Traditional Chinese medicine composition for treating mild depression, medicament and preparation method thereof

Abstract

The invention particularly discloses a traditional Chinese medicine composition for treating mild depression, a medicament and a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following components in parts by weight: 10 to 20 parts of karst medicine terminalia fruit pulp, 15 to 20 parts of medicine terminalia fruit pulp, 15 to 20 parts of emblic leafflower fruit peel, 15 to 20 parts of fructus chebulae immaturus, 5 to 10 parts of coreopsis tinctoria root, 7 to 10 parts of Japanese polypody rhizome, 7 to 10 parts of pogonatherum crinitum, 7 to 10 parts of lavender and 40 to 600 parts of refined honey. According to the traditional Chinese medicine composition for treating mild depression, the medicament and the preparation method of the traditional Chinese medicine composition, the honey cream has a more remarkable effect on depression treatment, particularly has a remarkable effect on animal behavioral change, and is easy for modern industrial production.

Description

Technical Field

[0001] This invention relates in particular to a traditional Chinese medicine composition, preparation, and method for treating mild depression. Background Technology

[0002] Depression is a common, relapsing, chronic affective disorder. It has a high prevalence, complex clinical symptoms, numerous comorbidities, a high risk of relapse, a high mortality rate, and is difficult to treat. It can occur at any stage of life, from childhood and adolescence to middle and old age, severely impacting patients' quality of life and even endangering their lives, placing a heavy burden on their families and society. With rapid societal development, stress has become one of the biggest environmental factors contributing to depressive disorders, with morbidity and mortality rates continuing to rise.

[0003] Mild depression is the initial stage of depression. Patients at this stage typically experience low mood and loss of interest, but can still maintain basic daily life and work. While the symptoms of mild depression may be mild, if left untreated, it can recur after the mild stage. Low response rates to medication lead to poor patient adherence, and the condition gradually worsens, developing into treatment-resistant depressive disorder, with a corresponding increase in suicide rates. Therefore, prevention and treatment of mild depressive disorder are particularly important.

[0004] In current clinical treatment of depressive disorders, medication is the primary approach. A similar prescription, "Maijuni Nujia," is listed in the *Ancient Classic Prescriptions Catalogue (Second Batch) – Uyghur Medicine*. It primarily consists of five herbs: roasted *Terminalia chebula*, pitted *Amla* (fermented), lavender, *Polygonum hydropiper*, and *Cuscuta chinensis*. Its main function is to "clear abnormal spleen fluids and treat malaria." However, it suffers from limitations such as low efficacy, delayed onset of action, adverse reactions, withdrawal symptoms, and drug tolerance. Therefore, there is an urgent need for a highly effective drug for treating mild depression with few side effects and no withdrawal symptoms. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition, preparation and preparation method for treating mild depression. This honey paste is more effective against depression drugs, especially for animal behavioral changes, and is easy to produce in modern industrial production.

[0006] To achieve the above objectives, the present invention provides a traditional Chinese medicine composition for treating mild depression, comprising the following weight proportions:

[0007] 10-20 parts of Terminalia chebula pulp, 15-20 parts of Terminalia chebula pulp, 15-20 parts of Phyllanthus emblica peel, 15-20 parts of Terminalia chebula fruit, 5-10 parts of cored Terminalia chebula vine root, 7-10 parts of Polygonum hydropiper, 7-10 parts of Cuscuta chinensis, 7-10 parts of Lavender, and 40-600 parts of refined honey.

[0008] This Uyghur medicine formula consists of medicinal materials such as Kabul Terminalia chebula fruit flesh, Terminalia chebula fruit flesh, Phyllanthus emblica pericarp, Tinospora cordifolia root, Drynaria fortunei, Cuscuta chinensis, and lavender. In the formula, Kabul Terminalia chebula fruit flesh, Terminalia chebula fruit flesh, Tinospora cordifolia root, and Phyllanthus emblica pericarp are the main herbs, forming the Itirfili medicine pair, which can remove abnormal body fluids such as splenic humor, dispel dampness, nourish the brain, enhance sensory drive, improve intelligence and memory, clear the mind, relieve vexation and depression, and is mainly used to treat damp-heat diseases, such as dry cerebral asthenia, decreased intelligence, restlessness and fear, and melancholy. Among them, Phyllanthus emblica pericarp is of the second-degree cold and the third-degree initial cold, and the milk-foamed product is of the first-degree cold and the second-degree dryness; it can remove abnormal splenic humor and mucus, nourish the governing organs such as the brain, heart, and liver, improve intelligence and memory, enhance the retentive power of the stomach, and dispel the foul smell of body fluids, and is mainly used to treat damp-heat diseases, such as cerebral asthenia, heart asthenia, liver asthenia, stomach asthenia, and decreased vision.

[0009] Drynaria fortunei and Cuscuta chinensis are auxiliary herbs, which enhance the effects of the main herbs. Drynaria fortunei is of the second-degree heat and the third-degree dryness; it can remove abnormal splenic humor and mucus, generate dryness and heat, nourish the brain, nourish the heart, delight the mind, dispel wind and cleanse the blood; it is mainly used to treat cold or splenic humor or mucus-related diseases, such as heart-brain asthenia, depression, and epilepsy. Cuscuta chinensis is of the second-degree dry heat; it can remove abnormal splenic humor and mucus, disperse qi and dredge obstruction, relieve depression and pressure, delight the mind, clear the brain and calm the nerves, soften hardness and reduce swelling.

[0010] The root of Tinospora cordifolia harmonizes the properties of the main and auxiliary herbs and is used for splenic humor or mucus-related diseases, such as cold depression, neurosis, cramps, and insomnia. Lavender is of the first-degree heat and the second-degree dryness; it generates dryness and heat, removes abnormal splenic humor and mucus, clears and nourishes the brain, strengthens muscles and bones, dispels wind and cold, and nourishes the meridians and soothes the nerves; it is mainly used to treat various nervous system diseases of damp-cold or splenic humor or mucus nature, such as paralysis, facial paralysis, tremor, epilepsy, amnesia, neurasthenia, and depression. When all the herbs are combined, the main effect is to dispel wind and dredge collaterals, supplemented by removing abnormal splenic humor or mucus, dispelling the foul smell of body fluids, clearing the brain and calming the nerves, relieving depression and mania, soothing the liver and regulating qi, and delighting the mind, etc. It can treat symptoms such as low mood, anxiety, insomnia, amnesia, and decreased desire caused by mild depression. At the same time, honey can enhance the immune function of the body.

[0011] Preferably, it includes the following components in parts by weight:

[0012] 16 to 18 parts of Kabul Terminalia chebula fruit flesh, 16 to 18 parts of Terminalia chebula fruit flesh, 16 to 18 parts of Phyllanthus emblica pericarp, 16 to 18 parts of Tinospora cordifolia root, 5 to 10 parts of defatted Tinospora cordifolia root, 7 to 10 parts of Drynaria fortunei, 7 to 10 parts of Cuscuta chinensis, 8 to 12 parts of lavender, and 40 to 600 parts of refined honey.

[0013] Preferably, it includes the following components in parts by weight:

[0014] 18 parts of Terminalia chebula pulp, 18 parts of Terminalia chebula pulp, 18 parts of Phyllanthus emblica peel, 18 parts of Terminalia chebula fruit, 5-10 parts of cored Terminalia chebula vine root, 7-10 parts of Polygonum hydropiper, 7-10 parts of Cuscuta chinensis, 12 parts of Lavender, and 40-600 parts of refined honey.

[0015] This invention also provides a method for preparing a traditional Chinese medicine composition for treating mild depression, comprising the following steps:

[0016] S1. Raw material pretreatment: The Terminalia chebula pulp in Kabul is stir-fried with almond oil, the Terminalia chebula pulp and Terminalia chebula are stir-fried with pitted almond oil, and the Phyllanthus emblica peel is soaked in milk.

[0017] S2. Take the Terminalia chebula pulp, Terminalia chebula pulp, Terminalia chebula fruit, and Phyllanthus emblica peel obtained in S1, mix and pulverize them, and pass them through a 100-mesh sieve to obtain drug mixture powder 1;

[0018] S3. The cored root of the fruit vine, water dragon bone, dodder and lavender are mixed and pulverized at low temperature and passed through a 100-mesh sieve to obtain drug mixture powder 2;

[0019] S4. Add drug mixture 1 obtained in S2 to drug mixture 2 obtained in S3, stir and mix, remove static electricity, and obtain drug mixture 3.

[0020] S5. Add the drug mixture powder 3 obtained in S4 to the refined honey, stir and mix to obtain the traditional Chinese medicine composition.

[0021] Preferably, in S1, the frying temperature is 100-140℃ and the frying time is 10-15 minutes.

[0022] Preferably, in step S4, drug powder 2 is added first and stirred for 5-10 minutes. Then, drug powder 1 is added slowly in multiple batches. The amount of drug powder 1 added at one time is 10%-20% of the weight of drug powder 2. The stirring time for drug powder 1 and drug powder 2 is 30-40 minutes.

[0023] Preferably, in step S4, drug mixture powder 2 is added first and stirred for 10 minutes. Then, drug mixture powder 1 is added slowly in multiple batches. The amount of drug mixture powder 1 added at one time is 10%-20% of the weight of drug mixture powder 2. The stirring time for drug mixture powder 1 and drug mixture powder 2 is 40 minutes.

[0024] Preferably, in step S5, honey with a moisture content of 20% to 24% is added first, the temperature is cooled to 25 to 30°C, and then the drug mixture powder 3 is added, and the mixing time is 20 to 30 minutes.

[0025] Preferably, in step S5, honey with a moisture content of 20% to 24% is added first, the temperature is cooled to 25°C, and then the drug mixture powder 3 is added, and the mixing time is 25 minutes.

[0026] The present invention also provides a medicament for treating mild depression, comprising pharmaceutically acceptable excipients and the traditional Chinese medicine composition, wherein the excipients are one or more selected from excipients, fillers, diluents, humectants, preservatives, sweeteners, and aromatics.

[0027] Preferably, the dosage form of the medicine is one of the following: honey paste, powder, or pill.

[0028] Preferably, the excipients also include one or more of starch, dextrin, and lactose.

[0029] Therefore, the present invention employs the above-mentioned traditional Chinese medicine composition, preparation, and preparation method for treating mild depression, and the beneficial effects are as follows:

[0030] Compared with "Maijuninujia", the Uyghur medicine composition prepared by this invention has obvious characteristics and advantages. The formula consists of 9 medicinal materials, among which Kabul Terminalia chebula pulp, Terminalia chebula, Phyllanthus emblica and Terminalia chebula form a classic Uyghur medicine pair combination "Yitirfili", which is mainly used for the treatment of brain diseases. The innovative addition of "Heguoteng root" is used to harmonize the medicinal properties of the various herbs. Secondly, the honey paste is made using a specific temperature process (20℃~25℃) for mixing, which significantly improves the fluidity of the honey paste compared with the traditional Uyghur medicine honey paste process. Finally, animal efficacy comparisons have confirmed that this honey paste prescription is more significant in improving the behavioral aspects of depression, biochemical indicators, and the pathological recovery of brain tissue.

[0031] The method of this invention is simple, has high fluidity, good stability, and is easy to produce in modern industrial production.

[0032] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0033] Figure 1 The HE staining results are from an embodiment of a traditional Chinese medicine composition, preparation and preparation method for treating mild depression according to the present invention, wherein A is the blank control group, B is the model group, C is the fluoxetine group, D is the low-dose group of Example 1, E is the medium-dose group of Example 1, F is the high-dose group of Example 1, and G is the comparative group.

[0034] Figure 2 This is a comparative study of mouse slices from an acute depression model, based on Example 1 of the present invention, which describes a traditional Chinese medicine composition, preparation, and preparation method for treating mild depression. Detailed Implementation

[0035] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0036] Unless otherwise defined, the technical or scientific terms used in this invention shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0037] The book *The Garden of Herbs* states that "Yellow Terminalia chebula bark is the pericarp of the Terminalia chebula tree; the fruit can be divided into four types according to maturity and origin: Yellow Terminalia chebula, Black Terminalia chebula (i.e., Xiqing fruit), Kabul Terminalia chebula, and Chinese Terminalia chebula; the ripe and yellow variety with thick flesh is called Yellow Terminalia chebula; the unripe variety is black with an unformed seed, called Black Terminalia chebula; the relatively ripe variety is yellowish-red, large, with thick flesh, a smooth surface, and is produced in Kabul, called Kabul Terminalia chebula; the semi-ripe variety is greenish-yellow and is produced in China, called Chinese Terminalia chebula." In this invention, the Kabul Terminalia chebula pulp comes from the aforementioned Kabul Terminalia chebula, and the Terminalia chebula pulp comes from the aforementioned Chinese Terminalia chebula.

[0038] Example 1

[0039] A traditional Chinese medicine composition for treating mild depressive symptoms, in the form of a Uyghur medicinal honey paste, comprising the following components:

[0040] 180g of Terminalia chebula pulp (roasted in almond oil), 180g of Terminalia chebula pulp (roasted in almond oil with pits removed), 180g of Phyllanthus emblica peel (soaked in milk), 180g of Terminalia chebula (roasted in almond oil with pits removed), 100g of Cycas revoluta root (core removed), 100g of Polygonum hydropiper, 100g of Cuscuta chinensis, 120g of Lavender, and 1.14kg of refined honey.

[0041] Its preparation method is as follows:

[0042] The mixed powder of Terminalia chebula pulp (roasted in almond oil), Terminalia chebula pulp (roasted in pitted almond oil), Phyllanthus emblica peel (soaked in milk), and Terminalia chebula (roasted in pitted almond oil) was pulverized and passed through a 100-mesh sieve to obtain drug mixed powder 1.

[0043] Mix and pulverize the roots of the fruit vine (with the core removed), water dragon bone, dodder and lavender at low temperature (<5℃), and pass through a 100-mesh sieve to obtain drug mixture powder 2.

[0044] First, add drug mixture powder 2 and stir for 10 minutes. Then, slowly add drug mixture powder 1 in multiple batches. The stirring time for drug mixture powder 1 and drug mixture powder 2 is 40 minutes. Remove static electricity to obtain drug mixture powder 3. Mix drug mixture powder 3 with refined honey (tender honey, 20% moisture) at 25℃ for 25 minutes to obtain Uyghur medicine honey ointment.

[0045] Example 2

[0046] A traditional Chinese medicine composition for treating mild depressive symptoms, in pill form, comprising the following components:

[0047] 180g of Terminalia chebula pulp (roasted in almond oil), 180g of Terminalia chebula pulp (roasted in almond oil with pits removed), 180g of Phyllanthus emblica peel (soaked in milk), 180g of Terminalia chebula (roasted in almond oil with pits removed), 100g of Cycas revoluta root (core removed), 100g of Polygonum hydropiper, 100g of Cuscuta chinensis, 120g of Lavender, and 400g of refined honey.

[0048] Its preparation method is as follows:

[0049] The mixed powder of Terminalia chebula pulp (roasted in almond oil), Terminalia chebula pulp (roasted in pitted almond oil), Phyllanthus emblica peel (soaked in milk), and Terminalia chebula (roasted in pitted almond oil) was pulverized and passed through a 100-mesh sieve to obtain drug mixed powder 1.

[0050] Mix and pulverize the roots of the fruit vine (with the core removed), water dragon bone, dodder and lavender at low temperature (<5℃), and pass through a 100-mesh sieve to obtain drug mixture powder 2.

[0051] First, add drug mixture powder 2 and stir for 10 minutes. Then, slowly add drug mixture powder 1 in multiple batches. The stirring time for drug mixture powder 1 and drug mixture powder 2 is 40 minutes. Remove static electricity to obtain drug mixture powder 3. Mix drug mixture powder 3 with honey (moisture content < 24%) at 50℃ for 30 minutes to obtain a soft material. Add excipients to make honey pills.

[0052] Comparative Example 1

[0053] A traditional Chinese medicine composition, namely "Mai Zhuni Nujia", differs from Example 1 in that it does not include Kabul Terminalia chebula pulp (roasted with almond oil), Terminalia chebula pulp (roasted with pitted almond oil), or He Guo Teng root (core removed).

[0054] Test

[0055] I. Animal experiments on chronic depression

[0056] Ninety Balb / C mice were used as experimental animals. After acclimatization and culture for 5 days, a sucrose preference test was conducted on the mice. The mice were randomly divided into a blank control group, a model group, a fluoxetine group, a low-dose group (1x the clinical dose) of Example 1, a medium-dose group (2x the clinical dose) of Example 1, a high-dose group (3x the clinical dose) of Example 1, and a control group (3x the clinical dose). The sucrose preference test was used as the criterion for successful model establishment. Mice were administered the drug by gavage at a dose of 0.1 mL / 10 g body weight for 14 consecutive days, once daily. The blank control group and the model group were given the same volume of physiological saline.

[0057] The experiment used a chronic, unpredictable, mild stress method to establish the model. Mice in the blank control group and the model group were placed in different housing rooms to ensure that the two groups of mice did not affect each other. The blank control group was normally fed without any stimulation, and its normal diet and water intake were guaranteed (except for a 12-hour water restriction before the 1-serving sugar water consumption experiment). The other groups were subjected to continuous chronic, unpredictable, mild stress stimulation, specifically including: 24-hour fasting, 24-hour water restriction, 24-hour damp bedding, tilted housing, 2-hour restraint, 5-minute tail clamping, 2-hour flashing noise, 5-minute tail hanging upside down, 4-minute swimming in 4°C cold water, 5-minute swimming in 45°C hot water, day-night reversal, horizontal shaking, and hot plate. The operation methods are shown in Table 1. Animals in the model group were randomly given one type of stress every day, with the stimulation time being uncertain, and each stress was not repeated every week.

[0058] Meanwhile, the low-dose group (0.4 g / kg), medium-dose group (0.8 g / kg), high-dose group (1.2 g / kg), and comparative example 1 group (1.2 g / kg) of Example 1, as well as the model group, were given the same amount of physiological saline once daily.

[0059] Table 1 Stimulation Procedures

[0060]

[0061]

[0062] Test methods: 1. Mouse weight measurement: The weight of mice was measured daily during the drug administration period, and the changes in the weight of mice in each group were recorded and analyzed.

[0063] 2. Sugar Water Consumption: Before the sugar water consumption experiment, each mouse was trained to drink sugar water. During training, two water bottles were placed in each cage. One bottle contained one dose of sucrose water, and the other contained the mouse's normal drinking water. The mouse was allowed to freely choose which bottle to drink from. The training lasted for 24 hours. After the training, the mouse was fasted and deprived of water for 24 hours. On days 0, 21, and 35 of the experiment, a sugar water consumption experiment was conducted, lasting for 1 hour, with the bottles being moved every 30 minutes. The water bottles were removed and weighed. The sugar water consumption before and after the experiment was compared, and the sugar water preference was calculated as: Sugar water preference = (Sucrose water consumption / (Sucrose water consumption + Normal water consumption)) × 100 doses.

[0064] 3. Behavioral experiments (open field test)

[0065] On day 14, one hour after drug administration, the open field test was initiated to assess the spontaneous activity and movement of the mice. An open box (50cm × 50cm × 50cm) was used, with the bottom divided into equal-sized squares (10cm × 10cm). Sixty minutes after drug administration, the mice were placed in the open field, always from the same location and direction. After a 3-minute acclimatization period, the mice were assessed, and their spontaneous movement during the 5-minute test period was recorded, including horizontal distance and number of vertical movements (number of times both forelimbs lifted more than 1cm off the ground, including standing and climbing walls).

[0066] 4. Morris water maze experiment

[0067] ① Orientation and navigation experiment: Eight groups of mice were trained and tested in water for seven consecutive days, with four training sessions per day, ensuring that each of the four quadrants was used once daily. Training was conducted at fixed times each day, with a 3-minute interval between each session. The training time was set to 60 seconds. If a mouse failed to find a platform within 60 seconds, it was guided to the platform and remained there for 10 seconds; the escape latency was recorded as 60 seconds. The mean escape latency was used as a parameter for data analysis.

[0068] ② Spatial exploration experiment: The experiment lasted for 1 day. The concealed platform was removed, and the mice were placed in the water from the first quadrant entry point. The time the mice spent in the target quadrant in the constant temperature pool for 60 seconds and the number of times they crossed the target (original platform position) were tested.

[0069] 5. Tail Suspension Test

[0070] On day 15 of drug administration, the mouse tail (1 cm from the tip) was taped to a workbench to make it upside down. The mouse struggled to overcome the abnormal position, but after a period of activity, it intermittently stopped, indicating a state of frustration. After 1 minute of adaptation, the cumulative immobility time of the mouse within 5 minutes was recorded. (The state of immobility was defined as the mouse stopping struggling or stopping).

[0071] 6. Forced swimming experiment

[0072] On day 15 of drug administration, mice were placed in a swimming tank with a water temperature of 20-25℃ and a water depth of 10cm and forced to swim for 6 minutes. The time the mice remained still within the last 4 minutes was observed and recorded. The time the mice remained still while floating and stopped struggling was recorded (the time the mice made only slight movements to keep their heads afloat was also considered as swimming stillness).

[0073] 7. Biochemical indicator testing

[0074] After the experiment, the mice were euthanized after blood was collected from their eyes. The cortex and cerebellum were quickly separated and placed in 5ml EP tubes. The tubes were then placed at -20℃ for 2 hours and subsequently stored at -80℃ for testing. Four portions of intact brain tissue were taken and stored in formaldehyde at room temperature for testing.

[0075] After the blood sample was left to stand at room temperature for 30 min, it was centrifuged at 3500 r / min for 15 min, and the supernatant was collected, aliquoted and transferred to EP tubes, and stored at -80℃. The contents of 5-HT, DA, BDNF and IL-10 in the mouse hippocampus, cortex and serum were detected by ELISA. All procedures were performed according to the kit.

[0076] 8. He staining of mouse hippocampus

[0077] The fixed brain tissue was injected with formaldehyde in advance. After fixing with 10 parts of formaldehyde solution for 24 hours, the hippocampus was dehydrated. The dehydration process was as follows: 50 parts ethanol for 15 min, 80 parts ethanol for 15 min, 90 parts ethanol for 15 min, 100 parts ethanol for 5 min, 100 parts ethanol for 7 min, xylene I for 5 min, xylene II for 5 min; tissue was then immersed in paraffin at 65℃ for 4 h.

[0078] After embedding the tissue blocks, they were frozen and sectioned to a thickness of 8 μm. After sectioning, the section rack was placed in a 75°C oven and baked for 1 hour. The sections were then dewaxed and rehydrated in a gradient: xylene I for 5 min, xylene II for 5 min, 100 parts of anhydrous ethanol I for 5 min, 100 parts of anhydrous ethanol II for 5 min, 90 parts of ethanol for 5 min, 80 parts of ethanol for 5 min, 70 parts of ethanol for 2 min, and distilled water for 2 min.

[0079] Immerse the prepared sections in hematoxylin staining solution for 5 minutes, wash away excess stain with distilled water, differentiate and return to blue with 1 part hydrochloric acid ethanol solution for 1 minute, rinse with tap water for 3 minutes, immerse in eosin solution for 1 minute, rinse with distilled water, and then quickly dehydrate with 75 parts, 80 parts, 90 parts, and 100 parts each for 2-3 seconds, and 100 parts ethanol, xylene I, and xylene II solutions for 1 minute each. After drying, mount with neutral resin and observe and photograph under an upright microscope.

[0080] Test Results

[0081] The results of the weight comparison of mice in each group are shown in Table 2.

[0082] Table 2 Comparison of mouse body weight in each group

[0083]

[0084]

[0085] As shown in Table 1, there was no significant difference in body weight among the groups before modeling (P > 0.05). After modeling, the body weight of mice in the model groups decreased significantly compared with the normal group. After 16 days of drug administration, the body weight of mice in the normal group and the fluoxetine group increased significantly compared with the model group, and there was no significant difference in body weight between the drug administration groups in Example 1 and Comparative Example 1 (P > 0.05).

[0086] The results of the comparison of sucrose preferences among the mice in each group are shown in Table 3.

[0087] Table 3 Comparison of sucrose preferences among mice in each group

[0088] Before administration / dose After administration / dose Blank control group 69.83±5.06 74.66±7.79 Model group 55.09±3.30 43.52±0.18** Fluoxetine group 56.35±8.97 57.42±8.11 Example 1 Low-dose group 59.63±6.18 61.59±4.81 In Example 1, the dosage group 60.54±1.59 68.55±0.29# Example 1 High-dose group 56.96±6.83 72.39±1.64## Comparative Example 1 61.58±2.56 49.57±1.79

[0089] Note: Compared with the blank control group, **p<0.01; compared with the model group, #p<0.05, ##p<0.01.

[0090] As shown in Table 3, compared with the blank control group, the sucrose preference of mice in the model group was significantly reduced (p<0.01). Compared with the model, the percentage of sucrose preference of mice in each treatment group was significantly increased. The groups in this invention were more effective in regulating the mood disorders of depressed mice than the control group, and had a good effect in preventing and / or treating mild depression.

[0091] The results of comparisons of open field movement, number of upright movements, tail suspension time, and forced swimming immobility time for each group of mice are shown in Table 4.

[0092] Table 4 Comparison of open field movement, number of uprighting events, tail-suspended stillness time, and forced swimming immobility time among different groups of mice.

[0093]

[0094]

[0095] Note: Compared with the control group, *p < 0.05, **p < 0.01; compared with the model group, #p < 0.05, ##p < 0.01.

[0096] As shown in Table 4, compared with the blank control group, the model group mice showed significantly reduced open field movement distance and number of upright movements (p < 0.05), and significantly increased tail suspension immobility time and forced swimming immobility time (p < 0.01). Compared with the model, the low and medium dose groups in the examples showed significantly increased open field movement distance and number of upright movements (p < 0.05), while the dose groups in the examples showed significantly reduced forced swimming immobility time (p < 0.01). The example group of this invention improved the behavioral performance of depressed mice more effectively than the control group 1, and has a good effect on the prevention and / or treatment of mild depression.

[0097] The comparison results of 5-HT', BDNF and DA in each group of mice are shown in Table 5.

[0098] Table 5 Comparison of 5-HT', BDNF and DA in each group of mice

[0099] Group 5-HT' (ng / mL) BDNF (pg / mL) DA (pg / mL) Blank control group 81.18±3.87 148.65±3.44 95.98±1.94 Model group 73.94±2.39** 97.23±4.07** 75.21±0.87** Fluoxetine group 81.44±4.39## 144.58±4.69## 85.59±2.09# Example 1 Low-dose group 76.42±1.67 120.00±1.96## 77.03±2.13 In Example 1, the dosage group 77.18±3.09# 130.87±4.34## 77.91±1.96 Example 1 High-dose group 79.69±5.44# 149.70±4.77## 87.19±6.80# Comparative Example 1 74.89±8.26 122.87±3.63## 83.81±6.75#

[0100] Note: Compared with the control group, *p < 0.05, **p < 0.01; compared with the model group, #p < 0.05, ##p < 0.01.

[0101] As shown in Table 5, compared with the blank control group, the levels of serotonin (5-HT'), brain neurotrophic factor (BDNF), and dopamine (DA) in the model group were significantly reduced (p < 0.01); compared with the model, the low-dose group of Example 1 showed a significant increase in BDNF content (p < 0.05), and the high-dose group of Example 1 showed a significant increase in both 5-HT' and BDNF content (p < 0.05); the example groups of this invention significantly restored the levels of key cytokines in depressed mice more effectively than the control group, and have a good effect on the prevention and / or treatment of mild depression.

[0102] HE staining results of the CA1 region of the hippocampus in each group of mice (×200, n=3) are as follows: Figure 1 As shown.

[0103] Depend on Figure 1 The study found that in the normal group, the cells in the CA1 region of the hippocampus were neatly arranged, with clear cell structure and normal nucleus morphology. In the model group, the CA1 region of the hippocampus of mice was severely damaged, with solidified, atrophied, and deeply stained nuclei. Compared with the model group, the number of damaged neurons in each dose group and the fluoxetine group in Example 1 was reduced to varying degrees, and the staining results of the medium-dose group and the high-dose group were close to those of the normal group.

[0104] II. Animal experiments on acute depression

[0105] Seventy Balb / C mice were used as experimental animals and cultured for 5 days. The mice were then randomly divided into a blank control group, a model group, a fluoxetine group, a low-dose group (1x the clinical dose) of Example 1, a medium-dose group (2x the clinical dose) of Example 1, a high-dose group (4x the clinical dose) of Example 1, and a control group (4x the clinical dose). After 14 days of drug administration, all groups except the blank control group received an intraperitoneal injection of 4 mg / kg reserpine. Changes in the mice were assessed 24 hours later. The mouse groupings are shown in Table 6.

[0106] Table 6 Mouse grouping

[0107]

[0108]

[0109] Criteria for judging the degree of ptosis: 0 degrees when fully open; 1 degree when 1 / 4 of the eyelid is drooping; 2 degrees when 1 / 2 of the eyelid is drooping; 3 degrees when 3 / 4 of the eyelid is drooping; 4 degrees when fully closed.

[0110] Rectal temperature measurement: The rectal temperature was measured 1 cm from the anus to the rectum of the mouse.

[0111] Out-of-circle rate: Observe each mouse within a 7.5cm diameter white paper circle for 15 seconds to see if it has left the circle, record the number of mice that have left the circle, and calculate the out-of-circle rate for each group of animals.

[0112] Behavioral Science – Water Maze: The mouse water maze is 120 cm in diameter and approximately 30 cm deep. A platform that can be submerged in the water is placed in the center of the pool, with a height such that the animal can easily leave the water surface when standing on it. A tracking system, such as a camera, is also required to record the animal's movement within the water maze, and appropriate tracking software is used for data analysis. The laboratory environment should be maintained under constant temperature and lighting conditions. Generally, the room and water temperature should be approximately 22 degrees Celsius, and the lighting should be as dim as possible to reduce animal stress and platform visibility, while ensuring sufficient illumination for the tracking software to perform its detection.

[0113] Pre-training: Place the animals in a pool without hidden platforms to explore freely and adapt to the experimental environment. Each mouse will be trained for 2 minutes, 5-7 times.

[0114] Acquisition training (localization training): Place the animal head-first into the water, randomly selecting one of four starting positions: east, west, south, or north. Record the time it takes for the animal to find the underwater platform. In the first few training sessions, if this time exceeds 60 seconds, guide the animal to the platform and allow it to remain there for 10 seconds. Each animal undergoes 8 training sessions, with a 15-20 minute interval between each session.

[0115] Exploration and alignment training: After the acquisition training is completed, the platform is placed in a certain quadrant. The mouse is placed in the water from the opposite side of the platform quadrant. The mouse is trained to find the platform, stay on the platform for 10 seconds, and the training is repeated 5 times (all training is performed before the injection of reserpine to establish the model).

[0116] Test method: Alignment detection, same detection alignment training, record the time to find the platform within 90 seconds. If not found, record the time spent in the target quadrant and the number of crossings within 90 seconds.

[0117] After euthanasia, whole brain tissue was collected from 3 animals per group and immediately placed at -80℃ for the detection of protein content such as BDNF, CREB, p-CREB, and PKC in the brain tissue.

[0118] After euthanasia, whole brain tissue was collected from 3 animals in each group and immediately placed at -80℃ for proteomics and metabolomics analysis.

[0119] After sacrifice, whole brain tissue was collected from 3 mice in each group and fixed in 4 portions of formaldehyde solution. The tissue was then used for HE staining of the hippocampus of the mouse brain tissue and immunofluorescence staining of p-CREB protein.

[0120] Test Results

[0121] The changes in body weight of mice in each group after administration are shown in Table 7.

[0122] Table 7. Changes in body weight of mice in each group after drug administration (n=10)

[0123] Group body weight / g Blank control group 25.1±0.77 Model group 25.09±0.88 Fluoxetine group 26.15±0.77 Example 1 Low-dose group 25.25±0.45 In Example 1, the dosage group 26.61±0.48 Example 1 High-dose group 26.96±0.56 Comparative Example 1 25.4±0.52

[0124] The degree of eyelid ptosis in each mouse is shown in Table 8.

[0125] Table 8. Degree of ptosis in each mouse

[0126] Group / Animal Number 1 2 3 4 5 6 7 8 9 10 Blank control group 0 0 0 0 0 0 0 0 0 0 Model group 2 3 4 4 0 3 4 4 3 3 Fluoxetine group 4 2 4 0 4 2 4 4 0 2 Example 1 Low-dose group 3 1 2 1 3 4 2 4 4 0 In Example 1, the dosage group 0 1 2 1 0 0 3 2 0 2 Example 1 High-dose group 0 0 0 0 1 1 1 3 1 0 Comparative Example 1 3 2 1 2 0 2 4 2 4 4

[0127] The scores for the degree of ptosis in each mouse are shown in Table 9.

[0128] Table 9 Scoring of eyelid ptosis in each group of mice

[0129] Group Degree of ptosis / point Blank control group 0 Model group 3±0.39** Fluoxetine group 2.4±0.42 Example 1 Low-dose group 2.4±0.45 In Example 1, the dosage group <![CDATA[1.1±0.34 ## ]]> Example 1 High-dose group <![CDATA[0.78±0.32 ## ]]> Comparative Example 1 2.6±0.52

[0130] Note: Compared with the control group, **p < 0.01; compared with the model group, ##p < 0.01.

[0131] As shown in Tables 8 and 9, when the degree of eyelid ptosis in mice was observed half an hour after reserpine injection, the degree of eyelid ptosis in the model group was significantly higher than that in the blank group (p < 0.01); the degree of eyelid ptosis in the low-dose group in Example 1 was significantly reduced compared with that in the model group (p < 0.01), and this was dose-dependent.

[0132] The comparison of the escape rates of mice in each group is shown in Table 10.

[0133] Table 10 Comparison of mouse escape rates in each group

[0134] Group Number of those who have broken out of the circle Total number of animals Out-of-circle rate / share Blank control group 10 10 100 Model group 0 10 0 Fluoxetine group 5 10 50 Example 1 Low-dose group 3 10 30 In Example 1, the dosage group 3 10 30 Example 1 High-dose group 6 9 66.67 Comparative Example 1 1 10 10

[0135] As shown in Table 10, the mice in the blank group had normal activity and an out-of-circle rate of 100; the original prescription group (comparative example 1) had an out-of-circle rate of 10; the mice in the new prescription group were significantly more active than the model group, with an out-of-circle rate of 30 in the low-dose group, 30 in the medium-dose group, and 66.7 in the high-dose group.

[0136] The plateau finding rates of each group of mice are compared in Table 11. The total distance traveled, latency, and average speed in the water maze of each group of mice are compared in Table 12.

[0137] Table 11 Comparison of platform finding rates among mice in each group

[0138] Group Number of logins Total number of animals Platform access rate / shares Blank control group 8 10 80 Model group 2 10 20 Fluoxetine group 4 10 40 Example 1 Low-dose group 4 10 40 In Example 1, the dosage group 2 10 20 Example 1 High-dose group 1 9 11.11 Comparative Example 1 1 10 10

[0139] Table 12 Comparison of total distance, latency, and average speed in the water maze for each group of mice.

[0140] Group Incubation period Total distance average speed Blank control group 45.01±9.79 687.9±135.9 13.69±1.26 Model group 82.77±4.51** 320.7±48.33** 3.857±0.50** Fluoxetine group 58.71±12.77# 289.4±57.85 5.430±0.65 Example 1 Low-dose group 76.84±6.41 577.9±80.11## 7.938±1.22## In Example 1, the dosage group 88.28±1.32 583.4±105.6## 6.683±1.25# Example 1 High-dose group 83.24±6.35 399.5±79.57 4.719±0.84 Comparative Example 1 83.16±6.44 523.3±111.5## 6.425±1.19

[0141] Note: Compared with the control group, *p < 0.05, **p < 0.01; compared with the model group, #p < 0.05, ##p < 0.01.

[0142] The water maze test results showed that after reserpine injection, mice exhibited despair, stopped swimming, and merely floated on the surface, while the control group swam normally and had a shorter latency period to detect the platform. Analysis of latency, total distance traveled, and average speed revealed that the model group mice had a significantly longer latency period than the control group (p < 0.01); a significantly shorter total distance traveled (p < 0.01); and a significantly shorter average speed (p < 0.01). In Example 1, the medium-dose group showed significantly increased total distance traveled and average speed (p < 0.05).

[0143] The comparison results of 5-HT, DA, and BDNF levels in the serum of each group of mice are shown in Table 13. The comparison results of 5-HT, DA, and BDNF levels in the brain homogenates of each group of mice are shown in Table 14.

[0144] Table 13 Comparison of serum 5-HT, DA and BDNF levels in each group of mice

[0145]

[0146]

[0147] Table 14 Comparison of 5-HT, DA, and BDNF levels in mouse brain homogenates of each group

[0148] Group 5-HT (ng / mL) DA (ng / mL) BDNF (ng / mL) Blank control group 222.5±1.929 127.2±12.28 579.1±65.19 Model group 144.7±1.705** 32.16±10.40** 435.0±2.354 Fluoxetine group 136.6±4.110 261.0±8.804## 388.3±24.44 Example 1 Low-dose group 135.4±4.914 255.7±8.584## 482.1±14.73 In Example 1, the dosage group 128.3±4.290 242.2±9.865## 428.9±22.72 Example 1 High-dose group 143.5±4.139 260.2±10.51## 420.5±26.20 Comparative Example 1 213.7±40.33## 226.3±2.628## 436.3±23.25

[0149] As shown in Table 13, the serum levels of 5-HT, DA, and BDNF in the model group mice were significantly lower than those in the blank group (p < 0.05). The example groups showed varying degrees of increase compared to the model group, with significant increases in DA and BDNF in the low, medium, and high dose groups, which were dose-dependent.

[0150] As shown in Table 14, the contents of 5-HT, DA and BDNF in the brain homogenate of mice in the model group were significantly lower than those in the blank group (p < 0.05). The contents of DA in the example group were significantly higher than those in the model group, while there was no significant difference in 5-HT and BDNF.

[0151] For example, mouse slices of acute depression model Figure 2As shown.

[0152] Depend on Figure 2 It was found that, compared to the control group, the model group showed a decrease in the number of neurons in the cerebral cortex and disordered cell nuclei; disordered neuronal arrangement and cell nuclei in the CA1 and CA3 areas of the hippocampus; a decrease in the number of neurons in the DG area of ​​the hippocampus, significantly enlarged gaps, and overall downward shrinkage of the hippocampus. Compared to the model group, the example group showed disordered and reduced number of cortical neurons, disordered cell arrangement in the CA area of ​​the hippocampus, and some recovery observed in the DG area, but the cell arrangement remained disordered.

[0153] Therefore, the present invention adopts the above-mentioned traditional Chinese medicine composition, medicine and preparation method for treating mild depression. This honey paste is more effective against depression, especially against changes in animal behavior, and is easy to produce in modern industrial production.

[0154] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A traditional Chinese medicine composition for treating mild depression, characterized in that, Includes the following weight groups: 10-20 parts of Terminalia chebula pulp, 15-20 parts of Terminalia chebula pulp, 15-20 parts of Phyllanthus emblica peel, 15-20 parts of Terminalia chebula fruit, 5-10 parts of cored Terminalia chebula vine root, 7-10 parts of Polygonum hydropiper, 7-10 parts of Cuscuta chinensis, 7-10 parts of Lavender, and 40-600 parts of refined honey.

2. The traditional Chinese medicine composition for treating mild depression according to claim 1, characterized in that, Includes the following weight groups: 16-18 parts of Terminalia chebula pulp, 16-18 parts of Terminalia chebula pulp, 16-18 parts of Phyllanthus emblica peel, 16-18 parts of Terminalia chebula fruit, 5-10 parts of cored Terminalia chebula vine root, 7-10 parts of Polygonum hydropiper, 7-10 parts of Cuscuta chinensis, 8-12 parts of Lavender, and 40-600 parts of refined honey.

3. The traditional Chinese medicine composition for treating mild depression according to claim 1, characterized in that, Includes the following weight groups: 18 parts of Terminalia chebula pulp, 18 parts of Terminalia chebula pulp, 18 parts of Phyllanthus emblica peel, 18 parts of Terminalia chebula fruit, 5-10 parts of cored Terminalia chebula vine root, 7-10 parts of Polygonum hydropiper, 7-10 parts of Cuscuta chinensis, 12 parts of Lavender, and 40-600 parts of refined honey.

4. A method for preparing a traditional Chinese medicine composition for treating mild depression, characterized in that, Includes the following steps: S1. Raw material pretreatment: The Terminalia chebula pulp in Kabul is stir-fried with almond oil, the Terminalia chebula pulp and Terminalia chebula are stir-fried with pitted almond oil, and the Phyllanthus emblica peel is soaked in milk. S2. Take the Terminalia chebula pulp, Terminalia chebula pulp, Terminalia chebula fruit, and Phyllanthus emblica peel obtained in S1, mix and pulverize them, and pass them through a 100-mesh sieve to obtain drug mixture powder 1; S3. Mix and pulverize the cored fruit vine root, water dragon bone, dodder and lavender at low temperature, and pass through a 100-mesh sieve to obtain drug mixture powder 2; S4. Add drug mixture 1 obtained in S2 to drug mixture 2 obtained in S3, stir and mix, remove static electricity, and obtain drug mixture 3. S5. Add the drug mixture powder 3 obtained in S4 to the refined honey, stir and mix to obtain the traditional Chinese medicine composition.

5. A method for preparing a traditional Chinese medicine composition for treating mild depression according to claim 4, characterized in that, In S1, the frying temperature is 100-140℃ and the frying time is 10-15 minutes.

6. The method for preparing a traditional Chinese medicine composition for treating mild depression according to claim 4, characterized in that, In step S4, first add drug powder 2 and stir for 5-10 minutes. Then slowly add drug powder 1 in multiple batches. The amount of drug powder 1 added at one time is 10%-20% of the weight of drug powder 2. The stirring time for drug powder 1 and drug powder 2 is 30-40 minutes.

7. A method for preparing a traditional Chinese medicine composition for treating mild depression according to claim 4, characterized in that, In S5, first add refined honey with a moisture content of 20% to 24%, cool the temperature to 25 to 30°C, then add the drug mixture powder 3, and stir for 20 to 30 minutes.

8. A medication for treating mild depression, characterized in that, It includes pharmaceutically acceptable excipients and the traditional Chinese medicine composition, wherein the excipients are one or more of the following: excipients, fillers, diluents, humectants, preservatives, sweeteners, and aromatics.

9. A medicament for treating mild depression according to claim 8, characterized in that, The dosage form of the medicine is one of the following: honey paste, powder, or pill.

10. A medicament for treating mild depression according to claim 8, characterized in that, The excipients also include one or more of starch, dextrin, and lactose.

Images