A Chinese medicine composition for treating adolescent depression, preparation method and application

Abstract

The present invention provides a traditional Chinese medicine composition for treating adolescent depression, a preparation method and an application thereof. The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 5 to 15 parts of bupleurum, 5 to 15 parts of angelica, 5 to 15 parts of poria, 5 to 15 parts of lily, 5 to 15 parts of julibrissin bark and 5 to 10 parts of mint. The traditional Chinese medicine composition can effectively treat adolescent depression.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and in particular relates to a Chinese medicine composition for treating adolescent depression, a preparation method and an application thereof. Background Art

[0002] From the perspective of traditional Chinese medicine, depression belongs to the category of "depression syndrome". Traditional Chinese medicine has a rich description of its causes, symptoms and treatment methods. For example, "Huangdi Neijing·Suwen·Liuyuan Zhengji Dalun" says: "Depression is extreme and it will take effect when the time is right... Wood depression will release it, fire depression will release it, earth depression will take it away, metal depression will release it, and water depression will break it." The concept of "five depressions" was initially proposed, that excessive or insufficient five-element qi can lead to wood depression, fire depression, earth depression, metal depression and water depression. Zhang Bingcheng said in "Chengfangbiandu": "The liver belongs to wood, which is the place where vitality resides... If the seven emotions hurt the inside, or the six evils restrain the outside, then the wood will be depressed and many diseases will occur." The liver is responsible for dredging and dispersing, and is the organ of wind and wood. Worry and worry will cause qi stagnation, and the liver wood will not dredge, indicating that the occurrence of depression is closely related to liver qi stagnation and dysfunction of dredging and dispersing. Adolescents have the physiological characteristics of "delicate internal organs and insufficient physical qi" and the pathological characteristics of "weak internal organs, easy to be empty or full, easy to be cold or hot". The pathological nature of depression is real at the beginning, but the physical energy of adolescents is not yet full, so real symptoms can often quickly transform into virtual symptoms, which are virtual or a mixture of real and virtual. Depending on the organs affected and the loss of qi, blood, yin and yang, different diseases of the heart, spleen, liver, and kidney deficiency are formed.

[0003] As depression has become younger in recent years, adolescent depression has become a hot topic, but the pathogenesis of adolescent depression is still unclear. Adolescence is an important stage of physical and mental development. Depression, which is characterized by continuous and persistent low mood, seriously affects the physical and mental health and learning life of adolescents. If it is allowed to develop, there will be a certain risk of suicide. A large number of studies have shown that the pathogenesis of adolescent depression involves multiple levels of neurodevelopment, genetics and psychosocial fields, but the pathophysiological mechanism of adolescent depression is still unclear. At present, there are not many therapeutic drugs for adolescent depression, and most of them copy the treatment methods of adult depression. However, based on the cognition that the adolescent brain is not fully developed and the significant physical and mental differences between adolescents and adults, the pathogenesis of adolescent depression must be different from that of adult depression. Therefore, treatment plans and related drug research for adolescent depression are urgent.

[0004] The current antidepressants on the market generally have the disadvantages of single ingredient target, long taking time, serious side effects and strong dependence. Traditional Chinese medicine and its compound prescriptions are guided by the syndrome differentiation and treatment of traditional Chinese medicine and take a holistic approach. They have the advantages of less toxic side effects and fewer withdrawal symptoms. They are expected to play a better therapeutic effect in the clinical treatment of adolescent depression. Therefore, it is of great clinical significance to develop a traditional Chinese medicine composition for the treatment of adolescent depression. Summary of the invention

[0005] The purpose of the present invention is to solve the deficiencies of the prior art and provide a Chinese medicine composition, preparation method and application for effectively treating adolescent depression.

[0006] To achieve the above object, the technical solution of the present invention is achieved as follows:

[0007] Based on one aspect of the present invention, a traditional Chinese medicine composition for treating adolescent depression is provided, which is composed of the following raw materials in parts by weight: 5-15 parts of bupleurum, 5-15 parts of angelica, 5-15 parts of poria, 5-15 parts of lily, 5-15 parts of julibrissin bark, and 5-10 parts of mint.

[0008] In one embodiment, the Chinese medicine composition for treating adolescent depression is composed of the following raw materials in parts by weight: 10 parts of bupleurum, 10 parts of angelica, 10 parts of poria, 10 parts of lily, 10 parts of julibrissin bark and 6 parts of mint.

[0009] According to another aspect of the present invention, a method for preparing a Chinese medicine composition for treating adolescent depression is provided, comprising the following steps:

[0010] 1) Crush bupleurum, angelica and julibrissin bark, add 6 to 10 times the weight of 60 to 90% ethanol, extract twice, each time for 1 to 3 hours, filter, combine the filtrate, and concentrate to obtain an alcohol-extracted clear paste;

[0011] 2) After the Poria cocos and lily are crushed, 6 to 10 times the weight of water are added and refluxed for extraction twice, each time for 2 to 4 hours, filtered, the filtrate is combined and concentrated to obtain a water-extracted clear paste;

[0012] 3) After crushing the mint, add 6 to 10 times the weight of water, use steam distillation, extract twice, each time for 5 to 8 hours, to obtain a volatile extract;

[0013] 4) combining the alcohol-extracted clear paste obtained in step 1) and the water-extracted clear paste obtained in step 2), mixing them evenly, concentrating and drying them, and adding the volatile extract obtained in step 3) to obtain the product.

[0014] In one embodiment, the weight of the ethanol in step 1) is 8 times the weight of the medicinal material, the ethanol concentration is 75%, and the extraction time is 2 hours each time.

[0015] In one embodiment, the weight of the water in step 2) is 8 times the weight of the medicinal material, and each extraction time is 3 hours.

[0016] In one embodiment, the weight of the water in step 3) is 8 times the weight of the medicinal material, and each extraction time is 6 hours.

[0017] In one embodiment, in step 1), bupleurum, angelica, and julibrissin bark are crushed and passed through an 80-mesh sieve, in step 2), Poria and lily are crushed and passed through an 80-mesh sieve, and in step 3), mint is crushed and passed through an 80-mesh sieve.

[0018] According to another aspect of the present invention, there is provided a use of a traditional Chinese medicine composition for treating adolescent depression as described in any one of the above items in the preparation of a drug for treating adolescent depression.

[0019] In one embodiment, the drug for treating adolescent depression is a preparation prepared from a Chinese medicine composition and pharmaceutically acceptable excipients or auxiliary ingredients.

[0020] In one embodiment, the preparation is one or more of capsules, tablets, granules, oral liquids, pills, powders and pills.

[0021] The beneficial effects of the present invention are as follows: the Chinese medicine composition for treating depression in adolescents of the present invention uses Bupleurum as the main ingredient, which can relieve liver qi and relieve depression, regulate liver qi, and relieve qi stagnation in the liver meridian; Angelica sinensis nourishes blood, promotes blood circulation and harmonizes blood, and is a qi medicine in the blood; Albizzia julibrissin bark calms the heart and relieves depression; the two are assistant medicines, which harmonize the heart and spleen, can nourish the liver to assist the liver, and restrain the excessive release of Bupleurum; Poria replenishes qi, strengthens the spleen and calms the heart, lily clears the heart and calms the mind, and peppermint relieves the liver, promotes qi and dissipates heat. The above medicines are adjuvant medicines, which can help the main ingredient and assistant ingredient to relieve liver qi, nourish the heart and calm the mind. The whole formula has the effects of "soothing the liver and relieving depression, nourishing blood and strengthening the spleen, calming the mind and calming the mind", and can effectively treat depression in adolescents.

[0022] Other advantages of the present invention will be described in detail in the following specific implementation section. DETAILED DESCRIPTION

[0023] To further explain the technical solution of the present invention, the present invention is described in detail below in conjunction with specific embodiments.

[0024] Example 1

[0025] The Chinese medicine composition for treating adolescent depression in this embodiment is composed of the following raw materials in parts by weight: 10 parts of bupleurum, 10 parts of angelica, 10 parts of poria, 10 parts of lily, 10 parts of albizzia bark and 6 parts of mint. It is prepared by the following method:

[0026] 1) Crush bupleurum, angelica and julibrissin bark, add 8 times the weight of 75% ethanol, extract twice, each time for 2 hours, filter, combine the filtrate, and concentrate to obtain an alcohol-extracted clear paste;

[0027] 2) After the Poria cocos and lily are crushed, 8 times the weight of water is added and refluxed for extraction twice, each time for 3 hours, filtered, the filtrate is combined and concentrated to obtain a water-extracted clear paste;

[0028] 3) After crushing the mint, add 8 times the weight of water, use steam distillation, extract twice, each time for 6 hours, to obtain a volatile extract;

[0029] 4) combining the alcohol-extracted clear paste obtained in step 1) and the water-extracted clear paste obtained in step 2), mixing them evenly, concentrating and drying them, and adding the volatile extract obtained in step 3) to obtain a traditional Chinese medicine composition.

[0030] Comparative Example 1

[0031] The Chinese medicine composition for treating adolescent depression in this comparative example is composed of the following raw materials in parts by weight: 30 parts of bupleurum, 30 parts of angelica, 30 parts of poria, 30 parts of white peony, 30 parts of atractylodes, and 15 parts of liquorice. The specific preparation method is: after all the medicinal materials are crushed, 8 times the weight of water is added to reflux and extract twice, each time for 3 hours, filtered, the filtrate is combined, and concentrated to obtain a water-extracted clear paste.

[0032] Comparative Example 2

[0033] The Chinese medicine composition for treating adolescent depression in this comparative example is composed of the following raw materials in parts by weight: 10 parts of bupleurum, 10 parts of angelica, 10 parts of poria, 10 parts of lily, 10 parts of julibrissin bark and 6 parts of mint. The raw material ratio is the same as that in Example 1, and the preparation method is different from that in Example 1. The specific preparation method is: after all the medicinal materials are crushed, 8 times the weight of water is added for reflux extraction twice, each time for 3 hours, filtered, the filtrate is combined, and concentrated to obtain a water-extracted clear paste.

[0034] Based on Example 1, Comparative Example 1 and Comparative Example 2, the following results were tested:

[0035] 1. Animal experiments were conducted using the extracts of the Chinese medicine composition for treating adolescent depression obtained in Example 1, Comparative Example 1, and Comparative Example 2, respectively, to compare the effects of the three in treating adolescent depression. The specific experimental methods and test results are as follows;

[0036] SPF grade 3-week-old male SD rats were randomly divided into six groups according to body weight: Group I with 8 rats was a normal control group, Group II with 8 rats was a model group of juvenile depression (hereinafter referred to as the "model group"), Group III with 8 rats was Example 1 group, Group IV with 8 rats was Comparative Example 1 group, and Group V with 8 rats was Comparative Example 2 group. The modeling method for adolescent depression was as follows: 32 rats in Groups II, III, IV, and V were subjected to 28 days of chronic unpredictable stress, specifically including 4°C ice water bath for 5 minutes, cage tilting at 45° for 24 hours, noise for 8 hours, day and night reversal for 24 hours, and tail clamping for 1 minute. 2-3 stimuli were used every day, and the same stimuli did not appear continuously. At the same time as the 28 days of chronic unpredictable stress, the drug was administered by gavage. The normal control group and the model group were given an equal volume of physiological saline, and the III, IV, and V groups were given the same dose of the extract of the Chinese medicine composition obtained from Example 1, Comparative Example 1, and Comparative Example 2 (obtained by converting the daily dose of normal people), and behavioral tests were performed 28 days after administration. The results are shown in Tables 1 to 3. Then various indicators were tested.

[0037] Table 1 Results of sucrose preference experiment of rats in each group (n=8, )

[0038] Group Dosage Sucrose preference value (%) Normal control group / 98.98±1.21 Model Group / 54.18±7.82** Example 1 Group 7.1g / kg <![CDATA[96.15±3.44 ## ]]> Comparative Example 1 7.1g / kg <![CDATA[88.46±5.83 ## ]]> Comparative Example 2 7.1g / kg <![CDATA[67.36±9.78 ## ]]>

[0039] Note: **P<0.01 compared with the normal control group; **P<0.01 compared with the model group ## P<0.01.

[0040] From the data in Table 1, it can be seen that compared with the normal control group, the sucrose preference rate of the rats in the model group was significantly reduced (P < 0.01); compared with the model group, the sucrose preference rates of the rats in Example 1, Comparative Example 1, and Comparative Example 2 groups were significantly increased (P < 0.01, P < 0.01, P < 0.01), among which the sucrose preference value of the rats in Example 1 group was greater than the sucrose preference value of the rats in Comparative Example 1 and Comparative Example 2 groups.

[0041] Table 2 Results of open field test in rats of each group (n=8, )

[0042] Group Dosage Total distance (cm) Distance to central area (cm) Total number of activities (times) Normal control group / 1581.79±228.53 121.32±5.29 69.40±10.67 Model Group / 930.43±120.58** 25.11±40.42** 45.00±8.27** Example 1 Group 7.1g / kg <![CDATA[1550.43±180.61 ## ]]> <![CDATA[162.24±23.29 ## ]]> <![CDATA[84.17±7.00 ## ]]> Comparative Example 1 7.1g / kg <![CDATA[1426.50±100.69 ## ]]> <![CDATA[157.94±35.21 ## ]]> <![CDATA[75.80±6.14 ## ]]> Comparative Example 2 7.1g / kg <![CDATA[1285.01±287.33 ## ]]> <![CDATA[143.67±71.82 ## ]]> <![CDATA[65.33±16.56 ## ]]>

[0043] Note: **P<0.01 compared with the normal control group; **P<0.01 compared with the model group ## P<0.01.

[0044] From the data in Table 2, it can be seen that compared with the normal control group, the total distance, central area distance and total activity times of the rats in the model group were significantly reduced (P < 0.01, P < 0.01, P < 0.01); compared with the model group, the total distance, central area distance and total activity times of the rats in Example 1 group, Comparative Example 1 group and Comparative Example 2 group were significantly increased, among which the total distance, central area distance and total activity times of the rats in Example 1 group were greater than the total distance, central area distance and total activity times of the rats in Comparative Example 1 group and Comparative Example 2 group.

[0045] Table 3 Results of water maze test of rats in each group (n=8, )

[0046]

[0047]

[0048] Note: **P<0.01 compared with the normal control group; **P<0.01 compared with the model group ## P<0.01.

[0049] From the data in Table 3, it can be seen that compared with the normal control group, the escape latency of the rats in the model group was significantly prolonged (P < 0.01); compared with the model group, the escape latency of the rats in Example 1, Comparative Example 1, and Comparative Example 2 groups were significantly shortened (P < 0.01, P < 0.01, P < 0.01). Among them, the escape latency of the rats in Example 1 group was shorter than the escape latency of the rats in Comparative Example 1 and Comparative Example 2 groups.

[0050] 2. The Chinese medicine for treating adolescent depression obtained in Example 1 was used for animal experiments to verify its effect in treating adolescent depression. The specific experimental methods and test results are as follows;

[0051] SPF 3-week-old male SD rats were randomly divided into six groups according to body weight: Group I with 8 rats as normal control group, Group II with 8 rats as adolescent depression group (hereinafter referred to as "model group"), Group III with 8 rats as fluoxetine group (6 mg / kg), i.e., positive drug group, Group IV with 8 rats as low-dose Chinese medicine group, Group V with 8 rats as medium-dose Chinese medicine group, and Group VI with 8 rats as high-dose Chinese medicine group. The modeling method for adolescent depression was as follows: 48 rats in Groups II, III, IV, V, and VI were subjected to 28 days of chronic unpredictable stress, including 5 minutes of 4°C ice water bath, 24 hours of cage tilt at 45°, 8 hours of noise, 24 hours of day and night reversal, and 1 minute of tail clamping. 2-3 stimuli were used every day, and the same stimuli did not appear continuously. At the same time as the 28-day chronic unpredictable stress, the drug was administered by gavage. The normal control group and the model group were given an equal volume of physiological saline, the positive drug group was given fluoxetine, and the Chinese medicine low-dose group, the Chinese medicine medium-dose group, and the Chinese medicine high-dose group were all given the extract of the Chinese medicine composition obtained in Example 1, and pure water was added to make three different concentrations of low, medium, and high. The respective dosages are shown in Table 4. Behavioral tests were performed 28 days after administration, and the results are shown in Tables 4 to 6. Then various indicators were tested.

[0052] (1) Effects on sugar consumption in adolescent rats with depression

[0053] Table 4 Results of sucrose preference experiment of rats in each group (n=8, )

[0054] Group Dosage Sucrose preference value (%) Normal control group / 98.58±2.08 Model Group / 55.91±8.49** Positive drug group 2mg / kg 63.05±6.53 Low dose Chinese medicine group 3.5g / kg 64.56±11.59# Chinese medicine medium dose group 7.1g / kg 86.96±6.63## High-dose Chinese medicine group 14.1g / kg 95.29±3.88##

[0055] Note: Compared with the normal control group *P<0.05, **P<0.01; compared with the model group # P<0.05, ## P<0.01.

[0056] From the data in Table 4, it can be seen that compared with the normal control group, the sucrose preference rate of rats in the model group was significantly reduced (P < 0.01); compared with the model group, the sucrose preference rate of rats in the positive drug group was not significantly different, and the sucrose preference rate of rats in the Chinese medicine intervention group was significantly increased in a concentration-dependent manner (Chinese medicine low-dose group P < 0.05, Chinese medicine medium-dose group P < 0.01, Chinese medicine high-dose group P < 0.01).

[0057] (2) Effects on autonomous behavior of adolescent rats with depression

[0058] Table 5 Results of open field test in rats of each group (n=8, )

[0059]

[0060] Note: Compared with the normal control group *P<0.05, **P<0.01; compared with the model # P<0.05,## P<0.01.

[0061] From the data in Table 5, it can be seen that compared with the normal control group, the total distance, central area distance and total activity times of the rats in the model group were significantly reduced (P < 0.01, P < 0.05, P < 0.05); compared with the model group, the total distance, central area distance and total activity times of the rats in the positive drug group were significantly increased (P < 0.01, P < 0.05, P < 0.05), the total distance, central area distance and total activity times of the rats in the low-dose Chinese medicine group were significantly increased (P < 0.05, P < 0.01, P < 0.05), the total distance, central area distance and total activity times of the rats in the medium-dose Chinese medicine group were significantly increased (P < 0.01, P < 0.01, P < 0.01), and the total distance and total activity times of the rats in the high-dose Chinese medicine group were significantly increased (P < 0.05, P < 0.01).

[0062] (3) Effects on cognitive function in adolescent rats with depression

[0063] Table 6 Morris water maze test results of rats in each group (n=8, )

[0064] Group Dosage Escape latency(s) Number of times crossing platforms (times) Normal control group / 16.32±11.37 3.00±2.10 Model Group / 44.28±11.52** 1.57±1.05 Positive drug group 2mg / kg <![CDATA[13.96±8.38 ## ]]> 1.86±1.12 Low dose Chinese medicine group 3.5g / kg <![CDATA[17.14±6.75 ## ]]> 2.00±0.53 Chinese medicine medium dose group 7.1g / kg <![CDATA[12.80±6.43 ## ]]> 2.43±0.90 High-dose Chinese medicine group 14.1g / kg <![CDATA[7.17±3.80 ## ]]> 2.14±1.12

[0065] Note: Compared with the normal control group *P<0.05, **P<0.01; compared with the model # P<0.05, ## P<0.01.

[0066] From the data in Table 6, it can be seen that compared with the normal control group, the escape latency of the rats in the model group was significantly prolonged (P < 0.01); compared with the model group, the escape latency of the rats in the positive drug group, the low-dose Chinese medicine group, the medium-dose Chinese medicine group and the high-dose Chinese medicine group were significantly shortened (P < 0.01, P < 0.01, P < 0.01, P < 0.01). The experimental results show that the positive drug and the Chinese medicine combination can effectively improve the learning ability of rats.

[0067] From the above experimental results, it can be seen that the Chinese medicine composition for treating adolescent depression prepared according to the raw materials and methods described in the present invention is equivalent to positive drugs in therapeutic effect, and is even better than positive drugs in regulating sucrose preference, spatial memory learning (corresponding to escape latency), spatial memory retention (corresponding to the number of platform crossings), etc.

[0068] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention (including the claims) is limited to these examples. Under the concept of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.

[0069] The embodiments of the present invention are intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating adolescent depression, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5-15 parts of bupleurum, 5-15 parts of angelica, 5-15 parts of tuckahoe, 5-15 parts of lily, 5-15 parts of julibrissin bark, and 5-10 parts of mint; The method for preparing the Chinese medicine composition for treating adolescent depression comprises the following steps: 1) Crush Bupleurum, Angelica and Albizzia julibrissin, add 6 to 10 times the weight of 60 to 90% ethanol, extract twice, each time for 1 to 3 hours, filter, combine the filtrate, and concentrate to obtain an alcohol-extracted clear paste; 2) After grinding Poria cocos and lily, add 6-10 times the weight of water and reflux and extract twice, each time for 2-4 hours, filter, combine the filtrate, and concentrate to obtain a water-extracted clear paste; 3) After crushing the mint, add 6 to 10 times the weight of water, use steam distillation, extract twice, each time for 5 to 8 hours, to obtain a volatile extract; 4) The alcohol-extracted clear paste obtained in step 1) and the water-extracted clear paste obtained in step 2) are combined, mixed, concentrated, and dried, and the volatile extract obtained in step 3) is added to obtain a traditional Chinese medicine composition.

2. The Chinese medicine composition according to claim 1, characterized in that The invention is prepared from the following raw materials in parts by weight: 10 parts of bupleurum root, 10 parts of angelica root, 10 parts of tuckahoe, 10 parts of lily, 10 parts of julibrissin bark and 6 parts of mint.

3. A method for preparing a Chinese medicine composition for treating adolescent depression as claimed in claim 1 or 2, characterized in that: The steps include: 1) Crush Bupleurum, Angelica and Albizzia julibrissin, add 6 to 10 times the weight of 60 to 90% ethanol, extract twice, each time for 1 to 3 hours, filter, combine the filtrate, and concentrate to obtain an alcohol-extracted clear paste; 2) After grinding Poria cocos and lily, add 6-10 times the weight of water and reflux and extract twice, each time for 2-4 hours, filter, combine the filtrate, and concentrate to obtain a water-extracted clear paste; 3) After crushing the mint, add 6 to 10 times the weight of water, use steam distillation, extract twice, each time for 5 to 8 hours, to obtain a volatile extract; 4) The alcohol-extracted clear paste obtained in step 1) and the water-extracted clear paste obtained in step 2) are combined, mixed, concentrated, and dried, and the volatile extract obtained in step 3) is added to obtain a traditional Chinese medicine composition.

4. The preparation method according to claim 3, characterized in that Step 1) The weight of the ethanol is 8 times the weight of the medicinal material, the ethanol concentration is 75%, and the extraction time is 2 hours each time.

5. The preparation method according to claim 3, characterized in that: Step 2) The weight of the water is 8 times the weight of the medicinal material, and each extraction time is 3 hours.

6. The preparation method according to claim 3, characterized in that: Step 3) The weight of the water is 8 times the weight of the medicinal material, and each extraction time is 6 hours.

7. The preparation method according to claim 3, characterized in that: In step 1), the bupleurum root, angelica root and julibrissin bark are crushed and passed through an 80-mesh sieve, in step 2), the poria cocos and lily bulb are crushed and passed through an 80-mesh sieve, and in step 3), the mint is crushed and passed through an 80-mesh sieve.

8. Use of the Chinese medicine composition for treating adolescent depression according to claim 1 or 2 in the preparation of a drug for treating adolescent depression.

9. Use of the Chinese medicine composition for treating adolescent depression as claimed in claim 8 in preparing a drug for treating adolescent depression, characterized in that: The drug for treating adolescent depression is a preparation prepared from a traditional Chinese medicine composition and pharmaceutically acceptable auxiliary materials.

10. Use of the Chinese medicine composition for treating adolescent depression according to claim 9 in preparing a drug for treating adolescent depression, characterized in that: The preparation is one or more of capsules, tablets, granules, oral liquids, pills, powders and pills.

Images