requires a high level of operator skill. To overcome the drawbacks of needle-based injection, needle-free liquid jet technology has emerged. This technology uses high-pressure gas to accelerate and spray liquid drugs to penetrate the skin. While achieving needle-free delivery, its penetration depth is unstable, especially for high-viscosity solutions. The jet is prone to splashing and rebounding upon impact with the skin, resulting in drug waste, and the shear force generated by the high-pressure liquid flow may damage the activity of biomolecules such as proteins and exosomes.

[0004] Son et al. proposed a pisimetric ice particle delivery technology (PIPD), representing a cutting-edge exploration in the field of needle-free transdermal drug delivery. Its core working principle utilizes a supersonic cryogenic jet to simultaneously complete the atomization, freezing, and acceleration of liquid drugs within an extremely short time (<300 μs). Specifically, this technology uses a high-speed cryogenic jet to shear and exchange heat with the liquid drug, breaking it down into tiny droplets. These droplets are then rapidly frozen into solid ice particles at approximately -3°C, and accelerated to approximately 100 m / s by a supersonic airflow. The kinetic energy of the solid ice particles is then used to penetrate the skin barrier, thereby achieving transdermal drug delivery.

[0005] Despite the progress made in needle-free drug delivery, PIPD technology still suffers from several significant technical limitations. First, the technology uses liquid CO2 as a refrigerant. Due to the physical properties of CO2 (critical temperature 31°C, expanding to approximately -3°C), its freezing rate and the resulting ice particles have low hardness, leading to brittle ice particles and limited penetration. Second, in terms of drug delivery control, PIPD systems rely on continuous liquid supply and jet flow, making it difficult to precisely control the overall dose per administration down to the microliter level. Furthermore, the ice particle volume depends on the statistical distribution of jet breakup, preventing deterministic control. Additionally, its nozzles are mostly single-hole structures, resulting in a conical jet diffusion, which is less suitable for treatment scenarios requiring differentiated drug delivery areas (such as acne scar repair and targeted scar injection).

[0006] Further analysis revealed significant shortcomings in the PIPD technology regarding its auxiliary mechanisms and device engineering. The technology operates under normal atmospheric pressure, causing skin deformation and rebound upon impact with the ice particles, resulting in some kinetic energy loss and difficulty in suppressing drug splashing. More critically, the prototype device heavily relies on high-pressure liquid CO2 cylinders for gas supply, leading to a bulky and heavy machine with poor portability and hindering handheld operation. This fundamentally limits its application and promotion in home or non-medical settings. Summary of the Invention

[0007] To address the technical problems of existing technologies, such as large and uneven drug delivery and intense pain for patients, this invention provides a needle-free transdermal drug delivery device. The technical solution is as follows:

[0008] This invention provides a needle-free transdermal drug delivery device, comprising:

[0009] Liquid medicine reservoir, used to store liquid medicines;

[0010] Refrigerant supply compartment, used to store refrigerant;

[0011] The drug delivery chamber includes a drug delivery cavity and a negative pressure cavity. Multiple drug delivery microchannels and multiple refrigerant microchannels are arranged in an array within the drug delivery cavity. The drug delivery microchannels and refrigerant microchannels are staggered. Each drug delivery microchannel is a tree-shaped microchannel with a multi-stage diversion structure. One end of each microchannel is connected to the outlet of the drug liquid cavity via a main pipe, and the other end is an opening for progressively dividing the liquid drug into microdroplets. The refrigerant microchannel is connected to the refrigerant supply cavity and is used to freeze the microdroplets within the drug delivery microchannel to form micro-ice columns. One end of the negative pressure cavity is connected to the drug delivery cavity, and the other end is used to contact the surface of human skin to form a sealed space.

[0012] The vacuum chamber, connected to the negative pressure chamber, is used to provide a negative pressure source to the negative pressure chamber to drive the micro-ice column in the drug delivery chamber to detach from the drug delivery microchannel and puncture the skin.

[0013] Optionally, the tree-like microchannel includes a main channel and multiple branch channels connected in sequence; the input end of each branch channel is connected to the output end of the previous branch channel, and the output end of each branch channel is split and connected to multiple next-level branch channels.

[0014] Optionally, the refrigerant microchannel includes multiple serpentine microchannel units arranged in parallel and spaced apart along a first direction. Two adjacent serpentine microchannel units are connected in series through a return bend to form a continuous meandering flow path.

[0015] Optionally, a first control valve is provided on the connecting pipeline between the vacuum chamber and the negative pressure chamber.

[0016] Optionally, the drug delivery device further includes: an air inlet pipe; the air inlet pipe is connected to the negative pressure chamber; and a second control valve is provided on the pipe connecting the air inlet pipe and the negative pressure chamber.

[0017] Optionally, the liquid drug chamber includes: a chamber body, a piston, and a drive assembly; the piston is slidably disposed in the chamber body, and the output end of the drive assembly abuts against the piston, for driving the piston to move axially along the chamber body to squeeze the liquid drug.

[0018] Optionally, the injection rate of the driving component is not less than 5 μl / min.

[0019] Optionally, the diameter of the main channel is 0.5-2 mm; the cross-section of the branch channel is square, with a side length of 10-200 μm.

[0020] Optionally, the diameter of the refrigerant microchannel is 0.5-2 mm.

[0021] Optionally, the cooling medium is liquid nitrogen.

[0022] The beneficial effects of the technical solutions provided in the embodiments of the present invention include at least the following:

[0023] The needle-free transdermal drug delivery device of this invention integrates a tree-like multi-level diversion microfluidic channel to precisely divide the drug solution into nano-level discrete microdroplets and instantly freeze them into high-hardness solid micro-ice columns, achieving micro-quantification and deterministic control of the drug dosage. Combined with a vacuum negative pressure auxiliary mechanism, this invention not only effectively counteracts skin elastic recoil and inhibits drug splashing, but also enables programmable "dot-matrix" precise delivery based on lesion characteristics, significantly improving drug penetration depth and bioactivity retention rate. While ensuring painlessness, minimal invasiveness, and extremely low infection risk, this device overcomes the shortcomings of existing technologies such as coarse dosage, uneven distribution, and bulky equipment, combining high efficiency and portability, greatly improving patient compliance and clinical application value. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1 This is a schematic diagram of the structure of the needle-free transdermal drug delivery device provided in an embodiment of the present invention;

[0026] Figure 2 This is a schematic diagram of the drug delivery microchannel provided in an embodiment of the present invention;

[0027] Figure 3 This is a schematic diagram of the refrigerant microchannel provided in an embodiment of the present invention;

[0028] Figure 4 This is a schematic diagram of the staggered array distribution structure of drug delivery microchannels and refrigerant microchannels provided in an embodiment of the present invention.

[0029] Figure label:

[0030] 1-Medicine liquid reservoir;

[0031] 2-Refrigerant supply compartment;

[0032] 3-Drug delivery chamber; 3-1-Drug delivery cavity; 3-2-Negative pressure cavity; 31-Drug delivery microchannel; 311-Main channel; 312-Branch channel; 32-Refrigerant microchannel;

[0033] 4-Vacuum chamber; 5-Air inlet pipe; 6-Liquid outlet pipe; 7-1-First control valve; 7-2-Second control valve. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the described embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0035] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning understood by one of ordinary skill in the art to which this invention pertains. The terms "an," "a," or "the," and similar words used in this invention do not indicate a limitation of quantity, but rather indicate the presence of at least one. Terms such as "comprising" or "including" mean that the element or object preceding the word encompasses the elements or objects listed following the word and their equivalents, without excluding other elements or objects. Terms such as "connected" or "linked" are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect.

[0036] like Figure 1-4 As shown, the needle-free transdermal drug delivery device of this invention includes: a drug solution chamber 1, a refrigerant supply chamber 2, a drug delivery chamber 3, and a vacuum chamber 4.

[0037] The liquid medication reservoir 1 is used to store the liquid medication to be injected. In this embodiment, the liquid medication reservoir 1 may specifically include: a reservoir body, a piston, and a drive assembly. The piston is slidably disposed within the reservoir body, and the output end of the drive assembly abuts against the piston, used to drive the piston to move axially along the reservoir body to squeeze and deliver the liquid medication. Preferably, the drive assembly may be an injection pump, whose injection speed can be precisely controlled, with a minimum injection speed of 5 μl / min, to ensure the accuracy of the dosage.

[0038] The refrigerant supply chamber 2 is used to store the refrigerant. In this embodiment, the refrigerant is preferably liquid nitrogen. Liquid nitrogen has an extremely low temperature (approximately -196°C), which can provide an extremely high freezing rate, ensuring that drug microdroplets are instantly frozen into micro ice columns with high hardness and strong penetrating power, while maximizing the preservation of the activity of bioactive drugs (such as proteins and exosomes).

[0039] The drug delivery chamber 3 includes: a drug delivery chamber 3-1 and a negative pressure chamber 3-2.

[0040] Multiple drug delivery microchannels 31 and multiple refrigerant microchannels 32 are arranged in an array within the drug delivery chamber 3-1.

[0041] like Figure 2As shown, the drug delivery microfluidic channel 31 has a tree-like multi-level branching structure. Specifically, the tree-like multi-level branching structure includes a main channel 311 and multi-level branch channels 312 connected in sequence. The input end of each branch channel 312 is connected to the output end of the previous branch channel 312, and the output end of each branch channel 312 is split and connected to multiple lower-level branch channels 312. This hierarchical microfluidic structure can divide the drug solution delivered by the main channel 311 step by step, and finally form microdroplets with precise volume control at the end (reaching the nanoliter level). In terms of size design, the diameter of the main channel 311 is preferably 0.5-2 mm; the cross-section of the branch channel 312 is preferably square, and its side length is preferably 10-200 μm, so as to form micron-sized ice columns suitable for skin puncture. The drug delivery microfluidic channel 31 is connected to the outlet of the drug solution tank 1 through the main channel 311, and the end of the last branch channel 312 of the drug delivery microfluidic channel 31 forms an outlet for the high-speed ejection of the micro-ice columns after the microdroplets are frozen and formed.

[0042] like Figure 3 As shown, the refrigerant microchannel 32 is used to accommodate the flow of refrigerant media such as liquid nitrogen and to exchange heat with adjacent drug delivery microchannels 31. The diameter of the refrigerant microchannel 32 is preferably 0.5-2 mm. To ensure freezing efficiency and prevent premature vaporization of liquid nitrogen, the refrigerant microchannel 32 is preferably designed as a serpentine microchannel unit. The refrigerant microchannel 32 includes: multiple microchannels along a first direction (e.g., ...). Figure 4 The serpentine microchannel units (as shown in the x-direction) are arranged in parallel and spaced intervals. Adjacent serpentine microchannel units are connected in series through a return bend, forming a continuous meandering flow path. The drug delivery chamber 3-1 of the drug delivery container 3 may also be equipped with a liquid outlet pipe 6 that is connected to the refrigerant microchannel 32.

[0043] like Figure 4 As shown, multiple drug delivery microchannels 31 and multiple refrigerant microchannels 32 are arranged alternately, that is, a refrigerant microchannel 32 is set on each side of a drug delivery microchannel 31. This alternating arrangement maximizes the heat exchange area and ensures that the drug solution is completely frozen into solid micro-ice columns before flowing through the end opening. Preferably, the flow direction of the refrigerant medium such as liquid nitrogen in the refrigerant microchannel 32 is countercurrent to the flow direction of the drug solution in the drug delivery microchannel 31. The present invention arrays multiple drug delivery microchannels 31, each with an independent tree-like multi-level diversion structure and end opening, forming a "point-matrix" geometric matrix drug delivery. When it is necessary to deliver to a specific area, the injection pump is controlled to drive the piston to inject a quantitative amount of drug solution into the corresponding branch channel 312. Since each drug delivery microchannel 31 is independent of each other, the drug delivery device can precisely control the formation of microdroplets and freezing into ice columns at the end of the target channel, while the other channels remain empty, thereby achieving precise "point-matrix" delivery based on lesion characteristics.

[0044] One end of the negative pressure chamber 3-2 is connected to the drug delivery chamber 3-1, and the other end of the negative pressure chamber 3-2 has an open bottom for contact with the surface of human skin. In this embodiment, a sealing ring made of soft silicone is provided at the edge of the bottom opening of the negative pressure chamber 3-2, so that a sealed drug delivery space can be formed when the bottom of the negative pressure chamber 3-2 is in contact with the skin.

[0045] Vacuum chamber 4 is connected to negative pressure chamber 3-2 via a pipeline. Vacuum chamber 4 is supplied with negative pressure by an external vacuum pump or a built-in miniature vacuum pump. A first control valve 7-1 is installed on the pipeline connecting vacuum chamber 4 and negative pressure chamber 3-2. When the first control valve 7-1 is opened, the negative pressure environment inside vacuum chamber 4 is rapidly transferred to drug delivery chamber 3-1 via negative pressure chamber 3-2, generating an adsorption force on the frozen micro-ice columns, causing them to be ejected towards the human skin.

[0046] In some embodiments, the needle-free transdermal drug delivery device further includes an air inlet pipe 5. One end of the air inlet pipe 5 is connected to the outside atmosphere, and the other end is connected to the negative pressure chamber 3-2, for introducing air into the negative pressure chamber 3-2 to release the negative pressure after drug delivery. A second control valve 7-2 is provided on the pipe connecting the air inlet pipe 5 and the negative pressure chamber 3-2.

[0047] The working process of this invention embodiment is as follows:

[0048] 1) Preparation stage: Load a small amount of liquid drug into the drug tank 1 and remove air, then inject liquid nitrogen into the refrigerant supply tank 2. Ensure the bottom opening of the negative pressure chamber 3-2 of the drug delivery tank 3 is tightly sealed to the human skin to create a sealed environment.

[0049] 2) Diversion and Freezing: Upon activation of the drive assembly, the piston in the drug reservoir 1 pushes the drug into the main channel 311 of the drug delivery microchannel 31, and then diverts it through the multi-level branch channels 312, forming microdroplets at the end. Simultaneously, liquid nitrogen flows in the refrigerant microchannel 32, instantly freezing the microdroplets into solid micro-ice columns through heat exchange.

[0050] 3) Negative pressure emission: The control system opens the first control valve 7-1 and simultaneously closes the second control valve 7-2. The negative pressure inside the vacuum chamber 4 rapidly acts on the drug delivery chamber 3-1, creating an instantaneous negative pressure environment. Driven by the negative pressure, the micro-ice columns inside the drug delivery chamber 3-1 detach from the drug delivery microchannel 31 and penetrate the skin tissue at high speed.

[0051] 4) Reset: After administration, suspend the supply of liquid medicine and liquid nitrogen, close the first control valve 7-1, and open the second control valve 7-2 to allow outside air to enter the negative pressure chamber 3-2, restoring normal pressure and allowing the administration chamber 3 to detach smoothly from the skin. At this point, the administration chamber 3 can be removed to administer the next dose or end the treatment.

[0052] This invention utilizes microfluidic technology to achieve precise drug segmentation, uses liquid nitrogen and other cold media to achieve instantaneous solid-state formation of drugs, and combines negative pressure assisted delivery technology to achieve needle-free, painless, and highly active transdermal drug delivery, effectively solving the problems of uneven drug delivery, strong pain, and easy loss of drug activity in existing technologies.

[0053] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A needle-free transdermal drug delivery device, characterized in that, include: Liquid medicine reservoir, used to store liquid medicines; Refrigerant supply compartment, used to store refrigerant; The drug delivery chamber includes a drug delivery cavity and a negative pressure cavity. Multiple drug delivery microchannels and multiple refrigerant microchannels are arranged in an array within the drug delivery cavity. The drug delivery microchannels and refrigerant microchannels are staggered. Each drug delivery microchannel is a tree-shaped microchannel with a multi-stage diversion structure. One end of each microchannel is connected to the outlet of the drug liquid cavity via a main pipe, and the other end is an opening for progressively dividing the liquid drug into microdroplets. The refrigerant microchannel is connected to the refrigerant supply cavity and is used to freeze the microdroplets within the drug delivery microchannel to form micro-ice columns. One end of the negative pressure cavity is connected to the drug delivery cavity, and the other end is used to contact the surface of human skin to form a sealed space. The vacuum chamber, connected to the negative pressure chamber, is used to provide a negative pressure source to the negative pressure chamber to drive the micro-ice column in the drug delivery chamber to detach from the drug delivery microchannel and puncture the skin.

2. The needle-free transdermal drug delivery device according to claim 1, characterized in that, The tree-like microchannel includes a main channel and multiple branch channels connected in sequence; the input end of each branch channel is connected to the output end of the previous branch channel, and the output end of each branch channel is split and connected to multiple next-level branch channels.

3. The needle-free transdermal drug delivery device according to claim 1, characterized in that, The refrigerant microchannel includes multiple serpentine microchannel units arranged in parallel and spaced apart along a first direction. Two adjacent serpentine microchannel units are connected in series through a return bend to form a continuous meandering flow path.

4. The needle-free transdermal drug delivery device according to claim 1, characterized in that, A first control valve is installed on the connecting pipe between the vacuum chamber and the negative pressure chamber.

5. The needle-free transdermal drug delivery device according to claim 1, characterized in that, Also includes: An air intake pipe; the air intake pipe is connected to the negative pressure chamber; a second control valve is provided on the pipe connecting the air intake pipe and the negative pressure chamber.

6. The needle-free transdermal drug delivery device according to claim 1, characterized in that, The liquid drug chamber includes a chamber body, a piston, and a drive assembly; the piston is slidably disposed within the chamber body, and the output end of the drive assembly abuts against the piston, for driving the piston to move axially along the chamber body to squeeze the liquid drug.

7. The needle-free transdermal drug delivery device according to claim 6, characterized in that, The injection rate of the driving component is not less than 5 μl / min.

8. The needle-free transdermal drug delivery device according to claim 2, characterized in that, The diameter of the main channel is 0.5-2mm; the cross-section of the branch channel is square, with a side length of 10-200μm.

9. The needle-free transdermal drug delivery device according to claim 1, characterized in that, The diameter of the refrigerant microchannel is 0.5-2mm.

10. The needle-free transdermal drug delivery device according to claim 1, characterized in that, The cooling medium is liquid nitrogen.

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