Plant component extraction method for preparing cough syrup

Abstract

The invention relates to the technical field of chromatography component analysis, in particular to a plant component extraction method for preparing cough syrup. The method comprises the following steps: firstly, extracting spectrum peaks, and obtaining the interference degree between the adjacent spectrum peaks according to the distance between the adjacent spectrum peaks and the content difference of corresponding substance components; according to the interference degree and the difference between the cut-off points on the two sides of the spectrum peak, obtaining the anomaly degree and screening out an abnormal spectrum peak; further quantizing the offset degree by combining the difference between the spectral peak areas on the two sides of the peak value according to the proportion and the anomaly of the peak bottom width and the full width at half maximum of each spectral peak; and finally, correcting the abnormal spectrum peaks according to the deviation degree difference of each abnormal spectrum peak and the connected spectrum peak and the difference of the spectrum peak area in combination with the deviation degree. According to the method, based on the interference degree between the spectrum peaks and the morphological characteristics of the spectrum peaks, the abnormal degree and the offset degree of the spectrum peaks are recognized and quantified, the correction coefficient is extracted, automatic correction of the spectrum peaks is achieved, and accurate data support is provided for extraction control and optimization of plant components.

Description

Technical Field

[0001] The invention relates to the technical field of chromatography component analysis, and in particular to a method for extracting plant components for preparing cough syrup. Background Art

[0002] Traditional extraction processes for plant-based cough syrup ingredients use a single water extraction method, resulting in low dissolution rates for fat-soluble components (such as limonene in dried tangerine peel and flavonoid glycosides in velvetleaf grass), requiring ethanol gradient extraction. Furthermore, the presence of macromolecules such as pectin and starch in the crude extract can affect subsequent component determination. Modern processes, combined with HPLC (high-performance liquid chromatography), enable simultaneous quantification of multiple components, such as the simultaneous determination of amygdalin, menthol, and glycyrrhizic acid in cough syrup with minimal relative standard deviation.

[0003] Cough syrups often contain multiple active ingredients (such as amygdalin, ephedrine, platycoside, etc.), which need to be separated by mobile phase gradient elution. For example, ephedrine and pseudoephedrine need to be baseline separated by a precise gradient ratio of methanol-acetonitrile-water. However, the sugars, pigments and excipients in the syrup matrix can easily cause chromatographic peak tailing, peak broadening or peak position shift, resulting in the inability to accurately identify the component content, which in turn makes condition optimization time-consuming and difficult to correct in a timely manner. Summary of the Invention

[0004] In order to solve the technical problem that the syrup matrix interference leads to abnormal chromatographic peaks and the component content cannot be accurately identified and corrected in time, the purpose of the present invention is to provide a plant component extraction method for the preparation of cough syrup. The technical solution adopted is as follows: Obtain an HPLC chromatogram of cough syrup; Extracting spectral peaks based on the fluctuation of the signal curve in the high performance liquid chromatogram; obtaining the interference degree between adjacent spectral peaks based on the distance between adjacent spectral peaks and the difference in the content of corresponding material components; obtaining the abnormality degree of each spectral peak based on the interference degree between each spectral peak and all adjacent spectral peaks, combined with the difference in the cutoff points on both sides of the spectral peak itself; and screening out abnormal spectral peaks based on the abnormality degree; According to the ratio of the base width and half-height width of each spectral peak and the abnormality, combined with the difference in the spectral peak areas on both sides of the peak, the offset of each spectral peak is obtained; according to the difference in the offset between each abnormal spectral peak and the connected spectral peak and the difference in the spectral peak areas, combined with the offset, the correction coefficient of each abnormal spectral peak is obtained; and the abnormal spectral peak is corrected based on the correction coefficient.

[0005] Furthermore, the calculation formula of the interference degree includes: ; Where a and b represent the serial numbers of two adjacent peaks; Indicates the interference degree corresponding to the a-th spectrum peak and the b-th spectrum peak; represents the linear normalization function; Indicates the horizontal distance between the maximum points of the a-th spectrum peak and the b-th spectrum peak; Indicates the absolute value of the difference between the data values of the maximum points of the a-th peak and the b-th peak.

[0006] Furthermore, the calculation formula of the abnormality degree includes: ; in, Indicates the abnormality of the a-th spectrum peak; Indicates the number of adjacent peaks of the a-th peak; Indicates the sequence number of the adjacent peak of the a-th peak; Indicates the interference degree corresponding to the a-th spectrum peak and the n-th adjacent spectrum peak; represents the mean value of all interferences corresponding to the a-th spectrum peak; The data value representing the left cutoff point of the a-th spectral peak; The data value representing the right cutoff point of the a-th spectral peak; Indicates the absolute value of the difference between the data values of the cutoff points on both sides of the a-th spectrum peak; represents the linear normalization function.

[0007] Furthermore, the method for obtaining the offset degree includes: Based on a preset curve fitting algorithm, the curve at the higher cutoff point of the spectral peak is extended so that the height of the extended fitting cutoff point is consistent with the cutoff point on the other side, the distance between the fitting cutoff point and the other cutoff point is taken as the peak base width, and the width at half height of the spectral peak is taken as the half-height width; the integral value from the left cutoff point to the maximum point is obtained by the integration method as the left area, and the integral value from the maximum point to the right cutoff point is obtained as the right area; The calculation formula for the offset includes: ; in, Indicates the deviation of the ath spectral peak; Indicates the abnormality of the a-th spectrum peak; represents the half-height width of the a-th spectral peak; Indicates the base width of the a-th peak; represents the left side area of the ath spectral peak; represents the right side area of the ath spectral peak; Represents the minimum function, which is used to obtain the minimum value of all elements in the brackets; represents an exponential function with the natural constant e as the base; Indicates taking the absolute value.

[0008] Furthermore, the method for obtaining the correction coefficient includes: For each abnormal spectral peak, connected spectral peaks are selected one by one as target spectral peaks; the calculation formula of the correction coefficient includes: ; Where, represents the correction coefficient of the i-th abnormal spectrum peak; Indicates the number of target spectrum peaks corresponding to the i-th abnormal spectrum peak; Indicates the sequence number of the target spectrum peak corresponding to the i-th abnormal spectrum peak; Indicates the deviation of the i-th abnormal spectrum peak; Indicates the deviation of the yth target spectrum peak corresponding to the i-th abnormal spectrum peak; represents the area of the i-th abnormal spectrum peak; Indicates the area of the yth target spectrum peak corresponding to the i-th abnormal spectrum peak; Indicates taking the absolute value.

[0009] Furthermore, the method for correcting the abnormal spectrum peak includes: Obtaining the horizontal distance between two cutoff points of the abnormal spectrum peak as the initial spacing; The calculation formula for the corrected spacing includes: ; in, represents the corrected spacing of the i-th abnormal peak; represents the correction coefficient of the i-th abnormal spectrum peak; represents the initial spacing of the i-th abnormal spectrum peak; The cutoff point on the right side of the abnormal spectrum peak is moved so that the horizontal distance between the cutoff point on the right side and the cutoff point on the left side after the movement is the correction distance.

[0010] Furthermore, the method for obtaining the spectrum peak includes: The spectrum peak is obtained according to the distribution of the extreme value points of the signal curve in the chromatogram.

[0011] Furthermore, the method for obtaining a spectral peak according to the distribution of extreme points of the signal curve in the chromatogram includes: The signal curve between the maximum point and the adjacent minimum points on both sides is regarded as the spectrum peak where the maximum point is located.

[0012] Furthermore, the method for obtaining the abnormal spectrum peak includes: The spectrum peak whose abnormality degree is greater than a preset abnormality threshold is determined as an abnormal spectrum peak.

[0013] Furthermore, when the horizontal distance between the maximum value points of two spectrum peaks is less than a preset distance threshold, it is determined that the corresponding two spectrum peaks are connected.

[0014] The present invention has the following beneficial effects: The invention first obtains a high-performance liquid chromatogram of the cough syrup to obtain an analysis basis; further, in order to be able to correct the offset and tailing spectral peaks, the spectral peaks are first extracted; further, according to the difference in the spacing between adjacent spectral peaks and the content of corresponding material components, the interference between adjacent spectral peaks is quantified, providing a basis for subsequent evaluation of the abnormality of the spectral peaks; further, according to the difference in the cutoff points on both sides of the spectral peaks themselves, the influence of the baseline caused by the influence of other spectral peaks on the spectral peaks is analyzed, and the abnormality of each spectral peak is obtained in combination with the interference, and the abnormal degree of the spectral peak is characterized; further, abnormal spectral peaks are screened out, and the spectral peaks with abnormalities are located, providing objects for subsequent spectral peak correction; further, the asymmetric characteristics of the spectral peaks due to overlap and offset are analyzed, and the offset of each spectral peak is obtained in combination with the abnormality, and the abnormal offset degree of the spectral peak is quantified; finally, according to the difference in the offset between each abnormal spectral peak and the connected spectral peaks and the difference in the spectral peak area, the influence of the abnormal spectral peaks is analyzed, and the abnormal spectral peaks are corrected in combination with the offset, so as to improve the accuracy of the chromatogram. This method is based on the inter-peak interference and its own morphological characteristics, identifies and quantifies the peak anomaly and deviation, extracts the correction coefficient, and realizes automatic peak correction, thereby improving the HPLC quantitative accuracy of cough syrup in complex matrices and providing accurate data support for the control and optimization of plant ingredient extraction. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more clearly illustrate the technical solutions and advantages of the embodiments of the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the prior art descriptions. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0016] Figure 1 A flow chart of a method for extracting plant ingredients for preparing cough syrup provided in one embodiment of the present invention; Figure 2 A high performance liquid chromatogram of a cough syrup provided in one embodiment of the present invention; Figure 3 A schematic diagram of an abnormal spectral peak provided by one embodiment of the present invention. DETAILED DESCRIPTION

[0017] To further illustrate the technical means and efficacy of the present invention to achieve its intended purpose, the following, in conjunction with the accompanying drawings and preferred embodiments, describes in detail a method for extracting plant components for preparing cough syrup according to the present invention, including its specific implementation, structure, features, and efficacy. In the following description, references to different "one embodiment" or "another embodiment" do not necessarily refer to the same embodiment. Furthermore, specific features, structures, or characteristics of one or more embodiments may be combined in any suitable manner.

[0018] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0019] The following describes in detail a specific scheme of a method for extracting plant components for preparing cough syrup provided by the present invention in conjunction with the accompanying drawings.

[0020] See also Figure 1 , which shows a flow chart of a method for extracting plant ingredients for preparing cough syrup provided by one embodiment of the present invention, specifically comprising: Step S1: obtaining a high performance liquid chromatogram of the cough syrup.

[0021] In one embodiment of the present invention, the sample is pretreated to remove interfering substances: solid phase extraction (SPE) is used to purify the sample, for example, using an Oasis MCX mixed cation exchange column (500 mg / 6 mL), which is activated with 5 mL of methanol and equilibrated with 5 mL of water before loading. The target components (such as ephedrine and amygdalin) are then eluted stepwise with 0.1 M hydrochloric acid and 5% ammonia methanol to remove interfering substances such as sugars and colloids.

[0022] For high-viscosity syrups, pre-dilution (e.g., adding 50% methanol to 10 mL of syrup) and ultrasonic treatment for 10 minutes are required to improve the solubility of the target component.

[0023] Ultrasonic extraction (30°C, 30 minutes) with 80% methanol solution is used, which is suitable for heat-sensitive components such as amygdalin and glycyrrhizic acid.

[0024] Chromatographic condition settings: 1. Mobile phase and gradient program: Prepare acetonitrile-phosphoric acid aqueous solution (containing 0.05% phosphoric acid) or acetonitrile-glacial acetic acid solution (0.2% glacial acetic acid). Gradient elution program example: acetonitrile 5% → 25% in 0-10 minutes, acetonitrile 25% → 40% in 10-20 minutes, flow rate 0.8-1.0 mL / min, to achieve baseline separation of components with different polarity, such as amygdalin, ephedrine, and platycodin.

[0025] 2. Chromatographic column and temperature control: Use a C18 column (such as Agilent Poroshell 120 EC-C18, 250 mm × 4.6 mm, 1.9 μm), maintain a column temperature of 30°C, and a theoretical plate number of 5000 or more to ensure a resolution of 1.5 or more between glycyrrhizic acid and its structural analogs such as liquiritin.

[0026] 3. Detector parameters: Use multi-wavelength detection (e.g., 210 nm for amygdalin, 254 nm for magnolol, and 283 nm for hesperidin) to distinguish different components and avoid interference from syrup pigments.

[0027] A high-performance liquid chromatogram of the cough syrup is obtained, and a rectangular coordinate system is established, in which the horizontal axis of the coordinate system corresponds to the time axis of the high-performance liquid chromatogram; the vertical axis of the coordinate system corresponds to the data axis of the electrical signal of the high-performance liquid chromatogram, which facilitates subsequent analysis of the distance between two points in the graph.

[0028] See also Figure 2 , which shows a high performance liquid chromatogram of a cough syrup provided by one embodiment of the present invention, Figure 2 In the figure, a is the chromatogram of the mixed reference solution, b is the chromatogram of the sample solution, the horizontal axis is the time axis, and the vertical axis is the amplitude (data value) axis; the numbers in the figure are 1-chlorogenic acid, 2-forsythiaside, 3-baicalin, 4-quercetin, 5-worcesterol, 6-quercetin, and 7-worcesterol.

[0029] A high-performance liquid chromatogram of the cough syrup is obtained, and a rectangular coordinate system is established, in which the horizontal axis of the coordinate system corresponds to the time axis of the high-performance liquid chromatogram; the vertical axis of the coordinate system corresponds to the data axis of the electrical signal of the high-performance liquid chromatogram, which facilitates subsequent analysis of the distance between two points in the graph.

[0030] Step S2: Extract spectral peaks based on the fluctuations of the signal curve in the HPLC graph; obtain the interference between adjacent spectral peaks based on the distance between adjacent spectral peaks and the content difference of the corresponding material components; obtain the abnormality of each spectral peak based on the interference between each spectral peak and all adjacent spectral peaks, combined with the difference in the cutoff points on both sides of the spectral peak itself; and screen out abnormal spectral peaks based on the abnormality.

[0031] In the determination of botanical ingredients in cough syrups, differences in the content of each ingredient can significantly affect the accuracy of the assay. For example, high levels of glycyrrhizic acid can cause peak broadening or tailing due to column overloading, masking the peaks of nearby low-level ingredients and causing integration errors. Low-level ingredients near the detection limit can lead to false positives or quantitative deviations due to matrix interference (sugars, pectins) or baseline noise.

[0032] In addition, the polarity differences between components (such as chlorogenic acid polarity > ephedrine) may cause retention time drift in gradient elution, reduce the separation of co-eluting components (such as platycoside D and E), and then change the peak area response value through competitive adsorption or solvent effect.

[0033] When peaks tail and shift, tailing peaks lead to deviations in peak area measurements, especially for low-concentration components due to the extended tails. Furthermore, tailing peaks overlap with adjacent peaks, resulting in reduced resolution. Peak drift can shift the retention time of the same component, leading to misalignment of the peak integration region and deviations in peak area calculations. In complex samples, drifting peaks may overlap with adjacent peaks or be misidentified as impurity peaks, affecting the reliability of the principal component quantitative results.

[0034] Therefore, in order to correct the shifted and tailed spectral peaks, the spectral peaks are first extracted according to the fluctuation of the signal curve in the HPLC graph, thereby screening out the abnormal spectral peaks.

[0035] Preferably, in one embodiment of the present invention, considering that the extreme points correspond to the local fluctuation turning points of the signal curve, including the peak points and dividing points of the spectrum peak, the spectrum peak is obtained according to the distribution of the extreme points of the signal curve in the chromatogram.

[0036] As an example: the signal curve between the maximum point and the minimum points adjacent to both sides is regarded as the spectrum peak where the maximum point is located.

[0037] It should be noted that, in another embodiment of the present invention, in order to prevent false extreme points caused by noise from leading to the identification of false spectral peaks, the signal curve can be smoothed and denoised, such as Savitzky-Golay filtering, moving average, etc., which are all existing technologies and will not be described in detail.

[0038] Considering that adjacent spectral peaks may interfere with each other, the difference in the spacing between spectral peaks and the content of the components reflects the possibility of mutual interference. Therefore, the interference degree between adjacent spectral peaks is obtained according to the difference in the spacing between adjacent spectral peaks and the content of the corresponding material components, which provides a basis for the subsequent evaluation of the abnormality of the spectral peaks.

[0039] Preferably, in one embodiment of the present invention, considering that the time of the maximum point of the spectral peak is the retention time of the corresponding substance, the larger the horizontal distance between the maximum points of adjacent spectral peaks, the farther the retention times are apart, the less likely they are to interfere with each other, and the lower the interference degree; considering that the data value of the maximum point reflects the content of the corresponding substance, the larger the difference between the maximum points of adjacent spectral peaks, the greater the difference in the substance content, and the less likely they are to affect each other; Based on this, the interference degree between adjacent spectral peaks is obtained according to the horizontal distance between the maximum points of adjacent spectral peaks and the difference between the maximum points; the difference between the maximum points is negatively correlated with the interference degree.

[0040] As an example, the product of the reciprocal of the absolute value of the difference between the data values of the maximum points of adjacent spectrum peaks and the reciprocal of the horizontal distance between the maximum points is linearly normalized and used as the interference degree corresponding to the two adjacent spectrum peaks.

[0041] The calculation formula for interference degree includes: ; Where a and b represent the serial numbers of two adjacent peaks; Indicates the interference degree corresponding to the a-th spectrum peak and the b-th spectrum peak; represents the linear normalization function; Indicates the horizontal distance between the maximum points of the a-th spectrum peak and the b-th spectrum peak; Indicates the absolute value of the difference between the data values of the maximum points of the a-th peak and the b-th peak; Indicates taking the absolute value.

[0042] The data value difference of the spectral peak maximum is expressed by the absolute value of the difference, thereby indicating the content difference of the material component; the spacing between the spectral peaks is expressed by the horizontal distance between the maximum points, and negative correlation mapping is performed by taking the inverse method. Finally, fusion is performed by multiplication to quantify the degree of interference between adjacent spectral peaks.

[0043] In other embodiments of the present invention, the implementer may also obtain the interference degree by using the area difference of adjacent spectral peaks and the absolute value of the difference in the spectral peak areas to express the content difference of the material components; or may also linearly normalize the sum of the reciprocal of the absolute value of the difference in the data values of the maximum points of adjacent spectral peaks and the reciprocal of the horizontal distance between the maximum points by adding them together to obtain the interference degree corresponding to the two adjacent spectral peaks.

[0044] It should be noted that when taking the inverse, if an extreme case of zero occurs, a very small positive parameter such as 0.1 is given to it to avoid the denominator being zero; when normalizing the interference, the chromatograms of several samples can be obtained in advance, such as the interference of all 10 chromatograms before normalization, to construct a sample space, thereby performing linear normalization. This linear normalization is normalized under the corresponding data dimension. The normalization adopted in the embodiment of the present invention can adopt this method. The implementer can adjust the number of selected samples. The specific technical means are well known to those skilled in the art and will not be described in detail here.

[0045] Taking into account the interference degree between a spectral peak and all adjacent spectral peaks, it reflects the mutual interference between the spectral peak and the left and right adjacent spectral peaks. The difference in the cutoff points on both sides also reflects the influence of the baseline of the spectral peak caused by the influence of other spectral peaks. Therefore, according to the interference degree between each spectral peak and all adjacent spectral peaks, combined with the difference in the cutoff points on both sides of the spectral peak itself, the abnormality of each spectral peak is obtained to characterize the abnormal degree of the spectral peak, providing a basis for screening abnormal spectral peaks.

[0046] Preferably, in one embodiment of the present invention, the larger the mean value of all interference degrees corresponding to a spectral peak, the greater the mutual interference degree between the spectral peak and its adjacent spectral peaks, the greater the possible deviation degree of the spectral peak, and the greater the abnormality; the larger the absolute value of the difference between the cutoff points on both sides of the spectral peak itself, the greater the difference in the baseline heights of the left and right minimum points, reflecting the presence of co-elution interference (such as adjacent peaks not completely separated, resulting in the baseline on one side being raised by the adjacent peak), and the higher the abnormality; Based on this, the absolute value of the difference between the data values of the cutoff points on both sides of the spectrum peak itself and the mean value of all corresponding interference degrees are fused to obtain the abnormality of the corresponding spectrum peak.

[0047] As an example, the calculation formula for abnormality includes: ; in, Indicates the abnormality of the a-th spectrum peak; Indicates the number of adjacent peaks of the a-th peak; Indicates the sequence number of the adjacent peak of the a-th peak; Indicates the interference degree corresponding to the a-th spectrum peak and the n-th adjacent spectrum peak; represents the mean value of all interferences corresponding to the a-th spectrum peak; The data value representing the left cutoff point of the a-th spectral peak; The data value representing the right cutoff point of the a-th spectral peak; Indicates the absolute value of the difference between the data values of the cutoff points on both sides of the a-th spectrum peak; represents the linear normalization function.

[0048] In the calculation formula of the abnormality, the product of the absolute value of the difference between the data values of the cutoff points on both sides of the spectrum peak itself and the mean of all corresponding interference degrees is used as the abnormality of the spectrum peak; the difference between the cutoff points on both sides is expressed by the absolute value of the difference, and the mean of all interference degrees represents the interference degree between the spectrum peak and all adjacent spectrum peaks; the abnormality of the spectrum peak is obtained by multiplication and fusion.

[0049] The cutoff points are the endpoints on both sides of the spectrum peak, and the data values of the cutoff points are the vertical coordinates of the endpoints of the spectrum peak.

[0050] After obtaining the abnormal degree of the spectral peak quantified by the abnormality metric, the abnormal spectral peaks can be screened out based on the abnormality degree, and the abnormal spectral peaks can be located to provide objects for subsequent spectral peak correction.

[0051] In one embodiment of the present invention, a spectrum peak whose abnormality is greater than a preset abnormality threshold is determined to be an abnormal spectrum peak.

[0052] As an example, the preset abnormality threshold is 0.45; the abnormality degree is compared with the preset abnormality threshold to screen out abnormal spectrum peaks.

[0053] It should be noted that the abnormality of all spectral peaks in a number of samples, such as 10 samples, is pre-selected to obtain a sample space of the data dimension of abnormality, thereby performing linear normalization.

[0054] Step S3: Based on the ratio and abnormality of the base width and half-height width of each spectral peak, combined with the difference in the spectral peak areas on both sides of the peak, the offset of each spectral peak is obtained; based on the difference in the offset between each abnormal spectral peak and the connected spectral peaks and the difference in the spectral peak areas, combined with the offset, a correction coefficient for each abnormal spectral peak is obtained; and the abnormal spectral peak is corrected based on the correction coefficient.

[0055] Ideally, the left and right sides of a peak are symmetrical, with the peak's area approximately equal around its maximum point. The ratio of the peak's base width to its full width at half maximum also reflects the peak's symmetry. However, when peaks overlap or shift, a portion of the peak is lost, causing changes in the ratio of the peak's base width to its full width at half maximum and the difference in peak area. The anomaly quantifies the degree of peak anomaly. Therefore, the peak's shift is calculated based on the ratio and degree of each peak's base width to full width at half maximum, combined with the difference in peak area. This quantifies the degree of peak anomaly.

[0056] Preferably, in one embodiment of the present invention, in order to accurately analyze the changes in the spectral peak itself, the missing spectral peak is filled: based on a preset curve fitting algorithm, the curve at the higher cutoff point of the spectral peak is extended so that the height of the extended fitting cutoff point is consistent with the height of the cutoff point on the other side, and the distance between the fitting cutoff point and the other cutoff point is used as the peak base width; As an example, the preset curve fitting algorithm is the least squares method. Among the two cutoff points of a single spectral peak, the cutoff point with a larger amplitude is selected, and the least squares fitting algorithm is used to perform curve fitting on the side of the larger cutoff point. The cutoff point of the fitting curve is at the same height as the cutoff point on the other side.

[0057] See also Figure 3 , which shows a schematic diagram of an abnormal spectrum peak provided by an embodiment of the present invention, Figure 3The peaks at the maximum point A and the peaks at the maximum point C overlap abnormally, causing the cutoff point B to be too high. Figure 3 The dotted line at the lower right of point B is the fitting curve of the spectrum peak with the maximum point A, and the end is the fitting cutoff point; the dotted line at the lower left of point B is the fitting curve of the spectrum peak with the maximum point C, and the end is the fitting cutoff point.

[0058] Figure 3 The height h and half-height h / 2 of the spectrum peak with the maximum point A are also marked, and the width at half height of the spectrum peak is the half-height width.

[0059] Considering that the greater the difference in peak area on both sides of the maximum point of the peak, the more asymmetric the peak is, the greater the degree of peak shift is, and the greater the degree of shift is; the greater the ratio of peak base width to half-height width is, the greater the degree of baseline shift of the cutoff point on one side is, and the greater the degree of peak shift is; at the same time, the greater the abnormality is, the more abnormal the peak is, and the greater the degree of shift is; Based on this, the deviation of the spectral peak is obtained according to the difference in spectral peak area on both sides of the maximum point of the spectral peak, combined with the ratio of the peak base width to the half-height width and the abnormality; the difference in spectral peak area on both sides of the maximum point, the ratio of the peak base width to the half-height width and the abnormality are all positively correlated with the deviation.

[0060] As an example, the integral value from the left cutoff point to the maximum point is obtained by the integration method as the left area, and the integral value from the maximum point to the right cutoff point is obtained as the right area; the absolute value of the difference between the left area and the right area is used as the numerator, and the minimum value of the left area and the right area is used as the denominator to better highlight the difference in area on both sides. The fraction ratio is used as the independent variable, and after mapping through the exp(x) function, the mapped value is used as the area asymmetry coefficient to express the difference in spectral peak area on both sides of the peak; where x is the independent variable, and exp(x) is an exponential function with the natural constant e as the base; The product of the ratio of the peak base width to the half-height width, the anomaly degree and the area asymmetry coefficient is taken as the deviation degree of the corresponding spectral peak.

[0061] The calculation formula for the offset includes: ; in, Indicates the deviation of the ath spectral peak; Indicates the abnormality of the a-th spectrum peak; represents the half-height width of the a-th spectral peak; Indicates the base width of the a-th peak; represents the left side area of the ath spectral peak; represents the right side area of the ath spectral peak; Represents the minimum function, which is used to obtain the minimum value of all elements in the brackets; represents an exponential function with the natural constant e as the base; Indicates taking the absolute value.

[0062] In other embodiments of the present invention, the ratio of the peak base width to the half-height width, the anomaly degree, and the area asymmetry coefficient may also be fused by weighted summation or addition.

[0063] It should be noted that the least square method and the integral area calculation method are both existing technologies and will not be described in detail.

[0064] Taking into account that when connected to an abnormal spectral peak, the connected spectral peaks will be offset and affect each other, and the offset degrees are relatively similar; at the same time, the difference in spectral peak area represents the difference in substance content, reflecting the impact of the abnormal spectral peak. At the same time, the offset quantifies the offset degree of the abnormal spectral peak, and together reflects the degree of correction required for the abnormal spectral peak. Therefore, according to the difference in offset degree between each abnormal spectral peak and the connected spectral peak and the difference in spectral peak area, combined with the offset degree, the correction coefficient of each abnormal spectral peak is obtained.

[0065] In one embodiment of the present invention, when the horizontal distance between the maximum points of two spectrum peaks is less than a preset distance threshold, it is determined that the corresponding two spectrum peaks are connected.

[0066] As an example, the horizontal axis of the chromatogram is the time axis, and the preset distance threshold is set to T=0.25 (hour).

[0067] Preferably, in one embodiment of the present invention, considering that the abnormal spectrum peak may be connected to one spectrum peak or two spectrum peaks, for each abnormal spectrum peak, the connected spectrum peaks are selected one by one as target spectrum peaks to be analyzed one by one; Considering that the greater the difference in area between the abnormal peak and the target peak, the greater the difference in the content of the material component, the smaller the impact on the abnormal peak, and the smaller the correction degree; the smaller the difference in the offset, the greater the mutual influence, resulting in a large offset coefficient, the greater the correction degree of the abnormal peak needs to be, and the larger the correction coefficient; the greater the offset of the abnormal peak itself, the greater the offset degree, and the greater the correction degree; Based on this, the product of the area difference and the deviation difference between the abnormal peak and the target peak is used as the denominator, the deviation of the abnormal peak is used as the numerator, and the fractional ratio is used as the correction coefficient corresponding to the abnormal peak and the target peak; The correction coefficients of the abnormal spectral peak and all connected spectral peaks are fused to obtain the correction coefficient of the abnormal spectral peak.

[0068] As an example, the calculation formula for the correction factor includes: ; Where, represents the correction coefficient of the i-th abnormal spectrum peak; Indicates the number of target spectrum peaks corresponding to the i-th abnormal spectrum peak; Indicates the sequence number of the target spectrum peak corresponding to the i-th abnormal spectrum peak; Indicates the deviation of the i-th abnormal spectrum peak; Indicates the deviation of the yth target spectrum peak corresponding to the i-th abnormal spectrum peak; represents the area of the i-th abnormal spectrum peak; Indicates the area of the yth target spectrum peak corresponding to the i-th abnormal spectrum peak; Indicates taking the absolute value.

[0069] Among them, the absolute value of the difference between the areas of the abnormal spectrum peak and the target spectrum peak is taken as the area difference value, the absolute value of the difference in the offset is taken as the offset difference value, and the sum of all the correction sub-coefficients of the abnormal spectrum peak and all its connected spectrum peaks is taken as the correction coefficient of the corresponding abnormal spectrum peak.

[0070] When the abnormal spectrum peak has only one connected spectrum peak, the correction sub-coefficient is directly used as the correction coefficient.

[0071] It should be noted that when no spectral peak is connected to the abnormal spectral peak, the correction coefficient is set to 1 and no correction is performed. At the same time, it indicates that the preset abnormal threshold may be inappropriate and needs to be adjusted in time. When an extreme case of a value of zero occurs, a very small positive parameter such as 0.1 is assigned to avoid the denominator being zero. This method can be used to prevent the denominator from being zero in the embodiments of the present invention.

[0072] After quantifying the degree of correction of the abnormal spectral peaks through the correction coefficient, the abnormal spectral peaks can be corrected based on the correction coefficient to improve the accuracy of the chromatogram, thereby accurately analyzing the substance content, providing accurate data support for the control and optimization of plant ingredient extraction, and making it easier to improve the extraction process of plant ingredients in the preparation of cough syrup.

[0073] Preferably, in one embodiment of the present invention, considering that the horizontal distance between the two cutoff points of the abnormal spectral peak reflects the base width before correction, after integrating the correction coefficient, the right cutoff point is moved to the corrected width position to eliminate the problem of the peak base being too high or too narrow on one side caused by tailing or retention time drift, thereby restoring the original peak profile; Based on this, the horizontal distance between the two cutoff points of the abnormal spectrum peak is obtained as the initial spacing; the correction coefficient and the initial spacing are fused to obtain the corrected spacing; the cutoff point on the right side of the abnormal spectrum peak is moved so that the horizontal distance between the cutoff point on the right side and the cutoff point on the left side after the movement is the corrected spacing.

[0074] As an example, the product of the correction coefficient and the initial distance is used as the corrected distance.

[0075] The calculation formula for the corrected spacing includes: ; in, represents the corrected spacing of the i-th abnormal peak; represents the correction coefficient of the i-th abnormal spectrum peak; represents the initial spacing of the i-th abnormal peak.

[0076] The horizontal distance between the two cutoff points is the absolute value of the difference in the horizontal coordinates.

[0077] It should be noted that the height of the spectral peak remains unchanged during the movement.

[0078] In another embodiment of the present invention, the right curve can be reconstructed by cubic spline interpolation, the original data point set is retained, and a new point set is generated. The second-order continuity of the curve is maintained through constraints (baseline starting point, peak height conservation, baseline end point and vertex curvature continuity, etc.) to ensure peak smoothness. This is already existing technology and will not be repeated here.

[0079] In one embodiment of the present invention, after correcting the abnormal spectral peak based on the correction coefficient, the method further includes: obtaining the content of each substance component in the cough syrup according to the corrected spectral peak, and improving the extraction process according to the substance content, specifically including: 1. Target component characteristics analysis ‌1. Identification of ingredient polarity‌ (1) If the low-polarity components (such as volatile oils and fat-soluble substances) do not meet the standards, the alcohol extraction method (ethanol concentration 60%-80%) should be used as a priority, referring to the experience in optimizing the alcohol extraction process of indigo carmine in Indigo Naturalis.

[0080] (2) If the content of water-soluble components (such as polysaccharides and flavonoids) is insufficient, a gradient water extraction method (such as 3 extractions with 12 times the amount of water) is used, combined with the optimization case of cough granules.

[0081] ‌2. Thermal stability evaluation‌ For heat-sensitive ingredients (such as terpenoids), low-temperature dynamic extraction (40-50°C) or vacuum extraction is used to avoid high temperature destruction of active substances.

[0082] 2. Extraction Process Parameter Optimization ‌(1) Optimization of raw material pretreatment‌ ‌Particle size control‌: Medicinal materials are crushed to 20-40 mesh (0.2-0.8mm) to balance extraction efficiency and filtration performance‌.

[0083] Adjustment of drying method: Freeze drying is used for easily oxidized ingredients, and low-temperature drying is used for conventional medicinal materials.

[0084] ‌(2) Key parameter adjustment‌ Extraction time and number: Determine the optimal combination through orthogonal test (e.g., 3 times × 1 hour), referring to the process verification results of cough granules.

[0085] Temperature control: adopt staged temperature control (40℃ for extracting volatile components in the initial stage, and then raising the temperature to boiling point in the later stage).

[0086] In summary, in view of the technical problem that the syrup matrix interference causes the chromatographic peak to be abnormal, and the component content cannot be accurately identified and corrected in time, the present invention proposes a plant component extraction method for the preparation of cough syrup. The present invention first obtains the high-performance liquid chromatogram of the cough syrup; further extracts the peak, and obtains the interference between adjacent peaks according to the difference in the spacing between adjacent peaks and the content of the corresponding material components; further obtains the abnormality and filters out the abnormal peaks according to the difference in the interference and the cutoff points on both sides of the peak; further quantifies the deviation according to the ratio and abnormality of the peak base width and half-height width of each peak, combined with the difference in the peak area on both sides of the peak; finally, according to the difference in the deviation between each abnormal peak and the connected peak and the difference in the peak area, combined with the deviation, the abnormal peak is corrected. This method is based on the interference between peaks and its own morphological characteristics, identifies and quantifies the abnormality and deviation of the peak, extracts the correction coefficient, and realizes automatic correction of the peak, thereby improving the HPLC quantitative accuracy in the complex matrix of cough syrup, and providing accurate data support for the control and optimization of plant component extraction.

[0087] It should be noted that the order in which the embodiments of the present invention are described above is for illustrative purposes only and does not necessarily represent the superiority or inferiority of the embodiments. The processes depicted in the accompanying drawings do not necessarily require the specific order or sequential order shown to achieve the desired results. In certain embodiments, multitasking and parallel processing are also possible or may be advantageous.

[0088] The various embodiments in this specification are described in a progressive manner, and the same or similar parts between the various embodiments can be referred to each other. Each embodiment focuses on the differences from other embodiments.

Claims

1. A method for extracting plant ingredients for preparing cough syrup, characterized in that: The method comprises: Obtain an HPLC chromatogram of cough syrup; Extracting spectral peaks based on the fluctuation of the signal curve in the high performance liquid chromatogram; obtaining the interference degree between adjacent spectral peaks based on the distance between adjacent spectral peaks and the difference in the content of corresponding material components; obtaining the abnormality degree of each spectral peak based on the interference degree between each spectral peak and all adjacent spectral peaks, combined with the difference in the cutoff points on both sides of the spectral peak itself; and screening out abnormal spectral peaks based on the abnormality degree; According to the ratio of the base width and half-height width of each spectral peak and the abnormality, combined with the difference in the spectral peak areas on both sides of the peak, the offset of each spectral peak is obtained; according to the difference in the offset between each abnormal spectral peak and the connected spectral peak and the difference in the spectral peak areas, combined with the offset, the correction coefficient of each abnormal spectral peak is obtained; and the abnormal spectral peak is corrected based on the correction coefficient.

2. The method for extracting plant components for preparing cough syrup according to claim 1, wherein: The calculation formula of the interference degree includes: ； Where a and b represent the serial numbers of two adjacent peaks; Indicates the interference degree corresponding to the a-th spectrum peak and the b-th spectrum peak; represents the linear normalization function; Indicates the horizontal distance between the maximum points of the a-th spectrum peak and the b-th spectrum peak; Indicates the absolute value of the difference between the data values of the maximum points of the a-th peak and the b-th peak.

3. The method for extracting plant components for preparing cough syrup according to claim 1, wherein: The calculation formula of the abnormality degree includes: ； in, Indicates the abnormality of the a-th spectrum peak; Indicates the number of adjacent peaks of the a-th peak; Indicates the sequence number of the adjacent peak of the a-th peak; Indicates the interference degree corresponding to the a-th spectrum peak and the n-th adjacent spectrum peak; represents the mean value of all interferences corresponding to the a-th spectrum peak; The data value representing the left cutoff point of the a-th spectral peak; The data value representing the right cutoff point of the a-th spectral peak; Indicates the absolute value of the difference between the data values of the cutoff points on both sides of the a-th spectrum peak; represents the linear normalization function.

4. The method for extracting plant components for preparing cough syrup according to claim 1, wherein: The method for obtaining the offset degree includes: Based on a preset curve fitting algorithm, the curve at the higher cutoff point of the spectral peak is extended so that the height of the extended fitting cutoff point is consistent with the cutoff point on the other side, the distance between the fitting cutoff point and the other cutoff point is taken as the peak base width, and the width at half height of the spectral peak is taken as the half-height width; the integral value from the left cutoff point to the maximum point is obtained by the integration method as the left area, and the integral value from the maximum point to the right cutoff point is obtained as the right area; The calculation formula for the offset includes: ； in, Indicates the deviation of the ath spectral peak; Indicates the abnormality of the a-th spectrum peak; represents the half-height width of the a-th spectral peak; Indicates the base width of the a-th peak; represents the left side area of the ath spectral peak; represents the right side area of the ath spectral peak; Represents the minimum function, which is used to obtain the minimum value of all elements in the brackets; represents an exponential function with the natural constant e as the base; Indicates taking the absolute value.

5. The method for extracting plant components for preparing cough syrup according to claim 1, characterized in that: The method for obtaining the correction coefficient includes: For each abnormal spectral peak, connected spectral peaks are selected one by one as target spectral peaks; the calculation formula of the correction coefficient includes: ； Where, represents the correction coefficient of the i-th abnormal spectrum peak; Indicates the number of target spectrum peaks corresponding to the i-th abnormal spectrum peak; Indicates the sequence number of the target spectrum peak corresponding to the i-th abnormal spectrum peak; Indicates the deviation of the i-th abnormal spectrum peak; Indicates the deviation of the yth target spectrum peak corresponding to the i-th abnormal spectrum peak; represents the area of the i-th abnormal spectrum peak; Indicates the area of the yth target spectrum peak corresponding to the i-th abnormal spectrum peak; Indicates taking the absolute value.

6. The method for extracting plant components for preparing cough syrup according to claim 1, characterized in that: The method for correcting the abnormal spectrum peak includes: Obtaining the horizontal distance between two cutoff points of the abnormal spectrum peak as the initial spacing; The calculation formula for the corrected spacing includes: ; in, represents the corrected spacing of the i-th abnormal peak; represents the correction coefficient of the i-th abnormal spectrum peak; represents the initial spacing of the i-th abnormal spectrum peak; The cutoff point on the right side of the abnormal spectrum peak is moved so that the horizontal distance between the cutoff point on the right side and the cutoff point on the left side after the movement is the correction distance.

7. The method for extracting plant components for preparing cough syrup according to claim 1, characterized in that: The method for obtaining the spectrum peak includes: The spectrum peak is obtained according to the distribution of the extreme value points of the signal curve in the chromatogram.

8. The method for extracting plant components for preparing cough syrup according to claim 7, characterized in that: The method for obtaining a spectrum peak according to the distribution of extreme value points of the signal curve in the chromatogram includes: The signal curve between the maximum point and the adjacent minimum points on both sides is regarded as the spectrum peak where the maximum point is located.

9. The method for extracting plant components for preparing cough syrup according to claim 1, characterized in that: The method for obtaining the abnormal spectrum peak includes: The spectrum peak whose abnormality degree is greater than a preset abnormality threshold is determined as an abnormal spectrum peak.

10. The method for extracting plant components for preparing cough syrup according to claim 1, characterized in that: When the horizontal distance between the maximum points of two spectrum peaks is less than a preset distance threshold, it is determined that the corresponding two spectrum peaks are connected.

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