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CN-121987597-A - Dexmedetomidine transdermal patch as well as preparation method and application thereof

CN121987597ACN 121987597 ACN121987597 ACN 121987597ACN-121987597-A

Abstract

The application provides a dexmedetomidine transdermal patch which comprises a backing layer, a release film and a high polymer matrix layer arranged between the backing layer and the release film, wherein the high polymer matrix layer comprises, by the total mass of the high polymer matrix layer, 4-10% of dexmedetomidine, 2-12% of povidone and 78-94% of pressure-sensitive adhesive, and the pressure-sensitive adhesive comprises at least one of carboxyl-or hydroxyl-functionalized polymers.

Inventors

  • LU DI
  • ZHANG ZHIBING
  • WANG YONG
  • Feng Deyue
  • WANG HUI

Assignees

  • 北京泰德制药股份有限公司

Dates

Publication Date
20260508
Application Date
20211111

Claims (10)

  1. 1. A method of preparing a dexmedetomidine transdermal patch, the method comprising the steps of: 1) Dissolving 4-10 parts by mass of dexmedetomidine and 2-12 parts by mass of povidone in ethanol to obtain a medicinal solution; 2) Mixing 78-94 parts by mass of pressure-sensitive adhesive with the drug solution, wherein the total amount of dexmedetomidine, povidone and the pressure-sensitive adhesive is 100 parts by mass; 3) After defoaming, coating the colloidal solution on a release film, and drying to remove a solvent to obtain a high polymer matrix layer; 4) And covering the backing layer on the high polymer matrix layer, and cutting to obtain the dexmedetomidine transdermal patch.
  2. 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, further preferably 0.6, 0.625, 0.67, 0.75, 0.83, 1.0 or 1.2.
  3. 3. The preparation method of claim 1, wherein the drug loading of the dexmedetomidine in the dexmedetomidine transdermal patch is 0.3-1.5 mg/patch.
  4. 4. The preparation method of claim 1, wherein the transdermal rate of dexmedetomidine in the dexmedetomidine transdermal patch is 6-25 μg/cm 2 /h.
  5. 5. The method of manufacturing according to claim 1, wherein the material of the backing layer comprises at least one of polyester, polyethylene, polypropylene, polyvinyl acetate, a copolymer of ethylene and vinyl acetate, polyvinyl chloride, and polyurethane.
  6. 6. The preparation method according to claim 1, wherein the pressure-sensitive adhesive is selected from at least one of 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 9073、GELVA GMS 788、GELVA GMS 3253、GELVA GMS 3083, preferably from at least one of DURO-TAK 387-2516, DURO-TAK 87-2074.
  7. 7. The preparation method according to claim 1, wherein in step 1), a penetration enhancer selected from at least one of azone and oleic acid is dissolved together with the dexmedetomidine and the povidone in ethanol.
  8. 8. The preparation method of claim 1, wherein the dexmedetomidine transdermal patch comprises the following components in mass percent based on the total mass of the polymeric matrix layer: Dexmedetomidine 10%, povidone K30% 5%, DURO-TAK 387-2516 85%; dexmedetomidine 10%, povidone K30% 5%, DURO-TAK 387-2074 85%; dexmedetomidine 5%, povidone K30%, DURO-TAK 387-2516 92%; Dexmedetomidine 4%, povidone K30.5%, 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%, DURO-TAK 387-2516 84%; 10% dexmedetomidine, 30% povidone K30%, DURO-TAK 387-2516 80%, or 10% Of dexmedetomidine, 30% of povidone K, DURO-TAK 387-2516 78%.
  9. 9. The preparation method according to claim 1, wherein the mass ratio of the total mass of povidone to dexmedetomidine to ethanol is 1:4-5.
  10. 10. Use of dexmedetomidine transdermal patch prepared by the method of any one of claims 1 to 9 in the manufacture of a medicament for the treatment of refractory insomnia.

Description

Dexmedetomidine transdermal patch as well as preparation method and application thereof The application relates to a dexmedetomidine transdermal patch, which is a divisional application of Chinese patent application with the application number of 202111331613.X, the application date of 2021, 11 months and 11 days, and the name of the dexmedetomidine transdermal patch, and a preparation method and application thereof. Technical Field The application relates to the technical field of medicinal preparations, in particular to a dexmedetomidine transdermal patch, and a preparation method and application thereof. Background Intractable insomnia is a common severe sleep disorder, has high treatment difficulty, particularly has high incidence rate in the old, and has serious harm to physical and mental health of the old, particularly serious damage to cognitive functions. At present, common medicines for treating refractory insomnia comprise benzodiazepines and non-benzodiazepines, which all have influence on the cognitive function of patients. The sleep quality of patients after drug treatment is improved, but the cognitive decline caused by insomnia is not improved, and drug treatment has not been popularized due to the effects of respiratory depression, drug resistance and reduction in sleep depth. Dexmedetomidine is a highly potent, highly selective alpha 2 receptor agonist with a variety of pharmacological properties including sedation, analgesia, anxiolytic, hypnotic, etc., and induces sleep that is highly similar to the natural sleep of healthy people. The existing dexmedetomidine is used for treating refractory insomnia usually in the form of micropump injection, however, the micropump injection usually needs hospitalization, and meanwhile, the defects of poor patient compliance and the like exist, so that the effective treatment of patients is not facilitated. Disclosure of Invention In order to facilitate the treatment of patients with refractory insomnia, the application provides a dexmedetomidine transdermal patch, and a preparation method and application thereof. The application provides a dexmedetomidine transdermal patch, which comprises a backing layer, a release film and a high polymer matrix layer arranged between the backing layer and the release film, wherein the high polymer matrix layer comprises, by the total mass of the high polymer matrix layer, 4-10% of dexmedetomidine, 2-12% of povidone and 78-94% of pressure-sensitive adhesive, and the pressure-sensitive adhesive comprises at least one of carboxyl-or hydroxyl-functionalized polymers. The second aspect of the present application provides a method for preparing the dexmedetomidine transdermal patch of the first aspect of the present application, which includes the steps of: 1) Dissolving 4-10 parts by mass of dexmedetomidine and 2-12 parts by mass of povidone in ethanol to obtain a medicinal solution; 2) Mixing 78-94 parts by mass of pressure-sensitive adhesive with the drug solution, wherein the total amount of dexmedetomidine, povidone and the pressure-sensitive adhesive is 100 parts by mass; 3) After defoaming, coating the colloidal solution on a release film, and drying to remove a solvent to obtain a high polymer matrix layer; 4) And covering the backing layer on the high polymer matrix layer, and cutting to obtain the dexmedetomidine transdermal patch. In a third aspect, the application provides the use of a transdermal dexmedetomidine patch of the first aspect of the application in the manufacture of a medicament for the treatment of refractory insomnia. The transdermal patch provided by the application is taken as a percutaneous absorption preparation, can be applied and administrated through skin, and the active ingredients are absorbed through skin to enter the systemic blood circulation, so that the acting time can be prolonged, the administration is convenient, the patient compliance is good, and the effective treatment of refractory insomnia is facilitated. Drawings In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described, and it is apparent that the drawings in the description below are only one embodiment of the present application, and other embodiments may be obtained according to these drawings by those skilled in the art. Fig. 1 is a patch scanning electron micrograph of example 5. Figure 2 is an average dosing curve for subjects. Fig. 3 is a high performance liquid chromatogram of the patch composition of example 4. FIG. 4 is a high performance liquid chromatogram of the patch composition of example 4 after 30 days of illumination. FIG. 5 is a high performance liquid chromatogram of the patch composition of example 4 after 30 days of high temperature storage. Detailed Description In order to make the objects, technical solutions and advantages of the presen