WO2005088295A1

WO2005088295A1 - A quality controlling method for the compound danshen dropping pills

Info

Publication number: WO2005088295A1
Application number: PCT/CN2005/000332
Authority: WO
Inventors: Yiyu Cheng; Zhengliang Ye; Yongjiang Wu; Xiaohui Fan; Yi Wang; Yuxia Sun; Shuju Li
Original assignee: Tianjin Tasly Pharmaceutical Co., Ltd.
Priority date: 2004-03-17
Filing date: 2005-03-17
Publication date: 2005-09-22

Abstract

The present invention relates to a quality controlling method for the compound danshen dropping pills, which comprises: obtaining the fingerprint of the conference compound danshen dropping pills by HPLC under the condition described in the invention; under the same condition, obtaining the fingerprint of the detecting compound danshen dropping pills by the same method; comparing these two fingerprints, when they have the same chromatographic peak number as the value described in the present invention, the quality of the detecting compound danshen dropping pills is considered to be good.

Description

Quality control method of compound Danshen dripping pills

Technical field

The invention relates to a method for quality control of fangshen dripping pills, in particular to control the quality of the compound danshen dripping pills by using a fingerprint pattern detection method.

Background technique

Cardiovascular and cerebrovascular diseases are common diseases that seriously endanger humans. In recent years, due to social development, changes in work, life, diet structure and environment, cardiovascular and cerebrovascular diseases have been on the rise. For the treatment of cardiovascular disease, although the strength of a single target of traditional Chinese medicine is lower than that of western medicine, its multi-path, multi-target, dynamic overall treatment, and small toxic and side effects are far beyond the reach of western medicine, and the Chinese medicine has exact curative effects. The comprehensive treatment effect is better than western medicine. Compound Danshen preparations are mostly used to treat cardiovascular and cerebrovascular diseases, such as Compound Danshen Tablets, Compound Danshen Drop Pills, and Guanxin Danshen Drop Pills. These compound salvia miltiorrhiza preparations (both containing salvia miltiorrhiza and Panax notoginseng) have different treatment effects due to different formulations, or different formulation ratios, or different extraction and refining methods, or different dosage forms. In addition, because the quality control methods of these compound Danshen preparations are not comprehensive, it is difficult to fully characterize their physical and chemical characteristics. Therefore, improving the extraction and refining methods and quality control methods of compound Danshen preparations has become an active research topic.

Salvia miltiorrhiza is the dry roots and rhizomes of Salvia miltiorrhiza Bge. It is produced in most parts of the country. Because the quality of Salvia miltiorrhiza varies due to different varieties, places of production, and harvesting time, it is difficult to guarantee the stability of a wide range of manufactured products. At present, the identification of salvia miltiorrhiza and its compound preparations is usually to determine the content of one or two active ingredients or index ingredients of salvia miltiorrhiza, and determine the quality based on its content. For example, tanshinone Π A content (58 pages of Chinese Pharmacopoeia 2000 edition) or danshensu content (Zhang Youqin et al., Chinese Journal of Traditional Chinese Medicine, 2000, 28 (3): 68) are used to identify the quality of danshen medicinal materials; Panaxone to determine Salvia miltiorrhiza variety and origin (Zhi Feijun, China Modern Applied Pharmacy, 1998, 15 (5): 16; Hu Shilin et al., Chinese Journal of Chinese Materia Medica, 1999, 24 (12): 721); using danshensu content ( Yan Changkai et al., Chinese Journal of Hospital Pharmacy, 2000, 20 (10): 600), Protocatechuic aldehyde content (Zheng Mojing et al., China Pharmaceutical Affairs, 2000, 14 (4): 254) or Tanshinone IIA content (Lin Weizhong Et al., Chinese Patent Medicine, 2000, 22 (11): 766) etc. to judge the quality of compound salvia miltiorrhiza preparations', and use the content of tanshinone II A to identify the quality of compound salvia miltiorrhiza tablets produced by different manufacturers (Shao Shuijuan, China Pharmaceutical, 2000, 9 (7 ): 27) etc. There are dozens of known chemical components of salvia miltiorrhiza, and most of its fat-soluble components are quinone red-yellow substances, such as tanshinone I, ΠΑ, ΠΒ, tanshinone A, B, C, tanshinate potassium lipid, isotanshinone I, II , Cryptotanshinone and so on. Most of its water-soluble components are phenolic aldehydes, phenolic acids, and diterpene acids, such as succinic acid, salvianolic acid A, B, C, 3, 4-dihydroxybenzoic acid and the like. In addition, β-sitosterol and vitamin E were also isolated (Editor Wang Boxiang, Chinese Medicine Hepatobiliary Medicine, First Edition, China Medical Science and Technology Press, 1993, 96 pages). Panax notoginseng is the dried root of the Panaxnotoginseng (Burk.) FH Chen plant of the Araliaceae family, which is mainly produced in Yunnan, Guangxi, and Sichuan. It is a precious specialty medicinal material in China and is commonly used in traditional Chinese medicine. Its sweetness, slightly bitterness, warm nature, return to the liver and kidney meridian, have the functions of dispersing blood stasis and hemostasis, swelling and analgesia. It is traditionally used to treat bruises and various bleeding diseases. Studies have shown that Panax notoginseng mainly contains chemical constituents such as soap ring, polysaccharides, amino acids, etc. The saponin part is the material basis for the effect of activating blood circulation and removing blood stasis, and is the main effective ingredient of panax notoginseng. Notoginsenosiole containing ginsenoside _{_{_{R bl, R b2, R c}}} , Rd, R e, Rf, Rgi, Rg2, Bhi, twenty-seven urgent "^ 20 kinds of saponins R, R_2, R3, R4, R6 and so on. These ingredients belong to the Dammarane type of tetracyclic triterpenoid saponins, among which ginsenosides R _bl and R _g „notoginsenosides! ^ Is the highest content of the three ingredients, notoginsenosides are the most representative compounds of notoginseng.

The fingerprint of traditional Chinese medicine refers to the chromatogram or spectrum of a certain type or several types of components that are common in a certain Chinese herbal medicine or proprietary Chinese medicine. At this stage, the active ingredients of Chinese medicine must never In most cases, the fingerprint of traditional Chinese medicine is of great significance to effectively control the quality of traditional Chinese medicine or proprietary Chinese medicines. The major manufacturers of Japanese traditional Chinese medicine in the 1980s have already adopted high-performance liquid-phase fingerprints to control the quality within the company. During the joint development of Ginkgo biloba extract in Germany and France, it was discovered that the medical effect of Ginkgo biloba extract is the result of the overall action of the substance group obtained from the extract. For such an overall quality control, high-performance liquid fingerprints were also used method. The FDA's guidelines for botanical herbs developed in recent years have explicitly used fingerprints as a quality control method for mixture masses (FD A. Guidance of Industry: Botanical Drug (Draft). 2000 August). With the deepening of research, it has been discovered that as a practical product of traditional Chinese medicine theory, traditional Chinese medicine, especially compound traditional Chinese medicine, cannot contain any of the ingredients that represent its overall efficacy. People have gradually realized that the current quality standards referring to the quality control model of western medicine (synthetic medicine) cannot properly reflect the inherent quality of traditional Chinese medicine. From the development trend, it is a development trend from the current quality control mode to a comprehensive, macroscopic, quantifiable identification combined with the determination of the content of main active ingredients.

The current standard for the quality evaluation of traditional Chinese medicines is the identification and determination of one or more active ingredients, active ingredients or index components, as well as routine inspection items prescribed by the Pharmacopoeia, by means of spectrum or chromatography. For example, the 2000 edition of the Chinese Pharmacopoeia [1] contains a total of 602 medicinal materials and proprietary medicines. Among them, 992 were identified by thin layer chromatography, and 308 varieties were determined by content [volume method, spectrometry, liquid color pan method, gas chromatography, and thin layer chromatography scanning method]. Most varieties have general inspection items. Obviously, these quality standards are set to mimic the model of chemicals. Other countries such as the United Kingdom, India, and the United States Herbal Code, Chinese medicine in the Japanese Pharmacy, and the German Herbal Monograph edited by the German Commission E also used basically the same content. For chemical drugs, its active ingredient is a single compound with a clear structure and a clear structure-activity relationship. Its content and purity directly express its effectiveness and safety. However, the characteristics of traditional Chinese medicine are compound compatibility, and the content of any single effective or active ingredient cannot express its integrity. Body effect. For example, astragaloside A (astrastralosidelV) contained in astragalus is currently the most common target for identification and content determination of quality standards, but there is no basis to prove a clear link between astragaloside and astragalus. Similarly, Coptis chinensis, Phellodendron amurense and the three needles all contain trabeine, and they are generally used as the detection target, but their functional indications are quite different. The situation with compound preparations is even more complicated. This kind of non-linear one-on-one theory and practice of traditional Chinese medicine shows that the quality of traditional Chinese medicine should adopt some kind of macroscopic and comprehensive quality evaluation method.

Fufang Danshen Diwan is a drip preparation made from Danshen and Sanqi as the main raw materials. It is clinically used to treat various diseases caused by cardiovascular and cerebrovascular diseases, coronary heart disease, angina pectoris, myocardial ischemia, and microcirculation disorders. Its therapeutic effect has been clinically verified, and whether the quality of the drug and the content of active ingredients in the compound Danshen dripping pills can be guaranteed is the basis for determining the efficacy of the compound Danshen dripping pills. If one or two active ingredients of Danshen are used to explain the intrinsic quality of Fufang Danshen Diwan, it has a certain one-sidedness, not to mention the non-medicinal index component. To control the efficacy of Fufang Danshen Diwan, it is not enough to characterize and control its one or two chemical components. It is necessary to control its substance group as a whole. Therefore, in addition to "micro analysis", some "macro analysis" method should also be used to effectively characterize the quality of traditional Chinese medicines as a whole. As a quality control method for Chinese herbal medicine and its extracts, fingerprints have now become an international consensus. At present, there are many methods for measuring active ingredients in salvia, such as tanshinone and danshensu. For active ingredients in panax notoginseng, such as notoginsenoside R _gl and ginsenoside! ^ There are many determination methods, but how to control the quality of Fufang Danshen Diwan pills from a more macro perspective has not been reported.

Summary of the invention

The object of the present invention is to provide a method for quality control of compound Danshen dripping pills, by which the quality of compound Danshen dripping pills can be controlled. The purpose of the present invention is to establish a method for quality control of traditional Chinese medicine compound preparations. Under a certain condition, the present invention uses a large number of experiments to compare the fingerprint of a compound Danshen dripping pill control sample with the fingerprint of a Danshen medicinal material and the fingerprint of a compound Danshen dripping pill intermediate. Compare the spectra, observe the reproducibility of the chromatographic peaks under the same chromatographic test conditions, and determine whether the effective chemical components in the salvia miltiorrhizae medicine have entered the intermediates of the compound Danshen dripping pills and the control of the compound salvia miltiorrhiza by using the fingerprint. In the sample. It has been proved through experiments that the control sample of the compound Danshen dripping pills in the present invention contains most of the chemical constituents of the salvia miltiorrhiza, so the fingerprint of the chemical constituents of the salvia miltiorrhiza in the compound Danshen dripping pills is determined and compared with the corresponding control fingerprint In contrast, the quality of Fufang Danshen Diwan can be controlled.

The invention can be implemented by the following steps:

(a). Establishment of control fingerprint of Fufang Danshen Diwan

Preparation of Compound Danshen Dropping Pill Control Sample Solution:

Take a control sample of compound Danshen dripping pills, weigh it, place it in a volumetric flask, add distilled water for ultrasonic dissolution, make up the volume, and filter to obtain the control sample solution;

Determination of Comparative Fingerprint of Compound Danshen Dripping Pills 镨

The above reference solution was sucked and injected into a liquid chromatograph, and the measurement was performed using high performance liquid chromatography to obtain a comparative fingerprint of the compound Danshen dripping pills. Chromatographic parts: The column was filled with octadecylsilane bonded silica gel; Mobile phase A is an aqueous phosphoric acid solution; mobile phase B is an acetonitrile phosphoric acid aqueous solution; the detection wavelength is 275-285nm;

(b). Determination of the fingerprint of the product of Fufang Danshen Diwan:

Take the product of the compound Danshen dripping pill and measure the fingerprint of the product according to the steps and conditions described in (a) above;

(c) comparing the fingerprint of the product of the compound Danshen dripping pills with the fingerprint of the compound Danshen dripping pills, and identifying the number of the same chromatographic peaks to determine whether the product quality is acceptable. The preferred method of the invention comprises the following steps:

(a). Establishment of control fingerprint of Fufang Danshen Diwan

Preparation of Compound Danshen Dropping Pill Control Sample Solution:

Determination of control fingerprint of Fufang Danshen Diwan:

The above reference solution was sucked and injected into a liquid chromatograph, and the measurement was performed using high performance liquid chromatography to obtain a comparative fingerprint of compound Danshen dripping pills. Chromatographic conditions: The column was filled with octadecylsilane bonded silica gel. The gradient elution was used. Mobile phase A is an aqueous phosphoric acid solution; mobile phase B is an acetonitrile phosphoric acid aqueous solution with a flow rate of 0.500 to 1.500 ml / min, a detection wavelength of 278 to 283 legs, and a column temperature of 20 to 40. C;

(b). Determination of fingerprint of compound Danshen dripping pills:

(c) comparing the fingerprint of the product of the compound Danshen dripping pills with the fingerprint of the compound Danshen dripping pills, and identifying the number of the same chromatographic peaks to determine whether the product quality is acceptable.

A more preferred method of the present invention includes the following steps:

(a). Establishment of control fingerprint of Fufang Danshen Diwan

Preparation of compound Danshen dripping pills reference solution:

Take 5 to 20 tablets of compound Danshen dripping pills, accurately weigh, place in a 10ml volumetric flask, add distilled water for 15min, dissolve, adjust volume, and filter to obtain the reference sample solution; suck the above reference solution and inject it into a liquid chromatograph Using high-performance liquid color pan method to determine the fingerprint of the compound Danshen dripping pills;

Chromatographic conditions: The column is filled with octadecylsilane bonded silica; The mobile phase A is 0.02% phosphoric acid aqueous solution; the mobile phase B is 80% acetonitrile 0.02% phosphoric acid aqueous solution; the gradient elution procedure is as follows:

At Omin, mobile phase A is 90% 0.02% phosphoric acid aqueous solution, and mobile phase B is 10% 80% acetonitrile 0.02% phosphoric acid aqueous solution;

At 8 minutes, the mobile phase A is 78% 0.02% phosphoric acid in water, and the mobile phase B is

22% 80% acetonitrile 0.02% phosphoric acid aqueous solution;

At 15min, mobile phase A is 74% 0.02% phosphoric acid aqueous solution, and mobile phase B is 26% 80% acetonitrile 0.02% phosphoric acid aqueous solution;

At 55min, mobile phase A is 48% 0.02% phosphoric acid aqueous solution, and mobile phase B is 52% 80% acetonitrile 0.02% phosphoric acid aqueous solution; the flow rate is 1.000ml / min, the detection wavelength is 280nm, and the column temperature is 30 ° C. Volume 10 μl;

(b). Determination of fingerprint of compound Danshen dripping pills:

In the establishment of the control fingerprint of the compound Danshen dripping pill according to the present invention, the preparation ratio of the mobile phase A solution is prepared by volume ratio, and the preparation ratio of the mobile phase B solution is prepared by volume ratio.

In the establishment of the control fingerprint, there were 8 chromatographic peaks in the control fingerprint of the compound Danshen Diwan obtained by high-performance liquid chromatography. Among them, there were 3 chromatographic peaks with a single peak area exceeding 10% of the total peak area. They are:

Peak No. 1, average retention time RT is 6.04min, RSD is 0.31%, peak area is 1627.92, RSD is 5.91%; Peak No. 2, with an average retention time RT of 9.90πήη, RSD of 0.25%, a peak area of 2575.54, and an RSD of 13.53%;

Peak No. 8, the average retention time RT is 31.02min, the RSD is 1.18%, the peak area is 1852.33, and the RSD is 14.84%;

In the establishment of the control fingerprint, there were 8 chromatographic peaks in the control fingerprint of the compound Danshen Diwan obtained by high performance liquid chromatography. Among them, there were 4 chromatographic peaks with a single peak area exceeding 5% of the total peak area. They are:

Peak No. 1, average retention time RT is 6.04min, RSD is 0.31%, peak area is 1627.92, RSD is 5.91%;

Peak No. 2, with an average retention time RT of 9.90 min, an RSD of 0.25%, and a peak area of

2575.54, RSD is 13.53%;

Peak No. 6, with an average retention time RT of 23.74min, an RSD of 0.76%, a peak area of 555.35, and an RSD of 10.48%;

Peak No. 8, with an average retention time RT of 31.02min, an RSD of 1.18%, a peak area of 1852.33, and an RSD of 14.84%;

In the establishment of the control fingerprint, there were 8 chromatographic peaks in the control fingerprint of the compound Danshen Diwan obtained by high performance liquid chromatography. Among them, there were 8 chromatographic peaks with a single peak area exceeding 2% of the total peak area. They are:

Peak No. 1, average retention time RT is 6.04miii, RSD is 0.31%, peak area is 1627.92, RSD is 5.91%;

Peak No. 2, with an average retention time RT of 9.90 min, RSD of 0.25%, a peak area of 2575.54, and an RSD of 13.53%;

Peak No. 3, with an average retention time RT of 16.89 min, an RSD of 0.61%, a peak area of 366.89, and an RSD of 10.92%;

Peak No. 4, average retention time RT is 17.84min, RSD is 0.07%, peak area is 381.40, RSD is 13.81%;

Peak No. 5, with an average retention time RT of 20.31 min, an RSD of 0.96%, a peak area of 186.08, and an RSD of 12.04%;

Peak No. 6, with an average retention time of 23.74 min, RSD of 0.76%, peak area of 555.35, and RSD ^ 10.48%;

Peak 7, the average retention time RT was 27.73min, the RSD was 0.50%, the peak area was 281.91, and the RSD was 18.08%;

No. 8 peak, with an average retention time RT was 31.02min, RSD 1.18%, peak area is 1852.33, RSD 14.84 ^_0/0.

In the present invention, the following methods are used to control the quality of Fufang Danshen Dripping Pills, the Fufang Danshen Dripping Pills to be tested are taken, and the preparation method, chromatographic conditions, and measuring methods of Fufang Danshen Dripping Pills are exactly the same, and the fingerprint is obtained. Compare the fingerprint of the product of the compound Danshen dripping pills with the fingerprint of the compound Danshen dripping pills. When the fingerprints of the two have three or more identical chromatographic peaks, the quality of the compound Danshen dripping pills is determined. qualified.

Preferably, the fingerprint of the product of the compound Danshen dripping pill is compared with the fingerprint of the compound Danshen dripping pill. If the fingerprints of the two have 5 or more identical chromatographic peaks, the quality of the product of the compound Danshen dripping pill is considered to be qualified. .

More preferably, the fingerprint of the product of the compound Danshen dripping pill is compared with the fingerprint of the compound Danshen dripping pill. When the fingerprints of the two have 7 or more identical chromatographic peaks, the quality of the product of the compound Danshen dripping pill is determined. qualified.

Most preferably, the fingerprint of the product of the compound Danshen dripping pill is compared with the fingerprint of the compound Danshen dripping pill. When the fingerprints of the two have the same color borrowing peaks, the product of the compound Danshen dripping pill is considered to be qualified.

In the present invention, the chemical constituents in the salvia miltiorrhiza and the compound salvia miltiorrhiza intermediate The determination method is as follows:

The method for determining the high-performance liquid standard fingerprint of chemical constituents in Salvia miltiorrhiza is as follows: Preparation of Salvia miltiorrhiza standard specimens: Crush the salvia miltiorrhiza, place it in a flask, add water, heat to reflux, let cool, collect the reflux solution, and add water to the residue Heating and refluxing, cooling, collecting the refluxing liquid, combining the two refluxing liquids, adjusting the volume, and filtering, as the standard sample solution of Salvia miltiorrhiza;

Chromatographic conditions: The column uses octadecylsilane bonded silica as a filler; gradient elution is used, and mobile phase A is ringworm acid ~ water solution; mobile phase B is acetonitrile phosphoric acid aqueous solution, flow rate LOOOml / min, detection wavelength 280nm, column temperature 30. C;

Measurement: Precisely draw the standard sample solution of Salvia miltiorrhiza into a liquid chromatograph, and use high performance liquid chromatography to determine the standard fingerprint of the chemical composition of Salvia miltiorrhiza.

• if

The preferred method for determining the chemical composition of Salvia miltiorrhiza by high-performance liquid fingerprints is as follows: Preparation of Salvia miltiorrhiza standard sample: Take 2.5 g of crushed salvia miltiorrhiza, place it in a flask, add 50 ml of water, heat under reflux for 1.5 hours, and let cool. Collect the reflux solution, add 50 ml of water to the residue, and heat reflux for 1 hour, let it cool, collect the reflux solution, combine the two decoction reflux solutions in a 100 ml volumetric flask, make up the volume, and filter as the standard sample of Salvia miltiorrhiza.

Chromatographic conditions: The column uses octadecylsilane bonded silica as the filler; gradient elution is used, and the mobile phase A phase is 0.02% phosphoric acid aqueous solution; the mobile phase B phase is 80% acetonitrile 0.02% phosphoric acid aqueous solution; color i 瞽The mobile phase elution gradient is as follows:

At 8 minutes, mobile phase A is 78% 0.02% phosphoric acid aqueous solution, and mobile phase B is 22% 80% acetonitrile 0.02% phosphoric acid aqueous solution;

At 15min, mobile phase A is 74% 0.02% phosphoric acid aqueous solution, mobile phase B 26% 80% acetonitrile 0.02% phosphoric acid aqueous solution;

At 55min, mobile phase A is 48% 0.02% aqueous solution of plaque acid, mobile phase B is 52% 80% acetonitrile 0.02% phosphoric acid aqueous solution; the flow rate is 1.000ml / min, the detection wavelength is 280nm, and the column temperature is 30 ° C. Sample volume ΙΟμΙ;

Determination: Precisely suck the standard sample solution and inject it into a liquid chromatograph, and use high-performance liquid chromatography to determine the standard fingerprint of the chemical components of Salvia miltiorrhiza;

In the fingerprint, the chemical composition of the salvia miltiorrhiza component in the salvia miltiorrhiza component has 9 chromatographic peaks, of which there are 9 chromatographic peaks whose single peak area exceeds 2% of the total peak area, respectively:

Peak No. 1, average retention time RT is 5.99min, RSD is 0.45%, peak area is 784.93, RSD is 7.34%;

Peak No. 2 has an average retention time RT of 9.85 min, an RSD of 0.47%, a peak area of 916.57, and an RSD of 6.06%;

Peak No. 3, with an average retention time RT of 20.13 min, an RSD of 0.46%, a peak area of 778.87, and an RSD of 8.78%;

Peak No. 4, with an average retention time of 22.37 min, an RSD of 0.77%, a peak area of 1165.13, and an RSD of 7.60%;

Peak No. 5, with an average retention time of 23.49min, RSD of 0.45%, peak area of 1076.7, and RSD of 3.70%;

Peak No. 6, with an average retention time RT of 24.51min, an RSD of 0.46%, a peak area of 802.43, and an RSD of 8.21%;

Peak 7, average retention time RT is 27.26min, RSD is 0.44%, peak area is 9017.8, RSD is 10.82%;

Peak No. 8, with an average retention time of 29.71 min, RSD of 0.32%, peak area of 539.37, and RSD of 13.30%;

No. 9 peak, with an average retention time RT was 30.68min, RSD is 0 · ^29% peak area 496.67, RSD 15.23% ₀

The chemical composition of the salvia miltiorrhiza component in the salvia medicinal material has 9 color peaks, of which there are 7 chromatographic peaks with a single peak area exceeding 5% of the total peak area, which are:

Peak No. 2, with an average retention time RT of 9.85min, RSD of 0.47%, peak area of 916.57, and RSD of 6.06%;

Peak No. 4, with an average retention time of 22.37min, an RSD of 0.77%, a peak area of 1165.13, and an RSD of 7.60%;

Peak No. 5, with an average retention time of 23.49 min, RSD of 0.45%, peak area of 1076.7, and RSD of 3.70%;

No. 7 front, average retention time RT is 27.26min, RSD is 0.44%, peak area is 9017.8, RSD is 10.82%

The chemical constituents of Salvia miltiorrhiza in the Salvia miltiorrhiza component have 9 chromatographic peaks, of which there is 1 chromatographic peak with a single peak area exceeding 10% of the total peak area, and the peak is as follows:

Peak No. 7 had an average retention time RT of 27.26 min, an RSD of 0.44%, a peak area of 9017.8, and an RSD of 10.82%.

The high-performance liquid-phase standard fingerprint of the chemical components of Salvia miltiorrhiza in the compound Danshen Diwan Intermediate is determined as follows:

Preparation of standard sample of compound Danshen dripping pill intermediate: Take the extract of salvia miltiorrhiza, put it in a volumetric flask, add distilled water to dissolve it with ultrasound, make up the volume, and filter. Chromatographic conditions: The column uses octadecylsilane bonded silica as a filler; gradient elution is used, and mobile phase A is a phosphoric acid aqueous solution; mobile phase B is an acetonitrile phosphoric acid aqueous solution, the flow rate is 1.000 ml / min, the detection wavelength is 280 nm, and the column temperature is 30 ° C;

Measurement: Precisely draw the standard sample solution of the compound Danshen dripping pill intermediate and inject it into a liquid chromatograph, and use high-performance liquid chromatography to determine the standard fingerprint of the chemical constituents of the salvia miltiorrhiza in the compound Danshen dripping pill intermediate;

The method for determining the HPLC fingerprint of the chemical components of Danshen in the preferred compound Danshen Diwan intermediates is as follows:

Preparation of standard samples of compound Danshen dripping pills intermediate: take Danshen extract O.lg, accurately weigh, place in a 10ml volumetric flask, add distilled water for 15min, dissolve, make volume, and filter, which is the middle of the compound Danshen dripping pills Body standard sample

Chromatographic conditions: The chromatographic column is filled with octadecylsilane bonded silica gel; gradient elution is adopted, and the mobile phase A phase is 0.02% phosphoric acid aqueous solution; the mobile phase B phase is 80% acetonitrile 0.02% phosphoric acid aqueous solution; chromatographic mobile phase The elution gradient is as follows:

At 15min, the mobile phase A is 74% 0.02% phosphoric acid aqueous solution, and the mobile phase B is 26% 80% acetonitrile 0.02% steric acid aqueous solution;

At 55min, mobile phase A is 48% of 0.02% gramic acid aqueous solution, and mobile phase B is 52% of 80% acetonitrile 0.02% phosphoric acid aqueous solution; the flow rate is 1.000 ml / min, the detection wavelength is 280 nm, and the column temperature is 30 ° C. Sample volume ΙΟμΙ;

Determination: Precisely draw the compound standard sample solution of compound Danshen dripping pills into the liquid phase A chromatograph using high-performance liquid chromatography to obtain a standard fingerprint of the chemical constituents of Salvia miltiorrhiza in the compound Danshen Diwan Intermediate;

In the fingerprint, the chemical composition of the salvia miltiorrhiza component in the compound Danshen Diwan Intermediate has 8 chromatographic peaks, of which there are 8 chromatographic peaks whose single peak area exceeds 2% of the total peak area, respectively:

Peak No. 1, average retention time RT is 6.12min, RSD is 0.83%, peak area is 2554.6, RSD is 10.68%;

Peak No. 2, with an average retention time RT of 10,000 min, RSD of 0.77%, peak area of 4438.6, and RSD of 14.63%;

Peak No. 3, average retention time RT is 15.96min, RSD is 0.58%, peak area is 740.16, RS is 13.18%;

Peak No. 4, average retention time RT is 17.89min, RSD is 1.17%, peak area is 667.68, RSD is 13.47%;

Peak No. 5, with an average retention time RT of 20.27min, an RSD of 2.94%, a peak area of 654.73, and an RSD of 15.01%;

Peak No. 6, with an average retention time RT of 23.83 min, an RSD of 0.88%, a front area of 1140.51, and an RSD of 16.45%;

Peak 7, average retention time RT is 27.67min, RSD is 0.61%, peak area is 880.14, RSD is 11.49%;

Peak No. 8 had an average retention time RT of 30.93 min, an RSD of 0.47%, a peak area of 2965.29, and an RSD of 10.21%.

In the fingerprint, the chemical composition of the salvia miltiorrhiza component in the compound Danshen Diwan Intermediate has 8 chromatographic peaks, of which there are 6 chromatographic peaks with a single peak area exceeding 5% of the total peak area, respectively:

Peak No. 2 with an average retention time RT of 1000 min, RSD of 0.77%, and peak area Is 4438.6, RSD is 14.63%;

Peak No. 3, average retention time RT is 15.96min, RSD is 0.58%, peak area is 740.16, RSD is 13.18%;

Peak No. 6, with an average retention time of 23.83 min, RSD of 0.88%, a peak area of 1140.51, and an RSD of 16.45%;

Peak No. 7, with an average retention time RT of 27.67min, an RSD of 0.61%, a peak area of 880.14, and an RSD of 11.49%;

In the fingerprint, the chemical constituents of Salvia miltiorrhiza in the compound Danshen Diwan Intermediate have 8 color language peaks, of which there are 3 color language peaks with a single area exceeding 10% of the total peak area, respectively:

Peak No. 2, with an average retention time RT of 10.00mm, an RSD of 0.77%, a peak area of 4438.6, and an RSD of 14.63%;

According to the present invention, by measuring fingerprints of Fufang Danshen Diwan, intermediates of Fufang Danshen Diwan, and Danshen medicinal materials, it is found that the number of chromatographic peaks in the three is almost the same, indicating that the fingerprint of Fudan Danshen Diwan is used as the compound Danshen Diwan The quality control standard can objectively reflect the presence and content of the internal ingredients of the product in order to comprehensively control the quality of the product.

The advantages of the invention are as follows:

(1). The HPLC standard fingerprints established by using the chemical constituents of Danshen in the compound Danshen Dripping Pills as indicators, represent most of the pharmacological activities of the compound Danshen Dripping Pills. Can effectively characterize the quality of Fufang Danshen Diwan. Therefore, the largest possible chemical composition of Fufang Danshen Diwan can be detected, which is beneficial to the comprehensive monitoring of the quality of traditional Chinese medicine.

(2) Treat the fingerprints of the active ingredients of Danshen in Fufang Danshen Diwan as a whole, pay attention to the sequence and relationship between the peaks of the fingerprint characteristics and the overall appearance, and avoid the determination of only one or two chemistry The one-sidedness of the compound to determine the overall quality of the compound Danshen dripping pills reduces the possibility of artificial treatment for quality compliance. The present invention provides a new control standard for a complete and accurate evaluation of the quality of Fufang Danshen Diwan, and will contribute to improving the quality and efficacy of Fufang Danshen Diwan and other prescriptions with Danshen and Panax notoginseng as main ingredients.

(3) The invention has the characteristics of simple method, stable, high precision, good reproducibility, and easy to handle.

The invention provides a method for identifying compound Danshen dripping pills, and the invention is a practical method obtained through a large number of experiments. In the present invention, the high-performance liquid standard fingerprint fingerprints of the chemical components of Danshen in compound Danshen dripping pills obtained by high-performance liquid and under the same test conditions have the characteristics of good reproducibility, so it can be established by the above determination method. The fingerprint of Compound Danshen Diwan pills is used as a standard fingerprint to identify traditional Chinese medicine preparations containing the active ingredients of Danshen and Panax notoginseng.

To those skilled in the art, according to the technical content disclosed by the present invention, those skilled in the art will be aware of other embodiments of the present invention, and the examples of the present invention are merely examples. Various changes and improvements can be made to the present invention without departing from the spirit and scope of the present invention. For example, the measurement results obtained by using different detection instruments may be different, but as long as the quality control method described in the present invention is used, it is within the scope of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The fingerprints of chemical constituents in Salvia miltiorrhizae and the intermediates of Fufang Danshen Diwan are given below. The fingerprints of the chemical components of Salvia miltiorrhiza, the fingerprints of the chemical components of Salvia miltiorrhiza in the compound Danshen dripping pills, and the comparison of the HPLC fingerprints of the chemical components of Salvia miltiorrhiza from different sources are intended to further illustrate the present invention, but not to limit the present invention.

Figure 1 HPLC fingerprint of Salvia miltiorrhiza chemical constituents

Figure 2 HPLC fingerprint of the chemical constituents of Salvia miltiorrhiza in the compound Danshen Diwan Pills Figure 3 HPLC fingerprint of the chemical constituents of Salvia miltiorrhiza in the compound Danshen Diwan pills

Figure 4. Comparison of HPLC fingerprints of Salvia miltiorrhiza chemical components from different sources

Of which: 1 is Fufang Danshen Diwan

2 is the intermediate of Fufang Danshen Diwan

3 for Salvia miltiorrhiza

detailed description

The following provides examples of preparation to further illustrate the present invention. This example is only used to illustrate the present invention, and does not limit the present invention.

Example 1 (Preparation Example)

Weigh 41.06g of Salvia miltiorrhiza, 8.03g of Panax notoginseng, and cook with water for two times, the first 4 times the amount of water for 2 hours, the second 3 times the amount of water for 1 hour, filter, and combine the filtrates and concentrate to

1.19-1.20 (75 ± 1 ° C), add ethanol at a concentration of about 90% to 65% (20 ° C), leave it for 12 hours, separate the supernatant, recover the ethanol, and concentrate to the relative density of the drug At 1.37 (55-60 ° C), Danshen Sanqi extract was obtained. Take 0.46g of Salvia miltiorrhiza extract and borneol, mix with 18g of polyethylene glycol-6000, and heat to a temperature of 85 ° C. After 80 minutes, transfer to a tank temperature of 86. C's pill machine drips into the jar. Drop the liquid medicine into liquid paraffin at 8 ° C, take out the dropping pills, remove the oil, and select the pills by the sieve to obtain.

Example 2 (Preparation Example)

Weigh 59.36g of Salvia miltiorrhiza, 6.38g of Panax notoginseng, and cook twice with water, 4 times the amount of water for the first time 2.5 hours, the second 3 times the amount of water for 1.5 hours, filtered, and the filtrates were combined and concentrated to a specific gravity of 1.19-1.20 (75 ± 1 ° C), and the ethanol was added to a concentration of about 85% to an ethanol content of 70% (20 ° C). Allow to stand for 10 hours, separate the supernatant, recover ethanol, and concentrate to a relative density of 1.35 (55-60 ° C) of the medicinal solution to obtain Danshen Sanqi extract. Take 0.34g of Salvia miltiorrhiza extract and borneol, mix with 23g of polyethylene glycol-6000, heat to 89 ° C, and after 100 minutes of chemical conversion, transfer to a dripping machine with the tank temperature kept at 85 ° C. In the jar. Drop the liquid medicine into 8 ° C methyl silicone oil, take out the dropping pill, remove the oil, and select the pill through the sieve to obtain it.

Example 3 (Preparation Example)

Weigh 31.12 g of salvia miltiorrhiza and 9.21 g of panax notoginseng, add 0.5% sodium hydroxide to the total amount of medicinal materials, and cook twice, the first 4 times the amount of water for 1.5 hours, the second 3 times the amount of water for 1.5 hours, filter, and filtrate Combined and concentrated to a specific gravity of 1.19-1.20 (75 ± 1.C), add ethanol at a concentration of about 88% to an ethanol content of 66% (20 ° C), leave it for 10 hours, separate the supernatant, and recover the ethanol. Concentrated to a relative density of 1.40 (55-60 ° C), the salvia miltiorrhiza root extract was obtained. Take the above salvia miltiorrhiza extract and borneol 0.50g, 90g mannitol, 15g sodium edetate and 15ml distilled water, mix the above components and freeze-dry to make powder injection.

Example 4 (Preparation Example)

Weigh 116.35 g of salvia miltiorrhiza and 58.21 g of panax notoginseng, add 2.0% sodium bicarbonate to the total amount of medicinal materials, cook twice, first 4 times the amount of water for 2 hours, the second 3 times the amount of water for 1.5 hours, filter, and filtrate Combined and concentrated to a specific gravity of 1.19-1.20 (75 ± 1 ° C), add a concentration of about 88% ethanol to an ethanol content of 66% (20 ° C), leave it for 10 hours, separate the supernatant, and recover the ethanol. Concentrated to a relative density of 1.40 (55-60 ° C), the salvia miltiorrhiza root extract was obtained. Take the above-described oil drop and Salvia extract thirty-seven 1.8g, 40g of microcrystalline cellulose was uniformly mixed with ₅ plus 3% povidone-ethanol solution made of soft material, homing through 18 mesh granules, 60 ° C and dried for 35 minutes Whole Add 4g of talc powder, mix well, and fill in the capsules to get.

Example 5 (Preparation Example) Salvia weighed 116.35g, thirty-seven 58. ² lg, add boiling water twice, four times the amount of water for the first time 2 hours, 3 times the amount of water a second time 1.5 hours, filtered and the filtrate were combined, concentrated to a specific gravity of 1.19- At 1.20 (75 ± 1 ° C), add ethanol at a concentration of about 88% to an ethanol content of 66% (20 ° C), leave it for 10 hours, separate the supernatant, recover the ethanol, and concentrate to a relative density of 1.40. (55-60 ° C) to obtain Danshen Sanqi extract. Take 0.9 g of Danshen Sanqi extract and water tablets, mix with 120 _{g of} microcrystalline cellulose, 40 _{g of} hydroxypropyl methylcellulose, 5 _g of xylitol, and 2 _{g of} magnesium stearate, and press the tablets to obtain.

Example 6 (Preparation Example)

Weigh 140.35g of Salvia miltiorrhiza and 36.42g of Panax notoginseng, add 2.5% sodium bicarbonate to the total amount of medicinal materials, cook twice, first 4 times the amount of water for 2 hours, and the second 3 times the amount of water for 1.5 hours. Combined and concentrated to a specific gravity of 1.19-1.20 (75 ± 1 ° C), add ethanol at a concentration of about 90% to 65% (20 ° C), and leave it for 8 hours to separate the supernatant and recover the ethanol. Concentrated to a relative density of 1.35 (55-60 ° C), the salvia miltiorrhiza extract was obtained. Take the above salvia miltiorrhiza extract and borneol l.Og, mix it with 46g microcrystalline cellulose, add 3% povidone ethanol solution to make the material, granulate through 18 mesh, dry at 60 ° C for 30 minutes, whole granule Add 4g of talcum powder, mix well, and press tablet to obtain.

Embodiment 7 (Finger Danshen Diwan Pill Danshen Component Fingerprint Detection Example)

1. Instruments and reagents

Instrument: Agilent 1100 liquid chromatography, including quaternary pump, online degassing device, autosampler, DAD detector, column oven, Chemstation workstation; BS210S electronic balance (l / l (T ⁴ g) (Beijing Stopper Doris), METTLER AE240 electronic balance

(l / 10 " ⁴ g or l / 10_ ⁵ _g ) (METTLER TOLEDO (Shanghai) Co., Ltd.), LD4-2 centrifuge (4000 r / min) (Beijing Medical Centrifuge Factory), digital display thermostat Water Bath (Tianjin Changfeng Co., Ltd.), RE-52AA Rotary Evaporator (Shanghai Yarong Biochemical Instrument Factory), SHE- (ΠΙ) Circulating Water Vacuum Pump (Gongyi Yingyu Yuhua Instrument Factory), KQ-250B Ultrasonic Cleaner (Kun Shanshi Ultrasonic Instrument Co., Ltd.), HENGAO T & D filter (HENGGAO T & D), synthetic fiber filter membrane (pore diameter 0.45μm) (Shanghai Xingya Purification Material Factory);

Reagents: acetonitrile (chromatographically pure, American Merck), phosphoric acid (superior pure), Wahaha purified water.

Preparation of control sample of Fufang Danshen Diwan:

Preparation of control sample of compound Danshen dripping pills: Take 10 tablets of compound Danshen dripping pills in each batch of Example 1, accurately weigh them, place them in a 10ml volumetric flask, add distilled water for 15 minutes, dissolve, make volume, and filter, which is the control. sample.

Preparation of standard sample of compound Danshen dripping pill intermediate: Take each batch of Danshen Sanqi extract O.lg of Example 1, accurately weighed, place it in a 10ml volumetric flask, add distilled water to sonicate for 15min, dissolve, make volume, and filter Is the standard sample.

Preparation of Salvia miltiorrhiza standard sample: Take 2.5 _{g of} salvia miltiorrhiza (crush), place it in a flask, add 50 ml of water, heat to reflux for 1.5 hours, let it cool, and collect the reflux solution. 50 ml of water was added to the residue, and the mixture was heated under reflux for 1 hour, allowed to cool, and the reflux solution was collected. The two decoction reflux solutions were combined in a 100 ml volumetric flask, and the volume was adjusted and filtered to obtain the standard sample.

3. HPLC analysis

Agilent ZoRBAx SB-C ₁₈ (4.6x250mm, 5μιη) chromatographic column, mobile phase: phase A is 0.02% phosphoric acid aqueous solution; phase B is 80% acetonitrile 0.02% phosphoric acid aqueous solution. The flow rate was 1.000 ml / min, the detection wavelength was 280 nm, the column temperature was 30 ° C, and the injection volume was 10 μ1.

The chromatographic mobile phase elution gradient is as follows:

Retention time Mobile phase A (v / v) Mobile phase Β (ν / ν)

Omin 90% 10%

8min 78% 22%

15min 74% 26%

55min 48% 52% Ingredient Name:

Peak1 Peak2 Peak3 Peak4 Danshensu protocatechuic acid isonic acid A isonic acid B Peak 5 Peak 6 Peak 7 Peak 8

Salvianolic acid D rosemary acid salvianolic acid B salvianolic acid A data analysis

A total of more than 200 batches of compound salvia miltiorrhiza extracts were analyzed by fingerprint analysis of salvia miltiorrhiza, and their similarities were above 90%. The retention time, the average of the peak area, and the RSD values are summarized as follows:

Salvia fingerprints

A total of more than 200 batches of Compound Danshen Diwan were analyzed for fingerprints of Salvia miltiorrhiza, and their similarities were above 90%. The retention time, the average of the peak area, and the RSD values are summarized as follows:

Fingerprint of Fufang Danshen Diwan

Peak area Single peak in total peak area Peak number Average retention time Retention time RSD% Average peak area

RSD%

1 6.04 0.31 1627.92 5.91 20.80%

2 9.90 0.25 2575.54 13.53 32.90%

3 16.89 0.61 366.89 10.92 4.69%

4 17.84 0.70 381.40 13.81 4.87%

5 20.31 0.96 186.08 12.04 2.38%

6 23.74 0.76 555.35 10.48 7.09%

7 27.73 0.50 281.91 18.08 3.60%

8 31.02 1.18 1852.33 14.84 23.66% In the establishment of the control fingerprint, there were 8 chromatographic peaks in the control fingerprint of the compound Danshen Diwan obtained by high-performance liquid chromatography. Among them, there were 3 chromatographic peaks with a single peak area exceeding 10% of the total peak area. They are:

Peak No. 2, average retention time RT is 9.90min, RSD is 0.25%, peak area is

2575.54, RSD is 13.53%;

In the establishment of the control fingerprint, there were 8 chromatographic peaks in the control fingerprint of the compound Danshen Diwan obtained by high-performance liquid chromatography. Among them, there were 8 chromatographic peaks with a single peak area exceeding 2% of the total peak area. For:

Peak No. 1, average retention time RT is 6.04min, RSD is 0.31%, peak area is 1627.92, RSD is 5.91%; Peak No. 2, with an average retention time RT of 9.90 min, an RSD of 0.25%, a peak area of 2575.54, and an RSD of 13.53%;

Peak No. 4, with an average retention time RT of 17.84min, an RSD of 0.70%, a peak area of 381.40, and an RSD of 13.81%;

Peak 7, average retention time RT is 27.73min, RSD is 0.50%, peak area is 281.91, RSD is 18.08%;

Peak No. 8 had an average retention time RT of 31.02 min, an RSD of 1.18%, a peak area of 1852.33, and an RSD of 14.84%.

Claims

Claim

1. A quality control method of Fufang Danshen Diwan, which comprises the following steps:

(a). Establishment of control fingerprint of Fufang Danshen Diwan

Preparation of Compound Danshen Dropping Pill Control Sample Solution:

Take a control sample of compound Danshen dripping pills, weigh it, place it in a volumetric flask, add distilled water to dissolve it with ultrasound, make up the volume, and filter to obtain the control sample solution;

Determination of control fingerprint of Fufang Danshen Diwan:

. Pick up the above reference sample solution and inject it into a liquid chromatograph, and use high performance liquid chromatography to determine the fingerprint of the compound Danshen dripping pills. Chromatographic conditions: The column is filled with octadecylsilane bonded silica gel; Mobile phase A is an aqueous phosphoric acid solution; mobile phase B is an acetonitrile phosphoric acid aqueous solution; the detection wavelength is 275-285nm;

(b). Determination of fingerprint of compound Danshen dripping pills:

Take the compound product of compound Danshen dripping pills and measure the fingerprint of the product according to the steps and conditions described in (a) above;

(c) comparing the fingerprint of the product of the compound Danshen dripping pills with the fingerprint of the compound Danshen dripping pills, and identifying the number of the same chromatographic peaks of the two, to determine whether the product quality is acceptable. 2. The quality control method of compound Danshen dripping pills according to claim 1, characterized in that: the flow rate of the mobile phase in the step (a) is 0.500 to 1.500 ml / min, the detection wavelength is 278 to 283 pictures, and the column temperature is 20 ~ 40. C.

3. The method for quality control of compound Danshen dripping pills according to claim 1, characterized in that: in the step (a), the preparation method of the compound Danshen dripping pills control sample solution is to take compound Danshen 5 to 20 capsules of Shendiwan control sample, accurately weighed, placed in a 10ml volumetric flask, ultrasonically distilled water for 15min, dissolved, fixed volume, and filtered;

Chromatographic conditions: mobile phase A is 0.0 ² % phosphoric acid aqueous solution; mobile phase B is 80% acetonitrile 0.02% phosphoric acid aqueous solution;

The gradient elution procedure is as follows:

At 15 minutes, mobile phase A is 74% 0.02% aqueous solution of stilbene acid, and mobile phase B is 26% 80% acetonitrile 0.02% phosphoric acid aqueous solution;

At 55min, mobile phase A is 48% of 0.02% aqueous solution of practic acid, and mobile phase B is 52% of 80% acetonitrile and 0.02% phosphoric acid in water; flow rate is 1.000ml / min, detection wavelength is 280nm, column temperature is 30 ° C, The sample volume was 10 μ1.

4. The method for quality control of compound Danshen dripping pills according to claim 1, 2 or 3, characterized in that, in the establishment of the compound fingerprint of the compound Danshen dripping pills, the mobile phase A solution is prepared by volume ratio, The mobile phase B solution is formulated in a volume ratio. 5. The quality control method for compound Danshen dripping pills according to claim 1, 2 or 3, characterized in that the control fingerprint of the compound Danshen dripping pills has 8 chromatographic peaks, wherein the area of a single peak exceeds the total peak There are 3 chromatographic peaks with an area of 10%, which are:

Peak No. 1, average retention time RT is 6.04min, RSD is 0.31%, and peak area is

1627.92, RSD is 5.91%;

Peak No. 2, average retention time RT is 9.90 min, RSD is 0.25%, and peak area is

2575.54, RSD is 13.53%;

No. 8 peak, with an average retention time RT was 31.02min, RSD 1.18%, peak area is 1852.33, RSD 14.84 ^_0/0. 6. The quality control method for compound Danshen dripping pills according to claim 1, 2 or 3, characterized in that the control fingerprint of the compound Danshen dripping pills has 8 chromatographic peaks, wherein the area of a single peak exceeds the total peak area There are 4 5% chromatographic peaks, which are:

Peak No. 1, average retention time RT is 6.04min, RSD is 0.31%, peak area is

1627.92, RSD is 5.91%;

Peak 2, average retention time RT is 9.90min, RSD is 0.25%, peak area is

2575.54, RSD is 13.53%;

Peak 6, average retention time RT is 23.74min, RSD is 0.76%, peak area is 555.35, RSD is 10.48%;

Peak No. 8 has an average retention time RT of 31.02 min, an RSD of 1.18%, a peak area of 1852.33, and an RSD of 14.84%.

7. The method for quality control of compound Danshen dripping pills according to claim 1, 2 or 3, characterized in that the control fingerprint of the compound Danshen dripping pills has 8 chromatographic peaks, and the area of a single peak all exceeds the total There are 8 chromatographic peaks with 2% of the peak area, which are:

1627.92, RSD is 5.91%;

Peak No. 2, average retention time RT is 9.90min, RSD is 0.25%, and peak area is

2575.54, RSD is 13.53%;

Peak No. 3, with an average retention time RT of 16.89 min, an RSD of 0.61%, a peak area of 366.89, and an RSD of 10.92%; Peak No. 4, with an average retention time RT of 17.84min, an RSD of 0.07%, a peak area of 381.40, and an RSD of 13.81%;

Peak No. 6, with an average retention time of 23.74 min, RSD of 0.76%, peak area of 555.35, and RSD of 10.48%;

Peak 7, the average retention time RT is 27.73min, the RSD is 0.50%, the peak area is 281.91, and the RSD is 18.08%;

Peak No. 8 with half-average retention time RT of 31.02min, RSD of 1.18%, and peak area of

At 1852.33, the RSD was 14.84%.

8. The quality control method of compound Danshen dripping pills according to claim 1, 2 or 3, characterized in that the fingerprint of the product of the compound Danshen dripping pills to be compared with the fingerprint of the compound Danshen dripping pills is compared; When the fingerprint of the compound has three or more identical chromatographic peaks, the quality of the product to be tested of the compound Danshen dripping pills is considered to be qualified.

9. The quality control method for compound Danshen dripping pills according to claim 8, wherein the fingerprint of the product of the compound Danshen dripping pills is compared with the fingerprint of the compound Danshen dripping pills, and the fingerprints of the two are When there are 5 or more identical chromatographic peaks, the quality of the product to be tested of the compound Danshen Diwan is considered to be qualified.

10. The method for quality control of compound Danshen dripping pills according to claim 8, characterized in that the fingerprint of the product of the compound Danshen dripping pills to be compared with the fingerprint of the compound Danshen dripping pills is compared with the fingerprints of the two When there are 7 or more identical chromatographic peaks, the quality of the product to be tested of the compound Danshen Diwan is considered to be qualified. 11. The quality control method of compound Danshen dripping pills according to claim 8, characterized in that the fingerprint of the product of the compound Danshen dripping pills to be tested is compared with the fingerprint of the compound Danshen dripping pills, and the fingerprints of the two are When there are 8 identical chromatographic peaks, the quality of the product of the compound Danshen Diwan is considered to be qualified.