A traditional Chinese medicine composition, a traditional Chinese medicine preparation, its preparation method, and its application.

Abstract

This invention provides a traditional Chinese medicine composition, a traditional Chinese medicine preparation, a preparation method, and its application, specifically belonging to the field of traditional Chinese medicine preparation technology. The traditional Chinese medicine composition of this invention comprises the following raw materials in parts by weight: 100-200 parts of Chinese yam, 10-25 parts of wolfberry, and 10-15 parts of longan. The traditional Chinese medicine composition of this invention can treat neurogenic insomnia and has a good therapeutic effect on neurogenic insomnia in the elderly and sleep disorders in children with cerebral palsy.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a traditional Chinese medicine composition, a traditional Chinese medicine preparation, a preparation method, and its application. Background Technology

[0002] Neurogenic insomnia, also known as primary insomnia or psychophysiological insomnia, is the most common type of insomnia. It is not directly caused by other diseases, medications, or substances (such as caffeine), but rather is an independent disorder resulting from the interaction of nervous system, psychological, and behavioral factors. Simply put, it's like "the brain has learned to be insomnia."

[0003] The core of insomnia is an imbalance between the "sleep" and "wake" systems. Neurotic insomnia is more prominently characterized by: 1. Hyperarousal: The body and mind are in a state of "high alert." Even at night, the brain and body's "alert system" cannot smoothly switch to "sleep mode"; 2. Conditioned arousal: A conditioned reflex is formed where "bed = wakefulness / anxiety." Patients may easily doze off in other places (such as on the sofa or in the car), but become abnormally awake as soon as they enter the bedroom and lie down in bed; 3. Unable to relax: While lying in bed, the brain is actively thinking and cannot stop, often with content related to worries about insomnia or daily stress.

[0004] Therefore, it can be seen that there is a difference between neurotic insomnia and ordinary insomnia. There are many drugs on the market for treating ordinary insomnia, but there are few drugs for neurotic insomnia. Therefore, there is an urgent need to provide a drug to improve neurotic insomnia. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition, a traditional Chinese medicine preparation, a preparation method, and its application. The traditional Chinese medicine composition of this invention can treat neurogenic insomnia.

[0006] The present invention provides a traditional Chinese medicine composition, which is composed of the following raw materials in parts by weight: 100-200 parts of Chinese yam, 10-25 parts of wolfberry and 10-15 parts of longan.

[0007] Preferably, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 180-200 parts of Chinese yam, 20-25 parts of wolfberry, and 12-15 parts of longan.

[0008] Preferably, the traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 200 parts of Chinese yam, 25 parts of wolfberry and 15 parts of longan.

[0009] The present invention also provides a method for preparing the traditional Chinese medicine composition described in the above technical solution, comprising the following steps: Mix Chinese yam, wolfberry, longan and water, soak them, and you will get a clear liquid; The aqueous solution is precipitated, and the supernatant is concentrated to obtain the traditional Chinese medicine composition.

[0010] The present invention also provides the application of the traditional Chinese medicine composition described in the above technical solutions or the traditional Chinese medicine composition prepared by the preparation method described in the above technical solutions in any one of the following: ①Prepare products to improve nervous insomnia; ② Medications for treating nervous insomnia; ③Medications to improve and / or treat sleep disorders in cerebral palsy; ④ Medications that help improve cerebral palsy.

[0011] The present invention also provides a traditional Chinese medicine preparation for improving and / or treating neurotic insomnia, comprising the traditional Chinese medicine composition described in the above technical solution or the traditional Chinese medicine composition prepared by the preparation method described in the above technical solution and pharmaceutically acceptable excipients.

[0012] Preferably, the dosage form of the traditional Chinese medicine preparation includes granules.

[0013] Preferably, when the traditional Chinese medicine preparation is in granule form, the excipients include a binder and a flavoring agent; the binder includes maltodextrin; and the flavoring agent includes white sugar.

[0014] This invention also provides a traditional Chinese medicine granule for improving and / or treating neurotic insomnia, comprising the following steps: Mix Chinese yam, wolfberry, longan and water, soak them, and you will get a clear liquid; The aqueous solution was precipitated, and the supernatant was concentrated to obtain an extract. The extract is spray-dried to obtain spray-dried powder; The spray-dried powder, flavoring agent, and binder are mixed to prepare granules.

[0015] Preferably, the soaking temperature is 25~55℃; and the soaking time is 10~18h.

[0016] This invention provides a traditional Chinese medicine composition. This composition can treat neurogenic insomnia and has a good therapeutic effect on neurogenic insomnia in the elderly and sleep disorders in children with cerebral palsy. Animal experiments have verified that this composition can significantly improve behavioral abnormalities in KM mice after neurotransmitter depletion induced by intraperitoneal injection of PCPA; increase the sleep onset rate induced by sodium pentobarbital and prolong the total sleep duration; and regulate the neurotransmitter content in brain tissue. The components of this composition synergistically exert a significant effect against neurogenic insomnia. Furthermore, the formulation has undergone safety assessment, demonstrating high safety. Clinical results show that this composition has good therapeutic effects on patients with neurogenic insomnia and sleep disorders in patients with cerebral palsy, and can help improve cerebral palsy. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 The standard chart for the comprehensive scoring provided by this invention. Detailed Implementation

[0019] The present invention provides a traditional Chinese medicine composition, which is composed of the following raw materials in parts by weight: 100-200 parts of Chinese yam, 10-25 parts of wolfberry and 10-15 parts of longan.

[0020] The traditional Chinese medicine composition of this invention comprises 100-200 parts of Chinese yam, specifically 180-200 parts, 190 parts, or 200 parts. In this invention, Chinese yam is sweet and neutral in nature, and enters the spleen, lung, and kidney meridians; its functions include strengthening the spleen and stomach, and it is rich in amylase, polyphenol oxidase, and other substances. It has good therapeutic effects on people with weak spleen and stomach, poor digestion and absorption, abdominal distension, fatigue, and weakness after illness. It is also rich in mucoprotein, vitamins, and trace elements, and has good health benefits. The Chinese yam of this invention has a good effect on improving neurasthenia in users. This invention does not have a special limitation on the source of Chinese yam; commercially available Chinese yam known to those skilled in the art can be used.

[0021] The traditional Chinese medicine composition of this invention comprises 10-25 parts of wolfberry, specifically 22, 24, or 25 parts. In this invention, wolfberry is sweet and neutral in nature, and enters the liver and kidney meridians; its function is to nourish the liver and kidneys, and improve eyesight. This invention does not have a specific limitation on the source of the wolfberry; commercially available wolfberry commonly known to those skilled in the art can be used.

[0022] The traditional Chinese medicine composition of this invention includes 10-15 parts of longan, specifically 13, 14, or 15 parts. Longan is warm in nature, sweet in taste, and enters the heart, spleen, liver, and kidney meridians. Its functions include nourishing the heart and spleen, replenishing blood, and calming the mind; it is suitable for excessive thinking, overwork affecting the heart and spleen, palpitations, insomnia, and forgetfulness. This invention does not specifically limit the source of the longan; commercially available longan familiar to those skilled in the art can be used.

[0023] The present invention also provides a method for preparing the traditional Chinese medicine composition described in the above technical solution, comprising the following steps: Mix Chinese yam, wolfberry, longan and water, soak them, and you will get a clear liquid; The aqueous solution is precipitated, and the supernatant is concentrated to obtain the traditional Chinese medicine composition.

[0024] Chinese yam, wolfberry, longan, and water are mixed and soaked to obtain a clear liquid. Before mixing, the Chinese yam, wolfberry, and longan are washed. In a specific embodiment, the washing can be rinsing with clean water 2-3 times to remove ash, pesticides, fertilizers, and heavy metal residues such as lead, arsenic, and mercury. In a specific embodiment, the Chinese yam can be pulverized before mixing. There are no special limitations on the pulverization method; conventional mechanical pulverization is sufficient. In a specific embodiment, the soaking temperature is 25-55℃, specifically 25-35℃ or 30-50℃, and the soaking time is 10-18 hours, specifically 10-16 hours, and the soaking time is 10 hours, 12 hours, 13 hours, 16 hours, 17 hours, or 18 hours. In a specific embodiment, the mass ratio of the Chinese herbal raw materials to water can be 1:(6-10), specifically 1:7, 1.8, or 3:25. In a specific embodiment, the soaking process involves multiple stirrings to ensure even soaking.

[0025] After obtaining the clear aqueous solution, the present invention precipitates the clear aqueous solution, and concentrates the supernatant to obtain the traditional Chinese medicine composition. In a specific embodiment, the precipitation is carried out at 25~35℃, specifically 30~35℃. In a specific embodiment, the precipitation time can be 20~28h, specifically 24h. In a specific embodiment, the concentration can be vacuum concentration. In a specific embodiment, the vacuum concentration temperature can be 80℃.

[0026] This invention also provides the application of the traditional Chinese medicine composition described in the above-described technical solutions or the traditional Chinese medicine composition prepared by the preparation method described in the above-described technical solutions in any of the following: ① preparing products for improving neurotic insomnia; ② drugs for treating neurotic insomnia; ③ drugs for improving and / or treating sleep disorders in cerebral palsy; ④ drugs for assisting in the improvement of cerebral palsy. In a specific embodiment, the product for improving neurotic insomnia includes health products for improving neurotic insomnia. The health products prepared from the traditional Chinese medicine composition of this invention can improve neurotic insomnia, can achieve the treatment of neurotic insomnia, and can achieve the improvement and / or treatment of sleep disorders in cerebral palsy, thereby improving cerebral palsy.

[0027] This invention also provides a traditional Chinese medicine preparation for improving and / or treating neurogenic insomnia, comprising the traditional Chinese medicine composition described in the above-described technical solution or the traditional Chinese medicine composition prepared by the preparation method described in the above-described technical solution and pharmaceutically acceptable excipients. In a specific embodiment, the dosage form of the traditional Chinese medicine preparation includes granules. In a specific embodiment, when the traditional Chinese medicine preparation is in granule form, the excipients include a binder and a flavoring agent; the binder includes maltodextrin; the flavoring agent includes white sugar. Based on the mass of 100-200 parts of Chinese yam, the weight of the flavoring agent can be 8-10 parts, specifically 9 parts, and the amount of binder added can be 12-15 parts, specifically 13.5 parts.

[0028] This invention also provides a traditional Chinese medicine granule for improving and / or treating neurotic insomnia, comprising the following steps: Mix Chinese yam, wolfberry, longan and water, soak them, and you will get a clear liquid; The aqueous solution was precipitated, and the supernatant was concentrated to obtain an extract. The extract is spray-dried to obtain spray-dried powder; The spray-dried powder, flavoring agent, and binder are mixed to prepare granules.

[0029] The steps and conditions before concentration are the same as described above and will not be repeated here. After concentration, an extract is obtained.

[0030] After obtaining the extract, the present invention spray-dries the extract to obtain spray-dried powder. In a specific embodiment, the spray drying can be: spraying the extract into powder, collecting the powder, pulverizing it, and sieving it to obtain spray-dried powder. In a specific embodiment, the spraying temperature can be 105~115℃, specifically 110℃. In a specific embodiment, the collecting temperature can be room temperature, specifically 25~35℃. In a specific embodiment, the sieving can be through a 70~90 mesh sieve.

[0031] After obtaining the spray-dried powder, this invention mixes the spray-dried powder, flavoring agent, and binder to prepare granules. This invention can use a granulator for granulation. This invention mixes the spray-dried powder, flavoring agent, and binder, places them in a mixer, and stirs them evenly to prepare wet granules. After obtaining the wet granules, this invention dries them. In a specific embodiment, the wet granules can be dried in a stainless steel tray. In a specific embodiment, the drying can be carried out in a hot air circulating drying oven. In a specific embodiment, the drying includes a first drying and a second drying; the temperature of the first drying can be 40~60℃, and the time of the first drying can be 20~30 min; the temperature of the second drying can be 80~85℃, and the time of the second drying can be 4~5 h. During the drying process, this invention agitates the granules. The entire preparation method of this invention is carried out in a cleanroom. In a specific embodiment, the humidity of the cleanroom is ≤35%, and the temperature is ≤25℃. After obtaining the granules, this invention also includes packaging. In a specific embodiment, the packaging can be 5g / bag or 8g / bag.

[0032] To further illustrate the present invention, the following detailed description, in conjunction with embodiments, provides a traditional Chinese medicine composition, a traditional Chinese medicine preparation, a preparation method, and an application provided by the present invention, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0033] The ambient temperature in the examples refers to 25~35℃.

[0034] Example 1 1) Weigh 200kg of Chinese yam, 25kg of wolfberry and 15kg of longan, and rinse them twice with clean water to remove ash, pesticides, fertilizers and residues of lead, arsenic and mercury; 2) Since the size of Chinese yam varies, crush the Chinese yam into small pieces; 3) Put the wolfberries, longan and crushed Chinese yam into a jacketed kettle, add 2000 kg of water and heat to 50°C, soak for 10 hours, stirring several times during the soaking period to obtain a clear liquid.

[0035] 4) Take the clear liquid and let it settle at room temperature for 24 hours. Take the supernatant and concentrate it under reduced pressure (80℃) to obtain 20 kg of extract. 5) Spray the concentrated extract into powder (at 110℃ in the upper spray tower), collect the powder (at room temperature), pulverize (at room temperature), and sieve (80 mesh). After sieving, put 9 kg of white sugar and 13.5 kg of maltodextrin into a mixer, stir evenly, and then granulate into wet granules using a granulator.

[0036] 6) Spread the wet granules separately into stainless steel trays and place them in a hot air circulating drying oven. Initially, control the temperature between 40℃ and 60℃. After 20 to 30 minutes, turn the granules over and continue to raise the temperature, controlling it between 80℃ and 85℃. Dry for 4 to 5 hours, then perform metal testing (at room temperature) to ensure that the metal content does not exceed the standard. The entire process is completed in a cleanroom where the humidity is controlled at ≤35% and the temperature at ≤25℃. 8) Finally, the granules are packaged into bags (5g / bag) to obtain traditional Chinese medicine granules, also known as Salmai.

[0037] Example 2 1) Weigh 180kg of Chinese yam, 20kg of wolfberry and 12kg of longan, and rinse them twice with clean water to remove ash, pesticides, fertilizers and residues of lead, arsenic and mercury; 2) Since the size of Chinese yam varies, crush the Chinese yam into small pieces; 3) Put the wolfberries, longan and crushed Chinese yam into a jacketed kettle, add 1800 kg of water and heat to 50°C, soak for 10 hours, stirring several times during the soaking period to obtain a clear liquid.

[0038] 4) Take the clear liquid and let it settle at room temperature for 24 hours. Take the supernatant and concentrate it under reduced pressure (80℃) to obtain 18 kg of extract. 5) Spray the concentrated extract into powder (at 110℃ in the upper spray tower), then collect the powder (at room temperature), pulverize (at room temperature), and sieve (80 mesh). After sieving, put 8.5 kg of white sugar and 13 kg of maltodextrin into a mixer, stir evenly, and then granulate into wet granules using a granulator.

[0039] 6) Spread the wet granules separately into stainless steel trays and place them in a hot air circulating drying oven. Initially, control the temperature between 40℃ and 60℃. After 20 to 30 minutes, turn the granules over and continue to raise the temperature, controlling it between 80℃ and 85℃. Dry for 4 to 5 hours, then perform metal testing (at room temperature). The entire process is completed in a cleanroom where humidity is controlled at ≤35% and temperature at ≤25℃. 8) Finally, the granules are packaged into bags (6g / bag) to obtain traditional Chinese medicine granules, also known as Salmai.

[0040] Example 3 1) Weigh 190kg of Chinese yam, 20kg of wolfberry and 10kg of longan, and rinse them twice with clean water to remove ash, pesticides, fertilizers and residues of lead, arsenic and mercury. 2) Since the size of Chinese yam varies, crush the Chinese yam into small pieces; 3) Put the wolfberries, longan and crushed Chinese yam into a jacketed kettle, add 1800 kg of water and heat to 50°C, soak for 12 hours, stirring several times during the soaking period to obtain a clear liquid.

[0041] 4) Take the clear liquid and let it settle at room temperature for 24 hours. Take the supernatant and concentrate it under reduced pressure (80℃) to obtain 17.5 kg of extract. 5) Spray the concentrated extract into powder (at 110℃ in the upper spray tower), then collect the powder (at room temperature), pulverize (at room temperature), and sieve (at room temperature). After sieving, put 8.5kg of white sugar and 14kg of maltodextrin into a mixer, stir evenly, and then granulate into wet granules using a granulator.

[0042] 6) Spread the wet granules separately into stainless steel trays and place them in a hot air circulating drying oven. Initially, control the temperature between 40℃ and 60℃. After 20 to 30 minutes, turn the granules over and continue to raise the temperature, controlling it between 80℃ and 85℃. Dry for 4 to 5 hours, then perform metal testing (at room temperature). The entire process is completed in a cleanroom where humidity is controlled at ≤35% and temperature at ≤25℃. 8) Finally, the granules are packaged into bags (5g / bag) to obtain traditional Chinese medicine granules, also known as Salmai.

[0043] Comparative Example 1 1) Rinse 200kg of Chinese yam, 25kg of wolfberry and 15kg of longan raw materials twice with clean water to remove ash, pesticides, fertilizers and residues of lead, arsenic and mercury; since the Chinese yam are of different sizes, crush them into small pieces. 2) Soak the coarse yam powder and the other two raw medicinal materials together in 2000 kg of warm water at 50°C for 4 hours, stirring frequently during the soaking process; 3) Filter the soaked wolfberries, longans and crushed Chinese yam powder solution through a 250-mesh vibrating sieve; 4) Spray dry the filtrate to make a dry powder; the spray drying conditions are the same as in Example 1; 5) Mix 20kg of dry powder with 10kg of dextrin and 30g of steviol glycoside; 6) Granulate the mixed material, dry it, and then package it into small bags, each bag containing 5g. The granulation conditions are the same as in Example 1.

[0044] Clinical records of the extract from Comparative Example 1 showed that it was not as effective as that from Example 1.

[0045] Example 4 Preparation of experimental materials (1) Test substance ① Salmai-1: Prepared from Chinese yam (200kg), wolfberry (25kg), ginseng (10kg, artificially cultivated) and longan (15kg), the preparation method is the same as in Example 1. It is an orange-yellow powder, dissolved in warm water and taken orally. The human dosage is 5g / day. ②Shalemai-2: Prepared from wolfberry (200 kg), ginseng (25 kg, artificially cultivated), and longan (25 kg). The preparation method is the same as in Example 1. It is an orange-yellow powder, orally administered after dissolving in warm water. The human dosage is 5 g / day. ③Shalemai-3: Prepared from Chinese yam (200 kg), ginseng (25 kg, artificially cultivated), and longan (25 kg). The preparation method is the same as in Example 1. It is an orange-yellow powder, orally administered after dissolving in warm water. The human dosage is 5 g / day. ④Shalemai-4: Prepared from Chinese yam (200 kg), wolfberry (25 kg), and longan (25 kg). The preparation method is the same as in Example 1. It is an orange-yellow powder, orally administered after dissolving in warm water. The human dosage is 5 g / day.

[0046] ⑤Positive control drug compound diazepam tablets, specification: diazepam 1.25 mg, oryzanol 40 mg, vitamin B1 10 mg, tablet weight 0.2 g / tablet; indications: anxiety neurosis, neurasthenia; usage and dosage: orally, 2 tablets / day; batch number: 20240301, Jining Ninkang Pharmaceutical Co., Ltd.

[0047] All the above test substances were formulated into solutions with distilled water and administered by gavage before use.

[0048] (2) Reagents Pentobarbital sodium, batch number: P3761, Sigma Company, USA; 4-chloro-DL-phenylalanine (PCPA), batch number: A12IS208585, Shanghai Yuanye Biotechnology Co., Ltd.; 5-hydroxytryptamine (5-HT) ELISA kit, batch number: WK0826JNB8850, γ-aminobutyric acid (GABA) colorimetric test kit, batch number: WK11H442T5572, glutamic acid (GLU) colorimetric test kit, batch number: WK1042R062133. All the above were purchased from Wuhan Eclight Biotechnology Co., Ltd.

[0049] (3) Experimental animals ICR mice, male, provided by the Animal Experiment Center of Xinjiang Medical University, production license number: SCXK(Xin)2018-0002. The animals were housed in the Animal Center of Xinjiang Uygur Autonomous Region Institute of Materia Medica, use license number: SYXJ(Xin)2022-0002. This experiment has been approved by the Animal Ethics Review Committee of Xinjiang Uygur Autonomous Region Institute of Materia Medica, ethical approval number: XJIMM-20250701.

[0050] (4) Instrument and equipment LT1000B electronic balance, Changshu Tianliang Instrument Co., Ltd.; BS323S electronic balance, Sartorius Scientific Instrument Co., Ltd., Beijing; Open Field Test Analysis System for Rats and Mice, Elevated Plus Maze, Shanghai Xinruan Information Technology Co., Ltd.; Animal Behavior Video Analysis System; JXFSTPRP-CL Automatic Sample Freezing Grinder, Shanghai Jingxin Industrial Development Co., Ltd.; H1650R Refrigerated High-Speed Centrifuge, Shanghai LUXIANGYI Centrifuge Instrument Co., Ltd.; Cytation3 Multifunctional Microplate Reader, BioTek Instruments, Inc., USA; SC082132 Ultra-Pure Water Instrument, Sichuan Wote Experimental Instrument Equipment.

[0051] (5)Experimental animal feed Mouse feed (SPF level), purchased from Beijing Keao Xieli Feed Co., Ltd. (Production License No.: SCXK (Beijing) 2019-0003).

[0052] (6)Animal laboratory conditions Humidity 30-50%, temperature control 20-26 °C. 12h:12h light-dark alternating lighting; keep the cage environment clean and dry; add feed and water to animals daily; keep animals free to move.

[0053] Grouping for drug administration and model establishment Take 84 ICR mice, weighing 17-24 g, male. After 3 days of adaptive feeding, they were randomly divided into 7 groups according to body weight, namely blank control group, model group, positive control group (compound diazepam tablets, 0.4 mg / kg), and Shalemai-1 (ELD-1) group (1.025 g / kg), Shalemai-2 (ELD-2) group (1.025 g / kg), Shalemai-3 (ELD-3) group (1.025 g / kg), Shalemai-4 (ELD-4) group (1.025 g / kg), with 12 mice in each group. Before use, they were prepared into corresponding concentrations with distilled water. The mice in each drug administration group were intraperitoneally injected with PCPA suspension (300 mg / kg, dissolved in normal saline), and the mice in the control group were intraperitoneally injected with an equal volume of normal saline, once a day for 3 consecutive days. During this period, the mice in each drug administration group were intragastrically administered with the corresponding drugs, and the blank control group and the model group were intragastrically administered with an equal volume of distilled water, once a day for 14 consecutive days of intragastric administration. The body weight and behavioral changes of the mice were observed and recorded during model establishment and drug administration.

[0054] Open field test On the 12th day, 1 hour after drug administration, the open field test was carried out. During the test, the laboratory was kept quiet, the room temperature was constant, and the light was uniform. The mice were placed in the center of the open field box. After 1 minute of adaptation, the mice in each group were placed back in the center of the open field box, and the total movement distance, movement time in the central area, and number of entries into the central area of the mice were observed and recorded within 3 minutes. Between two experiments, the feces and urine of the mice were removed, and the odor was removed by spraying with 75% alcohol.

[0055] Elevated Cross Maze Experiment On day 13, one hour after drug administration, the elevated cruciate maze test was performed on mice. During the test, the laboratory was kept quiet and the room temperature constant. Mice were placed in the center of the maze with their heads facing the open arms, and the observer was at least 1 meter away from the center of the maze to minimize interference. The number of times the mice entered the open and closed arms within 5 minutes and the time spent in each arm were observed and recorded (the criteria for entering and exiting the arms should be strictly defined, with all four limbs entering the arm or both forepaws exiting the arm as the standard). Between two experiments, the mice were wiped with 75% alcohol to remove fecal and urine odor.

[0056] Open arm entry percentage (OE%) = Open arm entry count / (Open arm entry count + Closed arm entry count).

[0057] Open arm dwell time percentage (OT%) = Open arm dwell time / (Open arm dwell time + Closed arm dwell time).

[0058] Effects of subthreshold doses of sodium pentobarbital on hypnosis On day 14 of drug administration, mice were fasted but allowed free access to water for 12 hours. On day 11 of drug administration, one hour after administration, each mouse was injected intraperitoneally with sodium pentobarbital (30 mg / kg), and the number of mice in each group whose retrograde reflex disappeared within 30 minutes was observed and recorded.

[0059] Effect of sodium pentobarbital on sleep-inducing time On day 16, the mice were fasted but allowed free access to water for 12 hours. On day 14, one hour after administration, each mouse was intraperitoneally injected with sodium pentobarbital (45 mg / kg), and the sleep latency and sleep duration of each group of mice were observed and recorded. Sleep latency: the time from drug administration to the disappearance of the righting reflex; sleep duration: the time from the disappearance of the righting reflex to its restoration.

[0060] Sample collection and index determination After the experiment, the mice were euthanized, their brains were quickly removed, rinsed with physiological saline to remove blood, blotted dry with filter paper, weighed, and then a tissue homogenate was prepared. The supernatant was collected by centrifugation, and the contents of 5-HT, GABA, and GLU in the brain tissue were determined according to the kit instructions.

[0061] Verification of the efficacy and preliminary safety evaluation of Salamis in treating neurogenic insomnia Single-dose acute toxicity test Dosage and volume: The maximum dosing concentration of the drug is prepared, and the dosing volume is 0.4 ml / 10 g.

[0062] Twenty KM mice (half male and half female, weighing 18–22 g) were randomly divided into two groups according to body weight: a control group (n=10) and a treatment group (n=10). The mice were fasted for 12 hours but allowed free access to water. The treatment group received a 30% concentration of cipa sedative (12.0 g / kg) via gavage. The mice's condition was observed after administration, including changes in body weight, food intake, appearance, behavior, secretions, excretions, mortality, and toxic reactions, for 14 consecutive days. Gross dissection was performed at the end of the observation period.

[0063] Data processing Measurement data adopted Description. Data comparison: Analysis of variance was used for comparisons among multiple groups; non-parametric tests were used for non-normally distributed continuous data (significance level α = 0.05). All data were processed using SPSS 22.0 statistical software.

[0064] result Impact on daily activities and weight Compared with the blank control group, mice in the model group, after intraperitoneal injection of PCPA, exhibited significantly increased activity, increased sensitivity to external stimuli, greater excitability, increased aggression, and disrupted circadian rhythms, with continuous activity during the day and night, indicating a successful model. At the end of the modeling process, the body weight of the model mice was lower than that of the blank control group, but the difference was not statistically significant. By the end of the experiment, the body weight of all treatment groups had increased compared with the model group, but no statistically significant difference was observed. The results are shown in Table 1.

[0065] Table 1 shows the changes in mouse body weight ( (n=10)

[0066] Note: Compared with the blank control group, Compared with the model group, # P<0.05, ## P<0.01.

[0067] Impact on behavioral science The results of the open field experiment (see Table 2) showed that, compared with the blank control group, the total distance traveled and the average speed of the PCPA model group mice were significantly increased. P< 0.05), but the time spent in the central and peripheral regions did not change significantly. This result indicates that the PCPA model induced a phenotype centered on 'behavioral hyperactivity,' rather than typical anxiety-like behavior. In efficacy evaluation, the positive control drugs, compound diazepam and salami-2, effectively reversed PCPA-induced behavioral hyperactivity, restoring mouse activity levels to normal. Compared with the model group, salami-3 and salami-4 significantly reduced the total distance traveled ( P< 0.01), the average speed and dwell time in the central region of Salmay-4 were significantly reduced ( P<0.01), exhibiting a stronger central inhibitory effect, significantly reducing the amount of spontaneous activity in mice ( P< 0.01).

[0068] Table 2 shows the results of the mouse open field experiment. (n=10)

[0069] Note: Compared with the blank control group, Compared with the model group, # P< 0.05, ## P< 0.01.

[0070] The results of the elevated cross maze experiment (Table 3) showed that the percentage of mice in the PCPA model group entering the open arm was significantly higher than that in the blank control group. P< The value was 0.05, indicating that the model animals were in a state of reduced anxiety. After treatment with compound diazepam and salami-1, salami-2, salami-3, and salami-4, this indicator was significantly reversed, returning to levels comparable to the blank control group (compared to the model group). P< 0.05).

[0071] Table 3 shows the impact of the elevated cross maze experiment. (n=10)

[0072] Note: Compared with the blank control group, Compared with the model group, # P< 0.05, ## P< 0.01.

[0073] Effects on sleep latency and sleep duration In a subthreshold dose hypnotic experiment using sodium pentobarbital, the positive control drug, compound diazepam, exhibited a strong synergistic effect, achieving a sleep onset rate of 100.0%. The sleep onset rate in the PCPA model group was lower than that in the blank control group, at 50%. Among the formulations, salami-1, salami-2, salami-3, and salami-4 all showed sleep onset rates exceeding 50.0%, demonstrating a clear synergistic hypnotic effect.

[0074] Table 4. Effects of subthreshold doses of sodium pentobarbital on sleep induced in mice ( (n=10)

[0075] Note: Compared with the blank control group, Compared with the model group,# P< 0.05, ## P< 0.01.

[0076] In the suprathreshold dose experiment of sodium pentobarbital (as shown in Table 5), the total sleep duration of mice in the PCPA model group was significantly shorter than that in the blank control group. P <0.05%. The positive control drug, compound diazepam, not only significantly shortens sleep latency ( P <0.05, and can also significantly prolong the total duration of sleep ( P< 0.01). Compared with the model group, Salamis-2 and Salamis-4 significantly prolonged the total sleep duration ( P <0.05).

[0077] Table 5 Effects of suprathreshold doses of sodium pentobarbital on sleep induced by sodium ( (n=10)

[0078] Note: Compared with the blank control group, Compared with the model group, # P< 0.05, ## P< 0.01.

[0079] Effects on the levels of 5-HT, GLU, and GABA in brain tissue Compared with the blank control group, the levels of 5-HT and GABA in the brain tissue of mice in the model group were decreased, while the level of GLU was increased, which was statistically significant. P< 0.05 or P< 0.01). Compared with the model group, the levels of 5-HT and GABA in the brain tissue of mice treated with compound diazepam and Salmer-4 mice were increased, and the level of GLU was decreased, which was statistically significant. P< 0.05 or P< 0.01).

[0080] Table 6. Effects on the levels of neurotransmitters 5-HT, GLU, and GABA in brain tissue ( (n=10)

[0081] Note: Compared with the blank control group, Compared with the model group, # P< 0.05, ## P< 0.01.

[0082] Preliminary safety assessment of the Salami-4 KM mice were administered salami-4 (12.0 g / kg) at a single dose of 40 ml / kg at the maximum therapeutic concentration of 30%, while the control group received the same volume of distilled water. Mice were observed for 14 consecutive days after administration; no general abnormalities were observed, and no deaths or toxic reactions occurred. Gross dissections were performed at the end of the observation period, and no abnormalities were found in any organs. Following administration, the body weight of mice in all groups increased, and at the end of the administration period, there was no statistically significant difference between the administered and control groups.

[0083] Mice were administered salmer-4 once daily via gavage at the maximum concentration and volume. Twenty mice were observed for 14 consecutive days, and no deaths or toxic reactions were observed. Therefore, the maximum tolerated dose of salmer-4 is 12.0 g / kg, which is 144 times the adult daily dose per kg of body weight, indicating no significant toxicity and safe administration. Table 7 shows the body weight in the acute toxicity test after a single dose of salmer-4.

[0084] Table 7. Weight table of acute toxicity test results for single dose of Salerme-4 (Salmer-4) (n=10)

[0085] in conclusion: Mice were induced to develop PCPA suspension via intraperitoneal injection. They were then treated with different traditional Chinese medicine combinations (Salmer-1, Salmer-2, Salmer-3, and Salmer-4). During the experiment, mouse weight, behavior, duration of sodium pentobarbital-induced sleep, and neurotransmitter levels in brain tissue were observed. Results showed that the weight gain in each group was slightly lower than the control group, but the difference was not statistically significant, indicating no significant effect on body weight. In the open field test, compared with the model group, the total distance traveled by Salmer-3 and Salmer-4 was significantly reduced (…). P < 0.01), the average speed and dwell time in the central region of Salmay-4 were significantly reduced ( P< 0.01), indicating a stronger central inhibitory effect. In the elevated cruciate maze test: the percentage of arm-opening attempts for Salamis-1, Salamis-2, Salamis-3, and Salamis-4 was significantly lower than that of the model group ( P< 0.05). In the subthreshold dose hypnotic experiment of sodium pentobarbital: the sleep onset rate of salami-1, salami-2, salami-3, and salami-4 all exceeded 50.0%, showing a clear synergistic hypnotic effect. In the suprathreshold dose experiment of sodium pentobarbital, salami-2 and salami-4 significantly prolonged the total sleep duration ( P< 0.05). Results from the determination of neurotransmitter content in brain tissue showed that Salamis-4 significantly increased the levels of 5-HT and GABA in mouse brain tissue and decreased the level of GLU ( ). P< 0.05 or P<0.01). Acute toxicity test results of salmer-4 showed that when KM mice were administered salmer-4 once a day by gavage at the maximum concentration and maximum volume for 14 consecutive days, no mice died or showed toxic reactions. Therefore, the maximum tolerated dose of salmer-4 is 12.0 g / kg, which is 144 times the daily dose per kg body weight for adults, indicating that there is no obvious toxicity and the drug is safe to use.

[0086] In summary, the results indicate that salami-4 significantly improved behavioral abnormalities in KM mice after PCPA intraperitoneal injection-induced neurotransmitter depletion; increased pentobarbital-induced sleep onset rate and prolonged total sleep duration; and regulated neurotransmitter content in brain tissue. Compared with other treatment groups, salami-4 showed superior performance in the mining experiment in terms of average speed, central zone dwell time, and regulation of neurotransmitters 5-HT and GABA. These results suggest that salami-4 has a good sleep-regulating effect, and the acute toxicity test results indicate no significant toxicity, making it a safe drug.

[0087] Example 5 Clinical Cases The traditional Chinese medicine granules (Shalemai) prepared in Example 1 were used to treat 200 patients with neurotic insomnia and 500 patients with cerebral palsy sleep disorders. In fact, 200 patients with neurotic insomnia showed improvement and treatment effects, and 500 patients with cerebral palsy sleep disorders showed improvement. Tables 8 and 9 below only list some of the clinical case data.

[0088] The improvement in patients with neurotic insomnia is shown in Table 8: Table 8 Clinical case data of patients with neurotic insomnia

[0089] Notes: During the course of treatment of patients with the herbal composition of this invention, there were also cases where no improvement was observed (a small percentage). The main reasons for the lack of effect were: 1) The patient did not take the medication on time or in the prescribed dosage (i.e., the medication was taken intermittently). These patients were not included in the table. 2) The patient did not avoid certain foods during the course of treatment and ate greasy foods. 3) The patient took health supplements indiscriminately, consuming more health supplements than the medication. 4) The patient took the medication only when they remembered and forgot about it, resulting in a lack of continuity and no improvement.

[0090] As shown in Table 8, the traditional Chinese medicine granules (Shalemai) prepared in Example 1 of this invention have a good therapeutic effect on patients with neurotic insomnia.

[0091] Detailed case data of sleep disorders in children with cerebral palsy are shown in Table 9. The comprehensive scoring criteria in Table 9 are detailed below. Figure 1 : Table 9: Case data on improvement in children with cerebral palsy.

[0092] Notes: During the administration of the herbal composition product of this invention to the consulted children, there were also cases where no improvement was observed (a small percentage). The main reasons for the lack of effect were: 1) the child was not given the medicine on time and in the prescribed dosage; 2) no dietary restrictions were observed during the course of treatment, and the child ate spicy food continuously (one parent took their child to eat spicy hot pot for 16 consecutive days in a month, resulting in diarrhea); 3) some children had poor intestinal absorption; 4) the child found the medicine of this invention very bitter and added a large amount of sweeteners such as white sugar or rock sugar; 5) the dosage that should have been taken for 30 days was delayed until 60 days, etc.

[0093] During clinical record-keeping, regarding the treatment of sleep disorders in children with cerebral palsy, the combined use of the herbal composition product of this invention and rehabilitation therapy is necessary for better results. This is because if a child does not get a good night's sleep, rehabilitation therapy the following day will be ineffective. Whether in terms of motor skills, intelligence, or language, rehabilitation therapy and learning will not improve the child's development while they are in a dazed state. Currently, surgical treatment is not widely available and has certain sequelae. As shown in Table 9, the herbal granules of this invention (Shalemai) have a good therapeutic effect on patients with sleep disorders due to cerebral palsy and can play a good auxiliary role in the treatment of cerebral palsy.

[0095] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, The traditional Chinese medicine composition is composed of the following raw materials in parts by weight: 100-200 parts of Chinese yam, 10-25 parts of wolfberry, and 10-15 parts of longan.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 180-200 parts of Chinese yam, 20-25 parts of wolfberry, and 12-15 parts of longan.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition consists of the following raw materials in parts by weight: 200 parts of Chinese yam, 25 parts of wolfberry and 15 parts of longan.

4. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, comprising the following steps: Mix Chinese yam, wolfberry, longan and water, soak them, and you will get a clear liquid; The aqueous solution is precipitated, and the supernatant is concentrated to obtain the traditional Chinese medicine composition.

5. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine composition prepared by the preparation method according to claim 4 in any one of claims ① to ④: ①Prepare products to improve nervous insomnia; ② Medications for treating nervous insomnia; ③Medications to improve and / or treat sleep disorders in cerebral palsy; ④ Medications that help improve cerebral palsy.

6. A traditional Chinese medicine preparation for improving and / or treating neurotic insomnia, characterized in that, It includes the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine composition prepared by the preparation method according to claim 4 and pharmaceutically acceptable excipients.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, The dosage form of the traditional Chinese medicine preparations includes granules.

8. The traditional Chinese medicine preparation according to claim 6, characterized in that, When the traditional Chinese medicine preparation is in granule form, the excipients include a binder and a flavoring agent; the binder includes maltodextrin; and the flavoring agent includes white sugar.

9. A traditional Chinese medicine granule for improving and / or treating neurotic insomnia, characterized in that, Includes the following steps: Mix Chinese yam, wolfberry, longan and water, soak them, and you will get a clear liquid; The aqueous solution was precipitated, and the supernatant was concentrated to obtain an extract. The extract is spray-dried to obtain spray-dried powder; The spray-dried powder, flavoring agent, and binder are mixed to prepare granules.

10. The granule according to claim 9, characterized in that, The soaking temperature is 25~55℃; the soaking time is 10~18h.

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