Traditional Chinese medicine preparation for treating or improving depression and preparation method thereof

Abstract

The application provides a traditional Chinese medicine preparation for treating or improving depression and a preparation method thereof, and relates to the technical field of biological medicine, wherein the traditional Chinese medicine preparation is composed of Hypericum perforatum, triticum repen, purple salvia miltiorrhiza, perilla frutescens, orange peel, sweet pine, tribulus terrestris, common rush, amber, bamboo shavings, cassia seed and astragalus complanatus; the results of rat in-vivo experiments show that the traditional Chinese medicine preparation can significantly improve the depressive behavior of depressive model rats, regulate the serum inflammatory factor IL-10, IL-1beta and IL-6 levels of the rats, and simultaneously increase the hippocampus monoamine neurotransmitter DA, NE and 5-HT levels of the rats, so as to play an anti-depression role; the results of clinical experiments show that the traditional Chinese medicine preparation can significantly improve the total effective rate of clinical treatment of depression, reduce the TCM syndrome score, HAMD and PSQI scores of patients, alleviate the clinical symptoms of patients, simultaneously improve the sleep quality of patients, and has no obvious adverse reactions, so that the application provides a treatment scheme with the advantages of multi-target regulation and good safety for the treatment of depression.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a traditional Chinese medicine preparation for treating or improving depression and its preparation method. Background Technology

[0002] Depression is a common mental disorder characterized by significant and persistent low mood, loss of interest, and cognitive impairment; in severe cases, it can lead to suicidal behavior. The World Health Organization (WHO) estimates that over 300 million people worldwide suffer from depression, and the incidence rate is increasing annually, making it a serious public health problem. Currently, first-line clinical treatment for depression primarily relies on Western medicine. Antidepressants available domestically and internationally are mainly classified into seven categories based on their mechanisms of action: tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), serotonin reuptake inhibitors (SSRIs), norepinephrine reuptake inhibitors (NaRIs), norepinephrine and serotonin dual reuptake inhibitors (SNRIs), norepinephrine and specific serotonergic antidepressants (NaSSAs), and serotonin receptor blockers (SRIs). However, these drugs have significant side effects and may threaten other bodily functions during treatment. For example, adverse reactions such as weight fluctuations, gastrointestinal discomfort, allergic reactions, sexual dysfunction, and insomnia may occur, leading to poor treatment compliance and a high risk of relapse. In addition, Western medicines are slow to take effect, requiring an average of 47 days to become effective, and the clinical efficacy rate is only 1 / 3. One-third to one-half of patients will relapse within one year after the onset of the disease, making it difficult to meet the treatment needs of patients.

[0003] In contrast, Traditional Chinese Medicine (TCM) possesses unique advantages in the treatment of depression. Traditional Chinese medicine theory holds that depression is primarily related to pathogenesis such as "liver qi stagnation," "phlegm-heat disturbing the mind," and "qi and blood deficiency." Treatment emphasizes holistic regulation, employing methods such as soothing the liver and relieving stagnation, resolving phlegm and opening the orifices, and tonifying qi and nourishing blood to achieve both symptomatic and root-cause relief. Furthermore, TCM treatments generally utilize compound formulas, characterized by the diversity of chemical components and multi-target pharmacological effects. These formulas can act through multiple pathways, exhibiting synergistic effects while avoiding the side effects and toxicity caused by single-pathway action. Although some TCM herbs have shown efficacy in antidepressant treatment, the variety of TCM preparations specifically for antidepressant use on the market remains limited, and some TCM preparations suffer from unstable efficacy and unclear mechanisms of action. Therefore, developing a TCM preparation for antidepressant treatment with definite efficacy, a clear mechanism of action, and high safety is of significant practical importance. Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] In view of the shortcomings of the prior art, the present invention provides a traditional Chinese medicine preparation for treating or improving depression and a method for preparing the same.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] This invention provides a traditional Chinese medicine preparation for treating or improving depression, the preparation comprising the following parts by weight of traditional Chinese medicine raw materials: 20-40 parts of St. John's wort, 15-35 parts of wheat bran, 15-35 parts of Salvia miltiorrhiza, 13-32 parts of Perilla frutescens stem, 10-30 parts of Citrus reticulata peel, 10-30 parts of Nardostachys jatamansi, 3-20 parts of Tribulus terrestris, 5-25 parts of Juncus effusus, 3-20 parts of amber, 5-25 parts of bamboo shavings, 3-22 parts of Cassia tora seed, and 5-25 parts of Astragalus complanatus seed.

[0009] Furthermore, the traditional Chinese medicine preparation is composed of the following traditional Chinese medicine raw materials in parts by weight: 25-35 parts of St. John's wort, 20-30 parts of wheat bran, 20-30 parts of Salvia miltiorrhiza, 18-26 parts of Perilla frutescens stem, 15-25 parts of Citrus reticulata peel, 15-25 parts of Nardostachys jatamansi, 5-15 parts of Tribulus terrestris, 10-20 parts of Juncus effusus, 5-15 parts of amber, 10-20 parts of bamboo shavings, 8-16 parts of Cassia tora seed, and 10-20 parts of Astragalus complanatus seed.

[0010] Furthermore, the traditional Chinese medicine preparation is composed of the following traditional Chinese medicine raw materials in parts by weight: 30 parts of St. John's wort, 25 parts of wheat bran, 25 parts of Salvia miltiorrhiza, 22 parts of Perilla frutescens stem, 20 parts of Citrus reticulata peel, 20 parts of Nardostachys jatamansi, 10 parts of Tribulus terrestris, 15 parts of Juncus effusus, 10 parts of amber, 15 parts of bamboo shavings, 12 parts of Cassia tora seed, and 15 parts of Astragalus complanatus seed.

[0011] This invention provides a method for preparing the traditional Chinese medicine preparation, wherein the preparation is prepared into an oral dosage form, including pills, powders, granules, oral liquids, decoctions, and tablets, using conventional pharmaceutical methods and with medically acceptable excipients.

[0012] Furthermore, the preparation method of the traditional Chinese medicine granules includes the following steps:

[0013] (1) Weigh each Chinese herbal raw material according to the above weight proportions, wash, dry, and pulverize into coarse powder, and pass through a 24-mesh sieve;

[0014] (2) Mix the above coarse powder evenly, add 3-8 times the weight of 50% ethanol solution and soak for 30-60 min, then extract by ultrasonication 2-3 times, 30-50 min each time, combine the extracts, concentrate under reduced pressure and vacuum to an extract with a relative density of 1.05-1.30, and then spray dry to granulate to obtain the Chinese medicine preparation granules of the present invention.

[0015] Furthermore, in step (2), the frequency of ultrasonic extraction is 40 kHz; the temperature of vacuum concentration is 45-55℃ and the vacuum degree is -0.08MPa; the inlet air temperature of spray drying is 180℃ and the outlet air temperature is 90℃.

[0016] This invention provides the use of the aforementioned traditional Chinese medicine preparation in the preparation of drugs for treating and / or improving depression.

[0017] The pharmacological effects of each raw material in the traditional Chinese medicine preparation of this invention are as follows:

[0018] Hypericum perforatum L. (family Clusiaceae): The dried aerial parts of the plant Hypericum perforatum L. It has a pungent taste and is cold in nature. It enters the liver meridian. It has the effects of soothing the liver and relieving depression, clearing heat and promoting diuresis, reducing swelling and promoting lactation. It is used for liver qi stagnation, emotional distress, chest tightness, joint swelling and pain, mastitis, and insufficient lactation.

[0019] Purple Salvia: The dried root of *Alvia przewalskii* Maxim. (Lamiaceae family). It has a bitter taste and slightly cold nature. It enters the heart, pericardium, and liver meridians. It has the effects of promoting blood circulation and removing blood stasis, calming the mind and soothing the nerves, draining pus, and relieving pain. It is used for angina pectoris, irregular menstruation, dysmenorrhea, amenorrhea, metrorrhagia, leukorrhea, abdominal masses, accumulations, abdominal pain due to blood stasis, joint pain, palpitations, insomnia, and malignant sores and carbuncles.

[0020] Floating wheat: The dried, light, and shriveled fruit of *Triticum aestivum* L., a plant in the Poaceae family. It has a sweet taste and cool properties. It is used to invigorate qi, stop sweating, and clear heat. It is used for spontaneous sweating, night sweats, yin deficiency fever, and steaming bone fever.

[0021] Perilla stem: The dried stem of Perilla frutescens (L.) Britt., a plant in the Lamiaceae family. It has a pungent taste and warm properties. It enters the lung and spleen meridians. It has the effects of regulating qi, relieving chest tightness, alleviating pain, and calming the fetus. It is used for chest tightness, stomach pain, belching and vomiting, and threatened miscarriage.

[0022] Green peel: The dried peel of the young or immature fruit of Citrus reticulata Blanco and its cultivated varieties, belonging to the Rutaceae family. It tastes bitter and pungent, and is warm in nature. It enters the liver, gallbladder, and stomach meridians. It has the effects of soothing the liver and regulating qi, eliminating stagnation and resolving masses. It is used for chest and rib pain, hernia pain, mastopathy, breast abscess, food stagnation and qi stagnation, and abdominal distension and pain.

[0023] Nardostachys jatamansi DC., a plant in the Valerianaceae family, is a dried root and rhizome. It has a pungent and sweet taste, and is warm in nature. It enters the spleen and stomach meridians. It has the effects of regulating qi and relieving pain, relieving stagnation and invigorating the spleen. It is used for abdominal distension, loss of appetite, and vomiting; externally, it is used to treat toothache and beriberi with swelling and sores.

[0024] Tribulus terrestris L., the dried, ripe fruit of the plant Tribulus terrestris L. (family Zygophyllaceae). It has a pungent and bitter taste, and is slightly warm in nature. It enters the liver meridian. It has the effects of calming the liver and relieving depression, promoting blood circulation and dispelling wind, improving eyesight, and relieving itching. It is used for headaches and dizziness, chest and rib pain, mastitis, red and pterygium eyes, and itchy rashes.

[0025] Juncus effusus L. (Juncus effusus L.), a plant in the Juncaceae family. It has a sweet and bland taste, and is slightly cold in nature. It enters the heart, lung, and small intestine meridians. It has the effects of clearing heart fire and promoting urination. It is used for insomnia due to irritability, scanty and painful urination, and mouth and tongue sores.

[0026] Amber: A hydrocarbon compound formed from the resin of ancient pine trees that has been buried underground for a long time and solidified. It has a sweet taste and neutral properties. It enters the heart, liver, and small intestine meridians. It has the effects of calming the nerves and relieving convulsions, dispersing blood stasis and stopping bleeding, and promoting urination. It is used for infantile convulsions, epilepsy, palpitations, insomnia, hematuria, urinary retention, amenorrhea, postpartum abdominal pain due to blood stasis, carbuncles, boils, and traumatic injuries.

[0027] Bamboo shavings: The dried middle layer of the stems of several grasses, including *Bambusa tuldoides* Munro, *Sinocalamus beecheyanus* (Munro) McClure var. pubescens PF Li, or *Phyllostachys nigra* (Lodd.) Munro var. henonis (Mitf.) Stapf ex Rendle. It has a sweet taste and slightly cold nature. It enters the lung, stomach, heart, and gallbladder meridians. It has the effects of clearing heat and resolving phlegm, relieving irritability, and stopping vomiting. It is used for cough with phlegm-heat, phlegm due to gallbladder fire, palpitations, insomnia, phlegm-induced coma due to heart irritability, aphasia due to stroke, vomiting due to stomach heat, morning sickness during pregnancy, and threatened abortion.

[0028] Cassia seed: The dried, mature seed of *Cassia obtusifolia* L. or *Cassia tora* L., both belonging to the legume family. It tastes sweet, bitter, and salty, and is slightly cold in nature. It enters the liver and large intestine meridians. It has the effects of clearing heat and improving eyesight, moistening the intestines and relieving constipation. It is used for red, sore eyes, photophobia with excessive tearing, headache and dizziness, blurred vision, and constipation.

[0029] Astragalus complanatus R. Br., a legume, is the dried, mature seed of the plant. It has a sweet taste and warm properties. It enters the liver and kidney meridians. It tonifies the kidneys and strengthens yang, consolidates essence and reduces urination, nourishes the liver and improves eyesight. It is used for kidney deficiency causing lower back pain, seminal emission and premature ejaculation, enuresis and frequent urination, leukorrhea, dizziness, and blurred vision.

[0030] (III) Beneficial Effects

[0031] This invention provides a traditional Chinese medicine preparation for treating or improving depression and its preparation method.

[0032] The formula uses Hypericum perforatum, Salvia miltiorrhiza, and Triticum aestivum as the principal herbs, targeting the Qi, Blood, and Heart meridians respectively. One herb relieves Qi stagnation, another clears blood stasis, and the third nourishes Heart Qi, directly addressing the core pathogenesis of depression. Hypericum perforatum is a key herb for soothing the liver, relieving depression, and regulating emotions. Its clear and penetrating nature allows it to relieve stagnation of Qi in the Liver meridian and clear away latent pathogenic heat in the Qi level. Salvia miltiorrhiza is good at activating blood circulation, removing blood stasis, and clearing blood stasis caused by prolonged Qi stagnation; it also clears the heart, relieves irritability, cools the blood, and calms the mind, treating insomnia, palpitations, and restlessness caused by blood stasis and heat disturbing the heart. Triticum aestivum nourishes the heart, relieves irritability, invigorates Qi, and calms the mind, specifically treating restlessness caused by depression. Perilla frutescens stem, Citrus reticulata peel, Nardostachys jatamansi, and Tribulus terrestris are used as assistant herbs, simultaneously soothing the liver and regulating the spleen, and mutually reinforcing Qi and relieving depression, assisting the principal herbs in relieving depression, promoting Qi circulation, and alleviating pain. Perilla stem regulates qi, soothes the stomach, and invigorates the spleen, effectively treating epigastric and abdominal distension caused by liver qi stagnation affecting the spleen and impaired function of the middle jiao. Green tangerine peel is bitter, pungent, and warm, specifically entering the liver meridian, effectively soothing the liver, dispersing qi stagnation, and relieving chest and rib pain. Nardostachys jatamansi is aromatic and dispersing, relieving stagnation, invigorating the spleen, regulating qi, and relieving pain, invigorating spleen qi, smoothing qi flow, and relieving stagnation, assisting the principal herb in promoting the flow of qi in the epigastric and abdominal regions, and improving spleen and stomach disharmony caused by emotional depression. Tribulus terrestris soothes the liver, relieves stagnation, invigorates blood, and dispels wind, assisting the principal herb in soothing the liver, regulating qi, and relieving stagnation, while also calming liver yang, clearing the head and eyes, and alleviating dizziness and eye distension caused by heat rising upwards. Juncus effusus, amber, bamboo shavings, cassia seed, and astragalus complanatus are used as adjuvant herbs, employing both cold and warm properties, and harmonizing ascending and descending functions, both assisting the principal and adjuvant herbs in attacking pathogens and enhancing efficacy, and also guiding the herbs to the appropriate meridians. Juncus effusus clears heat and reduces internal fire, guiding heat downwards to assist the principal herb in clearing stagnant heat and calming the mind. Amber calms the nerves, invigorates blood circulation, and dispels blood stasis, effectively relieving palpitations and soothing the five internal organs. It not only assists wheat bran and salvia miltiorrhiza in calming the mind but also enhances their effects of invigorating blood circulation, clearing stagnation, and removing blood stasis. Bamboo shavings clear heat, resolve phlegm, relieve irritability, and stop vomiting, assisting the principal herb in clearing heat from the gallbladder and stomach to calm the mind, while also restraining the warming and drying properties of tangerine peel and nardostachys chinensis. Cassia seed clears the liver, improves eyesight, and moistens the intestines to relieve constipation. It can calm dizziness caused by upward disturbance of stagnant heat and promote bowel movement, allowing stagnant heat to be released from below. Astragalus complanatus tonifies the kidneys, strengthens yang, consolidates essence, reduces urination, nourishes the liver, and improves eyesight. It effectively replenishes the essence and blood of the liver and kidneys, protects the lower body, and prevents excessive excretion from harming the body's vital energy. At the same time, it can guide all the herbs in the formula to the liver and kidney meridians, allowing the medicinal effects to return to their root and strengthen the body's foundation.

[0033] In vivo experiments in rats showed that the traditional Chinese medicine preparation of this invention has a significant antidepressant effect and can significantly improve the depressive-like behavior of rats with depression. Mechanistic studies showed that the traditional Chinese medicine preparation of this invention can bidirectionally regulate the levels of inflammatory factors, significantly reduce the secretion levels of pro-inflammatory cytokines IL-1β and IL-6 in rat serum, and increase the secretion level of anti-inflammatory cytokine IL-10, thereby effectively alleviating neuroinflammatory responses. In addition, the traditional Chinese medicine preparation of this invention can also significantly increase the levels of monoamine neurotransmitters DA, NE, and 5-HT in the rat hippocampus, protect hippocampal neurons from damage, and effectively exert an antidepressant effect.

[0034] Clinical trial results demonstrate that the traditional Chinese medicine preparation of this invention exhibits significant efficacy and safety advantages in the treatment of depression. Clinical data show that the traditional Chinese medicine preparation of this invention can significantly improve the overall effective rate of clinical treatment for depression, while reducing patients' TCM syndrome scores and improving clinical symptoms. Furthermore, the traditional Chinese medicine preparation of this invention can significantly reduce patients' HAMD and PSQI scores, alleviate depressive-like behaviors, and improve sleep quality. No significant adverse reactions were observed during treatment, providing a treatment option for depression that combines multi-target regulatory advantages with good safety. Attached Figure Description

[0035] Figure 1 Comparison of serum inflammatory factor levels in rats of different groups; Note: Compared with the control group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01.

[0036] Figure 2 Comparison of serum hippocampal neurotransmitter levels in each group of rats; Note: Compared with the control group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] Example 1

[0039] A traditional Chinese medicine preparation for treating or improving depression, the preparation comprising the following parts by weight of traditional Chinese medicine raw materials: 30 parts of St. John's wort, 25 parts of wheat bran, 25 parts of Salvia miltiorrhiza, 22 parts of Perilla frutescens stem, 20 parts of Citrus reticulata peel, 20 parts of Nardostachys jatamansi, 10 parts of Tribulus terrestris, 15 parts of Juncus effusus, 10 parts of amber, 15 parts of bamboo shavings, 12 parts of Cassia tora seed, and 15 parts of Astragalus complanatus seed.

[0040] The traditional Chinese medicine preparations are prepared into oral dosage forms, including pills, powders, granules, oral liquids, decoctions, and tablets, using conventional pharmaceutical methods and with medically acceptable excipients.

[0041] The preparation method of the traditional Chinese medicine granules includes the following steps:

[0042] (1) Weigh each Chinese herbal raw material according to the above weight proportions, wash, dry, and pulverize into coarse powder, and pass through a 24-mesh sieve;

[0043] (2) Mix the above coarse powder evenly, add 8 times the mass of 50% ethanol solution and soak for 30 min, then extract twice by ultrasound for 45 min each time, combine the extracts, concentrate under reduced pressure and vacuum to an extract with a relative density of 1.10, and then spray dry to granulate to obtain the Chinese medicine preparation granules of the present invention.

[0044] In step (2), the frequency of ultrasonic extraction is 40 kHz; the temperature of vacuum concentration is 50℃ and the vacuum degree is -0.08MPa; the inlet air temperature of spray drying is 180℃ and the outlet air temperature is 90℃.

[0045] Example 2

[0046] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 25 parts of St. John's wort, 20 parts of wheat bran, 20 parts of Salvia miltiorrhiza, 18 parts of Perilla frutescens stem, 15 parts of Citrus reticulata peel, 15 parts of Nardostachys jatamansi, 5 parts of Tribulus terrestris, 10 parts of Juncus effusus, 5 parts of amber, 10 parts of bamboo shavings, 8 parts of Cassia tora seed, and 10 parts of Astragalus complanatus seed.

[0047] Example 3

[0048] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 35 parts of St. John's wort, 30 parts of wheat bran, 30 parts of Salvia miltiorrhiza, 26 parts of Perilla frutescens stem, 25 parts of Citrus reticulata peel, 25 parts of Nardostachys jatamansi, 15 parts of Tribulus terrestris, 20 parts of Juncus effusus, 15 parts of amber, 20 parts of bamboo shavings, 16 parts of Cassia tora seed, and 20 parts of Astragalus complanatus seed.

[0049] Example 4

[0050] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 37 parts of St. John's wort, 32 parts of wheat bran, 32 parts of Salvia miltiorrhiza, 29 parts of Perilla frutescens stem, 27 parts of Citrus reticulata peel, 28 parts of Nardostachys jatamansi, 17 parts of Tribulus terrestris, 22 parts of Juncus effusus, 18 parts of amber, 22 parts of bamboo shavings, 19 parts of Cassia tora seed, and 22 parts of Astragalus complanatus seed.

[0051] Example 5

[0052] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 20 parts of St. John's wort, 15 parts of wheat bran, 15 parts of Salvia miltiorrhiza, 13 parts of Perilla frutescens stem, 10 parts of Citrus reticulata peel, 10 parts of Nardostachys jatamansi, 3 parts of Tribulus terrestris, 5 parts of Juncus effusus, 3 parts of amber, 5 parts of bamboo shavings, 3 parts of Cassia tora seed, and 5 parts of Astragalus complanatus seed.

[0053] Example 6

[0054] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 22 parts of St. John's wort, 18 parts of wheat bran, 18 parts of Salvia miltiorrhiza, 15 parts of Perilla frutescens stem, 12 parts of Citrus reticulata peel, 13 parts of Nardostachys jatamansi, 4 parts of Tribulus terrestris, 8 parts of Juncus effusus, 4 parts of amber, 7 parts of bamboo shavings, 6 parts of Cassia tora seed, and 8 parts of Astragalus complanatus seed.

[0055] Example 7

[0056] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 40 parts of St. John's wort, 35 parts of wheat bran, 35 parts of Salvia miltiorrhiza, 32 parts of Perilla frutescens stem, 30 parts of Citrus reticulata peel, 30 parts of Nardostachys jatamansi, 20 parts of Tribulus terrestris, 25 parts of Juncus effusus, 20 parts of amber, 25 parts of bamboo shavings, 22 parts of Cassia tora seed, and 25 parts of Astragalus complanatus seed.

[0057] Experimental Example 1

[0058] 1. Materials and Methods

[0059] 1.1 Experimental Animals

[0060] Forty-two male SPF-grade SD rats, weighing 200±20g and aged 6-8 weeks, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. Husbandry conditions: temperature 25±1℃, humidity (50±5)%, with 12h / 12h light / dark alternation in the animal room. The rats had free access to food and water during the rearing period.

[0061] 1.2 Test Drugs

[0062] The traditional Chinese medicine preparation of this invention is as follows: 30g of St. John's wort, 25g of wheat bran, 25g of Salvia miltiorrhiza, 22g of Perilla frutescens stem, 20g of Citrus reticulata peel, 20g of Nardostachys jatamansi, 10g of Tribulus terrestris, 15g of Juncus effusus, 10g of amber, 15g of bamboo shavings, 12g of Cassia tora seed, and 15g of Astragalus complanatus seed. Weigh each raw material according to the above weight proportions, wash them, boil them in 8 times the amount of water for 30 minutes, filter them, and obtain the filtrate. Repeat the process twice, combine the two filtrates, and concentrate them to a raw herb content of 1g / mL to obtain the original traditional Chinese medicine solution. Store at 4℃ for later use.

[0063] Fluoxetine hydrochloride is manufactured by Eli Lilly Suzhou Pharmaceutical Co., Ltd.

[0064] Chaihu Shugan Pills are produced by Yaodu Pharmaceutical Group Co., Ltd.

[0065] 1.3 Establishment of a chronic stress rat depression (CUMS) model

[0066] After acclimatizing to the environment for 5 days, all rats were randomly divided into 7 groups of 6 rats each according to their body weight: blank group, model group, western medicine control group, traditional Chinese medicine control group, high-dose group of the traditional Chinese medicine preparation of this invention (hereinafter referred to as high-dose group), medium-dose group of the traditional Chinese medicine preparation of this invention (hereinafter referred to as high-dose group), and low-dose group of the traditional Chinese medicine preparation of this invention (hereinafter referred to as high-dose group). The blank group rats were fed routinely, while the other groups of rats were used to establish a depressive rat model using the CUMS combined with single-cage housing method. CUMS included tail clamping for 5 minutes, forced swimming in 4-8℃ cold water for 5 minutes, restraint for 5 hours, noise stimulation for 30 minutes, fasting for 24 hours, 45° tilted housing for 24 hours, wet housing for 24 hours, exposure to empty cages for 24 hours, and day-night reversal for 24 hours. Two stimuli were randomly selected to stimulate the rats each day, and the same stimuli were not used on two consecutive days. The modeling period lasted for 28 days.

[0067] 1.4 Grouping and Administration

[0068] After successful CUMS modeling, rats were administered the following medications by gavage according to their group: Western medicine control group (fluoxetine hydrochloride, 2 mg / kg), traditional Chinese medicine control group (Chaihu Shugan Wan, 12 g / kg), high-dose group (traditional Chinese medicine preparation of this invention, 30 g / kg), medium-dose group (traditional Chinese medicine preparation of this invention, 15 g / kg), and low-dose group (traditional Chinese medicine preparation of this invention, 7.5 g / kg). The blank group and model group were administered an equal volume of physiological saline by gavage. The administration was once daily for 28 consecutive days. During the administration period, all groups of rats continued to receive CUMS stress combined with isolation stimulation.

[0069] 1.5 Behavioral Testing Methods

[0070] 1.5.1 Sugar Water Preference Test

[0071] Before starting the sucrose preference experiment, rats should be housed individually and then allowed to acclimatize for 3 days. On day 1, they are given two bottles of 1% sucrose solution for 24 hours. On day 2, they are given one bottle of sucrose solution and one bottle of deionized water for 24 hours. On day 3, the positions of the sucrose solution and pure water are switched, and the acclimatization ends after 24 hours. On day 4, they are fasted and deprived of water for 24 hours. On day 5, they are given one bottle of sucrose solution and one bottle of pure water after weighing. After 12 hours, their positions are switched, and after 24 hours, they are taken out and weighed again to calculate the sucrose preference rate.

[0072] Sugar water preference rate = (Sugar water consumption / (Sugar water consumption + Pure water consumption)) × 100%

[0073] 1.5.2 Open Field Test

[0074] Each rat was first placed in the center compartment of a self-made open box. The room was kept dark and quiet during the test. The total horizontal movement distance of each group of rats within 5 minutes was then observed and recorded. Before testing each rat, the bottom of the box was thoroughly cleaned with 75% ethanol to avoid odor interference with the experimental results of the next rat.

[0075] 1.5.3 Tail Suspension Test

[0076] The rats were suspended by their tails with their heads at a certain distance from the ground. The rats' struggles were recorded over 6 minutes, and the immobility time in the last 5 minutes was analyzed.

[0077] 1.5.4 Forced Swimming Test

[0078] Each group of rats was placed head-down in an opaque circular plastic bucket with an upper diameter of 40 cm and a lower diameter of 33 cm. The water depth was 30 cm and the water temperature was 25℃. During the experiment, the rats were kept quiet and slowly lowered into the bucket to swim freely. The immobility time of the rats was recorded within 5 minutes. After the experiment, the rats were removed, dried, and returned to their cages. The immobility time of the rats was calculated as the time when only their heads were above water for breathing or when they occasionally paddled on the surface, maintaining their balance and not sinking.

[0079] 1.6 ELISA detection of serum inflammatory factors and hippocampal neurotransmitter levels in rats

[0080] After sacrificing the rats, serum was collected, and the whole brain of the rats was removed. The hippocampus was isolated, and PBS buffer was added. The brain was then centrifuged at 8000 r / min for 15 min to obtain the supernatant. The levels of IL-10, IL-1β, IL-6 in the rat serum and 5-HT, DA, and NE in the hippocampus were measured according to the ELISA kit instructions.

[0081] 1.7 Statistical Analysis

[0082] Data statistical analysis and graphing were performed using GraphPad Prism 8.0 software. The results are expressed as mean ± standard deviation (Mean ± SD). One-way ANOVA was used to compare differences between groups, and P < 0.05 was considered statistically significant.

[0083] 2 Results

[0084] 2.1 Effects of the traditional Chinese medicine preparation of this invention on the behavior of CUMS depression model rats

[0085] As shown in Table 1, compared with the blank group, the sucrose consumption of rats in the model group was significantly reduced (P<0.01), the forced swimming and tail suspension immobility time was significantly increased (P<0.01), and the movement distance was significantly shortened (P<0.01). Compared with the model, the Western medicine control group, the traditional Chinese medicine control group, and the high-dose, medium-dose, and low-dose groups of the traditional Chinese medicine preparation increased the sucrose consumption (P<0.05 or P<0.01) and movement distance (P<0.05 or P<0.01) of the model rats, and reduced the tail suspension and swimming immobility time of the model rats (P<0.05 or P<0.01), suggesting that this traditional Chinese medicine preparation has the effect of improving depressive-like behavior in rats, with the high-dose group showing better results.

[0086] Table 1. Behavioral evaluation results of CUMS depression model rats in each group

[0087]

[0088] Note: Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, * P<0.05, ** P<0.01.

[0089] 2.2 Effects of the herbal preparation of this invention on serum IL-10, IL-1β and 5-HT levels in rats

[0090] Depend on Figure 1 It was found that, compared with the blank group, the serum IL-10 level in the model group rats was significantly decreased (P<0.01), while the IL-1β and IL-6 levels were significantly increased (P<0.01). Compared with the model group, the Western medicine control group, the traditional Chinese medicine control group, and the high-, medium-, and low-dose traditional Chinese medicine preparations significantly reduced the serum IL-6 and IL-1β levels in the depressed model rats (P<0.01 or P<0.05) and significantly increased the IL-10 level (P<0.01 or P<0.05). This suggests that the traditional Chinese medicine preparation has a regulatory effect on the inflammatory response in rats, with the high-dose group showing better results.

[0091] 2.3 Effects of the herbal preparation of this invention on the levels of 5-HT, DA, and NE in the hippocampus of rats

[0092] Depend on Figure 2 It was found that, compared with the blank group, the levels of 5-HT, DA, and NE in the hippocampus of rats in the model group were significantly reduced (P<0.01); compared with the model group, the levels of 5-HT, DA, and NE were significantly increased in the Western medicine control group, the traditional Chinese medicine control group, and the high-dose, medium-dose, and low-dose groups of the traditional Chinese medicine preparation (P<0.01 or P<0.05), suggesting that this traditional Chinese medicine preparation can increase the level of monoamine neurotransmitters in rats, with the high-dose group showing better results.

[0093] 3. Conclusion

[0094] The above experimental results show that the traditional Chinese medicine preparation of this invention can significantly improve the depressive-like behavior of a rat model of depression, suggesting that it has a significant antidepressant therapeutic effect. Mechanistic studies show that the traditional Chinese medicine preparation of this invention can bidirectionally regulate the level of inflammatory factors, significantly reduce the secretion levels of pro-inflammatory cytokines IL-1β and IL-6 in rat serum, and increase the secretion level of anti-inflammatory cytokine IL-10, thereby effectively alleviating neuroinflammatory responses. In addition, the traditional Chinese medicine preparation of this invention can also significantly increase the levels of monoamine neurotransmitters DA, NE, and 5-HT in the rat hippocampus, protect hippocampal neurons from damage, and effectively exert an antidepressant effect.

[0095] Experimental Example 2

[0096] 1. Clinical Data

[0097] 1.1 Diagnostic criteria

[0098] The patient meets the diagnostic criteria for depression in the CCMD-3 Chinese Classification and Diagnostic Criteria for Mental Disorders. The main symptoms include depressed mood, chest tightness, shortness of breath, decreased consciousness, poor concentration, and reduced activity; a Hamilton Depression Rating Scale (HAMD) score ≥17; psychomotor agitation and lack of energy; sleep disturbances; frequent feelings of guilt or self-blame; or self-harm or suicidal behavior.

[0099] 1.2 Dialectical Criteria

[0100] The patient meets the diagnostic criteria for depression in the "Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine Internal Medicine: Section on Traditional Chinese Medicine Diseases and Syndromes," and is diagnosed with liver qi stagnation syndrome. Primary symptoms: emotional depression, chest and rib distension, frequent sighing, and irritability; secondary symptoms: muscle pain, dizziness, headache, insomnia, epigastric fullness, belching, and poor appetite; tongue and pulse: pale tongue with a thin white coating, and wiry pulse.

[0101] 1.3 Inclusion Criteria

[0102] Candidates must meet the above diagnostic and syndrome differentiation criteria; be ≥20 years old and <80 years old; have a disease duration of ≥3 months; have not taken any antidepressants or antipsychotics within the past week; and be aware of and voluntarily participate in this study.

[0103] 1.4 Exclusion Criteria

[0104] Individuals with bipolar disorder or schizophrenia; individuals with malignant tumors or other primary diseases of vital organs; and pregnant or lactating women.

[0105] 1.5 General Information

[0106] Eighty patients with depression were selected and randomly divided into an observation group and a control group, with 40 patients in each group. The observation group consisted of 13 males and 27 females, with a mean age of (38.78±5.91) years and a mean disease duration of (8.02±3.12) months. The control group consisted of 15 males and 25 females, with a mean age of (36.77±6.84) years and a mean disease duration of (7.49±2.88) months. There were no statistically significant differences in general characteristics between the two groups (P>0.05), indicating comparability.

[0107] 2 Treatment methods

[0108] Control group: Paroxetine hydrochloride tablets, 20 mg each time, once a day, for 8 consecutive weeks.

[0109] Observation group: In addition to the control group, the patient was given oral administration of the traditional Chinese medicine preparation of this invention. The prescription is as follows: 30g of St. John's wort, 25g of wheat bran, 25g of Salvia miltiorrhiza, 22g of Perilla frutescens stem, 20g of Citrus reticulata peel, 20g of Nardostachys jatamansi, 10g of Tribulus terrestris, 15g of Juncus effusus, 10g of amber, 15g of bamboo shavings, 12g of Cassia tora seed, and 15g of Astragalus complanatus seed. Weigh the above ingredients according to their weight, add 4 times their weight of water and decoct for more than 30 minutes until 400mL of decoction remains. Take the decoction twice a day, morning and evening, for 8 consecutive weeks.

[0110] 3. Observation Indicators and Standards

[0111] 3.1 Clinical efficacy

[0112] Based on the relevant standards in the "Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine Internal Medicine: TCM Diseases and Syndromes" and combined with clinical practice, this document was formulated.

[0113] Cure: Clinical symptoms disappear, efficacy index ≥95%, HAMD score reduction rate ≥75%;

[0114] Significant improvement: Clinical symptoms are significantly improved, with 70% ≤ efficacy index < 95% and 50% ≤ HAMD score reduction rate < 75%;

[0115] Effective: Clinical symptoms are relieved, with 30% ≤ efficacy index < 70% and 25% ≤ HAMD score reduction rate < 50%;

[0116] Ineffective: Clinical symptoms do not improve or worsen, and the efficacy index and HAMD reduction rate are <25%.

[0117] 3.2 Traditional Chinese Medicine Syndrome Scoring

[0118] According to the scoring criteria for liver qi stagnation syndrome in the "Guidelines for Diagnosis and Treatment of Common Internal Medicine Diseases in Traditional Chinese Medicine: TCM Syndromes", the primary symptoms (emotional depression, chest and rib distension, frequent sighing, and irritability) are scored as 0, 2, 4, and 6 points respectively, and the secondary symptoms (insomnia, belching, epigastric fullness, poor appetite, headache and dizziness, and muscle pain) are scored as 0, 1, 2, and 3 points respectively. The TCM syndrome score is obtained by adding the scores of the primary and secondary symptoms. The higher the score, the more severe the symptoms.

[0119] 3.3 Depression level

[0120] The HAMD scale was used to assess the degree of depression in patients before and after treatment. The scale includes 24 items, each item is scored from 0 to 4; a total score of 0-8 is normal, 9-19 indicates possible depression, 20-34 indicates definite depression, and ≥35 indicates severe depression.

[0121] 3.4 Sleep quality

[0122] The Pittsburgh Sleep Quality Index (PSQI) was used to assess patients' sleep quality before and after treatment. The scale consists of 7 items, each scored from 0 to 3, for a total of 21 points. The higher the score, the worse the sleep quality.

[0123] 4 Statistical Methods

[0124] SPSS 18.0 statistical software was used. Quantitative data were expressed as mean ± standard deviation. Independent samples t-tests were used between groups, and paired samples t-tests were used within groups. Count data were expressed as percentages (%). Chi-square tests were used for comparisons between groups. 2 The test showed that P < 0.05 was statistically significant.

[0125] 5 Results

[0126] 5.1 Comparison of clinical efficacy between the two groups

[0127] As shown in Table 2, the total effective rate of the control group was 77.50%, while the total effective rate of the observation group was 95.00%, which was significantly higher than that of the control group (P<0.05), indicating that the traditional Chinese medicine preparation of the present invention has significant clinical effects in the treatment of depression.

[0128] Table 2 Comparison of clinical efficacy between the two groups [n(%)]

[0129]

[0130] 5.2 Comparison of TCM syndrome scores before and after treatment in the two groups

[0131] As shown in Table 3, there was no significant difference in TCM syndrome scores between the two groups before treatment (P>0.05). After treatment, the TCM syndrome scores of both the control group and the observation group were significantly lower than before treatment (P<0.05), and the TCM syndrome scores of the observation group were significantly lower than those of the control group (P<0.05). This indicates that the TCM preparation of the present invention can significantly alleviate the clinical symptoms of patients with depression, thereby achieving an antidepressant effect.

[0132] Table 3 Comparison of TCM syndrome scores before and after treatment in the two groups (points)

[0133]

[0134] Note: Compared with the pre-treatment level in this group. * P<0.05, ** P<0.01; After treatment, compared with the control group, # P<0.05, ## P<0.01.

[0135] 5.3 Comparison of HAMD and PSQI scores before and after treatment in the two groups

[0136] As shown in Table 4, there were no significant differences in HAMD and PSQI scores between the two groups before treatment (P>0.05). After treatment, both the HAMD and PSQI scores in the observation and treatment groups decreased significantly (P<0.01), and the HAMD and PSQI scores in the observation group were significantly lower than those in the control group (P<0.05). This indicates that the traditional Chinese medicine preparation of the present invention has significant advantages in improving depressive symptoms and sleep quality.

[0137] Table 4 Comparison of HAMD and PSQI scores before and after treatment in the two groups (points)

[0138]

[0139] Note: Compared with the pre-treatment level in this group. * P<0.05, ** P<0.01; After treatment, compared with the control group, # P<0.05, ## P<0.01.

[0140] 5.4 Adverse Reactions

[0141] No significant adverse reactions occurred in either group of patients during the treatment process, and no significant abnormalities were found in blood routine, urine routine, liver and kidney function and electrocardiogram examinations of all patients.

[0142] 6. Conclusion

[0143] The above experimental results demonstrate that the traditional Chinese medicine preparation of this invention exhibits significant efficacy and safety advantages in the treatment of depression. Clinical data show that the traditional Chinese medicine preparation of this invention can significantly improve the overall effective rate of clinical treatment for depression, while reducing patients' TCM syndrome scores and improving their clinical symptoms. In addition, the traditional Chinese medicine preparation of this invention can also significantly reduce patients' HAMD and PSQI scores, alleviate patients' depressive-like behaviors, and improve patients' sleep quality. Moreover, no significant adverse reactions were observed during the treatment, providing a treatment option for depression that combines the advantages of multi-target regulation with good safety.

[0144] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine preparation for treating or improving depression, characterized in that, The traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 20-40 parts of St. John's wort, 15-35 parts of wheat bran, 15-35 parts of Salvia miltiorrhiza, 13-32 parts of Perilla frutescens stem, 10-30 parts of Citrus reticulata peel, 10-30 parts of Nardostachys jatamansi, 3-20 parts of Tribulus terrestris, 5-25 parts of Juncus effusus, 3-20 parts of amber, 5-25 parts of bamboo shavings, 3-22 parts of Cassia tora seed, and 5-25 parts of Astragalus complanatus seed.

2. The traditional Chinese medicine preparation according to claim 1, characterized in that, The traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 25-35 parts of St. John's wort, 20-30 parts of wheat bran, 20-30 parts of Salvia miltiorrhiza, 18-26 parts of Perilla frutescens stem, 15-25 parts of Citrus reticulata peel, 15-25 parts of Nardostachys jatamansi, 5-15 parts of Tribulus terrestris, 10-20 parts of Juncus effusus, 5-15 parts of amber, 10-20 parts of bamboo shavings, 8-16 parts of Cassia tora seed, and 10-20 parts of Astragalus complanatus seed.

3. As described in claim 1, characterized in that, The traditional Chinese medicine preparation is composed of the following parts by weight of traditional Chinese medicine raw materials: 30 parts of St. John's wort, 25 parts of wheat bran, 25 parts of Salvia miltiorrhiza, 22 parts of Perilla frutescens stem, 20 parts of Citrus reticulata peel, 20 parts of Nardostachys jatamansi, 10 parts of Tribulus terrestris, 15 parts of Juncus effusus, 10 parts of amber, 15 parts of bamboo shavings, 12 parts of Cassia tora seed, and 15 parts of Astragalus complanatus seed.

4. A method for preparing a traditional Chinese medicine preparation as described in any one of claims 1 to 3, characterized in that, The preparation is made into oral dosage forms, including pills, powders, granules, oral liquids, decoctions, and tablets, using conventional pharmaceutical methods and with medically acceptable excipients.

5. The preparation method according to claim 4, characterized in that, The preparation method of the traditional Chinese medicine granules includes the following steps: (1) Weigh each Chinese herbal raw material according to the above weight proportions, wash, dry, and pulverize into coarse powder, and pass through a 24-mesh sieve; (2) Mix the above coarse powder evenly, add 3-8 times the weight of 50% ethanol solution and soak for 30-60 min, then extract by ultrasonication 2-3 times, 30-50 min each time, combine the extracts, concentrate under reduced pressure and vacuum to an extract with a relative density of 1.05-1.30, and then spray dry to granulate to obtain the Chinese medicine preparation granules of the present invention.

6. The method for preparing traditional Chinese medicine granules according to claim 5, characterized in that, In step (2), the ultrasonic extraction frequency is 40 kHz; the vacuum concentration temperature is 45-55℃ and the vacuum degree is -0.08MPa; the spray drying inlet temperature is 180℃ and the outlet temperature is 90℃.

7. The use of the traditional Chinese medicine preparation according to any one of claims 1 to 3 in the preparation of drugs for the prevention and / or treatment of depression.

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