CN108295168A - A kind of Chinese medicine composition for treating Poststroke Depression - Google Patents

A kind of Chinese medicine composition for treating Poststroke Depression Download PDF

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Publication number
CN108295168A
CN108295168A CN201810198638.9A CN201810198638A CN108295168A CN 108295168 A CN108295168 A CN 108295168A CN 201810198638 A CN201810198638 A CN 201810198638A CN 108295168 A CN108295168 A CN 108295168A
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parts
radix
chinese medicine
medicine composition
rhizoma
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CN108295168B (en
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盛蕾
刘元月
胡丹
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Second Hospital Of Jiangsu Province
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Second Hospital Of Jiangsu Province
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    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
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Abstract

The present invention discloses a kind of Chinese medicine composition for treating Poststroke Depression, includes the raw material composition of following parts by weight：15 30 parts of radix bupleuri, 10 20 parts of rhizoma cyperi, 10 20 parts of Radix Angelicae Sinensis, 10 20 parts of Radix Rehmanniae, 10 20 parts of peach kernel, 10 15 parts of safflower, 10 20 parts of Fructus Aurantii, 10 20 parts of dried orange peel, 10 20 parts of radix paeoniae rubra, 10 20 parts of Rhizoma Atractylodis Macrocephalae, 10 15 parts of Radix Glycyrrhizae, 10 20 parts of campanulaceae, 6 20 parts of the root of bidentate achyranthes, 10 20 parts of Rhizoma Chuanxiong, 46 parts of leech, 10 15 parts of Radix Notoginseng, 15 20 parts of Poria cocos, 15 20 parts of grass-leaved sweetflag, 12 20 parts of arisaema cum bile, 36 parts of Herba Hyperici Monogyni, 12 20 parts of wilsonii, 36 parts of the coptis, all medicines share, soothing liver-qi stagnation is played altogether, regulating qi-flowing for eliminating phlegm, the work(of blood circulation promoting and dispersing pathogen accumulation.Chinese medicine composition of the present invention and antidepressant are used in conjunction significant in efficacy to treatment Poststroke Depression, and reliable effect is without side-effects, and shortens the onset time of antidepressants.

Description

A kind of Chinese medicine composition for treating Poststroke Depression
Technical field
The present invention relates to a kind of Chinese medicine compositions for treating Poststroke Depression, belong to field of traditional Chinese.
Background technology
The common psychological mental disease of Post stroke includes Poststroke Depression, not only influences the quality of life of patient, simultaneously also Neurological rehabilitation is influenced, the death rate and homicide rate are increased.Currently, the key agents for the treatment of Poststroke Depression are selective 5- hydroxyls The novel antidepressants such as reuptake inhibitors (SSRIs).Although such drug can effectively release depressive mood and adjoint Anxiety, anxiety and somatization, but still have about 20~40% somatization such as gastrointestinal side effects etc. and be not eased, cause Patient compliance declines or interrupts treatment.Simultaneously there is the delay that works, increase cerebral hemorrhage, cerebral apoplexy, myocardial infarction in such Western medicine Equivalent risk further limits the clinical treatment effect of Poststroke Depression.
Invention content
Goal of the invention：The technical problem to be solved by the present invention is in view of the deficiencies of the prior art, provide a kind of treat finally The Chinese medicine composition of middle retarded depression, preferable therapeutic effect can be played by being used in conjunction with antidepressants.
In order to solve the above-mentioned technical problem, the invention discloses a kind of Chinese medicine compositions for treating Poststroke Depression, including The raw material of following parts by weight forms：15-30 parts of radix bupleuri, 10-20 parts of rhizoma cyperi, 10-20 parts of Radix Angelicae Sinensis, 10-20 parts of Radix Rehmanniae, peach kernel 10- 20 parts, 10-15 parts of safflower, 10-20 parts of Fructus Aurantii, 10-20 parts of dried orange peel, 10-20 parts of radix paeoniae rubra, 10-20 parts of Rhizoma Atractylodis Macrocephalae, 10-15 parts of Radix Glycyrrhizae, 10-20 parts of campanulaceae, 6-20 parts of the root of bidentate achyranthes, 10-20 parts of Rhizoma Chuanxiong, 4-6 parts of leech, 10-15 parts of Radix Notoginseng, 15-20 parts of Poria cocos, grass-leaved sweetflag 15-20 parts, 12-20 parts of arisaema cum bile, 3-6 parts of Herba Hyperici Monogyni, 12-20 parts of wilsonii, 3-6 parts of the coptis.
Preferably, which includes the raw material composition of following parts by weight：15 parts of radix bupleuri, 15 parts of rhizoma cyperi, Radix Angelicae Sinensis 10 Part, 15 parts of Radix Rehmanniae, 12 parts of peach kernel, 12 parts of safflower, 10 parts of Fructus Aurantii, 10 parts of dried orange peel, 10 parts of radix paeoniae rubra, 10 parts of Rhizoma Atractylodis Macrocephalae, 12 parts of Radix Glycyrrhizae, tangerine 10 parts of stalk, 15 parts of Rhizoma Chuanxiong, 6 parts of leech, 10 parts of Radix Notoginseng, 15 parts of Poria cocos, 15 parts of grass-leaved sweetflag, 15 parts of arisaema cum bile, passes through leaf at 15 parts of the root of bidentate achyranthes 6 parts of Hypericum Chinense, 15 parts of wilsonii, 6 parts of the coptis.
The generation of Poststroke Depression and cerebrovascular events are closely related, in most cases, the basis disease of cerebral arterial thrombosis Because being " therefore evil phlegm-blood stasis ".Ischemic Stroke is visceral dysfunction, generates wind, fire, phlegm, the stasis of blood, void, sudden and violent of liver (wind) sun, wind fire It mutually incites, empty wind inward turning, press from both sides phlegm-turbidity and blood stasis blood and walks, it is this disease to cause brain vessle-Bi symptom-complex resistance hair, and with the passing of time, wind, fire are gradually put out apoplexy, and phlegm-blood stasis Heresy glue is solid always；The palsy middle-aged and the old is multiple, and " over four ten days, half of YIN QI consumed ", liver kidney yin essence is gradually lost, hyperactivity of yang due to yin deficiency, the fire of deficiency type It burns Tianjin, body fluid cream fat gathers turbid for phlegm, and blood is not smooth, and causes phlegm stagnation in collateral.Poststroke Depression is caused a disease on the basis of apoplexy, i.e., " strongly fragrant because of disease ", therefore had become from pathologically analysis PSD phlegm-blood stasis retardance.Liver controlling conveyance and dispersion, harmonizing emotions, regulating functional activities of vital QI are the whole body gas The hinge of machine, it is being caused because of feelings will internal injury that mechanism of qi, which loses freely, and feelings will and liver are in close relations.Patient faces precipitate change after apoplexy Therefore feelings will is unsuccessful, liver dysfunction, functional activity of QI being not smooth, causes pent-up difficulty to be relaxed, i.e., " because strongly fragrant and sick ", then stagnation of liver qi has again.Meanwhile Liver dysfunction, mechanism of qi are become estranged, and the blood stasis of blood is stagnant, and Tianjin is stopped as phlegm；Phlegm is turbid, hemostasis numbness resistance train of thought, and ascending or descending movement of vital Qi is not normal, reciprocal causation, Patient's condition is further aggravated.Therefore, it is considered that " stagnation of QI due to depression of the liver, phlegm stagnation in collateral " is the basic pathogenesis of palsy depression comorbidity, with the soothing the liver logical stasis of blood Circulation Resolving Phlegm is the therapeutic rule of palsy depression comorbidity.
Radix bupleuri master enters Liver Channel in the formula of the present invention, is the first key medicine of soothing liver-qi stagnation, orderly and clearly irritability and up to the machine of raw liter, be Think monarch；Rhizoma cyperi property processed is pungent, slight bitter, micro-sweet, for the Directorate-General DG of gas disease, it is pungent can be current, it is bitter can catharsis, qi-regulating is soothing the liver, help radix bupleuri with Solve liver depression；The Rhizoma Chuanxiong promoting flow of qi and blood circulation helps radix bupleuri solution Liver Channel stasis；Herba Hyperici Monogyni, wilsonii soothing liver-qi stagnation；Radix Angelicae Sinensis is preced with nourshing blood and promoting blood circulation, First of tonifying liver nourishing the liver medicine, safflower, radix paeoniae rubra, pseudo-ginseng blood-circulation-invigovating dissolving stasis, leech dissipating blood stasis with potent drugs, Radix Rehmanniae, Chinese Angelica blood replonishing benefit are cloudy, and heat-clearing is lived Blood, and the pungent profit dredging collateral of stir-baked SEMEN PERSICAE, ease constipation of invigorating blood circulation are with for minister the benefits of nourishing the liver ease constipation altogether at the promoting blood circulation of soft liver；Fry Fructus Aurantii qi-regulating Product, sending down abnormally ascending lead to internal organs；It is shared with dried orange peel, mutual causality of ascending and descending, mediation mechanism of qi；Fructus Aurantii, Poria cocos phlegm-eliminiating and qi-regulating；And fluent middle gas, promote stomach and intestine Power improves depression, is with for assistant；Grass-leaved sweetflag fragrance is walked to alter, slit phlegm of having one's ideas straightened out, and priming uplink is to reach mountain peak top；Arisaema cum bile heat-clearing ceases Weathering phlegm.Raw Rhizoma Atractylodis Macrocephalae, two medicine strengthening the spleen and replenishing qi of honey-fried licorice root help soil and press down wood, the criminal of more anti-irritability, and campanulaceae and root of bidentate achyranthes compatibility rise clear Drop turbid, phase factor is coordinated in the regulation of qi and blood, and a little coptis and radix bupleuri be total to purge the green, is also allowed to product to help.
The Chinese medicine composition preparation method is：It is the radix bupleuri, rhizoma cyperi, Radix Angelicae Sinensis, Radix Rehmanniae, peach kernel, safflower, Fructus Aurantii, dried orange peel, red Chinese herbaceous peony, Rhizoma Atractylodis Macrocephalae, Radix Glycyrrhizae, campanulaceae, the root of bidentate achyranthes, Rhizoma Chuanxiong, leech, Radix Notoginseng, Poria cocos, grass-leaved sweetflag, arisaema cum bile, Herba Hyperici Monogyni, wilsonii and The coptis adds water to mix by formula ratio, impregnates 30~60min, is advisable with 25~50 DEG C of room temperature or warm water, decocts twice, each water Liquid level did not had 1~2cm of raw material, merging filtrate both to obtain, and can be made into common internal dosage form.
Wherein, 30min or more, second of decoction 15min or more are decocted for the first time.
The application method of the Chinese medicine composition is：Twice a day, lunch, supper half an hour after, twice of decocting, once about 400ml, seven days as a treatment course.
The present invention also provides a kind of pharmaceutical compositions for treating Poststroke Depression, including：
(1) antidepressants；
(2) Chinese medicine composition described in claim 1.
The antidepressants are antidepression Western medicine, selected from citalopram hydrobromate, paroxetine hydrochloride, hydrochloric acid text daraf(reciprocal of farad) Any one in pungent, Mirtazapine, Prozac or several combinations.
The application method of the pharmaceutical composition is：One time a day, each 20mg or so, Chinese medicine composition is each for antidepressants It 400 milliliters, twice a day, as a treatment course was taken with 8 weeks.The Chinese medicine composition for being further continued for taking 2 course for the treatment of after producing effects (deactivates anti- Depressant drug), it is assessed according to physician specialty to decide whether to continue to take to 1 year.
Cerebral apoplexy is global major disease, and Post stroke not only needs neurological rehabilitation, it is also desirable to hearts such as antidepressions Manage the brought negative effect of mental disease.But the effect of Poststroke Depression cause of disease is complicated, and mechanism is unclear, traditional antidepressant has Limit, while there is also different degrees of medication side reactions.Show that the Chinese medicine preparation is reasonable according to clinical verification, all medicines share is played altogether Soothing liver-qi stagnation, regulating qi-flowing for eliminating phlegm, the work(of blood circulation promoting and dispersing pathogen accumulation, patient HAMD scorings are reduced compared with control group after Chinese medicine is treated 6~8 weeks, BI refers to It is several litres high.In addition, above-mentioned Chinese medicine composition produces synergistic effect with antidepressants, and advantage increases after treating 8 weeks, carries Show party's auxiliary treatment Poststroke Depression good effect, and as time went on, effect is more preferable, clinical efficacy total effective rate reaches 94%, cure rate 74%.
Advantageous effect：
1, the application Chinese medicine composition is made of pure Chinese medicine, and drug price is low, and abundant raw materials are easy to get, and is easy to be connect by patient By side reaction is small, safe, is easy to patient and adheres to taking；
2, when the application Chinese medicine composition joint anti-depressant therapy, Western medicine onset time can be shortened, long-term effect is excellent Gesture is apparent, and curative effect can maintain higher level for a long time, and can after the treatment the phase gradually replace antidepressants, maintain curative effect, Coordinate Comprehensive rehabilitation effect more notable in therapeutic process.
Description of the drawings
The present invention is done with reference to the accompanying drawings and detailed description and is further illustrated, of the invention is above-mentioned And/or otherwise advantage will become apparent.
Fig. 1 is influence of 8 Chinese medicine composition of embodiment to PSD rat model depression indexs of correlation；
Fig. 2 is influence of 8 Chinese medicine composition of embodiment to PSD rat model nervous function indexs of correlation；
Fig. 3 is that each group rat BDNF, TrkB, PSD95 compare in embodiment 8.
Specific implementation mode
According to following embodiments, the present invention may be better understood.
Embodiment 1
The Chinese medicine composition is made of the raw material of following parts by weight：15 parts of radix bupleuri, 15 parts of rhizoma cyperi, 10 parts of Radix Angelicae Sinensis, Radix Rehmanniae 15 Part, 12 parts of peach kernel, 12 parts of safflower, 10 parts of Fructus Aurantii, 10 parts of dried orange peel, 10 parts of radix paeoniae rubra, 10 parts of Rhizoma Atractylodis Macrocephalae, 12 parts of Radix Glycyrrhizae, 10 parts of campanulaceae, ox 15 parts of knee, 15 parts of Rhizoma Chuanxiong, 6 parts of leech, 10 parts of Radix Notoginseng, 15 parts of Poria cocos, 15 parts of grass-leaved sweetflag, 15 parts of arisaema cum bile, Herba Hyperici Monogyni 6 Part, 15 parts of wilsonii, 6 parts of the coptis.
Embodiment 2
The Chinese medicine composition is made of the raw material of following parts by weight：20 parts of radix bupleuri, 10 parts of rhizoma cyperi, 15 parts of Radix Angelicae Sinensis, Radix Rehmanniae 20 Part, 15 parts of peach kernel, 15 parts of safflower, 15 parts of Fructus Aurantii, 10 parts of dried orange peel, 12 parts of radix paeoniae rubra, 15 parts of Rhizoma Atractylodis Macrocephalae, 15 parts of Radix Glycyrrhizae, 12 parts of campanulaceae, ox 12 parts of knee, 12 parts of Rhizoma Chuanxiong, 3 parts of leech, 15 parts of Radix Notoginseng, 10 parts of Poria cocos, 12 parts of grass-leaved sweetflag, 12 parts of arisaema cum bile, Herba Hyperici Monogyni 3 Part, 10 parts of wilsonii, 3 parts of the coptis.
Embodiment 3
The Chinese medicine composition is made of the raw material of following parts by weight：25 parts of radix bupleuri, 20 parts of rhizoma cyperi, 20 parts of Radix Angelicae Sinensis, Radix Rehmanniae 15 Part, 20 parts of peach kernel, 12 parts of safflower, 20 parts of Fructus Aurantii, 15 parts of dried orange peel, 15 parts of radix paeoniae rubra, 20 parts of Rhizoma Atractylodis Macrocephalae, 20 parts of Radix Glycyrrhizae, 15 parts of campanulaceae, ox 15 parts of knee, 15 parts of Rhizoma Chuanxiong, 6 parts of leech, 12 parts of Radix Notoginseng, 20 parts of Poria cocos, 20 parts of grass-leaved sweetflag, 15 parts of arisaema cum bile, Herba Hyperici Monogyni 6 Part, 20 parts of wilsonii, 6 parts of the coptis.
Embodiment 4
Examples 1 to 3 presses respective formula combination, produces medicament according to conventional decocting method, is impregnated with normal-temperature water before decocting 30min, liquid level did not had medicine materical crude slice two is horizontal to refer to about 2 centimetres, decoct twice, decocting liquid is exported after decocting 30min for the first time, and again plus water does not have It crosses about 2 centimetres of medicine materical crude slice and then decocts 15min, merge twice that filtrate to obtain the final product.
Embodiment 5
The present invention does clinical efficacy summary with the Chinese medicine composition given in embodiment 1, as follows：
General information：Clinical observation case 100, man 50, female 50,50~65 years old age.
Diagnosis basis：Reference《Chinese medical disease Standardization of diagnosis and curative effect》Middle apoplexy and depression card diagnostic criteria, CM syndrome differentiation criterion Meet《New Chinese medicine guideline of clinical investigations (tentative)》Middle stagnation of liver-QI with deficiency of the spleen CM syndrome differentiation criterion.
Usage and dosage：Twice a day, lunch, supper half an hour after, twice of decocting, once about 400ml.It is treated for one within seven days Journey.
Criterion of therapeutical effect：HAMD deduction rates are taken to judge clinical efficacy.It cures：HAMD deduction rate >=75%；It is effective：50%≤ HAMD deduction rates ＜ 75%；Effectively：30%≤HAMD deduction rates ＜ 50%；In vain：HAMD deduction rates ＜ 30%.
Therapeutic effect：The 6-8 course for the treatment of of medication, cures 74, no relapse；Effective 11, effective 8, invalid 7.Nothing Serious adverse reaction occurs.
Embodiment 6
Chinese drugs agentia prepared by Example 1 carries out clinical test.
Research method
1. research object
1.1 case sources：All cases are all from this Out-patient Department and ward.
1.2 diagnostic criteria
(1) Western medicine diagnostic criteria：Meet the cerebral arterial thrombosis diagnostic criteria that national 4th cerebrovascular disease meeting is formulated, Meet simultaneously《Chinese Spirit Obstacles classification and diagnostic criteria (the 3rd edition)》(CCMD-3) criteria for depression in, cerebrovascular disease After sick acute stage (2 weeks), it is confirmed the existence of cranial vascular disease through head B-sonography, and have serious dysnoesia before excluding disease；According to depression Self-assessment Scale (SDS) scores >=30 points, and Hamilton depressive scale (HAMD) scores >=8 points；It is not used or deactivates other anti-suppressions Strongly fragrant drug 2 weeks or more；Informed consent process meets regulation.Without depression medical history before selected case disease, and during excluding observation Because infectious diseases, cancer, diabetes, heart failure, liver function and renal failure or other reasons are dead.
(2) tcm diagnosis standard：Reference《Chinese medical disease Standardization of diagnosis and curative effect》Middle apoplexy and depression card diagnostic criteria, are distinguished Card standard meets《New Chinese medicine guideline of clinical investigations (tentative)》Middle stagnation of liver-QI with deficiency of the spleen CM syndrome differentiation criterion.
1.3 inclusion criteria：
(1) meet above-mentioned diagnostic criteria person；
(2) age 50~80 years old, male or female；
(3) any one without following exclusion criterias.
1.4 exclusion criteria：
(1) family numbers of patients and patient mismatch this experimental study person；
(2) merge hypothyroidism, Liver and kidney function damage, heart disease etc.；
(3) there are organic mental disorders, dementia, cognitive disorder；
(4) communication disorder can not complete mental scale test and appraisal inspection；
(5) severe depression HAMD >=25 point or there is introgression；
(6) there are other social factor interventions, such as administrative, family quarrel.
2. criterion of therapeutical effect
HAMD deduction rates are taken to judge clinical efficacy.It cures：HAMD deduction rate >=75%；It is effective：50%≤HAMD deductions Rate ＜ 75%；Effectively：30%≤HAMD deduction rates ＜ 50%；In vain：HAMD deduction rates ＜ 30%.Deduction rate=(before treatment Point-score after treatment)/score total effective rate=(curing number of cases+effective number of cases+effective number of cases)/total number of cases before treating
3. grouping and random device
Patient in group is randomly divided by treatment group and each 50 of control group using table of random number.Two groups of patient's general information Comparing difference is not statistically significant (P ＞ 0.05), is comparable.
4. concrete operations
4.1 control groups give Oral antidepressant medicine citalopram hydrobromate (Xian-Janssen Pharmaceutical Ltd., specification 20mg/), one time a day, 1 tablet each time, the course for the treatment of 8 weeks and not other anti depressant medications of reselection.Give the cerebrovascular simultaneously Sick conventional therapy, and reinforce the auxiliary treatments such as rehabilitation training, psychological intervention.Treatment group gives above-mentioned on the basis of control group is administered Chinese drugs agentia, 400 milliliters every time, twice a day, the course for the treatment of 8 weeks.
The scoring of 4.2 Degree of Depression is scored according to HAMD standards of grading, before two groups of patients treatment and treatment 4,8 weeks respectively into 1 scoring of row.
4.3 daily life active abilities use Barthel Index (BI) index, and treatment is preceding and treats each evaluation 1 in 4,8 weeks It is secondary.
Respectively extracted before 4.4 serum BDNF detection treatments and when treatment 4,8 weeks patient's limosis vein blood 2mL, 3000r/min from Heart 15min takes supernatant to be put into preservation in -80 DEG C of refrigerators to be measured.It is horizontal that BDNF is measured using ELISA method.BDNF kits are purchased From Promage companies of the U.S..
5. statistical analysis technique
It is analyzed using 16.0 softwares of SPSS.Normal distribution continuous data is indicated with x ± s, is examined using t, is multifactor Variance analysis, duplicate measurements variance analysis；Qualitative data uses chi-square criterion.
Clinical treatment outcome
1 clinical data
The ischemic PSD patient 100 that the court is hospitalized is chosen, patient in group is randomly divided by treatment using table of random number Group and each 50 of control group.Man 30, female 20 wherein in treatment group；54~80 years old age, average (67.94 ± 8.07) year； A month of cerebral apoplexy average course of disease (3.40 ± 1.40), the PSD courses of disease are 15~33d, average (24.44 ± 6.19) d.It is male in control group 30, female 20；55~78 years old age, average (67.58 ± 6.77) year；A month of cerebral apoplexy average course of disease (3.50 ± 1.50), PSD 15~32d of the course of disease, average (23.82 ± 5.58) d.Two groups of not statistically significant (P ＞ of patient's general information comparing difference 0.05) it, is comparable.
2 data preparations
100 patients with post-stroke depression are randomly divided into Chinese herbs group and control group.Chinese medicine composition is combined after 8 weeks to control Effective percentage is treated up to 94.0%, is shown in Table 1.
1 two groups of PSD patient clinical curative effects of table compare
Table 1 Comparison on clinical effect on PSD patients between two groups
Compared with the control group：*P ＜ 0.05
*0.05 vs control group of P ＜
Observation evaluation each group patient HAMD scorings, BI indexes and Serum Levels of BDNF situation of change, be shown in Table 2.Research knot Fruit finds that Chinese medicine composition can reduce the HAMD scorings of patients with post-stroke depression, improves BI indexes, increases Serum Levels of BDNF, table Bright Chinese medicine composition of the present invention has certain therapeutic effect to PSD, and shortens Western medicine onset time.
The pretherapy and post-treatment different time HAMD scorings of 2 two groups of patients of table, BI indexes and Serum Levels of BDNF compare
2 Comparison on HAMD, Barthel Index, and levels of BDNF in serum of Table of patients between two groups at different time points before and after treatment
With this group before treatment：**P ＜ 0.01：Compared with after being treated 4 weeks with this group：ΔΔP ＜ 0.01；Simultaneously with control group Between compare：▲P ＜ 0.05▲▲P ＜ 0.01
◆◆0.01 vs pretreatment of same group of P ＜；△△0.01 vs treatment for 4 of P ＜ weeks of same group；▲P ＜ 0.05▲▲0.01 vs control group at same time point of P ＜
Embodiment 7
Chinese drugs agentia prepared by Example 1, whole animal level investigate the Chinese drugs agentia to PSD therapeutic effects.
1.1 Chinese drugs agentia sample preparations and quality control：
It is prepared by prescription：Medicinal extract is made in Chinese drugs agentia decocting liquid prepared by Example 1, and -20 ° of refrigerators preserve.
The preparation of Contained Serum：SD rat oral gavages are given with quantity × animal equivalent dose ratio, continuous 10 days.In 1h rows abdominal aorta is taken a blood sample after the last administration, detaches serum, is filtered with 0.22 millipore filter, and -80 ° of refrigerators preserve.Drug quality Control：Finger-print is established to more parts of decocting liquids and Contained Serum application UPLC methods, and combines UPLC/Q-TOF-MS technologies to it Carry out multicomponent Structural Identification.With reference to internal standard, using HPLC-DAD/HPLC-DAD-MS methods in decocting liquid and Contained Serum Main component carry out quantitative analysis.Two methods combine, and establish the method for quality control of Chinese drugs agentia, before and after ensureing sample Consistency.
It is prepared by 1.2PSD models：With reference to Koizumi (Koizumi et al.Jpn J Stroke, 1986,8:1-8) method Establish arteria cerebri media line bolt (MCAO) model, it is postoperative press for 24 hours Longa (Longa et al.Stroke, 1989,20:84-89) Standard row Neuroscore chooses the rat that >=1 and ＜ 4 divides, and single cage orphan supports, post-operative recovery 7d.With reference to Willner (Willner.Neuropsychobiology.2005；52:90-110) method carries out chronic unpredictable mild stimulation foundation PSD models, process are as follows：Tail (1min) is pressed from both sides to all rats, prohibits water (for 24 hours), fasting (for 24 hours), hot environment (45 DEG C, 5min), ice water swimming (4 DEG C, 5min), overturn (for 24 hours) and level round the clock and rock (160 times/min, 30min) totally 7 kinds of methods Stimulation uses a kind of stimulation in 1 week daily, repeatedly 3 weeks altogether, i.e., in Induction Process each stimulation execute altogether 3 times, it is during which all Rat orphan supports.
1.3 groupings and administration：Sucrose water consumption test and spacious field experiment (open-field test, OFT) are carried out first, And carry out neurological deficit score.Sucrose water consumption test and the baseline value of OFT are measured, the uniform rat of score is therefrom filtered out.Greatly Mouse is randomly divided into 6 groups (n=10)：Sham-operation group (gives sham-operation processing, in addition to bolt line is not inserted into arteria carotis communis, with operation Group), simple stroke groups (focal cerebral ischemia MCAO models, neurological deficits score are prepared using line brush>1 point and<4 points Rat enter group), simple depressed group (CUMS combines lonely foster method), PSD model groups (be subject to lonely support after MCAO model post-operative recoveries 7d Method combination CUMS methods), the high, medium and low dosage group of Chinese drugs agentia decocting liquid, Prozac group and Chinese medicine combine Prozac group.Administration：It removes For sham-operation group with outside simple stroke groups, remaining each group stress modeling 21d.Each group animal with stress modeling be administered simultaneously, do evil through another person Art group, simple stroke groups, simple depressed group, PSD group gavage distilled water, the high, medium and low dosage group difference gavage of Chinese drugs agentia are different Dosage decocting liquid, Prozac group gavage Prozac solution.
The Behavioral assessment (applying U.S.'s Clever Sys Inc. systems) of 1.4 depressions：According to the laboratory of team unity Established method carry out (Tang, J et al, Scientific Reports, 2015,5:13573).
Tail-suspention test (TST)：Behavioral despair for reflecting animal.Mouse is fallen with adhesive tape at the position away from tail point 1cm It is hung on horizontal iron (diameter about 1cm), mouse head is apart from ground level about 30cm.Using DepressionScan systems The behavior of mouse in record 6 minutes, the mouse four limbs time completely motionless with trunk in 4 minutes after measurement.
Forced swim test (FST)：Behavioral despair for reflecting animal.Mouse training swimming 15min before experiment, for 24 hours After test.Mouse is put into the glass jar of depth of water 15cm (high 20cm, diameter 14cm), 25 DEG C of water temperature.Using DepressionScan records the motion state of mouse in 6min, mouse body and four limbs motionless time in 4min after measurement.
Syrup preference experiment (SPT)：Reflect depression animal anhedonia symptom.Distilled water and 1% sugarcane will be respectively provided with The water bottle of sugar aqueous solution is put on mouse cage, and to prevent mouse generation position from having a preference for, the position of two water bottles is exchanged after 5 hours.Note The amount of mouse intake distilled water and syrup, calculates the syrup preference rate (ratio of syrup intake and total water intake in record 10 hours Value).
Open field test (OPT)：Evaluation experimental animal in strange environment independent behaviour, exploratory behavior and tensity one kind Method.Animal is put into case (40 × 40 × 35cm) bottom center, is carried out at the same time camera shooting and timing.It is recorded in total in 5min Activity distance and activity time in middle section, behavioural analysis use ANY-maze softwares.
New environment feeds Inhibition test (NSF)：After mouse fasting for 24 hours, it is placed in a new mouse cage, bottom is spread Weighed grain is placed at the bedding and padding of thickness about 1cm, center.Detection mouse starts the latent time of food.With the latent of food The weight of phase and consumption food is observation index.It is 10min that latent time is defined as if no food in mouse 10min.
General behavior is observed：Mouse 24 hours general activity feelings in rearging cage are recorded using HomeCageScan systems Condition, observes its mechanics and circadian rhythm changes.
1.5 experimental result
Inventor has found that PSD group rat syrup preference rates are compared with sham-operation group, MCAO groups and CUMS groups stress be 14th day latter It is remarkably decreased (P ＜ 0.01), Chinese drugs agentia can reverse the syrup preference (P ＜ 0.01) of reduction；When motionless in forced swimming Between compared with sham-operation group, MCAO groups, CUMS groups significantly extend (p<0.01) dead time caused by, Chinese drugs agentia reverses PSD models prolongs Long (P ＜ 0.05).
Embodiment 8
Influence of the Chinese drugs agentia to PSD rat models nervous function and depressed index of correlation
Inventor's early period has been successfully established PSD models with MCAO+CUMS.The results show that model group rats forced swimming (FST) dead time dramatically increases in, and Chinese drugs agentia decocting liquid group is motionless in FST and tail-suspention test (TST) compared with model group Time shortens, and neurologic impairment centainly repaired, and sees Fig. 1 and Fig. 2, and * represents P in figure<0.05, * * represents P<0.01.
Western blot testing results show that the expression of PSD rat models intracerebral BDNF/TrkB accesses and PSD95 are dropped It is low.Chinese drugs agentia and Prozac can increase brain-derived neurotrophic factor (BDNF), phosphorylation tyrosine kinase b (pTrkB) With the expression of tyrosine kinase b (TrkB), while PSD95 can be also raised, see Fig. 3.
The present invention provides a kind of thinkings and method of Chinese medicine composition that treating Poststroke Depression, implement the technology There are many method and approach of scheme, the above is only a preferred embodiment of the present invention, it is noted that for the art Those of ordinary skill for, various improvements and modifications may be made without departing from the principle of the present invention, these change Protection scope of the present invention is also should be regarded as into retouching.The available prior art of each component part being not known in the present embodiment adds To realize.

Claims (6)

1. a kind of Chinese medicine composition for treating Poststroke Depression, which is characterized in that the Chinese medicine composition includes following parts by weight Raw material forms：15-30 parts of radix bupleuri, 10-20 parts of rhizoma cyperi, 10-20 parts of Radix Angelicae Sinensis, 10-20 parts of Radix Rehmanniae, 10-20 parts of peach kernel, safflower 10- 15 parts, 10-20 parts of Fructus Aurantii, 10-20 parts of dried orange peel, 10-20 parts of radix paeoniae rubra, 10-20 parts of Rhizoma Atractylodis Macrocephalae, 10-15 parts of Radix Glycyrrhizae, 10-20 parts of campanulaceae, 6-20 parts of the root of bidentate achyranthes, 10-20 parts of Rhizoma Chuanxiong, 4-6 parts of leech, 10-15 parts of Radix Notoginseng, 15-20 parts of Poria cocos, 15-20 parts of grass-leaved sweetflag, arisaema cum bile 12-20 parts, 3-6 parts of Herba Hyperici Monogyni, 12-20 parts of wilsonii, 3-6 parts of the coptis.
2. a kind of Chinese medicine composition for treating Poststroke Depression according to claim 1, which is characterized in that the Chinese traditional medicine composition Object includes the raw material composition of following parts by weight：15 parts of radix bupleuri, 15 parts of rhizoma cyperi, 10 parts of Radix Angelicae Sinensis, 15 parts of Radix Rehmanniae, 12 parts of peach kernel, safflower 12 parts, 10 parts of Fructus Aurantii, 10 parts of dried orange peel, 10 parts of radix paeoniae rubra, 10 parts of Rhizoma Atractylodis Macrocephalae, 12 parts of Radix Glycyrrhizae, 10 parts of campanulaceae, 15 parts of the root of bidentate achyranthes, 15 parts of Rhizoma Chuanxiong, 6 parts of leech, 10 parts of Radix Notoginseng, 15 parts of Poria cocos, 15 parts of grass-leaved sweetflag, 15 parts of arisaema cum bile, 6 parts of Herba Hyperici Monogyni, 15 parts of wilsonii, the coptis 6 parts.
3. the Chinese medicine composition preparation method for the treatment of Poststroke Depression as claimed in claim 1 or 2, which is characterized in that will be described Radix bupleuri, rhizoma cyperi, Radix Angelicae Sinensis, Radix Rehmanniae, peach kernel, safflower, Fructus Aurantii, dried orange peel, radix paeoniae rubra, Rhizoma Atractylodis Macrocephalae, Radix Glycyrrhizae, campanulaceae, the root of bidentate achyranthes, Rhizoma Chuanxiong, leech, three Seven, Poria cocos, grass-leaved sweetflag, arisaema cum bile, Herba Hyperici Monogyni, wilsonii and the coptis add water to mix by formula ratio, impregnate 30~60min, It decocts twice, each water liquid level did not had 1~2cm of raw material, merging filtrate both to obtain.
4. preparation method according to claim 3, which is characterized in that decoct 30min or more, second of decoction for the first time 15min or more.
5. a kind of pharmaceutical composition for treating Poststroke Depression, which is characterized in that including
(1) antidepressants；
(2) Chinese medicine composition described in claim 1.
6. a kind of pharmaceutical composition for treating Poststroke Depression according to claim 5, which is characterized in that the antidepression Medicine in citalopram hydrobromate, paroxetine hydrochloride, VENLAFAXINE HCL, Mirtazapine, Prozac any one or Several combinations.
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Granted publication date: 20210511