Abstract:
The present invention discloses a traditional Chinese medicine preparation for cardio-cerebral blood vessel diseases, it is prepared through extracting danshen and  Notoginseng  by lye, precipitating with alcohol, concentrating, and adding other medicine and excipients. Then using the HAPLY-MS and HAPLY fingerprint Atlas to characterize its Physicochemical properties completely. Using the fingerprint Atlas analysis method of the present invention, the structure and comparative content of biologically active component can be known. Characterization of the physical chemical properties of danshen and  Notoginseng  of traditional Chinese medicine preparation with this way is better than other methods of the prior art.

Description:
RELATED APPLICATIONS 
     This application is a continuation under 35 U.S.C. 111(a) of PCT/CN2005/000333, filed Mar. 17, 2005 and published as WO 2005/087242 A1, filed Sep. 22, 2005, which claimed priority under 35 U.S.C. 119 to Chinese Application No. 200410018758.4, filed Mar. 17, 2004, which applications and publication are incorporated herein by reference and made a part hereof. 
    
    
     TECHNICAL FIELD 
     The invention relates to a medicine, and in particular, to a traditional Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular diseases. 
     BACKGROUND ART 
     Cardiovascular and cerebrovascular diseases are common ones which do great harm to health of human beings. Recently, such diseases have an increasing occurrence due to the changes of works, livings, diet patterns, environments and the like with social development. The traditional Chinese medicine (TCM), in spite of its lower activity toward a single target relative to the Western medicine, is characterized by its multiple routes and targets, dynamic and holistic treatment, and low side effects, which are far beyond the effects of the Western medicine. The TCM preparation with definite therapeutic effect will have an overall therapeutic effect superior to that of the Western medicine. There have been now a plurality of TCM preparations for the treatment of cardiovascular and cerebrovascular diseases, such as compound Danshen tablets and its TCM preparations, Guanxin Danshen drop pills, and Xinkeshu tablets etc. These TCM preparations, all of which contain  Radix Salviae Miltiorrhizae  (also known as danshen) and  Radix Notoginseng , have different therapeutic effects for their different formulations, proportions of ingredients, extraction and purification processes, or dosage forms. In addition, these TCM preparations can hardly be controlled in quality, since no effective quality detection method is available at present for completely characterizing the physical and chemical properties of these medicines, and instead, only one or two compounds, such as Danshensu or Tanshinone IIA, are used to represent the complex biologically active ingredients in these medicines. Therefore, it is necessary to improve the process for extracting and purifying such TCM preparations and also the method for controlling their qualities. 
     SUMMARY OF THE INVENTION 
     It is an object of the present invention to provide a more effective TCM preparation for the treatment of cardiovascular and cerebrovascular diseases. Also provided herein is a detection method for relatively complete and exact characterization of the physical and chemical properties thereof. 
     It is another object of the present invention to provide a process for preparing the above TCM preparation. 
     The objects of the present invention are achieved through the following embodiments. 
     The TCM preparation according to the present invention can be prepared through a process comprising the following steps of: 
     mixing  Radix Salviae Miltiorrhizae  and  Radix Notoginseng  with sodium hydroxide, sodium bicarbonate, sodium carbonate, potassium hydroxide, potassium bicarbonate, potassium carbonate or a mixture thereof in an amount of 0.5%-4.0% based on the total weight of said medicinal materials to obtain a mixture; 
     boiling the mixture out in 3-6 folds of water for 2-4 times; 
     subjecting the mixture to filtration and concentrating the combined filtrates; 
     adding an ethanol with a high concentration (above 70%) in an amount sufficient to obtain a 65-70% content of the ethanol; 
     allowing the mixture to stand and separating the supernatant; recovering the ethanol from the supernatant and concentrating the residue until it has a relative density of 1.20-1.50 (55-60° C.), which is an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng;    
     mixing the above extract with Borneol (or an oil of  Lignum Dalbergiae Odoriferae ); and 
     adding one or more pharmacological excipients, such as starch, dextrin, lactose, microcrystalline cellulose, hydroxypropyl methyl cellulose, polyethylene glycol, magnesium stearate, micro silicon gel, xylitol, lactitol, glucose, glycine, mannitol, methyl starch sodium, cross-linked sodium carboxyl methyl cellulose, cross-linked polyvinylpyrrolidone etc., to formulate the mixture into various dosage forms, such as injection, tablet, sustained-release tablet, drop pill, granule, injection powder, capsule, microgranule, oral disintegrant. 
     Preferably, the above TCM preparation is prepared through a process comprising the following steps of: 
     weighing  Radix Salviae Miltiorrhizae  and  Radix Notoginseng;    
     adding sodium bicarbonate in an amount of 1.4%-1.9% based on the total weight of said medicinal materials to obtain a mixture; 
     boiling the mixture out in 4-5 folds of water for 2-3 hours, and then in 3-4 folds of water for another 1-2 hours; 
     subjecting the mixture to filtration and concentrating the combined filtrates until a specific gravity of 1.16-1.20 (80±5° C.) is achieved; 
     adding an ethanol with a high concentration (above 70%) in an amount sufficient to obtain a 65-70% content (20° C. of the ethanol; 
     allowing the mixture to stand for 8-12 hours and separating the supernatant; 
     recovering the ethanol from the supernatant and concentrating the residue until it has a relative density of 1.32-1.40 (55-60° C.), which is an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng ; mixing the above extract with Borneol (or an oil of  Lignum Dalbergiae Odoriferae ); and adding one or more pharmacological excipients selected from the group consisting of starch, dextrin, lactose, microcrystalline cellulose, hydroxypropyl methyl cellulose, polyethylene glycol, magnesium stearate, micro silicon gel, xylitol, lactitol, glucose, glycine, mannitol, methyl starch sodium, cross-linked sodium carboxyl methyl cellulose, cross-linked polyvinylpyrrolidone etc. to formulate the mixture into tablet, drop pill, injection powder, capsule, granule, microgranule, or oral disintegrant. 
     The Borneol used herein can be a naturally occurring or synthesized one. The oil of  Lignum Dalbergiae Odoriferae  used herein is obtained through distillation of  Lignum Dalbergiae Odoriferae.    
     The above TCM preparation is preferably in the dosage form of drop pill. 
     The TCM preparation according to the present invention is characterized using the following physical and chemical parameters: 
     in the HPLC spectrum, there are 8 peaks which have a ratio of single peak area to total peak area greater than 2%; the average retention time of these 8 peaks is 6.04, 9.90, 16.89, 17.84, 20.31, 23.74, 27.73 and 31.02 respectively, and the RSD % of the retention time is 0.31, 0.25, 0.61, 0.70, 0.96, 0.76, 0.50 and 1.18 respectively; their average peak area is 1627.92, 2575.54. 366.89, 381.40, 186.08, 555.35, 281.91 and 1852.33 respectively, and the RSD % of the peak area is 5.91, 13.53, 10.92, 13.81, 12.04, 10.48, 18.08 and 14.84 respectively; and the ratio of single peak area to total peak area accounts for 19.6%-22.0%, 28.5%-37.4%, 4.2%-5.2%, 4.2%-5.5%, 2.1%-2.7%, 6.4%-7.8%, 3.0%-4.3% and 20.2%-27.2% respectively. 
     The above physical and chemical parameters were obtained under the following detection conditions: 
     (1) High Performance Liquid Chromatography Octadecylsilyl-silica gel was used as a filler for the chromatography column, with flow rate of 1.000 ml/min and detection wavelength of 280 nm. The Elution was carried out under the following conditions: mobile phase A being a 0.02% aqueous phosphoric acid solution, mobile phase B being a 80% acetonitrile-0.02% aqueous phosphoric acid solution, mobile phase A being changed from 90% to 78% homogeneously and mobile phase B being changed from 10% to 22% homogeneously during 0 to 8 min; mobile phase A from 78% to 74% and mobile phase B from 22% to 26% during 8 to 15 min; and mobile phase A from 74% to 48% and mobile phase B from 26% to 52% during 15 to 55 min. 
     (2) Preparation and Determination of Sample Solution 
     10 pills of the TCM preparation according to the present invention are weighed accurately, and then, added into a 10 ml measuring bottle. Distilled water was added in an amount sufficient to dissolve the pills through shaking with ultrasound for 15 minutes. And more distilled water was then added to achieve a volume of 10 ml. The resultant solution was subjected to centrifugation or filtration to obtain a sample solution. An accurate 10 μl of the sample solution was injected into a HPLC apparatus, and then determined by way of HPLC chromatography to obtain a HPLC spectrum. 
     With the aid of an analysis method, such as a comparison with a standard sample and Mass Spectra, the above 8 peaks with an average retention time of 6.04, 9.90, 16.89, 17.84, 20.31, 23.74, 27.73 and 31.02 were identified to correspond with Danshensu, Protocatechualdehyde, Isolithospermic acid A, Isolithospermic acid B, Salvianolic acid D, Rosmarinic acid, Salvianolic acid B and Salvianolic acid A, respectively (see  FIG. 1 ). 
     Using a particular HPLC-MS method, the TCM preparation of the present invention was determined to comprise Danshensu, Protocatechualdehyde, Isolithospermic acid A, Isolithospermic acid B, Salvianolic acid D, Salvianolic acid E, Rosmarinic acid, Salvianolic acid B, Salvianolic acid G, Salvianolic acid A, Tanshinone I , Tanshinone II A, Notoginsenoside R 1 , Ginsenoside Re, Ginsenoside Rg1, Ginsenoside Rb1, Notoginsenoside R2, Notoginsenoside R2 iso., Ginsenoside Rg2, Ginsenoside Rh1, Ginsenoside Rh1 iso., Ginsenoside Rd, Ginsenoside Rd iso., Ginsenoside Rf-H2O, Notoginsenoside R2-H2O, Ginsenoside Rg6 or F4, Ginsenoside Rk3, Ginsenoside (Rh4), Ginsenoside 20(R)-Rg3, Ginsenoside 20(S)-Rg3, Ginsenoside (Rk1), Ginsenoside (Rg5) and the like. 
     
       
         
               
               
             
               
               
               
             
               
             
               
               
               
               
             
               
             
               
               
               
               
               
               
             
               
             
               
               
               
               
               
             
               
             
               
               
               
               
               
             
           
               
                   
               
             
             
               
                   
                 1 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 2 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 3 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 4 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 5 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 6 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 7 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 8 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 9 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 10 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                   
                 11 
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 1. 
                 Danshensu 
                 MW = 198 
               
               
                 2. 
                 Protocatechualdehyde 
                 MW = 138 
               
               
                 3. 
                 Salvianolic acid A 
                 MW = 494 
               
               
                 4. 
                 Salvianolic acid B 
                 MW = 718 
               
               
                 5. 
                 Salvianolic acid C 
                 MW = 492 
               
               
                 6. 
                 Salvianolic acid D 
                 MW = 418 
               
               
                 7. 
                 Salvianolic acid E 
                 MW = 718 
               
               
                 8. 
                 Salvianolic acid G 
                 MW = 340 
               
               
                 9. 
                 Isolithospermic acid A 
                 MW = 538 
               
               
                 10. 
                 Isolithospermic acid B 
                 MW = 538 
               
               
                 11. 
                 Rosmarinic acid 
                 MW = 360 
               
               
                   
               
             
          
           
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 Structure Type A 
               
             
          
           
               
                 Ginsenoside 
                 R 1   
                 R 2   
                 Molecular Weight (MW) 
               
               
                   
               
               
                 Ginsenoside Rb 1   
                 Glc-Glc 
                 Glc-Glc 
                 1108 
               
               
                 Ginsenoside Rd 
                 Glc-Glc 
                 Glc 
                 946 
               
               
                 Ginsenoside Rg 3   
                 Glc-Glc 
                 H 
                 784 
               
               
                 Ginsenoside F 2   
                 Glc 
                 Glc 
                 784 
               
               
                   
               
             
          
           
               
                 Structure Type B 
               
             
          
           
               
                   
                 Ginsenoside 
                 R 1   
                 R 2   
                 R 3   
                 MW 
               
               
                   
                   
               
               
                   
                 Ginsenoside Re 
                 H 
                 Glc 
                 O-Glc-Rham 
                 946 
               
               
                   
                 Ginsenoside Rf 
                 H 
                 H 
                 O-Glc-Glc 
                 800 
               
               
                   
                 Ginsenoside Rg 1   
                 H 
                 Glc 
                 O-Glc 
                 800 
               
               
                   
                 Ginsenoside Rg 2   
                 H 
                 H 
                 O-Glc-Rham 
                 784 
               
               
                   
                 Ginsenoside Rh 1   
                 H 
                 H 
                 O-Glc 
                 638 
               
               
                   
                 Notoginsenoside R 2   
                 H 
                 H 
                 O-Glc-Xyl 
                 770 
               
               
                   
                 Notoginsenoside R 1   
                 H 
                 Glc 
                 O-Glc-Xyl 
                 932 
               
               
                   
                 Ginsenoside F 1   
                 H 
                 Glc 
                 OH 
                 638 
               
               
                   
                   
               
             
          
           
               
                 Structure Type C 
               
             
          
           
               
                   
                 Ginsenoside 
                 R 1   
                 R 2   
                 MW 
               
               
                   
                   
               
               
                   
                 Ginsenoside Rg 5   
                 Glc-Glc- 
                 H 
                 766 
               
               
                   
                 Ginsenoside Rh 4   
                 H 
                 Glc-O— 
                 620 
               
               
                   
                 Ginsenoside F 4   
                 H 
                 Rham-Glc-O— 
                 766 
               
               
                   
                   
               
             
          
           
               
                 Structure Type D 
               
             
          
           
               
                   
                 Ginsenoside 
                 R 1   
                 R 2   
                 MW 
               
               
                   
                   
               
               
                   
                 Ginsenoside Rg 6   
                 H 
                 Rham-Glc-O— 
                 766 
               
               
                   
                 Ginsenoside Rk 1   
                 Glc-Glc 
                 H 
                 766 
               
               
                   
                 Ginsenoside Rk 3   
                 H 
                 Glc-O— 
                 620 
               
               
                   
                   
               
               
                   
                 Glc = β-D-glucose 
               
               
                   
                 Rham = α-L-rhamnose 
               
               
                   
                 Xyl = β-D-xylose 
               
             
          
         
       
     
     In the extraction process and analysis method of the present invention, fingerprint atlas was used for completely characterizing the physical and chemical properties of the  Radix Salviae Miltiorrhizae  and the  Radix Notoginseng  in the TCM preparation. Compared to the prior art in which only one or two compounds are used to represent complex biologically active ingredients in TCM preparations, this characterization means is more suitable for controlling the quality of the TCM preparations. 
     The biologically active ingredients in the present TCM preparations were detected using the HPLC-MS analysis method according to the present invention. As a result, 12 components from  Radix Salviae Miltiorrhizae  and 21 components from  Radix Notoginseng  have been identified in total. The compounds were identified mainly based on an analysis of the MS n  data and comparison with data from literature. Finally, a large number of the components were completely confirmed with respect to their structures through comparison with the control samples. It can be concluded thereby that the analysis for the chemical composition of the present TCM preparation using the HPLC-MS method of the present invention can produce abundant information on the structure of the biologically active ingredients. The characterization by these information for the physical and chemical properties of  Radix Salviae Miltiorrhizae  and  Radix Notoginseng  in the present TCM preparation has consequently a much better effect than those methods in the prior art. 
     The following tests demonstrate that the present TCM preparation has an effect on the treatment of cardiovascular and cerebrovascular diseases. 
     1. Effects of the TCM Preparation on Myocardial Ischemia and Myocardial Infarction in Anaesthetized Dog 
     An epicardial electrogram was used to map a range of myocardial ischemia and to indicate the extent thereof. Quantitative histology (N-BT staining method) was used to determine an area of myocardial infarction. Also determined were changes of blood flow of coronary artery, myocardial oxygen consumption, and activities of serum CK and LDH, and blood plasma ET, TXB 2 , and 6-Keto-PGF 1a . The TCM preparation according to the present invention was studied upon alimentary administration with regard to its effect on acute myocardial ischemia, myocardial infarction, and related indicators in test dogs. 
     The test results show that the TCM preparation according to the present invention has a significant effect in improving acute myocardial ischemia and myocardial infarction of dogs. It can lead to a reduced extent of myocardial ischemia (Σ-ST) indicated by the epicardial electrogram (P&lt;0.001 relative to the control group using normal saline), a significantly reduced area of infarction indicated through N-ST staining (P&lt;0.001 relative to the control group using normal saline), and a significantly increased blood flow of coronary artery in an ischemic heart (P&lt;0.001 relative to the control group using normal saline). It has an inhibitory action against the release of serum lactate dehydrogenase (LDH) resulted from myocardial ischemia and myocardial infarction (with a relative change ratio significantly lower than that of the control group using normal saline, P&lt;0.001), as well as against the increase of the activity of creatine phosphokinase (CK) (with a relative change ratio significantly lower than that of the control group using normal saline, P&lt;0.05). It has also an effect in reducing blood plasma ET (P&lt;0.001 relative to the control group using normal saline)and TXB 2  level (P&lt;0.001 relative to the control group using normal saline, P&lt;0.05 relative to the group using a TCM preparation) of blood plasma, and improving the ratio of 6-Keto-PGF 1a /TXB 2  (P&lt;0.001 relative to the control group using normal saline, P&lt;0.05 relative to the group using a TCM preparation). 
     2. Effects of the TCM Preparation on Myocardial Infarction Caused by Ischemic Reperfusion 
     It was found through an observation on a rat model with the damage of myocardial ischemia reperfusion that, the TCM preparation according to the present invention could lead to a significantly reduced extent of myocardial damage, a decreased area of myocardial infarction (p&lt;0.05-0.01 relative to the model group), and a less weight of an infarction part (p&lt;0.05 relative to the model group). It has also an effect in significantly increasing the activity of superoxide dismutase (SOD) (p&lt;0.01 relative to the model group). 
     3. Effects of the TCM Preparation on Dynamics of Cardiac Blood Flow and Myocardial Oxygen Consumption in Dogs 
     The TCM preparation of the present invention was evaluated with respect to its effect on dynamics of cardiac blood flow and myocardial oxygen consumption in anaesthetized normal dogs. 
     The results show that the TCM preparation according to the present invention can lead to a significantly improved blood flow of coronary artery (p&lt;0.01-0.001 relative to the group before administration and the control group using normal saline), an expanded coronary vessel, an increased oxygen content in coronary vein sinus (p&lt;0.05-0.001 relative to the group before administration and the control group using normal saline), a reduced myocardial oxygen consumption indicator, an improved supply of blood and oxygen to cardiac muscle, and an increased output per heartbeat and cardiac output (p&lt;0.05-0.01 relative to the group before administration and the control group using normal saline) without enhancing left ventricular work. The present TCM preparation has also an effect in adjusting cardiac complaisance, and thus, in adapting and improving a cardiovascular system. 
     4. Effects of the TCM Preparation on Platelet Agglutination in Rabbits 
     The TCM preparation of the present invention was evaluated through Born nephelometry with respect to its effect on platelet agglutination in rabbits. 
     The results show that the TCM preparation can, upon an intragastric administration for 7 successive days, lead to a significant reduction of the platelet agglutination in rabbits induced by arachidonic acid (AA) (p&lt;0.05-0.01 relative to the control group using distilled water) and collagen (p&lt;0.01 relative to the control group using distilled water). This indicates that the TCM preparation according to the present invention has an inhibitory effect on platelet agglutination. 
     5. Effects of the TCM Preparation on Thrombogenesis in Vitro and Blood Viscosity in Rats 
     The TCM preparation of the present invention was evaluated with respect to its effect on thrombogenesis in vitro and blood viscosity in rats. 
     The results show that the TCM preparation can, upon an intragastric administration for 7 successive days, lead to a considerably shortened thrombus (p&lt;0.01 relative to the control group using distilled water), a decreased wet and dry weight of the thrombus (p&lt;0.05 relative to the control group using distilled water), a reduced viscosity of blood plasma (p&lt;0.001 relative to the control group using distilled water), and a decreased whole blood viscosity at various shear rates (p&lt;0.05 relative to the control group using distilled water). This indicates that the TCM preparation according to the present invention has an effect in inhibiting thrombogenesis, and reducing viscosity of blood plasma and of whole blood. 
     6. Effects of the TCM Preparation on Hyperlipidemia and Atherosclerosis in Rabbits 
     A hyperlipidemia and atherosclerosis (AS) model for test was established through feeding fodder with a high content of cholesterol to a rabbit. The TCM preparation of the present invention was evaluated with respect to its effect on this model. 
     The results show that the TCM preparation according to the present invention can lead to a significantly decreased concentration of TC, TG, LDL-C, VLDL-C in serum and a decreased TC/HDL-C ratio (p&lt;0.05-0.001 relative to the control group suffering from Hyperlipidemia) in rabbits, a significantly increased HDL-C concentration (p&lt;0.05 relative to the control group suffering from Hyperlipidemia), a decreased content of TC in the aorta (p&lt;0.05 relative to the control group suffering from Hyperlipidemia), a decreased content of TG in the liver (p&lt;0.05 relative to the control group suffering from Hyperlipidemia), and a decreased content of MDA in the liver (p&lt;0.001 relative to the control group suffering from Hyperlipidemia). The present TCM preparation has a significant effect in improving the activity of SOD in the liver (p&lt;0.01 relative to the control group suffering from Hyperlipidemia). Furthermore, it has a significant effect in reducing the thickness of aorta plaque and the amount of the foam cells formed in the aorta (p&lt;0.05 relative to the control group suffering from Hyperlipidemia). It also leads to a decreasing tendency of the area of the aorta plaque. These indicate that the TCM preparation according to the present invention has an effect in adjusting blood fat, and at the same time, a certain effect of the anti-peroxidation of lipid and prevention of arteriosclerosis. 
     7. Effects of the TCM Preparation on Localized Cerebral Ischemia in Rats 
     Using a rat model with a middle cerebral artery thrombosis (MCAT), the TCM preparation of the present invention was determined with respect to its effect on an area of cerebral infarction in MCAT rats. 
     The results demonstrate that the TCM preparation according to the present invention has a significant effect of anti-cerebral ischemia. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1  is a fingerprint atlas of the components of the  Radix Salviae Miltiorrhizae  in the drop pills as one of the dosage forms of the present TCM preparation. In this figure, peak  1  represents Danshensu; peak  2  represents Protocatechualdehyde; peak  3  represents Isolithospermic acid A; peak  4  represents Isolithospermic acid B; peak  5  represents Salvianolic acid D; peak  6  represents Rosmarinic acid; peak  7  represents Salvianolic acid B; and peak  8  represents Salvianolic acid A. 
         FIG. 2  is a HPLC spectrum of the water-soluble components of the  Radix Salviae Miltiorrhizae  in the present TCM preparation. In this figure, peak  1  represents Danshensu; peak  2  represents Protocatechualdehyde; peak  3  represents Isolithospermic acid A; peak  4  represents Isolithospermic acid B; peak  5  represents Salvianolic acid D; peak  6  represents Salvianolic acid E; peak  7  represents Rosmarinic acid; peak  8  represents Salvianolic acid B; peak  9  represents Salvianolic acid G; and peak  10  represents Salvianolic acid A. 
         FIG. 3  is a MS-TIC spectrum of the water-soluble components of the  Radix Salviae Miltiorrhizae  in the present TCM preparation. 
         FIG. 4  is a HPLC spectrum of the liposoluble components of the  Radix Salviae Miltiorrhizae  in the present TCM preparation. In this figure, peak  1  represents Tanshinonel; and peak  2  represents Tanshinone IIA. 
         FIG. 5  is a MS-TIC spectrum of the liposoluble components of the  Radix Salviae Miltiorrhizae  in the present TCM preparation. 
         FIG. 6  is a MS-TIC spectrum of the components of the  Radix Notoginseng  in the present TCM preparation. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
     The invention will be further illustrated in details by reference to the following examples. The examples are for illustrative purpose and are not intended to limit the scope of the invention. 
     EXAMPLES 
     Example 1 
     Preparation Example 
     41.06 g of  Radix Salviae Miltiorrhizae  and 8.03 g of  Radix Notoginseng  were weighed out, to which sodium bicarbonate was added in an amount of 1.8% based on the total weight of said medicinal materials. The resulting mixture was boiled out in 4 folds of water for 2 hours, and then in 3 folds of water for another 1 hour. After filtration, the combined filtrates were concentrated until a specific gravity of 1.19-1.20 (75±1° C.) was achieved. Then, a 95% ethanol was added in an amount sufficient to obtain a 65% content of the ethanol (20° C.). The mixture was subsequently allowed to stand for 12 hours, and the supernatant was separated. The ethanol was recovered from the supernatant, and the residue was concentrated until it had a relative density of 1.37 (55-60° C. ), which was an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng.    
     The above extract was then mixed uniformly with 0.46 g of Borneol and 18 g of polyethylene glycol-6000. The mixture was melted at a temperature of 85° C. for 80 mins. The melting liquor was then introduced into the dropping tank of a drop-pill machine with the tank temperature being maintained at 86° C., in which the liquor was dropped into a liquid paraffin at 8° C. The obtained drop pills were taken out, subjected to an oil removal and then screened through a sieve to obtain the desired preparation. 
     Example 2 
     Preparation Example 
     59.36 g of  Radix Salviae Miltiorrhizae  and 6.38 g of  Radix Notoginseng  were weighed out, to which potassium carbonate was added in an amount of 1.0% based on the total weight of said medicinal materials. The resulting mixture was boiled out in 4 folds of water for 2.5 hours, and then in 3 folds of water for another 1.5 hours. After filtration, the combined filtrates were concentrated until a specific gravity of 1.19-1.20 (75±1° C.) was achieved. Then, a 85% ethanol was added in an amount sufficient to obtain a 70% content of the ethanol (20° C.). The mixture was subsequently allowed to stand for 10 hours, and the supernatant was separated. The ethanol was recovered from the supernatant, and the residue was concentrated until it had a relative density of 1.35 (55-60° C. ), which was an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng.    
     The above extract was then mixed uniformly with 0.34 g of Borneol and 23 g of polyethylene glycol-6000. The mixture was melted at a temperature of 89° C. for 100 mins. The melting liquor was then introduced into the dropping tank of a drop-pill machine with the tank temperature being maintained at 85° C., in which the liquor was dropped into a methyl silicone oil at 8° C. The obtained drop pills were taken out, subjected to an oil removal and then screened through a sieve to obtain the desired preparation. 
     Example 3 
     Preparation Example 
     12.60 g of  Radix Salviae Miltiorrhizae  and 56.15 g of  Radix Notoginseng  were weighed out, to which potassium bicarbonate was added in an amount of 1.0% based on the total weight of said medicinal materials. The resulting mixture was boiled out in 4 folds of water for 2.5 hours, and then in 3 folds of water for another 1.5 hours. After filtration, the combined filtrates were concentrated until a specific gravity of 1.19-1.20 (75±1° C.) was achieved. Then, a 95% ethanol was added in an amount sufficient to obtain a 70% content of the ethanol (20° C.). The mixture was subsequently allowed to stand for 10 hours, and the supernatant was separated. The ethanol was recovered from the supernatant, and the residue was concentrated until it had a relative density of 1.35 (55-60° C.), which was an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng.    
     The above extract was then mixed with 0.34 g of Borneol and 23 g of polyethylene glycol-6000. The mixture was melted at a temperature of 89° C. for 100 mins. The melting liquor was then introduced into the dropping tank of a drop-pill machine with the tank temperature being maintained at 85° C., in which the liquor was dropped into a methyl silicone oil at 8° C. The obtained drop pills were taken out, subjected to an oil removal and then screened through a sieve to obtain the desired preparation. 
     Example 4 
     Preparation Example 
     31.12 g of  Radix Salviae Miltiorrhizae  and 9.21 g of  Radix Notoginseng  were weighed out, to which sodium hydroxide was added in an amount of 0.5% based on the total weight of said medicinal materials. The resulting mixture was boiled out in 4 folds of water for 1.5 hours, and then in 3 folds of water for another 1.5 hour. After filtration, the combined filtrates were concentrated until a specific gravity of 1.19-1.20 (75±1° C.) was achieved. Then, a 88% ethanol was added in an amount sufficient to obtain a 66% content of the ethanol (20° C.). The mixture was subsequently allowed to stand for 10 hours, and the supernatant was separated. The ethanol was recovered from the supernatant, and the residue was concentrated until it had a relative density of 1.40 (55-60° C. ), which was an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng.    
     The above extract was then mixed uniformly with 0.50 g of Borneol, 90 g of mannitol, 15 g of calciumedetate sodium and 15 ml of distilled water. The resultant mixture was lyophilized, and finally formulated into injection powders. 
     Example 5 
     Preparation Example 
     116.35 g of  Radix Salviae Miltiorrhizae  and 58.21 g of  Radix Notoginseng  were weighed out, to which sodium bicarbonate was added in an amount of 2.0% based on the total weight of said medicinal materials. The resulting mixture was boiled out in 4 folds of water for 2 hours, and then in 3 folds of water for 1.5 hour. After filtration, the combined filtrates were concentrated until a specific gravity of 1.19-1.20 (75±1° C.) was achieved. Then, a 88% ethanol was added in an amount sufficient to obtain a 66% content of the ethanol (20° C.). The mixture was subsequently allowed to stand for 10 hours, and the supernatant was separated. The ethanol was recovered from the supernatant, and the residue was concentrated until it had a relative density of 1.40 (55-60° C. ), which was an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng.    
     The above extract was then mixed uniformly with 1.80 g oil of  Lignum Dalbergiae Odoriferae  and 40 g of microcrystalline cellulose. A 3% solution of polyvidone in ethanol was added to soften the mass. The softened mass was then sieved through an 18-size mesh to form granules. The granules were dried at a temperature of 60° C. for 35 mins, trimmed, and then mixed uniformly with 4 g of talcum powders. The mixture obtained was encapsulated to obtain the desired preparation. 
     Example 6 
     Preparation Example 
     116.35 g of  Radix Salviae Miltiorrhizae  and 58.21 g of  Radix Notoginseng  were weighed out, to which sodium bicarbonate was added in an amount of 2.0% based on the total weight of said medicinal materials. The resulting mixture was boiled out in 4 folds of water for 2 hours, and then in 3 folds of water for 1.5 hour. After filtration, the combined filtrates were concentrated until a specific gravity of 1.19-1.20 (75±1° C.) was achieved. Then, a 88% ethanol was added in an amount sufficient to obtain a 66% content of the ethanol (20° C.). The mixture was subsequently allowed to stand for 10 hours, and the supernatant was separated. The ethanol was recovered from the supernatant, and the residue was concentrated until it had a relative density of 1.40 (55-60° C. ), which was an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng.    
     The above extract was then mixed uniformly with 0.90 g of Borneol, 120 g of microcrystalline cellulose, 40 g of hydroxypropyl methyl cellulose, 5 g of xylitol, and 2 g of magnesium stearate. The obtained mixture was compressed into tablets to obtain the desired preparation. 
     Example 7 
     Preparation Example 
     140.35 g of  Radix Salviae Miltiorrhizae  and 36.42 g of  Radix Notoginseng  were weighed out, to which sodium bicarbonate was added in an amount of 2.5% based on the total weight of said medicinal materials. The resulting mixture was boiled out in 4 folds of water for 2 hours, and then in 3 folds of water for 1.5 hour. After filtration, the combined filtrates were concentrated until a specific gravity of 1.19-1.20 (75±1° C.) was achieved. Then, a 90% ethanol was added in an amount sufficient to obtain a 65% content of the ethanol (20° C.). The mixture was subsequently allowed to stand for 8 hours, and the supernatant was separated. The ethanol was recovered from the supernatant, and the residue was concentrated until it had a relative density of 1.35 (55-60° C. ), which was an extract of  Radix Salviae Miltiorrhizae - Radix Notoginseng.    
     The above extract was then mixed uniformly with 1.00 g of Borneol and 46 g of microcrystalline cellulose. A 3% solution of polyvidone in ethanol was added to soften the mass. The softened mass was then sieved through an 18-size mesh to form granules. The granules were dried at a temperature of 60° C. for 30 mins, trimmed, and then mixed uniformly with 4 g of talcum powders. The mixture obtained was compressed into tablets to obtain the desired preparation. 
     Example 8 
     Detection Example for Active Component 
     1. Preparation of Sample 
     (1) The Water-Soluble Components of the  Radix Salviae Miltiorrhizae  in the Present TCM Preparation 
     148.4 mg was weighed out each for the TCM drop pills from example 1, 2 and 3, the TCM injection powders from example 4, the TCM capsules from example 5, the TCM oral disintegrant tablets from example 6, and the TCM tablets from example 7. Said preparations were dissolved in 6 ml of water through ultrasound for 15 mins, and then filtered through a 0.45 μm nylon film to obtain a yellow sample solution, respectively. 
     (2) The Components of the  Radix Notoginseng  and Liposoluble Components of the  Radix Salviae Miltiorrhizae  in the Present TCM Preparation 1003.8 mg was weighed out each for the TCM drop pills from example 1, 2 and 3, the TCM injection powders from example 4, the TCM capsules from example 5, the TCM oral disintegrant tablets from example 6, and the TCM tablets from example 7. Said preparations were dissolved in 10 ml of 4% aqueous ammonia through ultrasound for 15 mins, and then filtered through a 0.45 μm nylon film, respectively. The filtrate was pretreated on an Extract-Clean C 18  (Alltech Associates, Inc, U.S.) column. This sample, upon loaded into the column, was washed with 10 ml of water, and then eluted with 2 ml of methanol to obtain the test sample as a yellow eluent, respectively. 
     2. Analysis of Sample 
     (1) Instruments and Agents 
     Agilent Series-1100 Liquid Chromatograph (Agilent); G1315A Diode Array Detector G1313A Automatic Sample Injector; G1316A Thermostat; G1322A Deaerator and Duplex Pump; HP Instrument Chromatographic Work Station. 
     Type G2445A Series 1100 LC-MSD/Trap Mass Spectrograph (Bruker); Ionization was carried out by means of electro-spraying; Extract-Clean C 18  Column(100 mg/ml, Alltech Associates, Inc, U.S.), acetonitrile being chromatographically pure (TEDIA), water being redistilled water , and acetic acid being analytically pure. 
     (2) Detection Conditions of Instruments 
     Agilent Zorbax SB-C18 chromatographic column (5 μm, 4.6 mm×25 cm , Agilent, SN USCL009296) was used for HPLC analysis. The gradient elution and mass spectrum detection of each sample were performed under following conditions. 
     {circle around (1)} The Water-soluble Components of the  Radix Salviae Miltiorrhizae  in the TCM Preparation from Each Example 
     HPLC Elution Conditions: 
     
       
         
               
               
               
             
               
               
               
             
           
               
                   
               
               
                 time (min) 
                 mobile phase A (%) 
                 mobile phase B (%) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 0 
                 95.0 
                 5.0 
               
               
                 15 
                 78.3 
                 21.7 
               
               
                 33 
                 78.3 
                 21.7 
               
               
                 38 
                 65.0 
                 35.0 
               
               
                   
               
               
                 mobile phase A: acetic acid:water = 0.01:100 
               
               
                 mobile phase B: acetic acid:acetonitrile = 0.01:100 
               
               
                 flow rate: 0.5 ml/min 
               
               
                 temperature: 30° C. 
               
               
                 detection wavelength: multiple wavelength (280 nm of indicated wavelength) 
               
             
          
         
       
     
     MS Analysis Conditions: 
     
       
         
               
               
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
                   
               
               
                   
                 HPLC-MS 
                 HPLC-MS n   
               
             
          
           
               
                   
                 Ion detection manner 
                 negative ion detection 
                   
               
               
                   
                   
               
             
          
           
               
                   
                 Dry gas flow rate (L/min) 
                 10 
                 10 
               
               
                   
                 Nebulizer pressure (psi) 
                 60 
                 60 
               
               
                   
                 Dry temperature (° C.) 
                 350 
                 350 
               
               
                   
                 Capillary voltage (v) 
                 3500 
                 3500 
               
               
                   
                 Mass scan range (m/z) 
                 100-1200 
                 100-800 
               
               
                   
                 Fragment amplitude (ev) 
                   
                 1.5-3.0 
               
               
                   
                   
               
             
          
         
       
     
     {circle around (2)} The components of the  Radix Notoginseng  in the TCM Preparation from Each Example 
     HPLC Elution Conditions: 
     
       
         
               
               
               
             
               
               
               
             
           
               
                   
               
               
                 time (min) 
                 mobile phase A (%) 
                 mobile phase B (%) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 0 
                 80 
                 20 
               
               
                 15 
                 65 
                 35 
               
               
                 25 
                 65 
                 35 
               
               
                 40 
                 57 
                 43 
               
               
                 50 
                 54 
                 46 
               
               
                 65 
                 42 
                 58 
               
               
                 75 
                 25 
                 75 
               
               
                   
               
               
                 mobile phase A: acetic acid:water = 0.01:100 
               
               
                 mobile phase B: acetic acid:acetonitrile = 0.01:100 
               
               
                 flow rate: 0.8 ml/min 
               
               
                 temperature: 30° C. 
               
               
                 detection wavelength: multiple wavelength (203 nm of indicated wavelength) 
               
             
          
         
       
     
     MS Analysis Conditions: 
     
       
         
               
               
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                   
                   
               
               
                   
                 HPLC-MS 
                 HPLC-MS n   
               
             
          
           
               
                   
                 Ion detection manner 
                 negative ion detection 
                   
               
               
                   
                   
               
             
          
           
               
                   
                 Dry gas flow rate (L/min) 
                 10 
                 10 
               
               
                   
                 Nebulizer pressure(psi) 
                 60 
                 60 
               
               
                   
                 Dry temperature (° C.) 
                 350 
                 350 
               
               
                   
                 Capillary voltage (v) 
                 3500 
                 3500 
               
               
                   
                 Mass scan range (m/z) 
                 400-1500 
                  400-1200 
               
               
                   
                 Fragment amplitude (ev) 
                   
                 1.2-1.5 
               
               
                   
                   
               
             
          
         
       
     
     3. Analysis Results and Peak Identification 
     The components were identified in the following two aspects: (1) using control samples; (2) using the UV absorption properties and ion fragment information from MS n  in combination with literature data 
     4. Identification Results 
     (1) The Water-soluble Components of the  Radix Salviae Miltiorrhizae  in the  Radix Salviae Miltiorrhizae  Preparation from Each Example of the Present Invention (see tables 1 and 2, and  FIGS. 2 and 3 ). 
     
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 HPLC-MS Data and Identification Results 
               
             
          
           
               
                   
                   
                   
                   
                 Max. 
               
               
                   
                   
                 Quasi-Molecular 
                   
                 Absorption 
               
               
                 Peak 
                 Retention 
                 Ion Mass Peak 
                   
                 Wavelength 
               
               
                 No. 
                 Time 
                 m/z [M−H] −   
                 Identity 
                 λmax 
               
               
                   
               
             
          
           
               
                 1 
                 12.73 
                 197 
                 Danshensu 
                 280 
               
               
                 2 
                 19.69 
                 137 
                 Protocatechual- 
                 231, 280, 
               
               
                   
                   
                   
                 dehyde 
                 310 
               
               
                 3 
                 22.99 
                 537 
                 Isolithospermic 
                 327 
               
               
                   
                   
                   
                 acid A 
               
               
                 4 
                 23.83 
                 537 
                 Isolithospermic 
                 327 
               
               
                   
                   
                   
                 acid B 
               
               
                 5 
                 24.89 
                 417 
                 Salvianolic acid D 
                 247, 321 
               
               
                 6 
                 26.70 
                 717 
                 Salvianolic acid E 
                 330 
               
               
                 7 
                 28.51 
                 359 
                 Rosmarinic acid 
                 329 
               
               
                 8 
                 31.93 
                 717 
                 Salvianolic acid B 
                 254, 286, 
               
               
                   
                   
                   
                   
                 309 
               
               
                 9 
                 34.86 
                 339 
                 Salvianolic acid G 
                 395 
               
               
                 10 
                 44.64 
                 493 
                 Salvianolic acid A 
                 288 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 HPLC-MS n  Data 
               
             
          
           
               
                 Peak 
                   
                   
               
               
                 No. 
                 Identity 
                 Fragment ion m/z 
               
               
                   
               
             
          
           
               
                 3 
                 Isolithospermic 
                 Second(537): 493[M-H—CO 2 ] − , 
               
               
                   
                 acid A 
                 295[M-CO 2 —R—H 2 O] −   
               
               
                   
                   
                 Third (295): 159, 109 
               
               
                 4 
                 Isolithospermic 
                 Second (537): 493[M-H—CO 2 ] − , 
               
               
                   
                 acid B 
                 295[M-CO 2 —R—H 2 O] −   
               
               
                   
                   
                 Third (295): 159, 109 
               
               
                 5 
                 Salvianolic 
                 Second (417): 175[M-CO 2 —R—H 2 O] − , 
               
               
                   
                 acid D 
                 373[M-H—CO 2 ] −   
               
               
                   
                   
                 Third (175): 147, 157, 133 
               
               
                 6 
                 Salvianolic 
                 Second (717): 519[M-R—H 2 O] − , 
               
               
                   
                 acid E 
                 321[M-2R—2H 2 O] −   
               
               
                   
                   
                 Third (519): 321[M-R—H 2 O] − , 
               
               
                   
                   
                 339[M-R] −   
               
               
                   
                   
                 Third (321): 279, 293, 249, 223, 185 
               
               
                 7 
                 Rosmarinic 
                 Second (359): 161[M-R—H 2 O] − , 
               
               
                   
                 acid 
                 179[M-R] − , 195 
               
               
                 8 
                 Salvianolic 
                 Second (717): 519[M-R—H 2 O] − , 
               
               
                   
                 acid B 
                 321[M-2R—2H 2 O] −   
               
               
                   
                   
                 Third (519): 321[M-R—H 2 O] − , 
               
               
                   
                   
                 339[M-R] −   
               
               
                   
                   
                 Fourth (321): 279, 293, 249, 233, 185 
               
               
                 9 
                 Salvianolic 
                 Second (339): 321[M-H—H 2 O] − , 
               
               
                   
                 acid G 
                 295[M-H—CO 2 ] −   
               
               
                   
                   
                 Third (295): 279, 267 
               
               
                   
                   
                 Fourth (279): 251 
               
               
                 10 
                 Salvianolic 
                 Second (493): 295[M-R—H 2 O] −   
               
               
                   
                 acid A 
                 Third (295): 159, 109 
               
               
                   
               
             
          
         
       
     
     it can be seen from the MS n  results that the second and third peak have very similar structures as that of lithospermic acid. They are considerably different from lithospermic acid, however, with respect to UV absorption. Lithospermic acid has a relatively strong absorption near 253 nm due to its phenyl coumaran backbone, while the second and third peak do not have such a absorption property. Both of these peaks have UV absorption very similar with that of Salvianolic acid E, which demonstrates that the two compounds corresponding to these two peaks are likely to have the same backbone as Salvianolic acid E, i.e. the structure of carboxyl diphenyl ethylene backbone. It is thereby concluded that they have structures as those of Isolithospermic acids A and B shown in the above structure formula for components. 
     These two structures have never been reported, and are therefore named as Isolithospermic acids A and B herein. 
     (2) The Liposoluble Components of the  Radix Salviae Miltiorrhizae  in the TCM Preparation of the Present Invention (see table 3, and  FIGS. 4 and 5 ). 
     
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 HPLC-MS Data and Identification Results 
               
             
          
           
               
                   
                 Peak 
                 Retention 
                 Quasi-Molecular 
                   
               
               
                   
                 No. 
                 Time 
                 Ion Mass Peak m/z −   
                 Identity 
               
               
                   
                   
               
               
                   
                 1 
                 24.36 
                 277 [M + H] + , 
                 Tanshinone I 
               
               
                   
                   
                   
                 575 [2M + Na] +   
               
               
                   
                 2 
                 34.85 
                 295 [M + H] + , 
                 Tanshinone IIA 
               
               
                   
                   
                   
                 611 [2M + Na] +   
               
               
                   
                   
               
             
          
         
       
     
     (3) The Components of the  Radix Notoginseng  in the  Radix Salviae Miltiorrhizae  Drop Pills of the Present Invention (see tables 4 and 5, and  FIG. 6 ). 
     
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 HPLC-MS Data and Identification Results 
               
             
          
           
               
                   
                   
                 Quasi-Molecular 
                   
               
               
                 Peak 
                 Retention 
                 Ion Mass Peak 
               
               
                 No. 
                 Time 
                 m/z [M-H] −   
                 Identity 
               
               
                   
               
             
          
           
               
                 1 
                 11.27 
                 931 
                 Notoginsenoside R 1   
               
               
                 2 
                 12.38 
                 945 
                 Ginsenoside Re 
               
               
                 2 
                 12.53 
                 799 
                 Ginsenoside Rg 1   
               
               
                 3 
                 20.81 
                 1107  
                 Ginsenoside Rb 1   
               
               
                 4 
                 21.25 
                 769 
                 Notoginsenoside R 2   
               
               
                 5 
                 22.53 
                 769 
                 Notoginsenoside R 2  iso. 
               
               
                 6 
                 22.85 
                 783 
                 Ginsenoside Rg 2   
               
               
                 7 
                 23.77 
                 637 
                 Ginsenoside Rh 1   
               
               
                 8 
                 25.00 
                 637 
                 Ginsenoside Rh 1  iso. (F 1 ) 
               
               
                 9 
                 30.05 
                 945 
                 Ginsenoside Rd 
               
               
                 10 
                 34.81 
                 945 
                 Ginsenoside Rd iso. 
               
               
                 11 
                 40.00 
                 781 
                 Ginsenoside Rf-H 2 O 
               
               
                 12 
                 41.57 
                 751 
                 Notoginsenoside R 2 —H 2 O 
               
               
                 13 
                 43.72 
                 751 
                 Notoginsenoside R 2 —H 2 O 
               
               
                 14 
                 44.89 
                 765 
                 Ginsenoside Rg 6 /F 4   
               
               
                 15 
                 46.43 
                 619 
                 Ginsenoside Rk 3 /Rh 4  (Rk 3 ) 
               
               
                 16 
                 48.68 
                 619 
                 Ginsenoside Rk 3 /Rh 4  (Rh 4 ) 
               
               
                 17 
                 54.97 
                 783 
                 Ginsenoside 20(R)Rg 3   
               
               
                 18 
                 56.48 
                 783 
                 Ginsenoside 20(S)Rg 3   
               
               
                 19 
                 68.35 
                 765 
                 Ginsenoside Rk 1 /Rg 5  (Rk 1 ) 
               
               
                 20 
                 69.53 
                 765 
                 Ginsenoside Rk 1 /Rg 5  (Rg 5 ) 
               
               
                   
               
             
          
         
       
     
     
       
         
               
             
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 HPLC-MS n  Data 
               
             
          
           
               
                 Retention 
                   
                 Quasi-Molecular Ion 
               
               
                 Time 
                 Identity 
                 Mass Peak m/z −   
               
               
                   
               
               
                 11.27 
                 Notoginsenoside R 1   
                 799[M-H-Xyl] − ; 
               
               
                   
                   
                 637[M-H-Xyl-Glc] − ; 
               
               
                   
                   
                 475[M-H-Xyl-2Glc] −   
               
               
                 12.38 
                 Ginsenoside Re 
                 799[M-H-Rham] − ; 
               
               
                   
                   
                 783[M-H-Glc] − ; 
               
               
                   
                   
                 637[M-H-Rham-Glc] − ; 
               
               
                   
                   
                 475[M-H-Rham-2Glc] −   
               
               
                 12.53 
                 Ginsenoside Rg 1   
                 637[M-H-Glc] − ; 
               
               
                   
                   
                 475[M-H-2Glc] −   
               
               
                 20.81 
                 Ginsenoside Rb 1   
                 945[M-H-Glc] − ; 
               
               
                   
                   
                 783[M-H-2Glc] − ; 
               
               
                   
                   
                 621[M-H-3Glc] − ; 
               
               
                   
                   
                 459[M-H-4Glc] −   
               
               
                 21.25 
                 Notoginsenoside R 2   
                 637[M-H-Xyl] − ; 
               
               
                   
                   
                 475[M-H-Xyl-Glc] −   
               
               
                 22.53 
                 Notoginsenoside R 2  iso. 
                 637[M-H-Xyl] − ; 
               
               
                   
                   
                 475[M-H-Xyl-Glc] −   
               
               
                 22.85 
                 Ginsenoside Rg 2   
                 637[M-H-Rham] − ; 
               
               
                   
                   
                 475[M-H-Rham-Glc] −   
               
               
                 23.77 
                 Ginsenoside Rh 1   
                 475[M-H-Glc] −   
               
               
                 25.00 
                 Ginsenoside Rh 1  iso. (F 1 ) 
                 475[M-H-Glc] −   
               
               
                 30.05 
                 Ginsenoside Rd 
                 783[M-H-Glc] − ; 
               
               
                   
                   
                 621[M-H-2Glc] − ; 
               
               
                   
                   
                 459[M-H-3Glc] −   
               
               
                 34.81 
                 Ginsenoside Rd iso. 
                 783[M-H-Glc] − ; 
               
               
                   
                   
                 621[M-H-2Glc] − ; 
               
               
                   
                   
                 459[M-H-3Glc] −   
               
               
                 40.00 
                 Ginsenoside Rf-H 2 O 
                 619[M-H-Glc] − ; 
               
               
                   
                   
                 457[M-H-2Glc] −   
               
               
                 41.57 
                 Notoginsenoside R 2 —H 2 O 
                 619[M-H-Xyl] −   
               
               
                 43.72 
                 Notoginsenoside R 2 —H 2 O 
                 619[M-H-Xyl] −   
               
               
                 44.89 
                 Ginsenoside Rg 6 /F 4   
                 619[M-H-Rham] − ; 
               
               
                   
                   
                 457[M-H-Rham-Glc] −   
               
               
                 54.97 
                 Ginsenoside 20(R)Rg 3   
                 621[M-H-Glc] − ; 
               
               
                   
                   
                 459[M-H-2Glc] −   
               
               
                 56.48 
                 Ginsenoside 20(S)Rg 3   
                 621[M-H-Glc] − ; 
               
               
                   
                   
                 459[M-H-2Glc] −   
               
               
                 68.35 
                 Ginsenoside Rk 1 /Rg 5  (Rk 1 ) 
                 603[M-H-Glc] − ; 
               
               
                   
                   
                 441[M-H-2Glc] −   
               
               
                 69.53 
                 Ginsenoside Rk 1 /Rg 5  (Rg 5 ) 
                 603[M-H-Glc] − ; 
               
               
                   
                   
                 441[M-H-2Glc] −   
               
               
                   
               
             
          
         
       
     
     Based on the above research, the extraction process and analysis method for the TCM preparation of the present invention are established, which include: 
     (1) A Solid-Phase Process for Extracting the Liposoluble Components of  Radix Salviae Miltiorrhizae  and the Components of Notoginsenoside from the Drop Pills of  Radix Salviae Miltiorrhizae;    
     (2) a Method of HPLC-MS Analysis for Each Sample 
     12 components from  Radix Salviae Miltiorrhizae  and 21 saponin components from  Radix Notoginseng  have been identified in total. Among them, 4 water-soluble components of  Radix Salviae Miltiorrhizae,  2 liposoluble components of  Radix Salviae Miltiorrhizae  and 9 components of saponin have been identified through comparison with the control samples, while other compounds were identified mainly based on an analysis of MS n  data and comparison with data from literature. 
     Example 9 
     Detection Example of the Fingerprint Atlas for the Components of  Radix Salviae Miltiorrhizae  in the TCM Preparation 
     1. Instruments and Agents 
     Instruments: Agilent 1100 Liquid Chromatograph, comprising: quad-pump, online deaerating system, automatic sample injector, DAD detector, column temperature tank, Chemstation work station; BS210S electronic balance (1/10 −4  g) (Beijing Sartorius Company), METTLER AE240 electronic balance ((1/10 −4  g or 1/10 −5  g) (Mettler-Toledo Corporation, Shanghai), LD4-2 centrifuge (4000 r/min) (Beijing Medical Centrifuge Factory), Digital thermostatic water-bath kettle (Tianjing Changfeng Corporation), RE-52AA rotary evaporator (Shanghai Yarong Biochemical Instrumentation Factory), SHE-(III) water-circulating vacuum pump (Gongyi Yingyuyuhua Instrumentation Factory), KQ-250B ultrasonic cleanser (Kunshan Ultrasonic Instrumentation Corporation), HENGAO T&amp;D filter(HENGGAO T&amp;D), synthetic fiber membrane filter (aperture 0.45 μm)(Shanghai Xingya Purifying Materials Factory). 
     Agents: acetonitrile (chromatographically pure, Merck Company, US), phosphoric acid (top grade), Wahaha pure water. 
     2. Preparation of Test Sample 
     10 pills of the TCM preparation from each batch of Example 1 were weighed accurately and then introduced into a 10 ml measuring bottle. Distilled water was added to in an amount sufficient to dissolve the pills through shaking with ultrasound for 15 mins. And more distilled water was then added to achieve a volume of 10 ml. The obtained solution was subjected to centrifugation or filtration to obtain a sample solution. 
     3. HPLC Analysis Conditions 
     Agilent ZoRBAx SB-C18 (4.6×250 mm, 5 μm) chromatographic column; Mobile phase: mobile phase A being a 0.02% aqueous phosphoric acid solution, mobile phase B being a 80% acetonitrile-0.02% aqueous phosphoric acid solution; flow rate: 1.000 ml/min; detection wavelength: 280 nm , column temperature: 30° C.; injected sample volume: 10 μl. 
     Elution Gradient of Mobile Phase: 
     
       
         
               
               
               
             
           
               
                   
               
               
                 Retention time 
                 Mobile Phase A(v/v) 
                 Mobile Phase B(v/v) 
               
               
                   
               
             
             
               
                  0 min 
                 90% 
                 10% 
               
               
                  8 min 
                 78% 
                 22% 
               
               
                 15 min 
                 74% 
                 26% 
               
               
                 55 min 
                 48% 
                 52% 
               
               
                   
               
             
          
         
       
     
     4. Detection Results (see table 7) 
     
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Detection Results for Components of  Radix Salviae Miltiorrhizae   
               
               
                 in 200 Batches of Above TCM Drop Pills 
               
             
          
           
               
                   
                 Average 
                 RSD % of 
                 Average 
                 RSD % 
                 Percentage of Single 
                 Percentage Range of 
               
               
                 Peak 
                 Retention 
                 Retention 
                 Peak 
                 of Peak 
                 Peak Area to Total 
                 Single Peak Area to 
               
               
                 No. 
                 Time 
                 Time 
                 Area 
                 Area 
                 Peak Area 
                 Total Peak Area 
               
               
                   
               
             
          
           
               
                 1 
                 6.04 
                 0.31 
                 1627.92 
                 5.91 
                 20.80% 
                 19.6%-22.0% 
               
               
                 2 
                 9.90 
                 0.25 
                 2575.54 
                 13.53 
                 32.90% 
                 28.5%-37.4% 
               
               
                 3 
                 16.89 
                 0.61 
                 366.89 
                 10.92 
                 4.69% 
                 4.2%-5.2% 
               
               
                 4 
                 17.84 
                 0.70 
                 381.40 
                 13.81 
                 4.87% 
                 4.2%-5.5% 
               
               
                 5 
                 20.31 
                 0.96 
                 186.08 
                 12.04 
                 2.38% 
                 2.1%-2.7% 
               
               
                 6 
                 23.74 
                 0.76 
                 555.35 
                 10.48 
                 7.09% 
                 6.4%-7.8% 
               
               
                 7 
                 27.73 
                 0.50 
                 281.91 
                 18.08 
                 3.60% 
                 3.0%-4.3% 
               
               
                 8 
                 31.02 
                 1.18 
                 1852.33 
                 14.84 
                 23.66% 
                 20.2%-27.2% 
               
               
                   
               
               
                 Note: 
               
               
                 Peak 1 represents Danshensu; peak 2 represents Protocatechualdehyde; peak 3 represents Isolithospermic acid A; peak 4 represents Isolithospermic acid B; peak 5 represents Salvianolic acid D; peak 6 represents Rosmarinic acid; peak 7 represents Salvianolic acid B; and peak 8 represents Salvianolic acid A (see FIG. 1). 
               
             
          
         
       
     
     Table 7 shows the relative positions and ratios of area (retention time and peak area) of 8 peaks, wherein 3 peaks have a ratio of single peak area to total peak area greater than 10% and all the 8 peaks have a ratio of single peak area to total peak area greater than 2%. 
     All publications, patents and patent applications are incorporated herein by reference. While in the foregoing specification this invention has been described in relation to certain preferred embodiments thereof, and many details have been set forth for purposes of illustration, it will be apparent to those skilled in the art that the invention is susceptible to additional embodiments and that certain of the details described herein may be varied considerably without departing from the basic principles of the invention.