WO2008019588A1 - A chinese medicine composition for treating depression, neurasthenia and process thereof - Google Patents

Abstract

A Chinese medicine composition for treating depression, insomnia and neurasthenia, its process, quality detection method and uses. The Chinese medicine composition is prepared by using rhizoma zingiberis recens, caulis bambusae in taenia, rhizoma pinelliae preparata, rhizoma coptidis, radix paeoniae alba, ramulus cinnamomi, radix glycyrrhizae preparata, radix bupleuri, concha ostreae, and os draconis.

Description

 Traditional Chinese medicine composition for treating depression and neurasthenia and preparation method thereof

 The invention relates to a traditional Chinese medicine composition, a preparation method thereof and a quality control method, in particular to a traditional Chinese medicine composition for treating insomnia, depression and neurasthenia, a preparation method thereof and a quality detecting method.

Background technique

 Insomnia, depression, and neurasthenia refer to excessive mental stress caused by certain long-standing mental factors, resulting in a decrease in mental activity. Its main clinical features are easy to get excited and easy to fatigue. Often accompanied by a variety of physical discomfort and sleep disorders, many patients have a certain predisposition or bad personality before the disease. Busy life, intense work, all kinds of unpleasant annoyances can cause people's brain function to be at high speed or super high speed, leading to neurological disorders, resulting in a series of clinical symptoms, such as insomnia, dizziness, dizziness, Forgetfulness, irritability, fatigue and other symptoms, long-term insomnia can lead to other serious diseases. Although there are dozens of treatments for insomnia in modern medicine, there are many dependences and addictions after taking them, and there are side effects after taking the medicine.

Summary of the invention

 The object of the present invention is to provide a traditional Chinese medicine composition and a preparation method thereof. Another object of the present invention is to provide a method for quality detection of the preparation of the traditional Chinese medicine composition; and the object of the present invention is to provide the use of the traditional Chinese medicine composition.

 The object of the present invention is achieved by the following technical solutions:

 The composition of the drug substance of the traditional Chinese medicine composition of the present invention is as follows:

 Oyster 4-35 parts by weight keel 4-35 parts by weight Bupleurum 2-20 parts by weight Method Pinellia 5-30 parts by weight Bamboo radish 5-30 parts by weight Zhigancao 1-12 parts by weight Huanglian 0. 5-3 parts by weight ginger 2-20 parts by weight of cassia twig 2-20 parts by weight of chalk 2-20 parts by weight.

 The preferred weight ratio of the above-mentioned ten-flavor drug substance of the present invention is as follows:

Oyster 8 parts by weight keel 30 parts by weight Bupleurum 6 parts by weight Method Pinellia 25 parts by weight Zhuru 28 parts by weight of licorice 3 parts by weight of berberine 1 part by weight of ginger 14 parts by weight of cassia twig 5 parts by weight of white peony 17 parts by weight.

 The preferred weight of the ten-flavor drug substance of the present invention is as follows:

 Oyster 20 parts by weight keel 20 parts by weight Bupleurum 10 parts by weight Pinellia 15 parts by weight Bamboo rugs 15 parts by weight Licorice 6 parts by weight Coptis 2 parts by weight Ginger 10 parts by weight Cinnamon 10 parts by weight Preferred in the present invention The weight is as follows:

 Oyster 28 parts by weight keel 7 parts by weight Bupleurum 16 parts by weight Method Pinellia 7 parts by weight Bamboo rug 10 parts by weight Licorice 10 parts by weight Coptis 1. 5 parts by weight Ginger 5 parts by weight Cinnamon sticks 18 parts by weight White peony 3 parts by weight.

 The above-mentioned traditional Chinese medicine composition of the present invention may further comprise the following parts by weight of schisandra, salvia, fried jujube kernel, jujube, and fried rhubarb composed of fifteen flavor raw materials on the basis of the ten-flavor bulk medicine: schisandra 1-14 parts by weight of salvia miltiorrhiza 5-30 parts by weight of fried jujube kernels 2-20 parts by weight of jujube 1-12 parts by weight of fried rhubarb 1-10 parts by weight.

 Preferred weight ratios are

 Schisandra 3 parts by weight Salvia miltiorrhiza 9 parts by weight Fried jujube kernels 15 parts by weight Jujube 10 parts by weight Fried rhubarb 3 parts by weight;

 Schisandra 7 parts by weight Salvia 15 parts by weight Fried dates 10 parts by weight Jujube 6 parts by weight Fried rhubarb 4. 5 parts by weight;

 Or Schisandra 12 parts by weight Salvia 25 parts by weight Fried dates 3 parts by weight

 Jujube 4 parts by weight Fried rhubarb 8 parts by weight.

 The ten- or fifteen-flavor drug substance of the traditional Chinese medicine composition is added into a conventional auxiliary preparation according to a conventional process, such as: a capsule, a pill, a tablet, a granule, an oral liquid preparation or an injection. .

The preparation method of the pharmaceutical composition of the present invention may be as follows: A. Take the drug substance, add water to cook 2-4 times, add 8-12 times the total weight of the drug substance for the first time, decoct for 1-3 hours, add 8-12 times the total weight of the drug substance for the second time. Water, decocted 0. 5-1. 5 hours, the third time plus 8-12 times the total weight of the drug substance, boiling 0. 5-1 hours; while collecting the volatile oil during the boiling process, combined with the decoction Filtered, the filtrate was concentrated to 80 Ό - 90 * C relative density of 1.2, ethanol was added to make the alcohol content 60%, stirred, allowed to stand for 10-16 hours, the supernatant was taken to recover ethanol and concentrated to 60 Π - 70 The thick paste having a relative density of 1.30-1.35 is added to a conventional excipient, and is prepared into a capsule, a pill, a tablet, a granule, an oral liquid preparation or an injection according to a conventional method.

 B. Take the drug substance, mix it, pulverize it into 10 ~ 20 mesh coarse particles, add 5 ~ 7 times the total weight of the drug substance, use microwave extraction method for 60r: extract 2-4 times, extract the liquid for centrifugation The immersion liquid is concentrated to a relative density of 1.30 - 1.35, and a conventional adjuvant is added to prepare a capsule, a pill, a tablet, a granule, an oral liquid preparation or an injection according to a conventional method.

 The preparation method of the pharmaceutical composition of the present invention is preferably as follows:

 A. Take the raw material medicine, add water to cook three times, add 10 times the total weight of the raw material medicine for the first time, decoct for 2 hours, add the first time 8 times the total weight of the raw material medicine, and boil for 1 hour. 3 之间并添加为3。 The alcohol content is 60%, stirred, and allowed to stand for 12 hours. The supernatant is taken to recover ethanol and concentrated to 60 thick paste having a relative density of 1.30 ~ 1.35, added with conventional excipients, and prepared into a plasticizer according to a conventional method. , pills, tablets, granules, oral liquid preparations or injections.

 B. Take the drug substance, mix it, pulverize it into 15 mesh coarse particles, add 6 times the total weight of the drug substance, and extract it twice under 60"C by microwave extraction method. The extract is centrifuged and the immersion liquid is concentrated to The relative density is 1.35, and the conventional excipients are added, and the capsules, pills, tablets, granules, oral liquid preparations or injections are prepared according to a conventional method.

 The relationship between parts by weight and parts by volume of the present invention is: gram per liter.

 The quality detecting method of the present invention includes the following identification method and/or content determination method. The identification method includes one or more of the following identifications:

A. Take 1/3-1/2 of the daily dose of the pharmaceutical composition, which is equivalent to 21 to 42 g of the crude drug. Grinding, adding 30 ml of ethanol, immersing for 1 hour at room temperature, shaking at any time, filtering, and evaporating the filtrate, adding 20 ml of water to the residue to dissolve, and extracting with water-saturated n-butanol for 3 times, 20 ml each time, combined with n-butanol extraction The solution is washed with water saturated with n-butanol, and the water layer is removed. The solution of the solution is evaporated to dryness. The residue is added with 1 ml of ethanol to dissolve. Add 0.6 g of water on a water bath, dry, ^ Pre-packed a neutral alumina adsorption column with a particle size of 200-300 mesh, a weight of lg, and an inner diameter of 10-15 legs. The neutral alumina adsorption column was eluted with 60 ml of ethanol, and the eluate was collected and evaporated to dryness. The residue is added with 1 ml of ethanol to dissolve, and used as a test solution; another reference substance of paeoniflorin is added, and ethanol is added to make a solution containing 1 mg per 1 ml as a reference solution; according to the thin layer color test, the above two solutions are aspirated. 10 μ ΐ , respectively on the same silica gel G thin plate, with 40: 5: 10: 0.2 chloroform - ethyl acetate - methanol - citric acid as a developing agent, unroll, take out, dry, spray 5% Vanilla sulphuric acid solution, heated to spots, clear color; test Chromatography, with the reference position corresponding to the color words, the same color spots;

Β, take 1/3-1/2 of the daily dose of the pharmaceutical composition, equivalent to 21-42g of crude drug, finely ground, add 20ml of ethanol, immerse for 1 hour at room temperature, filter, the filtrate is evaporated to dryness, and the residue is added with methanol 1ml. Dissolve as the test solution; take 50mg of berberine reference medicine, add 10ml of methanol, heat and reflux for 10 minutes on the water bath, filter, and evaporate the filtrate, add 1ml of methanol to dissolve the residue, as a reference drug solution; then take hydrochloric acid檗 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照Above, using 7: 1: 2 n-butanol-glacial acetic acid as the developing agent, unrolling, taking out, drying, and setting it under 365nm ultraviolet light; in the chromatogram of the test sample, corresponding to the chromatogram of the reference drug a fluorescent spot of the same color; a yellow fluorescent spot that is identical to the color corresponding to the reference color;

C. Take 1/3-1/2 of the daily dose of the pharmaceutical composition, which is equivalent to the crude drug amount of 21 ~ 42g, grind finely, add 30ml of ethanol, heat reflux for 30 minutes, let cool, filter, take 10ml, steam dry Add 10 ml of water to the residue to dissolve, add 1 ml of hydrochloric acid, heat on a water bath for 30 minutes, immediately cool, extract twice with diethyl ether, 10 ml each time, combine with ether extract, remove ether, residue and ethyl acetate 1 ml Dissolved, as a test solution; another rhubarb reference material 0. 5g, prepared in the same way as the test solution prepared by the test solution; then take chrysophanol, large The flavin reference substance was added with methanol to make a mixed solution containing 0.5 mg per 1 ml, which was used as a reference solution; according to the thin layer chromatography test, 5 μl of each of the above solutions was taken, and the same was used for the same carboxymethyl cellulose. Sodium as a binder on a silica gel thin layer plate, using 15: 5: 1 30-60 petroleum ether monoethyl citrate monocarboxylic acid as a developing solution, unrolling, taking out, drying, setting 365nm ultraviolet light In the chromatogram of the test sample, in the position corresponding to the color of the reference drug, the same five orange-yellow fluorescent spots are displayed, and the same orange-yellow fluorescent spot is displayed at the position corresponding to the reference color; Smoked in ammonia, examined in daylight, and the spots turn red.

 The method for determining the content in the quality control method includes the following:

Determination by high performance liquid chromatography; chromatographic conditions and system suitability test; using octadecane bonded silica as a filler; 14: 86 acetonitrile - 0.05 mol / L potassium dihydrogen phosphate solution as mobile phase; detection wavelength is 230mg; The number of theoretical plates should be no less than 1500 according to the peak of paeoniflorin; Preparation of reference solution: Accurately weigh the appropriate amount of paeoniflorin reference substance, add 50% ethanol to make each lml containing 0. lmg solution, that is; Preparation of the product solution: Take the daily dose of the pharmaceutical composition of 1 / 6 ~ 1 / 9, equivalent to the amount of crude drug 5. 3 ~ 16. 1g, research fine, mix, set in a triangular bottle, precision addition of 50% ethanol 50ml, weighed, sonicated for 30 minutes, let cool, then weighed, used 50% ethanol to make up the lost weight, shake, filter, take the filtrate, filter with 0. 45 μ ιη microporous membrane After the measurement method: respectively, accurately draw the reference solution and the test solution for each ΙΟ μ Ι, inject into the liquid chromatograph, and determine, that is, the paeoniflorin (C ₂₃ H ₂₈ 0„) shall not be less than 16 0-24. Omg / daily dose.

 The daily dose (daily dose or daily dose) of the different preparations of the pharmaceutical composition of the present invention varies depending on the preparation, but the daily dose of the different preparations contains the same amount of the raw medicine (the crude drug amount is 64 to 96 g). The quality detecting method of the present invention uses a daily dosage as a unit of measurement.

The pharmaceutical composition of the invention has the functions of soothing liver and relieving stagnation, dissolving phlegm and dispersing phlegm, and calming the mind, and is suitable for upset depression caused by liver qi stagnation, chest fullness, insomnia anxiety, diet and tastelessness; Heart and kidney do not pay less than dreams, upsets, fatigue, body fatigue and other neurasthenia, clinical trials set up a total of 308 cases in the observation group, 112 cases in the control group. Clinical observations show that: the pharmaceutical composition of the invention has obvious curative effect on neurasthenia, and the total curative effect is superior to that of the nymidine granules (Ρ<0· 01) compared with the control group of Ningning granules. From the perspective of classification and punishment, this The pharmaceutical composition of the invention has high curative effect on turbidity and heart-dissipation type, heart-kidney non-crossing type and heart-spleen deficiency type, and the curative effect of turbidity and disturbing heart type is obviously superior to that of Ningning granules (P<0.05). It is indicated that the pharmaceutical composition of the present invention and the Ningning Granule are satisfactory for both types of effects, but the pharmaceutical composition of the present invention is superior in terms of the percentage of efficiency, and the dosage is small and convenient to take. Judging from the curative effect of symptom improvement, the therapeutic effect of the pharmaceutical composition of the present invention on insomnia and dreams was significantly better than that of Ningning Granules (P<0.01), and the improvement of irritability, dizziness, brain swelling and forgetfulness was better than night. Ning granules.

 The following experiments and examples are provided to further illustrate but not limit the invention.

Experimental Example 1 Clinical study on treatment of insomnia and neurasthenia

 First, the experimental method

 Observation group: 308 cases, including 138 males and 170 females, aged 21-65 years old, with an average age of 44. 8 years old, ranging from 1 month to 30 years, with an average of 5.20 years. TCM classification was 70 cases of heart and spleen deficiency type, 108 cases of heart and kidney disharmony type, 13 cases of heart gallbladder qi deficiency type, and 117 cases of turbidity and disturbance type.

 Control group: 112 cases, including 51 males and 61 females, aged 29-65 years old, with an average age of 46.87 years old, ranging from 1 month to 26 years, with an average of 4.12 years, TCM classification is diphtheria There were 36 cases, 46 cases of heart and kidney disharmony, 4 cases of heart and qi deficiency, and 26 cases of turbidity and heart.

 Case selection: Sickness chooses neurasthenia with insomnia and dreams as the main syndrome, and excludes serious heart, liver, kidney, brain and other organic lesions. Dialectical of TCM belongs to (1) turbidity and disturbing heart type: Insomnia and more dreams, and the head is heavy, chest tightness, dizziness, pale tongue, greasy fur, slippery pulse. (2) heart and kidney non-crossing type: upset, dreaming, dizziness, tinnitus, palpitations, forgetfulness, dry mouth Shaojin, backache or mouth sores, tongue red, pulse breakdown. (3) Heart qi deficiency type: Insomnia and heart 悸 悸 怯, shortness of breath, sputum, pale tongue, pulse breakdown. (4) Heart and spleen deficiency type: Insomnia and dreams and heart and mind are divided into forgetfulness, head-spotted, distressed, pale-skinned, thin white fur, weak pulse.

 Observation group: The granules prepared in Example 1 were taken one to two bags (6 g) each time, 2 to 3 times a day. Control group: Ningning granules, 20 grams each time, 2 times a day, 1 time in the morning and evening.

Treatment and precautions: Both groups of patients took a 7-day course of treatment. Each case required to take a course of treatment before counting the statistics, and taking the drug to prevent sleeping pills, so as not to affect the observation. The accuracy of the fruit.

Observation indicators: All cases were based on insomnia and dreams, combined with tongue image and pulse image as observation indicators, and graded observation. Other symptoms of neurasthenia are sub-acceptors. Such as dizziness, bloating, irritability, forgetfulness, distress, and so on, the changes to the sub-test are expressed as (a) ( + ) ( ++ ). (-) is normal, (+) is normal, and (++) is severe.

 Insomnia Grading: (1) Level 0: Asymptomatic. (2) Level I: It is difficult to fall asleep, it takes about half an hour to fall asleep, or sleep time is short. After waking up, I feel that my body is more relaxed, or I don’t know how to squat, when I wake up, I wake up and wake up easily. (3) Π grade: It is difficult to fall asleep, tossing and turning, it takes half an hour to sleep above, wake up early, feel sleepy after waking up, fatigue or weakness, sleep when awake, wake up is more difficult to fall asleep. (4) m level: sleepless nights or sleep more dreams, sleep or not sleep 3 to 4 hours, although there is sleep but fatigue, dizziness and brain swelling and other symptoms did not improve significantly.

 Dream rating: (1) Level 0: No dreams or less dreams. (2) Level I: More dreams. (3) Π Level: Dreaming more, still sleep after waking up. (4) m level: Dreams are different, wake up and wake up.

 Treatment outcome

 Efficacy criteria:

 1. Cure: Insomnia and dreaming are level 0.

 2, markedly effective: Insomnia and dreams to improve above the second level, or insomnia to dream to improve the level, the second V card has more than half disappeared.

 3. Effective: Insomnia and dreams improve by more than one level, and the sub-certificate disappears by less than half.

 4, invalid: Insomnia and dreams have not improved.

 Second, the experimental results:

 1, the total efficacy is shown in Table 1

 Comparison of the total efficacy of the two groups Table 1:

 Group 17 cure effective effective invalid effective P observation group 308 30 ( 9. 74 ) 103 (33. 44) 149 (48. 38) 26 (8. 44)

 Control group 112 2 ( 1. 79 ) 22 (19. 64) 58 (51. 79) 30 (26. 78)

The results showed that the efficacy of the observation group was significantly different from that of the control group. The granules prepared in Example 1 were significantly better than the control yin granules.

 2. Comparison of clinical efficacy of major syndromes: see Table 2

 Comparison of the efficacy of the main clinical syndromes 2

 Group heart and spleen deficiency type heart and kidney non-cross type heart gallbladder ^ ^ type turbidity disturbing heart type

 Example number Effective rate 3⁄4 Case number Effective rate 3⁄4 Case number Effective rate % Case efficiency X Observation group 62/70 88.57 98/108 90.74 10/13 76.92 98/117 83.76 Control group 28/36 77.78 38/46 82.60 2/ 4 50.00 16/26 61.54

P value >0.05 >0.05 > 0.05 >0.05

 The results showed that the granules prepared in the observation group, ie, the granules prepared in Example 1 were effective for various types of neurasthenia, such as turbidity, heart and kidney, heart and spleen deficiency, heart and spleen qi deficiency type, and the curative effect was significantly better than night. Ning granules.

 3. Comparison of symptom improvement: See Table 3

 Comparison of the improvement of symptoms in the two groups

 Symptom observation group control group

 Number of cases Efficiency (%) Number of cases Efficiency (%) Insomnia 282/308 91.56* 82/112 73.21

 Dream 282/308 91.56* 82/112 73.21

 Irritating 233/275 84.73 78/100 78.00

 God fatigue 232/287 80.84 86/98 87.76

 Weakness 230/287 80.14 86/98 87.76

 Heart 悸 237/283 83.75 72/84 85.71

 Dizziness 229/295 77.63 66/106 62.26

 Brain swelling 209/280 74.64 58/90 64.44

 Forgetful 146/227 64.32 60/98 61.22

 Irritable 163/220 74.09 60/70 85.71

 *P<0.01

The results showed that the effect of insomnia and multi-dream was more extreme in the observation group and the control group. Significant difference, indicating that the granules prepared in Example 1 have a better therapeutic effect on insomnia and multiple dreams than the Ningning granules.

 4. Observation of side effects: No adverse reactions were observed in the observation group and the control group after administration. Experimental Example 2 Clinical study experiment for treating depression

 First, the experimental materials:

 Experimental drug: The present invention is a granule (that is, the granule prepared in Example 7), formulated into a suspension of 8% and 4% with water, and administered to Kunming mice by intragastric administration; , Lot number 9908056, produced by Sino-American Shike Pharmaceutical Co., Ltd.

 Second, the experimental method

 1. Mouse forced swimming time experiment

 19.6±l. lg mice, male and female, were divided into groups and administered once daily for 20 days. The mice were placed in an open glass jar (high 19 cm, diameter 12 cm, water depth 8 cm, water temperature 22-23) 1 hour after the second administration, and the time was recorded from the time when the mice entered the water for 6 minutes, and accumulated within 4 minutes after the recording. Do not move time. The results are shown in Table 4. Each of the administration groups significantly shortened the time during which the mice were forced to swim.

 Table 4 Effect on forced swimming time in mice Group Number of animals 4 'Intra-immobility time accumulation /S

 (n) (X±SD)

 Control group 10 151.0±48.6

 Celite 5mg x 20 10 81.9 ±31.9**

 Granules of the invention lg"0 10 103.2 ± 39.5*

 Granules of the invention 2gx 20 10 96.1 ± 36.2*

 t test: compared with the control group *P<0.05, **P<0.01

 2. Rat forced swimming time experiment

178 ± 6 g male rats were selected, grouped and administered once daily according to the dose of Table 5, for ²⁰ consecutive days. One hour after the 19th day of administration, the rats were individually placed in an open glass jar (40 cm high, 80 cm in diameter, 15 cm in water depth, 24 to 26 ° C), and the rats were exposed to water for 15 minutes. Take out, dry at 32*C; 1 hour after the administration on the 20th day, measure the cumulative immobility time in the rats for 5 minutes. The results are shown in Table 5. Each of the administration groups significantly shortened the time of forced swimming in rats.

 Table 5 Effect on forced swimming time in rats

 Group Dosage Number of animals Internal time constant /S

 ( /kg d) (π) (X±SD)

 Control group 10 191.3±47.4

 Celite 4mg 20 10 86.8 ±27.2**

 Granules of the invention 0.8gx 20 10 146.9 ±29.2*

 Granules of the invention 1.6gx 20 10 134.6 ±25.5*

 t test: compared with the control group *P<0.05, **P<0.01.

 Third, the experimental results

 Through the above experiments on the anti-depressant effect of rats, it was shown that the granules of the present invention can significantly shorten the time of forced swimming, increase the mood of animals and enhance the behavior of animals. These experimental results show that the granules of the present invention can be used for the treatment of depression with symptoms of anxiety, insomnia, restlessness, and fatigue, and have a good antidepressant effect.

 The effects of the above experimental examples can be achieved by the following examples.

Implementation method

Example 1: Preparation of granules

 Guizhi 10kg White Pelican 10kg Oyster 20kg

 Keel 20kg Bupleurum 10kg French Pinelli 15kg

 Schisandra 7kg Bamboo Ru 15kg Salvia 15kg

 Fried jujube 10kg licorice 6kg jujube 6kg

 Coptis 2kg Ginger 10kg Fried Rhubarb 4.5kg

The above 15 flavors of raw materials, boiled three times with water, add 1605 liters of water for the first time, decoct for 2 hours, add 1284 liters of water for the second time, decoct for 1 hour, add 1284 liters of water for the third time, decoct for 0.5 hour; The volatile oil was collected at the same time, and the decoction was combined and filtered. The filtrate was concentrated to 80 TC and the relative density was 1.2. The ethanol was added to make the alcohol content 60%, stirred, and allowed to stand for 12 hours. The supernatant was taken to recover ethanol and concentrated to 60 TC thick paste having a relative density of 1.30-1.35, vacuum dried, and pulverized into a fine powder. According to the ratio of fine powder, lactose and dextrin 1: 1:1, add ethanol, make granules, dry, spray the above volatile oil, mix and mix to make granules. The unit preparation is 6 grams per bag.

 Example 2: Preparation of granules

 Guizhi 5kg White Pelican 17 kg Oyster 8 kg

 Keel 30 kg Bupleurum 6 kg Pinellia 25 kg

 Schisandra 3 kg Bamboo Ru 28 kg Salvia 9 kg

 Fried jujube 15 kg licorice 3 kg jujube 10 kg

 Coptis 1 kg Ginger 14 kg Stirred rhubarb 3 kg

 The above 15 flavors of raw materials, boiled three times with water, the first time added 1770 liters of water, boiling for 2 hours, the second time added 1416 liters of water, boiling for 1 hour, the third time added 1416 liters of water, boiling 0. 5 hours; During the cooking process, the volatile oil was collected, and the decoction was combined, filtered, and the filtrate was concentrated to 80. The relative density was 1.2. The ethanol was added to make the alcohol content 60%, stirred, and allowed to stand for 12 hours. The supernatant was taken to recover ethanol and concentrated. A thick paste having a relative density of 1.30-1.35, dried in a vacuum, and pulverized into a fine powder. Take 1 part, 1 part of lactose, 1 part of dextrin, add ethanol, make granules, dry, spray the above volatile oil, mix and mix to make granules. The unit preparation is 6 grams per bag.

Example 3: Preparation of an anthraquinone

 Oyster 20kg keel 20 kg Bupleurum 10 kg

 French Pinelli 15kg Bamboo Ru 15kg Zhigancao 6kg

 Coptis 2kg Ginger 10kg Cinnamon 10kg

 White 芍 10kg

The above ten flavor raw materials, boiled three times with water, add 1416 liters of water for the first time, decoct for 2 hours, add 1416 liters of water for the second time, decoct for 1 hour, add 1133 liters of water for the third time, decoct for 1 hour; The volatile oil was collected at the same time, and the decoction was combined, filtered, and the filtrate was concentrated to 80 t. The relative density was 1.2. The ethanol was added to make the alcohol content 60%, stirred, and allowed to stand for 12 hours. The supernatant was taken to recover ethanol and concentrated. To 60 thick paste with a relative density of 1. 30-1. 35, vacuum thousand 5克。 Each granules, each granules, each granules, each granules, each granules, each granules.

Example 4: Preparation of pellets

 Oyster 28kg keel 7kg Bupleurum 16kg

 French Pinellia 7kg Bamboo Ru 10kg Licorice 10kg

 Coptis 1. 5kg Ginger 5kg Cinnamon 10 kg

 Chalk 10 kg

 The raw material is mixed, pulverized into 15 mesh coarse particles, added with water 6 liters, and extracted by microwave extraction method for 60 times or less, and the extract is centrifuged, and the immersion liquid is concentrated to a relative density of 1.30 ~ 1. 35 , adding conventional excipients, and making pills according to conventional methods.

Example 5: Preparation of tablets

 Guizhi 10kg White Pelican 10kg Oyster 20kg

 Keel 20kg Bupleurum 10kg French Pinelli 15kg

 Schisandra 7kg Bamboo Ru 15 kg Salvia 15kg

 Fried jujube 10kg licorice 6kg jujube 6kg

 Coptis 2kg Ginger 10kg Fried Rhubarb 4. 5kg

 The raw material is mixed, pulverized into a 17-mesh coarse particle, and 7 liters of water is added, and the mixture is extracted by a microwave extraction method for 60 times or less, and the extract is centrifuged, and the immersion liquid is concentrated to a relative density of 1.30 ~ 1. 35 5克。 Each tablet, each tablet, each tablet 0. 5 grams.

Example 6: Preparation of oral liquid

 Oyster 28kg keel 7kg Bupleurum 16kg

 French Pinellia 7kg Bamboo Ru 10kg Licorice 10kg

 Coptis 1. 5kg ginger 5kg cassia twig 18kg

 White 芍 3kg

至1. The relative density is 1. 30 ~ 1. The organic material is mixed and pulverized into 20 mesh coarse particles, and added with water, 7 liters, and extracted by microwave extraction method for 60 times or less, and the extract is centrifuged, and the immersion liquid is concentrated to a relative density of 1. 30 ~ 1. 35, adding conventional excipients, making oral liquid preparations according to conventional methods, single The formulation is 10 liters per bottle.

 Example 7: Preparation of granules

 Oyster 8kg keel 30kg Bupleurum 6kg

 Method Pinellia 25kg Bamboo Ru 28kg Zhigancao 3kg

 Coptis 1kg Ginger 14kg Cinnamomum 5 kg

 White peony 17 kg

 The above ten flavor raw materials, boiled 3 times with water, add 1644 liters of water for the first time, decoct for 1.5 hours, add 1370 liters of water for the second time, decoct for 1 hour, add 1096 liters of water for the third time, and decoct for 1 hour; During the boiling process, the volatile oil was collected at the same time, and the decoction was combined and filtered. The filtrate was concentrated to 80 relatively dense; ^ was 1. 2, ethanol was added to make the alcohol content 60%, stirred, allowed to stand for 12 hours, and the supernatant was taken for recovery. Ethanol and concentrated to a 60 mil thick paste having a relative density of 1.30-1.35, vacuum dried, and pulverized into a fine powder. Take 1 part of fine powder, 1 part of lactose, 1 part of dextrin, add ethanol, make granules, dry, spray the above volatile oil, mix well, and make granules. The unit preparation is 6 g per bag.

Example 8: Identification method in quality inspection

A. Take 6 g of the pharmaceutical composition granules of Example 1, which is equivalent to a crude drug amount of 32 g, and add 30 ml of ethanol, immersed for 1 hour at room temperature, shaken occasionally, filtered, and the filtrate is evaporated to dryness. The residue is added with water 20 ml to dissolve, and saturated with water. The n-butanol was shaken and extracted three times, 20 ml each time, and the n-butanol extract was combined, washed once with water saturated with n-butanol, and the aqueous layer was discarded. The n-butanol solution was evaporated to dryness in a water bath, and the residue was added with ethanol. Lml is dissolved, added with alumina 0.6 g, stirred on a water bath, dried, and charged into a pre-packed neutral alumina adsorption column with a particle size of 200-300 mesh, a weight of lg, and an inner diameter of 10-15 mm. The neutral alumina adsorption column was eluted with 60 ml of ethanol, and the eluate was collected, evaporated to dryness, and the residue was added with 1 ml of ethanol to dissolve, and used as a test solution; another reference substance of paeoniflorin was added, and ethanol was added to prepare a solution containing 1 mg per ml. As a reference solution; according to the thin layer chromatography test, take 10 μ 各 of each of the above two solutions, respectively, on the same silica gel G thin layer plate, to 40: 5: 10: 0.2 chloroform-ethyl acetate - Methanol-formic acid as a developing agent, unroll, remove, and dry Vanilla wake sprayed with 5% sulfuric acid solution was heated to a clear spot color; chromatography test, with color reference position corresponding to speak, the same color spots; B. Take 6 g of the granules of the pharmaceutical composition of Example 1, which is equivalent to a crude drug amount of 32 g, and add 20 ml of ethanol, immersed for 1 hour at room temperature, filtered, and the filtrate is evaporated to dryness. The residue is dissolved in methanol to dissolve it as a test solution. Another 50 mg of berberine reference medicine, 10 ml of sterol, and heated to reflux for 10 minutes on a water bath, filtered, and the filtrate was evaporated to dryness. The residue was dissolved in 1 ml of decyl alcohol as a reference drug solution; Adding sterol to make a solution containing 0.5 mg per 1 ml as a reference solution; according to the thin layer chromatography test, 2 μl of each of the above three solutions is taken up on the same silica gel G thin layer plate, 7: 1: 2 n-butanol monohydrate acetic acid-water as a developing agent, unroll, take out, dry, and set under 365nm ultraviolet light; in the chromatogram of the test sample, the same color at the position corresponding to the color error of the reference drug a fluorescent spot; a yellow fluorescent spot that is identical in position corresponding to the color term of the reference;

 C. Take 6 g of the pharmaceutical composition granules of Example 1, which is equivalent to a crude drug amount of 32 g, and add 30 ml of ethanol, reflux under heating for 30 minutes, let cool, filter, take 10 ml, evaporate to dryness, and add 10 ml of water to dissolve the residue. Add 1 ml of hydrochloric acid, heat on a water bath for 30 minutes, immediately cool, extract twice with diethyl ether, 10 ml each time, combine the ether extract, remove the ether, and add 1 ml of ethyl acetate to dissolve the solution as a test solution; 5mg的混合溶液,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, As a reference solution; according to the thin layer chromatography test, take 5 μl of each of the above solutions, respectively, on the same silica gel crucible plate with sodium carboxymethyl cellulose as a binder, to 15:5:1 30 — The upper layer solution of 601C petroleum ether ethyl formate monocarboxylic acid is used as a developing solvent, unrolled, taken out, dried, and placed under a 365 nm ultraviolet light. In the chromatogram of the test sample, the corresponding position in the chromatogram of the reference drug Was the same five orange fluorescent spots, in a position corresponding to the reference color on the pan, was the same orange and yellow fluorescent spots; smoked opposed ammonia, sunlight view, the spot turns red. Example 9: Method for determining content in quality testing

Determination by high performance liquid chromatography; chromatographic conditions and system suitability test; using octadecylsilane bonded silica as a filler; 14: 86 acetonitrile - 0. 05mol / L potassium dihydrogen phosphate solution as mobile phase; detection wavelength 230 nm; the number of theoretical plates should be no less than 1500 according to the peak of paeoniflorin; preparation of reference solution: accurately weigh the appropriate amount of paeoniflorin reference substance, add 50% ethanol to make each Lml containing 0. lmg solution, that is; the preparation of the test solution: Take the content of the granule loading difference of the pharmaceutical composition of Example 2, research fine, mix, take about 2g, equivalent to the amount of crude drug 10. 7g precision weighing, placed in a triangular bottle, precision added 50ml ethanol 50ml, weighed, sonicated for 30 minutes, let cool, then weighed, use 50% ethanol to make up the lost weight, shake, filter After the filtrate is taken up, it is filtered through a 0. 45 μ πι microporous membrane to obtain the same method. The method is as follows: respectively, the reference solution and the test solution are respectively accurately injected into the liquid chromatograph, and the measurement is performed. Obtained with paeoniflorin (^^(^ must not be less than 16. Omg / daily dose.

Example 10: Quality Inspection Method

 A, taking the pharmaceutical composition granules of Example 1 6g, corresponding to the crude drug amount 32g plus ethanol 30ml, immersed for 1 hour at room temperature, shaking at any time, filtered, the filtrate is evaporated to dryness, the residue is added with water 20ml to dissolve, water is saturated with n-butyl The alcohol was shaken and extracted three times, 20 ml each time, and the n-butanol extract was combined, washed once with water saturated with n-butanol, and the aqueous layer was discarded. The n-butanol solution was evaporated to dryness in a water bath, and the residue was dissolved in ethanol to dissolve 1 ml. Add 0. 6g of alumina, stir well on a water bath, dry, and put into a pre-filled neutral alumina adsorption column with a particle size of 200-300 mesh, a weight of lg, and an inner diameter of 10-15 legs, to 60ml. Ethanol elutes the neutral alumina adsorption column, collects the eluent, evaporates to dryness, and dissolves the residue with ethanol 1 ml to dissolve it as the test solution. Another reference substance of paeoniflorin is added with ethanol to make a solution containing 1 mg per lml. Reference solution; according to the thin layer chromatography test, take 10 μl of each of the above two solutions, respectively, on the same silica gel G thin-layer plate, to 40: 5: 10: 0.2 chloroform-ethyl acetate-sterol a citric acid as a developing agent, expand , take out, dry, spray with 5% vanillin sulfuric acid solution, heat to the spots to develop color clear; for the test sample, in the position corresponding to the reference color, the same color spots;

6, taking the pharmaceutical composition granules of Example 1 6g, corresponding to the amount of 32g of crude drug, 20ml of ethanol, immersed for 1 hour at room temperature, filtered, the filtrate was evaporated to dryness Another 50mg of berberine reference medicine, add 10ml of methanol, heated on a water bath for 10 minutes, filtered, the filtrate was evaporated to dryness, the residue was added with methanol 1ml to dissolve, as a reference drug solution; then take berberine hydrochloride reference substance, add methanol Prepare a solution containing 0.5 _μg per lml as a reference solution; according to the thin layer chromatography test, take 2 μ ΐ of each of the above three solutions, respectively, on the same silica gel G thin layer plate, to 7: 1: 2 n-butanol monohydrate acetic acid-water For the developing agent, unfold, take out, dry, and set it under the 365nm ultraviolet light; in the chromatogram of the test sample, the fluorescent spot of the same color is displayed at the position corresponding to the color term of the reference drug; The same position, the same yellow fluorescent spot;

C. Take 6 g of the pharmaceutical composition granules of Example 1, which is equivalent to a crude drug amount of 32 g, and add 30 ml of ethanol, reflux under heating for 30 minutes, let cool, filter, take 10 ml, evaporate to dryness, and add 10 ml of water to dissolve the residue. Add 1 ml of hydrochloric acid, heat on a water bath for 30 minutes, immediately cool, extract twice with diethyl ether, 10 ml each time, combine the ether extract, remove the ether, and add 1 ml of ethyl acetate to dissolve the solution as a test solution; 5mg的混合溶液,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, As a reference solution; according to the thin layer chromatography test, draw 5 μ 1 of each of the above solutions, respectively, on the same silica gel crucible plate with sodium carboxymethyl cellulose as a binder, to 15:5:1 30 — 60 Ό petroleum ether ethyl formate mono carboxylic acid as the developing agent, unfolded, taken out, dried, placed under 365 nm UV light; in the chromatogram of the test sample, in the position corresponding to the color error of the reference drug, Same 5 oranges Yellow fluorescent spots, the same orange-yellow fluorescent spots at the position corresponding to the chromatogram of the reference substance; smoked in ammonia, examined in daylight, spots turned red; determined by high performance liquid chromatography; chromatographic conditions and system application Test: using octadecylsilane bonded silica as a filler; 14: 86 acetonitrile - 0. 05mol / L potassium dihydrogen phosphate solution as mobile phase; detection wavelength is 230nm; theoretical plate number according to paeoniflorin peak should not be calculated Below the 1500; Preparation of the reference solution: Accurately weigh the appropriate amount of paeoniflorin reference substance, add 50% ethanol to make each lml containing 0. lmg solution, that is; Preparation of the test solution: Take the pharmaceutical combination of Example 2g of granules, equivalent to the amount of raw drug 10. 7g finely ground, mix well, take about 2g, accurately weighed, set in a triangular flask, precisely add 50ml of 50ml ethanol, weigh the weight, sonicate for 30 minutes, let cool, Weigh the weight again, make up the lost weight with 50% ethanol, shake it, filter it, take the filtrate, filter it with 0. 45 μ πι microporous membrane, ie, the method: Determination: precision draw the reference solution 10 μΐ each with the test solution, Inject liquid phase color spectrometer, determine, that is;; containing paeoniflorin ( ₂₃ 11 ₂₈ 0 „ not less than 20.0 m _g / daily dose.

Example 11: Quality Inspection Method A. Take 4 g of the pharmaceutical composition capsule of Example 3, which is equivalent to 32 g of crude drug and 30 ml of ethanol, immersed for 1 hour at room temperature, shaken occasionally, filtered, and the filtrate is evaporated to dryness. The residue is added with water 20 ml to dissolve, and the water is saturated. The butanol was shaken and extracted three times, 20 ml each time, and the n-butanol extract was combined, washed once with water saturated with n-butanol, and the aqueous layer was discarded. The n-butanol solution was evaporated to dryness on a water bath, and the residue was added with 1 ml of ethanol. Dissolve, add 0. 6g of alumina, stir well on a water bath, dry, and put into a pre-packed neutral alumina adsorption column with a particle size of 200-300 mesh, a weight of lg, and an inner diameter of 10-15. A neutral alumina adsorption column was eluted with 60 ml of ethanol, and the eluate was collected, evaporated to dryness, and the residue was added with 1 ml of ethanol to dissolve, and used as a test solution; another reference substance of paeoniflorin was added, and ethanol was added to make a solution containing 1 mg per lml. As a reference solution; according to the thin layer chromatography test, draw 10 μl of each of the above two solutions, respectively, on the same silica gel G thin layer plate, to 40: 5: 10: 0.2 chloroform-ethyl acetate-methanol - citric acid as a developing agent, unroll, remove, dry, spray 5% Grass wake sulfuric acid solution was heated to a clear spot color; test chromatogram, the mass with a color corresponding to the reference position, substantially the same color spots;

 4, 4 g of the pharmaceutical composition capsule of Example 3, corresponding to a crude drug amount of 32 g, finely added, 20 ml of ethanol, immersed for 1 hour at room temperature, filtered, and the filtrate was evaporated to dryness, and the residue was dissolved in 1 ml of decyl alcohol to be dissolved. The product solution; another take Huanglian reference medicine 50mg, add methanol 10ml, placed in a water bath and heated to reflux for 10 minutes, filtered, the filtrate was evaporated to dryness, the residue was added with methanol 1ml to dissolve, as a reference drug solution; then take berberine hydrochloride reference substance, Adding decyl alcohol to make a solution containing 0.5 mg per 1 ml, as a reference solution; according to the thin layer chromatography test, 2 μ ΐ of each of the above three solutions is taken up, respectively, on the same silica gel G thin layer plate, 7: 1: 2 n-butanol-glacial acetic acid-water as a developing agent, unroll, take out, dry, and set under 365mn ultraviolet light; in the chromatogram of the test sample, the same color is displayed at the position corresponding to the chromatogram of the reference drug a fluorescent spot; a yellow fluorescent spot that is identical to the position corresponding to the color of the control;

C, taking the pharmaceutical composition capsule of Example 3 4g, corresponding to the amount of 32g of crude drug, adding 30ml of ethanol, heating and refluxing for 30 minutes, allowing to cool, filtering, taking 10ml, evaporated to dryness, adding 10ml of water to dissolve the residue, Add 1 ml of hydrochloric acid, heat on a water bath for 30 minutes, immediately cool, extract twice with diethyl ether, 10 ml each time, combine the ether extract, remove the ether, and add 1 ml of ethyl acetate to dissolve the solution. 5g, The reference drug solution was prepared in the same manner as the test solution; the chrysophanol and the emodin reference substance were added, and methanol was added to make a mixed solution containing 0.5 mg each of 1 ml, as a reference solution; In the test, 5 μl of each of the above solutions was taken up on the same silica gel crucible plate with sodium carboxymethylcellulose as a binder, and 15:5:1 of 30-60* petroleum ether monoethyl ester The upper layer of monoformic acid is used as a developing solvent, unrolled, taken out, dried, and placed under a 365 nm ultraviolet light. In the chromatogram of the test sample, the same five orange-yellow fluorescent spots are displayed at the position corresponding to the chromatogram of the reference drug. In the position corresponding to the color term of the reference substance, the same orange-yellow fluorescent spot is displayed; smoked in ammonia gas, examined in daylight, and spotted in red; determined by high performance liquid chromatography; chromatographic conditions and system suitability test; Using octadecylsilane bonded silica as a filler; 14: 86 acetonitrile - 0. 05mol / L potassium dihydrogen phosphate solution as mobile phase; detection wavelength is 230nm; theoretical plate number should be no less than 1500 according to paeoniflorin peak ; The preparation of the drug composition capsules of Example 3 is obtained by the method of accurately weighing the paeoniflorin reference substance, adding 50% ethanol to make a solution containing 0. lmg per lml; , equivalent to the amount of raw drug 10. 7g finely ground, mixed, accurately weighed, placed in a triangular bottle, precision added 50ml ethanol 50ml, weighed, sonicated for 30 minutes, let cool, then weighed, 50% The weight of the lost weight of ethanol is adjusted, shaken, filtered, and the filtrate is taken and filtered through a 0. 45 μ ιη microporous membrane. The determination method: precision extraction of the reference solution and the test solution respectively. Ι , injected into the liquid chromatograph, measured, that is;; containing paeoniflorin C ₂₃ H ₂₈ 0 „ not less than 24. Omg / daily dose.

Example 12: Quality Inspection Method

A. Take 8 g of the pharmaceutical composition tablet of Example 5, which is equivalent to 32 g of crude drug and 30 ml of ethanol, immersed for 1 hour at room temperature, shaken occasionally, filtered, and the filtrate is evaporated to dryness. The residue is added with water 20 ml to dissolve, and the mixture is saturated with water. The alcohol was shaken and extracted three times, 20 ml each time, and the n-butanol extract was combined, washed once with water saturated with n-butanol, and the aqueous layer was discarded. The n-butanol solution was evaporated to dryness in a water bath, and the residue was dissolved in ethanol to dissolve 1 ml. Add 0. 6g of alumina, stir well on a water bath, dry, and put into a pre-packed neutral alumina adsorption column with a particle size of 200-300 mesh, a weight of lg, and an inner diameter of 10-15 mm, with 60 ml of ethanol. Eluting the neutral alumina adsorption column, collecting the eluent, evaporating and drying, adding 1 ml of ethanol to the residue to dissolve, as a test solution; The reference substance is added with ethanol to make a solution containing 1 mg per 1 ml as a reference solution; according to the thin layer chromatography test, 10 μ ΐ of each of the above two solutions is taken up, and respectively placed on the same silica gel G thin layer plate, to 40 : 5: 10: 0. 2 chloroform-ethyl acetate-methanol-formic acid as a developing solvent, unroll, remove, dry, spray with 5% vanilla sulphuric acid solution, heat to spot, clear color; test color , at the position corresponding to the color term of the reference, the spot of the same color;

 8, 8 g of the pharmaceutical composition tablet of Example 5, corresponding to a crude drug amount of 32 g, finely added, 20 ml of ethanol, immersed for 1 hour at room temperature, filtered, and the filtrate was evaporated to dryness, and the residue was dissolved in methanol to dissolve it as a test solution. Another 50mg of berberine reference medicine, add 10ml of methanol, heated on a water bath for 10 minutes, filtered, the filtrate was evaporated to dryness, the residue was added with 1ml of sterol to dissolve, as a reference drug solution; then take berberine hydrochloride reference substance, add Methanol is made into a solution containing 0.5 mg per 1 ml, as a reference solution; according to the thin layer chromatography test, 2 μ ΐ of each of the above three solutions is taken up, respectively, on the same silica gel G thin layer plate, 7: 1: 2 n-butanol monohydrate acetic acid-water as a developing agent, unfold, take out, dry, and set under 365nm ultraviolet light; in the chromatogram of the test sample, the fluorescence of the same color is displayed at the position corresponding to the color of the reference drug Spot; the same yellow fluorescent spot at the position corresponding to the chromatogram of the control;

C. Take 8 g of the pharmaceutical composition tablet of Example 5, corresponding to a crude drug amount of 32 g, and add 30 ml of ethanol, reflux under heating for 30 minutes, let cool, filter, take 10 ml, evaporate to dryness, add 10 ml of water to dissolve the residue, and then dissolve. Add 1 ml of hydrochloric acid, heat on a water bath for 30 minutes, immediately cool, extract twice with diethyl ether, each time 10 ml, combine the ether extract, remove the ether, and add the residue to ethyl acetate 1 ml to dissolve, as the test solution; 5mg的混合溶液,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, As a reference solution; according to the thin layer chromatography test, take 5 μl of each of the above solutions, respectively, on the same silica gel crucible plate with sodium carboxymethyl cellulose as a binder, to 15:5:1 30 — 60TC petroleum ether ethyl methacrylate monocapric acid as the developing agent, unfolded, taken out, air-dried, and placed under 365nm ultraviolet light; in the test color, in the position corresponding to the chromatogram of the reference drug, The same 5 orange yellow Fluorescent spots, in the position corresponding to the reference color, the same orange-yellow fluorescent spots; smoked in ammonia, examined in daylight, spots turned red; Determination by high performance liquid chromatography; chromatographic conditions and system suitability test; using octadecane bonded silica as a filler; 14: 86 acetonitrile - 0. 05mol / L potassium dihydrogen phosphate dissolved 3⁄4 as mobile phase; detection wavelength The amount of the theoretical plate is not less than 1500 according to the peak of paeoniflorin; the preparation of the reference solution: the amount of the paeoniflorin reference substance is accurately weighed, 50% ethanol is added to make each lml containing 0. lmg solution, that is; Preparation of the test solution: Take the pharmaceutical composition tablet of Example 5 2. 7g, equivalent to the amount of raw drug 10. 7g finely ground, mix, accurately weighed, placed in a triangular flask, precision added 50% ethanol 50ml, Weigh the weight, sonicate for 30 minutes, let cool, then weigh the weight, make up the lost weight with 50% ethanol, shake the hook, filter, take the filtrate, filter with 0. 45 μ ιη microporous membrane, Immediately; Determination method: respectively, accurately draw the reference solution and the test solution, each ΙΟ μ Ι, into the liquid chromatograph, determine, that is; the paeoniflorin CuI Ju should not be less than 18. Omg / daily dose.

Claims

Rights request A traditional Chinese medicine composition for treating depression, insomnia or neurasthenia, characterized in that the raw material composition of the traditional Chinese medicine composition is:  Oyster 4-35 parts by weight keel 4-35 parts by weight Bupleurum 2-20 parts by weight method Pinellia 5-30 parts by weight bamboo ruthenium 5-3Q parts by weight licorice 1-12 parts by weight of berberine 0. 5- 3 parts by weight ginger 2-20 parts by weight of cassia twig 2-20 parts by weight of chalk 2-20 parts by weight.  2. The traditional Chinese medicine composition according to claim 1, wherein the raw material composition of the traditional Chinese medicine composition is:  Oyster 8 parts by weight Dragon bone 30 parts by weight Bupleurum 6 parts by weight Method Pinellia 25 parts by weight Bamboo rug 28 parts by weight Radix licorice 3 parts by weight Coptis 1 part by weight Ginger 14 parts by weight Cinnamon branch 5 parts by weight White peony 17 parts by weight.  3. The traditional Chinese medicine composition according to claim 1, wherein the raw material composition of the traditional Chinese medicine composition is:  Oyster 20 parts by weight Keel 20 parts by weight Bupleurum 10 parts by weight Method Pinellia 15 parts by weight Bamboo rug 15 parts by weight Licorice 6 parts by weight Coptis 2 parts by weight Ginger 10 parts by weight Cinnamon 10 parts by weight White peony 10 parts by weight.  4. The traditional Chinese medicine composition according to claim 1, wherein the raw material composition of the traditional Chinese medicine composition is:  Oyster 28 parts by weight keel 7 parts by weight Bupleurum 16 parts by weight Method Pinellia 7 parts by weight Bamboo rug 10 parts by weight Licorice 10 parts by weight Coptis 1. 5 parts by weight Ginger 5 parts by weight Cinnamon sticks 18 parts by weight White peony 3 parts by weight. 5. The traditional Chinese medicine composition according to claim 1, 2, 3 or 4, characterized in that the pharmaceutical composition further comprises the following weight parts of the drug substance: Schisandra 1-14 parts by weight of Salvia miltiorrhiza 5-30 children  Fried jujube 2-20 parts by weight Jujube 1-12 parts by weight  Fried rhubarb b 10 parts by weight.  6. The traditional Chinese medicine composition according to claim 5, wherein the drug substance to be added to the pharmaceutical composition is:  Schisandra 3 parts by weight Salvia 9 parts by weight  Fried jujube 15 parts by weight jujube 10 parts by weight  Fried rhubarb 3 parts by weight.  7. The traditional Chinese medicine composition according to claim 5, wherein the pharmaceutical substance to be added to the pharmaceutical composition is:  Schisandra 7 parts by weight Salvia 15 parts by weight  Fried jujube 10 parts by weight jujube 6 parts by weight  Fried rhubarb 4. 5 parts by weight.  8. The traditional Chinese medicine composition according to claim 5, wherein the pharmaceutical composition is added with the raw material medicine:  Schisandra 12 parts by weight Salvia 25 parts by weight  Fried jujube 3 parts by weight jujube 4 parts by weight Fried rhubarb 8 parts by weight _β  9. A method of preparing a traditional Chinese medicine composition according to claim 1, 2, 3, 4, 6, 7 or 8, characterized in that the method is optionally as follows: 取 Take the raw material medicine, add water to cook 2-4 times, add 8-12 times the total weight of the raw material medicine for the first time, decoct for 1-3 hours, add 8-12 times the total weight of the raw material medicine for the second time. Water, decoction 0. 5-1. 5 hours, the third time plus 8-12 times the total weight of the drug substance of the water, boiling 0. 5-1 hours; while collecting the volatile oil during the boiling process, combined with the decoction, After filtration, the filtrate was concentrated to 80" - 901 C. The relative density was 1.2. The ethanol was added to make the alcohol content 60%, stirred, and allowed to stand for 10-16 hours. The supernatant was taken to recover ethanol and concentrated to 60*C - 70 a thick paste having a relative density of 1.30-1.35, added to a conventional excipient, and prepared into a capsule, a pill, a tablet, a granule, an oral liquid preparation or an injection according to a conventional method; B. Take the drug substance, mix it, pulverize it into 10 ~ 20 mesh coarse particles, add 5 ~ 7 times the total weight of the drug substance, and extract it by 2-4 times with 60N C or less by microwave extraction method. Separation, the immersion liquid is concentrated to a relative density of 1.30 ~ 1. 35, adding conventional excipients, and preparing a capsule, a pill, a tablet, a granule, an oral liquid preparation or an injection according to a conventional method.  The method for preparing a traditional Chinese medicine composition according to claim 5, wherein the method is as follows:  A. Take the raw material medicine, add water for 2 to 4 times, add 8-12 times of the total weight of the raw material medicine, boil for 1-3 hours, add 8-12 times the total weight of the raw material medicine. Water, decocted 0. 5-1. 5 hours, the third time plus 8-12 times the total weight of the drug substance of the water, boiling 0. 5-1 hours; while collecting the volatile oil during the boiling process, combined with the decoction, After filtration, the filtrate was concentrated to 801 C - 90 and the relative density was 1.2. The ethanol was added to make the alcohol content 60%, stirred, and allowed to stand for 10-16 hours. The supernatant was taken to recover ethanol and concentrated to a relative density of 60 - 70 C. a thick paste of 1. 30-1. 35, adding conventional excipients, and preparing a capsule, a pill, a tablet, a granule, an oral liquid preparation or an injection according to a conventional method;  B. Take the drug substance, mix it, pulverize it into 10 ~ 20 mesh coarse particles, add 5 ~ 7 times the total weight of the drug substance, and extract it by 2-4 times with 60N C or less by microwave extraction method. Separation, the immersion liquid is concentrated to a relative density of 1.30 ~ 1. 35, adding conventional excipients, and preparing a capsule, a pill, a tablet, a granule, an oral liquid preparation or an injection according to a conventional method.  The method for preparing a traditional Chinese medicine composition according to claim 9, wherein the preparation method of the capsule preparation agent is as follows:  A. Take the raw material medicine, add water to cook three times, add 10 times the total weight of the raw material medicine for the first time, boil for 2 hours, add the first time 8 times the total weight of the raw material medicine, and boil for 1 hour. 3 之间添加添加。 Adding 8 times the total weight of the drug substance to the water, boiling 0. 5 hours; while collecting the volatile oil, the decoction is combined, filtered, the filtrate is concentrated to 80 * € relative density of 1. 2, with ethanol The alcohol content was 60%, stirred, and allowed to stand for 12 hours. The supernatant was taken to recover ethanol and concentrated to 60 thick paste having a relative density of 1.30. The conventional auxiliary materials were added, and the capsules and pills were prepared according to a conventional method. Tablets, granules, oral liquid preparations or injections; B. Take the drug substance, mix it, crush it into 15 mesh coarse particles, add 6 times the total weight of the drug substance. The water is extracted by microwave extraction method for 60 times or less continuously, and the extract is centrifuged, and the liquid immersion liquid is concentrated to a relative density of 1.35, and the conventional auxiliary materials are added, and the capsules, pills, tablets are prepared according to a conventional method. , granules, oral liquid preparations or injections.  The method for preparing a traditional Chinese medicine composition according to claim 10, wherein the preparation method of the capsule preparation agent is as follows:  A. Take the raw material medicine, add water to cook three times, add 10 times the total weight of the raw material medicine for the first time, boil for 2 hours, add the first time 8 times the total weight of the raw material medicine, and boil for 1 hour. Three times plus 8 times the total weight of the drug substance, boiled for 0.5 hours; while collecting the volatile oil during the boiling process, the decoction is combined, filtered, and the filtrate is concentrated to 80". The relative density is 1.'2, and ethanol is added. The alcohol content was 60%, stirred, and allowed to stand for 12 hours. The supernatant was taken to recover ethanol and concentrated to 60" thick paste having a relative density of 1.30. The conventional auxiliary material was added and a plasticizer was prepared according to a conventional method; The drug substance, mixed, pulverized into 15 mesh coarse particles, and added with water 6 times the total weight of the drug substance, extracted by microwave extraction method for 60 times or less, and the extract is centrifuged, and the net immersion liquid is concentrated to a relative density of 1. 35, adding conventional excipients, and making capsules according to conventional methods.  A method for mass detection of a traditional Chinese medicine composition according to claim 6, 7 or 8, characterized in that the method comprises one or more of the following identifications: A. Take 1/3-1/2 of the daily dose of the pharmaceutical composition, which is equivalent to the crude drug amount of 21 ~ 42g, finely grind, add 30ml of ethanol, immerse for 1 hour at room temperature, shake at any time, filter, and evaporate the filtrate. Add 20 ml of water to the residue, dissolve it, and shake it with water-saturated n-butanol for 3 times, 20 ml each time, add n-butanol extract, wash once with water saturated with n-butanol, discard the water layer, and place the n-butanol solution. The mixture was evaporated to dryness on a water bath, and the residue was dissolved in 1 ml of ethanol, and alumina was added. 0.6 g was stirred on a water bath, dried, and pre-filled with a particle size of 200-300 mesh, a weight of lg, and an inner diameter of 10-15 mm. On the alumina adsorption column, the neutral alumina adsorption column was eluted with 60 ml of ethanol, and the eluent was collected, evaporated to dryness, and the residue was added with 1 ml of ethanol to dissolve it, which was used as a test solution; another reference substance of paeoniflorin was added with ethanol. 1 mg of solution per lml, as a reference solution; according to thin-layer chromatography test, take 10 μl of each of the above two solutions, respectively, on the same silica gel G thin-layer plate, to 40: 5: 10: 0. 2 Chloroform-ethyl acetate-nonanol-formic acid as a developing agent, Unfold, remove, dry, spray with 5% vanillic acid solution, and heat until the spots are clear. In the chromatogram of the test sample, the spots of the same color are displayed at the position corresponding to the reference color; B. Take 1/3-1/2 of the daily dose of the pharmaceutical composition, corresponding to 21-42 g of crude drug, grind finely, add 20 ml of ethanol, immerse for 1 hour at room temperature, filter, and evaporate the filtrate, and add 1 ml of sterol to the residue. Dissolve as the test solution; take 50mg of berberine reference medicine, add 10ml of methanol, heat and reflux for 10 minutes in a water bath, filter, and evaporate the filtrate, add 1ml of methanol to dissolve the residue, as a reference drug solution; then take hydrochloric acid檗 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照 对照On the plate, 7: 1: 2 n-butanol-glacial acetic acid-water as the developing agent, unroll, remove, dry, and set under 365nm ultraviolet light; in the chromatogram of the test sample, corresponding to the color of the reference drug a fluorescent spot of the same color at the position; a yellow fluorescent spot that is identical to the position corresponding to the color of the control;  C. Take 1/3-1/2 of the daily dose of the pharmaceutical composition, which is equivalent to the crude drug amount of 21 ~ 42g, finely grind, add 30ml of ethanol, heat reflux for 30 minutes, let cool, filter, take 10ml, steam Dry, add 10ml of water to dissolve, add 1ml of hydrochloric acid, heat on water bath for 30 minutes, immediately cool, extract twice with ether, 10ml each time, combine with ether extract, remove ether, residue and ethyl acetate 1ml Dissolve, as a test solution; another rhubarb reference material 0. 5g, using the same method as the test solution prepared to prepare a reference drug solution; then take chrysophanol, emodin reference substance, add methanol to make each lml Each mixed solution containing 0.5 mg was used as a reference solution; according to the thin layer chromatography test, 5 μl of each of the above solutions was taken up and placed on the same silica gel crucible plate with sodium carboxymethyl cellulose as a binder. , using 15: 5: 1 of 30-60 petroleum ether ethyl formate monocarboxylic acid as the developing agent, unrolling, unpacking, drying, and setting it under 365nm ultraviolet light; in the chromatogram of the test sample, in comparison with the control The corresponding position of the drug chromatography On the display, the same five orange-yellow fluorescent spots are displayed, and the same orange-yellow fluorescent spots are displayed at the position corresponding to the reference color pan; the ammonia is smoked, the sunlight is examined, and the spots turn red.  A method for mass detecting a traditional Chinese medicine composition according to claim 6, 7 or 8, characterized in that the method comprises the following content determination: Determination by high performance liquid chromatography; chromatographic conditions and system suitability test; using octadecane The alkane-bonded silica gel is a filler; 14: 86 acetonitrile - 0. 05mol / L potassium dihydrogen phosphate solution is the mobile phase; the detection wavelength is 23 Onm; the theoretical plate number is not less than 1500 according to the paeoniflorin peak; Preparation: Accurately weigh the appropriate amount of paeoniflorin reference substance, add 50% ethanol to make 0.1 ml of solution per lml, that is, obtain the test solution: Take 1/6 ~ 1 of the daily dose of the pharmaceutical composition /9, equivalent to the crude drug amount of 5. 4 ~ 16. 1g, finely ground, mix, set in a triangular flask, precisely add 50ml of 50ml ethanol, weigh the weight, sonicate for 30 minutes, let cool, then weigh the weight, The weight of the lost weight was made up with 50% ethanol, shaken, filtered, and the filtrate was taken and filtered through a 0. 45 μ ιη microporous membrane. The determination method: precision extraction of the reference solution and the test solution respectively Each 10 μ ΐ , injected into the liquid chromatograph, measured, that is;; containing paeoniflorin ( ₂₃ 11 ₂₈ 0 „ not less than 16. 0-24. Omg / daily dose.  The use of a traditional Chinese medicine composition according to Claim 1, 2, 3, 4, 6, 7 or 8 for the preparation of a medicament for the treatment of depression, insomnia or neurasthenia.  16. Use of a traditional Chinese medicine composition according to claim 5 for the manufacture of a medicament for the treatment of depression, insomnia or neurasthenia.  17. The use according to claim 15, wherein the treatment of depression means that the composition has the effects of a heart, kidney, phlegm, stagnation, stagnation or stagnation.