CN102228659B - Chinese medicinal composition for treating generalized anxiety disorder and preparation method thereof - Google Patents

Chinese medicinal composition for treating generalized anxiety disorder and preparation method thereof Download PDF

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CN102228659B
CN102228659B CN2011101771050A CN201110177105A CN102228659B CN 102228659 B CN102228659 B CN 102228659B CN 2011101771050 A CN2011101771050 A CN 2011101771050A CN 201110177105 A CN201110177105 A CN 201110177105A CN 102228659 B CN102228659 B CN 102228659B
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高松
车彦忠
郭水柱
陈克宇
陈洪英
章运典
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ZHONGJING WANXI PHARMACEUTICAL CO., LTD.
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WANXI PHARMACEUTICAL CO Ltd HENAN PROV
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Abstract

The invention relates to a Chinese medicinal composition for treating generalized anxiety disorder and a preparation method thereof. The Chinese medicinal composition comprises the following Chinese herbal medicines in part by weight: 5 to 25 parts of bupleurum, 5 to 25 parts of gardenia jasminoides, 10 to 80 parts of manyprickle acanto-panax root, 5 to 40 parts of juncus effusus linne, 5 to 40 parts of common selfheal fruit-spike, 10 to 30 parts of villous amomum fruit and 10 to 40 parts of nacre. The invention also provides a preparation method of the composition. The Chinese medicinal composition has the advantages of quick response, definite curative effect, small toxic and side effects, high compliance of patients and the like in the clinical practice of the treatment of the generalized anxiety disorder (GAD), can improve the generation and development of the disease tendency of the GAD obviously and has a bright wide clinical application prospect.

Description

Chinese medicine composition of treatment generalized anxiety disorder and preparation method thereof
Technical field
The present invention relates to a kind of Chinese medicine composition, particularly a kind of Chinese medicine composition of treating generalized anxiety disorder, and preparation method thereof, belong to the field of Chinese medicines.
Background technology
(generalized anxiety disorder GAD) as the clinical commonly encountered diseases of psychiatric department, frequently-occurring disease, is serious harm human physical and mental health's a spirit type illness to generalized anxiety disorder.According to " Chinese mental disorder classification with the diagnostic criteria third edition " criteria for classification (CCMD-3), primary disease panic disorder normal and acute attack closes and is called anxiety neurosis, but is its topmost form of expression with GAD in clinical.Modern clinical research shows that GAD patient's clinical symptoms is various, pathogeny is complicated, and primary disease is the chronic course of disease more and is prone to recurrence; Symptom is delayed repeatedly, and is associated with many physical diseases, also sick altogether depressed and other anxiety disorders of the patient of significant proportion; The patient not only exists and is difficult to the psychic pain of standing and can't break away from; Severe patient can cause social function impaired, even occurs committing suiside, and causes serious spirit and financial burden for individual, family, society.Therefore, carrying out effective study on prevention of GAD and be not only great public health problem, also is comparatively outstanding social problem, has become the problem that society and medical circle are widely paid close attention to.
With regard to the clinical characters of disease, GAD is a core symptom with the spirituality anxiety, mainly shows as the frightened or on tenterhooks of frequent or lasting no clear and definite object or immobilized substance, and its nervous degree with worry does not conform to actual environment very much, but is difficult to automatic control.In addition; Normal performance with somatic anxiety; Mainly be that autonomic nervous function hyperfunction (more common with respiratory system, cardiovascular system, nervous system, genitourinary system and skin heart reaction symptom) and motion are uneasy, also there are cognitive dysfunction such as attention, memory, execution function in the patient who has.
GAD is the modern medicine name of disease, though Chinese medicine does not have this name of disease, with regard to its cause of disease and clinical manifestation, belongs to feelings will disease category more.According to the different manifestations of its primary symptom, can it be belonged in a plurality of disease of tcm such as " epilepsy ", " lantern disease ", " being insomnia ", " hysteria ", " Bulbus Lilii syndrome ", " globus hystericus ".Because the GAD clinical symptoms is various, pathogeny is complicated; Sum up the tame argumentation to the GAD etiology and pathogenesis of traditional Chinese medical science doctor and roughly can reduce the case of a physically strong patient running a high fever, deficient syndrome and three aspects of simulataneous insufficiency and excessive, wherein most families that cure tend to think that the outbreak of GAD is its basic pathogenesis with pathogenic fire derived from stagnation of liver-QI.
At present, the treatment of GAD mainly is that medicine is main, especially Western medicine; Although structure novel anxiolytic thing different, various in style continues to bring out, for the treatment of GAD provides different selections, in the treatment of generalized anxiety disorder; The past first-selected benzodiazepine medicine (BZD); Its obvious effective rate is 41%~59%, but it has side effect such as addiction property, drug resistance and withdrawal symptom, is prone to cause iatrogenic addiction with BZD treatment generalized anxiety disorder.And the Western medicine that is usually used in treating GAD at present has buspirone, alprazolam and paroxetine hydrochloride etc.; Can be used for treatment with patients such as slightly depressed generalized anxiety disorder (GAD), depressions; The addiction property of no benzodiazepine medicine and drug resistance; But have mostly that onset is slow, grow the course of treatment, cost an arm and a leg, the toxic and side effects of medicine, cause problems such as untoward reaction, untoward reaction is mainly dizziness, insomnia, xerostomia, feels sick, perspiration, constipation, blurred vision etc. are seen more.In addition, anxiolytic drugs is often to certain single link effect mostly, and the treatment spectrum of disease is narrow; In the face of the multiformity of patient's clinical symptoms, pathogenetic complexity often is difficult to obtain satisfactory effect; Cause patient's compliance relatively poor, limited the application of this type medicine to a certain extent.Aspect treatment by Chinese herbs, there have been some correlational studyes, but, caused the effective percentage of medicine low owing to select the limitation of medical material and the science limitation of prescription for use, therefore many patients also can't reach satisfied curative effect.
The present invention is based on the principle of organic conception and determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, is characteristic with the individualized treatment, has proposed this kind Chinese medicine composition, and it has the motility of principle-method-recipe-medicines and the safety of drug effect.To its clinical symptoms multiformity, pathogenetic complexity; Chinese medicine composition of the present invention can launch treatment from many target spots, too many levels, multipath; In clinical practice, have rapid-action, determined curative effect, patient's compliance is good; Can obviously improve the advantage such as generation and development of GAD patient's condition, have broad clinical application prospect.
Summary of the invention
To above-mentioned situation, technical problem to be solved by this invention provides a kind of Chinese medicine composition of treating generalized anxiety disorder, and the inventor already cures and teaches 30 over-carriages, learns that to test tool rich, and the diagnosis and treatment of anxiety neurosis are quite had one's own knack.Behind Clinical symptoms reductive analysis to anxiety patient, find that the pattern of syndrome of pathogenic fire derived from stagnation of liver-QI is the most common, adopt dispersing the stagnated live-QI to relieve the stagnation of QI clearing away heat method treatment anxiety neurosis, develop Chinese medicine composition of the present invention, clinical efficacy is definite.
A kind of Chinese medicine composition of treating generalized anxiety disorder provided by the invention is characterized in that being made up of each crude drug of following weight portion: Radix Bupleuri 5-25 part, Fructus Gardeniae 5-25 part; Radix Et Caulis Acanthopanacis Senticosi 10-80 part; Medulla Junci 5-40 part, Spica Prunellae 5-40 part, Fructus Amomi 10-30 part and Concha Margaritifera 10-40 part;
Preferably, described Chinese medicine composition is made up of each crude drug of following weight portion: 15 parts of Radix Bupleuri, 15 parts of Fructus Gardeniaes, 40 parts of Radix Et Caulis Acanthopanacis Senticosis, 10 parts of Medulla Juncies, 15 parts of Spica Prunellaes, 20 parts of 20 parts of Fructus Amomis and Concha Margaritiferas.
Used each crude drug property of medicine is analyzed in the Chinese medicine composition of the present invention:
Radix Bupleuri: bitter in the mouth, suffering, cold nature, dispersing the stagnated live-QI to relieve the stagnation of QI are monarch drug; Fructus Gardeniae: bitter in the mouth, cold in nature, the pathogenic fire purging relieving restlessness, Radix Et Caulis Acanthopanacis Senticosi: acrid in the mouth, little hardship, warm in nature, the kidney invigorating is nourished heart, and transfers dirty calming the nerves to be ministerial drug, principal drug assistance liver clearing and depression relieving, the relieving restlessness of calming the nerves altogether; Medulla Junci: sweet in the mouth, light, cool in nature, the relieving restlessness that clears away heart-fire, Spica Prunellae: bitter in the mouth, suffering, cool in nature, purging liver-fire, Concha Margaritifera: distinguish the flavor of, cool in nature, suppressing the hyperactive liver and subsiding YANG, make eye bright and calm the nerves, the three is adjuvant drug altogether, strengthens the effect that purging liver-fire is calmed the nerves; Fructus Amomi: acrid in the mouth, little hardship, warm in nature, warming middle-JIAO is regulated the flow of vital energy, the article imapirment of the spleen and stomach of anti-above-mentioned bitter cold.
In order to solve above-mentioned technical problem, the present invention also provides the method for this Chinese medicine composition of preparation, it is characterized in that method for preparing comprises following steps:
(1) each crude drug takes by weighing respectively by said weight portion;
(2) add 8 times of weight 70% concentration ethanol to the Medulla Junci that weighs up, Concha Margaritifera, Fructus Amomi, Radix Et Caulis Acanthopanacis Senticosi, heating and refluxing extraction 4 hours, filtration, decompression filtrate recycling ethanol, and be concentrated in right amount, process A;
(3) add 8 times of weight decoctings to the Spica Prunellae that weighs up, Radix Bupleuri, Fructus Gardeniae and boil twice, each 1.5 hours, collecting decoction, filtration, filtrate decompression are concentrated in right amount, process B;
(4) mix A and B, be concentrated under 50 ℃, relative density is the clear paste of 1.10-1.30, adds appropriate amount of auxiliary materials, makes suitable clinically various preparations according to the pharmaceutical preparation conventional method;
Said adjuvant is that sucrose, starch, dextrin, Pulvis Talci, magnesium stearate or calcium sulfate etc. are wherein at least a.
Prepared Chinese medicine composition can be made suitable clinically various preparations according to the pharmaceutical preparation conventional method, is used for treating generalized anxiety disorder;
Described preparation is capsule, pill, granule, tablet or oral liquid etc.
Chinese medicine composition of the present invention can be applicable to prepare in the medicine of treating generalized anxiety disorder.
The present invention treats the principle that GAD is based on organic conception and determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, is characteristic with the individualized treatment, has the motility of principle-method-recipe-medicines and the safety of drug effect.To its clinical symptoms multiformity, pathogenetic complexity; Chinese medicine can launch treatment from many target spots, too many levels, multipath; In clinical practice, have rapid-action, determined curative effect, patient's compliance is good; Can obviously improve the advantage such as generation and development of GAD patient's condition, have broad clinical application prospect.
The specific embodiment
Through pharmacological and clinical observation experiment and combine embodiment that the present invention is further specified, it should be understood that these embodiment only are used for the purpose of illustration, never limit protection scope of the present invention below.
The preparation of embodiment 1, granule
The preparation of granule is specifically carried out according to following steps:
(1) takes by weighing each raw material respectively by following weight portion: Radix Bupleuri 150g, Fructus Gardeniae 150g, Radix Et Caulis Acanthopanacis Senticosi 400g, Medulla Junci 100g, Spica Prunellae 150g, Fructus Amomi 200g and Concha Margaritifera 200g;
(2) add 8 times of weight 70% concentration ethanol to the Medulla Junci that weighs up, Concha Margaritifera, Fructus Amomi, Radix Et Caulis Acanthopanacis Senticosi, heating and refluxing extraction 4 hours, filtration, decompression filtrate recycling ethanol, and be concentrated in right amount, process A;
(3) add 8 times of weight decoctings to the Spica Prunellae that weighs up, Radix Bupleuri, Fructus Gardeniae and boil twice, each 1.5 hours, collecting decoction, filtration, filtrate decompression are concentrated in right amount, process B;
(4) mix A and B, be concentrated under 50 ℃, relative density is 1.10 clear paste, and adding sucrose 650g and dextrin are an amount of, process granule, and drying is processed 1000g.
The preparation of embodiment 2, tablet
The preparation of tablet is specifically carried out according to following steps:
(1) takes by weighing each raw material respectively by following weight portion: Radix Bupleuri 150g, Fructus Gardeniae 150g, Radix Et Caulis Acanthopanacis Senticosi 400g, Medulla Junci 100g, Spica Prunellae 150g, Fructus Amomi 200g and Concha Margaritifera 200g;
(2) add 8 times of weight 70% concentration ethanol to the Medulla Junci that weighs up, Concha Margaritifera, Fructus Amomi, Radix Et Caulis Acanthopanacis Senticosi, heating and refluxing extraction 4 hours, filtration, decompression filtrate recycling ethanol, and be concentrated in right amount, process A;
(3) add 8 times of weight decoctings to the Spica Prunellae that weighs up, Radix Bupleuri, Fructus Gardeniae and boil twice, each 1.5 hours, collecting decoction, filtration, filtrate decompression are concentrated in right amount, process B;
(4) mix A and B, be concentrated under 50 ℃, relative density is 1.30 clear paste, adds an amount of starch mixing, and drying is pulverized, and adds an amount of Pulvis Talci and magnesium stearate, mixes, and tabletting is processed 1000.
Embodiment 3, capsular preparation
Capsular preparation is specifically carried out according to following steps:
(1) takes by weighing each raw material respectively by following weight portion: Radix Bupleuri 150g, Fructus Gardeniae 150g, Radix Et Caulis Acanthopanacis Senticosi 400g, Medulla Junci 100g, Spica Prunellae 150g, Fructus Amomi 200g and Concha Margaritifera 200g;
(2) add 8 times of weight 70% concentration ethanol to the Medulla Junci that weighs up, Concha Margaritifera, Fructus Amomi, Radix Et Caulis Acanthopanacis Senticosi, heating and refluxing extraction 4 hours, filtration, decompression filtrate recycling ethanol, and be concentrated in right amount, process A;
(3) add 8 times of weight decoctings to the Spica Prunellae that weighs up, Radix Bupleuri, Fructus Gardeniae and boil twice, each 1.5 hours, collecting decoction, filtration, filtrate decompression are concentrated in right amount, process B;
(4) mix A and B, be concentrated into 50 ℃ of following relative densities and be 1.20 clear paste, adds an amount of starch mixing, drying, pulverizing adds an amount of calcium sulfate, Pulvis Talci, and mixing is processed granule, incapsulates, and processes 1000, promptly gets.
Embodiment 4, clinical research
Treat in the open clinical research of anxiety neurosis curative effect in various degree inquiring into the liver heat removing and kidney replenishing method, we find to use liver heat removing and kidney replenishing ruling by law and treat GAD better curative effect is arranged.
1, clinical data
Formulate tcm diagnosis standard and western medicine diagnostic criteria.
The order of severity evaluation of anxiety neurosis is with reference to (DSM-IV) diagnostic criteria formulation of APA,American Psychiatric Association's " mental disorder Diagnostic Statistical Manual the 4th edition ".
Inclusion criteria: (1) age: 18-65 year.(2) meet generalized anxiety disorder diagnosis light, in, severe constitutional anxiety patient; (3) vital sign is steady, and sanity has certain ability to express; (4) it is vigorous to meet traditional Chinese medical science liver-fire, the deficiency of kidney-YIN person.
Exclusion standard: vital sign is not steady; There is some fissility symptom; The anxiety that Western medicine diagnose occurs together for other mental sickness; Refuse to take medicine (being reluctant to take traditional Chinese medicine) and serious suicidal tendency person is arranged.
Selected patient's 85 examples, women's 48 examples (56.5%) wherein, male's 37 examples (43.5%); Married 58 examples (68.2%), unmarried 22 examples (25.9%), 5 examples of divorcing (5.9%); Single 66 examples (77.6%) of showing effect; 19 examples of showing effect repeatedly (22.4%).All patient's mild or moderate 36 examples (42.4%); Moderate 33 examples (38.8%); Severe 16 examples (18.8%).
2, Therapeutic Method
Selected patient's 85 examples give the Chinese medicine composition (granule) that the inventive method prepares.Each raw material medicines in portions by weight of this Chinese medicine composition is: 15 parts of Radix Bupleuri, 15 parts of Fructus Gardeniaes, 40 parts of Radix Et Caulis Acanthopanacis Senticosis, 10 parts of Medulla Juncies, 15 parts of Spica Prunellaes, 20 parts of 20 parts of Fructus Amomis and Concha Margaritiferas; According to the method for preparing that provided of invention, and add an amount of sucrose and dextrin, make granule.
Usage: 10g/ time, 3 times/day, 6 weeks of successive administration.
3, therapeutic outcome
Adopt the HAMA scale respectively before treatment, the treatment back evaluated in the 1st, 2,4,6 weeks, efficacy evaluation target case is that scoring and the HAMA of baseline after treating for 6 weeks subtracts the branch rate.Clinic control: HAMA subtracts branch rate >=75%; Marked improvement: HAMA subtracts branch rate >=50%; Progressive: HAMA subtracts branch rate >=25%; Invalid: HAMA subtracts branch rate<25%.Safety assessment: respectively before treatment, the 1st, 2,4,6 weeks of treatment back adopt TESS evaluation untoward reaction, date, degree take place, handle and lapse in itemized record untoward reaction and symptom, and make analysis.
85 routine patient HAMA overall scores dropped to 8.78 minutes after the treatment before by treatment in average 26.57 minutes, and both relatively have statistical significance.The percentage ratio of treatment back 6 all points of observation and baseline HAMA scoring minimizing>=50% is 88.2%; Treatment back HAMA total points≤6 fens person's 24 examples.Wherein to LA person obvious effective rate 94.4%; Moderate anxiety person obvious effective rate 87.9%; Severe anxiety person obvious effective rate 75%.Onset time accounts for 49.4% in 1-2 week person 42 examples, its mild or moderate person 22 examples, moderate person's 18 examples, severe person's 2 examples; In 2-4 week onset person's 31 examples, account for 36.5%, its mild or moderate person 14 examples, moderate person's 12 examples, severe person's 5 examples; In treatment 4-6 week side onset person 12 examples, account for 14.1%, its mild or moderate person 0 example, moderate person's 3 examples, severe person's 9 examples.The research shows that the liver heat removing and kidney replenishing method has better curative effect to the treatment generalized anxiety disorder.
Test Example 1, pharmacological experiment
Used Chinese medicine composition prepares according to following method:
The weight portion of getting each composition crude drug is: 15 parts of Radix Bupleuri, 15 parts of Fructus Gardeniaes, 40 parts of Radix Et Caulis Acanthopanacis Senticosis, 10 parts of Medulla Juncies, 15 parts of Spica Prunellaes, 20 parts of 20 parts of Fructus Amomis and Concha Margaritiferas; According to the method for preparing that provided of invention, and add an amount of sucrose and dextrin, process granule, be used for following research:
1. general pharmacology experimentation
The granular preparation that Chinese medicine composition of the present invention is made; To anesthetized rat blood pressure, heart rate, left ventricular pressure; Respiratory frequency and degree of depth general pharmacology are learned result of the test and are shown; These article self compare there was no significant difference (each item index test does not all have significant difference before and after the administration of normal saline group) to anesthetized rat heart rate, left ventricular pressure, respiratory frequency and the degree of depth before the administration with after the administration, explain that this medicine does not have the significance influence to rat normal physiological index.
2. the acute toxicological experiment result of study shows, Chinese medicine composition of the present invention is not seen tangible toxic action.
3. Chinese medicine composition angst resistance effect Study on Mechanism of the present invention
On the basis of original research neurotransmitter and receptor; Transmit angle and utilize the nuclear-magnetism methodology to observe the form and the energy change situation of brain on the whole through anxiety rat behavior, neuropeptide, cell information; Further inquire into the pathogenesis and the Chinese medicine mechanism of action of GAD, seek the target spot of Chinese medicine angst resistance effect.
The foundation of animal model: 32 Wistar rats (SPF level, 2~3 monthly ages, body weight (200 ± 10) g.The quality certification number is provided: SCXK (Shanghai) 2007-0005 by Shanghai Si Laike Experimental Animal Center.Animal is bought the drinking-water of freely ingesting in 1 week of back precuring.(relative humidity is 50%~60% to illumination rhythm and pace of moving things 12L/12D, keeps quite for 6:00~18:00), room temperature (20 ± 2) ℃.), rat is divided into normal group, model group, matched group and treatment group at random after 1 laundering period in week, and 8 every group, model group: aquae destillata is irritated stomach; Matched group: buspirone hydrochloride is irritated stomach, 2.0mg/ (kgd); Treatment group: the present composition, 12.5g/ (kgd), medication 7 days.Except that normal group, model group, matched group and treatment are organized single cage raising and are accepted the stimulation of uncertain empty bottle drinking-water and set up the anxiety Stress model.Concrete grammar is following: regularly feed water training 7 days, promptly every day, 9:00~9:10 and 21:00~21:10 were to the animal 10min that drinks water, and all the other times remove water bottle and do not feed water.Regularly feeding the water phase begins and stress test after finishing, and in above-mentioned two time periods, giving uncertain empty bottle stimulates, and keeps every day 1~2 time, continues for 2 weeks.Normal group is not accepted any processing, freely drinks water and ingests.What empty bottle stimulated began to give pharmaceutical intervention in the 2nd week, and model group gives distilled water and irritates stomach, and matched group gives buspirone and irritates stomach; The treatment group gives Chinese medicine composition of the present invention and irritates stomach; Continuous use 7 days, is calculated corresponding filling stomach dosage according to the weighing machine of animal at every day 1 time.Normal group is not accepted any processing, freely drinks water and ingests.All animals carry out overhead cross labyrinth behavioristics after stress finishing measures, and each group intersection is carried out.The animal all test laboratory of 2h entering in advance conforms.
The result: MRI scanner uni MRS detects
(7.0T superconducting magnetic resonance appearance is produced by German Bruker company through high field intensity (7.0T).) superconduction animal magnetic resonance device detects bilateral Hippocampus and prefrontal cortex N-acetyl aspartic acid (NAA), choline (Cho), creatine (Cr), glutamic acid metabolite levels such as (Glu); Calculate the ratio of NAA, Cho, Glu and Cr respectively, observe the intervention effect of Chinese medicine composition of the present invention.The miniature high field intensity magnetic resonance imaging system (phar-mascan70/167.0T) that German Bruker company produces, gradient switching rate 300mT/ (ms) are used in nuclear magnetic resonance.Animal is adopted the isoflurane inhalation anesthesia, and induced anesthesia concentration is 4%, keeps anesthetic concentration and is 1.5%~2.0% and suck with oxygen mix.Anesthesia back rat is got the ventricumbent position, and head is fixed on the stereotactic apparatus support, puts into the dual pathways head radio-frequency coil of aperture 60mm, carries out MRI scanning.The location picture adopts the scanning of T2 weighting picture, TR=4200ms, TE=36ms, scanning bed thickness 1.0mm, interlamellar spacing 1.2mm, visual field 3.5cm * 3.5cm, matrix 256 * 256.1H-MRS adopts point to differentiate spin echo wave spectrum (PRESS) sequence, TR=2500ms, TE=20ms; Chosen axis position and sagittal plain T2WI confirm that region of interest (VOI) is bilateral prefrontal cortex and Hippocampus; Volume: 3mm * 3mm * 3mm avoids structures such as skull and cerebrospinal fluid, and shimming and water suppress to accomplish by automatic scanner; The average time that sampling adds up is 512 times, and be 21min20s. sweep time.Free damping signal to collecting carries out fourier transform; Use MRS scanner analysis software and data are carried out processing such as phase place, baseline correction; Observe the variation of N-acetyl aspartic acid (NAA), choline (Cho), creatine (Cr), glutamic acid metabolite signal intensitys such as (Glu); The chemical shift of 4 kinds of metabolite lays respectively at 2.02ppm, 3.20ppm, 3.03ppm and 2.36ppm, measures the peak height value of each metabolite under the curve, is the relative ratio that confidential reference items calculate each metabolite with Cr.Room temperature is controlled at 20~22 ℃ in the scanning process, and the respiratory frequency of animal is controlled at 65~70 times/min (Wave Spectrum is determined at Jiangsu Province Southeast China University molecular image laboratory and accomplishes).
Statistical method
Each is organized data and representes with x ± s.Date processing adopts SPSS 15.0 statistical softwares, relatively adopts one factor analysis of variance between group.It is more as shown in table 1 that each organizes rat bilateral prefrontal cortex metabolite; It is more as shown in table 2 that each organizes rat bilateral Hippocampus survey metabolite.
Table 1 is respectively organized relatively (x ± s) of rat bilateral prefrontal cortex metabolite relative concentration
Figure BDA0000071683170000081
Annotate: compare * P<001 with normal group; Compare △ P<001 with model group; Compare with matched group, ▲ P<005, ▲ ▲ P<001
Table 2 is respectively organized relatively (x ± s) of rat bilateral Hippocampus metabolite relative concentration
Figure BDA0000071683170000082
Result of study is pointed out, and signal transduction pathway (like cyclic adenosine monophosphate path, phosphatidylinositols path, NMDA path, MAPK path) is relevant behind the neuropeptide (like CCK, CRF, NPY etc.) that the approach of Chinese medicine composition angst resistance effect of the present invention maybe be relevant with influencing anxiety, the receptor.In addition; Nuclear magnetic resonance and the MRS technology that we adopt high field intensity carried out real-time monitored to the tissue metabolism's state and the functional activity of live body brain; Observe normal and the variation of anxiety rat cerebral tissue morphology, be intended to explain the pathophysiological mechanism that anxiety neurosis is fallen ill from the angle of molecular imaging with neuron metabolite N-acetyl aspartic acid (NAA), creatine (Cr), choline (Cho), glutamic acid indexs such as (Glu).Through discovering of nuclear magnetic resonance and wave spectrum; The metabolism of anxiety rat brain right side prefrontal cortex exists unusual, and wherein NAA/Cr, Cho/Cr reduce, and Glu/Cr raises; Show the damage that neuron and neurogliocyte are arranged of anxiety rat prefrontal cortex; And the rising of anxiety and excitatory amino acid has certain dependency, and through pharmaceutical intervention, we find that Chinese medicine composition of the present invention can reduce the damage of neuron and neurogliocyte; The concentration of downward modulation irritability propylhomoserin, but the intervention effect of buspirone is not obvious.
4. the pharmacodynamic experiment of Chinese medicine composition of the present invention
Adopt the uncertain empty bottle stress stimulation of Beijing professor Lin Wenjuan of psychological research institute of academy of science initiative to prepare chronic anxiety rat model; With internationally recognized overhead cross maze test its behavioristics is tested; With the buspirone is control drug; Experimental technique carries out according to the method described above, estimates the anxiety of rat and the intervention effect of degree and Chinese medicine composition of the present invention.Research shows that this emotional stress method can be brought out animal and occurred attacking, and baits bottle and cage, frequently modifies anxiety reactions such as irritability.In the project of overhead cross labyrinth test, get into the anxiety degree that open arms number of times ratio (OE%) and open arms time of staying ratio (OT%) have been reacted animal, classical anxiolytic drugs then makes both raise.Research shows; Chinese medicine composition of the present invention can alleviate the attack of rat, frequently anxiety such as modification and irritability and behavior performance, can obviously increase animal than Western medicine in early days and get into open arms number of times ratio (OE%) and open arms time of staying ratio (OT%).Therefore basic research prompting, Chinese medicine composition of the present invention has effect antianxity.
The above is merely the preferred embodiments of the present invention, only is illustrative for the purpose of the present invention, and nonrestrictive; Those of ordinary skills understand, and in spirit that claim of the present invention limited and scope, can carry out many changes to it, revise, even equivalence change, but all will fall in protection scope of the present invention.

Claims (6)

1. a Chinese medicine composition of treating generalized anxiety disorder is characterized in that being processed by each crude drug of following weight portion: Radix Bupleuri 5-25 part, Fructus Gardeniae 5-25 part; Radix Et Caulis Acanthopanacis Senticosi 10-80 part; Medulla Junci 5-40 part, Spica Prunellae 5-40 part, Fructus Amomi 10-30 part and Concha Margaritifera 10-40 part.
2. Chinese medicine composition as claimed in claim 1 is characterized in that being processed by each crude drug of following weight portion: 15 parts of Radix Bupleuri, 15 parts of Fructus Gardeniaes, 40 parts of Radix Et Caulis Acanthopanacis Senticosis, 10 parts of Medulla Juncies, 15 parts of Spica Prunellaes, 20 parts of 20 parts of Fructus Amomis and Concha Margaritiferas.
3. the method for preparing claim 1 or 2 described Chinese medicine compositions is characterized in that this method for preparing comprises following steps:
(1) each crude drug takes by weighing respectively by said weight portion;
(2) add 8 times of weight 70% concentration ethanol to the Medulla Junci that weighs up, Concha Margaritifera, Fructus Amomi, Radix Et Caulis Acanthopanacis Senticosi, heating and refluxing extraction 4 hours, filtration, decompression filtrate recycling ethanol, and be concentrated in right amount, process A;
(3) add 8 times of weight decoctings to the Spica Prunellae that weighs up, Radix Bupleuri, Fructus Gardeniae and boil twice, each 1.5 hours, collecting decoction, filtration, filtrate decompression are concentrated in right amount, process B;
(4) mix A and B, be concentrated under 50 ℃, relative density is 1.10-1.30 clear paste, adds appropriate amount of auxiliary materials, makes suitable clinically various preparations according to the pharmaceutical preparation conventional method.
4. method for preparing as claimed in claim 3 is characterized in that said adjuvant is that sucrose, starch, dextrin, Pulvis Talci, magnesium stearate or calcium sulfate are wherein at least a.
5. method for preparing as claimed in claim 3 is characterized in that described preparation is capsule, pill, granule, tablet or oral liquid.
6. claim 1 or the 2 described Chinese medicine compositions application in preparation treatment generalized anxiety disorder disease drug.
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