Preparation method of low solid content astragalus membranaceus extract oral liquid

Abstract

The application provides a preparation method of low-solid-content astragalus membranaceus fine oral liquid. The method introduces a chitosan-diatomite composite flocculating agent on the basis of a traditional percolation process, removes macromolecular impurities in the percolation liquid by optimizing flocculation process conditions, and achieves the purposes of greatly reducing the solid content, improving the retention rate of core pharmacodynamic components, and shortening the production cycle.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparations, and in particular to a method for preparing a low-solids-content Astragalus extract oral liquid. Background Technology

[0002] Astragalus extract oral liquid is a single-ingredient oral liquid made from the dried root of Astragalus membranaceus, a legume, through percolation extraction, concentration, and preparation. Its core active ingredients are flavonoids such as astragaloside A and verbascoside, as well as polysaccharides, amino acids, and other active components. Clinically, it is used to tonify Qi and raise Yang, strengthen the exterior and stop sweating, promote diuresis and reduce edema, and generate fluids and nourish blood. It is a commonly used traditional Chinese medicine for treating Qi deficiency and fatigue, spontaneous sweating due to exterior deficiency, and edema due to Qi deficiency. The traditional preparation method is as follows: Take coarse Astragalus powder, and according to the percolation method under the section on fluid extracts and extracts, use 30% ethanol as a solvent, soak for 24 hours, then percolate. Collect the percolate, concentrate to an appropriate volume, dilute with water to 1000ml, stir well, let stand, filter, and seal to obtain the final product.

[0003] The traditional process has the following technical defects:

[0004] (1) Poor impurity removal effect and poor stability: The percolate contains a large number of non-pharmaceutical macromolecular impurities such as starch, resin, protein, and pectin. It cannot be completely removed by simple static filtration, resulting in high solid content in the finished product, easy precipitation and turbidity during storage, and poor clarity.

[0005] (2) Serious loss of effective ingredients: During the static filtration process, some astragaloside A and astragalus polysaccharide will be lost due to adsorption and encapsulation with the precipitate.

[0006] (3) Long production cycle and high cost: The long settling time (usually more than 24 hours) is not conducive to continuous production. The settling effect is significantly affected by factors such as temperature, time and drug viscosity, and there are large batch-to-batch differences.

[0007] Although some studies have disclosed other preparation methods to try to overcome the above-mentioned defects, such as using chitosan in the clarification process of Astragalus oral liquid, these technical solutions still cannot simultaneously meet the dual technical goals of "low solid content" and "high retention rate of effective ingredients".

[0008] Therefore, there is an urgent need to develop a preparation process for Astragalus extract oral liquid that can efficiently reduce solid content, improve clarity and stability, and without losing the medicinal components. Summary of the Invention

[0009] To address the problems of excessively high solid content, poor clarity, significant loss of active ingredients, and long production cycle in existing technologies for Astragalus extract oral liquid, this invention provides a method for preparing low-solid-content Astragalus extract oral liquid. This method introduces a chitosan-diatomaceous earth composite flocculant based on the traditional percolation process. By optimizing the flocculation process conditions, it selectively removes macromolecular impurities in the percolate, thereby achieving the goals of significantly reducing solid content, improving the retention rate of core active ingredients, and shortening the production cycle.

[0010] In a first aspect, this application provides a method for preparing Astragalus extract oral liquid, comprising the following steps:

[0011] (1) Preparation of Astragalus percolate

[0012] Take 666.7g of crude Astragalus powder, use 30% ethanol as solvent, soak for 24 hours and then percolate at a rate of 2.0ml / min-2.5ml / min. Collect the percolate, filter it, and obtain Astragalus percolate.

[0013] (2) Flocculation and clarification treatment

[0014] Concentrate the Astragalus membranaceus percolate to a relative density of 1.05-1.10 (compared to pure water) at 60℃, boil, cool to room temperature, add water to 700mL, adjust the pH of the solution to 4.5-6.0, and maintain the temperature in a water bath at 40-50℃. While stirring, slowly add the chitosan-diatomaceous earth composite flocculant at a stirring speed of 120-180r / min for 30min. Stop stirring and allow to stand for 2-3 hours to settle, completing the flocculation and clarification process. The amount of the composite flocculant added is 0.12-0.18g per 100ml of solution; the mass ratio of chitosan to diatomaceous earth is 1:3.

[0015] (3) Solid-liquid separation

[0016] The flocculated medicinal solution was centrifuged at 5000 r / min for 10 min, then filtered through a plate and frame filter to remove the flocculent precipitate, thus obtaining refined Astragalus percolate.

[0017] (4) Formulation

[0018] Transfer the refined Astragalus percolate into a mixing tank, add purified water to dilute to 1000ml, stir well, add steviol glycosides, ethylparaben, and lemon flavoring in sequence, stir to dissolve, mix well, filter, fill and seal, and sterilize to obtain Astragalus extract oral liquid.

[0019] In some implementations, the pH of the solution is adjusted to 5.0 during the flocculation and clarification process.

[0020] In some implementation schemes, the water bath temperature is 45°C during the flocculation and clarification process.

[0021] In some implementation schemes, the amount of composite flocculant added in the flocculation and clarification treatment step is 0.15g per 100ml of solution.

[0022] In some implementations, the stirring speed is 170 r / min during the flocculation and clarification step.

[0023] In some implementations, the flocculation clarification step involves stirring for 30 minutes.

[0024] In some implementation schemes, the flocculation clarification step involves a settling period of 2.5 hours.

[0025] Beneficial effects

[0026] Based on the traditional percolation process, this invention effectively reduces the solid content of Astragalus extract oral liquid by adding flocculation clarification technology, while fully preserving the core active ingredients such as astragaloside A, flavonoids, and polysaccharides. It overcomes the defect of large loss of active ingredients in the traditional ethanol percolation process, improves the clarity and long-term stability of the finished product, and has good adaptability and reproducibility. Attached Figure Description

[0027] Figure 1 Appearance comparison between "traditional process sample" and "invention process sample" Detailed Implementation

[0028] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to these embodiments.

[0029] Example 1: Preparation method of low-solids-content Astragalus extract oral liquid

[0030] 1. Experimental materials

[0031] (1) Active pharmaceutical ingredient

[0032] Astragalus

[0033] (2) Experimental drugs and reagents

[0034] 30% ethanol (percolation solvent), chitosan-diatomaceous earth composite flocculant (chitosan deacetylation degree ≥90%), purified water, steviol glycosides, ethylparaben, and lemon flavor (all meeting pharmaceutical standards).

[0035] Chitosan: ① Qingdao Boyite Biomaterials Co., Ltd.; ② Jiangsu Aoxin Biotechnology; ③ Jiangsu Kangting Biotechnology Co., Ltd.

[0036] Diatomaceous earth: Xilong Scientific Co., Ltd.

[0037] Steviosides: Shandong Haigen Biotechnology Co., Ltd.

[0038] Ethylparaben: Jiangxi Alpha High-Tech Pharmaceutical Co., Ltd.

[0039] Lemon Flavoring: Senxin Flavor & Pigment Technology (China) Co., Ltd.

[0040] 2. Preparation method

[0041] (1) Preparation of Astragalus percolate

[0042] Take 666.7g of crude Astragalus powder, and according to the percolation method under the section on fluid extracts and extracts, use 30% ethanol as solvent, soak for 24 hours, and then percolate at a rate of 2.0ml / min-2.5ml / min. Collect the percolate, filter it, and obtain Astragalus percolate.

[0043] (2) Flocculation and clarification treatment

[0044] Concentrate the Astragalus membranaceus percolate to a relative density of 1.05-1.10 at 60℃, boil, cool to room temperature, add water to 700mL, adjust the pH of the solution to 4.5-6.0, and maintain the temperature in a water bath at 40-50℃. While stirring, slowly add the chitosan-diatomaceous earth composite flocculant at a stirring speed of 120-180 rpm for 30 minutes. Stop stirring and allow the solution to stand for 2-3 hours to settle, completing the flocculation and clarification process. The amount of the composite flocculant added is 0.12-0.18g per 100ml of solution; the mass ratio of chitosan to diatomaceous earth is 1:3.

[0045] (3) Solid-liquid separation

[0046] The flocculated medicinal solution was centrifuged at 5000 r / min for 10 min, then filtered through a plate and frame filter to remove the flocculent precipitate, thus obtaining refined Astragalus percolate.

[0047] (4) Formulation

[0048] Transfer the refined astragalus percolate into a mixing tank, add purified water to dilute to 1000ml, stir well, then add steviol glycosides, ethylparaben, and lemon flavoring in sequence, stir to dissolve, mix well, filter, fill and seal, and sterilize to obtain low solids content astragalus extract oral liquid.

[0049] Example 2: Optimization Experiment of Chitosan to Diatomite Mass Ratio

[0050] To determine the optimal ratio of chitosan to diatomaceous earth, seven experimental groups were set up: chitosan:diatomaceous earth mass ratios of 1:0 (i.e., pure chitosan), 1:1, 1:2, 1:3, 1:4, 1:5, and 0:1 (i.e., pure diatomaceous earth). All experimental groups underwent "flocculation and clarification treatment" under the same conditions: pH 5.0, temperature 45℃, composite flocculant dosage of 0.15g per 100ml of solution, stirring speed of 170r / min, stirring for 30 min, and settling for 2.5h.

[0051] The optimal formulation was selected based on the following evaluation indicators: total solids removal rate, astragaloside A retention rate, total polysaccharide retention rate, total flavonoid retention rate, and floc settling time (the time required for the supernatant to reach a turbidity of ≤10 NTU).

[0052] Explanation of the calculation formula:

[0053] Total solids removal rate (%) = (Solids content in the original solution before flocculation − Solids content in the supernatant after flocculation) ÷ Solids content in the original solution before flocculation × 100%.

[0054] Component retention rate (%) = (Component content in the supernatant after flocculation ÷ Component content in the original solution before flocculation) × 100%.

[0055] The results for each experimental group are shown in Table 1.

[0056] Table 1

[0057] 1:0 28.3±1.5 84.6±1.2 86.2±1.3 85.3±1.4 150±10 1:1 33.7±1.2 87.4±1.1 88.9±1.0 88.1±1.1 110±8 1:2 36.2±1.0 90.1±0.9 91.3±0.8 90.7±0.9 85±6 1:3 35.9±0.8 93.5±0.7 94.8±0.6 93.6±0.7 60±5 1:4 34.9±0.9 93.1±0.8 94.4±0.7 93.2±0.8 65±6 1:5 33.4±1.1 92.3±0.9 93.0±0.9 92.5±0.9 75±7 0:1 — — — — The flocs are fine and fragmented, making sedimentation difficult (unclear for more than 240 minutes).

[0058] Note: All indicators are calculated based on the corresponding components contained in the un-flocculated Astragalus percolate (concentrated to a relative density of 1.05-1.10) as 100%; the solid content was determined by the drying method under General Chapter 0832 of Part IV of the 2025 edition of the Chinese Pharmacopoeia; astragaloside A was determined by HPLC-ELSD; total flavonoids were determined by ultraviolet spectrophotometry; and total polysaccharides were determined by the phenol-sulfuric acid method.

[0059] Results analysis:

[0060] The pure diatomaceous earth group (0:1) had fine and highly dispersible flocs. Even after standing for more than 240 minutes, it could not be effectively separated and clarified, indicating extremely weak flocculation. Therefore, no solids and effective components were tested for this group.

[0061] The pure chitosan group (1:0) has good flocculation and sedimentation performance, but the flocs are light and soft, and the sedimentation speed is relatively slow (150 min). The retention rate of effective components in the early stage of flocculation is low, which may be related to the loss of effective components such as astragaloside A and polysaccharides due to the flocs formed when chitosan is excessive.

[0062] With the increase of the proportion of diatomaceous earth (1:1-1:3), the composite flocculant exerted a significant synergistic effect:

[0063] (1) The porous structure of diatomaceous earth provides a large number of adsorption sites, which can effectively adsorb chitosan molecules to form dense flocs, increasing the floc density and significantly accelerating the settling speed. The settling time at a 1:3 ratio is only 60 min, which is much lower than the 150 min of the pure chitosan group.

[0064] (2) After the introduction of diatomaceous earth, the actual effective amount of chitosan added is reduced, which reduces the loss of effective components due to excessive chitosan encapsulation. Astragaloside A, total polysaccharides and total flavonoids are significantly improved, reaching peak values ​​at a 1:3 ratio (retention rates of 93.5%, 94.8% and 93.6%, respectively).

[0065] (3) The composite flocculant enhances the synergistic adsorption-flocculation effect on macromolecular impurities such as pectin, protein, and starch, and the solid removal rate increases significantly from 28.3% for pure chitosan to 35.9%. When the proportion of diatomaceous earth is further increased to 1:4 and 1:5, both the solid removal rate and the retention rate of effective components show a slight decrease.

[0066] in conclusion:

[0067] When the mass ratio of chitosan to diatomaceous earth is 1:3, all indicators reach their optimal levels. The solids removal rate and the retention rate of effective components are both at the optimal inflection point of the ratio curve, and the floc settling time is the shortest (60 min). At the same time, the composite flocculant exhibits the most stable overall clarification performance and the smallest batch-to-batch coefficient of variation (RSD < 3%) at this ratio. Therefore, a mass ratio of chitosan to diatomaceous earth of 1:3 is determined to be the optimal composite ratio.

[0068] Example 3: Investigation on the effects of different types / sources of chitosan and diatomaceous earth on flocculation effect

[0069] To verify the adaptability of the process of this invention to raw materials from different suppliers and the universality of the 1:3 mass ratio of chitosan to diatomaceous earth, this experiment systematically investigated the flocculation and clarification effects of chitosan and diatomaceous earth from three different sources at a 1:3 ratio. The experimental conditions were the same as in Example 2 (pH 5.0, temperature 45℃, composite flocculant addition 0.15%). The experimental results are shown in Table 2.

[0070] Table 2

[0071] Qingdao Boyite Xilong Science 35.7±0.9 93.2±0.8 94.5±0.7 93.3±0.8 62±6 Jiangsu Aoxin Biotechnology Xilong Science 36.0±0.8 93.7±0.6 94.9±0.6 93.8±0.7 59±5 Jiangsu Kangting Biotechnology Xilong Science 36.2±0.7 93.4±0.7 94.6±0.6 93.5±0.7 58±5

[0072] Results analysis:

[0073] Under the condition of a chitosan to diatomaceous earth mass ratio of 1:3, chitosan and diatomaceous earth from different sources and with different degrees of deacetylation were combined with each other, and all flocculation and clarification indicators remained at a stable and excellent level, with little difference in indicators between the combinations.

[0074] in conclusion:

[0075] The 1:3 mass ratio of chitosan to diatomaceous earth and the corresponding process parameters show good adaptability and reproducibility for chitosan and diatomaceous earth from different sources.

[0076] Example 4: Comparison of products obtained by conventional processes and the process of this invention

[0077] Using Astragalus membranaceus of the same quality and source as the starting material, Astragalus membranaceus oral liquid was prepared by both traditional and the process of this invention, and a comparative study was conducted. The results are shown in Table 3.

[0078] Table 3

[0079] Astragaloside A content (mg / mL) 0.12±0.02 0.14±0.01 Increased by 16.7% Total polysaccharide content (mg / mL) 2.20±0.15 2.75±0.10 Increased by 25.0% Total flavonoid content (mg / mL) 0.18±0.01 0.22±0.01 Increased by 22.2% Solid content (%, w / v) 3.15±0.20 2.02±0.12 Reduced by 35.9% Accelerated stability testing over 6 months (40℃ / 75%RH) Visible precipitate and turbidity appear Clear and transparent, without sediment or turbidity. —

[0080] Note: Astragaloside A was determined by HPLC-ELSD; total flavonoids were determined by UV spectrophotometry; total polysaccharides were determined by phenol-sulfuric acid method; and the solid content was determined by drying method according to Section 0832 of General Chapter IV of the 2025 edition of the Chinese Pharmacopoeia.

[0081] Results analysis:

[0082] (1) Significant retention of effective components: The flocculation process is gentle and no additional organic solvents are added throughout the process, which can effectively compensate for the loss of flavonoids and polysaccharides caused by traditional 30% ethanol percolation. Compared with the finished product of the traditional process, the astragaloside A content of the finished product of this invention is increased by 16.7%, the total flavonoid content is increased by 22.2%, and the total polysaccharide retention rate is increased by 25.0% (P<0.01), which fully meets the pharmacopoeia quality standards.

[0083] (2) The solid content is greatly reduced: Compared with the traditional percolation and static filtration process, the solid content in the finished product of the present invention is reduced by 35.9%, the liquid is clear and transparent, and there is no precipitation, turbidity or stratification when the sample is retained for a long time (6 months, 40℃ / 75%RH), which greatly improves the stability and solves the problem of easy turbidity and precipitation in the finished product of the traditional process.

[0084] (3) High specificity: The mass ratio of chitosan to diatomaceous earth and the flocculation process parameters are optimized for Astragalus extract oral liquid, which specifically removes macromolecular impurities such as starch and pectin from Astragalus percolate without affecting the core active ingredients. It is compatible with 30% ethanol percolate and the impurity removal effect is stable and reliable.

[0085] (4) Improve the quality of the preparation: The drug solution has high clarity and better taste, reduces the intake of ineffective impurities, and improves patient compliance; at the same time, it reduces the interference of impurities in the filling and sterilization process, and improves the finished product qualification rate; the flocculation clarification step replaces the traditional long-term static filtration, shortens the production cycle, reduces filter material consumption, reduces the safety management cost brought about by the use of ethanol, and effectively reduces multiple production costs such as labor, energy consumption, and material consumption.

Claims

1. A method for preparing Astragalus extract oral liquid, comprising the following steps: (1) Preparation of Astragalus percolate Take 666.7g of crude Astragalus powder, use 30% ethanol as solvent, soak for 24 hours and then percolate at a rate of 2.0ml / min-2.5ml / min. Collect the percolate, filter it, and obtain Astragalus percolate. (2) Flocculation and clarification treatment Concentrate the Astragalus membranaceus percolate to a relative density of 1.05-1.10 at 60℃, boil, cool to room temperature, add water to 700mL, adjust the pH of the solution to 4.5-6.0, and maintain the temperature in a water bath at 40-50℃. While stirring, slowly add the chitosan-diatomaceous earth composite flocculant at a stirring speed of 120-180r / min for 30min. Stop stirring and allow the solution to stand for 2-3 hours to settle, completing the flocculation and clarification process. The amount of the composite flocculant added is 0.12-0.18g per 100ml of solution; the mass ratio of chitosan to diatomaceous earth is 1:

3. (3) Solid-liquid separation The flocculated medicinal solution was centrifuged at 5000 r / min for 10 min, then filtered through a plate and frame filter to remove the flocculent precipitate, thus obtaining refined Astragalus percolate. (4) Formulation Transfer the refined Astragalus percolate into a mixing tank, add purified water to dilute to 1000ml, stir well, add steviol glycosides, ethylparaben, and lemon flavoring in sequence, stir to dissolve, mix well, filter, fill and seal, and sterilize to obtain Astragalus extract oral liquid.

2. The method for preparing Astragalus extract oral liquid according to claim 1, wherein, In the flocculation and clarification process, the pH of the solution is adjusted to 5.

0.

3. The method for preparing Astragalus extract oral liquid according to claim 1 or 2, wherein, In the flocculation and clarification process, the water bath temperature is 45℃.

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