Application of compound Liangjinshu capsule in preparation of medicament for treating insomnia

Abstract

The invention relates to a traditional Chinese medicine preparation, in particular to application of a compound live brain soothing capsule in preparation of a medicament for treating insomnia. The dosage of the medicine is 200 mg / kg. Experiments show that the sleep improvement effect of the compound Shuonaoshu capsule on an anesthesia reviving experiment evaluation test medicine, a high-dose group (200 mg / kg) of the compound Shuonaoshu capsule can effectively prolong sleep time, dose dependence exists, sleep quality can be moderately improved, the higher the concentration is, the more obvious the improvement effect is, and the more obvious the effect is. The invention reveals that the compound Liangjinshu capsule has a treatment effect on insomnia, and is expected to provide a certain experimental basis for the development of new drugs for insomnia.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine preparation, namely, use of compound Huonaoshu capsule in preparing insomnia medicine. Background Art

[0002] Fufang Huonaoshujiaonang Capsules are currently approved by the China Food and Drug Administration (CFDA) under the drug standard number WS-10884(ZD-0884)-2002-2012Z. Ingredients: 2000g pig brain, 200g Schisandra chinensis, 100g Ophiopogon japonicus, 50g Ginseng, 50g Lycium barbarum, 50g Rehmannia root, and 50g Salvia miltiorrhiza. Preparation: Grind the above seven ingredients and the ginseng into a fine powder and set aside. Homogenize the pig brain with 1100ml of water, adjust the pH to 1.5-2.0 with hydrochloric acid, add 60g of pepsin, stir well, and incubate at 37-40°C for 8-10 hours, then at 100°C for 40 minutes. Allow to stand, centrifuge, and remove the supernatant, spray-dry, and set aside. Add water to the remaining five herbs, including Schisandra chinensis, and boil twice, the first time for 3 hours and the second time for 2 hours. Combine the decoctions, filter, and concentrate the filtrate to a thick paste with a relative density of 1.30-1.35 (50°C). Dry, grind into a fine powder, sieve, and mix with the above-mentioned fine powder and an appropriate amount of dextrin. Encapsulate into 1,000 capsules. This product is ready. Functions and Indications: Tonifies Qi and nourishes blood, invigorates the brain and improves intelligence. It is used to improve forgetfulness, Qi and blood deficiency, memory loss, fatigue, dizziness, palpitations, and the above symptoms of Alzheimer's disease. Dosage and Administration: Oral, 3 capsules at a time (5 capsules for severe cases), twice daily, after meals; a course of treatment is 12-15 days. Specifications: 0.25g per capsule.

[0003] Insomnia, also known as "bu mei" in Traditional Chinese Medicine, is a common sleep disorder characterized by dissatisfaction with sleep duration and quality, despite adequate sleep opportunities and a suitable sleep environment, which can affect daytime function or cause physical discomfort. Therefore, when insomnia reaches a certain frequency and duration, and interferes with daily life, medical treatment should be sought. There are no reports on the use of Fufang Huo Nao Shu Capsules for the treatment of insomnia. Summary of the Invention

[0004] The purpose of the present invention is to provide a use of a compound Huo Nao Shu capsule in the preparation of insomnia medicine in view of the above-mentioned deficiencies.

[0005] The technical solution of the present invention is to use the compound Huo Nao Shu capsule in preparing an insomnia medicine. The compound Huo Nao Shu capsule is prepared from 2000g of pig brain, 200g of Schisandra chinensis, 100g of Radix Ophiopogonis, 50g of Ginseng, 50g of Lycium barbarum, 50g of Rehmannia root and 50g of Salvia miltiorrhiza.

[0006] The dosage for rodents is 100-200 mg / kg, which translates to a 10-20 mg / kg adult dosage based on body surface area. The preferred dosage for rodents is 200 mg / kg, which translates to a 20 mg / kg adult dosage based on body surface area.

[0007] The advantages of this invention are as follows: 1. Studies evaluating the sleep-improving effects of the test drug through anesthesia recovery experiments demonstrated that the high-dose group (200 mg / kg) of Compound Huo Nao Shu Capsules effectively increased sleep time in a dose-dependent manner, moderately improving sleep quality. 2. Efficacy studies of the test drug in a PCPA (para-chlorophenylalanine)-induced insomnia mouse model demonstrated that both the medium (100 mg / kg) and high (200 mg / kg) doses of the test drug Compound Huo Nao Shu Capsules significantly improved PCPA-induced insomnia symptoms in mice, demonstrating promising anti-insomnia efficacy. 3. Experimental results demonstrate that Compound Huo Nao Shu Capsules have therapeutic effects on insomnia, providing experimental evidence for the development of new insomnia drugs.

[0008] The embodiments of the present invention will be described in further detail below with reference to the examples. DETAILED DESCRIPTION Example

[0009] Compound Huo Nao Shu Capsules are used in the preparation of insomnia medications. The compound Huo Nao Shu capsules are prepared from 2000g of pig brain, 200g of Schisandra chinensis, 100g of Radix Ophiopogonis, 50g of Panax ginseng, 50g of Lycium barbarum, 50g of Rehmannia root, and 50g of Salvia miltiorrhiza. The dosage for rodents is 100 mg / kg or 200 mg / kg. The adult dosage, calculated based on body surface area, is 10 mg / kg or 20 mg / kg.

[0010] Anesthesia recovery experiment to evaluate the sleep-improving effect of test drugs 1. Experimental purpose: This experiment is to observe the efficacy of the test drug in anesthesia recovery mouse model.

[0011] 2. Test materials (1) Test substance

[0012] (2) Preparation of test substances Use 0.5% CMC-Na for dissolution and dilution. Preparation frequency: Prepare immediately before use and store at room temperature.

[0013] Preparation method: Formal experiment G5 group: Take one capsule, open it and place it in a centrifuge tube (containing 0.25 g of the test substance). Add 12.5 mL of 0.5% CMC-Na solution to dissolve it into a 20 mg / mL test substance solution, and sonicate or vortex to dissolve. Preliminary experiment group G3 and formal experiment group G4: Take one capsule, open it and place it in a centrifuge tube (containing 0.25 g of the test substance). Add 25 mL of 0.5% CMC-Na solution to dissolve it into a 10 mg / mL test substance solution, and sonicate or vortex to dissolve it. Formal experiment G3 group: Take one capsule, open it and put it into a centrifuge tube (containing 0.25g of the test substance), add 50mL of 0.5% CMC-Na solution to dissolve it into 5 mg / mL test substance solution, and dissolve it by ultrasonication or vortexing.

[0014] (3) Positive drugs The following positive drugs are purchased from the market and relevant information is provided.

[0015]

[0016] (4) Preparation of positive drugs Preliminary experiment: Zaoren Anshen Capsules: Take one capsule, open it, and place it in a centrifuge tube (containing 0.45g). Add 30 mL of 0.5% CMC-Na to dilute to 15 mg / mL. Prepare once a week and store at room temperature.

[0017] Formal experiment: Zaoren Anshen Capsules: Open four capsules and place them in a centrifuge tube (containing 0.45g). Add 60mL of 0.5% CMC-Na to dilute to 30 mg / mL. Prepare once a week and store at room temperature.

[0018] (5) Solvent information

[0019] (6) Solvent preparation Preliminary experiment: Weigh 2.0080g of sodium carboxymethyl cellulose and add 401.60mL of double-distilled water. Stir and dissolve until clear. Preparation frequency: Prepare once a month and store at room temperature.

[0020] For the experiment: Weigh 7.6300g of sodium carboxymethyl cellulose and add 1526.00mL of double-distilled water. Stir and dissolve until clear. Preparation frequency: Prepare once a month and store at room temperature.

[0021] (7) Main reagents Xylazine: TGI, batch number: GH5QM-WV, expiration date: 2026.12.24.

[0022] Virbac: Batch number: 9C1RA, Product number: BN8V4RA, Expiration date: 2025.06.01.

[0023] (8) Main instruments and equipment Electronic balance: TP-602; Sartorius, Beijing; Validity date: 2025.07.03.

[0024] 3. Experimental process (1) Animals Animal species and strain: C57BL / 6J mice.

[0025] Medication record: No medication history.

[0026] Sex, age, weight Male, 7 - 9 weeks, 20-25 g.

[0027] Breeder / supplier: Jihui Experimental Animal Breeding Co., Ltd.

[0028] Animal use license number: SYXK(Shanghai)2023-0011.

[0029] Supplier license number: SCXK (Shanghai) 2022-0009.

[0030] Animal quality certificate number: 20220009034389.

[0031] Experimental institution: animal room.

[0032] Adaptation period: 4 days.

[0033] Room: SPF area room.

[0034] Animal husbandry: 2-5 mice (same dosing group).

[0035] A total of 77 C57BL / 6J mice were purchased from a commercial supplier. Seven of these mice were used as spares to select suitable animals for group entry and were euthanized after the completion of the experiment. All animals were pathogen-free and approximately 6-8 weeks of age upon arrival at the animal facility.

[0036] (2) Animal reception, health assessment and adaptation period Upon arrival, animal room staff will transfer the animals from their shipping packaging to their cages and conduct an inspection of each animal. The inspection will include appearance, limbs, and orifices, as well as any abnormalities observed while the animal is at rest or moving.

[0037] (3) Environment Mice were housed in cages (cage specifications are detailed in the report) in the animal room. Cage bedding consisted of autoclaved corn cobs (Chenfu Eden Garden Bedding Processing Factory, Dachang Hui Autonomous County), which were changed every 7–10 days. The animal room was equipped with a high-efficiency air filter and ventilated at 15–25 air changes per hour. The temperature was maintained between 20–26°C (68–79°F) and relative humidity between 30–70%. Temperature and humidity were continuously monitored and recorded. Lighting conditions consisted of 12 hours of fluorescent lighting per day (08:00–20:00) and 12 hours of no lighting.

[0038] (4) Food and water Experimental mice had unlimited access to a dedicated mouse diet (irradiated and sterilized, Jiangsu Collaborative Pharmaceutical Bioengineering Co., Ltd., China). Throughout the experiment, mice had unlimited access to treated drinking water, obtained from municipal tap water treated by reverse osmosis or autoclaving. Drinking water was tested twice annually for heavy metals, nitrates, dissolved minerals, total bacterial count, and E. coli. Test reports were archived. The levels of known contaminants in the animal diet and drinking water were not expected to affect the objectives or procedures of this study.

[0039] (5) Cages and animal identification Each experimental mouse is assigned a unique number. Before grouping the animals, label the cages with the project number, species / strain, sex, cage number, and animal number. After grouping, label the cages with group information. Grouping should be recorded in the randomization documentation. Use cage racks to stratify the cages to minimize the impact of environmental factors on the experiment.

[0040] (6) Preliminary experiment Based on animal weight, 15 animals were randomly assigned to treatment groups using the BioBook random allocation function to achieve similar mean weights within each group and reduce inter-group bias. The day of group assignment was designated Day 1.

[0041]

[0042] Mice were grouped and orally administered twice daily. Two hours after the first dose on Day 7, all animals were anesthetized with 30 mg / kg of Zotalitol and 5 mg / kg of xylazine via intraperitoneal injection until they completely lost their reflexes (e.g., loss of the tail pinch reflex), ensuring deep anesthesia. Sleep latency and sleep duration were recorded (loss of the righting reflex was used to determine sleep onset). The time from the time of anesthesia and drug administration until the recovery of the righting reflex (i.e., the ability to flip to a normal, belly-down position) was defined as the time of awakening.

[0043] Through preliminary experiments, it was determined that the animals were sensitive to a certain dose of anesthetics, could quickly fall asleep, and could wake up healthily; through preliminary experiments, the effects of the drugs in groups G2 and G3 were preliminarily judged.

[0044] The animals were weighed and their health was checked three times a week.

[0045] The animals were euthanized by carbon dioxide overdose and cervical dislocation at the end of the experiment.

[0046] (7) Formal experiment The formal experiment was conducted after the preliminary study. For the formal experiment, 55 animals were randomly assigned to treatment groups based on body weight using the BioBook randomization function to achieve similar group average weights and minimize inter-group variability. The day of group assignment was designated Day 1.

[0047]

[0048] (8) Experimental design Experiment on prolonging sleep time of mice given Shutai and xylazine 1) Weighing Body weight was measured three times a week.

[0049] 2) Medication The specific grouping method and administration method are shown in Table 2.

[0050] 3) Anesthetize the animal On the morning of Day 7, 2 hours after the animals were dosed, all animals were anesthetized by intraperitoneal injection of the doses of Zoltrate and xylazine determined in the pre-experiment. The mice were anesthetized until they completely lost their reflex ability (such as the disappearance of the tail clamp reflex) to ensure that they were in a deep anesthesia state.

[0051] 4) Record sleep latency, sleep time and wake time The sleep latency and sleep time were recorded (the mice were judged to have fallen asleep by the disappearance of the righting reflex). The time from the administration of anesthesia to the recovery of the mouse's reversal reflex (i.e., the ability to turn over to the normal position with the abdomen facing down) was recorded as the awakening time.

[0052] 5) Euthanasia After all experiments, animals were euthanized using carbon dioxide overdose and cervical dislocation.

[0053] (9) Experimental observation Observe the animals' health and overall drug response daily. Any abnormal appearance or behavior should be recorded in detail on the biological experiment observation form. For example, if the animal experiences significant weight loss (over 15%) or other side effects (e.g., lethargy, inactivity, or mental fatigue) after drug administration, administer 5% glucose saline solution for rehydration, add agar, and add additional animal toys.

[0054] 4. Statistical analysis Experimental data are expressed as mean ± SEM and analyzed using Graphpad Prism or SPSS. P A value <0.05 was considered to be significantly different.

[0055] 5. Results (1) Preliminary experimental results 1) Weight The animals were weighed during the experiment (Day 1 to Day 7), and the results are shown in Table 3. Compared with the G1 blank group, there was no significant difference in body weight among the groups.

[0056]

[0057] 2) Sleep latency, sleep time and wake time On day 7, mice were anesthetized by injection of Zotal and xylazine, and sleep latency, sleep time and awakening time were observed. The results are shown in Table 4.

[0058]

[0059] (2) Formal experimental results 1) Weight The animals were weighed during the experiment (Day 1 to Day 7), and the results are shown in Table 5. Compared with the G1 blank group, there was no significant difference in body weight among the groups.

[0060]

[0061] 2) Sleep latency, sleep time and wake time On Day 7, mice were anesthetized with Zotal and xylazine, and sleep latency, sleep duration, and awakening time were observed. The results are shown in Table 6.

[0062]

[0063] 6. Discussion Preliminary results showed that sleep latency, sleep duration, and awakening time were prolonged in mice anesthetized with sutane and xylazine. Compared with the G1 blank group, the G2 Zaoren Anshen Capsule (150 mg / kg) and G3 Fufang Huonaoshu Capsule (100 mg / kg) groups showed a trend toward prolonged sleep and awakening times after anesthesia, but no statistical differences were found. This was likely due to a slightly insufficient dose of the test drug and the small number of animals, making statistical significance difficult to achieve. Therefore, in the final experiment, the Zaoren Anshen Capsule dose was increased, and the number of animals enrolled was increased.

[0064] The results of the formal experiment showed that after observing the sleep latency, sleep time and wake-up time, the sleep latency of mice in each drug-treated group was shortened to a certain extent compared with the G1 blank group, but no statistical difference was found; compared with the G1 blank group, the G2 Zaoren Anshen Capsule group (300 mg / kg) and the G4 Compound Huonaoshu Capsule medium-dose group (100 mg / kg) could significantly prolong the sleep time and wake-up time of mice, and there was a significant difference ( p <0.01), the low-dose group (50 mg / kg) of G3 compound Huo Nao Shu capsule had no significant difference in prolonging sleep time and wake-up time, while the high-dose group (200 mg / kg) of G5 compound Huo Nao Shu capsule could significantly prolong sleep time and wake-up time with significant statistical difference ( p <0.001).

[0065] In summary, the high-dose group of Compound Huo Nao Shu Capsule (200 mg / kg) can effectively increase sleep time in a dose-dependent manner and can moderately improve sleep quality.

[0066] Experimental Example 2 Study on the efficacy of the test drug in the PCPA (p-chlorophenylalanine)-induced insomnia model in mice 1. Experimental Purpose This study observed the efficacy of the test drug in the p-chlorophenylalanine (PCPA)-induced insomnia model in mice.

[0067] 2. Test materials (1) Test substance

[0068] (2) Preparation of test substances Use 0.5% CMC-Na for dissolution and dilution. Preparation frequency: Prepare immediately before use and store at room temperature.

[0069] Preparation method: Group G4: Take one capsule, open it and place it in a centrifuge tube (containing 0.25 g of the test substance). Add 50 mL of 0.5% CMC-Na solution to dissolve it into a 5 mg / mL test substance solution, and sonicate or vortex to dissolve it.

[0070] Group G5: Take one capsule, open it and place it in a centrifuge tube (containing 0.25 g of the test substance). Add 25 mL of 0.5% CMC-Na solution to dissolve it into a 10 mg / mL test substance solution, and sonicate or vortex to dissolve it.

[0071] Group G6: Take one capsule, open it and place it in a centrifuge tube (containing 0.25 g of the test substance). Add 12.5 mL of 0.5% CMC-Na solution to dissolve it into a 20 mg / mL test substance solution, and dissolve it by ultrasonication or vortexing.

[0072] (3) Positive drugs

[0073] (4) Preparation of positive drugs Zaoren Anshen Capsules: Take two open capsules and place them together in a centrifuge tube (containing 0.45g). Add 60 mL of 0.5% CMC-Na and dilute to 15 mg / mL. Prepare once a week and store at room temperature.

[0074] (5) Solvent information

[0075] (6) Solvent preparation Weigh 17.59000g of sodium carboxymethyl cellulose and add 3518.00mL of double-distilled water. Stir and dissolve until clear. Prepare once a month and store at room temperature.

[0076] (7) Main reagents p-Chlorophenylalanine: Sigma, product number: C6506, batch number: SHBQ3488, expiration date: 2028.2.19.

[0077] Xylazine: TGI, batch number: GH5QM-WV, expiration date: 2026.12.24.

[0078] Virbac, batch number: 9C1RA, item number: BN8V4RA, expiration date: 2025.06.01.

[0079] Dopamine detection kit: Shanghai Keaibo Biotechnology, product number: CB10272-Mu, batch number: APR 25, expiration date: OCT 25.

[0080] (8) Main instruments and equipment Electronic balance: TP-602. Sartorius Beijing. Expiry date: 2025.07.03.

[0081] 3. Experimental procedure (1)Animals Animal species and strain: C57BL / 6J mice.

[0082] Medication record: No medication history.

[0083] Sex, age, weight: Male, 7 - 9 weeks old, 20 - 25 g.

[0084] Breeder / supplier: Jihui Laboratory Animal Breeding Co., Ltd.

[0085] Animal use license number: SYXK(Shanghai)2023 - 0011.

[0086] Supplier license number: SCXK(Shanghai)2022 - 0009.

[0087] Animal quality certificate number: 20220009035866.

[0088] Experimental institution: Animal house.

[0089] Adaptation period: 7 days.

[0090] Room: SPF area room.

[0091] Animal housing: 2 - 5 mice (in the same dosing group). [[ID=三十九]]

[0092] A total of 61 C57BL / 6J mice were purchased from the supplier. Among them, 6 were spare animals, used for selecting suitable animals for the group, and euthanized after the overall experiment. None of the animals carried specific pathogens and they were about 6 - 8 weeks old when they arrived at the animal house.

[0093] (2)Animal receipt, health assessment and adaptation period After the animals arrived, the animal house staff transferred the animals from the transport packaging to the cages and examined each animal. The examination scope included appearance, limbs and cavities, etc., and whether there were any abnormal manifestations when the animals were stationary or moving.

[0094] (3)Environment Mice were housed in cages (cage specifications are detailed in the report) in the animal room. Cage bedding consisted of autoclaved corn cobs (Chenfu Eden Garden Bedding Processing Factory, Dachang Hui Autonomous County), which were changed every 7–10 days. The animal room was equipped with a high-efficiency air filter and ventilated at 15–25 air changes per hour. The temperature was maintained between 20–26°C (68–79°F) and relative humidity between 30–70%. Temperature and humidity were continuously monitored and recorded. Lighting conditions consisted of 12 hours of fluorescent lighting per day (08:00–20:00) and 12 hours of no lighting.

[0095] (4) Food and water Experimental mice had unlimited access to specialized mouse chow (irradiated, sterilized, Jiangsu Collaborative Pharmaceutical Bioengineering Co., Ltd., China). Samples of each batch of animal feed were retained for analysis as needed, and the resulting certificates of analysis were archived. Throughout the experiment, experimental mice had unlimited access to in-house treated drinking water, obtained from municipal tap water treated by reverse osmosis or autoclaving. Drinking water was tested twice annually for heavy metals, nitrates, dissolved minerals, total bacterial counts, and E. coli. Test reports were archived. The levels of known contaminants in the animal food and drinking water did not foreseeably affect the objectives or procedures of this study.

[0096] (5) Cages and animal identification Each experimental mouse is assigned a unique number. Before grouping animals, cage labels should be labeled with the project number, species / strain, sex, cage number, and animal number. After grouping, cages should be labeled with group information. Grouping should be recorded in the randomization documentation. Cages should be separated into different groups using cage racks to minimize the impact of environmental factors on the experiment.

[0097] (6) Experimental groups Based on animal weight, 55 animals were randomly assigned to treatment groups using the BioBook randomization function to achieve similar mean weights within each group and reduce intergroup bias. The day of group assignment was designated Day 1.

[0098]

[0099] (7) Experimental design 1) Animal modeling Animals in the G2-G6 modeling groups received intraperitoneal injections of 300 mg / kg of PCPA (dissolved in pH 7.4 saline containing 0.1% Tween 80). Injection time: once on Day 8 and once on Day 9. Animals in the G1 normal group received intraperitoneal injections of pH 7.4 saline.

[0100] 2) Medication Animals were dosed starting on Day 1 and continuing until the day of behavioral assessment. The dosing time was recorded on the day of behavioral assessment. Detailed grouping and dosing methods are shown in Table 1.

[0101] 3) Behavioral assessment Conduct behavioral assessments on Day 10 - Day 15 (estimated) using the Light-Dark Box Test (LDB): Methods: Mice were gently placed in a dark area with their heads facing the light area. Mice were allowed to move freely between the dark and light areas. Each mouse was observed for 5 minutes, and the following behaviors were recorded: Number of entries into the light area: the number of times the mouse entered the light area from the dark area.

[0102] Time spent in the light zone: the total time (in seconds) that the mouse stayed in the light zone.

[0103] Latency to first entry into the light zone: the time (in seconds) from the start of the experiment to the time the mouse first entered the light zone.

[0104] 4) Biochemical index detection At the end of the experiment, all animals were anesthetized with 1-4% isoflurane, and a maximum amount of serum was collected from the orbital vein for later use. Brain tissue was collected and frozen at -80°C. The hypothalamus was isolated for dopamine level analysis and loaded into a single well.

[0105] 5) Euthanasia and sample collection After serum collection at the end of the experiment, all animals were euthanized using carbon dioxide and cervical dislocation.

[0106] (8) Experimental observation The animals' health status and overall drug response were observed daily. No abnormalities were found in the animals during this experiment.

[0107] 4. Statistical analysis Experimental data are expressed as mean ± SEM and analyzed using Graphpad Prism or SPSS. P A value <0.05 was considered to be significantly different.

[0108] 5. Results (1) Weight During the experiment, body weight was measured every week. As shown in Table 2, there was no significant difference among the groups compared with the G2 model group.

[0109]

[0110] (2) Behavioral assessment Behavioral assessments were conducted from Day 10 to Day 15. Specific data are shown in Tables 3, 4, and 5.

[0111]

[0112]

[0113]

[0114] (3) Dopamine content detection At the end of the experiment, the brain tissues of the mice were collected and the dopamine content in the hypothalamus was detected. The results are shown in Table 6.

[0115]

[0116] 6. Discussion The purpose of this study was to evaluate the efficacy of the test drug in a PCPA-induced insomnia mouse model. After PCPA administration, the model animals became agitated, resisted violently when grasped, showed lethargy, and had matted fur. This increased anxiety-like behavior in the mice indicated successful modeling.

[0117] Behavioral assessment results showed that compared with the G2 model group, the G1 blank group mice showed significant behavioral differences on days 1-6 after modeling (i.e., observation period of Day 10-Day 15). Among them, the number of times they entered the bright area increased significantly, especially on Day 11-Day 13 ( p <0.0001). The time spent in the bright area was significantly prolonged, with a very significant difference on Day 13 ( p <0.0001). The latency of first entering the bright area was significantly shortened, and the difference was extremely significant between Day 12 and Day 13 ( p <0.0001). The above results fully demonstrate that PCPA successfully induced an insomnia model in mice.

[0118] In terms of efficacy verification, compared with the G2 model group, the G3 positive drug Zaoren Anshen Capsule (150mg / kg) group significantly improved the insomnia caused by PCPA modeling, as shown by an increase in the number of times entering the bright area, with a significant statistical difference on Day 12 ( p <0.01), the residence time in the bright area was significantly prolonged, with significant statistical differences between Day 13 and Day 14 ( p <0.01) and shortened the latency time of first entering the bright area, with significant differences between Day 12 and Day 14 ( p <0.001).

[0119] The study of the test drug Compound Huo Nao Shu Capsule found that different dose groups showed different efficacy. Compared with the G2 model group, the low-dose group of G4 Compound Huo Nao Shu Capsule (50 mg / kg) failed to improve the symptoms of insomnia induced by PCPA. The medium-dose group of G5 Compound Huo Nao Shu Capsule (100 mg / kg) significantly increased the number of times mice entered the bright area on Day 13 (p < 0.01) and significantly prolonged the time mice stayed in the bright area from Day 12 to Day 13 ( p <0.05, and significantly shortened the latency time of first entry into the bright area on Day 11-Day 12 ( p <0.0001). The high-dose group of G6 Compound Huonaoshu Capsules (200 mg / kg) significantly increased the number of times mice entered the bright area on Day 13 ( p <0.0001), and significantly prolonged the time mice stayed in the bright area on Day 11, Day 12, and Day 14 ( p <0.0001), and the latency to first enter the bright area was significantly shortened during Day 11-Day 12 ( p <0.0001).

[0120] In summary, both the medium dose (100 mg / kg) and high dose (200 mg / kg) of the test drug Compound Huo Nao Shu Capsule can significantly improve the insomnia symptoms induced by PCPA in mice, showing good anti-insomnia efficacy potential.

[0121] The above description is only a specific embodiment of the present invention, and the various examples do not limit the essential content of the present invention.

Claims

1. Use of Compound Huo Nao Shu Capsules in the preparation of insomnia medicine; the Compound Huo Nao Shu Capsules are prepared from 2000g of pig brain, 200g of Schisandra chinensis, 100g of Ophiopogon japonicus, 50g of Ginseng, 50g of Lycium barbarum, 50g of Rehmannia glutinosa and 50g of Salvia miltiorrhiza.

2. The use according to claim 1, characterized in that The dosage is 10-20 mg / kg.

3. The use according to claim 1 or 2, characterized in that The dosage is 20 mg / kg.

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