Sugar-free type of qi and blood oral liquid and preparation method thereof

Abstract

This invention belongs to the field of biopharmaceutical preparations, specifically relating to a sugar-free oral liquid for invigorating qi and nourishing blood and its preparation method. Using fifteen traditional Chinese medicines, including deer antler, codonopsis, astragalus, angelica, polygonatum, and yam, as core components, a sugar-free oral liquid for invigorating qi and nourishing blood is obtained. Deer antler, as the core medicinal material for invigorating essence and blood, is modified with chitosan complexation to enhance the water solubility, in vivo stability, and bioavailability of deer antler polypeptides. Codonopsis and astragalus synergistically regulate spleen and stomach function and form a synergistic effect with the blood-nourishing effect of angelica. Polygonatum and yam can regulate the body's immunity, optimize the spleen and stomach's digestive function, and balance the medicinal properties, achieving a highly effective and gentle effect of invigorating qi and nourishing blood. Furthermore, the excipient polyoxyethylene (35) castor oil can improve the solubility and formulation stability of poorly soluble components such as ginsenosides and deer antler polypeptides. β-cyclodextrin can encapsulate and protect the volatile oil components of angelica and tangerine peel and achieve slow release, forming a synergistic effect with the core components, ensuring a stable and lasting overall therapeutic effect.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical preparations, and in particular to a sugar-free oral liquid for invigorating qi and nourishing blood and its preparation method. Background Technology

[0002] In Traditional Chinese Medicine (TCM) theory, Qi and blood are the core substances of life activities, supporting the functions of the internal organs and overall health. Deficiency of Qi and blood easily leads to a series of uncomfortable symptoms such as physical weakness, sallow complexion, fatigue, palpitations, and shortness of breath, seriously affecting health and quality of life. Nourishing Qi and blood is a classic TCM concept for treating Qi and blood deficiency. Its core lies in using scientific combinations of medicinal herbs to stimulate the body's own Qi and blood generation and circulation functions, achieving a holistic treatment effect. With the accelerated pace of modern life and the prominence of irregular work and rest schedules and diets, the demand for Qi and blood conditioning is increasing. Oral liquids, due to their convenience and easy absorption, have become the mainstream dosage form. Although there are many types of oral preparations for invigorating qi and nourishing blood on the market, most of them rely on adding high-sugar excipients to mask the inherent bitterness or off-taste of Chinese herbal extracts. This makes them unsuitable for people with low-sugar diets, such as diabetics, and limits their applicability. At the same time, traditional preparations often rely on a single warming and tonifying herb combination, which can easily lead to dryness and discomfort with long-term use. Moreover, the core active ingredients are often easily lost due to insufficient stability, making it difficult to guarantee the long-term and stable efficacy of the medicine and failing to meet the increasingly sophisticated conditioning needs of people with different constitutions. Summary of the Invention

[0003] To address the shortcomings of existing technologies, the present invention aims to provide a sugar-free Qi-nourishing and blood-tonifying oral liquid and its preparation method. The liquid uses fourteen traditional Chinese medicines, including deer antler, codonopsis, astragalus, angelica, polygonatum, and yam, as its core components. Deer antler, as the core ingredient for nourishing essence and blood, undergoes chitosan complexation to modify its polypeptides, enhancing their water solubility, in vivo stability, and bioavailability. Codonopsis and astragalus synergistically regulate spleen and stomach function and work in conjunction with the blood-nourishing effects of angelica. Polygonatum and yam regulate immunity, optimize spleen and stomach function, and balance medicinal properties, achieving a highly effective and gentle Qi-nourishing and blood-tonifying effect. Furthermore, the excipient polyoxyethylene (35) castor oil enhances the solubility and formulation stability of poorly soluble components such as ginsenosides and deer antler polypeptides. β-cyclodextrin encapsulates and protects the volatile oil components of angelica and tangerine peel, enabling slow release and synergistic effects with the core components, ensuring a stable and lasting overall therapeutic effect.

[0004] To achieve the above objectives, the present invention employs the following technical solution:

[0005] In a first aspect, the present invention provides a sugar-free Qi-nourishing and blood-tonifying oral liquid, the oral liquid comprising traditional Chinese medicine components and excipients;

[0006] The Chinese medicine components include fifteen Chinese herbs, namely deer antler, codonopsis, astragalus, angelica, polygonatum, yam, ginseng, ophiopogon, atractylodes, rehmannia, prepared he shou wu, schisandra, tangerine peel, lycium bark, and epimedium.

[0007] The excipients include β-cyclodextrin, steviol glycosides, polyoxyethylene (35) castor oil, ethylparaben, and orange flavoring; the β-cyclodextrin is used to encapsulate the volatile oils, which include angelica volatile oil and tangerine peel volatile oil, which are obtained by decocting angelica and tangerine peel with purified water.

[0008] Further, the mass ratio of the deer antler, codonopsis, astragalus, angelica, polygonatum, yam, ginseng, ophiopogon, atractylodes, rehmannia, processed he shou wu, schisandra, tangerine peel, lycium bark, and epimedium is (8-10):(40-50):(58-68):(32-40):(10-15):(15-20):(8-10):(10-15):(15-20):(24-30):(20-25):(8-1) 0): (10-15): (8-10): (10-15); The amount of β-cyclodextrin used is 1.8-2.2 times the total weight of the volatile oil; The mass-volume ratio of the deer antler, steviol glycoside, polyoxyethylene (35) castor oil, ethylparaben and orange flavor is (8-10) g: (0.18-0.22) g: (0.08-0.12) g: (0.025-0.035) g: (0.4-0.5) mL.

[0009] Secondly, the present invention provides a method for preparing a sugar-free Qi-nourishing and blood-tonifying oral liquid, comprising the following steps:

[0010] S1. Take fifteen kinds of Chinese medicine. Among them, deer antler is quickly sprayed and washed with purified water, then crushed to obtain pretreated deer antler powder. The remaining fourteen kinds of Chinese medicine are sprayed with purified water to moisten them, cut into thin slices, and dried to obtain pretreated Chinese medicinal materials.

[0011] S2. Take the pretreated deer antler powder, add purified water and decoct. The decoction is coarsely filtered, finely filtered and concentrated under reduced pressure to obtain a concentrated solution. Add ethanol, let stand, filter, collect the filtrate, add chitosan, adjust the pH with citric acid to obtain a deer antler polypeptide-chitosan complex solution, concentrate to obtain deer antler extract.

[0012] S3. Take the remaining fourteen pre-treated Chinese medicinal materials, add purified water and decoct them, collect the volatile oil, which includes volatile oil of Angelica sinensis and volatile oil of Citrus reticulata. Filter the decoction to obtain filtrate. Mix the collected volatile oil with β-cyclodextrin to form a volatile oil-β-cyclodextrin inclusion complex. Concentrate the filtrate, add the volatile oil-β-cyclodextrin inclusion complex, and concentrate under reduced pressure to obtain a clear extract of the fourteen Chinese medicinal materials.

[0013] S4. Heat purified water to the first set temperature, add steviol glycosides, cool to the second set temperature, add polyoxyethylene (35) castor oil, add deer antler extract and fourteen kinds of Chinese herbal extract, heat to the third set temperature, boil to sterilize, cool to the fourth set temperature, adjust the pH with citric acid, add orange flavor and ethylparaben, add purified water to make up the volume, filter, and obtain the medicine solution; fill the medicine solution into a pharmaceutical composite film bag, sterilize, and obtain sugar-free Qi-nourishing and blood-tonifying oral liquid.

[0014] In one feasible implementation, in S1, the particle size of the pulverized material is 80-100 mesh; the thickness of the sheet is 1.5-2.5 mm; the drying temperature is 60-80℃; and the drying time is 1-2 hours.

[0015] Cleaning removes impurities, dust, and potential contaminants from the surface of medicinal materials, ensuring their purity and preventing impurities from affecting the quality of the preparation in subsequent processes. Further wetting allows moisture to penetrate evenly into the materials, softening their texture and creating conditions for the subsequent dissolution of active ingredients. Crushing deer antler and cutting other medicinal materials increases the contact area between the materials and the extraction medium, improving the dissolution efficiency of active ingredients during extraction. Drying removes excess moisture, reduces the risk of microbial growth, and ensures the storage stability of the pre-treated materials. It also prevents excessive moisture from affecting the extraction concentration and component stability, ensuring the efficiency and stability of subsequent extraction processes and laying the foundation for preparing high-purity, high-quality active ingredients.

[0016] In one feasible implementation, in step S2, the mass-to-volume ratio of the pretreated deer antler powder to purified water is (8-10) g:(48-60) mL; the decoction step is as follows: maintain a stirring speed of 40-50 r / min, heat to boiling, then simmer for 2.5-3.5 h each time; the coarse filtration medium is a pharmaceutical-grade filter paperboard containing diatomaceous earth with a pore size of 4-6 μm; the fine filtration medium is a pharmaceutical-grade filter paperboard containing diatomaceous earth with a pore size of 0.8-1.2 μm; the mass ratio of the pretreated deer antler powder to chitosan is (8-10):(0.02-0.04); and the adjusted pH is 5.0-5.5.

[0017] The core blood-nourishing components in deer antler, such as deer antler polypeptides, are extremely sensitive to the temperature, pH, and coexisting components of the extraction environment. If extracted in combination with other medicinal materials, the tannins in the other materials may form insoluble complexes with the polypeptides, and polysaccharides may adsorb the polypeptides, leading to impaired dissolution. The synergistic effect of high temperature may also cause the polypeptides to denature and become inactive. Therefore, separate extraction can construct an independent extraction system, precisely control the extraction conditions to match the stability requirements of polypeptide components, and ensure their full dissolution. Purification is carried out through a multi-stage filtration process. Coarse filtration can quickly remove large particulate impurities such as medicinal residues from the extract, while fine filtration can retain fine impurities and colloidal particles, significantly improving the purity of the extract.

[0018] In one feasible implementation, in step S2, the conditions for vacuum concentration are: vacuum degree 0.06-0.09 MPa, temperature 50-60℃; the relative density of the concentrate at 20℃ is 1.20-1.25; the mass fraction of ethanol is 95%, and the amount of ethanol is 2.5-3.5 times the volume of the concentrate; the settling time is 20-28 h; the filtration medium is diatomaceous earth filter paper with a pore size of 0.8-1.2 μm; and the relative density of the concentrated liquid at 20℃ is 1.00-1.15.

[0019] By utilizing the polarity difference between ethanol and water for alcohol precipitation, water-soluble impurities such as starch and protein in the extract are precipitated due to reduced solubility. Filtering out these impurities further enriches and purifies the active ingredients. Furthermore, by lowering the concentration temperature under reduced pressure, the concentration of active ingredients in the extract is gradually increased while avoiding high temperatures that could damage their activity. This results in a high-purity, high-activity deer antler extract, maximizing the retention of the core active ingredients in deer antler that regulate endocrine and hematopoietic system functions. This provides a high-purity, high-activity material basis for the preparation to exert its core function of nourishing essence and blood, while also improving the uniform dispersion of active ingredients in subsequent preparation processes.

[0020] In one feasible implementation, in step S3, the decoction step is as follows: add 7-9 times the total weight of the remaining fourteen Chinese medicinal herbs in purified water, heat to boiling, then reduce to a simmer, maintain the liquid temperature at 95-98℃, and continuously stir at a speed of 40-50 r / min for 2.5-3.5 hours. After filtration, add 6-8 times the amount of purified water to the dregs and decoct again for 1.5-2.5 hours. The filtration medium is a diatomaceous earth-containing filter paper with a pore size of 4-6 μm. The relative density of the concentrated liquid at 20℃ is 1.14-1.17. The conditions for vacuum concentration are: vacuum degree 0.06-0.09 MPa, temperature 50-60℃. The relative density of the vacuum-concentrated liquid at 20℃ is 1.19.

[0021] The mixed extraction of fourteen Chinese medicinal herbs utilizes a synergistic extraction effect to fully dissolve the core components of the herbs that nourish qi and blood, while specifically protecting easily lost volatile oil components. During the mixed decoction process, qi-nourishing herbs such as Codonopsis pilosula and Astragalus membranaceus, along with blood-nourishing herbs such as Angelica sinensis, form a stable component system during co-extraction, avoiding the low dissolution efficiency problem of single-component extraction and laying a material foundation for the subsequent qi-nourishing and blood-nourishing effects. The volatile oil collection device uses the principle of condensation reflux to capture the volatile components volatilized by Angelica sinensis and Citrus reticulata during high-temperature decoction, preventing the large-scale loss of these components due to their low boiling point and easy volatilization.

[0022] β-Cyclodextrin, with its unique hydrophobic cavity structure, can encapsulate volatile oil components to form stable inclusion complexes, isolating them from external oxygen and heat, and preventing the oxidation and decomposition of components such as ligustilide and limonene in the volatile oil. It also imparts a slow-release characteristic to the volatile oil; that is, after the inclusion complex enters the intestine, it slowly dissociates under the influence of intestinal flora or body fluids, continuously releasing the volatile oil components. Mixing the inclusion complex with a concentrated extract of fourteen Chinese medicinal herbs ensures that the volatile oil components are evenly dispersed in the concentrate, avoiding problems such as layering and floating due to hydrophobicity. This achieves a synergistic integration of the blood-nourishing effects of the volatile oil with the qi-tonifying and blood-nourishing effects of core components such as Codonopsis and Astragalus, enhancing the overall therapeutic effect and its longevity.

[0023] In one feasible implementation, in step S4, the mass-to-volume ratio of steviol glycosides to purified water is (0.18-0.22) g : (40-50) mL; the first set temperature is 55-65℃; the second set temperature is 40-50℃; the third set temperature is 95-105℃; the boiling sterilization time is 25-35 min; and the fourth set temperature is 30-40℃.

[0024] Steviosides, as sugar-free sweeteners, improve the taste of the preparation and are suitable for people with low-sugar diets such as diabetic patients. Polyoxyethylene (35) castor oil, as a solubilizer, can encapsulate poorly soluble components such as ginsenosides and deer antler polypeptides by forming micellar structures, thereby improving their solubility and dispersion stability in the aqueous system, avoiding the loss of efficacy due to component leaching, and improving the absorption efficiency of poorly soluble components in the intestine. Adjusting the pH value to a suitable range of 3.8-5.0 can stabilize the molecular structure of the active ingredients, such as avoiding the hydrolysis of amide bonds of polypeptide components and the oxidation of volatile oil components, reducing the degradation of active ingredients during storage, and maintaining the colloidal stability of the preparation system, avoiding the problems of layering and turbidity caused by pH fluctuations.

[0025] In one feasible implementation, in step S4, the pH adjustment range is 3.8-5.0; the volume of the final volume is 85-95 mL; the filtration medium is a 0.7-0.9 μm filter membrane; the sterilization temperature is 95-105 °C; and the sterilization time is 25-35 min.

[0026] The sterilization and filling processes form a complete protection system. The initial boiling sterilization can quickly kill most bacteria, fungi, and other microorganisms in the preparation. The subsequent filtration treatment before filling can intercept any fine sediments and impurities that may be generated during sterilization, ensuring that the liquid is clear and transparent. The high-temperature drying sterilization of the oral liquid bottle can eliminate the risk of microbial contamination of the packaging container. The secondary sterilization after filling and sealing can further kill any remaining heat-resistant microorganisms through continuous high temperature, forming a complete chain of sterilization protection to thoroughly ensure medication safety. Adding purified water to adjust the total volume can achieve standardized dosage control of the preparation, ensuring that the content of effective ingredients in each unit volume of preparation is uniform and consistent. In the end, a sugar-free Qi-nourishing and blood-tonifying oral liquid with a suitable taste, stable effective ingredients, microbial compliance, and precise dosage is produced. It not only meets the medication needs of people who need long-term conditioning, but also adapts to the safe use requirements of people with special dietary restrictions, achieving a unity of efficacy, safety, and compliance.

[0027] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0028] This formula uses fifteen traditional Chinese medicines, including deer antler, codonopsis, astragalus, angelica, polygonatum, and yam, as core components, combined with excipients to create a sugar-free oral liquid for invigorating qi and nourishing blood. It achieves a highly effective and gentle effect in invigorating qi and nourishing blood, making it particularly suitable for those requiring long-term conditioning and for individuals with low-sugar diets, such as diabetics. Deer antler, as a core ingredient for invigorating essence and blood, contains deer antler polypeptides and amino acids that can regulate the endocrine and hematopoietic systems, promote the proliferation of hematopoietic stem cells and the synthesis and metabolism of qi and blood, and strengthen the generation of essence and blood by stimulating the body's own functions. Through chitosan complexation modification of deer antler polypeptides, an electrostatic complexation barrier is constructed to protect the active ingredients, improving the water solubility and dispersion uniformity of the deer antler polypeptides, effectively slowing down the degradation process of deer antler polypeptides by gastrointestinal enzymes, and significantly improving the in vivo stability and bioavailability of the deer antler polypeptides. Codonopsis and astragalus, as core qi-invigorating herbs, synergistically regulate spleen and stomach function, laying a solid functional foundation for the generation of qi and blood. Together with the blood-nourishing effect of angelica, they strengthen the pathway of qi and blood generation from the root. Polygonatum odoratum contains polysaccharides and steroidal saponins, which can interact with receptors on the surface of immune cells to regulate the body's immune function. This helps protect the integrity of the intestinal mucosal barrier, preventing abnormal intestinal function from affecting blood circulation. Its slightly cold nature balances the warming and drying properties of deer antler and epimedium, avoiding discomfort from excessive heat during tonification. Dioscorea opposita contains mucoproteins and polysaccharides that synergistically regulate the intestinal microecology, improve gastrointestinal motility, and further optimize spleen and stomach function. Furthermore, yam's neutral nature complements Polygonatum odoratum, balancing their medicinal properties and making the effects of tonifying qi and nourishing blood more gentle and suitable for long-term use.

[0029] In addition, the excipient polyoxyethylene (35) castor oil, as a solubilizer, can uniformly disperse poorly soluble core components such as ginsenosides and deer antler polypeptides in the aqueous phase system by forming micelles, thereby improving their solubility and formulation stability, avoiding the loss of efficacy caused by component leaching, increasing the effective concentration of drugs in the intestine, and promoting the absorption of core components. β-cyclodextrin encapsulates the volatile oils of Angelica sinensis and Citrus reticulata through hydrophobic cavities, ensuring the integrity of blood-nourishing components such as ligustilide in Angelica sinensis volatile oil and limonene in Citrus reticulata volatile oil, avoiding their oxidative decomposition, and the encapsulated volatile oils can be slowly released in the intestine, prolonging the time of blood-nourishing effect, thereby forming a synergistic effect with the qi-tonifying and blood-nourishing effects of the core components, ensuring a stable and lasting overall therapeutic effect. Attached Figure Description

[0030] Figure 1 This is a schematic diagram of the preparation process of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to the present invention.

[0031] Figure 2 This is a cumulative dissolution curve of ligustilide in a sugar-free, qi-nourishing and blood-tonifying oral liquid of the present invention.

[0032] Figure 3This is a cumulative dissolution curve of limonene in a sugar-free, qi-nourishing and blood-tonifying oral liquid of the present invention. Detailed Implementation

[0033] To make the technical problems, technical solutions, and beneficial effects to be solved by this application clearer, the application will be further described in detail below with reference to embodiments. However, this should not be construed as limiting the scope of this application to the following examples. All other embodiments obtained by those skilled in the art without creative effort without departing from the above-described methodological spirit of this application are within the scope of protection of this application.

[0034] The singular forms “for,” “or,” “a,” “any,” and “described” used in this application are intended to include the plural forms unless the context clearly indicates otherwise. Furthermore, the terms “first” and “second” are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0035] Example 1

[0036] like Figure 1 As shown, a sugar-free Qi-nourishing and blood-tonifying oral liquid and its preparation method include the following steps:

[0037] S1. Take 9g of deer antler, 45g of codonopsis, 63g of astragalus, 36g of angelica, 13.5g of polygonatum, 18g of yam, 9g of ginseng (without the root), 13.5g of ophiopogon, 18g of atractylodes macrocephala (stir-fried), 27g of rehmannia, 22.5g of prepared polygonum multiflorum, 9g of schisandra, 13.5g of tangerine peel, 9g of lycium chinense root bark, and 13.5g of epimedium, totaling fifteen Chinese medicinal herbs. Among them, the deer antler is quickly sprayed and washed with purified water, and the other fourteen Chinese medicinal herbs are sprayed with purified water to moisten thoroughly, with the moistening time controlled within 30 minutes. Then, the moistened deer antler is pulverized to 90 mesh to obtain pre-treated deer antler powder. The other fourteen Chinese medicinal herbs are cut into 2mm thin slices and dried at 70℃ for 1.5h to obtain pre-treated Chinese medicinal materials.

[0038] S2. Add the pretreated deer antler powder to 54 mL of purified water, heat to boiling, then reduce to a simmer, maintaining the liquid temperature at 97°C. Decoct twice, 3 hours each time, maintaining a stirring speed of 45 r / min during decoction. Combine the two decoctions and allow to settle for 30 minutes. Collect the supernatant and pass it through a pharmaceutical-grade filter paper containing diatomaceous earth, first through a 5 μm coarse filter and then through a 1 μm fine filter. Concentrate the filtrate under reduced pressure at 0.07 MPa and 55°C to a relatively stable concentration. A concentrated solution with a density of 1.22 (20℃) was slowly mixed with 95% ethanol at a volume three times that of the concentrated solution. After standing for 24 hours, impurities were precipitated. The solution was then filtered again through a 1μm pore size diatomaceous earth filter paper. The filtrate was collected and the ethanol was recovered. 0.03g of chitosan was added to the filtrate, and the pH of the system was adjusted to 5.2 with citric acid solution. The solution was stirred in a sealed container at room temperature for 40 minutes to obtain a deer antler polypeptide-chitosan complex solution. The solution was further concentrated to a relative density of 1.10 (20℃) to obtain deer antler extract.

[0039] S3. Take fourteen pre-treated Chinese medicinal herbs: Codonopsis pilosula, Astragalus membranaceus, Angelica sinensis, Polygonatum odoratum, Dioscorea opposita, Panax ginseng (without the root), Ophiopogon japonicus, Atractylodes macrocephala (fried), Rehmannia glutinosa, processed Polygonum multiflorum, Schisandra chinensis, Citrus reticulata peel, Lycium chinense root bark, and Epimedium brevicornu. Add purified water at 8 times the total weight of the herbs, heat to boiling, then reduce to a simmer, maintaining the decoction temperature at 95-98℃. During extraction, maintain continuous stirring at 45 r / min. Attach a volatile oil collection device to the top of the extraction tank to collect volatile oils, including Angelica sinensis volatile oil and Citrus reticulata peel volatile oil. After the first decoction for 3 hours, filter. Add purified water at 7 times the weight of the dregs and decoct again for 2 hours. Combine the two decoctions and filter using a filter with a pore size of [insert pore size here]. The residue was removed by filtering through a 4μm diatomaceous earth-containing filter paper to obtain a combined filtrate. The collected volatile oil was immediately mixed with twice the mass of β-cyclodextrin and stirred at a constant temperature of 50℃ for 3 hours to form a volatile oil-β-cyclodextrin inclusion complex. The combined filtrate was concentrated to a relative density of 1.15 (20℃), and the volatile oil-β-cyclodextrin inclusion complex was slowly added at a rate of 0.15 g / min. The stirring speed was maintained at 60 r / min for 20 min. The mixture was then concentrated under reduced pressure at a vacuum of 0.07 MPa and a temperature of 55℃ to a relative density of 1.19 (20℃) to obtain a fourteen-ingredient traditional Chinese medicine extract.

[0040] S4. Take 45 mL of purified water and heat it to 60 °C. Add 0.2 g of steviol glycosides and stir continuously at 80 r / min until completely dissolved. Cool to 45 °C and add 0.1 g of polyoxyethylene (35) castor oil. Stir at 45 °C for 20 min. Add deer antler extract and fourteen-ingredient Chinese herbal extract. Reduce the stirring speed to 50 r / min and heat to 100 °C while stirring. Boil for 30 min for sterilization. During boiling, adjust the stirring speed to 30 r / min. Stop heating and wait for the material to cool to below 40℃. Adjust the pH of the system to 4.6 with citric acid, stir evenly, add 0.45mL of orange flavoring and 0.03g of ethylparaben, continue stirring for 15min, add purified water to adjust the total volume to 90mL, stir thoroughly, and filter through a 0.8μm filter membrane to remove impurities to obtain the drug solution. Inject the clarified drug solution into pharmaceutical composite film bags for filling, heat seal, and sterilize at 100℃ for 30min to obtain sugar-free Qi-nourishing and blood-tonifying oral liquid.

[0041] Example 2

[0042] like Figure 1 As shown, a sugar-free Qi-nourishing and blood-tonifying oral liquid and its preparation method include the following steps:

[0043] S1. Take 8g of deer antler, 40g of codonopsis, 58g of astragalus, 32g of angelica, 10g of polygonatum, 15g of yam, 8g of ginseng (without the root), 10g of ophiopogon, 15g of atractylodes macrocephala (stir-fried), 24g of rehmannia, 20g of prepared he shou wu, 8g of schisandra, 10g of tangerine peel, 8g of lycium chinense root bark, and 10g of epimedium, totaling fifteen Chinese medicinal herbs. Among them, the deer antler is quickly rinsed with purified water, and the other fourteen Chinese medicinal herbs are rinsed with purified water and moistened for 30 minutes. Then, the moistened deer antler is pulverized to 80 mesh to obtain pre-treated deer antler powder. The other fourteen Chinese medicinal herbs are cut into 1.5mm thin slices and dried at 60℃ for 1 hour to obtain pre-treated Chinese medicinal materials.

[0044] S2. Add the pretreated deer antler powder to 48 mL of purified water, heat to boiling, then reduce to a simmer, maintaining the liquid temperature at 95°C. Decoct twice, 2.5 h each time, maintaining a stirring speed of 40 r / min during decoction. Combine the two decoctions, allow to settle for 30 min, collect the supernatant, and pass it through a pharmaceutical-grade filter paper containing diatomaceous earth, first through a 4 μm coarse filter and then through a 0.8 μm fine filter. Concentrate the filtrate under reduced pressure at 0.06 MPa and 50°C to a relatively stable concentration. A concentrated solution with a density of 1.20 (20℃) was slowly mixed with 2.5 times its volume of 95% ethanol. After standing for 20 hours to precipitate impurities, the solution was filtered again through a 0.8μm pore size diatomaceous earth filter paper. The filtrate was collected and the ethanol was recovered. 0.02g of chitosan was added to the filtrate, and the pH of the system was adjusted to 5.0 with citric acid solution. The solution was stirred at room temperature in a sealed container for 40 minutes to obtain a deer antler polypeptide-chitosan complex solution. The solution was further concentrated to a relative density of 1.00 (20℃) to obtain deer antler extract.

[0045] S3. Take fourteen pre-treated Chinese medicinal herbs: Codonopsis pilosula, Astragalus membranaceus, Angelica sinensis, Polygonatum odoratum, Dioscorea opposita, Panax ginseng (without the root), Ophiopogon japonicus, Atractylodes macrocephala (fried), Rehmannia glutinosa, processed Polygonum multiflorum, Schisandra chinensis, Citrus reticulata peel, Lycium chinense root bark, and Epimedium brevicornu. Add purified water at 7 times the total weight of the herbs, heat to boiling, then reduce to a simmer, maintaining the decoction temperature at 95-98℃. During extraction, maintain continuous stirring at 40 rpm. Attach a volatile oil collection device to the top of the extraction tank to collect volatile oils, including Angelica sinensis volatile oil and Citrus reticulata peel volatile oil. After the first decoction for 2.5 hours, filter. Add purified water at 6 times the weight of the dregs and decoct again for 1.5 hours. Combine the two decoctions and extract using a filter with a small aperture. The residue was removed by filtering through a 5μm diatomaceous earth-containing filter paper to obtain a combined filtrate. The collected volatile oil was immediately mixed with 1.8 times the mass of β-cyclodextrin and stirred at a constant temperature of 50℃ for 3 hours to form a volatile oil-β-cyclodextrin inclusion complex. The combined filtrate was concentrated to a relative density of 1.14 (20℃), and the volatile oil-β-cyclodextrin inclusion complex was slowly added at a rate of 0.1 g / min. The stirring speed was maintained at 60 r / min for 20 min. The mixture was then concentrated under reduced pressure at a vacuum of 0.06 MPa and a temperature of 50℃ to a relative density of 1.19 (20℃) to obtain a fourteen-ingredient traditional Chinese medicine extract.

[0046] S4. Take 40 mL of purified water and heat it to 55 °C. Add 0.18 g of steviol glycosides and stir continuously at 80 r / min until completely dissolved. Cool to 40 °C and add 0.08 g of polyoxyethylene (35) castor oil. Stir at 45 °C for 20 min. Add deer antler extract and fourteen-ingredient Chinese herbal extract. Reduce the stirring speed to 50 r / min and heat to 95 °C while stirring. Boil for 25 min for sterilization. During boiling, adjust the stirring speed to 30 r / min. Stop heating and wait for the material to cool to 30℃. Adjust the pH of the system to 3.8 with citric acid. After stirring evenly, add 0.4mL of orange flavoring and 0.025g of ethylparaben. Continue stirring for 15min. Add purified water to adjust the total volume to 85mL. After stirring thoroughly, filter through a 0.7μm filter membrane to remove impurities and obtain the drug solution. Inject the clarified drug solution into a pharmaceutical composite film bag for filling. After heat sealing, sterilize at 95℃ for 25min to obtain a sugar-free Qi-nourishing and blood-tonifying oral liquid.

[0047] Example 3

[0048] like Figure 1 As shown, a sugar-free Qi-nourishing and blood-tonifying oral liquid and its preparation method include the following steps:

[0049] S1. Take 10g of deer antler, 50g of codonopsis, 68g of astragalus, 40g of angelica, 15g of polygonatum, 20g of yam, 10g of ginseng (without the root), 15g of ophiopogon, 20g of atractylodes macrocephala (fried), 30g of rehmannia, 25g of prepared he shou wu, 10g of schisandra, 15g of tangerine peel, 10g of lycium chinense root bark, and 15g of epimedium, totaling fifteen Chinese medicinal herbs. Among them, the deer antler is quickly sprayed and washed with purified water, and the other fourteen Chinese medicinal herbs are sprayed with purified water to moisten thoroughly, with the moistening time controlled within 30 minutes. Then, the moistened deer antler is pulverized to 100 mesh to obtain pre-treated deer antler powder. The other fourteen Chinese medicinal herbs are cut into 2.5mm thin slices and dried at 80℃ for 2 hours to obtain pre-treated Chinese medicinal materials.

[0050] S2. Add the pretreated deer antler powder to 60 mL of purified water, heat to boiling, then reduce to a simmer, maintaining the liquid temperature at 97°C. Decoct twice, 3.5 h each time, maintaining a stirring speed of 50 r / min during decoction. Combine the two decoctions, allow to settle for 30 min, collect the supernatant, and pass it through a pharmaceutical-grade filter paper containing diatomaceous earth, first through a 6 μm coarse filter and then through a 1.2 μm fine filter. Concentrate the filtrate under reduced pressure at 0.09 MPa and 60°C to a relatively stable concentration. A concentrated solution with a density of 1.25 (20℃) was slowly mixed with 3.5 times its volume of 95% ethanol. After standing for 28 hours to precipitate impurities, the solution was filtered again through a 1.2μm pore size diatomaceous earth filter paper. The filtrate was collected and the ethanol was recovered. 0.03g of chitosan was added to the filtrate, and the pH of the system was adjusted to 5.2 with citric acid solution. The solution was stirred at room temperature in a sealed container for 40 minutes to obtain a deer antler polypeptide-chitosan complex solution. The solution was further concentrated to a relative density of 1.15 (20℃) to obtain deer antler extract.

[0051] S3. Take fourteen pre-treated Chinese medicinal herbs: Codonopsis pilosula, Astragalus membranaceus, Angelica sinensis, Polygonatum odoratum, Dioscorea opposita, Panax ginseng (without the root), Ophiopogon japonicus, Atractylodes macrocephala (fried), Rehmannia glutinosa, processed Polygonum multiflorum, Schisandra chinensis, Citrus reticulata peel, Lycium chinense root bark, and Epimedium brevicornu. Add purified water at 9 times the total weight of the herbs, heat to boiling, then reduce to a simmer, maintaining the decoction temperature at 95-98℃. During extraction, maintain continuous stirring at 50 rpm. Attach a volatile oil collection device to the top of the extraction tank to collect volatile oils, including Angelica sinensis volatile oil and Citrus reticulata peel volatile oil. After the first decoction for 3.5 hours, filter. Add purified water at 8 times the weight of the residue and decoct again for 2.5 hours. Combine the two decoctions and extract using a filter with a small aperture. The residue was removed by filtering through a 6μm diatomaceous earth-containing filter paper to obtain a combined filtrate. The collected volatile oil was immediately mixed with 2.2 times the mass of β-cyclodextrin and stirred at a constant temperature of 50℃ for 3 hours to form a volatile oil-β-cyclodextrin inclusion complex. The combined filtrate was concentrated to a relative density of 1.17 (20℃), and the volatile oil-β-cyclodextrin inclusion complex was slowly added at a rate of 0.2 g / min. The stirring speed was maintained at 60 r / min for 20 min. The mixture was then concentrated under reduced pressure at a vacuum of 0.09 MPa and a temperature of 60℃ to a relative density of 1.19 (20℃) to obtain a fourteen-ingredient traditional Chinese medicine extract.

[0052] S4. Take 50 mL of purified water and heat it to 65 °C. Add 0.22 g of steviol glycosides and stir continuously at 80 r / min until completely dissolved. Cool to 50 °C and add 0.12 g of polyoxyethylene (35) castor oil. Stir at a constant temperature of 45 °C for 20 min. Add deer antler extract and fourteen-ingredient Chinese herbal extract. Reduce the stirring speed to 50 r / min and heat to 105 °C while stirring. Boil for 35 min for sterilization. During boiling, adjust the stirring speed to 30 r / min. Stop heating and wait for the material to cool to 40℃. Adjust the pH of the system to 5.0 with citric acid. After stirring evenly, add 0.5mL of orange flavoring and 0.035g of ethylparaben. Continue stirring for 15min. Add purified water to adjust the total volume to 95mL. Stir thoroughly and filter through a 0.9μm filter membrane to remove impurities to obtain the drug solution. Inject the clarified drug solution into a pharmaceutical composite film bag for filling. After heat sealing, sterilize at 105℃ for 35min to obtain a sugar-free Qi-nourishing and blood-tonifying oral liquid.

[0053] Comparative Example 1

[0054] A sugar-free Qi-nourishing and blood-tonifying oral liquid and its preparation method are disclosed. The implementation steps and parameters differ from those in Example 1 in that β-cyclodextrin is not added for inclusion treatment in step S3, and the collected Angelica sinensis volatile oil and Citrus reticulata volatile oil are directly added to the concentrate. The remaining steps and parameters are the same.

[0055] Comparative Example 2

[0056] A sugar-free Qi-nourishing and blood-tonifying oral liquid and its preparation method are disclosed. The implementation steps and parameters are different from those in Example 1 except that polyoxyethylene (35) castor oil is not added in step S4. The remaining steps and parameters are the same.

[0057] Comparative Example 3

[0058] A sugar-free Qi-nourishing and blood-tonifying oral liquid and its preparation method are disclosed. The implementation steps and parameters differ from those in Example 1 in that the step of preparing deer antler extract separately in S2 is omitted. Instead, deer antler powder is mixed with fourteen pre-treated Chinese medicinal materials and extracted and prepared into extract according to the process parameters in S3. The remaining steps and parameters are the same.

[0059] Performance testing:

[0060] Content determination of core components of volatile oils: The determination of the core components of volatile oils included the detection of ligustilide, a characteristic component of Angelica sinensis volatile oil, and limonene, a characteristic component of Citrus reticulata volatile oil. 5 mL of the oral liquid samples from Examples 1-3 and Comparative Examples 1-3 were placed in stoppered conical flasks, and extracted three times with 10 mL of ether for 15 min each time using ultrasonic extraction. The ether extracts were combined and the solvent was evaporated at 40°C in a water bath. The residue was dissolved in methanol and diluted to 2 mL, then filtered through a 0.22 μm filter membrane for later use. A DB-5 capillary column (30 m × 0.25 mm × 0.25 μm) was used for the detection of ligustilide. Nitrogen was used as the carrier gas at a flow rate of 1.2 mL / min. The injection port temperature was 250℃, and the flame ionization detector temperature was 280℃. The temperature program was as follows: initial temperature 60℃, held for 2 min, then increased to 180℃ at a rate of 10℃ / min and held for 5 min. For the detection of limonene, the temperature program was adjusted to an initial temperature of 50℃, held for 2 min, then increased to 150℃ at a rate of 8℃ / min and held for 3 min. The remaining chromatographic conditions were the same as those for the detection of ligustilide. Finally, 1 μL each of the reference solution and the test solution were precisely injected into the gas chromatograph, and the contents of ligustilide and limonene were calculated by peak area using the external standard method.

[0061] In vitro release rate test of volatile oil: 10 mL of oral liquid samples from Examples 1-3 and Comparative Examples 1-3 were taken and placed in a dissolution vessel. 900 mL of 0.1 mol / L pH 6.8 phosphate buffer was added as the release medium. The test temperature was set at 37℃ and the stirring speed at 50 r / min. 5 mL samples were taken at time points of 0.5 h, 1 h, 2 h, 4 h, and 6 h. After each sampling, an equal amount of isothermal release medium was added simultaneously to maintain the volume stability of the dissolution system. The samples were then extracted with 10 mL of diethyl ether by ultrasonication for 15 min and combined. The solvent in the ether solution was evaporated in a water bath at 40℃. The residue was dissolved in methanol and diluted to 2 mL. After filtration through a 0.22 μm organic phase filter membrane, the contents of ligustilide and limonene in the filtrate were determined by the above-mentioned gas chromatography method. The cumulative release rate at different time points was calculated based on the detection results to evaluate the release characteristics of the volatile oil. The calculation formula is: Cumulative release rate (%) = (Cumulative release amount of ligustilide and limonene / Initial total amount of ligustilide and limonene) × 100%, where the initial total amount of ligustilide and limonene was obtained from the content test of the core components of the volatile oil.

[0062] Test for the content of insoluble components: The determination of the content of insoluble components includes the detection of deer antler polypeptide and ginsenosides; 1 mL of the oral liquid of Examples 1-3 and Comparative Examples 1-3 was placed in a 10 mL volumetric flask, and ultrapure water was added to make up to 10 mL and shaken well. A C18 column was used, with acetonitrile-0.1% phosphoric acid solution gradient elution as the mobile phase, flow rate 1.0 mL / min, detection wavelength 220 nm, and column temperature 30 °C. 10 μL each of the deer antler polypeptide reference solution, ginsenoside reference solution, and test solution were injected into the liquid chromatograph, and the chromatograms were recorded. The content of deer antler polypeptide and ginsenosides was calculated by peak area using the external standard method.

[0063] Formulation stability testing: This includes clarity testing and accelerated stability testing. Clarity testing: 5 mL of the oral liquid samples from Examples 1-3 and Comparative Examples 1-3 were placed in 10 mL colorimetric tubes and visually observed under natural light for turbidity, precipitation, or stratification. Turbidity values ​​(unit: NTU) were measured using a turbidimeter. Accelerated stability testing: Oral liquid samples from Examples 1-3 and Comparative Examples 1-3 were placed in a constant temperature and humidity chamber at 40°C and 75% relative humidity for 6 months. Samples were taken at 0, 1, 2, 3, and 6 months to determine the content of active ingredients (deer antler polypeptide, ginsenosides, ligustilide, and limonene) and the pH value. The retention rate of active ingredients was calculated (retention rate of a single ingredient = content of that ingredient at each time point / content of that ingredient at 0 months × 100%). The appearance of the samples at each time point was also observed.

[0064] Table 1. Test results of volatile oil and poorly soluble components in oral liquid.

[0065]

[0066] Table 2 Results of accelerated stability test of oral liquid

[0067]

[0068] From Table 1-Table 2 and Figures 2-3 It can be seen that the content of the core volatile oil components ligustilide and limonene, the poorly soluble components deer antler polypeptide and ginsenoside in the oral liquids of Examples 1-3, and the retention rate of the core components within 6 months are higher than those of Comparative Examples 1-3. Furthermore, the initial turbidity of the oral liquids of Examples 1-3 is lower than that of Comparative Examples 1-3. This indicates that the retention rate of the effective components, stability and efficacy of the oral liquids prepared in Examples 1-3 are all superior to those of Comparative Examples 1-3.

[0069] Comparative Example 1, which did not employ the β-cyclodextrin inclusion complex, exhibited significantly lower levels of its core volatile oil components compared to the Example, and its in vitro release was rapid, with slight turbidity observed during accelerated stability testing. This is because ligustilide and limonene in the volatile oils of Angelica sinensis and Citrus reticulata are heat-sensitive and volatile components. β-cyclodextrin molecules possess a unique hydrophobic cavity structure, enabling them to encapsulate the volatile oil components into stable inclusion complexes. This isolates the volatile oil from oxygen and heat in the external environment, preventing oxidative decomposition and volatilization during concentration, sterilization, and long-term storage of the formulation. Simultaneously, the inclusion complexes can slowly dissociate and release the volatile oil components in the intestinal environment, achieving long-lasting sustained release to ensure sustained efficacy. Volatile oils lacking β-cyclodextrin inclusion protection not only lose a significant amount of components during formulation preparation but also suffer from insufficient sustained efficacy due to rapid release. This result fully demonstrates the indispensability of the β-cyclodextrin inclusion complex process in ensuring the integrity of volatile oil components, formulation stability, and sustained efficacy.

[0070] Comparative Example 2, without the addition of polyoxyethylene (35) castor oil, showed that the core active ingredients, such as deer antler polypeptides and ginsenosides, are poorly soluble in water and difficult to disperse spontaneously and stably in aqueous formulations. Polyoxyethylene (35) castor oil, as a non-ionic solubilizer, can bind to these poorly soluble components through its hydrophobic groups and interact with water molecules through its hydrophilic groups, forming a micellar dispersion system. This significantly improves the solubility and dispersion stability of the poorly soluble components in the aqueous phase. Without this solubilizer, the poorly soluble components will aggregate and precipitate due to insufficient solubility. This not only reduces the content of extractable active ingredients during testing but also disrupts the physical homogeneity of the formulation, causing precipitation and turbidity. Furthermore, the precipitated components are more prone to degradation during storage, further affecting the stability and efficacy of the formulation. This test result clearly highlights the crucial role of the solubilization process in ensuring the effectiveness of poorly soluble components and the physical stability of the formulation.

[0071] Comparative Example 3 eliminated the separate extraction process of deer antler and extracted it by mixing it with fourteen other medicinal herbs. The content of deer antler polypeptides in this example was significantly lower than in the previous example. The active polypeptide components in deer antler are highly sensitive to extraction temperature and time. Other medicinal herbs contain tannins and polysaccharides, which can interact with deer antler polypeptides during mixed extraction, leading to insufficient dissolution and even denaturation due to unsuitable extraction conditions. By employing a separate extraction process for deer antler, the extraction temperature, stirring speed, and decoction time can be controlled, minimizing the damage to deer antler polypeptides from external factors and avoiding interference with other medicinal components. This improves the extraction efficiency and activity retention rate of the core components. Subsequent compounding with the fourteen-herb herbal extract further enhances the synergistic effect of the components in nourishing qi and blood. This result demonstrates the significant importance of the separate extraction process for deer antler in ensuring the effectiveness of the core components and the overall efficacy of the preparation.

[0072] Comparative Examples 1-3 lacked the β-cyclodextrin inclusion process, the polyoxyethylene (35) castor oil solubilization process, and the deer antler separate extraction process, resulting in the oxidation and loss of the core components of the volatile oil, the reduction of the content of the poorly soluble components, the obstruction of the dissolution of deer antler peptides, and the damage to their activity. These factors collectively manifested as insufficient retention of the effective components in the formulations and a significant decrease in stability and efficacy persistence.

[0073] The above results demonstrate and describe the basic principles and main features of this application, as well as its advantages.

[0074] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A sugar-free oral liquid for invigorating qi and nourishing blood, characterized in that, The oral liquid includes traditional Chinese medicine components and excipients; The Chinese medicine components include fifteen Chinese herbs, namely deer antler, codonopsis, astragalus, angelica, polygonatum, yam, ginseng, ophiopogon, atractylodes, rehmannia, prepared he shou wu, schisandra, tangerine peel, lycium bark, and epimedium. The excipients include β-cyclodextrin, steviol glycosides, polyoxyethylene (35) castor oil, ethylparaben, and orange flavoring; the β-cyclodextrin is used to encapsulate the volatile oils, which include angelica volatile oil and tangerine peel volatile oil, which are obtained by decocting angelica and tangerine peel with purified water.

2. The sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 1, characterized in that, The mass ratio of the following ingredients is (8-10):(40-50):(58-68):(32-40):(10-15):(15-20):(8-10):(10-15):(15-20):(24-30):(20-25):(8-10) : (10-15): (8-10): (10-15); The amount of β-cyclodextrin used is 1.8-2.2 times the total weight of the volatile oil; The mass-volume ratio of the deer antler, steviol glycosides, polyoxyethylene (35) castor oil, ethylparaben and orange flavor is (8-10) g: (0.18-0.22) g: (0.08-0.12) g: (0.025-0.035) g: (0.4-0.5) mL.

3. A method for preparing a sugar-free Qi-nourishing and blood-tonifying oral liquid as described in claim 1 or 2, characterized in that, Includes the following steps: S1. Take fifteen kinds of Chinese medicine. Among them, deer antler is quickly sprayed and washed with purified water, then crushed to obtain pretreated deer antler powder. The remaining fourteen kinds of Chinese medicine are sprayed with purified water to moisten them, cut into thin slices, and dried to obtain pretreated Chinese medicinal materials. S2. Take the pretreated deer antler powder, add purified water and decoct. The decoction is coarsely filtered, finely filtered and concentrated under reduced pressure to obtain a concentrated solution. Add ethanol, let stand, filter, collect the filtrate, add chitosan, adjust the pH with citric acid to obtain a deer antler polypeptide-chitosan complex solution, concentrate to obtain deer antler extract. S3. Take the remaining fourteen pre-treated Chinese medicinal materials, add purified water and decoct them, collect the volatile oil, which includes volatile oil of Angelica sinensis and volatile oil of Citrus reticulata. Filter the decoction to obtain filtrate. Mix the collected volatile oil with β-cyclodextrin to form a volatile oil-β-cyclodextrin inclusion complex. Concentrate the filtrate, add the volatile oil-β-cyclodextrin inclusion complex, and concentrate under reduced pressure to obtain a clear extract of the fourteen Chinese medicinal materials. S4. Heat purified water to the first set temperature, add steviol glycosides, cool to the second set temperature, add polyoxyethylene (35) castor oil, add deer antler extract and fourteen kinds of Chinese herbal extract, heat to the third set temperature, boil to sterilize, cool to the fourth set temperature, adjust the pH with citric acid, add orange flavor, add purified water to make up the volume, filter, and obtain the medicine solution; fill the medicine solution into a pharmaceutical composite film bag, sterilize, and obtain sugar-free Qi-nourishing and blood-tonifying oral liquid.

4. The preparation method of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 3, characterized in that, In step S1, the particle size of the pulverized material is 80-100 mesh; the thickness of the sheet is 1.5-2.5 mm; the drying temperature is 60-80℃; and the drying time is 1-2 hours.

5. The preparation method of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 3, characterized in that, In step S2, the mass-to-volume ratio of the pretreated deer antler powder to purified water is (8-10) g: (48-60) mL; the decoction step is as follows: maintain a stirring speed of 40-50 r / min, heat to boiling, then simmer for 2.5-3.5 h each time; the coarse filtration medium is a pharmaceutical-grade filter paperboard containing diatomaceous earth with a pore size of 4-6 μm; the fine filtration medium is a pharmaceutical-grade filter paperboard containing diatomaceous earth with a pore size of 0.8-1.2 μm; the mass ratio of the pretreated deer antler powder to chitosan is (8-10): (0.02-0.04); the adjusted pH is 5.0-5.

5.

6. The preparation method of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 3, characterized in that, In step S2, the conditions for vacuum concentration are: vacuum degree 0.06-0.09 MPa, temperature 50-60℃; the relative density of the concentrate at 20℃ is 1.20-1.25; the mass fraction of ethanol is 95%, and the amount of ethanol is 2.5-3.5 times the volume of the concentrate; the settling time is 20-28 h; the filtration medium is diatomaceous earth filter paper with a pore size of 0.8-1.2 μm; and the relative density of the concentrated liquid at 20℃ is 1.00-1.

15.

7. The preparation method of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 3, characterized in that, In step S3, the decoction process is as follows: add 7-9 times the total weight of the remaining fourteen Chinese medicinal herbs in purified water, heat to boiling, then reduce to a simmer and maintain the decoction temperature at 95-98°C. Stir continuously at a speed of 40-50 r / min for 2.5-3.5 hours, then filter. Add 6-8 times the amount of purified water to the dregs and decoct again for 1.5-2.5 hours. The filtration medium is a diatomaceous earth-containing filter paper with a pore size of 4-6 μm.

8. The preparation method of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 3, characterized in that, In step S3, the relative density of the concentrated liquid at 20°C is 1.14-1.17; the conditions for vacuum concentration are: vacuum degree 0.06-0.09 MPa and temperature 50-60°C; the relative density of the vacuum-concentrated liquid at 20°C is 1.

19.

9. The preparation method of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 3, characterized in that, In step S4, the mass-to-volume ratio of steviol glycosides to purified water is (0.18-0.22) g : (40-50) mL; the first set temperature is 55-65℃; the second set temperature is 40-50℃; the third set temperature is 95-105℃; the boiling sterilization time is 25-35 min; and the fourth set temperature is 30-40℃.

10. The preparation method of a sugar-free Qi-nourishing and blood-tonifying oral liquid according to claim 3, characterized in that, In step S4, the pH adjustment range is 3.8-5.0; the volume of the final volume is 85-95 mL; the filtration medium is a 0.7-0.9 μm filter membrane; the sterilization temperature is 95-105℃; and the sterilization time is 25-35 min.

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