CN101890135B - Antidepressant traditional Chinese medicine composition and application thereof - Google Patents
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Abstract
The invention provides an antidepressant traditional Chinese medicine composition, which is prepared from the following components in parts by weight: 15-50 parts of gypsum, 3-10 parts of rhizoma anemarrhenae, 10-30 parts of uncaria rhynchophylla, 3-10 parts of radix ophiopogonis, 5-15 parts of rehmanniae praeparatum, 5-15 parts of Inula japonica, 3-15 parts of officinal magnolia bark, 3-15 parts of medicinal cyathula root, 3-10 parts of raw hematite,10-30 parts of rhizoma phragmitis, 3-10 parts of immature bitter orange and 3-12 parts of semen raphani. The antidepressant traditional Chinese medicine composition in the invention has the following beneficial effects: (1) the composition can cure depression effectively; (2) as for curative effect, the composition is similar to or stronger than fluoxetine hydrochloride, and the composition has the functions of invigorating food stagnation and relaxing bowel; (3) as for price, the cost of the composition is lower than that of fluoxetine hydrochloride; and (4) in long-term clinic observation, side effects such as excitement, anxiety, thirsty, hydrosis, headache, drowsiness in day, insomnia at night, astriction and sexual dysfunction, damaged liver kidney function and the like do not occur.
Description
(1) technical field
The present invention relates to a kind of antidepressant Chinese medicine composition and application thereof.
(2) background technology
Depression is a kind of common mental sickness, mainly shows as depressedly, and interest lowers, pessimism, retardation of thinking lacks initiative, and self-accusation is from crime, and diet, sleep are poor, worry oneself to suffer from various diseases, feel whole body many places discomfort, suicidal thought and behavior can appear in severe patient.Depression is a kind of " from our nearest mental illness ".Along with being growing more intense of social competition, the physiology that people need bear and the pressure of psychological aspects are increasing, and the sickness rate of depression constantly raises, and the depression sickness rate that various diseases (coronary heart disease, diabetes, cancer) is followed also increases day by day.In the ten big diseases in the whole world (comprising developing country), depression is listed in the 5th, and the whole world has 300,014,000 patients with depression approximately, The World Health Organization's prediction, to the year two thousand twenty, depression will become the second largest disease that threatens human health, be only second to ischemic heart desease.
The pathogenic factor of depression is a lot.It mainly is bad social and psychological factor.The people lives in the society, and its life-span, health and disease are closely bound up with it invariably, people's worry, happiness, grief, happy, anxiety etc., and everything emotion of keeping or destroying people's normal physiological function all closely links to each other with society.The living condition comprises the variation of society, culture and objective environment, the variation of marriage, family, individual health and inter personal contact, changes in economic, individual school work success or failure etc.Allly in the life can cause powerful stress, conditions such as serious psychic trauma or depression experience all can become psychological factor.People find that also the brain function of depressive patients or brain structure have change.Also there are people and inherited genetic factors, characteristics of personality relevant.In a word, the cause of disease complexity of depression, countries in the world are still among constantly studying at present.
Owing to the reason that causes depression has a lot, and its pathogenetic influence factor also had a lot, at present, still do not have a kind of effective Therapeutic Method can be aspect depression curative effect, untoward reaction and prevention of recurrence fully up to expectations.The chemicals curative effect of treatment depression is obvious, but also exist onset time slow, the antidepressant spectrum is narrow, the many drawbacks of easy recurrence or the like.Patients with depression often changes with some biological rhythm and pace of moving things, as sleep disorder, inappetence, constipation, xerostomia, health is weak, energy goes down, sexual dysfunction etc., these physiological signs are difficult to solve with the antidepressant Western medicine, even some antidepressants also bring above-mentioned untoward reaction, and Chinese herbal medicine specimen is ruled together, can effectively improve the malaise symptoms of patients with depression, demonstrate distinctive feature than Western medicine.
Over year, Chinese medicine has carried out experiment and clinical research in various degree based on secular clinical treatment experience and advantage thereof from three aspects such as compound recipe, single medicinal material and effective ingredient, has showed good prospect surplus in the of nearly ten.But most of people think that the stagnation of QI is obstructed, and disorder of movement of QI is the basic cause of disease of early stage depression, and treatment is worked as based on the mediation mechanism of qi.
(3) summary of the invention
The present invention treats early prevention and treatment and delays the Chinese medicine composition that depression develops in order to provide a kind of, and the application of this Chinese medicine composition in preparation treatment depression medicine.
The technical solution used in the present invention is:
A kind of antidepressant Chinese medicine composition is made up of the component that the quality proportioning is following: 15～50 parts of Gypsum Fibrosum, 3～10 parts of the Rhizoma Anemarrhenaes, 10～30 parts of Ramulus Uncariae Cum Uncis, 3～10 parts of Radix Ophiopogonis, 5～15 parts in the Radix Rehmanniae, 5～15 parts of Flos Inulaes, 3～15 parts of Cortex Magnoliae Officinalis, 3～15 parts of Radix Cyathulaes, 3～10 parts of Haematitum, 10～30 parts of Rhizoma Phragmitiss, 3～10 parts of Fructus Aurantii Immaturuss, 3～12 parts of Semen Raphanis.
Cold in nature, the bitter in the mouth of the Rhizoma Anemarrhenae in the side, is moisturized laxation at the clearing away heat-fire relieving restlessness, can the long-pending heat of clear patients with depression gastrointestinal." property of medicine opinion " said: " ... cure mainly vexed hot-tempered vexedly, the back postpartum debility is produced in the contact of the hot labor of bone, kidney qi labor, and the loathing of cold is deficient, suffers from people's void and xerostomia, adds and uses it.Zhang Yuansu: the cool heart reduces phlegm and internal heat, and controls positive naked light heat, rushes down bladder kidney channel fire, pyretic headache, the dysentery lumbago is stench in the larynx.Fructus Aurantii Immaturus, bitter in the mouth, suffering, acid, temperature, cold nature is returned spleen, stomach warp, function dispelling the stagnated QI removing food stagnancy, the diffusing painful abdominal mass of reducing phlegm ".The Compendium of Material Medica cloud: " on the whole its merit all can promoting the circulation of QI.The next phlegm dyspnea of gas ends, and the capable then painful abdominal mass of gas expands and disappears, and the gas general rule is stung bitterly and ended, and diarrhea due to disorder of QI removes after then ... right Zhong Jing controls thoracic obstruction feeling of fullness, is key medicine with the Fructus Aurantii Immaturus "." Japan hanako materia medica ": " spleen invigorating, appetizing transfer five to hide, the therapeutic method to keep the adverse QI flowing downwards, preventing or arresting vomiting is contrary ".The Rhizoma Anemarrhenae, Fructus Aurantii Immaturus share altogether and to be monarch drug, and the heat clearing away circulation of qi promoting removes positive bright pathogenic heat, eliminate fullness and distention in the chest and hypochondrium, gastral cavity abdomen painful abdominal mass is vexed, the merit of playing the heat clearing away resolving depression altogether.Gypsum Fibrosum attaches to the lung and stomach meridians in sweet, hot, Great Cold, and function clearing away heat-fire, relieving restlessness are quenched the thirst; Radix Ophiopogonis, sweet, little hardship, be slightly cold.GUIXIN, lung, stomach warp, function YIN nourishing and the production of body fluid promoting, lung moistening clear away heart-fire; Rhizoma Phragmitis, sweet, cold, attach to the lung and stomach meridians function clearing away heat and promoting production of body fluid, relieving restlessness, preventing or arresting vomiting, diuresis; The Radix Rehmanniae, sweet, cold, GUIXIN, liver, kidney channel, the function clearing away heat and cooling blood, yin nourishing is promoted the production of body fluid.Wherein the heat of Gypsum Fibrosum lung heat clearing stomach, grow the moon of lung stomach; Clear away heart-fire Radix Ophiopogonis heat, grow the heart-yin, the heat of Rhizoma Phragmitis lung heat clearing stomach, grows the moon of lung stomach, and draw heat from urinating, but sore-throat relieving promotes the production of body fluid again; Can the purify the blood heat of branch of the Radix Rehmanniae, removing heat from blood clears away heart-fire, relieving restlessness, above four Chinese medicine bitter in the mouth and sweet is clear and rich medicine, heat clearing away and do not stay dry, again can YIN nourishing and the production of body fluid promoting, strengthen the merit of Rhizoma Anemarrhenae heat clearing away, be ministerial drug, play the effect that the relieving restlessness of promoting the production of body fluid is calmed the nerves.Cortex Magnoliae Officinalis, bitter, hot, temperature.Return spleen, stomach, lung, large intestine channel, the expectorant of function dampness, the therapeutic method to keep the adverse QI flowing downwards is removed full.Descending, the dyspepsia and intestinal stasis relieving of Cortex Magnoliae Officinalis energy dispelling the stagnated QI, auxiliary Fructus Aurantii Immaturus reaches the effect of the contrary gas of degraded; Flos Inulae, hardship, hot, one-tenth, tepor.Return lung, spleen, stomach, large intestine channel, function sending down the abnormal ascending QI, expectorant, row water, preventing or arresting vomiting.Flos Inulae moistens and falls, and it acts on the part of the body cavity above the diaphragm housing the heart and lungs, and the contrary gas of the part of the body cavity above the diaphragm housing the heart and lungs falls in auxiliary Rhizoma Phragmitis; Semen Raphani, hot, sweet, flat, return lung, spleen, stomach warp, function helps digestion and remove to expand, lowering the adverse-rising QI to resolve phlegm, help Fructus Aurantii Immaturus, Cortex Magnoliae Officinalis fall in Jiao's contrary gas, more than three medicines of distinguishing the flavor of be adjuvant drug altogether, play regulating QI and lowering the adverseness; Radix Cyathulae, property is flat, and sweet in the mouth, little hardship are returned liver, kidney channel, eliminating blood stasis and inducing menstruation, easing joint movement, inducing diuresis for treating stranguria syndrome, the Radix Cyathulae conducting blood to flow downwards, it is descending by heart channel to take stagnant heat, is full side's messenger drug.Antidepressant composition medication of the present invention is well-thought, and compatibility is precise and appropriate, and full side plays the heat clearing away resolving depression altogether, the merit of the relieving restlessness of promoting the production of body fluid, regulating QI and lowering the adverseness.
We develop as the basis with Baihu Tang, Baihu Tang comes from the treatise on Febrile Diseases of Eastern Han Dynasty's Zhang Zhongjing, and former side is by Gypsum Fibrosum, the Rhizoma Anemarrhenae, Semen oryzae sativae, Radix Glycyrrhizae is formed, and the kind affection of exogenous wind-cold of controlling passes the bright warp of sun in the heat-transformation, edema caused by disorder of QI heat syndrome due to the epidemic febrile disease wound biography edema caused by disorder of QI, be that pathogenic factor in the exterior is separated, strong, the promptly usually said Yangming Channel four big symptoms of high fever flushed complexion, excessive thirst taking fluids profusely, sweating, full and large pulse that the evil gradually flower in lining occurs.Depression belongs to Yangming Channel heat, causes disorder of movement of QI, the stagnation of QI obstructed, available Baihu Tang master it, dialectical plus-minus is formed.
The patients with depression overwhelming majority is seen food stagnation, heat stagnation, is the Yangming Channel calentura, and patients with depression is because the long-pending heat of gastrointestinal causes deficiency of stomach-Yin, spleen loses fortuneization, the spleen being the foundation of acquired constitution, dysfunction of the spleen in transportation, being difficult hemopoietic gas, and making the liver failing to be nourished, the catharsis function is influenced, causes depression of liver-QI; The taste insufficiency of generating and transforming QI and blood causes painstaking effortization to give birth to not enough, deficiency of heart-QI, and makes the dysfunction that The heart controls mental activities, causes malaise, irritated irritability, gloomy not easypro, the few dormancy or insomnia and dreamful sleep.So think that causing patient's disorder of movement of QI, the reason that the stagnation of QI is obstructed, most of patients is that Yangming Channel heat causes.Therefore the principles of formulating prescriptions are clear Yangming Channel heat, and YIN nourishing and the production of body fluid promoting makes transporting and transforming function of the spleen and stomach normal, and the heart is foster to some extent, fall simultaneously, middle Jiao's contrary gas, and it is descending to draw heat, thereby plays the effect of dredging mechanism of qi, relieving restlessness resolving depression.
Preferably, described Chinese medicine composition is made up of the following component of quality proportioning: 50 parts of Gypsum Fibrosum, 10 parts of the Rhizoma Anemarrhenaes, 30 parts of Ramulus Uncariae Cum Uncis, 10 parts of Radix Ophiopogonis, 15 parts in the Radix Rehmanniae, 15 parts of Flos Inulaes, 10 parts of Cortex Magnoliae Officinalis, 10 parts of Radix Cyathulaes, 10 parts of Haematitum, 30 parts of Rhizoma Phragmitiss, 10 parts of Fructus Aurantii Immaturuss, 12 parts of Semen Raphanis.
The invention still further relates to the application of described Chinese medicine compositions in the medicine of preparation treatment depression.Can be used for treating that dysphoria with smothery sensation is gloomy, depressed, hebetude, various depressive symptoms such as suicidal tendency are arranged when serious.
For increasing curative effect, described medicine can use jointly with oxidase inhibitor (MAOI) or selectivity oxidase inhibitor (RIMA).
Described medicine can add conventional pharmaceutic adjuvant, makes one of following dosage form: 1. decoction, 2. syrup, 3. granule, 4. capsule, 5. drop pill, 6. tablet.
The invention still further relates to that described Chinese medicine compositions is had a dizzy spell in preparation treatment, dryness of the mouth and throat, fullness and distention in the chest and hypochondrium, gastral cavity abdomen painful abdominal mass is vexed, stool is smooth or constipation, muscle is aching and tired, dorsal muscles is weak, shortness of breath and palpitation, malaise, irritated irritability, gloomyly do not relax, few sleep or insomnia and dreamful sleep in the medicine of one or more diseases in application.
Subordinate act is seen: antidepressant composition has certain therapeutical effect to the chronic unpredictability depression model of mice.Compare with normal group, the model group weight of mice is slow, and sucrose solution consumption is starkly lower than normal group, and the autonomic activities number of times reduces, and non-swimming time increases.Antidepressant composition high dose group of the present invention is in the 7th, the mice body weight change is apparently higher than model group in the time of 14 days, the sucrose solution consumption of the high, medium and low dosage group of antidepressant composition of the present invention mice is apparently higher than model group, in, low dose group mice autonomic activities number of times is obviously more than model group, the non-swimming time of low dose group mice is starkly lower than model group, thereby point out antidepressant composition that control depression and various depressed performance thereof are had certain effect, have exploitation value preferably.
From mechanism of action: Sichuan Cortex Magnoliae Officinalis (processed), Flos Inulae, Fructus Aurantii Immaturus (parched), the Radix Rehmanniae presents relatively than obvious inhibiting activity monoamine oxidase-B (MAOB), and suppression ratio all reaches more than 50%.Similar with MAOB, antidepressant composition of the present invention, Sichuan Cortex Magnoliae Officinalis (processed), Flos Inulae, Fructus Aurantii Immaturus (parched), the Radix Rehmanniae presents relatively than obvious inhibiting activity monoamine oxidase A (MAOA), in addition, Ramulus Uncariae Cum Uncis, Rhizoma Phragmitis also show and must suppress active, and suppression ratio all reaches more than 35%.Oxidase inhibitor is by the activity of monoamine oxidase, MAO, make that the monoamine transmitters degraded reduces, in the synaptic space effectively the mediator level increase and play the effect of treatment depression.Side of antidepressant is external to have certain inhibitory action to monoamine oxidase, MAO, further discloses, and its antidepressant effect mechanism suppresses relevant with monoamine oxidase, MAO.In the brain mensuration of dopamine mediator also point out its antidepressant effect mechanism may with increase brain in the content of monoamine neurotransmitter relevant.
The beneficial effect of antidepressant Chinese medicine composition of the present invention is mainly reflected in: (1) can effectively treat depression; (2) similar to fluoxetine Hydrochloride or stronger on action effect, and have the conditioning food stagnation, the effect of loosening bowel to relieve constipation; (3) on price, cost is lower than fluoxetine Hydrochloride; (4) in secular clinical observation, find no excitement, anxiety, xerostomia, hyperhidrosis, headache, daytime is drowsiness, insomnia in evening, constipation and sexual dysfunction, the side effect of the impaired grade of hepatic and renal function.
(4) description of drawings
Fig. 1 is the influence of antidepressant composition of the present invention to depression model mice body weight change;
The influence that Fig. 2 consumes depressed mice sucrose solution for antidepressant composition of the present invention;
Fig. 3 is the influence of antidepressant composition of the present invention to behavioristics's (non-swimming time);
Fig. 4 is the influence of antidepressant composition of the present invention to behavioristics's (autonomic activities number of times).
(5) specific embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
Embodiment 1: antidepressant Chinese medicine composition
Single prescription amount is as follows: Gypsum Fibrosum 50 grams, and the Rhizoma Anemarrhenae 10 grams, Ramulus Uncariae Cum Uncis 30 grams, restrain Radix Ophiopogonis 10, the Radix Rehmanniae 15 grams, Flos Inulae 15 grams, Cortex Magnoliae Officinalis 10 grams, Radix Cyathulae 10 grams, Haematitum 10 restrains, Rhizoma Phragmitis 30 grams, Fructus Aurantii Immaturus 10 grams, Semen Raphani 12 grams; By above-mentioned composition, get the prepared slices of Chinese crude drugs of 8 prescription amounts, added 10 times of quality water very hot oven decoctings 60 minutes, decoct three times, remove sediment, being concentrated into density is 1.20g/ml, and 60 ℃ add ethanol precipitation to determining alcohol down is 50% (v/v), cold preservation 48 hours, remove precipitation, get supernatant, supernatant is evaporated to the extractum that no ethanol is distinguished the flavor of, promptly get antidepressant Chinese medicine composition.
Embodiment 2: antidepressant Chinese medicine composition
Single prescription amount is as follows: Gypsum Fibrosum 17 grams, and the Rhizoma Anemarrhenae 3 grams, Ramulus Uncariae Cum Uncis 10 grams, restrain Radix Ophiopogonis 3, the Radix Rehmanniae 5 grams, Flos Inulae 5 grams, Cortex Magnoliae Officinalis 3 grams, Radix Cyathulae 3 grams, Haematitum 3 restrains, Rhizoma Phragmitis 10 grams, Fructus Aurantii Immaturus 3 grams, Semen Raphani 4 grams; Get the prepared slices of Chinese crude drugs of 8 prescription amounts, added 8 times of quality water very hot oven decoctings 60 minutes, decoct three times, remove sediment, being concentrated into density is 1.20g/ml, 60 ℃ add ethanol precipitation to determining alcohol down is 50%, precipitation is removed in cold preservation 48 hours, gets supernatant, the extractum 84.90 that supernatant is evaporated to no ethanol flavor restrains, and promptly gets antidepressant Chinese medicine composition.Embodiment 3: antidepressant Chinese medicine composition
Single prescription amount is as follows: Gypsum Fibrosum 9 grams, and the Rhizoma Anemarrhenae 2 grams, Ramulus Uncariae Cum Uncis 5 grams, restrain Radix Ophiopogonis 2, the Radix Rehmanniae 3 grams, Flos Inulae 3 grams, Cortex Magnoliae Officinalis 2 grams, Radix Cyathulae 2 grams, Haematitum 2 restrains, Rhizoma Phragmitis 5 grams, Fructus Aurantii Immaturus 2 grams, Semen Raphani 2 grams; Get the prepared slices of Chinese crude drugs of 8 prescription amounts, added 15 times of quality water very hot oven decoctings 60 minutes, decoct three times, remove sediment, being concentrated into density is 1.20g/ml, 60 ℃ add ethanol precipitation to determining alcohol down is 50%, precipitation is removed in cold preservation 48 hours, gets supernatant, the extractum 42.45 that supernatant is evaporated to no ethanol flavor restrains, and promptly gets antidepressant Chinese medicine composition.
Embodiment 4: antidepressant Chinese medicine composition
Single prescription amount is as follows: Gypsum Fibrosum 34 grams, and the Rhizoma Anemarrhenae 6 grams, Ramulus Uncariae Cum Uncis 20 grams, restrain Radix Ophiopogonis 6, the Radix Rehmanniae 10 grams, Flos Inulae 10 grams, Cortex Magnoliae Officinalis 6 grams, Radix Cyathulae 6 grams, Haematitum 6 restrains, Rhizoma Phragmitis 20 grams, Fructus Aurantii Immaturus 6 grams, Semen Raphani 8 grams; Get the prepared slices of Chinese crude drugs of 8 prescription amounts, added 12 times of quality water very hot oven decoctings 60 minutes, decoct three times, remove sediment, being concentrated into density is 1.20g/ml, 60 ℃ add ethanol precipitation to determining alcohol down is 50%, precipitation is removed in cold preservation 48 hours, gets supernatant, the extractum 169.80 that supernatant is evaporated to no ethanol flavor restrains, and promptly gets antidepressant Chinese medicine composition.
Embodiment 5: the water extracting alcohol hypostasis of antidepressant Chinese medicine composition is treated chronic unpredictability stress depression experiment
One. materials and methods
1. medicine: positive drug fluoxetine (fluoxetine hydrochloride capsules) is Lilly Co., Eli.'s product, batch number: 9202B;
2. modeling: except the blank group, other are respectively organized and accept a kind of stimulation every day, totally 14 days, every kind of stimulation mode can not be above 2 times and irregular, stress comprise: fasting 24h, prohibit water 24h, put upside down round the clock, moist bedding and padding, suspention 15min, 10 ℃ of cold stimulation 5min, 45 ℃ of thermostimulation 5min, folder tail 1min, whirlpool concussion 1min etc.
3. grouping and administration:
60 of healthy Kunming mouses are raised a week to conform, and carry out behavioristics's scoring with the Open-Field method after the week, select the close mice of scoring, are divided into 6 groups at random, and except that the blank group, all the other are respectively organized all single cage of mice and raise.In modeling simultaneously, each organizes gastric infusion, and normal group and model group give the normal saline of equivalent, stimulate after administration every day, once a day, totally 14 days.Be grouped as follows:
(1) normal group, 10, do not stimulate, irritate stomach every day and give the equivalent normal saline.
(2) model group, 10, irritate stomach every day and give the equivalent normal saline, stimulate simultaneously.
(3) low dose group, 10; Be model+embodiment 3 gained antidepressant composition 4.8g/kg, be equivalent to crude drug in whole 0.74g/kg, being mixed with concentration is to stimulate after 0.037g/ml administration every day, once a day, and totally 14 days.
(4) dosage group in, 10; Be model group+embodiment 2 gained antidepressant composition 9.6g/kg, be equivalent to crude drug in whole 1.48g/kg, being mixed with concentration is to stimulate after 0.074g/ml administration every day, once a day, and totally 14 days.
(5) high dose group, 10; Be model group+embodiment 4 gained antidepressant composition 19.2g/kg, be equivalent to crude drug in whole 2.96g/kg, being mixed with concentration is to stimulate after 0.148g/ml administration every day, once a day, and totally 14 days.
(6) positive drug group, 10, i.e. model group+fluoxetine Hydrochloride group.Be equivalent to 0.003g/kg, stimulate after administration every day, once a day, totally 14 days.
4. testing index
(1) body weight change: respectively at modeling d1, measuring the mice body weight in 8,15 days, is basic body weight with modeling d1 body weight, calculates the mice body weight change.
(2) sucrose solution consumption: D7 prohibited water in 14 days, prohibited behind the water second day, gave 1% sucrose water 150ml, measured the amount of drinking in the 1h;
(3) the mice autonomic activities is measured: 1h after the last administration in d14 days, mice is placed wooden case [(40*40*40cm (the wide * height of long *)], the bottom is divided into 25 grids, spontaneous activity in mice in the record 5min, observation index: 1. horizontal anomalous movement number of times: stride into adjacent lattice number of times more than the three-jaw; 2. number of times moves both vertically: the above number of times of the liftoff 1cm of two forelimbs.
(4) mice forced swimming experiment: 1h after the last administration in d14 days, each is organized the container that mice is put into depth of water 10cm respectively, water temperature is observed 6min for 25 ℃, observes and write down the interior dead time of 4min after each group.
(5) to the influence of monoamine neurotransmitters in the chronic stress depression model mouse brain
The rat broken end is got brain, peel off full brain on ice, the back of weighing adds reagent, handles postcooling to room temperature, with fluorescence spectrophotometry DA light absorption value.Calculate dopamine neurotransmitter content in the brain according to formula.
5. date processing
Experimental data adopts SPSS11.5 analytical applications software to carry out statistical analysis, and continuous data all adopts mean ± standard deviation
Expression.Two samples are relatively with the T check, and a plurality of sample means relatively adopt one factor analysis of variance (One-way ANONA).P＜0.05 expression difference has statistical significance; P＜0.01 expression difference has remarkable statistical significance.
Two. the result
1. to the influence of body weight change
The result is referring to table 1 and Fig. 1.Compare with the blank group, the existing remarkable reduction trend of model group mice weight increase after the 7th day, the weight increase after the 14th day also has remarkable meaning (P＜0.01), illustrates that the chronic stress depression model can make the mice weight increase obviously descend.Compare with model group, antidepressant composition high dose group of the present invention, positive drug mice weight increase be apparently higher than model group (P＜0.01), in, the low dose group mice has the trend that increases, but do not have tangible significant difference.
Table 1: antidepressant composition of the present invention is to the influence of depression model mice body weight change
Annotate: compare △: P＜0.05 with the blank group, *: P＜0.05 is compared with normal group in △ △: P＜0.01; *: P＜0.01 (table 2～table 4 together)
2. to the influence of sucrose solution consumption
The result is referring to table 2 and Fig. 2.Compare with the blank group, the sucrose solution consumption of model group mice after the 7th day has remarkable reduction trend (P＜0.01), and obvious reduction (P＜0.05) was also arranged after the 14th day.Compare with model group, the high, medium and low dosage group of antidepressant composition of the present invention mice all shows significant sucrose solution hobby (P＜0.01), and the positive drug mice has tangible sucrose solution consumption to increase (P＜0.05).
Table 2: the influence that antidepressant composition of the present invention consumes depressed mice sucrose solution
3. to ethological influence
The result is referring to table 3 and Fig. 3, Fig. 4.Compare with the blank group, model group mice horizontal anomalous movement obviously lacks (P＜0.05) than the movable number of times of blank group with vertical movable number of times, and non-swimming time obviously is longer than blank group (P＜0.05); Compare with model group, low, the middle dosage group of antidepressant composition of the present invention can significantly increase mice autonomic activities number of times (P＜0.01); Low dose group mice non-swimming time obviously reduces (P＜0.05).
Table 3: antidepressant composition of the present invention is to ethological influence
3.4 influence to Dopaminergics neurotransmitter content in the brain
The result is referring to table 4.With the blank group relatively, antidepressant composition low dose group of the present invention is to the content of dopamine mediator be significantly improved (P＜0.05); With matched group relatively, antidepressant composition low dose group of the present invention is to DOPAMINE CONTENT IN RABBIT also be significantly improved (P＜0.05).
Table 4: antidepressant composition of the present invention is to the influence of Dopaminergics neurotransmitter content in the brain
4 discuss
Pathogenesis about depression has a variety of sayings, does not have clear and definite pathogenesis at present.One of hypothesis that generally believes is most thought: the pathogeny of depression is owing to reduce in contain quantity not sufficient or the function of specific nerve conduction path epineural mediator serotonin (5-HT), and norepinephrine (NE) miopragia causes on this basis.The antidepressants of clinical practice at present are developed into according to this mechanism, yet take the antidepressants of chemosynthesis for a long time, will serious toxic and side effects occur.Therefore, from plant, seek, develop rational antidepressants, come into one's own day by day.
This experimentation shows, the specificity height of chronic unpredictability stress depression model can significantly cause depression, can be widely used in the pharmacodynamic study of antidepressant drug.Antidepressant composition of the present invention can significantly increase sucrose solution consumption, suppresses to lose weight, and shortens the mice forced swimming dead time, promotes the mice autonomic activities, and can improve the content of monoamine neurotransmitter in the chronic depression mouse brain.This result of experiment is clear and definite, points out antidepressant composition water extract-alcohol precipitation solution of the present invention to have certain antidepressant effect, and its antidepressant effect mechanism may be relevant with the content of monoamine neurotransmitter in the increase brain.
Embodiment 6: external inhibitory action to monoamine oxidase, MAO
Oxidase inhibitor is a first generation antidepressant Western medicine.Oxidase inhibitor is by suppressing the activity of monoamine oxidase, MAO, make that the monoamine transmitters degraded reduces, in the synaptic space effectively the mediator level increase and play the effect of treatment depression.In vitro tests is adopted in this research, has studied the external inhibitory action to monoamine oxidase, MAO of each flavour of a drug of antidepressant composition of the present invention and prescription, to inquire into its mechanism of action.
Method: in the EP pipe, add 4 μ l BSA, (the inhibitor sample is antidepressant composition of the present invention or one-component Chinese medicine wherein to 4 μ l inhibitor samples (its empty group replaces the inhibitor sample with 4 μ lDMSO), or Sichuan Cortex Magnoliae Officinalis (processed), Flos Inulae, Fructus Aurantii Immaturus (parched), the Radix Rehmanniae are pressed the extracting solution of the crude drug content 1.20g/ml that embodiment 1 extracting method obtains), 12 μ l crude enzyme liquids (MAOB), add borate buffer (pH=8.4) to 500 μ l, place 38 ℃ of water-bath reactions 3 hours.Add 2 μ l fluorescent probes then, water-bath is 2 hours again, gets 100 μ l in 96 orifice plates, measures fluorescent value with microplate reader under ex/lem=360/450nm.The results are shown in Table 5.
From showing antidepressant composition of the present invention as can be seen, Sichuan Cortex Magnoliae Officinalis (processed), Flos Inulae, Fructus Aurantii Immaturus (parched), the Radix Rehmanniae monoamine oxidase-B (MAOB) is presented relatively than obvious inhibiting activity.Suppression ratio all reaches more than 50%.Similar with MAOB, antidepressant composition of the present invention, Sichuan Cortex Magnoliae Officinalis (processed), Flos Inulae, Fructus Aurantii Immaturus (parched), the Radix Rehmanniae present relatively than obvious inhibiting activity monoamine oxidase A (MAOA), in addition, Ramulus Uncariae Cum Uncis, Rhizoma Phragmitis also show and must suppress active, and suppression ratio all reaches more than 35%.
The results are shown in Table 5.
Table 5: the external inhibitory action of each flavour of a drug of antidepressant composition of the present invention and prescription to monoamine oxidase, MAO
| Inhibitor | Monoamine oxidase A suppression ratio (%) | Monoamine oxidase-B suppression ratio (%) |
| Antidepressant composition of the present invention | ?36.11 | ?51.98 |
| The Rhizoma Anemarrhenae | ?4.18 | ?4.19 |
| Fructus Aurantii Immaturus | ?42.59 | ?76.85 |
| Gypsum Fibrosum | ?1.60 | ?7.71 |
| Radix Ophiopogonis | ?25.24 | ?40.15 |
| Rhizoma Phragmitis | ?49.26 | ?15.59 |
| Flos Inulae | ?63.76 | ?73.19 |
| Cortex Magnoliae Officinalis | 58.08 | 68.42 |
| The Radix Rehmanniae | 58.05 | 51.75 |
| Haematitum | 25.98 | 6.66 |
| Ramulus Uncariae Cum Uncis | 35.32 | 43.13 |
| Radix Cyathulae | 6.30 | 41.60 |
Oxidase inhibitor is by the activity of monoamine oxidase, MAO, make that the monoamine transmitters degraded reduces, in the synaptic space effectively the mediator level increase and play the effect of treatment depression.Antidepressant composition of the present invention is external to have certain inhibitory action to monoamine oxidase, MAO, further discloses, and its antidepressant effect mechanism suppresses relevant with monoamine oxidase, MAO.
Embodiment 7: clinical observation on the therapeutic effect
One, case is selected and criterion
(1) physical data
Take in the patient of prescription on individual diagnosis in 2002～2006 years altogether.60 examples are diagnosed as patients with depression.They all meet following 1.2 diagnostic criterias of listing and include standard in.Wherein 30 examples are organized in treatment, man's 16 examples, woman's 14 examples, 19 years old to 52 years old age, 32.6 years old mean age (32.6 ± 5.3), matched group 30 examples, man's 15 examples, woman's 15 examples, 18 years old to 56 years old age, 33.1 years old mean age (33.1 ± 5.6). two groups of patients' sex, age, the course of disease, this four aspect of clinical symptoms credit are by statistics analysed that there are no significant difference (P＜0.05) are had comparability.
(2) diagnostic criteria
Depression outbreak symptom is lost based on mental state, and has in following 94 at least.1. hebetude does not have happy sense; 2. energy goes down, and feeling of fatigue is arranged; 3. psychomotor is blunt or intense; 4. self evaluation is crossed low self-accusation, and feeling of guilt is arranged; 5. association difficulty, elaborative faculty descends; 6. occur the thought of wanting to die repeatedly or suicide, autolesionism are arranged; 7. insomnia, early awakening or sleep more; 8. inappetence, weight loss; 9. hyposexuality.After being defined as depression, the scoring of its degree, according to " Chinese mental disorder classification and the diagnostic criteria " third edition (CCMD-3), the scoring of depression diagnosis HAMD Hamilton depressive scale, (wherein 0～8 was divided into no depressive symptom greater than 17 minutes, 9～16 are divided into slight depression, and 17～24 are divided into the moderate depression, are severe depression more than 25 minutes).
(3) include standard in
1. meet above-mentioned diagnostic criteria, and cause its social function impaired, cause suffering and the lasting at least 2 all persons of adverse consequences to me; 2. can there be some fissility symptom, but do not meet the standard of Split disease, after the division remission, satisfy at least 2 weeks of paralepsy standard, Hamilton depressive scale HAMD scoring 〉=17 minutes.
(4) exclusion standard: depressed due to the 1. organic mental disorders, psychoactive drug substance and non-addiction material; 2. serious suicidal tendency person is arranged; 3. be associated with cardiovascular, liver, kidney and hemopoietic system primary disease person; 4. bipolar affective disorder person; 5. the depression of spiritedness characteristic of disease symptom; 6. nearly 2 weeks are used antidepressants and antipsychotic drug person.
Two, treatment grouping
(1) treatment group: based on clear Yangming Channel heat, assistant is with regulating QI and lowering the adverseness, with antidepressant composition decoction of the present invention.Medicine is formed: Gypsum Fibrosum 50 grams, and the Rhizoma Anemarrhenae 10 grams, Ramulus Uncariae Cum Uncis 30 grams, restrain Radix Ophiopogonis 10, the Radix Rehmanniae 15 grams, Flos Inulae 15 grams, Cortex Magnoliae Officinalis 10 grams, Radix Cyathulae 10 grams, Haematitum 10 grams, Rhizoma Phragmitis 30 grams, Fructus Aurantii Immaturus 10 grams, Semen Raphani 12 gram, every day potion, decocting twice divides 2 decoction being taken warmly sooner or later, 8 weeks of logotype.
(2) matched group: take Western medicine fluoxetine (fluoxetine Hydrochloride) every day 1 time, each 20mg, 8 weeks of logotype.
Three, criterion of therapeutical effect
Antidepressant efficacy assessment standard: adopt Hamilton depressive scale (HAMD-3).Recovery from illness: HAMD subtracts the branch rate more than 75%.Marked improvement: HAMD subtracts branch rate 50%～74%.Progressive: HAMD subtracts branch rate 25%～49%.Invalid: HAMD subtracts the branch rate below 25%.
Enumeration data adopts x
2Check, measurement data adopt variance analysis P＜0.05 for difference statistical significance to be arranged.
Four, therapeutic outcome
The comparison of two groups of curative effects: treatment group satisfactory effect, total effective rate reaches 93.3%, wherein recovery from illness and marked improvement totally 26 examples, 2 examples that improve, invalid 2 examples.The matched group total effective rate reaches 80%, wherein fully recovers and marked improvement 19 examples progressive 5 examples, invalid 6 examples.Two groups of total effective rate comparing differences have statistical significance.(P＜0.05) illustrates that treatment group curative effect obviously is better than matched group.Chinese medicine is described when 8 courses of treatment in week, curative effect is better than Western medicine.
(1) two group of curative effect sees Table 6.
Table 6: two groups of curative effects relatively
| Group | The example number | Recovery from illness | Marked improvement | Progressive | Invalid | Total effective rate % |
| The |
30 | 16(53.3) | 10(33.3) | 2(6.77) | 2(6.7) | 93.3 |
| Matched |
30 | 10(33.3) | 9(30.0) | 5(16.7) | 6(20.0) | 80.0 |
Annotate: compare △ P＜0.05 with matched group
The HAMD scoring relatively sees Table 7 before and after two groups of treatments.
Table 7: the HAMD scoring relatively before and after two groups of treatments
| Group | The example number | Before the treatment | After the treatment |
| The |
30 | 27±5 | 8±5 |
| Matched |
30 | 27±4 | 13±4 |
Annotate: treatment group and matched group compare △ P＜0.05 after treatment
5, discuss
Depression is one of commonly encountered diseases, frequently-occurring disease in the psychosis.Its reason relates to many-sides such as heredity, individual quality, Physiology and biochemistry, social factor.Pathogenesis is not clear and definite as yet so far.The modern depression cause of disease, pathogenesis that the traditional Chinese medical science is thought are more numerous and diverse, mostly are irritability stasis, strongly fragrant and heat-transformation, in disturb the mind or dysfunction of the spleen in transportation, body fluid stops gathering into expectorant, mental disorder is obstructed and is caused lack of preservation of spirit, or qi-blood-body fluid loses emptyly, brain is refreshing to be lost and supports and cause morbidity.Also there is the scholar to think that the spleen kidney plays an important role in this disease.But a variety of causes thinks that all the stagnation of QI is obstructed, the basic cause of disease of early stage depression during disorder of movement of QI.
The inventor thinks and causes patient's disorder of movement of QI, the reason that the stagnation of QI is obstructed, most of patients are that Yangming Channel heat causes, and patients with depression is because the long-pending warm of gastrointestinal, cause deficiency of stomach-Yin, spleen loses fortuneization, the spleen being the foundation of acquired constitution, dysfunction of the spleen in transportation, being difficult hemopoietic gas, and making the liver failing to be nourished, the catharsis function is influenced, causes depression of liver-QI; The taste insufficiency of generating and transforming QI and blood causes painstaking effortization to give birth to not enough, deficiency of heart-QI, and makes the dysfunction that The heart controls mental activities, causes malaise, irritated irritability, gloomy not easypro, the few dormancy or insomnia and dreamful sleep.So think that causing patient's disorder of movement of QI, the reason that the stagnation of QI is obstructed, most of patients is that Yangming Channel heat causes.Therefore the principles of formulating prescriptions are clear Yangming Channel heat, and YIN nourishing and the production of body fluid promoting makes transporting and transforming function of the spleen and stomach normal, and the heart is foster to some extent, fall simultaneously, middle Jiao's contrary gas, and it is descending to draw heat, thereby plays the effect of dredging mechanism of qi, relieving restlessness resolving depression.Antidepressant composition of the present invention determined curative effect clinically has certain therapeutical effect to depression, therefore is worth further enlarging clinical research.
Claims (5)
1. an antidepressant Chinese medicine composition is made up of the component that the quality proportioning is following: 15～50 parts of Gypsum Fibrosum, 3～10 parts of the Rhizoma Anemarrhenaes, 10～30 parts of Ramulus Uncariae Cum Uncis, 3～10 parts of Radix Ophiopogonis, 5～15 parts in the Radix Rehmanniae, 5～15 parts of Flos Inulaes, 3～15 parts of Cortex Magnoliae Officinalis, 3～15 parts of Radix Cyathulaes, 3～10 parts of Haematitum, 10～30 parts of Rhizoma Phragmitiss, 3～10 parts of Fructus Aurantii Immaturuss, 3～12 parts of Semen Raphanis.
2. Chinese medicine composition as claimed in claim 1 is characterized in that described Chinese medicine composition is made up of the following component of quality proportioning: 50 parts of Gypsum Fibrosum, 10 parts of the Rhizoma Anemarrhenaes, 30 parts of Ramulus Uncariae Cum Uncis, 10 parts of Radix Ophiopogonis, 15 parts in the Radix Rehmanniae, 15 parts of Flos Inulaes, 10 parts of Cortex Magnoliae Officinalis, 10 parts of Radix Cyathulaes, 10 parts of Haematitum, 30 parts of Rhizoma Phragmitiss, 10 parts of Fructus Aurantii Immaturuss, 12 parts of Semen Raphanis.
3. the application of Chinese medicine compositions as claimed in claim 1 or 2 in the medicine of preparation treatment depression.
4. application as claimed in claim 3 is characterized in that described medicine and oxidase inhibitor use jointly.
5. application as claimed in claim 3 is characterized in that described medicine makes one of following dosage form:
1. decoction, 2. syrup, 3. granule, 4. capsule, 5. drop pill, 6. tablet.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1491713A (en) * | 2003-04-04 | 2004-04-28 | 清华大学 | Chinese medicine compound preparation for treating depression |
| CN1895562A (en) * | 2006-05-31 | 2007-01-17 | 胡红芳 | Decoction for treating exuberance of heart-liver fire depressive disorders and its preparation |
| CN101085231A (en) * | 2007-06-20 | 2007-12-12 | 济南新境界企业管理咨询有限公司 | Internal-applied traditional Chinese medicine composition for treating depression |
| CN101711847A (en) * | 2009-12-08 | 2010-05-26 | 中国人民解放军第三医院 | Oral traditional Chinese medicine preparation for treating melancholia and anxiety neurosis |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1491713A (en) * | 2003-04-04 | 2004-04-28 | 清华大学 | Chinese medicine compound preparation for treating depression |
| CN1895562A (en) * | 2006-05-31 | 2007-01-17 | 胡红芳 | Decoction for treating exuberance of heart-liver fire depressive disorders and its preparation |
| CN101085231A (en) * | 2007-06-20 | 2007-12-12 | 济南新境界企业管理咨询有限公司 | Internal-applied traditional Chinese medicine composition for treating depression |
| CN101711847A (en) * | 2009-12-08 | 2010-05-26 | 中国人民解放军第三医院 | Oral traditional Chinese medicine preparation for treating melancholia and anxiety neurosis |
Non-Patent Citations (1)
| Title |
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| 修丽娟等.抑郁症中医研究回顾与展望.《中西医结合学报》.2008,第6卷(第4期), * |
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