Pharmaceutical composition for treating post-stroke depression

Abstract

The invention relates to a pharmaceutical composition for preparing a medicine for treating heart-kidney disharmony type post-stroke depression, a preparation and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. The invention discloses a traditional Chinese medicine composition for treating post-stroke depression. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 20 to 35 parts of radix acanthopanacis semticosi, 20 to 35 parts of radix salviae miltiorrhizae, 6 to 15 parts of fructus gardeniae, 5 to 20 parts of radix morindae officinalis, 5 to 20 parts of rhizoma polygonati, 5 to 20 parts of radix rehmanniae, 5 to 20 parts of radix curcumae, 6 to 15 parts of radix polygalae, 6 to 15 parts of radix angelicae sinensis and 3 to 10 parts of liquorice root. The invention also discloses a preparation of the traditional Chinese medicine composition and a preparation method thereof. Pharmacology shows that the traditional Chinese medicine composition can be used for treating or relieving post-stroke depression and can be used for preparing the medicine for treating post-stroke depression.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine compositions, and in particular to a pharmaceutical composition for treating post-stroke depression. Background Art

[0002] Post-stroke depression (PSD) is a common complication after stroke. After the onset of the disease, serious symptoms occur in terms of emotion, spirit, autonomic nervous function, cognition, etc., such as poor emotional control, inattention, difficulty falling asleep, decreased appetite, inferiority complex, strong sense of guilt, and even despair and suicide.

[0003] Studies have shown that about 30% of stroke patients are at risk of developing depressive symptoms within two weeks of onset, and the prevalence rate can be as high as 42% after one year. Given the high incidence of post-stroke depression and the reduced quality of life it brings, the significant psychological and physiological impact on patients makes the treatment and rehabilitation process of this type of disease more complicated and difficult. Therefore, timely detection and early intervention of post-stroke depression are very important.

[0004] According to existing data, Western medicine believes that the pathogenesis of post-stroke depression may be related to a variety of factors, including brain damage, changes in neurotransmitters, social and psychological factors, etc. Therefore, treatment includes drug therapy, psychotherapy, surgical treatment, electroconvulsive therapy, music therapy, etc. Commonly used antidepressants include selective 5-HT reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, selective 5-HT and norepinephrine reuptake dual inhibitors, and statins. However, studies have shown that the efficacy of the above drugs is not ideal, and excessive use of them increases gastrointestinal adverse reactions on the one hand, and also has a greater impact on the central nervous system on the other hand, such as confusion, excessive sedation, tremors, etc.

[0005] Modern Chinese medicine believes that post-stroke depression is usually related to heart and kidney dysfunction, and belongs to the category of "depression" and "stroke". The disease can be divided into liver qi stagnation type and heart and kidney disharmony type. Therefore, the research focus is on tonifying the kidney, soothing the liver and strengthening the spleen, relieving depression, awakening the brain and opening the orifices. Among them, heart and kidney disharmony type stroke depression is a common complication after stroke. Its clinical manifestations are diverse, including low mood, slow thinking, and loss of will, which are closely related to heart and kidney dysfunction. For the treatment of heart and kidney disharmony type stroke depression, Chinese medicine adopts the method of harmonizing the heart and kidney, generally by tonifying the heart and kidney, calming the mind and calming the mind, etc., to improve the symptoms of patients with post-stroke depression. Based on the multi-target and personalized characteristics of traditional Chinese medicine, in the treatment of complex diseases such as post-stroke depression, traditional Chinese medicine has more significant advantages than Western medicine.

[0006] The efficacy of existing technologies for treating post-stroke depression is not satisfactory, the disease is complicated and the course of the disease is prolonged, and patients suffer great pain both physically and mentally. Therefore, it is extremely important to seek drugs to improve or treat post-stroke depression. Summary of the invention

[0007] The purpose of the present invention is to provide a new Chinese medicine composition, preparation and use for treating post-stroke depression.

[0008] The first object of the present invention is to provide a traditional Chinese medicine composition for depression.

[0009] Specifically, the Chinese medicine composition includes the following components in parts by weight:

[0010] Acanthopanax senticosus 20-35 weight parts Salvia miltiorrhiza 20-35 weight parts Gardenia jasminoides 6-15 weight parts

[0011] Morinda officinalis 5-20 parts by weight Polygonatum sibiricum 5-20 parts by weight Rehmannia glutinosa 5-20 parts by weight

[0012] 5-20 parts by weight of Curcuma aromatica 6-15 parts by weight of Polygala tenuifolia 6-15 parts by weight of Angelica sinensis 6-15 parts by weight

[0013] Licorice 3-10 parts by weight.

[0014] Furthermore, the inventors found that when the licorice in the traditional Chinese medicine composition is roasted licorice and the rehmannia is cooked rehmannia, the efficacy of the medicine can be significantly improved and clinical symptoms can be alleviated.

[0015] In a preferred embodiment, the Chinese medicine composition comprises the following components in parts by weight:

[0016] Acanthopanax senticosus 30 weight parts Salvia miltiorrhiza 30 weight parts Gardenia jasminoides 12 weight parts

[0017] Morinda officinalis 15 weight parts Polygonatum sibiricum 15 weight parts Rehmannia glutinosa 15 weight parts

[0018] 15 parts by weight of Curcuma Radix Polygala Tenuifolia 9 parts by weight of Radix Angelicae Sinensis 12 parts by weight

[0019] 6 parts by weight of licorice root.

[0020] The second object of the present invention is to provide a clinical dosage form of the above-mentioned Chinese medicine composition. In view of the shortcomings of traditional decoction drugs such as poor stability, inconvenience in carrying, and large volume, the inventors first prepare conventional oral preparations during the preparation process. At the same time, the inventors further carry out inclusion treatment on the volatile oil component in order to increase the efficacy and avoid degradation loss of the effective ingredients based on the medicinal properties of each Chinese medicinal material in the prescription and the physical and chemical properties of its effective ingredients.

[0021] Specifically, the Chinese medicine composition can be prepared into a conventional preparation, preferably one of the oral preparations, and more preferably one of the decoctions, granules, tablets or pills.

[0022] The third object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition, which is as follows:

[0023] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0024] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 3-8 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir at room temperature for 15-40 minutes, and obtain a cyclodextrin-encapsulated volatile oil extract, and store the residue separately for later use;

[0025] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6-8 times the weight of water and boil, boil for 1-3 hours each time, boil 1-3 times, filter, and concentrate under reduced pressure to a liquid density of 1.20-1.25 mg / ml, and set aside;

[0026] (4) combining the volatile oil extract of step (2) and the concentrated medicinal solution of step (3), stirring them evenly, and adding conventional pharmaceutical excipients to prepare a conventional preparation.

[0027] In the examples, the inventors found that when the mass ratio of volatile oil:β-cyclodextrin:sodium carboxymethyl cellulose in step (2) is 1:4-10:1-3, the prepared Chinese medicine composition has a better effect.

[0028] Furthermore, the vacuum degree of the reduced pressure concentration in step (3) is preferably -0.08-0.1 MPa, and the temperature is preferably 65-80°C.

[0029] Specifically, the preparation method of the above-mentioned Chinese medicine composition is:

[0030] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0031] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 3-8 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir for 15-40 minutes at room temperature to obtain a cyclodextrin-encapsulated volatile oil extract, and store the residue for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:4-10:1-3;

[0032] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6-8 times the weight of water and boil, boil for 1-3 hours each time, boil 1-3 times, filter, and concentrate under reduced pressure at a vacuum degree of -0.08-0.1 MPa and a temperature of 65-80° C. to a liquid density of 1.20-1.25 mg / ml, and set aside;

[0033] (4) combining the volatile oil extract of step (2) and the concentrated medicinal solution of step (3), stirring them evenly, and adding conventional pharmaceutical excipients to prepare a conventional preparation.

[0034] In a preferred embodiment, the preparation method of the above-mentioned Chinese medicine composition is:

[0035] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0036] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 6 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir at room temperature for 30 minutes, and obtain a cyclodextrin-encapsulated volatile oil extract. The residue is stored separately for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:8:2.5;

[0037] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6-8 times the weight of water and boil it, boil it for 3 hours each time, boil it for 3 times, filter it, and concentrate it under reduced pressure at a vacuum degree of -0.08-0.1Mpa and a temperature of 65-80°C to a liquid density of 1.22mg / ml, and set it aside; (4) Combine the volatile oil extract from step (2) and the concentrated liquid medicine from step (3), stir them evenly, add conventional pharmaceutical excipients in pharmacy, and prepare a conventional preparation.

[0038] The fourth object of the present invention is to provide the use of the above-mentioned Chinese medicine composition, specifically, the use of the Chinese medicine composition in the preparation of a drug for treating depression.

[0039] Furthermore, the Chinese medicine composition is used in the preparation of a drug for treating depression caused by stroke.

[0040] Preferably, the Chinese medicine composition is used in the preparation of a drug for treating post-stroke depression of the heart-kidney disharmony type.

[0041] The inventor has relied on many years of clinical experience and based on the pathogenesis of post-stroke depression in stroke blood stasis and heart-kidney disharmony, he adopted the therapy of "activating blood circulation and unblocking meridians, and benefiting the kidney and clearing the heart". On the one hand, blood circulation and unblocking meridians are used to make the meridians smooth, qi and blood flow, and the spirit has a place to stay; on the other hand, kidney-benefiting and heart-clearing are used to make the kidney yin essence carry up to the heart, nourish the heart yin, and the heart yang descend to the kidney, warming and nourishing the kidney yang, so that the heart and kidney can restore the dynamic balance of yin and yang. At the same time, this prescription also takes into account the deficiency of the root and the excess of the superficial, and uses both tonification and purgation, and treats heart-kidney disharmony type post-stroke depression with the treatment principles of activating blood circulation and unblocking meridians, benefiting the kidney and strengthening the will, and clearing the heart and relieving depression.

[0042] Compared with the prior art, this solution has the following beneficial effects:

[0043] (1) The Chinese medicine compound of the present invention has excellent therapeutic effect, short treatment course and low recurrence rate during the treatment process;

[0044] (2) The Chinese medicine compound developed by the present invention is composed entirely of natural herbs, has no chemical toxicity or side effects, and is particularly suitable for young people;

[0045] (3) The Chinese medicine composition of the present invention has a reasonable formula and compatibility, the Chinese medicinal materials are cheap and easy to obtain, the preparation method is practical, and it is convenient for clinical promotion and Chinese medicine research and development, and has a high promotion and application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 It is the result of the volatile oil inclusion rate of the Chinese medicine composition of the present invention;

[0047] Figure 2 It is the result of the content of Tanshinone ⅡA in the Chinese medicine composition preparation of the present invention in the accelerated test;

[0048] Figure 3 The effect of the Chinese medicine composition of the present invention on the body weight of the post-stroke depression rat model (compared with the sham operation group: P < 0.01 ** Compared with the model group, P<0.01 was used ## express);

[0049] Figure 4 The effect of the Chinese medicine composition of the present invention on the number of horizontal movement grids in the open field test of the post-stroke depression rat model (compared with the sham operation group: P < 0.01 ** Compared with the model group, P<0.01 was used ## express);

[0050] Figure 5 The effect of the Chinese medicine composition of the present invention on the sugar preference rate of the post-stroke depression rat model (compared with the sham operation group: P < 0.01 ** Compared with the model group, P<0.01 was used ## express);

[0051] Figure 6 The effect of the Chinese medicine composition of the present invention on the grooming time in the splash test of post-stroke depression rats (compared with the sham operation group: P < 0.01 ** Compared with the model group, P<0.01 was used ## express);

[0052] Figure 7 The effect of the Chinese medicine composition of the present invention on the novelty inhibition of feeding latency in the post-stroke depression rat model (compared with the sham operation group: P < 0.01 with ** Compared with the model group, P<0.01 was used ## express). DETAILED DESCRIPTION

[0053] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention.

[0054] Similar modifications, replacements or changes made to the technical solution of the present invention based on the routine selection and industry experience of those skilled in the art are all within the protection scope of the present invention.

[0055] Example 1 Preparation of tablets

[0056] Formula:

[0057]

[0058] The preparation method is:

[0059] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0060] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 6 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir at room temperature for 30 minutes, and obtain a cyclodextrin-encapsulated volatile oil extract. The residue is stored separately for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:6:2.5;

[0061] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 8 times the weight of water, decoct for 3 hours each time, decoct 3 times, filter, and concentrate the filtrate under reduced pressure at a vacuum degree of -0.08-0.1 MPa and a temperature of 70°C to a liquid density of 1.20 mg / ml, and set aside;

[0062] (4) combining the volatile oil extract of step (2) and the concentrated drug solution of step (3), stirring them evenly, adding conventional pharmaceutical excipients, and preparing tablets.

[0063] Example 2 Preparation of granules

[0064] Formula:

[0065]

[0066] The preparation method is:

[0067] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0068] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 3 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir at room temperature for 40 minutes, and obtain a cyclodextrin-encapsulated volatile oil extract. The residue is stored separately for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:5:2;

[0069] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 8 times the mass of water, decoct for 3 hours each time, decoct 3 times, filter, and concentrate the filtrate under reduced pressure at a vacuum degree of -0.08-0.1 MPa and a temperature of 65°C to a liquid density of 1.22 mg / ml, and set aside;

[0070] (4) combining the volatile oil extract of step (2) and the concentrated medicinal solution of step (3), stirring them evenly, and adding conventional pharmaceutical excipients to prepare granules.

[0071] Example 3 Preparation of granules

[0072] Formula:

[0073]

[0074] The preparation method is:

[0075] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0076] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 8 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir for 15 minutes at room temperature, and obtain a cyclodextrin-encapsulated volatile oil extract. The residue is stored separately for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:4:1;

[0077] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6 times the weight of water, decoct for 3 hours each time, decoct 3 times, filter, and concentrate the filtrate under reduced pressure at a vacuum degree of -0.08-0.1Mpa and a temperature of 80°C to a liquid density of 1.25mg / ml, and set aside;

[0078] (4) combining the volatile oil extract of step (2) and the concentrated medicinal solution of step (3), stirring them evenly, and adding conventional pharmaceutical excipients to prepare granules.

[0079] Example 4 Preparation of granules

[0080] Formula:

[0081]

[0082] The preparation method is:

[0083] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0084] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 6 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir for 15 minutes at room temperature, and obtain a cyclodextrin-encapsulated volatile oil extract. The residue is stored separately for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:10:3;

[0085] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6 times the mass of water, decoct for 1 hour each time, decoct once, filter, and concentrate the filtrate under reduced pressure at a vacuum degree of -0.08-0.1 MPa and a temperature of 80° C. to a liquid density of 1.20 mg / ml, and set aside;

[0086] (4) combining the volatile oil extract of step (2) and the concentrated medicinal solution of step (3), stirring them evenly, and adding conventional pharmaceutical excipients to prepare granules.

[0087] Example 5 Preparation of granules

[0088] Formula:

[0089]

[0090] The preparation method is:

[0091] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0092] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 6 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir at room temperature for 30 minutes, and obtain a cyclodextrin-encapsulated volatile oil extract. The residue is stored separately for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:8:2.5;

[0093] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6-8 times the weight of water and boil it, boil it for 3 hours each time, boil it for 3 times, filter it, and concentrate it under reduced pressure at a vacuum degree of -0.08-0.1Mpa and a temperature of 65-80°C to a liquid density of 1.22mg / ml, and set it aside; (4) Combine the volatile oil extract from step (2) and the concentrated liquid medicine from step (3), stir them evenly, add conventional pharmaceutical excipients in pharmacy, and prepare granules.

[0094] Preparation of Comparative Example 1 Granules

[0095] Formula:

[0096]

[0097] The preparation method is the same as Example 5.

[0098] Preparation of Comparative Example 2 Granules

[0099] Formula:

[0100]

[0101] Weigh the above-mentioned Chinese medicinal materials by weight and mix them evenly; add water to cover all the raw materials, soak for 30 minutes, boil over high heat until boiling, then turn to low heat and boil for 40 minutes, add water and boil for 30 minutes for the second time, collect the decoction and concentrate it, add conventional pharmaceutical excipients, and prepare it into granules according to conventional methods.

[0102] Preparation of Comparative Example 3 Granules

[0103] Formula:

[0104]

[0105] The preparation method is the same as Example 5.

[0106] Preparation of Comparative Example 4 Granules

[0107] Formula:

[0108]

[0109] The preparation method is:

[0110] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0111] (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, and Licorice, add 6 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir for 30 minutes at room temperature to obtain a cyclodextrin-encapsulated volatile oil extract, and store the residue for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:8:2.5;

[0112] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6-8 times the weight of water and boil it, boil it for 3 hours each time, boil it for 3 times, filter it, and concentrate it under reduced pressure at a vacuum degree of -0.08-0.1Mpa and a temperature of 65-80°C to a liquid density of 1.22mg / ml, and set it aside; (4) Combine the volatile oil extract from step (2) and the concentrated liquid medicine from step (3), stir them evenly, add conventional pharmaceutical excipients in pharmacy, and prepare granules.

[0113] Preparation of Comparative Example 5 Granules

[0114] Formula:

[0115]

[0116] The preparation method is:

[0117] (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass it through a 100-mesh sieve for later use;

[0118] (2) Take Astragalus, Angelica, and Licorice, add 6 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir at room temperature for 30 minutes, and obtain a cyclodextrin-encapsulated volatile oil extract. The residue is stored separately for later use, wherein, by mass ratio, the volatile oil: β-cyclodextrin: sodium carboxymethyl cellulose = 1:8:2.5;

[0119] (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6-8 times the weight of water and boil, boil for 3 hours each time, boil for 3 times, filter, and concentrate under reduced pressure at a vacuum degree of -0.08-0.1Mpa and a temperature of 65-80°C to a liquid density of 1.22mg / ml, and set aside; (4) Combine the volatile oil extract from step (2) and the concentrated liquid medicine from step (3), stir evenly, add conventional pharmaceutical excipients, and prepare granules. Comparative Example 5 Preparation of Granules

[0120] Verification experiment

[0121] (I) Evaluation of factors affecting volatile oil inclusion rate and stability during preparation:

[0122] 1. Test method:

[0123] The Chinese medicinal materials of Danshen, Polygonatum, Angelica, Curcuma and Licorice were crushed into a 100-mesh sieve, 3 times the amount of water was added, and the volatile oil was extracted by water distillation. The above volatile oils were divided into 18 groups, and β-cyclodextrin, sodium carboxymethyl cellulose or other additives were added to each volatile oil, and stirred at room temperature for 40 minutes to obtain cyclodextrin-encapsulated volatile oil extracts.

[0124] Table 1 Amount of each component

[0125]

[0126]

[0127] 2. Detection indicators:

[0128] After the volatile oil inclusion compound is prepared according to the above method, the inclusion rate is calculated according to the following method:

[0129] Inclusion rate = [actual oil content in inclusion compound kg / oil input kg] × 100%

[0130] 3 Experimental results:

[0131] The results are as follows Figure 1 As shown. Figure 1 The results show that when the mass ratio of volatile oil to β-cyclodextrin is the same, the inclusion rate obtained by using sodium carboxymethyl cellulose is higher.

[0132] (II) Stability evaluation:

[0133] 1. Test method:

[0134] The Chinese medicine granules prepared in Examples 2-5 and Comparative Examples 1-5 were subjected to accelerated stability study at 40°C and 75% RH, and their properties were observed at 0 day, 3 months and 6 months, respectively.

[0135] 2. Detection indicators:

[0136] The experimental results of each group were recorded. At the same time, tanshinone ⅡA was used as a representative detection index to detect the active ingredients in the drug to determine its stability.

[0137] 3 Experimental results:

[0138] The clarity, solubility and dissolution are shown in Table 2.

[0139] Table 2 Experimental results of each group

[0140]

[0141]

[0142] Dissolution clarity: clear (++++), a small amount of floccules (+++), slightly turbid (++), turbid (+).

[0143] Using Tanshinone ⅡA as a representative test index to detect the active ingredients in drugs, the accelerated test results are as follows Figure 2 As shown in the figure, after 6 months of accelerated test, the amount of paeoniflorin in each example decreased to varying degrees, and the decrease in the comparative example 2 was the most obvious, and the total impurity content was the highest.

[0144] (III) Study on the effect of the Chinese medicine composition of the present invention on the rat model of post-stroke depression

[0145] 1 Materials and Methods

[0146] 1.1 Experimental animals and feeding

[0147] Healthy SPF SD rats, 8-10 weeks old, weight: 220±20g. Experimental animal license number: SYXK(Lu)2018-0008.

[0148] The experiment began after the animals were acclimatized to the laboratory for 1 week.

[0149] 1.2 Modeling method

[0150] Healthy rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital, the skin, myofascia and muscles were cut, the round ligament at the femoral trochanter was cut, the hip joint was exposed and dislocated, the capsule fibers were removed, and the femoral neck periosteum was scraped, then repositioned and sutured layer by layer. Penicillin was injected intramuscularly for anti-inflammatory treatment for 3 days after surgery, and clear necrosis and subchondral fracture under imaging CT were used as the standard for successful modeling.

[0151] 1.3 Modeling method

[0152] The rat model of cerebral ischemia / reperfusion injury was established. The common carotid artery was separated from the rats, and the external carotid artery was double ligated and cut off. A small incision was made on the cut external carotid artery, and the thread plug was slowly pushed into the internal carotid artery at a 45° angle and fixed with a thread plug at an appropriate position. One hour later, when the thread plug was pulled and resistance was felt, the excess thread plug was cut off. For the rats in the sham operation group, only the common carotid artery was separated and no other operations were performed. After surgery, the rats were treated with penicillin (100,000 units per rat) every day for 3 consecutive days. After 3 days, the post-stroke depression model was established according to the following method: ① 36 hours of circadian rhythm reversal; ② 18 hours of water deprivation; ③ 24 hours of food deprivation; ④ Let the rats live in a humid environment for 24 hours; ⑤ Tilt the cage at 45° for 18 hours; ⑥ Force the rats to swim in 4°C cold water for 5 minutes; ⑦ Place the rats in a 45° hot environment for 5 minutes; ⑧ Clamp the rats' tails for 1 minute. A method was randomly selected at a fixed time every day to stimulate the rats. Each stimulation method was used up to 4 times, and the whole stimulation process lasted for 21 days.

[0153] 1.4 Experimental drug administration

[0154] The rats with successful modeling were divided into 7 groups, namely, model group, positive control group, Example 2 group, Example 5 low-dose group, Example 1 high-dose group, Comparative Example 2 group, and Comparative Example 5 group, with 10 rats in each group.

[0155] Among them, the low-dose group of Example 5 and the high-dose group of Example 5 were gavaged with the Chinese medicine composition, with the combined raw drug content of 11g / kg / d and 22g / kg / d respectively, the Example 2 group, the Comparative Example 2 group, and the Comparative Example 5 group were gavaged with the combined raw drug content of 11g / kg / d, the positive control group was gavaged with 20mg / kg / d of fluoxetine hydrochloride, and the sham operation group and the model group were gavaged with an equal volume of normal saline, once a day, for 3 consecutive weeks.

[0156] 2. Detection indicators and methods

[0157] 2.1 Body weight measurement: After the administration on the 21st day, the body weight of the rats was measured.

[0158] 2.2 Open field test: After the administration on the 21st day, an open field test was conducted to record the number of grids that the rats crawled across within 3-7 minutes.

[0159] 2.3 Sugar water preference experiment: After the end of the drug administration on the 21st day, the rats were fasted and deprived of water for 24 hours, and the rats' preference percentage for 1% sugar water within 6 hours was calculated. The formula for calculating the sugar water preference percentage is as follows:

[0160] Sugar water preference percentage = (sugar water consumption / total liquid consumption) × 100%

[0161] 2.4 Splash test: After the administration on the 21st day, 10% sucrose water was sprayed on the back of the rats for 3 consecutive times, 2 mL / time, and then the time of the rats' grooming behavior on the back sprayed with sucrose water was recorded within 5 minutes.

[0162] 2.5 Novelty inhibition feeding test: After the end of the drug administration on the 21st day, the rats were fasted for 48 hours but not water. A white paper platform was placed in the center of a homemade open box (1m×1m×0.5m). Granular rat food was placed on the platform and illuminated with a vertical light source. During the experiment, the rats were placed in the corner of the open box and the timer was immediately started to record the time when the rats started to eat.

[0163] 2.6 Detection of related indicators such as serum neurotransmitters in rats: After the administration on the 21st day, blood was collected from the carotid artery, and the serum was separated and the 5-hydroxytryptamine and norepinephrine levels in the serum were detected using a kit.

[0164] 2.7 Statistical analysis:

[0165] SPSS 22.0 software was used for statistical analysis, and the experimental data were expressed as “mean ± standard deviation”. ” is expressed in the form of .

[0166] 3 Experimental results

[0167] 3.1 Observation results of rat body weight:

[0168] After the experiment began, the amount of food and water consumed by rats in each group decreased, and the increase in body weight was not obvious. After administration, the body weight of rats in each group increased to varying degrees, among which the body weight of rats in the Example group increased more, especially the increase in body weight of the high-dose group in Example 5 was significant (P < 0.01). The specific results are as follows Figure 3 shown.

[0169] 3.2 Open field test results:

[0170] Through observation, it was found that compared with the sham operation group, the number of horizontal grids of rats in the comparative example 2 group and the comparative example 5 group decreased, and the static time was significantly increased (P < 0.01). After taking the Chinese medicine composition of the present invention for 21 days, compared with the model group, the group of the present invention can significantly increase the number of horizontal movement grids of rats (P < 0.01). The specific results are as follows Figure 4 shown.

[0171] 3.3 Results of the sugar water preference experiment:

[0172] The experiment found that after 21 days of administration, compared with the model group, the Chinese medicine composition of the present invention increased the sugar preference rate of the model rats and significantly increased the sugar preference rate of the rats (P < 0.01). Figure 5 shown.

[0173] 3.4 Splash test results:

[0174] Compared with the model group, the Chinese medicine composition of the present invention can significantly prolong the grooming time of rats after 21 days of administration (P < 0.01). Figure 6 shown.

[0175] 3.5 Novelty inhibition feeding test:

[0176] 21 days after the start of the experiment, the model group rats' food intake latency significantly increased compared with the sham operation group. After the administration of the Chinese medicine composition of the present invention to the rats, compared with the model group, each dosage group of the present invention can significantly shorten the food intake latency of the rats (P < 0.01). Figure 7 shown.

[0177] 3.6 Test results of rat serum neurotransmitters and other related indicators

[0178] After 21 days of administration, compared with the sham operation group, the levels of 5-HT (5-hydroxytryptamine) and NA (norepinephrine) in the serum of the experimental model group rats were significantly reduced (P<0.01). Compared with the experimental model group, the levels of 5-HT and NA in the serum of the rats of the present invention at each dose were significantly increased (P<0.05 or P<0.01), and the specific data are shown in Table 3. This shows that the composition of the present invention can improve the neurotransmitter level of rats.

[0179] Table 3 Effect of the present invention on the content of monoamine neurotransmitter in rat blood

[0180]

[0181] Compared with the sham operation group: P < 0.01 ** Compared with the model group, P<0.01 was used ## express.

[0182] (IV) Clinical Cases 1.

[0184] Refer to the fifth edition of "Chinese Internal Medicine. Depression" heart-kidney disharmony type depression syndrome differentiation criteria, symptoms: depression, emotional restlessness, restlessness, insomnia, dreaminess, fever, night sweats, dry mouth and throat, red tongue with little fluid, and weak pulse. According to the symptoms listed in the fifth edition of "Chinese Internal Medicine. Depression", a self-made "Chinese Medicine Symptom Scoring Table" was made to analyze the patient's Chinese medicine symptoms using this table. Patients with a score of 8 points or above on the scale meet this syndrome type.

[0185] The Chinese medicine compound of the present invention has been carefully formulated, and the experimental results show that it has a significant regulatory effect on the relevant indicators of post-stroke depression. Compared with fluoxetine hydrochloride, the Chinese medicine composition of the present invention exhibits better efficacy and more advantages.

Claims

1. A Chinese medicine composition for improving or treating depression, characterized in that: The Chinese medicine composition comprises the following components in parts by weight: Acanthopanax senticosus 20-35 weight parts Salvia miltiorrhiza 20-35 weight parts Gardenia jasminoides 6-15 weight parts Morinda officinalis 5-20 parts by weight Polygonatum sibiricum 5-20 parts by weight Rehmannia glutinosa 5-20 parts by weight 5-20 parts by weight of Curcuma aromatica 6-15 parts by weight of Polygala tenuifolia 6-15 parts by weight of Angelica sinensis 6-15 parts by weight Licorice 3-10 parts by weight.

2. The Chinese medicine composition according to claim 1, characterized in that In the traditional Chinese medicine composition, the licorice is roasted licorice, and the rehmannia root is cooked rehmannia root.

3. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition comprises the following components in parts by weight: Acanthopanax senticosus 30 weight parts Salvia miltiorrhiza 30 weight parts Gardenia jasminoides 12 weight parts Morinda officinalis 15 weight parts Polygonatum sibiricum 15 weight parts Rehmannia glutinosa 15 weight parts 15 parts by weight of Curcuma Radix Polygala Tenuifolia 9 parts by weight of Radix Angelicae Sinensis 12 parts by weight 6 parts by weight of licorice root.

4. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition can be prepared into a conventional preparation, preferably an oral preparation.

5. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition can be prepared into one of decoction, granules, tablets or pills.

6. The Chinese medicine composition according to claim 1, characterized in that: The preparation method of the Chinese medicine composition is as follows: (1) Grind the above-mentioned Chinese medicinal materials by weight into a powder and pass through a 100-mesh sieve for later use; (2) Take Acanthopanax senticosus, Salvia miltiorrhiza, Polygonatum sibiricum, Angelica sinensis, Curcuma aromatica, and Licorice, add 3-8 times the amount of water, extract volatile oil by water distillation, add β-cyclodextrin and sodium carboxymethyl cellulose to the volatile oil, stir at room temperature for 15-40 minutes, and obtain a cyclodextrin-encapsulated volatile oil extract, and store the residue separately for later use; (3) Take the residue from step (2) and combine it with other Chinese medicinal materials, add 6-8 times the weight of water and boil, boil for 1-3 hours each time, boil 1-3 times, filter, and concentrate under reduced pressure to a liquid density of 1.20-1.25 mg / ml, and set aside; (4) combining the volatile oil extract of step (2) and the concentrated medicinal solution of step (3), stirring them evenly, and adding conventional pharmaceutical excipients to prepare a conventional preparation.

7. The Chinese medicine composition according to claim 6, characterized in that: In terms of mass ratio, in the step (2), the volatile oil:β-cyclodextrin:sodium carboxymethyl cellulose=1:4-10:1-3.

8. The Chinese medicine composition according to claim 6, characterized in that: The vacuum degree of the reduced pressure concentration in step (3) is -0.08-0.1Mpa, and the temperature is 65-80°C.

9. The Chinese medicine composition according to claim 1, characterized in that: Application of the Chinese medicine composition in preparing medicine for treating post-stroke depression.

10. The use according to claim 1, characterized in that: The application of the traditional Chinese medicine composition in preparing a medicine for treating post-stroke depression of the heart-kidney disharmony type.

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