Prejudgment method for clarity stability of traditional Chinese medicine oral liquid, application of prejudgment method and modified Huoxiang Zhengqi mixture

Abstract

The invention provides a traditional Chinese medicine oral liquid clarity stability pre-judgment method and application thereof and a modified Huoxiang Zhengqi mixture, and relates to the technical field of medicine detection. According to the pre-judgment method, by quantitatively detecting the content of known macromolecular substances prone to precipitation in the liquid medicine and comparing the content with a preset critical value which is scientifically verified, whether precipitation occurs in the whole preset storage period or not can be predicted when product production is completed or the product is released; the pre-judgment method can be effectively applied to pre-judgment of the clarity stability of the flavored Huoxiang Zhengqi mixture. Meanwhile, the invention further provides the modified Huoxiang Zhengqi mixture, the total content of neutral sugar, acid sugar and protein in the modified Huoxiang Zhengqi mixture oral liquid is smaller than or equal to 106 mg / ml, the content of the neutral sugar is smaller than 100 mg / ml, and it can be pre-judged that the modified Huoxiang Zhengqi mixture oral liquid has qualified clarity stability under the long-term storage condition as long as the standard is met through verification.

Description

Technical Field

[0001] This invention relates to the field of drug detection technology, and in particular to a method for predicting the clarity and stability of traditional Chinese medicine oral liquids and its application, as well as a modified Huoxiang Zhengqi compound. Background Technology

[0002] Oral liquid preparations, especially traditional Chinese medicine oral liquids, often contain a large amount of macromolecular substances such as polysaccharides, proteins, and tannins due to the complex composition of their raw materials. These substances are in a metastable state in the liquid environment and often precipitate due to the disruption of their solubility balance during storage. This seriously affects the appearance, taste, and uniformity of the product's internal quality, and has long been a technical challenge for the traditional Chinese medicine oral liquid industry.

[0003] Currently, the industry generally relies on long-term accelerated stability tests and long-term stability tests (such as the General Chapter 9001 Guideline in the Chinese Pharmacopoeia) to assess the clarity and stability of oral solutions. This method is time-consuming and significantly lags behind the pace of research and development and production. Moreover, this "post-hoc" assessment model leads to inefficiency during the process development and screening stages, making it impossible to quickly and effectively evaluate the effects of purification processes. More importantly, at the product release stage, existing quality standards lack key testing items and control indicators that can effectively predict the clarity and stability of a product throughout its shelf life, posing a potential risk to the quality and stability of the product after it is launched on the market.

[0004] The modified Huoxiang Zhengqi compound is listed in the Chinese Pharmacopoeia. Its prescription is complex (containing thirteen herbs), and its preparation process involves multiple extraction methods such as percolation, distillation, and decoction. The composition is even more complex after combining the extracted parts. Samples prepared according to the current pharmacopoeia process showed obvious precipitation after only one month of storage in accelerated testing (40℃±2℃) and long-term testing (25℃±2℃), demonstrating that the product has significant potential for clarity and stability issues.

[0005] Therefore, those skilled in the art have long needed to develop a rapid detection method and process control standard that can be correlated with the long-term stability results of oral liquids, so as to quickly and quantitatively predict the risk of precipitation in the final product during storage during the production process or when the product is released, and realize the "in-process" prediction and proactive control of the clarity stability, thereby improving the controllability of product quality.

[0006] In view of this, the present invention is hereby proposed. Summary of the Invention

[0007] The primary objective of this invention is to provide a method for predicting the clarity and stability of oral liquids of traditional Chinese medicine. This method can quickly and objectively predict whether precipitation will occur during the entire predetermined storage period when the product is completed or released, thereby fundamentally solving the problems of long cycle, low efficiency, and strong subjectivity of traditional methods.

[0008] The second objective of this invention is to provide a method for predicting the clarity stability of the flavored Huoxiang Zhengqi compound.

[0009] The third objective of this invention is to provide a flavored Huoxiang Zhengqi compound.

[0010] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted: This invention provides a method for predicting the clarity stability of traditional Chinese medicine oral liquids, the method comprising the following steps: The precipitating components in the oral liquid sample to be tested are detected, and the content of the precipitating components is compared with the preset critical value. When the content of the precipitating components is lower than the preset critical value, it is predicted that the clarity of the oral liquid to be tested will be stable within the predetermined storage period. The components that are prone to precipitation include neutral sugars, acidic sugars, and proteins.

[0011] Furthermore, the oral liquid to be tested is a modified Huoxiang Zhengqi Mixture.

[0012] The above-mentioned method provided by the present invention is applied to the prediction of the clarity and stability of the modified Huoxiang Zhengqi compound.

[0013] This invention provides a method for predicting the clarity stability of a flavored Huoxiang Zhengqi compound, the method comprising the following steps: S1: Provide a sample of the flavored Huoxiang Zhengqi compound to be tested and detect the content of easily precipitating components in the sample, including neutral sugars, acidic sugars and proteins; The modified Huoxiang Zhengqi compound is an oral liquid; S2: Compare the content of the easily precipitating component detected with the preset critical value. When the content of the easily precipitating component is lower than the preset critical value, it is predicted that the clarity of the oral liquid to be tested will be stable within the predetermined storage period. The preset critical value is: the total content of neutral sugar, acid sugar and protein is ≤106mg / ml, and the content of neutral sugar is <100 mg / ml.

[0014] Furthermore, the method for determining the neutral sugar content is the anthrone-sulfuric acid method; Preferably, the method for determining the neutral sugar content includes reacting the test sample with anthrone-sulfuric acid reagent and measuring the absorbance at a wavelength of 625 nm; Preferably, the method for determining the acid sugar content is the m-hydroxybiphenyl method; Preferably, the method for determining protein content is the Coomassie brilliant blue method.

[0015] The present invention provides a modified Huoxiang Zhengqi oral liquid, wherein the total content of neutral sugar, acid sugar and protein in the modified Huoxiang Zhengqi oral liquid is ≤106mg / ml, and the content of neutral sugar is <100 mg / ml.

[0016] This invention provides a method for preparing the above-mentioned flavored Huoxiang Zhengqi compound, the method comprising: The modified Huoxiang Zhengqi compound was purified, and the contents of neutral sugar, acid sugar and protein in the solution were determined. When the total contents of neutral sugar, acid sugar and protein were ≤106mg / ml and the neutral sugar content was <100 mg / ml, the purification was completed and the modified Huoxiang Zhengqi compound was obtained.

[0017] Furthermore, the purification method is alcohol precipitation, and the amount of ethanol added during the alcohol precipitation process is controlled in the following way: Real-time monitoring of the neutral sugar concentration Cm and volume V of the drug solution; According to the formula Calculate the volume of ethanol to be added, Ve, where: Ct = 100 mg / ml; Ve is the volume of ethanol to be added.

[0018] Furthermore, the purification method is membrane filtration.

[0019] The present invention provides a method for predicting the clarity stability of the above-mentioned flavored Huoxiang Zhengqi compound, which is applied in the production control of the flavored Huoxiang Zhengqi compound.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: The present invention provides a method for predicting the clarity and stability of oral liquid Chinese medicine. The method accurately and quantitatively detects the content of known precipitating macromolecules (neutral sugars, acidic sugars, and proteins) in the liquid and compares them with scientifically verified preset critical values. This method can quickly and objectively predict whether precipitation will occur during the entire predetermined storage period when the product is completed or released, thus fundamentally solving the problems of long cycle, low efficiency, and strong subjectivity of traditional methods.

[0021] This invention provides a method for predicting the clarity stability of Jiawei Huoxiang Zhengqi Mixture. This method establishes a composite quantitative standard combining total content control and core component limits by identifying easily precipitating components such as neutral sugars, acidic sugars, and proteins in Jiawei Huoxiang Zhengqi Mixture (total content of neutral sugars, acidic sugars, and proteins ≤ 106 mg / ml, and neutral sugar content < 100 mg / ml). This transforms the traditional stability assessment, which relies on long-term observation and subjective evaluation, into a rapid, quantitative, in-process prediction that can be achieved through objective testing at the end of production. This fundamentally solves the long-standing industry problem of delayed and uncontrollable clarity stability assessment for this product.

[0022] The method for predicting the clarity stability of the modified Huoxiang Zhengqi compound provided by this invention can be widely applied to the production control of the modified Huoxiang Zhengqi compound.

[0023] This invention provides a modified Huoxiang Zhengqi oral liquid, wherein the total content of neutral sugars, acidic sugars, and proteins in the modified Huoxiang Zhengqi oral liquid is ≤106 mg / ml, and the neutral sugar content is <100 mg / ml. This application establishes an objective and quantifiable intrinsic quality benchmark for the product by setting clear chemical limits for the total content of neutral sugars, acidic sugars, and proteins, as well as the neutral sugar content, in the modified Huoxiang Zhengqi oral liquid. Attached Figure Description

[0024] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0025] Figure 1 This is a flowchart of the detection of precipitated substances in the flavored Huoxiang Zhengqi compound provided in Example 1 of the present invention; Figure 2 This is a full-wavelength scanning characteristic spectrum of the precipitate of the flavored Huoxiang Zhengqi compound provided in Example 1 of the present invention; Figure 3 Images showing the clarity of six batches of prepared samples provided in Example 2 of this invention. Detailed Implementation

[0026] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0027] According to one aspect of the present invention, a method for predicting the clarity stability of a traditional Chinese medicine oral liquid, the method comprising the following steps: The precipitating components in the oral liquid sample to be tested are detected, and the content of the precipitating components is compared with the preset critical value. When the content of the precipitating components is lower than the preset critical value, it is predicted that the clarity of the oral liquid to be tested will be stable within the predetermined storage period. The components that are prone to precipitation include neutral sugars, acidic sugars, and proteins.

[0028] The present invention provides a method for predicting the clarity and stability of oral liquid Chinese medicine. The method accurately and quantitatively detects the content of known precipitating macromolecules (neutral sugars, acidic sugars, and proteins) in the liquid and compares them with scientifically verified preset critical values. This method can quickly and objectively predict whether precipitation will occur during the entire predetermined storage period when the product is completed or released, thus fundamentally solving the problems of long cycle, low efficiency, and strong subjectivity of traditional methods.

[0029] In a preferred embodiment of the present invention, the oral liquid to be tested is a modified Huoxiang Zhengqi mixture.

[0030] According to one aspect of the present invention, the above method is applied in the prediction of the clarity and stability of the modified Huoxiang Zhengqi compound.

[0031] The method for predicting the clarity stability of oral Chinese medicine liquids provided by this invention can be widely applied to the prediction of the clarity stability of Jiawei Huoxiang Zhengqi Mixture.

[0032] According to one aspect of the present invention, a method for predicting the clarity stability of a modified Huoxiang Zhengqi compound is provided, the method comprising the following steps: S1: Provide a sample of the flavored Huoxiang Zhengqi compound to be tested and detect the content of easily precipitating components in the sample, including neutral sugars, acidic sugars and proteins; The modified Huoxiang Zhengqi compound is an oral liquid; S2: Compare the content of the easily precipitating component detected with the preset critical value. When the content of the easily precipitating component is lower than the preset critical value, it is predicted that the clarity of the oral liquid to be tested will be stable within the predetermined storage period. The preset critical value is: the total content of neutral sugar, acid sugar and protein is ≤106mg / ml, and the content of neutral sugar is <100 mg / ml.

[0033] This invention provides a method for predicting the clarity stability of Jiawei Huoxiang Zhengqi Mixture. This method establishes a composite quantitative standard combining total content control and core component limits by identifying easily precipitating components such as neutral sugars, acidic sugars, and proteins in Jiawei Huoxiang Zhengqi Mixture (total content of neutral sugars, acidic sugars, and proteins ≤ 106 mg / ml, and neutral sugar content < 100 mg / ml). This transforms the traditional stability assessment, which relies on long-term observation and subjective evaluation, into a rapid, quantitative, in-process prediction that can be achieved through objective testing at the end of production. This fundamentally solves the long-standing industry problem of delayed and uncontrollable clarity stability assessment for this product.

[0034] In a preferred embodiment of the present invention, the method for determining the neutral sugar content is the anthrone-sulfuric acid method; Preferably, the method for determining the neutral sugar content includes reacting the test sample with anthrone-sulfuric acid reagent and measuring the absorbance at a wavelength of 625 nm; Preferably, the method for determining the acid sugar content is the m-hydroxybiphenyl method; Preferably, the method for determining protein content is the Coomassie brilliant blue method.

[0035] According to one aspect of the present invention, a modified Huoxiang Zhengqi oral liquid contains a total content of neutral sugars, acidic sugars and proteins of ≤106 mg / ml, and a neutral sugar content of <100 mg / ml.

[0036] This invention provides a modified Huoxiang Zhengqi oral liquid, wherein the total content of neutral sugars, acidic sugars, and proteins in the modified Huoxiang Zhengqi oral liquid is ≤106 mg / ml, and the neutral sugar content is <100 mg / ml. This application establishes an objective and quantifiable intrinsic quality benchmark for the product by setting clear chemical limits for the total content of neutral sugars, acidic sugars, and proteins, as well as the neutral sugar content, in the modified Huoxiang Zhengqi oral liquid.

[0037] According to one aspect of the present invention, a method for preparing the above-mentioned flavored Huoxiang Zhengqi compound, the method comprising: The modified Huoxiang Zhengqi compound was purified, and the contents of neutral sugar, acid sugar and protein in the solution were determined. When the total contents of neutral sugar, acid sugar and protein were ≤106mg / ml and the neutral sugar content was <100 mg / ml, the purification was completed and the modified Huoxiang Zhengqi compound was obtained.

[0038] In a preferred embodiment of the present invention, the purification method is alcohol precipitation, and the amount of ethanol added during the alcohol precipitation process is controlled by the following method: Real-time monitoring of the neutral sugar concentration Cm and volume V of the drug solution; According to the formula Calculate the volume of ethanol to be added, Ve, where: Ct = 100 mg / ml; Ve is the volume of ethanol to be added.

[0039] In a preferred embodiment of the present invention, the purification method is membrane filtration.

[0040] According to one aspect of the present invention, a method for predicting the clarity stability of the above-mentioned modified Huoxiang Zhengqi compound is applied in the production control of the modified Huoxiang Zhengqi compound.

[0041] The method for predicting the clarity stability of the modified Huoxiang Zhengqi compound provided by this invention can be widely applied to the production control of the modified Huoxiang Zhengqi compound.

[0042] The technical solution of the present invention will be further described below with reference to the embodiments.

[0043] Example 1 Detection of precipitates in Jiawei Huoxiang Zhengqi Mixture: Figure 1 This is a flowchart for the detection of precipitated substances in the flavored Huoxiang Zhengqi compound provided in this embodiment.

[0044] (i) Take multiple batches of laboratory-prepared samples of the prepared Huoxiang Zhengqi compound that show obvious precipitation.

[0045] The sample was vacuum filtered through a 0.45 μm microporous membrane to separate the precipitate. The precipitate was washed twice with purified water, approximately 10 mL each time, to remove residual soluble components. The washed precipitate was then dried in a 60 °C oven to constant weight, accurately weighed, and set aside for later use.

[0046] (II) Systematic detection and qualitative and quantitative analysis of precipitate components: (1) Screening of small molecule substances (HPLC characteristic chromatographic method): Chromatographic conditions: An Agilent 5TC-C18 column (250 mm × 4.6 mm) was used at a column temperature of 25℃; the flow rate was 1.0 mL / min; and the detection wavelength was full-wavelength scan. The mobile phase consisted of acetonitrile (A) and 0.1% formic acid aqueous solution (B), with the following gradient elution program:

[0047] Preparation of test solution: Accurately weigh 5.00 mg of the dried precipitate from step (I), place it in a 10 mL volumetric flask, add 0.5 mL of dimethyl sulfoxide (DMSO), vortex to mix, sonicate (250 W, 40 kHz) for 10 min to completely dissolve the precipitate, dilute to the mark with purified water, shake well, and filter through a 0.22 μm filter membrane to obtain the test solution.

[0048] Determination: Accurately pipette 10 μL of the test solution and inject it into the liquid chromatograph, then record the chromatogram. The results showed that no obvious characteristic peaks of small molecules were observed in the HPLC chromatogram of the precipitate, suggesting that the precipitate was not composed of small molecule active ingredients or degradation products.

[0049] Figure 2 The full-wavelength scanning characteristic spectrum of the precipitate of the flavored Huoxiang Zhengqi compound provided in this embodiment.

[0050] (2) Quantitative analysis of macromolecules: Determination of neutral sugar content (anthrone-sulfuric acid method): Anhydrous glucose was used as a reference. The precipitate was accurately weighed, and the test solution was prepared using the same method. 1 mL of the test solution was added to 4 mL of freshly prepared anthrone-sulfuric acid reagent. The mixture was heated in a boiling water bath for 10 min, cooled in an ice bath, and the absorbance was measured at 625 nm. The neutral sugar content was calculated based on the standard curve. The average result was 43.1%.

[0051] Determination of acidic sugar content (m-hydroxybiphenyl method): D-galacturonic acid was used as a reference. 1 mL of the test solution was added to 6 mL of sodium tetraborate-sulfuric acid solution, heated in a boiling water bath for 10 min, cooled in an ice bath, and then 0.2 mL of m-hydroxybiphenyl colorimetric solution was added. The solution was incubated at room temperature in the dark for 40 min, and the absorbance was measured at 525 nm. The acidic sugar content was calculated based on the standard curve. The average result was 35.0%.

[0052] Protein content determination (Coomassie Brilliant Blue G-250 method): Bovine serum albumin was used as a reference. 1 mL of the test solution was added to 5 mL of Coomassie Brilliant Blue G-250 staining solution. After mixing, the absorbance was immediately measured at 595 nm. The protein content was calculated based on the standard curve. The average result was 28.7%.

[0053] (3) Conclusion: Systematic analysis of the precipitate from Jiawei Huoxiang Zhengqi Mixture revealed that its main components are macromolecular colloidal substances, with neutral sugars, acidic sugars, and proteins accounting for over 100% (due to possible bound states). These components are the core material basis for its unstable clarity. This finding provides a clear target for subsequent targeted control.

[0054] Example 2 (i) In order to reduce the content of the above-mentioned macromolecular impurities in the drug solution, this embodiment provides two commonly used purification techniques to prepare a series of samples.

[0055] (1) Alcohol precipitation process group: The decoction was concentrated to a relative density of 1.20 (60℃), and ethanol was added to achieve an alcohol content of 60%, 70%, and 80%, respectively. After standing, the decoction was combined with the percolation concentrate and then processed according to the pharmacopoeia process to obtain three samples, numbered 250101, 250102, and 250103.

[0056] (2) Ultrafiltration membrane separation group: Prepare the concentrate (approximately 1000 mL) according to the pharmacopoeia process. After centrifugation, filter the supernatant using PVDF ultrafiltration membranes with molecular weight cutoffs of 50 KD, 100 KD, and 300 KD, respectively. Subsequent processes are the same as in the pharmacopoeia, resulting in three samples, numbered 250201, 250202, and 250203.

[0057] Meanwhile, a batch of original process samples that were not specially purified were retained as a control (before optimization).

[0058] (II) Determination of key impurity content and stability study in samples: Content determination: The optimized method established in Example 1 (the test sample was taken directly from the drug solution and appropriately diluted) was used to determine the content of neutral sugars, acid sugars, and proteins in each sample (0 months). The results are shown in Table 1, which shows that the removal effects of different processes on impurities vary significantly.

[0059] Table 1:

[0060] Stability correlation study: All the above samples were subjected to accelerated testing (40℃±2℃) and long-term testing (25℃±2℃) simultaneously, and the time when visible precipitation appeared was observed and recorded periodically. The results are shown in Table 2.

[0061] Table 2:

[0062] Note: Although precipitates were visible to the naked eye in all six batches of prepared samples, they were all in trace amounts and could be dispersed by shaking. This meets the quality requirements of the 2025 edition of the Chinese Pharmacopoeia (0181 compound preparation), which allows for a small amount of easily dispersed precipitates.

[0063] Figure 3 Clarity images of the six batches of prepared samples provided in this embodiment.

[0064] (III) Establishment of the prediction model: Comparing the data in Table 1 and Table 2, the following correlation patterns can be observed: (1) Total content is negatively correlated with stability: the higher the total impurity content, the earlier precipitation occurs. The original process sample (total content 200.27 mg / ml) precipitated in only 9 days under accelerated conditions.

[0065] (2) Neutral sugar is a key control indicator: Among various impurities, neutral sugar has the highest content and its change trend is most consistent with the stability trend.

[0066] (3) Determination of stability threshold: Analysis revealed that all samples (250102, 250103, 250201, 250202) that did not show precipitation or only showed trace amounts of easily dispersed precipitate upon shaking in the later stages of the 6-month accelerated test had neutral sugar content below 100 mg / ml and total impurity content below or close to 106 mg / ml. Samples with neutral sugar content higher than this value all showed precipitation within 3-5 months of accelerated testing.

[0067] Therefore, based on the above correlation studies, this invention establishes a rapid predictive model for the clarity stability of Jiawei Huoxiang Zhengqi Compound: The critical internal control quality limits are established as follows: "neutral sugar content in the liquid solution <100 mg / ml" and / or "total content of neutral sugar, acid sugar, and protein ≤106 mg / ml". As long as the product meets this standard, it can be predicted that it will have satisfactory clarity stability under long-term storage conditions.

[0068] Application Example 1 Precision online control (PAT) applied to the alcohol precipitation process: 1. Control Principle: The target concentration Ct is set at 100 mg / ml. The online process analysis technology (PAT) system monitors the current neutral sugar concentration (Cm) and volume (V) of the drug solution in the alcohol concentration tank in real time.

[0069] 2. Control Algorithm: Based on the principle of material balance, the system automatically calculates the required volume of ethanol (Ve) to be added. The calculation formula is as follows: ; 3. Application Example: The online PAT system provided real-time monitoring results of Cm = 200 mg / ml, V = 1000 L, and Ct = 100 mg / ml. Automatic calculations were performed. ; The control system then instructed the metering pump to precisely add 414 L of ethanol. Verification showed that under these conditions, the neutral sugar concentration of the precipitated solution could be reduced below the target value, achieving minimal ethanol consumption while ensuring quality.

[0070] Application Example 2 Rapid evaluation and screening for use in membrane filtration processes: 1. Evaluation method: When examining different membrane modules (such as different pore sizes and materials), the neutral sugar content of their permeate is directly measured.

[0071] 2. Judgment criteria: If the neutral sugar content in the permeate can be stably maintained at <100 mg / ml, then the membrane module and its process parameters are deemed to meet the long-term stability requirements of the product and can be considered as an alternative; otherwise, it will be eliminated.

[0072] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for predicting the clarity stability of oral Chinese medicine liquids, characterized in that, The prediction method includes the following steps: The precipitating components in the oral liquid sample to be tested are detected, and the content of the precipitating components is compared with the preset critical value. When the content of the precipitating components is lower than the preset critical value, it is predicted that the clarity of the oral liquid to be tested will be stable within the predetermined storage period. The components that are prone to precipitation include neutral sugars, acidic sugars, and proteins.

2. The prediction method according to claim 1, characterized in that, The oral liquid to be tested was a modified Huoxiang Zhengqi Mixture.

3. The application of the method according to claim 1 or 2 in the prediction of the clarity and stability of Jiawei Huoxiang Zhengqi Compound.

4. A method for predicting the clarity stability of a flavored Huoxiang Zhengqi mixture, characterized in that, The prediction method includes the following steps: S1: Provide a sample of the flavored Huoxiang Zhengqi compound to be tested and detect the content of easily precipitating components in the sample, including neutral sugars, acidic sugars and proteins; The modified Huoxiang Zhengqi compound is an oral liquid; S2: Compare the content of the easily precipitating component detected with the preset critical value. When the content of the easily precipitating component is lower than the preset critical value, it is predicted that the clarity of the oral liquid to be tested will be stable within the predetermined storage period. The preset critical value is: the total content of neutral sugar, acid sugar and protein is ≤106mg / ml, and the content of neutral sugar is <100 mg / ml.

5. The prediction method according to claim 4, characterized in that, The method for determining neutral sugar content is the anthrone-sulfuric acid method; Preferably, the method for determining the neutral sugar content includes reacting the test sample with anthrone-sulfuric acid reagent and measuring the absorbance at a wavelength of 625 nm; Preferably, the method for determining the acid sugar content is the m-hydroxybiphenyl method; Preferably, the method for determining protein content is the Coomassie brilliant blue method.

6. A flavored Huoxiang Zhengqi compound, characterized in that, The total content of neutral sugars, acidic sugars and proteins in the mixture is ≤106mg / ml, and the content of neutral sugars is <100mg / ml.

7. A method for preparing the flavored Huoxiang Zhengqi compound according to claim 6, characterized in that, The preparation method includes: The modified Huoxiang Zhengqi compound was purified, and the contents of neutral sugar, acid sugar and protein in the solution were determined. When the total contents of neutral sugar, acid sugar and protein were ≤106mg / ml and the neutral sugar content was <100 mg / ml, the purification was completed and the modified Huoxiang Zhengqi compound was obtained.

8. The preparation method of the flavored Huoxiang Zhengqi compound according to claim 7, characterized in that, The purification method is alcohol precipitation, and the amount of ethanol added during the alcohol precipitation process is controlled in the following way: Real-time monitoring of the neutral sugar concentration Cm and volume V of the drug solution; According to the formula Calculate the volume of ethanol to be added, Ve, where: Ct = 100 mg / ml; Ve is the volume of ethanol to be added.

9. The preparation method of the flavored Huoxiang Zhengqi compound according to claim 7, characterized in that, The purification method is membrane filtration.

10. The application of a method for predicting the clarity stability of the modified Huoxiang Zhengqi compound according to claim 4 or 5 in the production control of the modified Huoxiang Zhengqi compound.

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