CN101670075B - Traditional Chinese medicine composition for treating depression - Google Patents
Traditional Chinese medicine composition for treating depression Download PDFInfo
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- CN101670075B CN101670075B CN2009102363282A CN200910236328A CN101670075B CN 101670075 B CN101670075 B CN 101670075B CN 2009102363282 A CN2009102363282 A CN 2009102363282A CN 200910236328 A CN200910236328 A CN 200910236328A CN 101670075 B CN101670075 B CN 101670075B
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Abstract
The invention discloses a traditional Chinese medicine composition for treating depression, which comprises the following bulk drugs in parts by weight: 500 to 2500 parts of radix paeoniae alba, 50 to 250 parts of acorus gramineus, 125 to 625 parts of bighead atractylodes rhizome, 125 to 625 parts of Chinese angelica, 75 to 375 parts of white mustard seed, 125 to 625 parts of tuckahoe, 25 to 125 parts of radix curcumae and 25 to 125 parts of polygala root. The traditional Chinese medicine composition has the effects of soothing the liver, strengthening the spleen, removing phlegm and relieving depression, and can be used for patients with liver depression and spleen deficiency discriminated by depression in the traditional Chinese medicine; and the traditional Chinese medicine composition not only can be used together with western medicines, but also can be used singly.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition, particularly relate to a kind of Chinese medicine composition that is used for the treatment of depression.
Background technology
Depression is a kind of commonly encountered diseases frequently-occurring disease, mainly show as feel depressed, energy goes down, pessimism, mild depression be oneself feel that mood is low, grievance, indifferent to, appetite descends and insomnia, is reluctant activity, mental retardation, appearance be can't see obviously unusual mostly.Because this feel depressed and common people are running on the downhearted gloomy surface of short-term that bad mental stimulates the back to occur there is not what difference, allow many people depression be produced a period of time the illusion of " take things too hard or petty " easily.In fact, as long as one has depressive emotion to continue for two weeks or more than two weeks, simultaneously with any four in following nine symptoms, and depressive emotion do not cause by other disease, is exactly typical depression.Nine symptoms are: 1. hebetude or do not have happy sense; 2. energy goes down or continues tired; 3. movable the minimizing or the action sluggishness; 4. undue self-accusation or compunction; 5. association's difficulty or attention can not be concentrated; 6. idea of committing suicide repeatedly or behavior; 7. have a sleepless night or early awakening; 8. body weight reduces or appetite decline; 9. libido descends.
Tool WHO statistics, the depression sickness rate is 3-5%, some areas are up to more than 10%.In addition, many people do not remove hospital admission, and therefore, actual sickness rate may be higher.70% be that depression causes in the suicide according to statistics, in the U.S. because of the 10th of the depression suicide row cause of death.Along with the continuous aggravation of social change, competition is fierce more, and depression will be paid attention to by people's door more and more.According to " meeting of emotion disease " prediction 21 century of holding in Hong Kong in 1996 will be " depression century ".Therefore, good antidepressant drug will have vast market prospect.
The market of China's antidepressants also is huge, by conservative estimation 4-5 10,000,000 patients are arranged, and ill crowd has the gesture of quickening risings in recent years, and Western medicine such as fluoxetine and clomipramine are mainly used in present treatment that clinically should disease, still do not have this sick Chinese patent medicine of comparatively ideal treatment.
External antidepressant development generally is divided into: 1, central stimulants, and as uncommon propylamine.2, oxidase inhibitor is as moclobemide.3, two lopps are as Zelmid.4, tricyclic antidepressants is as imipramine.5, new tricyclic antidepressants is as Clomipramine.6, Fourth Ring class is as maprotiline.From the fifties, the application of tricyclic antidepressant has obtained favorable effects, but significant side reaction is restricted it.Along with to the pathogenetic continuous understanding of depression, the emphasis of research turns in recent years: 1, selectivity 5-HT cell reabsorption inhibitor, and as fluoxetine.2, reversibility monoamine oxidase, MAO two types are selected inhibitor, as moclobemide.The report of relevant compound of Chinese medicine depression is more, as: Radix Bupleuri adds Os Draconis Concha Ostreae soup, the strongly fragrant refreshing peace soup, five that disappears is spent Chinese herbaceous peonies grass soup, lilii and Rehmanniae Decoction, GANMAI DAZAO TANG, ERXIAN TANG, DACHENGQI TANG, Herba Sidae Rhombifoliae soup etc.But curative effect is very little.And the Western medicine that uses clinically at present, the cycle of taking long more, side effect is big, as sexual dysfunction, sinus rhythm overrun, blurred vision etc., and cost an arm and a leg, the patient burden is overweight.
Summary of the invention
The purpose of this invention is to provide a kind of differential diagnosis in tcm that is used for depression with effect of the liver soothing and the spleen invigorating, clearing away phlegm resolving depression is the patient's of liver-depression and spleen-insufficiency type Chinese medicine composition.
The present invention further provides Chinese medicine preparation of its clinical practice and preparation method thereof.This product promptly can be share also and can use separately with Western medicine, for the treatment of depression provides a new selection.
For achieving the above object, technical scheme of the present invention provides a kind of Chinese medicine composition that is used for the treatment of depression, and the weight portion of its crude drug is: the Radix Paeoniae Alba: 500-2500 part; Rhizoma Acori Graminei: 50-250 part; The Rhizoma Atractylodis Macrocephalae: 125-625 part; Radix Angelicae Sinensis: 125-625 part; Semen Sinapis Albae: 75-375 part; Poria: 125-625 part; Radix Curcumae: 25-125 part; Radix Polygalae: 25-125 part.
Chinese medicine composition of the present invention, the weight portion of its crude drug is preferably: the Radix Paeoniae Alba: 1000-2000 part; Rhizoma Acori Graminei: 100-200 part; The Rhizoma Atractylodis Macrocephalae: 250-500 part; Radix Angelicae Sinensis: 250-500 part; Semen Sinapis Albae: 150-300 part; Poria: 250-500 part; Radix Curcumae: 50-100 part; Radix Polygalae: 50-100 part.
Chinese medicine composition of the present invention, the weight portion of its crude drug most preferably is: the Radix Paeoniae Alba: 1500 parts; Rhizoma Acori Graminei: 150 parts; The Rhizoma Atractylodis Macrocephalae: 375 parts; Radix Angelicae Sinensis: 375 parts; Semen Sinapis Albae: 225 parts; Poria: 375 parts; Radix Curcumae: 75 parts; Radix Polygalae: 75 parts.
Wherein said weight portion can be the known measurement units of field of medicaments such as g, kg.
Chinese medicine composition of the present invention can grasp by traditional folk prescription, and usefulness is decocted in water for oral dose; Also can be prepared into various Chinese patent medicine dosage forms, convenient clinical use.
Further, the invention provides a kind of Chinese medicine preparation that is used for the treatment of depression, it is to make clinical acceptable forms by above-mentioned Chinese medicine composition and pharmaceutically acceptable carrier and/or excipient.Described clinical acceptable forms can be tablet, pill, capsule, granule, electuary or oral liquid etc.The preferred particulates agent.
The preparation method of above-mentioned Chinese medicine preparation, wherein a kind ofly be, Rhizoma Acori Graminei, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Semen Sinapis Albae, Poria, Radix Curcumae and Radix Polygalae seven flavor medicine material are added water distillation and extraction volatile oil, and obtain medicinal liquid and medicinal residues, after decocting with water again, described medicinal residues get medicinal liquid, itself and aforementioned medicinal liquid merge back adding ethanol and leave standstill, and get alcohol deposit fluid; Centrifuging and taking supernatant behind the merging medicinal liquid will repeatedly be decocted with water after the Radix Paeoniae Alba section; Described supernatant merges back recovery ethanol with above-mentioned alcohol deposit fluid after crossing the adsorbent resin remove impurity, gets medicinal liquid, adds pharmaceutically acceptable carrier and/or excipient at last, sprays into volatile oil again, makes clinical acceptable forms.
It specifically may further comprise the steps:
1. take by weighing raw materials of traditional Chinese medicinal materials according to consumption;
2. Rhizoma Acori Graminei, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Semen Sinapis Albae, Poria, Radix Curcumae and Radix Polygalae seven flavor medicine material add the water that 6-10 doubly measures (preferred 8 times of amounts), extract volatile oil 3-7h (preferred 5h) with the way of distillation, and gained volatile oil and medicinal liquid are standby;
3. the said extracted medicinal residues of crossing volatile oil add water 4-8 again and doubly measure (preferred 6 times of amounts) and decoct 0.5-2h (preferred 1h), merge medicinal liquid, filter, it is 1.12-1.20 that filtrate decompression is concentrated into 80 ℃ of relative densities, cooling, add 95% ethanol and make medicinal liquid contain alcohol amount to reach more than 75%, leave standstill the back and filter, alcohol deposit fluid;
4. get Radix Paeoniae Alba section in addition, add the water that 6-10 doubly measures (preferred 8 times of amounts), decoct 2-4 time (preferred 3 times), each 0.5-1 hour, merge medicinal liquid, filter, filtrate decompression is concentrated into 1: 1 (containing 1 gram medical material in every 1mL medicinal liquid), and is centrifugal, gets supernatant;
5. above-mentioned supernatant is crossed macroporous adsorbent resin, with using 60% ethanol elution behind the distilled water flush away impurity, collects eluent and above-mentioned alcohol deposit fluid and merges, and reclaims ethanol to there not being the alcohol flavor, collects medicinal liquid;
6. above-mentioned medicine liquid spray drying adds pharmaceutically acceptable carrier and/or excipient, sprays into volatile oil again, makes clinical acceptable forms.
Above-mentioned preparation method, 5. wherein said step crosses the ZTC-1 macroporous adsorbent resin for supernatant, with distilled water 1500mL flush away impurity, then use 3000mL 60% ethanol elution, elution speed be 2.4BV (amount of resin)/hour, collect eluent and above-mentioned alcohol deposit fluid and merge, reclaim ethanol, collect medicinal liquid to there not being the alcohol flavor.
Motherland's traditional medicine is thought: melancholia is that a class is not relaxed the caused abnormal mind disease of depression and stagnation of QI because of feelings will.Chinese medicine is thought the generation of melancholia, because of disgruntled, ponder over, grief, worried damaged by excess of seven emotions causes the liver failing to maintain the normal flow of QI, spleen loses fortuneization, brain god is not normal, the internal organs yin and yang qi and blood disorder forms.Disgruntled not smooth, liver is transferred reached, gas loses to dredge and stagnates, so that depression of liver-QI.So the traditional Chinese medical science thinks: " strongly fragrant disease does not have not impairing the liver person yet ... ".If stagnation of liver-QI and spleen cause dysfunction of the spleen in transportation, can accumulate humidogene expectorant again and form phlegm stagnancy.If stagnation of phlegm converting into heat then can develop into damp-stagnancy, food stagnancy, all cards of heat stagnation.Traditional Chinese medical science ancient Chinese medicine doctor is advocated mostly: " controlling Yu Xianzhi gas, regulating QI elder generation treating the liver ".This is viscus attriguted to wind and wood's stored blood because of liver, in post mutually fire, property happiness catharsis bar reaches, and is how moving changeable, suitable to be upgraded to, be the hinge of the whole body gas phase, the mediation of personal internal organs QI and blood, passages through which vital energy circulates operation circulation, up and down fluent of the harmony defended of battalion, the exterior and the interior all reaches relevant with the catharsis bar of irritability.Chinese medicine is also thought: " prolonged illness must empty ", must cause deficiency of the liver melancholia time one for a long time.So the nourishing the liver resolving depression, invigorating the spleen for dissipating phlegm is the excellent method of melancholia treating both the principal and the secondary aspects of a disease at the same time.
Chinese medicine composition provided by the invention is a pure Chinese medicinal preparation, with motherland's traditional medicine is the Therapeutic Principle, the reasonable compatibility of Chinese medicine medical material and the purification that separates of effective components of Chinese medicinal on the modern pharmacy basis, have been carried out, improved the therapeutic effect of medicine, this product has the effect of the liver soothing and the spleen invigorating, clearing away phlegm resolving depression, can be used for the patient that the depression differential diagnosis in tcm is a liver-depression and spleen-insufficiency type.This product promptly can be share also and can use separately with Western medicine.
The preparation method of Chinese medicine preparation provided by the invention has adopted macroporous adsorbent resin to extract active ingredient in the Radix Paeoniae Alba especially, it is extracted goodly fully and removed assorted molecule and disturbed the drug effect of this product is raise, and clinical consumption can suitably reduce.
The specific embodiment
Below in conjunction with embodiment, the specific embodiment of the present invention is described in further detail.Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.
Embodiment 1: a kind of capsule that is used for the treatment of depression and preparation method thereof
(1) takes by weighing following raw materials by weight proportions: Radix Paeoniae Alba 500g, Rhizoma Acori Graminei 250g, Rhizoma Atractylodis Macrocephalae 625g, Radix Angelicae Sinensis 125g, Semen Sinapis Albae 375g, Poria 125g, Radix Curcumae 25g, Radix Polygalae 125g.
(2) wherein seven flavor medicine materials such as Rhizoma Acori Graminei, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Semen Sinapis Albae, Poria, Radix Curcumae, Radix Polygalae add the water of 10 times of amounts, extract volatile oil 7h with the way of distillation, and volatile oil and medicinal liquid are standby.
(3) said extracted is crossed medicinal residues after the volatile oil and is added 4 times of amounts of water again and decoct 2h, merges medicinal liquid, filters, it is 1.12-1.20 (80 ℃ of surveys) that filtrate decompression is concentrated into relative density, and cooling adds 95% ethanol and makes medicinal liquid contain alcohol amount to reach 75%, leave standstill 24h, filter, get alcohol deposit fluid.
(4) get Radix Paeoniae Alba section in addition, add the water of 6 times of amounts, decoct 3 times, each 0.5 hour, merge medicinal liquid, filter, filtrate decompression is concentrated into 1: 1, and is centrifugal, gets supernatant.
(5) above-mentioned supernatant is crossed the ZTC-1 macroporous adsorbent resin, with distilled water 1500mL flush away impurity, then uses 3000mL 60% ethanol elution earlier, elution speed be 2.4BV (amount of resin)/hour, collect eluent and above-mentioned alcohol deposit fluid and merge, reclaim ethanol, collect medicinal liquid to there not being the alcohol flavor.
(6) above-mentioned medicine liquid spray drying adds starch, dextrin is an amount of, and mixing is made granule with 5%PVP solution, sprays into volatile oil, incapsulates, promptly.
Embodiment 2: a kind of tablet that is used for the treatment of depression and preparation method thereof
(1) weight proportion that takes by weighing is: Radix Paeoniae Alba 1000g, Rhizoma Acori Graminei 200g, Rhizoma Atractylodis Macrocephalae 500g, Radix Angelicae Sinensis 250g, Semen Sinapis Albae 300g, Poria 250g, Radix Curcumae 100g, Radix Polygalae 50g.
(2) wherein seven flavor medicine materials such as Rhizoma Acori Graminei, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Semen Sinapis Albae, Poria, Radix Curcumae, Radix Polygalae add the water of 6 times of amounts, extract volatile oil 4h with the way of distillation, and volatile oil and medicinal liquid are standby.
(3) above-mentioned medicinal residues add 8 times in water amount again and decoct 1h, merge medicinal liquid, filter, and it is 1.12-1.20 (80 ℃ of surveys) that filtrate decompression is concentrated into relative density, and cooling adds 95% ethanol and makes medicinal liquid contain the alcohol amount to reach 75%, leave standstill 24h, filter, alcohol deposit fluid.
(4) get Radix Paeoniae Alba section in addition, add the water of 10 times of amounts, decoct 3 times, each 1 hour, merge medicinal liquid, filter, filtrate decompression is concentrated into 1: 1, and is centrifugal, gets supernatant.
(5) above-mentioned supernatant is crossed the ZTC-1 macroporous adsorbent resin, with distilled water 1500mL flush away impurity, then uses 3000mL 60% ethanol elution earlier, elution speed be 2.4BV (amount of resin)/hour, collect eluent and above-mentioned alcohol deposit fluid and merge, reclaim ethanol, collect medicinal liquid to there not being the alcohol flavor.
(6) above-mentioned medicine liquid spray drying adds starch, dextrin is an amount of, and mixing is made granule with 5%PVP solution, sprays into volatile oil, tabletting, promptly.
Embodiment 3: a kind of granule that is used for the treatment of depression and preparation method thereof
(1) weight proportion that takes by weighing is: Radix Paeoniae Alba 1500g, Rhizoma Acori Graminei 150g, Rhizoma Atractylodis Macrocephalae 375g, Radix Angelicae Sinensis 375g, Semen Sinapis Albae 225g, Poria 375g, Radix Curcumae 75g, Radix Polygalae 75g.
(2) wherein seven flavor medicine materials such as Rhizoma Acori Graminei, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Semen Sinapis Albae, Poria, Radix Curcumae, Radix Polygalae add the water of 8 times of amounts, extract volatile oil 5h with the way of distillation, and volatile oil and medicinal liquid are standby.
(3) above-mentioned medicinal residues add 6 times in water amount again and decoct 1h, merge medicinal liquid, filter, and it is 1.12-1.20 (80 ℃ of surveys) that filtrate decompression is concentrated into relative density, and cooling adds 95% ethanol and makes medicinal liquid contain the alcohol amount to reach 75%, leave standstill 24h, filter, alcohol deposit fluid.
(4) get Radix Paeoniae Alba section in addition, add the water of 8 times of amounts, decoct 3 times, each 0.5 hour, merge medicinal liquid, filter, filtrate decompression is concentrated into 1: 1, and is centrifugal, gets supernatant.
(5) above-mentioned supernatant is crossed the ZTC-1 macroporous adsorbent resin, with distilled water 1500mL flush away impurity, then uses 3000mL 60% ethanol elution earlier, elution speed be 2.4BV (amount of resin)/hour, collect eluent and above-mentioned alcohol deposit fluid and merge, reclaim ethanol, collect medicinal liquid to there not being the alcohol flavor.
(6) above-mentioned medicine liquid spray drying, stevioside and dextrin: lactose (2: 1) is an amount of, and mixing is made granule with 85% ethanol, sprays into volatile oil, packing, promptly.
Embodiment 4:
Except that crude drug weight proportion difference, all the other are all identical with embodiment 3:
Radix Paeoniae Alba 2500g, Rhizoma Acori Graminei 50g, Rhizoma Atractylodis Macrocephalae 125g, Radix Angelicae Sinensis 625g, Semen Sinapis Albae 75g, Poria 625g, Radix Curcumae 125g, Radix Polygalae 25g.
Embodiment 5:
Except that crude drug weight proportion difference, all the other are all identical with embodiment 3:
Radix Paeoniae Alba 2000g, Rhizoma Acori Graminei 100g, Rhizoma Atractylodis Macrocephalae 250g, Radix Angelicae Sinensis 500g, Semen Sinapis Albae 150g, Poria 500g, Radix Curcumae 50g, Radix Polygalae 100g.
The test example: the pharmacological toxicology of the granule of embodiment 3 (tentative Radix Paeoniae Alba resolving depression granule by name) is learned test
One, Pharmacodynamic test of active extract
1, to the influence of mouse tail suspension dead time
[test objective] observes the influence of Radix Paeoniae Alba resolving depression granule to " behavior despair " depression model.
[test method]
The reference literature method, choose 50 of kunming mices, be divided into 5 groups at random, pressed table 1 dosage successive administration 7 days, and measured during 30min after time administration, the part at its afterbody 2cm place is attached on the horizontal waddy, make animal become the reversal of the natural order of things state, the about 5cm of its head destage face hangs both sides and separates the animal sight line with plate, observed and recorded administration group and the matched group dead time in 6min.The results are shown in Table 1.
Table 1 Radix Paeoniae Alba resolving depression granule forces the influence of outstanding tail dead time to mice
Annotate: compare with the normal saline group
*P＜0.01.
[result of the test]
As known from Table 1, after Radix Paeoniae Alba resolving depression granule gives mice, equally with clomipramine all shorten mice and force the outstanding tail dead time, analyzing middle and high dosage group by statistics compares with the normal saline group and has significant difference (P＜0.01), though the outstanding tail dead time of low dose group shortens to some extent, but, illustrate that Radix Paeoniae Alba resolving depression granule can resist the depressive symptom of mice because of forcing outstanding tail to cause with normal saline comparing difference nonsignificance (P＞0.05).
2, to the influence of mice forced swimming dead time
[test objective] observes the influence of Radix Paeoniae Alba resolving depression granule to " behavior despair " depression model.
[test method]
The reference literature method with 50 of kunming mices, is divided into 5 groups at random, press table 2 dosage successive administration 7 days, and behind time administration 30min, do not put into water vat (2000mL beaker, high 20cm, diameter 14cm, depth of water 10cm places in the water-bath), regulate 23-25 ℃ of water temperature, one in every cylinder is put and is observed 6min in the water, the accumulative total dead time in the 4min behind the record mice.The results are shown in Table 2.
Table 2 Radix Paeoniae Alba resolving depression granule is to the influence of mice forced swimming dead time
Annotate: compare with the normal saline group
*P＜0.05,
*P＜0.01.
[result of the test]
As known from Table 2, after Radix Paeoniae Alba resolving depression granule gives mice, equally with clomipramine all shorten the mice forced swimming dead time, analyze by statistics, the basic, normal, high dosage group (P＜0.05-0.01) that compares with the normal saline group and have significant difference, but do not have obvious dose-effect relationship, illustrate that Radix Paeoniae Alba resolving depression granule can resist the depressive symptom that mice is caused because of forced swimming.
3, the blepharoptosis degree influence that mice is caused because of reserpine
[test objective] observes the influence of Radix Paeoniae Alba resolving depression granule to drug induced depression model.
[test method]:
The reference literature method, with 60 of kunming mices, be divided into 6 groups at random, press table 3 dosage successive administration 7d, behind time administration 30min, every mice is not pressed 2.5mg/kg lumbar injection reserpine (0.1mL/10g), observes mice blepharoptosis situation, blepharoptosis degree and body temperature during accurate recording 1h are observed situations such as spontaneous activity, ear tail color and diarrhoea.Press the Rubin grade scale, judge sag.The results are shown in Table 3.
0 degree: normally open order
1 degree: blepharoptosis 1/4
2 degree: blepharoptosis 1/2
3 degree: blepharoptosis 3/4
4 degree: eyelid is closed fully
Table 3 Radix Paeoniae Alba resolving depression causes influence (n=10, the x ± s) of mice depression model to reserpine
Annotate: compare with the normal saline group
△ △P＜0.01; Compare with the reserpine group
*P＜0.05,
*P＜0.01.
[result of the test]
Through experiment, after mice gives reserpine (2.5mg/kg), occurred the tangible ptosis, motion can not with the body temperature symptom that descends, relatively have utmost point significant difference (P＜0.01) with normal mouse, illustrate to behind the normal mouse lumbar injection reserpine, can cause depressed animal model.We treat for the depression model animal with antidepressant new drug Radix Paeoniae Alba resolving depression and clomipramine, the depressive symptom of results model animal be improved significantly, blepharoptosis degree and body temperature decline degree reduce.The blepharoptosis degree of the basic, normal, high dosage treated animal of Radix Paeoniae Alba resolving depression is compared with the normal saline group and is had than significant difference (P＜0.05-0.01), the body temperature decline of the middle and high dosage treated animal of Radix Paeoniae Alba resolving depression is compared with the normal saline group and is had significant difference (P＜0.05), illustrates that Radix Paeoniae Alba resolving depression granule can resist the depressive symptom that mice causes because of reserpine.
4, the mortality rate influence that mice is caused because of pentobarbital sodium
The particulate antidepressant effect of [test objective] test Radix Paeoniae Alba resolving depression.
[test method]
The reference literature method with 50 of kunming mices, is divided into 5 groups at random, each treated animal is pressed table 4 dosed administration 6d, 30min after the administration in the 7th day, the pentobarbital sodium 0.3mL/10g (being 150mg/kg) of every mouse peritoneal injection 5mg/mL observes in the 24h and respectively organizes mortality of mice.The results are shown in Table 4.
The mouse death rate influence that table 4 Radix Paeoniae Alba resolving depression granule causes pentobarbital sodium
Annotate: compare with the normal saline group
*P＜0.05,
*P＜0.01.
[result of the test]
By table 4 result as seen, behind the normal mouse lumbar injection pentobarbital sodium toxic dose (being 150mg/kg), mortality rate is 100%, take the mortality rate that can reduce animal behind antidepressant new drug Radix Paeoniae Alba resolving depression and the clomipramine, the mortality rate of the basic, normal, high dosage treated animal of Radix Paeoniae Alba resolving depression is respectively 50%, 50%, 40%, analysis is compared with normal saline by statistics, and there were significant differences (P＜0.05), illustrate that antidepressant new drug Radix Paeoniae Alba resolving depression has certain excitation, can reduce the mouse death rate that causes because of pentobarbital sodium.
5, to the influence of depression rat model
[test objective] observes the influence of Radix Paeoniae Alba resolving depression granule to depression rat model body weight, behavior, sucrose solution consumption and the monoamine neurotransmitter that stress cause.
[test method]
Animal grouping and Preparation of model: reference literature method, select 48 of the close rats of Open-Field method scoring for use, be divided into 6 groups at random, it is the normal saline group, model group, the clomipramine group, Radix Paeoniae Alba resolving depression is low, in, high dose group, except that the normal saline group, each group accept altogether 21 days various stress, comprise electric shock vola (36V alternating current, stimulated 1 time every 1 minute, each stimulation 10 seconds, totally 30 times), frozen water swimming (4 ℃, 5 minutes), (45 ℃ of heat stresss, 5 minutes), rock (1 speed time/second, 15 minutes), folder tail (1 minute), prohibit water (24 hours), fasting (48 hours) and stimulation such as put upside down round the clock, average every kind stimulates each 2 times, takes turns by above-mentioned order continued stimulus 2, the first round stimulates and finishes the beginning administration, Radix Paeoniae Alba resolving depression is low, in, high dose group gives Radix Paeoniae Alba resolving depression granule 1mL/100g (5 respectively, 10,15g/kg), the clomipramine group gives clomipramine solution 1mL/100g (20mg/kg), and normal saline group and model group give the normal saline of equivalent respectively.
(1) to the influence of depression model rat body weight
Test method
The measurement of body weight: the body weight change (the results are shown in Table 5) of measuring animal respectively at the 1st, 7,14 and 21 day that tests.
The influence that table 5 Radix Paeoniae Alba resolving depression granule changes depressed rat body weight (g, x ± s, n=8)
Annotate: compare with the normal saline group
△P＜0.05,
△ △P＜0.01; Compare with model group
#P＞0.05
Result of the test
As seen from Table 5, by 21 days various distinct methods stress, compare with the normal saline group, increase at the 7th day the weight of animals reduces, the 14th day (P＜0.05), 21 days (P＜0.01) body weight change have significantly and extremely remarkable meaning, and explanation stress make the increase generation significant change of the weight of animals.After taking Radix Paeoniae Alba resolving depression granule and clomipramine, animal is reduced no tangible improvement effect in response to swashing the weight increase that causes.
(2) influence that the depression model rat behavior is learned
Test method
Behavioristics measures: measured the behavior variation of animal respectively on the the 7th, 14 and 21 day in experiment.The Open-Field method is measured behavior.This tests used spacious case is cylindrical, high 40cm, and diameter 80cm, perisporium are black, the bottom surface is divided into 25 that area equates by fan-shaped.Passing through the bottom surface block number with animal is horizontal anomalous movement (crossing) score, and animal generally keeps to the side to walk, and passing through 1 lattice is 1 time, by the diametric(al) walking, is 1 time with every 10cm as animal generally; With upright number of times is vertical movable (rearing) score, and the animal biped leaves the bottom surface for vertical movable, and no matter animal is stood, and how long to put down until the animal biped be 1 activity.Every animal is only once measured at every turn, and each minute is 3 minutes (the results are shown in Table 6).
Table 6 Radix Paeoniae Alba resolving depression granule to the influence of depressed rat behavior (x ± s, n=8)
Annotate: compare with the normal saline group
△P＜0.05,
△ △P＜0.01; Compare with model group
*P＜0.05,
*P＜0.01; Animal was since administration in the 12nd day, and animals administer is only 3 days in the time of the 14th day.
Result of the test
As seen from Table 6, through 21 days various distinct methods stress after, we measure horizontal anomalous movement (crossing) score and vertical movable (rearing) score of animal behavior by the Open-Field method, compare with the normal saline group, reduce day level activity number of times P＜0.01, the 14th day two kinds of equal P of activity＜0.05, the 21, vertical movable number of times P＜0.05 at two kinds of movable number of times of the 7th day animal, explanation stress make the movable of animal obviously reduce, and produces depressive symptom.We treat depressed animal with Radix Paeoniae Alba resolving depression granule and clomipramine, and the result was at the 21st o'clock, and dosage and heavy dose of group can increase the movable number of times (P＜0.05～P＜0.01) of depressed animal in the Radix Paeoniae Alba resolving depression, have equal pharmacological action with clomipramine.
(3) to the influence of depression model rat sucrose solution consumption
Test method
Sucrose solution consumption experiment: the 22nd day mensuration sucrose solution consumption, the all single cage of all animals is raised when carrying out sucrose solution consumption experiment, every animal adds 1% sucrose solution 130mL, and all animals carry out fasting simultaneously, calculates the amount (the results are shown in Table 7) that animal was drunk 1% sucrose solution in 24 hours.
Table 7 Radix Paeoniae Alba resolving depression granule to the influence of depressed rat sucrose solution consumption (x ± s, n=8)
Annotate: compare with the normal saline group
△ △P＜0.01; Compare with model group
*P＜0.05,
*P＜0.01
Result of the test
As seen from Table 7, by various distinct methods stress after, compare with the normal saline group, the sucrose solution consumption of model group animal obviously reduces (P＜0.01).After taking Radix Paeoniae Alba resolving depression granule and clomipramine, can obviously increase in response to the decline that swashs the animal sucrose solution consumption that causes, basic, normal, high dosage group of Radix Paeoniae Alba resolving depression and model group relatively are respectively P＜0.01, P＜0.05, P＜0.05, but there is not tangible dose-effect relationship, clomipramine group P＜0.01 of comparing with model group.
(4) to the influence of monoamine neurotransmitter
Test method
The mensuration of monoamine neurotransmitter: the 23rd day mensuration central neurotransmitter content.Animal successive administration 12 days, after 30～60 minutes, the sacrificed by decapitation rat removes skull in the last administration, exposes cerebral tissue fully, cuts off oblongata rapidly at the Foramen magnum place, takes out cerebral tissue, removes cerebral cortex, is put on the template and weighs.Rapidly cerebral tissue is put into the acid butanol solution that the 3mL pre-cooling is housed, stripping paper is heavy, obtains the cerebral tissue net weight.Replenish acid n-butyl alcohol to 7mL in 1: 30 left and right sides ratio, the preparation tissue homogenate.Tissue homogenate is poured in the band plug centrifuge tube, vibration 5min, centrifugal 10min under 3000r/min gets an amount of acid n-butyl alcohol supernatant and extracts and measure by literature method, and it is 290nm that NE surveys periodic excitation wavelength, emission wavelength is 374nm, it is 326nm that DA surveys periodic excitation wavelength, and emission wavelength is 381nm, and it is 360nm that 5-HT and 5-HTAA survey periodic excitation wavelength, emission wavelength is 500nm, calculates the content (the results are shown in Table 8) of each treated animal maincenter monoamine neurotransmitter.
Table 8 Radix Paeoniae Alba resolving depression granule to the influence of depressed rat neurotransmitter content (ng/g, x ± s, n=8)
Annotate: compare with the normal saline group
△P＜0.05,
△ △P＜0.01; Compare with model group
*P＜0.05,
*P＜0.01,
#P＞0.05
Result of the test
Through 21 days various distinct methods stress after, we measure the content of animal central neurotransmitter with the fluorophotometer method, compare with the normal saline group, the content of NE, DA, 5-HT, 5-HIAA all obviously reduces (P＜0.01) in the big mesencephalic centre of results model treated animal, explanation stress cause the variation of animal central neurotransmitter content, and difference has remarkable meaning.After animal is taken Radix Paeoniae Alba resolving depression granule and clomipramine, the content of NE in the animal pattern maincenter is obviously raise (P＜0.05), the content of 5-HT, 5-HIAA is obviously rising (P＜0.05～P＜0.01) also, the content of DA has rising trend, but there is not significant difference (P＞0.05), Radix Paeoniae Alba resolving depression granule is compared with clomipramine has equal pharmacological action, but does not have tangible dose-effect relationship.
[conclusion]
We comprehensively stress support two kinds of classical animal models with dividing, utilize the moderate strength of long-term Unpredictability stress, cause branch to support the animal depressive state, depressed animal shows as in behavior: horizontal anomalous movement at the appointed time reduces with vertical movable number of times, weight increase alleviates, and the sucrose solution consumption reduces.The mobility of horizontal anomalous movement reflection animal, vertical movable reflection animal is to the curious degree of fresh environment, the award extent of reaction of sucrose solution consumption reflection animal.The forfeiture of psychomotor change, interest or pleasant sensation in the depressive state that this animal pattern shows, hebetude, anhedonia and the depression clinical diagnosis has similarity to a certain degree.Simultaneously, by to animal central neurotransmitter Determination on content, find that depressed animal central neurotransmitter NE, 5-HT, 5-HIAA content reduce, consistent with bibliographical information, experiment finds that Radix Paeoniae Alba resolving depression granule can improve the negative behavior symptom of depression model animal, showing as horizontal anomalous movement increases with vertical movable number of times increase, sucrose solution consumption, and the content that can resist in response to the central neurotransmitter NE, the DA that swash the depression model rat of being caused and 5-HT, 5-HIAA descends.
Two, acute toxicity test
The particulate acute toxicity of [test objective] test Radix Paeoniae Alba resolving depression.
[experimental technique]
Get 40 of mices, sub-cage rearing 2 days, behind fasting (the freely drinking water) 12h, every Mus ig gives Radix Paeoniae Alba resolving depression 0.8mL/20g, and with Isodose repeat administration 3 times, matched group gives isopyknic normal saline, breeding observing 7 days in the 24h.
[result]
1. animal toxicity response situation: administration group mice is moving phase after each administration, and spirit is not good enough to reducing, and diet reduces, and loose stool occurs after 1 hour, and number of times increases, and recovers after 3～4 hours.Administration treated animal hair after the administration first time has slight pollution, and all other indexs are compared no significant difference with matched group, and all indexs all recover normal in administration after 24 hours.After this animal is in the behavior activity, and aspect such as mental status and matched group relatively do not have significant change.
2. body weight change before and after the filling stomach:
Body weight does not have significant change before and after irritating stomach, sees table 9 for details.
Table 9 is irritated stomach front and back mice body weight situation (g)
P＞0.05，n＝10
3. feed consumption before and after the filling stomach
The administration treated animal reduces than matched group in filling stomach food-intake on the same day, and mice appetite every day were compared no significant change before and after all the other irritated stomaches with matched group, saw table 10 for details.
Table 10 is irritated average every the mouse feed consumption (g) in stomach front and back
4. death condition: observed 7 days none animal dead after the administration continuously.
[conclusion]
We carry out the maximum dosage-feeding test with Kunming mouse, and observed every index is all normal, does not see 1 animal dead.Show that Radix Paeoniae Alba resolving depression granule does not have obvious acute toxicity effect, the oral maximum dosage-feeding of this product mice (MTD) is 720g/kg, is equivalent to 720 times of clinical plan consumption.
Three, long term toxicity test
The particulate long term toxicity effect of [test objective] test Radix Paeoniae Alba resolving depression.
[test method]
Route of administration: oral (filling stomach), at 8～11 o'clock in the morning every day gastric infusion.Successive administration is 6 days weekly, drug withdrawal on Sunday one day.
Dosage: high dose is 100g/kg, and middle dosage is 50g/kg, and low dosage is 25g/kg, and equivalent coefficient is 2 between group.Matched group gives the equal-volume normal saline.
Administration volume: 1.4mL/100g Mus.
Dosage and toxic reaction result during trial test: mice oral maximum dosage-feeding on the one is 720g/kg, presses the body surface area conversion and is rat 360g/kg.100g/kg dosage is 27.8% (100/360) of this dosage.Pharmacodynamics test rat effective dose is 5g/kg.The clinical plan consumption of this side is 1.0g/kg, and high dose group 100g/kg is 100 times of clinical plan consumption, and middle dosage group 50g/kg is 50 times of clinical plan consumption, and low dose group 25g/kg is 25 times of clinical plan consumption.Test period: 26 weeks, totally 180 days.Observed for 1 week before the administration, administration after 90 days every group put to death 16 earlier, the long term toxicity test of submitting 3 months reports that all the other continue administration, put to death 16 again for every group after 180 days, reversibility observed for 2 weeks after the drug withdrawal of being left.Next day after the last administration, use the etherization animal, by the ventral aorta blood sampling, carry out hemogram and biochemical indicator and detect, separate internal organs and calculate organ coefficient, send pathological examination at last.
Statistical analysis: calculate the mean and the standard deviation of each group respectively, administration group and matched group carry out the t check, and the results list is represented.
[observation index]
1. general performance: the food-intake of rat, gastrointestinal reaction, body weight, outward appearance sign and behavioral activity, feces character etc.Weigh once weekly, and adjust dose once according to the body weight gain situation.Routine blood test: erythrocyte (RBC), platelet (PLT), leukocyte (WBC) counting.Hemoglobin (HGB), clotting time (BT), bleeding time (CT), leukocyte differential count (lymphocyte LYM, neutrophil GRA, mononuclear cell MID).
2. hepatic and renal function: referring to biochemistry.
3. blood biochemical: aspartic acid conversion enzyme (AST), ALT (ALT), alkali phosphatase (ALP), blood urea nitrogen (BUN), total protein (TP), albumin (ALB), blood glucose (GLU), total bilirubin (T-BIL), bilirubin direct (D-BIL), creatinine (GRE), T-CHOL (T-CHO), triglyceride (TG).
4. system becomes celestial and histopathologic examination:
, put to death 16 rats, do becoming celestial and histological examination for every group after 3 months and 6 months respectively at administration.The remaining reversibility of doing was observed 14 days.
Internal organs are weighed and organ coefficient: the heart, liver, spleen, lung, kidney, brain, adrenal gland, thyroid, thymus, testis, ovary.
Histological examination: the heart, liver, spleen, lung, kidney, brain, adrenal gland, thyroid, thymus, testis, ovary, stomach, small intestinal.
2 weeks of drug withdrawal are observed the convalescent period variation, do coherence check.
[result]
General performance: in the whole administration process, each administration group and control rats are at aspect Non Apparent Abnormalities such as sign outward appearance, behavioral activity and diet.The activity in the 3rd day after irritating stomach of administration height, middle dosage group is few slightly, and feces is thinning soft, and hair and afterbody have slight pollution.After the 3rd week of administration, the body weight gain of administration treated animal slows down than matched group, but not statistically significant also maintains this level later on always.Administration second during week the animal food-intake increase and reduce along with administration concentration, later difference reduces gradually, but still maintains certain level (seeing Table 11,12).
Blood routine examination: with the full-automatic blood cell instrument of AC-900 the routine blood test of each treated animal is checked, as a result platelet of high dose group animal and numeration of leukocyte P＜0.05 of comparing with the normal saline group; In the platelet count of dosage treated animal P＜0.01 of comparing with the normal saline group; But this two index still belongs to normal range.Each group difference not statistically significant of all the other indexs (seeing Table 13,14).Illustrate that Radix Paeoniae Alba resolving depression granule does not have obvious influence to the rat hemogram.
Blood biochemical is learned and is checked: the blood parameters of each treated animal is checked biochemical numerical value no difference of science of statistics (seeing Table 15,16) between each group of result with Mei Liai-150 type automatic clinical chemistry analyzer.Point out the Radix Paeoniae Alba resolving depression granule of used dosage to give rat for a long time, the hepatic and renal function of animal is not had obvious influence.
Blood glucose and lipid examination: with blood glucose and the lipid examination of Mei Liai-150 type automatic clinical chemistry analyzer to each treated animal, the blood glucose value of administration group has as a result been compared significance meaning (P＜0.05) with matched group, but all blood glucose values are all in normal range.Numerical value no difference of science of statistics (seeing Table 16) between all the other each groups.
Organ coefficient: rat was dissected after blood sampling caused death, and after the perusal, got main organs and claimed weight in wet base, calculated organ coefficient (organ weights/100g body weight).By table 17,18 as seen, the organ coefficient administration group of surveying and matched group differences not statistically significant.
Histological examination: each organs and tissues to every group every animal carries out pathological observation, primary part observation each organs and tissues whether pathological changes such as hyperemia, degeneration, necrosis, inflammation are arranged.The result shows: have in the matched group that 4 Hepar Mus are dirty a Mild edema degeneration, 2 Mus lungs bronchial walls have the special mess lymphocytic infiltration; Have in the low dose group that 3 Hepar Mus are dirty a Mild edema degeneration, 1 Hepar Mus is dirty little focal necrosis and mild inflammation, and 1 Mus lungs bronchial wall has the special mess lymphocytic infiltration; Middle dosage group has 2 dirty mild hyperaemias of Hepar Mus, 1 lungs mild hyperaemia, and 2 Mus lungs bronchial walls have the special mess lymphocytic infiltration; Have in the high dose group that 1 Hepar Mus is dirty little focal necrosis and mild inflammation, 1 dirty mild hyperaemia of Hepar Mus, 1 dirty Mild edema degeneration of Hepar Mus, 1 dirty little focal hemorrhage of Ren Mus.All the other animal visceras are organized and are not seen obvious pathological change.The comprehensive observing result, Radix Paeoniae Alba resolving depression granule give rat after three months animal viscera organize and do not see obvious pathological change; Pathological change no significant difference between each dosage group; Prompting Radix Paeoniae Alba resolving depression granule does not have obvious drug-induced toxicity pathological effect to laboratory animal.
[conclusion]
Radix Paeoniae Alba resolving depression granule high dose is 100g/kg, is equivalent to 100 times of clinical plan consumption.Rat was taken medicine for 13 weeks continuously, and appetite increases and reduces along with administration concentration when second week, and later difference reduces gradually, but still maintains certain level, the body weight change no significant difference.Administration group and matched group be routine blood test relatively, blood parameters, and hepatic and renal function does not have significant change.Histological examination does not have obvious pathological changes, does not have obvious poisoning target organ.
The variation of table 11 rat body weight (X ± S)
P＞0.05；n＝22～23；
Table 12 rat 24h food-intake (X ± S)
n＝22～23
The conventional part index number of table 13 rat serum (X ± S)
Annotate: compare with matched group
*P＜0.05
*P＜0.01; N=8
Table 14 rat leukocyte and classification (X ± S)
Annotate: compare with matched group
*P＜0.05; N=8
The biochemical part index number of table 15 rat blood (X ± S)
P＞0.05；n＝8
The biochemical part index number of table 16 rat blood (X ± S)
Annotate: compare with matched group
*P＜0.05
*P＜0.01; N=8
Table 17 Rats Organs and Tissues coefficient (X ± S)
P＞0.05；n＝8
The religion of table 18 Rats Organs and Tissues system
P＞0.05；n＝8
Can draw from above test example, Chinese medicine composition provided by the invention and Chinese medicine preparation be the alleviate depression symptom effectively, and clinical practice safety.It is each 10g that the particulate human body of wherein preferred Radix Paeoniae Alba resolving depression is recommended consumption, and every day twice, be 30 days the course of treatment.
The above only is a preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the technology of the present invention principle; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (9)
1. a Chinese medicine composition that is used for the treatment of depression is characterized in that, the weight portion of its crude drug is: the Radix Paeoniae Alba: 500-2500 part; Rhizoma Acori Graminei: 50-250 part; The Rhizoma Atractylodis Macrocephalae: 125-625 part; Radix Angelicae Sinensis: 125-625 part; Semen Sinapis Albae: 75-375 part; Poria: 125-625 part; Radix Curcumae: 25-125 part; Radix Polygalae: 25-125 part.
2. Chinese medicine composition as claimed in claim 1 is characterized in that, the weight portion of its crude drug is: the Radix Paeoniae Alba: 1000-2000 part; Rhizoma Acori Graminei: 100-200 part; The Rhizoma Atractylodis Macrocephalae: 250-500 part; Radix Angelicae Sinensis: 250-500 part; Semen Sinapis Albae: 150-300 part; Poria: 250-500 part; Radix Curcumae: 50-100 part; Radix Polygalae: 50-100 part.
3. Chinese medicine composition as claimed in claim 2 is characterized in that, the weight portion of its crude drug is: the Radix Paeoniae Alba: 1500 parts; Rhizoma Acori Graminei: 150 parts; The Rhizoma Atractylodis Macrocephalae: 375 parts; Radix Angelicae Sinensis: 375 parts; Semen Sinapis Albae: 225 parts; Poria: 375 parts; Radix Curcumae: 75 parts; Radix Polygalae: 75 parts.
4. a Chinese medicine preparation that is used for the treatment of depression is characterized in that, it is to make clinical acceptable forms by each described Chinese medicine composition of claim 1-3 and pharmaceutically acceptable carrier and/or excipient.
5. Chinese medicine preparation as claimed in claim 4 is characterized in that, described clinical acceptable forms is tablet, pill, capsule, granule or oral liquid.
6. the preparation method of the described Chinese medicine preparation of claim 4, it is characterized in that, Rhizoma Acori Graminei, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Semen Sinapis Albae, Poria, Radix Curcumae and Radix Polygalae seven flavor medicine material are added water distillation and extraction volatile oil, and obtain medicinal liquid and medicinal residues, after decocting with water again, described medicinal residues get medicinal liquid, itself and aforementioned medicinal liquid merge back adding ethanol and leave standstill, and get alcohol deposit fluid; The Radix Paeoniae Alba is decocted with water centrifuging and taking supernatant behind the merging medicinal liquid; Described supernatant merges back recovery ethanol with above-mentioned alcohol deposit fluid after crossing the adsorbent resin remove impurity, gets medicinal liquid, adds pharmaceutically acceptable carrier and/or excipient at last, sprays into volatile oil again, makes clinical acceptable forms.
7. preparation method as claimed in claim 6 is characterized in that, may further comprise the steps:
1. take by weighing raw materials of traditional Chinese medicinal materials according to consumption;
2. Rhizoma Acori Graminei, the Rhizoma Atractylodis Macrocephalae, Radix Angelicae Sinensis, Semen Sinapis Albae, Poria, Radix Curcumae and Radix Polygalae seven flavor medicine material add the water that 6-10 doubly measures, and extract volatile oil 3-7h with the way of distillation, and gained volatile oil and medicinal liquid are standby;
3. the said extracted medicinal residues of crossing volatile oil add water 4-8 again and doubly measure and decoct 0.5-2h, merge medicinal liquid, filter, it is 1.12-1.20 that filtrate decompression is concentrated into 80 ℃ of relative densities, and cooling adds 95% ethanol and makes medicinal liquid contain alcohol amount to reach more than 75%, leave standstill the back and filter, get alcohol deposit fluid;
4. get Radix Paeoniae Alba section in addition, add the water that 6-10 doubly measures, decoct 2-4 time, each 0.5-1 hour, merge medicinal liquid, filter, filtrate decompression is concentrated in every 1mL medicinal liquid and contains the 1g medical material, and is centrifugal, gets supernatant;
5. above-mentioned supernatant is crossed macroporous adsorbent resin, with using 60% ethanol elution behind the distilled water flush away impurity, collects eluent and above-mentioned alcohol deposit fluid and merges, and reclaims ethanol to there not being the alcohol flavor, collects medicinal liquid;
6. above-mentioned medicine liquid spray drying adds pharmaceutically acceptable carrier and/or excipient, sprays into volatile oil again, makes clinical acceptable forms.
8. preparation method as claimed in claim 7, it is characterized in that, 5. described step crosses the ZTC-1 macroporous adsorbent resin for supernatant, with distilled water 1500mL flush away impurity, then use 3000mL 60% ethanol elution, elution speed is 2.4BV/ hour, collects eluent and above-mentioned alcohol deposit fluid and merges, reclaim ethanol to there not being the alcohol flavor, collect medicinal liquid.
9. the application of each described Chinese medicine composition of claim 1-3 on the medicine of preparation treatment depression.
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| CN103212019B (en) * | 2012-12-10 | 2014-10-22 | 宋爱民 | Chinese materia medica preparation for treating depression |
| CN105250412B (en) * | 2015-11-10 | 2018-09-18 | 首都医科大学附属北京中医医院 | A kind of application of the Chinese medicine composition of soothing liver and strengthening spleen in the drug for preparing treatment anxiety-depression |
| CN105727121A (en) * | 2016-03-25 | 2016-07-06 | 谢春红 | Urine retention eliminating decoction for treating dysuria of elderly women |
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