CN112691112A - New application of asperulosidic acid in promoting gastrointestinal motility - Google Patents
New application of asperulosidic acid in promoting gastrointestinal motility Download PDFInfo
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract
The invention provides an application of asperulosidic acid or a pharmaceutically acceptable salt thereof in preparing a medicament for promoting gastrointestinal motility. The medicine takes asperulosidic acid or pharmaceutically acceptable salts thereof as an active ingredient, and pharmaceutically acceptable auxiliary materials or auxiliary ingredients are added to prepare a common preparation. By analyzing the spectrum effect of the paederia scandens, the asperulosidic acid is found to improve the gastric emptying rate and the small intestine propulsion rate, and the clinical prospect is excellent.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a new application of asperulosidic acid in promoting gastrointestinal motility.
Background
Asperulosidic acid (1) is an iridoid glycoside active substance generated by plant metabolism, mainly exists in plants of Rubiaceae such as herba Paederiae, herba Hedyotidis Diffusae and radix Morindae officinalis, and has antitumor, antioxidant, distortion resisting and blood lipid reducing effects.
At present, no report about the function of promoting gastrointestinal peristalsis is found. The inventor finds that the asperuloside is highly related to the action of the paederia scandens on promoting gastrointestinal peristalsis through the research of paederia scandens spectrum-effect relationship.
Disclosure of Invention
The invention provides application of asperulosidic acid or medicinal salt thereof in preparing a medicament for promoting gastrointestinal motility.
The invention provides application of asperulosidic acid or medicinal salt thereof in preparing a medicament for promoting digestion.
Further, the salt is a pharmaceutically acceptable base addition salt.
Further, the salt is a sodium salt.
Further, the medicament is a medicament for increasing the rate of gastric emptying and/or the rate of small intestine advancement.
Furthermore, the medicine takes asperulosidic acid or pharmaceutically acceptable salts thereof as an active ingredient, and pharmaceutically acceptable auxiliary materials or auxiliary ingredients are added to prepare a common preparation.
Further, the preparation is in the form of oral preparation or injection.
The invention finally provides the application of the asperulosidic acid or the medicinal salt thereof in the index components of the medicament for promoting gastrointestinal motility.
Further, the medicine is an alcohol extract of Chinese fevervine herb; the Paederia scandens (Lour.) Merr or Paederia scandens (Lour.) Merr.
Further, the drug is detected by liquid chromatography, and the steps are as follows:
a. preparation of reference solutions: dissolving herba Paederiae glycoside control in 75% ethanol solution to obtain reference solution containing 0.1mg herba Paederiae glycoside per 1 mL;
b. preparation of a test solution: extracting the medicinal material sample with 75% ethanol, filtering, evaporating filtrate, dissolving the residue with 75% ethanol, and filtering;
c. respectively sucking reference substance solution and test solution, injecting into a liquid chromatograph under the following chromatographic conditions:
a chromatographic column: agent ZORBAX SB-C182.1mm × 50mm, 1.8 μm; mobile phase: performing gradient elution by taking 0.1% formic acid as a mobile phase A and acetonitrile as a mobile phase B; the gradient elution procedure was: 0-2 min, 3% -10% of B; 2-3 min, 10% B; 3-4 min, 10% -14%; 4-16 min, 14% -15%; 16-17 min, 15% -100%. Flow rate: 0.25 mL/min-1(ii) a Detection wavelength: 250 nm; column temperature: 30 ℃; sample introduction amount: 1 μ L.
Furthermore, in the liquid chromatogram of the drug, the peak corresponding to the paederoside reference substance is the S peak, and the relative peak area of the asperuloside chromatographic peak is 0.211-1.370.
Unless stated to the contrary, the terms used in the specification and claims have the following meanings.
The term "pharmaceutically acceptable" as used herein means, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and other mammals without undue toxicity, irritation, allergic response, and the like.
The application of the asperuloside acid or the medicinal salt thereof in preparing the medicine for promoting gastrointestinal motility is proved by experiments that the asperuloside acid in the fevervine can obviously improve the gastric emptying rate and promote the small intestine peristalsis, so the asperuloside acid can be further used for preparing the medicine for promoting digestion and has wide clinical prospect.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
Figure 120 fingerprint of paederia scandens medicinal materials;
FIG. 2 UPLC-Q-TOF-MS total ion flow graph of Paederia scandens sample S11;
figure 3 secondary mass spectrum of compound identified in paederia scandens medicinal material fingerprint (a, deacetyl asperuloside, b, neochlorogenic acid, c, asperuloside, d, quercetin-3-O-rutinose-7-O-glucoside, e, asperuloside, f, paederinucleotide, g, paederioside, h, paederinucleotide methyl ester).
Detailed Description
Example 1 spectral effect relationship study of Paederia scandens to promote gastrointestinal motility
1 Material
1.1 medicinal materials
The information of 20 Chinese fevervine herbs is shown in table 1, and the Chinese fevervine herbs are identified as dried aerial parts of Paederia scandens (Lour.) Merr. or Paederia scandens (Lour.) Merr. var. tominosa (Bl.) hand-Mazz. of Rubiaceae by professor Jiang Guihua of Chinese medicine university.
Table 120 Paederia scandens medicinal material information
1.2 reagents and instruments
1.2.1 reagents
Aspirin enteric-coated tablet (yabao pharmaceutical taiyuan pharmaceutical co ltd., national drug standard H14024002); atropine sulfate injection (Henan Red pharmaceuticals Co., Ltd., specification 0.5mg/mL, lot number 1409262). Analytical grade ethanol, glacial acetic acid, and sodium carboxymethylcellulose (medeto chemical reagent plant); acetonitrile is chromatographically pure (Fisher company, USA), and water is self-made ultrapure water. Paederin was purchased from Goldmann Biotech limited (batch number: MUST-15101422). Nutritional semi-solid paste: dissolving 5g of sodium carboxymethylcellulose in 25mL of distilled water, respectively adding 8g of milk powder, 4g of sugar and 4g of starch, stirring uniformly to prepare 150mL (about 150g) of semisolid paste, placing in a refrigerator for refrigeration for 12h, and taking out before use to recover to normal temperature. 0.8mL of the nutritional paste was 1.0 g.
1.2.2 instruments
SQP one-ten-thousandth analytical balance, T125D one-ten-thousandth analytical balance (sytsic instruments ltd, beijing), Agilent 1290Infinity LC ultra high performance liquid chromatograph, Xevo G2-XS QTof time-of-flight mass spectrometer (Agilent, usa).
1.3 Experimental animals
KM mice, SPF level, half male and female, 18-22 g weight, provided by the institute of laboratory animals, Daoshuo, Sichuan province, and the production license number: SCXK (Chuan) 2015-030. After being purchased, the chicken is placed in the animal house of science and technology building of Wenjiang school district of Chengdu Chinese medicine university for adaptive feeding for 3 days. Feeding conditions are as follows: temperature (25 ℃), humidity (60%), 12 h/day and 12 h/night. The animal feed is provided by the institute of animal research in the national institute of science of Sichuan province and people's hospital of Sichuan province.
2 method
2.1 experiment of Paederia scandens for promoting gastrointestinal peristalsis
2.1.1 sample preparation
Taking herba Paederiae powder (sieved with No. three sieve) 10g, adding 10 times of 75% ethanol, and heating and refluxing for 3 times, each time for 1 hr. Mixing the decoctions for 3 times, filtering, rotary evaporating the filtrate under reduced pressure to obtain fluid extract, and concocting the fluid extract with 0.5% CMC-Na to obtain sample solution containing 0.05g/mL of crude drug powder.
2.1.2 experiments on the Effect of Paederia scandens alcohol extract on gastrointestinal motility
The test solution was administered at a dose of 0.05g/mL as determined by preliminary experiments. 240 mice, randomized into 24 groups: the Chinese medicinal herbs are divided into two groups of Chinese fevervine and Chinese fevervine according to medicinal material sources, and each group comprises 12 groups: blank group 1 (0.5% CMC-Na), model group 1 (0.5% CMC-Na), and herba Paederiae 75% ethanol extract group (1.00g/Kg)10 groups. Feeding 0.5% CMC-Na to the blank group and the model group of mice by intragastric administration; the paederia scandens medicinal material 75% ethanol extract group is added with corresponding 0.05mg/mL paederia scandens medicinal material 75% ethanol extract; all groups were gavaged continuously for 7d, 1 d/time, at equal volume (0.2mL/10 g). Fasting for 24h before the last administration, and freely drinking water; after 20min of administration, except for the mice of the blank control group, the mice of other groups were injected with atropine sulfate (0.0018mg/Kg) subcutaneously in a volume of 1mL/10 g. After 20min of injection, each mouse was gavaged with 0.8mL of the semisolid paste; the mouse is killed by removing cervical vertebra after 20min of gastric perfusion, dissecting the abdominal cavity, ligating the cardia and pylorus of the stomach, taking out the stomach, wiping the stomach with filter paper, weighing the whole weight, cutting the stomach body along the greater curvature of the stomach, washing off the gastric contents, wiping the stomach, and weighing the net weight. The difference between the total weight and the net weight of the stomach is taken as the weight of the residue in the stomach, and the weight percentage of the gastric excrements in the filled semisolid paste is calculated as the gastric emptying rate. At the same time, the small intestine was quickly removed, gently peeled and developed, and then laid on white paper, and the distance from the pylorus to the full length of the ileocecal section and the distance from the pylorus to the front edge of the black semisolid paste were measured. The small intestine propulsion rate is the percentage of the distance from the pylorus to the front edge of the black semisolid paste to the whole length of the ileocecal part of the pylorus.
2.2 analysis of chemical composition of Paederia scandens alcohol extract
2.2.1 preparation of test solutions
Taking herba Paederiae powder (sieved with No. three sieve) 10g, adding 10 times of 75% ethanol, and heating and refluxing for 3 times, each time for 1 hr. Mixing the decoctions for 3 times, filtering, rotary evaporating the filtrate under reduced pressure to obtain fluid extract, and diluting the fluid extract with 75% ethanol to obtain sample solution containing 0.05g/mL of the original powder.
2.2.2 preparation of control solutions
Accurately weighing appropriate amount of herba Paederiae glycoside reference substance, dissolving with 75% ethanol, diluting to desired volume, shaking, and making into reference substance solution containing 0.1mg herba Paederiae glycoside per 1 mL.
2.2.3 chromatographic conditions
The chromatographic column is an agent ZORBAX SB-C18(2.1 mm. times.50 mm, 1.8 μm); mobile phase: a: b ═ 0.1% formic acid: acetonitrile, gradient elution: 0-2 min, 3% -10% of B; 2-3 min, 10% B; 3-4 min, 10% -14%; 4-16 min, 14% -15%; 16-17 min, 15% -100%. Flow rate: 0.25mL·min-1(ii) a Detection wavelength: 250 nm; column temperature: 30 ℃; sample introduction amount: 1 μ L.
2.2.4 methodology investigation
And (3) precision test: taking 75% ethanol extract (S11) of the same Chinese fevervine herb sample, preparing the sample according to the item of 2.2.1, continuously injecting the sample for 6 times according to the item of 2.2.3, and measuring the retention time and the peak area of each common peak in the sample. The results show that the RSD values of all relative retention times and relative peak areas are less than 2%, and the instrument precision is good.
And (3) stability test: taking 75% ethanol extract (S11) of the same Chinese fevervine herb sample, preparing samples according to the item of '2.2.1', injecting samples according to the item of '2.2.3' at 0, 2, 4, 6, 8 and 24h respectively, and measuring the retention time and peak area of each common peak in the samples. The results show that the RSD values of the relative retention time and the relative peak area are both less than 3%, which indicates that the method has good stability.
And (3) repeatability test: taking 75% ethanol extract (S11) of the same Chinese fevervine herb sample, preparing samples according to the item of '2.2.1', paralleling 6 parts, injecting samples according to the item of '2.2.3', analyzing, and measuring the retention time and peak area of each common peak in the samples. The results show that the RSD values of the relative retention time and the relative peak area are both less than 3%, which indicates that the method has good repeatability.
Samples were prepared under the "2.2.1" protocol and assayed under the "2.2.3" protocol.
2.2.5 Mass Spectrometry conditions
ESI ion source, ion source temperature 120 deg.C, capillary voltage 2.5 kv; positive ion/negative ion mode; taper hole voltage: 25V; desolventizing temperature: 400 ℃; desolventizing gas flow rate: 1000L/hr; scanning range: 100 to 1200 amu; scanning mode: MSe are provided.
2.3 data processing
SPSS18.0 statistical software is adopted for data processing, and data are all used
And (3) representing that single-factor analysis of variance is adopted for comparison among multiple groups of data, and LSD (least squares discriminant) is adopted for pairwise comparison among the groups. Merging by means of PeakView1.2 and other softwareAnalyzing and identifying the common peaks of the Chinese fevervine herb in the synthetic literature.
3 results
3.1 Effect of Paederia scandens alcohol extract on gastrointestinal motility
As shown in tables 2 and 3, compared with the blank control group, the small intestine propulsion rate of the mice in the model control group is significantly reduced (P <0.01), which represents the success of the atropine sulfate induced small intestine peristalsis model. Compared with a model control group, the 75% ethanol extract group (1.00g/Kg) of the Chinese fevervine herb sample can obviously promote the small intestine peristalsis of the mouse, and the propulsion rates of the Chinese fevervine P.scandens var.tominosa and the Chinese fevervine P.scandens on the small intestine of the mouse are 54.24-80.61% and 56.00-64.45% respectively; in addition, the 75% ethanol extract group (1.00g/Kg) of the Chinese fevervine herb sample has a certain promotion tendency on the gastric emptying of the mice, and the gastric emptying rates of the Chinese fevervine P.scandens var.tominosa and the Chinese fevervine P.scandens on the gastric emptying of the mice are respectively 16.44% -39.70% and 25.7% 1-51.95%
TABLE 210 Effect of Paederia tomentosa on atropine sulfate-induced intestinal writhing and gastric emptying in mice: (
n＝10)
Note: comparison with model control group: p <0.05, P <0.01
TABLE 310 Effect of Paederia scandens on atropine sulfate-induced intestinal inhibition and gastric emptying in mice: (
n＝10)
Note: comparison with model control group: p <0.05, P <0.01
3.2 establishment of reference fingerprint
Introducing UPLC chromatograms of 75% alcohol extract of herba Paederiae in 20 batches into a similarity evaluation system (2004A) of chromatogram fingerprints of Chinese medicine of the national pharmacopoeia Committee, taking the sample of S11 as a reference chromatogram, taking the generation method of the reference chromatogram as a median, setting the width of a time window to be 0.50, analyzing and searching common peaks through multi-point correction and automatic matching, establishing a reference fingerprint with 9 common peaks, and obtaining a result shown in figure 1.
3.3 identification of chemical Components of Paederia scandens alcohol extract
UPLC-Q-TOF-MS chromatogram obtained from 75% ethanol extract of herba Paederiae sample is shown in FIG. 2. Through comparison of relative retention time, 8 common peaks are identified from the Chinese fevervine herb, and the identification results are detailed in table 4.
TABLE 4 identification of common peaks in fingerprint of herba Paederiae
3.4 Peak area of UPLC fingerprint of Paederia scandens alcohol extract
The relative peak area of each common peak of 75% alcohol extract of each batch of paederia scandens medicinal material is calculated and shown in table 5. As can be seen from Table 5, the relative peak area RSD% of the UPLC fingerprint spectrum common peak of 20 batches of Chinese fevervine herb samples is 51.02-143.66, which shows that the content difference of the chemical components of the 20 batches of Chinese fevervine herb samples is large.
TABLE 5 relative peak area of common peak of UPLC fingerprint of herba Paederiae medicinal materials
3.5 analysis of the "Spectrum-Effect" Grey correlation degree of the alcohol extract of the Paederia scandens
3.5.1 calculating the correlation coefficient
Averaging of raw data by ExcelAfter the processing (tables 6 and 7), the degree of association is calculated according to the formula. The data-transformed consensus peak-to-peak area is the parent sequence label [ X0(k)]The small intestine propulsion rate is marked as subsequence [ Xi(k)]Then [ X ]0(k)]And [ X ]i(k)]Is related to0i(K) Can be calculated from the following formula:
delta in the formulaoi(k) Comparing the absolute difference of the sequences for the mother and child, i.e. Δoi(k)＝|X0(k)-Xi(k) L (≦ 1 ≦ i ≦ m); Δ max and Δ min represent the maximum and minimum of the absolute differences of all compared sequences, respectively. Since the comparison sequences intersect, Δ min is generally taken as 0; rho is called as a respective coefficient, and the significance of rho is to weaken the distortion caused by too large maximum absolute difference value and improve the significance of the difference between the related coefficients, and the general situation can be 0.1-0.5. The correlation coefficient shows the closeness of the two compared sequences, and the range of the correlation coefficient is 0 < L ≦ 1.
Table 620 averaged data of 9 common peak areas in paederia scandens medicinal materials
Table 720 averaged data of drug effect results of fevervine herb batches
3.5.2 calculate the degree of correlation
The correlation degree is calculated according to the mean value of the correlation coefficients of the pairwise comparison sequences:
in the formula of gammaoiThe degree of association between the subsequence i and the parent sequence O,n is the number of data of the comparison sequence.
3.5.3 analysis of correlation between fingerprint of herba Paederiae and grey color of promoting gastrointestinal peristalsis
Through the analysis of the correlation degree of the fingerprint of the paederia scandens medicinal material and the gray color of the effect of promoting the gastrointestinal motility, when the correlation degree is more than 0.8, the chemical components represented by the common peaks are highly correlated with the effect of promoting the gastrointestinal motility. The contribution degree is 4>1>2>5>3>6>8>9>7 in turn according to the magnitude of the degree of association (see table 8). The correlation degree of the No. 4 peak is greater than 0.8, which indicates that the correlation between the asperuloside acid and the action of the paederia scandens for promoting the gastrointestinal motility is high.
TABLE 8 Grey correlation degree of common peak of fingerprint of herba Paederiae and its function of promoting gastrointestinal peristalsis
In conclusion, the correlation between the active ingredients such as asperuloside acid, deacetyl asperuloside acid and the like in the Chinese fevervine and the gastrointestinal motility promoting effect of the Chinese fevervine is obtained through the spectral efficiency analysis of the Chinese fevervine, wherein the high correlation between the asperuloside acid and the Chinese fevervine gastrointestinal motility promoting effect is obtained.
Experimental example 2 pharmacological experiment of asperulosidic acid for promoting gastrointestinal motility
1. Experimental equipment and medicine
The device comprises a syringe, a mouse gavage device, surgical scissors, surgical forceps, a ruler, a balance, asperulosidic acid (Chengdu's method biotechnology limited company, batch number: AF20112801), atropine sulfate injection (0.5mg/ml, sui patent medicine industry, batch number: 61909032), neostigmine methosulfate (0.5mg/ml, Zhejiang Xian medicine industry, batch number: 190505), 0.9% physiological saline, semisolid paste, picric acid and sodium carboxymethylcellulose (CMC-Na).
2. Laboratory animal
60 KM mice, male and female half, weight 18 ~ 22 g.
3. Experimental methods
Mice are randomly divided into 6 groups, namely a blank group, a model group, a positive group, a low-dose group, a medium-dose group and a high-dose group, wherein the blank group, the model group and the positive group are respectively subjected to intragastric administration of 0.5% of CMC-Na (0.2mL/10g) every day, the low-dose group is intragastric administered of 0.125mg/mL of asperuloside (0.2mL/10g) every day, the medium-dose group is intragastric administered of 0.25mg/mL of asperuloside (0.2mL/10g) every day, the high-dose group is intragastric administered of 0.5mg/mL of asperuloside (0.2mL/10g) every day, continuous intragastric administration is carried out for 7 days, fasting is carried out for 24 hours after the completion of intragastric administration on the 6 th day, free drinking water is carried out, the intragastric administration is carried out on the 7 th day, and the injection of 0.11 mg/. After administration for 20min on day 7, injecting physiological saline (1ml/10g) subcutaneously into the blank group, injecting atropine sulfate (1ml/10g) of 0.0018mg/kg subcutaneously into other groups, injecting for 20min, intragastrically irrigating 0.8ml of semisolid paste into each mouse, removing cervical vertebra after 20min, killing the mice, dissecting the abdominal cavity, ligating the cardia and pylorus of the stomach, taking out the stomach, wiping the stomach with filter paper, weighing the whole weight, cutting the stomach along the greater curvature of the stomach, washing the stomach content, wiping the stomach, and weighing the net weight. The difference between the total weight and the net weight of the stomach is taken as the weight of the residue in the stomach, and the weight percentage of the gastric excrements in the filled semisolid paste is calculated as the gastric emptying rate. At the same time, the small intestine was quickly removed, gently peeled and developed, and then laid on white paper, and the distance from the pylorus to the full length of the ileocecal section and the distance from the pylorus to the front edge of the black semisolid paste were measured. The small intestine propulsion rate is the percentage of the distance from the pylorus to the front edge of the black semisolid paste to the whole length from the pylorus to the ileocecal part.
4. Results of the experiment
The results of the effect of asperuloside on gastrointestinal motility in mice are shown in Table 9.
TABLE 9 Effect of asperuloside on intestinal inhibition and gastric emptying in mice by atropine sulfate: (
n＝10)
Comparison with model groups: p <0.05
As can be seen from table 9, asperuloside has a promoting effect on gastric emptying in mice, wherein the high dose group has a significant effect; asperuloside also has promoting effect on small intestine peristalsis, wherein the low dose group has the best effect.
In conclusion, the active ingredient of the asperuloside in the paederia scandens has the function of promoting gastrointestinal motility, can be used for preparing the medicine for promoting the gastrointestinal motility and further can be used for preparing the medicine for promoting digestion, and has wide clinical application prospect.
Claims (10)
1. Application of asperulosidic acid or pharmaceutically acceptable salts thereof in preparing medicines for promoting gastrointestinal motility.
2. Application of asperulosidic acid or pharmaceutically acceptable salts thereof in preparing medicines for promoting digestion.
3. Use according to claim 1 or 2, wherein the salt is a pharmaceutically acceptable base addition salt.
4. Use according to claim 3, characterized in that the salt is a sodium salt.
5. Use according to any of claims 1 or 2, wherein the medicament is a medicament for increasing the rate of gastric emptying and/or the rate of small intestine propulsion.
6. The use according to any one of claims 1 or 2, wherein the medicament is prepared into a common preparation by taking asperulosidic acid or pharmaceutically acceptable salts thereof as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients; the preparation is in the form of oral preparation or injection.
7. The application of asperulosidic acid or pharmaceutically acceptable salts thereof in index components of medicines for promoting gastrointestinal motility.
8. The use of claim 7, wherein the medicament is an alcohol extract of fevervine herb; the Paederia scandens (Lour.) Merr or Paederia scandens (Lour.) Merr.
9. Use according to claim 7 or 8, wherein the drug is detected by liquid chromatography, comprising the following steps:
a. preparation of reference solutions: dissolving herba Paederiae glycoside control in 75% ethanol solution to obtain reference solution containing 0.1mg herba Paederiae glycoside per 1 mL;
b. preparation of a test solution: extracting the medicinal material sample with 75% ethanol, filtering, evaporating filtrate, dissolving the residue with 75% ethanol, and filtering;
c. respectively sucking reference substance solution and test solution, injecting into a liquid chromatograph under the following chromatographic conditions:
a chromatographic column: agent ZORBAX SB-C182.1mm × 50mm, 1.8 μm; mobile phase: performing gradient elution by taking 0.1% formic acid as a mobile phase A and acetonitrile as a mobile phase B; the gradient elution procedure was: 0-2 min, 3% -10% of B; 2-3 min, 10% B; 3-4 min, 10% -14%; 4-16 min, 14% -15%; 16-17 min, 15% -100%. Flow rate: 0.25 mL/min-1(ii) a Detection wavelength: 250 nm; column temperature: 30 ℃; sample introduction amount: 1 μ L.
10. The use of claim 8, wherein the drug has a liquid chromatogram with an S peak corresponding to a paederoside reference and a relative peak area of a asperulosidic acid chromatogram peak of 0.211-1.370.
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