A traditional Chinese medicine functional oral liquid for improving sleep and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine functional oral liquid for improving sleep and a preparation method thereof. The oral liquid is prepared from traditional Chinese medicine extracts and auxiliary materials, and is prepared according to the theory of monarch, minister, assistant and guide in traditional Chinese medicine. The preparation method comprises five steps of medicine classification, batch pre-treatment, extraction, product preparation and sterilization filling. The low-temperature solid-state pre-fermentation of plant lactobacillus and saccharomyces cerevisiae is adopted for the fermentation medicine, and the physical pre-treatment is adopted for the medicine not suitable for fermentation. The three-stage extraction is carried out by using composite enzymes, composite solvents and composite wrapping systems. The application solves the technical defects of low extraction rate, poor stability, bitter taste, poor industrial suitability and the like of traditional Chinese medicine functional oral liquid, the particle size of the effective components of the product is controlled to be between 100-300 nm, the product has high dissolution rate, strong stability and suitable taste, has the effects of improving sleep and resisting anxiety, has high safety, has low energy consumption and cost, and is suitable for industrial popularization and application.

Description

Technical Field

[0001] This invention relates to the field of functional food and traditional Chinese medicine extraction technology, specifically to a functional oral liquid of traditional Chinese medicine with the effects of improving sleep and relieving anxiety, and its industrial preparation method. Background Technology

[0002] With the fast pace of modern life, insomnia and anxiety have become prevalent physical and mental health problems, seriously affecting people's quality of life. The "2025 China Sleep Health Survey Report" shows that the sleep disturbance rate among people aged 18 and above in my country reaches 48.5%. Among them, the sleep disturbance rate for women (51.1%) is higher than that for men (45.9%), and the highest rate of sleep disturbance is 73.7% in the 65-year-old and above age group. Those born in the 2000s (18-24 years old) often experience insufficient energy and drowsiness due to sleep problems. Currently, commonly used chemically synthesized sedative-hypnotic and anti-anxiety drugs have a rapid onset of action, but long-term use can easily lead to dependence, drug tolerance, and side effects such as dizziness and drowsiness, and rebound effects are common after discontinuation.

[0003] Traditional Chinese medicine has accumulated rich experience in calming the mind and aiding sleep. Many related herbal formulas use ingredients such as jujube seed and fleeceflower root as core raw materials. However, existing herbal calming products suffer from significant technical defects when converted into functional oral liquids: First, the extraction rate of effective components is low. Traditional decoction or single-solvent extraction processes are insufficient to fully dissolve both fat-soluble and water-soluble active ingredients, and the dense cell wall structure of medicinal materials makes it difficult to release the effective components. Second, the product has poor stability; effective components are easily oxidized, precipitated, and separated, resulting in a short shelf life. Existing encapsulation technologies are also ill-suited to the complex component systems of traditional Chinese medicine. Third, the taste is bitter and unpalatable to consumers; traditional flavoring methods cannot neutralize the medicinal taste at its source. Fourth, the formulation lacks systematic optimization, failing to establish a clear principal-assistant-adjuvant system, resulting in insignificant synergistic effects. Fifth, the process lacks innovation, mostly relying on conventional extraction-concentration-blending processes without incorporating advanced technologies such as fermentation and enzymatic hydrolysis. This fails to solve common technical problems in the industry, and results in high energy consumption, high costs, and limited industrial applicability.

[0004] In the existing technology, some Chinese medicine extraction processes still have many shortcomings, failing to effectively solve problems such as insufficient extraction of effective components and poor product stability, and thus failing to meet the production needs of related functional oral liquids.

[0005] Therefore, developing a functional oral liquid of traditional Chinese medicine with a scientific formula, innovative process, high dissolution rate of effective ingredients, strong stability, pleasant taste, and dual effects of improving sleep and relieving anxiety, especially by optimizing the preparation process and solving the defects of the existing process, has important practical application value. Summary of the Invention

[0006] This invention addresses the shortcomings of existing technologies by providing a functional oral liquid made from traditional Chinese medicine (TCM) for improving sleep and relieving anxiety, along with its preparation method. By classifying and processing the medicinal materials, combining fermentation pretreatment, enzymatic hydrolysis, and compound solvent extraction techniques, and employing a composite encapsulation system, the invention achieves synergistic enhancement of active ingredients, improved product stability, and improved taste, overcoming the technical defects of low extraction rate and poor stability in traditional products. The technical solution adopted by this invention is as follows: A functional oral liquid made from traditional Chinese medicine for improving sleep and relieving anxiety, comprising TCM extracts and excipients: The TCM extracts are made from the following raw materials in parts by weight: 18-22 parts roasted jujube seed, 15-18 parts Polygonum multiflorum vine, 12-15 parts Salvia miltiorrhiza, 12-15 parts Ligustrum lucidum, 6-9 parts vinegar-processed Bupleurum chinense, 1.5-2.5 parts cinnamon, 22-28 parts calcined oyster shell, 10-12 parts Poria cocos, and 9-12 parts lily bulb. The excipients include: gum arabic, xylitol, citric acid, steviol glycosides, and xanthan gum.

[0007] The formula of this invention follows the traditional Chinese medicine theory of "principal, assistant, adjuvant, and guide," with rigorous formulation. The principal ingredient is stir-fried jujube seed, which nourishes the heart and liver, calms the mind and soothes the nerves, serving as the core ingredient for treating insomnia and anxiety, directly targeting the pathogenesis. The assistant ingredients are calcined oyster shell, Polygonum multiflorum vine, and Salvia miltiorrhiza. Calcined oyster shell has a strong calming effect, Polygonum multiflorum vine nourishes blood, calms the mind, clears the heart and relieves irritability, and Salvia miltiorrhiza invigorates blood and cools the blood; these three ingredients work synergistically with the principal ingredient to enhance sleep-aiding and anti-anxiety effects. The adjuvant ingredients are Ligustrum lucidum, vinegar-processed Bupleurum chinense, and lily bulb. Ligustrum lucidum nourishes yin and tonifies the kidneys, vinegar-processed Bupleurum chinense soothes the liver and regulates qi, and lily bulb nourishes yin, moistens the lungs, clears the heart and soothes the nerves; these three ingredients work together to nourish yin, soothe the liver, and clear deficiency fire, improving insomnia caused by deficiency and irritability. The guiding ingredients are cinnamon and Poria cocos. Cinnamon guides the fire back to its source and directs the medicine to the heart and kidneys, while Poria cocos strengthens the spleen, calms the mind, and harmonizes the other ingredients, balancing therapeutic effects with spleen and stomach care, ensuring the formula is mild and non-irritating. Optionally, the following proportions of Chinese medicinal materials by weight are: 20 parts of stir-fried jujube seed, 16 parts of Polygonum multiflorum vine, 13 parts of Salvia miltiorrhiza, 13 parts of Ligustrum lucidum, 7 parts of vinegar-processed Bupleurum chinense, 2 parts of cinnamon, 25 parts of calcined oyster shell, 11 parts of Poria cocos, and 10 parts of lily bulb.

[0008] The preparation method of the above-mentioned functional oral liquid of traditional Chinese medicine follows the process route of medicinal material classification, batch pretreatment, combined extraction, and finished product formulation, and specifically includes the following steps: (1) Classification of medicinal materials: Chinese medicinal materials are classified into "suitable for fermentation / unsuitable for fermentation". Medicinal materials suitable for fermentation include: stir-fried jujube seed, Polygonum multiflorum vine, Salvia miltiorrhiza, Ligustrum lucidum, lily bulb, and Poria cocos. These medicinal materials are rich in cellulose and pectin, which can promote the release of effective components after fermentation and are less prone to degradation of medicinal components. Medicinal materials unsuitable for fermentation include: vinegar-processed Bupleurum chinense, cinnamon, and calcined oyster shell. These medicinal materials contain volatile oils or heat-sensitive components, and fermentation will lead to component loss and decreased efficacy.

[0009] (2) Batch pretreatment: First, for medicinal materials suitable for fermentation: solid-state low-temperature pre-fermentation is adopted, using Lactobacillus plantarum + Saccharomyces cerevisiae (weight ratio 1:1) as the strains, with the amount of each strain added being 0.05% of the dry weight of the medicinal material. Fermentation conditions: material moisture content is controlled at 55% to 65%, fermentation temperature is 30℃ to 35℃, fermentation time is 48h to 72h, and the entire process is kept away from light and sealed to ensure stable fermentation and avoid contamination by other microorganisms. After fermentation, the material is dried at 60℃ until the moisture content is ≤10%, pulverized to 40 mesh, and screened to remove impurities for later use. This mesh size ensures sufficient contact with the solvent during subsequent extraction and avoids clogging of the filter due to excessively fine particles. For medicinal materials unsuitable for fermentation, physical pretreatment is carried out directly, pulverizing to 40 mesh and screening to remove impurities. This avoids loss of volatile oils and degradation of heat-sensitive components, ensuring maximum preservation of efficacy.

[0010] (3) Combined Extraction: According to the formula ratio, the fermented pretreated medicinal materials and the physically pretreated medicinal materials are mixed evenly and put into the extraction tank. Low-speed stirring is used during mixing. Then the extract is prepared. Among them, pectinase:cellulase = 1:1 (weight ratio), and the amount used is 0.4% of the dry weight of the medicinal materials. It synergistically decomposes the cell wall and intercellular adhesion substances of the medicinal materials, and improves the dissolution rate of effective ingredients; and hydroxylated soybean phospholipid:glycerol:mono- and diglycerides = 1:1:3 (weight ratio) is used as a composite encapsulation system to protect the effective ingredients. The total amount of composite emulsifying encapsulation agent is 2% to 4% of the dry weight of the medicinal materials. The solvent used is: ethanol:propylene glycol:purified water = 12:6:82 (volume ratio) to form a gradient polarity solvent system, which takes into account the dissolution of lipid-soluble, water-soluble and moderately polar effective ingredients. The extraction solution preparation method is: first add the enzyme and encapsulation system to the composite solvent. The total amount of solvent is 4 or 5 times the volume of the dry weight of the medicinal materials (weight KG / volume L). Stir at 40-50℃ and 80r / min until completely transparent to ensure uniformity of the system and avoid excessively high local concentrations that could affect enzyme activity and encapsulation effect.

[0011] This invention employs a three-stage extraction method. The first stage involves adding the aforementioned extract (containing 5 times the weight of the medicinal materials by volume of a compound solvent, in kg / L) to the mixed medicinal materials, stirring thoroughly, adjusting the pH to 4.5–5.0, and extracting at a constant temperature of 50°C for 60 minutes. The extract is then filtered through a 300-mesh filter, and the first-stage extract and residue are collected. The second stage involves adding the extract (containing 4 times the weight of the medicinal materials by volume of a compound solvent, in kg / L) to the residue, extracting at a constant temperature of 50°C for 60 minutes, and filtering through a 300-mesh filter. The second-stage extract and residue are collected. The third stage involves repeating the second stage, extracting at a constant temperature of 50°C for 60 minutes, filtering through a 300-mesh filter, and collecting the third-stage extract and residue. The residue is discarded, and the first, second, and third-stage extracts are combined and mixed thoroughly for later use.

[0012] (4) Preparation of finished product: First, transfer the combined three-stage extract into a vacuum concentrator. Flash evaporate the ethanol at 50-55℃ and a vacuum of -0.092 to -0.095 MPa, using the ethanol vapor phase to carry some propylene glycol, until the liquid has no alcohol odor and the ethanol content of the condensate is <3%. Then, concentrate the solution under vacuum at 60℃, controlling the vacuum degree to -0.08 to -0.09 MPa. After the solution becomes viscous, continue to add pure water. When the water vaporizes, the water vapor carries the propylene glycol and evaporates simultaneously. Repeat this process 3-5 times, adding water to concentrate the solution until the specific gravity is 1.04-1.05 g / mL. The concentrate is concentrated at low temperature to avoid oxidative degradation of heat-sensitive active ingredients. Then, the concentrate is filtered through a 400-mesh sieve to remove minute impurities and insoluble particles, improving the clarity of the finished product. Finally, the finished product is formulated: excipients such as xylitol, citric acid, steviol glycosides, gum arabic, and xanthan gum are added to the filtered concentrate. The total amount of excipients is added at 8% of the total weight of the concentrate, and the proportions of the excipients are: gum arabic 4 parts, xylitol 80 parts, citric acid 0.8 parts, steviol glycosides 0.8 parts, and xanthan gum 0.8 parts. Gum arabic and xanthan gum can be pre-dissolved or mixed with other dry powders and stirred at 80°C until completely dissolved.

[0013] (5) Filling and sterilization: The prepared liquid is aseptically filled and sterilized by high-pressure steam at 120℃ for 15-30 minutes. After cooling to room temperature, it is packaged to obtain the finished product.

[0014] This invention breaks through the limitations of traditional Chinese medicine extraction processes. Based on the characteristics of the medicinal materials, it categorizes them into "suitable for fermentation" and "unsuitable for fermentation." Suitable fermentation materials undergo dual-strain solid-state low-temperature pre-fermentation, while unsuitable materials are subjected to low-temperature physical pulverization. This achieves both cell wall disruption and enhanced efficacy for suitable fermentation materials and avoids the loss of efficacy for unsuitable materials, solving the technical problem of existing processes where pretreatment methods are singular and efficacy preservation and extraction efficiency cannot be simultaneously achieved. Furthermore, it employs a 1:1 blend of *Lactobacillus plantarum* and *Saccharomyces cerevisiae*. *Lactobacillus plantarum* produces cellulase and pectinase to decompose cell walls, and lactic acid regulates the optimal pH for enzymatic hydrolysis, eliminating the need for additional acidification. *Saccharomyces cerevisiae* supplements the decomposition of β-glucan and lignin, achieving more thorough cell wall disruption. Simultaneously, the trace amounts of ethanol produced enhance the solubility of fat-soluble components, and ester aroma substances neutralize the bitterness of the Chinese medicine. The effect is significantly better than single-strain fermentation, and the resulting food-grade strains are highly safe and suitable for the production of functional oral liquids. This invention designs an extraction system combining "compound enzymes, compound solvents, and compound encapsulation" to enhance the dissolution and stability of active ingredients, solving the industry problems of easy precipitation and oxidation in traditional Chinese medicine oral liquids. The oral liquid of this invention utilizes nano-encapsulation technology to process Chinese medicine components, possessing multiple core advantages: First, it boasts a high extraction rate of active ingredients and excellent dispersibility; the nano-sized particles ensure uniform dispersion of active ingredients within the system, preventing clumping and stratification, significantly improving stability. Second, it offers a superior sensory experience; the oral liquid is highly transparent, clear, visually appealing, and has a smooth, impurity-free taste. Third, it exhibits outstanding solubility; active ingredients dissolve quickly and fully without additional stirring, making it convenient to drink. Fourth, it significantly improves absorption efficiency; nano-encapsulation technology breaks down the biological barriers of active ingredients, promoting rapid dissolution and preventing precipitation, greatly enhancing the bioavailability of active ingredients in Chinese medicine. This allows the body to better absorb and utilize the effects of nourishing the heart and calming the mind, nourishing yin and soothing the liver, fully realizing the medicinal value of the formula. Attached Figure Description

[0015] Figure 1 The particle size of the product in Example 1 is determined by dynamic evaporation light scattering detection.

[0016] Figure 2 This refers to the particle size of the product in Example 2 of the dynamic evaporation light scattering detection.

[0017] Figure 3 The particle size of the product in Example 3 is determined by dynamic evaporation light scattering detection.

[0018] Figure 4 This refers to the particle size of the product in Example 4 of the dynamic evaporation light scattering detection. Detailed Implementation

[0019] Example 1 Industrial Production 1. Classification of medicinal materials: Divided into those suitable for fermentation and those unsuitable for fermentation. Suitable for fermentation: Fried jujube seed 23.32kg, Polygonum multiflorum vine 15.90kg, Salvia miltiorrhiza 15.90kg, Ligustrum lucidum 12.72kg, Lilium brownii 12.72kg, Poria cocos 12.72kg; Unsuitable for fermentation: Vinegar-processed Bupleurum chinense 9.54kg, Cinnamomum cassia 2.12kg, Calcined oyster shell 28.62kg.

[0020] 2. Batch preprocessing: ① Suitable for fermented medicinal materials: Take 0.09 kg each of Lactobacillus plantarum and Saccharomyces cerevisiae (1:1), spray them evenly on the surface of the medicinal materials, adjust the humidity of the materials to 60%, and ferment them at 32℃ in the dark for 60 hours. After fermentation, dry them at 60℃ until the moisture content is ≤10%, crush them to 40 mesh, screen them to remove impurities, and set them aside for later use. ② Not suitable for fermented medicinal materials: Grind to 40 mesh and screen to remove impurities.

[0021] 3. Combined extraction + enzymatic hydrolysis + compound solvent extraction: ① Material mixing: Mix the two types of pretreated medicinal materials evenly, put them into the extraction tank, and stir at low speed (60r / min) for 5 minutes to ensure uniform mixing; ② Preparation of extract: Take 0.53 kg of pectinase, 0.53 kg of cellulase (1:1), 0.80 kg of hydroxylated soybean lecithin, 0.80 kg of glycerol, and 2.40 kg of mono- and diglycerides (1:1:3), add 80 L of ethanol, 40 L of propylene glycol, and 548 L of purified water, stir at 50 °C and 80 r / min until completely transparent to prepare a single extract; ③ Three-stage extraction: For the first-stage extraction, add the above-mentioned extract, stir evenly, adjust the pH to 4.5-5.0, extract at 50℃ for 60 minutes, filter with a 300-mesh filter cloth, and collect the first-stage extract and the residue; For the second-stage extraction, add the same extract to the residue, wherein the volume of ethanol, propylene glycol, and purified water in the extract is 80% of the solvent volume in the first-stage extraction, extract at 50℃ for 60 minutes, filter and collect the second-stage extract and the residue; For the third-stage extraction, repeat the second-stage operation and collect the third-stage extract and the residue; Combine the third-stage extracts and mix well.

[0022] 4. Preparation of finished product: Transfer the combined extract into a vacuum concentrator. Maintain a temperature of 50-55℃ and a vacuum of -0.092 to -0.095 MPa until the liquid has no alcohol odor and the ethanol content of the condensate is <3%. Then, concentrate under vacuum at 60℃ and -0.085 MPa. After the solution becomes viscous, add water four more times and concentrate under vacuum until the specific gravity is 1.045 g / mL. Filter through a 400-mesh sieve to obtain 33 L of concentrated liquid. Add 0.122 kg of gum arabic, 2.442 kg of xylitol, 0.024 kg of citric acid, 0.024 kg of steviol glycosides, and 0.024 kg of xanthan gum. Gum arabic and xanthan gum can be pre-dissolved or the above powders can be mixed before adding the concentrate. Stir at 80℃ and 100 r / min for 20 min until completely dissolved, and keep warm for 15 min.

[0023] 5. Filling and sterilization: Fill aseptically at 20mL / bottle, autoclave at 120℃ for 15min, cool to room temperature and then package to obtain the finished product.

[0024] Example 2: Industrial Production of Other Formulas The principal herb is Ziziphus jujuba seed, which nourishes the heart and liver, and calms the mind and spirit. The assistant herb is Gastrodia elata combined with Ganoderma lucidum and jujube, which calms wind and stops spasms, suppresses liver yang, and replenishes qi and calms the mind. The adjuvant herb is Ostrea gigas combined with Dendrobium officinale, mulberry, cinnamon, and Rehmannia glutinosa, which sedates the mind, subdues yang and replenishes yin. The guiding herb is Glycyrrhiza uralensis, which tonifies the spleen and replenishes qi, and harmonizes the effects of the other herbs.

[0025] 1. Classification of medicinal materials: Suitable for fermentation: 22.90kg of jujube seed, 23.20kg of mulberry, 13.19kg of jujube, 13.19kg of dendrobium officinale, 13.19kg of ganoderma lucidum, 15.82kg of rehmannia glutinosa, and 15.82kg of gastrodia elata; Unsuitable for fermentation: 7.92kg of cinnamon, 23.20kg of calcined oyster shell, and 7.92kg of licorice.

[0026] 2. Pre-treatment in batches ~ 5. Filling and sterilization: Same as the steps in Example 1, with the amounts of enzyme, encapsulation system and solvent adjusted according to the dry weight of the medicinal materials.

[0027] Example 3: Industrial production of other formulations The principal herb is stir-fried jujube seed, which nourishes the heart and liver, and calms the mind. The assistant herb is arborvitae seed combined with wolfberry, Solomon's seal, and ophiopogon. Arborvitae seed nourishes the heart and calms the mind, and moistens the intestines to relieve constipation. Wolfberry nourishes the liver and kidneys, and benefits essence and improves eyesight. Solomon's seal nourishes yin and moistens dryness, and generates fluids to quench thirst. Ophiopogon nourishes yin and generates fluids, and moistens the lungs and clears the heart. The four herbs work together to assist the principal herb in calming the mind. The adjuvant herb is calcined oyster shell combined with albizia bark, polygala root, and tangerine peel. Calcined oyster shell has a strong calming effect, and can suppress yang and nourish yin. Albizia bark relieves depression, calms the mind, promotes blood circulation and reduces swelling. Polygala root calms the mind and improves intelligence. Tangerine peel regulates qi and strengthens the spleen. The guiding herb is licorice root, which tonifies the spleen and benefits qi, and harmonizes the herbs.

[0028] 1. Classification of medicinal materials: Suitable for fermentation: stir-fried jujube seed 24.42kg, cypress seed 14.65kg, wolfberry 24.42kg, Solomon's seal 12.21kg, ophiopogon japonicus 12.21kg, dried tangerine peel 7.33kg, albizia bark 14.65kg; Not suitable for fermentation: calcined oyster shell 24.42kg, polygala tenuifolia 9.77kg, licorice 7.33kg.

[0029] 2. Pre-treatment in batches ~ 5. Filling and sterilization: Same as the steps in Example 1, with the amounts of enzyme, encapsulation system and solvent adjusted according to the dry weight of the medicinal materials.

[0030] Example 4: Industrial production of other formulations The principal herb is Ziziphus jujuba seed, which nourishes the heart and liver, and calms the mind. The assistant herbs are Polygonum multiflorum stem combined with Schisandra chinensis, Nelumbo nucifera seed, and Dioscorea opposita. Polygonum multiflorum stem nourishes blood and calms the mind, dispels wind and unblocks the meridians. Schisandra chinensis astringes and consolidates, replenishes qi and generates fluids, and tonifies the kidneys and calms the mind. Nelumbo nucifera seed tonifies the spleen and stops diarrhea, benefits the kidneys and astringes essence, and nourishes the heart and calms the mind. Dioscorea opposita tonifies the spleen and stomach, generates fluids and benefits the lungs, and tonifies the kidneys and astringes essence. The four herbs work together to assist the principal herb in calming the mind and are thus the assistant herbs. The adjuvant herbs are calcined oyster shell combined with Paeonia lactiflora, Ligusticum chuanxiong, and ginger. Calcined oyster shell has a strong calming effect, suppresses yang and replenishes yin. Paeonia lactiflora nourishes blood and softens the liver. Ligusticum chuanxiong invigorates blood and promotes qi circulation. Ginger relieves exterior symptoms and dispels cold and is thus the adjuvant herbs. The guiding herb is Glycyrrhiza uralensis, which tonifies the spleen and replenishes qi, and harmonizes the herbs.

[0031] 1. Classification of medicinal materials: Suitable for fermentation: 24.42 kg of jujube seed, 19.54 kg of Polygonum multiflorum stem, 9.77 kg of Schisandra chinensis fruit, 14.65 kg of lotus seed, 19.54 kg of yam, and 12.21 kg of white peony root; Not suitable for fermentation: 28.56 kg of calcined oyster shell, 7.33 kg of Ligusticum chuanxiong rhizome, 7.33 kg of licorice root, and 5.50 kg of ginger.

[0032] 2. Pre-treatment in batches ~ 5. Filling and sterilization: Same as the steps in Example 1, with the amounts of enzyme, encapsulation system and solvent adjusted according to the dry weight of the medicinal materials.

[0033] Example 5: Quality testing was performed on the products from Examples 1-4 above. Testing of the product formulated in Example 1 Sensory indicators: The finished product is a clear and transparent liquid with a light brown color. It has no sediment, layering or suspended matter. It has the unique fragrance of Chinese medicine and a faint natural aroma produced by fermentation. It has a mellow taste and no bitterness. Physicochemical properties: specific gravity 1.04~1.05g / mL, pH value 4.8~5.5, total solid content ≥8.5%, jujube seed saponin A content ≥0.22mg / mL; Microbiological indicators: total bacterial count ≤100 CFU / mL, coliform bacteria ≤3 CFU / mL, molds and yeasts ≤10 CFU / mL, pathogenic bacteria (Salmonella, Staphylococcus aureus, Shigella) not detected; Stability test: The product was stored at room temperature and sealed for 24 months. The sensory, physicochemical and microbiological indicators all met the requirements. There was no precipitation or stratification. The stability was improved compared with the traditional process.

[0034] Testing of the formulation product of Example 2 Sensory indicators: Clear and transparent liquid, dark brown in color, without sediment, layering or suspended matter, with the unique aroma of Ganoderma lucidum and jujube as well as the natural aroma of fermentation, sweet taste and no off-flavor; Physicochemical properties: specific gravity 1.04~1.05g / mL, pH value 5.0~5.8, total solids content ≥9.0%, jujube seed saponin A content ≥0.18mg / mL, Ganoderma lucidum polysaccharide content ≥0.28mg / mL; Microbiological and stability indicators: Same as the formulation standard in Example 1, with improved stability compared to traditional processes.

[0035] Testing of the formulation product of Example 3 Sensory indicators: Clear and transparent liquid, light brownish-yellow, with the unique aroma of cypress seed and goji berry, as well as the natural aroma of fermentation, and a sweet and slightly sour taste; Physicochemical properties: specific gravity 1.04~1.05g / mL, pH value 4.9~5.6, total solid content ≥8.8%, jujube seed saponin A ≥0.19mg / mL, cypress seed oil ≥0.12mg / mL; Microbiological and stability indicators: Same as the formulation standard in Example 1, with improved stability compared to traditional processes.

[0036] Testing of the formulation product of Example 4 Sensory indicators: Clear and transparent liquid, brownish-yellow in color, with a fragrance of Polygonum multiflorum vine, lotus seeds and natural fermentation aroma, and a sweet and mild taste with no off-flavors; Physicochemical properties: specific gravity 1.04~1.05g / mL, pH value 5.1~5.9, total solid content ≥8.7%, jujube seed saponin A ≥0.16mg / mL, schisandrin A ≥0.09mg / mL; Microbiological and stability indicators: Same as the formulation standard in Example 1, with improved stability compared to traditional processes.

[0037] Furthermore, dynamic evaporation light scattering is used for particle size detection of the product of this invention, and the particle size is controlled within the range of 100-300 nanometers. The particle size test results for Examples 1-4 are shown below. Figures 1-4 As shown.

[0038] Example 6: Process Comparison Test Comparative Example 1 (Traditional Process) The medicinal materials of Example 1 were processed using traditional steps: raw material pretreatment (pulverized to 40 mesh) → extract preparation (20% ethanol + 80% water) → gradient reduction three-stage extraction (50℃, 3h, 2h, 1h) → simultaneous inclusion and concentration → blending → filtration (400 mesh) → filling and sterilization; the remaining parameters were the same as those of Example 1 (same formula and raw material dosage).

[0039] Comparative Example 2 (Fermentation Pretreatment Only) Process steps: Medicinal material classification in Example 1 → Suitable for fermentation: single Lactobacillus plantarum fermentation (without Saccharomyces cerevisiae) → Unsuitable for fermentation: physical pretreatment → Combined extraction (single 20% ethanol solvent, no enzymatic hydrolysis, no complex encapsulation) → Concentration → Filtration → Blending → Filling and sterilization; other parameters are the same as in Example 1.

[0040] Comparative Example 3 (enzymatic hydrolysis only + compound solvent) Process steps: The medicinal materials in Example 1 are not classified or fermented, and are directly pulverized to 40 mesh → preparation of integrated extract (compound enzyme + compound solvent, no compound coating) → three-stage extraction → concentration → filtration → blending → filling and sterilization; the remaining parameters are the same as in Example 1.

[0041] Comparative Example 4 (Medicinal herbs are not classified, all are fermented) Process steps: All medicinal materials were fermented with two strains under the fermentation conditions of Example 1 → combined extraction + enzymatic hydrolysis + compound solvent → concentration → filtration → blending → filling and sterilization; the remaining parameters were the same as in Example 1.

[0042] Table 1 Comparative test results As can be seen from the above comparative experiments, all indicators of Example 1 of the present invention are significantly better than those of the comparative examples: (1) Extraction rate of effective components: The extraction rates of jujube seed saponin A and tanshinone IIA in Example 1 reached 89.6% and 87.3% respectively, which were 46.4% and 48.2% higher than those of traditional processes, and also higher than those of comparative examples 2, 3 and 4; the cell walls of the medicinal materials were completely broken, and the dissolution of effective components with different polarities was taken into account, which solved the problem of insufficient extraction by traditional processes.

[0043] (2) Stability of finished product: After being stored at room temperature and sealed for 24 months, Example 1 showed a 100% sedimentation and stratification rate, which is 35 percentage points higher than the traditional process and 18-25 percentage points higher than other comparative examples. The composite encapsulation system works synergistically with the polysaccharides and mannans produced by fermentation to provide full protection for the active ingredients, avoiding oxidative degradation and precipitation, thus solving the common industry problem of poor stability of traditional Chinese medicine oral liquids.

[0044] (3) Taste score: The taste score of Example 1 was 9.2 points, which was significantly higher than that of each comparison ratio (6.8~7.8 points). The reason is that the esters and alcohols produced by the dual-strain fermentation neutralized the bitter taste of the Chinese medicine, while the peptides and amino acids improved the taste. No additional flavoring agents were needed, which improved the taste and reduced the cost.

[0045] Test data (a) Animal experiments 1. Experimental Materials and Design Experimental animals: 144 ICR mice, weighing 20-22g, were randomly divided into 12 groups (n=12 per group): blank control group, model control group, positive control group (diazepam tablets, 0.5mg / kg), the complete formula of Example 1, the formula of Example 2, the formula of Example 3, the formula of Example 4, the single-herb stir-fried jujube seed group, the single-herb calcined oyster shell group, the formula of Example 1 without the principal herb (removing the stir-fried jujube seed), the formula of Example 2 without jujube seed, and the formula of Example 3 without cypress seed.

[0046] Model establishment: An insomnia model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA), and an anxiety model was established by an elevated cross maze.

[0047] Administration method: Each Chinese medicine group was administered 10g / kg of raw herb by gavage once a day for 7 consecutive days; the positive control group was administered diazepam by gavage at a dose of 0.5mg / kg, and the blank control group and the model control group were administered an equal volume of physiological saline by gavage.

[0048] 2. Experimental Results Table 2 Effects on sleep in mice (X±SD, n=12) Note: A blank control group was set up simultaneously in this experiment. The sleep latency and sleep duration of the mice in this group were within the normal physiological range, and the difference compared with the model control group was statistically significant (P<0.01), confirming the successful establishment of the insomnia model. This table focuses on showing the intervention effect of each group of drugs on the insomnia model, so the specific values ​​of the blank group are not listed. Compared with the model control group, P<0.05, P<0.01; Compared with the complete formula group of Example 1, the sleep latency of the formula groups of Examples 2-4 was increased and the sleep duration was decreased (P<0.05). The single herb group and the group without the main herb were significantly weaker than the complete formula group of Example 1 (P<0.05).

[0049] Table 3 Effects on anxiety behavior in mice (elevated cross maze, X±SD, n=12) Note: Compared with the model control group. P<0.05, P<0.01; Compared with the full formula group of Example 1, the number of times the open arm entered and the dwell time of the open arm in the formula groups of Examples 2-4 were statistically different (P<0.05), and there was a gradient difference between the groups; the single herb group and the group without the principal herb were weaker than the full formula group of Example 1 (P<0.05).

[0050] Table 4 Effects on neurotransmitters and BDNF in mice (X±SD, n=12) Note: Compared to the model group, P<0.05, P<0.01; Compared with the formulation group of Example 1, the levels of 5-HT, GABA, and BDNF in the formulation groups of Examples 2-4 were all reduced, the level of Glu was increased, and the GABA / Glu ratio was reduced (all P<0.05), showing a gradient difference between groups; the improvement effect of the single herb group and the group without the principal herb was significantly weaker than that of the full formula group of Example 1 (P<0.05).

[0051] (II) Clinical Validation 1. Clinical trial 1: The formula in Example 1 improves sleep. Subjects: 60 patients with insomnia who met the diagnostic and therapeutic criteria of traditional Chinese medicine were randomly divided into an experimental group (n=30) and a control group (n=30). Methods: The experimental group took the finished product of the formula in Example 1 (1 bottle / time, once a day, 30 minutes before bedtime, one bottle is equivalent to the original dose of raw herbs (30g / bottle)), while the control group received routine health guidance. The cycle was 14 days. The results are as follows: Table 5. Improvement effect on insomnia (X±SD) Note: Compared with the pre-treatment values ​​in this group. P<0.01; Compared with the control group after treatment, ##P<0.01.

[0052] 2. Clinical Validation 2: Anxiety Relief Effect of Formula in Example 1 Methods: The SAS (Self-Rating Anxiety Scale) and SDS (Self-Rating Depression Scale) were used for assessment, with other conditions the same as in Clinical Validation 1; Results are as follows: Table 6. Effects on Mood Improvement (X±SD) Note: Compared with the pre-treatment values ​​in this group. P<0.01; Compared with the control group after treatment, ##P<0.01.

[0053] 3. Clinical validation 3, the improvement effect of the formulation in Example 2. Subjects: 60 patients with insomnia and anxiety due to yin deficiency and blood deficiency were randomly divided into an experimental group (n=30) and a control group (n=30). Methods: The experimental group took the finished product formula from Example 2 (1 bottle / time, once a day, 30 minutes before bedtime, one bottle is equivalent to the original dose of raw herbs (30g / bottle)), while the control group received routine health guidance (a light and balanced diet, drinking plenty of water, eating less oily and sweet foods, maintaining moderate exercise, and relieving stress and regulating emotions). The treatment period was 14 days. The results are as follows: Table 7. Improvement in insomnia and anxiety (X±SD) Note: Compared with the pre-treatment values ​​in this group. P<0.01; compared with the control group after treatment, ##P<0.01; compared with the experimental group of the formulation in Example 1, P<0.05.

[0054] 4. Clinical validation 4, the improvement effect of the formulation in Example 3. Subjects: 60 patients with insomnia and anxiety due to deficiency of both heart and spleen were randomly divided into an experimental group (n=30) and a control group (n=30). Methods: Same as clinical trial 3; Results are as follows: Table 8. Improvement in insomnia and anxiety (X±SD) Note: Compared with the pre-treatment values ​​in this group. P<0.01; compared with the control group after treatment, ##P<0.01; compared with the experimental group of the formulation in Example 1, P<0.05.

[0055] 5. Clinical validation 5, the improvement effect of the formulation in Example 4. Subjects: 60 patients with insomnia and anxiety due to liver stagnation and blood deficiency were randomly divided into an experimental group (n=30) and a control group (n=30). Methods: Same as clinical trial 3; Results are as follows: Table 9. Improvement in insomnia and anxiety (X±SD) Note: Compared with the pre-treatment values ​​in this group. P<0.01; compared with the control group after treatment, ##P<0.01; compared with the experimental group of the formulation in Example 1, P<0.05.

[0056] 6. Summary of Clinical Validation All clinical validation results showed that the formulations in Example 1 and Examples 2-4 could significantly improve insomnia and anxiety-related symptoms, with the formulation in Example 1 showing the best effect, and the formulations in Examples 2-4 showing significantly better effects than the control group. During clinical use, no significant adverse reactions were observed in any of the subjects, indicating good safety. This demonstrates that the functional oral liquid of traditional Chinese medicine of the present invention has significant effects in improving sleep and relieving anxiety, and is highly safe.

[0057] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, alterations, and equivalent transformations made to the above embodiments based on the technical essence of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A functional oral liquid made from traditional Chinese medicine, characterized in that, It is made from Chinese herbal extracts and excipients; the Chinese herbal extracts are made from the following raw materials in parts by weight: 18-22 parts of stir-fried jujube seed, 15-18 parts of Polygonum multiflorum vine, 12-15 parts of Salvia miltiorrhiza, 12-15 parts of Ligustrum lucidum, 6-9 parts of vinegar-processed Bupleurum chinense, 1.5-2.5 parts of cinnamon, 22-28 parts of calcined oyster shell, 10-12 parts of Poria cocos, and 9-12 parts of lily bulb; the excipients include: gum arabic, xylitol, citric acid, steviol glycosides, and xanthan gum.

2. The functional oral liquid of traditional Chinese medicine according to claim 1, characterized in that, The weight proportions of the Chinese medicinal materials are as follows: 20 parts of stir-fried jujube seed, 16 parts of Polygonum multiflorum vine, 13 parts of Salvia miltiorrhiza, 13 parts of Ligustrum lucidum, 7 parts of vinegar-processed Bupleurum chinense, 2 parts of cinnamon, 25 parts of calcined oyster shell, 11 parts of Poria cocos, and 10 parts of lily bulb.

3. A method for preparing a functional oral liquid of traditional Chinese medicine, characterized in that, Includes the following steps: (1) Classification of medicinal materials: Chinese medicinal materials are divided into those suitable for fermentation and those unsuitable for fermentation; (2) Batch pretreatment: Solid-state low-temperature pre-fermentation is suitable for fermentable medicinal materials. After fermentation, the materials are dried at low temperature, crushed, and screened for later use. For medicinal materials that are not suitable for fermentation, they are directly crushed and screened for later use. (3) Combined extraction: The two types of medicinal materials after pretreatment are mixed evenly, and the extract is added for three-stage extraction. The extracts are combined for later use. The extract is prepared by enzyme, composite encapsulation system and composite solvent. (4) Preparation of finished product: The combined extract is concentrated under vacuum and filtered, and the excipients are added, stirred and dissolved, and kept warm to obtain the finished product liquid; (5) Filling and sterilization: The finished liquid is aseptically filled, sterilized by high pressure steam, cooled and packaged to obtain the finished product.

4. The preparation method according to claim 3, characterized in that, In step (1), the following medicinal materials can be selected: Suitable for fermentation: 23.32 kg of stir-fried jujube seed, 15.90 kg of Polygonum multiflorum vine, 15.90 kg of Salvia miltiorrhiza, 12.72 kg of Ligustrum lucidum, 12.72 kg of lily bulb, and 12.72 kg of Poria cocos; Unsuitable for fermentation: 9.54 kg of vinegar-processed Bupleurum chinense, 2.12 kg of cinnamon, and 28.62 kg of calcined oyster shell; or, suitable for fermentation: 22.90 kg of jujube seed, 23.20 kg of mulberry fruit, 13.19 kg of jujube, 13.19 kg of Dendrobium officinale, 13.19 kg of Ganoderma lucidum, 15.82 kg of Gastrodia elata, and 15.82 kg of Rehmannia glutinosa; Unsuitable for fermentation: 7.92 kg of cinnamon, 23.20 kg of calcined oyster shell, and 7.92 kg of licorice root. kg; or, suitable for fermentation: stir-fried jujube seed 24.42kg, cypress seed 14.65kg, wolfberry 24.42kg, Solomon's seal 12.21kg, ophiopogon japonicus 12.21kg, dried tangerine peel 7.33kg, albizia bark 14.65kg; unsuitable for fermentation: calcined oyster shell 24.42kg, polygala tenuifolia 9.77kg, licorice 7.33kg; or, suitable for fermentation: jujube seed 24.42kg, polygonum multiflorum 19.54kg, schisandra chinensis 9.77kg, lotus seed 14.65kg, yam 19.54kg, white peony root 12.21kg; unsuitable for fermentation: calcined oyster shell 28.56kg, chuanxiong rhizome 7.33kg, licorice 7.33kg, ginger 5.50kg.

5. The preparation method according to claim 3 or 4, characterized in that, In step (2), the strains for solid-state low-temperature pre-fermentation can be Lactobacillus plantarum or Saccharomyces cerevisiae, with a weight ratio of 1:

1. The amount of a single strain added is 0.05% of the dry weight of the medicinal material. The fermentation conditions are: material moisture 55%~65%, fermentation temperature 30℃~35℃, fermentation time 48h~72h, and the entire process should be kept away from light and sealed. After fermentation, the material is dried at 60℃ until the moisture content is ≤10%, and then pulverized to 40 mesh. Medicinal materials that are not suitable for fermentation should be pulverized to 40 mesh.

6. The preparation method according to any one of claims 3-5, characterized in that, In step (3), the preparation method of the extract is as follows: pectinase, cellulase, hydroxylated soybean lecithin, glycerol, and mono- and diglycerides are added to the composite solvent and stirred at 50℃ and 80r / min until completely transparent; wherein, the weight ratio of pectinase to cellulase is 1:1, and the amount of each is 0.4% of the dry weight of the medicinal material; the weight ratio of hydroxylated soybean lecithin, glycerol, and mono- and diglycerides is 1:1:3, and the total amount is 2% to 4% of the dry weight of the medicinal material; the composite solvent is ethanol: propylene glycol: purified water = 12:6:82, and the total amount is 4 or 5 times the volume of the dry weight of the medicinal material (weight KG / volume L).

7. The preparation method according to any one of claims 3-6, characterized in that, In step (3), the specific process of the three-stage extraction is as follows: For the first-stage extraction, an extractant is added to the mixed medicinal materials. The extractant is an extractant containing 5 times the weight of the medicinal materials by volume (kg / L). The pH is adjusted to 4.5-5.0, and the extraction is carried out at a constant temperature of 50°C for 60 minutes. The mixture is then filtered through a 300-mesh filter cloth, and the first-stage extract and the residue are collected. For the second-stage extraction, an extractant is added to the residue. The extractant is an extractant containing 4 times the weight of the medicinal materials by volume (kg / L). The mixture is then extracted at a constant temperature of 50°C for 60 minutes, and the second-stage extract and the residue are collected by filtration. The third-stage extraction process is repeated with the second-stage operation. The third-stage extract and the residue are collected; the residue is discarded, and the third-stage extracts are combined.

8. The preparation method according to any one of claims 3-7, characterized in that, In step (4), the vacuum concentration conditions are: temperature 50-55℃, vacuum degree -0.092--0.095MPa until the liquid has no alcohol smell and the ethanol content of the condensate is <3%, and 60℃, vacuum degree -0.08--0.09MPa. After the solution becomes viscous, pure water is added. When the water vaporizes, the water vapor carries propylene glycol and evaporates simultaneously. This process is repeated 3-5 times, and water is added to concentrate the solution to a specific gravity of 1.04-1.05g / mL. The concentrate is filtered through a 400-mesh sieve. After the auxiliary materials are added, the mixture is stirred at 80℃ and 100r / min for 20min until completely dissolved, and then kept warm for 15min.

9. The preparation method according to any one of claims 3-8, characterized in that, In step (5), the aseptic filling specifications can be selected as 20 mL / bottle, 30 mL / bottle, or 50 mL / bottle, and the high-pressure steam sterilization conditions are 120℃ for 15-30 min.

10. A functional oral liquid made from traditional Chinese medicine, characterized in that, The oral liquid is prepared according to any one of claims 3-9.

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