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CN-121971468-A - Application of spinosin in preparation of drugs for promoting non-rapid eye movement and sleep

CN121971468ACN 121971468 ACN121971468 ACN 121971468ACN-121971468-A

Abstract

The invention is suitable for the technical field of medicines, provides application of spinosin in preparation of a medicine for promoting non-rapid eye movement sleep, shortens the sleep latency of mice, increases the NREM sleep time and reduces wakefulness, and is different from benzodiazepine medicines, does not change EEG power spectral density and does not influence movement performance in a stick rotating test, so that the spinosin is suitable for insomnia treatment. The invention solves the problems of adverse reaction and sleep quality reduction of the existing hypnotic, and is suitable for treating insomnia, especially insomnia accompanied with anxiety and nerve disorder.

Inventors

  • Zhao Minrui
  • WANG JUAN

Assignees

  • 深圳平乐骨伤科医院(深圳市坪山区中医院、深圳市骨伤科医院)

Dates

Publication Date
20260505
Application Date
20260312

Claims (10)

  1. 1. Use of spinosin in the manufacture of a medicament for treating insomnia or promoting non-rapid eye movement sleep.
  2. 2. The use according to claim 1, wherein the medicament acts to promote non-rapid eye movement sleep by agonizing the adenosine receptor and/or acting at the benzodiazepine site of the GABA A receptor.
  3. 3. The use according to claim 2, wherein the medicament exerts an effect of promoting non-rapid eye movement sleep, primarily by agonizing the adenosine receptor, and the effect is completely blocked by the adenosine receptor antagonist.
  4. 4. The use according to claim 2, wherein the drug moiety exerts a non-rapid eye movement sleep promoting effect by acting on the GABA A receptor benzodiazepine site and the effect is blocked by the GABA A receptor benzodiazepine site antagonist moiety.
  5. 5. The use of claim 1, wherein the medicament does not decrease the electroencephalogram delta wave power spectral density during non-rapid eye movement sleep while increasing the non-rapid eye movement sleep duration.
  6. 6. The use according to claim 1, wherein said medicament does not produce muscle relaxant action or cause motor coordination disorders at an effective hypnotic dose.
  7. 7. The use of claim 1, wherein the medicament is capable of activating ventral lateral pre-optic zone neurons and inhibiting tuberose papillary nucleus neurons.
  8. 8. The use according to any one of claims 1 to 7, wherein the medicament is for the preparation of an oral, injectable or nasal formulation.
  9. 9. The use according to claim 8, wherein the oral formulation is a tablet, capsule, granule or oral liquid; the injection preparation is water injection or freeze-dried powder injection.
  10. 10. A pharmaceutical composition for treating insomnia comprising a therapeutically effective amount of spinosin and a pharmaceutically acceptable carrier or excipient, the pharmaceutical composition being for increasing the duration of non-rapid eye movement sleep without decreasing sleep quality.

Description

Application of spinosin in preparation of drugs for promoting non-rapid eye movement and sleep Technical Field The invention relates to the technical field of medicines, in particular to application of spinosin in preparation of a medicine for promoting non-rapid eye movement and sleep. Background Insomnia is a clinically common sleep disorder, and is mainly manifested by difficulty in falling asleep, sleep maintenance disorder and poor sleep quality. Benzodiazepines (e.g., diazepam, chlorazepine) and analogs thereof (e.g., zolpidem, zopiclone) have been widely used for the treatment of insomnia since the 60 s of the 20 th century. However, such drugs present significant adverse effects including drug dependence, tolerance, rebound insomnia, amnesia, and muscle relaxation, where muscle relaxation tends to increase the risk of falls, especially for the elderly, with fatal risks. More importantly, a large number of documents report that benzodiazepine drugs reduce delta wave activity in non-rapid eye movement (NREM) sleep, and delta wave activity is a key indicator reflecting sleep quality, which means that the drugs can induce sleep, but often sacrifice sleep quality. Semen Ziziphi Spinosae (Semen Zizhiphi Spinozae) is used as tranquilization medicinal material commonly used in Asian traditional medicine, and one of its main active ingredients is spinosin (Spinosin, chemical name: 2' -beta-O-D-glucopyranosyl swertisin). While prior studies have demonstrated that the extract of Zizyphi Spinosae semen has sedative effects and that spinosin enhances the hypnotic effect of barbiturates or counteracts caffeine-induced hyperactivity, there are also studies suggesting that it may act through the 5-HT1A receptor. However, there is no direct evidence to suggest whether spinosin alone has an exact hypnotic effect, particularly its specific effect on sleep-wake states (e.g., differential effects on NREM and REM sleep), on the electroencephalogram (EEG) power spectrum, and its exact molecular mechanism of sleep-promoting effect (whether it involves adenosine receptors or GABA receptors) are all ambiguous. Therefore, in view of the above situation, there is an urgent need to provide the application of spinosin in the preparation of drugs for promoting non-rapid eye movement sleep, so as to overcome the defects in the current practical application. Disclosure of Invention The invention aims to provide application of spinosin in preparation of a medicament for promoting non-rapid eye movement and sleep, and effectively solves the problems in the background technology. The invention is realized in this way, the use of spinosin in the manufacture of a medicament for treating insomnia or promoting non-rapid eye movement sleep. As a further aspect of the invention, the medicament acts to promote non-rapid eye movement sleep by agonizing the adenosine receptor and/or acting at the benzodiazepine site of the GABA A receptor. As a further aspect of the invention, the agent exerts a non-rapid eye movement sleep promoting effect primarily by agonizing the adenosine receptor and this effect may be completely blocked by the adenosine receptor antagonist. As a further aspect of the invention, the drug moiety exerts a non-rapid eye movement sleep promoting effect by acting on the GABA A receptor benzodiazepine site and this effect is partially blocked by the GABA A receptor benzodiazepine site antagonist. As a further proposal of the invention, the medicine does not reduce the electroencephalogram delta wave power spectral density during the non-rapid eye movement sleep period while increasing the non-rapid eye movement sleep period. As a further aspect of the invention, the medicament does not produce muscle relaxant effects or cause motor coordination disorders at an effective hypnotic dose. As a further aspect of the invention, the agent is capable of activating ventral lateral optic anterior zone neurons and inhibiting tuberose papillary nucleus neurons. As a further aspect of the present invention, the medicament is used for preparing an oral preparation, an injection preparation or a nasal preparation. The invention further provides a further scheme that the oral preparation is a tablet, a capsule, a granule or an oral liquid; the injection preparation is water injection or freeze-dried powder injection. The invention also provides a pharmaceutical composition for treating insomnia, which comprises a therapeutically effective amount of spinosin and a pharmaceutically acceptable carrier or auxiliary material, and is used for increasing the non-rapid eye movement sleep time without reducing the sleep quality. Compared with the prior art, the invention has the beneficial effects that: the spinosin does not reduce the delta wave activity in the NREM sleep while increasing the NREM sleep time, which means that the spinosin induces high-quality sleep close to a physiological state, and overcomes the defect that benzodiazepine drugs red