Transdermal diffusion experiment device

Abstract

The invention discloses a transdermal diffusion experiment device. The device comprises a base, an anti-rotation limiting gasket and a pressing ring. A diffusion chamber is formed in the base, and a circle of step surface is arranged on the inner side wall of the base. The anti-rotation limiting gasket is arranged on the step face in a non-relative-rotation mode. The pressing ring is detachably installed above the anti-rotation limiting gasket. A liquid channel and an exhaust channel which are communicated with the diffusion cavity are formed in the outer wall of the base at intervals, the liquid channel extends to one side of the diffusion cavity from the outer wall of the base, and the bottom wall of the part, close to the diffusion cavity, of the liquid channel is flush with the bottom wall of the diffusion cavity. The exhaust channel extends to the outer wall of the base from the other side of the diffusion cavity, and the top wall of the part, close to the diffusion cavity, of the exhaust channel is flush with the top opening of the diffusion cavity. And a transdermal test membrane is detachably clamped between the opposite surfaces of the step surface and the anti-rotation limiting gasket. The transdermal diffusion experiment device disclosed by the invention has the advantages of small volume of the diffusion chamber and convenience in use.

Description

Technical Field

[0001] The invention relates to the technical field related to experimental equipment, and in particular to a transdermal diffusion experimental device. Background Art

[0002] Transdermal diffusion cells are used to test the speed and extent of topical drug preparations penetrating through membranes or skin. They are mainly composed of a sample chamber, a membrane or skin, and a receiving chamber. Based on the transdermal diffusion test method, the sample penetrates through the membrane or skin at the bottom of the sample cell into the receiving medium of the receiving cell, and the release or penetration effect of the sample is evaluated by quantitative detection of the receiving medium.

[0003] In actual application, the solubility of the drug in the receiving medium and the effective contact area between the drug or receiving medium and the membrane or skin have an important impact on the testing process. Among them, the solubility of the drug poses a huge challenge to the current transdermal testing methods. At present, the status quo of drug development is: there are more and more poorly soluble drugs, and the transdermal amount is very low. Drug developers often encounter that the drug concentration in the diffusion cell is too low to be quantitatively detected by conventional HPLC (high performance liquid chromatography) or UPLC (ultra-high performance liquid chromatography) methods. Therefore, it is necessary to optimize the current transdermal testing method, create favorable conditions for drug transdermal or transmembrane penetration, and increase the effective concentration of the drug in the diffusion cell to adapt to the development trend of topical skin drug products.

[0004] However, the diffusion cell of the existing transdermal diffusion test device is relatively large in volume, with an extended sampling arm, or requires external piping, and the sampling cavity volume is relatively large, which is not conducive to improving the effective concentration of the drug in the receiving medium. The height and cross-sectional diameter of the receiving chamber cavity inside the existing diffusion cell are relatively large, so that the contact area between the unit volume of the receiving medium and the membrane or skin is low, which is not conducive to drug diffusion. Therefore, the transdermal diffusion test device in the prior art has the problem of large volume, which is not conducive to improving the effective concentration of the drug in the medium, and requires an extended sampling arm and external piping to be used in conjunction during use, which is inconvenient to use. Summary of the invention

[0005] The purpose of the present application is to solve the problems in the prior art of transdermal diffusion testing devices, such as large size, inconvenience in improving the effective concentration of the drug in the medium, and inconvenience in use.

[0006] In order to solve the above technical problems, the present application discloses a transdermal diffusion experimental device, which includes a base, an anti-rotation limiting gasket and a pressure ring.

[0007] A diffusion chamber is formed in the base, the diffusion chamber is provided with a top opening, and a circle of step surfaces are provided on the inner side wall of the base and along the circumference of the base. The anti-rotation limit washer is placed on the step surface so as not to rotate relatively. The pressure ring is detachably installed above the anti-rotation limit washer.

[0008] A liquid channel and an exhaust channel connected to the diffusion chamber are provided at intervals on the outer wall of the base, wherein the liquid channel extends from the outer wall of the base to one side of the diffusion chamber, and the bottom wall of the channel near the diffusion chamber is flush with the bottom wall of the diffusion chamber, and the exhaust channel extends from the other side of the diffusion chamber to the outer wall of the base, and the top wall of the channel near the diffusion chamber is flush with the top opening of the diffusion chamber, wherein a clamping portion is formed between the step surface and the relative surface of the anti-rotation limit washer, and the clamping portion can detachably clamp a transdermal test membrane covering the top opening of the diffusion chamber.

[0009] By adopting the above technical solution, the present application opens the liquid channel and the exhaust channel on the outer wall of the base, that is, opens the liquid channel and the exhaust channel on the existing outer wall of the base. Compared with the existing extended sampling arm and sampling pipeline structure, the outer wall of the device does not have any extended structure, which significantly reduces the volume of the device and also reduces the volume of the diffusion chamber. The structure and volume are smaller and more compact, reducing the occupation of external space, making it more convenient to use and conducive to more efficient layout in limited experimental or production environments. After the external structure is eliminated, the stability and reliability of the device are higher, it is not easily affected by the external environment, and the service life is longer.

[0010] Furthermore, the transdermal diffusion testing device disclosed in the present application includes a base, an anti-rotation limit washer and a pressure ring. A complete testing device can be combined into a complete testing device by simple assembly using multiple parts. During the transdermal test, a transdermal test membrane is placed in the clamping portion formed between the step surface and the relative surface of the anti-rotation limit washer for testing. It has the advantages of simple structure, mass production and standardization. The operation process is simplified during assembly and use, thereby reducing the operation time and workload, and reducing the difficulty and complexity of operation.

[0011] Furthermore, in the transdermal diffusion testing device disclosed in the present application, the bottom wall of the portion of the liquid channel close to the diffusion chamber is flush with the bottom wall of the diffusion chamber. Such an arrangement can completely remove the liquid in the diffusion chamber each time the liquid is taken out, thereby avoiding liquid residue in the diffusion chamber that affects the experimental precision and accuracy. The top wall of the portion of the exhaust channel close to the diffusion chamber is flush with the top opening of the diffusion chamber, which can discharge bubbles more quickly and effectively, reduce residual bubbles, and thereby improve transdermal efficiency.

[0012] Further preferably, in the present application, the diffusion chamber in the base is a cylindrical cavity, and an anti-rotation protrusion is provided on the anti-rotation limit washer to prevent rotation during the installation of the anti-rotation limit washer. The pressure ring and the base are connected by a threaded connection, which is simpler and more convenient to assemble.

[0013] More preferably, the inner diameter of the diffusion chamber in the present application gradually increases from the bottom wall side toward the top opening side, so as to more effectively perform the transdermal experiment. And the volume of the diffusion chamber is in the range of 0.2-5 ml, which is smaller and more compact.

[0014] The present invention also discloses a transdermal test method applied to the transdermal diffusion experimental device, the method comprising:

[0015] S1. Select a transdermal experimental membrane to be used in the experiment, and then place the transdermal experimental membrane on the step surface of the base;

[0016] S2, placing the anti-rotation limiting gasket on the step surface and above the transdermal test membrane, and the anti-rotation protrusion and the anti-rotation limiting groove of the anti-rotation limiting gasket are engaged and limited, and when the anti-rotation limiting gasket is placed on the step surface, the transdermal test membrane is located in the clamping portion formed between the step surface and the opposite surface of the anti-rotation limiting gasket, and the transdermal test membrane covers the top opening of the diffusion chamber;

[0017] S3, tighten the pressure ring to the inner ring of the base by rotating the mounting seat, and press the pressure ring to the top of the anti-rotation limit washer;

[0018] S4, applying the drug preparation on the upper surface of the transdermal test membrane, and injecting the receiving medium from the liquid channel into the diffusion chamber through the infusion needle, when the medium liquid is injected through the infusion needle, the spherical or conical protrusions provided on the head of the infusion needle are adapted to the inner peripheral contour of the variable diameter infusion port of the liquid channel, or first injecting the receiving medium through the infusion needle, and then applying the drug preparation on the upper surface of the transdermal test membrane after the temperature and state of the transdermal test membrane in the diffusion pool are balanced;

[0019] S5. When taking liquid, use a liquid taking needle to directly reach the bottom of the second liquid channel to absorb the receiving medium, or use an infusion needle to absorb the receiving medium.

[0020] In the above method, the cover ring can be placed on the top of the base to cover the liquid channel and the exhaust channel for use as required. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 A schematic diagram of the transdermal diffusion testing device provided in Example 1 of the present invention when the cover is provided with a cover ring;

[0022] Figure 2 A schematic diagram of a transdermal diffusion testing device and an infusion needle provided in Example 1 of the present invention;

[0023] Figure 3 A half-section schematic diagram of a base of a transdermal diffusion testing device provided in Example 1 of the present invention;

[0024] Figure 4 A schematic diagram of the explosion structure of the transdermal diffusion testing device provided in Example 1 of the present invention;

[0025] Figure 5 A schematic diagram of a transdermal diffusion testing device provided in Example 2 of the present invention when the cover is provided with a cover ring;

[0026] Figure 6 A schematic diagram of the explosion structure of the transdermal diffusion testing device provided in Example 2 of the present invention;

[0027] Figure 7 A flow chart of a method for using the transdermal diffusion test device provided in Example 1 of the present invention;

[0028] Figure 8 is a schematic diagram of the explosion structure of the transdermal diffusion testing device provided in Example 3 of the present invention;

[0029] Fig. 9 It is a schematic diagram of the assembly structure of the transdermal diffusion testing device provided in Example 3 of the present invention.

[0030] Description of reference numerals:

[0031] 100. Base;

[0032] 110. Diffusion chamber;

[0033] 111. Top opening;

[0034] 120, step surface; 130, outer wall; 140, anti-rotation limit groove;

[0035] 150, first base; 160, second base; 170, sealing ring; 180, protrusion; 190, internal thread;

[0036] 101, auxiliary step surface; 102, height direction of the base; 103, clamping fixing portion; 104, anti-rotation clamping groove; 105, clamping protrusion;

[0037] 200, transdermal experimental membrane;

[0038] 300, anti-rotation limit washer;

[0039] 310, anti-rotation protrusion; 320, clamping portion;

[0040] 400, pressure ring;

[0041] 410, positioning hole; 420, external thread;

[0042] 500, liquid channel;

[0043] 510, first liquid channel; 520, second liquid channel; 530, variable diameter infusion channel;

[0044] 600, exhaust passage;

[0045] 610, first exhaust channel; 620, second exhaust channel;

[0046] 700, rotating mounting seat;

[0047] 710, positioning protrusion;

[0048] 800, cover ring;

[0049] 900, infusion needle;

[0050] 910, infusion hole; 920, protrusion;

[0051] A. Inner diameter of the diffusion chamber; B. Height of the diffusion chamber. DETAILED DESCRIPTION

[0052] As mentioned in the background technology of the present application, the existing transdermal diffusion test pool or test device are all set to have a larger structural volume, all with an extended sampling arm or need external pipelines. For example, some need to be provided with a sampling arm for sampling, and some need to be provided with external pipelines, liquid inlet pipelines and liquid outlet pipelines and some other external structures, etc., which all increase the volume and occupied space of the transdermal device or transdermal diffusion pool, especially when using, it is necessary to pay attention to the external structure, further increase the complexity of operation, and require the operator to adopt more sophisticated operating skills to ensure the accuracy of sampling. During operation, the sampling arm may be disturbed by the external environment, such as temperature fluctuations, vibrations, etc., thereby affecting the stability of sampling, and the sampling arm may interfere with each other during use or in the experimental process, increasing the maintenance cost of the equipment. And the existing diffusion pool is mostly provided with a larger volume, and it is impossible to perform a small volume transdermal test, so the existing transdermal diffusion test pool has the problem of inconvenient use.

[0053] In order to solve the problems of inconvenience in using the transdermal diffusion test pool in the prior art and inability to perform small-volume transdermal tests, the present application provides a transdermal diffusion test device that can be assembled and used, has a small volume and has good transdermal test effects, eliminates the sampling arm and external pipeline structures of the existing diffusion pool, and multiple components are assembled and used, thereby facilitating maintenance and repair, and can also be mass-produced and mass-tested or sold. The specific structure of the transdermal diffusion test device disclosed in the present application is explained in detail below:

[0054] Example 1

[0055] This embodiment discloses a transdermal diffusion experimental device, see Figure 1 The transdermal diffusion experimental device provided in the present application comprises a detachable base 100, an anti-rotation limiting washer 300 and a pressure ring 400 ( Figure 1 The cover ring 800 in the device can be selected according to the needs). Specifically, by assembling the base 100, the transdermal test membrane 200, the anti-rotation limit washer 300 and the pressure ring 400 together in sequence, a transdermal diffusion test device can be obtained. The transdermal test membrane 200 can be an artificial synthetic membrane, an animal or human skin membrane, etc., such as a polyvinylidene fluoride membrane, a cellulose membrane, a polypropylene membrane, a mouse skin membrane, a pig skin membrane, a human skin membrane, etc. When different transdermal test membranes 200 are needed for different transdermal test experiments, the corresponding transdermal test membranes 200 are disassembled, reassembled and replaced.

[0056] The base 100 of the present application has a diffusion chamber 110 formed therein. The diffusion chamber 110 is provided with a top opening 111. The top opening 111 of the diffusion chamber 110 can be seen in FIG. Figure 3 , and a circle of step surfaces 120 are provided on the inner side wall of the base 100 and along the circumference of the base 100. Those skilled in the art should understand that the diffusion chamber 110 is a cavity formed in the base 100. The cavity can be of any various structural shapes as long as it has a top opening 111 open to the outside. In the present embodiment, it is preferably set as a cylindrical cavity. Further, in the present application, the base 100 is also a columnar structure. For example, the base 100 can be set as a square columnar, a circular columnar or other structures. In a preferred implementation method disclosed in the present embodiment, the base 100 is also set as a cylindrical shape. The diffusion chamber 110 is a cavity provided in the middle of the top of the base 100. Those skilled in the art should understand that in some specific experimental processes, the diffusion chamber 110 can also be called a receiving chamber.

[0057] See also Figure 1 as well as Figure 2The anti-rotation limit washer 300 is placed on the step surface 120 in a non-rotatable manner. The anti-rotation limit washer 300 should be configured as a thin sheet ring washer with a shape similar to that of the step surface 120. For example, when looking down from the top of the anti-rotation limit washer 300 and the step surface 120, the anti-rotation limit washer 300 and the step surface 120 are overlapped. When the step surface 120 is in a circular ring shape, the anti-rotation limit washer 300 is also configured as a circular thin sheet washer. For example, the thickness of the anti-rotation limit washer 300 may be in the range of 0.2 to 2 mm. The pressure ring 400 is detachably mounted above the anti-rotation limit washer 300, and the pressure ring 400 is also configured to be an annular structure with a shape similar to that of the step surface 120, and when looking downward from above the pressure ring 400, the pressure ring 400, the anti-rotation limit washer 300 and the step surface 120 are overlapped, and when the step surface 120 is in a circular ring shape, the pressure ring 400 is also configured to be in a circular ring shape, and because the pressure ring 400 is to press and fix the anti-rotation limit washer, in one of the preferred implementations the thickness of the pressure ring 400 is greater than the thickness of the anti-rotation limit washer 300.

[0058] A clamping portion 320 is formed between the step surface 120 and the opposite surface of the anti-rotation limiting washer 300, and the clamping portion 320 detachably clamps the transdermal test membrane 200 covering the top opening 111 of the diffusion chamber 110. Figure 1 as well as Figure 4 , those skilled in the art should understand that the step surface 120 and the anti-rotation limit washer 300 form the opposite surface of the clamping portion 320 refers to the relative surface of the step surface 120 and the anti-rotation limit washer 300 in the installed state or Figure 1 In the state shown, a clamping portion 320 is formed between the upper surface of the step surface 120 and the lower surface of the anti-rotation limit washer 300. The gap of the clamping portion 320 is small and is used to clamp the transdermal test membrane 200. That is to say, the clamping portion 320 formed between the relative surfaces of the step surface 120 and the anti-rotation limit washer 300 can more stably clamp and fix the transdermal test membrane 200 for drug transdermal testing.

[0059] And because in this embodiment, the step surface 120 is a circular ring, and the anti-rotation limit washer 300 is also a circular ring, the clamping portion 320 is also formed in a ring shape, and the transdermal test membrane 200 is a circular sheet structure. The outer diameter of the transdermal test membrane 200 is equal to or slightly smaller than the outer diameter of the step surface 120 to ensure that the transdermal test membrane 200 is stably clamped and fixed in the clamping portion 320. It should be understood that the shape of the clamping portion is determined by the step surface 120 and the anti-rotation limit washer 300. For example, when the step surface 120 and the anti-rotation limit washer 300 are square ring structures, the clamping portion 320 is also square ring-shaped. Those skilled in the art can design and adjust according to actual needs, and this embodiment does not make specific limitations on this.

[0060] When a transdermal test is required, a transdermal test membrane 200 is placed between the upper surface of the step surface 120 and the lower surface of the anti-rotation limit washer 300, and the transdermal test membrane 200 covers the top opening of the diffusion chamber 110. Specifically, the transdermal test membrane 200 is first placed on the step surface 120 and then the anti-rotation limit washer 300 is placed. The transdermal test membrane 200 fits tightly with the anti-rotation limit washer 300, and the periphery of the transdermal test membrane 200 is clamped and fixed by the clamping portion 320. More specifically, the clamping portion 320 can fix and clamp part of the annular outer periphery of the transdermal test membrane 200, and the middle part of the transdermal test membrane 200 covers the top opening 111 of the diffusion chamber 110. When the clamping portion 320 does not place the transdermal test membrane 200, the step surface 120 and the anti-rotation limit washer 300 form a relative surface fit of the clamping portion 320.

[0061] It should be noted that, in this embodiment, reference is made to Figure 4 and Figure 1 When assembling a device for a transdermal test, a transdermal test membrane 200 is first placed on the step surface 120, and the transdermal test membrane 200 covers the top opening 111 of the diffusion chamber 110 (see Figure 2 ), an important step in conducting a transdermal experiment is to place a transdermal experiment membrane 200 on the step surface 120 of the base 100, see Figure 3 and Figure 4 In this embodiment, a circle of step surfaces 120 arranged on the circumference of the base 100 is a circular step surface, and has such a structure that the circular step surface 120 is adapted to the shape of the circular transdermal test membrane 200. When the transdermal test membrane 200 is installed, the transdermal test membrane 200 can be accurately and quickly placed on the step surface 120 and cover the top opening 111 of the diffusion chamber 110. In the actual transdermal experiment process, the experimenter can first select different transdermal test membranes according to the experiment to be performed, and after the transdermal test membrane 200 is placed, the interior of the diffusion chamber 110 becomes a relatively closed chamber. In the process of performing the transdermal experiment after the device is assembled, the test drug or test medicine is placed above the transdermal test membrane 200, and the diffusion chamber 110 is a receiving medium, which can be a solvent or saline, and then the transdermal experiment is performed.

[0062] Furthermore, in some common transdermal tests, the clamping portion 320 generally only clamps one transdermal test membrane 200 for testing. In some other transdermal tests, the clamping portion 320 may also clamp two or more identical transdermal test membranes 200 for testing, or may clamp two or more different transdermal test membranes 200 for testing. Those skilled in the art may use them according to actual needs, and this embodiment does not make any specific limitations on this.

[0063] The anti-rotation limiting washer 300 needs to play the role of anti-rotation positioning, so the anti-rotation limiting washer 300 must be placed above the transdermal test membrane 200 in a manner that it cannot rotate relative to each other (such as clamping, etc.). Specifically, in a preferred implementation method disclosed in this embodiment, the anti-rotation limiting washer 300 is set in a circular ring shape and has a relatively thin thickness, and the side of the anti-rotation limiting washer 300 close to the transdermal test membrane 200 is tightly fitted with the transdermal test membrane 200 or the step surface 120 (the state where the transdermal test membrane 200 is not placed), and the outer ring of the anti-rotation limiting washer 300 is provided with at least one anti-rotation protrusion 310, and the inner side wall of the base 100 is provided with an anti-rotation limiting groove 140 adapted to the anti-rotation protrusion 310. For example, 1, 2, 3, 4 or even more anti-rotation protrusions 310 can be set. In this embodiment, Figure 4 In a preferred implementation disclosed, three anti-rotation protrusions 310 are provided, and the anti-rotation positioning effect is good. The thickness of the anti-rotation limiting gasket 300 is preferably set in the range of 0.2-2 mm, and the material can be set to polytetrafluoroethylene, rubber, silicone and other materials with good flexibility and toughness, so as to achieve the protection and fixation effect of the transdermal experimental membrane 200.

[0064] The pressure ring 400 and the base 100 can be fixed by various detachable connection methods such as clamping, threading, etc. For example, when connected by clamping, a clamping protrusion is set on the outer wall of the pressure ring 400, and a clamping groove is set at a corresponding position of the inner wall of the base 100, and the clamping protrusion and the clamping groove are adapted to fix. Alternatively, a threaded groove is set at a corresponding position of the outer wall of the pressure ring 400 and the inner wall of the base 100 for connection. See Figure 4 In this embodiment, the pressure ring 400 and the base 100 are preferably connected in a threaded connection manner, and the outer wall of the pressure ring 400 is provided with an outer thread 420, and the inner wall of the base 100 is provided with an inner thread 190 adapted to the outer thread. In the axial direction of the base 100, the anti-rotation limit washer 300 and the inner wall of the pressure ring 400 are flush with the inner wall of the diffusion chamber 110. When the pressure ring 400 is fastened to the base 100, the anti-rotation limit washer 300 can provide an additional resistance to ensure that the pressure ring 400 and the transdermal experimental membrane 200 remain in the correct position, and along the axial direction of the base 100, ensure that the anti-rotation limit washer 300 and the inner wall of the pressure ring 400 are flush with the inner wall of the diffusion chamber 110. Such a design can keep the interior of the device smooth and flat, and ensure that the transdermal diffusion area remains consistent.

[0065] Furthermore, compared to the existing diffusion cells that rely on clips to clamp the supply cell and the receiving cell, relative sliding is prone to occur during experimental operations, resulting in displacement, misalignment of the upper cell and the lower cell, and thus affecting the diffusion area. In the present application, the connection is performed through a threaded connection, which can be precisely aligned, has better sealing performance and no risk of relative sliding, thereby providing a stable transdermal test environment during the transdermal test.

[0066] Because the pressing ring 400 in this embodiment is installed in a threaded connection manner, in order to facilitate the installation and removal of the pressing ring 400, see Figure 4 , a swivel mounting seat 700 is also provided, which actually plays the role of assisting the screwing and installing the pressure ring 400. The swivel mounting seat 700 is adapted to the pressure ring 400, and a positioning protrusion 710 is provided on one side of the swivel mounting seat 700, and a positioning hole 410 is also provided on the side of the pressure ring 400 away from the anti-rotation limit washer 300, and the positioning protrusion 710 is adapted and connected with the positioning hole 410, and then the swivel mounting seat 700 is rotated to simultaneously rotate the pressure ring 400 to tighten or loosen the thread. In order to improve the effect of assisting the screwing installation, it is preferred that the number of the positioning protrusion 710 and the positioning hole 410 is set to 2 or more. Those skilled in the art can design and select according to actual needs, and this embodiment does not make specific limitations on this.

[0067] In a preferred implementation method disclosed in the present embodiment, the width dimension of the step surface 120, the circular ring width dimension of the anti-rotation limit washer 300, and the circular ring width dimension of the pressure ring 400 are the same, for example, they are all set to a width of 4mm, 5mm, 6mm, etc., and the present embodiment does not make any specific limitation on this. Moreover, because the pressure ring 400 is to play a threaded fixing role, the number of thread turns on the pressure ring 400 should be greater than 0.5 turns. In addition, because the thickness of the pressure ring 400 determines the upper limit of the thickness of the loaded medicine, there should be sufficient loading thickness. Therefore, the thickness of the pressure ring 400 is set to be not less than 1mm, for example, any value within the thickness dimension of 2~6mm, such as 2mm, 4mm, 6mm, etc. Those skilled in the art can adjust and design according to actual needs, and the present embodiment does not make any specific limitation on this.

[0068] Further preferably, see Figure 1 as well as Figure 3The outer wall 130 of the base 100 is provided with a liquid channel 500 and an exhaust channel 600 which are connected to the diffusion chamber 110 at intervals. The liquid channel 500 and the exhaust channel 600 are formed with two holes at the top of the outer wall 130 of the base 100. The liquid channel 500 extends from the outer wall 130 of the base 100 to one side of the diffusion chamber 110, and the bottom wall of the channel near the diffusion chamber 110 is flush with the bottom wall of the diffusion chamber 110. This structure is conducive to taking out the receiving medium in the diffusion chamber 110 when taking liquid. The exhaust channel 600 extends from the other side of the diffusion chamber 110 to the outer wall 130 of the base 100, and the top wall of the channel near the diffusion chamber 110 is flush with the top opening 111 of the diffusion chamber 110. In other words, the top wall of the channel near the diffusion chamber 110 of the exhaust channel 600 is infinitely close to the transdermal experimental membrane 200 on the horizontal plane. The purpose of this arrangement is to be more conducive to the discharge of bubbles.

[0069] It should be noted that the liquid channel 500 in this embodiment has a dual function. The liquid channel 500 can be used as an infusion channel and can also be used as a liquid collection channel. Figure 2 When used as an infusion channel, the receiving medium is injected from the liquid channel 500 into the diffusion chamber 110 through the infusion needle 900. When the receiving liquid needs to be sampled, the receiving liquid is sucked out through the liquid collection needle.

[0070] Furthermore, the liquid channel 500 and the exhaust channel 600 are arranged at intervals on the outer wall 130 of the base 100. In this embodiment, it is preferably arranged that the liquid channel 500 and the exhaust channel 600 are arranged relative to each other and the interval angle is 180 degrees. Technical personnel in this field can also adjust the positions of the liquid channel 500 and the exhaust channel 600 according to actual needs, and this embodiment does not make any specific limitations on this.

[0071] With the above-mentioned structural design, the present application first opens the liquid channel 500 and the exhaust channel 600 on the outer wall 130 of the base 100, that is, opens the liquid channel 500 and the exhaust channel 600 on the existing outer wall 130 of the base 100. Compared with the existing extended sampling arm and sampling pipeline structure, the outer wall 130 of the device does not have any extended structure, which significantly reduces the volume of the device, and the structure, volume and size are smaller and more compact, and also reduces the occupation of external space, which is conducive to more efficient layout in heating devices or experimental environments with limited space, and can also be more conveniently integrated with other equipment for use. In addition, the stability and reliability of the device are high, it is not easily affected by the external environment, and has a long service life.

[0072] Furthermore, the transdermal diffusion test device disclosed in the present application includes a base 100, an anti-rotation limit washer 300 and a pressure ring 400. A complete device can be realized by simply assembling multiple parts and installing and placing a transdermal test membrane 200. It has the advantages of simple structure, standardization and batch production. It also simplifies the operation process during assembly and use, reduces the operation time and workload, and reduces the difficulty and complexity of operation. Similarly, it is safer and more hygienic.

[0073] Furthermore, in the transdermal diffusion testing device disclosed in the present application, the bottom wall of the liquid channel 500 close to the diffusion chamber 110 is flush with the bottom wall of the diffusion chamber 110. Such a setting can completely remove the liquid in the diffusion chamber 110 each time the liquid is taken out, thereby avoiding residual liquid in the diffusion chamber 110 that affects the experimental precision and accuracy. The top wall of the exhaust channel 600 close to the diffusion chamber 110 is flush with the top opening 111 of the diffusion chamber 110, which can discharge bubbles more quickly and effectively, reduce residual bubbles, and thereby improve the transdermal efficiency.

[0074] Next, the specific configuration of the liquid channel 500 and the exhaust channel 600 disclosed in the present application is further explained and illustrated:

[0075] In this embodiment, only one liquid channel 500 and one exhaust channel 600 are provided, and they are arranged on both sides of the outer wall 130 of the base 100 in an opposed manner and at intervals, for example Figure 1 as well as Figure 2 As shown, in the cross-sectional view along one of the axial directions, the liquid channel 500 and the exhaust channel 600 can be seen at the same time, and because the liquid channel 500 is used for infusion and liquid extraction, the bottom of the liquid channel 500 is flush with and tangent to the bottom of the diffusion chamber 110, and the exhaust channel 600 is basically flush with and tangent to the top of the diffusion chamber 110. It should be noted that in other implementations, the liquid channel 500 and the exhaust channel 600 are not limited to being set to one. For example, when the exhaust requirement is high, 2, 3 or other numbers of exhaust channels 600 can be set at intervals. Similarly, the liquid channel 500 can also be set to 2, 3 or other numbers according to requirements, and this embodiment does not make specific limitations on this.

[0076] Further, see Figure 1 as well as Figure 3 The liquid channel 500 includes a first liquid channel 510 and a second liquid channel 520 which are opened in the outer wall 130 of the base 100 and communicate with each other. Figure 3In the cross-sectional view taken along the axial direction of the base 100, the first liquid channel 510 and the second liquid channel 520 are in an "L" shape, wherein the first liquid channel 510 extends along the axial direction of the base 100, the top opening 111 of the first liquid channel 510 is on the top wall of the base 100, and includes a variable diameter infusion passage 530 whose diameter gradually decreases along the liquid flow direction, for example, the variable diameter infusion passage 530 can be set to a funnel shape, a trumpet shape or other variable diameter structure. The second liquid channel 520 extends along the radial direction of the base 100, one side opening of the second liquid channel 520 is connected to the outlet end of the first liquid channel 510, the other side opening is connected to the diffusion chamber 110, and the bottom wall is flush with the bottom wall of the diffusion chamber 110, that is, the variable diameter infusion passage 530, the first liquid channel 510 and the second liquid channel 520 in the liquid channel 500 are connected in sequence and finally connected to the diffusion chamber 110.

[0077] Preferably, the inner diameter of the first liquid channel 510 and the second liquid channel 520 does not exceed 5 mm, for example, it can be set to 1 mm, 1.5 mm, 3 mm, 5 mm, etc., more preferably not exceeding 1.5 mm, and technical personnel in this field can design and adjust it according to actual needs, and this embodiment does not make a sole limitation on this.

[0078] Specifically, in this embodiment, the variable diameter infusion passage 530 disposed at the top of the first liquid channel 510 is in the shape of a trumpet, and the purpose of such a configuration is to more conveniently adapt to the infusion needle 900. The middle part of the infusion needle 900 is provided with an infusion hole 910, and the head of the infusion needle 900 is provided with a spherical or conical protrusion 920, and the shape of the spherical or conical protrusion 920 is adapted to the inner peripheral contour of the variable diameter infusion port (trumpet) of the liquid channel 500. When the infusion needle 900 transports the receiving medium toward the diffusion chamber 110, the receiving medium first flows downward through the first liquid channel 510, and then flows into the diffusion chamber 110 through the second liquid channel 520. When it is necessary to take liquid, a liquid taking needle (not shown in the figure) can be used. It should be noted that in this embodiment, the outer diameter of the liquid taking needle is smaller than the inner diameter of the first liquid channel 510 and the second liquid channel 520, so that the liquid taking needle can directly reach the bottom of the second liquid channel 520, and because the bottom of the second liquid channel 520 is flush with and tangent to the bottom wall of the diffusion chamber 110, the liquid taking needle can completely take away all the receiving medium inside. When the experiment is finished, the liquid taking needle can also be used instead of the liquid taking needle, and the infusion needle 900 can be used for sampling. The receiving medium is sucked out into the infusion needle 900 through the second liquid channel 520 and the first liquid channel 510 in turn. Because the inner diameters of the second liquid channel 520 and the first liquid channel 510 are very thin, when the shape of the head of the liquid taking needle changes to fit closely with the bell mouth of the variable diameter infusion passage 530, all the receiving medium inside can be completely taken away.

[0079] In this embodiment, the first liquid channel 510 and the second liquid channel 520 are arranged in an "L" shape, which effectively utilizes the space and makes the flow path of the liquid more reasonable. No additional structure is set outside the base 100, and the diffusion behavior inside the base 100 is not affected. The first liquid channel 510 and the second liquid channel 520 are arranged in an "L" shape, which also helps the liquid to be stirred or further processed inside the base 100. The variable diameter infusion passage 530 with a gradually decreasing diameter along the liquid flow direction is set at the top. This design allows the infusion needle 900 to be pressed down and sealed even when there is a certain error in the alignment of the first liquid channel 510.

[0080] In addition, one side opening of the second liquid channel 520 is connected to the outlet end of the first liquid channel 510, ensuring that the liquid can smoothly enter the second liquid channel 520 from the first liquid channel 510. The other side opening is connected to the diffusion chamber 110, which helps to further disperse or mix the liquid in the diffusion chamber 110. The bottom wall is flush with the bottom wall of the diffusion chamber 110. In addition to the effects of liquid extraction and infusion, it also helps to maintain uniform distribution of liquid in the diffusion chamber 110. That is to say, the liquid in the second liquid channel 520 can flow into the diffusion chamber 110 to avoid accumulation of liquid in the chamber or formation of dead corners.

[0081] See also Figure 3 The exhaust channel 600 includes a first exhaust channel 610 and a second exhaust channel 620 which are opened in the outer wall 130 of the base 100 and are connected to each other, wherein the exhaust channel 600 and the liquid channel 500 are arranged on opposite sides in the radial direction of the base 100, and the first exhaust channel 610 extends along the radial direction of the base 100, one side opening of the first exhaust channel 610 is connected to the diffusion chamber 110, and the top wall is flush with the top opening 111 of the diffusion chamber 110; the second exhaust channel 620 is arranged along the axial direction of the base 100, one side opening of the first exhaust channel 610 is connected to the other side end of the first exhaust channel 610, and the other side opening extends to the top wall of the base 100; and the diameter of the first exhaust channel 610 is larger than the diameter of the second exhaust channel 620.

[0082] Further, it should be noted that, in this embodiment, the liquid channel 500 and the exhaust channel 600 are arranged with a height difference in the diffusion chamber 110 along the height direction of the diffusion chamber 110, see Figure 3The relative height of the second liquid channel 520 of the liquid channel 500 is lower than the first exhaust channel 610 of the exhaust channel 600. This arrangement is designed based on the needs of infusion or liquid extraction and exhaust. The bottom wall of the second liquid channel 520 is flush with the diffusion chamber 110, which helps to remove the receiving medium. The top wall of the first exhaust channel 610 is flush with the top opening 111 of the diffusion chamber 110, which helps to remove bubbles.

[0083] In this embodiment, the exhaust channel 600 includes a first exhaust channel 610 and a second exhaust channel 620. This design can effectively utilize the space of the base 100 while ensuring smooth discharge of gas. The top wall is flush with the top opening 111 of the diffusion chamber 110. When the diffusion pool is tilted so that the second exhaust channel 620 is upward, this helps the bubbles in the diffusion chamber 110 to float up into the first exhaust channel 610, avoiding gas accumulation in the chamber or forming a dead corner. Specifically, because the bubbles will float upward, when they float to the top of the diffusion chamber 110, if they cannot be removed in time, it will affect the contact between the top transdermal experimental membrane 200 and the receiving medium, and it may even accumulate in the chamber or in the dead corner area. When the top wall is flush with the top opening 111 of the diffusion chamber 110, the bubbles will flow to the first exhaust channel 610 and the second exhaust channel 620, and then be discharged along the second exhaust channel 620, thereby achieving the beneficial effect of avoiding gas accumulation in the chamber or forming a dead corner.

[0084] Furthermore, the diameter of the first exhaust channel 610 is larger than the diameter of the second exhaust channel 620, which helps larger bubbles to enter the exhaust channel 600 from the diffusion chamber 110, thereby improving the gas discharge efficiency. At the same time, as described above, the larger diameter of the first exhaust channel 610 can further prevent gas from accumulating in the chamber (exhaust channel 600 area) or forming a dead angle. For example, in this embodiment, the diameter of the first exhaust channel 610 is set to 3 mm, 4 mm, etc., and the diameter of the second exhaust channel 620 is only set to 1.5 mm, 2 mm, etc.

[0085] In another preferred implementation, the first exhaust channel 610 can also be configured to be flat, such as an elliptical or waist-shaped hole, to increase the contact area for bubble discharge. Such a configuration structure can further improve the exhaust efficiency.

[0086] The embodiment of the present invention also discloses a transdermal diffusion experimental device, which also includes a cover ring 800 (see Figure 1), the cover ring 800 is removably disposed on the top of the base 100, the lower end surface of the cover ring 800 is tightly fitted with the top wall of the base 100, and at least covers the liquid channel 500 and the exhaust channel 600 to prevent the solvent in the receiving liquid from volatilizing through the openings of the liquid channel 500 and the exhaust channel 600. It should be noted that the cover ring 800 is selected for use according to actual needs. For example, during the transdermal experiment, when it is necessary to cover the liquid channel 500 and the exhaust channel 600, the cover ring 800 is placed on the top of the base 100, so that the liquid channel 500 and the exhaust channel 600 are covered by the cover ring 800.

[0087] To further solve the problem that the height and cross-sectional diameter of the receiving chamber cavity inside the existing diffusion pool are relatively large, resulting in a low contact area between the unit volume of receiving medium and the membrane or skin, which is not conducive to drug diffusion, the inner diameter of the diffusion chamber 110 is set to be larger than the height of the diffusion chamber 110.

[0088] In the transdermal diffusion experimental device disclosed in the embodiment of this embodiment, please refer to Figure 2 For ease of marking, the arrow indicating the inner diameter A of the diffusion chamber 110 is moved upward and marked at the top. In one preferred implementation, the inner diameter A of the diffusion chamber 110 is larger than the height B of the diffusion chamber 110. The purpose of this arrangement is to increase the contact area between the receiving medium and the transdermal diffusion membrane in the diffusion chamber 110. This can be achieved even with a small volume by reducing the height. In one preferred implementation, the inner diameter of the diffusion chamber 110 is slightly smaller than the diameter of the transdermal diffusion membrane and larger than the height of the diffusion chamber 110. For example, in one implementation, the inner diameter of the diffusion chamber 110 can be set to between 10 and 30 mm, and the height of the diffusion chamber 110 can be within the range of 3 to 8 mm. This embodiment does not impose a sole limitation on this. Along the axial direction of the base 100, the inner diameter of the diffusion chamber 110 gradually increases from the bottom wall side toward the top opening 111 side. For example, in Figure 2 In the cross-sectional view shown, the inner side wall of the diffusion chamber 110 is in an inverted trapezoidal shape, so as to more effectively perform the transdermal experiment.

[0089] Furthermore, when conducting a small-volume diffusion experiment, the diameter and height of the diffusion chamber 110 can be reduced, and the inner diameter of the diffusion chamber 110 from the bottom wall side toward the top opening 111 side can be gradually increased to reduce the actual effective volume, so that the effective volume of the diffusion chamber 110 is in the range of 0.2~5ml. For example, the effective volume can be 0.2ml, 0.8ml, 3ml, 5ml, etc., which is smaller and more compact, and can meet the needs of testing with fewer doses.

[0090] The transdermal diffusion experimental device disclosed in the embodiment of the present embodiment also includes a magnetic rotor, which is located in the diffusion chamber 110. Specifically, the magnetic rotor is placed in the diffusion chamber 110 before the transdermal experimental membrane 200 is installed. The magnetic rotor can rotate and stir the receiving medium inside the diffusion chamber 110 under the action of the magnetic field, thereby improving the efficiency of transdermal diffusion or transdermal reaction. Furthermore, the magnetic rotor can be replaced with different volumes, so that the volume of the receiving medium in the diffusion chamber 110 can be further adjusted to obtain receiving solutions of different concentrations. More preferably, in this embodiment, the effective volume can be within the range of 0.2mL-2mL by setting a variable diameter diffusion chamber 110 and a magnetic rotor. For example, after placing the magnetic rotor, the effective volume can be 0.2ml, 0.8ml, 1.2ml, 2ml, etc., so as to reduce the volume of the receiving medium and increase the drug content in the receiving medium.

[0091] Finally, the assembly and experimental steps of the transdermal diffusion experimental device disclosed in this embodiment are briefly described:

[0092] First, when assembling the transdermal diffusion experimental device, the first step is to select and determine the transdermal experimental membrane 200 to be used for the experiment. Then, in the second step, the transdermal experimental membrane 200 is placed on the step surface 120 of the base 100 (when the magnetic rotor is needed, the magnetic rotor is first installed in the diffusion chamber 110). In the third step, the anti-rotation limit washer 300 is placed on the step surface 120 and above the transdermal experimental membrane 200, and during the placement process, the anti-rotation protrusion 310 and the anti-rotation limit groove 140 of the anti-rotation limit washer 300 are engaged and limited. At this time, the transdermal experimental membrane 200 is located in the clamping portion 320 between the step surface 120 and the anti-rotation limit washer 300. In the fourth step, the pressure ring 400 is installed and tightened on the inner ring of the base 100 through the auxiliary rotation mounting seat 700, and is pressed and installed on the top of the anti-rotation limit washer 300, and the assembly process of the transdermal diffusion experimental device is completed.

[0093] When conducting a transdermal experiment, the drug preparation can be first applied to the upper surface of the transdermal experiment membrane 200 according to the needs, or the receiving medium can be first injected into the diffusion chamber 110 through the infusion needle 900 and the liquid channel 500. When the cover ring 800 is needed, the cover ring 800 is placed on the top of the base 100 for the experiment, for example, placed in a magnetic field, and the magnetic rotor is driven by the magnetic field to stir to improve the mixing efficiency. After diffusion, the receiving medium is taken away by the liquid collection needle for concentration testing, etc., and the experiment can also be batched to perform multiple groups of experiments at the same time, for example, six or twelve groups are used for parallel experiments at the same time, and this embodiment does not make specific limitations on this.

[0094] Furthermore, this embodiment also includes a method for applying the transdermal diffusion experimental device, see Figure 7 , the method comprising:

[0095] S1, selecting a transdermal experimental membrane 200 to be used in the experiment, and then placing the transdermal experimental membrane 200 on the step surface 120 of the base 100;

[0096] S2, placing the anti-rotation limiting gasket 300 on the step surface 120 and above the transdermal experimental membrane 200, and the anti-rotation protrusion 310 of the anti-rotation limiting gasket 300 and the anti-rotation limiting groove 140 are engaged and limited, and when the anti-rotation limiting gasket 300 is placed on the step surface 120, the transdermal experimental membrane 200 is located in the clamping portion 320 formed between the step surface 120 and the opposite surface of the anti-rotation limiting gasket 300, and the transdermal experimental membrane 200 covers the top opening 111 of the diffusion chamber 110;

[0097] S3, the pressure ring 400 is installed and tightened on the inner ring of the base 100 and the top of the anti-rotation limit washer 300 by rotating the mounting seat 700;

[0098] S4, applying the drug preparation on the upper surface of the transdermal experimental membrane 200, and injecting the receiving medium from the liquid channel into the diffusion chamber 110 through the infusion needle 900. When the medium liquid is injected through the infusion needle 900, the spherical or conical protrusion 920 provided on the head of the infusion needle 900 is adapted to the inner peripheral contour of the variable diameter infusion port 530 of the liquid channel 500, or the receiving medium is injected through the infusion needle 900 first, and then the drug preparation is applied on the upper surface of the transdermal experimental membrane 200 after the temperature and state of the transdermal experimental membrane 200 in the diffusion cell are balanced;

[0099] S5. When taking liquid or after the test, use the liquid taking needle to directly reach the bottom of the second liquid channel 520 to absorb the receiving medium, or use the infusion needle 900 to absorb the receiving medium;

[0100] In the above method, the cover ring 800 can be placed on the base 100 to cover the liquid channel 500 and the exhaust channel 600 for use as required. In the above method, the magnetic rotor can also be installed in the diffusion chamber 110 before the transdermal test membrane 200 is placed. Further, in step S4, the time, sequence, dosage, etc. of applying the drug preparation or injecting the receiving medium can be adjusted by those skilled in the art according to the actual test requirements. This embodiment does not make a sole limitation thereto, and in step S4, it is preferred that the upper surface of the liquid surface of the medium injected into the diffusion chamber 110 is flush with the transdermal test membrane 200.

[0101] Example 2

[0102] It should be noted that the structure and working mode of the transdermal diffusion experimental device disclosed in this embodiment are the same as those in Example 1. The only difference is that the structure of the base 100 in this embodiment is different from that in Example 1. The base 100 in Example 1 is an integrated base 100, and the base 100 in this embodiment includes a detachable first base 150 and a second base 160.

[0103] For details, see Figure 5 and Figure 6 In the transdermal diffusion experimental device disclosed in the embodiment of the present embodiment, the base 100 includes a first base 150 and a second base 160 which are sequentially arranged in the axial direction and detachably connected to each other, the first base 150 is arranged on the top wall of the second base 160, and a sealing ring 170 is arranged between the first base 150 and the second base 160. In one preferred implementation, the first base 150 is in the shape of a hollow cylinder, and a protrusion 180 adapted to the inner wall of the lower end of the first base 150 is arranged in the middle of the second base 160, and the protrusion 180 is in the shape of a cylinder, and in order to facilitate the installation of the sealing ring 170, a step and an installation groove for installing the sealing ring 170 are arranged on the protrusion 180 in this embodiment, so as to improve the sealing performance of the first base 150 and the second base 160. Furthermore, this embodiment only shows one connection method between the split first base 150 and the second base 160 , and those skilled in the art can adjust and design it according to actual needs, and this embodiment does not make any specific limitation to this.

[0104] Further preferably, the first base 150 includes but is not limited to being made of any one of acrylic material, quartz, crystal, tempered glass, plastic, and ceramic, preferably made of transparent acrylic material, quartz, crystal, tempered glass, transparent plastic, etc., and the second base 160 includes but is not limited to being made of any one of metal material with good thermal conductivity, quartz, crystal, tempered glass, ceramic, acrylic material, and plastic. The inner side wall of the first base 150 is provided with an internal thread, the protrusion 180 is provided with an external thread adapted to the internal thread, and the sealing ring 170 is sleeved on the protrusion 180.

[0105] With the above-mentioned structural design, the first base 150 is preferably made of acrylic material, quartz, crystal, or tempered glass, which has good transparency, chemical stability, and is lightweight. The first base 150 is made of acrylic material, quartz, crystal, or tempered glass so that visual observation and recording can be performed during transdermal diffusion. The first base 150 and the second base 160 are threadedly connected and cooperate with the sealing ring 170 to ensure that the connection between the first base 150 and the second base 160 is firm and the sealing is reliable to prevent loosening. The presence of the sealing ring 170 can ensure a reliable seal and further prevent leakage of the receiving medium.

[0106] That is to say, under some specific requirements, the base 100 in this embodiment can be threadedly assembled using a two-part structure. For example, when visual observation is required, the upper first base 150 can be set to acrylic or tempered glass to meet different experimental requirements. For example, when there is a higher demand for heat conduction, the lower second base 160 is set to a metal material base. The experimental use method of the transdermal diffusion experimental device disclosed in Example 2 is basically the same as that in Example 1. The only difference is that in this embodiment, the first base 150 and the second base 160 are installed before the experiment and the connection is sealed.

[0107] Example 3

[0108] The implementation method of this embodiment also discloses a transdermal diffusion experimental device. It should be noted that the transdermal diffusion experimental device disclosed in this embodiment is basically the same as that of Embodiment 1 and Embodiment 2, and includes a base 100, an anti-rotation limit washer 300, a pressure ring 400, and a cover ring 800 that needs to be selected according to needs. The difference is that in this embodiment, an auxiliary step surface 101 is provided on the outer wall of the base 100 and along the outer periphery of the base 100. It should be noted that in order to distinguish this embodiment from Embodiments 1 and 2, the height direction of the base 100 is marked as shown in FIG. Figure 8 As shown by the arrow 102 in FIG. 1 , in the height direction of the base 100 , the auxiliary step surface 101 is flush with the step surface 120 . In addition, the openings of the liquid channel 500 and the exhaust channel 600 are both opened on the auxiliary step surface 101 .

[0109] Please note that, see Figure 2 as well as Figure 5In the schemes disclosed in Examples 1 and 2, the top openings of the liquid channel 500 and the exhaust channel 600 are both higher than the height of the transdermal test membrane 200 and the step surface 120. In the transdermal test process, the most commonly used experimental scenario is that the liquid surface of the receiving medium in the diffusion chamber 110 is flush with the transdermal test membrane 200, thereby simulating the transdermal test process. Therefore, in the configuration of Examples 1 and 2, a certain volume of the receiving medium needs to be accurately injected to make the liquid surface of the receiving medium in the diffusion chamber 110 flush with the transdermal test membrane 200. When the liquid surface height in the liquid channel 500 is higher than the transdermal test membrane 200, the liquid surface of the receiving medium in the diffusion chamber 110 is flush with the transdermal test membrane 200. 00 and the step surface 120, it is necessary to absorb the excess receiving medium through the infusion needle 900, otherwise, based on the principle of communicating vessels, the receiving medium in the liquid channel 500 will gradually enter the diffusion chamber 110. When the liquid level in the liquid channel 500 is flush with the liquid level of the receiving medium in the diffusion chamber 110, the liquid level of the receiving medium will exceed the transdermal experimental membrane 200, resulting in direct contact between the receiving medium and the drug, thereby affecting the experimental accuracy or even making it impossible to conduct a transdermal experiment. Therefore, Examples 1 and 2 have higher requirements for the accuracy of the liquid level of the receiving medium in the diffusion chamber 110.

[0110] In this embodiment, the auxiliary step surface 101 is flush with the step surface 120, and the transdermal test membrane 200 placed on the step surface 120 is basically flush with the step surface 120, and the top openings of the liquid channel 500 and the exhaust channel 600 are flush with the auxiliary step surface 101. Therefore, in the height direction of the base 100, the transdermal test membrane 200 is basically flush with the top opening of the liquid channel 500. Taking the injection of the receiving medium into the liquid channel 500 as an example, the receiving medium is injected from the liquid channel 500 into the diffusion chamber 110 through the infusion needle 900, and the injection of the receiving medium is stopped when the diffusion chamber 110 is filled with the receiving medium or the receiving medium is flush with the transdermal test membrane 200. Therefore, each time the receiving medium is injected into the diffusion chamber 110, it can always be ensured that the receiving medium and the transdermal test membrane 200 are flush, thereby accurately simulating the transdermal test process. Further, the auxiliary step surface 101 and the step surface 120 are flush with each other, which helps to maintain the stability and position of the receiving medium and the transdermal experimental membrane 200 during the experiment, and prevents the experimental error caused by the change of the liquid level of the receiving medium. It is also simpler and more convenient when injecting the receiving medium. When the liquid level in the liquid channel 500 on the auxiliary step surface 101 is flush with the auxiliary step surface 101, the liquid level of the receiving medium in the diffusion chamber 110 is also flush with the transdermal experimental membrane 200.

[0111] Further preferably, see Figure 8The base 100 further includes a clamping fixing portion 103 protruding from the inner periphery of the auxiliary step surface 101 and around the step surface 120. The clamping fixing portion 103 is annular in shape as a whole, the anti-rotation limiting washer 300 is non-rotatably adapted to the inner side of the clamping fixing portion 103, and the inner wall of the clamping fixing portion 103 is detachably adapted to the outer wall of the pressure ring 400.

[0112] It should be noted that the anti-rotation limiting washer 300 is arranged in the same manner as in Embodiment 1 and Embodiment 2, and is also adapted to the inner side of the clamping fixing portion 103 in a non-rotatable manner relative to each other, and a clamping portion 320 for clamping the transdermal experimental membrane is formed between the anti-rotation limiting washer 300 and the step surface 120. While the inner wall of the clamping fixing portion 103 is detachably adapted to the outer wall of the pressure ring 400, the pressure ring 400 needs to be arranged to be able to move along the inner wall of the clamping fixing portion 103 (in the same direction as the height direction of the base), that is, during the installation and disassembly process, the pressure ring 400 must be able to move along the height direction of the inner wall of the clamping fixing portion 103. Therefore, the pressure ring 400 and the inner wall of the clamping fixing portion 103 can be detachably connected by a threaded connection, or by a clamping protrusion and a slide groove. Those skilled in the art can design and select according to actual needs, and this embodiment does not make specific limitations on this.

[0113] Further preferably, the diffusion chamber 110 in the base 100 is a cylindrical cavity. The clamping fixing portion 103 is in the shape of a ring protruding from the auxiliary step surface 101, and is provided with a plurality of anti-rotation slots 104 along the circumferential direction, for example, 2, 3, 4 or even more anti-rotation limit washer 300 is in the shape of a ring, and is provided with at least one clamping protrusion 105 on the outer peripheral side wall, and the clamping protrusion 105 can be adapted to a corresponding anti-rotation slot 104. And the inner wall of the clamping fixing portion 103 and the outer wall of the pressure ring are detachably adapted to each other through threaded connection. The detachable connection method of the pressure ring 400 disclosed in this embodiment is the same as that of Embodiment 1 and Embodiment 2, both of which are detachably connected by threaded connection, and the rotating mounting seat 700 can also be used to screw and install the pressure ring, and the functional rotating mounting seat 700 can also be used for screwing and installation when disassembling.

[0114] See also Figure 8 In a preferred implementation method disclosed in this embodiment, three anti-rotation slots 104 are provided on the snap-fit ​​fixing portion 103, and each anti-rotation slot 104 penetrates the snap-fit ​​fixing portion 103 along the height direction of the base 100. With such a structure, each snap-fit ​​protrusion 105 of the anti-rotation limiting washer 300 will adapt to the anti-rotation slot 104 and then move along the anti-rotation slot 104 to fit the step surface 120.

[0115] Finally, the installation and use of the transdermal diffusion experimental device disclosed in this embodiment are briefly described:

[0116] First, assemble the first base 150 and the second base 160 together to ensure the bottom sealing of the diffusion chamber 110, then select the transdermal test membrane 200 used in the experiment and place it on the step surface 120 of the base 100, then adapt the snap-in protrusion 105 and the anti-rotation slot 104 of the anti-rotation limit washer 300 to the snap-in limit and place them on the step surface 120, above the transdermal test membrane 200, when the anti-rotation limit washer 300 is placed on the step surface 120, the transdermal test membrane 200 is located in the clamping portion 320 formed between the relative surfaces of the step surface 120 and the anti-rotation limit washer 300, and the transdermal test membrane 200 covers the top opening 111 of the diffusion chamber 110, screw the pressure ring 400 on the inner wall of the snap-in fixing portion 103 by rotating the mounting seat 700, apply the drug preparation on the upper surface of the transdermal test membrane 200, and infuse the receiving medium from the liquid into the liquid through the infusion needle 900. The channel 500 is injected into the diffusion chamber 110. When the liquid level in the liquid channel 500 approaches the top opening, the liquid level in the diffusion chamber 110 and the transdermal test membrane 200 are close to or flush with each other, and then a transdermal test is performed. Alternatively, the receiving medium is first injected using the infusion needle 900, and the drug preparation is applied to the upper surface of the transdermal test membrane 200 after the temperature and state of the transdermal test membrane 200 in the diffusion pool are balanced. When taking the liquid or after the test, the liquid taking needle is used to directly reach the bottom of the liquid channel 500 to absorb the receiving medium, or the infusion needle 900 is used to absorb the receiving medium. The cover ring 800 can be placed on the auxiliary step surface 101 as needed to cover the liquid channel 500 and the exhaust channel 600 for use. Similarly, those skilled in the art can adjust the time, sequence, dosage, etc. of applying the drug preparation or injecting the receiving medium according to actual test requirements, and this embodiment does not make a sole limitation on this.

[0117] It should be noted that, in addition to the implementation methods of the present invention described in the above-mentioned specific specific embodiments, those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Although the description of the present invention will be introduced in conjunction with the preferred embodiment, this does not mean that the features of this invention are limited to this implementation method. On the contrary, the purpose of introducing the invention in conjunction with the implementation method is to cover other options or modifications that may be extended based on the claims of the present invention. In order to provide a deep understanding of the present invention, the above description contains many specific details, and the present invention can also be implemented without using these details. In addition, in order to avoid confusion or blurring the focus of the present invention, some specific details will be omitted in the description. It should be noted that the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

[0118] It should be noted that in this specification, similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, it does not need to be further defined and explained in the subsequent drawings.

[0119] In the description of this embodiment, it should be noted that the terms "upper", "lower", "inner", "bottom", etc. indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, or are the orientations or positional relationships in which the inventive product is usually placed when used. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0120] The terms “first”, “second”, etc. are only used for distinguishing descriptions and should not be understood as indicating or implying relative importance.

[0121] In the description of this embodiment, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms "set", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in this embodiment can be understood according to specific circumstances.

[0122] Although the present invention has been illustrated and described with reference to certain preferred embodiments of the present invention, it should be understood by those skilled in the art that the above is a further detailed description of the present invention in conjunction with specific embodiments, and it cannot be determined that the specific implementation of the present invention is limited to these descriptions. Those skilled in the art may make various changes in form and details, including making several simple deductions or substitutions, without departing from the spirit and scope of the present invention.

Claims

1. A transdermal diffusion experimental device, characterized in that: include A base, wherein a diffusion chamber is formed in the base, the diffusion chamber is provided with a top opening, and a circle of step surfaces is provided on the inner side wall of the base and along the circumference of the base; An anti-rotation limiting washer, the anti-rotation limiting washer is placed on the step surface in a non-rotatable manner; A pressure ring, the pressure ring is detachably mounted above the anti-rotation limiting washer; wherein A liquid channel and an exhaust channel connected to the diffusion chamber are provided at intervals on the outer wall of the base, wherein the liquid channel extends from the outer wall of the base to one side of the diffusion chamber, and the bottom wall of the channel near the diffusion chamber is flush with the bottom wall of the diffusion chamber, and the exhaust channel extends from the other side of the diffusion chamber to the outer wall of the base, and the top wall of the channel near the diffusion chamber is flush with the top opening of the diffusion chamber; A clamping portion is formed between the step surface and the opposite surface of the anti-rotation limiting washer, and the clamping portion can detachably clamp the transdermal test membrane covering the top opening of the diffusion chamber.

2. The transdermal diffusion experimental device according to claim 1, characterized in that: The liquid channel comprises a first liquid channel and a second liquid channel which are opened in the outer wall of the base and communicate with each other; and In a cross-sectional view taken along the axial direction of the base, the first liquid channel and the second liquid channel are in an "L" shape, wherein the first liquid channel extends along the axial direction of the base, the top of the first liquid channel opens to the top wall of the base, and includes a variable diameter infusion passage with a diameter gradually decreasing along the liquid flow direction; the second liquid channel extends along the radial direction of the base, one side opening of the second liquid channel is connected to the outlet end of the first liquid channel, the other side opening is connected to the diffusion chamber, and the bottom wall is flush with the bottom wall of the diffusion chamber.

3. The transdermal diffusion experimental device according to claim 2, characterized in that: The exhaust channel includes a first exhaust channel and a second exhaust channel which are opened in the outer wall of the base and communicate with each other; in The exhaust channel and the liquid channel are arranged on opposite sides in the radial direction of the base; and The first exhaust channel extends along the radial direction of the base, one side opening of the first exhaust channel is connected to the diffusion chamber, and the top wall is flush with the top opening of the diffusion chamber; the second exhaust channel is arranged along the axial direction of the base, one side opening of the first exhaust channel is connected to the other side end of the first exhaust channel, and the other side opening extends to the top wall of the base; and the diameter of the first exhaust channel is larger than the diameter of the second exhaust channel.

4. The transdermal diffusion experimental device according to claim 1, characterized in that: The diffusion chamber in the base is a cylindrical cavity; The anti-rotation limiting washer is in a circular ring shape, wherein the outer ring of the anti-rotation limiting washer is provided with at least one anti-rotation protrusion; The inner side wall of the base is provided with an anti-rotation limiting groove adapted to the anti-rotation protrusion.

5. The transdermal diffusion experimental device according to claim 4, characterized in that: The outer wall of the pressure ring is provided with an external thread, and the inner wall of the base is provided with an internal thread adapted to the external thread; wherein Along the axial direction of the base, the inner side walls of the anti-rotation limiting washer and the pressure ring are flush with the inner side wall of the diffusion chamber; and It also includes a rotating mounting seat, which is adapted to the pressure ring, and a positioning protrusion is arranged on one side of the rotating mounting seat, and a positioning hole is arranged on the side of the pressure ring away from the anti-rotation limiting washer, and the positioning protrusion is adapted to be connected with the positioning hole.

6. The transdermal diffusion experimental device according to claim 1, characterized in that: It also includes a cover ring, which is removably arranged on the top of the base, the lower end surface of the cover ring is tightly fitted with the top wall of the base, and at least covers the liquid channel and the exhaust channel.

7. The transdermal diffusion experimental device according to claim 1, characterized in that: Along the axial direction of the base, the inner diameter of the diffusion chamber gradually increases from the bottom wall side toward the top opening side; and The volume of the diffusion chamber is in the range of 0.2-5 ml.

8. The transdermal diffusion experimental device according to claim 1, characterized in that: The base comprises a first base and a second base which are sequentially arranged along the axial direction and detachably connected to each other, the first base is arranged on the top wall of the second base, and a sealing ring is arranged between the first base and the second base; The interior of the first base is cylindrical, and a protrusion that is adapted to the inner wall of the lower end of the first base is provided in the middle of the second base, and the protrusion is cylindrical.

9. The transdermal diffusion experimental device according to claim 8, characterized in that: The first base is made of any one of acrylic material, quartz, crystal, tempered glass, plastic, and ceramic, and the second base is made of any one of metal material, quartz, crystal, tempered glass, ceramic, acrylic material, and plastic; and The inner side wall of the first base is provided with an internal thread, the protruding portion is provided with an external thread matching the internal thread, and the sealing ring is sleeved on the protruding portion.

10. The transdermal diffusion experimental device according to claim 1, characterized in that: Also included is a magnetic rotor located in the diffusion chamber; and It also includes an infusion needle, wherein an infusion hole is arranged in the middle of the infusion needle, and a spherical or conical protrusion is arranged at the head of the infusion needle, and the shape of the spherical or conical protrusion is adapted to the inner peripheral contour of the variable diameter infusion port of the liquid channel.

11. The transdermal diffusion experimental device according to claim 1, characterized in that: An auxiliary step surface is provided on the outer wall of the base along the outer periphery of the base, and the auxiliary step surface is flush with the step surface in the height direction of the base; and The openings of the liquid channel and the exhaust channel are both opened on the auxiliary step surface.

12. The transdermal diffusion experimental device according to claim 11, characterized in that: The base also includes a clamping fixing portion protruding from the inner periphery of the auxiliary step surface and surrounding the step surface; wherein The clamping fixing portion is annular as a whole, the anti-rotation limiting washer is non-rotatably adapted to the inner side of the clamping fixing portion, and the inner wall of the clamping fixing portion is detachably adapted to the outer wall of the pressure ring.

13. The transdermal diffusion experimental device according to claim 12, characterized in that: in The diffusion chamber in the base is a cylindrical cavity; The clamping fixing portion is annular and protrudes from the auxiliary step surface, and is provided with a plurality of anti-rotation grooves along the circumferential direction; the anti-rotation limiting washer is annular and is provided with at least one clamping protrusion on the outer peripheral side wall, and the clamping protrusion can be adapted to a corresponding one of the anti-rotation grooves; and The inner wall of the clamping fixing portion and the outer wall of the pressure ring are detachably adapted to each other through a threaded connection.

14. A transdermal test method applied to a transdermal diffusion experimental device, the method comprising: S1. Select a transdermal experimental membrane to be used in the experiment, and then place the transdermal experimental membrane on the step surface of the base; S2, placing the anti-rotation limiting gasket on the step surface and above the transdermal test membrane, and the anti-rotation protrusion and the anti-rotation limiting groove of the anti-rotation limiting gasket are engaged and limited, and when the anti-rotation limiting gasket is placed on the step surface, the transdermal test membrane is located in the clamping portion formed between the step surface and the opposite surface of the anti-rotation limiting gasket, and the transdermal test membrane covers the top opening of the diffusion chamber; S3, tighten the pressure ring to the inner ring of the base by rotating the mounting seat, and press the pressure ring to the top of the anti-rotation limit washer; S4, applying the drug preparation on the upper surface of the transdermal test membrane, and injecting the receiving medium from the liquid channel into the diffusion chamber through the infusion needle, when the medium liquid is injected through the infusion needle, the spherical or conical protrusions provided on the head of the infusion needle are adapted to the inner peripheral contour of the variable diameter infusion port of the liquid channel, or first injecting the receiving medium through the infusion needle, and then applying the drug preparation on the upper surface of the transdermal test membrane after the temperature and state of the transdermal test membrane in the diffusion pool are balanced; S5. When taking liquid, use a liquid taking needle to directly reach the bottom of the second liquid channel to absorb the receiving medium, or use an infusion needle to absorb the receiving medium.

Images