CN101732427B - 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
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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 through decoction.
Application number be 200510019033.1 be entitled as " Chinese medicine of a kind of depression and preparation method thereof " patent application Chinese medicine of a kind of depression and preparation method thereof is provided, it is prepared from through following method: get the full dose of Radix Angelicae Sinensis 1/2, the Rhizoma Atractylodis Macrocephalae 1/2, the Radix Paeoniae Alba 1/2 and Poria thereof, cross 100 mesh sieves after the drying and crushing; Dusting cover is subsequent use, and thick slag decocts with 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, the river is red and Radix Glycyrrhizae) medicine, and be 2 hours the first time; For the second time, three times each 45 minutes, the ratio of water and medicine is 2.5-3.5:1, the filtration; Merging filtrate is concentrated into the thick paste shape, mixes with fine powder; Dry again; Crushing screening is processed 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 through following method: hook taking rattan, Radix Bupleuri half and half amount are 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, the decocte with water of Caulis Polygoni Multiflori Six-element Chinese medicine 2-3 time, each 60-180 minute, collecting decoction; Filter, filtrating is concentrated into the clear paste that relative density is 1.2-1.4, adds above-mentioned Ramulus Uncariae Cum Uncis, Chinese Thorowax Root mixing; Process granule; The patient takes behind this medicine and is aided with spiritual healing, reaches 90% through detecting effective percentage, 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.
One side of the 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 following:
Saikoside d molecular formula C
42H
68O
13, molecular weight 780.98, cas number: 20874-52-6, structural formula is following:
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 said 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 the I that filtrates, the I simmer down to thick paste of will filtrating adds ethanol in described 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 processed 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, the step b that then carries out, c, d, e also every kind carry out respectively, all mixture that just in step f, will obtain and Radix Bupleuri fine powder mix, and obtain the active component in the pharmaceutical composition.
Preferably, said fine powder is the 80-300 order.
Preferably, in described step a, soaked at ambient temperature said 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 the I that filtrates, and the I simmer down to thick paste of will filtrating 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.
Different with prior art is; Adopt the pharmaceutical composition that prevents and/or treats depression and climacteric syndrome of technical scheme preparation of the present invention 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 XIAOYAO WAN, 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 scheme of the present invention had the therapeutic effect that reaches identical with respect to traditional XIAOYAO WAN 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 on climacteric syndrome, all having good effect.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 representes+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
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, and obtains the I that filtrates, the I simmer down to thick paste of will filtrating; 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 volatile matter with six parts of filtrate II I of above merging, adds adjuvant system granule, dries, and tabletting is processed the about 20Kg of tablet.
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 the I that filtrates, and the I simmer down to thick paste of will filtrating adds 4 times of amount 80% ethanol precipitations 24 hours in thick paste, filter, 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.
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 the I that filtrates, and the I simmer down to thick paste of will filtrating adds 3 times of amount 95% ethanol precipitations 24 hours in thick paste, filter, 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.
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 the I that filtrates, and totally six kinds, with every kind of filtrating 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 volatile matter with six parts of filtrate II I of above merging, adds adjuvant system granule, dries, and tabletting is processed 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 processed 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, adds 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, with spectrophotometer in the 490nm wavelength; 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 the I that filtrates, and the I simmer down to thick paste of will filtrating 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 processed 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 dose groups of blank control group (C), positive controls (fluoxetine P) and pharmaceutical composition of the present invention, each organizes dosage and positive drug fluoxetine dosage is seen table 1 again, and the supplement scale is seen table 1.
Table 1 dosage table
The oral commensurability aqueous solution 0.1mL/10g of blank control 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 through photography playback track identification statistics mice stand number of times and active path length, thereby judges that the independent activity of animals ability is strong and weak.Test between 9:00-17:00, in the quiet special-purpose laboratory of 25 ℃ of room temperatures, carry out, 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 the influence of spontaneous activity in mice amount such as Fig. 6, Fig. 7, shown in Figure 8.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 all is lower than the blank group with the number of times downward trend of standing; Total distance has been compared significant difference with the number of times of standing with blank control group; Explain 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 with the movable total distance of blank group, pharmaceutical composition high dose of the present invention (P < 0.01), middle dosage (P 0.05) the remarkable meaning of tool.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 the trend of rising respectively after 30 minutes and 40 minutes; Explain 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 high, medium and low dose groups of blank control group (C), positive controls (P) and pharmaceutical composition of the present invention.Blank control group is given distilled water 0.1mL/10g.Continuous 5 days gastric infusions before the experiment made an experiment 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 that the height of pharmaceutical composition of the present invention, middle dosage all can significantly increase the runner rotation (P < 0.01); 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 control group (C), positive controls (P) and the high, medium and low dose groups of pharmaceutical composition of the present invention.Blank control 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 that with this tablet is strong and weak to the depressed inhibition of mice.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, can find out; Compare with blank control 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 demonstration drug action (43.8 ± 12.57 vss 25.20 ± 7.49s, 33.2 ± 7.58 vss 25.20 ± 7.49s) suitable with fluoxetine.
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 the high, medium and low dose groups that normal control group, fasting are prohibited water matched group, Stress model group, positive drug group (P), blank control group (C) and pharmaceutical composition of the present invention.Blank control 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 receives 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 the 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 subsequent use 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 representes+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 representes the graph of a relation between various dose group and the rotating cage rat monoamine neurotransmitter amount content, compares #p with matched group<0.05; 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.Experimental result by Figure 13 can be found out; 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 is prohibited water group rat monoamine neurotransmitters a little less than blank control group, but no difference of science of statistics.With stress compare by load model group rat; Give fluoxetine and can significantly improve the neurotransmitter downward trend (NE:20.96 ± 5.46 vs 14.21 ± 5.71 that stress load and cause; 5-HT:217.49 ± 17.37 vs 182.28 ± 25.26); The DA level does not show significant difference, but still shows certain improvement trend (66.76 ± 7.17 vs53.87 ± 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 through improving the partial nerve mediator, show the good drug effect of antidepressant.In addition, each organizes the blood plasma neurotransmitter downward trend that all stress cause rotating cage has improvement effect in various degree.
To sum up, through the mensuration to the blood plasma neurotransmitter, we find, prohibit the water group with blank control 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 dose groups of extract descends and is showing the improvement effect in varying degrees.
Claims (12)
1. pharmaceutical composition that prevents and/or treats depression and climacteric syndrome; This pharmaceutical composition is in 1 weight portion; Effective ingredient is 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, and said pharmaceutical composition makes through the method that 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;
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 the I that filtrates, the I simmer down to thick paste of will filtrating adds ethanol in described 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 processed described pharmaceutical composition.
2. pharmaceutical composition according to claim 1, wherein said pharmaceutical composition comprises Radix Bupleuri total saponin, peoniflorin and polysaccharide.
3. pharmaceutical composition according to claim 2, wherein said Radix Bupleuri total saponin comprises saikoside a and saikoside d.
4. pharmaceutical composition according to claim 3 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.
5. pharmaceutical composition according to claim 2, wherein said polysaccharide comprises one or more in Radix Angelicae Sinensis polysaccharide, Radix Paeoniae Alba polysaccharides, Rhizoma Atractylodis polysaccharide, pachyman and the Angelica Polysaccharide.
6. according to each described pharmaceutical composition in the claim 1 to 5, wherein in described step a, soaked at ambient temperature said Chinese crude drug 10-60 minute with Chinese crude drug weight 5-10 water doubly.
7. according to each described pharmaceutical composition in the claim 1 to 5, 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 pharmaceutical composition in the claim 1 to 5; Wherein in described step c; Described decoction liquor is at room temperature filtered, and obtains the I that filtrates, the I simmer down to thick paste of will filtrating; At room temperature, the ethanol that in described thick paste, adds thick paste volume 2-6 70-100% concentration doubly.
9. according to each described pharmaceutical composition in the claim 1 to 5, wherein in described step f, said fine powder is the 80-300 order.
10. according to each described pharmaceutical composition in the claim 1 to 5, wherein the dosage form of this pharmaceutical composition is tablet, capsule, pill or granule.
11. pharmaceutical composition according to claim 10 is characterized in that, described pill is the watered pill, honeyed pill or concentrated pill.
12. pharmaceutical composition according to claim 10 is characterized in that, described pill is a drop pill.
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| CN103751318B (en) * | 2014-01-20 | 2015-05-27 | 于建梅 | Traditional Chinese medicinal composition for treating insomnia caused by lack of spirit preservation |
| 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 |
| CN107625813A (en) * | 2017-10-12 | 2018-01-26 | 山西大学 | A kind of Chinese medical extract with antidepression effect and its preparation method and application |
| 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 |
| CN110655593B (en) * | 2019-11-12 | 2021-08-31 | 东北师范大学 | Mint polysaccharide composition and preparation method and application 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 |
| CN114949150B (en) * | 2022-07-27 | 2022-11-04 | 广州科犁医学研究有限公司 | Pharmaceutical composition for treating perimenopausal syndrome and preparation method and application thereof |
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| 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 |
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| Title |
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| 宝丽等.逍遥丸对小鼠行为绝望和应激性抑郁的影响.《中药材》.2008,第31卷(第9期),第1360-1364页. * |
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