CN102106919B - Method for controlling quality in extraction process of traditional Chinese medicine chuanhong blood circulation-activating capsules - Google Patents
Method for controlling quality in extraction process of traditional Chinese medicine chuanhong blood circulation-activating capsules Download PDFInfo
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Abstract
The invention provides a method for controlling the quality in the extraction process of traditional Chinese medicine chuanhong blood circulation-activating capsules. The method comprises the following steps of: 1, determining the content of paeoniflorin in qualified chuanhong blood circulation-activating traditional Chinese medicine extract, and acquiring a near infrared spectrum; 2, establishing corresponding models between the near infrared spectrum of the chuanhong blood circulation-activating traditional Chinese medicine extract and the content of the paeoniflorin in the extract respectively by adopting chemical metrology software; 3, determining a near infrared spectrum of a chuanhong blood circulation-activating traditional Chinese medicine extract sample to be tested; and 4, and testing the content of the paeoniflorin in the chuanhong blood circulation-activating traditional Chinese medicine extract to be tested by using the chemical metrology software according to the corresponding models.
Description
Technical field
A kind of Chinese medicine river red Huoxue Capsule leaching process method of quality control is specifically related to the method for a kind of Fast Measurement Chinese medicine river red Huoxue Capsule extract paeoniflorin content.
Technical background
Chinese medicine is one of China's industry of having original and independent intellectual property right most.Chinese patent drug and medicine materical crude slice are the main clinical practice forms of Chinese medicine.Because the complicacy of the material base of Chinese Herbs, the Quality Control Technology means that Chinese patent drug is produced are comparatively extensive, what be embodied in that the quality control of Chinese patent drug adopts is process recipes control, adds that representational chemical index component quantifying detects and the preparation qualitative examination.That is, " on qualitative the adding some points on the process quantitatively ".Do not have overall process take physical and chemical index as the basis total quality control, this is one of major reason that causes Quality of Chinese Traditional Proprietary Medicine, clinical efficacy poor stability.
The red Huoxue Capsule in river is for the Chinese medicine compound prescription new drug of coronary disease and angina pectoris (heart blood silt), goes on the market at present, and prescription is comprised of Six-element Chinese medicines such as Ligusticum wallichii, the radix paeoniae rubrathe, peach kernel, safflower, radix bupleuri, Fructus Aurantiis, has merit promoting blood circulation and removing blood stasis, regulating qi-flowing for relieving pain.Its preparation production adopts water boiling and extraction, the technique such as concentrated, dry to form, and the quality of leaching process adopts extracting mode and technological parameter " amount of water, time, number of times " to control.
Near infrared (NIR) spectrum has and contains much information, but the overlapping situation of spectral signal is serious, state of matter information is disturbed large characteristics, must rely on a large amount of wave spectrum calculating and analysis and just can be applied to analytical work.Therefore, the NIR technology was once come to a halt on material applied analysis Technical Development History.Follow the development of NIR spectral technique theory and light splitting technology, the simultaneously development of computer technology and Chemical Measurement, the NIR spectral analysis technique has more and more entered into application, and is widely used in the fast on-line analyzing of chemistry, pharmacy, food industry.
NIR spectrum qualitative and quantitative detection technology is the secondary analysis method that is based upon on traditional physico-chemical analysis means basis, depending near infrared spectrometer, computer technology and Chemical Measurement basis of software, is to be applied at present the comparatively ripe online and fast detecting means of the industries such as chemical industry tobacco, oil.Near-infrared spectral analysis technology is green, quick, nondestructive quality control, attributional analysis and on-line analysis technology, has become one of the fastest analysis and testing technology of development in recent years.But not yet there is the NIR of employing spectral technique to be used for river red Huoxue Capsule extract paeoniflorin content analysis, carries out the report of leaching process method of quality control.
Summary of the invention
For the quality of production that further improves and the red Huoxue Capsule in stable river extracts, overcome Chinese patent drug without production run component target On-line Control, the present invention uses near-infrared spectrum technique river red Huoxue Capsule extract index components is run continuous samples and on-the site analysis, quantitatively detect in conjunction with tradition, set up the extract proportion of online application, the near-infrared model of index components.
The invention provides the red Huoxue Capsule in a kind of Chinese medicine river and extract the production run method of quality control, be specifically related to the method for paeoniflorin content in the red Huoxue Herbs extract in a kind of Fast Measurement river, it is characterized in that comprising the steps:
Step 1, the qualified river of mensuration red Huoxue Herbs extract paeoniflorin content, and gather near infrared spectrum;
Step 3, measure the near infrared spectrum of river red Huoxue Herbs extract sample to be measured;
The red Huoxue Herbs extract in wherein said Chinese medicine river, its prescription and preparation method are as follows, Ligusticum wallichii, the radix paeoniae rubrathe, peach kernel, safflower, radix bupleuri, Fructus Aurantii, each medicine merges decoction, water total amount is 2-20 doubly (weight ratio), and extraction time is 1-3 time, each extraction time 0.5-3 hour.Preferred method is as follows: each medicine merges and decocts, and water consumption is 2-20 doubly (weight ratio), extracts for the first time to add 10 times in water, decocted 2 hours, adds 7 times in water for the second time, decocts 1.5 hours, most preferredly sees embodiment.
Wherein the assay method of the preparation method of the red Huoxue Herbs extract in river and paeoniflorin content is as follows:
Carry out the extraction of the red Huoxue Herbs extract in river by the prescription method for making, the on-the-spot extract of collecting continuously, the sampling and measuring paeoniflorin content gathers near infrared spectrum simultaneously.
Method of the present invention, it is characterized in that: when gathering Chinese medicine river red Huoxue Herbs extract near infrared spectrum, adopt transmission mode to carry out, each Zhang Guangpu is the average result of 1-1000 scanning, resolution 0.3-20nm, the scanning optical spectrum scope is 1100-2300nm.
Method of the present invention, it is characterized in that: when gathering Chinese medicine river red Huoxue Herbs extract near infrared spectrum, adopt transmission mode to carry out, each Zhang Guangpu is the average result of 200-500 scanning, resolution 1-5nm, the scanning optical spectrum scope is 1100-2300nm.
Method of the present invention is characterized in that: when gathering Chinese medicine river red Huoxue Herbs extract near infrared spectrum, adopt transmission mode to carry out, each Zhang Guangpu is the average result of 300 scannings, resolution 2nm, and the scanning optical spectrum scope is 1100-2300nm.
Method of the present invention is characterized in that: when gathering Chinese medicine river red Huoxue Herbs extract near infrared spectrum, carry out with one of on-site sampling mode, online sampling mode and side line sampling mode.
Method of the present invention, it is characterized in that: sample adopts RP-HPLC that all concentrate samples of continuous collection are carried out the paeoniflorin content analysis, analysis condition is as follows: chromatographic column YMC ODS analytical column (6 * 150mm, 5 μ m, 25 ℃ of column temperatures), mobile phase is acetonitrile-water (16: 84), sampling volume 20uL, flow velocity 1ml/min, UV detects wavelength 230nm.
Method of the present invention is characterized in that: the foundation of model comprises the pre-service of 9 smoothing methods of (1) first order derivative (savitzky-golay) spectrum in the step 2; (2) adopt partial least square method (PLS1), intersection-proof method (cross-validation) to set up model with the Unscrambler quantitative analysis software; (3) model tuning and prediction effect checking.
Method of the present invention is characterized in that: the foundation of model comprises the pre-service of 9 smoothing methods of (1) first order derivative (savitzky-golay) spectrum in the step 2; (2) adopt partial least square method (PLS1), intersection-proof method (cross-validation) to set up model with the Unscrambler quantitative analysis software; (3) model tuning and prediction effect checking; (4) precision test; (5) stability test.The present invention uses the NIR spectral technique index components Paeoniflorin in the red Huoxue Capsule leaching process in Chinese medicine river is run continuous samples and on-the site analysis, quantitatively detect in conjunction with tradition, set up the river red Huoxue Capsule extract index components Paeoniflorin near-infrared model of online application.The method is the online detection in index components fast quantitative analysis and the production run in the red Huoxue Capsule leaching process in river, and the quality of control product provides effective analytical approach.
Description of drawings
Fig. 1 Paeoniflorin reference substance HPLC figure
Fig. 2 river red Huoxue Capsule extract sample HPLC figure
The original total spectrogram of Fig. 3 river red Huoxue Capsule extract sample NIR spectrum
Fig. 4 river red Huoxue Capsule extract sample NIR spectrum first derivative spectrum figure
Embodiment
Further specify the present invention below in conjunction with embodiment, but do not show the restriction to claim of the present invention.
Embodiment 1
Instrument and reagent
Instrument AOTF Luminar 5030-731 near-infrared spectrometers (U.S. BRIMROSE company), matching used SNAP spectra collection software and CAMO Chemical Measurement software; Aglient1100 chromatograph (U.S. Agilent company), the DAD diode array detector; Multi-function extractor (Medical Chemical Equipment General Factory, Chang Shu City).
Reagent prescription: Ligusticum wallichii, the radix paeoniae rubrathe, peach kernel, safflower, radix bupleuri, Fructus Aurantii (Jiangxi Huiren Pharmaceutical Co., Ltd); Paeoniflorin reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute); Acetonitrile is chromatographically pure reagent, and water is ultrapure water.
Method and result
1 sample preparation and collection
According to prescription, get peach kernel and be broken into meal, merge with other five tastes and decoct secondary, add 10 times of water gagings for the first time and decocted 2 hours, add 7 times of water gagings for the second time and decocted 1.5 hours, filter, merge the filtrate of secondary, stand-by.In the decoction process, with self-control sampler sampling 50ml, gather near infrared spectrum every 4min, and the working sample paeoniflorin content, take a sample altogether 50 parts.
2 sample Paeoniflorin HPLC analyze
Adopt RP-HPLC that all liq sample of continuous collection is carried out the paeoniflorin content analysis, analysis condition is as follows: chromatographic column YMC ODS analytical column (6 * 150mm, 5 μ m, 25 ℃ of column temperatures), mobile phase is acetonitrile-water (16: 84), sampling volume 20uL, flow velocity 1ml/min, UV detects wavelength 230nm.Collection of illustrative plates is seen accompanying drawing 1, accompanying drawing 2.The calibration set sample result is brought software into and is set up model, and checking collection sample is used for modelling verification.
3 obtain NIR spectrum
Immerse the optical fiber transmission-type probe that the NIR spectrometer carries during scanning optical spectrum in sample solution, the long 2m of optical fiber treats the solution-stabilized laggard line scanning of bubble that there is no. test condition is: and scanning times 300 times, resolution 2nm, the scanning optical spectrum scope is 1100～2300nm.Obtain altogether total spectrogram of 50 samples, see accompanying drawing 3.
4 set up model
4.1 the spectrum pre-service is carried out the spectrum pre-service to the original absorption spectrum that scanning obtains, to abate the noise and the impact of baseline wander.The preprocess method that adopts is 9 smoothing methods of first order derivative (savitzky-golay).First derivative spectrum figure sees accompanying drawing 4.Can eliminate sample because spectrum base-line shift and the drift that color distinction causes through the first order derivative processing.
4.2 set up respectively serial number of PLS1 mathematical model sample, select at random 10 to test as the outside and just to collect sample, all the other are as modeling sample.To analyze data through pretreated spectroscopic data and HPLC and carry out relatedly, and adopt partial least square method (PLS1), intersection-proof method (cross-validation) is set up model with the Unscrambler quantitative analysis software.The exceptional value that NIR and HPLC measure adopts respectively spectrum influence value Leverage and these 2 statistics of chemical score error Residual to check rejecting.Rejecting through exceptional value is optimized, and obtains comparatively desirable calibration model.Correlativity is good between the NIR Forecast of Spectra value of the sample Paeoniflorin that obtains and the HPLC assay value, and the determination data deviation is less.The major component dimension of sample Paeoniflorin model is 4, R2=0.9916, RMSECV=0.014393.
4.3 the calibration model that forecast result of model is verified to set up to 10 especially section test and just collect sample analysis.The test result of sample Paeoniflorin sees Table 1.The coefficient R 2 that NIR Forecast of Spectra value and sample Paeoniflorin HPLC measure true value is 0.995.The result shows that correlativity is good between the pre-side value of NIR spectrum and the sample HPLC assay value.
Table 1 calibration model is to the paeoniflorin content analysis result (mg/mL) of external certificate collection sample
5 precision tests
Get 1 prediction sample, multiple scanning 20 times, the calibration model of gained spectrum being brought into foundation calculates content, and with the precision of investigation method, predicted value RSD is 2.70%, illustrates that the smart precision of instrument is good.
6 stability tests
Get 1 prediction sample, every 1h run-down, multiple scanning is 5 times in 5h, investigates the stability of sample.The RSD of results sample paeoniflorin content is 2.07%, and interpret sample is relatively stable in 5h.
7 prediction recovery tests
Get 5 prediction samples, scanning is brought gained spectrum the calibration model of foundation into respectively, the ratio (the prediction recovery) between the true value that calculating Paeoniflorin predicted value and HPLC measure, and the consensus forecast recovery of sample Paeoniflorin is respectively 96.7%.
After the Chinese medicine river red Huoxue Capsule extract NIR spectrum correction model that this method is set up was established, the measurement of finishing 1 paeoniflorin content only needed 2min, and traditional HPLC mensuration process needs 2-4h approximately.Paeoniflorin in the red Huoxue Capsule extract in AOTF-near infrared ray river, integrating quick, direct, many index measures simultaneously and can realize on-the site analysis, solved in the Chinese Traditional Medicine long without effective mass control device, the complicated operation that adopts traditional analysis, analytical cycle, can not be used for the online problem that detects, analysis result is satisfied, and every analytical parameters can satisfy the requirement of assay in the drug production process.
The foundation of NIR spectral model and analysis means thereof is a dynamic process, and the quantity by sample constantly increases, and the representativeness of sample strengthens, and can set up more stable model, and its analysis result can more stablize and be accurate.
Claims (1)
1. a method of measuring river red Huoxue Herbs extract paeoniflorin content is characterized in that comprising the steps:
Step 1, the qualified river of mensuration red Huoxue Herbs extract paeoniflorin content, and gather near infrared spectrum; Sample preparation and collection
According to prescription, get peach kernel and be broken into meal, merge with other five tastes and decoct secondary, adding for the first time 10 times of water gagings decocted 2 hours, add for the second time 7 times of water gagings and decocted 1.5 hours, filter, merge the filtrate of secondary, stand-by, in the decoction process, with self-control sampler sampling 50ml, gather near infrared spectrum every 4min, and the working sample paeoniflorin content, take a sample altogether 50 parts;
Sample Paeoniflorin HPLC analyzes
Adopt RP-HPLC that all liq sample of continuous collection is carried out the paeoniflorin content analysis, analysis condition is as follows: chromatographic column YMC ODS analytical column, model are 6 * 150mm, 5 μ m, 25 ℃ of column temperatures, mobile phase is 16: 84 acetonitrile-water, sampling volume 20uL, flow velocity 1ml/min, UV detects wavelength 230nm, collection of illustrative plates is seen accompanying drawing 1, accompanying drawing 2, and the calibration set sample result is brought software into and set up model, and checking collection sample is used for modelling verification; Obtain NIR spectrum
In sample solution, immerse the optical fiber transmission-type probe that the NIR spectrometer carries during scanning optical spectrum, the long 2m of optical fiber, treat the solution-stabilized laggard line scanning of bubble that there is no. test condition is: scanning times 300 times, resolution 2nm, the scanning optical spectrum scope is 1100～2300nm, obtain altogether total spectrogram of 50 samples, see accompanying drawing 3;
Step 2, adopt Chemical Measurement software to set up respectively corresponding model between river red Huoxue Herbs extract near infrared spectrum and the extract paeoniflorin content;
The spectrum pre-service is carried out the spectrum pre-service to the original absorption spectrum that scanning obtains, to abate the noise and the impact of baseline wander, the preprocess method that adopts is 9 smoothing method savitzky-golay of first order derivative, first derivative spectrum figure sees accompanying drawing 4, processes through first order derivative and can eliminate sample because spectrum base-line shift and the drift that color distinction causes;
Set up respectively serial number of PLS1 mathematical model sample, select at random 10 to test as the outside and just to collect sample, all the other are as modeling sample, to analyze data with HPLC through pretreated spectroscopic data carries out related, adopt partial least square method PLS1, intersection-proof method cross-validation, set up model with the Unscrambler quantitative analysis software, the exceptional value that NIR and HPLC measure adopts respectively spectrum influence value Leverage and these 2 statistics of chemical score error Residual to check rejecting, rejecting through exceptional value is optimized, obtain comparatively desirable calibration model, correlativity is good between the NIR Forecast of Spectra value of the sample Paeoniflorin that obtains and the HPLC assay value, and the determination data deviation is less, and the major component dimension of sample Paeoniflorin model is 4, R2=0.9916, RMSECV=0.014393;
Step 3, measure the near infrared spectrum of river red Huoxue Herbs extract sample to be measured;
Step 4, utilize corresponding model, obtain river red Huoxue Herbs extract paeoniflorin content to be measured by Chemical Measurement software.
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| CN104089915A (en) * | 2014-07-16 | 2014-10-08 | 广州白云山汉方现代药业有限公司 | Method for detecting total flavone in production of herba epimedii |
| CN105548030A (en) * | 2015-12-17 | 2016-05-04 | 江西汇仁药业有限公司 | Naoxinshu oral liquid quality control model building method and use |
| CN109646303B (en) * | 2019-02-18 | 2022-01-28 | 安徽华润金蟾药业股份有限公司 | Quality control method for processing traditional Chinese medicine decoction pieces |
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Address after: 1266 No. 330052 Nanchang Huiren Jiangxi economic and Technological Development Zone Avenue. Patentee after: JIANGXI HUIREN PHARMACEUTICAL CO.,LTD. Patentee after: SHANGHAI ZHONGCHUANG PHARMACEUTICAL TECHNOLOGY CO.,LTD. Address before: 330043 1189 Yingbin Avenue, Nanchang, Jiangxi Patentee before: Jiangxi Huiren Pharmaceutical Co.,Ltd. Patentee before: SHANGHAI ZHONGCHUANG PHARMACEUTICAL TECHNOLOGY CO.,LTD. |
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