CN104840527A - Composition containing tenuifoliside and ginsenoside - Google Patents

Abstract

The invention provides a composition containing tenuifoliside and ginsenoside. The composition is formed by tenuifoliside and ginsenoside in a weight ratio in a range of 0.5:0.5 to 0.11:0.89. Single effective tenuifoliside and ginsenoside are extracted from tenuifoliside and ginsenoside medicine materials, and both reach more than 50%. The composition can be applied to preparation of medicine for treating and improving depression. Two effective parts are combined, and accordingly, the mouse yohimbine toxicity is enhanced apparently, and the mouse forced swimming unmovable time is shortened apparently. By combining the two effective parts, the effect is enhanced compared with the effect of single use of any one part. By means of the composition, medicine definitive in curative effect and slight in adverse reaction is provided for treating and improving depression.

Description

A composition containing polygala sugar ester and ginsenoside and its application

technical field

The invention belongs to natural medicine composition, and in particular relates to the composition of polygala sugar ester and ginsenoside and its application in preparing medicine for treating and improving depression.

Background technique

Depression, also known as depressive disorder, is the main type of mood disorder with significant and persistent low mood as the main clinical feature. According to the statistics of the World Health Organization, the incidence of depression in the world is about 53.1%, while in developed countries it is close to 60%. 100 million. Among the adult population over the age of 18, the number of patients with depression is increasing at a rate of 41.3% per year. The situation of depression in our country is not optimistic. At present, the incidence of depression in our country is about 24%. According to epidemiological survey data in some areas, the prevalence of depression is about 29-35%, which is similar to that of developed countries. . The World Health Organization predicts that by 2020, depression will become the second most prevalent disease after cardiovascular disease. Depression is one of the important risk factors for suicide, and 90% of suicides are related to depression. At the same time, depression is often accompanied by cardiovascular and cerebrovascular diseases, diabetes, Alzheimer's disease and tumors.

Antidepressant chemical drugs have a series of problems, such as slow onset, easy relapse, and many adverse reactions. At present, people have turned more research and development of antidepressant drugs to the field of traditional medicine. Polygala is the dried root of Polygala tenuifolia Willd. or Polygala sibirica L., a plant of the Polygalaceae family. It has the effects of calming the nerves and improving the mind, communicating with the heart and kidney, eliminating phlegm and reducing swelling. It is clinically used to treat insomnia caused by heart-kidney disharmony. Dreams, forgetfulness, palpitations, trance, coughing up phlegm, swelling of sores and sores, breast swelling and pain. The study of chemical composition shows that the chemical composition of polygala mainly includes saponins, sugar esters, ketones, alkaloids and fatty oils. Modern pharmacological research shows that Polygala saponin has the effect of eliminating phlegm and relieving cough, and it is also the main toxic component of Polygala (with obvious gastric irritation and hemolysis); Polygala ketone has antifungal and analgesic effects; Polygala sugar ester is considered to be the The physical basis of antidepressants. Ginseng is the dried root and rhizome of Panax ginseng C. A. Mey. It has the functions of invigorating vital energy, recovering the veins and strengthening the spleen, nourishing the spleen and lungs, promoting body fluid and nourishing blood, calming the nerves and improving intelligence. It is clinically used for physical weakness, cold extremities, weak pulse, lack of food due to spleen deficiency, cough due to lung deficiency, thirsty body fluid wound, Internal heat and thirst, qi and blood deficiency, chronic illness and weakness, palpitations and insomnia, impotence and uterine cold. Chemical composition research shows that ginseng contains saponins, sugars, volatile components, organic acids and their esters, proteins, enzymes, sterols and their glycosides, polypeptides, nitrogenous compounds, lignin, flavonoids, vitamins, inorganic elements etc. Among them, the main active ingredients are ginsenosides and ginseng polysaccharides. Modern pharmacological studies have shown that the effect of ginseng on diseases of the central nervous system is related to ginsenosides. Polygala and ginseng are often used in combination in the treatment of depression in clinical practice. Representative prescriptions such as Kaixin San and Dingzhi Xiaowan have shown good antidepressant effects in animal experiments and clinical studies.

Contents of the invention

One object of the present invention is to provide polygala sugar ester and ginsenoside composition, the composition is composed of polygala polygala sugar ester: ginsenoside weight ratio is 0.5: 0.5 ~ 0.11: 0.89, polygala polygala sugar ester and ginsenoside are obtained from the traditional Chinese medicine polygala polygala and ginsenoside A single active active part is extracted from ginseng.

Another object of the present invention is to provide the application of the composition in the preparation of medicaments for treating depression.

Another object of the present invention is to provide the application of the composition in the preparation of medicaments for improving depression.

The formulations prepared from the composition and pharmaceutical excipients mainly include liquid formulations and solid formulations. Solid preparations mainly include granules, tablets, capsules (including soft capsules), and dropping pills. Liquid preparations mainly include oral liquid preparations and injection liquid preparations.

The administration form of the preparation mainly includes oral administration or parenteral administration.

The medicinal materials polygala and ginseng used in the composition of the invention are often clinically used in combination for the treatment of depression, and have a unique theoretical basis of traditional Chinese medicine that has been proven by long-term medication in my country. The composition can solve the problem of obvious lack of drugs with certain curative effect and mild adverse reactions in the treatment of such diseases. Animal pharmacodynamic experiments prove that the composition has the following effects: (1) Significantly enhance the toxicity of yohimbine in mice. (2) Significantly shorten the immobility time of mice in forced swimming. The combined use of the two effective parts has a more significant effect than any one of them alone, and it is not a simple superposition of effects. The research results of the toxicological action of the composition show that the results of the acute toxicity research in mice of the combined use of the two effective parts are similar to those of any one of them alone, and no death or obvious symptoms of poisoning appear. The present invention extracts single effective parts polygala sugar ester and ginsenoside from polygala and ginseng medicinal materials, each reaching more than 50%.

Detailed ways

The following examples are to further illustrate the present invention, rather than limit the present invention.

Embodiment 1 : the preparation method of polygala sugar ester and ginsenoside of the present invention

(1) The effective part of polygala sugar esters used in the present invention can be obtained by referring to the method disclosed in Patent No. 201410215399.5: the polygala medicinal material is used as raw material, and the ethanol solution reflux method is used to extract, specifically: 70% ethanol with 10 times the mass of polygala medicinal material The solution was used as the extraction solvent, refluxed for 3 times, 1.5 h each time, the extracts were combined, concentrated under reduced pressure until there was no alcohol smell (60 ℃), and the Polygala extract was obtained. The obtained Polygala extract was purified by D130 macroporous resin. The concentration of the sample solution is 0.25 g/ml containing crude drug, the sample loading speed is 2 Bv/h, and the sample volume is 4 Bv; in the elution process, it is first washed with 5 Bv water, and the water washing speed is 4 Bv/h , followed by elution with 5 Bv of 20% ethanol solution at a rate of 2 Bv/h, and then elution with 6 Bv of 35% ethanol solution at a rate of 2 Bv/h . The eluate of 35% ethanol solution was concentrated under reduced pressure until it had no alcohol smell (60 ℃), and the sugar ester enriched part was obtained. A liquid-liquid extraction method is used to purify the obtained sugar ester-enriched fraction. The sugar ester-rich part was dispersed with water to obtain a sample solution with a concentration of 6.81 mg/ml sugar ester, the extraction solvent was ethyl acetate, and the extraction times were 3 times, and the amount of each extraction solvent was 3 times the sample liquid volume. The ethyl acetate layers were combined and concentrated to dryness under reduced pressure (60°C) to obtain the effective fraction of polygala sugar esters (analyzed by HPLC, the sum of the contents of tenuifoliside A, tenuifoliside B, tenuifoliside C and 3',6-dierucanoyl sucrose is 64.84%).

(2) The active part of ginsenoside used in the present invention is prepared according to the following method: take 300 g of ginseng, cut into thick slices, add 8 times the amount of water, decoct twice, the first time for 2 hours, the second time for 1.5 hours, Boil and filter, combine the filtrates, pass through D101 macroporous adsorption resin (column volume: 300 mL), elute with water until colorless, then elute with 60% ethanol, collect the 60% ethanol eluate, load and wash The removal rate is 2 Bv/h), the filtrate is concentrated to a clear paste with a relative density of 1.06 (80°C), dried, and pulverized to obtain ginsenosides (by HPLC analysis, the content of ginsenosides is 73.48%).

Embodiment 2 : the maximum tolerated dose experiment of the composition of the present invention

(1) Materials and methods

Polygala sugar esters and ginsenosides were obtained by referring to the method in Example 1, and were prepared as a suspension with 0.5% sodium carboxymethylcellulose. Before use, the polygala sugar ester: ginsenoside weight ratios are respectively 0.5:0.5 and 0.11:0.89, and mixed to form a composition.

The maximum concentration and maximum administration volume of 0.4 mL/10 g/time were administered orally, administered twice a day with an interval of 6 hours, and the body weight and various symptoms of the mice were observed on the day of administration and within the following two weeks.

(2) Results:

On the day and the next day after intragastric administration of the mice, no death occurred in all the administration groups, and no apparent adverse symptoms were observed in the following two weeks. There was no apparent adverse condition in the next two weeks.

(3) Conclusion:

Mice were given 160 mg/kg of the composition and individual extracts of the two medicinal materials by intragastric administration, and no death or other obvious toxic reactions occurred.

Embodiment 3 : mouse yohimbine toxicity enhancement experiment

(1) Materials and methods:

Polygala sugar esters and ginsenosides were obtained by referring to the method in Example 1, according to the weight ratio of polygala sugar esters: ginsenosides 0.11:0.89.

Yohimbine hydrochloride: Aladdin Chemistry Co., Ltd. Batch number: 29107. Normal saline: Hangzhou Jiutian Animal Health Products Co., Ltd. Batch number: 2014071901.

Male ICR mice, clean grade, weighing 18-24 g, were given standard pelleted feed and pure drinking water during the feeding period. Set solvent control group, fluoxetine positive drug control group (20 and 40 mg/kg), polygala sugar ester group (2.5, 5 and 10 mg/kg), ginsenoside group (20, 40 and 80 mg/kg), Polygala sugar ester and ginsenoside composition group (11.25 and 22.5 mg/kg), administered by intraperitoneal injection. After administration of the test drug or vehicle, a sublethal dose of yohimbine (25 mg/kg) was subcutaneously injected 0.5 h later. The mortality rate of the mice in the test group and the control group was observed within 24 h.

(2) Results

The experimental results are shown in Table 1. Polygala sugar esters (10 and 20 mg/kg) alone, ginsenosides (80 and 120 mg/kg) alone, and polygala sugar esters and ginsenosides in combination (11.25 and 22.5 mg/kg) can both Significantly enhanced the toxicity of yohimbine in mice.

(3) Conclusion

Polygala sugar esters and ginsenoside composition groups (11.25 and 22.5 mg/kg) can significantly strengthen the lethal effect of yohimbine, which is more significant than that of any effective part alone.

Embodiment 4 : mouse forced swimming experiment

(1) Materials and methods:

Polygala sugar esters and ginsenosides are obtained by referring to the method in Example 1, according to the weight ratio of polygala sugar esters: ginsenosides 0.5:0.5.

Fluoxetine hydrochloride: Lilly Suzhou Pharmaceutical Co., Ltd. Normal saline: Hangzhou Jiutian Animal Health Products Co., Ltd. Batch number: 2014071901.

Male ICR mice, clean grade, weighing 18-24 g, started the experiment after one week of adaptation to the environment, and were given standard pelleted feed and pure drinking water during the feeding period. Set solvent control group, fluoxetine positive drug control group (50 mg/kg), polygala sugar ester group (25, 50 and 100 mg/kg), ginsenoside group (50 and 100 mg/kg), polygala sugar ester and The ginsenoside composition group (5, 100 and 200 mg/kg) was intragastrically administered for one week.

On the day of the experiment, after being placed in the experiment room for 1 hour to adapt, give the test drug or solvent for 1 hour, place it in the glass fiber reinforced plastic, and observe the immobility time of the mice forced to swim. The total observation time is 6 minutes, and the immobility time within 4 minutes after recording .

(2) Results:

The experimental results are shown in Table 2. Polygala sugar esters (100 mg/kg) alone, ginsenosides (100 mg/kg) alone, and polygala sugar esters and ginsenosides in combination (50+50 and 100+100 mg/kg) can both Significantly shorten the immobility time of forced swimming in ICR mice.

(3) Conclusion:

Polygala sugar esters and ginsenoside composition groups (50+50 and 100+100 mg/kg) can significantly shorten the immobility time of forced swimming in ICR mice, which is more significant than that of any effective part alone.

Claims (4)

1. a Polygala sugar ester and ginsenoside composition, it is characterized in that, composition is composed of Polygala sugar ester: the weight ratio of ginsenoside is 0.5:0.5～0.11:0.89, and described Polygala sugar ester and ginsenoside are obtained from A single active active part is extracted from the traditional Chinese medicine polygala and ginseng. 2. the application of polygala sugar ester described in claim 1 and ginsenoside composition in the medicine of preparation treatment depression. 3. The application of polygala sugar ester and ginsenoside composition described in claim 1 in the preparation of the medicine for improving depression. 4. The application according to claim 2 or 3, wherein the medicine is made of a composition and a pharmaceutical excipient, and the preparation forms of the medicine are liquid preparation and solid preparation.