CN101732427A - Medicinal composition for preventing and/or treating melancholia and climacteric syndrome - Google Patents
Medicinal composition for preventing and/or treating melancholia and climacteric syndrome Download PDFInfo
- Publication number
- CN101732427A CN101732427A CN200810180836A CN200810180836A CN101732427A CN 101732427 A CN101732427 A CN 101732427A CN 200810180836 A CN200810180836 A CN 200810180836A CN 200810180836 A CN200810180836 A CN 200810180836A CN 101732427 A CN101732427 A CN 101732427A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- extract
- filtrate
- radix
- weight portion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a medicinal composition for preventing and/or treating melancholia and climacteric syndrome, which comprises the following components: fine powder of bupleurum, Chinese Angelica Extract, White peony root extract, langehead atractylodes rhizome extract, Indian buead extract, liquoric root extract and mint extract. The invention also provides a preparation method for the medicinal composition. The medicinal composition is available in formulations such as tablets, capsules, pills and granules. The medicinal composition has the advantages of simple preparation method, simple variety and easily available raw materials and good prevention and/or treatment effects on both the melancholia and the climacteric syndrome.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that prevents and/or treats depression and climacteric syndrome and preparation method thereof.
Background technology
Depression is that what to be caused by a variety of causes is the one group of mood disorders or the affective disorder of cardinal symptom with the depression.According to the estimation of World Health Organization (WHO), the whole world has 500,000,000 people just suffering from various mental sickness, that is to say, per 10 philtrums have 1 people's spiritedness disease.Therefore, depression is the emphasis of research of mental health circle and service as a kind of commonly encountered diseases and frequently-occurring disease in the modern society." climacteric syndrome " is meant that the sex hormones secretion amount reduces day by day owing to ovary and hypo-orchidia, and temporary imbalance takes place endocrine function, causes some people that the syndrome of multiple physiology and mental dysfunction takes place because of maladjustment.According to the investigation of " women's health " magazine in 2002, it is relevant with climacteric syndrome that China women suffers from major disease, and annual have 1,200,000 women to die from the major disease that climacteric syndrome causes approximately.Untoward reaction symptom on multiple physiology and the health usually appears in male menopause, so climacteric syndrome has become the problem that modern medicine is more and more paid attention to.
Tablet also has the effect of treatment treatment of women's climacteric syndrome as traditional gynecological's good medicine, " Heilungkiang medical science " in the 6th phase of calendar year 2001 published " the 90 routine clinical observations of tablet in treatment climacteric syndrome " literary composition, mentioned tablet in the literary composition and can treat climacteric syndrome, and can not have side effects.Traditional tablet is that Radix Bupleuri, Radix Angelicae Sinensis, the Radix Paeoniae Alba, the Rhizoma Atractylodis Macrocephalae, Poria, Radix Glycyrrhizae, Herba Menthae and Rhizoma Zingiberis Recens eight flavor medicines are prepared from by decoction.
Application number is that 200510019033.1 patent applications that are entitled as " Chinese medicine of a kind of depression and preparation method thereof " provide Chinese medicine of a kind of depression and preparation method thereof, it is prepared from by the following method: get Radix Angelicae Sinensis 1/2, the Rhizoma Atractylodis Macrocephalae 1/2, the full dose of the Radix Paeoniae Alba 1/2 and Poria thereof, cross 100 mesh sieves after the drying and crushing, dusting cover is standby, thick slag and Radix Angelicae Sinensis 1/2, the Rhizoma Atractylodis Macrocephalae 1/2, the Radix Paeoniae Alba 1/2 and other flavor (Radix Bupleuri, Radix Scutellariae, Semen Persicae, Fructus Gardeniae, Cortex Moutan, red and the Radix Glycyrrhizae in river) medicine decocts together, it is 2 hours for the first time, for the second time, three times each 45 minutes, the ratio of water and medicine is 2.5-3.5: 1, filter, merging filtrate is concentrated into the thick paste shape, mixes with fine powder, dry again, crushing screening is made granule, and tabletting is prepared from.
Application number is 200410079950.4 to be entitled as the composition that " a kind of antidepressant drugs " discloses medicine, comprises Radix Bupleuri 5%-15%, Radix Angelicae Sinensis 10%-15%, Rhizoma Chuanxiong 5%-10%, Poria 15%-20%, Ramulus Uncariae Cum Uncis 15%-20%, Caulis Polygoni Multiflori 15%-20%, Rhizoma Atractylodis Macrocephalae 15%-20%, Radix Glycyrrhizae 5%-10%.This medicine is prepared from by the following method: hook taking rattan, Radix Bupleuri half and half amount, be ground into fine powder, sieving for standby, second half of hook taking rattan, Radix Bupleuri and remaining Poria, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Radix Glycyrrhizae, Rhizoma Chuanxiong, Caulis Polygoni Multiflori Six-element Chinese medicine decoct with water 2-3 time, each 60-180 minute, collecting decoction, filter, filtrate is concentrated into the clear paste that relative density is 1.2-1.4, add above-mentioned Ramulus Uncariae Cum Uncis, Chinese Thorowax Root mixing, make granule, the patient takes behind this medicine and is aided with spiritual healing, effective percentage reaches 90% after testing, and cure rate reaches 80%.
Summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical composition that prevents and/or treats depression and climacteric syndrome, and the dosage form of this preparation of drug combination method and this pharmaceutical composition.
An aspect of of the present present invention provides a kind of pharmaceutical composition that prevents and/or treats depression and climacteric syndrome, and this pharmaceutical composition comprises Radix Bupleuri fine powder, Radix Angelicae Sinensis extract, Radix Paeoniae Alba extract, Rhizoma Atractylodis Macrocephalae extract, Poria extract, Radix Glycyrrhizae extract and Folium Menthae extract.
Preferably, described pharmaceutical composition comprises 0.40-0.70 weight portion Radix Bupleuri fine powder, 0.05-0.17 weight portion Radix Angelicae Sinensis extract, 0.015-0.06 weight portion Radix Paeoniae Alba extract, 0.035-0.085 weight portion Rhizoma Atractylodis Macrocephalae extract, 0.003-0.011 weight portion Poria extract, 0.045-0.085 weight portion Radix Glycyrrhizae extract and 0.005-0.03 weight portion Folium Menthae extract in 1 weight portion.
Preferably, described pharmaceutical composition comprises Radix Bupleuri total saponin, peoniflorin and polysaccharide.
More preferably, described Radix Bupleuri total saponin comprises saikoside a and saikoside d.Saikoside a molecular formula C
42H
68O
13, molecular weight 780.98, cas number: 20736-09-8, structural formula is as follows:
Saikoside d molecular formula C
42H
68O
13, molecular weight 780.98, cas number: 20874-52-6, structural formula is as follows:
Preferably, contain the saikoside a of this pharmaceutical composition gross weight 0.1%-0.5%, the saikoside d of 0.08%-0.45%, the peoniflorin of 0.45%-0.2% and the polysaccharide of surplus in the described pharmaceutical composition.
Preferably, described polysaccharide comprises one or more in Radix Angelicae Sinensis polysaccharide, Radix Paeoniae Alba polysaccharides, Rhizoma Atractylodis polysaccharide, pachyman and the Angelica Polysaccharide.
One side more of the present invention also provides a kind of preparation described method for compositions, and this method may further comprise the steps:
A. at first Radix Angelicae Sinensis, the Radix Paeoniae Alba, the Rhizoma Atractylodis Macrocephalae, Poria, Radix Glycyrrhizae and Herba Menthae are soaked in water respectively or jointly;
The soak that b. will contain Chinese crude drug decocts, and obtains volatile matter and decoction liquor, collects described volatile matter;
C. filter described decoction liquor, obtain filtrate I,, in described thick paste, add ethanol filtrate I simmer down to thick paste;
D. will add alcoholic acid thick paste and filter, obtain filtrate II, reclaim the ethanol in the filtrate II, obtain removing alcoholic acid filtrate II I;
E. the volatile matter that step b is obtained mixes with the filtrate II I that steps d obtains, and obtains mixture;
F. Radix Bupleuri being pulverized is fine powder, and mixture and described fine powder that step e is obtained mix, and drying and dehydrating obtains the active component in the pharmaceutical composition;
G. adding or not adding under the situation of pharmaceutically acceptable adjuvant, described active component is made described pharmaceutical composition.
In above-mentioned step a, Radix Angelicae Sinensis, the Radix Paeoniae Alba, the Rhizoma Atractylodis Macrocephalae, Poria, Radix Glycyrrhizae and Herba Menthae can be soaked in water respectively, also can be soaked in water jointly.When this Six-element medicine is soaked in water respectively, obtain soak separately, then the step b that carries out, c, d, e also every kind carry out respectively, just all mixture that will obtain in step f and Radix Bupleuri fine powder mix, and obtain the active component in the pharmaceutical composition.
Preferably, described fine powder is the 80-300 order.
Preferably, in described step a, soaked at ambient temperature described Chinese crude drug 10-60 minute with Chinese crude drug weight 5-10 water doubly.
Preferably, in described step b, the described soak boiling twice continuously that contains Chinese crude drug is carried out decocting in 1-4 hour altogether.
Preferably, in described step c, described decoction liquor is at room temperature filtered, and obtains filtrate I, with filtrate I simmer down to thick paste, at room temperature, adds the ethanol of thick paste volume 2-6 70%-100% concentration doubly in described thick paste.
Preferably, the dosage form of this pharmaceutical composition is tablet, capsule, pill or granule.
Preferably, described pill is the watered pill, honeyed pill or concentrated pill.
Preferably, described pill is a drop pill.
Unlike the prior art be, adopt the pharmaceutical composition that prevents and/or treats depression and climacteric syndrome of technical solution of the present invention preparation to adopt seven flavor Chinese medicines altogether, and the effective ingredient that Radix Angelicae Sinensis, the Radix Paeoniae Alba, the Rhizoma Atractylodis Macrocephalae, Poria, Radix Glycyrrhizae and Herba Menthae adopt decoction method to extract acquisition mixes with the Radix Bupleuri of pulverizing, and oven dry obtains.Compare with traditional ease pill, the Radix Bupleuri in the pharmaceutical composition of the present invention exists with the form of fine powder form rather than its extract, and this pharmaceutical composition not only can prevent and/or treat depression, can also prevent and/or treat climacteric syndrome.
Climacteric syndrome is two kinds of different diseases with depression, but is existing similar performance aspect the emotion symptom again.The women is climacteric, along with ovarian function degenerate gradually and body in the minimizing day by day of estrogen, the symptom that some physiology and psychological aspects can occur, main performance has: hectic fever, perspiration, tired, osteoporosis, anxiety and tense, insomnia and dreamful sleep, anxious state of mind, attention are poor, worried depression etc., are referred to as " climacteric syndrome " clinically.And depression is low except being in a bad mood, disheartened, self evaluation low, also with anxiety, tired, insomnia, hypomnesis etc. and the similar emotion symptom of climacteric syndrome.Climacteric syndrome is many by due to caused by liver and kidney deficiency, the imbalance of YIN and YANG, and clinical manifestation is being irritable and getting angry easily, vexed insomnia, hectic fever sweating, often has the not easypro pathological changes of pathogenic fire derived from stagnation of liver-QI, the stagnation of QI concurrently.Treating different diseases with the same therapeutic principle is the advantage place of the traditional Chinese medical science.Though more than two sick sick plant differently, belong to stagnation of liver-QI with deficiency of the spleen together and have hot and suffocating disease concurrently, so treat, all can get effect with medicine composite for curing of the present invention with soothing liver-QI reason spleen clearing away heat method.
In addition, when the pharmaceutical composition that obtains with technical solution of the present invention had the therapeutic effect that reaches identical with respect to traditional ease pill on the treatment climacteric syndrome, the advantage that dose is few was more suitable for clinical life-time service.Compare with the pharmaceutical composition of the treatment depression of mentioning in the background technology, preparation of drug combination method of the present invention is simple, raw material type is few, is easy to obtain, and is preventing and/or treating depression or all have good effect on climacteric syndrome.In addition, pharmaceutical composition of the present invention is compared with the Western medicine of antidepressant, does not have dependency and side effect.
Description of drawings
Fig. 1 is the high-efficient liquid phase chromatogram of Radix Bupleuri standard substance.
Fig. 2 is the high-efficient liquid phase chromatogram of Radix Bupleuri fine powder.
Fig. 3 is the high-efficient liquid phase chromatogram of peoniflorin standard substance.
Fig. 4 is the high-efficient liquid phase chromatogram of the filtrate II I that makes of peoniflorin.
Fig. 5 is the crude polysaccharides ultraviolet-visible light measurement collection of illustrative plates of filtrate II I mixed liquor.
Fig. 6 is stand number of times and the time relation figure of mice.
Fig. 7 is the different group mice autonomic activitieses number of times mean values figure that stand.
Fig. 8 is the total course diagrams of different group mice autonomic activitieses.
Fig. 9 is different group mice runner number of times and time relation figure.
Figure 10 is different group mice forced swimming runner number of times figure.
Figure 11 is different group mouse tail suspension dead time figure.
Figure 12 is a monoamine neurotransmitter standard substance electrochemical detector determining collection of illustrative plates, and each neurotransmitter is measured figure under the wherein last figure expression+450mV voltage, figure below represents+350mV voltage under each neurotransmitter mensuration figure.
Figure 13 is a mice plasma sample neurotransmitter electrochemical detector determining collection of illustrative plates.
The specific embodiment
Embodiment 1
Radix Angelicae Sinensis medical material 10Kg, white Peony Root 10Kg, Rhizoma Atractylodis Macrocephalae medical material 10Kg, Poria medical material 10Kg, licorice medicinal materials 8Kg, Herba Menthae medical material 2Kg with water logging bubble 10min, decoct 2 times separately, each 1 hour, collect the volatile matter that obtains.The decoction liquor room temperature is filtered, obtain filtrate I, with filtrate I simmer down to thick paste, in thick paste, add 6 times of amount 95% ethanol precipitations 24 hours, filter, obtain filtrate II, reclaim the ethanol of filtrate II, obtain filtrate II I, totally six parts of filtrate II I, the dry extract 1.9Kg of the Radix Angelicae Sinensis that wherein obtains, Radix Paeoniae Alba dry extract 0.75Kg, Rhizoma Atractylodis Macrocephalae dry extract 1.1Kg, Poria dry extract 0.045Kg, Radix Glycyrrhizae dry extract 1.0Kg, Herba Menthae dry extract 0.07Kg.It is 80 order fine powders that Radix Bupleuri medical material 10Kg pulverizes, and mixes with the six parts of filtrate II I and the volatile matter of above merging, adds adjuvant system granule, dries, and tabletting is made the about 20Kg of tablet.
Embodiment 2
Radix Angelicae Sinensis medical material 10Kg, white Peony Root 10Kg, Rhizoma Atractylodis Macrocephalae medical material 10Kg, Poria medical material 10Kg, licorice medicinal materials 8Kg, Herba Menthae medical material 2Kg, the mixed medical material and the medical material mixture 30min that is soaked in water, the soak that will contain the Chinese crude drug mixture decocts 2 times continuously, 1 hour for the first time, 1.5 hours for the second time, collect the volatile matter that obtains.The decoction liquor room temperature is filtered, and obtains filtrate I, with filtrate I simmer down to thick paste, adds 4 times of amount 80% ethanol precipitations 24 hours in thick paste, filters, and obtains filtrate II, reclaims the ethanol of filtrate II, obtains filtrate II I.It is 200 order fine powders that Radix Bupleuri medical material 10Kg pulverizes, and mixes with above filtrate II I and volatile matter, and oven dry gets the about 16Kg of blended drug powder, and is encapsulated.
Embodiment 3
Radix Angelicae Sinensis medical material 10Kg, white Peony Root 10Kg, Rhizoma Atractylodis Macrocephalae medical material 10Kg, Poria medical material 10Kg, licorice medicinal materials 8Kg, Herba Menthae medical material 2Kg, the mixed medical material and the medical material mixture 60min that is soaked in water decoct 2 times, each 1 hour, collect the volatile matter that obtains.The decoction liquor room temperature is filtered, and obtains filtrate I, with filtrate I simmer down to thick paste, adds 3 times of amount 95% ethanol precipitations 24 hours in thick paste, filters, and obtains filtrate II, reclaims the ethanol of filtrate II, obtains filtrate II I.It is 300 order fine powders that Radix Bupleuri medical material 10Kg pulverizes, and mixes with above filtrate II I and volatile matter, adds the adjuvant pill, and oven dry obtains pill 21Kg.
Embodiment 4
Radix Angelicae Sinensis medical material 10Kg, white Peony Root 10Kg, Rhizoma Atractylodis Macrocephalae medical material 10Kg, Poria medical material 10Kg, licorice medicinal materials 8Kg, Herba Menthae medical material 2Kg, the 30min that is soaked in water separately decocts 2 times, each 1 hour, collects the every kind of volatile matter that obtains respectively.All decoction liquor room temperatures are filtered, and obtain filtrate I, and totally six kinds, with every kind of filtrate I simmer down to thick paste, in every kind of thick paste, add 2 times of amount 95% ethanol precipitations 24 hours respectively, filter, obtain filtrate II, reclaim the ethanol of filtrate II, obtain filtrate II I.Totally six parts of filtrate II I, the dry extract 1.7Kg of the Radix Angelicae Sinensis that wherein obtains, Radix Paeoniae Alba dry extract 0.60Kg, Rhizoma Atractylodis Macrocephalae dry extract 0.85Kg, Poria dry extract 0.11Kg, Radix Glycyrrhizae dry extract 0.85Kg, Herba Menthae dry extract 0.03Kg.It is 80 order fine powders that Radix Bupleuri medical material 5.5Kg pulverizes, and mixes with the six parts of filtrate II I and the volatile matter of above merging, adds adjuvant system granule, dries, and tabletting is made the about 20Kg of tablet.
It is 160 order fine powders that Radix Bupleuri medical material 5.5Kg pulverizes, and mixes with above-mentioned filtrate II I and volatile matter, adds adjuvant system granule, oven dry, and tabletting is made the about 22Kg of tablet.
The assay of active component
1, the HPLC method is measured saikoside: the Radix Bupleuri fine powder of Radix Bupleuri standard substance and pulverizing is dissolved in the methanol, measures.
Immobile phase: C
18Post (5 μ m, 250mm * 4.6mm); Mobile phase: methanol-water (68: 32); Flow velocity: 1.000mL/min; Detect wavelength: 204nm; Column temperature: 26 ℃.The testing result of Radix Bupleuri standard substance is seen accompanying drawing 1, and 1 peak among the figure is a saikoside a, and 2 peaks are saikoside d.The high-efficient liquid phase chromatogram of Radix Bupleuri fine powder is seen accompanying drawing 2, and 1 peak among the figure is a saikoside a, and 5 peaks are saikoside d.
2, the HPLC method is measured peoniflorin: analyze the Radix Paeoniae Alba content in the finished product
Immobile phase: C
18Post (5 μ m, 250mm * 4.6mm); Mobile phase: acetonitrile-0.1% phosphoric acid solution (15: 85v/v); Detect wavelength: 230nm, testing result is seen accompanying drawing 3 and accompanying drawing 4, and wherein accompanying drawing 3 is represented the high-efficient liquid phase chromatogram of peoniflorin standard substance, and accompanying drawing 4 expressions contain the high-efficient liquid phase chromatogram of Radix Paeoniae Alba finished product, and No. 4 peaks among the figure are peoniflorin.
3, sulfuric acid-phynol method is measured polysaccharide:
Sample determination liquid 2.0ml after filtrate II I that obtains in the above and volatile matter are mixed places the 25ml color comparison tube, add phenol solution 2.0ml, behind mixing on the impeller, the careful adding behind the concentrated sulphuric acid 10.0ml behind mixing on the impeller, place water-bath to boil 10min, be cooled to room temperature, use spectrophotometer at 490nm wavelength place, with the reagent blank is reference, and cuvette is measured absorbance.Crude polysaccharides content from glucose standard curve and regression equation calculation sample is seen accompanying drawing 5.Each sample needs to obtain content value by regression equation calculation.
Radix Angelicae Sinensis medical material 10Kg, white Peony Root 10Kg, Rhizoma Atractylodis Macrocephalae medical material 10Kg, Poria medical material 10Kg, licorice medicinal materials 8Kg, Herba Menthae medical material 2Kg, water logging bubble 30min decocts 2 times, each 1 hour, extracts volatile matter simultaneously.The decocting liquid room temperature is filtered, and obtains filtrate I, with filtrate I simmer down to thick paste, adds 3 times of amount 95% ethanol precipitations 24 hours, filters, and obtains filtrate II, reclaims the ethanol of filtrate II, obtains filtrate II I.It is 160 order fine powders that Radix Bupleuri medical material 10Kg pulverizes, and mixes with above filtrate II I and volatile matter, adds adjuvant system granule, oven dry, and tabletting is made the about 22Kg of tablet.
Effect experiment 1: to the influence of mice autonomic activities
Experimental technique: 40 male mice in kunming are divided into 5 groups at random, every group 8, mice is divided into the high, medium and low dosage group of blank group (C), positive controls (fluoxetine P) and pharmaceutical composition of the present invention, each organizes dosage and positive drug fluoxetine dosage sees Table 1 again, and the supplement scale sees Table 1.
Table 1 dosage table
The oral commensurability aqueous solution 0.1mL/10g of blank group mice.Test continuous gastric infusion of first three day, administration was after 30 minutes in the 4th day, mice was put into toy autonomic activities analyzer (modelWW3002 system, mice Digbehv-LM4 animal inner directed behavior detection system) adaptation after 3 minutes, the active situation of observing mice in 60 minutes.Experiment finishes the back by photography playback track identification statistics mice stand number of times and active path length, thereby judges independent activity of animals ability power.Test between 9:00-17:00, carry out in the quiet special-purpose laboratory of 25 ℃ of room temperatures, experimental result is seen Fig. 6, stand number of times and the time relation figure of mice; Fig. 7 represent different group mice autonomic activitieses stand number of times figure (
*P＜0.01,
*P＜0.05), Fig. 8 represent the total distance of different group mice autonomic activitieses (
*P＜0.01,
*P＜0.05).
Experiment conclusion:
Each administration group is to influence such as Fig. 6, Fig. 7, shown in Figure 8 of spontaneous activity in mice amount.Along with the prolongation of time, mice reduces for the exploration motion of new environment, and the autonomic activities amount shows tangible downward trend.After the successive administration three days, the total distance of autonomic activities of positive control drug fluoxetine group mice and the number of times downward trend of standing all are lower than the blank group, total distance has been compared significant difference with the number of times of standing with the blank group, illustrate that fluoxetine can increase mice autonomic activities amount to a certain extent, has alleviated the depressive state of mice.
Compare with the number of times of standing of blank group, adopt pharmaceutical composition high dose of the present invention, middle dosage (P＜0.01) to have statistical significance; Compare pharmaceutical composition high dose of the present invention (P＜0.01), the remarkable meaning of middle dosage (P＜0.05) tool with movable total distance of blank group.Therefore give the total distance of mice autonomic activities of the high dose of pharmaceutical composition of the present invention, middle dosage and the number of times of standing had rising respectively after 30 minutes and 40 minutes trend, illustrate that the high dose of pharmaceutical composition of the present invention, middle dosage can increase mice autonomic activities amount to a certain extent, have tangible depression effect.
Effect experiment 2: mice forced swimming experiment
Experimental technique: 50 Male Kunming strain mice are divided into 5 groups at random, 10 every group, are respectively the blank high, medium and low dosage group of organizing (C), positive controls (P) and pharmaceutical composition of the present invention.Blank group is given distilled water 0.1mL/10g.Continuous 5 days gastric infusions before the experiment were tested after the administration in the 6th day in 30 minutes.The forced swimming of mice is tested water tank and multichannel enumerator that used instrument comprises 57 * 25 * 24cm.In water tank, discharge water to the middle part of rotating cage and regulate water temperature to 22～23 ℃.Formal experiment was trained mice in preceding 2 days, was about to mice and placed separately in the water tank, and forced swimming 10 minutes is put back in the mouse cage then.During formal the experiment, the swimming time of mice is 15 minutes.Per 1 minute statistics of enumerator one next round is changeed number of times, and experiment finishes the back sense data, judges the improvement situation of tablet to the mice depressive symptom with this.Experiment, is carried out between 9:00-17:00 in 25 ℃ of rooms of room temperature in peace and quiet, and experimental result is seen Fig. 9, and the wheel of mice changes number of times and the graph of a relation between the time, the graph of a relation of Figure 10 different tests group and forced swimming wheel commentaries on classics number of times (
*P＜0.01,
*P＜0.05).
Experiment conclusion: cause in the desperate behavioral experiment of mice (Figure 10) at forced swimming, irritate stomach and give the number of turns (P＜0.01) that the height of pharmaceutical composition of the present invention, middle dosage all can significantly increase the runner rotation, think that promptly these administration groups all can increase the positive mobility of mice in various degree, under dosage, obviously prolong holding time of mice flight behavior.The increase effect of positive control drug fluoxetine is lower than these groups slightly, compares with the blank group still to have a significance meaning.
Effect experiment 3: mouse tail suspension experiment (tail suspension test)
Experimental technique: 50 Male Kunming strain mice are divided into 5 groups at random, 10 every group, are respectively blank group (C), positive controls (P) and the high, medium and low dosage group of pharmaceutical composition of the present invention.Blank group is given distilled water 0.1mL/10g.Gastric infusion for three days on end before the experiment, administration in the 4th day be after 30 minutes, fixedly the mice tail end, make its reversal of the natural order of things, liftoff about 5cm isolates the animal sight line with plate washer, animal is for overcoming undesired position struggle activity, but it is motionless discontinuity to occur after movable a period of time, shows desperate state.Write down in 6 minutes the mice dead time and be the desperate time (with motionless more than the lasting 3s be effective dead time).Judge the inhibition power of tablet with this to the mice depression.Experiment, is carried out between 9:00-17:00 in 25 ℃ of rooms of room temperature in peace and quiet, and experimental result is seen Figure 11, the motionless graph of a relation of various dose group and outstanding tail (
*P＜0.01,
*P＜0.05).
Experiment conclusion: from the experimental result of Figure 11 as can be seen, compare with the blank group, the positive drug fluoxetine can significantly shorten outstanding tail dead time (25.20 ± 7.49 vs 78.1 ± 9.42s), we notice that also dosage in the extract, high dose group also can significantly shorten the motionless tail time simultaneously, and (43.8 ± 12.57vs, 25.20 ± 7.49s, 33.2 ± 7.58vs 25.20 ± 7.49s) in the drug action that demonstration and fluoxetine are suitable.
Effect experiment 4: to activities in rats runner Stress model (activity stress)
Experimental technique:
56 male Wister rats are divided into 8 groups immediately, 7 every group, are respectively normal control group, fasting taboo water matched group, Stress model group, positive drug group (P), the blank high, medium and low dosage group of organizing (C) and pharmaceutical composition of the present invention.Blank group is given distilled water 1mL/100g.Test the 1st day 9:00 rat is put into the rotating cage device, and sliding door is opened free activity in period, second day 9:00 begins rat is closed into rotating cage one side, and locks sliding door, beginning official record rat motor state.18:00 filling every day stomach gives rat and is subjected to the reagent thing, puts it into feed drinking-water in lobby after finishing, and 20:00 closes it into rotating cage one side again, continues 14 days.The rotating cage stress rats taken out in the 15th day and use etherization, postcava to get behind the blood broken end immediately, the full brain of taking-up on ice pan separates cerebral cortex rapidly.
Maincenter monoamine neurotransmitter assay method: the cerebral cortex of getting is weighed and is placed in the 2mL round bottom centrifuge tube, holds 1: 1 ratio according to anharmonic ratio and adds 3% perchloric acid Deproteinization, and tissue refiner grinds to form homogenate in the ice bath, centrifugal 10 minutes of 4 ℃ of 10000rpm.Blood plasma 1: 1 adds 6% perchloric acid Deproteinization, centrifugal 10 minutes of 4 ℃ of 10000rpm, and supernatant is the level of-80 ℃ of freezing preservation of refrigerator monoamine neurotransmitters to be measured behind 0.2 μ m membrane filtration all.
The HPLC-ECD of monoamine neurotransmitter analyzes: U.S. ESA company high performance liquid chromatogram coulomb array electrochemical detection system, mobile phase: monohydrate potassium 15g, trisodium citrate 20.2g, EDTA Na
20.036g eight sodium alkyl sulfonate 0.18g with chromatograph pure water (〉=18M Ω) 900mL ultrasonic dissolution, add methanol constant volume to 1000mL, ultrasonic degas, and it is standby that 0.2 μ m crosses film.38 ℃ of column temperatures, flow velocity 0.8mL/min.Coulomb array electrochemical detector is set three channel electrode electromotive forces: passage 1:-150mV (reduction potential); Passage 2:+350mV; Passage 3:+450mV.
The monoamine neurotransmitter standard curve is drawn: this experimental group is to norepinephrine (NE), 3,4 dihydroxyphenyl acetic acids (DOPAC), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxy tryptamine (5-HT) and 6 kinds of monoamine neurotransmitters of 4-hydroxy-3-methoxy-.alpha.-toluic acid. (HVA) and metabolite thereof have carried out the drafting of standard curve, and it is relevant that experimental result has shown that index is favorable linearity in 10～2000ng/mL scope.Its HPLC chromatogram, standard curve and equation of linear regression and correlation coefficient are seen Figure 12 and table 2 respectively, and each neurotransmitter is measured figure under the last figure expression+450mV voltage of Figure 12, figure below represents+350mV voltage under each neurotransmitter mensuration figure.Each peak is 6 kinds of standard substance NE, DOPAC, DA, 5-HIAA, 5-HT and HVA among the figure.Figure 13 represents the graph of a relation between various dose group and the rotating cage rat monoamine neurotransmitter amount content, compares #p＜0.05 with matched group; Compare with model group,
*P＜0.05.
The equation of linear regression and the correlation coefficient r of 6 kinds of neurotransmitteies of table 2 and metabolite
Experiment conclusion: it is generally acknowledged that monoamine neurotransmitters becomes negative correlation with depressed degree.Monoamine neurotransmitters is low more, and depressed degree is obvious more.Monoamine neurotransmitters raises more near normal level, and depressed degree is light more.By the experimental result of Figure 13 as can be seen, compare with the blank group, after the rat rotating cage stress be loaded 14 days, neurotransmitter content significantly reduced in the Stress model group blood plasma, fasting taboo water group rat monoamine neurotransmitters is organized a little less than blank, but no difference of science of statistics.With stress compare by load model group rat, giving fluoxetine can significantly improve and stress load that (NE:20.96 ± 5.46vs 14.21 ± 5.71 for the neurotransmitter downward trend that causes, 5-HT:217.49 ± 17.37vs 182.28 ± 25.26), the DA level does not show significant difference, but still shows certain improvement trend (66.76 ± 7.17vs53.87 ± 10.16).Extract high dose group curative effect and positive control drug fluoxetine be (NE:22.11 ± 5.15 quite, DA:72.66 ± 6.01,5-HT:217.76 ± 17.83), compare with model group, NE, DA and 5-HT content rise 34.5%, 26.2% and 18.6% respectively, show and to play certain curative effect by improving the partial nerve mediator, show the good drug effect of antidepressant.In addition, each group blood plasma neurotransmitter downward trend that all stress cause rotating cage has improvement effect in various degree.
To sum up, by the mensuration to the blood plasma neurotransmitter, we find, prohibit the water group with blank group and fasting and compare, and 3 index content of Stress model group all significantly descend, and show that this model is provided with rationally.Wherein the positive control drug fluoxetine can significantly improve the content of NE, DA and three neurotransmitteies of 5-HT, shows certain antidepressant effect; The high dose group of the pharmaceutical composition of the present invention neurotransmitter contents level except that DA that can significantly raise shows and the similar drug effect of fluoxetine, and the DA downward trend is also made moderate progress.In addition, the blood plasma neurotransmitter levels that causes loading of each dosage group of extract descends and is showing the improvement effect in varying degrees.
Claims (10)
1. pharmaceutical composition that prevents and/or treats depression and climacteric syndrome, this pharmaceutical composition comprises the Radix Bupleuri fine powder, Radix Angelicae Sinensis extract, Radix Paeoniae Alba extract, Rhizoma Atractylodis Macrocephalae extract, Poria extract, Radix Glycyrrhizae extract and Folium Menthae extract, preferably, described pharmaceutical composition comprises 0.40-0.70 weight portion Radix Bupleuri fine powder in 1 weight portion, 0.05-0.17 weight portion Radix Angelicae Sinensis extract, 0.015-0.06 weight portion Radix Paeoniae Alba extract, 0.035-0.085 weight portion Rhizoma Atractylodis Macrocephalae extract, 0.003-0.011 weight portion Poria extract, 0.045-0.085 weight portion Radix Glycyrrhizae extract and 0.005-0.03 weight portion Folium Menthae extract.
2. pharmaceutical composition according to claim 1, wherein said pharmaceutical composition comprises Radix Bupleuri total saponin, peoniflorin and polysaccharide, and preferably, described Radix Bupleuri total saponin comprises saikoside a and saikoside d.
3. pharmaceutical composition according to claim 2 contains the saikoside a of this pharmaceutical composition gross weight 0.1%-0.5%, the saikoside d of 0.08%-0.45%, the peoniflorin of 0.45%-0.2% and the polysaccharide of surplus in the wherein said pharmaceutical composition.
4. according to each described pharmaceutical composition among the claim 1-3, wherein said polysaccharide comprises one or more in Radix Angelicae Sinensis polysaccharide, Radix Paeoniae Alba polysaccharides, Rhizoma Atractylodis polysaccharide, pachyman and the Angelica Polysaccharide.
5. method for preparing each described pharmaceutical composition among the claim 1-4, this method may further comprise the steps:
A. at first Radix Angelicae Sinensis, the Radix Paeoniae Alba, the Rhizoma Atractylodis Macrocephalae, Poria, Radix Glycyrrhizae and Herba Menthae are soaked in water respectively or jointly;
The soak that b. will contain Chinese crude drug decocts, and obtains volatile matter and decoction liquor, collects described volatile matter;
C. filter described decoction liquor, obtain filtrate I,, in described thick paste, add ethanol filtrate I simmer down to thick paste;
D. will add alcoholic acid thick paste and filter, obtain filtrate II, reclaim the ethanol in the filtrate II, obtain removing alcoholic acid filtrate II I;
E. the volatile matter that step b is obtained mixes with the filtrate II I that steps d obtains, and obtains mixture;
F. Radix Bupleuri being pulverized is fine powder, and preferably, described fine powder is the 80-300 order, and mixture and described fine powder that step e is obtained mix, and drying and dehydrating obtains the active component in the pharmaceutical composition;
G. adding or not adding under the situation of pharmaceutically acceptable adjuvant, described active component is made described pharmaceutical composition.
6. method according to claim 5 wherein in described step a, was soaked described Chinese crude drug 10-60 minute with Chinese crude drug weight 5-10 water doubly at ambient temperature.
7. according to claim 5 or 6 described methods, wherein in described step b, the described soak boiling twice continuously that contains the Chinese medicine medical material is carried out decocting in 1-4 hour altogether.
8. according to each described method among the claim 5-7, wherein in described step c, described decoction liquor is at room temperature filtered, obtain filtrate I, with filtrate I simmer down to thick paste, at room temperature, in described thick paste, add the ethanol of thick paste volume 2-6 70-100% concentration doubly.
9. according to each described pharmaceutical composition among the claim 1-4, wherein the dosage form of this pharmaceutical composition is tablet, capsule, pill or granule, and preferably, described pill is the watered pill, honeyed pill or concentrated pill.
10. pharmaceutical composition according to claim 9 is characterized in that described pill is a drop pill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200810180836 CN101732427B (en) | 2008-11-24 | 2008-11-24 | Medicinal composition for preventing and/or treating melancholia and climacteric syndrome |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200810180836 CN101732427B (en) | 2008-11-24 | 2008-11-24 | Medicinal composition for preventing and/or treating melancholia and climacteric syndrome |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101732427A true CN101732427A (en) | 2010-06-16 |
| CN101732427B CN101732427B (en) | 2012-12-12 |
Family
ID=42456795
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200810180836 Active CN101732427B (en) | 2008-11-24 | 2008-11-24 | Medicinal composition for preventing and/or treating melancholia and climacteric syndrome |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101732427B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103751318A (en) * | 2014-01-20 | 2014-04-30 | 于建梅 | Traditional Chinese medicinal composition for treating insomnia caused by lack of spirit preservation |
| CN104069171A (en) * | 2014-07-03 | 2014-10-01 | 成都中医药大学 | Antidepressant medicine composition as well as preparation method and application thereof |
| CN108210873A (en) * | 2018-04-08 | 2018-06-29 | 复旦大学附属金山医院 | A kind of Chinese medicine composition for increasing estrogen and its application |
| WO2019072051A1 (en) * | 2017-10-12 | 2019-04-18 | 山西大学 | Traditional chinese medicine extract with anti-depressive effect and preparation method and application thereof |
| CN110655593A (en) * | 2019-11-12 | 2020-01-07 | 东北师范大学 | Mint polysaccharide composition and preparation method and application thereof |
| CN112843201A (en) * | 2020-12-14 | 2021-05-28 | 李承毅 | Anti-depression mixture and preparation method thereof |
| WO2022022648A1 (en) | 2020-07-30 | 2022-02-03 | 天士力医药集团股份有限公司 | Traditional chinese medicine composition having mental relief and antidepressant effects and preparation method therefor |
| CN114949150A (en) * | 2022-07-27 | 2022-08-30 | 广州科犁医学研究有限公司 | Pharmaceutical composition for treating perimenopausal syndrome and preparation method and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1660403A (en) * | 2005-01-20 | 2005-08-31 | 北京勃然制药有限公司 | Carefree drop pills in use for soothing the liver and invigorating the spleen as well as enriching the blood and regulating menstruation, and preparing method |
-
2008
- 2008-11-24 CN CN 200810180836 patent/CN101732427B/en active Active
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103751318B (en) * | 2014-01-20 | 2015-05-27 | 于建梅 | Traditional Chinese medicinal composition for treating insomnia caused by lack of spirit preservation |
| CN103751318A (en) * | 2014-01-20 | 2014-04-30 | 于建梅 | Traditional Chinese medicinal composition for treating insomnia caused by lack of spirit preservation |
| CN104069171A (en) * | 2014-07-03 | 2014-10-01 | 成都中医药大学 | Antidepressant medicine composition as well as preparation method and application thereof |
| CN104069171B (en) * | 2014-07-03 | 2018-01-23 | 成都中医药大学 | A kind of antidepressant pharmaceutical composition and its production and use |
| WO2019072051A1 (en) * | 2017-10-12 | 2019-04-18 | 山西大学 | Traditional chinese medicine extract with anti-depressive effect and preparation method and application thereof |
| CN108210873B (en) * | 2018-04-08 | 2020-11-03 | 复旦大学附属金山医院 | Traditional Chinese medicine composition for increasing estrogen and application thereof |
| CN108210873A (en) * | 2018-04-08 | 2018-06-29 | 复旦大学附属金山医院 | A kind of Chinese medicine composition for increasing estrogen and its application |
| CN110655593A (en) * | 2019-11-12 | 2020-01-07 | 东北师范大学 | Mint polysaccharide composition and preparation method and application thereof |
| CN110655593B (en) * | 2019-11-12 | 2021-08-31 | 东北师范大学 | Mint polysaccharide composition and preparation method and application thereof |
| WO2022022648A1 (en) | 2020-07-30 | 2022-02-03 | 天士力医药集团股份有限公司 | Traditional chinese medicine composition having mental relief and antidepressant effects and preparation method therefor |
| CN114053337A (en) * | 2020-07-30 | 2022-02-18 | 天士力医药集团股份有限公司 | Traditional Chinese medicine composition with mental relief and anti-depression effects and preparation method thereof |
| CN114053337B (en) * | 2020-07-30 | 2023-12-26 | 天士力医药集团股份有限公司 | Traditional Chinese medicine composition with effects of relieving spirit and resisting depression and preparation method thereof |
| CN112843201A (en) * | 2020-12-14 | 2021-05-28 | 李承毅 | Anti-depression mixture and preparation method thereof |
| CN114949150A (en) * | 2022-07-27 | 2022-08-30 | 广州科犁医学研究有限公司 | Pharmaceutical composition for treating perimenopausal syndrome and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101732427B (en) | 2012-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101732427B (en) | Medicinal composition for preventing and/or treating melancholia and climacteric syndrome | |
| CN100493589C (en) | Herbal medical preparation for the treatment of arthritis | |
| CN1806846A (en) | Chinese medicinal composition, its preparation process and quality control method | |
| CN101919979B (en) | Detection method of traditional Chinese medicine composition for soothing liver-qi stagnation and tonifying spleen and removing dampness | |
| CN102091168A (en) | Quality control method for Chinese medicine preparation Xuefuzhuyu capsule | |
| CN101757322A (en) | Vegetable drug compound preparation for treating urarthritis as well as preparation and application thereof | |
| CN100415255C (en) | Composition of Chinese traditional medicine, and preparation method | |
| CN1887324B (en) | Chinese medicine composition for treating liver and kidney defect, and its preparation process and analysis method | |
| CN104950068B (en) | The kidney invigorating is dispeled the wind the quality determining method of climacteric mixture | |
| CN101829291B (en) | Traditional Chinese medicine preparation for treating rheumatism and preparation method thereof | |
| CN101129974A (en) | Traditional Chinese medicine composition for treating hepatopathy and method of preparing the same | |
| CN102920964A (en) | Traditional Chinese medicine preparation for curing cough | |
| CN101912540A (en) | Medicament for treating cerebral infarction | |
| CN102309543B (en) | Compound salvia miltiorrhiza concentrated preparation and preparation and detection method thereof | |
| AU2002338148B2 (en) | The pharmaceutical formulation of traditional chinese medicine for abstinence of drug and preparation method and use thereof | |
| CN103316074A (en) | Medicine composite of halenia corni extract, astragalus extract and liquorice extract as well as preparation and application of medicine composite | |
| CN107551099B (en) | It is a kind of to be used to treat Chinese medicine composition of senile dementia and preparation method thereof | |
| CN101422588A (en) | Quality control method of medicine for treating gynecologic disease | |
| CN1306949C (en) | Tendon relaxing and dampness removing traditional Chinese medicine compound preparation and preparation method thereof | |
| CN103961582A (en) | Traditional Chinese medicine composition for treating nephritis, and preparation and preparation method thereof | |
| CN105617251A (en) | Traditional Chinese medicine composition for treating depression and preparation method thereof | |
| CN105435162B (en) | Traditional Chinese medicine composition for treating allergic rhinitis, preparation method and traditional Chinese medicine preparation | |
| CN108478745A (en) | One seed ginseng Chinese herbaceous peony nourishing qi and blood particle Chinese medicine composition and preparation method thereof | |
| CN101485817B (en) | Chinese medicinal composition for treating syphilis infection as well as preparation method and quality control method thereof | |
| CN101991760A (en) | Chinese patent medicine for treating climacteric syndrome and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |