CN1233384C - Chinese medicine compound preparation for treating depression - Google Patents
Chinese medicine compound preparation for treating depression Download PDFInfo
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- CN1233384C CN1233384C CN 03153997 CN03153997A CN1233384C CN 1233384 C CN1233384 C CN 1233384C CN 03153997 CN03153997 CN 03153997 CN 03153997 A CN03153997 A CN 03153997A CN 1233384 C CN1233384 C CN 1233384C
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Abstract
The present invention relates to a Chinese medicine compound preparation for treating tristimania, which belongs to a Chinese patent medicine for treating tristimania prepared from common anemarrhena rhizome, epimedium herb and ginseng as raw materials. The Chinese patent medicine has the epimedium herb and the common anemarrhena rhizome as principal medicines; the Chinese patent medicine has the ginseng as a ministerial medicine; the Chinese patent medicine has a water extract or an alcohol extract as an active ingredient; the medicines are prepared into a capsule, a tablet, a granule, etc. The three medicines are combined with each other and has the advantages of replenishing and restoring qi and yin, nourishing heart spirit and maintaining the functional activities of the spleen manifesting in normal transformation and transportation, so that tristimania is eliminated. Pharmacological study on the effective fractions extracted from the formula indicates that the preparation has specially inhibiting effect on a plurality of depression models; moreover, the preparation can obviously raise the levels of 5-hydroxytryptamine and dopa and resist monoamine transmitter exhaustion caused by reserpine.
Description
Technical field
The present invention relates to a kind of Chinese traditional compound medicine and preparation technology thereof who treats depression, is the Chinese patent medicine of raw material according to specific prepared with the Rhizoma Anemarrhenae, Herba Epimedii and Radix Ginseng specifically, belongs to the field of Chinese medicines.
Background technology
Depression is a kind of with persistent depressed state, companion's anxiety, body discomfort, and sleep disorder is the neurosis of main performance.Along with the aging and the ever-increasing social pressure of society, the sickness rate of depression raises year by year, and a epidemiological study of the U.S. shows has 15% people depressive symptom (Blazer to occur in the community, D., Burcherr, B., Service, C., George, L.K.The association of age and depression aming the elderly:an epidemiologic exploration.J.Gerontol, 1991,46,210-215).The portion research in Europe has drawn identical conclusion (Dufouil, C., Dartigues, J.F., Fuhrer, R.Smptomes depressifs chez les personnes agees:conparisonentre des populations rurales et urbaines.Rev.Epidemiol.Sante Publique, 1995,43,308-315).Increasing in recent years research data shows the sickness rate of China's depression and prescription on individual diagnosis rate (yellow open-birth, Lu Lin, Sun Xueli etc. in rising trend.The dysthymic disorder of general practice mechanism research.West China medical science, 1998,13 (1): 11-13).Since the nearly more than ten years, the research and development of antidepressants is very fast, and many novel antidepressants emerge in an endless stream.At first the antidepressants of Fa Xianing are the oxidase inhibitor of the exploitation fifties, are tricyclic antidepressant after a while, and the latter is still the main clinical medication so far.After above-mentioned two class medicines, Fourth Ring class antidepressants have been developed again.Second filial generation tricyclic antidepressants medicine after the eighties, especially the development of 5-hydroxy tryptamine uptake inhibitor rapidly.According to the difference of chemical constitution, antidepressants roughly are divided three classes: tricyclic antidepressants, heterocyclic antidepressant, oxidase inhibitor etc.Depression belongs to chronic disease, and the Western medicine majority has side effect or addiction, takes above-mentioned antidepressants for a long time, not only incurs great expense, and has also brought great toxicity to the patient.
Still not having special antidepressant Chinese medicine at present and come out, and the clinical accumulation over the past thousands of years of motherland's medical science, have manyly to the effective side's medicine of depression, with its research and develop, has been inevitable.
Depression is the strongly fragrant impairment of the spleen of a specified duration, and diet reduces, biochemical weary source, disharmony between QI and blood then, deficiency of heart-blood, asthenia of both the spleen and kidney; The easy impairment of YIN blood of strongly fragrant fire-transformation of a specified duration involves in kidney, and causes all damages.It is then depressed that depression injures heart spleen, the kind worry of thinking much, and the speech action reduces, and is depressed.The heart is become homeless to support and is seen that then cardiopalmus is timid, and little sleep disturbed by dreams is forgetful.Insufficiency of vital energy and blood can not moisten and support in face, lustreless complexion, dizziness and fatigue.Insufficiency of the spleen insufficiency of vital energy and blood, lack of appetite fatigue and weakness, sight sluggishness.Strongly fragrantly undermine the moon for a long time or see vexedly, deficiency of spleen-YANG and kidneyYANG is then seen aversion to cold and cold limbs, the abdominal distention loose stool.Pale tongue, tongue is white, and thready and weak pulse is the performance of insufficiency of vital energy and blood.So control with supplementing QI and nourishing YIN, tonifying speen and tonifying kidney nourishes heart.
Summary of the invention
The purpose of this invention is to provide and a kind ofly can treat Chinese traditional compound medicine of depression and preparation method thereof.
The present invention is a kind of Chinese traditional compound medicine for the treatment of depression, it is characterized in that it is made as active component raw material by the water or the ethanol extraction of following component or following component:
The Rhizoma Anemarrhenae 1400～2400 weight portions
Herba Epimedii 500～1200 weight portions
Radix Ginseng 100～500 weight portions
The weight optimum ratio of raw material of the present invention is:
The Rhizoma Anemarrhenae 1600～2000 weight portions
Herba Epimedii 700～1000 weight portions
Radix Ginseng 200～400 weight portions
The best proportioning of the weight of raw material of the present invention is:
The Rhizoma Anemarrhenae 1800 weight portions
Herba Epimedii 900 weight portions
Radix Ginseng 300 weight portions
The Chinese traditional compound medicine of treatment depression provided by the invention is characterized in that this Chinese traditional compound medicine contains total flavones in icariin (C33H40015), and content is 15.0%～60.0%, and icariin content is 0.13%～3.04%; Contain total saponins in ginsenoside Re (C48H82018), content is 8.0%～30.0%, and Sarsasapogenin content is 0.30%～7.41%.
The said Rhizoma Anemarrhenae is the dry rhizome of liliaceous plant Rhizoma Anemarrhenae Anemarrhena asphodeloides Bge. among the present invention.Herba Epimedii is the dry aerial parts of Berberidaceae plant Herba Epimedii Epimedium brevicornum Maxim..Radix Ginseng is the dry root of Araliaceae Radix Ginseng Panax ginseng C..Above-mentioned whole component is all on the books in one one of Pharmacopoeia of People's Republic of China version in 2000.
Above-mentioned raw material can be prepared into various conventional formulations according to the practice of pharmacy of routine, for example, and capsule, tablet, granule, pill, oral liquid, powder, sublimed preparation, unguentum etc.
The present invention also provides a kind of preparation method of Chinese traditional compound medicine of above-mentioned treatment depression, and this method comprises the steps:
(1) at first choosing following traditional Chinese medicines is raw material:
The Rhizoma Anemarrhenae 1400～2400 weight portions
Herba Epimedii 500～1200 weight portions
Radix Ginseng 100～500 weight portions
(2) with above-mentioned three flavor raw materials, add entry or ethanol, preferred solvent is 70% ethanol; Heating and refluxing extraction 3～6 times, preferred 5 times; 6～10 times of quantity of solvent, preferred 8 times of amounts; Each 1.5～2.5 hours, preferred 2 hours; Extracting solution filters, and reclaims ethanol and is concentrated into the concentration that every 1ml contains crude drug amount 0.5g, [relative density is about 1.00～1.20 (20 ℃)], sucking filtration;
(3) filtrate is used the water elution of 6～10 times of amounts of resin volume earlier by treated macroporous adsorbent resin, preferred 8 times of amounts, and water liquid discards; 95% ethanol elution of 3～5 times of amounts of reuse resin column volume, preferred 4 times of amounts; The decompression recycling ethanol eluent, vacuum drying is pulverized, as the crude drug of compound preparation;
(4) crude drug is encapsulated, tabletting, system granule or make the other drug dosage form, for example capsule, tablet, granule, pill, oral liquid, powder, sublimed preparation or unguentum etc.
The present invention has the function that supplementing QI and nourishing YIN, tonifying speen and tonifying kidney nourish heart.Cure mainly depression due to deficiency of both vital energy and Yin, the deficiency of both the heart and spleen.Disease is seen depressed, the kind worry of thinking much, and the speech action reduces, and is depressed.Cardiopalmus is timid, and little sleep disturbed by dreams is forgetful, lustreless complexion, and dizziness and fatigue, the lack of appetite fatigue and weakness, the sight sluggishness, or vexed, or aversion to cold and cold limbs, or the abdominal distention loose stool, pale tongue, tongue is white, thready and weak pulse.
Be monarch drug with Herba Epimedii, the Rhizoma Anemarrhenae in the side, with the QI invigorating nourishing YIN, the QI and blood foot, heart spleen kidney must be supported, and is in high spirits, emotional health.Herba Epimedii Xin Ganwen returns the Liver and kidney warp.Have kidney invigorating and YANG supporting, the effect of expelling wind and removing dampness (is insulted a principle.High medical college teaching material.Chinese materia medica.The 1st edition.Shanghai science tech publishing house.1986：221，34：209)。The essentials of Matea Medica meaning: Herba Epimedii " is mended the gate of vitality, beneficial vital essence, hard muscles and bones, diuresis ".Shennong's Herbal meaning: Herba Epimedii " physical strength profiting, strong will "." Japan hanako materia medica " meaning: the Herba Epimedii master " the exhausted positive loss of fecundity of husband, the exhausted cloudy loss of fecundity of woman, old man's dusk octogenarian, middle institute is forgetful, all cold wind consumptive disease, the muscles and bones contraction is anxious, extremity are meciless, mend the waist knee joint, heart tonifying power ".Modern pharmacological research shows that Herba Epimedii has the ability (Guo Jun of obvious enhancing mice anoxia enduring.China's diseases prevention magazine, 1964,5 (3): 481), can obviously improve the effect (Liu Baoqing of adrenal cortex function.Chinese herbal medicine, 1980,11 (5): 201).Strengthen hypothalamo-pituitary-adrenal axis, the hormonal system function (LiBing Ru of gonad axis and thymus axle.Journal of Traditional Chinese Medicine, 1984, (7), 543).
The Rhizoma Anemarrhenae is bitter sweet cold, returns lung stomach kidney channel.Has clearing away heat-fire, nourishing yin and moistening dryness.Compendium of Material Medica meaning: the Rhizoma Anemarrhenae " the dry and YIN nourishing of next profit kidney, on then lung heat clearing gold and pathogenic fire purging "." Japan hanako materia medica " meaning: the Rhizoma Anemarrhenae " the profit cardiopulmonary, tonify deficiency is weary, the spasmolytic of feeling at ease is throbbed with fear ".Pharmacological research shows that the Rhizoma Anemarrhenae can make the B-adrenoceptor maximum combined number of sites that increases reduce, and M-cholinoceptor maximum combined site is increased, thereby adjust their mutual relation, makes cell function obtain correcting (Yi Ningyu unusually.Pharmacology and Clinics of Chinese Materia Medica, 1991,6 (3): 12).The plasma corticosterone determining alcohol that suppressed by dexamethasone is raise, and the effect (Chen Ruiqun that prevents atrophy of adrenal gland is arranged.The Shanghai first medical college journal, 1979, (6): 393).Experiment in vitro shows that the Rhizoma Anemarrhenae can weaken corticosterone C
4=5Two strong opening are reduced and C
17, 20-hydroxyl and C
20The variation of ketone group.Owing to protected hydrocortisone A ring C
4=5Two keys and C
3Ketone group is not reduced and side connects C
17And C
20Hydroxyl, ketone group are avoided degraded, therefore can delay the catabolism (Zhang Lili of hepatocyte to hydrocortisone.The Shanghai first medical college journal.1980，(1)，37)。N receptor in the old and feeble rat brain of increase of timosaponin energy dose dependent promotes ability of learning and memory (Wang Shunguan.Timosaponin is to old and feeble rat nootropic effect Study on Mechanism.Modern combination of Chinese and Western medicine magazine, 2000,9 (18): 1755-6).In the time of yin nourishing, has certain heat clearing away effect again, to restrict deficiency-heat because of strongly fragrant impairment of YIN of a specified duration was occurred.
Radix Ginseng is a minister in the side, helps Herba Epimedii with QI invigorating first, goes the merit of spleen invigorating first, and spleen is strong transports then QI and blood abundance, and the mind must be supported, and all diseases are treated.Radix Ginseng has again to calm the nerves and increases the intelligence effect in addition, is used for insufficiency of vital energy and blood, irritability, memory loss dreaminess, palpitation and amnesia etc. more.Radix Ginseng sweetness and bitterness tepor is returned the spleen lung meridian.Have big benefit depletion of QI, invigorating the spleen to benefit the lung, promoting the production of body fluid to quench thirst, calming the nerves increases the effect of intelligence.Shennong's Herbal: the Radix Ginseng tonifying five ZANG-organs, peace spirit is decided soul, and spasmolytic is throbbed with fear, and removes pathogen, makes eye bright, happy Fructus Alpiniae Oxyphyllae.The sweet temperature of " medication on the analogy of natural things " Radix Ginseng, can tonifying the lung in vigour, the prosperous then four dirty gas of lung qi are all prosperous, smart spontaneous and shape is from containing.Pharmacological research shows that Radix Ginseng has pharmacologically active widely, except adjusting the nervus centralis activity, promote outside the learning and memory, still can strengthen cholinergic systemic-function in the brain, the interior 5-HT of inhibition brain is ingested in the big brain synaptosome, thereby 5-HT content (SangD et al.Planta Med.1986, (4): 226 in the increase synaptic space; Wang Benxiang.Acta Pharmaceutica Sinica.1980，15(5)：312)。The ginsenoside has the secreting active effect of the adrenocortical hormone of increasing.Its site of action is (Zong Ruiyi etc. more than the hypophysis level.Norman Bethune Medical University's journal.1985，11(3)：254)。Radix Ginseng also has resisting fatigue in addition, anti-stress, the effect of defying age and enhance immunity.
Above-mentioned three medicines share, and gas the moon must be mended, and the mind must be supported, the strong fortune of temper.Then depression is eliminated.The effective part group pharmacological research that this side is extracted shows that this medicine all has inhibitory action specifically to multiple depression model, and 5-hydroxy tryptamine and DOPA level in the depressed animal brain that can significantly raise, and monoamine transmitters is exhausted due to the antagonism reserpine.
The specific embodiment
Embodiment 1
Prescription is formed:
Rhizoma Anemarrhenae 1400g
Herba Epimedii 500g
Radix Ginseng 100g
Preparation technology:
Raw material in the above-mentioned prescription adds 6 times of amount 95% ethanol, heating and refluxing extraction 3 times, each 1.5 hours.3 extracting solution are merged, decompression recycling ethanol and to be concentrated into liquor strength be 0.5g crude drug/mL, behind the sucking filtration, the relative density of filtrate is about 1.10 (20 ℃).Above-mentioned filtrate is the macroporous adsorptive resins of 10L through volume, and with the deionized water or the distilled water eluting of 6 times of resin column volumes, 95% ethanol elution of 3 times of resin column volumes of reuse is collected ethanol elution, removes solvent, obtains crude drug earlier.Incapsulate and promptly get capsule of the present invention.Every capsules dress 0.2g.
In the crude drug, contain total flavones with icariin (C
33H
40O
15) meter, content is 25.7%, and icariin content is 1.21%; Contain total saponins with ginsenoside Re (C
48H
82O
18) meter, content is 10.3%, and Sarsasapogenin content is 2.53%.
Embodiment 2
Prescription is formed:
Rhizoma Anemarrhenae 2400g
Herba Epimedii 1200g
Radix Ginseng 500g
Preparation technology:
Raw material in the above-mentioned prescription adds 10 times of water gagings, heating and refluxing extraction 6 times, each 2.5 hours.6 extracting solution are merged, decompression recycling ethanol and to be concentrated into liquor strength be 0.5g crude drug/mL, behind the sucking filtration, the relative density of filtrate is about 1.10 (20 ℃).Above-mentioned filtrate is the macroporous adsorptive resins of 10L through volume, and with the deionized water or the distilled water eluting of 10 times of resin column volumes, 95% ethanol elution of 5 times of resin column volumes of reuse is collected ethanol elution, removes solvent, obtains crude drug earlier.Incapsulate and promptly get capsule of the present invention.Every capsules dress 0.2g.
In the crude drug, contain total flavones with icariin (C
33H
40O
15) meter, content is 14.8%, and icariin content is 0.69%; Contain total saponins with ginsenoside Re (C
48H
82O
18) meter, content is 17.1%, and Sarsasapogenin content is 4.16%.
Embodiment 3
Prescription is formed:
Rhizoma Anemarrhenae 1800g
Herba Epimedii 900g
Radix Ginseng 300g
Preparation technology
Raw material in the above-mentioned prescription adds 8 times of amount 70% ethanol, heating and refluxing extraction 5 times, each 2 hours.5 extracting solution are merged, decompression recycling ethanol and to be concentrated into liquor strength be 0.5g crude drug/mL, behind the sucking filtration, the relative density of filtrate is about 1.10 (20 ℃).Above-mentioned filtrate is the macroporous adsorptive resins of 10L through volume, and with the deionized water or the distilled water eluting of 8 times of resin column volumes, 95% ethanol elution of 4 times of resin column volumes of reuse is collected ethanol elution, removes solvent, obtains crude drug earlier.Incapsulate and promptly get capsule of the present invention.Every capsules dress 0.2g.
In the crude drug, contain total flavones with icariin (C
33H
40O
15) meter, content is 34.0%, and icariin content is 1.60%; Contain total saponins with ginsenoside Re (C
48H
82O
18) meter, content is 16.0%, and Sarsasapogenin content is 3.90%.
Content assaying method:
(1) assay method of total flavones:
The preparation of reference substance solution: it is an amount of that precision takes by weighing the icariin reference substance, adds methanol and make every 1ml and contain 1.0mg solution approximately, in contrast product solution.
The preparation of standard curve: accurate icariin reference substance solution 0.2,0.4,0.6,0.8, the 1.0ml of drawing, place the 25ml measuring bottle respectively, add methanol and be diluted to scale, shake up.With methanol is blank, according to spectrophotography (an appendix V of Chinese Pharmacopoeia version in 2000 B), measures trap at 318nm wavelength place, is vertical coordinate with the trap, and concentration is abscissa, the drawing standard curve.
Algoscopy: get crude drug 50mg of the present invention, after accurate title is fixed, put in the 25ml measuring bottle, add absolute methanol 20ml, supersound process 30 minutes is taken out, add methanol constant volume to scale, 25 times of redilution (the accurate 1ml that draws places the 25ml measuring bottle, adds methanol constant volume to scale), the method under the sighting target directrix curve preparation, measure trap, read content Determination of Icariin the need testing solution from standard curve, calculate, promptly.
(2) assay method of total saponins:
The preparation of reference substance solution: precision takes by weighing ginsenoside R
eReference substance is an amount of, adds methanol and makes every 1ml and contain 0.1mg solution, in contrast product solution.
The preparation of standard curve: the accurate ginsenoside R that draws
eReference substance solution 0.4,0.8,1.2,1.6,2.0ml, place test tube respectively, water bath method, add 5% vanillin glacial acetic acid solution (get vanillin 0.5g, a little makes dissolving to add glacial acetic acid, adds glacial acetic acid again to 100ml) 0.5ml, add 70% sulfuric acid solution and (measure water 30ml, slowly add concentrated sulphuric acid 70ml, use the cooling back) 5ml, place 60 ℃ of water-bath heating 15 minutes, take out, in ice-water bath cooling 10 minutes, placed 10 minutes under the room temperature, be blank to make blank solution with method, according to spectrophotography (an appendix V of Chinese Pharmacopoeia version in 2000 B), measuring trap at 544nm wavelength place, is vertical coordinate with the trap, ginsenoside R
eAmount be abscissa, the drawing standard curve.Algoscopy: get crude drug 50mg of the present invention, the accurate title, decide, and places the 50ml measuring bottle, it is an amount of to add dehydrated alcohol, supersound extraction 30 minutes, and taking-up adds dehydrated alcohol to scale, shake up, filter, precision is measured subsequent filtrate 35ml, add Silon 0.4g, mix thoroughly, put volatilize solvent in the water-bath after, add and be equipped with in the chromatographic column of Silon 0.7g, the water eluting is collected the about 300ml of eluent, water bath method, residue adds dissolve with methanol, move in the 25ml measuring bottle, add methanol, the accurate 0.3ml that draws to scale, place test tube, water bath method, the method under the sighting target directrix curve preparation is from " adding 5% vanillin glacial acetic acid solution 0.5ml ", measure trap in accordance with the law, read the content of ginsenoside Re the need testing solution from standard curve, calculate, promptly.
(3) assay method of icariin:
Measure according to high performance liquid chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 D).
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler.Acetonitrile-water (30: 70) is a mobile phase; The detection wavelength is 270nm; 30 ℃ of column temperatures.Number of theoretical plate calculates by the icariin peak should be not less than 1500.The preparation of reference substance solution: it is an amount of that precision takes by weighing the icariin reference substance, adds methanol and make the solution that every 1ml contains 0.15mg, promptly.
The preparation of need testing solution: get the about 200mg of this product, the accurate title, decide, and puts in the 25ml measuring bottle, adds the about 20ml of methanol, and supersound extraction 40 minutes is taken out, and adds methanol to scale, shakes up, and with microporous filter membrane (0.45 μ m) filtration, gets subsequent filtrate, promptly.
Algoscopy: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, promptly.
(4) assay method of Sarsasapogenin
Measure according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000).
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler.Methanol is mobile phase; Detect with differential detector (2410 types, Waters company produces); 30 ℃ of column temperatures.Number of theoretical plate calculates by the Sarsasapogenin peak should be not less than 2000.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the Sarsasapogenin reference substance, adds methanol and make the solution that every 1ml contains 1.0mg, promptly.
The preparation of need testing solution: get the about 250mg of crude drug of the present invention, the accurate title, decide, and puts in the 25ml measuring bottle, adds the about 20ml of methanol, and supersound extraction 40 minutes is taken out, and adds methanol to scale.Filter, precision is measured subsequent filtrate 20ml, adds hydrochloric acid 1ml, put in the water-bath and slowly refluxed 1.0 hours, add water 15ml, reclaim methanol to there not being the alcohol flavor, add chloroform 20ml, extraction, totally 4 times, combining extraction liquid reclaims chloroform, the residue dissolve with methanol, be transferred in the measuring bottle of 10ml, add methanol, filter with microporous filter membrane (0.45 μ m) to scale, get filtrate, promptly.
Algoscopy: get each 5 μ l of reference substance solution and need testing solution, inject chromatograph of liquid respectively, measure, promptly.
Zoopery example 1: to the therapeutical effect of mice depression model
Observe the therapeutical effect of capsule of the present invention to the mice depression model.Capsule 0.243g/ grain of the present invention, lot number: 010802, the time spent is assigned to desired concn with distilled water.Other reagent chemicals has the reserpine injection, 1mg/mL, and lot number: 20000401, pharmaceutical Co. Ltd of Shanghai Medical Univ produces.
Experimental animal male KM mice, non-inbred line closed colony, body weight (21.50 ± 1.0) g, totally 60.Qualified disease number is provided by Inst. of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine (: the moving pipe in capital is betrothed to No. 038.18-22 ℃ of laboratory room temperature, relative humidity 40%～60%, the ventilation fan ventilation, lamp 12h/ day, raise in cages, 10 in every cage, per three days cleaning cage houses are once.
Get mice and be divided into 5 groups at random, 12 every group, test the 1st day every Mus and hang tail test and mandatory swimming test in advance, to induce depression model.In inductive the 2nd day beginning gastric infusion, 1h measured the mice autonomic activities behind the 1st medicine, repeated outstanding tail and swimming test then, continuously 7d.After experiment finished, every Mus subcutaneous injection of reserpine injection (3mg/kg) gave relative medicine simultaneously, measured dead mouse number in sagging, akinetic animal number in upper eyelid and the 7d behind the 1.5h respectively.
[observation index and testing time]
1. mice autonomic activities: cross-line number in the observation 5min (a rice word line is as the criterion), uprightly probe into number (lift be as the criterion with mice two forelimbs) and the two ratio.
2. mouse tail suspension test: the position of mice tail end 2cm is fixed with wooden clamp, hung by the feet in 12 * 27 * 27 (cm) case, its head is about 5cm from the bottom surface, hangs 6min, writes down thereafter and accumulates the dead time in the 4min.
3. the mandatory swimming test of mice: mice is put into high 20cm, in the column type glass jar of diameter 12cm, depth of water 12cm, 25 ℃ of water temperatures are observed 6min, write down thereafter the accumulation dead time in the 4min.Dead time is meant that mice stops to struggle in water, or is floating state, and the persistent period of tiny limb motion to keep head to keep afloat only arranged.
4. the flat antagonistic effect of blood:
4.1 the ptosis: observe closed at least half the animal number of 30sec palpebra interna.
4.2 motion can not: with the circular blank sheet of paper central authorities that mice is put into diameter 7.5cm, observe the animal number that still stays in the 15sec in the circle.
Determine following dosage regimen through prerun, capsule 600,300 of the present invention, 150mg/kg are equivalent to 30.8,15.4,7.7 times of people's consumption (19.44mg/kg) respectively.Paroxetine hydrochloride 4.67mg/kg is the clinical equivalent amount.Give mice oral administration gavage, 0.2mL/10g respectively.
The blank of this test is a distilled water, and the positive drug contrast is paroxetine hydrochloride sheet (paroxetine), the 20mg/ sheet, and it is a kind of antidepressants, can treat various types of depressions.Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product, lot number: 01020455, authentication code: (95) are defended the accurate word J-50 of medicine number.
This test data is all with the EXCEL software processes.
Table 1: capsule of the present invention is to the influence of mice autonomic activities (x ± s)
| Group | Dosage mg/kg | Probe into time for several times/5 minutes | Cross-line time several/5 minutes | Probe into/cross-line |
| Matched group | 20.25±16.71 | 48.75±18.91 | 0.37±0.22 | |
| Paroxetine | 4.67 | 21.33±18.02 | 54±19.99 | 0.36±0.23 |
| The present invention | 150 | 23.33±17.70 | 50.83±28.21 | 0.44±0.27 |
| The present invention | 300 | 20.67±14.30 | 47.5±23.11 | 0.42±0.42 |
| The present invention | 600 | 17.5±15.89 | 39±20.09 | 0.35±0.24 |
Compare P＞0.05 with matched group.n＝12
Table 2: capsule of the present invention is to the influence of mouse tail suspension dead time (x ± s)
| Group | Dosage mg/kg | The accumulation dead time (s) | ||||||
| Before the administration | The 1st day | The 2nd day | The 3rd day | The 4th day | The 5th day | The 6th day | ||
| The present invention of the present invention of matched group paroxetine | 4.67 150 300 600 | 113.07 ±5218 88.46 ±39.03 89.31 ±34.14 97.73 ±32.82 101.66 ±37.89 | 126.84 ±34.38 70.31 ±45.63 ** 98.98 ±44.35 97.26 ±36.98 105.96 ±36.28 | 122.12 ±34.02 69.07 ±26.81 ** 99.06 ±31.99 105.19 ±45.77 101.82 ±30.62 | 117.30 ±52.35 79.99 ±31.30 * 85.64 ±41.16 106.60 ±37.49 109.12 ±41.37 | 129.14 ±21.71 57.77 ±33.15 ** 106.66 ±43.11 103.56 ±47.05 96.23 ±37.26 * | 151.29 ±29.81 41.33 ±25.58 ** 101.58 ±27.04 ** 115.52 ±39.53 * 98.21 ±42.32 ** | 166.02 ±32.88 66.81 ±25.81 ** 107.10 ±31.08 ** 101.96 ±50.55 ** 91.61 ±38.85 ** |
Compare * P＜0.05 with matched group, * * P＜0.01.n＝12
Table 3: capsule of the present invention is to the influence of the mandatory swimming of mice (x ± s)
| Group | Dosage mg/k g | The accumulation dead time (s) | ||||||
| Before the administration | The 1st day | The 2nd day | The 3rd day | The 4th day | The 5th day | The 6th day | ||
| The present invention of the present invention of matched group paroxetine | 4.67 150 300 600 | 100.52 ±42.93 119.17 ±50.47 111.27 ±39.77 119.85 ±47.92 108.76 ±49.73 | 92.80 ±55.65 94.83 ±52.00 81.23 ±49.44 104.53 ±45.75 95.54 ±41.03 | 128.34 ±63.54 115.80 ±48.60 89.84 ±41.19 93.91 ±42.33 79.38 ±68.55 | 95.51 ±58.20 94.51 ±79.19 59.77 ±51.16 72.34 ±55.34 63.60 ±46.23 | 115.37 ±64.12 98.67 ±71.62 73.67 ±54.06 91.35 ±58.37 95.88 ±62.33 | 154.74 ±46.31 95.56 ±73.86 * 90.32 ±68.57 * 76.58 ±63.71 ** 67.55 ±50.29 ** | 142.67 ±57.51 71.19 ±53.54 ** 67.99 ±57.40 ** 69.76 ±52.12 ** 81.94 ±47.19 ** |
Compare * P＜0.05 with matched group, * * P＜0.01.n＝12
The influence that table 4 capsule of the present invention can not act on blepharoptosis, motion due to the reserpine (x ± s)
| Group | Dosage mg/kg | Blepharoptosis (only) | Antagonism percentage rate (%) | Motion can not (only) | Antagonism percentage rate (%) | Death toll (only) |
| The present invention of the present invention of matched group paroxetine | 4.67 150 300 600 | 12/12 6/12 9/12 7/12 5/12 | 0 50 ** 25 41.67 * 58.33 ** | 12/12 9/12 11/12 11/12 7/12 | 0 25 8.33 8.33 41.67 * | 1 0 2 0 1 |
x
2* * P＜0.01, * P＜0.05 are compared in check with matched group.n＝12
Experimental result shows that capsule of the present invention does not have obvious influence to the mice autonomic activities in the dosage range of being surveyed.After " behavior disappointment " modeling, capsule 150-600mg/kg of the present invention can make the dead time of mouse tail suspension dead time and mandatory swimming obviously reduce, and with matched group significant difference (p＜0.05 or p＜0.01) is arranged relatively.In the experiment of antagonism reserpine, along with capsule dosage of the present invention increases, blepharoptosis, akinetic animal number occur and also reduce thereupon, the antagonism rate reaches 25%, 41.67%, 58.33% respectively, through X
2Check has significant difference, explanation thus, and capsule of the present invention can resist reserpine and cause the mice blepharoptosis, and good dose-effect relationship is arranged.Therefore think that capsule of the present invention has certain antidepressant effect.Each administration treated animal death toll is compared with matched group in 7 days does not have obviously influence.
Zoopery example 2: the influence that 5-hydroxy tryptamine acid inducing mouse is got rid of monoamine neurotransmitter in a behavior and the brain
Observe capsule of the present invention the influence that mice gets rid of monoamine neurotransmitter in a behavior and the brain is brought out in 5-hydroxy tryptamine acid (5-HTP).Capsule 0.243g/ grain of the present invention, lot number: 010802, the time spent is assigned to desired concn with distilled water.Other reagent chemicals has 5-hydroxy tryptamine (5-HT), Sigma company, lot number: 67H0791; 5-hydroxyindoleacetic acid (5-HIAA), Sigma company, lot number: 26H0362; 5-hydroxy tryptamine acid (5-HTP), Sigma company, lot number: 89H0698; O-phthalaldehyde(OPA) (OPT), Beijing section Ward kind reagent joint development center produces, lot number: 981012; Sodium metaperiodate (A.R), the Beijing Chemical Plant produces, lot number: 840823; The L-cysteine, Kangda Amino-acid Factory of Shanghai's product, lot number: 940904; Restrain strongly fragrant (moclobemide tablet), the 0.1g/ sheet, Hunan Pharmaceutical Co product, lot number: 000611-1, this medicine are selectivity MAO-A inhibitor.All the other reagent are homemade analytical pure.Test apparatus be 850 type spectrofluorophotometers (HITACHI, Japan).
Experimental animal male KM mice, non-inbred line closed colony, body weight (22.38 ± 0.75) g, totally 60.Qualified disease number is provided by Inst. of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine (: the moving pipe in capital is betrothed to No. 038.18-20 ℃ of laboratory room temperature, relative humidity 50%～60%, the ventilation fan ventilation, lamp 12h/ day, raise in cages, 10 in every cage, per three days cleaning cage houses are once.
Get mice and be divided into 5 groups at random, 12 every group, give the corresponding dosage medicine 1 time every day, 3d continuously, the 4th day before test 1h filling stomach restrain strongly fragrant capsule (100mg/kg), irritate stomach then and be subjected to the reagent thing, dosage is the same.The positive drug paroxetine is to clinical equivalent amount (4.67mg/kg).Ip 5-HTP 20mg/kg again behind the 1h promptly begins to observe mice and gets rid of behind an incubation period and the injection 5-HTP the number of times that gets rid of in 25-35 minute after the injection.Experiment is put to death mice after finishing immediately, takes out brain rapidly, and-30 ℃ of refrigerators are preserved, with 5-HT, 5-HIAA content in the OPT condensation reaction fluorescence spectrophotometry cerebral tissue.
Determine following dosage regimen through prerun, capsule 600,300 of the present invention, 150mg/kg are equivalent to 30.8 of people's consumption (19.44mg/kg) respectively, 15.4,7.7 times, paroxetine hydrochloride 4.67mg/kg, be the clinical equivalent amount, give mice oral administration gavage, 0.2mL/10g respectively.
This experimental test index is 5-HT, the 5-HIAA mensuration in a number of times, the cerebral tissue of getting rid of in the mice 10min.
The blank of this test is a distilled water, and the positive drug contrast is paroxetine hydrochloride sheet (paroxetine), the 20mg/ sheet, and it is a kind of antidepressants, can treat various types of depressions.Sino-America Tianjin Shike Pharmaceutical Co., Ltd.'s product, lot number: 01020455, authentication code: (95) are defended the accurate word J-50 of medicine number.
This test data is all with the EXCEL software processes.
Table 5: capsule of the present invention to 5-hydroxy tryptamine acid bring out the influence that mice gets rid of a behavior (x ± s)
| Group | Dosage mg/kg | Get rid of an incubation period (min) | Get rid of a number of times (10min) |
| The present invention of the present invention of matched group paroxetine | 4.67 150 300 600 | 10.19±5.05 2.42±0.88 ** 8.42±3.62 7.41±2.08 6.86±2.12 * | 34±21.54 53.17±9.76 * 62.08±39.16 * 62.42±26.18 ** 64.83±26.18 ** |
Compare * P＜0.05, * * P＜0.01 with matched group.n＝12
Table 6: capsule of the present invention is penetrated the influence (x ± s) of product to 5-hydroxy tryptamine in the mouse brain and generation thereof
| Group | Dosage mg/kg | 5-HT (ng/g) | 5-HIAA (ng/g) | 5-HT/5-HIAA |
| The present invention of the present invention of matched group paroxetine | 4.67 150 300 600 | 5474.80±1903.58 8752.08±3691.50 * 5368.64±1346.30 8039.20±3722.64 * 9788.05±3403.23 ** | 453.12±271.25 351.55±142.55 340.75±141.39 465.55±308.72 451.46±90.77 | 16.01±11.08 30.14±19.95 * 19.05±11.41 26.52±28.37 22.43±8.80 |
Compare with matched group
*P＜0.05,
*P＜0.01.n＝12
5-hydroxy tryptamine acid is the precursor of 5-hydroxy tryptamine, under the prerequisite that monoamine oxidase, MAO is suppressed in brain, 5-hydroxy tryptamine content raises, gives 5-hydroxy tryptamine acid again, can increase 5-hydroxy tryptamine content in the brain, thereby the symptom of head occurs getting rid of.Therefore in drug research, the normal observation with this is subjected to the synergism of reagent thing to 5-hydroxy tryptamine acid.Experimental result shows, under the inducing of 5-hydroxy tryptamine acid, capsule administration group of the present invention is got rid of and is increased and shorten along with dosage an incubation period, getting rid of a number of times obviously increases, 5-hydroxy tryptamine content obviously raises in the brain, is certain dose-effect relationship, compares with matched group, difference highly significant (p＜0.05, p＜0.01).This shows that capsule of the present invention can be strengthened the inductive number of times that gets rid of of 5-hydroxy tryptamine acid, and play antidepressant effect by excited 5-hydroxy tryptamine nervous system.
Claims (8)
1. Chinese traditional compound medicine for the treatment of depression is characterized in that it is made as active component raw material by the water or the ethanol extraction of following component or following component:
The Rhizoma Anemarrhenae 1400～2400 weight portions;
Herba Epimedii 500～1200 weight portions;
Radix Ginseng 100～500 weight portions;
Described Chinese traditional compound medicine contains total flavones in icariin, and content is 15.0%～60.0%, and icariin content is 0.13%～3.04%; Contain total saponins in the ginsenoside Re, content is 8.0%～30.0%, and Sarsasapogenin content is 0.30%～7.41%.
2. Chinese traditional compound medicine according to claim 1 is characterized in that it is made as active component raw material by the water or the ethanol extraction of following component or following component:
The Rhizoma Anemarrhenae 1600～2000 weight portions
Herba Epimedii 700～1000 weight portions
Radix Ginseng 200～400 weight portions.
3. Chinese traditional compound medicine according to claim 1 is characterized in that it is made as active component raw material by the water or the ethanol extraction of following component or following component:
The Rhizoma Anemarrhenae 1800 weight portions;
Herba Epimedii 900 weight portions;
Radix Ginseng 300 weight portions.
4. according to the Chinese traditional compound medicine of claim 1,2 or 3 described treatment depressions, it is characterized in that: the pharmaceutical dosage form of described Chinese medicine preparation is any pharmaceutical dosage form in capsule, tablet, granule, pill, oral liquid, powder, sublimed preparation or the unguentum.
5. preparation method for the treatment of the Chinese traditional compound medicine of depression is characterized in that this method carries out as follows:
(1) at first choosing following traditional Chinese medicines is raw material:
The Rhizoma Anemarrhenae 1400～2400 weight portions;
Herba Epimedii 500～1200 weight portions;
Radix Ginseng 100～500 weight portions;
(2) with above-mentioned three flavor raw materials, add entry or ethanol, heating and refluxing extraction 3～6 times, 6～10 times of quantity of solvent, each 1.5～2.5 hours, extracting solution filtered, and reclaimed ethanol and was concentrated into the concentration that every 1ml contains crude drug amount 0.5g, sucking filtration;
(3) filtrate is used the water elution of 6～10 times of amounts of resin volume earlier by treated macroporous adsorbent resin, and water liquid discards, 95% ethanol elution of 3～5 times of amounts of reuse resin column volume, decompression recycling ethanol eluent, vacuum drying, pulverize, as the crude drug of compound preparation; Contain total flavones in icariin in the described crude drug, content is 15.0%～60.0%, and icariin content is 0.13%～3.04%; Contain total saponins in the ginsenoside Re, content is 8.0%～30.0%, and Sarsasapogenin content is 0.30%～7.41%;
(4) encapsulated, tabletting, system granule of crude drug or make pill, oral liquid, powder, sublimed preparation or unguentum.
6. preparation method according to claim 5 is characterized in that the weight proportion of raw material is:
The Rhizoma Anemarrhenae 1600～2000 weight portions;
Herba Epimedii 700～1000 weight portions;
Radix Ginseng 200～400 weight portions.
7. preparation method according to claim 5 is characterized in that the raw material weight proportioning is:
The Rhizoma Anemarrhenae 1800 weight portions;
Herba Epimedii 900 weight portions;
Radix Ginseng 300 weight portions.
8. according to claim 5,6 or 7 described preparation methoies, it is characterized in that: the alcohol heating reflux of use 70% extracts 5 times in the described step (2), 8 times of quantity of solvent, and each 2 hours, extracting solution was concentrated into the concentration that every 1ml contains crude drug amount 0.5g; Filtrate is used the water elution of 8 times of amounts of resin volume earlier in the described step (3) when volume is the macroporous adsorbent resin of 10L, and water liquid discards, 95% ethanol elution of 4 times of amounts of reuse resin column volume.
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| CN104189409A (en) * | 2014-07-30 | 2014-12-10 | 严中明 | Traditional Chinese medicine for treating idiopathic pulmonary fibrosis (IPF) |
| CN105535007A (en) * | 2016-02-05 | 2016-05-04 | 首都医科大学宣武医院 | Application of icariin and derivatives thereof for preventing and treating psychonosema |
| CN106963868A (en) * | 2016-11-09 | 2017-07-21 | 江苏金氏丹科技有限公司 | A kind of strengthen immunity Chinese medicine composition |
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