A traditional Chinese medicine composition for treating sleep disorders and its preparation method

Abstract

This invention relates to a traditional Chinese medicine composition for treating sleep disorders and its preparation method. The composition, by weight, is prepared from the following raw materials: 15-30 parts calcined amethyst, 10-20 parts Albizia bark, 5-15 parts *Gnaphalium affine*, 5-15 parts silkworm cocoon, 10-30 parts yam, 5-10 parts *Bupleurum chinense*, 15-30 parts wheat bran, 2-4 parts *Panax notoginseng* powder, 10-20 parts *Adenophora stricta*, 3-6 parts clove, and 3-6 parts nutmeg. Based on the principle of combining disease and syndrome differentiation in traditional Chinese medicine, this invention selects natural drugs with heart-nourishing and calming effects, and formulates them according to a specific weight ratio. This provides a traditional Chinese medicine composition for treating sleep disorders that is highly effective and low-cost. Simultaneously, it provides a corresponding preparation method that is simple, easy to implement, and readily produced, maximizing the extraction of the effective components of each drug element, and has good market application prospects.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for treating sleep disorders and its preparation method. Background Technology

[0002] Sleep disorders are generally characterized by prolonged sleep latency, shortened sleep duration, increased physiological arousal during sleep onset, and a relative increase in REM sleep. In recent years, with socioeconomic development and increased life stress, the incidence of sleep disorders has risen significantly. A 2002 global epidemiological cross-sectional survey of insomnia in China showed that 45.4% of Chinese people had experienced varying degrees of sleep disorders in the past month, and nearly half of severe sleep disorders could last for 10 years or more. Currently, traditional Chinese medicine (TCM) treatment for sleep disorders has attracted widespread attention from scholars. This is mainly because TCM not only avoids many adverse reactions but also effectively improves symptoms and quality of life, possessing distinct characteristics and advantages. Therefore, exploring a TCM composition for treating sleep disorders is crucial. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition for treating sleep disorders and a method for preparing the same, wherein the traditional Chinese medicine composition has significant therapeutic effect and low cost.

[0004] This invention also provides a traditional Chinese medicine composition for treating sleep disorders, comprising the following components by weight: 15-30 parts calcined amethyst, 10-20 parts Albizia bark, 5-15 parts *Gnaphalium affine*, 5-15 parts silkworm cocoon, 10-30 parts yam, 5-10 parts Bupleurum, 15-30 parts floating wheat, 2-4 parts Panax notoginseng powder, 10-20 parts North American ginseng, 3-6 parts clove, and 3-6 parts nutmeg.

[0005] Preferably, by weight, it includes the following components: 30 parts calcined amethyst, 15 parts Albizia bark, 10 parts *Gnaphalium affine*, 10 parts silkworm cocoon, 20 parts yam, 10 parts Bupleurum chinense, 30 parts floating wheat, 2 parts Panax notoginseng powder, 10 parts North American ginseng, 3 parts clove, and 3 parts nutmeg.

[0006] The present invention also includes 10-15 parts of Codonopsis pilosula and 10-15 parts of Atractylodes macrocephala, for the treatment of patients with concurrent symptoms of qi deficiency.

[0007] Preferably, by weight, it includes the following components: 15 parts calcined amethyst, 20 parts Albizia bark, 10 parts *Gnaphalium affine*, 10 parts silkworm cocoon, 30 parts yam, 5 parts Bupleurum, 30 parts floating wheat, 2 parts Panax notoginseng powder, 20 parts North American ginseng, 3 parts clove, 3 parts nutmeg, 10 parts Codonopsis pilosula, and 10 parts Atractylodes macrocephala.

[0008] The present invention also includes 10-15 parts of wolfberry and 10-15 parts of dodder seed, for the treatment of patients with concurrent symptoms of kidney deficiency.

[0009] Preferably, by weight, it includes the following components: 30 parts calcined amethyst, 15 parts Albizia bark, 15 parts *Gnaphalium affine*, 15 parts silkworm cocoon, 20 parts yam, 10 parts Bupleurum chinense, 15 parts wheat bran, 3 parts Panax notoginseng powder, 15 parts Adenophora stricta, 3 parts clove, 6 parts nutmeg, 15 parts wolfberry, and 15 parts dodder seed.

[0010] This invention also provides a method for preparing a traditional Chinese medicine composition for treating sleep disorders, comprising the following steps:

[0011] (1) Weigh out the corresponding weight portions of each component;

[0012] (2) Place each component in a medicine pot and add water to soak for 10-30 minutes;

[0013] (3) First decoct the calcined amethyst for 15-30 minutes, then add other Chinese medicines except Panax notoginseng powder and boil over high heat for 10-25 minutes; turn to low heat and continue to boil for 10-25 minutes.

[0014] (4) Turn off the fire, filter to remove the residue and obtain the filtrate. Add Panax notoginseng powder and stir well to obtain a traditional Chinese medicine composition for treating sleep disorders.

[0015] Preferably, the weight ratio of water to the total weight of each component in step (2) is 10:1.

[0016] The efficacy of the main components of the above-mentioned traditional Chinese medicine composition is as follows:

[0017] Calcined amethyst is sweet and warm, entering the kidney, heart, and lung meridians. It warms the kidneys and uterus, calms the mind and soothes the nerves. Albizia bark is sweet and neutral, entering the heart, liver, and lung meridians. It relieves depression and soothes the nerves, invigorates blood and reduces swelling. It is used for restlessness, depression, and insomnia. These two herbs are the principal herbs. Bupleurum is pungent, bitter, and slightly cold, entering the liver, gallbladder, and lung meridians. It soothes the liver and relieves depression, and raises yang qi. Floating wheat is sweet and cool, entering the heart meridian. It invigorates qi, clears heat, nourishes the heart and soothes the nerves. It is the assistant herb. Dioscorea opposita invigorates the spleen and stomach, generates fluids and benefits the lungs, and invigorates the kidneys and astringes essence. Panax notoginseng powder disperses blood stasis, stops bleeding, reduces swelling and relieves pain. Glehnia littoralis nourishes yin and clears the lungs, invigorates the stomach and generates fluids. Herba Lysimachiae clears heat and promotes diuresis, detoxifies and disperses blood stasis. Silkworm cocoons detoxify and quench thirst. Clove warms the middle jiao and descends rebellious qi, invigorates the kidneys and assists yang. Nutmeg warms the middle jiao and promotes qi circulation, astringes the intestines and stops diarrhea, and promotes drug absorption. It is the adjuvant herb. All the above herbs work together to invigorate qi and nourish yin, calm the mind and soothe the nerves, thereby treating sleep disorders.

[0018] Beneficial effects

[0019] Based on the principle of combining disease differentiation and syndrome differentiation in traditional Chinese medicine, this invention selects natural drugs with the effects of nourishing the heart and calming the mind, and formulates them according to a certain weight ratio. This provides a Chinese medicine composition for treating sleep disorders with significant efficacy and low cost. At the same time, it provides a corresponding preparation method that is simple, easy to implement, and easy to produce, and can maximize the extraction of the effective components of each drug component, showing good market application prospects. Detailed Implementation

[0020] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0021] Example 1

[0022] This embodiment provides a traditional Chinese medicine composition for treating sleep disorders. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 30g of calcined amethyst, 15g of Albizia bark, 10g of *Gnaphalium affine*, 10g of silkworm cocoon, 20g of yam, 10g of Bupleurum chinense, 30g of wheat bran, 2g of Panax notoginseng powder, 10g of Adenophora stricta, 3g of clove, and 3g of nutmeg.

[0023] The preparation method of the above-mentioned traditional Chinese medicine composition is as follows:

[0024] Step 1: Weigh out the corresponding weight proportions of each raw material.

[0025] Step 2: Place all ingredients in a medicine pot and add an appropriate amount of water to soak for 25 minutes.

[0026] Step 3: First, decoct the calcined amethyst for 30 minutes, then add the other Chinese herbs except for Panax notoginseng powder and boil over high heat for 15 minutes; then reduce to low heat and continue to boil for 25 minutes.

[0027] Step 4: Turn off the heat, filter to remove residue and obtain filtrate, add Panax notoginseng powder and stir well to obtain a traditional Chinese medicine composition for treating sleep disorders.

[0028] As a preferred option, in step two, the ratio of water to the total weight of each Chinese herbal medicine ingredient is 6:1.

[0029] Example 2

[0030] This embodiment provides a traditional Chinese medicine composition for treating sleep disorders. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 15g calcined amethyst, 20g Albizia bark, 10g *Gnaphalium affine*, 10g silkworm cocoon, 30g yam, 5g Bupleurum, 30g wheat bran, 2g Panax notoginseng powder, 20g *Adenophora stricta*, 3g clove, 3g nutmeg, 10g Codonopsis pilosula, and 10g Atractylodes macrocephala.

[0031] The preparation method of the above-mentioned traditional Chinese medicine composition is as follows:

[0032] Step 1: Weigh out the corresponding weight proportions of each raw material.

[0033] Step 2: Place all ingredients in a medicine pot and add an appropriate amount of water to soak for 30 minutes.

[0034] Step 3: First, decoct the calcined amethyst for 15 minutes, then add the other Chinese herbs except for Panax notoginseng powder and simmer over high heat for 25 minutes; then reduce to low heat and continue simmering for 25 minutes.

[0035] Step 4: Turn off the heat, filter to remove residue and obtain filtrate, add Panax notoginseng powder and stir well to obtain a traditional Chinese medicine composition for treating sleep disorders.

[0036] As a preferred option, in step two, the ratio of water to the total weight of each Chinese herbal medicine ingredient is 9:1.

[0037] Example 3

[0038] This embodiment provides a traditional Chinese medicine composition for treating sleep disorders. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 30g calcined amethyst, 15g Albizia bark, 15g *Gnaphalium affine*, 15g silkworm cocoon, 20g yam, 10g Bupleurum, 15g wheat bran, 3g Panax notoginseng powder, 15g *Adenophora stricta*, 3g clove, 6g nutmeg, 15g wolfberry, and 15g dodder seed.

[0039] The preparation method of the above-mentioned traditional Chinese medicine composition is as follows:

[0040] Step 1: Weigh out the corresponding weight proportions of each raw material.

[0041] Step 2: Place all ingredients in a medicine pot and add an appropriate amount of water to soak for 20 minutes.

[0042] Step 3: First, decoct the calcined amethyst for 20 minutes, then add the other Chinese herbs except for Panax notoginseng powder and boil over high heat for 15 minutes; then reduce to low heat and continue to boil for 20 minutes.

[0043] Step 4: Turn off the heat, filter to remove residue and obtain filtrate, add Panax notoginseng powder and stir well to obtain a traditional Chinese medicine composition for treating sleep disorders.

[0044] As a preferred option, in step two, the ratio of water to the total weight of each Chinese herbal medicine ingredient is 10:1.

[0045] Effect Test 1

[0046] Animal experiments were conducted using the above-mentioned traditional Chinese medicine composition, as detailed below:

[0047] 1. Materials and Methods

[0048] 1.1 Test drug

[0049] Prescription of traditional Chinese medicine composition: 30 g of calcined fluorite, 15 g of albizia bark, 10 g of hypericum japonicum, 10 g of silkworm cocoon, 20 g of Chinese yam, 10 g of bupleurum, 30 g of floating wheat, 2 g of panax notoginseng powder, 10 g of glehnia littoralis, 3 g of cloves, 3 g of nutmeg. Provided by the Traditional Chinese Medicine Pharmacy of the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Weigh the above traditional Chinese medicine materials according to the prescription ratio, add 10 times the amount of water, soak for 0.5 h, decoct 3 times, 40 min each time, filter, combine the filtrates of the above 3 times, concentrate by heating in a water bath at 37 °C, concentrate the medicinal liquid according to the actual situation, and match the actual drug concentration for clinical use at medium mass concentration. Concentrate to 0.535 g / mL at medium mass concentration, the low dose of the traditional Chinese medicine composition is 0.2675 g / mL, the medium dose of the traditional Chinese medicine composition is 0.535 g / mL, and the high dose of the traditional Chinese medicine composition is 1.07 g / mL, and store them in a refrigerator at 4 °C for later use respectively.

[0050] Alprazolam tablets: Trade name Jiajing Anding, produced by Shanghai Shangyao Xinyi Pharmaceutical Factory Co., Ltd., national drug approval number H31021282, batch number: 01230301, specification 0.4 mg / tablet.

[0051] 1.2 Animals

[0052] 60 healthy SPF-grade male SD rats, body weight (160 ± 20) g, purchased from Shanghai Lingchang Biotechnology Co., Ltd., animal production license number: SCXK (Shanghai) 2018-003. Raised in the animal house of Shanghai Genechem Co., Ltd. Before the experiment, the animals were placed in an environment with a room temperature of (21 ± 3) °C, a relative humidity of 50% - 60%, free access to food and water, regular replacement of bedding, avoidance of strong light, clean, dry and quiet for adaptive feeding for 1 week.

[0053] 1.3 Reagents p-Chlorophenylalanine (PCPA, Sigma Company, USA, batch number: 1002993176); pentobarbital sodium (Foshan Chemical Industry Experimental Factory, batch number: 20160121); 5-HT, MT, DA detection kits (Shanghai Xitang Biotechnology Co., Ltd., batch numbers are: 2010271, 2104251, 2105181).

[0054] 1.4 Instruments Nexera X2 ultra-high performance liquid chromatography (UPLC) (SHIMADZU Corporation, Japan); 6500QTRAP tandem mass spectrometry (MS / MS); Infinite M200 Pro microplate reader (TECAN Company, Switzerland).

[0055] 1.5 Methods

[0056] 1.5.1 Animal grouping, model establishment and drug administration

[0057] After one week of acclimatization feeding, 10 SD rats were randomly selected as the normal control group using a random number table, and the remaining 50 rats were used to establish a rat model of insomnia. Modeling method: From 8:00 to 10:00 AM daily, rats were intraperitoneally injected with 3% 0.3g / kg PCPA suspension at a ratio of 10mL / kg for 3 consecutive days. Twelve hours after the last injection of PCPA suspension, the rats' behavioral characteristics and eating habits were observed. In addition, the success of the model was determined using the sodium pentobarbital synergistic sleep test; a prolonged sleep latency and shortened sleep duration compared to the blank control group indicated successful modeling. The 50 successfully modeled rats were randomly divided into a model group, a low-dose traditional Chinese medicine (TCM) composition group, a medium-dose TCM composition group, a high-dose TCM composition group, and an alprazolam group, with 10 rats in each group. Drug administration began the day after grouping. Rats in the low-, medium-, and high-dose TCM composition groups and the alprazolam group were administered the corresponding dose of the TCM composition solution or diazepam solution by gavage daily. Based on the conversion factor for human and animal body surface area, the low, medium, and high doses of the traditional Chinese medicine composition were 10 mg / kg, 20 mg / kg, and 40 mg / kg, respectively, prepared with distilled water; the dose of alprazolam was 0.9 mg / kg, prepared with distilled water, and all were administered by gavage for 4 weeks. Rats in the normal group and model group were also administered the same amount of distilled water by gavage for 4 weeks.

[0058] 1.5.2 Observe the general condition of the rats. Observe the rats' mental state, fur color, and fecal color.

[0059] 1.5.3 Observation of Sleep Latency and Sleep Duration in Rats Using Sodium Pentobarbital-Assisted Sleep Method: Thirty minutes after the last administration, rats in each group were intraperitoneally injected with 30 mg / kg of sodium pentobarbital (5 mL / kg, the minimum dose determined in the preliminary experiment to induce 100% sleep in animals). Sleep was measured by the disappearance of the righting reflex, defined as rats maintaining a back-facing position for more than 30 seconds. The time from intraperitoneal injection of sodium pentobarbital to the disappearance of the righting reflex was observed and recorded as the sleep latency, and the time from the disappearance of the righting reflex to its recovery was recorded as the sleep duration.

[0060] 1.5.4 ELISA Method for Detecting the Content of 5-HT, 5-HIAA, MT, and DA in the Hypothalamus of Rats Ten rats from each group were taken, homogenized, and aliquoted into centrifuge tubes, and stored at -80℃ for later use. The contents of 5-HT, 5-HIAA, MT, and DA were detected using the ELISA kit according to the reagent instructions.

[0061] 1.5.5 Statistical Methods

[0062] Data analysis was performed using SSPS 22.0 software, and the experimental data results were expressed as mean and standard deviation. The results indicate that one-way ANOVA was used for comparisons between groups. In post-hoc analysis, the least significant difference (LSD) t-test was used for comparisons between groups when the variances were homogeneous, and Dunnett's T3 test was used for comparisons between groups when the variances were unequal. A p-value < 0.05 was considered statistically significant.

[0063] 2 Results

[0064] 2.1 Comparison of general condition of rats in each group

[0065] The normal group rats had smooth and shiny fur, black or dark brown feces, and were highly responsive, mostly gathering and curling up to sleep during the day. The model group rats had rough and dull fur, grayish-white feces, and were abnormally sensitive to external stimuli in the early stages, easily startled and fighting, and highly aggressive. As time went on, the rats showed sluggishness, fatigue, and lethargy. After treatment, the general condition of the rats in each dose group of the traditional Chinese medicine composition and the alprazolam group improved to varying degrees.

[0066] 2.2 Comparison of sleep latency and sleep duration among different groups of rats

[0067] Compared with the normal group, the sleep latency of rats in the model group was significantly prolonged and the sleep duration was significantly shortened, with statistically significant differences (all P < 0.01). Compared with the model group, the sleep latency of rats in each drug-treated group was shortened and the sleep duration was prolonged, with statistically significant differences (P < 0.05 or P < 0.01). Compared with the low-dose group of the traditional Chinese medicine composition, the sleep latency of rats in the medium- and high-dose groups of the traditional Chinese medicine composition and the alprazolam group was shortened and the sleep duration was prolonged, with statistically significant differences (P < 0.05 or P < 0.01). Compared with the medium-dose group of the traditional Chinese medicine composition and the alprazolam group, the sleep latency of rats in the high-dose group of the traditional Chinese medicine composition was shortened and the sleep duration was prolonged, with statistically significant differences (all P < 0.05). See Table 1.

[0068] Table 1 Comparison of sleep latency and sleep duration among different groups of rats ( n=10)

[0069]

[0070] Note: Compared with the normal group, ① P < 0.01; compared with the model group, ② P < 0.05 ③ P < 0.01; compared with the low-dose group of traditional Chinese medicine composition, ④ P < 0.05 ⑤ P < 0.01; compared with the dosage group of the traditional Chinese medicine composition, ⑥ P < 0.05; compared with the alprazolam group, ⑦ P < 0.01.

[0071] 2.3 Comparison of 5-HT, 5-HIAA, MT and DA levels in the hypothalamus of rats in different groups

[0072] Compared with the normal group, the levels of 5-HT, 5-HIAA, MT, and DA in the hypothalamus of rats in the model group were significantly decreased, and the differences were statistically significant (all P < 0.01). Compared with the model group, the levels of 5-HT, 5-HIAA, MT, and DA in the hypothalamus of rats in each treatment group were increased, and the differences were statistically significant (P < 0.05 or P < 0.01). Compared with the low-dose group of the traditional Chinese medicine composition, the levels of 5-HT, 5-HIAA, MT, and DA in the hypothalamus of rats in the medium-dose group, high-dose group, and alprazolam group were increased, and the differences were statistically significant (P < 0.05 or P < 0.01). Compared with the medium-dose group of the traditional Chinese medicine composition and the alprazolam group, the levels of 5-HT, 5-HIAA, MT, and DA in the hypothalamus of rats in the high-dose group of the traditional Chinese medicine composition were increased, and the differences were statistically significant (all P < 0.05). See Table 2.

[0073] Table 2 Comparison of 5-HT, 5-HIAA, MT and DA levels in the hypothalamus of rats in different groups ( n=10)

[0074]

[0075] Note: Compared with the normal group, ① P < 0.01; compared with the model group, ② P < 0.05 ③ P < 0.01; compared with the low-dose group of traditional Chinese medicine composition, ④ P < 0.05 ⑤ P < 0.01; compared with the dosage group of the traditional Chinese medicine composition, ⑥ P < 0.05; compared with the alprazolam group, ⑦ P < 0.01.

[0076] Effect Experiment 2

[0077] The clinical efficacy of the above-mentioned traditional Chinese medicine composition in treating sleep disorders was observed, as follows.

[0078] 1. Objects and Methods

[0079] 1.1 Research Subjects

[0080] A total of 300 patients with sleep disorders who visited Shanghai Sixth People's Hospital between March 2021 and March 2023 were selected. They were randomly divided into a control group and an observation group using a random number table, with 150 patients in each group.

[0081] 1.2 Case Selection Criteria

[0082] 1.2.1 Diagnostic criteria for sleep disorders

[0083] According to the diagnostic criteria for sleep disorders established by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) of the American Psychiatric Association: ① The prominent complaint is difficulty falling asleep or maintaining sleep, or failure to recover energy after sleep, lasting for at least one month. ② Sleep problems (or accompanying daytime fatigue) cause clinically significant distress or impairment in social, occupational, or other important functioning. ③ The sleep problem does not occur during the course of narcolepsy, breathing-related sleep disorders, etc. ④ The sleep problem does not occur during the course of other mental disorders (such as severe depressive disorders, bipolar disorder, generalized anxiety disorder, delirium). ⑤ The sleep problem is not due to the direct physiological effects of medications or physical states.

[0084] 1.2.2 Inclusion Criteria

[0085] ① Meets the diagnostic criteria for sleep disorders (DSM-IV-TR). Age between 18 and 60 years, gender not limited. ② Duration of illness longer than 1 month. ③ Pittsburgh Sleep Quality Index (PSQI) total score ≥ 7. ④ Hamilton Depression Rating Scale (HAMD) 17-item score < 7. ⑤ Hamilton Anxiety Rating Scale (HAMA) 14-item score < 14. ⑥ Normal cognitive ability, clear consciousness, no mental illness, and able to cooperate in completing relevant treatment; ⑦ Patients who voluntarily participate in this study and sign an informed consent form.

[0086] 1.2.3 Exclusion Criteria

[0087] ① Patients who do not meet the inclusion criteria; ② Patients with serious diseases of vital organs such as the heart, liver, and kidneys; ③ Patients with hematological diseases, tumors, or autoimmune diseases; ④ Patients with sleep disorders caused by medication or other factors; ⑤ Patients with poor adherence to the treatment plan, who do not follow the treatment plan, or who add other treatment measures on their own, thus affecting the assessment of efficacy.

[0088] 1.2 Methods

[0089] 1.2.1 Administration method Control group: Alprazolam tablets (trade name: Jiajing An Ding, produced by Shanghai Shangyao Xinyi Pharmaceutical Co., Ltd., National Drug Approval Number H31021282, batch number: 01230301, specification 0.4mg / tablet) were administered orally once a day, 0.4mg each time.

[0090] Observation group: Treatment was administered a combination of traditional Chinese medicine (TCM) and alprazolam tablets (Jiajing Anding). Alprazolam treatment was the same as the control group. TCM prescription: 30g calcined amethyst, 15g Albizia julibrissin bark, 10g *Gnaphalium affine*, 10g silkworm cocoon, 20g yam, 10g *Bupleurum chinense*, 30g wheat bran, 2g *Panax notoginseng* powder, 10g *Adenophora stricta*, 3g clove, 3g nutmeg. All ingredients were placed in a pot with an appropriate amount of water to soak. The calcined amethyst was decocted for 30 minutes first, followed by the other herbs. The decoction was brought to a boil over high heat for 15 minutes, then simmered over low heat for another 25 minutes. The *Panax notoginseng* powder was then added and mixed well. One dose was taken daily, 30 minutes after noon and before bedtime.

[0091] Both treatment courses lasted 4 weeks. Throughout the trial, patients were prohibited from using any medications that might cause sleep disturbances or other medications used to treat sleep disorders, and were also advised to abstain from tobacco, alcohol, tea, and coffee.

[0092] 1.2.2 Observation Indicators

[0093] (1) Polysomnography

[0094] Polysomnography was performed using an S-2000PSG polysomnography analyzer manufactured by Shanghai Hanfei Medical Instrument Co., Ltd. before and after treatment. Specific sleep process monitoring indicators included total sleep time (TST), awake time (AWT), and sleep efficiency (SE).

[0095] Overall clinical efficacy:

[0096] (2) Evaluation criteria for therapeutic effect

[0097] The efficacy was evaluated based on the improvement in sleep before and after treatment. Specific efficacy evaluation criteria were as follows: Markedly effective: TST prolonged by more than 2 hours after treatment, accompanying symptoms completely or substantially disappeared, and sleep onset time <30 minutes; Effective: TST prolonged by 1–2 hours after treatment, with significant relief of accompanying symptoms, and sleep onset time 30–45 minutes; Ineffective: No significant improvement in TST, sleep onset time, or accompanying symptoms after treatment. The overall effective rate was calculated as: (Number of markedly effective cases + Number of effective cases) / Total number of cases × 100%.

[0098] (3) Sleep quality

[0099] The Pittsburgh Sleep Quality Index (PSQI) (Chinese revised version) was used to evaluate the sleep status of the two groups before and after treatment. This scale contains 19 self-report items, which are divided into 7 categories: subjective sleep quality, sleep latency, sleep efficiency, sleep duration, cumulative sleep disturbances, use of sleep medications, and daytime functional disorders. Each item is scored from 0 to 3 points, and the total score is from 0 to 21 points. A total score of more than 7 points indicates the presence of sleep disorders, and the higher the score, the worse the patient's sleep quality.

[0100] (4) Quality of life

[0101] The SF-36 Quality of Life Scale was used to evaluate the quality of life of the two groups before and after treatment. It included eight dimensions: emotional role, bodily pain, mental health, physical role, social function, physical function, vitality, and overall health. Higher scores indicated better quality of life.

[0102] (5) Anxiety assessment

[0103] The Self-Rating Anxiety Scale (SAS) was developed by Chinese-American professor W.K. Zung in 1971. The SAS was used to assess the anxiety levels of two groups of patients before and after treatment, with 50 points as the cutoff. Higher scores indicate more severe anxiety.

[0104] (6) Assessment of depressive state

[0105] The Self-Rating Depression Scale (SDS), developed by William W.K. Zung in 1965, is a self-report scale used to measure the severity of depressive symptoms and their changes during treatment. The SDS was used to assess the depressive status of two groups of patients before and after treatment, with 53 points as the cutoff value. Higher scores indicate more severe depressive symptoms.

[0106] (7) Polysomnography

[0107] Polysomnography was performed using an S-2000PSG polysomnography analyzer manufactured by Shanghai Hanfei Medical Instrument Co., Ltd., before and after treatment. The monitoring indicators were as follows: total sleep time (TST), awake time (AWT), and sleep efficiency (SE).

[0108] (8) Measurement of blood rheological parameters

[0109] Before and after treatment, 4 mL of fasting antecubital venous blood was collected from patients in the morning using anticoagulation vacuum tubes. Blood rheological parameters, including whole blood high shear viscosity, whole blood low shear viscosity, and plasma viscosity, were measured using an LBY-N6A rotating blood rheometer manufactured by Beijing Pulisheng Company.

[0110] (9) Neurotransmitter index measurement

[0111] Before and after treatment, 3 mL of fasting antecubital venous blood was collected from patients in the morning using non-anticoagulated vacuum tubes. The blood was centrifuged (centrifugation radius 10 cm, speed 3500 r / min, time 15 min), and the supernatant serum was collected. The levels of norepinephrine (NE), serotonin (5-HT), and neuropeptide Y (NPY) were measured using an enzyme-linked immunosorbent assay kit from Beijing Lier Biomedical Technology Co., Ltd.

[0112] (10) Safety evaluation

[0113] Safety was evaluated by observing vital signs (temperature, respiration, pulse, blood pressure), routine blood tests, cardiac, hepatic, renal, and coagulation function, as well as the incidence of adverse events, before and after treatment in both groups of patients.

[0114] 1.2.3 Statistical Methods

[0115] All data were analyzed using SPSS 18.0 statistical software. Quantitative data were presented as follows: For data expressed as percentages (%), a t-test was performed for comparisons. For count data expressed as rates (%), a χ² test was performed for comparisons. P < 0.05 indicated a statistically significant difference.

[0116] 2 Results

[0117] 2.1 Comparison of baseline data between the two groups of patients

[0118] There were no statistically significant differences in baseline data such as gender, age, disease duration, and occupation between the two groups of patients (P > 0.05), indicating that the baseline characteristics of the two groups were basically consistent and comparable. See Table 3.

[0119] Table 3 Comparison of baseline data between the two groups of patients

[0120]

[0121]

[0122] 2.2 Comparison of clinical efficacy between the two groups

[0123] The total effective rate in the observation group was 94.67%, while that in the control group was 77.33%. The observation group was significantly higher than that in the control group, and the difference was statistically significant (P < 0.01). See Table 4.

[0124] Table 4 Comparison of clinical efficacy between the two groups [cases (%)]

[0125]

[0126] Note: Compared with the control group, ** P < 0.01.

[0127] 2.3 Comparison of sleep quality before and after treatment in the two groups

[0128] Before treatment, there were no statistically significant differences in the scores of subjective sleep quality, sleep latency, sleep efficiency, sleep duration, cumulative sleep disturbances, use of sleep medications, and daytime functional disorders on the PSQI scale between the two groups (P > 0.05). After treatment, the scores of all the above indicators in both groups decreased compared with those before treatment, and the differences were statistically significant (P < 0.05, P < 0.01). Moreover, the scores of all indicators in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). See Table 5.

[0129] Table 5 Comparison of sleep quality before and after treatment in the two groups ( point)

[0130]

[0131] Note: Compared with before treatment, * P < 0.05 ** P < 0.01; compared with the control group, # P < 0.05.

[0132] 2.4 Comparison of quality of life before and after treatment in the two groups

[0133] Before treatment, there were no statistically significant differences in the scores of the two groups on the SF-36 scale for affective functioning, bodily pain, mental health, physical functioning, social functioning, physical functioning, vitality, and overall health (P > 0.05). After treatment, the scores of all the above quality of life indicators in both groups improved compared with before treatment, and the differences were statistically significant (P < 0.05, P < 0.01). Moreover, the scores of all the above indicators in the observation group were higher than those in the control group, and the differences were statistically significant (P < 0.05). See Table 6.

[0134] Table 6 Comparison of quality of life before and after treatment in the two groups ( point)

[0135]

[0136]

[0137] Note: Compared with before treatment, * P < 0.05 ** P < 0.01; compared with the control group, # P < 0.05.

[0138] 2.5 Comparison of SAS and SDS scores before and after treatment in the two groups of patients

[0139] Before treatment, there were no statistically significant differences in SAS and SDS scores between the two groups (P > 0.05). After treatment, both SAS and SDS scores in both groups decreased significantly compared to before treatment (P < 0.05, P < 0.01). Compared with the control group, the reduction in SAS and SDS scores in the observation group after treatment was significantly greater than that in the control group (P < 0.05). See Table 7.

[0140] Table 7 Comparison of SAS and SDS scores before and after treatment in the two groups of patients ( point)

[0141]

[0142] Note: Compared with before treatment, * P < 0.05 ** P < 0.01; compared with the control group, # P < 0.05.

[0143] 2.6 Comparison of polysomnography monitoring indicators between the two groups of patients before and after treatment

[0144] Before treatment, there were no statistically significant differences in polysomnography (PSG) indicators such as TST, AWT, and SE between the two groups (P > 0.05). After treatment, TST was prolonged, AWT was shortened, and SE was increased in both groups, with statistically significant differences (P < 0.05, P < 0.01). Compared with the control group, the improvement in PST, AWT, and SE indicators in the observation group after treatment was significantly greater than that in the control group, with statistically significant differences (P < 0.05). See Table 6.

[0145] Table 6 Comparison of polysomnography monitoring indicators before and after treatment in the two groups of patients.

[0146]

[0147] Note: Compared with before treatment, * P < 0.05 ** P < 0.01; compared with the control group, # P < 0.05.

[0148] 2.7 Comparison of hemorheological parameters between the two groups of patients before and after treatment

[0149] Before treatment, there were no statistically significant differences in whole blood high-shear viscosity, whole blood low-shear viscosity, and plasma viscosity between the two groups (P > 0.05). After both treatments, whole blood high-shear viscosity, whole blood low-shear viscosity, and plasma viscosity were all lower than before treatment (P < 0.05, P < 0.01). The observation group showed a greater reduction in whole blood high-shear viscosity, whole blood low-shear viscosity, and plasma viscosity after treatment than the control group, and the differences were statistically significant (P < 0.05). See Table 8.

[0150] Table 8 Comparison of hemorheological parameters before and after treatment in the two groups of patients ( mPa·s)

[0151]

[0152] Note: Compared with before treatment, * P < 0.05 ** P < 0.01; compared with the control group, # P < 0.05.

[0153] 2.8 Comparison of neurotransmitter indices before and after treatment in the two groups of patients

[0154] Before treatment, there were no statistically significant differences in serum NE, 5-HT, and NPY levels between the two groups (P > 0.05). After treatment, serum NE levels in both groups decreased compared to before treatment, while 5-HT and NPY levels increased significantly (P < 0.05, P < 0.01). Compared with the control group, the observation group showed significantly greater reductions in serum NE levels and increases in 5-HT and NPY levels after treatment (P < 0.05). See Table 9.

[0155] Table 9 Comparison of neurotransmitter indices before and after treatment in the two groups of patients.

[0156]

[0157] Note: Compared with before treatment, * P < 0.05 ** P < 0.01; compared with the control group, # P < 0.05.

[0158] 2.9 Comparison of adverse reaction rates between the two groups

[0159] During the trial, the control group experienced 3 cases of stomach pain, 2 cases of diarrhea, 7 cases of dizziness, and 12 cases of headache, with an adverse reaction rate of 16.00%. In contrast, the observation group experienced 2 cases of stomach pain, 1 case of diarrhea, and 1 case of dizziness, with an adverse reaction rate of only 2.67%. The adverse reaction rate in the observation group was significantly lower than that in the control group, and the difference was statistically significant (P < 0.01). See Table 10.

[0160] Table 10 Comparison of adverse events between the two groups

[0161] Adverse reaction events Control group (n=150) Observation group (n=150) Stomach pain (example, %) 3(2.00) 2(1.33) Diarrhea (e.g., %) 2(1.33) 1(0.67) Dizziness (e.g., %) 7(4.67) 1(0.67) Headache (e.g., %) 12(8.00) 0(0.00) Adverse reaction rate (e.g., %) 24(16.00) <![CDATA[4(2.67) ## ]]>

[0162] Note: Compared with the control group, ## P < 0.01.

[0163] Effect Test 3

[0164] In clinical practice, the traditional Chinese medicine composition provided by this invention has been used to treat various diseases with sleep disorders as the main manifestation, and good results have been achieved. A case study is presented below.

[0165] Mr. Xu, male, 30 years old, first visit on December 9, 2023. Insomnia for 3 months. Three months prior, the patient experienced difficulty falling asleep due to high work pressure and overwork, accompanied by tinnitus, headache, dizziness, chest and rib distension, low mood, and poor appetite. His tongue was purplish-dark with a thin white coating, and his pulse was wiry. Traditional Chinese Medicine diagnosis: Insomnia, liver stagnation and blood stasis syndrome. Treatment mainly consisted of the herbal composition provided in this invention. Prescription: 30g calcined amethyst, 15g Albizia bark, 15g *Gnaphalium affine*, 15g silkworm cocoon, 20g yam, 10g *Bupleurum chinense*, 15g wheat bran, 3g *Panax notoginseng* powder, 15g *Adenophora stricta*, 3g clove, 6g nutmeg. 7 doses, one dose daily, decocted in water and taken twice daily. Second visit on December 18: Insomnia and tinnitus significantly reduced, dizziness relieved. Recently, he experienced lower back pain after prolonged sitting, and the topical application of loxoprofen sodium gel was ineffective. Add 15 grams of wolfberry and 15 grams of dodder seed to the initial prescription to tonify the kidneys and strengthen the lower back, 14 doses. Third visit on January 2, 2024: Sleep is normal, no tinnitus or dizziness, lower back pain has lessened, and the patient is instructed to continue taking the medication for conditioning.

[0166] Although the present invention has been described in detail above with general descriptions and specific embodiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A traditional Chinese medicine composition for treating sleep disorders, characterized in that: It is made from the following components in parts by weight: 15-30 parts calcined amethyst, 10-20 parts Albizia bark, 5-15 parts *Gnaphalium affine*, 5-15 parts silkworm cocoons, 10-30 parts Dioscorea opposita, 5-10 parts Bupleurum chinense, 15-30 parts wheat bran, 2-4 parts Panax notoginseng powder, 10-20 parts Adenophora stricta, 3-6 parts cloves, and 3-6 parts nutmeg.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: It is made from the following components in parts by weight: 30 parts calcined amethyst, 15 parts Albizia bark, 10 parts Clematis chinensis, 10 parts silkworm cocoon, 20 parts Dioscorea opposita, 10 parts Bupleurum chinense, 30 parts wheat bran, 2 parts Panax notoginseng powder, 10 parts Adenophora stricta, 3 parts clove, and 3 parts nutmeg.

3. A traditional Chinese medicine composition for treating sleep disorders, characterized in that: It is made from the following components in parts by weight: 15-30 parts calcined amethyst, 10-20 parts Albizia bark, 5-15 parts *Gnaphalium affine*, 5-15 parts silkworm cocoon, 10-30 parts yam, 5-10 parts Bupleurum chinense, 15-30 parts floating wheat, 2-4 parts Panax notoginseng powder, 10-20 parts North American ginseng, 3-6 parts clove, 3-6 parts nutmeg, 10-15 parts wolfberry, and 10-15 parts dodder seed.

4. The traditional Chinese medicine composition according to claim 3, characterized in that: The product is made from the following components in parts by weight: 30 parts calcined amethyst, 15 parts Albizia bark, 15 parts Clematis chinensis, 15 parts silkworm cocoon, 20 parts Dioscorea opposita, 10 parts Bupleurum chinense, 15 parts Triticum aestivum, 3 parts Panax notoginseng powder, 15 parts Adenophora stricta, 3 parts clove, 6 parts nutmeg, 15 parts wolfberry, and 15 parts Cuscuta chinensis.

5. A method for preparing a traditional Chinese medicine composition for treating sleep disorders as described in any one of claims 1-4, comprising the following steps: (1) Weigh out the corresponding weight portions of each component; (2) Place each component in a medicine pot and add water to soak for 10-30 minutes; (3) First decoct the calcined amethyst for 15-30 minutes, then add other Chinese medicines except Panax notoginseng powder and boil over high heat for 10-25 minutes; turn to low heat and continue to boil for 10-25 minutes. (4) Turn off the fire, filter to remove the residue and obtain the filtrate. Add Panax notoginseng powder and stir well to obtain the Chinese medicine composition for treating sleep disorders.

6. The preparation method according to claim 5, characterized in that: In step (2), the ratio of water to the total weight of each component is 10:1.

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