Pharmaceutical composition, preparation method and application

Abstract

The invention provides a pharmaceutical composition as well as a preparation method and application thereof. The composition comprises 50-70% of a traditional Chinese medicine extract composition, 4-15% of a bioactive component and 25-45% of an auxiliary material, the traditional Chinese medicine extract is prepared from multiple raw materials including rhizoma coptidis, agilawood, cortex cinnamomi and the like; the bioactive components comprise melatonin, 5-hydroxytryptophan and rosmarinic acid; the preparation method relates to a plurality of steps, and comprises the steps of composite extraction, mixing and concentration, microencapsulation treatment, layered mixing, gradient heating for continuous mixing and preparation forming. Wherein the microencapsulation treatment is used for wrapping bioactive components and improving the stability; the pharmaceutical composition can be used for improving the sleep quality, shortening the sleep time and prolonging the deep sleep stage. Through a specific preparation process, the effectiveness and stability of the pharmaceutical composition are ensured, and a new solution is provided for improving sleep.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a pharmaceutical composition, a preparation method and an application thereof. Background Art

[0002] With the accelerated pace of life and the increasing pressure of life in modern society, sleep problems have become an important factor that troubles people's physical and mental health. More and more people are suffering from sleep disorders such as difficulty falling asleep, poor sleep quality, and short deep sleep time. In order to improve sleep conditions, a variety of solutions have emerged in the market and the medical field.

[0003] At present, drugs used to improve sleep are mainly divided into two types: Western medicine and traditional Chinese medicine. In terms of Western medicine, common drugs such as benzodiazepines and non-benzodiazepines can quickly shorten the time to fall asleep to a certain extent, but they are often accompanied by some adverse reactions. For example, some patients may experience dizziness, fatigue, memory loss, etc. after using them. Long-term use is also prone to dependence, and even withdrawal reactions will occur after stopping the drug, affecting the normal order of life, limiting its long-term and safe use in clinical practice.

[0004] Traditional Chinese medicine is mostly formulated based on TCM theory to improve sleep. It works by regulating the body's overall qi and blood, and organ functions. It is relatively safe, but has the problem of relatively slow onset of effect. In addition, Chinese herbal compound preparations also face challenges in terms of ingredient complexity and quality control stability, making it difficult to meet the needs of different individuals for fast and effective sleep improvement.

[0005] In addition, there are some pharmaceutical products that simply combine Western medicine and Chinese medicine, but most of them lack scientific and reasonable compatibility and sophisticated preparation technology, and fail to give full play to the advantages of each ingredient and enhance synergy. The comprehensive effect of improving sleep is unsatisfactory. For example, it is impossible to effectively improve sleep quality, shorten the time to fall asleep, and prolong the deep sleep stage at the same time, and it is difficult to comprehensively deal with complex and diverse sleep disorders.

[0006] In view of the above-mentioned deficiencies of the existing technology in improving sleep, there is an urgent need to develop a new pharmaceutical composition that can not only integrate the advantages of Chinese and Western medicines, but also has a scientific and reasonable preparation method, so as to better meet people's needs for improving sleep quality, shortening the time to fall asleep and prolonging the deep sleep stage, and provide a more ideal solution to solve the problem of sleep disorders. Summary of the invention

[0007] In view of this, the present invention proposes a pharmaceutical composition, a preparation method and an application to solve the above problems.

[0008] The technical solution of the present invention is achieved as follows: a raw material comprising the following weight percentages: 50-70% of a Chinese medicine extract composition, 4-15% of a biologically active ingredient, and 25-45% of an auxiliary material; the Chinese medicine extract comprises the following raw materials in weight: 45-65 parts of coptis chinensis, 12-20 parts of agarwood, 15-30 parts of cinnamon, 1-3 parts of saffron, 15-30 parts of spiny jujube seeds, 15-25 parts of polygala tenuifolia extract, 20-30 parts of smilax china extract, and 18-30 parts of valerian extract.

[0009] Furthermore, the bioactive ingredients include melatonin, 5-hydroxytryptophan and rosmarinic acid in a mass ratio of (32-55):(10-30):(8-12).

[0010] Furthermore, the auxiliary materials include, by weight: 20-30 parts of microcrystalline cellulose, 5-10 parts of cross-linked polyvinylpyrrolidone, 3-6 parts of magnesium stearate, and 5-10 parts of sodium carboxymethyl cellulose.

[0011] Furthermore, the Chinese medicine extract includes the following raw materials in parts by weight: 55 parts of coptis root, 16 parts of agarwood, 25 parts of cinnamon, 2 parts of saffron, 22 parts of spiny jujube seeds, 20 parts of polygala root extract, 25 parts of tuberose extract, and 26 parts of valerian extract.

[0012] Furthermore, the polygala extract is prepared by taking polygala medicinal material, removing impurities and cutting into sections, adding water 8-12 times its weight, soaking for 1-2 hours, heating to boiling, maintaining a slightly boiling state for extraction for 2-3 hours, filtering, concentrating the filtrate and then performing adsorption separation on a macroporous resin column, eluting with an ethanol solution with a volume fraction of 40-60%, collecting the eluate, and concentrating and drying to obtain the polygala extract.

[0013] Furthermore, the preparation method of the tuberculosis extract is: take the tuberculosis, wash and dry it, and then crush it into 60-80 mesh, extract it with supercritical carbon dioxide, the extraction pressure is 20-30MPa, the extraction temperature is 40℃-50℃, the extraction time is 2-3 hours, and the extract is collected to obtain the tuberculosis extract.

[0014] Furthermore, the valerian extract is prepared by taking fresh or dried valerian, crushing it to 80-100 meshes, adding 70%-80% ethanol solution in an amount 10-15 times its weight, immersing and extracting it at a temperature of 55°C-65°C for 12-24 hours, filtering, collecting the filtrate and concentrating it under reduced pressure to a relative density of 1.2-1.4, thereby obtaining the valerian extract.

[0015] Furthermore, a method for preparing a pharmaceutical composition comprises the following steps: S1. Composite extraction of coptis root and cinnamon bark: mix coptis root and cinnamon bark and crush them into 60-80 mesh, put them in an ultrasonic extraction tank, add 70%-80% ethanol solution with a volume fraction of 10-12 times the total weight of the medicinal materials, first ultrasonically treat for 30-40 minutes at room temperature, with an ultrasonic power of 400-600W to initially break the cell wall, then heat to 50℃-60℃, continue ultrasonic extraction for 1-2 hours, maintain the temperature after the end of ultrasonication, immerse and extract for 1-2 hours, filter, collect the filtrate, and keep the residue for later use; this composite extraction utilizes the synergistic effect of coptis root and cinnamon bark in a specific solvent and temperature to better dissolve alkaloids, volatile oils and other effective ingredients, and is more efficient than traditional single extraction; S2, agarwood, saffron composite extraction: agarwood, saffron are crushed to 80-100 mesh, put into a percolation cylinder, and 12-15 times the total weight of the volume fraction of 85%-95% ethanol solution is used for percolation extraction at a flow rate of 2-3ml / min, the percolation liquid is collected, and the ethanol is recovered under low temperature and reduced pressure until there is no alcohol taste, to obtain an extract concentrate; this composite percolation extraction fully takes into account that the fat-soluble, volatile and other active ingredients in agarwood and saffron can be better extracted under high concentration ethanol, and the percolation process avoids the damage of high temperature to heat-sensitive components; S3, mixing and concentrating: mixing the Polygala root extract, the Polygonum multiflorum extract, the Valerian root extract, the drug residue of S1, and the extract concentrate of S2, and concentrating under reduced pressure to a relative density of 1.2-1.4 under a vacuum degree of -0.08 MPa to -0.1 MPa and a temperature of 50° C.-60° C. to obtain a Chinese medicine extract composition; S4, microencapsulation treatment: accurately weigh melatonin, 5-hydroxytryptophan and rosmarinic acid, add them to the wall material solution heated to 50°C-60°C, emulsify for 10-15 minutes under high-speed stirring at 1000-1500rpm to form a uniform emulsion, adjust the pH value to 4-5, and reduce the temperature to 10°C-15°C, stir for 30-45 minutes, so that the active ingredients condense to form microcapsules, and then dry them at 40°C-50°C and vacuum degree 0.08MPa-0.1MPa for 6-8 hours to obtain microencapsulated biologically active ingredients; S5, layered mixing: put the Chinese herbal extract composition prepared in S3 into a mixing container, add microcrystalline cellulose, mix for 15-20 minutes at a speed of 10-15rpm and a temperature of 30°C-35°C to form a first layer of material, then add the microencapsulated bioactive ingredients to the first layer of material, increase the temperature to 40°C-45°C, adjust the speed to 15-20rpm, mix for 10-15 minutes, and form a second layer of material; this layered mixing method helps to evenly disperse the ingredients of different properties first, and then gradually merge them, avoiding the uneven problem that may occur when directly mixing; S6, gradient temperature increase and continue mixing: add cross-linked polyvinylpyrrolidone to the second layer of materials, gradually increase the temperature to 50°C-55°C at a rate of 2°C-3°C / min, maintain the rotation speed at 15-20rpm, mix for 10-15min, then add sodium carboxymethyl cellulose, continue mixing at the temperature and speed for 5-10min, make the materials fully mixed, finally add magnesium stearate, reduce the temperature to 35°C-40°C, adjust the rotation speed to 10-15rpm, mix for 5-10min, and obtain the final pharmaceutical composition mixture; the gradient temperature increase process can utilize temperature changes to promote better interaction between components, such as making some components better adsorbed and fused at different temperature stages, thereby improving the overall efficacy; S7. Formulation: Granulate the above-mentioned mixed material to obtain granules, or compress the granules into tablets and fill the granules into capsule shells to obtain a pharmaceutical composition in the form of granules, tablets or capsules.

[0016] Furthermore, the wall material solution of S4 is prepared by adding gum arabic and gelatin in a mass ratio of 1-2:1 into deionized water to a total concentration of 10%-15% (w / v), heating to 50°C-60°C, and stirring until completely dissolved to prepare a wall material solution.

[0017] Furthermore, the pharmaceutical composition is used to improve sleep quality, shorten the time to fall asleep and prolong the deep sleep stage.

[0018] Compared with the prior art, the present invention has the following beneficial effects: 1. The pharmaceutical composition of the present invention organically combines a Chinese medicine extract composition with specific bioactive ingredients, wherein the Chinese medicine extracts include coptis root, agarwood, cinnamon, saffron, spiny jujube seeds, polygala extract, smilax china extract and valerian extract and other multi-flavor medicinal ingredients. These Chinese medicine ingredients are compatible with each other according to traditional Chinese medicine theory, and jointly play a sedative and tranquilizing effect from multiple angles such as regulating human qi and blood, viscera functions, etc., which helps to improve sleep conditions. At the same time, with bioactive ingredients such as melatonin, 5-hydroxytryptophan and rosmarinic acid in a specific mass ratio, they work together to help regulate human neurotransmitters, biological rhythms, etc., and can more comprehensively and effectively improve sleep quality, shorten the time to fall asleep, and prolong the deep sleep stage.

[0019] 2. Efficient extraction process: In the preparation process of Chinese medicine extracts, a variety of targeted extraction methods are used for a variety of medicinal materials. When extracting coptis root and cinnamon bark, ultrasound is first used to initially break the wall at room temperature, and then the temperature is raised for ultrasound and immersion extraction to fully dissolve the alkaloids, volatile oils and other effective ingredients; the extract of Polygala tenuifolia uses supercritical carbon dioxide extraction technology to accurately obtain its active ingredients under specific temperature, pressure and time conditions; and the extract of Polygala tenuifolia can effectively enrich the target ingredients through water extraction combined with macroporous resin column adsorption separation and elution. These advanced and suitable extraction methods ensure the high extraction rate and activity retention of the effective ingredients in each medicinal material, laying the foundation for the excellent efficacy of the pharmaceutical composition.

[0020] 3. Microencapsulation pretreatment of active ingredients: Microencapsulation of biologically active ingredients can improve their stability in the pharmaceutical composition, enable more accurate and slow release in the body, prolong the duration of action, improve bioavailability, and enhance the effect of improving sleep.

[0021] 4. Layered mixing and gradient temperature rise process: When mixing the raw materials to form a pharmaceutical composition, layered mixing combined with gradient temperature rise is used to make the components more evenly dispersed, reduce agglomeration, and further promote the physical and chemical interactions between the components through temperature changes, thereby improving the overall efficacy. DETAILED DESCRIPTION

[0022] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0023] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0024] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources. Example 1

[0025] A pharmaceutical composition comprises the following raw materials in weight percentage: 50% of a Chinese herbal medicine extract composition, 15% of a biologically active ingredient, and 35% of an auxiliary material; the Chinese herbal medicine extract comprises the following raw materials in weight percentage: 45 parts of coptis root, 12 parts of agarwood, 15 parts of cinnamon bark, 1 part of saffron, 15 parts of spiny jujube seeds, 15 parts of polygala root extract, 20 parts of smilax china extract, and 18 parts of valerian extract; the biologically active ingredient comprises melatonin, 5-hydroxytryptophan, and rosmarinic acid in a mass ratio of 32:10:8; the auxiliary materials comprise, by weight percentage, 20 parts of microcrystalline cellulose, 5 parts of cross-linked polyvidone, 3 parts of magnesium stearate, and 5 parts of sodium carboxymethyl cellulose. Example 2

[0026] A pharmaceutical composition comprises the following raw materials in weight percentage: 70% of a Chinese herbal medicine extract composition, 5% of a biologically active ingredient, and 25% of an auxiliary material; the Chinese herbal medicine extract comprises the following raw materials in weight percentage: 65 parts of coptis root, 20 parts of agarwood, 30 parts of cinnamon bark, 3 parts of saffron, 30 parts of spiny jujube seeds, 25 parts of polygala root extract, 30 parts of smilax china extract, and 30 parts of valerian extract; the biologically active ingredient comprises melatonin, 5-hydroxytryptophan, and rosmarinic acid in a mass ratio of 55:30:12; the auxiliary materials comprise, by weight percentage, 30 parts of microcrystalline cellulose, 10 parts of cross-linked polyvinylpyrrolidone, 6 parts of magnesium stearate, and 10 parts of sodium carboxymethyl cellulose. Example 3

[0027] A pharmaceutical composition comprises the following raw materials in weight percentage: 60% of a Chinese herbal medicine extract composition, 15% of a biologically active ingredient, and 25% of an auxiliary material; the Chinese herbal medicine extract comprises the following raw materials in weight percentage: 55 parts of coptis root, 16 parts of agarwood, 25 parts of cinnamon bark, 2 parts of saffron, 22 parts of spiny jujube seeds, 20 parts of polygala root extract, 25 parts of smilax china extract, and 26 parts of valerian extract; the biologically active ingredient comprises melatonin, 5-hydroxytryptophan, and rosmarinic acid in a mass ratio of 45:20:10; the auxiliary materials comprise, by weight percentage, 25 parts of microcrystalline cellulose, 8 parts of cross-linked polyvinylpyrrolidone, 5 parts of magnesium stearate, and 8 parts of sodium carboxymethyl cellulose.

[0028] The polygala root extract, smilax china extract, and valerian root extract of Examples 1-3 were extracted according to the following method: The polygala extract is prepared by taking polygala medicinal material, removing impurities and cutting into sections, adding water 10 times its weight, soaking for 2 hours, heating to boiling, maintaining a slightly boiling state for extraction for 3 hours, filtering, concentrating the filtrate and performing adsorption separation using a macroporous resin column, eluting with an ethanol solution with a volume fraction of 50%, collecting the eluate, and concentrating and drying to obtain the polygala extract.

[0029] The preparation method of the tuberculosis extract is as follows: take the tuberculosis, wash and dry it, then crush it into 70 meshes, extract it with supercritical carbon dioxide, the extraction pressure is 25MPa, the extraction temperature is 45°C, the extraction time is 2 hours, and the extract is collected to obtain the tuberculosis extract.

[0030] The valerian extract is prepared by taking fresh or dried valerian, crushing it into 100 meshes, adding 75% ethanol solution with a volume fraction of 13 times its weight, immersing and extracting it at a temperature of 60° C. for 20 hours, filtering, collecting the filtrate and concentrating it under reduced pressure to a relative density of 1.3 to obtain the valerian extract.

[0031] The preparation method comprises the following steps: S1. Composite extraction of coptis root and cinnamon bark: mix coptis root and cinnamon bark and grind them into 70 mesh, put them in an ultrasonic extraction tank, add 75% ethanol solution with a volume fraction of 10 times the total weight of the medicinal materials, first ultrasonically treat for 35 minutes at room temperature with an ultrasonic power of 500W to initially break the cell wall, then heat to 55℃ and continue ultrasonic extraction for 2 hours. After the ultrasonic treatment, maintain the temperature and immerse and extract for 2 hours. Filter, collect the filtrate, and keep the residue for later use.

[0032] S2. Composite extraction of agarwood and saffron: Grind agarwood and saffron into 90 mesh, put into a percolation cylinder, use a 90% ethanol solution with a volume fraction of 14 times the total weight, and perform percolation extraction at a flow rate of 3 ml / min. Collect the percolation liquid, and recover the ethanol under low temperature and reduced pressure until there is no alcohol taste, to obtain an extract concentrate.

[0033] S3, mixing and concentrating: Mix the Polygala tenuifolia extract, the Polygonum multiflorum extract, the Valerian extract, the medicinal residues of S1, and the extract concentrate of S2, and concentrate under reduced pressure at a vacuum degree of -0.1 MPa and a temperature of 55°C to a relative density of 1.3 to obtain a Chinese medicine extract composition.

[0034] S4. Microencapsulation treatment: accurately weigh melatonin, 5-hydroxytryptophan and rosmarinic acid, and add them to a wall material solution heated to 55°C. The wall material solution is a 2:1 mass ratio of gum arabic and gelatin added to deionized water to a total concentration of 10% (w / v). Heat to 55°C, stir until completely dissolved, emulsify at 1300 rpm high-speed stirring for 13 minutes to form a uniform emulsion, adjust the pH value to 4, and reduce the temperature to 13°C. Stir for 40 minutes to allow the active ingredients to condense into microcapsules, and then dry at 45°C and vacuum degree -0.1 MPa for 7 hours to obtain microencapsulated bioactive ingredients.

[0035] S5. Layered mixing: put the Chinese herbal extract composition prepared in S3 into a mixing container, add microcrystalline cellulose, mix for 20 minutes at a rotation speed of 13 rpm and a temperature of 33°C to form a first layer of material, then add the microencapsulated bioactive ingredients to the first layer of material, increase the temperature to 40°C, adjust the rotation speed to 20 rpm, and mix for 15 minutes to form a second layer of material.

[0036] S6. Continue mixing by increasing the temperature in a gradient: add cross-linked polyvinylpyrrolidone to the second layer of material, gradually increase the temperature to 55°C at a rate of 2°C / min, maintain the rotation speed at 20 rpm, and mix for 15 minutes. Then add sodium carboxymethyl cellulose, and continue mixing at the temperature and rotation speed for 10 minutes to fully mix the materials. Finally, add magnesium stearate, lower the temperature to 35°C, adjust the rotation speed to 10, and mix for 5 minutes to obtain the final pharmaceutical composition mixture. Comparative Example 1

[0037] The difference between this comparative example and Example 3 is that the raw materials in the pharmaceutical composition do not contain biologically active ingredients, and the ratio is 65% of the Chinese herbal extract composition and 35% of the auxiliary materials. Comparative Example 2

[0038] The difference between this comparative example and Example 3 is that the Chinese herbal extract in the pharmaceutical composition includes the following raw materials in parts by weight: 30 parts of Coptis chinensis, 10 parts of Aquilaria sinensis, 11 parts of Cinnamon bark, 6 parts of Saffron, 10 parts of Ziziphus jujuba seeds, 12 parts of Polygala tenuifolia extract, 33 parts of Polygonum multiflorum extract, and 15 parts of Valerian extract. Comparative Example 3

[0039] The difference between this comparative example and Example 3 is that the bioactive ingredients in the preparation method of the pharmaceutical composition are not microencapsulated. Specifically, melatonin, 5-hydroxytryptophan and rosmarinic acid are accurately weighed and added to the first layer of materials during the layering and mixing process. Comparative Example 4

[0040] The difference between this comparative example and Example 3 is that the preparation method of the pharmaceutical composition does not perform gradient temperature increase and continuous mixing, and specifically, cross-linked polyvinylpyrrolidone, sodium carboxymethyl cellulose and magnesium stearate are added to the second layer material.

[0041] Test Example 1-Pharmacodynamic Test

[0042] 1. Experimental Materials Experimental animals: 90 SD rats, weighing 250-320 g, with random gender.

[0043] Experimental groups: Blank control group: an equal volume of normal saline was administered to simulate the normal physiological state, for comparative observation of the effect of the pharmaceutical composition.

[0044] Positive control group: administered with an equal volume of estazolam.

[0045] Drug Group 1-7: the drug compositions of Examples 1-3 and Comparative Examples 1-4 in the present application.

[0046] 2. Experimental Methods Intragastric administration: The drug composition is prepared into a suspension with a concentration of 5% (w / v). The drug is administered by intragastric administration using a gavage needle inserted through the mouth into the esophagus. The drug is administered accurately according to the set dose. The administration volume is controlled at 1 ml / 100 g body weight (rat) to ensure that the administration process is accurate and to avoid damage to the animal's esophagus and other parts.

[0047] 3. Sleep latency test method 1. Experimental preparation: Before drug administration, place the animals individually in a special sleep monitoring box to adapt to the environment for 30-60 minutes. The sleep monitoring box must be soundproof and lightproof, and equipped with electroencephalogram (EEG) and electromyogram (EMG) electrodes to accurately record the animal's EEG and EMG activities. At the same time, a camera is installed in the box to facilitate the observation of animal behavioral changes.

[0048] 2. Drug administration and monitoring: After administering the corresponding drugs or saline according to the grouping and administration method, immediately start the EEG and EMG monitoring equipment and camera recording system, and continuously observe and record the time from the start of drug administration to the appearance of characteristic EEG and EMG changes in sleep (EEG shows high-amplitude slow waves, EMG activity weakens, and the animal's righting reflex disappears). This time is the sleep latency. The disappearance of the righting reflex can be judged by placing the animal in a supine position and observing whether it can restore its normal position within 30 seconds. If it cannot recover, it is judged to have entered a sleep state.

[0049] 3. Recording and data analysis: The sleep latency data of each group of animals were recorded separately, and the mean ± standard deviation of each group was calculated. Statistical software (SPSS) was used for data analysis. The differences in sleep latency between each drug group and the blank control group and the positive control group were compared by one-way ANOVA combined with LSD post hoc test method. If the sleep latency of the drug combination group was significantly shorter than that of the blank control group (P<0.05 or P<0.01), and the difference was not statistically significant or close to that of the positive control group, it indicates that the drug combination can effectively shorten the sleep latency and has a rapid effect in improving sleep.

[0050] 4. Methods for measuring prolonged sleep time 1. Continuous monitoring: After completing the sleep latency monitoring, continue to use EEG, EMG monitoring equipment and cameras to record the animal's sleep state throughout the process, and observe the total sleep time experienced by the animal from entering the sleep state to natural awakening, including the time of different sleep stages such as slow-wave sleep (SWS) and rapid eye movement sleep (REMS) (the EEG waveform characteristics can be used to distinguish and count the duration of different stages).

[0051] 2. Recording and analysis: Record the total sleep time and the time data of each sleep stage of each group of animals, calculate the mean ± standard deviation, and use statistical methods to compare and analyze between groups. If the total sleep time of the drug combination group is significantly longer than that of the blank control group (P<0.05 or P<0.01), it means that the drug combination has a positive effect on prolonging sleep time. At the same time, analyze the changes in the proportion of time in each sleep stage, further understand the effect of the drug on sleep structure, and comprehensively evaluate its characteristics of improving sleep.

[0052] 5. Sleep quality assessment method 1. Awakening times statistics: By analyzing EEG, EMG records and behavioral performance of animals during sleep observed by cameras, the number of awakenings of animals during the entire sleep process is counted, that is, the number of times the animal recovers from the sleeping state to the awake state (EEG, EMG show characteristic changes of wakefulness and active behavior).

[0053] 2. Sleep depth assessment: The depth of sleep is comprehensively judged based on parameters such as the frequency, amplitude and duration of different brain waves (δ waves, θ waves, α waves, β waves, etc.) in the EEG. Generally, when δ waves are dominant, it represents the deep sleep stage. The proportion of deep sleep time to total sleep time and other indicators are statistically analyzed to reflect the sleep quality.

[0054] 3. Data analysis and evaluation: Perform data statistics and analysis on sleep quality-related indicators such as the number of awakenings and the proportion of deep sleep time of each group of animals, and compare the differences between each drug group and the control group. If the drug combination group can significantly reduce the number of awakenings and increase the proportion of deep sleep time (P<0.05 or P<0.01), it means that the drug combination helps to improve sleep quality and has a positive significance for improving sleep disorders.

[0055] 6. Experimental Results Table 1: Sleep latency measurement results (unit: minutes) Grouping Mean ± SD Blank control group 25.3±3.2 Positive control group (Estazolam) 12.5±2.1 Example 1 13.2±2.1 Example 2 12.8±2.3 Example 3 11.6±2.0 Comparative Example 1 19.1±2.8 Comparative Example 2 16.2±1.3 Comparative Example 3 17.5±1.5 Comparative Example 4 15.8±2.1 Judging from the results of sleep latency measurements, the sleep latency of the positive control group and each dose of the drug composition group was significantly shortened compared with the blank control group, among which the shortening effect of the drug composition group in the embodiment group was closer to that of the positive control group, indicating that the drug composition effectively accelerates the speed of animals falling asleep and plays a role in improving sleep.

[0056] Table 2: Results of sleep time extension measurement (unit: hours) Grouping Mean ± SD Blank control group 6.2±0.8 Positive control group (Estazolam) 8.5±1.0 Example 1 8.3±2.0 Example 2 8.5±1.5 Example 3 8.8±1.2 Comparative Example 1 7.1±1.8 Comparative Example 2 8.0±1.1 Comparative Example 3 7.5±1.2 Comparative Example 4 7.3±2.0 In terms of prolonging sleep time, each drug group can significantly prolong the total sleep time of animals compared with the blank control group. The prolongation effect of the drug composition group in the embodiment group is the most obvious, and is even slightly better than the positive control group, indicating that the drug composition of the present invention has a positive effect on increasing the sleep time of animals, and with the increase of dosage, the effect tends to increase.

[0057] Table 3: Sleep quality assessment results Grouping Number of awakenings (mean ± SD) Deep sleep time percentage (mean ± standard deviation, %) Blank control group 5.8±1.2 28.3±3.5 Positive control group 2.5±0.8 42.5±4.0 Example 1 2.6±0.6 44.0±4.8 Example 2 2.3±0.5 45.0±4.5 Example 3 2.2±0.7 46.0±4.0 Comparative Example 1 4.2±1.0 32.5±3.8 Comparative Example 2 3.1±0.7 35.2±4.2 Comparative Example 3 3.0±0.8 36.5±4.5 Comparative Example 4 2.8±0.9 38.1±4.4 The results of sleep quality assessment showed that each dosage group of the drug composition could reduce the number of awakenings during the sleep of animals and increase the proportion of deep sleep time compared with the blank control group. The performance of the embodiment group in improving sleep quality was similar to that of the positive control group, which means that the drug composition helps to improve the stability and depth of sleep of animals and has a good improvement effect on the overall sleep quality.

[0058] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A pharmaceutical composition, characterized in that: The invention comprises the following raw materials in weight percentage: 50-70% of a Chinese medicine extract composition, 4-15% of a biologically active ingredient, and 25-45% of an auxiliary material; the Chinese medicine extract comprises the following raw materials in weight percentage: 45-65 parts of coptis root, 12-20 parts of agarwood, 15-30 parts of cinnamon bark, 1-3 parts of saffron, 15-30 parts of spiny jujube seeds, 15-25 parts of polygala root extract, 20-30 parts of smilax china extract, and 18-30 parts of valerian extract.

2. A pharmaceutical composition according to claim 1, characterized in that: The bioactive ingredients include melatonin, 5-hydroxytryptophan and rosmarinic acid in a mass ratio of (32-55):(10-30):(8-12).

3. A pharmaceutical composition according to claim 1, characterized in that: The auxiliary materials include, by weight: 20-30 parts of microcrystalline cellulose, 5-10 parts of cross-linked polyvinylpyrrolidone, 3-6 parts of magnesium stearate, and 5-10 parts of sodium carboxymethyl cellulose.

4. A pharmaceutical composition according to claim 1, characterized in that: The Chinese medicine extract comprises the following raw materials in parts by weight: 55 parts of coptis root, 16 parts of agarwood, 25 parts of cinnamon bark, 2 parts of saffron, 22 parts of spiny jujube seeds, 20 parts of polygala root extract, 25 parts of polyphylla extract, and 26 parts of valerian extract.

5. A pharmaceutical composition according to claim 4, characterized in that: The polygala extract is prepared by taking polygala medicinal material, removing impurities and cutting into sections, adding water 8-12 times of its weight, soaking for 1-2 hours, heating to boiling, maintaining a slightly boiling state for extraction for 2-3 hours, filtering, concentrating the filtrate and performing adsorption separation using a macroporous resin column, eluting with an ethanol solution with a volume fraction of 40-60%, collecting the eluate, and concentrating and drying to obtain the polygala extract.

6. A pharmaceutical composition according to claim 4, characterized in that: The preparation method of the tuberculosis extract is as follows: taking the tuberculosis, washing, drying and then crushing to 60-80 mesh, extracting with supercritical carbon dioxide, the extraction pressure is 20-30MPa, the extraction temperature is 40℃-50℃, the extraction time is 2-3 hours, and the extract is collected to obtain the tuberculosis extract.

7. A pharmaceutical composition according to claim 4, characterized in that: The valerian extract is prepared by taking fresh or dried valerian, crushing it into 80-100 meshes, adding 70%-80% ethanol solution in a volume fraction of 10-15 times of the weight of the valerian, immersing and extracting it at a temperature of 55° C.-65° C. for 12-24 hours, filtering, collecting the filtrate and concentrating it under reduced pressure to a relative density of 1.2-1.4, so as to obtain the valerian extract.

8. The method for preparing a pharmaceutical composition according to claim 1, characterized in that: The following steps are involved: S1. Coptis chinensis and cinnamon bark composite extraction: mix coptis chinensis and cinnamon bark and crush them into 60-80 mesh, put them in an ultrasonic extraction tank, add 70%-80% ethanol solution with a volume fraction of 10-12 times the total weight of the medicinal materials, first ultrasonically treat for 30-40 minutes at room temperature, with an ultrasonic power of 400-600W to initially break the cell wall, then heat to 50℃-60℃, continue ultrasonic extraction for 1-2 hours, maintain the temperature after the end of ultrasonication, immerse and extract for 1-2 hours, filter, collect the filtrate, and keep the residue for later use; S2, agarwood, saffron composite extraction: take agarwood, saffron crushed to 80-100 mesh, put into the percolation cylinder, with the total weight of 12-15 times the volume fraction of 85%-95% ethanol solution, percolation extraction at a flow rate of 2-3ml / min, collect the percolation liquid, low temperature and reduced pressure to recover ethanol until there is no alcohol taste, to obtain the extract concentrate; S3, mixing and concentrating: mixing the Polygala root extract, the Polygonum multiflorum extract, the Valerian root extract, the drug residue of S1, and the extract concentrate of S2, and concentrating under reduced pressure to a relative density of 1.2-1.4 under a vacuum degree of -0.08 MPa to -0.1 MPa and a temperature of 50° C.-60° C. to obtain a Chinese medicine extract composition; S4, microencapsulation treatment: accurately weigh melatonin, 5-hydroxytryptophan and rosmarinic acid, add them to the wall material solution heated to 50°C-60°C, emulsify for 10-15 minutes under high-speed stirring at 1000-1500rpm to form a uniform emulsion, adjust the pH value to 4-5, and reduce the temperature to 10°C-15°C, stir for 30-45 minutes, so that the active ingredients condense to form microcapsules, and then dry them at 40°C-50°C and vacuum degree 0.08MPa-0.1MPa for 6-8 hours to obtain microencapsulated biologically active ingredients; S5, layered mixing: put the Chinese herbal extract composition prepared in S3 into a mixing container, add microcrystalline cellulose, mix for 15-20 minutes at a speed of 10-15 rpm and a temperature of 30°C-35°C to form a first layer of material, then add the microencapsulated bioactive ingredients to the first layer of material, increase the temperature to 40°C-45°C, adjust the speed to 15-20 rpm, mix for 10-15 minutes, and form a second layer of material; S6, continue mixing by gradient heating: add cross-linked polyvinylpyrrolidone to the second layer material, gradually increase the temperature to 50°C-55°C at a rate of 2°C-3°C / min, maintain the rotation speed at 15-20rpm, mix for 10-15min, then add sodium carboxymethyl cellulose, continue mixing at the temperature and rotation speed for 5-10min to fully mix the materials, finally add magnesium stearate, reduce the temperature to 35°C-40°C, adjust the rotation speed to 10-15rpm, mix for 5-10min, and obtain the final pharmaceutical composition mixture; S7. Formulation: Granulate the above-mentioned mixed material to obtain granules, or compress the granules into tablets and fill the granules into capsule shells to obtain a pharmaceutical composition in the form of granules, tablets or capsules.

9. The method for preparing a pharmaceutical composition according to claim 8, characterized in that: The wall material solution of S4 is prepared by adding gum arabic and gelatin in a mass ratio of 1-2:1 into deionized water to a total concentration of 10%-15% (w / v), heating to 50°C-60°C, and stirring until completely dissolved to prepare a wall material solution.

10. Use of the pharmaceutical composition according to any one of claims 1 to 7 for improving sleep quality, shortening sleep onset time and prolonging deep sleep stage.