A traditional Chinese medicine composition with the functions of sedation, hypnotization and treatment of insomnia and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition with the functions of calming and hypnotizing and treating insomnia and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials in parts of mass: fried date kernel 10-30, Chinese date 10-25, licorice 5-15, ganoderma lucidum 5-15, longan arillus 5-15, lily 10-20, bergamot 10-20, wheat 10-30, day lily 10-20 and Gastrodia elata 5-15. The application can achieve the functions of calming the heart and soothing the nerves, clearing the heart and relieving the irritability, nourishing yin and reducing fire, calming and hypnotizing and treating insomnia, and has a remarkable therapeutic effect on insomnia.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition that has both sedative and hypnotic effects and a method for treating insomnia, and its preparation method. Background Technology

[0002] Insomnia is a neuropsychiatric disorder characterized by difficulty falling asleep or maintaining sleep under conditions of sufficient sleep time and a suitable environment, leading to daytime dysfunction. Its main symptoms include difficulty falling asleep, frequent awakenings, early awakenings, and non-restorative sleep.

[0003] Currently, sedative-hypnotic drugs remain the primary means of treating insomnia in clinical practice, including benzodiazepines such as diazepam and lorazepam. Class II and non-benzodiazepines, represented by zaleplon and zopiclone. These are all commonly used clinical drugs. However, currently used sedative-hypnotic drugs have varying degrees of side effects and medication safety issues. Benzodiazepines Long-term use of these drugs can lead to addiction and dependence, and has side effects such as drowsiness, fine motor incoordination, and memory loss. Non-benzodiazepines While the side effects of this type of drug, such as memory impairment and rebound insomnia after discontinuation, are relatively minor, it can still cause daytime functional disorders such as headaches, dizziness, and drowsiness. Long-term use can also lead to drug tolerance and dependence.

[0004] Chemical drugs often target single points to exert their therapeutic effects, making it difficult to provide a holistic intervention for the disease, failing to achieve a recovery effect close to physiological sleep, and having significant side effects. Traditional Chinese medicine (TCM) compound formulas, on the other hand, have complex components and possess holistic regulatory and therapeutic effects across multiple targets, components, and pathways. Numerous clinical studies have shown that TCM compound treatment can achieve a recovery effect closer to physiological sleep, improving sleep quality with fewer side effects. In recent years, the use of complementary and alternative medications for insomnia, represented by TCM herbs, has also shown an increasing trend in Western societies. However, due to a lack of long-term clinical experience and the guidance of TCM theory, ideal therapeutic effects are difficult to achieve. TCM's diagnostic theories and classic formulas have significant advantages in research on sleep-regulating drugs.

[0005] "Medicine and food share the same origin" is an important concept in traditional Chinese medicine, emphasizing the close relationship between drugs and food. Based on the TCM syndrome differentiation, we select medicinal herbs from the list that share the same origin as food to formulate prescriptions. By fully utilizing the advantages of multi-target holistic regulation of TCM compound prescriptions, we can further improve the safety and compliance of the drugs. Summary of the Invention

[0006] Based on the technical problems existing in the prior art, the inventors have creatively combined the Chinese medicinal materials of fried jujube seed, jujube, liquorice, ganoderma, longan arillus, lily, bergamot, day lily, hui wheat and gastrodia tuber into a prescription to provide a Chinese medicinal composition with the effects of calming and treating insomnia and a preparation method thereof. The Chinese medicinal composition is safe and effective and has the effects of calming and treating insomnia.

[0007] In order to achieve the above-mentioned object, the present application adopts the following technical solutions:

[0008] According to a first aspect of the technical solutions of the present application, the present application provides a Chinese medicinal composition made of the following Chinese medicinal raw materials in mass parts: fried jujube seed 10-30, jujube 10-25, liquorice 5-15, ganoderma 5-15, longan arillus 5-15, lily 10-20, bergamot 10-20, hui wheat 10-30, day lily 10-20 and gastrodia tuber 5-15.

[0009] Preferably, the Chinese medicinal composition is made of the following Chinese medicinal raw materials in mass parts: fried jujube seed 15-25, jujube 12-20, liquorice 7-12, ganoderma 7-12, longan arillus 7-12, lily 12-20, bergamot 12-20, hui wheat 15-25, day lily 12-20 and gastrodia tuber 7-12.

[0010] Preferably, the mass ratio of the Chinese medicinal raw materials in the Chinese medicinal composition is 20:15:9:9:9:15:15:20:15:9.

[0011] According to a second aspect of the technical solutions of the present application, a preparation method of the Chinese medicinal composition is provided, which comprises the following steps:

[0012] Step S1: Chinese medicinal raw materials are weighed according to mass parts, and the Chinese medicinal raw materials include fried jujube seed, jujube, liquorice, ganoderma, longan arillus, lily, bergamot, hui wheat, day lily and gastrodia tuber;

[0013] Step S2: water is added to the Chinese medicinal raw materials obtained in step S1 in an amount of 5-30 times the mass parts, the Chinese medicinal raw materials obtained in step S1 are heated, then refluxed and filtered to obtain a first extract and a residue;

[0014] Step S3: the first extract obtained in step S2 is evaporated under reduced pressure to obtain a solid of the first extract, which is reserved.

[0015] Preferably, in some embodiments, in step S2, the water is 10 times the amount of the Chinese medicinal raw materials obtained in step S1.

[0016] Preferably, in some embodiments, in step S2, the water is 5-15 times the amount of the traditional Chinese medicine raw material obtained in step S1, the traditional Chinese medicine raw material soaked with water is heated so that the water is heated to boiling, and then reflux extraction is carried out for 1-3 hours.

[0017] According to a third aspect of the technical scheme of the present application, the present application provides a pharmaceutical preparation made of the traditional Chinese medicine composition as described above and a pharmaceutically acceptable carrier, and the dosage form is any pharmaceutically acceptable dosage form, including but not limited to oral preparations, injection preparations, transdermal absorption preparations, etc.

[0018] Preferably, the pharmaceutical preparation is in the form of an oral preparation, including but not limited to tablets, capsules, granules, pills, powders, pills, syrup, oral solution, oral suspension.

[0019] In some embodiments, the pharmaceutical preparation is in the form of an injection preparation, including but not limited to injection solution, injection suspension, injection emulsion, injection powder, etc.

[0020] According to a fourth aspect of the technical scheme of the present application, the present application provides a use of the traditional Chinese medicine composition as described above in the preparation of a drug for sedation and insomnia treatment.

[0021] Compared with the prior art, the present application has the following beneficial technical effects:

[0022] 1. The traditional Chinese medicine composition of the present application is a compound prepared from the homology of medicine and food of fried jujube kernel, jujube, licorice, ganoderma, longan meat, lily, bergamot, huai wheat, gastrodia, day lily, etc. It is used for treating insomnia, sedation and other effects. Fried jujube kernel belongs to heart-nourishing and spirit-soothing medicine, and its medicinal properties are sweet, sour and flat, and it belongs to heart, liver and gallbladder meridians, and has the effects of nourishing heart and liver, soothing the nerves and stopping sweating. It can be used to treat palpitation and insomnia. Licorice can tonify heart qi and restore pulse, and licorice has the effect of tonifying heart qi and restoring pulse. Ganoderma has the effect of tonifying qi, soothing the nerves and supporting the body. Bergamot is warm, sour, bitter and sweet, and can be used for liver and spleen, and has the effect of soothing liver and regulating qi, and is suitable for treating liver stagnation caused by rib pain, irritability, chest tightness, insomnia and other symptoms.

[0023] 2. The composition of the present application has the effects of sedation and insomnia treatment. Systematic pharmacological studies have shown that the traditional Chinese medicine composition has multiple effects of sedation and insomnia treatment, and the combination of single medicinal materials in the prescription has the best synergistic anti-insomnia effect, which is better than the extract of single medicinal material and the extract of part of single medicinal material combination.

[0024] 3、The traditional Chinese medicine composition has the effects of sedation and hypnosis, and good safety characteristics of homology of medicine and food support its use for the prevention of the above diseases, and has potential values of health guarantee forward shift, slow disease management and promotion of national health.

[0025] 4、The pharmaceutical preparation can prolong the righting reflex disappearance time of mice, shorten the righting reflex disappearance latency, has excellent sedative and hypnotic activity, and has the effects of sedation and hypnosis, treatment or prevention of work insomnia compared with chemical drugs. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1A is a comparison chart of sleep latency time of mice using the traditional Chinese medicine composition and each control drug.

[0027] Figure 1B is a comparison chart of sleep duration of mice using the traditional Chinese medicine composition and each control drug.

[0028] Figure 2 is a comparison chart of spontaneous activity distance of mice using the traditional Chinese medicine composition and each control drug.

[0029] Figure 3A is a comparison chart of 24-hour total sleep time of mice using the traditional Chinese medicine composition and each control group.

[0030] Figure 3B is a comparison chart of 24-hour sleep-wake total time of mice using the traditional Chinese medicine composition and each control group.

[0031] Figure 3C is a comparison chart of fragment average length of 24-hour sleep-wake state of mice using the traditional Chinese medicine composition and each control group.

[0032] Figure 3D is a comparison chart of fragment number of 24-hour sleep-wake state of mice using the traditional Chinese medicine composition and each control group.

[0033] Figure 4A is a comparison chart of sleep latency of mice using the traditional Chinese medicine composition and each control drug in PCPA-induced insomnia experiment.

[0034] Figure 4B is a comparison chart of sleep duration of mice using the traditional Chinese medicine composition and each control drug in PCPA-induced insomnia experiment. DETAILED DESCRIPTION

[0035] In order to make the technical problems solved by the present application, the technical solutions adopted and the beneficial effects obtained more clear and understandable, the present application is further described in detail below in combination with specific embodiments. The specific embodiments described herein are only used to explain the present application and do not constitute any limitation to the present application. Unless otherwise defined, all the terms used in the present application have the same meaning as commonly used in the field of the present application.

[0036] The following specific embodiments are provided to help understand the present application, but it should be understood that the listed embodiments and test examples of the present application are only used to illustrate the present application, but do not constitute any limitation, and the actual protection scope of the present application is set forth in the claims.

[0037] The present application provides a traditional Chinese medicine composition with the effects of sedation, hypnotic and treatment of insomnia, which is a traditional Chinese medicine composition with the effects of sedation, hypnotic and treatment of insomnia. The present inventors creatively combine the medicinal and edible traditional Chinese medicinal materials fried jujube kernel, jujube, liquorice, ganoderma, longan meat, lily, bergamot, day lily, huaisheng wheat, and gastrodia to form a prescription, hereinafter referred to as "Bai Fulong Za An Shen Fang". The Bai Fulong Za An Shen Fang of the present application can synergistically prolong the righting reflex disappearance time of mice, shorten the righting reflex disappearance latency, and has excellent sedative and hypnotic activity; it has the effects of sedation, hypnotic, treatment or prevention of high-intensity work insomnia.

[0038] The Bai Fulong Za An Shen Fang of the present application has a clear effect on insomnia and high safety, and the traditional Chinese medicine composition also has a sedative and hypnotic effect. The combination of single medicinal materials in the prescription of the present application has the best synergistic antidepressant effect, which is better than the extract of single medicinal material and the extract of combination of part of single medicinal material.

[0039] The traditional Chinese medicinal raw materials fried jujube kernel, jujube, liquorice, ganoderma, longan meat, lily, bergamot, day lily, huaisheng wheat, and gastrodia used in the Bai Fulong Za An Shen Fang of the present application are purchased from Beijing Tong Ren Tang, diazepam is purchased from Shanghai Wanda Pharmaceutical Co., Ltd., and ICR mice are purchased from Spafas (Beijing) Experimental Animal Co., Ltd.

[0040] The traditional Chinese medicine composition of the Bofulongzao Nian Shen Fang is made of the following traditional Chinese medicine raw materials in mass parts: Fried Jujube Seed 10-30, Jujube 10-25, Licorice 5-15, Ganoderma 5-15, Longan Meat 5-15, Lily 10-20, Bergamot 10-20, Huai Wheat 10-30, Day Lily 10-20, and Gastrodia 5-15. In preferred embodiments, the traditional Chinese medicine composition of the Bofulongzao Nian Shen Fang is made of the following traditional Chinese medicine raw materials in mass parts: Fried Jujube Seed 15-25, Jujube 12-20, Licorice 7-12, Ganoderma 7-12, Longan Meat 7-12, Lily 12-20, Bergamot 12-20, Huai Wheat 15-25, Day Lily 12-20, and Gastrodia 7-12. Further, the mass ratio of the traditional Chinese medicine raw materials in the traditional Chinese medicine composition is 20:15:9:9:9:15:15:20:15:9, for example, the Bofulongzao Nian Shen Fang is composed of the following raw materials and in the following proportions: Fried Jujube Seed 20g, Jujube 15g, Licorice 9g, Ganoderma 9g, Longan Meat 9g, Lily 15g, Bergamot 15g, Huai Wheat 20g, Day Lily 15g, and Gastrodia 9g.

[0041] In another aspect, the present application provides a preparation method of the traditional Chinese medicine composition as described above, comprising the following steps:

[0042] Step S1: The traditional Chinese medicine raw materials are weighed according to the mass parts, and the traditional Chinese medicine raw materials include Fried Jujube Seed, Jujube, Licorice, Ganoderma, Longan Meat, Lily, Bergamot, Huai Wheat, Day Lily, and Gastrodia;

[0043] Step S2: The traditional Chinese medicine raw materials obtained in step S1 are heated with 5-30 times the amount of water in mass parts, then refluxed and filtered to obtain a first extract and a residue;

[0044] Step S3: The first extract obtained in step S2 is evaporated under reduced pressure to obtain a solid of the first extract, which is ready for use.

[0045] Preferably, in some embodiments, in step S2, the water is 10 times the amount of the traditional Chinese medicine raw materials obtained in step S1, and the reflux extraction is performed for 2 hours.

[0046] Preferably, in some embodiments, in step S2, the water is 5-15 times the amount of the traditional Chinese medicine raw materials obtained in step S1, and the water-soaked traditional Chinese medicine raw materials are heated to boiling, and then refluxed and extracted for 1-3 hours.

[0047] Further, the present application provides a pharmaceutical preparation made of the traditional Chinese medicine composition as described above and a pharmaceutically acceptable carrier, in any pharmaceutically acceptable dosage form, including but not limited to oral preparations, injection preparations, transdermal absorption preparations, etc. The pharmaceutical preparation is in the form of an oral preparation, including but not limited to tablets, capsules, granules, pills, powders, pills, syrups, oral solutions, oral suspensions. In some embodiments, the pharmaceutical preparation is in the form of an injection preparation, including but not limited to injection solutions, injection suspensions, injection emulsions, injection powders, and other pharmaceutically acceptable injection dosage forms. Further, the traditional Chinese medicine composition as described above can be used for sedation and treatment of insomnia.

[0048] The preparation method of the traditional Chinese medicine composition of the present application and examples of its application are further illustrated below in conjunction with specific embodiments.

[0049] Embodiment one, the preparation method of a traditional Chinese medicine composition with the functions of sedation and treatment of insomnia, comprises the following steps:

[0050] Step S1: The traditional Chinese medicine raw materials are weighed according to the mass fraction, including fried jujube seeds, jujube, licorice, ganoderma lucidum, longan meat, lily, bergamot, Huai wheat, day lily, and Gastrodia elata.

[0051] The traditional Chinese medicine raw materials are weighed according to the mass fraction, which means that fried jujube seeds 10-30, jujube 10-25, licorice 5-15, ganoderma lucidum 5-15, longan meat 5-15, lily 10-20, bergamot 10-20, Huai wheat 10-30, day lily 10-20, and Gastrodia elata 5-15 are weighed according to the mass fraction.

[0052] In a preferred embodiment, the Bofulong Zaoren Decoction is: fried jujube seeds 15-25, jujube 12-20, licorice 7-12, ganoderma lucidum 7-12, longan meat 7-12, lily 12-20, bergamot 12-20, Huai wheat 15-25, day lily 12-20, and Gastrodia elata 7-12.

[0053] In this embodiment, fried jujube seeds 20g, jujube 15g, licorice 9g, ganoderma lucidum 9g, longan meat 9g, lily 15g, bergamot 15g, Huai wheat 20g, day lily 15g, and Gastrodia elata 9g.

[0054] The step comprises removing impurities from all traditional Chinese medicine crude drugs, preferably removing impurities by combining manual impurity removal and mechanical impurity removal. After removing impurities, the surface of the above-mentioned traditional Chinese medicine crude drugs is quickly cleaned with clean room temperature water, preferably cleaned with flowing water, or sprayed and cleaned with a water spray gun with a water pressure of 0.2-1.0 MPa, preferably a water spray gun with a water pressure of 0.25-0.80 MPa. It has been verified by experiments that the water spray gun with a water pressure of 0.50 MPa is used for spraying and cleaning Zizyphus jujuba Mill. var. sativa, Glycyrrhiza uralensis, Ganoderma lucidum, Citrus medica, Flos Lonicerae Japonicae and Gastrodia elata Blume, and the water spray gun with a water pressure of 0.30 MPa is used for spraying and cleaning Zizyphus jujuba Mill., Semen Litchi chinensis, Flos Lilii and Triticum aestivum L.

[0055] Zizyphus jujuba Mill. var. sativa is used for calming the heart and soothing the nerves, and for stopping sweating. Zizyphus jujuba Mill. var. sativa is sweet and sour, and has the characteristics of internal supplementation and external astringency. It can not only internally supplement the blood to calm the nerves, but also externally astringe the yin to stop sweating. Zizyphus jujuba Mill. var. sativa is preferably harvested in autumn, the flesh is removed and dried, the jujube kernel is broken, the seeds are taken out, and the roasted seeds are used after roasting. Zizyphus jujuba Mill. var. sativa is used for neurasthenia, body weakness and sweating, and people with thin body and weakness can use it. The contraindication of Zizyphus jujuba Mill. var. sativa is that it can drain the true qi if used for too long.

[0056] Zizyphus jujuba Mill. is used for blood nourishment, spleen and stomach nourishment, heart and mind calming, liver nourishment and nutrient supplementation. Glycyrrhiza uralensis is used for spleen and qi tonification, and has a certain conditioning effect on symptoms such as fatigue, weakness, weak spleen and stomach, palpitation and shortness of breath. Glycyrrhiza uralensis can also relieve cough and promote the excretion of sputum. Ganoderma lucidum is preferably grown in the forest, and has the highest medicinal effect. It can also be grown in a greenhouse. Ganoderma lucidum has the effects of softening blood vessels, calming nerves, lowering blood sugar and the like.

[0057] In the present application, Zizyphus jujuba Mill. var. sativa, Zizyphus jujuba Mill., Glycyrrhiza uralensis and Ganoderma lucidum are used in combination, which is one of the innovations of the present application. The blood nourishment and spleen and stomach nourishment of Zizyphus jujuba Mill. are used to make up for the deficiency of Zizyphus jujuba Mill. var. sativa in draining the true qi. The combination of Glycyrrhiza uralensis and Ganoderma lucidum achieves the effects of calming nerves and lowering blood sugar.

[0058] Semen Litchi chinensis is used for blood and qi nourishment, fatigue elimination and mind calming, so that the human body can quickly replenish energy, recover energy and eliminate physical fatigue after fatigue, and at the same time, eliminate symptoms such as palpitation, nervousness and insomnia of the nervous system.

[0059] Lily is used to clear the heart and relieve irritability, calm the heart and tranquilize the mind, and can be used for the treatment of heat after fever, dizziness, insomnia, depression and other symptoms. Lily is rich in vitamins and has the effect of clearing heat and moistening dryness, which can relieve dryness of the lungs, cough and other symptoms. The smell of bergamot is fragrant, and it can enter the lungs, liver, spleen and stomach, and is used to treat lung stagnation, chest tightness and spleen and stomach stagnation. Combined with wheat, day lily and Gastrodia, it can achieve the effects of stopping sweating, benefiting qi, nourishing the heart, clearing heat, especially reducing edema, reducing blood pressure, calming wind and stopping convulsions, and calming liver yang. The use of the combination makes the body's water transform into urine and be excreted smoothly.

[0060] Step S2: Soak the traditional Chinese medicine raw material obtained in step S1 with 5-30 times the amount of water by mass, heat the soaked traditional Chinese medicine raw material, then reflux and filter to obtain a first extract and a residue;

[0061] This step S2 further includes step S21, which uses clean water to wash the traditional Chinese medicine raw material obtained in step S1, and then places it in a cool room with a temperature of 18-25 degrees Celsius for natural cooling. The cool room needs to be kept ventilated and clean.

[0062] Step S22: In a preferred embodiment, the large pieces of clean traditional Chinese medicine raw material are crushed into small particles with a particle size of less than 1 centimeter, preferably less than 0.5 centimeters. For example, liquorice, ganoderma lucidum, lily, bergamot, day lily and gastrodia are cut into small particles. The cut and mixed traditional Chinese medicine raw material is mixed with 5-30 times the amount of water, preferably distilled water or purified water. In another embodiment, the mixed traditional Chinese medicine raw material is soaked in 7-15 times the amount of water for 1-10 hours, preferably 3-5 hours.

[0063] Step S23, heating and boiling: after soaking, the soaked traditional Chinese medicine raw material mixture is heated to boiling with a low fire, and kept boiling for 15-30 minutes, preferably 20 minutes. The temperature of the low fire in this embodiment is preferably controlled at any temperature between 120 and 260 degrees Celsius, more preferably between 150 and 180 degrees Celsius. In a preferred embodiment, a 160-degree low fire is used.

[0064] Step S24, micro-boiling heating: then reduce the heating temperature so that the soaked traditional Chinese medicine raw material mixture is kept in weak boiling for 15-30 minutes, preferably reduce the low fire heating temperature to any temperature between 80 and 100 degrees Celsius; in a preferred embodiment, a low fire of 90 degrees Celsius, 95 degrees Celsius or 98 degrees Celsius is used.

[0065] Step S25, reflux extraction step: the heated traditional Chinese medicine raw material mixture is used to separate the effective component material to be extracted from the soaked traditional Chinese medicine raw material mixture by using a reflux extraction device. The reflux extraction device preferably uses a high-temperature condensation reflux device.

[0066] Further, the concentrated traditional Chinese medicine raw material mixture is filtered by a traditional Chinese medicine liquid filter residue, and a traditional Chinese medicine liquid filter with any one of 100 meshes to 800 meshes of pore size or mesh size is used for residue filtration; preferably, a traditional Chinese medicine liquid filter with a pore size or mesh size of 300 meshes, 400 meshes or 500 meshes is used for residue filtration, to obtain the first extract (i.e. filtrate) and residue.

[0067] Step S3: The first extract obtained in step S2 is evaporated under reduced pressure to obtain a solid state of the first extract, which is ready for use.

[0068] The reduced pressure evaporation in this embodiment refers to placing the first extract in a reduced pressure drying system, and the pressure of the reduced pressure drying system is 0.5-0.8 standard atmosphere, preferably 0.7 standard atmosphere. In a reduced pressure state, the liquid first extract is evaporated and dried to obtain a solid state of the first extract, which is ready for use.

[0069] The reduced pressure drying system is the core equipment of the reduced pressure evaporation, and its main feature is that it can control the changes of pressure and temperature in a closed space, thereby controlling the evaporation speed and drying degree of the liquid first extract. The reduced pressure drying system is composed of a vacuum system, a heating system, a temperature sensor and the like. Among them, the vacuum pump is used to pump out the gas in the closed space to form a low-pressure environment; the vacuum pump is preferably a mechanical vacuum pump, a rotary oil seal vacuum pump or a rotary dry vacuum pump.

[0070] The reduced pressure drying system further comprises a low-temperature condenser, which is used to receive the evaporated moisture and condense it into liquid state to ensure the drying degree inside the reduced pressure drying system.

[0071] Example two, which is improved on the basis of example one. It provides a preparation method of a traditional Chinese medicine composition of Baifulongzao Nian Shen Fang, and the step S2: the first extract and residue are obtained after heating and reflux filtering the traditional Chinese medicine raw material 5-15 times the amount of water in step S1. Preferably, in some embodiments, the water in step S2 is 10 times the amount. Preferably, in some embodiments, the water in step S2 is heated to boiling. Preferably, in some embodiments, the reflux extraction in step S2 is 2 hours

[0072] According to the above-mentioned preparation method of the traditional Chinese medicine composition, the present application provides a pharmaceutical preparation, which is made of a pharmaceutically acceptable carrier and has any pharmaceutically acceptable dosage form, including but not limited to oral preparations, injection preparations, transdermal absorption preparations, etc.

[0073] In some embodiments, the pharmaceutical preparation is an oral preparation, including but not limited to tablets, capsules, granules, pills, powders, pills, syrups, oral solutions, oral suspensions.

[0074] In some embodiments, the pharmaceutical preparation is an injection preparation, including but not limited to injection solution, injection suspension, injection emulsion, injection powder and other pharmaceutically acceptable injection dosage forms. Further, the above-mentioned pharmaceutical preparation is applied to sedation and treatment of insomnia.

[0075] Example three, which is improved on the basis of example one. It provides a Baifulongzao Nian Shen Fang, a traditional Chinese medicine composition with the effects of sedation and treatment of insomnia, which is prepared from fried jujube kernel, jujube, licorice, ganoderma, longan meat, lily, bergamot, huaixi wheat, day lily, and Gastrodia.

[0076] The preparation method comprises the following steps:

[0077] Step S1: according to the mass fraction, 20g of fried jujube kernel, 15g of jujube, 9g of licorice, 9g of ganoderma, 9g of longan meat, 15g of lily, 15g of bergamot, 20g of huaixi wheat, 15g of day lily, and 9g of Gastrodia are weighed;

[0078] Step S2: the traditional Chinese medicine raw materials in step S1 are extracted with 10 times the amount of water by heating reflux for 2 hours, and the first extract and residue are obtained after filtration.

[0079] Step S3: the first extract in step S2 is evaporated under reduced pressure to obtain the extract.

[0080] The preparation of the traditional Chinese medicine composition with the effects of sedation and treatment of insomnia of the above-mentioned Baifulongzao Nian Shen Fang is tested and verified in the test of hypnotic effect, central inhibition and intervention of PCPA model of insomnia.

[0081] Test example 1: hypnotic effect of traditional Chinese medicine extract:

[0082] 1.1 Experimental animals: ICR mice, male, SPF level, 22-25g, purchased from Sibeifu (Beijing) Experimental Animal Co., Ltd.

[0083] 1.2 Test sample: a traditional Chinese medicine composition with the effects of sedation and treatment of insomnia is prepared according to the foregoing, and the corresponding mass of extract is weighed according to the extraction rate and dosage of medicinal materials, and physiological saline is added to prepare a suspension for intragastrical administration.

[0084] 1.3 Test method: After the mice were purchased, they were adaptively fed for one week, and then randomly divided into 4 groups according to the body weight, 10 mice in each group, namely a solvent control group (vehicle, normal saline), a positive control group (diazepam, 3 mg / kg), a traditional Chinese medicine composition low-dose group (5 g / kg in terms of crude drug quality), a traditional Chinese medicine composition medium-dose group (10 g / kg in terms of crude drug quality) and a traditional Chinese medicine composition high-dose group (20 g / kg in terms of crude drug quality). The administration method is as follows:

[0085] (1) The positive control group and the traditional Chinese medicine composition groups were respectively given corresponding drugs (20 ml / kg) by gavage for 5 consecutive days, once a day. The solvent control group was given the same volume of normal saline by gavage.

[0086] (2) 40 min after the last gavage administration, pentobarbital sodium (42 mg / kg, 5 ml / kg) was injected intraperitoneally to each group, and the mice were placed in an independent space at about 25°C, and the administration time was recorded.

[0087] (3) The sleep state of the mice was observed, and the disappearance time of the righting reflex was recorded, that is, the mouse kept the supine position for 60 seconds without recovery, and then it was considered to enter sleep; the recovery time of the righting reflex was recorded, that is, the mouse could recover independently within 60 seconds, and then it was considered to end sleep.

[0088] (4) The sleep latency and sleep time were calculated respectively, the sleep latency was the disappearance time of the righting reflex minus the administration time, and the sleep time was the recovery time of the righting reflex minus the disappearance time of the righting reflex.

[0089] 1.4 Experimental results: see Figure 1A and Figure 1B .

[0090] Figure 1A is a comparison chart of the sleep latency time of mice using the traditional Chinese medicine composition of the application and each control drug, Figure 1A The results specifically show that the sleep latency of the positive drug diazepam group is significantly shortened (p<0.001). The single gavage administration of the medium-dose traditional Chinese medicine composition (10 g / kg) and the high-dose traditional Chinese medicine composition (20 g / kg) of the traditional Chinese medicine composition of the application can shorten the sleep latency induced by pentobarbital sodium, and there is a significant difference compared with the solvent control group (p<0.01).

[0091] Figure 1B is a comparison chart of the sleep time duration of mice using the traditional Chinese medicine composition of the application and each control drug, Figure 1B The results specifically show that the positive drug diazepam can significantly prolong the sleep time of the mice (p<0.001). The single gavage administration of 20 g / kg of the traditional Chinese medicine composition of the application also significantly improves the sleep duration of the mice, and the difference compared with the solvent control group has statistical significance (p<0.01).

[0092] Pentobarbital sodium synergistic hypnotic experiment is a classic experiment for verifying the sedative and hypnotic effect of a drug. The "first extract of the present application + pentobarbital sodium" is superior to pentobarbital sodium alone, which can indicate that the extract of the traditional Chinese medicine composition in the present application has a sedative and hypnotic effect, and can prolong the righting reflex disappearance time of mice when synergized with pentobarbital sodium. The results show that the extract of the traditional Chinese medicine composition in the present application has a clear sedative and hypnotic effect.

[0093] Test Example 2: Central inhibition effect of the extract of the traditional Chinese medicine composition.

[0094] 1.1 Experimental animals: ICR mice, male, SPF level, 22-25 g, purchased from Sibeifu (Beijing) Experimental Animal Co., Ltd.

[0095] 1.2 Test samples: The extract of the traditional Chinese medicine composition prepared is weighed according to the extraction rate and the dosage of medicinal materials, and is added into physiological saline to prepare a suspension for intragastrical administration. Diazepam is converted into the dosage for mice according to the clinical dosage, and is weighed to prepare a physiological saline solution for intragastrical administration.

[0096] 1.3 Experimental instruments: Open field experiment box.

[0097] 1.4 Experimental method: After the mice are purchased, they are adaptively fed for one week, and are randomly divided into 3 groups according to the body weight, 10 mice in each group, which are respectively a solvent control group (vehicle, physiological saline), a positive control (diazepam, 3 mg / kg) group, a low-dose traditional Chinese medicine composition group (5 g / kg of crude drug), a medium-dose traditional Chinese medicine composition group (10 g / kg of crude drug) and a high-dose traditional Chinese medicine composition group (20 g / kg of crude drug). The treatment method is as follows:

[0098] (1) The positive control group and the traditional Chinese medicine composition extract groups of different dosages are respectively given corresponding drugs (20 ml / kg) by intragastrical administration for 5 consecutive days, once a day. The solvent control group is given the same volume of physiological saline by intragastrical administration.

[0099] (2) 40 min after the last intragastrical administration, the mice are placed into a general test box (50x50x40 cm) for spontaneous activity experiment, and the test is started after the mice are adapted for 5 min, and the spontaneous activity trajectory of the mice in the last 10 min is analyzed. The DigBehv behavior analysis system is used to record the spontaneous activity trajectory of the mice, and the total distance of spontaneous activity is analyzed.

[0100] 1.5 Experimental results: see Figure 2 , Figure 2 is a comparison chart of the spontaneous activity distance of mice using the traditional Chinese medicine composition of the present application and various control drugs.

[0101] The results show that, compared with the solvent control group, the total distance of spontaneous activity of the positive drug diazepam group decreased significantly, and the difference was statistically significant (p<0.001). The total distance of spontaneous activity of the high-dose group of the traditional Chinese medicine composition was also significantly reduced (p<0.005).

[0102] The results show that the traditional Chinese medicine composition extract has a central inhibitory effect.

[0103] Test example 3: Regulation of normal rat sleep by traditional Chinese medicine composition extract

[0104] Experimental animals: 8 male SD rats, SPF level, 180-250g, purchased from Beijing Huafukang Biotechnology Co., Ltd.

[0105] Experimental instruments: DSI wireless physiological signal acquisition system (Dataquest A.R.T.4.31), HD-S02 type small animal wireless physiological signal telemetry implant, NeuroScore 3.1.1 electroencephalogram analysis software.

[0106] Test sample: Based on the previous experimental results, the high-dose traditional Chinese medicine composition with significant effect (20g / kg of crude drug) was selected as the preferred dose for subsequent experiments. The prepared traditional Chinese medicine composition extract was immersed in the corresponding concentration extract according to the extraction rate for gavage. Diazepam was converted to the rat administration dose according to the clinical use dose, and the corresponding mass of solid was made into a physiological saline solution for gavage.

[0107] Experimental method:

[0108] (1) Implant surgery

[0109] After the animals were purchased, they were adaptively fed for one week before surgery. The rats were anesthetized by intraperitoneal injection of 10% chloral hydrate 3ml / kg. The skin of the head and neck area was prepared, and the skin was disinfected with iodophor and alcohol cotton ball after shaving. The rats were placed in a prone position on the brain stereotaxic instrument operating table, the adapter position was adjusted, and the rat's head was fixed. The head skin was cut longitudinally, the incision length was 2cm, the skull was exposed, and the periosteum was scraped. The bregma point was found, and marks were drawn on both sides of it 2mm apart with a surgical knife. The skull was drilled, and the metal guide wire at the front end of the implant lead wire sheath was exposed by peeling off the lead wire sheath. After bending, it was placed under the skull without penetrating the dura mater for recording brain electrical activity. The main part of the implant was placed subcutaneously on the back of the rat. After the operation was completed, the wound was sutured, and the rat was placed in a warm environment until it woke up. Antibiotics were injected intraperitoneally for one week after the operation.

[0110] (2) Drug administration and signal acquisition

[0111] The baseline data of sleep and spontaneous activity of rats were collected one week after the operation as self-control (Baseline), and the next day, the rats were randomly divided into two groups, 4 rats in each group, and divided into positive control (diazepam 3 mg / kg, i.g.) group and Chinese medicine food homologous formula (20 g / kg, i.g.) group. After administration, the rats were put back into the original feeding cage, and 30 min later, the EEG signal collection was started by opening the implant. The duration was 24 hours. After the first round of EEG test, the drug washout period was 7 days, and the inter-group cross-repeated measurement was performed.

[0112] (3) EEG analysis

[0113] The EEG signal was scored in units of 10s using the default rodent sleep scoring model of NeuroScore 3.1.1 EEG analysis software, and the original signal was classified according to the EEG characteristics, including wakefulness, active wakefulness, non-rapid eye movement sleep, and rapid eye movement sleep.

[0114] The experimental results are shown in Figure 3A 、 Figure 3B 、 Figure 3C 、 Figure 3D . Figure 3A is a comparison chart of the 24-hour total sleep time of the Chinese medicine composition of the application and each control group, Figure 3B is a comparison chart of the 24-hour sleep-wake total time of the Chinese medicine composition of the application and each control group, Figure 3C is a comparison chart of the fragment average length of the 24-hour sleep-wake state of the Chinese medicine composition of the application and each control group, Figure 3D is a comparison chart of the fragment number of the 24-hour sleep-wake state of the Chinese medicine composition of the application and each control group.

[0115] Figure 3A It is shown that the total sleep time of the Chinese medicine composition compared with the self-control is significantly different (p<0.01), and the Chinese medicine food homologous formula can increase the total sleep time of the rats.

[0116] Figure 3B It is shown that the Chinese medicine composition can significantly increase the non-rapid eye movement sleep period of the rats (p<0.01) and inhibit the active wakefulness time (p<0.01). The results show that the Chinese medicine food homologous formula can increase the sleep depth of the rats, and the effect is equivalent to that of diazepam.

[0117] Figure 3C It is shown that the Chinese medicine food homologous formula extract can significantly prolong the average duration of the non-rapid eye movement sleep period and shorten the average duration of the active wakefulness period. In Figure 3DIn the statistical results of the number of sleep-wake segments, the medicinal food formula reduced the number of non-rapid eye movement (NREM) sleep segments, showing a significant difference compared with the control group (p<0.05). The results indicate that the medicinal food formula increases the average duration of slow-wave sleep while reducing the number of slow-wave sleep segments, thus improving sleep continuity.

[0118] The results showed that the extract from the food-medicine homology formula could increase sleep time and sleep depth in rats at the electroencephalogram (EEG) level, increase the number of non-rapid eye movement (NREM) sleep segments, prolong the duration of NREM sleep segments, and reduce activity, thus promoting sleep.

[0119] Test Example 4: The effect of traditional Chinese medicine composition extract on insomnia in PCPA model.

[0120] 1.1 Experimental animals: ICR mice, male, SPF grade, 22-25g, purchased from Spaford (Beijing) Experimental Animal Co., Ltd.

[0121] 1.2 Test Samples: The prepared herbal extracts were weighed according to the extraction rate and the dosage of the medicinal materials, and a suspension was prepared by adding physiological saline for gavage. Diazepam was converted to the clinical dosage for mouse administration, and a corresponding mass of solid was weighed to prepare a physiological saline solution for gavage.

[0122] 1.3 Experimental Methods: Mice were acclimatized for one week after purchase and then randomly divided into 6 groups (n=10 per group) according to body weight: solvent control group (vehicle, physiological saline), positive control group (diazepam, 3 mg / kg), PCPA model group (400 mg / kg, ip), low-dose (based on crude drug weight, 5 g / kg) group of traditional Chinese medicine composition, medium-dose (based on crude drug weight, 10 g / kg) group of traditional Chinese medicine composition, and high-dose (based on crude drug weight, 20 g / kg) group of traditional Chinese medicine composition. The administration method is as follows:

[0123] (1) The positive control group and each dose group of the traditional Chinese medicine composition were administered the corresponding drug (20 ml / kg) by gavage for 5 consecutive days, once a day. The solvent control group was administered an equal volume of physiological saline by gavage. Starting from the third day of administration, except for the solvent control group, mice in each group were injected intraperitoneally with PCPA (400 mg / kg, 10 ml / kg) to establish the model for 3 consecutive days, once a day. The solvent control group was injected intraperitoneally with an equal volume of physiological saline.

[0124] (2) 40 minutes after the last gavage in each group, sodium pentobarbital (42 mg / kg, 5 ml / kg) was injected into the peritoneum. The mice were placed in an independent space at about 25°C and the administration time was recorded.

[0125] (3) Observe the sleep state of the mouse, and record the disappearance time of the righting reflex, that is, the mouse maintains the supine position for 60 seconds without recovery, and then it is considered to enter sleep; record the recovery time of the righting reflex, that is, the mouse can recover autonomously within 60 seconds, and then it is considered to end sleep. Calculate the sleep latency and sleep time, respectively, the sleep latency is the disappearance time of the righting reflex minus the administration time, and the sleep time is the recovery time of the righting reflex minus the disappearance time of the righting reflex.

[0126] 1.4 Experimental results: see Figure 4A and Figure 4B . Figure 4A is a comparison chart of the sleep latency of mice using the traditional Chinese medicine composition of the application and each control drug in the PCPA-induced insomnia experiment, Figure 4B is a comparison chart of the sleep duration of mice using the traditional Chinese medicine composition of the application and each control drug in the PCPA-induced insomnia experiment.

[0127] The PCPA-induced insomnia experiment results show that, compared with the solvent control group, the sleep latency (sleeping time) of the PCPA model group of mice has a tendency to be prolonged ( Figure 4A ), and the sleep duration is significantly shortened ( Figure 4B ). The positive drug diazepam and the medium and high dose traditional Chinese medicine composition can significantly shorten the sleep latency of the model mice, and the effects are comparable. The positive drug diazepam and the medium and high dose traditional Chinese medicine composition can significantly prolong the sleep duration of the model mice.

[0128] The results show that the traditional Chinese medicine composition extract can improve the insomnia performance of mice caused by PCPA.

[0129] Through the above description of the technical solutions of the application, the beneficial effects of the traditional Chinese medicine composition of the application on sedation, hypnotism, and the treatment of insomnia are further illustrated. The application combines the concept of treating disease before disease occurs, preventing disease from changing after disease occurs, and preventing recurrence after recovery with the treatment principle of early detection and early treatment, and is assisted by the characteristics of traditional Chinese medicine of multi-target and multi-system whole regulation, and is widely applied in the prevention and treatment of depression, anxiety, and various fatigue.

[0130] Medicinal food is a summary of the relationship between medicine and food and its application in traditional Chinese medicine. Since ancient times, traditional Chinese medicine has recognized that medicine comes from food, food has the function of medicine, and medicine has the nature of food, and has used the medicinal value of food for health preservation, health care, disease prevention and treatment, that is, "food nourishment" and "food therapy". The treatment of insomnia with medicinal food traditional Chinese medicine prescription has significant advantages in drug safety and compliance compared with chemical drugs while taking advantage of the multi-pathway synergistic regulation characteristics of traditional Chinese medicine compounds.

[0131] The homology of medicine and food is deeply implemented by the formula, the homology of medicine and food refers to being able to be used as medicine and food, the homology of medicine and food of traditional Chinese medicine in the application can further reduce the security risk of long-term medication, and improve the compliance of patients. The homology of medicine and food of traditional Chinese medicine is the "component" of healthy China construction and the development of the big health industry, is the material basis of the human health community facing chronic diseases, and has important potential value in the treatment of chronic diseases.

[0132] The preferred embodiments of the application are described in detail above. However, the application is not limited to the specific details in the above-described embodiments, and various simple modifications can be made to the technical solutions of the application within the technical concept of the application. These simple modifications all belong to the protection scope of the application.

[0133] In addition, it should be noted that various specific technical features described in the above specific embodiments can be combined in any manner without contradiction. In order to avoid unnecessary repetition, various possible combinations are not described again in the application. In addition, various different embodiments of the application can also be combined in any manner, as long as it does not deviate from the idea of the application, it should also be considered as disclosed in the application.

Claims

1. A traditional Chinese medicine composition, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 10-30 parts roasted jujube seeds, 10-25 parts jujubes, 5-15 parts licorice root, 5-15 parts Ganoderma lucidum, 5-15 parts longan pulp, 10-20 parts lily bulbs, 10-20 parts Buddha's hand, 10-30 parts wheat, 10-20 parts daylily, and 5-15 parts Gastrodia elata.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, It is made from the following Chinese medicinal materials in parts by weight: 15-25 parts roasted jujube seeds, 12-20 parts jujubes, 7-12 parts licorice root, 7-12 parts Ganoderma lucidum, 7-12 parts longan pulp, 12-20 parts lily bulbs, 12-20 parts Buddha's hand, 15-25 parts wheat, 12-20 parts daylily, and 7-12 parts Gastrodia elata.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The mass ratio of the raw materials in the traditional Chinese medicine composition, namely, stir-fried jujube seed, jujube, licorice, Ganoderma lucidum, longan pulp, lily bulb, Buddha's hand, wheat, daylily, and gastrodia elata, is 20:15:9:9:9:15:15:20:15:

9.

4. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, Includes the following steps: Step S1: Weigh out the Chinese medicinal materials according to the mass proportions. The Chinese medicinal materials include stir-fried jujube seeds, jujubes, licorice, Ganoderma lucidum, longan pulp, lily bulbs, Buddha's hand, wheat, daylily, and gastrodia elata. Step S2: Using 5-30 times the amount of water obtained in step S1, heat the raw Chinese medicine obtained in step S1, then reflux and filter to obtain the first extract and residue. Step S3: Evaporate the first extract obtained in step S2 under reduced pressure to obtain a solid product of the first extract for later use.

5. The method for preparing the traditional Chinese medicine composition according to claim 4, characterized in that, In step S2, the amount of water is 10 times the amount of the Chinese herbal medicine raw materials obtained in step S1.

6. The method for preparing the traditional Chinese medicine composition according to claim 4, characterized in that, In step S2, the amount of water is 5-15 times that of the Chinese herbal medicine raw materials obtained in step S1. The Chinese herbal medicine raw materials soaked in water are heated until the water boils, and then refluxed for 2 hours for extraction.

7. A pharmaceutical preparation, characterized in that, It is made from the traditional Chinese medicine composition according to any one of claims 1-3 and a pharmaceutically acceptable carrier, and the dosage form is any pharmaceutically acceptable dosage form.

8. The pharmaceutical preparation according to claim 7, characterized in that, The dosage form is an oral preparation, an injectable preparation, or a transdermal absorption preparation.

9. The pharmaceutical preparation according to claim 7, characterized in that, The pharmaceutical preparation dosage form is an oral preparation, selected from tablets, capsules, granules, pills, powders, elixirs, oral solutions, or oral suspensions.

10. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of sedative-hypnotic and insomnia-treating drugs.

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