A Chinese medicine composition for treating cardiac neurosis and its preparation method and application

Abstract

The present invention discloses a Chinese medicine composition for treating cardiac neurosis, and a preparation method and application thereof. The Chinese medicine composition of the present invention is prepared from the following raw materials in parts by weight: 30 parts of Chinese date seeds, 10 parts of cypress seeds, 10 parts of ophiopogon japonicus, 10 parts of stir-fried white peony root, 10 parts of angelica sinensis, 12 parts of schisandra chinensis, 30 parts of tuckahoe, and 15 parts of roasted liquorice. Many years of clinical studies have shown that the Chinese medicine composition of the present invention can achieve significant clinical efficacy in treating cardiac neurosis. The prescription significantly improves clinical symptoms, and is highly safe and tolerable, and can improve or restore its social function. The medicinal materials of the present invention are easy to obtain, low in cost, and reasonable in prescription. It has the characteristics of good efficacy, short course of treatment, and no side effects, and can effectively treat cardiac neurosis of heart and liver yin deficiency type.

Description

Technical Field

[0001] The invention relates to a Chinese medicine composition for treating cardiac neurosis and a preparation method and application thereof, in particular to a Chinese medicine composition prepared with Chinese herbal medicine as raw materials, belonging to the field of traditional Chinese medicine. Background Art

[0002] Cardiac Neurosis, also known as cardiac neurosis, belongs to the category of somatic symptom disorder or medically inexplicable symptoms. It is a neurosis with cardiovascular symptoms as the main clinical manifestation, accompanied or not accompanied by anxiety, depression, fear, among which cardiovascular symptoms mainly include palpitation, chest tightness or precordial pain. Although cardiac neurosis has no organic lesions and is defined as a functional disease, it does not mean that the patient is "disease-free" or "falsely ill", and the patient's quality of life and mental health are greatly affected.

[0003] Cardiac neurosis was first proposed by Oppenholzer, a clinician in Vienna, in 1867. Foreign studies have shown that the incidence of cardiac neurosis is 20-30%, and about one-third of heart diseases are related to psychological disorders. The symptoms of cardiac neurosis are divided into two aspects: one is cardiovascular system symptoms, including palpitations, precordial pain, chest tightness and shortness of breath, and the other is nervous system symptoms, including anxiety, depression, fear, compulsion, insomnia, sweating, etc. The World Health Organization lists psychological disorders as the fourth largest disease in the world, which shows that many diseases are closely related to psychological disorders. King Kong et al. (King Kong, etc. 2013) investigated 180 patients with cardiac neurosis and found that nearly half of them had obvious symptoms of depression and anxiety. Due to the unclear understanding of cardiac neurosis in medicine, the current treatment plan is mainly based on beta-blockers, anti-anxiety and depression drugs, and psychotherapy. Patients with cardiac neurosis have the following clinical characteristics: many symptoms but few positive signs; many examinations but few abnormal results; many misdiagnoses but few missed diagnoses; varying lengths of disease courses but few serious consequences. Repeated examinations and inability to make a diagnosis have resulted in a lack of clear treatment plans and a serious waste of medical resources. Summary of the invention

[0004] In view of this, the purpose of the present invention is to provide a Chinese medicine composition for treating cardiac neurosis, and its preparation method and application. The Chinese medicine composition has the advantages of definite efficacy, wide target, small toxic and side effects, and overall regulation in treating cardiac neurosis of heart and liver yin deficiency type.

[0005] The present invention provides a Chinese medicine composition, which is made from the following raw materials in parts by weight:

[0006] 30 parts of spiny jujube seeds, 10 parts of cypress seeds, 10 parts of ophiopogon japonicus, 10 parts of stir-fried white peony root, 10 parts of angelica sinensis, 12 parts of schisandra chinensis, 30 parts of poria cocos, and 15 parts of roasted liquorice root.

[0007] In the present invention, the dosage form of the traditional Chinese medicine composition can be any dosage form acceptable to traditional Chinese medicine preparations, such as a decoction.

[0008] The present invention further provides a method for preparing the Chinese medicine composition, comprising the following steps:

[0009] 1) mixing the raw materials of the Chinese medicine composition, adding water for the first time, soaking and then boiling to obtain a medicinal liquid;

[0010] 2) adding water to the medicinal solution obtained in step 1) for a second time, boiling, and obtaining the medicinal solution;

[0011] 3) Mixing the medicinal solutions of step 1) and step 2) to obtain the Chinese medicine composition.

[0012] In the above preparation method, the ratio of the first water addition and the second water addition is as follows: 600 mL of water is added to the raw materials of 30 g of spiny jujube seeds, 10 g of cypress seeds, 10 g of ophiopogon japonicus, 10 g of stir-fried white peony root, 10 g of angelica sinensis, 12 g of schisandra chinensis, 30 g of poria cocos, and 15 g of roasted licorice, and 500 mL of water is added to the resulting liquid;

[0013] In step 1), the soaking time is 30 to 60 minutes;

[0014] In step 1), the decocting is performed slowly over low heat, and after boiling, decocting is continued for 40 minutes;

[0015] In step 2), the decocting is performed slowly over low heat, and decocting is continued for 20 minutes after boiling.

[0016] The present invention also provides the use of the Chinese medicine composition in any of the following:

[0017] A1) Preparation of a medicament for the treatment of cardiac neurosis;

[0018] A2) Use in the preparation of a medicament for treating cardiac neurosis in coordination with or in combination with individual behavioral cognitive therapy;

[0019] A3) Use in the preparation of a medicament for treating cardiac neurosis in patients undergoing individual behavioral cognitive therapy.

[0020] Preferably, the cardiac neurosis is of the heart and liver yin deficiency type. Symptoms include restlessness, insomnia, frequent dreams, easy startle, dizziness, dry eyes, dry mouth and throat, emaciation, red tongue, less tongue coating, thin or rapid pulse, accompanied by low fever or hot flashes, night sweats, hot palms and soles, red cheeks, scanty and dark red menstruation, etc.

[0021] The present invention also protects the use of any of the above-mentioned Chinese medicine compositions in any of the following:

[0022] B1) preparing medicines for improving TCM symptoms of cardiac neurosis;

[0023] B2) Preparation of drugs that cooperate with individual behavioral cognitive therapy to improve the TCM symptoms of cardiac neurosis;

[0024] B3) Application in the preparation of a drug for improving TCM symptoms of cardiac neurosis in patients undergoing individual behavioral cognitive therapy;

[0025] B4) preparing drugs for treating, alleviating, improving or suppressing anxiety;

[0026] B5) preparing drugs that cooperate with individual behavioral cognitive therapy to treat or relieve or improve or inhibit anxiety;

[0027] B6) Use in the preparation of a drug for treating or alleviating or improving or suppressing anxiety in a patient undergoing individual behavioral cognitive therapy;

[0028] B7) preparing drugs for treating, alleviating, improving or inhibiting depression;

[0029] B8) preparing drugs that cooperate with individual behavioral cognitive therapy to treat or relieve or improve or inhibit depression;

[0030] B9) preparing drugs for treating or alleviating or improving or inhibiting depression in patients undergoing individual behavioral cognitive therapy;

[0031] B10) preparing drugs for improving cardiac autonomic nervous function;

[0032] B11) preparing drugs that cooperate with individual behavioral cognitive therapy to improve cardiac autonomic nervous function;

[0033] B12) preparing a drug for improving cardiac autonomic nervous function in patients undergoing individual behavioral cognitive therapy;

[0034] B13) preparing drugs for regulating whole-brain neurotransmitters or treating whole-brain neurotransmitter disorders;

[0035] B14) preparing drugs for coordinating individual behavioral cognitive therapy to regulate whole-brain neurotransmitters or treat whole-brain neurotransmitter disorders;

[0036] B15) preparing drugs for regulating whole brain neurotransmitters or treating whole brain neurotransmitter disorders in patients undergoing individual behavioral cognitive therapy;

[0037] B16) preparing a medicine for improving palpitations, panic and / or insomnia.

[0038] Specifically, the TCM symptoms of cardiac neurosis are at least one of palpitations, shortness of breath, chest pain, chest tightness, dry eyes, dry mouth, insomnia and frequent dreams.

[0039] Specifically, the improvement of cardiac autonomic nervous function is reflected in improving at least one of the heart rate variability indicators SDNN, SDANN, and rMSSD.

[0040] Specifically, the whole-brain neurotransmitter includes at least one of whole-brain 5-HT, DA and EXC.

[0041] A product for treating cardiac neurosis, comprising the Chinese medicine composition as described in any one of the above claims and an individual cognitive behavioral therapy device, is also within the protection scope of the present invention.

[0042] The use of any of the above-mentioned traditional Chinese medicine compositions and individual cognitive behavioral therapeutic apparatuses in the preparation of products for treating cardiac neurosis also falls within the protection scope of the present invention.

[0043] The use of the Chinese medicine composition and individual cognitive behavioral therapy device described in any of the above items in any of the following items is also within the protection scope of the present invention;

[0044] C1) preparing products for improving TCM symptoms of cardiac neurosis;

[0045] C2) preparing products for treating, alleviating, improving or suppressing anxiety;

[0046] C3) preparing products for treating, alleviating, improving or inhibiting depression;

[0047] C4) preparing products for improving cardiac autonomic nervous function;

[0048] C5) Prepare products for regulating whole-brain neurotransmitters or treating whole-brain neurotransmitter disorders.

[0049] Specifically, the individual cognitive behavioral therapy device is a product that can implement the following treatment steps:

[0050] Step 1: Problem assessment, identify the patient's pathogenic factors, understand the psychological model of the patient's symptom problem; make a detailed assessment of the patient's symptoms, degree of limitation, current coping methods, and beliefs about the cause; at the same time, understand the interaction pattern of the patient's physiology, cognition, emotion, and behavior in the formation of symptoms;

[0051] Step 2: Use cognitive techniques to correct the patient's distorted and erroneous thinking, including subjective assumptions, misinterpretations, and negative perceptions;

[0052] Step 3: Address factors that maintain the problem; use problem-solving techniques to identify and address lifestyle and personality factors that maintain symptoms; use cognitive methods to identify and challenge the patient's unhelpful assumptions;

[0053] Step 4: Guide patients to correctly deal with conflicts in society and family, explore their inner desire for material and spiritual things, help them restore their self-improvement attitude towards life, and actively participate in outdoor group sports;

[0054] Step 5: At the end of the visit period, provide the patient with cognitive behavioral therapy points based on the psychosocial causes of the patient's illness to reduce the relapse rate.

[0055] In the present invention, the subjects are patients with cardiac neurosis, and the usage and dosage are as follows: one dose of the Chinese medicine composition made from the following amounts of raw materials: 30g of Ziziphus jujuba seed, 10g of Platycladus orientalis seed, 30g of Poria cocos, 10g of Ophiopogon japonicus, 10g of White Peony Root, 10g of Angelica sinensis, 12g of Schisandra chinensis, and 15g of Radix Glycyrrhizae Preparata; one dose per day, twice a day.

[0056] The present invention has the following beneficial effects:

[0057] The inventor of the present invention has continuously studied the syndrome rules and effective drugs of cardiac neurosis, and found that the deficiency of heart and liver yin is the core syndrome of the disease. For this symptom, the inventor has summarized and extracted the moistening liver and nourishing heart prescription for its treatment based on the previous research results and clinical experience of traditional Chinese medicine, that is, the Chinese medicine composition of the present invention, which can play the role of moistening the liver, restraining yin, nourishing the heart and calming the mind. Many years of clinical studies have shown that the use of the Chinese medicine composition of the present invention to treat cardiac neurosis can obtain obvious clinical efficacy, the prescription significantly improves clinical symptoms, and is safe and highly tolerable, and can improve or restore its social function. The medicinal materials of the present invention are easy to obtain, low in cost, reasonable in prescription, and have the characteristics of good efficacy, short course of treatment, no side effects, etc., and can effectively treat cardiac neurosis of deficiency of heart and liver yin.

[0058] Invention solution:

[0059] Main medicine: Ziziphus jujuba seed, Platycladus orientalis seed

[0060] The Chinese date seed is sweet and mild in nature, and enters the heart, liver, and gallbladder meridians. It nourishes yin and liver, calms the mind and tranquilizes the spirit; the cypress seed is sweet and mild in nature, and enters the heart, kidney, and large intestine meridians. It nourishes the heart and tranquilizes the spirit, nourishes blood and relieves constipation, and stops sweating. The Chinese date seed and cypress seed are both sweet and mild in nature, and enter the heart meridian. They are both monarch drugs and play the role of nourishing yin and softening the liver, nourishing the heart and tranquilizing the spirit, helping the heart and liver to have sufficient yin and blood, and calming the mind and stabilizing the spirit.

[0061] Assistant medicine: white peony root, angelica root, ophiopogon japonicus, schisandra chinensis, poria cocos, roasted licorice root

[0062] White peony root is sour, bitter and slightly cold in nature. It enters the liver and spleen meridians. It nourishes yin and softens the liver in the whole formula, nourishes the heart, the mother organ, and regulates the heart and liver. Angelica sinensis is sweet and warm in nature. It enters the heart, liver and spleen meridians. It is best at nourishing blood and activating blood circulation, moistening the intestines and relieving constipation. Angelica sinensis and white peony root are combined to nourish yin and blood. When yin and blood are sufficient, the mind is at peace. Ophiopogon japonicus is sweet and cold in nature. It enters the heart, stomach and lung meridians. It nourishes yin and produces body fluid, clears the heart and moistens the lungs. Schisandra chinensis is sour and warm in nature. It enters the heart, lung and kidney meridians. It has the effects of producing body fluid and replenishing qi, nourishing the kidney and calming the heart, and astringing and consolidating. It plays a role in synchronizing the heart and kidney, balancing water and fire, and calming the mind. Poria cocos is sweet and mild in nature. It enters the heart, spleen, lung, and kidney meridians. It has the effects of strengthening the spleen and eliminating dampness, as well as calming the mind and tranquilizing the nerves. Roasted licorice is sweet and mild in nature. It mainly enters the spleen and stomach meridians. Its main function is to regulate the middle and relieve urgency, and to harmonize various medicines. The roasted licorice in the prescription harmonizes the medicines for moistening the liver and nourishing the heart, allowing each Chinese medicine to exert its efficacy, each with its own expertise, and complement each other.

[0063] The combination of all the herbs in the formula for nourishing the liver and nourishing the heart focuses on "nourishing" and "nourishing". Ziziphus jujuba seeds and cypress seeds nourish the heart and nourish the spirit, moisten the intestines and relieve constipation, white peony and angelica nourish the blood and soften the liver, Ophiopogon japonicus and Schisandra chinensis nourish yin and promote fluid production, and Poria cocos and roasted licorice nourish the spleen and stomach and help the source of qi and blood production. Wood is the mother of fire. White peony and angelica nourish the liver, enrich the mother organs and nourish the child organs; fire is the mother of earth. Poria cocos eliminates dampness and strengthens the spleen, and roasted licorice harmonizes the spleen and stomach, protects the spleen and earth, enriches the child organs, and relieves the mother organs; Schisandra chinensis consolidates and nourishes the essence, harmonizes the heart and kidney, and balances water and fire. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] Figure 1 This is a flow chart of the experiment in Example 2 of the present invention. DETAILED DESCRIPTION

[0065] In order to further understand the present invention, the Chinese medicine composition for treating cardiac neurosis provided by the present invention and its preparation method and application are described in detail in conjunction with the examples below. The examples given are only for illustrating the present invention, not for limiting the scope of the present invention. The examples provided below can be used as a guide for further improvements by ordinary technicians in the technical field, and do not constitute a limitation of the present invention in any way.

[0066] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the materials, reagents, etc. used, unless otherwise specified, can be obtained from commercial channels.

[0067] The raw materials of the following embodiments, such as Semen Ziziphi Spinosae, Semen Platycladi, Radix Ophiopogonis, Radix Paeoniae Alba, Radix Angelicae Sinensis, Fructus Schisandrae Chinensis, Poria, and Radix Glycyrrhizae are all medicinal materials listed in the Chinese Pharmacopoeia or the Chinese Medicine Processing Specifications. After identification, all indicators meet the requirements.

[0068] Example 1: Preparation of a Chinese medicine composition for treating cardiac neurosis

[0069] 1. Formulation

[0070] 30g of Ziziphus jujuba seed, 10g of Torreya grandis seed, 30g of Poria cocos, 10g of Ophiopogon japonicus, 10g of White Peony Root, 10g of Angelica sinensis, 12g of Schisandra chinensis, and 15g of Roasted Licorice Root.

[0071] 2. Preparation method

[0072] Preparation method of water decoction: Take the corresponding mass of raw materials according to the above formula, put all the raw materials in the above Chinese medicine composition into a casserole, add 600ml of tap water, soak for 45 minutes, simmer over low heat, and continue to simmer for 40 minutes after boiling to obtain the liquid medicine. Add 500ml of water for the second time, simmer over low heat, and continue to simmer for 20 minutes after boiling to obtain the liquid medicine. Mix the two liquid medicines (one dose) and divide them into two equal parts.

[0073] 3. Usage and Dosage

[0074] Take warm, one dose per day, twice a day.

[0075] Example 2, clinical trial

[0076] 2.1 Diagnostic criteria

[0077] 2.1.1 Western medicine diagnostic criteria: Based on the "Practical Internal Medicine" (15th edition) and ICD-10, with reference to the key points of somatoform autonomic dysfunction, the following diagnostic criteria are formulated: (1) Persistent autonomic nervous system symptoms: mainly anxiety and hypochondriasis, but also depression, fear, compulsion, etc., may be accompanied by varying degrees of insomnia, tension, dizziness, sweating, fatigue, tremors, etc.; (2) Persistent symptoms of cardiovascular system dysfunction: such as palpitations, precordial pain, shortness of breath and hyperventilation; (3) After comprehensive and systematic cardiovascular examinations (such as electrocardiogram, dynamic electrocardiogram, echocardiogram, coronary artery CT or coronary angiography, etc.), no organic heart disease diagnosis basis has been found or the existing organic basis cannot explain the current clinical symptoms, or satisfactory results are often not obtained after treatment for heart disease.

[0078] 2.1.2 TCM Syndrome Differentiation Standard: Based on the Syndrome Part of TCM Clinical Diagnosis and Treatment Terminology and the previous clinical research of the research team, the syndrome differentiation of cardiac neurosis is carried out. Heart and Liver Yin Deficiency Type: Symptoms include restlessness, insomnia, frequent dreams, easy startle, dizziness, dry eyes, dry mouth and throat, emaciation, red tongue, less tongue coating, thin or rapid pulse, accompanied by low fever or hot flashes, night sweats, hot palms and soles, red cheeks, and scanty and dark red menstruation.

[0079] 2.2 Case selection

[0080] 2.2.1 Source of cases

[0081] This study enrolled patients with cardiac neurosis who met the inclusion criteria and visited the outpatient department of psychosomatic medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences from April to October 2022 as research subjects. Thirty patients with cardiac neurosis who met the inclusion and exclusion criteria were selected, and there were 30 qualified cases.

[0082] 2.2.2 Case inclusion criteria

[0083] The cases included in this study were based on Practical Internal Medicine (15th edition) and ICD-10, with reference to the key points of somatoform autonomic dysfunction, and the following criteria were used as the inclusion criteria for this topic:

[0084] (1) Meet the diagnostic criteria for cardiac neurosis, age 18 to 60 years, regardless of gender.

[0085] (2) The patient should meet the diagnostic criteria of TCM differentiation of heart and liver yin deficiency syndrome.

[0086] (3) Patients had not taken anti-anxiety drugs, antidepressants, or psychotropic drugs within 2 weeks before enrollment.

[0087] (4) The patient signs the informed consent form.

[0088] 2.2.3 Case Exclusion Criteria

[0089] Those with any of the following conditions were not included in this study.

[0090] (1) Patients with organic heart diseases such as coronary heart disease, myocarditis, mitral valve prolapse, etc., with clear heart lesions indicated by electrocardiogram, 24-hour dynamic electrocardiogram, echocardiogram, coronary CT, and PCI examinations;

[0091] (2) Combined endocrine and metabolic diseases, such as hyperthyroidism and diabetes;

[0092] (3) Patients with ST-T segment changes caused by other reasons that cannot be corrected, such as hypokalemia, digitalis or other drug reactions, and "juvenile T wave" changes;

[0093] (4) Chronic infection, drug-induced diseases, other serious physical diseases such as kidney and brain diseases, epilepsy, etc.;

[0094] (5) Those with severe mental illness or a family history of mental illness;

[0095] (6) Pregnant or lactating women or women who wish to become pregnant;

[0096] (7) Participated in another clinical trial of research drug within one month before inclusion in this study.

[0097] 2.2.4 Termination criteria

[0098] (1) Anyone who is found to be not in compliance with the trial protocol after enrollment;

[0099] (2) Patients who refuse to continue to participate in the trial study;

[0100] (3) lost to follow-up;

[0101] (4) Those who were found to have serious physical illness or other non-drug reasons after enrollment and discontinued the trial;

[0102] (5) Failure to follow medication regulations;

[0103] (6) Combined with prohibited drugs or other treatments.

[0104] 2.2.5 Termination criteria

[0105] (1) All blind disclosures during clinical trials;

[0106] (2) The emergency letter opening rate exceeds 20%;

[0107] (3) The Ethics Committee has the right to terminate or suspend;

[0108] (4) Clinical drugs have serious side effects.

[0109] 2.2.6 Shedding Standard

[0110] Any of the following situations will be considered as shedding.

[0111] (1) Subjects with poor treatment compliance and failure to take medication as prescribed;

[0112] (2) Those who dropped out naturally or were lost to follow-up during the observation period, including those whose treatment was effective but who did not complete the entire course of treatment and whose data were incomplete, thus affecting the determination of efficacy and safety;

[0113] (3) Adverse reactions or serious adverse events occurred during the observation period, and the observation could not be continued and was terminated.

[0114] 2.3 Treatment methods

[0115] The patients were divided into a treatment group and a control group using a randomized double-blind method, with 18 cases in the treatment group and 12 cases in the control group. This study was a double-blind trial, and the drugs taken by the patients were consistent in appearance and packaging.

[0116] 2.3.1 Treatment regimen for the experimental group: water decoction of Example 1 + cognitive behavioral therapy.

[0117] Treatment principle: nourish liver yin, nourish the heart and calm the mind

[0118] Specifications and usage: The preparation method of decoction is the same as that of Example 1: Take the corresponding mass of raw materials according to the formula of Example 1, put all the raw materials in the above-mentioned Chinese medicine composition into a casserole, add 600ml of tap water, soak for 45 minutes, simmer over low heat, and continue to simmer for 40 minutes after boiling to take the liquid medicine. Add 500ml of water for the second time, simmer over low heat, and continue to simmer for 20 minutes after boiling to take the liquid medicine. Mix the two liquid medicines (one dose) and divide them into two portions. Take warm, one dose a day, once in the morning and evening after meals, for a total of 8 weeks.

[0119] Individual cognitive behavioral therapy frequency: 1 time / week, treatment steps are as follows:

[0120] Step 1: Problem assessment, identify the patient's pathogenic factors, and understand the psychological model formed by the patient's symptom problem. In this stage, a detailed assessment should be made of the patient's symptoms, degree of limitation, current coping style, and beliefs about the cause. At the same time, the interaction pattern of the patient's physiological, cognitive, emotional, and behavioral aspects of the symptom should be understood.

[0121] Step 2: Use cognitive techniques to correct the patient's distorted and inaccurate thinking including subjective assumptions, misinterpretations, and negative perceptions.

[0122] Step 3: Address factors that maintain the problem. Use problem-solving techniques to identify and address lifestyle and personality factors that maintain symptoms, such as a high-stress lifestyle. Use cognitive techniques to identify and challenge the patient's unhelpful assumptions.

[0123] Step 4: Guide patients to correctly deal with conflicts in society and family, explore their inner desire for material and spiritual things, help patients restore a self-reliant attitude towards life, and actively participate in outdoor group sports such as mountain climbing, running, etc.

[0124] Step 5: At the end of the visit period, we develop cognitive behavioral therapy points for patients based on the psychosocial causes of their illness to reduce the relapse rate.

[0125] 2.3.2 Treatment plan for the control group: Chinese medicine placebo + cognitive behavioral therapy.

[0126] The patients were treated with a Chinese herbal decoction placebo, which had the same appearance as the experimental group. Ingredients: 1 / 20 of the original dose of the drug and a decoction placebo made of edible bitter substances. Take it warm, once a day, once in the morning and once in the evening after meals, for a total of 8 weeks.

[0127] The steps for individual cognitive behavioral therapy are the same as before.

[0128] 2.4 Efficacy indicators and observation period

[0129] 2.4.1 Main efficacy indicators

[0130] 2.4.1.1 TCM Symptom Score Scale The TCM symptom score scale was developed based on the "Guidelines for Clinical Research of New Chinese Medicines" and the "Terms of Clinical Diagnosis and Treatment of TCM" formulated by the Medical Administration Department of the State Administration of Traditional Chinese Medicine. Changes in symptoms such as palpitations, shortness of breath, chest pain, chest tightness, insomnia, dyspnea, fatigue, tension, anxiety, and depression were recorded. Each symptom was divided into four levels: none, mild, moderate, and severe. The main symptoms included palpitations, shortness of breath, chest pain, chest tightness, irritability, dry eyes, dry mouth, insomnia, and dreaminess, which were scored 0, 2, 4, and 6 points respectively. The secondary symptoms included dyspnea, fatigue, night sweats, hot flashes, tension, and depression, which were scored 0, 1, 2, and 3 points respectively, or the absence or presence of each symptom was scored 0 and 1 point respectively. The TCM symptom score scale should be filled in before treatment, 2, 4, 6, and 8 weeks after treatment for each included patient, and the individual scores and total scores were calculated.

[0131] With reference to the relevant standards in the "Guidelines for Clinical Research of New Chinese Medicines (Trial)" (2002 edition), it is considered that the reduction rate of all symptom scores before and after treatment (T) is used for evaluation: T ≥ 95% is cured; 70% ≤ T < 95% is effective; 30% ≤ T < 70% is effective; T < 30% is ineffective.

[0132] 2.4.1.2 Anxiety and Depression Scale Scores

[0133] Each patient was assessed with the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) before treatment and after 2, 4, 6, and 8 weeks of treatment. A score of <7 on the Hamilton Anxiety Rating Scale indicates no anxiety, a score of 8 to 21 indicates mild anxiety, a score of 22 to 28 indicates moderate anxiety, and a score of ≥29 indicates severe anxiety. The Hamilton Depression Rating Scale uses a 24-item scale, a score of <8 indicates no depression, a score of 8 to 19 indicates mild anxiety, a score of 20 to 34 indicates moderate anxiety, and a score of ≥35 indicates severe anxiety.

[0134] The HAMA and HAMD score reduction rates (T) were used for evaluation respectively, and the score reduction rate = (baseline score - score at the time of evaluation) / baseline score × 100%: T ≥ 75% was cured; 50% ≤ T < 75% was markedly effective; 25% ≤ T < 50% was effective; T < 25% was ineffective.

[0135] 2.4.1.3 Heart rate variability index

[0136] Data were collected before and after treatment, including short-term time domain analysis indicators and frequency domain analysis indicators. According to the heart rate variability detection recommendations given by the Heart Rate Variability Countermeasures Task Force of the Editorial Board of the Chinese Journal of Cardiovascular Diseases, the selected time domain analysis indicators included the standard deviation of the normal RR interval (SDNN) and the root mean square of adjacent RR intervals (RMSSD), a total of 2 items, and the frequency domain analysis indicators included total power (TP), low frequency (LF), high frequency (HF), low frequency normalization (LFnorm), high frequency normalization (HFnorm), and low frequency / high frequency (LF / HF), a total of 6 items.

[0137] Heart rate variability analysis and evaluation criteria: ① Significantly effective: the examination results returned to normal after treatment; ② Effective: the examination results improved significantly after treatment; ③ Ineffective: the examination results did not change after treatment.

[0138] 2.4.1.4 24-hour dynamic electrocardiogram indicators

[0139] A 24-hour Holter test was performed before and after treatment. The selected indicators of the 24-hour Holter test included: average heart rate, presence of ventricular premature beats, presence of atrial premature beats, and presence of ST-T segment changes.

[0140] Evaluation criteria for 24-hour dynamic electrocardiogram: ① Recovery: no premature contractions and normal heart rate within 24 hours; ② Improvement: the number of premature contractions and tachycardia in 24 hours decreased by >50% compared with the original number; ③ Ineffectiveness: the number of premature contractions and tachycardia in 24 hours decreased by <50% or increased compared with the original number.

[0141] 2.4.2 Secondary efficacy indicators

[0142] 2.4.2.1 EEG indicators

[0143] EEG ultra-diffuse fluctuation analysis before and after treatment. EEG ultra-slow fluctuation analysis technology (SET) analyzes the EEG signal through software spectrum analysis to determine the activation of neurotransmitters in the brain, including the activation of 6 neurotransmitters: inhibitory mediator (INH), excitatory mediator (EXC), serotonin (5-HT), acetylcholine (ACh), norepinephrine (NE), and dopamine (DA).

[0144] 2.4.2.2 Psychosocial Factors Indicators

[0145] The included patients will undergo an assessment of psychosocial factors, mainly the Social Readjustment Assessment Scale, and statistical analysis will be conducted on factors such as the cause of the disease and occupation.

[0146] 2.4.3 Follow-up efficacy evaluation

[0147] After the 8-week treatment period, the population that meets the protocol will be followed up once at 8 weeks and 16 weeks. Follow-up can be conducted by telephone, letter or re-examination, and TCM symptom score, HAMA and HAMD evaluation will be conducted. The TCM symptom score evaluation is the same as 2.4.1.1, and the HAMA and HAMD evaluation is the same as 2.4.1.2.

[0148] 2.4.4 Safety indicators

[0149] Before and after treatment, blood routine, urine routine, feces routine, liver and kidney function, electrocardiogram, etc. were tested twice. If abnormalities occur during and after treatment, they must be re-examined at an appropriate time, and a comprehensive analysis must be conducted with the subject's onset and treatment to determine whether it is related to the test drug. Adverse events are determined according to the standards and the adverse event scale is filled in: the assessment time is synchronized with the efficacy assessment.

[0150] Statistical methods: Measurement data were expressed as mean ± standard deviation or median and interquartile range. For comparison of measurement data between groups, the Mann-Wnitney rank sum test was used for groups that did not conform to normal distribution; for groups that conformed to normal distribution, the variance was determined to be homogeneous, and the independent sample t test was used for groups with homogeneous variance. For comparison of measurement data within two groups, the Wilcoxon rank sum test was used for data that did not conform to normal distribution, and the paired sample t test was used for data that conformed to normal distribution. The chi-square test was used for count data. SPSS26.0 statistical software was used to analyze the data, and P < 0.05 was considered statistically significant.

[0151] 2.5 Treatment results and analysis

[0152] 2.5.1 General data analysis

[0153] This study enrolled 30 patients with cardiac neurosis who met the inclusion criteria and visited the outpatient department of psychosomatic medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences from April to October 2022 as research subjects. The patients were divided into a treatment group and a control group using a randomized double-blind method. There were 18 cases in the treatment group and 12 cases in the control group. There was no significant statistical difference in gender, age, TCM symptom score, and degree of depression and anxiety between the two groups (P>0.05), and the baseline data were comparable.

[0154] 2.5.2 Evaluation of efficacy

[0155] 2.5.2.1 Comparison of the scores of each symptom of the main TCM symptoms between the two groups after 8 weeks of treatment

[0156] Table 1. Symptom scores of the main TCM symptoms after 8 weeks of treatment

[0157]

[0158] *P<0.05, the difference is statistically significant.

[0159] After treatment, the comparison of the main TCM symptoms between the two groups showed that the treatment group had lower palpitations, shortness of breath, chest pain, chest tightness, dry eyes, dry mouth, insomnia and frequent dreams than the control group, and the difference was statistically significant (P<0.05).

[0160] 2.5.2.2 Comparison of TCM syndrome efficacy between the two groups

[0161] The efficacy judgment standard of clinical TCM symptoms is formulated with reference to the "Guidelines for Clinical Research of New Chinese Medicines", and the main symptoms before and after treatment are compared by points. Efficacy index T (%) = (score before treatment - score after treatment) ÷ score before treatment × 100%.

[0162] (1) Cured: The original symptoms basically disappeared, and the clinical symptom score decreased by more than or equal to 90%; (2) Significantly effective: The clinical symptoms and signs were significantly alleviated, and the clinical symptom score decreased by more than or equal to 70%; (3) Effective: The clinical symptoms and signs were improved, and the symptom score decreased by more than or equal to 30%; (4) Ineffective: The clinical symptoms and signs were not significantly improved, or even aggravated, and the symptom score decreased by less than 30%.

[0163] Table 2. TCM syndrome efficacy

[0164]

[0165] There was a statistically significant difference in the effective rate between the two groups after treatment (P<0.05), and the effective rate of the treatment group was higher than that of the control group.

[0166] 2.5.2.3 Comparison of Hamilton Depression Rating Scale 24 (HAMD-24) scores between the two groups after 8 weeks of treatment

[0167] Table 3. HAMD-24 scores after 8 weeks of treatment ( point)

[0168]

[0169] After 8 weeks of treatment, the HAMD-24 scores of the two groups were significantly different (P<0.01), and the HAMD-24 scores of the treatment group were lower than those of the control group.

[0170] 2.5.2.4 Comparison of Hamilton Anxiety Rating Scale (HAMA) scores between the two groups after 8 weeks of treatment

[0171] Table 4. HAMA score after 8 weeks of treatment (M(QR), points)

[0172]

[0173] After 8 weeks of treatment, the difference in HAMA scores between the two groups was statistically significant (P<0.01), and the HAMA score in the treatment group was lower than that in the control group.

[0174] 2.5.2.5 Comparison of heart rate variability index SDNN between the two groups after 8 weeks of treatment

[0175] Table 5. SDNN after 8 weeks of treatment ( m / s)

[0176]

[0177] After 8 weeks of treatment, the difference in heart rate variability index SDNN between the two groups was statistically significant (P<0.01), and the SDNN in the treatment group was higher than that in the control group.

[0178] 2.5.2.6 Comparison of heart rate variability index SDANN between the two groups after 8 weeks of treatment

[0179] Table 6. SDANN after 8 weeks of treatment ( m / s)

[0180]

[0181] There was no significant difference in heart rate variability index SDANN between the two groups after 8 weeks of treatment (P>0.05).

[0182] 2.5.2.6 Comparison of heart rate variability index rMSSD between the two groups after 8 weeks of treatment

[0183] Table 7. rMSSD (M (QR)) after 8 weeks of treatment

[0184]

[0185] After 8 weeks of treatment, the difference in rMSSD of heart rate variability between the two groups was statistically significant (P<0.05), and the rMSSD of the treatment group was higher than that of the control group.

[0186] After 8 weeks of treatment, SDNN and rMSSD in the treatment group were higher than those in the control group (P<0.05), indicating that the Chinese medicine composition of the present invention is superior to the placebo in improving cardiac autonomic nerve function, reducing sympathetic nerve tension, and improving the prognosis of cardiac neurosis.

[0187] 2.5.2.7 Comparison of whole brain neurotransmitters between the two groups after 8 weeks of treatment

[0188] Table 8. Neurotransmitters in the whole brain after 8 weeks of treatment

[0189]

[0190] Note: * indicates that the difference within the group is statistically significant (P < 0.05), △ indicates that the difference between the groups is statistically significant (P < 0.05).

[0191] After 8 weeks of treatment, the treatment group showed statistically significant differences in whole-brain 5-HT, DA, and EXC before and after treatment (P < 0.05), which was manifested by higher whole-brain 5-HT levels after treatment, lower whole-brain DA levels after treatment, and lower whole-brain EXC levels after treatment than before treatment. Compared with the control group, the whole-brain DA and EXC levels of the two groups after treatment were statistically significant (P < 0.05), which was manifested by lower whole-brain DA and EXC levels in the test group after treatment than in the control group. This shows that the Chinese medicine composition of the present invention is better than the placebo in improving the whole-brain 5-HT level and balancing the DA and EXC levels. The Chinese medicine composition of the present invention helps to improve the whole-brain neurotransmitters, thereby improving depression and anxiety.

[0192] 2.5.2.8 Comparison of the scores of each symptom of the main TCM symptoms between the two groups at the 16-week visit

[0193] Table 9. Symptom scores of each TCM main symptom at the 16-week visit (M(QR), points)

[0194]

[0195]

[0196] *P<0.05, the difference is statistically significant.

[0197] When the two groups were visited at 16 weeks, the main TCM symptoms were compared. The treatment group had lower rates of palpitations, shortness of breath, chest pain, chest tightness, dry eyes, dry mouth, insomnia and frequent dreams than the control group, and the difference was statistically significant (P<0.05).

[0198] After 8 weeks of treatment, the scores of palpitations, shortness of breath, chest pain, chest tightness, dry eyes, dry mouth, insomnia, and dreaminess in the treatment group were lower than those in the control group (P<0.05), and the effective rate and effective rate of the treatment group were higher than those in the control group (P<0.05). At the 16-week follow-up, the scores of palpitations, shortness of breath, chest pain, chest tightness, dry eyes, dry mouth, insomnia, and dreaminess in the treatment group were lower than those in the control group, and the difference was statistically significant (P<0.05). It shows that the effective rate of the Chinese medicine composition of the present invention in treating cardiac neurosis is higher than that in the control group, and the efficacy of alleviating the main symptoms of cardiac neurosis after 8 weeks of treatment and at the 16-week follow-up is better than that of the placebo.

[0199] 2.5.2.9 Comparison of Hamilton Depression Rating Scale 24 (HAMD-24) scores between the two groups at the 16-week visit

[0200] Table 10. HAMD-24 scores at the 16-week visit ( point)

[0201]

[0202] At the 16-week visit, the difference in HAMD-24 scores between the two groups was statistically significant (P<0.01), and the HAMD-24 score in the treatment group was lower than that in the control group.

[0203] After 8 weeks of treatment, the HAMD-24 score of the treatment group was lower than that of the control group (P<0.05). At the 16-week follow-up, the HAMD-24 score of the treatment group was lower than that of the control group (P<0.05). This indicates that the Chinese medicine composition of the present invention is more effective than the control group in improving depression in patients with cardiac neurosis after 8 weeks of treatment and at the 16-week follow-up.

[0204] 2.5.2.10 Comparison of Hamilton Anxiety Rating Scale (HAMA) scores between the two groups at the 16-week visit

[0205] Table 11. HAMA scores at the 16-week visit ( point)

[0206]

[0207] At the 16-week visit, the difference in HAMA scores between the two groups was statistically significant (P < 0.01), and the HAMA score in the treatment group was lower than that in the control group.

[0208] After 8 weeks of treatment, the HAMA score of the treatment group was lower than that of the control group (P<0.05). At the 16-week follow-up, the HAMA score of the treatment group was lower than that of the control group (P<0.05). This indicates that the Chinese medicine composition of the present invention is more effective than the control group in improving anxiety in patients with cardiac neurosis after 8 weeks of treatment and at the 16-week follow-up.

[0209] 2.5.3 Safety evaluation

[0210] The urine and stool routine tests, liver and kidney function tests, and electrocardiograms of the two groups of patients were compared before treatment and 8 weeks after treatment. No abnormalities were found in either group, and the incidence of adverse reactions in the treatment group was lower than that in the control group.

[0211] Table 12. Comparison of changes in urine, stool routine, liver and kidney function, and electrocardiogram in the treatment groups

[0212]

[0213] Table 13. Comparison of changes in urine, stool routine, liver and kidney function, and electrocardiogram in the control group

[0214]

[0215] Table 14. Comparison of adverse reactions

[0216]

[0217] The urine and stool routine, liver and kidney function, and electrocardiogram of the two groups of patients were compared before treatment and 8 weeks after treatment. No abnormalities were found in the two groups of patients, and the incidence of adverse reactions in the treatment group was lower than that in the control group. This shows that the Chinese medicine composition of the present invention has good safety.

[0218] In summary, the treatment group has a higher efficacy than the control group in improving TCM symptoms, depression, anxiety, cardiac autonomic nerve function, and whole brain neurotransmitters, indicating that the Chinese medicine composition of the present invention can effectively treat cardiac neurosis of heart and liver yin deficiency type. In addition, no obvious abnormalities were found in the blood routine, urine routine, feces routine, liver and kidney function, and electrocardiogram of each group of patients before and after treatment, and no obvious adverse reactions occurred in the patients during the administration period, which fully demonstrated the safety of the Chinese medicine composition of the present invention.

[0219] Example 3, typical case:

[0220] Examples of Cases of Cardiac Neurosis

[0221] The patient, female, 73 years old. On March 30, 2023, she was treated in the outpatient clinic of the Department of Psychosomatic Medicine of Guang'anmen Hospital. Chief complaint: palpitations accompanied by insomnia for 1 year, aggravated for 3 months. The patient had palpitations without obvious cause 1 year ago, accompanied by difficulty falling asleep and dreaming. She was treated in the community hospital and given Zopiclone tablets 7.5mg orally 1 / night and other medications, and her sleep improved slightly. 3 months ago, there was no obvious cause for palpitations and palpitations to worsen, accompanied by dizziness, tightness in the head, irritability, depression, memory loss, no chest tightness and wheezing, and no obvious abnormalities were found in cardiac ultrasound, coronary CT and other examinations, but the palpitations were still obvious, so she was treated in our department. At present: palpitations, no obvious aggravation after exercise, no chest tightness or shortness of breath, accompanied by dizziness, tightness in the head, tension, anxiety, irritability, foreign body sensation in the throat, thirst and dry throat, good appetite, yellow or red urine, dry stool, frequent urination at night, dark red tongue, little coating, and fine and stringy pulse.

[0222] TCM diagnosis: palpitations

[0223] Syndrome differentiation: Heart and liver yin deficiency syndrome

[0224] Treatment principle: nourish the liver and heart

[0225] The formula for moistening the liver and nourishing the heart is modified as follows:

[0226] 30g of Ziziphus jujuba seeds, 10g of Platycladus orientalis seeds, 10g of Radix Ophiopogonis, 10g of stir-fried white peony root, 10g of Radix Angelicae Sinensis, 12g of Schisandrae Chinensis, 30g of Poria cocos, and 15g of roasted Licorice root;

[0227] 7 doses, decocted in water (the decocting method is the same as in Example 1), one dose per day, taken in the morning and evening.

[0228] Note: The patient should have palpitations and insomnia as the main complaint, and related examinations such as cardiac ultrasound and coronary CT have been performed without obvious abnormalities. Combined with the accompanying physical signs, it can be diagnosed as cardiac neurosis. Heart and liver yin deficiency, insufficient qi and yin, and the heart loses nourishment, which will cause palpitations and palpitations; restlessness and disharmony between yin and yang will cause insomnia and dreams; insufficient qi and yin, long-term yin deficiency and yang hyperactivity will cause dizziness and tightness in the head; yin deficiency generates heat, which will cause irritability, yellow and red urine, foreign body sensation in the throat, and constipation. When heat forces the bladder and body fluids flow downward, frequent urination at night will occur. Dark red tongue, less coating, and stringy and thin pulse are also signs of qi and yin deficiency, yang hyperactivity and deficiency heat. The recipe for moistening the liver and nourishing the heart is a proven recipe in the field of psychosomatic medicine. It is composed of sour jujube seeds, cypress seeds, ophiopogon japonicus, stir-fried white peony root, angelica, schisandra, poria, and roasted licorice, which has the effects of nourishing the heart and liver, calming the mind and tranquilizing the mind. The Golden Chamber says: "If the soul is disturbed by evil crying, it is because of the lack of blood and qi. The lack of blood and qi belongs to the heart. If the heart qi is weak, the person will be afraid, close his eyes and want to sleep, dream of distant journeys with his spirit scattered, and his soul will wander." Albizzia julibrissin bark is also a medicine commonly used by Professor Xu Fengquan. The Shennong's Herbal Classic says: "Albizzia julibrissin is sweet and neutral. It can calm the five internal organs, benefit the mind, and make people happy and worry-free. Taking it for a long time will make the body light and the eyes bright and get what you want." Combined with a large dose of roasted licorice, it conforms to the principle of the Neijing "Liver bitterness is urgent, eat sweet food to relieve it."

[0229] Second visit: The patient's palpitations and panic were significantly reduced, and his nervousness and anxiety were relieved. He was advised to continue taking the previous 28 doses. After a follow-up call, his sleep and mood improved.

[0230] The present invention has been described in detail above. For those skilled in the art, the present invention can be implemented in a wide range without departing from the purpose and scope of the present invention. Although the present invention provides specific embodiments, it should be understood that further improvements can be made to the present invention. In short, according to the principles of the present invention, the application is intended to include any changes, uses or improvements to the present invention, including changes that depart from the disclosed scope in the application and are made with conventional techniques known in the art.

Claims

1. A Chinese medicine composition for treating cardiac neurosis, which is made from the following raw materials in parts by weight: 30 parts of spiny jujube seeds, 10 parts of cypress seeds, 10 parts of ophiopogon japonicus, 10 parts of stir-fried white peony root, 10 parts of angelica sinensis, 12 parts of schisandra chinensis, 30 parts of poria cocos, and 15 parts of roasted liquorice root.

2. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition is a water decoction.

3. Use of the Chinese medicine composition according to any one of claims 1 to 2 in the preparation of a medicament for treating cardiac neurosis.

4. The use according to claim 3, characterized in that: The cardiac neurosis is of heart-liver yin deficiency type.

5. Use of the Chinese medicine composition according to any one of claims 1 to 2 in any of the following: B1) Preparation of medicines for improving TCM symptoms of cardiac neurosis; B2) Preparation of drugs to improve cardiac autonomic nervous function.

6. The Chinese medicine composition according to any one of claims 1 to 2 is used in the preparation of a medicament for improving palpitations, panic and / or insomnia caused by cardiac neurosis.

7. A product for treating cardiac neurosis, comprising the Chinese medicine composition according to any one of claims 1 to 2 and an individual cognitive behavioral therapeutic device.

8. Use of the Chinese medicine composition and individual cognitive behavioral therapeutic apparatus according to any one of claims 1 to 2 in the preparation of a product for treating cardiac neurosis.

9. Use of the Chinese medicine composition and individual cognitive behavior therapy device according to any one of claims 1 to 2 in any of the following: C1) Preparation of products for improving TCM symptoms of cardiac neurosis; C2) Preparation of products for improving cardiac autonomic nervous system function.

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