Transdermal drug delivery device and transdermal drug delivery method

Abstract

According to the transdermal drug delivery device and the transdermal drug delivery method, a hollow cavity is formed, the hollow cavity is provided with a skin attaching opening and a drug injection opening, the drug injection opening is provided with an automatic control valve, the automatic control valve is used for controlling opening or closing of the drug injection opening so as to inject drug liquid into the hollow cavity, and the hollow cavity is used for loading the drug liquid; the skin attaching opening is used for making liquid medicine make contact with the skin, meanwhile, an air extractor is further arranged and communicates with the hollow cavity, and the air extractor is used for conducting air extraction on the hollow cavity so that the liquid medicine can be gasified to form cavitation liquid medicine bubbles in the negative pressure environment; the self-control valve is further used for converting the air pressure of the hollow cavity from negative pressure to normal pressure so that the cavitation liquid medicine bubbles can be broken and permeate into the skin in the process that the air pressure of the hollow cavity is converted from negative pressure to normal pressure, and then a large number of cavitation liquid medicine bubbles can be efficiently generated. And the liquid medicine is quickly broken to generate dense shock waves, and is converted into high-speed liquid medicine micro-jet to permeate into the skin, so that the administration efficiency of the liquid medicine is improved.

Description

Technical Field

[0001] The present application relates to the field of transdermal drug delivery, and in particular to a transdermal drug delivery device and a transdermal drug delivery method. Background Art

[0002] Transdermal drug delivery is another drug delivery method besides oral, intravenous and subcutaneous injections. It has unique advantages in some aspects and has become a rapidly developing hot industry in recent years. Transdermal drug delivery technology is mainly divided into two directions: chemical penetration and physical penetration.

[0003] Among the existing technologies, most transdermal drug delivery technologies use ultrasonic drug delivery technology, which uses the thermal effect and cavitation effect of ultrasound to promote the entry of drugs into the subcutaneous tissue. However, the drug delivery efficiency for large molecule drugs is limited, and ultrasonic drug delivery technologies are all low-frequency ultrasound. Low-frequency ultrasound makes it difficult to form effective vacuum bubbles between liquid drugs and the skin, and thus cannot generate shock waves caused by the rupture of vacuum bubbles at a high frequency to instantly push liquid drugs into the skin, reducing the drug delivery efficiency of liquid drugs. Summary of the invention

[0004] The main purpose of the embodiments of the present application is to propose a transdermal drug delivery device and a transdermal drug delivery method, which can efficiently form a large number of cavitation drug liquid bubbles between the liquid drug and the skin, and then enable a large number of cavitation drug liquid bubbles to burst rapidly, generating dense shock waves to convert the liquid drug into high-speed drug liquid microjets that penetrate into the skin, thereby improving the drug delivery efficiency of the liquid drug.

[0005] To achieve the above-mentioned purpose, a first aspect of an embodiment of the present application provides a transdermal drug delivery device, comprising: A hollow cavity, the hollow cavity is used to load liquid medicine, the hollow cavity is provided with a skin contact port and a medicine injection port, the skin contact port is used to contact the liquid medicine with the skin, the medicine injection port is provided with an automatic control valve, the automatic control valve is used to control the opening or closing of the medicine injection port to inject the liquid medicine into the hollow cavity; The vacuum pump is connected to the hollow cavity and is used to evacuate the hollow cavity so that the medicine liquid can be gasified under a negative pressure environment to form cavitation medicine liquid bubbles; The automatic control valve is also used to convert the air pressure of the hollow cavity from negative pressure to normal pressure so that the bubbles of the cavitation liquid burst and penetrate into the skin during the process of converting the air pressure of the hollow cavity from negative pressure to normal pressure.

[0006] Furthermore, in some embodiments, the transdermal drug delivery device further comprises: A compressed air chamber is connected to the hollow cavity and is used to release high-pressure gas into the hollow cavity so that bubbles of the cavitation liquid burst under a positive pressure environment exceeding normal pressure and penetrate into the skin; Wherein, a compressed air valve is provided at the connection point between the compressed air bin and the hollow cavity, and the compressed air valve is used to control the connection between the compressed air bin and the hollow cavity.

[0007] Furthermore, in some embodiments, the transdermal drug delivery device further comprises: An elastic membrane, which is arranged on the outer wall and the inner wall of the skin-applying opening, and is used to seal the skin-applying opening when the pressure in the hollow cavity changes; Alternatively, an elastic rubber pad is provided with a groove, an outer membrane and an inner membrane of the rubber pad, the hollow cavity is embedded in the elastic rubber pad based on the groove, the inner wall of the skin-contacting opening is in contact with the inner membrane of the rubber pad, and the outer wall of the skin-contacting opening is in contact with the outer membrane of the rubber pad, and the elastic rubber pad is used to seal the skin-contacting opening when the pressure in the hollow cavity changes.

[0008] The embodiments of the first aspect of the present application have the following beneficial effects: the present application is provided with a hollow cavity, the hollow cavity is provided with a skin-contacting port and a drug injection port, the drug injection port is provided with an automatic valve, the automatic valve is used to control the opening or closing of the drug injection port to inject liquid medicine into the hollow cavity, the hollow cavity is used to load the liquid medicine, the skin-contacting port is used to bring the liquid medicine into contact with the skin, thereby forming a closed cavity between the hollow cavity and the skin, so that the liquid medicine in the hollow cavity is not affected by atmospheric pressure, and at the same time, an air pump is provided, the air pump is connected to the hollow cavity, and the air pump is used to pump the liquid medicine into the hollow cavity. Air is pumped out to vaporize the drug liquid in a negative pressure environment to form cavitation drug liquid bubbles, thereby enabling the drug liquid to efficiently generate a large number of cavitation drug liquid bubbles in a negative pressure environment that is not disturbed by atmospheric pressure. In addition, the automatic control valve is also used to convert the air pressure of the hollow cavity from negative pressure to normal pressure so that the cavitation drug liquid bubbles can rupture and penetrate into the skin during the process of converting the air pressure of the hollow cavity from negative pressure to normal pressure, thereby enabling a large number of cavitation drug liquid bubbles to rupture rapidly, generating dense shock waves to convert liquid drugs into high-speed drug liquid microjets that penetrate into the skin, thereby improving the drug delivery efficiency of liquid drugs.

[0009] To achieve the above-mentioned purpose, a second aspect of an embodiment of the present application provides a transdermal drug delivery device, comprising: A hollow cavity, the hollow cavity is used to load liquid medicine, the hollow cavity is provided with a skin contact port and a medicine injection port, the skin contact port is used to contact the liquid medicine with the skin, the medicine injection port is provided with an automatic control valve, the automatic control valve is used to control the opening or closing of the medicine injection port to inject the liquid medicine into the hollow cavity; The intracavity piston is arranged inside the hollow cavity, and the intracavity piston is used to perform negative pressure treatment on the air pressure in the hollow cavity, so that the liquid medicine is gasified and converted into cavitation liquid medicine bubbles during the negative pressure treatment process, and the intracavity piston is also used to perform pulse positive pressure treatment on the air pressure in the hollow cavity, so that the cavitation liquid medicine bubbles are broken and penetrate into the skin during the positive pressure treatment process; A piston rod, the piston rod passes through the top of the hollow cavity, and one end of the piston rod is connected to the piston in the cavity; The piston linkage device is connected to the other end of the piston rod and is used to control the movement of the piston in the cavity.

[0010] Furthermore, in some embodiments, a spring is provided between the inner piston and the inner top wall of the hollow cavity, and the spring is used to reset the inner piston to a preset initial position.

[0011] Furthermore, in some embodiments, the transdermal drug delivery device further comprises: An elastic membrane, which is arranged on the outer wall and the inner wall of the skin-applying opening, and is used to seal the skin-applying opening when the pressure in the hollow cavity changes; Alternatively, an elastic rubber pad is provided with a groove, an outer membrane and an inner membrane of the rubber pad, the hollow cavity is embedded in the elastic rubber pad based on the groove, the inner wall of the skin-contacting opening is in contact with the inner membrane of the rubber pad, and the outer wall of the skin-contacting opening is in contact with the outer membrane of the rubber pad, and the elastic rubber pad is used to seal the skin-contacting opening when the pressure in the hollow cavity changes.

[0012] The embodiments of the second aspect of the present application have the following beneficial effects: the present application is provided with a hollow cavity, the hollow cavity is provided with a skin-contacting port and a drug injection port, the drug injection port is provided with an automatic valve, the automatic valve is used to control the opening or closing of the drug injection port to inject liquid medicine into the hollow cavity, the hollow cavity is used to load liquid medicine, the skin-contacting port is used to bring the liquid medicine into contact with the skin, thereby enabling a closed cavity to be formed between the hollow cavity and the skin, so that the liquid medicine in the hollow cavity is not affected by atmospheric pressure, and at the same time, an intra-cavity piston, a piston rod and a piston linkage device are provided, the intra-cavity piston is arranged inside the hollow cavity, the piston rod passes through the top of the hollow cavity, one end of the piston rod is connected to the intra-cavity piston, and the piston linkage device is connected to the other end of the piston rod The two ends are connected, wherein the intracavity piston is used to perform negative pressure treatment on the air pressure in the hollow cavity so that the medicine liquid is vaporized and converted into cavitation medicine liquid bubbles during the negative pressure treatment process, and the intracavity piston is also used to perform pulse positive pressure treatment on the air pressure in the hollow cavity so that the cavitation medicine liquid bubbles are broken and penetrate into the skin during the positive pressure treatment process, and the piston linkage device is used to control the movement of the intracavity piston, and then based on the push-pull cooperation between the piston linkage device and the intracavity piston, the medicine liquid can efficiently generate a large number of cavitation medicine liquid bubbles in the hollow cavity, and the cavitation medicine liquid bubbles are subjected to pulse positive pressure treatment by the intracavity piston, thereby enhancing the shock wave effect generated by the bubble rupture, and further improving the delivery efficiency of liquid medicine.

[0013] To achieve the above object, the third aspect of the embodiment of the present application proposes a transdermal drug delivery method, which is applied to the transdermal drug delivery device of the first aspect, the transdermal drug delivery device is worn by the user, the skin contact port and the skin surface of the user are attached to each other so that the hollow cavity forms a closed cavity, and the transdermal drug delivery method comprises: Control the automatic control valve to be in an open state so that the liquid medicine is injected into the hollow cavity from the injection port; After the liquid medicine is injected into the hollow cavity, the air pressure in the hollow cavity is treated with negative pressure by closing the hollow cavity and controlling the working state of the vacuum pump, so that the liquid medicine is gasified and converted into cavitation liquid medicine bubbles during the negative pressure treatment process; By controlling the working state of the automatic valve or the compressed air valve, the air pressure in the hollow cavity is treated with positive pressure, so that the bubbles of the cavitation liquid are broken and penetrate into the skin during the positive pressure treatment.

[0014] Furthermore, in some embodiments, the air pressure in the hollow cavity is treated with negative pressure by closing the hollow cavity and controlling the working state of the air extractor, including: Control the automatic control valve to be in a closed state; Control the compressed air valve to be in a closed state; The vacuum fan is controlled to evacuate the hollow cavity so that the air pressure of the hollow cavity is converted from normal pressure to negative pressure, wherein the value range of the negative pressure is -100 KPa to -0.1 KPa.

[0015] Furthermore, in some embodiments, the air pressure in the hollow cavity is positively pressurized by controlling the working state of the automatic control valve or the compressed air valve, including: The automatic control valve is controlled to be in an open state so that the air pressure in the hollow cavity is converted from negative pressure to normal pressure; Alternatively, the compressed air valve is controlled to be in an open state so that when the compressed air chamber releases high-pressure gas, the air pressure in the hollow cavity is converted from negative pressure to positive pressure exceeding normal pressure, wherein the positive pressure has a numerical range of 0.01 MPa to 1.00 MPa.

[0016] The embodiments of the third aspect of the present application have the following beneficial effects: the present application controls the automatic control valve to be in an open state so that the medicine liquid is injected into the hollow cavity from the medicine injection port. After the medicine liquid is injected into the hollow cavity, the air pressure in the hollow cavity is subjected to negative pressure treatment by controlling the working state of the automatic control valve and the vacuum pump, so that the medicine liquid is vaporized and converted into cavitation medicine liquid bubbles during the negative pressure treatment process, thereby enabling the medicine liquid to efficiently generate a large number of cavitation medicine liquid bubbles in a negative pressure environment that is not disturbed by atmospheric pressure. Finally, by controlling the working state of the automatic control valve or the compressed air bin, the air pressure in the hollow cavity is subjected to positive pressure treatment, so that the cavitation medicine liquid bubbles are broken and penetrated into the skin during the positive pressure treatment process, thereby enabling a large number of cavitation medicine liquid bubbles to break rapidly, generating dense shock waves, and converting liquid medicine into high-speed medicine liquid microjets that penetrate into the skin, thereby improving the drug delivery efficiency of liquid medicine.

[0017] To achieve the above object, the fourth aspect of the embodiment of the present application provides a transdermal drug delivery method, the transdermal drug delivery device of the second aspect is worn by a user, the skin contact opening and the skin surface of the user are attached to each other so that the hollow cavity forms a closed cavity, and the transdermal drug delivery method comprises: Control the automatic control valve to be in an open state so that the liquid medicine is injected into the hollow cavity from the injection port; After the liquid medicine is injected into the hollow cavity, the air pressure in the hollow cavity is treated with negative pressure by closing the hollow cavity and controlling the piston in the cavity to expand the internal volume of the hollow cavity, so that the liquid medicine is gasified and converted into cavitation liquid medicine bubbles during the negative pressure treatment process; When the piston in the cavity is in the preset downward position, the internal volume of the hollow cavity is instantaneously compressed by controlling the piston in the cavity to perform pulse positive pressure treatment on the air pressure in the hollow cavity, so that the bubbles of the cavitation liquid burst and penetrate into the skin during the pulse positive pressure treatment.

[0018] Furthermore, in some embodiments, the air pressure in the hollow cavity is treated with negative pressure by closing the hollow cavity and controlling the piston in the cavity to expand the internal volume of the hollow cavity, including: Controlling the automatic control valve to be in a closed state; The piston linkage device is controlled to move upward to drive the piston in the cavity to expand the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from normal pressure to negative pressure, wherein the value range of the negative pressure is -100KPa to -0.1KPa.

[0019] Furthermore, in some embodiments, the air pressure in the hollow cavity is subjected to pulse positive pressure treatment by controlling the piston in the cavity to instantaneously compress the internal volume of the hollow cavity, including: Within the preset positive pressure pulse time, the piston linkage device is controlled to accelerate downward movement to drive the piston in the cavity to instantaneously compress the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from negative pressure to instantaneous pulse high pressure; Alternatively, within a preset positive pressure pulse time, the piston linkage device is controlled to move downward at a uniform speed to drive the piston in the cavity to instantaneously compress the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from negative pressure to instantaneous pulse high pressure.

[0020] Furthermore, in some embodiments, the numerical range of the preset positive pressure pulse time is 2.0s to 0.01s, and the numerical range of the instantaneous pulse high pressure is 0.01MPa to 1.00MPa.

[0021] The embodiments of the fourth aspect of the present application have the following beneficial effects: the present application controls the automatic control valve to be in an open state so that the medicine liquid is injected into the hollow cavity from the medicine injection port. After the medicine liquid is injected into the hollow cavity, the internal volume of the hollow cavity is expanded by controlling the piston in the cavity, and the air pressure in the hollow cavity is subjected to negative pressure treatment, so that the medicine liquid is vaporized and converted into cavitation medicine liquid bubbles during the negative pressure treatment process, thereby enabling the medicine liquid to efficiently generate a large number of cavitation medicine liquid bubbles in a negative pressure environment that is not disturbed by atmospheric pressure. Then, when the piston in the cavity is in a preset downward pressure position, the internal volume of the hollow cavity is instantaneously compressed by controlling the piston in the cavity, and the air pressure in the hollow cavity is subjected to pulse positive pressure treatment, so that the cavitation medicine liquid bubbles are ruptured and penetrate into the skin during the pulse positive pressure treatment, thereby enhancing the shock wave effect generated by the rupture of the cavitation medicine liquid bubbles, and further improving the drug delivery efficiency of liquid medicines. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is a structural diagram of a transdermal drug delivery device provided in some embodiments of the present application; Figure 2 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application; Figure 3 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application; Figure 4 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application; Figure 5 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application; Figure 6 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application; Figure 7 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application; Figure 8 is a flow chart of a transdermal drug delivery method provided by some embodiments of the present application; Fig. 9 is a flow chart of a transdermal drug delivery method provided by other embodiments of the present application; Fig.10 A sampling result diagram of leuprolide acetate concentration in a sample provided in some embodiments of the present application; Fig.11 Liquid chromatograms of corresponding samples provided for some embodiments of the present application; Fig.12 A sampling result diagram of insulin concentration in a sample provided in some embodiments of the present application; Fig.13This is a comparison chart of the blood sugar changes of volunteer A after drinking glucose water two days before and after, provided in some embodiments of the present application.

[0023] Figure numerals: hollow cavity 110, skin contact port 111, drug injection port 112, automatic valve 113, vacuum pump 120, compressed air chamber 130, compressed air valve 131, elastic membrane 140, elastic rubber pad 150, groove 151, rubber pad outer membrane 152, rubber pad inner membrane 153, intracavity piston 160, piston rod 170, piston linkage device 180, spring 190. DETAILED DESCRIPTION

[0024] In order to make the purpose, technical solution and advantages of the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0025] In the description of the present application, it should be understood that descriptions involving orientation, such as up, down, front, back, left, right, etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application 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 should not be understood as a limitation on the present application.

[0026] It should also be noted that in the description of this application, "several" means more than one, "more" means more than two, "greater than", "less than", "exceed", etc. are understood to exclude the number itself, and "above", "below", "within", etc. are understood to include the number itself. If there is a description of "first" or "second", it is only used to distinguish the technical features, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features or implicitly indicating the order of the indicated technical features.

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein are only for the purpose of describing the embodiments of this application and are not intended to limit this application.

[0028] In the description of the present application, the description with reference to the terms "one embodiment", "some embodiments", "illustrative embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0029] First, some nouns involved in this application are analyzed: Bubbles refer to the formation of a large number of small bubbles in a liquid due to the vaporization of liquid under negative pressure, and this vaporization phenomenon is collectively referred to as cavitation. Bubbles contain a small amount of gas, which may come from the gas dissolved in the liquid or from the air mixed in the liquid, but more often from the vaporization of the liquid. Because the gas content in the bubbles is relatively small, they are basically in a vacuum state. When these bubbles suddenly burst for some reason, the surrounding liquid will quickly enter the space they originally occupied, forming liquid microjets. The microjets have extremely high speeds and will produce a shock wave effect on the surface of any object that contacts the cavitation, causing the surface dirt to break and peel off (ultrasonic cleaning effect), or corrosion and damage to the surface material (cavitation effect). Studies have shown that the shock wave speed of cavitation rupture can exceed the speed of sound, producing 5000 o Local high temperatures above 30°C can even make the liquid glow.

[0030] Among the existing technologies, most transdermal drug delivery technologies use ultrasonic drug delivery technology, which uses the thermal effect and cavitation effect of ultrasound to promote the entry of drugs into the subcutaneous tissue. However, the drug delivery efficiency for large molecule drugs is limited, and ultrasonic drug delivery technologies are all low-frequency ultrasound. Low-frequency ultrasound makes it difficult to form effective vacuum bubbles between liquid drugs and the skin, and thus cannot generate shock waves caused by the rupture of vacuum bubbles at a high frequency to instantly push liquid drugs into the skin, reducing the drug delivery efficiency of liquid drugs.

[0031] Based on this, the embodiments of the present application provide a transdermal drug delivery device and a transdermal drug delivery method.

[0032] In a first aspect, a transdermal drug delivery device provided in an embodiment of the present application is specifically described through the following embodiments.

[0033] Reference Figure 1 As shown, Figure 1 It is a structural diagram of a transdermal drug delivery device provided in some embodiments of the present application. The transdermal drug delivery device is provided with a hollow cavity 110. The hollow cavity 110 is used to load liquid medicine. The hollow cavity 110 is provided with a skin-applying port 111 and a drug injection port 112. The skin-applying port 111 is used to bring the liquid medicine into contact with the skin. The drug injection port 112 is provided with an automatic valve 113. The automatic valve 113 is used to control the opening or closing of the drug injection port 112 to inject the liquid medicine into the hollow cavity 110.

[0034] Furthermore, the transdermal drug delivery device is also provided with an exhaust fan 120, which is connected to the hollow cavity 110, and is used to exhaust air from the hollow cavity 110 so that the drug solution is gasified under a negative pressure environment to form cavitation drug solution bubbles.

[0035] It should be noted that the automatic valve 113 is also used to convert the air pressure of the hollow cavity 110 from negative pressure to normal pressure so that the cavitation liquid bubbles will burst and penetrate into the skin during the process of converting the air pressure of the hollow cavity 110 from negative pressure to normal pressure.

[0036] Further, refer to Figure 2 As shown, Figure 2 It is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application. The transdermal drug delivery device also includes a compressed air bin 130, which is connected to the hollow cavity 110. The compressed air bin 130 is used to release high-pressure gas to the hollow cavity 110 so that the cavitation liquid bubbles burst and penetrate into the skin under a positive pressure environment exceeding normal pressure. A compressed air valve 131 is provided at the connection between the compressed air bin 130 and the hollow cavity 110. The compressed air valve 131 is used to control the connection between the compressed air bin 130 and the hollow cavity 110.

[0037] In summary, the transdermal drug delivery device is attached to the skin surface through the skin-attaching port 111, so that the inside of the hollow cavity 110 forms a closed cavity containing a drug solution. When the vacuum pump 120 draws air to reduce the air pressure in the hollow cavity 110, the drug solution will be gasified due to the negative pressure environment to produce a large number of cavitation drug solution bubbles, and the bubble size is much larger than the bubble volume formed by ultrasound. When the automatic control valve 113 is opened to restore the air pressure in the hollow cavity 110 to the normal pressure (one atmosphere), or the compressed air chamber 130 is controlled to release high-pressure gas so that the hollow cavity 110 is subjected to a positive pressure exceeding the normal pressure, all cavitation drug solution bubbles will burst at the same time. As a result, the burst bubbles will generate a large number of high-speed drug solution microjets, and coupled with the auxiliary effect of the positive pressure exceeding the normal pressure, the speed of the drug solution microjets is faster and easier to pass through the stratum corneum into the subcutaneous layer, thereby improving the drug delivery efficiency of liquid drugs, and even for macromolecular drugs (such as polypeptides or protein drugs), the transdermal drug delivery efficiency that cannot be achieved by ordinary ultrasonic methods can be achieved.

[0038] In addition, the local high heat generated when the high-speed drug microjet impacts the skin will also soften the stratum corneum, facilitating the entry of large molecule drugs.

[0039] It should be noted that if cavitation bubbles of drug solution are not generated in advance in the hollow cavity 110 to form drug solution microjets, and only positive pressure is applied, no matter how high the air pressure in the hollow cavity 110 is, the drug solution layer under uniform pressure cannot break through the stratum corneum barrier, that is, the transdermal drug delivery device needs to utilize the cavitation bubble principle and the high-pressure impact principle for transdermal drug delivery.

[0040] In some possible embodiments, reference is made to Figure 3 As shown, Figure 31 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application. The transdermal drug delivery device also includes an elastic membrane 140, which is arranged on the outer wall and inner wall of the skin-applying port 111. The elastic membrane 140 is used to seal the skin-applying port 111 when the pressure in the hollow cavity 110 changes. After the skin-applying port 111 and the skin surface are attached to each other, the elastic membrane 140 is in close contact with the skin surface. When negative pressure appears in the hollow cavity 110, the elastic membrane 140 arranged on the outer wall of the skin-applying port 111 is deformed to be close to the outer wall of the skin-applying port 111 under the action of the atmospheric pressure outside the hollow cavity 110, so that it is difficult for the air outside the hollow cavity 110 to enter the hollow cavity 110 through the gap between the skin-applying port 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110. When positive pressure appears in the hollow cavity 110, the elastic membrane 140 provided on the inner wall of the skin-contacting opening 111 is deformed to fit tightly against the inner wall of the skin-contacting opening 111 under the action of the positive pressure in the hollow cavity 110, making it difficult for the liquid medicine in the hollow cavity 110 to enter the outside of the hollow cavity 110 through the gap between the skin-contacting opening 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110.

[0041] Or, in some possible embodiments, refer to Figure 4 As shown, Figure 4 This is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application. The transdermal drug delivery device also includes an elastic rubber pad 150. The elastic rubber pad 150 is provided with a groove 151, a rubber pad outer film 152 and a rubber pad inner film 153. The hollow cavity 110 is embedded in the elastic rubber pad 150 based on the groove 151. The inner wall of the skin-contacting port 111 is in contact with the rubber pad inner film 153, and the outer wall of the skin-contacting port 111 is in contact with the rubber pad outer film 152. The elastic rubber pad 150 is used to seal the skin-contacting port 111 when the pressure in the hollow cavity 110 changes. When negative pressure occurs in the hollow cavity 110, the outer film 152 of the adhesive pad that is in contact with the outer wall of the skin contact opening 111 is deformed to be close to the outer wall of the skin contact opening 111 under the action of the atmospheric pressure outside the hollow cavity 110, making it difficult for the air outside the hollow cavity 110 to enter the hollow cavity 110 through the gap between the skin contact opening 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110. When positive pressure occurs in the hollow cavity 110, the inner film 153 of the adhesive pad that is in contact with the outer wall of the skin contact opening 111 is deformed to be close to the inner wall of the skin contact opening 111 under the action of the positive pressure in the hollow cavity 110, making it difficult for the liquid medicine in the hollow cavity 110 to enter the outside of the hollow cavity 110 through the gap between the skin contact opening 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110.

[0042] In a second aspect, another transdermal drug delivery device provided in the embodiments of the present application is specifically described through the following embodiments.

[0043] Reference Figure 5 As shown, Figure 5 It is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application. The transdermal drug delivery device is provided with a hollow cavity 110. The hollow cavity 110 is used to load liquid medicine. The hollow cavity 110 is provided with a skin-applying port 111 and a drug injection port 112. The skin-applying port 111 is used to bring the liquid medicine into contact with the skin. The drug injection port 112 is provided with an automatic valve 113. The automatic valve 113 is used to control the opening or closing of the drug injection port 112 to inject the liquid medicine into the hollow cavity 110.

[0044] Further, from Figure 5 It can be seen that the transdermal drug delivery device is also provided with an intracavity piston 160, a piston rod 170 and a piston linkage device 180. The intracavity piston 160 is arranged inside the hollow cavity 110. The intracavity piston 160 is used to perform negative pressure treatment on the air pressure in the hollow cavity 110, so that the drug liquid is vaporized and converted into cavitation drug liquid bubbles during the negative pressure treatment. The intracavity piston 160 is also used to perform positive pressure treatment on the air pressure in the hollow cavity 110 so that the cavitation drug liquid bubbles are broken and penetrated into the skin during the positive pressure treatment. The piston rod 170 runs through the top of the hollow cavity 110, one end of the piston rod 170 is connected to the intracavity piston 160, and the piston linkage device 180 is connected to the other end of the piston rod 170. The piston linkage device 180 is used to control the movement of the intracavity piston 160.

[0045] It should be noted that a spring 190 is provided between the intracavity piston 160 and the inner top wall of the hollow cavity 110 , and the spring 190 is used to reset the intracavity piston 160 to a preset initial position.

[0046] In summary, the transdermal drug delivery device is attached to the skin surface through the skin-attaching port 111, so that the inside of the hollow cavity 110 forms a closed cavity containing liquid medicine. When the piston linkage device 180 links the piston 160 in the cavity to expand the volume of the hollow cavity 110 so that the air pressure in the hollow cavity 110 is reduced, the liquid medicine will be gasified due to the negative pressure environment to produce a large number of cavitation liquid medicine bubbles, and the bubble size is much larger than the bubble volume formed by ultrasound. When the piston linkage device 180 links the piston 160 in the cavity to instantly compress the volume of the hollow cavity 110 so that the pressure in the hollow cavity 110 exceeds the pulse positive pressure, all cavitation liquid medicine bubbles will burst at the same time. As a result, the burst bubbles will produce a large number of high-speed liquid medicine microjets, and coupled with the auxiliary effect of the pulse high pressure, the liquid medicine microjets will be faster and easier to pass through the stratum corneum into the subcutaneous layer, thereby improving the drug delivery efficiency of liquid medicines. Even for macromolecular drugs (such as polypeptides or protein drugs), the transdermal drug delivery efficiency that cannot be achieved by ordinary ultrasonic methods can be achieved.

[0047] In addition, the local high heat generated when the high-speed drug microjet impacts the skin will also soften the stratum corneum, facilitating the entry of large molecule drugs.

[0048] It should be noted that if cavitation bubbles of drug solution are not pre-generated in the hollow cavity 110 to form drug solution microjets, and only pulsed high pressure is applied, no matter how high the air pressure in the hollow cavity 110 is, the drug solution layer under uniform pressure cannot break through the stratum corneum barrier, that is, the transdermal drug delivery device needs to utilize the cavitation bubble principle and the pulsed high pressure impact principle for transdermal drug delivery.

[0049] In some possible embodiments, reference is made to Figure 6 As shown, Figure 6 1 is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application. The transdermal drug delivery device also includes an elastic membrane 140, which is arranged on the outer wall and inner wall of the skin-applying port 111. The elastic membrane 140 is used to seal the skin-applying port 111 when the pressure in the hollow cavity 110 changes. After the skin-applying port 111 and the skin surface are attached to each other, the elastic membrane 140 is in close contact with the skin surface. When negative pressure appears in the hollow cavity 110, the elastic membrane 140 arranged on the outer wall of the skin-applying port 111 is deformed to be close to the outer wall of the skin-applying port 111 under the action of the atmospheric pressure outside the hollow cavity 110, so that it is difficult for the air outside the hollow cavity 110 to enter the hollow cavity 110 through the gap between the skin-applying port 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110. When positive pressure appears in the hollow cavity 110, the elastic membrane 140 provided on the inner wall of the skin-contacting opening 111 is deformed to fit tightly against the inner wall of the skin-contacting opening 111 under the action of the positive pressure in the hollow cavity 110, making it difficult for the liquid medicine in the hollow cavity 110 to enter the outside of the hollow cavity 110 through the gap between the skin-contacting opening 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110.

[0050] In some possible embodiments, reference is made to Figure 7 As shown, Figure 7This is a structural diagram of a transdermal drug delivery device provided in some other embodiments of the present application. The transdermal drug delivery device also includes an elastic rubber pad 150. The elastic rubber pad 150 is provided with a groove 151, a rubber pad outer film 152 and a rubber pad inner film 153. The hollow cavity 110 is embedded in the elastic rubber pad 150 based on the groove 151. The inner wall of the skin-contacting port 111 is in contact with the rubber pad inner film 153, and the outer wall of the skin-contacting port 111 is in contact with the rubber pad outer film 152. The elastic rubber pad 150 is used to seal the skin-contacting port 111 when the pressure in the hollow cavity 110 changes. When negative pressure occurs in the hollow cavity 110, the outer film 152 of the adhesive pad that is in contact with the outer wall of the skin contact opening 111 is deformed to be close to the outer wall of the skin contact opening 111 under the action of the atmospheric pressure outside the hollow cavity 110, making it difficult for the air outside the hollow cavity 110 to enter the hollow cavity 110 through the gap between the skin contact opening 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110. When positive pressure occurs in the hollow cavity 110, the inner film 153 of the adhesive pad that is in contact with the outer wall of the skin contact opening 111 is deformed to be close to the inner wall of the skin contact opening 111 under the action of the positive pressure in the hollow cavity 110, making it difficult for the liquid medicine in the hollow cavity 110 to enter the outside of the hollow cavity 110 through the gap between the skin contact opening 111 and the skin surface, thereby enhancing the sealing effect of the hollow cavity 110.

[0051] In a third aspect, a transdermal drug delivery method provided in an embodiment of the present application is specifically described through the following embodiments. The transdermal drug delivery method is applied to the transdermal drug delivery device of the first aspect mentioned above, and the transdermal drug delivery device is worn by a user, and the skin contact port is in contact with the skin surface of the user so that the hollow cavity forms a closed cavity.

[0052] Reference Figure 8 As shown, Figure 8 It is a flow chart of a transdermal drug delivery method provided in some embodiments of the present application. The transdermal drug delivery method may include but is not limited to steps S810 to S830.

[0053] Step S810: Control the automatic control valve to be in an open state so that the drug solution is injected into the hollow cavity from the drug injection port.

[0054] The automatic control valve is controlled to be in an open state, and then liquid medicine is injected into the injection port of the hollow cavity. At this time, the liquid medicine is in contact with the skin surface of the user.

[0055] Step S820: After the drug solution is injected into the hollow cavity, the air pressure in the hollow cavity is subjected to negative pressure treatment by closing the hollow cavity and controlling the working state of the vacuum pump, so that the drug solution is gasified and converted into cavitation drug solution bubbles during the negative pressure treatment.

[0056] Specifically, after the medicine liquid is injected into the hollow cavity, the air pressure in the hollow cavity is treated with negative pressure by closing the hollow cavity and controlling the working state of the vacuum pump, so that the medicine liquid is vaporized and converted into cavitation medicine liquid bubbles during the negative pressure treatment process, thereby enabling the medicine liquid to efficiently generate a large number of cavitation medicine liquid bubbles in a negative pressure environment that is not disturbed by atmospheric pressure.

[0057] It should be noted that if there is air in the closed hollow cavity, when positive pressure needs to be applied, the air in the hollow cavity will be compressed, thereby reducing the pressure applied to the surface of the liquid medicine, causing the microjet speed to be significantly reduced, and the drug delivery efficiency to be significantly reduced. And the more air mixed in, the more serious the drug delivery efficiency will be, and even skin delivery cannot be achieved at all. Therefore, it is necessary to perform negative pressure treatment on the air pressure in the hollow cavity by closing the hollow cavity and controlling the working state of the vacuum pump.

[0058] It should also be noted that in order to eliminate the presence of air in the sealed hollow cavity, the entire hollow cavity can be filled with liquid medicine, thereby eliminating the air in the sealed hollow cavity and improving the drug administration efficiency.

[0059] The process of performing negative pressure treatment on the air pressure in the hollow cavity by closing the hollow cavity and controlling the working state of the vacuum pump includes the following steps S820a to S820c.

[0060] Step S820a: Control the automatic control valve to be in a closed state.

[0061] Step S820b: Control the compressed air valve to be in a closed state.

[0062] Step S820c: Control the vacuum pump to evacuate the hollow cavity so that the air pressure in the hollow cavity is converted from normal pressure to negative pressure.

[0063] Specifically, when the automatic control valve and the compressed air valve are both in a closed state, the hollow cavity is in a closed state. Then the vacuum pump is turned on to evacuate the hollow cavity. The air above the medicine liquid in the hollow cavity is evacuated, causing the medicine liquid in the hollow cavity to vaporize and produce a large number of cavitation medicine liquid bubbles. Finally, when the negative pressure in the hollow cavity reaches a predetermined value, the vacuum pump is controlled to stop evacuating.

[0064] Among them, the numerical range of negative pressure is -100KPa to -0.1KPa. Preferably, when the numerical range of negative pressure is between -85KPa and -10KPa, the cavitation bubbles generated by the liquid medicine in the negative pressure environment can be controlled to maintain a certain number, thereby reducing the simultaneous rupture of excessive cavitation bubbles and causing certain damage to the skin surface.

[0065] At the same time, for drug solutions with a dynamic viscosity lower than 5cps, the negative pressure value range is no higher than -20KPa to achieve ideal drug delivery efficiency. For drug solutions with a dynamic viscosity of 5cps-8cps, the negative pressure value range needs to be between -30KPa and -35KPa.

[0066] Step S830: By controlling the working state of the automatic valve or the compressed air chamber, the air pressure in the hollow cavity is positively pressurized so that the bubbles of the cavitation liquid burst during the positive pressure treatment and penetrate into the skin.

[0067] Specifically, the process of performing negative pressure treatment on the air pressure in the hollow cavity by closing the hollow cavity and controlling the working state of the vacuum fan includes the following steps S830a to S830b.

[0068] Step S830a: Control the automatic control valve to be in an open state, so that the air pressure in the hollow cavity is converted from negative pressure to normal pressure.

[0069] Specifically, the automatic control valve is controlled to be in an open state, and external air instantly enters the interior of the hollow cavity, so that the air pressure in the hollow cavity quickly recovers from negative pressure to normal pressure, causing the cavitation liquid bubble to burst, and then the liquid microflow generated by the cavitation liquid bubble burst enters the subcutaneous tissue at an extremely high speed.

[0070] At the same time, the automatic control valve and the vacuum pump automatically repeat the closing and opening process, which can achieve continuous drug delivery to the skin until the drug solution in the hollow cavity is exhausted. During this drug delivery process, the skin-contacting port of the hollow cavity needs to maintain close contact with the skin to prevent the drug solution from leaking out and air from entering the interior of the hollow cavity.

[0071] Step S830b: Alternatively, the compressed air valve is controlled to be in an open state, so that when the compressed air chamber releases high-pressure gas, the air pressure in the hollow cavity is converted from negative pressure to positive pressure exceeding normal pressure.

[0072] Specifically, the automatic control valve is controlled to be in an open state, and the high-pressure gas in the compressed air chamber instantly enters the interior of the hollow cavity, so that the air pressure in the hollow cavity is rapidly converted from negative pressure to positive pressure exceeding normal pressure, causing the cavitation liquid bubble to burst, and then the liquid microflow generated by the cavitation liquid bubble burst enters the subcutaneous tissue at an extremely high speed.

[0073] At the same time, the compressed air valve and the vacuum pump automatically repeat the closing and opening process, which can achieve continuous drug delivery to the skin until the drug solution in the hollow cavity is exhausted. During this drug delivery process, the skin-contacting port of the hollow cavity needs to maintain close contact with the skin to prevent the drug solution from leaking out and air from entering the interior of the hollow cavity.

[0074] Among them, the numerical range of the positive pressure is 0.01MPa to 1.00MPa. Preferably, when the numerical range of the positive pressure is between 0.1MPa and 0.5MPa, the micro-jet of the liquid medicine formed after the cavitation liquid bubble bursts can maintain a certain speed. At the same time, it can also reduce the damage to the skin surface caused by the bursting of the cavitation liquid bubble.

[0075] It should be noted that the user generally wears the transdermal drug delivery device in the forward direction (i.e., the hollow cavity is located above the skin surface). However, since the cavitation drug liquid bubbles generated in the hollow cavity float in the drug liquid due to their light specific gravity and leave the skin surface, the microjets generated when they burst will be blocked by the drug liquid. If the drug liquid layer is very thin, some of the microjets can still enter the subcutaneous tissue. If the drug liquid layer is thick, it is difficult to achieve transdermal drug delivery. For this reason, when the drug liquid layer is thick, the transdermal drug delivery device needs to be placed inverted (i.e., the skin surface is located above the hollow cavity), so that the cavitation drug liquid bubbles can float in the drug liquid and finally gather on the skin surface.

[0076] It should also be noted that in order to achieve close contact between the above-mentioned skin-applicable port and the user's skin surface and prevent the drug solution from leaking out and air from entering the tube, the skin-applicable port needs to be continuously pressed against the skin surface. If the drug delivery site is a limb, such as a wrist or an arm, the transdermal drug delivery device can be tied to the wrist or arm in the form of a strap. At the same time, in order to reduce the discomfort caused by skin pressure, the tube wall thickness of the skin-applicable port can be increased or a soft rubber pad can be added to the bottom of the tube wall of the skin-applicable port.

[0077] Furthermore, each time a negative pressure treatment and a positive pressure treatment are completed in a closed hollow cavity, a transdermal drug administration process is realized, wherein the more times the transdermal drug administration is performed per unit time, the higher the drug administration efficiency. The transdermal drug administration frequency range of the present application is 100Hz to 0.01Hz. Preferably, when the transdermal drug administration frequency range is 2.0Hz to 0.5Hz, damage to the skin surface can be reduced, and the time interval between the two administrations is long enough and will not affect the drug administration process of the two, so the drug administration efficiency (amount of drug administration per unit time) of 2.0Hz is twice that of 1.0Hz.

[0078] In a fourth aspect, a transdermal drug delivery method provided in an embodiment of the present application is specifically described through the following embodiments. The transdermal drug delivery method is applied to the transdermal drug delivery device of the third aspect mentioned above, and the transdermal drug delivery device is worn by a user, and the skin-contacting port is in contact with the skin surface of the user so that the hollow cavity forms a closed cavity.

[0079] Reference Fig. 9 As shown, Fig. 9It is a flow chart of a transdermal drug delivery method provided in some other embodiments of the present application. The transdermal drug delivery method may include but is not limited to steps S910 to S930.

[0080] Step S910: Control the automatic control valve to be in an open state so that the drug solution is injected into the hollow cavity from the drug injection port.

[0081] The automatic control valve is controlled to be in an open state, and then liquid medicine is injected into the injection port of the hollow cavity. At this time, the liquid medicine is in contact with the skin surface of the user.

[0082] Step S920: After the drug solution is injected into the hollow cavity, the air pressure in the hollow cavity is subjected to negative pressure treatment by closing the hollow cavity and controlling the piston in the cavity to expand the internal volume of the hollow cavity, so that the drug solution is vaporized and converted into cavitation drug solution bubbles during the negative pressure treatment.

[0083] Specifically, in the process of performing negative pressure treatment on the air pressure in the hollow cavity by closing the hollow cavity and controlling the piston in the cavity to expand the internal volume of the hollow cavity, the following steps S920a or S920b are included.

[0084] Step S920a: Control the automatic control valve to be in a closed state.

[0085] Step S920b: Control the piston linkage device to move upward to drive the piston in the cavity to expand the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from normal pressure to negative pressure.

[0086] Among them, the numerical range of negative pressure is -100KPa to -0.1KPa. Preferably, when the numerical range of negative pressure is between -85KPa and -10KPa, the cavitation bubbles generated by the liquid medicine in the negative pressure environment can be controlled to maintain a certain number, thereby reducing the simultaneous rupture of excessive cavitation bubbles and causing certain damage to the skin surface.

[0087] At the same time, for drug solutions with a dynamic viscosity lower than 5cps, the negative pressure value range is no higher than -20KPa to achieve ideal drug delivery efficiency. For drug solutions with a dynamic viscosity of 5cps-8cps, the negative pressure value range needs to be between -30KPa and -35KPa.

[0088] It should be noted that when the piston in the cavity rises to a predetermined position, the piston linkage device and the piston rod will be disengaged, thereby failing to drive the piston in the cavity to rise.

[0089] It should be noted that if there is air in the closed hollow cavity, when pulse high pressure needs to be applied, the air in the hollow cavity will be compressed, thereby reducing the pressure applied to the surface of the liquid medicine, causing the microjet speed to be significantly reduced, and the drug delivery efficiency to be significantly reduced. And the more air mixed in, the more serious the drug delivery efficiency will be, and even skin delivery cannot be achieved at all. Therefore, it is necessary to perform negative pressure treatment on the air pressure in the hollow cavity by closing the hollow cavity and controlling the working state of the vacuum pump.

[0090] It should also be noted that in order to eliminate the presence of air in the sealed hollow cavity, the entire hollow cavity can be filled with liquid medicine, thereby eliminating the air in the sealed hollow cavity and improving the drug administration efficiency.

[0091] Step S930: When the piston in the cavity is in a preset downward position, the internal volume of the hollow cavity is instantaneously compressed by controlling the piston in the cavity to perform pulse positive pressure treatment on the air pressure in the hollow cavity, so that the cavitation liquid bubbles burst and penetrate into the skin during the pulse positive pressure treatment.

[0092] Specifically, in the process of instantaneously compressing the internal volume of the hollow cavity by controlling the piston in the cavity to perform pulse positive pressure treatment on the air pressure in the hollow cavity, the following steps S930a or S930b are included.

[0093] Step S930a: within the preset positive pressure pulse time, control the piston linkage device to accelerate downward movement to drive the piston in the cavity to instantaneously compress the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from negative pressure to instantaneous pulse high pressure.

[0094] Step S930b: Alternatively, within the preset positive pressure pulse time, the piston linkage device is controlled to move downward at a uniform speed to drive the piston in the cavity to instantaneously compress the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from negative pressure to instantaneous pulse high pressure.

[0095] Among them, the numerical range of the preset positive pressure pulse time is 2.0s to 0.01s. Preferably, the numerical range of the preset positive pressure pulse time is generally between 1.0s and 0.01s, which can reduce the degree of skin damage caused by the rupture of cavitation liquid bubbles. For liquid medicine with a molecular weight exceeding 500Da, the preset positive pressure pulse time is generally not less than 0.1s.

[0096] Moreover, the value range of the instantaneous pulse high voltage is 0.01MPa to 1.00MPa. Preferably, when the value range of the instantaneous pulse high voltage is 0.1MPa to 0.5MPa, the micro-jet of the medicinal liquid formed after the cavitation medicinal liquid bubble bursts can maintain a certain speed. At the same time, it can also reduce the damage to the skin surface caused by the bursting of the cavitation medicinal liquid bubble.

[0097] It should be noted that, through the automatic repetitive push-pull process of the above-mentioned intracavitary piston and the piston linkage device, continuous skin drug administration can be achieved until the drug solution in the hollow cavity is exhausted. During the drug administration process, the pulse pressure of the cavitated drug solution bubbles in the transdermal drug administration method of the fourth aspect from the intracavitary piston is much greater than the air pressure recovery force of the transdermal drug administration method of the third aspect, so the rupture process of the cavitated drug solution bubbles will be completed in a shorter time, and the shock wave effect formed will be more obvious. At the same time, the pulse effect of the pulse pressure on the drug solution will be superimposed on the shock wave of the drug solution microjet, further allowing the drug solution microjet to enter the subcutaneous tissue at a faster speed.

[0098] It should also be noted that in the above-mentioned process of pulse positive pressure treatment of the air pressure in the hollow cavity, a sinusoidal pulse wave can be selected for pulse positive pressure treatment, a square pulse wave can be selected for pulse positive pressure treatment, or a sawtooth pulse wave can be selected for pulse positive pressure treatment. Preferably, using a square pulse wave for pulse positive pressure treatment can reduce the damage of pulse pressure to the skin surface.

[0099] Furthermore, each time a negative pressure treatment and a positive pressure treatment are completed in a closed hollow cavity, a transdermal drug administration process is realized, wherein the more times the transdermal drug administration is performed per unit time, the higher the drug administration efficiency. The transdermal drug administration frequency range of the present application is 100Hz to 0.01Hz. Preferably, when the transdermal drug administration frequency range is 2.0Hz to 0.5Hz, damage to the skin surface can be reduced, and the time interval between the two administrations is long enough and will not affect the drug administration process of the two, so the drug administration efficiency (amount of drug administration per unit time) of 2.0Hz is twice that of 1.0Hz.

[0100] Furthermore, the following experiments are conducted to prove that the above-mentioned transdermal drug delivery device and transdermal drug delivery method can deliver drugs to the skin safely and efficiently.

[0101] Experimental Example 1: Leuprorelin acetate administration experiment.

[0102] (1) Preparation of drug delivery prototype This drug delivery prototype is the same as the transdermal drug delivery device of the first aspect described above. The vacuum pump, automatic valve or compressed air valve is opened or closed at a preset frequency, thereby forming a cycle of negative pressure and positive pressure in the hollow cavity to achieve transdermal drug delivery.

[0103] Among them, the drug administration parameters of the prototype are as follows: the transdermal drug administration frequency is 1 Hz; the drug administration duration is 21 minutes; and the sampling time interval is 3 minutes / time.

[0104] (2) Transdermal experimental equipment A vertical Franz diffusion cell was used for drug transdermal testing. The Franz diffusion cell is a tool for quantitatively studying transdermal efficiency. A water solution simulating human tissue fluid was injected into the diffusion cell and maintained at 37 0 C water temperature. Experimental active skin is used as the drug permeation target. The inner side of the skin contacts the aqueous solution of the diffusion cell, and the outer side of the skin contacts the drug solution in the hollow cavity of the drug delivery prototype.

[0105] (3) Drug selection Leuprorelin Acetate is a peptide drug used to treat prostate cancer, premenopausal breast cancer and central precocious puberty. Due to its short half-life and inability to be taken orally, it needs to be made into a sustained-release microsphere drug for injection every 12 weeks. If it can be administered transdermally, the required concentration in the blood can be maintained for a long time, and the drug can be stopped immediately if side effects occur, which can significantly improve the safety of the drug. However, the drug has a high molecular weight (1396 Daltons), and ordinary chemical transdermal formulations cannot reach the level required for clinical administration.

[0106] (4) Analysis of test results During the 21-minute dosing process, the solution in the Franz diffusion cell was sampled every 3 minutes, and a total of 7 samples were obtained. The samples were placed in a liquid chromatograph to measure the concentration of leuprolide acetate in each sample. The results are shown in FIG. Fig.10 and Fig.11 As shown, Fig.10 A sampling result diagram of leuprolide acetate concentration in a sample provided in some embodiments of the present application, Fig.11 The liquid chromatograms of the corresponding samples provided for some embodiments of the present application are as follows: Fig.10 As can be seen in the figure, 3 minutes after administration, the concentration of the solution in the Franz diffusion cell can reach more than 10μg / ml, which means that 120μg of leuprolide acetate enters the subcutaneous tissue within 3 minutes. Within 21 minutes, 240μg of leuprolide acetate enters the subcutaneous tissue.

[0107] It should be noted that the injection dose of the drug is 30µg / kg / 4 weeks to 180µg / kg / 4 weeks. Calculated based on a body weight of 80kg, the maximum hourly dosage for a patient is 21µg. Therefore, the drug delivery efficiency of the transdermal drug delivery device of the present application has far exceeded clinical needs.

[0108] (5) Safety analysis After the test, the experimental active skin used in the test was carefully observed under a microscope, and no cracks, holes or other damage were found. Therefore, the transdermal drug delivery device of the first aspect of the present application has a high drug delivery efficiency and safety, and will not cause skin damage.

[0109] Experimental Example 2: Insulin administration experiment.

[0110] (1) Preparation of drug delivery prototype The drug delivery prototype is the same as the transdermal drug delivery device of the second aspect described above, wherein a stepper motor is provided between the piston rod and the piston linkage device, and the stepper motor has the characteristics of large torque, small size and easy control, and is suitable for occasions requiring frequent starting and precise regulation of linear stroke. Driven by the stepper motor, the piston linkage device moves up and down according to a preset frequency and stroke, thereby driving the piston in the cavity to repeatedly form a cycle of negative pressure and positive pressure in the hollow cavity to achieve transdermal drug delivery.

[0111] Among them, the drug delivery parameters of the prototype are as follows: the concentration of the drug solution is the original Humalog 25 concentration; the amount of insulin is 1 unit (1U); the transdermal drug delivery frequency is 1Hz; the preset positive pressure pulse time is 0.14s; the stroke of the piston in the cavity is 10mm; the drug delivery duration is 21min; and the sampling time interval is 3min / time.

[0112] (2) Experimental subjects A vertical Franz diffusion cell was used for drug transdermal testing. The Franz diffusion cell is a tool for quantitatively studying transdermal efficiency. A water solution simulating human tissue fluid was injected into the diffusion cell and maintained at 37 0 C water temperature. Experimental active skin is used as the drug permeation target. The inner side of the skin contacts the aqueous solution of the diffusion cell, and the outer side of the skin contacts the drug solution in the hollow cavity of the drug delivery prototype.

[0113] (3) Drug selection Insulin is an indispensable blood sugar control drug for all patients with type 1 diabetes and nearly half of patients with type 2 diabetes. However, due to its transient effect on the liver, insulin cannot be taken orally and can only be injected subcutaneously, which brings great inconvenience to patients. Giving insulin through the skin is an ideal new way. However, the molecular weight of insulin is as high as 5,800 Daltons, and the efficiency of ordinary insulin transdermal administration is far from meeting clinical requirements.

[0114] (4) Analysis of test results The results are as follows Fig.12 As shown, Fig.12 A sampling result diagram of insulin concentration in a sample provided in some embodiments of the present application. 1 unit (U) of insulin is equal to 0.0347 mg. The volume of the vertical Franz diffusion cell is 12 ml. The administration skin area is 1.12 cm 2 , the insulin flow rate entering the skin was calculated to be 2.7364µg / min / cm 2 Or 0.079U / min / cm2. So when the drug delivery area is expanded to 4cm 2In the case of urinary insufficiency, 1 unit of insulin can enter the subcutaneous tissue in about 3 minutes, which can reduce blood sugar by 30-100 mg / dL (average 50 mg / dL). If the administration time is extended to about 10 minutes, it can basically meet the dosage required in most clinical situations.

[0115] (5) Safety analysis After the test, the experimental active skin used in the test was carefully observed under a microscope, and no cracks, holes or other damage were found. Therefore, the transdermal drug delivery device of the second aspect of the present application has a high drug delivery efficiency and safety, and will not cause skin damage.

[0116] Experimental Example 3: Insulin administration experiment.

[0117] (1) Preparation of drug delivery prototype This drug delivery prototype is the same as the above-mentioned transdermal drug delivery device of the second aspect.

[0118] Among them, the drug delivery parameters of the prototype are as follows: the concentration of the drug solution is the original Humalog 25 concentration; the amount of insulin is 1 unit (1U); the transdermal drug delivery frequency is 1Hz; the preset positive pressure pulse time is 0.14s; the stroke of the piston in the cavity is 10mm; the drug delivery duration is 30s; the sampling time interval is 5min / time; and the drug delivery site is the abdomen.

[0119] (2) Experimental subjects Volunteer A, male, 45 years old, had normal fasting blood sugar, high postprandial blood sugar, and was diagnosed with prediabetes. Volunteer A was compared on two days. On the first morning, he kept fasting and drank glucose water (75g dissolved in 500ml water) at 10:00, and then began to measure blood sugar every 5 minutes with a blood glucose meter until 11:05. On the second day, at the same time, he drank the same amount of glucose water and measured blood sugar at the same time, but used a prototype to give insulin transdermally 5 minutes before drinking water.

[0120] (3) Analysis of test results The results are as follows Fig.13 As shown, Fig.13 This is a comparison chart of the blood sugar changes of volunteer A after drinking glucose water two days before and after, provided in some embodiments of the present application. Fig.13 It can be seen that on the first day when volunteer A did not use insulin, after drinking glucose water, the highest blood sugar level exceeded 10mmol / L, while on the second day of transdermal administration of insulin, the highest blood sugar level dropped to 9.1mmol / L, returning to the normal range, which shows the effectiveness of the transdermal drug delivery device of the present application.

[0121] At the same time, after the comparison experiment, the abdominal administration site of volunteer A was observed and no abnormalities were found. The volunteer also did not feel pain or itching. Therefore, under the above experimental parameters, the transdermal administration method of the present application is safe.

[0122] The embodiments described in the embodiments of the present application are intended to more clearly illustrate the technical solutions of the embodiments of the present application and do not constitute a limitation on the technical solutions provided in the embodiments of the present application. Those skilled in the art will appreciate that with the evolution of technology and the emergence of new application scenarios, the technical solutions provided in the embodiments of the present application are also applicable to similar technical problems.

[0123] Those skilled in the art will appreciate that the technical solutions shown in the figures do not constitute a limitation on the embodiments of the present application, and may include more or fewer steps than shown in the figures, or a combination of certain steps, or different steps.

[0124] The device embodiments described above are merely illustrative, and the units described as separate components may or may not be physically separated, that is, they may be located in one place or distributed on multiple network units. Some or all of the modules may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0125] Those skilled in the art will appreciate that all or some of the steps in the methods disclosed above, and the functional modules / units in the systems and devices may be implemented as software, firmware, hardware, or a suitable combination thereof.

[0126] The terms "first", "second", "third", "fourth", etc. (if any) in the specification of the present application and the above-mentioned drawings are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. It should be understood that the data used in this way can be interchangeable where appropriate, so that the embodiments of the present application described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including" and "having" and any of their variations are intended to cover non-exclusive inclusions, for example, a process, method, system, product or device comprising a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0127] It should be understood that in the present application, "at least one (item)" means one or more, and "plurality" means two or more. "And / or" is used to describe the association relationship of associated objects, indicating that three relationships may exist. For example, "A and / or B" can mean: only A exists, only B exists, and A and B exist at the same time, where A and B can be singular or plural. The character " / " generally indicates that the objects associated before and after are in an "or" relationship. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items. For example, at least one of a, b or c can mean: a, b, c, "a and b", "a and c", "b and c", or "a and b and c", where a, b, c can be single or multiple.

[0128] In the several embodiments provided in the present application, it should be understood that the disclosed systems and methods can be implemented in other ways. For example, the system embodiments described above are merely schematic. For example, the division of the above units is only a logical function division. There may be other division methods in actual implementation, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be an indirect coupling or communication connection through some interfaces, devices or units, which can be electrical, mechanical or other forms.

[0129] The units described above as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0130] In addition, each functional unit in each embodiment of the present application may be integrated into one processing unit, or each unit may exist physically separately, or two or more units may be integrated into one unit. The above-mentioned integrated unit may be implemented in the form of hardware or in the form of software functional units.

[0131] The preferred embodiments of the present application are described above with reference to the accompanying drawings, but the scope of the rights of the present application is not limited thereto. Any modification, equivalent substitution and improvement made by a person skilled in the art without departing from the scope and essence of the present application should be within the scope of the rights of the present application.

Claims

1. A transdermal drug delivery device, characterized in that: include: A hollow cavity, the hollow cavity is used to load liquid medicine, the hollow cavity is provided with a skin contact port and a medicine injection port, the skin contact port is used to contact the liquid medicine with the skin, the medicine injection port is provided with an automatic control valve, the automatic control valve is used to control the opening or closing of the medicine injection port to inject the liquid medicine into the hollow cavity; An air pump, the air pump is in communication with the hollow cavity, and the air pump is used to pump air from the hollow cavity so that the liquid medicine is gasified under a negative pressure environment to form cavitation liquid medicine bubbles; The automatic valve is also used to convert the air pressure of the hollow cavity from negative pressure to normal pressure so that the bubbles of the cavitation liquid burst and penetrate into the skin during the process of converting the air pressure of the hollow cavity from negative pressure to normal pressure.

2. The transdermal drug delivery device according to claim 1, characterized in that: Also includes: A compressed air chamber, the compressed air chamber is in communication with the hollow cavity, and the compressed air chamber is used to release high-pressure gas into the hollow cavity so that the bubbles of the cavitation liquid burst under a positive pressure environment exceeding normal pressure and penetrate into the skin; Wherein, a compressed air valve is provided at the connection point between the compressed air bin and the hollow cavity, and the compressed air valve is used to control the connection between the compressed air bin and the hollow cavity.

3. The transdermal drug delivery device according to claim 1 or 2, characterized in that: Also includes: An elastic membrane, the elastic membrane being arranged on the outer wall and the inner wall of the skin contact opening, the elastic membrane being used for sealing the skin contact opening when the pressure in the hollow cavity changes; Alternatively, an elastic rubber pad is provided with a groove, an outer membrane of the rubber pad and an inner membrane of the rubber pad, the hollow cavity is embedded in the elastic rubber pad based on the groove, the inner wall of the skin-contacting opening is in contact with the inner membrane of the rubber pad, the outer wall of the skin-contacting opening is in contact with the outer membrane of the rubber pad, and the elastic rubber pad is used to seal the skin-contacting opening when the pressure in the hollow cavity changes.

4. A transdermal drug delivery device, characterized in that: include: A hollow cavity, the hollow cavity is used to load liquid medicine, the hollow cavity is provided with a skin contact port and a medicine injection port, the skin contact port is used to contact the liquid medicine with the skin, the medicine injection port is provided with an automatic control valve, the automatic control valve is used to control the opening or closing of the medicine injection port to inject the liquid medicine into the hollow cavity; An intracavity piston, the intracavity piston is arranged inside the hollow cavity, the intracavity piston is used to perform negative pressure treatment on the air pressure in the hollow cavity, so that the liquid medicine is gasified and converted into cavitation liquid medicine bubbles during the negative pressure treatment, and the intracavity piston is also used to perform positive pressure treatment on the air pressure in the hollow cavity, so that the cavitation liquid medicine bubbles are broken and penetrate into the skin during the positive pressure treatment; A piston rod, the piston rod passes through the top end of the hollow cavity, and one end of the piston rod is connected to the piston in the cavity; A piston linkage device is connected to the other end of the piston rod and is used to control the movement of the piston in the cavity.

5. The transdermal drug delivery device according to claim 4, characterized in that: A spring is provided between the inner piston and the inner top wall of the hollow cavity, and the spring is used to reset the inner piston to a preset initial position.

6. The transdermal drug delivery device according to claim 4 or 5, characterized in that: Also includes: An elastic membrane, the elastic membrane being arranged on the outer wall and the inner wall of the skin contact opening, the elastic membrane being used for sealing the skin contact opening when the pressure in the hollow cavity changes; Alternatively, an elastic rubber pad is provided with a groove, an outer membrane of the rubber pad and an inner membrane of the rubber pad, the hollow cavity is embedded in the elastic rubber pad based on the groove, the inner wall of the skin-contacting opening is in contact with the inner membrane of the rubber pad, the outer wall of the skin-contacting opening is in contact with the outer membrane of the rubber pad, and the elastic rubber pad is used to seal the skin-contacting opening when the pressure in the hollow cavity changes.

7. A transdermal administration method, characterized in that: The transdermal drug delivery device according to any one of claims 1 to 3 is worn by a user, the skin-adhering port and the skin surface of the user are attached to each other so that the hollow cavity forms a closed cavity, and the transdermal drug delivery method comprises: Controlling the automatic control valve to be in an open state so that the liquid medicine is injected into the hollow cavity from the injection port; After the liquid medicine is injected into the hollow cavity, the air pressure in the hollow cavity is subjected to negative pressure treatment by closing the hollow cavity and controlling the working state of the vacuum pump, so that the liquid medicine is gasified and converted into cavitation liquid medicine bubbles during the negative pressure treatment process; By controlling the working state of the automatic valve or the compressed air valve, the air pressure in the hollow cavity is subjected to positive pressure treatment, so that the bubbles of the cavitation liquid are broken and penetrate into the skin during the positive pressure treatment.

8. The transdermal administration method according to claim 7, characterized in that: The method of performing negative pressure treatment on the air pressure in the hollow cavity by closing the hollow cavity and controlling the working state of the air pump comprises: Controlling the automatic control valve to be in a closed state; Controlling the compressed air valve to be in a closed state; The vacuum fan is controlled to evacuate the hollow cavity so that the air pressure of the hollow cavity is converted from normal pressure to negative pressure, wherein the value range of the negative pressure is -100 KPa to -0.1 KPa.

9. The transdermal administration method according to claim 7, characterized in that: The positive pressure treatment of the air pressure in the hollow cavity by controlling the working state of the automatic control valve or the compressed air valve comprises: Controlling the automatic control valve to be in an open state, so that the air pressure of the hollow cavity is converted from negative pressure to normal pressure when external air enters the hollow cavity; Alternatively, the compressed air valve is controlled to be in an open state so that when the compressed air bin releases high-pressure gas, the air pressure in the hollow cavity is converted from negative pressure to positive pressure exceeding normal pressure, wherein the positive pressure has a numerical range of 0.01 MPa to 1.00 MPa.

10. A transdermal administration method, characterized in that: The transdermal drug delivery device according to any one of claims 4 to 6 is worn by a user, the skin contact opening and the skin surface of the user are attached to each other so that the hollow cavity forms a closed cavity, and the transdermal drug delivery method comprises: Controlling the automatic control valve to be in an open state so that the liquid medicine is injected into the hollow cavity from the injection port; After the liquid medicine is injected into the hollow cavity, the air pressure in the hollow cavity is subjected to negative pressure treatment by closing the hollow cavity and controlling the piston in the cavity to expand the internal volume of the hollow cavity, so that the liquid medicine is gasified and converted into cavitation liquid medicine bubbles during the negative pressure treatment process; When the piston in the cavity is in a preset downward position, the piston in the cavity is controlled to instantaneously compress the internal volume of the hollow cavity, and the air pressure in the hollow cavity is subjected to pulse positive pressure treatment, so that the bubbles of the cavitation liquid burst and penetrate into the skin during the pulse positive pressure treatment.

11. The transdermal administration method according to claim 10, characterized in that: The method of performing negative pressure treatment on the air pressure in the hollow cavity by closing the hollow cavity and controlling the piston in the cavity to expand the internal volume of the hollow cavity comprises: Controlling the automatic control valve to be in a closed state; The piston linkage device is controlled to move upward to drive the piston in the cavity to expand the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from normal pressure to negative pressure, wherein the value range of the negative pressure is -100KPa to -0.1KPa.

12. The transdermal administration method according to claim 10, characterized in that: The method of controlling the piston in the cavity to instantaneously compress the internal volume of the hollow cavity to perform pulse positive pressure processing on the air pressure in the hollow cavity comprises: Within a preset positive pressure pulse time, the piston linkage device is controlled to accelerate downward movement to drive the piston in the cavity to instantaneously compress the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from negative pressure to instantaneous pulse high pressure; Alternatively, within a preset positive pressure pulse time, the piston linkage device is controlled to move downward at a uniform speed to drive the piston in the cavity to instantaneously compress the internal volume of the hollow cavity, so that the air pressure of the hollow cavity is converted from negative pressure to instantaneous pulse high pressure.

13. The transdermal administration method according to claim 12, characterized in that: The numerical range of the preset positive pressure pulse time is 2.0s to 0.01s, and the numerical range of the instantaneous pulse high pressure is 0.01MPa to 1.00MPa.

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