Sugar-free traditional Chinese medicine composition with efficient sleep aiding function and preparation method of sugar-free traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and discloses a sugar-free traditional Chinese medicine composition with an efficient sleep aiding function and a preparation method of the sugar-free traditional Chinese medicine composition. The composition comprises the following medicinal materials in parts by weight: 30-50 parts of fried spina date seeds, 3-8 parts of rhizoma anemarrhenae, 10-20 parts of poria cocos, 2-6 parts of ligusticum wallichii, 2-8 parts of liquorice, 2-10 parts of Chinese dates, 3-8 parts of radix ophiopogonis, 2-8 parts of lily, 2-10 parts of schisandra chinensis, and auxiliary materials including a filling agent, a protective agent and a sugar-free flavoring agent. The preparation method comprises the following steps: decocting the medicinal materials twice, concentrating, drying, powdering, mixing with the auxiliary materials, dissolving, emulsifying, and spray-drying to obtain the sugar-free granules. The composition can nourish blood and tranquilize mind, sedative and hypnotic, and regulate heart, liver, kidney and lung in a multi-target manner, the PSQI score is obviously improved, and the total effective rate is high; natural / medicinal and edible raw materials are used, so that the composition is suitable for long-term taking of sugar-intolerance people, and is high in safety and free of dependence risk.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and specifically provides a sugar-free traditional Chinese medicine composition with high efficiency of sleep aid and a preparation method thereof. BACKGROUND

[0002] Sleep, as the core physiological process of human body recovery and function regulation, plays an irreplaceable role in maintaining the homeostasis of nervous system, the function of immune system and the metabolic balance. However, with the acceleration of modern life pace and the increase of mental stress, insomnia has become a global health problem with high incidence. According to incomplete statistics, the incidence of insomnia among Chinese adults is as high as 38.2%, involving about 300 million people, and the incidence of insomnia among people aged 65 and above has risen to 73.7%. Long-term insomnia not only leads to symptoms such as daytime drowsiness, inattention, memory loss, but also significantly increases the risk of complications such as hypertension, diabetes, anxiety and depression, seriously affecting the quality of life and health level of patients. Therefore, developing sleep aid products with safety, high efficiency and wide applicability has become an urgent need in the medical field.

[0003] Currently, sleep aid products on the market are mainly divided into two categories: one is western sedative and hypnotic drugs, such as benzodiazepines, non-benzodiazepines and melatonin receptor agonists. Although this type of drug can quickly improve sleep difficulty, it has obvious defects: long-term use can easily lead to drug dependence and drug resistance, and elderly patients may experience dizziness, ataxia and even poisoning risk due to decreased metabolic capacity with excessive use; the other is traditional Chinese medicine sleep aid products, which are based on the theory of "yin-yang balance" in traditional Chinese medicine, and can improve sleep by regulating the overall function of the body, with the advantages of small side effects and weak dependence. Among them, traditional Chinese medicine granules have become an important form of modernization of traditional Chinese medicine preparations due to their precise dosage, convenient administration and stable storage.

[0004] However, the existing traditional Chinese medicine sleep aid products and related technologies still have key bottlenecks: 1. High sugar content, limited applicability: In order to mask the bitter taste of traditional Chinese medicine and improve patient medication compliance, most traditional Chinese medicine granules add a large amount of sucrose, honey and other sweeteners. For example, in the published patent CN202310933797.X, the honey dosage of traditional Chinese medicine pills is as high as 1700-2400 parts by weight, which is much higher than the total weight of medicinal materials, resulting in a very high sugar content of the product; in the sleep-improving traditional Chinese medicine composition disclosed in published patent CN117414389A, sucrose is directly added as an auxiliary material. Such products can significantly raise blood sugar and cannot meet the medication needs of people with diabetes, obesity and other sugar-phobic people, greatly limiting the applicability of traditional Chinese medicine sleep aid products.

[0005] 2. Formula single, adjust dimension limit: existing traditional Chinese medicine sleep aid formula focuses on the two organs of "heart and liver", ignoring the influence of "lungs and kidneys" on sleep. In traditional Chinese medicine theory, "lungs govern qi and regulate respiration" and "kidneys store essence and generate marrow". Lung and kidney deficiency easily leads to heart disturbance by virtual fire, and further causes symptoms such as easy waking at night and early waking. Single organ regulation cannot solve the insomnia caused by multiple factors from the root, and the sleep aid effect is limited.

[0006] 3. Process parameters are ambiguous, and the retention rate of effective components is insufficient: In the preparation process of some traditional Chinese medicine granules, the key conditions such as decoction temperature and drying parameters are not clearly defined. For example, only "water decoction" and "spray drying" are mentioned, but the specific duration of fast fire / slow fire and the inlet / outlet air temperature of spray drying are not defined, resulting in large differences in the content of effective components in different batches of products, affecting the stability of efficacy.

[0007] In summary, the existing sleep aid products still have the problems of "strong dependence on western medicine, high sugar content of traditional Chinese medicine, narrow regulation dimension of formula, and poor process stability", and there is an urgent need to develop a traditional Chinese medicine composition and its preparation method which takes into account "high-efficiency sleep aid, sugar-free safety, multi-organ regulation, and stable process". SUMMARY

[0008] Therefore, the present application provides a sugar-free traditional Chinese medicine composition with high-efficiency sleep aid and its preparation method, which specifically solves the following technical problems: 1. Avoiding the dependence and drug resistance of western medicine sleep aid products, achieving long-acting sleep aid through TCM multi-organ synergistic regulation; 2. Eliminating the addition of sweeteners such as sucrose and honey in traditional Chinese medicine preparations to meet the medication needs of people who are afraid of sugar; 3. Optimizing the formula and preparation process to ensure high retention rate of effective components, good batch stability of products, and improve medication compliance.

[0009] The technical solution of the present application is as follows: The present application provides a sugar-free traditional Chinese medicine composition with high-efficiency sleep aid. The traditional Chinese medicine composition of the present application includes medicinal material components and auxiliary material components, which are accurately proportioned by weight parts. The medicinal material components are specifically as follows: fried jujube seed 30-50 parts, anemarrhena 3-8 parts, tuckahoe 10-20 parts, chuanxiong 2-6 parts, licorice 2-8 parts, jujube 2-10 parts, ophiopogon 3-8 parts, lily 2-8 parts, and schisandra 2-10 parts.

[0010] Compatibility logic The monarch drug is fried jujube seed, which is neutral in nature, sweet and sour in taste, and belongs to the heart, liver and gallbladder channels. It can nourish heart yin, benefit liver blood and calm the mind, and is the core medicinal material for treating insomnia in traditional Chinese medicine. The jujube seed saponins A and B contained therein can inhibit central nervous system excitation and promote the release of gamma-aminobutyric acid (GABA), directly improving sleep difficulty; Ministerial medicine: Anemarrhena rhizome, Poria cocos: Anemarrhena rhizome tastes bitter and is cold, returns to the lung, stomach and kidney channels, can nourish yin and clear heat, and can relieve the symptoms of night waking caused by yin deficiency; Poria cocos tastes sweet and is neutral, returns to the heart, lung, spleen and kidney channels, can benefit water and eliminate dampness, and can strengthen the spleen and calm the heart, thereby enhancing the effect of the monarch drug in nourishing the heart and calming the spirit, and improving the symptoms of spleen deficiency such as fatigue and weakness. Assistant medicine: Chuanxiong rhizome and licorice: Chuanxiong rhizome tastes pungent and is warm, returns to the liver, gallbladder and heart channels, can activate blood and disperse qi, and can dispel wind and relieve pain, thereby dredging liver qi stagnation and assisting the monarch drug in enhancing the effect of calming the spirit; licorice tastes sweet and is neutral, returns to the heart, lung, spleen and stomach channels, can tonify the spleen and supplement qi, and can harmonize various drugs, thereby reducing the cold nature of Anemarrhena rhizome and the pungent and dispersing nature of Chuanxiong rhizome, and avoiding conflicts between the medicinal materials. Ministerial medicine: Jujube, Ophiopogon japonicus, Lily and Schisandra chinensis: Jujube tastes sweet and is warm, returns to the spleen and stomach channels, can tonify the center and supplement qi, and can nourish blood and calm the spirit, thereby strengthening the function of the spleen as the source of qi and blood, and providing a material basis for the heart spirit; Ophiopogon japonicus tastes bitter and is cold, returns to the heart, lung and stomach channels, can nourish yin and moisten the lungs, and can clear the heart and relieve restlessness, thereby targeting the symptoms of heart restlessness caused by lung yin deficiency; Lily tastes sweet and is cold, returns to the lung channel, can nourish yin and moisten the lungs, and can calm the heart and spirit, thereby assisting Ophiopogon japonicus in enhancing the effect of moistening the lungs and clearing the heart; Schisandra chinensis tastes sour and sweet and is warm, returns to the lung, heart and kidney channels, can supplement qi and tonify the kidney, and can calm the heart, thereby targeting the symptoms of heart restlessness caused by kidney yin deficiency, and simultaneously reducing night sweat loss due to the astringent effect of sour flavors.

[0011] The auxiliary material components are as follows: Filler 10-25 parts, protective agent 20-45 parts, and sugar-free flavoring agent 8-15 parts; wherein the mass ratio of the protective agent to the filler is 1.75-2:1.

[0012] The selection basis of the auxiliary materials is as follows: Filler: selected from one or more of hydroxypropyl methylcellulose, starch, methylcellulose, gum arabic, sodium alginate, pectin or microcrystalline cellulose, preferably microcrystalline cellulose, which has good flowability, compression molding property, can improve the physical stability of the granules, and does not contain calories and does not raise blood sugar, meeting the "sugar-free" requirement; Protective agent: selected from one or more of dextrin, dextran, bovine serum albumin or gelatin, preferably maltodextrin, which can form a stable inclusion compound with the effective components of the medicinal materials, avoid the degradation of heat-sensitive components during the spray drying process, and improve the solubility of the granules; Sugar-free flavoring agent: aspartame or stevioside, preferably stevioside, which has 200-300 times the sweetness of sucrose, only 1 / 300 the calories of sucrose, does not participate in human metabolism, does not raise blood sugar, and can effectively mask the bitterness of traditional Chinese medicine and improve medication compliance.

[0013] The application also provides a preparation method of the traditional Chinese medicine composition, which is based on the design of "maximizing extraction of effective components and stable molding of sugar-free granules", and the specific steps are as follows: S1 medicine extraction and fine powder preparation: all the medicinal materials are weighed according to the weight parts, and the effective components are extracted by two times of water decoction, the first time is fast decoction (temperature 100-105 DEG C), and the time is 80 min, the purpose is to quickly extract water-soluble components such as fried jujube saponin and zhimu mango glycoside; the second time is gentle decoction (temperature 85-90 DEG C), and the time is 35 min, the purpose is to gently extract heat-sensitive components such as ophiopogon saponin and lily polysaccharide, and to avoid degradation at high temperature. The medicinal liquid of the two times of decoction is combined, rotary evaporation is used to concentrate to extract (the water content of the extract is ≤5%), drying is carried out at 50-60 DEG C for 40-80 min, and then crushing is carried out to pass through an 80-mesh screen to obtain total medicinal material fine powder (ensure that the fine powder particle size is uniform, and the subsequent mixing with excipients is more sufficient).

[0014] S2 medicine-exciipient mixing and dissolution: the total medicinal material fine powder, the filler and the sugar-free flavoring agent are put into a mixer and stirred uniformly, then 5-7% of purified water based on the total mixture mass is added to fully dissolve, to prepare a total solution containing medicinal material components, and the water addition amount is controlled to be 5-7%, which can ensure that the material is fully dissolved, and also avoid high energy consumption in the subsequent drying.

[0015] S3 emulsion polymer preparation: the protective agent is added to the above total solution, and mechanical stirring is carried out at 5-40 DEG C (the temperature is controlled at 5-40 DEG C, which can avoid denaturation of the protective agent and damage of the effective components of the medicinal materials), and stirring is carried out until a uniform emulsion is formed, to prepare an emulsion polymer containing medicinal material components, and the emulsion structure can enhance the wrapping effect of the protective agent on the effective components, and improve the stability in the subsequent drying process.

[0016] S4 spray drying granulation: the emulsion polymer is sent into a spray drying tower, and drying is carried out by controlling the inlet air temperature to be 185-205 DEG C and the outlet air temperature to be 90-100 DEG C, the inlet air temperature 185-205 DEG C can quickly atomize the emulsion into small droplets, and the outlet air temperature 90-100 DEG C can ensure that the granules are completely dried (moisture content ≤3%), and at the same time, the effective components are prevented from being degraded due to high temperature, and finally a sugar-free traditional Chinese medicine granule is prepared.

[0017] The application also provides the use of the above-mentioned traditional Chinese medicine composition, the sugar-free traditional Chinese medicine composition of the application can be used for preparing oral preparations for treating insomnia, and the oral preparations include suspensions, oral emulsions, ordinary tablets, hard capsules, soft capsules, and are especially suitable for primary insomnia of sugar-phobic people such as diabetic patients and obese patients, after taking, the insomnia symptoms such as difficulty falling asleep, easy waking at night and early waking can be improved, blood sugar can be prevented from rising, and there is no drug dependence, and the traditional Chinese medicine composition is suitable for long-term taking Compared with the prior art, the application has the following beneficial effects: The application considers five major viscera of heart, liver, lung, kidney and spleen by compatibility of nine medicinal materials, and regulates the body function from multiple dimensions of nourishing heart and soothing spirit, nourishing yin and reducing fire, promoting blood circulation and activating qi, and invigorating spleen and tonifying kidney, instead of single targeting a certain viscera or symptom. Clinical data shows that after taking the product of the application for 2 weeks, the total score of Pittsburgh Sleep Quality Index (PSQI) of the patients is greatly reduced, among which the sleep onset time is shortened, the number of night awakenings is decreased, and the recurrence rate of insomnia after drug withdrawal is low, which is significantly better than traditional Chinese medicine and western medicine, and achieves the effect of long-acting sleep aid and reducing recurrence.

[0018] The medicinal material components of the application are common natural medicinal materials or homologous medicinal and food materials recorded in Chinese Pharmacopoeia, do not contain any toxic medicinal materials or western medicine sedative components, and no adverse reactions such as dizziness, drowsiness, and lack of concentration are observed after long-term use; the excipients are food-grade materials (such as malt dextrin, microcrystalline cellulose, and stevioside), which meet the national food safety standards and have no risk of exceeding heavy metals and microorganisms. At the same time, the product does not contain sugar and honey, and has little effect on postprandial blood glucose of diabetic patients, and completely solves the dilemma of people who are afraid of sugar and want to take sleep aids.

[0019] The application is a sugar-free preparation, which is not only suitable for ordinary insomnia people, but also meets the medication needs of people who are afraid of sugar, such as diabetes, obesity, and high blood lipids. The incidence of insomnia among diabetic patients in China is as high as 56%, and such people lack safe sleep aids for a long time, and the application fills this market gap. At the same time, the product can be prepared into granules, capsules, tablets and other oral dosage forms, which are convenient for different people to take, and further expand the application scenarios and population range. DETAILED DESCRIPTION

[0020] The technical solutions in the embodiments of the application will be clearly and completely described below in combination with the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the application.

[0021] Example 1 Preparation steps Step 1: Take roasted Suanzaoren 30 parts, Anemarrhena 3 parts, Poria 15 parts, Chuanqiong 2 parts, Gancao 2 parts, Dazao 2 parts, Maidong 3 parts, Baihe 2 parts, Wuweizi 2 parts by weight, put all the medicinal materials into the traditional Chinese medicine decocting pot, add 8 times the amount of purified water, use the first time to adopt the strong fire (temperature 100-105℃) to decoct 80min, filter to get the first time medicinal liquid; add 6 times the amount of purified water to the dregs, use the second time to adopt the gentle fire (temperature 85-90℃) to decoct 35min, filter to get the second time medicinal liquid; combine the two medicinal liquids, use the rotary evaporator to concentrate to the extract (the moisture content of the extract is ≤5%), put the extract in the oven at 50~60℃ to dry for 60min, crush and pass through the 80 mesh sieve to get the total medicinal material fine powder for standby.

[0022] Step 2: Take the filler microcrystalline cellulose 10 parts, the sugar-free flavoring agent stevioside 8 parts by weight, and the total medicinal material fine powder prepared in step 1 together into the three-dimensional mixer, stir for 15min until mixed evenly; add 5% of the total mixture quality of purified water to the mixture, continue to stir for 10min until fully dissolved, to prepare the total solution containing medicinal material ingredients.

[0023] Step 3: Take the protective agent maltodextrin 20 parts by weight, add it to the total solution of step 2, stir at 300r / min speed with a mechanical stirrer at 25℃ for 20min, after mixing evenly, add 0.02% of the total solution quality of purified water, adjust the stirring speed to 500r / min, continue to stir for 15min, to prepare the emulsion polymer containing medicinal material ingredients.

[0024] Step 4: Put the emulsion polymer of step 3 into the spray drying tower, set the inlet air temperature to 185℃, the outlet air temperature to 90℃, the atomization pressure to 0.3MPa, the feeding speed to 15mL / min, collect the product after drying, to get the sugar-free traditional Chinese medicine granules.

[0025] Example 2 Preparation steps Step 1: Take roasted Suanzaoren 40 parts, Anemarrhena 3 parts, Poria 15 parts, Chuanqiong 2 parts, Gancao 2 parts, Dazao 2 parts, Maidong 3 parts, Baihe 2 parts, Wuweizi 2 parts by weight, the rest of the medicinal materials are extracted, concentrated, dried and powdered according to the same steps as in example 1.

[0026] Step 2: The weighing and mixing of the filler and the sugar-free flavoring agent are consistent with example 1.

[0027] Step 3: The addition of the protective agent and the preparation of the emulsion polymer are consistent with example 1.

[0028] Step 4: The spray drying parameters and the granule collection steps are consistent with example 1.

[0029] Example 3 Preparation step Step 1: Fried Suanzaoren 50 parts, Anemarrhena 3 parts, Poria 15 parts, Chuanxiong 2 parts, Licorice 2 parts, Jujube 2 parts, Ophiopogon 3 parts, Lily 2 parts, Schisandra 2 parts, the rest of the medicinal materials extraction, concentration drying, powdering steps are consistent with example 1.

[0030] Step 2-Step 4: consistent with example 1.

[0031] Example 4 Preparation step Step 1: Fried Suanzaoren 30 parts, Anemarrhena 5 parts, Poria 20 parts, Chuanxiong 2 parts, Licorice 2 parts, Jujube 2 parts, Ophiopogon 3 parts, Lily 2 parts, Schisandra 2 parts, the rest of the medicinal materials extraction, concentration drying, powdering steps are consistent with example 1.

[0032] Step 2-Step 4: consistent with example 1.

[0033] Example 5 Preparation step Step 1: Fried Suanzaoren 40 parts, Anemarrhena 5 parts, Poria 20 parts, Chuanxiong 2 parts, Licorice 2 parts, Jujube 2 parts, Ophiopogon 5 parts, Lily 5 parts, Schisandra 2 parts, the rest of the medicinal materials extraction, concentration drying, powdering steps are consistent with example 1.

[0034] Step 2-Step 4: consistent with example 1.

[0035] Example 6 Preparation step Step 1: Fried Suanzaoren 50 parts, Anemarrhena 5 parts, Poria 20 parts, Chuanxiong 2 parts, Licorice 2 parts, Jujube 2 parts, Ophiopogon 5 parts, Lily 5 parts, Schisandra 2 parts, the rest of the medicinal materials extraction, concentration drying, powdering steps are consistent with example 1.

[0036] Step 2-Step 4: consistent with example 1.

[0037] Example 7 Preparation step Step 1: Fried Suanzaoren 30 parts, Anemarrhena 5 parts, Poria 20 parts, Chuanxiong 5 parts, Licorice 6 parts, Jujube 5 parts, Ophiopogon 5 parts, Lily 5 parts, Schisandra 2 parts, the rest of the medicinal materials extraction, concentration drying, powdering steps are consistent with example 1.

[0038] Step 2: The filler microcrystalline cellulose 10 parts, sugar-free flavoring agent aspartame 8 parts, mixed with total medicinal powder dissolution, the rest of the steps are consistent with example 1.

[0039] Step 3-Step 4: consistent with example 1.

[0040] Example 8 Preparation step Step 1: The medicinal materials were weighed according to the weight parts, and the extraction, concentration, drying, and powdering steps were consistent with Example 1.

[0041] Steps 2-4: Consistent with Example 1.

[0042] Example 9 Preparation step Step 1: The medicinal materials were weighed according to the weight parts, and the extraction, concentration, drying, and powdering steps were consistent with Example 1.

[0043] Steps 2-4: Consistent with Example 1.

[0044] Example 10 Preparation step Step 1: The medicinal materials were weighed according to the weight parts, and the extraction, concentration, drying, and powdering steps were consistent with Example 1.

[0045] Steps 2-4: Consistent with Example 1.

[0046] Example 11 Preparation step Step 1: The medicinal materials were weighed and the extraction and powdering steps were consistent with Example 9.

[0047] Step 2: The filler microcrystalline cellulose 20 parts by weight and the sugar-free flavoring agent stevioside 8 parts by weight were weighed and mixed with the total medicinal material fine powder, and the remaining steps were consistent with Example 1.

[0048] Step 3: The protective agent maltodextrin 35 parts by weight (protective agent: filler = 1.75:1) was weighed and added to the total solution to prepare a milky polymer, and the remaining steps were consistent with Example 1.

[0049] Step 4: The spray drying parameters and particle collection steps were consistent with Example 1.

[0050] Example 12 Preparation step Step 1: The medicinal materials were weighed and the extraction and powdering steps were consistent with Example 9.

[0051] Steps 2-3: Consistent with Example 1.

[0052] Step 4: The emulsified polymer was sent into the spray drying tower, the inlet temperature was set to 185℃, the outlet temperature was set to 90℃ (for comparison group 1: the inlet temperature was set to 170℃, the outlet temperature was set to 80℃; for comparison group 2: the inlet temperature was set to 210℃, the outlet temperature was set to 110℃), and the rest of the parameters were consistent with those in Example 1. The granules at different temperatures were collected.

[0053] Example 13 Preparation steps Step 1: The medicinal materials were weighed according to the weight parts, and the first decoction was carried out at high heat (100-105℃) for 80 min, and the second decoction was carried out at low heat (85-90℃) for 35 min (for comparison group 1: high heat for 60 min + low heat for 20 min; for comparison group 2: high heat for 100 min + low heat for 50 min), and the rest of the extraction, concentration, drying, and powdering steps were consistent with those in Example 1.

[0054] Steps 2-4: Consistent with Example 1.

[0055] Comparative Example 1 Preparation steps Step 1: Fried Suanzaoren 50 parts, Zhimu 8 parts, Fuling 20 parts, Chuanqiong 5 parts, and Gancao 8 parts were weighed according to the weight parts (without dates, Maidong, Baihe, and Wuweizi), and the rest of the medicinal materials were extracted, concentrated, dried, and powdered according to the steps consistent with Example 1.

[0056] Steps 2-4: Consistent with Example 9 (auxiliary materials and process same as the best ratio group).

[0057] Comparative Example 2 Preparation steps Step 1: Fried Suanzaoren 50 parts, Zhimu 8 parts, Fuling 20 parts, Chuanqiong 5 parts, Gancao 8 parts, dates 10 parts, Maidong 8 parts, Baihe 8 parts were weighed according to the weight parts (without Wuweizi), and the rest of the medicinal materials were extracted, concentrated, dried, and powdered according to the steps consistent with Example 1.

[0058] Steps 2-4: Consistent with Example 9.

[0059] Comparative Example 3 Preparation steps Step 1: The medicinal materials were weighed and extracted and powdered according to the steps consistent with Example 9.

[0060] Step 2: The filler microcrystalline cellulose 10 parts and sucrose 8 parts (instead of stevioside) were weighed according to the weight parts, mixed and dissolved with the total medicinal material fine powder, and the rest of the steps were consistent with Example 1.

[0061] Steps 3-4: Consistent with Example 9.

[0062] Comparative Example 4 Preparation steps Step 1: The medicinal materials were weighed and extracted and powdered according to the procedure of Example 9.

[0063] Step 2: The filler starch 10 parts and the sugar-free flavoring agent steviol glycoside 8 parts were weighed by weight parts, mixed and dissolved with the total medicinal material fine powder, and the remaining steps were consistent with Example 1.

[0064] Step 3: The protective agent gelatin 20 parts (instead of malt dextrin) was weighed by weight parts and added to the total solution to prepare a milky polymer, and the remaining steps were consistent with Example 1.

[0065] Step 4: Consistent with Example 9.

[0066] Comparative Example 5 Preparation Steps Step 1: The medicinal materials were weighed according to Example 9, and the first decoction was carried out with strong fire (100-105°C) for 60 min, and the second decoction was carried out with gentle fire (85-90°C) for 20 min (deviation from the original process), and the remaining extraction, concentration, drying and powdering steps were consistent with Example 1.

[0067] Steps 2-4: Consistent with Example 9.

[0068] Comparative Example 6 Preparation Steps Steps 1-3: Consistent with Example 9.

[0069] Step 4: The milky polymer was sent into the spray drying tower, the inlet air temperature was set to 170°C, the outlet air temperature was set to 80°C (deviation from the original process), and the remaining parameters were consistent with Example 1, and the granules were collected.

[0070] Performance Verification Active ingredient detection: The contents of acid jujube saponin A and ophiopogon saponin D in the granules were detected by high performance liquid chromatography (HPLC), the chromatographic column was C18 column (250 mm x 4.6 mm, 5 μm), the mobile phase was acetonitrile-water (30:70, v / v), the detection wavelength was 203 nm, the flow rate was 1.0 mL / min, and the column temperature was 30°C.

[0071] Efficacy evaluation: 20 patients who met the diagnostic criteria of primary insomnia in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the diagnostic criteria of spleen deficiency and liver heat syndrome in Chinese Internal Medicine were selected, 2 doses (each dose containing 3 g of granules) were taken daily, and the granules were taken with warm water 1 hour after meals, and were taken continuously for 2 weeks; Pittsburgh Sleep Quality Index (PSQI) scores were used before and after taking for 2 weeks, and the total effective rate (total effective = cure + significant + improvement) was calculated.

[0072] Safety evaluation: 10 cases of type 2 diabetes patients (fasting blood glucose ≤8.3 mmol / L) were selected, and the above scheme was taken. Before and after taking medicine for 2h, blood glucose meter was used to detect postprandial blood glucose, and blood glucose increment was calculated.

[0073] Particle quality detection: the bulk density was detected by cylinder method (10g particles were weighed and poured into a 10mL cylinder, the volume was recorded, and the bulk density = mass / volume); the complete dissolution time of particles in 37℃ warm water was recorded by stopwatch (dissolution time).

[0074] Taste score: 30 healthy volunteers were selected, and the taste of the granules after being taken was scored using a 1-5 point system (1 point = extremely bitter, 5 points = clear sweet).

[0075] Gastrointestinal reaction statistics: the incidence of gastrointestinal discomfort (abdominal distension, nausea) within 2 weeks of taking medicine in 20 patients was recorded.

[0076] Drowsiness / dizziness reaction statistics: the incidence of drowsiness and dizziness symptoms within 2 weeks of taking medicine in 20 patients was recorded.

[0077] Particle stability detection: the particles were stored in a constant temperature and humidity chamber at 40℃ and relative humidity 75% for 30 days, and the moisture absorption rate was detected, moisture absorption rate = (mass after storage-initial mass) / initial mass×100%.

[0078] The performance verification results of the above examples are as follows:

[0079] In the above example 12 data, the target group (185℃ inlet, 90℃ outlet): the content of jujuboside A was 1.52mg / g, and the content of ophiopogonin D was 1.25mg / g; Deviation group 1 (170℃ inlet, 80℃ outlet): the content of jujuboside A was 1.10mg / g, and the content of ophiopogonin D was 0.85mg / g (insufficient drying of the emulsion polymer due to too low temperature, incomplete wrapping of active ingredients, and decreased retention rate); Deviation group 2 (210℃ inlet, 110℃ outlet): the content of jujuboside A was 1.05mg / g, and the content of ophiopogonin D was 0.82mg / g (degradation of heat-sensitive ingredients such as ophiopogonin D due to too high temperature, and decreased retention rate).

[0080] Target group: granule dissolution time 2.0min, caking rate 0% (sufficient atomization, uniform particles, good solubility); Deviation group 1: granule dissolution time 3.5min, caking rate 12% (moisture absorption and caking of particles due to insufficient drying, and poor solubility); Deviation group 2: granule dissolution time 2.8min, caking rate 8% (surface hardening of particles due to high temperature, and decreased solubility).

[0081] Target group: PSQI score decreased from 29.6±4.5 to 16.6±3.3 (improvement range 44%), total effective rate 93.3%; Deviation group 1: PSQI score decreased from 29.6±4.5 to 21.5±3.6 (improvement range 27%), total effective rate 76%; Deviation group 2: PSQI score decreased from 29.6±4.5 to 22.1±3.8 (improvement range 25%), total effective rate 74%.

[0082] In the data of Example 13: Target group (80 min of strong fire + 35 min of gentle fire): content of jujuboside A 1.52 mg / g, content of ophiopogonin D 1.25 mg / g (sufficient and gentle boiling time, both water-soluble components (jujuboside A) and heat-sensitive components (ophiopogonin D) are fully extracted); Deviation group 1 (60 min of strong fire + 20 min of gentle fire): content of jujuboside A 0.95 mg / g, content of ophiopogonin D 0.72 mg / g (insufficient extraction of effective components due to too short time, content significantly decreased); Deviation group 2 (100 min of strong fire + 50 min of gentle fire): content of jujuboside A 1.02 mg / g, content of ophiopogonin D 0.92 mg / g (partial degradation of heat-sensitive components (ophiopogonin D) due to too long time, content decreased).

[0083] Target group: PSQI score decreased from 29.7±4.6 to 16.7±3.4 (improvement range 44%), total effective rate 93.3%; Deviation group 1: PSQI score decreased from 29.7±4.6 to 22.5±3.9 (improvement range 24%), total effective rate 76%; Deviation group 2: PSQI score decreased from 29.7±4.6 to 20.8±3.7 (improvement range 30%), total effective rate 79%.

[0084] Target group: extract water content 4.2%, extract appearance is light yellow loose powder (sufficient drying, no burnt paste); Deviation group 1: extract water content 6.8%, extract appearance is yellow-brown viscous (insufficient extraction leading to more impurities in extract, difficult to dry); Deviation group 2: extract water content 3.9%, extract appearance is dark brown (long time boiling leading to carbonization of medicinal material components, abnormal color of extract).

[0085] The performance verification results of the comparative examples are as follows:

[0086] From the above data, it can be seen that: Example 9 is the optimal ratio, with a content of 1.52 mg / g of Saponin A of Jujube and a content of 1.25 mg / g of Saponin D of Ophiopogon, an improvement of 43.6% in the Pittsburgh Sleep Quality Index (PSQI) score, and a total effective rate of 93.3%, which is significantly better than the control example 1 (total effective rate of 80%) and the control example 2 (total effective rate of 82%) which lack Jujube, Ophiopogon, Lily and Schisandra, proving that the multi-visceral synergistic compatibility of the nine medicinal materials cannot be replaced and is not simply a superposition of medicinal materials.

[0087] Examples 11-13 verify that the necessary parameters are “mass ratio of protective agent to filler 1.75-2:1” “spray drying inlet temperature 185-205℃ / outlet temperature 90-100℃” “boiling with strong fire for 80min and with gentle fire for 35min”: Example 11 (ratio 1.75:1) has an effective component retention rate that is 7% higher than the control group of 1.5:1, Example 12 (inlet temperature 185℃ / outlet temperature 90℃) has a granule melting time of 2.0min and a caking rate of 0%, while the control example 5 (boiling for 60min+20min) has a 37% decrease in effective component content and the control example 6 (inlet temperature 170℃ / outlet temperature 80℃) has a caking rate of 15%, proving that the process parameters can balance the extraction and retention of components, and deviation will lead to quality deterioration.

[0088] Example 9 has a 2h postprandial blood glucose increase of ≤0.48mmol / L (Example 9 only 0.35mmol / L) in diabetic patients, while the control example 3 (sucrose replacement) has a blood glucose increase of 1.80mmol / L and the control example 4 (starch+gelatin replacement) has a granule bulk density of 0.48g / cm 3 , a melting time of 5.2min, proving that sugar-free excipients can avoid blood glucose fluctuations, improve granule quality, and solve the application limitations of traditional sugar-containing preparations.

[0089] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A sugar-free traditional Chinese medicine composition with highly effective sleep-aiding properties, characterized in that, By weight, the raw materials include: 30-50 parts roasted jujube seeds, 3-8 parts anemarrhena rhizome, 10-20 parts poria cocos, 2-6 parts chuanxiong rhizome, 2-8 parts licorice root, 2-10 parts jujube, 3-8 parts ophiopogon root, 2-8 parts lily bulb, 2-10 parts schisandra fruit, 10-25 parts filler, 20-45 parts protectant, and 8-15 parts sugar-free flavoring agent; the filler is selected from one or more of hydroxypropyl methylcellulose, starch, methylcellulose, gum arabic, sodium alginate, pectin, or microcrystalline cellulose; the protectant is selected from one or more of dextrin, dextran, bovine serum albumin, or gelatin; the sugar-free flavoring agent is aspartame or steviol glycoside; and the mass ratio of the protectant to the filler is (1.75-2):

1.

2. The sugar-free traditional Chinese medicine composition with high efficacy in aiding sleep as described in claim 1, characterized in that, By weight, the ingredients include: 40-50 parts of stir-fried jujube seeds, 4-8 parts of anemarrhena rhizome, 15-20 parts of poria cocos, 4-6 parts of chuanxiong rhizome, 4-8 parts of licorice root, 5-10 parts of jujube, 5-8 parts of ophiopogon root, 5-8 parts of lily bulb, and 5-10 parts of schisandra fruit.

3. The sugar-free traditional Chinese medicine composition with high sleep-aiding efficacy as described in claim 1, characterized in that, The filler is microcrystalline cellulose, the preservative is maltodextrin, and the sugar-free flavoring agent is steviol glycoside.

4. The sugar-free traditional Chinese medicine composition with high efficacy in aiding sleep as described in claim 1, characterized in that, The mass ratio of the protective agent to the filler is 1.75:

1.

5. A method for preparing a sugar-free traditional Chinese medicine composition with high efficacy for sleep as described in any one of claims 1-4, characterized in that, Includes the following steps: S1: The Chinese medicinal materials in the Chinese herbal composition are decocted twice with water, and the decoctions are combined, concentrated and dried to prepare a fine powder of total medicinal materials; the first decoction is carried out over high heat for 80 minutes, and the second decoction is carried out over low heat for 35 minutes. S2: Mix the total fine powder of medicinal materials with fillers and sugar-free flavoring agents until uniform, then add water accounting for 5-7% of the total mixture mass to fully dissolve and prepare a total solution containing medicinal materials; S3: The protective agent and the total solution containing the medicinal ingredients are mechanically stirred and mixed evenly at 5-40°C, and then water is added and stirred into an emulsion to prepare an emulsion polymer containing the medicinal ingredients; S4: The emulsion polymer is placed in a spray drying tower for drying. The inlet air temperature of the spray drying tower is 185-205℃ and the outlet air temperature is 90-100℃ to prepare sugar-free granules.

6. The preparation method according to claim 5, characterized in that, In step S4, the inlet air temperature of the spray drying tower is 185°C and the outlet air temperature is 90°C.

7. The preparation method according to claim 5, characterized in that, In step S1, the temperature for the first decoction is 100-105℃, and the temperature for the second decoction is 85-90℃.

8. The preparation method according to claim 5, characterized in that, In step S1, the total medicinal material powder prepared after concentration and drying is passed through an 80-mesh sieve, and the concentration and drying temperature is 50-60℃, and the drying time is 40-80min.

9. The use of a sugar-free traditional Chinese medicine composition with high sleep-inducing efficacy as described in any one of claims 1-4 in the preparation of an oral formulation for treating primary insomnia in people with diabetes phobia, characterized in that, The group of people who are afraid of sugar includes patients with diabetes or obesity.

10. The application as described in claim 9, characterized in that, The oral preparation is a granule, hard capsule, or ordinary tablet.

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