Traditional Chinese medicine compound for improving negative emotion and insomnia and application thereof

Abstract

The invention provides a traditional Chinese medicine compound for improving negative emotion and insomnia and application thereof, and the traditional Chinese medicine compound comprises the following components in parts by weight: 5-15 parts of fried spina date seed, 10-20 parts of poria cocos, 5-15 parts of ligusticum wallichii, 10-20 parts of scutellaria baicalensis, 5-15 parts of ginger processed pinellia, 5-15 parts of rhizoma anemarrhenae, 5-15 parts of immature bitter orange, 5-15 parts of schisandra chinensis, 5-15 parts of bamboo shavings and 10-20 parts of fried white peony root. The traditional Chinese medicine compound can remarkably improve the negative emotion and insomnia conditions of insomnia patients, stabilize the emotion and improve the life quality of the patients, and the effect is remarkable.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine compound for improving negative emotions and insomnia and its application, belonging to the field of medical technology. Background Art

[0002] Negative emotions, also known as adverse emotions, are collectively referred to as emotions such as anxiety, tension, anger, depression, sadness, pain, etc. in psychology. These emotional experiences are usually not positive, and they can have a negative impact on the physical and mental health of individuals, and may even cause physical and mental harm, thereby affecting the smooth progress of work and life.

[0003] Adverse emotional stimuli are extremely likely to trigger sleep problems and are positively correlated with insomnia. Sleep is crucial for human survival. Due to the high life pressure of modern people, the incidence of sleep disorders is increasing day by day. Insomnia is the most common type of sleep disorder. As a psychosomatic disease, it not only causes stress to the patient's physiology and psychology, but may also trigger major diseases such as diabetes, metabolic syndrome, and tumors in the long run. Long-term insomniacs are prone to emotional irritability, anxiety, depression and other states, seriously affecting the quality of life. Lack of sleep can lead to disorders of the autonomic nervous system function, endocrine function imbalance, increased coagulation and oxidative stress responses, endothelial dysfunction, etc. Through various pathophysiological pathways, it promotes the occurrence and development of diseases such as type 2 diabetes, obesity, hyperlipidemia, fatty liver, impaired mood and cognitive function. However, in clinical diagnosis and treatment, problems such as abnormal emotions, blood sugar fluctuations, and metabolic function disorders accompanied by insomnia are often ignored, bringing potential risks to the prognosis of patients and having a major impact on their life and work.

[0004] In the clinical treatment of insomnia, it is found that pure insomnia patients are relatively rare and often coexist with emotional diseases such as anxiety disorder and depression. More than 80% of depressed patients are accompanied by severe insomnia, 20% of insomnia patients are accompanied by depression, and the probability of suffering from depression increases with the prolongation of the insomnia course. Some scholars have statistically shown that among the comorbidities of insomnia patients, common mental health diseases include anxiety disorder (41%) and depression (28%).

[0005] At present, during the long-term use of commonly used drugs for clinical treatment of insomnia and negative emotions, adverse reactions such as drug resistance, reduced memory, and gastrointestinal dysfunction may occur, further exacerbating the psychological and mental stress of patients. Insomnia is likely to trigger anxiety, and unstable emotions will further aggravate insomnia. This long-term cycle seriously affects the sleep and quality of life of patients. Although there are a wide variety of Western medicine drugs, drugs for insomnia and negative emotions often have various side effects, such as drug resistance, rebound after drug withdrawal, dizziness, vomiting, drowsiness, etc. It is not only difficult to adhere to in the long term but may also have a reverse impact, without obvious advantages in prevention and treatment. At the same time, as a chronic disease, insomnia and negative emotions can also be treated by taking traditional Chinese medicine for a long time to regulate the body constitution and improve sleep and emotions. However, long-term use of traditional Chinese medicine may also have adverse effects on patients with gastrointestinal diseases such as weak spleen and stomach. Summary of the Invention

[0006] The present invention provides a traditional Chinese medicine compound for improving negative emotions and insomnia and its application, which can effectively solve the above problems.

[0007] A traditional Chinese medicine compound for improving negative emotions and insomnia, calculated by weight, includes: stir-fried wild jujube seed 5 - 15 parts, poria cocos 10 - 20 parts, chuanxiong rhizome 5 - 15 parts, scutellaria baicalensis 10 - 20 parts, pinellia ternata processed with ginger 5 - 15 parts, anemarrhena asphodeloides 5 - 15 parts, immature bitter orange 5 - 15 parts, schisandra chinensis 5 - 15 parts, bamboo shavings 5 - 15 parts, stir-fried white peony root 10 - 20 parts.

[0008] In some embodiments, the traditional Chinese medicine compound for improving negative emotions and insomnia, calculated by weight, includes: stir-fried wild jujube seed 15 parts, poria cocos 15 parts, chuanxiong rhizome 10 parts, scutellaria baicalensis 15 parts, pinellia ternata processed with ginger 10 parts, anemarrhena asphodeloides 10 parts, immature bitter orange 10 parts, schisandra chinensis 10 parts, bamboo shavings 10 parts, stir-fried white peony root 15 parts.

[0009] A traditional Chinese medicine preparation for improving negative emotions and insomnia includes the above traditional Chinese medicine compound.

[0010] In some embodiments, the traditional Chinese medicine preparation for improving negative emotions and insomnia further contains pharmaceutically acceptable excipients and / or carriers.

[0011] In some embodiments, the dosage form of the preparation is a liquid dosage form or a solid dosage form.

[0012] An application of the above traditional Chinese medicine compound in the preparation of a drug for improving negative emotions and insomnia.

[0013] An application of the above traditional Chinese medicine compound in the preparation of a health product for improving negative emotions and insomnia.

[0014] In some embodiments, the negative emotion is depression or anxiety.

[0015] The beneficial effects of the present invention are:

[0016] Through the optimization of each raw material drug and their ratios, the clinical trial results show that the traditional Chinese medicine composition of the present invention can significantly improve the insomnia of patients with negative emotions combined with insomnia, stabilize emotions, and improve the quality of life of patients, having the advantage of remarkable effects.

[0017] In the traditional Chinese medicine preparation of the present invention, the combined use of bamboo shavings, immature bitter orange, and pinellia not only reflects the formula characteristics of "compatibility enhancing efficacy, regulating cold and heat together, and taking into account both the root and the branch" in traditional Chinese medicine theory. Moreover, for patients with relatively poor basic constitutions such as weak spleen and stomach and loose stools, through scientific proportional compatibility, the risk of damage to the spleen and stomach caused by single drug use is significantly reduced, and through "resolving phlegm, harmonizing the stomach, descending adverse qi, and eliminating fullness" to improve emotional and sleep problems, a unique synergistic effect advantage is formed, fully reflecting the innovation and superiority of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention, and thus should not be regarded as limiting the scope. For those of ordinary skill in the art, other related drawings can be obtained based on these drawings without creative efforts.

[0019] Figure 1 For the traditional Chinese medicine preparation of the present invention to improve the depressive and anxious-like emotions of mice caused by sleep deprivation; among them, A: open field test; B: elevated plus maze; C: tail suspension test; D: black and white box test.

[0020] Figure 2 For the RNA-seq analysis of the hippocampal tissue of the mice of the present invention. A: Column chart of differential genes in the control group, SD group, and low-dose treatment group of the traditional Chinese medicine preparation; B: Volcano plot of differential genes in the control group, SD group, and low-dose treatment group of the traditional Chinese medicine preparation; C: GO pathway enrichment map.

[0021] Figure 3 For the changes in the TNF signaling pathway in the hippocampal tissue of the mice of the present invention; among them, A: Western blot of MAPKs downstream of the TNF signaling pathway in the control group, SD group, and low-dose treatment group of the traditional Chinese medicine preparation; B: control group, SD group, low-dose treatment group of the traditional Chinese medicine preparation; C: GSEA analysis.

[0022] Figure 4 For the RNA-seq of the hippocampal tissue of the mice of the present invention; among them, A: Immunofluorescence staining of microglia and astrocytes in the DG area, CA1, and CA3 areas of the mouse hippocampus; B: Statistical count of the number of GFAP in each hippocampal area; C: Statistical count of the number of IBA1 in each hippocampal area; D: Statistical count of the area of IBA1 in each hippocampal area. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0023] To make the objectives, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention. Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely represents selected embodiments of the present invention.

[0024] In recent years, traditional Chinese medicine (TCM) has been continuously exploring the relationship between negative emotions and insomnia. In TCM, insomnia is classified as "insomnia" and negative emotions are classified as "depression syndrome". The occurrence is mainly closely related to the deficiency of both the heart and spleen caused by improper diet, prolonged illness and weakness, and emotional disorders. The heart governs blood and the spleen controls blood. If the spleen qi is weak, the production of qi and blood will be insufficient, leading to the heart losing its governance, and then symptoms such as insomnia, dreaminess, fatigue, and liver qi stagnation will occur. Clinically, based on its symptoms and clinical manifestations, syndrome differentiation and treatment are carried out, and a variety of TCM prescriptions are proposed. These prescriptions have the characteristics of treating both the symptoms and the root causes, flexible addition and subtraction of prescriptions, safety and reliability, etc., and can play a role from multiple levels and multiple targets. TCM believes that the pathogenesis of insomnia is mainly the disharmony between yin and yang, deficiency and excess. For example, emotional injury or emotional stagnation leads to liver qi stagnation, which turns into fire, disturbing the mind, and causing insomnia due to the restlessness of the mind; or excessive thinking damages the heart and spleen, consuming the heart blood secretly, the mind not being able to guard the residence, the spleen being deficient in qi production, and the nutrient blood being deficient, unable to nourish the mind. The etiological mechanisms of the two are the same. In treatment, nourish the liver with blood to soothe the five zang-organs, clear heat and resolve phlegm to remove external pathogens, so as to stabilize emotions and improve sleep.

[0025] The treatment of negative emotions and insomnia with TCM helps to improve relevant indicators and clinical symptoms, delay the progression of the disease, and has many advantages such as good curative effect, low cost, few adverse reactions, and diverse forms. However, there are also some deficiencies in the treatment with TCM: (1) Although there are standardized assessment criteria for the syndrome types of negative emotions and insomnia, there are still differences in the understanding of various doctors in clinical practice, making it difficult to unify the theoretical system; (2) The syndrome differentiation and medication of various doctors for negative emotions and insomnia are mainly based on experience, lacking evidence-based medical evidence; (3) There is a lack of large-scale, multi-center, and standardized clinical research, and the heterogeneity of the research is high. Therefore, it is necessary to further deepen the research on the above problems, improve the TCM treatment system for negative emotions and insomnia, attach importance to the standardization of clinical research, comprehensively apply various TCM treatment methods, and form a standardized TCM treatment method, so as to better play the advantages of TCM in the treatment of this disease.

[0026] An embodiment of the present invention provides a traditional Chinese medicine compound for improving negative emotions and insomnia. By weight, it includes: 5 - 15 parts of stir-fried wild jujube seeds, 10 - 20 parts of poria cocos, 5 - 15 parts of chuanxiong rhizome, 10 - 20 parts of scutellaria baicalensis, 5 - 15 parts of pinellia ternata processed with ginger, 5 - 15 parts of anemarrhena asphodeloides, 5 - 15 parts of immature bitter orange, 5 - 15 parts of schisandra chinensis, 5 - 15 parts of bamboo shavings, and 10 - 20 parts of stir-fried white peony root.

[0027] The formula of the above traditional Chinese medicine preparation follows the principles of "treating the whole body and treating different diseases with the same method". It is believed that the pathogenesis of negative emotions (such as depression and anxiety) combined with insomnia is based on the deficiency of zang-fu organs, and phlegm, dampness, heat, stasis, etc. are the secondary symptoms. In treatment, the strategy of tonifying the deficiency of zang-fu organs and purging the excess of exogenous pathogenic factors is adopted.

[0028] All the herbs in the formula are used with a combination of cold and warm properties, and the ascending and descending actions are coordinated. Through the characteristics of the four natures and five flavors, as well as the ascending, descending, floating, and sinking properties of traditional Chinese medicine, the qi mechanism of the human body is mobilized. Wild jujube seeds are sweet, sour, and moistening in nature, entering the heart and liver meridians; white peony root is sour in nature and slightly cold in taste, entering the liver and spleen meridians. The two herbs together play the roles of nourishing blood and softening the liver, calming the mind and tranquilizing the spirit, and astringing yin and stopping sweating, and they are the monarch herbs. Anemarrhena asphodeloides is bitter, cold, and moistening in nature, nourishing yin and moistening dryness, clearing heat and relieving vexation; chuanxiong rhizome regulates liver blood and soothes the liver qi; poria cocos strengthens the spleen and resolves phlegm; schisandra chinensis nourishes yin and astringes downward; scutellaria baicalensis purges heat, making the gall qi clear and purified. They are all ministerial herbs.

[0029] The above seven herbs, as the basic formula for treating insomnia traditionally, have significant curative effects in clinical applications. However, considering the complex and diverse factors of insomnia or negative emotions in modern people, which are not caused by a single factor, but mostly manifested as deficiency of zang-fu organs as the root, and phlegm, dampness, heat, stasis, etc. as multiple pathogenic factors as the secondary symptoms, with a mixture of cold and heat, intertwined with each other. In view of this, bamboo shavings are added to the basic formula to strengthen the effects of clearing heat and resolving phlegm, and relieving vexation; pinellia ternata processed with ginger resolves phlegm and reduces adverse qi, harmonizes the stomach and stops vomiting; immature bitter orange descends qi and induces qi movement, eliminates phlegm and relieves fullness. The combination of resolving phlegm and regulating qi, the consideration of both purging and nourishing, the balanced regulation of cold and heat, nourishing blood and softening the liver, unblocking the qi mechanism, clearing heat and eliminating phlegm, relieving vexation and tranquilizing the spirit, making the body clear and the mind peaceful, and the emotions smooth.

[0030] In the compound of the embodiment of the present invention, if used alone, the following deficiencies will occur:

[0031] Bamboo shavings are slightly cold in nature, light in texture and ascending in property, belonging to the lung, stomach, and gall meridians, and are good at clearing heat and resolving phlegm, relieving vexation and stopping vomiting, and are the key herb for clearing heat and resolving phlegm. However, bamboo shavings are cold, cool, slippery, and beneficial. If used alone for a long time or in large doses, it is easy to damage the yang qi of the spleen and stomach. Especially for those with deficiency-cold of the spleen and stomach and loose stools, adverse reactions such as cold pain in the stomach cavity, poor appetite, and diarrhea are likely to occur.

[0032] Immature bitter orange is bitter and slightly cold in nature, belonging to the spleen and stomach meridians, and has the functions of promoting qi movement and breaking stagnation, eliminating food stagnation and inducing qi movement. It is especially suitable for symptoms such as fullness and discomfort in the chest and abdomen, and constipation caused by food accumulation and qi stagnation. However, immature bitter orange is bitter, dry, and breaks qi, and it is easy to consume the healthy qi of the spleen and stomach. If used for a long time or for those with a relatively weak constitution, it is easy to cause damage to the yin fluid of the spleen and stomach, and instead aggravate intestinal dryness, resulting in constipation or unsmooth stools.

[0033] Pinellia ternata, warm in nature, enters the spleen, stomach, and lung meridians, and is the main herb for resolving phlegm and stopping vomiting. However, raw Pinellia ternata without processing has strong toxicity and directly stimulates the gastrointestinal mucosa, even causing adverse reactions such as nausea, vomiting, bitter taste in the mouth, and numbness of the tongue. Even processed Pinellia ternata, such as Pinellia ternata processed with ginger, if used alone, is also likely to aggravate the gastrointestinal irritation reaction, especially unfavorable for those with weak spleen and stomach.

[0034] In the compound of the embodiment of the present invention, the three herbs of bamboo shavings, immature bitter orange, and Pinellia ternata are combined in compatibility. Not only do they each exert their advantages of "clearing heat and resolving phlegm, promoting qi circulation and relieving distension, and descending adverse qi and stopping vomiting", but more importantly, through the compatibility relationship of coordinating cold and heat, moistening and drying, ascending and descending, the overall curative effect is enhanced and the damage to the spleen and stomach is effectively controlled, thus improving sleep and mood problems. Its mechanism of synergistic effect is manifested in the following aspects:

[0035] (1) Balancing cold and heat, enhancing curative effect and reducing side effects

[0036] Bamboo shavings are cold in nature, immature bitter orange is bitter and cold, and Pinellia ternata is pungent and warm. When the three herbs are used together, cold and heat are mutually coordinated, making the medicinal properties tend to be mild, neither overly cold to damage the stomach nor overly dry to consume body fluids, thus improving the tolerance of the gastrointestinal tract. Especially for those with weak spleen and stomach and loose stools, after combination, not only the gastrointestinal function is improved, but also the disadvantages of cold coagulation or dry heat caused by single herb use are reduced.

[0037] (2) Mutual coordination of dryness and moistening, regulating the intestine, and improving constipation or diarrhea

[0038] Bamboo shavings lubricate the intestine, immature bitter orange promotes digestion and removes stagnation, and Pinellia ternata dries dampness and resolves phlegm. The combination of the three herbs realizes the bidirectional regulation of intestinal function. For those with constipation, the effect of immature bitter orange in promoting digestion and clearing the bowels is enhanced, and the moistening and heat-clearing effect of bamboo shavings avoids excessive dryness and fluid consumption; for those with diarrhea, the warming the middle and resolving dampness effect of Pinellia ternata can protect the middle qi, and the heat-clearing and phlegm-resolving effect of bamboo shavings does not leave damp pathogens behind, thus restoring the normal defecation rhythm.

[0039] (3) Coordinating ascending and descending, smooth qi movement, calming the stomach and stopping vomiting

[0040] Bamboo shavings are light in quality and promote the upward movement of clear qi, immature bitter orange sinks and guides stagnation, and Pinellia ternata is pungent and disperses to descend adverse qi. The three herbs, one ascending, one descending, and one harmonizing, overall regulate the qi movement of the spleen and stomach. When the stomach qi is smooth, there is no vomiting, and when the intestinal qi moves smoothly, there is no stagnation. After combination, clinically it is observed that the symptoms such as epigastric fullness, acid regurgitation, belching, nausea, and vomiting of patients are significantly improved, especially for patients with functional dyspepsia caused by early gastrointestinal dysfunction, the effect is particularly remarkable.

[0041] (4) Resolving phlegm and descending adverse qi, treating both the symptoms and the root cause

[0042] Retention of phlegm in the middle-jiao is a common pathogenesis in patients with weak spleen and stomach. Phlegm turbidity accumulates internally, blocking the qi movement. When the qi movement is not smooth, the ascending and descending functions are disordered, manifested as epigastric and abdominal fullness, nausea and vomiting, poor appetite, and loose stools. Bamboo shavings, immature bitter orange, and Pinellia ternata work together to resolve phlegm and relieve distension. When the phlegm is removed and the qi is smooth, the qi movement of the spleen and stomach returns to normal, and the spleen and stomach function is gradually improved, thus achieving the therapeutic effect of treating both the symptoms and the root cause.

[0043] In some embodiments, the traditional Chinese medicine compound for improving negative emotions and insomnia, by weight, comprises: 15 parts of stir-fried wild jujube seeds, 15 parts of poria cocos, 10 parts of chuanxiong rhizome, 15 parts of scutellaria baicalensis, 10 parts of pinellia ternata processed with ginger, 10 parts of anemarrhena rhizome, 10 parts of immature bitter orange, 10 parts of schisandra chinensis, 10 parts of bamboo shavings, and 15 parts of stir-fried white peony root.

[0044] A traditional Chinese medicine preparation for improving negative emotions and insomnia comprises the above traditional Chinese medicine compound.

[0045] In some embodiments, the traditional Chinese medicine preparation for improving negative emotions and insomnia further comprises pharmaceutically acceptable excipients and / or carriers. The content range of the excipients and / or carriers in the traditional Chinese medicine preparation can be 1% to 98% by weight, including but not limited to 5% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 95% by weight, 98% by weight, and the specific ratio is not limited herein.

[0046] In some embodiments, the dosage form of the preparation can be a liquid dosage form or a solid dosage form. Specifically, the dosage forms of the traditional Chinese medicine preparation include decoctions, oral tablets, oral liquids, syrups, granules, capsules, tablets, or dripping pills. These dosage forms are not only convenient for carrying and taking, but also conducive to clinical promotion and practical application.

[0047] To realize the above dosage forms, pharmaceutically acceptable excipients need to be added during the preparation process, such as: ion exchangers, alumina, aluminum stearate, lecithin, serum proteins (such as human serum albumin), buffering substances (such as phosphates), glycerol, sorbitan esters, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes (such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, magnesium trisilicate, polyvinylpyrrolidone, etc.).

[0048] The oral tablets and capsules may contain excipients, such as binders (such as syrup, gum arabic, sorbitol, tragacanth gum, or polyvinylpyrrolidone), fillers (such as lactose, sucrose, corn starch, calcium phosphate, sorbitol, glycine), lubricants (such as magnesium stearate, talc, polyethylene glycol, silica), disintegrants (such as potato starch), or acceptable wetting agents (such as sodium lauryl sulfate). Oral tablets can be coated by methods well-known in the pharmaceutical art.

[0049] The oral liquid can be made into water-oil suspensions, solutions, emulsions, syrups, etc., or can also be made into dry products, with water or other suitable media added before use. Such liquid preparations may contain conventional additives, such as suspending agents, sorbitol, methylcellulose, glucose syrup, gels, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel, hydrogenated edible oils, emulsifiers (such as lecithin, sorbitan monooleate, gum arabic); or non-aqueous carriers, including almond oil, oils (such as glycerol, ethylene glycol or ethanol); preservatives, including methyl paraben, propyl paraben or sorbic acid.

[0050] An embodiment of the present invention provides an application of the traditional Chinese medicine compound in the preparation of a drug for improving and regulating negative emotions and treating insomnia symptoms. Through scientific proportioning, the traditional Chinese medicine compound can effectively target negative emotions such as depression and anxiety, and at the same time has a significant effect on relieving insomnia and improving sleep quality. It plays a key role in the preparation of drugs aimed at improving negative emotions and sleep disorders.

[0051] In addition, an embodiment of the present invention also provides an application of a compound preparation based on specific traditional Chinese medicine compatibility in the preparation of a health product for regulating emotions and relieving insomnia. Through the synergistic effect of various medicinal materials, the compound aims to condition the body and mind from the root, effectively improve emotional problems and sleep conditions, and is suitable for the preparation of health products with the improvement of negative emotions and insomnia symptoms.

[0052] Example 1

[0053] A traditional Chinese medicine preparation for improving negative emotions and insomnia, the active pharmaceutical ingredients of which include: 15 g of stir-fried wild jujube seeds, 15 g of Poria cocos, 10 g of Ligusticum chuanxiong, 15 g of Scutellaria baicalensis, 10 g of Pinellia ternata processed with ginger, 10 g of Anemarrhena asphodeloides, 10 g of Fructus aurantii immaturus, 10 g of Schisandra chinensis, 10 g of bamboo shavings, 15 g of stir-fried white peony root. After mixing the above raw materials, add 8 times the amount of clear water, soak for 15 minutes, then decoct for 15 minutes, and pour out the medicinal liquid; continue to add 6 times the amount of clear water to the medicinal residues, decoct for another 10 minutes, and finally mix the medicinal liquids obtained twice evenly to obtain the decoction.

[0054] Example 2

[0055] A traditional Chinese medicine preparation for improving negative emotions and insomnia, the active pharmaceutical ingredients of which include: 10 g of stir-fried wild jujube seeds, 15 g of Poria cocos, 15 g of Ligusticum chuanxiong, 15 g of Scutellaria baicalensis, 10 g of Pinellia ternata processed with ginger, 10 g of Anemarrhena asphodeloides, 15 g of Fructus aurantii immaturus, 10 g of Schisandra chinensis, 10 g of bamboo shavings, 15 g of stir-fried white peony root. After mixing the above raw materials, add 8 times the amount of clear water, soak for 15 minutes, then decoct for 15 minutes, and pour out the medicinal liquid; continue to add 6 times the amount of clear water to the medicinal residues, decoct for another 10 minutes, and finally mix the medicinal liquids obtained twice evenly to obtain the decoction.

[0056] Example 3

[0057] A traditional Chinese medicine preparation for improving negative emotions and insomnia, the active ingredients of which include: 6g of stir-fried wild jujube seeds, 10g of poria cocos, 10g of chuanxiong rhizome, 15g of scutellaria baicalensis, 10g of pinellia ternata processed with ginger, 10g of anemarrhena rhizome, 15g of immature bitter orange, 10g of schisandra chinensis, 15g of bamboo shavings, and 10g of stir-fried white peony root. After mixing the above raw materials, add 8 times the amount of clear water, soak for 15 minutes, then decoct for 15 minutes, and pour out the decoction; continue to add 6 times the amount of clear water to the medicinal residues, decoct for another 10 minutes, and finally mix the decoctions obtained twice evenly to obtain the decoction.

[0058] Effect verification

[0059] Clinical trial 1:

[0060] 1. Research subjects

[0061] The cases were sourced from outpatients with chronic insomnia who visited The First Affiliated Hospital of Xiamen University.

[0062] 2. Diagnostic criteria

[0063] 2.1 Refer to the diagnostic criteria for chronic insomnia in the "Diagnosis and Treatment Guidelines for Insomnia in Chinese Adults (2023 Edition)", which are as follows:

[0064] 1) There is one or more of the following sleep abnormality symptoms (self-reported by the patient or observed by the caregiver): (1) Difficulty falling asleep; (2) Difficulty maintaining sleep; (3) Waking up earlier than the expected wake-up time; (4) Unwillingness to go to bed at the appropriate time.

[0065] 2) There is one or more of the following daytime symptoms related to insomnia (self-reported by the patient or observed by the caregiver): (1) Fatigue or general discomfort; (2) Inattention or memory impairment; (3) Impairment of social, family, occupational, or academic functions; (4) Irritability or excitability of mood; (5) Daytime sleepiness; (6) Behavioral problems (such as hyperactivity, impulsivity, or aggression); (7) Decrease in energy and physical strength; (8) Prone to errors and accidents; (9) Excessive concern about sleep problems or dissatisfaction with sleep quality.

[0066] 3) The sleep abnormality symptoms and related daytime symptoms cannot be simply explained by the lack of appropriate sleep time or inappropriate sleep environment.

[0067] 4) The sleep abnormality symptoms and related daytime symptoms occur at least 3 times a week.

[0068] 5) The sleep abnormality symptoms and related daytime symptoms persist for at least 3 months.

[0069] 6) The sleep and awakening difficulties cannot be better explained by other types of sleep disorders.

[0070] 3. Inclusion criteria

[0071] 3.1 Meet the above diagnostic criteria;

[0072] 3.2 Aged 18 - 65 years old, regardless of gender;

[0073] 3.3 Not participating in other clinical traditional Chinese medicine drug trials;

[0074] 3.4 The patient agrees to participate and sign the informed consent form

[0075] 4. Exclusion criteria

[0076] 4.1 Do not meet the diagnostic criteria;

[0077] 4.2 Belong to somatic diseases such as headache, neck pain, shoulder pain, low back pain, knee pain, etc., or secondary insomnia caused by mental disorders, etc.;

[0078] 4.3 Patients with combined severe primary diseases of the cardiovascular and cerebrovascular system, liver, kidney, hematopoietic system, etc. and psychiatric patients;

[0079] 4.4 Those who are allergic to the traditional Chinese medicine compound drug of this study and pregnant and lactating women;

[0080] 4.5 The researcher believes that it is not suitable to enter the trial.

[0081] 5. Exclusion criteria

[0082] 5.1 Patients who request to withdraw from the study due to their own reasons;

[0083] 5.2 Those whose data is incomplete and affects the result analysis.

[0084] 6. Withdrawal cases: Those who are lost to follow-up during the study process are withdrawals.

[0085] 7. In order to further verify the effectiveness of the traditional Chinese medicine compound combination, the formula table in Table 1 is formed.

[0086] Table 1 Traditional Chinese medicine compound combination formula table (unit: g)

[0087]

[0088]

[0089] 8. Intervention method

[0090] 8.1 After screening and meeting the inclusion and exclusion criteria, collect the general information of the patients and the scale assessment situation (Athens Insomnia Scale (AIS), Generalized Anxiety Disorder Scale (GAD - 2) and Patient Health Questionnaire - 2 (PHQ - 2)) before the trial

[0091] 8.2 Course of treatment: 4 weeks.

[0092] 8.3 Administration method: 80 ml per pack, 1 pack each time, 3 times a day, to be taken half an hour after meals.

[0093] 9 Efficacy observation

[0094] 9.1 Observation indicators

[0095] Athens Insomnia Scale (AIS), Generalized Anxiety Disorder Scale (GAD-2) and Patient Health Questionnaire-2 (PHQ-2): Observe the scale scores, sleep quality and emotional status before and after treatment. The lower the score, the more obvious the symptom improvement and the higher the total effective rate.

[0096] 9.2 Safety indicators: Liver function, kidney function, urine routine.

[0097] 9.3 Drug adverse reaction conditions.

[0098] 10. Safety observation and adverse reactions: No obvious adverse reactions were found.

[0099] 11. Result analysis

[0100] A total of 105 cases were included and divided into 7 groups, with 15 cases in each group. Statistical analysis of the effective rate was performed on the included cases for analysis. The results showed that the scores of insomnia and negative emotions after 4 weeks of treatment decreased compared with those before treatment (see Table 2 for details). Among them, Formula 1 is the traditional Chinese medicine combination formula with all ingredients. On the basis of Formula 1, one of the three traditional Chinese medicines, Pinelliae Rhizoma Praeparatum, Caulis Bambusae in Taenia and Aurantii Fructus Immaturus, was reduced respectively to form Formulas 2, 3 and 4; two of the three traditional Chinese medicines, Pinelliae Rhizoma Praeparatum, Caulis Bambusae in Taenia and Aurantii Fructus Immaturus, were reduced respectively to form Formulas 5, 6 and 7.

[0101] As clearly shown in the data analysis results in Table 2, Formula 1 showed the most prominent efficacy among all the formulas, specifically in its most significant improvement effect on negative emotions and insomnia symptoms. This result indicates that the traditional Chinese medicine composition contained in Formula 1 has unique advantages in relieving and improving patients' negative emotions and insomnia symptoms. At the same time, through comparative analysis, it can be found that the efficacy of Formula 1 is not only significantly better than that of Formulas 2, 3 and 4, but also in terms of the total effective rate, Formula 1 even exceeds the combined efficacy of Formulas 5, 6 and 7. This significant difference further indicates that the three traditional Chinese medicine components, Pinelliae Rhizoma Praeparatum, Caulis Bambusae in Taenia and Aurantii Fructus Immaturus in Formula 1 do not simply have an additive effect, but produce a significant synergistic effect. It is precisely this synergistic mechanism that makes Formula 1 perform particularly well in jointly improving insomnia and negative emotions, thus showing higher efficacy and broader application prospects in clinical applications. The above results indicate that the traditional Chinese medicine preparation of the present invention has significant efficacy in improving negative emotions and insomnia symptoms.

[0102] Table 2 Summary of the total effective rates of each formula after treatment (unit: %)

[0103]

[0104] Clinical Trial II:

[0105] Based on Clinical Trial I, we found that the traditional Chinese medicine compound preparation containing Pinelliae Rhizoma Praeparatum, Aurantii Fructus Immaturus, and Caulis Bambusae in Taeniis has a synergistic effect in the treatment of insomnia and mood disorders. However, we found clinically that different proportions of Pinelliae Rhizoma Praeparatum, Aurantii Fructus Immaturus, and Caulis Bambusae in Taeniis result in different clinical effects. At the same time, for people with weak spleen and stomach such as loose stools, using these three herbs alone for a long time will cause varying degrees of irritation to the gastrointestinal tract (see Table 3 for details). How to reduce these side effects through a reasonable compatibility ratio is the key to this study. In order to optimize their compatibility ratio, give full play to the advantages of each drug, and avoid or reduce gastrointestinal adverse reactions, thereby improving the clinical treatment effect. This study will further explore the compatibility ratio relationship of these three herbs in the traditional Chinese medicine preparation formula, verify whether this ratio can effectively reduce the gastrointestinal side effects caused by single drug use, and at the same time evaluate whether this compound has the possibility of improving gastrointestinal symptoms.

[0106] Table 3 List of side effects of Pinelliae Rhizoma Praeparatum, Aurantii Fructus Immaturus, and Caulis Bambusae in Taeniis

[0107]

[0108] 1. The research objects, diagnostic and inclusion criteria refer to Clinical Trial I

[0109] 2. Exclusion criteria:

[0110] (1) Severe gastrointestinal diseases (such as ulcerative colitis, Crohn's disease).

[0111] (2) Pregnancy / lactation, drug allergy history, taking psychotropic drugs in the past month.

[0112] 3. Withdrawal criteria: Severe adverse reactions, compliance < 80%.

[0113] 4. Intervention methods

[0114] 4.1 After screening and meeting the inclusion and exclusion criteria, general information of patients and scale assessment (Athens Insomnia Scale (AIS), Generalized Anxiety Disorder Scale (GAD-2), Patient Health Questionnaire-2 (PHQ-2), Gastrointestinal Symptom Rating Scale (GSRS)) were collected before the trial.

[0115] 4.2 Grouping: According to the previous clinical summary, it is planned to be divided into 3 groups, specifically as follows:

[0116] (1) Formula 1 group (original formula group): 10 g of Pinelliae Rhizoma Praeparatum, 10 g of Aurantii Fructus Immaturus, 10 g of Caulis Bambusae in Taeniis, and other ingredients are the same as Formula 1 (i.e., Formula 1 in Clinical Trial I).

[0117] (2) Formulation 2 group (downward adverse qi compatibility group): Pinellia ternata (processed with ginger) 15 g, Fructus Aurantii Immaturus 10 g, Caulis Bambusae in Taeniam 5 g, and other ingredients are the same as those in Formulation 1 (enhancing phlegm-resolving and adverse qi descending).

[0118] (3) Formulation 3 group (heat-clearing compatibility group): Pinellia ternata (processed with ginger) 5 g, Fructus Aurantii Immaturus 10 g, Caulis Bambusae in Taeniam 15 g, and other ingredients are the same as those in Formulation 1 (enhancing heat-clearing and phlegm-resolving).

[0119] 4.3 Course of treatment: 4 weeks.

[0120] 4.4 Administration method: 80 ml per pack, 1 pack each time, 3 times a day, taken half an hour after meals.

[0121] 5 Efficacy observation

[0122] 5.1 Observation indicators

[0123] Athens Insomnia Scale (AIS), Generalized Anxiety Disorder Scale (GAD-2), Patient Health Questionnaire-2 (PHQ-2), Gastrointestinal Symptom Rating Scale (GSRS): Observe the scale scores, sleep quality, mood, and gastrointestinal conditions before and after treatment. The lower the score, the more obvious the symptom improvement and the higher the total effective rate.

[0124] 5.2 Safety indicators: Liver function, kidney function, urine routine.

[0125] 5.3 Recording of adverse events (AE): No obvious adverse reactions were observed.

[0126] 6. Result analysis:

[0127] A total of 45 cases were included and divided into 3 groups, with 15 cases in each group. Statistical analysis of the effective rate was performed on the included cases for analysis. As shown in Table 4, the results showed that the scores of insomnia, negative emotions, and gastrointestinal scales after 4 weeks of treatment decreased compared with those before treatment, and it was shown that Formulation 1 (the same traditional Chinese medicines and doses as Formulation 1 in Clinical Trial 1) had the best effect. (See Table 4 for details). It shows that the three herbs of Pinellia ternata, Caulis Bambusae in Taeniam, and Fructus Aurantii Immaturus can play the greatest role in the three groups of tests with a ratio of 1:1:1, and this compound formula can effectively improve the gastrointestinal conditions, and the ratio is optimal under the condition of 1:1:1.

[0128] Table 4 Summary of the total effective rate and gastrointestinal improvement after treatment with each formulation (unit: %)

[0129]

[0130] Animal experiment:

[0131] 1 Experimental materials

[0132] 1.1 Experimental animals and feeding

[0133] All experimental animals in this study were male C57BL / 6J mice, 6 - 8 weeks old, weighing between 22 - 24 g, of SPF grade, and purchased from Shanghai Slake Laboratory Animal Technology Co., Ltd. All mice were housed in the animal observation room of the School of Medicine, Xiamen University, with food and water provided. They were raised under SPF conditions, at room temperature (20 - 25 °C) and humidity of 45 - 55%, with a 12-hour light / dark cycle. The animal handling procedures in this study were all in accordance with the guidelines established by the Experimental Animal Management and Ethics Committee of Xiamen University.

[0134] 1.2 Traditional Chinese Medicine and Preparation

[0135] This traditional Chinese medicine compound was provided by the traditional Chinese medicine pharmacy of the First Affiliated Hospital of Xiamen University and consisted of the drugs in Example 1 above. After the drugs were decocted into a water decoction, they were concentrated using a rotary evaporator.

[0136] 2.1 Experimental Design

[0137] C57BL / 6 mice were randomly divided into a control group (n = 12), a sleep deprivation group (SD, n = 12), an SD + low-dose traditional Chinese medicine group (SXL, n = 12, dosage 1.543 g / ml), an SD + high-dose traditional Chinese medicine group (SXH, n = 12, dosage 3.086 g / ml), and an SD + agomelatine group (Ago, n = 12, dosage 0.3214 mg / ml). The mice in the SD, SXL, SXH, and Ago groups were placed in a slowly rotating single-bar sleep deprivation device and rotated continuously at a speed of 1 revolution per minute for 20 hours per day (18:00 - 14:00 + 1 day) for 21 consecutive days to deprive the mice of sleep. The mice were gavaged simultaneously during model establishment. The mice in the Control group and the SD group were given an equal amount of distilled water daily. The mice in each treatment group were gavaged from 14:00 to 18:00 once a day. According to the different weights of the mice, 1 ml of gavage was performed per 100 g. This was done for 21 consecutive days. The food and water were changed every 3 days.

[0138] 3 Result Analysis:

[0139] 3.1 The states of mice in different groups were different

[0140] The mental and emotional states as well as the basic metabolism of mice were observed under sleep deprivation. The results showed that: the mice in the control group (CON) were in good mental state, able to move and sleep freely, with bright eyes, and the fur of the whole mice was healthy, soft and shiny; the mice in the model group (SD) showed significant exhaustion, listless eyes, lethargy, dull and unglossy hair, irritable temperament and prone to fighting, and the feces were yellow, thin and soft; the exhaustion states of the mice in the three drug administration groups of the traditional Chinese medicine preparation low-dose group (SXL), high-dose group (SXH) and agomelatine (Ago) were relatively relieved, their hair was relatively smooth without obvious greasiness, they could groom their hair in time, and the feces were normal and granular. Our observation data indicate that sleep deprivation caused exhaustion in mice and may also have an adverse effect on the emotions and body metabolism of mice.

[0141] 3.2 This traditional Chinese medicine preparation can effectively improve the depressive and anxiety-like emotions of mice caused by sleep deprivation

[0142] We used the open field test, elevated plus maze test and black and white box test to evaluate the tension and exploratory behavior of mice, and the tail suspension test to detect the depressive-like behavior of mice. The behavioral results showed that: in the open field test, the total movement distance in the central area of the mice in the SD group was significantly lower than that of the control group and the traditional Chinese medicine preparation treatment group ( Figure 1 A), indicating that this traditional Chinese medicine preparation can effectively reduce the tension of mice and does not affect the spontaneous activity of mice; in the elevated plus maze test, compared with the control group, the proportion of time that the mice in the SD group entered the open arms decreased significantly, indicating that the mice were in an anxious state. After treatment with the three groups of high-dose, low-dose and agomelatine, the proportion of time that the mice stayed in the open arms increased significantly ( Figure 1 B), indicating that this traditional Chinese medicine preparation can relieve this kind of anxiety-like behavior change, and the treatment effect of the low-dose group was close to that of the control group, highly suggesting the effectiveness of the treatment; the results of the tail suspension test showed that, compared with the control group, the average immobility time of the mice in the SD group increased by 60 seconds, and the high-amplitude struggling time showed a decreasing trend compared with the control group. After high-dose and low-dose treatment, the immobility time of the mice was reduced by 65 seconds and 50 seconds respectively compared with the SD group, and the high-amplitude struggling time increased significantly compared with the SD group ( Figure 1 C, D) suggesting that the chronically sleep-deprived mice showed a behavior state of despair and depression, and this traditional Chinese medicine preparation has an antidepressant effect.

[0143] 3.3 Sleep deprivation induces gene changes in the hippocampal tissue of mice

[0144] To further clarify the effects of sleep deprivation on the emotions and central nervous system of mice, we conducted transcriptomic studies on the hippocampal tissues of the mice in the CON group, SD group and SXL group, as Figure 2As shown in Figure A, 238 genes were up-regulated and 103 genes were down-regulated in CON and SD mice. In SD and SXL mice, 85 genes were up-regulated and 162 genes were down-regulated ( Figure 2 A-B). Then, we performed GO analysis on the significantly differentially expressed genes in the hippocampal tissues of the three groups (SXL group) ( Figure 2 C). The results showed that the gene enrichment in the molecular functions indicated by all differentially expressed genes was mainly concentrated in signal pathways such as TNF, MAPK, and cAMP. These results predicted that the mood disorders caused by sleep deprivation might be related to neuroinflammation.

[0145] 3.4 Effects of this traditional Chinese medicine preparation on the TNF signaling pathway in the hippocampal tissues of sleep-deprived mice

[0146] Based on the prediction of transcriptomics, we selected downstream related genes (P38, JNK, NF-kB and their phosphorylations) of the TNF signaling pathway for verification experiments ( Figure 3 A). The results of Western blot showed that there were no significant differences in the protein levels of P38 and JNK in the hippocampal tissues of sleep-deprived mice among the groups, but the expressions of P-JNK and P-P38 were relatively high in the SD group. After treatment, the ratios of P-JNK, P-P38 to JNK and P38, and the protein expression level of NF-kB decreased significantly ( Figure 3 B). GSEA analysis based on RNA-seq indicated that there were significant differences between the sleep-deprived and treatment groups in "long-term depression" and "phagocytic function" ( Figure 3 C). Combining the above results, we verified that this traditional Chinese medicine preparation inhibited neuroinflammation by inhibiting the activation of MAPKs downstream of the TNF signaling pathway, and MAPKs might be the drug targets for treating depressive mood after sleep deprivation.

[0147] 3.5 Effects of the traditional Chinese medicine preparation on astrocytes and microglia in the hippocampal tissues of sleep-deprived mice

[0148] Neuroinflammation is characterized by the activation of microglia in the brain, and the TNF signaling pathway is closely related to the activation of microglia. We used immunofluorescence staining to further explore whether the microglia in the hippocampus were activated after SD ( Figure 4 A). It was observed that after sleep deprivation, the number of microglia in the DG area, CA1 and CA3 areas of the hippocampal tissues of mice increased significantly. After treatment with the traditional Chinese medicine preparation, the number of microglia in each area of the hippocampus decreased significantly to be close to that of the normal group mice ( Figure 4C). Moreover, after sleep deprivation, the area of microglia in the DG region, CA1, and CA3 regions of the mouse hippocampus also increased significantly, with reduced branches and fewer branch points, suggesting that sleep deprivation can lead to the activation of microglia in mice, while the traditional Chinese medicine preparation can effectively inhibit the activation of microglia, reduce the area of microglia, and restore the number of branches. Figure 4 D). Astrocytes are related to emotions, so we also explored the morphology of astrocytes in the hippocampal tissue of sleep-deprived mice. The results showed that sleep deprivation can increase the number of astrocytes in the DG region of the hippocampus, also suggesting neuroinflammation, while the traditional Chinese medicine preparation can effectively reduce the number of astrocytes in the DG region. Figure 4 B). Combining the morphological analysis of astrocytes and microglia, our results indicate that sleep deprivation has a more severe impact on microglia in the hippocampal tissue of mice. Therefore, we speculate that microglia may be the key nerve cells affected by sleep deprivation on emotions.

[0149] The above is only the preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A Chinese medicinal compound for improving negative emotions and insomnia, characterized in that: Calculated by weight, the invention comprises: 5-15 parts of stir-fried Chinese jujube seeds, 10-20 parts of Poria cocos, 5-15 parts of Chuanxiong, 10-20 parts of Scutellaria baicalensis, 5-15 parts of Pinellia ternata, 5-15 parts of Anemarrhena asphodeloides, 5-15 parts of Citrus aurantium, 5-15 parts of Schisandra chinensis, 5-15 parts of Rhizoma Anemarrhenae, and 10-20 parts of stir-fried White Peony Root.

2. The Chinese medicinal compound for improving negative emotions and insomnia according to claim 1, characterized in that: Calculated by weight, the invention comprises: 15 parts of stir-fried Chinese jujube seeds, 15 parts of Poria cocos, 10 parts of Chuanxiong rhizome, 15 parts of Scutellaria baicalensis, 10 parts of Pinellia ternata, 10 parts of Anemarrhena asphodeloides, 10 parts of Citrus aurantium, 10 parts of Schisandra chinensis, 10 parts of Rhizoma Anemarrhenae, and 15 parts of stir-fried White Peony Root.

3. A Chinese medicine preparation for improving negative emotions and insomnia, characterized in that: Including the Chinese medicine compound described in claim 1 or 2.

4. The Chinese medicine preparation for improving negative emotions and insomnia according to claim 3, characterized in that: It also contains pharmaceutically acceptable excipients and / or carriers.

5. The Chinese medicine preparation for improving negative emotions and insomnia according to claim 3, characterized in that: The dosage form of the preparation is a liquid dosage form or a solid dosage form.

6. Use of the Chinese medicinal compound according to claim 1 or 2 in preparing a medicine for improving negative emotions and insomnia.

7. Use of the Chinese medicinal compound according to claim 1 or 2 in preparing a health product for improving negative emotions and insomnia.

8. The use according to claim 6 or 7, characterized in that: The negative emotion is depression or anxiety.

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