A transdermal patch containing dexmedetomidine and a preparation method thereof

Abstract

The present application relates to the field of medicine biology, and particularly relates to a transdermal patch containing dexmedetomidine. By adding a penetration enhancer, the transdermal rate and the permeation amount are improved, the onset time is shortened, the patch content is reduced, the skin residue is reduced, and the skin redness / scarring at the administration site caused by the accumulation of the drug in the skin is effectively avoided.

Description

Technical Field

[0001] This invention relates to the field of pharmaceuticals and biotechnology, specifically to a transdermal patch containing dexmedetomidine and its preparation method. Background Technology

[0002] Insomnia is the most common sleep disorder, characterized by difficulty falling asleep, difficulty maintaining sleep, early awakening, poor sleep quality, and reduced total sleep time (usually less than 6 hours), often accompanied by daytime dysfunction. Sleep has a significant impact on human health; chronic insomnia can lead to weakened immunity, anxiety, and other health problems. Sleep disorders have become a major threat to people's health.

[0003] Dexmedetomidine, a highly selective ADAR2 agonist, inhibits noradrenergic nerve transmission from the locus coeruleus to the ventrolateral preoptic nucleus (VLPO), thereby relieving VLPO inhibition and triggering inhibition of cortical arousal nuclei, producing a sedative-hypnotic effect. Compared to commonly used drugs that reduce or have no significant effect on non-rapid eye movement (NREM) stage 3 sleep, dexmedetomidine can prolong total sleep time, improve sleep efficiency, and improve sleep structure, especially prolonging NREM stage 3 sleep time, thus treating insomnia. In recent years, transdermal absorption formulations for treating insomnia have become a hot research topic. Dexmedetomidine can be administered through a skin patch, with the active ingredient absorbed through the skin into the systemic bloodstream, making it convenient to use and resulting in good patient compliance.

[0004] The absorption process of transdermal patches is as follows: After the drug is applied to the skin surface, it is first released from the preparation onto the skin surface, then distributed into the stratum corneum, diffuses through the stratum corneum to the interface of the active epidermis, is then distributed into the aqueous active epidermis, continues to diffuse to the dermis, is absorbed by the capillaries into the blood circulation, and thus exerts its medicinal effect.

[0005] Non-clinical studies of conventional dexmedetomidine transdermal patches have shown that they have a long time to peak concentration and a slow absorption rate. Clinically, it is desirable for drugs to treat insomnia to take effect rapidly within half an hour to one hour. Therefore, it is necessary to develop transdermal patches that can improve the absorption rate of dexmedetomidine.

[0006] CN116098876A discloses a dexmedetomidine transdermal patch, its preparation method, and its application;

[0007] CN117582424 A discloses a dexmedetomidine transdermal composition, a transdermal patch, its preparation method, and its application;

[0008] CN117959268 A discloses a fat-soluble sedative-hypnotic drug sleep aid patch for insomnia patients and its preparation method.

[0009] The formulations of the three patented drugs mentioned above have a slow drug penetration rate. In porcine patch tests, the time to peak concentration was long, and in human patch tests, the drug could not be detected for 4 hours, indicating a slow onset of action. Furthermore, the drug accumulates in the skin, causing redness / scarring at the application site.

[0010] Clinically, insomnia treatment requires rapid onset of action within one hour, which is extremely disadvantageous for insomnia patients. It requires applying the patch well in advance, and forgetting to apply it in advance will affect the treatment of insomnia patients. Therefore, the solution is to address the slow onset of action of ordinary patches, improve the drug penetration rate, enable insomnia patients to fall asleep quickly, and avoid skin redness / scarring at the application site. Summary of the Invention

[0011] In view of the above-mentioned technical status, the present invention provides a transdermal patch containing dexmedetomidine, wherein the transdermal patch includes a penetrant selected from dimethyl sulfoxide, azone, isopropyl palmitate, isopropyl myristate, oleic acid, ethyl oleate, oleyl alcohol, propylene glycol, polyglycerol oleate, diethylene glycol monoethyl ether, eucalyptol, menthol or menthol, or a combination of two or more thereof; as one embodiment, azone is preferred.

[0012] In this invention, as one embodiment, the amount of penetrant in the transdermal patch, by mass fraction, is 3-30%, preferably 5-20%. As an example, the amount of penetrant can be 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30%.

[0013] In this invention, as one embodiment, the amount of dexmedetomidine in the transdermal patch is 4-10% by mass fraction, preferably 4-8%. As an example, it can be 4%, 5%, 6%, 7%, 8%, 9%, or 10%.

[0014] In this invention, as one embodiment, the transdermal patch further includes a crystallization inhibitor, which is selected from povidone. As one embodiment, the preferred crystallization inhibitors are povidone K25, povidone K17, povidone K12, povidone K30, povidone K90, and copovidone VA 64. As one embodiment, povidone K30 is further preferred.

[0015] In this invention, as one embodiment, the content of crystallization inhibitor in the transdermal patch is 2-12% by mass fraction, preferably 3-8%. As an example, it can be 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11% or 12%.

[0016] In this invention, as one embodiment, the transdermal patch further includes an colloid, wherein the colloid is selected from acrylic pressure-sensitive adhesives.

[0017] In this invention, as one embodiment, the pressure-sensitive adhesive is an acrylic pressure-sensitive adhesive, preferably DURO-TAK87-900A, DURO-TAK 87-9301, DURO-TAK 87-4098, DURO-TAK 387-2510, DURO-TAK 387-2287, DURO-TAK 87-4287, DURO-TAK 387-2516, DURO-TAK 87-2074, DURO-TAK 87-235A, DURO-TAK 387-2353, DURO-TAK 387-2852, DURO-TAK 387-2051, DURO-TAK 387-2052, DURO-TAK 387-2054, DURO-TAK 87-2194, DURO-TAK... 87-2196, DURO-TAK 87-2677, GELVA GMS9073, GELVA GMS 788, GELVA GMS 3253 or GELVA GMS 3083, or a combination of two or more thereof, as one of the implementation schemes, with DURO-TAK 387-2516 being more preferred.

[0018] In this invention, as one embodiment, the pressure-sensitive adhesive content in the transdermal patch is 48-94% by mass fraction, preferably 74-88%. As an example, the pressure-sensitive adhesive content in the transdermal patch is 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, or 87%.

[0019] In this invention, as one embodiment, the transdermal patch comprises:

[0020] The dosage of the drug is 4-10%;

[0021] The amount of penetrant is 3-30%;

[0022] The amount of povidone is 2-12%; and

[0023] The amount of colloid is 48-94%.

[0024] In this invention, as one embodiment, the transdermal patch comprises:

[0025] The dosage of the drug is 4-8%;

[0026] The amount of penetrant is 5-20%;

[0027] The amount of povidone is 3-8%; and

[0028] The amount of colloid is 74-88%.

[0029] In this invention, as one embodiment, the transdermal patch further includes:

[0030]

[0031]

[0032] In this invention, as one embodiment, the transdermal patch further includes a backing layer.

[0033] In this invention, as one embodiment, the material of the backing layer is selected from polyester, polyethylene polyvinyl acetate resin, copolymer of polyethylene and vinyl acetate, polyvinyl chloride, polyurethane, preferably ScotchPak. TM 1109 or Cotran TM 9720.

[0034] In this invention, as one embodiment, the transdermal patch further includes a protective layer.

[0035] In this invention, as one embodiment, the material of the protective layer is selected from Scotchpak. TM 9744 release film or Scotchpak TM 9709 release film, preferably Scotchpak TM 9709 release film.

[0036] This invention also provides a method for preparing a transdermal patch containing dexmedetomidine, characterized in that the method includes the following steps:

[0037] (1) Dissolve dexmedetomidine and povidone in an organic solvent of 2 to 10 times the weight of dexmedetomidine, add a penetration enhancer and mix well to obtain a drug solution.

[0038] (2) Mix the drug solution obtained in step (1) with the colloid and stir until homogeneous to obtain a colloidal mixture solution;

[0039] (3) After defoaming the colloidal mixture, it is coated onto the release film and dried to remove the organic solvent;

[0040] (4) Lay the backing and cut to obtain the transdermal patch.

[0041] In this invention, as one embodiment, the method further includes:

[0042] (1) Dissolve the prescribed amount of dexmedetomidine and povidone K30 in an organic solvent, add a penetration enhancer and mix well to obtain a drug solution;

[0043] (2) Mix the drug solution obtained in step (1) with the colloid at a ratio of 1:1 to 10 and stir until homogeneous to obtain a colloidal mixed solution; as an example, the ratio can be 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10.

[0044] (3) After the colloidal mixture solution is allowed to stand and defoam, it is coated onto the release film with a coating thickness of 0.22 mm. Then it is dried at 90°C for 20 min to remove the organic solvent.

[0045] (4) Lay the backing and cut to obtain the transdermal patch.

[0046] In this invention, as one embodiment, the amount of organic solvent in the transdermal patch, by mass fraction, is 5 to 10 times the weight of dexmedetomidine. For example, it can be 5, 6, 7, 7.5, 8, 9, or 10 times.

[0047] In this invention, as one embodiment, the organic solvent is selected from ethanol, ethyl acetate, n-heptane, dimethyl sulfoxide, and preferably ethanol.

[0048] The transparent patch of the present invention improves the transdermal rate and permeation by adding a penetration enhancer, thereby shortening the onset time; it also reduces the patch content, thereby reducing skin residue and shortening the application time, effectively avoiding skin redness / scarring at the drug administration site caused by drug accumulation in the skin.

[0049] The advantages of this invention are:

[0050] (1) Good adhesion performance, achieved through pressure-sensitive adhesive;

[0051] (2) Fast transdermal rate and high permeation rate.

[0052] (3) Reduces drug concentration and skin residue, with no obvious skin irritation;

[0053] (4) Good stability.

[0054] This invention has been verified through in vitro transdermal experiments, animal pharmacokinetics, and skin irritation tests. It has good patch performance, fast transdermal rate, high permeability, low skin irritation, and sleep-aiding effect. Attached Figure Description

[0055] Figure 1 Graph showing the change in cumulative permeation over time in an in vitro transdermal study of 30-day-old Bama miniature pigs.

[0056] Figure 2 : Drug-time curves for formulations 12-17. Detailed Implementation

[0057] The following examples are provided to further illustrate the present invention, but are not intended to limit the scope of the invention in any way.

[0058] Example 1 - Solvent Type and Dosage Screening

[0059] The dexmedetomidine transdermal patch of this invention is prepared using a solvent method. In the formulation, dexmedetomidine and povidone are solids, while the other materials are liquids. To ensure uniform mixing, a solvent is used to dissolve the solid materials before mixing. Commonly used solvents include methanol, ethanol, isopropanol, ethyl acetate, n-heptane, and dimethyl sulfoxide; methanol, ethanol, isopropanol, or dimethyl sulfoxide are preferred. Furthermore, according to the requirements of the solvent method, the solvent must be dried and removed, therefore a low boiling point is required, such as methanol, ethanol, or isopropanol, with ethanol being preferred. The amount of ethanol was determined by gradually adding the ethanol and observing the dissolution state of the solid materials. The results are shown in Tables 1 and 2.

[0060] Table 1

[0061] solvent boiling point Material dissolution ethanol 78.4℃ Completely dissolved Ethyl acetate 77.2℃ Incompletely dissolved n-Heptane 98.4℃ Incompletely dissolved Dimethyl sulfoxide 189℃ Completely dissolved

[0062] Table 2

[0063] Ethanol dosage Solid material in dissolution state Dexmedetomidine 1 times the weight The surface of the solid material was not completely wetted Dexmedetomidine twice the weight The solid material surface is completely wetted; polyvinyl ketone is viscous and dissolves slowly. Dexmedetomidine 5 times the weight The solid material surface was completely wetted, and the material was completely dissolved after magnetic stirring for 30 minutes. Dexmedetomidine 10 times the weight The solid material surface was completely wetted, and the material was completely dissolved after magnetic stirring for 10 minutes. Dexmedetomidine 7.5 times its weight The solid material surface was completely wetted, and the material was completely dissolved after magnetic stirring for 10 minutes. Dexmedetomidine 7 times the weight The surface of the solid material was completely wetted, and after magnetic stirring for 10 minutes, a small amount of material remained undissolved.

[0064] The results showed that the material was completely soluble in ethanol and dimethyl sulfoxide. Ethanol has a relatively low boiling point. Considering both the solubility of the material and the process requirements, ethanol was the preferred solvent. When the amount of ethanol was twice the weight of dexmedetomidine, the surface of the solid material was completely wetted. However, povidone is viscous, and after surface wetting, a sticky layer was formed, making it difficult for the solvent to penetrate the material, resulting in slow dissolution and requiring prolonged stirring for complete dissolution. When the amount of ethanol was five times the weight of dexmedetomidine, stirring for 30 minutes was required for complete dissolution. When the amount of ethanol was 7.5 times or more the weight of dexmedetomidine, stirring for 10 minutes was sufficient for complete dissolution. Therefore, an ethanol amount of 7.5 times the weight of dexmedetomidine was preferred. A solvent amount of 5 times or more (including 5 times) of dexmedetomidine was preferred, and a solvent amount of 7.5 times or more (including 7.5 times) of dexmedetomidine was further preferred.

[0065] Example 2 - Comparison of different colloids

[0066] DURO-TAK 387-2516 (ethyl acetate as solvent, solid content 41.5%, containing hydroxyl functional groups) and DURO-TAK 387-2074 (ethyl acetate as solvent, solid content 29.5%, containing hydroxyl and carboxyl functional groups) were selected. The formulations are shown in Table 3.

[0067] Table 3

[0068]

[0069] Note: Ethanol is used as a solvent and is eventually removed. The amount used is 7.5 times the weight of dexmedetomidine.

[0070] Dissolve the prescribed amounts of dexmedetomidine and povidone K30 in ethanol, then add the pressure-sensitive adhesive and stir until homogeneous. After allowing to stand and defoam, coat the mixture onto a release film, controlling the coating thickness to 0.22 mm, and then dry at 90°C for 20 minutes. Finally, lay the quilt backing and cut it into 2.5 cm pieces. 2 Size of the patch.

[0071] The average content of formulation 1 was 1.14 mg / patch, and the average content of formulation 2 was 1.09 mg / patch. To compare the actual skin permeability of the patches, one patch of each formulation was applied to the outer upper arm of six healthy volunteers. After 2 hours, the patches were removed, and the adhesion of the formulations to the skin was observed to analyze the drug residue. Drug permeability = (patch content - residue) / patch content. The results are shown in Table 4.

[0072] Table 4

[0073]

[0074]

[0075] The results showed that the DURO-TAK 387-2516 colloid had good adhesion and a relatively high transdermal rate. Since the volunteers wore two patches simultaneously, the transdermal absorption rate was high over 2 hours, exceeding 110 μg in each patch. Therefore, most volunteers (4 cases) experienced varying degrees of drowsiness after removing the patches.

[0076] In addition, no volunteers reported adverse reactions such as pain, swelling, or itching, indicating that the patch is safe. However, due to the high drug content of the patch, it may cause slight skin irritation, resulting in patch scarring in half of the volunteers (3 cases), which disappeared after about 2 days.

[0077] Example 3 - Comparison of Penetration Enhancers

[0078] Penetration enhancers such as azone, oleic acid, propylene glycol, diethylene glycol monoethyl ether, and polyglycerol oleate were selected and compared with samples without penetration enhancers. The formulations are shown in Table 5.

[0079] Table 5

[0080]

[0081] Note: Ethanol is used as a solvent, and the amount used is 7.5 times the weight of dexmedetomidine. It is eventually removed by drying.

[0082] Dissolve the prescribed amounts of dexmedetomidine and povidone K30 in ethanol, add the penetration enhancer and mix well, then add the pressure-sensitive adhesive and mix well. After standing to defoam, coat the mixture onto a release film, controlling the coating thickness to 0.18 mm, and then dry at 90°C for 10 minutes. Finally, lay the quilt backing and cut it into 10 cm pieces. 2 Square patches of a certain size.

[0083] Example 4 - In vitro transdermal test

[0084] Using the skin of 30-day-old Bama miniature pigs as the transdermal material, in vitro transdermal experiments were conducted using a Franz vertical diffusion cell. The receiving solution was phosphate buffer (pH 7.40), the bath temperature was 32℃ ± 0.5℃, and the rotation speed was 500 rpm. Four replicates were performed, with samples taken at 1h, 2h, 4h, 6h, 8h, 12h, and 24h as the test solution. A blank receiving solution was also added. The results are shown in Table 6 and Appendix. Figure 1 As shown:

[0085] Table 6

[0086]

[0087] The results show that the addition of penetration enhancers increased the transdermal permeation rate and permeation volume to varying degrees. Among them, the patch with added azone showed the most significant increase in transdermal permeation rate and permeation volume, with relatively less residue in the skin and high safety.

[0088] Example 5 - Screening of Penetration Enhancer Dosage

[0089] Patches containing azone showed the most significant increase in in vitro transdermal penetration rate and amount. Therefore, azone was selected as the penetration enhancer, and dosage screening was conducted. The formulation is shown in Table 7.

[0090] Table 7

[0091]

[0092]

[0093] Note: Ethanol is used as a solvent, and the amount used is 7.5 times the weight of dexmedetomidine. It is eventually removed by drying.

[0094] Dissolve the prescribed amounts of dexmedetomidine and povidone K30 in ethanol, add the penetration enhancer and mix well, then add the pressure-sensitive adhesive and mix well. After standing to defoam, coat the mixture onto a release film, controlling the coating thickness to 0.18 mm, and then dry at 90°C for 10 minutes. Finally, lay the quilt backing and cut it into 10 cm pieces. 2 The results for the square patches of various sizes are shown in Table 8:

[0095] Table 8

[0096]

[0097] The results showed that when the azone dosage was 5%, there was no significant increase in the in vitro transdermal rate and permeation volume; when the dosage was 10%, the in vitro transdermal rate and permeation volume increased significantly; further increasing the dosage to 15% and 30% did not show a significant increase in the in vitro transdermal rate and permeation volume compared to the 10% dosage. Therefore, a 10% azone dosage is preferred.

[0098] Example 6 - Pharmacokinetic Study

[0099] Six 4-month-old male Bama miniature pigs were divided into 6 groups, corresponding to formulations 12–17. One patch was applied to the skin of each pig after dehairing. Blood samples were collected 10 minutes before administration and at 0.5, 1, 2, 4, 6, 10, 24, 27, 30, and 48 hours after administration. Plasma drug concentrations at each time point were determined using LC-MS / MS. This was repeated three times, with animals changed each time, and a washing period of 5–7 days. The pharmacokinetic curves for formulations 12–17 were plotted, as shown in the attached figure. Figure 2 As shown in the figure. The results showed that the blood drug concentration of the patch with added azone increased rapidly and was higher.

[0100] Example 7 - Skin Irritation Test

[0101] Take formulation 13 from Example 3 and cut it into 2.5cm pieces. 2 One patch of each size was applied to the inner upper arm of six healthy volunteers. The preparation adhered well to the skin. After 3 hours, the patches were removed, and no obvious skin scars were found. All volunteers felt drowsy to varying degrees.

[0102] Example 8 - Stability Test

[0103] The formulation 13 samples of Example 3 were placed at 40°C and 75% RH accelerated conditions for 3 months, and the changes in related substances were analyzed.

[0104] Chromatographic conditions:

[0105] Detector: Ultraviolet detector (measurement wavelength: 210 nm)

[0106] Chromatographic column: Waters X-Bridge C18 (4.6×250mm, 5µm)

[0107] Column temperature: 35℃

[0108] Flow rate: 0.8 mL / min

[0109] Injection volume: 100 μL

[0110] Total analysis time: 40 min

[0111] Autosampler: Room temperature

[0112] Mobile phase: A: Take 3.2g of disodium hydrogen phosphate dodecahydrate and 0.12g of anhydrous sodium dihydrogen phosphate, place them in 1000mL of water, and adjust the pH to 5.50 with phosphoric acid; B: methanol; A:B (50:50).

[0113] The results for the relevant substances are shown in Table 9:

[0114] Table 9

[0115] time content% Maximum single impurity % Total miscellaneous % 0 days 101.7 Not detected Not detected 1 month 101.0 0.04 0.09 2 months 101.6 0.04 0.27 3 months 100.7 0.05 0.34

[0116] The results showed that after 3 months of storage under accelerated conditions, the active ingredients and related substances in the samples did not change significantly.

Claims

1. A transdermal patch containing dexmedetomidine, characterized in that, The transdermal patch includes a penetrant selected from dimethyl sulfoxide, azone, isopropyl palmitate, isopropyl myristate, oleic acid, ethyl oleate, oleyl alcohol, propylene glycol, polyglycerol oleate, diethylene glycol monoethyl ether, eucalyptol, menthol, or a combination of two or more of these.

2. The transdermal patch according to claim 1, characterized in that, The penetrant is selected from azone.

3. The transdermal patch according to claim 1, characterized in that, The amount of penetrant in the transdermal patch is 3-30% by mass fraction, preferably 5-20%.

4. The transdermal patch according to claim 1, characterized in that, The amount of dexmedetomidine in the transdermal patch is 4-10% by mass fraction, preferably 4-8%.

5. The transdermal patch according to claim 1, characterized in that, The transdermal patch further includes a crystallization inhibitor, which is selected from povidone, preferably povidone K25, povidone K17, povidone K12, povidone K30, povidone K90 or copovidone VA64, and more preferably povidone K30.

6. The transdermal patch according to claim 1, characterized in that, The transdermal patch also includes an colloid, which is selected from acrylic pressure-sensitive adhesives.

7. The transdermal patch according to claim 6, characterized in that, The acrylic pressure-sensitive adhesive is selected from DURO-TAK87-900A, DURO-TAK 87-9301, DURO-TAK 87-4098, DURO-TAK 387-2510, DURO-TAK 387-2287, DURO-TAK 87-4287, DURO-TAK 387-2516, DURO-TAK 87-2074, DURO-TAK 87-235A, DURO-TAK 387-2353, DURO-TAK 387-2852, DURO-TAK 387-2051, DURO-TAK 387-2052, DURO-TAK 387-2054, DURO-TAK 87-2194, DURO-TAK 87-2196、DURO-TAK 87-2677, GELVA GMS9073, GELVA GMS 788, GELVA GMS 3253, or GELVA GMS 3083, or a combination of two or more of them.

8. The transdermal patch according to claim 7, characterized in that, The pressure-sensitive adhesive content in the transdermal patch is 48-94% by mass fraction, preferably 74-88%.

9. The transdermal patch according to any one of claims 1 to 10, characterized in that, The transdermal patch includes: The dosage of the drug is 4-10%; The amount of penetrant is 3-30%; The amount of povidone is 2-12%; and The amount of colloid is 48-94%.

10. The transdermal patch according to claim 9, characterized in that, The transdermal patch includes: The dosage of the drug is 4-8%; The amount of penetrant is 5-20%; The amount of povidone is 3-8%; and The amount of colloid is 74-88%.

11. The transdermal patch according to claim 9, characterized in that, The transdermal patch also includes:

12. The transdermal patch according to claim 1, characterized in that, The transdermal patch also includes a backing layer.

13. The transdermal patch according to claim 12, characterized in that, The backing layer is made of polyester, polyethylene polyvinyl acetate resin, copolymer of polyethylene and vinyl acetate, polyvinyl chloride, or polyurethane, preferably ScotchPak. TM 1109 or Cotran TM 9720.

14. The transdermal patch according to claim 13, characterized in that, The transdermal patch also includes a protective layer.

15. The transdermal patch according to claim 14, characterized in that, The material of the protective layer is selected from Scotchpak. TM 9744 release film or Scotchpak TM 9709 release film, preferably Scotchpak TM 9709 release film.

16. A method for preparing a transdermal patch according to any one of claims 1-15, characterized in that, The method includes the following steps: (1) Dissolve dexmedetomidine and povidone in an organic solvent of 2 to 10 times the weight of dexmedetomidine, add a penetration enhancer and mix well to obtain a drug solution. (2) Mix the drug solution obtained in step (1) with the colloid and stir until homogeneous to obtain a colloidal mixture solution; (3) After defoaming the colloidal mixture, it is coated onto the release film and dried to remove the organic solvent; (4) Lay the backing and cut to obtain the transdermal patch.

17. The preparation method according to claim 16, characterized in that, The method includes: (1) Dissolve the prescribed amount of dexmedetomidine and povidone K30 in an organic solvent, add a penetration enhancer and mix well to obtain a drug solution; (2) Mix the drug solution obtained in step (1) with the colloid at a ratio of 1:1 to 10 and stir until homogeneous to obtain a colloidal mixed solution; (3) After the colloidal mixture solution is allowed to stand and defoam, it is coated onto the release film with a coating thickness of 0.22 mm. Then it is dried at 90°C for 20 min to remove the organic solvent. (4) Lay the backing and cut to obtain the transdermal patch.

18. The transdermal patch according to claim 16 or 17, characterized in that, The amount of organic solvent in the transdermal patch, by mass fraction, is 5 to 10 times the weight of dexmedetomidine.

19. The preparation method according to claim 16 or 17, characterized in that, The organic solvent is selected from ethanol, ethyl acetate, n-heptane, dimethyl sulfoxide, with ethanol being preferred.

Images