WO2008064592A1

WO2008064592A1 - A composition comprising chinese traditional medicine as active ingredient for treating cardiovascular diseases and quality control method thereof

Info

Publication number: WO2008064592A1
Application number: PCT/CN2007/070811
Authority: WO
Inventors: De'an Guo; Wanying Wu; Zhigang Gao
Original assignee: Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences
Priority date: 2006-11-28
Filing date: 2007-09-28
Publication date: 2008-06-05
Also published as: CN101032503A; CN100563662C

Abstract

A Danqi composition comprising the ingredients as followed: (a) 0.7-4.3 parts by weight of ginsenoside Rg1; (b) 1.0 parts by weight of salvianolic acid B; (c) 0.7-4.3 parts by weight of ginsenoside Rb1. A quality control method of Danqi composition comprising controlling ginsenoside Rg1 : salvianolic acid B : ginsenoside Rb1=0.7-4.3 : 1 : 0.7-4.3 in Danqi composition. The main ingredients for treating cardiovascular diseases effectively and preferred ratio thereof in red sage root and notoginseng as essential ingredients in Danqi formulation are disclosed for the first time. The range of ratio makes it conveniently that control the content of ingredient when the Danqi formulation is prepared to obtain preferably therapeutic effect, which solves the problem that the therapeutic effect is dissatisfactory as a result of the main active ingredients and content thereof being unknown when the Danqi formulation is prepared in the past.

Description

Traditional Chinese medicine active ingredient composition and quality control method for treating cardiovascular disease

The invention belongs to the technical field of medicines, and particularly relates to a traditional Chinese medicine active ingredient composition for treating cardiovascular diseases and a quality control method for the Danqi preparation. Background technique

With the changes in people's living environment, lifestyle and eating habits, the incidence of cardiovascular disease has increased year by year. At present, cardiovascular and cerebrovascular diseases have become the most important diseases affecting the health of residents. Among people over 40 years old in China, the incidence of coronary heart disease is 3-5%, and in some areas it is 8-10%, which has been on the rise in recent years. China has entered an aging society. By 2004, the proportion of the population over 65 years old has exceeded 10%, and the population of coronary heart disease will also expand. In China, there are about 2.6 million people every year, and about 7,000 people die every day from cardiovascular and cerebrovascular diseases. With the increase in the number of patients with cardiovascular and cerebrovascular diseases, cardiovascular and cerebrovascular drugs have become the world's largest drug market. According to IMS statistics, in 2003, cardiovascular drugs ranked first in the global pharmaceutical market, with a market share of 16.09. %, the market size is 75 billion US dollars. According to the CDCC model of the SFDA Southern Institute of Medical Economics, in 2003, China's cardiovascular and cerebrovascular drugs ranked second in the Chinese pharmaceutical market, second only to anti-infective drugs, with a market share of 14.36%. The pathogenesis of cardiovascular and cerebrovascular diseases is complex, and modern drug therapy based on molecular biology is still difficult to effectively exert therapeutic effects in some fields.

Cardio-cerebral vascular medicine is a proprietary Chinese medicine for treating cardiovascular and cerebrovascular diseases such as coronary heart disease, stroke, myocardial infarction and combined with shock, arrhythmia, angina pectoris and hypertension, including oral Chinese patent medicines, traditional Chinese medicine injections and other dosage forms. . As a traditional Chinese disease treatment method, proprietary Chinese medicines occupy a very important position in the market of cardiovascular and cerebrovascular drugs in China. Market size is the most important indicator to measure the characteristics of the market economy. According to the CDCC model of the Southern Institute of Medical Economics, in 2003, the total retail sales of the domestic cardiovascular and cerebrovascular proprietary Chinese medicine market was about 8.21 billion yuan (±10%), accounting for about cardiovascular and cerebrovascular drugs (including proprietary Chinese medicines and chemical drugs; The overall market is 25.41%, accounting for 3.64% of China's pharmaceutical market.

Salvia miltiorrhiza is the dry root and stem of Salvia miltiorrhiza, a plant of the Labiatae family. It has the effect of promoting blood circulation and removing phlegm. Sanqi is the dry root of Panax notoginseng, Panax notoginseng, which has the effect of dilating and stopping bleeding, reducing swelling and relieving pain, and tonifying Qi and nourishing blood. Danshen compound preparation consisting of Danshen and Sanqi compatibility is used for clinical treatment of cardiovascular diseases such as coronary heart disease and angina pectoris. The function and indication of Danqi Tablet is for promoting blood circulation and removing blood stasis. It is used for blood stasis, heart and chest pain, dizziness and headache, and menstrual abdominal pain. Because of its exact curative effect and few adverse reactions, it is a commonly used proprietary Chinese medicine for clinical treatment of coronary heart disease, chest tightness and angina pectoris. However, the Danqi products produced by the existing processes have large differences in active ingredients, unstable ratios, and the problems of large dosage, poor disintegration, and lack of perfect quality control standards cannot be ignored. Therefore, it is necessary to further improve the extraction process, to obtain the most effective part, to find the most effective active ingredient and its proportion range, so as to reduce the dosage of the drug and improve the effectiveness of taking. Summary of the invention

It is an object of the present invention to provide a composition for treating cardiovascular diseases.

It is also an object of the present invention to provide a method for quality control of a Danqi formulation.

In a first aspect of the invention, there is provided a composition comprising the following ingredients:

(a) 0.7-4.3 parts by weight of ginsenoside Rg _{1 ;}

(b) 1.0 part by weight of salvianolic acid B;

(c) 0.7-4.3 parts by weight of ginsenoside Rb _{1 ;}

(d) 6 to 100 parts by weight of a pharmaceutically or food acceptable carrier;

Wherein the total content of the components (a) X (b) X (c) is from 1 to 50% by weight based on the total weight of the composition.

In another preferred embodiment of the invention, the composition comprises:

The content of ginsenoside R _gl is 1.5-3.5 parts by weight;

The content of salvianolic acid B is 1.0 part by weight; or

The content of ginsenoside is 1.5 to 3.5 parts by weight.

In another preferred embodiment of the present invention, the dosage form of the composition is selected from the group consisting of (including but not limited to): a tablet, an orally disintegrating tablet, an injection, a lyophilized powder, a granule, a capsule, a pill, Pill or oral solution.

In another preferred embodiment of the present invention, the pharmaceutically or foodly acceptable carrier is selected from the group consisting of a filler, a disintegrant, a lubricant, a glidant, an effervescent agent, a flavoring agent, and a coating material. , or other excipients or excipients.

In another preferred embodiment of the present invention, the composition comprises: salvianolic acid and panax notoginseng saponins. In another preferred embodiment of the present invention, the composition comprises salvia total phenolic acid and panax notoginseng saponin, and wherein the weight ratio of ginsenoside Rgi, salvianolic acid B and ginsenoside Rbi satisfies 0.7-4.3: 1.0 : 0.7-4.3 o In a second aspect of the invention, there is provided the use of the composition for the preparation of a medicament for the prevention or treatment of cardiovascular diseases.

In a third aspect of the present invention, a method for quality control of a Danqi preparation is provided, the method comprising the steps of: controlling a content of ginsenoside R _gl , salvianolic acid B, and ginsenoside Rb in a _Danqi preparation, so that the three The weight ratio is:

Ginsenoside Rgi: Salvianolic acid B: Ginsenoside Rbi = 0.7-4.3: 1.0 : 0.7-4.3.

In another preferred embodiment of the present invention, the weight ratio of ginsenoside R _gl , salvianolic acid B, and ginsenoside Rbi in the Danqi preparation is controlled as follows:

Ginsenoside R _gl : Salvianolic acid B: Ginsenoside Rbi = 1.5-3.5: 1.0: 1.5-3.5. In another preferred embodiment of the present invention, the quality control includes the following steps:

Determination of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi in Danqi preparation, if the content of the three meets ginsenoside Rgi: salvianolic acid B: ginsenoside 1 ^ = 0.7-4.3: 1.0 : 0.7-4.3, The composition of the preparation is not adjusted; if the content of the three does not satisfy the ginsenoside R _gl : salvianolic acid B: ginsenoside Rb^O.7-4.3: 1.0 : 0.7-4.3, the amount of the corresponding component is adjusted according to the measurement result. , so that the content of the three meets ginsenoside Rgi: salvianolic acid B: ginsenoside 1 1 ^ = 0.7-4.3: 1.0: 0.7-4.3;

Or the control includes the following steps:

The contents of ginsenoside Rgi, salvianolic acid B and ginsenoside Rbi in Danshen and Sanqi raw materials were determined, and the ratio of the raw materials of the medicinal materials was determined according to the measurement results.

In another preferred embodiment of the present invention, the content of ginsenoside Rgl, salvianolic acid B, or ginsenoside Rbl in the Danqi preparation is determined by chromatography (e.g., liquid chromatography;

In another preferred embodiment of the invention, the content of salvianolic acid B is determined as follows:

The octadecylsilane-bonded silica gel is used as a filler; the acetonitrile-0.1% phosphoric acid (21:79) is used as the mobile phase; the detection wavelength is 286 nm, and the theoretical plate number is not less than 4000 according to the peak of salvianolic acid B;

A solution of 80 μ _§ salvianolic acid B/ml was prepared by adding 40% ethanol to the salvianolic acid B reference product to obtain a reference solution;

Add 40% ethanol to the Danqi preparation to be tested, prepare a solution of 2mg Danqi preparation/ml, and sonicate for 15 minutes to obtain the test solution;

The reference substance and the test sample were subjected to liquid chromatography to obtain the content of salvianolic acid B.

Or the content of ginsenoside R _gl is determined as follows:

The octadecylsilane bonded silica gel is used as a filler; the acetonitrile-water (18:82) is used as the mobile phase; the detection wavelength is 203 nm _{; the} theoretical plate number is not less than 4000 according to the ginsenoside R _gl peak;

Adding methanol to 400 μg of ginsenoside R _gl /ml in ginsenoside Rgi control to obtain a reference solution;

Methanol was added to the Danqi preparation to be tested to prepare a solution of 3 mg Danqi preparation/ml, and ultrasonicated for 30 minutes to obtain a test solution;

The reference substance and the test sample were subjected to liquid chromatography to obtain a content of ginsenoside R _gl .

Or the content of total phenolic acid of Salvia miltiorrhiza: as follows:

Adding 40% ethanol to the salvianolic acid B reference product to prepare a solution of 36 μ _§ salvianolic acid B/ml to obtain a reference solution;

Add 40% ethanol to the Danqi preparation to be tested, prepare a solution of 2mg Danqi preparation/ml, and sonicate for 15 minutes to obtain the test solution; The reference solution and the test solution were taken, and 40% ethanol was used as a blank control. The absorbance value was measured by ultraviolet-visible spectrophotometry at 286 nm, and the total phenolic acid content was obtained according to the following formula:

Total phenolic acid content (%) = 0.626 χ (Α-Β) + Β

In the formula:

The content of total phenolic acid in the test sample was determined by ultraviolet spectrophotometry with barium sulphate as the control.

B is the content of salvianolic acid B in the test sample measured by high performance liquid chromatography.

Or the content of total saponins of Panax notoginseng is determined as follows:

Adding methanol to the reference substance of ginsenoside Rgi to prepare a solution containing 80 (g g ginsenoside R _gl / ml, to obtain a reference product;

Add methanol to the Danqi preparation to be tested, and make a solution containing 10mg Danqi preparation /ml, sonicated

After 30 minutes, the solvent was evaporated, the solid matter was dissolved in water, and the column was solid-phase extracted, and then eluted with water, 20% methanol, methanol, and the methanol eluate was collected to obtain a test solution;

The reference solution and the test solution were separately evaporated to a solvent, and respectively added with 5% vanillin glacial acetic acid solution and perchloric acid, and incubated in a water bath at 60 ° C for 15 minutes, immediately cooled in ice water for 5 minutes, and added with glacial acetic acid 5 ml. The absorbance value is measured by ultraviolet-visible spectrophotometry at a wavelength of 545 nm, and the content of the total saponins of Panax notoginseng is obtained in another preferred embodiment of the present invention, and the ginseng in the Danqi preparation is determined by measuring the fingerprint of the Danqi preparation. Saponin Rgl, salvianolic acid B, or ginsenoside Rbl content.

In another preferred embodiment, the fingerprint is determined by high performance liquid chromatography.

In another preferred embodiment of the invention, the method of determining the fingerprint is as follows:

The octadecylsilane bonded silica gel was used as a filler; the flow rate was 1.0 ml/min _{; the} column temperature was 25 ° C _{; the} detection wavelength was 203 nm _{; and} the acetonitrile-0.1% phosphoric acid aqueous solution was used as the mobile phase, and the gradient washing was carried out according to the following gradient elution conditions. Take off, run for 50min;

At 0-30 minutes, the proportion of acetonitrile increased from 13% to 23%, the proportion of 0.026% aqueous solution of pity acid decreased from 87% to 77%; 30-45 minutes, the acetonitrile increased from 23% to 45%, 0.026% of pity The aqueous solution was reduced from 77% to 55%; 45-50 minutes, the acetonitrile-0.026% phosphoric acid aqueous solution was maintained at a ratio of 45:55. The obtained fingerprint is shown in Figure l o

In another aspect, the method of quality control comprises the steps of: controlling the content of total phenolic acid and total saponins of salvia miltiorrhiza in the Danqi preparation, so that the weight ratio of the two is:

Salvia total phenolic acid: Panax notoginseng saponins = 1: 2-8; more preferably control of Salvia total phenolic acid: Panax notoginseng saponins = 1 :

3-7.

In another preferred embodiment, the content of total phenolic acid and total saponins of Salvia miltiorrhiza is determined by colorimetry. Other aspects of the invention will be apparent to those skilled in the art from this disclosure. DRAWINGS

Figure 1 shows the HPLC fingerprint of Danqi preparation. 1 is ginsenoside Rgl, 2 is salvianolic acid

B, 3 is ginsenoside Rbl.

Figure 2 shows the fingerprint of the Danqi preparation established by the TSQ Quantum LC/MS/MS liquid/mass spectrometer. detailed description

Through extensive and in-depth research, the present inventors have found an effective ratio range and an optimal ratio range of active ingredients in total phenolic acid and total saponins of Panax notoginseng, thereby providing an active ingredient containing a suitable ratio. Compositions. Moreover, based on the effective ratio and the optimal ratio, quality control can be performed on various Danqi preparations. Based on this, the present invention has been completed. As used herein, "Danqi preparation" refers to a general term for preparations containing Salvia miltiorrhiza and Panax notoginseng as essential components, including but not limited to: a mixture of Salvia miltiorrhiza extract and Panax notoginseng extract, Salvia total phenolic acid and Panax notoginseng saponins. Mixtures, etc.

Specifically, the present invention is directed to the disadvantage that the content of the active ingredient in the Danqi preparation prepared by using the Salvia miltiorrhiza extract and the Panax notoginseng extract or the Salvia total phenolic acid and the Panax notoginseng saponin is unstable, resulting in unstable therapeutic effect. Intensive research was carried out, and it was found that the optimal ratio of total phenolic acid and total saponins of Salvia miltiorrhizae in the Danqi preparation is Danshen total phenolic acid: Panax notoginseng saponins = 1 : 2-8; further The present inventors tested the main components contained in the total phenolic acid and the total saponins of Panax notoginseng in the optimal ratio, and found that the main active ingredients were ginsenoside R _gl , salvianolic acid B, and ginsenoside. Rb Their effective ratio is ginsenoside Rg _{1 :} salvianolic acid B: ginsenoside Rl ^ zOJ AJ : 1.0: 0.7~4.3, and their preferred ratio is ginsenoside R _gl : salvianolic acid B : ginsenoside ! ^^二? ~? ^ : 1.0 : 2~2.8. Within this ratio, Danqi preparation has the best therapeutic effect.

Accordingly, the present invention provides a composition comprising ginsenoside R _gl , salvianolic acid B, and ginsenoside. Moreover, the novel findings of the present invention can also be used for quality control of Danqi preparations. combination

As used herein, the term "essential component" refers to the necessary Chinese herbal medicines, namely Salvia miltiorrhiza, and Panax notoginseng.

As used herein, the term "essential ingredient" refers to the essential chemical substance as an active ingredient, ie, salvia miltiorrhiza. Acid, and Panax notoginseng saponins.

As used herein, the term "main component" or "principal component" refers to a chemical component that exerts therapeutic efficacy in total phenolic acid or total saponins of Panax notoginseng, namely ginsenoside R _gl , salvianolic acid B and ginsenoside Rb.

As used herein, the term "comprising" or "including" includes "comprising," "consisting essentially of," and "consisting of."

As used herein, the term "consisting essentially of" means that in the composition, in addition to containing the essential ingredients or essential components, it may contain minor minor components which do not affect the active ingredient and/or Or impurities. For example, sweeteners may be included to improve taste, antioxidants to prevent oxidation, and other additives commonly used in the art.

As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier for the administration of a therapeutic agent, including various excipients and diluents. The term refers to pharmaceutical carriers which are not themselves essential active ingredients and which are not excessively toxic after administration. Suitable carriers are well known to those of ordinary skill in the art. A full discussion of pharmaceutically acceptable excipients can be found in Remington's Pharmaceutical Sciences (Mack Pub. Co. N. J. 1991). The pharmaceutically acceptable carrier in the composition may contain a liquid such as water, saline, glycerol and ethanol. In addition, auxiliary substances such as fillers, disintegrants, lubricants, glidants, effervescent agents, wetting or emulsifying agents, flavoring agents, pH buffering substances and the like may also be present in these carriers. Non-essential ingredients other than essential components (danshen total phenolic acid, panax notoginseng saponins) from Danshen and Panax notoginseng, and other non-essential ingredients (such as other auxiliary medicines), also included in pharmaceutically acceptable carriers In the definition.

In the composition of the present invention, as a main component, (1) ginsenoside Rg _{1 ;} (2) salvianolic acid B; and (3) ginsenoside Rb The composition of the present invention can be directly used for treating or relieving cardiovascular disease The disease may be co-administered with other drugs.

As used herein, the term "composition of the invention" includes pharmaceutical compositions, food compositions and/or dietary supplements as long as they comprise or consist essentially of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi. Generally, the weight of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi is from 1 to 50%, preferably from 3 to 40%, more preferably from 5 to 25% by weight based on the total weight of the composition.

The composition may be a mixture containing substantially pure of the above three compounds or their analogs, and a pharmaceutically acceptable carrier; or, the composition may be a total of ginseng total phenolic acid and notoginseng a saponin, and a mixture of pharmaceutically acceptable carriers; or the composition may be a mixture comprising Salvia miltiorrhiza extract and Panax notoginseng extract.

In the composition of the present invention, each main component may also be used in the form of "physiologically acceptable salt" or "physiologically acceptable acid or base derived salt" or in the form of "amide". The salts include, but are not limited to, salts formed with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and organic acids. Salt, while organic acids refer to acetic acid, oxalic acid, succinic acid, tartaric acid, methanesulfonic acid and maleic acid. Other salts include those formed with alkali or alkaline earth metals such as sodium, potassium, calcium or magnesium, in the form of esters, carbamates or other conventional "prodrugs" (when administered in this form) , can be converted into active part in the body).

The composition of the present invention can be prepared into any conventional preparation form by a conventional method, including but not limited to: a tablet, an orally disintegrating agent, an injection, a lyophilized powder injection, a granule, a capsule, a pill, a pill, or an oral preparation. liquid. From the standpoint of ease of preparation and administration, preferred compositions are solid compositions, especially tablets and solid filled or liquid filled capsules and the like.

The therapeutic effect of the compositions of the invention on cardiovascular disease is closely related to the level of essential active ingredients. Studies have shown that in order to achieve stable treatment and / or alleviate the effects of cardiovascular disease, the active ingredient content of the drug should be within a certain range. The range of reasonable amounts of each component in the compositions of the present invention is:

(a) 0.7-4.3 parts by weight of ginsenoside Rg _{1 ;}

(b) 1.0 part by weight of salvianolic acid B;

(c) 0.7-4.3 parts by weight of ginsenoside Rb _{1 ;}

(d) 6 to 100 parts by weight of a pharmaceutically or food acceptable carrier;

The amount of the composition of the present invention may vary depending on the mode of administration and the severity of the condition to be treated. However, usually, when the composition of the present invention is administered at a dose of about 1 to 50 mg/kg of animal body weight per day, a satisfactory effect can be obtained, preferably administered in a divided dose of 1 to 4 times per day, or as a sustained release. Formal administration. For most large mammals, the total daily dose is about 60-5000 mg, preferably about 80-2000 mg. This dosage regimen can be adjusted to provide the optimal therapeutic response. For example, several separate doses may be administered per day, or the dose may be proportionally reduced, as needed for the therapeutic condition.

As a preferred embodiment, the composition of the present invention can directly adopt the main components of the total phenolic acid and the total saponins of Panax notoginseng, and thus the active substance content is high and the stability is good, so that the patient can be greatly reduced. The use of a dose increases patient compliance while increasing efficacy. Method for extracting essential components

Methods for the preparation of salvianolic acid, panax notoginseng saponins or extracts thereof are known in the art.

For example, the total saponins of Panax notoginseng can be extracted according to the local standards of Yunnan Province. The standard number is

WS ₃ -B-3590-2001<;Z;).

The total phenolic acid of Salvia miltiorrhiza can be extracted with water and then purified with macroporous resin to obtain the effective part of total phenolic acid. Quality control method Based on the effective ratio and optimal ratio of ginsenoside R _gl , salvianolic acid B and ginsenoside provided by the present invention, the composition of salvia miltiorrhiza total phenolic acid and panax notoginseng saponins or the extract of Salvia miltiorrhiza and Panax notoginseng extract The composition is quality controlled.

As a preferred method, the quality control of Danqi preparation can be carried out by the following method: determining the content of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi in Danqi preparation, if the content of the three meets ginsenoside Rg _{1 :} Dan Phenolic acid B: ginsenoside Rb^O.7-4.3 : 1.0 : 0.7-4.3, the formulation ingredients are not adjusted; if the three contents do not meet the ginsenoside Rgi: salvianolic acid B: ginsenoside Rb^O.7- 4.3: 1.0: 0.7-4.3, the amount of the corresponding component is adjusted according to the measurement result, so that the three contents satisfy the ginsenoside R _gl : salvianolic acid B : ginsenoside Rbi = 0.7-4.3: 1.0: 0.7-4.3.

As another preferred method, the quality control of the Danqi preparation can also be carried out by the following methods: determining the contents of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi in Danshen and Sanqi raw materials, and determining the ratio of raw materials according to the measurement results. Thus, the content of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi obtained in the subsequent preparation satisfies the ginsenoside Rgi: salvianolic acid B: ginsenoside Rb^O.7-4.3: 1.0: 0.7-4.3.

It should be understood that after the effective ratio and the optimal ratio obtained by the skilled person in the art, various quality analysis methods can be used to achieve quality control of the preparation materials of the Danqi preparation or the Danqi preparation. The methods described include, but are not limited to, thin layer chromatography, high performance liquid chromatography, gas chromatography, ultraviolet spectroscopy, nuclear magnetic resonance, mass spectrometry, LC/MS, and the like. These methods are all included in the present invention.

As an alternative quality control method, high performance liquid chromatographic fingerprints can be used to characterize and quantify Danqi preparations.

Another alternative quality control method is to directly detect the main component of Danqi preparation (ginsenoside)

The content of Rgi, salvianolic acid B or ginsenoside Rbl) or essential ingredients is used to characterize and quantify the formulation of the Danqi composition. The main advantages of the invention are:

(1) The present invention finds the essential component of the Danqi preparation, which participates in the main components effective in the treatment of cardiovascular diseases, namely ginsenoside Rgl, salvianolic acid B and ginsenoside Rbl, and the invention is also found for the first time. The three components are effective for treating cardiovascular diseases, and the compositions formulated according to the preferred range have a good effect of treating cardiovascular diseases.

(2) In the past, when mandarin preparations were prepared, it was often impossible to know the content of the main components in which the activity was active, which often resulted in poor therapeutic effects; and various Dansiya preparations obtained by using different methods or conditions were often active. Different ingredients make it difficult to guarantee good results. The present invention provides a preferred range of the three components, thereby facilitating the control of the content of the components in the preparation of the Danqi preparation to obtain a better therapeutic effect, overcoming the past When the preparation of the Danqi preparation, the technical problem of poor therapeutic effect due to the inability to know the content of the main component in which the activity is exerted is not known. The invention is further illustrated below in conjunction with specific embodiments. It is to be understood that the examples are merely illustrative of the invention and are not intended to limit the scope of the invention. The experimental methods in the following examples, which do not specify the specific conditions, are generally based on conditions such as those described in the drug book or pharmacopoeia, or according to conventional conditions, unless otherwise stated, the percentages and parts are by weight.

Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those skilled in the art. In addition, any methods and materials similar or equivalent to those described can be applied to the present invention. The preferred embodiments and materials described herein are for illustrative purposes only. Example 1 Extraction of effective parts of drugs

The total saponins of Panax notoginseng are extracted according to local standards of Yunnan Province, and the standard number is

WS ₃ -B-3590-2001<;Z;).

The total phenolic acid of Salvia miltiorrhiza is prepared by the following method:

Take Salvia miltiorrhiza herbs, smash, extract twice with deionized water at 80 °C, concentrate the filtrate below 60 °C under reduced pressure to a relative density of about 1.2 (50 °C), add ethanol to 70% alcohol content, and let stand for 12 hours. Discard the precipitate, filter the supernatant, concentrate under reduced pressure at 60 ° C or less to a relative density of about 1.3 (room temperature), elute with X-5 macroporous resin, elute with low concentration of ethanol, and concentrate the eluent. To about 1.15 (50 ° C;), spray drying, that is, the total phenolic acid of Salvia miltiorrhiza. Example 2 Screening experiment of total phenolic acid and total saponins of Panax notoginseng

In this example, SD male rats, 200±20 g, were randomly divided into blank control group, 1:1 group, 1:2 group, 1:3 group, 1:5 group, 1:7 group, 1:8 group, 1 : 9 groups of these 8 groups, 30 mg/kg gavage 30 minutes before operation, anesthesia with ether, open the chest, ligation of the left anterior descending coronary artery, suture the skin, 4 hours after surgery, the animals were sacrificed by the medullary method, and the heart was quickly removed. Weighed whole heart, left heart weight, cut into l~2mm slices, stained in 37 ° C, 0.1% NBT dye solution for 15~20 minutes, stained white area for infarct area, cut off infarct area and accurately weighed. In order to achieve the stability and consistency of the experiment, the surgeon was fixed and the animals with more bleeding and poor status were eliminated. The experimental results are shown in Table 1. Table 1 Screening of the ratio of total phenolic acid and total saponins of Panax notoginseng

Group (Dan: 3) Weight (g) Total weight (mg) Left heart weight (mg) Infarct weight (mg) Infarct weight/left heart weight blank control group 209±6.1 1 962±97.1 633±53.0 209±25.3 0.33±0.04

1: 1 215±8.04 965±52.1 653±47.3 203±20.5 0.31±0.04

1: 2 202 ± 5.3 873 ± 18.9 591 ± 45.4 159 ± 15.9 * 0.28 ± 0.03 *

1: 3 207±3.64 976±40.1 636±42.0 156±31.5** 0.25±0.05**

1: 5 209±4.59 1007±62.4 648±34.4 152±39.3 ** 0.23±0.05**

1: 7 207 ± 6.43 983 ± 36.0 638 ± 31.6 175 ± 35.3 * 0.27 ± 0.05 *

1: 8 201±1 1.2 883±37.4 598±42.4 178±10.2* 0.29±0.04*

1: 9 206±8.52 953±49.1 631±29.6 188±43.5 0.29±0.07 Compared with the blank control group, *P<0.05 **P<0.01 Pharmacological experiments showed that total phenolic acid and total saponins of Panax notoginseng When the ratio is different, the effect of the drug is left rising.

The results show that, according to the weight fraction, the ratio of total phenolic acid: the total saponin of Panax notoginseng is 1: 2~8; more preferably, the ratio of total phenolic acid of Salvia miltiorrhiza: total saponins of Panax notoginseng is 1: 3~7; further preferred The ratio of total phenolic acid of Salvia miltiorrhiza: total saponins of Panax notoginseng is 1: 4~6; most preferably, total phenolic acid of Salvia miltiorrhiza: total saponins of Panax notoginseng is 1:5.

Further, in response to the pharmacological results, the inventors have also established a ratio range of ginsenoside Rgl, salvianolic acid B, and ginsenoside which are main components of Danqi. The ratio of ginsenoside R _gl : salvianolic acid B : ginsenoside Rbl is 0.7 to 4.3: 1.0: 0.7-4.3; more preferably, ginsenoside Rgi: salvianolic acid B: ginsenoside Rbi is calculated by weight 1 to 3.8: 1.0: 1 to 3.8; more preferably, ginsenoside Rg _{1 :} salvianolic acid B: ginsenoside RbJ ratio is 1.5 to 3.5: 1.0 : 1.5 to 3.5; further preferably, ginsenoside Rg _{1 :} dansolic Acid B: ginsenoside RbJ ratio is 2 to 2.8: 1.0: 2 to 2.8; most preferably, ginsenoside Rgi: salvianolic acid B: ginsenoside RbJ ratio is 2.2: 1.0: 2.4.

The results are shown in Tables 2 and 3.

Table 2 Different ratios of total phenolic acid and Panax notoginseng saponins in different ratios Sampling amount (mg) Content (%) Content ratio Danqi

Proportion of salvia miltiorrhiza total phenolic acid saponins S-B Rbi S-B Rbi

22.78

1 : 2 3 .70 7.37 28.72 24. .54 0. .79 1 .00 0.85

1 : 2 3 .25 6.66 23.10 30.55 24. .61 0. .76 1 .00 0.81

1 : 2 3 .16 6.30 22.58 30.77 24. .51 0. .73 1 .00 0.80

1 : 5 1 .05 5.39 28.50 13.32 30. .67 2. .14 1 .00 2.30

1 : 5 2 .50 12.31 28.66 12.86 30. .53 2. .23 1 .00 2.37

1 : 5 1 .31 6.59 28.71 12.50 30. .77 2. .30 1 .00 2.46

1 : 8 1 .20 9.62 30.56 10.06 32. .66 3. .04 1 .00 3.25

1 : 8 1 .43 1 1.59 30.44 9.41 32. .57 3. .23 1 .00 3.46

1 : 8 1 .44 1 1.47 30.50 7.73 32. .68 3. .95 1 .00 4.23 Table 3 The optimum ratio of the main component content and the effective ratio range

Danqi ratio

Salvia total phenolic acid: Panax notoginseng saponins

Best ratio 1: 5 2.2: 1.0: 2.4

Effective range 1: 2~8 0.7-4.3: 1.0: 0.7-4.3 Example 3 Danqi composition tablet formulation and preparation

In this embodiment, the formulation used is as shown in Table 4.

Table 4 Dan seven composition tablet formula

The preparation method is as follows: taking the total phenolic acid and the total saponins of Salvia miltiorrhiza prepared in Example 1 and mixing them in proportion, Microcrystalline cellulose, lactose, soft material made of 5% polyvinylpyrrolidone alcohol solution, 16 mesh sieved granules, dried and granulated, adding 5% disintegrant (carboxymethylcellulose sodium;), 1 % magnesium stearate, 0.5% micronized silica gel, mixed into tablets, or coated or coated.

After determination, the content of salvianolic acid B in each tablet was 5.46%; the content of ginsenoside Rbi was 19.39%, the content of ginsenoside R _gl was 18.43%; the total phenolic acid content of Salvia miltiorrhiza was 8.74%, and the total saponin content of Panax notoginseng was 43.71. %.

Example 4 Danqi composition orally disintegrating tablet formulation and preparation

In this embodiment, the formulation used is shown in Table 5.

Table 5 Danqi composition oral disintegration tablets formula

The preparation method is as follows: the salvianolic acid total phenolic acid prepared in Example 1 and the total saponin of Panax notoginseng are mixed in an appropriate ratio, and then mixed with other auxiliary materials listed in the above table, and the powder is directly compressed.

The content of salvianolic acid B in each tablet was determined to be 3.16%; the content of ginsenoside Rbi was 5.64%, the content of ginsenoside R _gl was 5.29%; the total phenolic acid content of salvia miltiorrhiza was 4.97%, total saponin content of Panax notoginseng It is 14.12%.

Example 5 Formulation and preparation of Danqi composition injection

In this embodiment, the formulation used is as shown in Table 6.

Table 6 Danqi composition injection liquid formula

Salvia total phenolic acid 60g

Panax notoginseng saponins 120g

Water for injection 2000ml

Made of 1000 Take the total phenolic acid and the Panax notoginseng saponins prepared according to the method of Example 1, add appropriate amount of water for injection to dissolve, add 0.1% activated carbon, stir at 40 ° C for 15 minutes, cool to room temperature, then filter with filter paper. Then use 0.2μηι microporous membrane to filter, add water for injection to 2000ml, potting, 2ml each, sterilized, that is. Example 6 Formulation and preparation of Danqi composition freeze-dried powder injection

In this embodiment, the formulation used is as shown in Table 7.

Table 7 Formulation and preparation of Danqi composition freeze-dried powder injection

Take Danshen total phenolic acid and Panax notoginseng saponins, add a certain amount of water for injection to dissolve, add 0.1% activated carbon, stir at 40 ° C for 15 minutes, cool to room temperature, filter with filter paper first, then use 0.2μηι microporous The filter membrane is filtered, diluted with water for injection to 8000ml, filled, 4ml each, freeze-dried, that is, 2000 powder needles.

The content of each of the dendritic acid B was determined to be 10.12%; the content of ginsenoside Rbi was 25.97%, the content of ginsenoside R _gl was 25.23%; the total phenolic acid content of Salvia miltiorrhiza was 13.68%, and the total saponin content of Panax notoginseng was 66.67. %.

Example 7 Formulation and preparation of Danqi composition granules

In this embodiment, the formulation used is as shown in Table 8.

Table 8 Formulation of Danqi Composition Granules

The phenolic acid of Salvia miltiorrhiza and the total saponin of Panax notoginseng were mixed, then dextrin was added, soft material was prepared with 90% alcohol solution, and sieved by 14 mesh sieve, and dried to obtain 1000 bags of granules, 1.5 g per bag.

The content of salvianolic acid B in each bag of granules was determined to be 4.06%; the content of ginseng saponin was 16.73%, the content of ginsenoside R _gl was 16.05%; the total phenolic acid content of salvia miltiorrhiza was 5.68%, and the total saponin content of panax notoginseng was 5.68%. 44.17%. Example 8 Formulation and preparation of Danqi composition capsule

In this embodiment, the formulation used is as shown in Table 9.

Table 9 Formulation of Danqi Composition Capsules

Mix the total phenolic acid of Salvia miltiorrhiza and the total saponins of Panax notoginseng, add 1% magnesium stearate, mix and fill the capsules, and obtain 1000 capsules.

The content of salvianolic acid B in each capsule was determined to be 9.9%; the content of ginsenoside Rbi was 26.40%, the content of ginsenoside R _gl was 25.87%; the total phenolic acid content of salvia miltiorrhiza was 13.50%, and the total saponin content of Panax notoginseng was 13.50%. 66.71%.

Example 9 Formulation and preparation of Danqi composition pellets

In this embodiment, the formulation used is as shown in Table 10.

Table 10 Formulation of Danqi Composition Pills

The polyethylene glycol 6000 was completely melted on the water bath, and the total phenolic acid and the total saponins of Panax notoginseng were added, dissolved and dissolved, and kept at a temperature of 80 ° C and dropped into a liquid paraffin at 15 ° C to prepare pellets of 1000 bags, each bag. 3.0 grams.

The content of salvianolic acid B in each bag was determined to be 9.30%; the content of ginsenoside Rbi was 26.75%, the content of ginsenoside R _gl was 26.32%; the total phenolic acid content of salvia miltiorrhiza was 13.740%, and the total saponin content of panax notoginseng was 66.34. %.

Example 10 Formulation and preparation of Danqi composition pellet

In this embodiment, the formulation used is shown in Table 11.

Table 1 Formulation of 1 Danqi Composition Pills

Salvia total phenolic acid 60g

Panax notoginseng saponins 360g

Deionized water

Made of 3000 capsules The total phenolic acid of Salvia miltiorrhiza and the total saponin of Panax notoginseng were mixed, and water was used as a wetting agent, and 3000 pellets were prepared by a conventional pan-pill method.

The content of salvianolic acid B in each capsule was determined to be 7.85%; the content of ginsenoside Rbi was 26.57%, the content of ginsenoside R _gl was 25.35%; the total phenolic acid content of Salvia miltiorrhiza was 11.64%, and the total saponin content of Panax notoginseng was 70.28. %. Example 11 Formulation and preparation of Danqi composition oral solution

In this embodiment, the formulation used is as shown in Table 12.

Add salvia total phenolic acid, panax notoginseng saponins and honey, sodium benzoate, add deionized water to 1000ml, stir well, filter, fill, sterilize, that is. Each pack is 10ml, a total of 1000.

After determination, the content of salvianolic acid B in each oral liquid was 8.65%; the content of ginsenoside Rbi was

24.59%, the content of ginsenoside R _gl was 23.48%; the total phenolic acid content of Salvia miltiorrhiza was 12.58%, and the total saponin content of Panax notoginseng was 62.92%. Example 12 Establishment of Fingerprints

Fingerprints were created using a Finnigan TSQ Quantum LC/MS/MS liquid/mass spectrometer (Finnigan MAT, San Jose, CA).

Liquid chromatography conditions:

Zorbax SB-C ₁₈ column (100x3. O mm); mobile phase: A is 0.1% formic acid (V/V), B is methanol; column temperature is 20 ° C, flow rate is 0.6 ml / min; elution procedure is:

0%, the ratio of methanol increased from 20% to 35%, the proportion of 0.1% formic acid decreased from 80% to 65%; 6-30 minutes, methanol increased from 35% to 55%, 0.1% formic acid The ratio decreased from 65% to 45%; in 30-40 minutes, the proportion of methanol increased from 55% to 70%, the proportion of 0.1% formic acid decreased from 45% to 30%, 40-50 minutes, and the proportion of methanol was 70%. Increased to 75%, the proportion of 0.1% formic acid decreased from 30% to 25% o Mass spectrometry conditions:

ESI source; negative ion detection; scan range: 120-1400 /z amu; sheath flow: 40 arb;

Auxiliary gas flow: 10 arb; Source voltage: 4.00 kV; Capillary temperature: 330 °C.

Preparation of test solution:

(1) Accurately weigh 1mg of salvianolic acid total phenolic acid, put it in a 5ml volumetric flask, dissolve it in water and dilute to the mark, shake it, filter it with 0.45μηι microporous membrane, and set aside.

(2) Accurately weigh 5mg of total saponins of Panax notoginseng, place in a 5ml volumetric flask, dissolve in water and dilute to volume, shake well, filter with 0.45μηι microporous membrane, and set aside.

(3) Measure each lml of the above-mentioned salvia miltiorrhiza phenolic acid solution and panax notoginseng saponin solution separately, mix well, and filter with 0.45μηι microporous membrane.

As a result, the obtained fingerprint is shown in Fig. 2. The corresponding retention times, compounds and their sources are shown in Table 13.

Table 13 Fingerprint peaks

Example 13 Determination of the content of main components

Salvianolic acid B

According to high performance liquid chromatography (Chinese Pharmacopoeia 2005 edition of an appendix VI D).

a. Chromatographic conditions and system suitability test

The octadecylsilane-bonded silica gel was used as a filler; the mobile phase was acetonitrile-0.1% phosphoric acid (21:79); the detection wavelength was 286 nm. The number of theoretical plates should be no less than 4000 according to the peak of salvianolic acid B.

b. Preparation of reference solution

Take the reference substance of salvianolic acid B (China Pharmaceutical and Biological Products Institute 111562-200403), accurately weighed, add 40% ethanol to make 80 μg solution per 1ml, that is. c. Preparation of test solution

Solid preparation: Take about 50mg of solid Danqi preparation, accurately weigh it, put it into 25ml volumetric flask, add 40% ethanol, sonicate (power 140W, frequency 42kHz) for 15 minutes, put it to room temperature, add 40% ethanol to the scale, Shake well, filter, and take the filtrate to obtain.

Liquid preparation: Take appropriate amount of liquid Danqi preparation, add deionized water to about 2mg/ml containing Dandan solids, that is.

d. Determination method

Each of the reference solution and the test solution are accurately taken up by 10 μl, injected into a liquid chromatograph, and measured.

2. Ginsenoside R _gl

a. Chromatographic conditions and system suitability test

The octadecylsilane-bonded silica gel was used as a filler; the acetonitrile-water (18:82) was used as the mobile phase; the detection wavelength was 203 nm _{; the} theoretical plate number was not less than 4,000 according to the ginsenoside Rgi peak.

b. Preparation of reference solution

Take ginsenoside Rgi reference substance (China National Institute for the Control of Pharmaceutical and Biological Products 1 10703-200322), accurately weighed, add methanol to make 400 μg solution per 1ml, that is.

c Preparation of test solution

Solid preparation: Take about 30mg of solid Danqi preparation, accurately weighed, put it in a 10ml volumetric flask, add appropriate amount of methanol, sonicate (power 140W, frequency 42kHz) for 30 minutes, place it at room temperature, add methanol to the mark, shake well, filter After that, take the filtrate and get it.

Liquid preparation: Take the appropriate amount of liquid Danqi preparation, add deionized water to about 3mg/ml containing Dandan solid, which is obtained.

d. Determination method

Separately draw the reference solution and the test solution 10μ1, inject into the liquid chromatograph, and measure.

3. Salvia total phenolic acid

It was determined by ultraviolet-visible spectrophotometry (Appendix V 《 of the Chinese Pharmacopoeia 2005 edition).

a. Preparation of reference solution

Take the reference substance of salvianolic acid B (China Pharmaceutical and Biological Products Institute 111562-200403), accurately weighed, add 40% ethanol to make a solution containing 36 μg per 1ml. b. Preparation of test solution

Accurately absorb 1 ml of the test solution for the determination of salvianolic acid B. Place it in a 5 ml volumetric flask, add 40% ethanol to the mark, and shake well.

c assay

Take the reference solution and the test solution about 5ml, use 40% ethanol as a blank, and measure the absorbance at 286nm by UV-visible spectrophotometry (Chinese Pharmacopoeia 2005 edition, Appendix VA). The total phenolic acid content.

Total phenolic acid content (%) = 0.626 χ (Α-Β) + Β

In the formula:

4. Panax notoginseng saponins

It was determined by ultraviolet-visible spectrophotometry (Appendix V A of the 2005 edition of Chinese Pharmacopoeia).

a. Preparation of reference solution

Take ginsenoside Rgi reference substance (China National Institute for the Control of Pharmaceutical and Biological Products 1 10703-200424) appropriate amount, accurately weighed, add methanol to make a solution containing 80 (^g per 1ml, that is.

b. Preparation of test solution

Solid preparation: Take 0.1g of solid Danqi preparation, accurately weighed, placed in 25ml stoppered conical flask, precision added methanol 10ml, densely packed, weighed, sonicated (power 140W, frequency 42kHz) for 30 minutes, placed to At room temperature, weigh the weight again, make up the lost weight with methanol, shake well, filter, take 2ml filtrate and dry, dissolve in 2ml water, make up to volume, take 0.5ml aqueous solution on the solid phase extraction cartridge, then use water, 20 % methanol and methanol were eluted in 2 ml each. The methanol eluate was collected into a 2 ml volumetric flask and shaken to obtain.

Liquid preparation: Take 0.5 ml of a liquid solution containing 10 mg/ml of liquid Danqi preparation, and apply a solid phase extraction cartridge, then elute with 2 ml each of water, 20% methanol and methanol, and collect the methanol eluate into a 2 ml volumetric flask. Shake well, that is.

c assay

Separately draw 100 μl of the reference solution and the test solution, respectively, and place them in a 10 ml stoppered test tube. Dissolve the solvent, add 0.2 ml of freshly prepared 5% vanillin glacial acetic acid solution, and 0.8 ml of perchloric acid. Incubate in a 60 ° C water bath for 15 minutes, immediately set to cool in ice water for 5 minutes, add 5 ml of glacial acetic acid, shake well, place for 10 min, according to UV-visible spectrophotometry ("Chinese Pharmacopoeia" 2005 edition of an appendix VA), at 545 nm The absorbance value is measured at the wavelength, that is, it is obtained. Example 14 Pharmacodynamic test of Danqi preparation

In this example, the inventors examined the efficacy of the two prescriptions of the Danqi preparation. Formulation 1 is a Danqi formulation prepared in accordance with the formulation described in Example 3. Prescription 2 is a Danqi preparation prepared by using total phenolic acid of Salvia miltiorrhiza and total saponins of Panax notoginseng. The formulation is determined as shown in the "Prescription 2" column in Table 14.

In this study, a myocardial infarction model was induced by anterior descending coronary artery ligation in anesthetized dogs. The prescription 1 and prescription 2 (see Table 14) were observed to have protective effects on acute myocardial infarction in anesthetized dogs. The experiment was divided into 3 groups: 1 solvent control group; 2 prescription 1 group; 3 prescription 2 groups. An acute myocardial infarction model was induced by two-step ligation of the anterior descending coronary artery by the Harris method. Changes in epicardial electrograms, myocardial infarction weight, and changes in serum myocardial enzymology were observed after administration.

The results are shown in Table 15-1, Table 15-2, Table 15-3, Table 15-4. Prescription 1 is administered intragastrically, which can reduce the degree of myocardial infarction after canine coronary artery ligation, reduce the scope of myocardial infarction, and reduce lactate decoction. The overflow of hydrogenase, the effect of prescription 2 after oral administration was not significant. Epicardial electrogram, histological quantitative test and serum enzymology test showed that the prescription 1 after intragastric administration can significantly reduce the degree of myocardial infarction after coronary artery ligation in anesthetized dogs, and narrow the scope of myocardial infarction. Myocardial infarction has a good protective effect. Table 14 Two different ratios of Danqi preparations

Table 15-1 Effect of ST segment sum (∑ ST) on canine coronary artery ligation epicardial electrogram

Before administration, after administration, mv

0 min 35min 60min 120min solution control group 1 17±28.0 203±31.8 218±36.5 194±23.7

Prescription 1 109±10.9 128±10.4** * 149±15.4** 136±19.2** *Prescription 2 1 1 1±22.7 180±21.2 194±22.2 180±39.5 Table 15-2 Effects on the range of myocardial infarction (extracardial electrogram NST)

Group Weight (kg) Left ventricular weight (g) Infarct area weight (g) Infarct area weight /

Left heart

Solvent control group 10.7±0.79 54.2±3.3 1 7.20±1.53 0.133±0.03 Prescription 1 1 1.3±0.74 58.2±7.47 5.05±2.42 0.0842±0.03 *Prescription 2 10.6±0.82 48.4±8.02 5.66±0.66 0.120±0.02 Solvent control phase Ratio, *p<0.05 **p<0.01 Table 15-3 Effect on myocardial infarction range (measured by NBT staining) Group weight (kg) Left ventricular weight (g) Infarct area weight (g) Infarct area weight/left Heart heavy solvent control group 10.7±0.79 54.2±3.3 1 7.20±1.53 0.133±0.03

Prescription 1 1 1.3±0.74 58.2±7.47 5.05±2.42 0.0842±0.03 *

Prescription 2 10.6±0.82 48.4±8.02 5.66±0.66 0.120±0.02

*p<0.05 **p<0.01 compared with the vehicle control group Table 15-4 Effect on serum biochemical parameters (LDH) in coronary artery ligation dogs

Group LDH (IU/L)

Solvent control group 285±106

Prescription 1 180±60.9

Prescription 2 238 ± 83.9 From the results of Table 15-1 - Table 15-4, it can be seen that the remission effect of prescription 1 on myocardial infarction in dogs is significantly higher than that in prescription 2 and solvent control group, while the effect of prescription 2 on myocardial infarction in dogs is relieved. Basically equivalent to the solvent control group, that is, the prescription 2 efficacy is not obvious.

The ginsenoside Rbi content is 9.83%, the ginsenoside R _gl content is 9.27%; the salvia miltiorrhiza totals. The phenolic acid content was 27.21%, and the total saponin content of Panax notoginseng was 28.92%. The content of the ginsenoside Rg l, the salvianolic acid B, and the ginsenoside Rb l contained in the prescription 2 is not in the range of the effective ratio of 0. 7-4. 3 : 1. 0 : 0. 7-4. According to the above measurement results, the inventors adjusted the prescription 2, and adjusted the total phenolic acid of the salvia miltiorrhiza. The whole is 80g, and the total saponin of Panax notoginseng is adjusted to 160g, that is, prescription 2, and the other formulas are unchanged. Again, it was found that the content of salvianolic acid B in the prescription 2' was 12.02%; the content of ginsenoside Rbi was 13.11%, and the content of ginsenoside R _gl was 14.86%, which was in the range of 0.7-4.3: 1.0: 0.7-4.3.

The inventors conducted a pharmacodynamic test on the prescription 2' and found that it has a good effect on the myocardial infarction of the dog, and the effect is very obvious.

It can be seen that it is very necessary to carry out quality control on various Danqi preparations, find out and remove unqualified drugs in time, and ensure that the content of active ingredients in Danqi preparations is within the effective range or better range, thereby greatly improving the drug effect. . All documents mentioned in the present application are hereby incorporated by reference in their entirety in their entireties in the the the the the the the the the In addition, it is to be understood that various modifications and changes may be made by those skilled in the art in the form of the appended claims.

Claims

Rights request

A composition comprising the following ingredients:

(a) 0.7-4.3 parts by weight of ginsenoside Rg _{1 ;}

(b) 1.0 part by weight of salvianolic acid B;

(c) 0.7-4.3 parts by weight of ginsenoside Rb _{1 ;}

(d) 6 to 100 parts by weight of a pharmaceutically or food acceptable carrier;

2. The composition of claim 1 wherein

The content of ginsenoside R _gl is 1.5-3.5 parts by weight;

The content of salvianolic acid B is 1.0 part by weight; or

The content of ginsenoside is 1.5 to 3.5 parts by weight.

3. The composition according to claim 1, wherein the composition is selected from the group consisting of: a tablet, an orally disintegrating tablet, an injection, a lyophilized powder, a granule, a capsule, a pill, Pills, or oral liquids.

The composition according to claim 1, wherein the composition contains salvianolic acid and panax notoginseng saponins, and the weight of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi The ratio satisfies 0.7-4.3: 1.0: 0.7-4.3.

Use of the composition according to claim 1, characterized in that it is used for the preparation of a medicament for preventing or treating cardiovascular diseases.

6. A method for quality control of a Danqi preparation, characterized in that the method comprises the steps of:

(i) Control the content of ginsenoside R _gl , salvianolic acid B, and ginsenoside Rb in _Danqi preparation, so that the weight ratio of the three is:

Ginsenoside Rgi: Salvianolic acid B: Ginsenoside Rbi = 0.7-4.3: 1.0 : 0.7-4.3.

7. The method according to claim 6, wherein the weight ratio of ginsenoside R _gl , salvianolic acid 8, and ginsenoside Rbi in the Danqi preparation is controlled as follows:

Ginsenoside R _gl : Salvianolic acid B: Ginsenoside Rbi = 1.5-3.5: 1.0: 1.5-3.5.

8. The method according to claim 6, wherein the quality control step (i) comprises: determining the content of ginsenoside R _gl , salvianolic acid B and ginsenoside Rbi in the Danqi preparation, if three The content meets the ginsenoside Rgi: salvianolic acid B: ginsenoside 1 ^ = 0.7-4.3: 1.0 : 0.7-4.3, the formulation ingredients are not adjusted; if the three contents do not meet the ginsenoside R _gl : salvianolic acid B: ginseng Saponin Rb^O.7-4.3: 1.0: 0.7-4.3, the amount of the corresponding component is adjusted according to the measurement result, so that the content of the three meets ginsenoside Rgi: salvianolic acid B: ginsenoside 1 1^=0.7- 4.3: 1.0: 0.7-4.3; Or the quality control step «includes:

The contents of ginsenoside Rgi, salvianolic acid B and ginsenoside Rbi in Danshen and Sanqi raw materials were determined, and the ratio of raw materials was determined according to the measurement results.

9. The method according to claim 8, wherein the ginsenoside R _gl , salvianolic acid B, or ginsenoside content in the Danqi preparation is determined by chromatography.

10. The method according to claim 8, wherein the ginsenoside R _gl , salvianolic acid B, or ginsenoside content in the Danqi preparation is determined by measuring the fingerprint of the Danqi preparation.