A kidney-tonifying and sleep-aiding medicinal composition, its preparation method and application

Abstract

This invention provides a kidney-tonifying and sleep-aiding medicinal composition, its preparation method, and its application. It is made from specific weight parts of the following ingredients: 10-20 parts of jujube seed, 5-15 parts of cornus officinalis, 2-4 parts of white hyacinth bean, 2-4 parts of dried tangerine peel, 2-4 parts of hawthorn, 4-6 parts of bitter melon, 2-4 parts of licorice root, 2-4 parts of cistanche deserticola, 2-4 parts of monk fruit, 1-3 parts of tangerine peel, 2-4 parts of raw astragalus, 2-4 parts of yam, and 2-4 parts of milk powder. With jujube seed and cornus officinalis as the principal ingredients, it achieves simultaneous regulation of the heart and kidneys, treating both the symptoms and the root cause. This composition can be prepared into various oral formulations. The preparation process is simple and the quality is controllable. It exerts its sleep-aiding effect by stimulating tryptophan hydroxylase, upregulating serotonin levels, and downregulating inflammatory factors. It is used to treat insomnia caused by heart-kidney disharmony, with definite efficacy, mild medicinal properties, high safety, and no addictive properties, making it suitable for industrial promotion.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and in particular to a kidney-tonifying and sleep-aiding medicinal composition, its preparation method and application. Background Technology

[0002] Insomnia is the most common sleep disorder in clinical practice, with its core clinical manifestations being difficulty falling asleep, difficulty maintaining sleep, early awakening, and impaired daytime function. Long-term insomnia can induce anxiety, depression, cognitive decline, endocrine disorders, and chronic diseases of multiple systems, seriously threatening public physical and mental health.

[0003] Modern medicine primarily treats insomnia with sedative-hypnotic drugs, mainly including benzodiazepines, non-benzodiazepine receptor agonists, and antidepressants. While these drugs can quickly relieve insomnia symptoms, they have significant clinical limitations: long-term use easily leads to drug tolerance, dependence, and addiction; rebound insomnia is common after discontinuation; and they can also cause adverse reactions such as daytime sleepiness, dizziness, fatigue, and cognitive decline. Furthermore, they only provide symptomatic relief and cannot address the root cause of insomnia's underlying pathological mechanisms, making it difficult to achieve long-term, stable therapeutic effects.

[0004] Traditional Chinese medicine (TCM) categorizes insomnia under the "insomnia" category, with "heart-kidney disharmony syndrome" being one of the most common core syndromes in clinical practice. It accounts for a very high percentage of patients with chronic insomnia, menopausal syndrome, chronic stress-related insomnia, and insomnia associated with chronic diseases. Currently, TCM treatment for heart-kidney disharmony insomnia focuses on "harmonizing the heart and kidneys," with classic formulas such as Huanglian Ejiao Tang and Jiaotai Wan. While these formulas have some clinical efficacy, they still have several insurmountable shortcomings: First, the formulations tend to be extreme, failing to address complex pathogenesis. Classic formulas often focus on clearing heart fire or nourishing kidney yin as a single target, failing to simultaneously address complex pathogenesis such as heart and kidney deficiency, spleen deficiency with dampness, and qi and blood deficiency. This results in insufficient overall regulation for most chronic insomnia patients, limited efficacy, and a high relapse rate. Second, the properties of the herbs are unbalanced, leading to poor safety and compliance with long-term use. Bitter and cold herbs in these formulas can easily damage the spleen and stomach's yang qi, while warm and drying herbs can easily exacerbate fire and damage yin. Long-term use can lead to... Third, many existing sleep aid formulas based on the same medicinal and edible ingredients use jujube seed as the core ingredient, lacking a rigorous principle of monarch, minister, assistant, and guide in their formulation. They do not systematically address the core pathogenesis of heart-kidney disharmony, resulting in a single efficacy and poor treatment of intractable insomnia. Furthermore, they often have a bitter taste and poor gastrointestinal tolerance with long-term use. Fourth, traditional decoctions are cumbersome to prepare, inconvenient to carry, and lack standardized dosages, making them unsuitable for the daily needs of modern fast-paced lifestyles. Meanwhile, existing modern preparations often suffer from complex processes, poor quality control, and high production costs, hindering their clinical application.

[0005] In summary, there is an urgent need for a kidney-tonifying and sleep-aiding medicinal composition that has a rigorous and balanced formulation, definite efficacy, mild medicinal properties, high safety, pleasant taste, and is easy to industrialize and take daily, in order to solve the above problems. Summary of the Invention

[0006] This invention provides a kidney-tonifying and sleep-aiding medicinal composition, its preparation method, and its application, in order to overcome the deficiencies in the prior art.

[0007] This invention provides a kidney-tonifying and sleep-aiding medicinal composition, made from the following raw materials in parts by weight: 10-20 parts of jujube seed, 5-15 parts of cornus officinalis, 2-4 parts of white hyacinth bean, 2-4 parts of dried tangerine peel, 2-4 parts of hawthorn, 4-6 parts of bitter melon, 2-4 parts of licorice root, 2-4 parts of cistanche deserticola, 2-4 parts of monk fruit, 1-3 parts of tangerine peel, 2-4 parts of raw astragalus, 2-4 parts of yam, and 2-4 parts of milk powder; the composition uses jujube seed and cornus officinalis as the principal herbs, with a weight ratio of (2-3):1, and is used to treat insomnia of the heart-kidney disharmony type, and also has the effects of tonifying the kidney and aiding sleep, harmonizing the heart and kidneys, and strengthening the spleen and stomach.

[0008] Preferably, it is made from the following ingredients in parts by weight: 15 parts jujube seed, 10 parts cornus officinalis, 3 parts white hyacinth bean, 3 parts dried tangerine peel, 3 parts hawthorn, 5 parts bitter melon, 3 parts licorice, 3 parts cistanche deserticola, 3 parts monk fruit, 2 parts tangerine peel, 3 parts raw astragalus, 3 parts yam, and 3 parts milk powder.

[0009] Preferably, the composition is an oral preparation, which is a tablet, capsule, granule, powder, pill, or oral solution.

[0010] A method for preparing the kidney-tonifying and sleep-aiding pharmaceutical composition as described above is provided, comprising the following steps: S1. Raw material pretreatment: Weigh out the following ingredients by weight: jujube seed, cornus officinalis, white hyacinth bean, tangerine peel, hawthorn, bitter melon, licorice, cistanche deserticola, monk fruit, tangerine peel, raw astragalus, and yam. After washing, dry them at 60-100℃ until the moisture content of the raw materials is less than 3.0%. After pulverizing, pass them through a 100-mesh sieve to obtain mixed medicinal powder. S2. Finished product preparation: Mix the mixed powder obtained in step S1 with milk powder in a certain proportion to obtain a powder product, or combine it with pharmaceutically acceptable excipients and prepare it into the required oral formulation through conventional pharmaceutical processes.

[0011] Preferably, in step S1, the drying temperature is 70-80℃ and the drying time is 4-8h.

[0012] Preferably, when the oral preparation is granules, the mixed drug powder, milk powder, and filler are mixed evenly, a wetting agent is added to form a soft mass, granulated by passing through an 18-24 mesh sieve, dried at 60-80℃ until the moisture content is below 5.0%, and granulated to obtain the finished granule product; the filler is one or more of microcrystalline cellulose, mannitol, and pregelatinized starch, and the wetting agent is an ethanol aqueous solution with a volume fraction of 30%-70%.

[0013] The aforementioned kidney-tonifying and sleep-aiding pharmaceutical composition is used in the preparation of drugs for treating insomnia caused by heart-kidney disharmony and in the preparation of tryptophan hydroxylase agonists.

[0014] Preferably, the drug improves sleep disorders by stimulating tryptophan hydroxylase, upregulating 5-hydroxytryptamine levels in brain tissue, and downregulating the expression of the inflammatory factor IL-1.

[0015] The present invention provides a kidney-tonifying and sleep-aiding medicinal composition, its preparation method, and its application, which have the following beneficial effects: (1) The formula uses jujube seed and cornus officinalis as the principal herbs, and the weight ratio of the two herbs is controlled at (2-3):1. Jujube seed nourishes the heart yin, benefits the liver blood, calms the mind and soothes the nerves, directly targeting the main symptom of insomnia; cornus officinalis tonifies the liver and kidneys, consolidates the kidney essence, and fills the root of kidney yin deficiency. The combination of the two herbs nourishes the heart and tonifies the kidneys, directly targeting the core pathogenesis of heart-kidney disharmony, achieving the harmony of heart and kidneys and the balance of water and fire. The assistant herbs are cistanche and yam to assist the principal herbs in warming the kidneys and benefiting the essence, strengthening the spleen and nourishing yin, achieving the yin within yang and the tonification of both yin and yang, so that the kidney yin has a source of production. Bitter melon and monk fruit clear the heart and drain fire, generate fluids and relieve irritability, clearing the heart fire that is flaring up, and together with the principal herbs, they clear and tonify, and harmonize the upper and lower parts of the body. The adjuvant herbs, including raw astragalus, white hyacinth bean, dried tangerine peel, hawthorn, and tangerine peel, invigorate the spleen and replenish qi, regulate qi and harmonize the stomach, and promote digestion. This prevents the cloying nature of nourishing herbs from hindering stomach function, and also counteracts the damage to the spleen and stomach's yang qi caused by bitter and cold herbs. It also addresses the common concurrent symptoms of spleen deficiency and dampness, and disharmony of qi and blood often present in patients with chronic insomnia. Licorice root harmonizes the various herbs, ensuring the overall formula is balanced, using both warming and cooling herbs, nourishing without causing stagnation, and clearing without harming. The addition of milk powder not only corrects the bitter taste of the herbs but also supplements tryptophan and high-quality protein, further enhancing the calming and soothing effects.

[0016] (2) The composition of the present invention has been verified by systematic pharmacodynamic experiments and has a clear therapeutic effect and target. The results of the verification using a PCPA-induced insomnia mouse model show that the composition of the present invention can significantly prolong the sleep time of insomnia model mice, and the efficacy is comparable to that of the positive control drug estazolam. It can correct the neurotransmitter disorder related to insomnia, regulate the sleep-wake rhythm from the root, and improve the chronic low-grade inflammatory state associated with insomnia.

[0017] (3) The composition of the present invention is balanced in terms of cold and heat, and is supplemented with spleen-strengthening and stomach-harmonizing ingredients. Long-term use does not irritate the gastrointestinal tract and has no risk of liver and kidney toxicity, so it has high safety. The preparation process is simple and the production cost is low. At the same time, it can be combined with conventional pharmaceutical excipients according to clinical needs to prepare a variety of oral preparations such as tablets, capsules, granules, pills, and oral solutions to meet the needs of different groups of people. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0019] Figure 1 This is a graph showing the test results of Example 8 of the present invention, which describes a kidney-tonifying and sleep-aiding medicinal composition, its preparation method, and its application. In the graph, (A) is a statistical graph of sleep time, (B) is a statistical graph of 5-HT, and (C) is a statistical graph of IL1. Detailed Implementation

[0020] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0021] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0022] It should be noted that similar reference numerals and letters in the following figures indicate similar items; therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures. Furthermore, the terms "first," "second," etc., are used only to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0023] In the description of the embodiments of the present invention, it should be noted that the terms "inner", "outer", "upper", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the product of the invention is usually placed when in use. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limiting the present invention.

[0024] The medicinal materials used in the following examples are all from the list of food and medicine homologous items published by the National Health Commission; the reagents, instruments and equipment used are all conventional commercial products and conventional experimental equipment in the field unless otherwise specified; the experimental methods used are all conventional technical methods in the field unless otherwise specified. Example 1

[0025] The kidney-tonifying and sleep-aiding medicinal composition of this embodiment is made from the following raw materials in parts by weight: 15 parts of jujube seed, 10 parts of cornus officinalis, 3 parts of white hyacinth bean, 3 parts of dried tangerine peel, 3 parts of hawthorn, 5 parts of bitter melon, 3 parts of licorice, 3 parts of cistanche deserticola, 3 parts of monk fruit, 2 parts of tangerine peel, 3 parts of raw astragalus, 3 parts of yam, and 3 parts of milk powder. Example 2

[0026] The kidney-tonifying and sleep-aiding medicinal composition of this embodiment is made from the following raw materials in parts by weight: 10 parts of jujube seed, 5 parts of cornus officinalis, 2 parts of white hyacinth bean, 2 parts of dried tangerine peel, 2 parts of hawthorn, 4 parts of bitter melon, 2 parts of licorice, 2 parts of cistanche deserticola, 2 parts of monk fruit, 1 part of tangerine peel, 2 parts of raw astragalus, 2 parts of yam, and 2 parts of milk powder. Example 3

[0027] The kidney-tonifying and sleep-aiding medicinal composition of this embodiment is made from the following raw materials in parts by weight: 18 parts of jujube seed, 6 parts of cornus officinalis, 4 parts of white hyacinth bean, 4 parts of dried tangerine peel, 4 parts of hawthorn, 6 parts of bitter melon, 4 parts of licorice, 4 parts of cistanche deserticola, 4 parts of monk fruit, 3 parts of tangerine peel, 4 parts of raw astragalus, 4 parts of yam, and 4 parts of milk powder.

[0028] Comparative Example 1 The composition of this comparative example is made solely from the following ingredients in parts by weight: 15 parts of jujube seed. No other ingredients are specified.

[0029] Comparative Example 2 The composition in this comparative example is made from the classic Jiaotai Pill formula: 15 parts Coptis chinensis and 1.5 parts Cinnamomum cassia. It is a classic representative formula for treating insomnia of the heart-kidney disharmony type in the prior art.

[0030] Comparative Example 3 The composition of this comparative example is identical to that of Example 1, except for the absence of Cornus officinalis. Specifically, it consists of: 15 parts of Ziziphus jujuba seed, 3 parts of white hyacinth bean, 3 parts of dried tangerine peel, 3 parts of hawthorn, 5 parts of bitter melon, 3 parts of licorice root, 3 parts of Cistanche deserticola, 3 parts of Luo Han Guo, 2 parts of tangerine peel, 3 parts of raw Astragalus membranaceus, 3 parts of Dioscorea opposita, and 3 parts of milk powder.

[0031] Comparative Example 4 The composition of this comparative example, except for the absence of milk powder, is the same as that in Example 1, specifically: 15 parts of jujube seed, 10 parts of cornus officinalis, 3 parts of white hyacinth bean, 3 parts of dried tangerine peel, 3 parts of hawthorn, 5 parts of bitter melon, 3 parts of licorice, 3 parts of cistanche deserticola, 3 parts of monk fruit, 2 parts of tangerine peel, 3 parts of raw astragalus, and 3 parts of yam. Example 4

[0032] This embodiment uses the formulation of Example 1 to prepare the powder, and the specific steps are as follows: Raw material pretreatment: Accurately weigh the following ingredients according to weight: jujube seed, cornus officinalis, white hyacinth bean, dried tangerine peel, hawthorn, bitter melon, licorice, cistanche deserticola, monk fruit, tangerine peel, raw astragalus, and yam. Quickly rinse with purified water, drain the surface moisture, and place in a hot air circulating oven to dry at a constant temperature of 75℃ for 6 hours. The moisture content of the raw materials is tested to be 2.4% (below 3.0%). Remove and let stand at room temperature. Grind using a hammer mill, pass through a 100-mesh standard sieve to remove coarse powder, and obtain a uniformly mixed medicinal powder. Preparation of finished product: Place the above-mentioned powdered medicine and the formula amount of milk powder in a three-dimensional motion mixer and mix for 30 minutes until completely uniform. After discharge, the mixture is aseptically packaged to obtain the powdered finished product, with a net content of 3g per bag. Example 5

[0033] This embodiment uses the formulation of Example 1 to prepare granules, and the specific steps are as follows: Raw material pretreatment: Same as step 1 in Example 4, to obtain mixed powder; Granulation preparation: Mix the mixed medicinal powder, the formula amount of milk powder and the pregelatinized starch filler at a mass ratio of 10:3. Add 50% ethanol aqueous solution as a wetting agent and stir to obtain a soft material that can be formed into a ball by hand and crumbles easily when touched. Pass the soft material through a 20-mesh standard sieve to make wet granules. Place the wet granules in a 65℃ hot air oven and dry for 3 hours. The moisture content of the granules is tested to be 3.8% (less than 5.0%). Take them out and let them cool to room temperature. Then, granulate them through an 18-mesh sieve to remove fine powder and coarse particles to obtain the finished granules. After aseptic packaging, each bag contains 3g of net content. Example 6

[0034] This embodiment uses the formulation from Example 1 to prepare capsules. The specific steps are as follows: Raw material pretreatment: Same as step 1 in Example 4, to obtain mixed powder; Capsule preparation: Mix the mixed medicine powder, the formula amount of milk powder, the filler microcrystalline cellulose, and the lubricant magnesium stearate in a mass ratio of 10:2:1:0.1 until uniform. Use a dry granulation machine to obtain 20-40 mesh dry granules. After the granules pass the tests for flowability and bulk density, use a fully automatic capsule filling machine to fill them into No. 0 hard capsule shells at a filling amount of 0.5g / capsule. After polishing and aluminum-plastic blister packaging, the finished capsules are obtained. Example 7

[0035] This embodiment uses the formulation of Example 1 to prepare an oral solution. The specific steps are as follows: Raw material pretreatment: Same as step 1 in Example 4, to obtain mixed powder; Solution preparation: Take 800 mL of purified water, heat to 40 °C, add the mixed medicinal powder and the formula amount of milk powder, stir for 30 min until completely dispersed and dissolved, add 50 g of flavoring agent sucrose, 0.5 g of antibacterial agent potassium sorbate and 0.2 g of antioxidant vitamin C in sequence, stir until completely dissolved, add purified water to make up to 1000 mL, stir evenly, and then filter through a 0.22 μm microporous membrane. The filtrate is filled into 10 mL brown oral liquid bottles, capped and sealed, and then sterilized by terminal moist heat at 115 °C for 30 min. After passing the light inspection, it is packaged to obtain the finished oral solution. Example 8

[0036] This embodiment uses an experimental mouse insomnia model induced by chlorophenylalanine (PCPA) to verify the sleep-aiding efficacy and mechanism of action of the composition of Example 1.

[0037] Experimental animals: SPF-grade adult male C57BL / 6J mice, 15 months old, weighing 32±3g.

[0038] Rearing environment: temperature 24±1℃, humidity 55±5%, 12h / 12h light and dark cycle, free access to food and water, and the experiment began after 1 week of acclimatization.

[0039] Test drugs: The powder prepared in Example 1 and the samples prepared in Comparative Examples 1-3 were prepared into suspensions of the corresponding concentrations with physiological saline before use; the positive control drug, estazolam tablets, was purchased from Shandong Xinyi Pharmaceutical Co., Ltd., and was prepared into a solution of 100 μg / mL with distilled water before use.

[0040] Reagents and instruments: PCPA (Sigma-Aldrich, USA); sodium pentobarbital (Shanghai Yuanye Biotechnology Co., Ltd.); mouse 5-hydroxytryptamine (5-HT) ELISA kit (catalog number JN719203, Shanghai Jining Biotechnology Co., Ltd.); mouse interleukin-1 (IL-1) ELISA kit (catalog number CEK1788, BioworldBiotechnology); SPARK multi-mode microplate reader (TECAN, USA).

[0041] Animal grouping and model preparation: Ninety mice were randomly divided into nine groups of ten mice each: normal control group, insomnia model group, estazolam positive group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group. Except for the normal control group, all other groups of mice were intraperitoneally injected with PCPA suspension at 450 mg / kg once daily for two consecutive days to establish an insomnia mouse model; the normal control group was intraperitoneally injected with an equal volume of physiological saline. Forty-eight hours after the first PCPA injection, the model group mice showed significantly increased activity, enhanced aggression, and disrupted diurnal rhythms, showing significant differences from the normal control group, indicating successful model establishment. 2.2 Drug administration method: After successful model establishment, drug administration began, and the drug administration regimens for each group were as follows: Normal control group and insomnia model group: administered physiological saline by gavage, 1 mL / 100 g, once daily; Estazolam positive group: Estazolam solution was administered by gavage at a dose of 2 mg / kg once daily; Examples 1-3: The test drug suspension was administered by gavage at a dose of 30 mg / kg once daily; Comparative Examples 1-3: The corresponding test drug suspension was administered by gavage at a dose of 30 mg / kg once daily; Each group was given the medication by gavage for 5 consecutive days, during which time they were allowed free access to food and water.

[0042] Sleep latency and sleep duration detection: 1 hour after the last administration, mice in each group were intraperitoneally injected with sodium pentobarbital 50 mg / kg. The disappearance of the righting reflex was used as the criterion for falling asleep. The sleep latency (time from the injection of sodium pentobarbital to the disappearance of the righting reflex) and total sleep duration (time from the disappearance of the righting reflex to its recovery) of each mouse were recorded.

[0043] Detection of neurotransmitters and inflammatory factors in brain tissue: After the sleep behavior test, mice were euthanized by cervical dislocation, and the whole brain tissue was quickly dissected. Brain tissue homogenate was prepared under ice bath, and the supernatant was collected by centrifugation. The contents of 5-HT and IL-1 in the brain tissue of each group of mice were detected strictly according to the ELISA kit instructions.

[0044] Statistical methods: Data analysis was performed using GraphPadPrism 9.0 software. Quantitative data are expressed as mean ± standard deviation (x ± s). One-way ANOVA was used for comparisons among multiple groups, and LSD-t test was used for pairwise comparisons between groups. P < 0.05 was considered statistically significant.

[0045] The effects on sleep behavior in insomnia mice are shown in Table 1.

[0046] Table 1. Comparison of sleep latency and total sleep time in mice of different groups (x±s, n=10) Note: Compared with the normal control group, ##P<0.0001; compared with the insomnia model group, *P<0.05, **P<0.01, ***P<0.001.

[0047] The results showed that compared with the normal control group, the sleep latency of mice in the insomnia model group was significantly prolonged and the total sleep time was significantly shortened (P<0.0001), indicating that the model was successfully established. Compared with the insomnia model group, all three groups of Examples 1-3 significantly shortened the sleep latency and prolonged the total sleep time of insomnia mice (P<0.001). The efficacy of the optimal formulation in Example 1 was comparable to that of the positive control drug estazolam. Although the comparative groups 1-3 showed some improvement, their efficacy was significantly weaker than that of the Example 1-3 groups (P<0.05), proving that the formulation of this invention has a clear synergistic effect, and the combination of principal drugs is the core of exerting the efficacy.

[0048] The effects on the levels of 5-HT and IL-1 in the brain tissue of insomnia mice are shown in Table 2.

[0049] Table 2 Comparison of 5-HT and IL-1 levels in the brain tissue of mice in each group (x±s, n=10) Note: Compared with the normal control group, ##P<0.0001; compared with the insomnia model group, there was no statistically significant difference in ns, *P<0.05, **P<0.01, ***P<0.001.

[0050] The results showed that compared with the normal control group, the 5-HT content in the brain tissue of mice in the insomnia model group was significantly reduced and the IL-1 content was significantly increased (P<0.0001). Compared with the insomnia model group, the 5-HT content in the brain tissue of Examples 1-3 was significantly upregulated (P<0.001), while the expression of the inflammatory factor IL-1 was significantly downregulated (P<0.001), with the best effect in Example 1. The estazolam positive group could only upregulate the 5-HT content and had no significant downregulation effect on IL-1. The regulatory effect of the Comparative Examples 1-3 groups was significantly weaker than that of the Examples 1-3 groups.

[0051] Experimental Conclusion: The kidney-tonifying and sleep-aiding pharmaceutical composition of the present invention can significantly improve sleep disorders in insomnia model mice by stimulating tryptophan hydroxylase, upregulating the level of central 5-HT neurotransmitter, and inhibiting the expression of the neuroinflammatory factor IL-1. It shortens sleep latency and prolongs total sleep time, with efficacy comparable to the first-line clinical sedative-hypnotic drug estazolam. It also has anti-inflammatory effects, higher safety, and no risk of addiction or central nervous system depression associated with Western medicines. The formulation of this invention is rigorously formulated, with significant synergistic effects of the principal drugs, demonstrating clear medicinal value and application advantages. Example 9

[0052] This embodiment uses experiments to systematically test the physicochemical properties of the samples from Example 1 and Comparative Example 4, verifying the formulation advantages of the composition of the present invention.

[0053] Test samples: finished powder product prepared in Example 1 and powder sample prepared in Comparative Example 4.

[0054] pH value detection: Take 3g of each of the samples from Example 1 and Comparative Example 4, dissolve them in 50mL of 40℃ warm water, stir thoroughly to dissolve, and use a calibrated precision electronic pH meter to detect the pH value of the solution under constant temperature of 25℃. Perform three parallel tests and take the average value.

[0055] Powder properties testing: The particle size distribution (D10, D50, D90) of the samples was detected using a laser particle size analyzer, and the angle of repose of the samples was detected using an angle of repose meter to evaluate the powder flowability; the compressibility of the samples was calculated using the Karl elliptic index method, and the tests were performed in triplicate and the average value was taken.

[0056] Solubility test: Take 10g of sample, add 200mL of hot water, stir for 5min, and observe the solubility and insoluble residue.

[0057] Accelerated stability test: The powder, granule and capsule products of Example 1 were placed in a constant temperature and humidity chamber at 40℃±2℃ and 75%±5% relative humidity for 6 months accelerated stability test. Samples were taken at 0 months, 1 month, 2 months, 3 months and 6 months to test the properties, moisture, content uniformity and microbial limit of the samples to examine the stability of the formulation.

[0058] pH test results: The pH value of the sample solution in Example 1 was 6.54, and the pH value of the sample solution in Comparative Example 4 was 6.47. The pH values ​​of both groups of samples were within the suitable range of 5.0-7.0 for the human gastrointestinal tract, with no significant difference, and they were not irritating to the gastrointestinal mucosa.

[0059] The results of the powder chemical property test are shown in Table 3.

[0060] Table 3. Results of powder properties testing of samples (x±s, n=3) The results showed that, compared with Comparative Example 4, the sample of Example 1 had a more uniform particle size distribution, a smaller angle of repose, lower compressibility, and significantly better powder flowability, which is more conducive to industrial production operations such as formulation dispensing and filling. This proves that the addition of milk powder can significantly improve the powder properties of traditional Chinese medicine powder.

[0061] Solubility test results: After stirring with hot water, the sample of Example 1 can be quickly and completely dispersed and dissolved without any insoluble matter such as burnt residue or hard lumps, and the solution is uniform; after stirring, the sample of Comparative Example 4 has a small amount of insoluble precipitate and poor dispersion uniformity, which proves that the addition of milk powder can significantly improve the water dispersibility and solubility of the composition.

[0062] Accelerated stability test results: After 6 months of accelerated stability testing, the powder, granules and capsules prepared in Example 1 showed no change in properties, the moisture content still met the pharmacopoeia standard, the content uniformity did not change significantly, the microbial limits met the requirements, and there was no contamination. This proves that the various preparations prepared by the composition of the present invention have good stability, the quality is controllable within the shelf life, and they are suitable for long-term storage and transportation.

[0063] Test results: The composition of this invention, when added with milk powder, not only improves the powder flowability, solubility, and dispersion uniformity of the preparation, making it suitable for large-scale industrial production, but also ensures that the pH value of the preparation is within the suitable range for the human body, does not irritate the gastrointestinal tract, has good stability in various dosage forms, and has controllable quality, demonstrating significant pharmaceutical advantages and industrial application value.

[0064] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A kidney-tonifying and sleep-aiding medicinal composition, characterized in that, It is made from the following raw materials in parts by weight: 10-20 parts of jujube seed, 5-15 parts of cornus officinalis, 2-4 parts of white hyacinth bean, 2-4 parts of dried tangerine peel, 2-4 parts of hawthorn, 4-6 parts of bitter melon, 2-4 parts of licorice, 2-4 parts of cistanche deserticola, 2-4 parts of monk fruit, 1-3 parts of tangerine peel, 2-4 parts of raw astragalus, 2-4 parts of yam, and 2-4 parts of milk powder; the composition is made with jujube seed and cornus officinalis in a weight ratio of (2-3):

1.

2. The kidney-tonifying and sleep-aiding medicinal composition according to claim 1, characterized in that, It is made from the following ingredients in parts by weight: 15 parts jujube seed, 10 parts cornus officinalis, 3 parts white hyacinth bean, 3 parts dried tangerine peel, 3 parts hawthorn, 5 parts bitter melon, 3 parts licorice, 3 parts cistanche deserticola, 3 parts monk fruit, 2 parts tangerine peel, 3 parts raw astragalus, 3 parts yam, and 3 parts milk powder.

3. The kidney-tonifying and sleep-aiding medicinal composition according to claim 1, characterized in that, The composition is an oral preparation, which may be a tablet, capsule, granule, powder, pill, or oral solution.

4. A method for preparing the kidney-tonifying and sleep-aiding medicinal composition according to claim 1, characterized in that, Includes the following steps: S1. Raw material pretreatment: Weigh out the following ingredients by weight: jujube seed, cornus officinalis, white hyacinth bean, tangerine peel, hawthorn, bitter melon, licorice, cistanche deserticola, monk fruit, tangerine peel, raw astragalus, and yam. After washing, dry them at 60-100℃ until the moisture content of the raw materials is less than 3.0%. After pulverizing, pass them through a 100-mesh sieve to obtain mixed medicinal powder. S2. Finished product preparation: Mix the mixed powder obtained in step S1 with milk powder in a certain proportion to obtain a powder product, or combine it with pharmaceutically acceptable excipients and prepare it into the required oral formulation through conventional pharmaceutical processes.

5. The method for preparing a kidney-tonifying and sleep-aiding medicinal composition according to claim 4, characterized in that, In step S1, the drying temperature is 70-80℃ and the drying time is 4-8h.

6. The method for preparing a kidney-tonifying and sleep-aiding medicinal composition according to claim 4, characterized in that, When the oral preparation is granules, the mixed medicine powder, milk powder, and filler are mixed evenly, a wetting agent is added to form a soft mass, which is then granulated by passing through an 18-24 mesh sieve, dried at 60-80℃ until the moisture content is below 5.0%, and granulated to obtain the finished granule product; the filler is one or more of microcrystalline cellulose, mannitol, and pregelatinized starch, and the wetting agent is an ethanol aqueous solution with a volume fraction of 30%-70%.

7. The use of the kidney-tonifying and sleep-aiding pharmaceutical composition as described in claim 1 in the preparation of a medicament for treating insomnia due to heart-kidney disharmony and in the preparation of a tryptophan hydroxylase agonist.

8. The application according to claim 7, characterized in that, The drug improves sleep disorders by stimulating tryptophan hydroxylase, upregulating 5-hydroxytryptamine levels in brain tissue, and downregulating the expression of the inflammatory factor IL-1.

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