Dexmedetomidine transdermal patch as well as preparation method and application thereof

Abstract

The invention provides a dexmedetomidine transdermal patch which comprises a backing layer, a release film and a polymer matrix layer arranged between the backing layer and the release film, the polymer matrix layer comprises dexmedetomidine, povidone and a pressure-sensitive adhesive, based on the total mass of the polymer matrix layer, the dexmedetomidine accounts for 4-10%, the povidone accounts for 5-10%, and the pressure-sensitive adhesive accounts for 5-10%. The povidone accounts for 2-12%, and the pressure-sensitive adhesive accounts for 78-94%; the pressure-sensitive adhesive comprises at least one of polymers containing carboxyl or hydroxyl functionalization.

Description

[0001] This application is a divisional application of Chinese patent application No. "202111331613.X", filed on November 11, 2021, entitled "A dexmedetomidine transdermal patch and its preparation method and application". Technical Field

[0002] This application relates to the field of pharmaceutical preparation technology, and in particular to a dexmedetomidine transdermal patch, its preparation method, and its application. Background Technology

[0003] Intractable insomnia is a common and severe sleep disorder that is difficult to treat, especially among the elderly, posing a significant threat to their physical and mental health, particularly cognitive function. Currently, commonly used medications for treating intractable insomnia include benzodiazepines and non-benzodiazepines, both of which affect cognitive function. While medication improves sleep quality, it does not address the cognitive decline caused by insomnia. Furthermore, drug treatment is not widely available due to respiratory depression, drug tolerance, and reduced sleep depth. Dexmedetomidine is a highly effective and selective α2-receptor agonist with sedative, analgesic, anti-anxiety, and hypnotic properties, inducing sleep that closely resembles natural sleep in healthy individuals. Current treatments for intractable insomnia with dexmedetomidine typically require infusion via a microinfusion pump. However, microinfusion often necessitates hospitalization and suffers from poor patient compliance, hindering effective treatment outcomes. Summary of the Invention

[0004] To facilitate the treatment of patients with intractable insomnia, this application provides a dexmedetomidine transdermal patch, its preparation method, and its application.

[0005] The first aspect of this application provides a dexmedetomidine transdermal patch, comprising a backing layer, a release film, and a polymer matrix layer disposed between the backing layer and the release film. The polymer matrix layer comprises dexmedetomidine, povidone, and pressure-sensitive adhesive. Based on the total mass of the polymer matrix layer, the dexmedetomidine accounts for 4-10%, the povidone accounts for 2-12%, and the pressure-sensitive adhesive accounts for 78-94%. The pressure-sensitive adhesive comprises at least one polymer containing carboxyl or hydroxyl functionalized groups.

[0006] The second aspect of this application provides a method for preparing the dexmedetomidine transdermal patch of the first aspect of this application, which includes the following steps:

[0007] 1) Dissolve 4-10 parts by weight of dexmedetomidine and 2-12 parts by weight of povidone in ethanol to obtain a drug solution;

[0008] 2) Mix 78-94 parts by weight of pressure-sensitive adhesive with the drug solution, wherein the total amount of dexmedetomidine, povidone and pressure-sensitive adhesive is 100 parts by weight; stir until homogeneous to obtain a colloidal solution;

[0009] 3) After the colloidal solution is defoamed, it is coated onto a release film, dried to remove the solvent, and a polymer matrix layer is obtained;

[0010] 4) Cover the polymer matrix layer with the backing layer and cut it to obtain the dexmedetomidine transdermal patch.

[0011] The third aspect of this application provides the use of the dexmedetomidine transdermal patch of the first aspect of this application in the preparation of a medicament for treating intractable insomnia.

[0012] The transdermal patch provided in this application is a transdermal absorption preparation that can deliver medication through skin application. The active ingredients are absorbed through the skin and enter the systemic blood circulation, which can prolong the duration of action, make the medication convenient, and improve patient compliance, thus facilitating effective treatment of intractable insomnia. Attached Figure Description

[0013] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only one embodiment of this application. For those skilled in the art, other embodiments can be obtained based on these drawings.

[0014] Figure 1 This is a scanning electron microscope image of the patch from Example 5.

[0015] Figure 2 The average drug-time curve for the subjects is shown.

[0016] Figure 3 This is a high-performance liquid chromatogram of the patch components from Example 4.

[0017] Figure 4 The image shows the high-performance liquid chromatogram of the patch components after 30 days of light exposure in Example 4.

[0018] Figure 5 The image shows the high-performance liquid chromatogram of the patch components after 30 days of high-temperature storage of the patch in Example 4. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided with reference to the accompanying drawings and embodiments. Obviously, the described embodiments are merely some embodiments of this application, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments in this application are within the scope of protection of this application.

[0020] The first aspect of this application provides a dexmedetomidine transdermal patch (hereinafter referred to as a patch), which includes a backing layer, a release film, and a polymer matrix layer disposed between the backing layer and the release film. The polymer matrix layer contains dexmedetomidine, povidone, and pressure-sensitive adhesive. Based on the total mass of the polymer matrix layer, the dexmedetomidine accounts for 4-10%, the povidone accounts for 2-12%, and the pressure-sensitive adhesive accounts for 78-94%. The pressure-sensitive adhesive includes at least one polymer containing carboxyl or hydroxyl functionalized groups.

[0021] The inventors discovered in their research that existing dexmedetomidine transdermal patches, typically used to treat conditions such as ADHD and anxiety disorders, often require prolonged, slow drug delivery, resulting in a generally slow transdermal rate. However, the dexmedetomidine transdermal patch of this application is intended for treating insomnia. The preferred delivery method is for the transdermal patch to rapidly deliver the drug into the body within a short time, achieving an effective blood concentration. Therefore, a faster transdermal rate is required for the dexmedetomidine transdermal patch used to treat insomnia. Unexpectedly, the inventors found that, by adjusting the ratio of dexmedetomidine, povidone, and pressure-sensitive adhesive, the transdermal rate of the dexmedetomidine transdermal patch obtained in this application reaches 6 μg / cm³. 2 With a speed of over / h, rapid drug delivery can be achieved.

[0022] In some embodiments of the first aspect of this application, the transdermal transdermal rate of dexmedetomidine is 6-25 μg / cm. 2 / h.

[0023] In some embodiments of the first aspect of this application, the mass ratio of povidone to dexmedetomidine is 0.5-1.2. The inventors have found that when the mass ratio of povidone to dexmedetomidine is within this range, it is beneficial to reduce dexmedetomidine crystallization, thereby improving the transdermal transdermal rate of dexmedetomidine and ensuring its full utilization.

[0024] In some embodiments of the first aspect of this application, the dexmedetomidine loading is 0.3-1.5 mg / patch.

[0025] In this application, the backing layer serves to prevent the polymer matrix layer from directly contacting the external environment, thus preventing drug loss. Those skilled in the art can conventionally select the material for the backing layer in a transdermal patch as needed; this application does not limit this selection. Exemplarily, the material of the backing layer may include at least one of polyester, polyethylene, polypropylene, polyvinyl acetate resin, copolymers of ethylene and vinyl acetate, polyvinyl chloride, and polyurethane. Specifically, materials such as ScotchPak from 3M can be used. TM1109 or Cotran TM 9720.

[0026] In some embodiments of the first aspect of this application, the pressure-sensitive adhesive is selected from DURO-TAK 87-900A, 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 387-2852, DURO-TAK 387-2051, DURO-TAK 387-2052, DURO-TAK 387-2054, DURO-TAK 87-2194, DURO-TAK 87-2196, DURO-TAK... At least one of the following: 87-2677, GELVA GMS 9073, GELVA GMS 788, GELVA GMS 3253, and GELVA GMS 3083, wherein the name of the above pressure-sensitive adhesive refers to the model number of the pressure-sensitive adhesive, and all of the above pressure-sensitive adhesives are commercially available, such as those from Henkel AG, Germany. The inventors have discovered that different pressure-sensitive adhesives have different solubilities for dexmedetomidine and different degrees of interaction with dexmedetomidine, thus affecting the drug content and transdermal rate of the dexmedetomidine transdermal patch. The inventors have discovered that when the pressure-sensitive adhesive of this application is used, mixed with dexmedetomidine and povidone in a specific ratio to prepare the dexmedetomidine transdermal patch, a higher transdermal rate can be obtained.

[0027] In this application, the release film is a commonly used protective layer in transdermal patches. It can be easily peeled off from the polymer matrix layer when using the transdermal patch. The release film is a commonly used material in the art, and this application does not limit its use. For example, the release film can be Scotchpak from 3M. TM 9744 release film or Scotchpak TM 9709 release film.

[0028] The second aspect of this application provides a method for preparing the dexmedetomidine transdermal patch of the first aspect of this application, which includes the following steps:

[0029] 1) Dissolve 4-10 parts by weight of dexmedetomidine and 2-12 parts by weight of povidone in ethanol to obtain a drug solution;

[0030] 2) Mix 78-94 parts by weight of pressure-sensitive adhesive with the drug solution, wherein the total amount of dexmedetomidine, povidone and pressure-sensitive adhesive is 100 parts by weight; stir until homogeneous to obtain a colloidal solution;

[0031] 3) After the colloidal solution is defoamed, it is coated onto a release film, dried to remove the solvent, and a polymer matrix layer is obtained;

[0032] 4) Cover the polymer matrix layer with the backing layer and cut it to obtain the dexmedetomidine transdermal patch.

[0033] In the preparation method of this application, the solvent removed by drying in step 3) includes ethanol in step 1) and the solvent already contained in the commercially available pressure-sensitive adhesive in step 2). The mass of the pressure-sensitive adhesive in this application refers to the mass without solvent. The amount of pressure-sensitive adhesive containing solvent can be calculated based on the mass fraction of the pressure-sensitive adhesive and the solid content of the commercially available pressure-sensitive adhesive.

[0034] In some embodiments of the second aspect of this application, in step 1), the mass ratio of povidone to dexmedetomidine is 0.5-1.2. When povidone and dexmedetomidine are mixed at the mass ratio of this application, it is easier to obtain a dexmedetomidine transdermal patch with a higher transdermal rate.

[0035] In some embodiments of the second aspect of this application, the total mass ratio of the povidone and the dexmedetomidine to the mass ratio of ethanol is 1:4-5; when the ratio is within the range, it is beneficial for the complete dissolution of povidone and dexmedetomidine, and also beneficial for the removal of solvent in subsequent steps.

[0036] This application does not limit the defoaming method; for example, static defoaming can be used.

[0037] In this application, the coating thickness is not limited; for example, the coating thickness can be selected as 0.1-0.25 mm. Excessive coating thickness will result in drug waste and is not conducive to reducing production costs.

[0038] This application does not limit the drying method, as long as it can achieve the purpose of this application. For example, it can be dried at 80-100℃ with forced air for 5-15 minutes.

[0039] The third aspect of this application provides the use of the dexmedetomidine transdermal patch of the first aspect of this application in the preparation of a medicament for treating intractable insomnia.

[0040] The following describes embodiments of this application. The embodiments described below are exemplary and are only used to explain this application, and should not be construed as limiting this application. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the art or according to the product instructions. Reagents or instruments used, unless otherwise specified, are all commercially available conventional products.

[0041] Example 1

[0042] 1) Dissolve 0.2g dexmedetomidine and 0.1g povidone K30 in 1.5g ethanol to obtain a drug solution;

[0043] 2) Mix 4.1g of commercially available pressure-sensitive adhesive DURO-TAK 387-2516 (solid content 41.5%) with the drug solution and stir until homogeneous to obtain a colloidal solution;

[0044] 3) After the colloidal 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 solvent and obtain the polymer matrix layer.

[0045] 4) Cover the polymer matrix layer with the backing layer and cut it into 2.5cm pieces. 2 The size is determined to obtain the dexmedetomidine transdermal patch.

[0046] The product contains 10% dexmedetomidine, 5% povidone, and 85% pressure-sensitive adhesive.

[0047] Example 2

[0048] Except for replacing the pressure-sensitive adhesive with 5.76g DURO-TAK 387-2074 (solid content of 29.5%), the rest is the same as in Example 1.

[0049] Example 3

[0050] Except for adjusting the polyvinylpyrrolidone K30 to 0.12g and the pressure-sensitive adhesive to 8.87g, the rest was the same as in Example 1.

[0051] Example 4

[0052] Except for adjusting the polyvinylpyrrolidone K30 to 0.125g and the pressure-sensitive adhesive to 11.26g, the rest was the same as in Example 1.

[0053] Comparative Examples 1-3

[0054] Except for adjusting the corresponding preparation parameters according to Table 1, everything else is the same as in Example 1.

[0055] The sample preparation parameters for each embodiment and comparative example are shown in Table 1.

[0056] Table 1

[0057] PIB / PB is a mixture of high molecular weight polyisobutylene PIB (5% Oppanol B100), low molecular weight PIB (25% Oppanol B12), and polybutene PB tackifier Indopol H1900 (20%) in heptane (50%).

[0058] Dexmedetomidine content determination:

[0059] Extraction solution I: 700 mL methanol, 300 mL isopropanol and 2.9 g concentrated phosphoric acid, mixed and shaken well, are then obtained.

[0060] Take the patch to be tested, remove the release film, place it in a headspace gas flask pre-filled with 10 mL of extraction solution I, seal, soak for 1 hour, sonicate for 5 min, centrifuge (14000 g, 5 min), collect the supernatant, and determine the content of dexmedetomidine in the patch using high performance liquid chromatography (HPLC). The chromatographic conditions are as follows:

[0061] Detector: Ultraviolet detector (measurement wavelength: 220nm)

[0062] Chromatographic column: Waters X-Bridge C18 (4.6×250mm, 5µm)

[0063] Column temperature: 30℃

[0064] Flow rate: 1.0 mL / min

[0065] Injection volume: 5 μL

[0066] Total analysis time: 10 min

[0067] Autosampler: Room temperature

[0068] Mobile phase: A: Take 3.2g of disodium hydrogen phosphate dodecahydrate and 0.12g of anhydrous sodium dihydrogen phosphate and place them in 1000 mL of water; B: methanol; A:B (30:70).

[0069] Transdermal penetration rate = (drug loading - residual amount) / drug loading, where the drug loading refers to the dexmedetomidine content in the patch before use; the residual amount refers to the remaining amount of dexmedetomidine in the patch after administration.

[0070] Transdermal rate = Transdermal rate × Drug loading / Patch area / Drug administration time.

[0071] The drug loading of the patches for each embodiment and comparative example is shown in Table 2 below. Six patches from each embodiment and comparative example were applied to the outer upper arm of six healthy volunteers. After 2 hours, the patches were removed, and the residual dexmedetomidine was analyzed. The transdermal transdermal rates of the patches for each embodiment and comparative example are shown in Table 2 below.

[0072] Table 2

[0073] The results show that the transdermal patches of this application all have high transdermal rates, with transdermal penetration rates exceeding 6 μg / cm². 2 / h. However, existing transdermal patches using different ingredients or concentrations cannot achieve the transdermal rate of this application.

[0074] In addition, no volunteers reported adverse reactions such as pain, swelling, or itching, indicating that the patch is safe.

[0075] Examples 5-13

[0076] Except for adjusting the corresponding preparation parameters according to Table 3, everything else is the same as in Example 1.

[0077] Table 3

[0078] The patches from Examples 5-13 were placed in a 40°C oven for accelerated testing. After 30 days, they were removed and the crystallization on the patch surface was observed. The results are shown in Table 4.

[0079] Table 4

[0080] As shown in Table 4, when the mass ratio of povidone to dexmedetomidine is higher than 0.5, no drug crystals are visible to the naked eye.

[0081] For trace crystallization in the sample, since the crystallization is not obvious, it cannot be observed and judged by the naked eye or electron microscope. Only under scanning electron microscopy at 5000x magnification can crystallized particles be found locally, with a particle size of less than 500 nm. Among them, the scanning electron microscopy results of Example 5 are as follows. Figure 1 As shown.

[0082] Examples 14-15

[0083] Except for adjusting the corresponding preparation parameters according to Table 5, the rest is the same as in Example 3. Azone and oleic acid, as penetration enhancers, are dissolved in ethanol along with dexmedetomidine and povidone.

[0084] Table 5

[0085] Six patches from Examples 3 and 14 & 15 were applied to the outer upper arm of six healthy volunteers. After 3 hours, the patches were removed, and the residual dexmedetomidine was analyzed. The transdermal transdermal rates of the patches from Examples 3, 14 & 15 are shown in Table 6 below.

[0086] Table 6

[0087] The results show that after adding the penetration enhancer, individual differences increased, and the average transdermal permeability and transdermal rate did not show a significant increase.

[0088] Preliminary pharmacokinetic studies in healthy subjects

[0089] Ten subjects (6 males and 4 females) were recruited at the General Hospital of the People's Liberation Army. All subjects underwent breath alcohol testing, urine nicotine testing, and urine drug screening the day before the trial. Female subjects also needed to undergo a blood pregnancy test. After passing the test, qualified subjects were admitted to the Phase I clinical trial ward the day before the trial.

[0090] Subjects applied the dexmedetomidine transdermal patch of Example 4 at 8:00 AM on the same day, with the patch applied to the undamaged skin on the outer side of the upper arm. The patch was removed 3 hours later, and vital signs were monitored within 30 minutes before administration and at 1, 3, 6, 12, and 24 hours after administration.

[0091] Blood samples were collected from the upper limb veins of the subjects 10 minutes before administration, and at 0.5 h, 1 h, 1.5 h, 2 h, 3 h (i.e. before patch removal), 3.5 h, 4 h, 6 h, 8 h, and 10 h after administration, using an indwelling intravenous catheter or disposable syringe. Each sample was approximately 3 mL and placed in an EDTA-K2 anticoagulant blood collection tube.

[0092] Blood sample processing: Gently invert to mix, centrifuge (1700g, 2~8ºC) for 10 min, take about 0.8 mL of the supernatant plasma and place it in the test cryovial. Place the remaining plasma in a backup cryovial and store at -70ºC (-60ºC~-90ºC). Blood sample separation and freezing should be completed within 2 hours after collection.

[0093] Blood sample analysis: The concentration of dexmedetomidine in blood samples taken at different times was determined by LC-MS / MS. The mean drug-time curve (plasma concentration-time curve) for the subjects is shown below. Figure 2 As shown.

[0094] from Figure 2 As can be seen, within 0-10 hours, the blood drug concentration generally showed an upward trend, and after 10 hours, the blood drug concentration may increase further. Overall, the blood drug concentration did not decrease within 7 hours after the patch was removed.

[0095] Because dexmedetomidine has certain side effects, such as hypotension, nausea, slowed heart rate, and tissue hypoxia, there is a risk to patients if the drug continues to enter the bloodstream through the skin after they fall asleep. The inventors unexpectedly discovered that with the transdermal patch of this application, 10-30% of the drug migrates from the patch to the epidermis or dermis within 3 hours of administration. Even after the patch is removed, the drug accumulated in the skin can continue to enter the bloodstream, maintaining a blood drug concentration for at least 7 hours, thus improving the efficacy and safety of the formulation.

[0096] Stability test

[0097] The patch from Example 4 was placed under light (illuminance 4500 lx ± 500 lx) and 40°C conditions for accelerated testing. After 30 days, it was removed and its related substances were analyzed.

[0098] Take 700 mL of methanol and 300 mL of isopropanol, mix them, and shake well to obtain extract II.

[0099] After removing the release film from the patch, a dexmedetomidine solution with a concentration of 100 μg / mL was prepared using Extraction Solution II (the dexmedetomidine content in the patch was obtained according to the aforementioned method). Specifically, the patch was placed in Extraction Solution II, sealed, soaked for 4 hours, sonicated for 5 minutes, centrifuged (14000g, 5 minutes), and 1 mL was collected. The solvent was evaporated (overnight, dried under nitrogen the next day), and 1 mL of water was added to dissolve. The content of related substances in the patch was determined by high-performance liquid chromatography (HPLC) under the following chromatographic conditions:

[0100] Detector: Ultraviolet detector (measurement wavelength: 210 nm)

[0101] Chromatographic column: Waters X-Bridge C18 (4.6×250mm, 5µm)

[0102] Column temperature: 35℃

[0103] Flow rate: 0.8 mL / min

[0104] Injection volume: 100 μL

[0105] Total analysis time: 40 min

[0106] Autosampler: Room temperature

[0107] Mobile phase: A: Take 3.2g of disodium hydrogen phosphate dodecahydrate and 0.12g of anhydrous sodium dihydrogen phosphate, place them in 1000 mL of water, and adjust the pH to 5.50 with phosphoric acid; B: methanol; A:B (50:50).

[0108] The test results are shown in Table 7. The high-performance liquid chromatograms of the patch on day 0, after 30 days of light exposure, and after 30 days of high temperature are shown below. Figures 3-5 As shown.

[0109] Table 7

[0110] The results show that the patch is more sensitive to light but not to high temperature, indicating that the patch should be stored away from light.

[0111] The above description is merely a preferred embodiment of this application and is not intended to limit the scope of protection of this application. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application are included within the scope of protection of this application.

Claims

1. A method for preparing a dexmedetomidine transdermal patch, the method comprising the following steps: 1) Dissolve 4-10 parts by weight of dexmedetomidine and 2-12 parts by weight of povidone in ethanol to obtain a drug solution; 2) Mix 78-94 parts by weight of pressure-sensitive adhesive with the drug solution, wherein the total amount of dexmedetomidine, povidone and pressure-sensitive adhesive is 100 parts by weight; stir until homogeneous to obtain a colloidal solution; 3) After the colloidal solution is defoamed, it is coated onto a release film, dried to remove the solvent, and a polymer matrix layer is obtained; 4) Cover the polymer matrix layer with the backing layer and cut it to obtain the dexmedetomidine transdermal patch.

2. The preparation method according to claim 1, wherein, The mass ratio of povidone to dexmedetomidine is 0.5-1.2, preferably 0.6-1.2, and more preferably 0.6, 0.625, 0.67, 0.75, 0.83, 1.0 or 1.

2.

3. The preparation method according to claim 1, wherein, The dexmedetomidine transdermal patch contains 0.3-1.5 mg of dexmedetomidine per patch.

4. The preparation method according to claim 1, wherein, The transdermal permeation rate of dexmedetomidine in the aforementioned dexmedetomidine transdermal patch is 6-25 μg / cm. 2 / h.

5. The preparation method according to claim 1, wherein, The material of the backing layer includes at least one of polyester, polyethylene, polypropylene, polyvinyl acetate resin, copolymer of ethylene and vinyl acetate, polyvinyl chloride, and polyurethane.

6. The preparation method according to claim 1, wherein, The pressure-sensitive adhesive is selected from DURO-TAK 87-900A, 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 387-2852, 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 GMS At least one of 9073, GELVA GMS 788, GELVA GMS 3253, and GELVA GMS 3083, preferably at least one of DURO-TAK 387-2516 and DURO-TAK 87-2074.

7. The preparation method according to claim 1, wherein, In step 1), the penetration enhancer is dissolved together with the dexmedetomidine and the povidone in ethanol, wherein the penetration enhancer is selected from at least one of azone and oleic acid.

8. The preparation method according to claim 1, wherein, Based on the total mass of the polymer matrix layer, the dexmedetomidine transdermal patch comprises the following components by mass percentage: Dexmedetomidine 10%, Povidone K30 5%, DURO-TAK 387-2516 85%; Dexmedetomidine 10%, Povidone K30 5%, DURO-TAK 387-2074 85%; Dexmedetomidine 5%, Povidone K30 3%, DURO-TAK 387-2516 92%; Dexmedetomidine 4%, Povidone K30 2.5%, DURO-TAK 387-2516 93.5%; Dexmedetomidine 6%, Povidone K30 4%, DURO-TAK 387-2516 90%; Dexmedetomidine 6%, Povidone K30 5%, DURO-TAK 387-2516 89%; Dexmedetomidine 8%, Povidone K30 6%, DURO-TAK 387-2516 86%; Dexmedetomidine 8%, Povidone K30 8%, DURO-TAK 387-2516 84%; Dexmedetomidine 10%, Povidone K30 10%, DURO-TAK 387-2516 80%; or Dexmedetomidine 10%, Povidone K30 12%, DURO-TAK 387-2516 78%.

9. The preparation method according to claim 1, wherein, The total mass ratio of the povidone and dexmedetomidine to the mass ratio of ethanol is 1:4-5.

10. Use of the dexmedetomidine transdermal patch prepared by any one of claims 1 to 9 in the preparation of a medicament for treating intractable insomnia.

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