阅读说明：本技术 一种脱水酸枣仁皂苷及其制备方法和应用 (Dehydrated spina date seed saponin and preparation method and application thereof ) 是由 肖伟 商晶 陈夏霖 陈超 常秀娟 吴云 王永香 杨彪 于 2019-02-20 设计创作，主要内容包括：本发明提出了一种脱水酸枣仁皂苷(JuA-H<Sub>2</Sub>O)以及脱水酸枣仁皂苷或酸枣仁皂苷脱水混合物,通过实验表明,酸枣仁皂苷一定程度下的脱水产物活性强,具有更好地镇静催眠的活性。(The invention provides dehydrated jujuboside (JuA-H) 2 O) and dehydrated jujuboside or dehydrated mixtures of jujuboside, experiments show that the dehydrated products of jujuboside have strong activity to a certain extent, and have better sedative and hypnotic activities.)

1. A dehydrated semen Ziziphi Spinosae saponin is shown in structure (1)

Or a compound formed by removing 1-4 glycosyl groups from the structure (1).

2. The dehydrated jujuboside according to claim 1, wherein the dehydrated jujuboside is prepared from jujuboside.

3. A method for preparing a dehydrated mixture of jujuboside, which is characterized by comprising the following steps:

dissolving the jujuboside in a solvent, adding 0.2-50% of acid by volume, and reacting for 0-150 h under the heating condition of 0-120 ℃.

4. The method of claim 3, wherein the solvent is selected from methanol, ethanol, acetone, ethyl acetate, DMSO, acetonitrile, DMF, THF, water, toluene, DME, or any mixture thereof.

5. The production method according to claim 3, wherein the acid is a protonic acid or a Lewis acid.

6. The method according to claim 5, wherein when the acid is selected from acetic acid, the proportion of the acetic acid is 2 to 9%;

the heating reaction temperature is 50-100 ℃, and the reaction time is 5-120 h.

7. The preparation method of claim 3, wherein 8mg of jujuboside A is dissolved in 1mL of ethanol solution, a certain amount of acetic acid is added to make the concentration of acetic acid to be 5% -9%, a stirrer is added, the rotation speed is controlled to be 700rpm/min, heating is carried out at 80 ℃, and the reaction is carried out in a sealed manner for 10 hours, so as to obtain the jujuboside A.

8. A dehydrated spina date seed saponin mixture prepared by the preparation method according to any one of claims 3-7.

9. Use of dehydrated jujuboside according to claims 1-2 or dehydrated mixtures of jujuboside according to claim 8 for the preparation of sedative-hypnotic drugs.

10. A sedative hypnotic drug, which is prepared by the dehydrated spina date seed saponin of claims 1-2 or the dehydrated spina date seed saponin mixture of claim 8 and a pharmaceutically acceptable carrier.

Technical Field

The invention relates to the field of Chinese herbal medicine application, and particularly relates to dehydrated spina date seed saponin and a preparation method and application thereof.

Background

The spina date seed is dry mature seed of Ziziphus jujuba Mill.var. spinosa (Bunge) HuexH.F.Chou in Rhamnaceae, has sweet and sour taste and neutral nature, enters liver, gallbladder and heart channels, has the effects of nourishing heart and liver, calming heart and tranquilizing mind, arresting sweating and promoting the production of body fluid, and is mainly used for treating symptoms such as dysphoria, palpitation and dreaminess, body deficiency and hyperhidrosis, body fluid deficiency and thirst and the like. The present study shows that the spina date seed contains various chemical components such as saponins, flavonoids, alkaloids, triterpenes, fatty acids and the like, and has the pharmacological effects of sedation and hypnosis, antianxiety, antidepressant, antiarrhythmic, anti-inflammatory and the like, wherein the spina date seed saponin A (JuA) is the main saponin component, and the structure is shown in figure 1.

Disclosure of Invention

The invention aims to provide dehydrated jujuboside, a dehydrated mixture of jujuboside, a preparation method and application thereof.

The invention is realized by the following scheme:

a dehydrated semen Ziziphi Spinosae saponin (JuA-H)₂O) having the structure:

specifically, JuA-H according to the difference in the position of the double bond₂O comprises three differently oriented dehydration products, JuA-H₂O may be selected from any one of the oriented dehydration products or a combination of any two or three of the dehydration products thereof.

Further, the dehydrated jujuboside is prepared from jujuboside.

Specifically, the jujuboside is a monomer compound or a mixture obtained by separating and identifying traditional Chinese medicine jujuboside, such as jujuboside A, jujuboside A1 and the like, or a mixture of the compounds and a jujuboside extract containing the compounds.

Preferably, the dehydrated jujuboside is prepared by dehydrating jujuboside A with 2-9% of protonic acid or Lewis acid and then separating.

Further, the protic acid is acetic acid.

The invention also provides a preparation method of the spina date seed saponin dehydration mixture, which is characterized by comprising the following steps:

dissolving the jujuboside in a solvent, adding 0.2-50% of acid by volume, and reacting for 0-150 h under the heating condition of 0-150 ℃.

Specifically, the solvent is selected from methanol, ethanol, acetone, ethyl acetate, DMSO, acetonitrile, DMF, THF, water, toluene, DME, or any mixture thereof.

Further, the acid is a protic acid or a lewis acid.

Specifically, the protonic acid is acetic acid, citric acid, ascorbic acid, sorbic acid, hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, oxalic acid, tartaric acid, malic acid, butyric acid, trifluoroacetic acid or p-toluenesulfonic acid, and the lewis acid is anhydrous zinc chloride, anhydrous aluminum trichloride, ferric trichloride, titanium tetrachloride or stannic chloride.

Preferably, when the acid is selected from acetic acid, the proportion of acetic acid is 2% to 9%;

further, the heating reaction temperature is 50-100 ℃, and the reaction time is 5-120 h.

In one preferable embodiment of the invention, 8mg of jujuboside A is dissolved in 1mL of ethanol solution, a certain amount of acetic acid is added to ensure that the concentration is 5% -9%, a stirrer is added, the rotating speed is controlled to be 700rpm/min, heating is carried out at 80 ℃, and the mixture is sealed and reacted for 10 hours, thus obtaining the jujuboside A.

The invention also provides a spina date seed saponin dehydration mixture prepared by any one of the preparation methods.

The invention also provides the application of the dehydrated spina date seed saponin or the dehydrated mixture of the spina date seed saponin in preparing sedative-hypnotic drugs.

The invention also provides a sedative hypnotic medicine which is prepared by the dehydrated spina date seed saponin or the dehydrated mixture of the spina date seed saponin and a pharmaceutically acceptable carrier.

Further, the sedative hypnotic drug also comprises sodium pentobarbital. Optionally, the weight ratio of the dehydrated jujuboside or the dehydrated mixture of jujuboside and sodium pentobarbital is 20: 25-40.

Specifically, the dosage form of the sedative-hypnotic drug is an oral administration dosage form, an injection administration dosage form or an external administration preparation.

Furthermore, the medicine can be any one of the dosage forms in pharmaceutics, including tablets, capsules, soft capsules, gels, oral preparations, suspensions, electuary, patches, ointments, pills, powders, injections, infusion solutions, freeze-dried injections, intravenous emulsions, liposome injections, suppositories, sustained-release preparations or controlled-release preparations.

In the earlier research, the JuA content is obviously reduced when the spina date seed and the vinegar schisandra are decocted, the further research shows that the JuA content is reduced because organic acid components in the vinegar schisandra are dissolved in water, so that hydroxyl on JuA aglycone is subjected to dehydration reaction firstly, and then glycosyl is continuously lost to generate a series of dehydration products, the reaction process is shown in figure 2, and experiments in the scheme show that the dehydration products of the spina date seed saponin under a certain degree have strong activity and better pharmacodynamic activity, and the spina date seed saponin can be used as the material basis of the spina date seed.

Drawings

FIG. 1 is the structural formula of the jujuboside A of the present invention;

FIG. 2 shows the reaction process of the reaction product of juA with the formation of dehydrate under acidic condition;

FIG. 3 is a liquid mass spectrum of JuA in the present invention after reaction with 15% acetic acid: a: TIC chart B JuA-H₂EIC diagram of O, C: JuA-H₂EIC diagram of O-Xyl, D: JuA-H₂EIC map of O-Rha;

FIG. 4 shows JuA-H of the present invention₂MS/MS plot of O;

FIG. 5 shows JuA-H of the present invention₂MS/MS plot of O-Xyl;

FIG. 6 shows compound JuA-H of the present invention₂MS/MS plot of O-Rha.

FIG. 7 is a liquid mass spectrum of JuA in the present invention after reaction with 12% acetic acid: a: a TIC graph; JuA-H₂An EIC map of O; JuA-H₂EIC diagram of O-Xyl; JuA-H₂EIC map of O-Rha;

FIG. 8 is a liquid mass spectrum of JuA in the present invention after reaction with 9% acetic acid: a: a TIC graph; JuA-H₂An EIC map of O; JuA-H₂EIC diagram of O-Xyl; JuA-H₂EIC map of O-Rha;

FIG. 9 is a liquid mass spectrum of JuA in the present invention after reaction with 5% acetic acid: a: a TIC graph; JuA-H₂An EIC map of O; JuA-H₂EIC diagram of O-Xyl; JuA-H₂EIC map of O-Rha;

FIG. 10 is a liquid mass spectrum of JuA in the present invention after reaction with 2% acetic acid: a: a total ion flow pattern; b: JuA-H₂BPC plot of O.

Detailed Description

The following detailed description of the present invention, taken in conjunction with the accompanying drawings and examples, is provided to enable the invention and its various aspects and advantages to be better understood. However, the specific embodiments and examples described below are for illustrative purposes only and are not limiting of the invention.

It is specifically noted that similar alternatives and modifications will be apparent to those skilled in the art, which are also intended to be included within the present invention. It will be apparent to those skilled in the art that the techniques of the present invention may be implemented and applied by modifying or appropriately combining the methods and applications described herein without departing from the spirit, scope, and content of the present invention.

Secondly, it is to be noted that the concentrations referred to in the present invention are in volume percent (v/v). All percentages, ratios, proportions, or parts are by weight unless otherwise specified. In addition, if the specific conditions are not indicated, the invention is carried out according to the conventional conditions or the conditions suggested by the manufacturer, and the used raw material drugs or auxiliary materials and the used reagents or instruments are the conventional products which can be obtained commercially.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention.

The invention is further illustrated by the following examples: