Traditional Chinese medicine preparation for soothing nerves and relieving depression and application thereof

Abstract

The invention provides a traditional Chinese medicine preparation for soothing nerves and resolving depression and application thereof, and relates to the technical field of traditional Chinese medicine preparation. The traditional Chinese medicine preparation is prepared from the following seven traditional Chinese medicines: tuber fleeceflower stem, ginkgo leaf, perilla stem, longan shell, lysimachia foenum-graecum hance, winged euonymus twig and spina date seed through optimized combination according to the principle of syndrome differentiation and treatment of traditional Chinese medicine. The traditional Chinese medicine preparation disclosed by the invention has the effects of nourishing the heart, soothing the nerves and relieving depression, can improve depression-like behaviors of depression model rats and regulate the balance of neurotransmitters 5-HT, DA, NE and GABA in brains of the rats; clinical test results show that the traditional Chinese medicine preparation can remarkably reduce secretion of serum inflammation related factors TNF-alpha, IL-1beta and IL-10 of insomnia patients suffering from depression co-disease, improve sleep quality of the patients, relieve depression degree, reduce the occurrence rate of adverse reactions and improve the total effective rate of clinical treatment, and has a good clinical application prospect. A scheme which is good in effect, safe and easy to accept is provided for treatment of insomnia caused by depression.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine pharmaceutical preparation, and in particular to a traditional Chinese medicine preparation for calming nerves and relieving depression and application thereof. Background Art

[0002] Depression, also known as depressive disorder, is a common mental illness. Most patients show obvious and persistent low mood, accompanied by decreased activity, cognitive impairment, slow thinking, and even suicidal behavior, which seriously affects the life and health of patients. Insomnia refers to a subjective experience that despite having a suitable sleep opportunity and sleep environment, one is still dissatisfied with the sleep time and / or sleep quality, and affects daytime function or causes physical discomfort. Abnormal emotions are closely related to insomnia, and there is a bidirectional relationship between insomnia and depression. Insomnia is an important risk factor for depression. About 20%-50% of insomnia patients show symptoms of depression, and 80% of patients in the depressive episode period show symptoms of insomnia. The two often co-occur in clinical practice, but the specific mechanism of co-morbidity of insomnia and depression is still unclear. Western medicine believes that it is closely related to inflammation, brain-derived neurotrophic factor, GABA system, hypothalamus-pituitary-adrenal axis, monoamine neurotransmitters, norepinephrine and dopamine release. At present, the clinical treatments for comorbid insomnia caused by depression mainly include drug therapy, psychotherapy, etc. However, the effective period of existing antidepressants and sleeping pills is usually 2-4 weeks, and there are problems such as poor symptom control, large side effects, strong dependence, and poor patient compliance, which have a great impact on the physical and mental health of patients.

[0003] Traditional Chinese medicine can treat depression and insomnia from the root based on the pathogenesis on the basis of dialectical analysis, and has the advantages of high safety, low trauma, and mild adverse reactions. According to clinical manifestations, traditional Chinese medicine classifies depression and insomnia into the categories of "depression" and "insomnia". The location of "depression" is mostly the heart and liver. It is believed that the liver and blood should be replenished to make the liver soul calm and the liver depression will be eliminated; the pathogenesis of "insomnia" is caused by the miscommunication of yin and yang, and the deficiency of yin cannot restrain yang, and the yang does not enter the yin and floats outside, causing insomnia. The location of the disease is in the heart, liver, lung, kidney and other internal organs; the pathogenesis of depression and insomnia is related to the restlessness of the spirit, the liver is not smooth, and the emotions are not smooth. The location of the disease involves the heart, liver, spleen, kidney, and brain. However, there is a lack of drugs specifically for the treatment of depression and insomnia on the market. Therefore, providing a drug that can effectively treat depression and insomnia is a technical problem that technicians in the field need to solve. Summary of the invention

[0004] 1. Technical issues to be resolved

[0005] In view of the deficiencies in the prior art, the present invention provides a Chinese medicine preparation for calming the nerves and relieving depression and its application.

[0006] (II) Technical solution

[0007] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0008] The invention provides a traditional Chinese medicine preparation for calming nerves and relieving depression. The traditional Chinese medicine preparation is composed of the following raw materials in parts by weight: 5-25 parts of tuberose, 5-25 parts of ginkgo leaves, 1-20 parts of perilla stems, 1-20 parts of longan shells, 1-15 parts of angelica sinensis, 1-20 parts of euphorbia pulex, and 5-25 parts of spiny jujube seeds.

[0009] Furthermore, the Chinese medicine preparation is composed of the following raw materials in parts by weight: 10-20 parts of Polygonum multiflorum, 10-18 parts of Ginkgo biloba leaves, 5-15 parts of Perilla stems, 5-15 parts of Longan shells, 3-8 parts of Lycopodiella vulgaris, 5-15 parts of Psoralea corylifolia, and 10-20 parts of Ziziphus jujuba seeds.

[0010] Furthermore, the Chinese medicine preparation is composed of the following raw materials in parts by weight: 15 parts of Polygonum multiflorum, 12 parts of Ginkgo biloba leaves, 10 parts of Perilla stems, 10 parts of Longan shells, 5 parts of Lycopodiella vulgaris, 10 parts of Psoralea corylifolia, and 15 parts of Ziziphus jujuba seeds.

[0011] The invention provides a traditional Chinese medicine preparation for calming nerves and relieving depression. The traditional Chinese medicine preparation is prepared into an acceptable oral dosage form by adding medically acceptable auxiliary materials according to a conventional traditional Chinese medicine pharmaceutical method.

[0012] Furthermore, the oral dosage forms include granules, powders, decoctions, pills, pastes, freeze-dried powders, etc.

[0013] Furthermore, a Chinese herbal decoction for calming the nerves and relieving depression is prepared according to the following steps:

[0014] (1) Weigh the raw materials according to the above weight proportions, add water until the water surface is 2-3 cm above the medicinal materials, and soak for 20-30 minutes;

[0015] (2) Transfer the above medicinal materials and soaking liquid to a casserole and boil, then continue to simmer for 20-30 minutes. Filter the decoction while it is still hot, repeat twice, and combine the decoctions.

[0016] The present invention provides application of the traditional Chinese medicine preparation in preparing medicine for preventing and / or treating depression comorbid with insomnia.

[0017] The pharmacological effects of each Chinese medicine component in the Chinese medicine composition of the present invention are as follows:

[0018] Polygonum multiflorum: sweet, slightly bitter, neutral in nature, enters the heart and liver meridians; has the effects of nourishing the heart and calming the mind, dispelling wind and unblocking the meridians; used for insomnia, strain, hyperhidrosis, body pain due to blood deficiency, carbuncle, scrofula, wind sore and scabies; Polygonum multiflorum mainly contains quinones, flavonoids, steroids, diphenylethylene derivatives, anthocyanins and volatile components, etc., with pharmacological activities such as sedation and hypnosis, hypoglycemic and lipid-lowering, anti-inflammatory and antioxidant.

[0019] Ginkgo leaves: sweet, bitter, astringent, neutral in nature, enter the heart and lung meridians; have the effects of promoting blood circulation and removing blood stasis, dredge meridians and relieve pain, astringe the lungs and relieve asthma; used for blood stasis blocking the meridians, chest pain and heart pain, hemiplegia due to stroke, lung deficiency cough and asthma, and hyperlipidemia; Ginkgo leaves contain flavonoids, terpenoid lactones, organic acids, alkylphenols, alkylphenolic acids and other chemical components, which have antibacterial, insecticidal, lipid-lowering, antitussive and asthmatic, anti-aging, antioxidant and other pharmacological activities.

[0020] Perilla stem: spicy in taste, warm in nature, enters the lung and spleen meridians; has the effects of regulating qi, relieving fullness, relieving pain, and calming the fetus; used for chest and diaphragm fullness, epigastric pain, belching and vomiting, and fetal movement disorder; Perilla stem contains volatile oils, fatty acids, phenolic acids, flavonoids, triterpenes, anthocyanins, glycosides and other chemical components, which have anti-tumor, anti-emetic, antibacterial, hypoglycemic, and antioxidant pharmacological activities.

[0021] Longan shell: sweet in taste, warm in nature, and belongs to the lung meridian; it has the effects of dispelling wind, detoxifying, healing sores, and promoting tissue regeneration; it is used for vertigo and deafness, carbuncles that do not disappear for a long time, and burns; longan shell is rich in flavonoids, phenolic acids and other chemical components, and has anti-oxidation, anti-aging, anti-tumor, improving blood circulation, lowering cholesterol, analgesic and other pharmacological effects.

[0022] Lingxiangcao: It tastes pungent and sweet, is warm in nature, and enters the lung, Taiyin meridian of the foot, and Yangming meridian; it has the effects of dispelling exterior pathogens, relieving pain, promoting qi, and expelling ascariasis; it is used for colds and headaches, sore throats, toothaches, chest and abdominal discomfort, and ascariasis; Lingxiangcao mainly contains chemical components such as volatile oils, flavonoids, saponins, sterols, coumarins, etc., which have anti-inflammatory, antioxidant, anti-tumor, and antibacterial pharmacological effects.

[0023] Ghost arrow feather: bitter and pungent in taste, cold in nature, and enters the liver meridian; it has the effects of breaking blood and dredging menstruation, detoxifying and reducing swelling, and killing insects. It is used for amenorrhea, abdominal masses, postpartum abdominal pain due to blood stasis, and abdominal pain due to worm accumulation; Ghost arrow feather mainly contains chemical components such as flavonoids, terpenes, lignans, steroids, alkaloids, etc., which have pharmacological effects such as lowering blood sugar, anti-tumor, anti-liver fibrosis, anti-inflammatory, antioxidant, and antibacterial.

[0024] Chinese jujube seeds: sweet and sour in taste, neutral in nature, enter the liver, gallbladder, and heart meridians; has the effects of nourishing the heart and liver, calming the mind and tranquilizing the nerves, astringing sweat, and promoting body fluid production; used for insomnia due to deficiency and restlessness, palpitations and nightmares, physical weakness and sweating, and thirst due to loss of body fluids; Chinese jujube seeds mainly contain saponins, flavonoids, fatty acids, volatile oils and other chemical components, which have pharmacological effects such as sedation and hypnosis, anti-depression, anti-anxiety, and improvement of learning and memory.

[0025] (III) Beneficial effects

[0026] The invention provides a traditional Chinese medicine preparation for calming nerves and relieving depression and application thereof. The traditional Chinese medicine preparation is composed of seven traditional Chinese medicines, namely, radix polyphyllae, ginkgo leaves, perilla stems, longan shells, angelica sinensis, euphorbia pulex and spiny jujube seeds. The prescription follows the principle of treatment based on syndrome differentiation in traditional Chinese medicine, with radix polyphyllae and angelica sinensis as monarch medicines, which have the effects of nourishing the heart and calming nerves, and relieving depression; with ginkgo leaves as ministerial medicines, which enhance the sedative and calming effect; with perilla stems and longan shells as adjuvant medicines, which help the monarch medicine and ministerial medicines to harmonize qi and blood, and calm the mind; with euphorbia pulex and spiny jujube seeds as guiding medicines, which can achieve the effects of promoting blood circulation, unblocking meridians, and promoting sleep and calming nerves. The Chinese medicine preparation of the present invention can improve the depressive-like behavior of depression model rats and regulate the balance of neurotransmitters 5-HT, DA, NE and GABA in the rat brain; clinical trial results show that the Chinese medicine preparation of the present invention can significantly reduce the HAMD and PSQI scores of patients with depression and insomnia, significantly reduce the secretion of serum inflammation-related factors TNF-α, IL-1β and IL-10 of patients, improve the sleep quality of patients, alleviate the degree of depression, reduce the incidence of adverse reactions, and improve the total effective rate of clinical treatment, thus providing a good, safe and easy-to-accept scheme for the treatment of depression and insomnia. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Example 1

[0029] A traditional Chinese medicine preparation for calming the nerves and relieving depression is composed of the following raw materials in parts by weight: 15 parts of tuberose, 12 parts of ginkgo leaves, 10 parts of perilla stems, 10 parts of longan shells, 5 parts of angelica sinensis, 10 parts of euphorbia pulex, and 15 parts of spiny jujube seeds.

[0030] Example 2

[0031] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is composed of the following raw materials in parts by weight: 5 parts of Polygonum multiflorum, 5 parts of Ginkgo biloba leaves, 1 part of Perilla stems, 1 part of Longan shells, 1 part of Lycopodiella vulgaris, 1 part of Psoralea corylifolia, and 5 parts of Semen Ziziphi spinulosae.

[0032] Example 3

[0033] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is composed of the following raw materials in parts by weight: 12 parts of Polygonum multiflorum, 10 parts of Ginkgo biloba leaves, 8 parts of Perilla stems, 8 parts of Longan shells, 7 parts of Lycopodiella vulgaris, 8 parts of Psoralea corylifolia, and 12 parts of Semen Ziziphi spinulosae.

[0034] Example 4

[0035] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is composed of the following raw materials in parts by weight: 25 parts of Polygonum multiflorum, 25 parts of Ginkgo biloba leaves, 20 parts of Perilla stems, 20 parts of Longan shells, 15 parts of Lycopodiella vulgaris, 20 parts of Psoralea corylifolia, and 25 parts of Semen Ziziphi spinulosae.

[0036] Example 5

[0037] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is composed of the following raw materials in parts by weight: 9 parts of Polygonum multiflorum, 7 parts of Ginkgo biloba leaves, 6 parts of Perilla stems, 6 parts of Longan shells, 4 parts of Lycopodiella vulgaris, 6 parts of Psoralea corylifolia, and 9 parts of Semen Ziziphi spinulosae.

[0038] Example 6

[0039] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is composed of the following raw materials in parts by weight: 22 parts of Polygonum multiflorum, 20 parts of Ginkgo biloba leaves, 18 parts of Perilla stems, 18 parts of Longan shells, 13 parts of Lycopodiella vulgaris, 18 parts of Psoralea corylifolia, and 22 parts of Semen Ziziphi spinulosae.

[0040] Example 7

[0041] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is composed of the following raw materials in parts by weight: 7 parts of Polygonum multiflorum, 6 parts of Ginkgo biloba leaves, 5 parts of Perilla stems, 5 parts of Longan shells, 3 parts of Lycopodiella vulgaris, 5 parts of Psoralea corylifolia, and 7 parts of Semen Ziziphi spinulosae.

[0042] Example 8

[0043] The difference between this embodiment and embodiment 1 is that the Chinese medicine preparation is composed of the following raw materials in parts by weight: 18 parts of Polygonum multiflorum, 15 parts of Ginkgo biloba leaves, 13 parts of Perilla stems, 13 parts of Longan shells, 10 parts of Lycopodiella vulgaris, 13 parts of Psoralea corylifolia, and 18 parts of Semen Ziziphi spinulosae.

[0044] Test Example 1

[0045] 1 Materials and methods

[0046] 1.1 Experimental animals

[0047] 42 SPF SD rats, weighing 180-200 g, were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd.

[0048] 1.2 Trial Drugs

[0049] Test substance 1: 15 parts of Polygonum multiflorum, 12 parts of Ginkgo biloba leaves, 10 parts of Perilla stems, 10 parts of Longan shells, 5 parts of Lycopodiella vulgaris, 10 parts of Psoralea corylifolia, and 15 parts of Semen Ziziphi spinulosae.

[0050] Test substance 2: 12 parts of Ginkgo biloba leaves, 10 parts of Perilla stems, 10 parts of Longan shells, 10 parts of Psoralea corylifolia, and 15 parts of Ziziphus jujuba seeds.

[0051] Test substance 3: 15 parts of Polygonum multiflorum, 5 parts of Lycopodiella cernua, 10 parts of Psoralea corylifolia, and 15 parts of Semen Ziziphi spinulosae.

[0052] Test substance 4: 15 parts of Polygonum multiflorum, 12 parts of Ginkgo biloba leaves, 10 parts of Perilla stems, 10 parts of Longan shells, and 5 parts of Lycopodiella vulgaris.

[0053] Weigh each raw material according to the weight portion in the above formula, wash and dry it, soak it in water for 20-30 minutes, transfer it to a casserole and boil it for 20-30 minutes, filter it while hot, repeat twice, combine the two filtrates, and concentrate it to a crude drug content of 1g / mL to obtain the original solution of each Chinese medicine.

[0054] Comparative drug: fluoxetine hydrochloride.

[0055] 1.3 Animal grouping, modeling and drug administration

[0056] After one week of adaptive feeding, 42 SD rats were randomly divided into blank control group, model control group, test group 1-4, and positive control group, with 6 rats in each group. The normal control group was fed with 3 rats per cage, and the model control group and each drug-treated group were fed with 1 rat per cage. The rats were given chronic unpredictable stimulation for five weeks to establish a rat model of depression. The stimulation factors included: fasting for 24 hours, water deprivation for 24 hours, overnight lighting, sleep deprivation environment plus noise, tilting mouse cage, ice water swimming (4℃, 5min), tail clamping (1-1.5min), restraint, and water platform. One stimulus was randomly arranged every day, and the same stimulus did not appear continuously. At the beginning of the stimulation, the drug was administered by gavage. The normal control group and the model control group were given an equal volume of physiological saline, and the test groups 1-4 were given the above-mentioned Chinese medicine stock solution of the test substance 1-4, with a dosage of 50mg / kg. The positive control group was given fluoxetine hydrochloride 3.3mg / kg, once a day, for 4 consecutive weeks.

[0057] 1.4 Behavioral testing

[0058] 1.4.1 Sugar water preference experiment

[0059] The mice were deprived of food and water for 24 hours before the experiment. During the formal experiment, the 1% sucrose solution and distilled water prepared in advance were placed in the mouse cage and changed positions after 1 hour. The consumption of sucrose solution and distilled water was calculated after 24 hours.

[0060] Sugar water preference rate = sugar water consumption / (sugar water consumption+distilled water consumption)×100%.

[0061] 1.4.2 Open field test

[0062] The rats were placed in the center of a 100 cm × 100 cm × 40 cm box and allowed to explore freely for 4 min. The total distance the rats moved and the time they were immobile were recorded using video tracking software. Before testing each rat, the bottom of the box was thoroughly cleaned with 75% ethanol to prevent odors from interfering with the experimental results of the next rat.

[0063] 1.4.3 Novelty inhibits food intake

[0064] Eight food pellets of equal size were placed in the center of an open box measuring 40cm×40cm×45cm. The pellets were put into the box from the same corner after the rats had fasted for 12 hours. The latency of the rats to first forage for food within 5 minutes was recorded. Before testing each rat, the bottom of the box was thoroughly cleaned with 75% ethanol to prevent odor from interfering with the experimental results of the next rat.

[0065] 1.5 Neurotransmitter level measurement

[0066] After the behavioral test, the rats in each group were weighed, anesthetized with 10% chloral hydrate intraperitoneally, decapitated and the brains were removed. The hippocampal tissue was isolated and weighed, and 9 times the amount of normal saline was added to homogenate. The homogenate was centrifuged at 4°C and 12000 rpm for 30 min, and the supernatant was taken. The levels of 5-HT, DA, NE, and GABA in the hippocampal tissue of the rats were detected according to the instructions of the ELISA kit.

[0067] 1.6 Statistical methods

[0068] Graphpad Prism 8.0 software was used for statistical analysis and graphing, and the results were expressed as average values. ± standard deviation (s), and the differences among the groups were compared using one-way analysis of variance, with P < 0.05 being considered statistically significant.

[0069] 2 Results

[0070] 2.1 Effects on the behavior of depression model rats

[0071] The effects of each group of drugs on the depressive-like behavior of depression model rats are shown in Table 1. Compared with the blank control group, the sugar water preference rate of rats in the model control group was significantly reduced (P<0.05), the open field movement distance was significantly shortened (P<0.05), and the foraging latency was significantly prolonged (P<0.05); compared with the model control group, the sugar water preference rate of rats in each drug-treated group was significantly increased (P<0.05), the open field movement distance was significantly increased (P<0.05), and the foraging latency was shortened to varying degrees, indicating that the Chinese medicine preparation of the present invention has the effect of improving the depressive-like behavior of depressed rats, among which the effect of test group 1 is the best.

[0072] Table 1 Comparison of depressive-like behaviors in each group of depression model rats

[0073] Grouping Sugar water preference rate (%) Open field exercise distance (cm) Foraging latency(s) Blank control group <![CDATA[76.58±1.48 a ]]> <![CDATA[177.93±3.74 a ]]> <![CDATA[77.68±11.16 d ]]> Model control group <![CDATA[45.50±1.23 e ]]> <![CDATA[84.13±5.18 e ]]> <![CDATA[182.96±11.91 a ]]> Test Group 1 <![CDATA[74.04±1.40 ab ]]> <![CDATA[189.26±3.89 a ]]> <![CDATA[86.31±6.83 d ]]> Test Group 2 <![CDATA[53.96±1.45 d ]]> <![CDATA[99.01±3.57 d ]]> <![CDATA[169.69±9.61 ab ]]> Experiment 3 groups <![CDATA[61.89±1.59 c ]]> <![CDATA[120.05±6.10 c ]]> <![CDATA[149.16±9.98 b ]]> Test 4 groups <![CDATA[71.33±1.07 b ]]> <![CDATA[152.32±5.44 b ]]> <![CDATA[117.16±8.99 c ]]> Positive control group <![CDATA[71.90±1.45 b ]]> <![CDATA[163.63±5.38 b ]]> <![CDATA[103.08±6.76 cd ]]>

[0074] Note: Data in the same column with different letters indicate significant differences (P<0.05), and data with the same letters indicate no significant differences (P>0.05).

[0075] 2.4 Effects on neurotransmitter levels in the brain of depression model rats

[0076] As shown in Table 2, compared with the blank control group, the neurotransmitter levels in the brain of rats in the model control group were significantly reduced (P<0.05); compared with the model control group, the neurotransmitter 5-HT, DA, NE, and GABA levels in rats in each drug-treated group were significantly increased (P<0.05, P<0.01), indicating that the Chinese medicine preparation of the present invention can promote the release of neurotransmitters in the brain of depression model rats, among which the effect of test group 1 was the best.

[0077] Table 2 Comparison of neurotransmitter levels in the brain of depression model rats in each group

[0078] Grouping 5-HT (ng / mL) DA (ng / mL) NE (ng / mL) GABA (μmol / L) Blank control group 169.34±4.08 117.08±2.05 156.21±3.73 108.25±1.30 Model control group <![CDATA[134.84±1.98 ## ]]> <![CDATA[74.41±2.51 ## ]]> <![CDATA[103.18±2.18 ## ]]> <![CDATA[65.40±1.13 ## ]]> Test Group 1 <![CDATA[161.02±1.90 ** ]]> <![CDATA[105.22±2.06 ** ]]> <![CDATA[144.16±1.50 ** ]]> <![CDATA[96.71±1.75 ** ]]> Test Group 2 <![CDATA[140.38±0.99 * ]]> <![CDATA[81.82±1.67 ** ]]> <![CDATA[112.84±2.46 ** ]]> <![CDATA[72.73±1.71 ** ]]> Experiment 3 groups <![CDATA[144.74±1.83 ** ]]> <![CDATA[85.65±1.40 ** ]]> <![CDATA[118.04±1.68 ** ]]> <![CDATA[78.36±0.82 ** ]]> Test 4 groups <![CDATA[153.70±1.45 ** ]]> <![CDATA[95.88±1.22 ** ]]> <![CDATA[135.92±1.18 ** ]]> <![CDATA[86.62±1.50 ** ]]> Positive control group <![CDATA[157.73±1.67 ** ]]> <![CDATA[99.88±2.14 ** ]]> <![CDATA[141.03±0.94 ** ]]> <![CDATA[92.44±1.08 ** ]]>

[0079] Note: Compared with the blank group, # P<0.01, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01.

[0080] 3 Discussions

[0081] The above test results show that the Chinese medicine preparation of the present invention can significantly increase the sugar water preference rate of depression model rats, increase the open field movement distance, shorten the foraging latency, and significantly improve the depression-like behavior of depression model rats; at the same time, the Chinese medicine preparation of the present invention can significantly increase the levels of neurotransmitters 5-HT, DA, NE, and GABA in the brain of depression model rats. Among the drug administration groups, the improvement effect of test group 1 on depression model rats is the most significant, and the effects of test groups 2-4 are weakened to varying degrees due to the lack of some Chinese medicines, indicating that the Chinese medicine preparation of the present invention is obtained through Chinese medicine syndrome differentiation and treatment, and reasonable optimization, and each Chinese medicine component is indispensable.

[0082] Test Example 2

[0083] 1 Materials and methods

[0084] 1.1 General Information

[0085] The clinical data of 96 patients with depression and insomnia admitted to a hospital in Zhengzhou from March 2023 to March 2024 were selected and randomly divided into a control group and an observation group, with 48 cases in each group. There were 22 males and 26 females in the control group, aged 22-50 years, with an average age of (34.67±11.83) years, and an average course of disease of (0.83±0.43) years; there were 19 males and 29 females in the observation group, aged 20-51 years, with an average age of (35.33±11.43) years, and an average course of disease of (0.92±0.37) years. There was no significant difference in gender, age, and course of disease between the two groups (P>0.05), and they were comparable.

[0086] 1.2 Diagnostic criteria

[0087] 1.2.1 Western medicine diagnostic criteria

[0088] Meet the diagnostic criteria for depression and insomnia in the "Chinese Classification and Diagnostic Criteria for Mental Disorders". Combined with the symptoms of depressive disorder, there is difficulty falling asleep for more than one month, frequent awakening, frequent awakening at night, difficulty falling asleep after waking up, drowsiness during the day, lack of sleep, etc., and there are also symptoms such as depression, frustration, fatigue, and low self-evaluation.

[0089] 1.2.2 TCM diagnostic criteria

[0090] It meets the dialectical criteria for depression in the "Standards for Diagnosis and Treatment of Chinese Medicine Diseases": mental depression, fullness in the chest and flanks, sighing, excessive worry, frequent dreams and easy awakening, insomnia and forgetfulness, poor appetite, palpitations, fatigue, dull complexion, pale tongue, thin coating, and a thready and weak pulse.

[0091] 1.3 Inclusion and Exclusion Criteria

[0092] 1.3.1 Inclusion criteria

[0093] Age over 18 years old; meet the Chinese and Western medicine diagnostic criteria for insomnia; complete clinical data; patients and their families agree to participate in the study and sign the informed consent form.

[0094] 1.3.2 Exclusion criteria

[0095] The patient's insomnia is related to external interference; accompanied by severe damage to the hematopoietic system and liver and kidney systems; allergy to therapeutic drugs; communication barriers, etc.

[0096] 1.4 Treatment

[0097] The control group was given fluoxetine hydrochloride capsules, 20 mg / time, twice a day; estazolam tablets, taken orally before bedtime, 2 mg / time, once a day, for 6 weeks.

[0098] The observation group was treated with the control drug in combination with the water decoction of the Chinese medicine preparation of the present invention. Prescription: 15 parts of Polygonum multiflorum, 12 parts of Ginkgo biloba leaves, 10 parts of Perilla stems, 10 parts of Longan shells, 5 parts of Lycopodiella vulgaris, 10 parts of Euphorbia milii, 15 parts of Semen Ziziphi spinulosae; 1 dose / day, decocted in water, taken in the morning and evening, and continued for 6 weeks.

[0099] 1.5 Observation indicators

[0100] 1.5.1 Hamilton Depression Rating Scale (HAMD) score

[0101] The 24-item HAMD version is used, including the total score and the level of depression status. The higher the total score, the more severe the depression state. The depression level grading standard is: normal: <8 points; 8≤possible depression≤19; 20≤depression≤35; severe depression>35 points.

[0102] 1.5.2 Pittsburgh Sleep Quality Index (PSQI) Score

[0103] The Pittsburgh Sleep Quality Index was used to assess the sleep status of patients before and after treatment. The Pittsburgh Sleep Quality Index includes 19 self-assessment items and 5 other-assessment items. The total score is 0-21 points, including sleep effect, sleep feeling, and sleep sustainability, each with 7 points. The score is positively correlated with the patient's sleep quality.

[0104] 1.5.3 Incidence of adverse reactions

[0105] Adverse reactions in the two groups were observed and recorded, including dry mouth, nausea, dizziness, drowsiness, weight gain, etc.

[0106] 1.6 Neurotransmitter levels

[0107] Before and after treatment, 4 mL of fasting venous blood was collected from the patients in the morning, and the supernatant was obtained after centrifugation at 3500 rpm for 15 min. ELISA kits were used to detect the levels of TNF-α, IL-1β, and IL-10 in serum.

[0108] 1.7 Criteria for determining efficacy

[0109] The efficacy evaluation criteria are formulated based on the HAMD score. Clinical cure: HAMD score reduction rate ≥ 75%, normal sleep at night or sleep > 6 hours; marked effect: HAMD score reduction rate ≥ 50%, increased sleep time at night ≥ 3 hours; effective: HAMD score reduction rate ≥ 25%, increased sleep time at night < 3 hours; ineffective: HAMD score reduction rate < 25%, no improvement in insomnia, or even worsening.

[0110] Total clinical efficacy = (clinical cure + marked effect + effective) cases / total number of cases × 100%

[0111] 1.8 Statistical methods

[0112] SPSS 20.0 statistical software was used for data analysis. Count data were expressed as percentages (%) and inter-group comparisons were performed using χ 2 Test; average ± standard deviation (s) represents measurement data. The inter-group comparison was performed with the non-independent sample t-test, and the intra-group comparison was performed with the paired sample t-test. The difference was considered statistically significant at P < 0.05.

[0113] 2 Results

[0114] 2.1 Effect on patients’ HAMD and PSQI scores

[0115] As shown in Table 3, there was no significant difference in HAMD and PSQI scores between the control group and the observation group before treatment (P>0.05); after 6 weeks of treatment, the HAMD and PSQI scores of the control group and the observation group were significantly lower than those before treatment (P<0.01), and the HAMD and PSQI scores of the observation group were significantly lower than those of the control group (P<0.01), indicating that the Chinese medicine preparation of the present invention can improve the sleep quality of patients and alleviate the degree of depression in patients.

[0116] Table 3 Comparison of HAMD and PSQI scores between the two groups before and after treatment (points)

[0117]

[0118] Note: Compared with the group before treatment, * P<0.05, ** P<0.01; compared with the control group after treatment, # P<0.01, ## P<0.01.

[0119] 2.2 Adverse reactions

[0120] As shown in Table 4, in the control group, 1 case of dry mouth, 1 case of nausea, 2 cases of nausea, 4 cases of drowsiness, 5 cases of weight gain occurred, and the incidence of adverse reactions was 27.08%; in the observation group, 1 case of dry mouth, 1 case of drowsiness, 2 cases of weight gain occurred, and the incidence of adverse reactions was 8.33%, which was significantly lower than that of the control group (P<0.05).

[0121] Table 4 Comparison of the incidence of adverse reactions between the two groups (cases, %)

[0122]

[0123] 2.3 Comparison of clinical efficacy

[0124] The clinical efficacy of the control group and the observation group is shown in Table 5. The total effective rate of the control group was 77.1%, and the total effective rate of the observation group was 93.8%, which was significantly higher than that of the control group, and the difference was statistically significant (P<0.05).

[0125] Table 5 Comparison of clinical efficacy between the two groups (cases, %)

[0126]

[0127] 2.4 Effects on the levels of serum inflammation-related factors in patients

[0128] Table 6 shows the effects of the control group and the observation group on the levels of serum inflammation-related factors in patients. There was no significant difference in the levels of serum inflammation-related factors between the control group and the observation group before treatment (P>0.05). After 6 weeks of treatment, the levels of serum inflammation-related factors in the two groups of patients were significantly reduced (P<0.01), and the levels of inflammation-related factors in the observation group were significantly lower than those in the control group (P<0.01), indicating that the Chinese medicine preparation of the present invention can significantly reduce the secretion of inflammation-related factors TNF-α, IL-1β, and IL-10 in the serum of patients, and effectively reduce the inflammatory response of the patient's body.

[0129] Table 6 Comparison of serum inflammation-related factor levels between the two groups of patients (ng / mL)

[0130]

[0131]

[0132] Note: Compared with the group before treatment, * P<0.05, ** P<0.01; compared with the control group after treatment, # P<0.01, ## P<0.01.

[0133] 3 Discussions

[0134] The above test results show that the Chinese medicine preparation of the present invention has the effects of nourishing the heart and calming the mind, relieving depression, can significantly reduce the secretion of serum inflammatory related factors TNF-α, IL-1β, and IL-10 in patients with depression and insomnia, reduce HAMD and PSQI scores, can effectively reduce the body's inflammatory response, improve the patient's sleep quality, reduce the degree of depression, reduce the incidence of adverse reactions, and improve the overall effective rate of clinical treatment, providing a good efficacy, high safety, and easy to accept solution for the treatment of depression and insomnia.

[0135] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Chinese medicine preparation for calming the nerves and relieving depression, characterized in that: The traditional Chinese medicine preparation is composed of the following raw materials in parts by weight: 5-25 parts of Polygonum multiflorum, 5-25 parts of Ginkgo biloba leaves, 1-20 parts of Perilla stems, 1-20 parts of Longan shells, 1-15 parts of Glechoma longifolia, 1-20 parts of Euphorbia milii, and 5-25 parts of Ziziphus jujuba seeds.

2. The Chinese medicine preparation according to claim 1, characterized in that: The traditional Chinese medicine preparation is composed of the following raw materials in parts by weight: 10-20 parts of Polygonum multiflorum, 10-18 parts of Ginkgo biloba leaves, 5-15 parts of Perilla stems, 5-15 parts of Longan shells, 3-8 parts of Lycopodiella vulgaris, 5-15 parts of Euphorbia milii, and 10-20 parts of Ziziphus jujuba seeds.

3. The Chinese medicine preparation according to claim 1, characterized in that: The traditional Chinese medicine preparation is composed of the following raw materials in parts by weight: 15 parts of Polygonum multiflorum, 12 parts of Ginkgo biloba leaves, 10 parts of Perilla stems, 10 parts of Longan shells, 5 parts of Lycopodiella vulgaris, 10 parts of Euphorbia milii, and 15 parts of Ziziphus jujuba seeds.

4. A method for preparing a Chinese medicine preparation for calming nerves and relieving depression according to any one of claims 1 to 3, characterized in that: The drug is prepared into an acceptable oral dosage form by conventional Chinese medicine pharmaceutical methods and combined with medically acceptable auxiliary materials.

5. Use of the Chinese medicine preparation according to any one of claims 1 to 3 in the preparation of a drug for preventing and / or treating depression and comorbid insomnia.

Images