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CN-122010915-A - Puerarin acid ester derivative with sleep promoting function and preparation method and application thereof

CN122010915ACN 122010915 ACN122010915 ACN 122010915ACN-122010915-A

Abstract

The invention discloses a puerarin acid ester derivative with a sleep promoting function, and a preparation method and application thereof. The puerarin acid ester derivative has the following molecular structural formula, combines L-tryptophan with puerarin through chemical modification, so that the original hydrophilic groups are esterified and blocked, the fat solubility is greatly improved, the bioavailability is improved, the content regulation and control of three neurotransmitters of 5-hydroxytryptamine, dopamine and norepinephrine are synergistically enhanced, and compared with the limitation of a single natural component in the aspect of sleep promotion function, the puerarin acid ester derivative has obviously enhanced efficacy and typical application advantages; 。

Inventors

  • YANG RONGJING
  • ZHU YAO
  • XING YONGFENG
  • ZHU HAILIANG

Assignees

  • 南京康可健生物科技有限公司

Dates

Publication Date
20260512
Application Date
20260202

Claims (10)

  1. 1. A puerarin acid ester derivative with a sleep promoting function is characterized by having the following molecular structural formula: 。
  2. 2. The method for producing puerarin acid ester derivative with sleep-promoting function according to claim 1, characterized by comprising the step of esterifying L-tryptophan with puerarin; After the reaction is finished, separating and purifying the product by alumina column chromatography, wherein the eluent is methylene dichloride-methanol mixed solution with the volume ratio of (10-100) being 1.
  3. 3. The method for preparing puerarin acid ester derivative with sleep promoting function according to claim 2, wherein the relative amount of raw materials is (1.2-1.8): 1.
  4. 4. The method for preparing puerarin acid ester derivative with sleep promoting function according to claim 2 or 3, wherein the reaction step comprises 1) reacting L-tryptophan in the presence of an acyl chloride reagent to obtain an acyl chloride intermediate, and 2) mixing the acyl chloride intermediate with puerarin, and continuing the reaction in the presence of an acid binding agent to obtain the target product.
  5. 5. The method for preparing puerarin acid ester derivative with sleep promoting function according to claim 4, wherein the acyl chloride reagent is one or more of thionyl chloride, oxalyl chloride and phosphoryl chloride, and the dosage of the acyl chloride reagent is preferably 1-2 times of the molar amount of L-tryptophan.
  6. 6. The method for preparing puerarin acid ester derivative with sleep promoting function according to claim 4, wherein the acid binding agent is one or more selected from pyridine, triethylamine and 4-dimethylaminopyridine, and the dosage of the acid binding agent is preferably 0.75-1.5 times of the molar amount of puerarin.
  7. 7. The method for preparing puerarin acid ester derivative with sleep promoting function according to claim 4, wherein the steps 1) and 2) are carried out under the conditions of inert atmosphere protection and anhydrous solvent, wherein the solvent is selected from any one of N, N-dimethylformamide and N, N-dimethylacetamide.
  8. 8. The method for preparing puerarin acid ester derivative with sleep promoting function according to claim 4, wherein the reaction conditions in step 1) are stirring at room temperature for 0.5-2h; Preferably, the reaction conditions in step 2) are stirring at room temperature for 8-24h.
  9. 9. The method for preparing puerarin acid ester derivative with sleep promoting function according to claim 2 or 3, characterized in that after the reaction, the solvent is distilled off, the residue is dissolved in dichloromethane, and the product is separated and purified by alumina column chromatography; Preferably, the eluent is methylene dichloride-methanol mixed solution with the volume ratio of (20-50): 1.
  10. 10. The puerarin acid ester derivative with sleep promoting function according to claim 1 or the puerarin acid ester derivative with sleep promoting function prepared by the method according to any one of claims 2-9, which is used for preparing a fat-soluble improved bioactive preparation, wherein the bioactive preparation comprises a sleep-promoting pharmaceutical preparation, a sleep-improving health-care food or a sleep-promoting cosmetic.

Description

Puerarin acid ester derivative with sleep promoting function and preparation method and application thereof Technical Field The invention relates to a puerarin derivative, in particular to a puerarin acid ester derivative with a sleep promoting function, and a preparation method and application thereof, and belongs to the field of medicines. Background Sleep is an indispensable physiological process of the human body, and its quality is directly related to neuroendocrine homeostasis, regulation of immune function, and maintenance of cognitive ability. Modern physiological studies have shown that the heart of regulation of the sleep-wake cycle is the dynamic balance of the central neurotransmitter, wherein 5-hydroxytryptamine (5-HT) is used as a key sleep inducing factor, the insufficient content or abnormal metabolism of which is one of the core mechanisms for insomnia, and excessive release of the wakefulness transmitters such as Dopamine (DA), norepinephrine (NE) and the like breaks the sleep balance and causes symptoms such as difficulty in falling asleep, shallow sleep, easy awakening and the like. With the aggravation of social stress, disturbance of work and rest and aging of population, the incidence rate of insomnia continuously rises, and the limitation of the traditional treatment scheme is increasingly prominent, so that development of novel sleep-promoting preparations with definite targeting and high safety is urgently needed. The current sleep-promoting drugs commonly used in clinic mainly comprise chemical synthesis, and can rapidly act by directly inhibiting central excitation or regulating transmitter receptors, but obvious short plates exist in long-term application, namely, benzodiazepine drugs are easy to cause addiction and dependency, non-benzodiazepine drugs can cause adverse reactions such as daytime sleepiness, cognitive function decline and the like, and long-term treatment requirements of chronic insomnia patients are difficult to meet. Under the background, the sleeping promoting component derived from natural products becomes a research and development hot spot in the field of medicine because of the advantages of mild effect, small side effect, conditioning effect and the like, and particularly the active component of the medicine and food homologous traditional Chinese medicine, and more accords with the modern health concept by virtue of the safety of medicine and food. The development and application of the active ingredients of the pueraria as classical medicine and food homologous plants are widely focused. The flavonoid component, puerarin, with the highest content in the kudzuvine root has definite effects of tranquilizing and allaying excitement, can improve cerebral microcirculation, dilate cerebral vessels, promote cerebral tissue oxygen supply and blood supply, indirectly relieve the nerve central hyperexcitation caused by cerebral ischemia, and can regulate the metabolism of central neurotransmitters, assist in improving the 5-HT content and inhibit excessive release of DA and NE. In addition, puerarin has additional pharmacological activities such as heart protection, antioxidation and the like, so that the puerarin can improve sleep and simultaneously has cardiovascular health, and is more suitable for middle-aged and elderly people or insomnia patients with cardiovascular basic diseases. However, puerarin has the problems of poor fat solubility, low bioavailability, limited sedative effect intensity and the like when being singly used, and limits the application effect in clinic. Disclosure of Invention In order to solve the technical problems, the invention provides a puerarin acid ester derivative with a sleep promoting function, and a preparation method and application thereof. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: as a first aspect of the present invention, there is provided a puerarin acid ester derivative having sleep-promoting function, having the following molecular structural formula: 。 When puerarin is used as a sleep-promoting medicament alone, the problems of poor fat solubility, low bioavailability, limited sedative effect intensity and the like exist, L-tryptophan is a direct precursor substance synthesized by 5-HT, but the absorption of the L-tryptophan in organisms is easily inhibited by competition of other neutral amino acids (such as leucine and isoleucine), so that the effective dosage actually entering the central nervous system is limited, the sleep-promoting effect is limited when the puerarin is used alone, and the ideal therapeutic effect is difficult to achieve alone. The puerarin acid ester derivative provided by the invention can combine the precursor supply advantage of L-tryptophan with the activity regulation advantage of puerarin through molecular structure design, so that a novel compound with high bioavailability and strong sleep-promoting effect is constructed, and th