MXPA06003219A - Pharmaceutical composition for the treatment of angiocardiopathy - Google Patents

Abstract

The present invention discloses a pharmaceutical composition for the treatment of angiocardiopathy which consists of Radix Salviae Miltiorrhizae extract 5.0%-70.0%, Radix Notoginseng extract 10.0%-85.0%, Radix Astragali extract 5.0%-70.0%, and Borneolum Syntheticum or Lignum Dalbergiae Odoriferae oil 1.0%-15.0%. The composition is active against cerebral ischemia and myocardial ischemia. The effects are superior to total phenic acid of Radix Salviae Miltiorrhizae or total saponin of Radix Notoginseng respectively, or the combination thereof. The composition of the invention can provide various kinds of preparations by the addition of various accessories. Thus the invention provides a more effective and convenient composition of TCM effective sections and its preparations.

Description

A PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF CARDIOVASCULAR AND CEREBROVASCULAR DISEASES TECHNICAL FIELD The invention relates to a medicament composition. In particular, it relates to a pharmaceutical composition for the treatment of cardiovascular and cerebrovascular diseases.

PREVIOUS TECHNIQUE Statistics have shown that morbidity and mortality from cardiovascular and cerebrovascular diseases in China have increased over the last five decades. During the 1950s and 1960s, cardiovascular and cerebrovascular diseases were classified as the fifth and sixth of all diseases that cause deaths. However, since 1975 they have risen to the second and third place respectively and death caused by cardiovascular and cerebrovascular diseases has reached the first place in the totality of deaths caused by diseases. In fact, mortality from cardiovascular and cerebrovascular diseases in the Chinese accounts for 42.6% of all deaths in 2001 and 12.07% in 1975. Currently, they cause approximately 2 million deaths each year. Some patients survive, but most survivors are disabled or unable to take care of themselves in their daily lives, which causes heavy burdens for family members and society. Cardiovascular and cerebrovascular diseases are also the leading cause of death in Western countries. Based on current epidemiological data, it is estimated that until 2020, coronary artery disease and cerebral hemorrhage will still remain the first and second cause of death in humans, although the order of causes of death due to human diseases It will change significantly. It is estimated that until then, deaths around the world due to coronary artery disease will increase from 6.3 million in 1990 to 11 million; and deaths from cerebral hemorrhage will be up to 4.4 million to 7.7 million. During these 30 years, deaths caused by diseases of the circulatory system will increase up to 59.6%. Deaths from coronary artery disease and stroke will increase to 74.6% and 75%, respectively. All these data show that cardiovascular and cerebrovascular diseases are not only the main diseases that detrimentally affect human health; They are also currently and will remain the "No. 1 eliminator" that leads to death or disability. Among the therapeutic drugs to treat cardiovascular and cerebrovascular diseases, traditional Chinese patent medicines and Western medicines are administered with effects that focus on different aspects; Traditional Chinese patent medicines have fewer side effects and therefore have taken a good part of the market. Among the traditional, Chinese patent medicines available for the treatment of cardiovascular and cerebrovascular diseases, those comprising, as active components, active ingredients of effective biological parts of herbs, such as notoginsenoside, salvianolic acid, Radix Puerarine isoflavones and gipenosides, they are attracting more and more attention. Since the effective, biological parts in the herbs for traditional Chinese patent medicines to treat cardiovascular and cerebrovascular diseases have achieved respective functions and effects that focus on different aspects, it is expected that they will find a wide potential use in the combined administration. On the other hand, currently, traditional Chinese patent medicines that are based on effective, biological, individual parts of herbs, especially in the form of injection solutions, such as XUESAITONG, XUESHUANTONG (trademarks), have insufficient demand for the combined administration. further, simply mixing some solutions for injection of traditional Chinese patent medicines without the prior approval of the Administration of .. State Foods and Drugs represents a great risk of unexpected adverse reactions, such as a rapid increase in blood pressure, fever and allergy . Therefore, it will be very important to provide more effective and convenient compositions of biologically active parts of herbs for clinical applications.

BRIEF DESCRIPTION OF THE INVENTION Accordingly, an object of the present invention is to provide a more effective and convenient composition of bioactive parts of herbs and a preparation thereof for the treatment of cardiovascular and cerebrovascular diseases, which makes it possible to overcome the defects of traditional Chinese patent medicines which are based on individual biologically active parts of herbs which do not meet the clinical need for combined administration and avoid the potential side reactions associated with simply mixing together the drugs.

The present invention can be implemented as summarized in the following embodiments. The pharmaceutical compositions of the present invention comprise Radix Salviae Miltiorrhizae Extract; Radix Notoginseng Extract; Excerpt from Radix Astragali; and Borneol or Lignum Dalbergiae Odoriferae oil. In a preferred embodiment of the present invention, the inventive composition comprises 5.0% - 70.0% extract of Radix Salviae Miltiorrhizae; 10.0% - 85.0% Radix Notoginseng extract; 5.0% - 70.0% extract of Radix Astragali; and 1.0% - 15.0% Borneol or Lignum oil Dalbergiae Odoriferae. In a further preferred embodiment of the present invention, the inventive composition comprises 15.0% - 50.0% extract of Radix Salviae Miltiorrhizae; 25.0% - 65.0% Radix Notoginseng extract; 15.0% - 50.0% extract of Radix Astragali; and 2.0% - 12.0% Borneol or Lignum Dalbergiae Odoriferae oil. In a still further preferred embodiment of the present invention, the inventive composition comprises 20.0% - 30.0% of Radix Salviae Miltiorrhizae extract, - 30.0% - 55.0% of Radix Notoginseng extract; 20.0% - 30.0% extract of Radix Astragali; and 4.0% - 10.0% Borneol or Lignum Dalbergiae Odoriferae oil. In a still further preferred embodiment of the present invention, the inventive composition comprises 23% extract of Radix Salviae Miltiorrhizae; 45.0% Radix Notoginseng extract; 23% extract of Radix Astragali; and 9% Borneol or Lignum Dalbergiae Odoriferae oil. In a still further preferred embodiment of the inventive composition, the extract of Radix Salviae Miltiorrhizae comprises 45% -70% of the salvianolic acid B, 2% -10% of the salvianolic acid E, 4% -20% of the rosmarinic acid, 1% - 10% of the lithospermic acid and more than 70% of salvianolic acids. In a still further preferred embodiment of the inventive composition, the Radix Notoginseng extract comprises 2% -10% of notoginsenoside R1, 2% -6% of ginsenoside Re, 15% -40% of ginsenoside Rgl, 15% -40% of ginsenoside Rbl, 5% - 12% ginsenoside Rd and more than 70%, preferably more than 80%, of Radix Notoginseng saponins. In a still further preferred embodiment of the inventive composition, the extract of Radix Astragali comprises 5% -15% of Astragaloside I and more than 70% of Saponins of Radix Astragali. In a still further preferred embodiment of the inventive composition, the extract of Radix Salviae Miltiorrhizae comprises more than 80% salvianolic acids; Radix Notoginseng extract comprises more than 80% of Radix Notoginseng saponins; and the extract of Radix Astragali comprises more than 80% of saponins from Radix Astragali. In a still further preferred embodiment of the inventive composition, this is an injection, tablets, sustained release tablets, droplet pills, granules, powders for injection, capsules and microgranules. In a still further preferred embodiment of the inventive composition, this is an injection or a powder for injection. The inventive composition is used for the treatment of cardiovascular and cerebrovascular diseases. The Radix Salviae Miltiorrhizae extract of the above pharmaceutical compositions can be prepared by means of the prior art processes, for example, by means of the processes described in Patent Applications CN1352985A, CN1247855A, CN1242364A, CN1384090A, CN1459448A and Guo Ying et al., The Journal of Yunnan University and Traditional Chinese Medicine, 2001, 24 (4): 6. It can also be obtained through processes similar to the previous ones with appropriate modifications. The present extract of Radix Salviae Miltiorrhizae comprises 45% -70% of salvianolic acid B, 2% -10% of salvianolic acid E, 4% -20% of rosmarinic acid, 1% -10% of lithospermic acid and more than 70% , preferably more than 80%, of salvianolic acids. Regardless of the preparation process of the extract of Radix Salviae Miltiorrhizae, the expression "extract of Radix Salviae Miltiorrhizae" used in this document means that the content of the extracts is within the ranges listed; and for that purpose, the crude extracts may be further refined, such as by means of concentration, to satisfy the requirements in terms of the content of the components. The components and their content can be characterized and determined as follows, respectively: 1. Determination of the contents of salvianolic acid B, salvianolic acid E, rosmarinic acid and lithospermic acid in the extract of Radix Salviae Miltiorrhizae (HPLC) a. Chromatographic Conditions Filling Material: Octadecylsilyl-Silica Gel; Mobile phase: acetonitrile-water-phosphoric acid (23.5: 76.5: 0.02); Detection wavelength: 288 nm. The theoretical plates are not less than 5000, calculated based on the peak of salvianolic acid B. b. Preparation of Control Solutions: 0.2 mg / ml of salvianolic acid control solution B is prepared by mixing the control sample with the mobile phase. Likewise, 0.02 mg / ml of the control solution of salvianolic acid E, 0.05 mg / ml of control solution of aric acid acid and 0.01 mg / ml of control solution of litospermic acid are also prepared. c. Preparation of Sample Solutions: 35 mg of Radix Salviae Miltiorrhizae extract is accurately weighed in a 25 ml measuring bottle. The mobile phase is added to the bottle to dissolve the sample. The resulting solution is further diluted with simultaneous stirring to 25 ml with the mobile phase. 5 ml of sample solution are taken in a 25 ml measuring bottle and to the bottle the mobile phase is added to complete 25 ml, the resulting solution is stirred to mix it completely. d. The Test Procedure. 10 μl of each of the control solutions and the sample solutions are tested in liquid chromatography, respectively. 2. Determination of salvianolic acids in the previous Radix Salviae Miltiorrhizae extract (Spectrophotometry) a. Preparation of Control Solutions: 20 μg / ml salvianolic acid solution B is prepared by mixing the sample with the mixture of acetonitrile-water-phosphoric acid (23.5: 76.5: 0.02). b. Preparation of Sample Solutions: 25 mg of Radix Salviae Miltiorrhizae extract are weighed accurately in a 50 ml measuring bottle. To the bottle is added the acetonitrile-water-phosphoric acid mixture (23.5: 76.5: 0.02). The resulting solution is diluted with simultaneous stirring to 25 ml with the mixture. 2 ml of the sample solution are accurately taken in a 50 ml measuring bottle. The mixture is added and 25 ml are added, the resulting solution is stirred to mix it completely. c. The Test Procedure The mixture of acetonitrile-water-phosphoric acid (23.5: 76.5: 0.02) is taken as a blank solution, the absorption value of the control solutions and the sample solutions is determined individually under the wavelength of 288. nm using spectrophotometry. { China Pharmacopoeia, 1995 edition, volume 1, appendix VA). The calculations are based on the following formula: Salvianolic acids (%) = f (A-B) + B Where, F is 0.626, correlation factor; A is the content of salvianolic acids determined by means of spectrophotometry against salvianolic acid B; B is the content of salvianolic acid B determined by means of HPLC. 3. CLAR Digital Printing Spectrum of the Radix Salviae Miltiorrhizae Extract For the determination method, reference is made to the description in connection with the determination of salvianolic acid B and E, rosmarinic acid, lithospermic acid in point (1) above .

The record of the duration is 60 minutes. Of all common digital printing peaks, the salvianolic acid peak B, a common peak representing a relatively large and stable peak area, is selected as the reference peak. The relative retention time and the relative peak area are calculated against the retention time and the peak area of the reference peak. There are 5-7 common peaks in the digital printing of the Radix Salviae Miltiorrhizae extract above and there are typically 6 common peaks. The relative retention times of the 6 common peaks are in the order of 0.55 - 0.65 (peak of salvianolic acid E), 0.66 - 0.70 (peak of rosmarinic acid), 0.71 - 0.79 (peak of litospermic acid), 1 (peak of salvianolic acid B), 1.03 - 1.12, 1.21 - 1.30. Of all common peaks, only the peak of salvianolic acid B, the reference peak, has a ratio of the individual peak area to the total peak area that is greater than 20%. The peak area of salvianolic acid B accounts for 57% - 87% of the total peak area; its relative peak area is 1. With the relative retention time of 0.66 - 0.70, the peak area of the common rosmarinic acid peak accounts for 3% - 18% of the total peak area; and its relative peak area is 0.03 - 0.25. The total peak area of the uncommon peak is less than 10% of the total peak area. The Radix Notoginseng extract of the above pharmaceutical compositions can be prepared by means of the processes of the prior art, for example, by means of the processes described in the Chinese patent ZL1095363C, Chinese Patent Application CN1352985A, Qian Tianxiang et al., Foreign Medical Sciences, Plant Medicine Section, 1997, 12 (4)), Tang Diguang, The Journal of Chinese Traditional Patent Medicine, 1990, 12 (8): 5, The Standard of Public Heal Ministry of China WS3 -B-2590- 2001 (z). It can also be obtained through processes similar to the previous ones with appropriate modifications. It is also commercially available in the market, such as in the form of an extract comprising 95% (determined by means of ultraviolet radiation) of Radix Notoginseng saponins (Rbl >; 30%, Rgl > 20%, Rl > 15%, determined through the CLAR). The present extract of Radix Notoginseng comprises 2% -10% of notoginsenoside Rl, 2% -6% of ginsenoside Re, 15% -40% of ginsenoside Rgl, 15% -40% of ginsenoside Rbl, 5% -12% of ginsenoside Rd and more than 70%, preferably more than 80%, of Radix Notoginseng saponins. Regardless of the preparation process of the Radix Notoginseng extract, the expression "Radix Notoginseng extract" used in this document means that the contents of the extract are within the ranges listed; and for that purpose, the crude extracts may be further refined, such as by means of concentration, to meet the requirements in terms of the contents of the components. The components and their content can be characterized and determined respectively as follows: 1. Determination of the contents of ginsenoside Re, ginsenoside Rd, notoginsenoside Rl, ginsenoside Rgl and ginsenoside Rbl in the extract of Radix Notoginseng (HPLC) a. Chromatographic Conditions and Adaptability Test of the System Filler Material: Octadecylsilyl-Silica Gel; Column temperature: 40 ° C; Flow Rate: 0.7 ml / minute; Detection wavelength: 203 nm; The Gradient of the Mobile Phase is as follows: b. Preparation of Control Solutions: 0.2 mg / ml of the control solution of ginsenoside Re is prepared by mixing the control sample with methanol. Similarly, 0.4 mg / ml of the control solution of ginsenoside Rd, 0.2 mg / ml of the control solution of ginsenoside Rl, 0.4 mg / ml of the solution of notoginsenoside Rgl and 0.4 / ml of the solution are also prepared. of control of ginsenoside Rbl, respectively. c. Preparation of Sample Solutions: 20 mg of Radix Notoginseng extract are weighed accurately in a 50 ml measuring bottle. The mobile phase is added to the bottle to dissolve the sample. The resulting solution is further diluted with simultaneous stirring to 50 ml with the mobile phase, d. The Test Procedure 10 μl of each of the standard solutions and the sample solutions are injected into the HPLC system and analyzed. The HPLC spectrum of the Radix Notoginseng extract of the present invention is then obtained. (1) Determination of the Radix Notoginseng saponins in the previous Radix Notoginseng extract (Spectrophotometry) (2) CLAR Digital Printing Spectrum of the Radix Notoginseng extract The method of determination is referring to the description of ginsenoside Re, ginsenoside Rd, ginsenoside Rl, notoginsenoside Rgl and ginsenoside Rbl, previous (1) by means of CLAR. The duration record is 30 minutes. Of all the common digital print peaks, the peak of the ginsenoside Rgl, which represents a relatively large and stable peak area, is selected as the reference peak. The relative retention time and the relative peak area are calculated against the retention time and the peak area of the reference peak. There are 9-12 common peaks in the digital printing spectrum of the Radix Notoginseng extract above and there are typically 11 common peaks. The relative retention times of the 11 common peaks are in the order of 0.77-0.85 (peak of notoginsenoside Rl), 0.87 - 0.97 (peak of ginsenoside Re), 1 (peak of ginsenoside Rgl, ie peak of reference), 2.58 - 2.67, 0.68 - 2.76, 2.77 - 2.81, 2.82 - 2.91 (ginsenoside peak Rbl), 2.95 - 3.03, 3.05 - 3.13, 3.15 - 3.22 (peak of ginsenoside Rd), 3.24 - 3.91. Of all the common peaks, only the peak of the ginsenoside Rgl and the peak of the ginsenoside Rbl have the ratio of the individual peak area to the total peak area greater than 20%. The peak area of ginsenoside Rgl, the reference peak area, accounts for 20% - 35% of the total peak area, its relative peak area is 1. The peak area of the ginsenoside Rbl accounts for 30% - 50% of the total peak area; its relative peak area is 0.85 - 2.50. The peak area of the notoginsenoside Rl accounts for 2% - 8% of the total peak area; its relative peak area is 0.06 - 0.40. The peak area of the ginsenoside Rd accounts for 5% - 14% of the total peak area, its relative peak area is 0.14 -0.70. The total peak area of the uncommon peak is less than 10% of the total peak area. The Radix Astragali extract of the above pharmaceutical composition can be prepared by means of the prior art, for example, by means of the disclosures of the Chinese patent CN1096269C, Yu Hao et al., West China Journal of Pharmaceutical Sciences, 1993, 8 ( 3): 163, Teng Xinglong et al., Heilongjiang Medical Journal, 2002, 15 (5): 340, Wang Zhijie et al., Journal of Zhejiang College of Traditional Chinese Medicine, 2001, 25 (5): 43. It can also be obtained by means of procedures similar to the previous ones with appropriate modifications. It is also commercially available in the market, such as in the form of an extract comprising 80% -98% (determined by means of ultraviolet radiation) of the Radix Astragali extract. The present extract of Radix Astragali comprises % -15% Astragaloside I and Radix Astragali saponins greater than 70% or Radix Astragali saponins greater than 80%, preferably. Regardless of the preparation process of the Radix Astragali extract, the expression "Radix Astragali extract" used in this document means that the contents of the extracts are within the ranges listed; and for that purpose, raw extracts can be further refined, to meet the requirements in terms of the contents of the components. The Borneol used in the above composition can be of natural origin or can be synthesized. The Lingnum Dalbergiae Odoriferae oil used in the composition can be obtained by means of the distillation of Lignum Dalbergiae Odoriferae.

The compositions of the present invention can be formulated into various dosage forms when combined with one or more pharmaceutically acceptable adjuvants. The adjuvant includes, but is not limited to, starch, dextrin, lactose, microcrystalline cellulose (avicel), hydroxypropylmethylcellulose (HPMC), polyethylene glycol, magnesium stearate, micro silicon gel, xylitol, lactitol, glucose, glycine, D-mannitol. and similar. The present pharmaceutical composition can take the forms of injections, tablets, sustained-release tablets, drop pills, granules, powders for injection, capsules, microgranules and the like. Preferred are tablets, drop pills, powder for injection and capsules. The total content of salvianolic acids, Radix Notoginseng saponins and Radix Astragali saponins are preferably greater than 80%, if the compositions of the present invention are formulated in injections or powder for injection. The raw materials of the inventive composition are easily obtained and thus facilitate the commercial production of the inventive composition. The present composition can be formulated in various forms as desired and can provide a more convenient, efficient and high-quality controlled traditional Chinese traditional medicine for clinical applications.

The present invention compares the cerebral anti-ischemic effects of the inventive compositions; salvianolic acids plus saponins of Radix Notoginseng plus Borneol or oil of Lignum Dalbergiae Odoriferae; salvianolic acids plus Radix Notoginseng saponins; salixolic acids and saponins of Radix Notoginseng, using the model of localized cerebral ischemia that is caused by the application of iron (III) chloride hexahydrate locally in the middle cerebral artery and by means of the determination of the neurological symptoms and the area of the cerebral stroke . The results show that the present composition has a significant anti-cerebral ischemia effect. Its therapeutic effects are more significant than those of salvic acids or individual Radix Notoginseng saponins, more significant than salvianolic acids plus Radix Notoginseng saponins and more significant than salvianolic acids plus Radix Notoginseng saponins plus Borneol or Lignum Dalbergiae oil Odoriferae . The results indicate that the pharmaceutical composition of the present invention, that is, the combination of Radix Salviae Miltiorrhizae extract plus Radix Notoginseng extract plus Radix Astragali and Borneol extract or Radix Salviae Miltiorrhizae extract plus Radix Notoginseng extract plus Radix extract Astragali and oil of Lignum Dalbergiae Odoriferae, has a synergistic effect means ivo.

BRIEF DESCRIPTION OF THE FIGURES Figure 1: CLAR digital printing spectrum of the Radix Salviae Miltiorrhizae extract (0-60 minutes); Figure 2: CLAR digital printing spectrum of the Radix Notoginseng extract (0-30 minutes). In the descriptions of the present invention, all percentages are by weight, unless otherwise indicated.

DETAILED DESCRIPTION OF THE MODALITIES The invention will be better understood by reference to the following examples. The following examples are presented for illustrative purposes and are not intended to limit the scope of the invention.

EXAMPLE 1 Extract of Radix Salviae Miltiorrhizae: The extract of Radix Salviae Miltiorrhizae was prepared by the method described in Chinese Patent Application CN1459448A. In this way, 5 kg of Radix Salviae Miltiorrhizae were ground to a coarse powder and then extracted 3 times with deionized water at 100 ° C under mild boiling conditions. For the first extraction, 27.5 kg of water were added and heated for 1 hour; for the second and third extraction, 15 kg of water were added and heated for 0.5 hours, respectively. The acidity of the extract was adjusted to pH 2 with 10% HCl and then filtered. The filtrate was loaded onto a polyamide resin column (the amount of dry resin is two thirds of the amount of the crude extract). The column was eluted with deionized water 5 times the volume of the column, followed by 5 times the volume of the column of a 0.1% NaHCO 3 solution. The eluate was collected. After adjusting the pH to 2 with 10% HCl, the eluate was loaded on an absorbent, macroporous resin D_.0? . The resin was eluted with deionized water until the eluate became neutral. Then, the column eluted with. 95% ethanol and the color band was collected. The collected solution was concentrated under reduced pressure to dryness. The dried material was dissolved in water and then stored in a refrigerator overnight. After filtering through a microporous filter film of mixed cellulose 0.3 μm, a salvianolic acid extract was obtained. It was adjusted to pH 6.0 with a 2% NaOH solution and immediately lyophilized to yield 221 g of a frozen dry powder of the Radix Salviae Miltiorrhizae extract material. The yield was 4.4% of the crude material of Radix Salviae Miltiorrhizae. The extract of Radix Salviae Miltiorrhizae obtained in this way contained salvianolic acid A, salvianolic acid B, salvianolic acid C, salvianolic acid D, salvianolic acid E, salvianolic acid G, milionone I, rosmarinic acid, lithospermic acid, danshensu and other substances . Where salvianolic acid B was 53.73%, salvianolic acid E was 3.7%, rosmarinic acid was 5.2%, lithospermic acid was 1.7% and salvianolic acids were 83.94%. There were 6 common peaks shown in the CLAR digital printing spectrum of the Radix Salviae Miltiorrhizae extract (the average of 6 lots). The averages of the relative retention times for these 6 common peaks were, in the given order, 0.60 (peak of salvianolic acid E), 0.68 (peak of rosmarinic acid), 0.73 (peak of litospermic acid), 1 (peak of acid salvianolic B), 1.08, 1.26. Of the common peaks, only the peak of salvianolic acid B, which was the reference peak, had the ratio of the individual peak area to the total peak area greater than 20%. The peak area of salvianolic acid B accounted for 72% (average) of the total peak area; and its relative peak area was 1; the peak area of rosmarinic acid accounted for 10% (average) of the total peak area; and its relative peak area was 0.14 (average). The total peak area of uncommon peaks was less than 10% of the total peak area. The CLAR digital printing spectrum of Radix Salviae Miltiorrhizae is shown in Figure 1.

Radix Notoginseng Extract: Radix Notoginseng saponins that were commercially available were further refined to produce the desired Radix Notoginseng extract. The obtained extract contained ginsenoside Rbl, ginsenoside Rd, ginsenoside Re, ginsenoside Rgl, ginsenoside Rg2, ginsenoside Rg3, ginsenoside Rhl, gnosenoside Rh2, panaxitriol, notoginsenoside Rl, notoginsenoside R2, notoginsenoside R3, 20-gluco-ginsenoside Rf. Where, ginsenoside Re is 3.9%, ginsenoside Rgl is 34.3%, ginsenoside Rbl was 31.0%, ginsenoside Rd is 8.8%, notoginsenoside Rl was 6.8% and the saponins of Radix Notoginseng were 94%. There were 11 common peaks shown in the CLAR digital printing spectrum (the average of 10 batches) of the Radix Notoginseng extract. The averages of the relative retention times for the 11 common peaks were, in the given order, 0.82 (peak of notoginsenoside Rl), 0.94 (peak of ginsenoside Re), 1 (peak of ginsenoside Rgl, reference peak), 2.63, 2.74, 2.79, 2.85 (peak of ginsenoside Rbl), 2.99, 3.08, 3.18 (peak of ginsenoside Rd) and 3.28. Of all common peaks, the ginsenoside peak Rgl and the peak of ginsenoside Rbl had the ratio of the individual peak area to the total peak area greater than 20%. The peak area of the ginsenoside Rgl (ie the reference peak) accounted for 28% (average) of the total peak area; and its relative peak area was 1. The peak area of the ginsenoside Rbl accounted for 39% (average) of the total peak area; and its relative peak area was 1.36 (average). The peak area of the notoginsenoside Rl accounted for 6% (average) of the total peak area; and its area, relative peak was 0.20 (average).

The peak area of the ginsenoside Rd accounted for 10% (average) of the total peak area; and its relative peak area was 0.37 (average). The total peak area of uncommon peaks was less than 10% of the total peak area. The CLAR digital printing spectrum of Radix Notoginseng is shown in Figure 2.

Radix Astragali extract: The Radix Astragali extract that was commercially available was further refined. The extract obtained contained acetilastragaloside, astragaloside I, astragaloside II, astragaloside III, astragaloside IV, isoastragaloside I, isoastragaloside II, astramembranin II, cycloastragenol, soyasaponin I, lupeod, β-sitosterol, daucosterin. Where, Astragaloside I was 9.5% and the contents of Radix Astragali extract were 88.9%. 75 mg of the Radix Salviae Miltiorrhizae extract, 150 mg of the Radix Notoginseng extract, 75 mg of the Radix Astragali extract, all obtained previously and 30 mg of Borneol were sufficiently mixed. Then, the mixture was lyophilized to obtain the composition of the invention.

Example 2 100 mg of the Radix Salviae Miltiorrhizae extract, 200 mg of the Radix Notoginseng extract, 75 mg of the Radix Astragali extract, obtained from the present example 1, and 30 mg of Lignum Dalbergiae Odoriferae oil were mixed with 400 mg of polyethylene glycol- 6000 and melted to provide a mixture. Then, the mixture was allowed to cool and the composition of the invention was obtained.

Example 3 96 mg of the Radix Salviae Miltiorrhizae extract, 136 mg of the Radix Notoginseng extract, 70 mg of the Radix Astragali extract, obtained from the present example 1, and 28 mg of Borneol were sufficiently mixed.

Then, the mixture was allowed to lyophilize and the composition of the invention was obtained.

Example 4 70 mg of Radix Salviae extract Miltiorrhizae, 150 mg of the Radix Notoginseng extract, 90 mg of the Radix Astragali extract, obtained from the present example 1, and 20 mg of Borneol were sufficiently mixed. Then, the mixture was allowed to lyophilize to obtain the composition of the invention.

Example 5 165 mg of the Radix Salviae Miltiorrhizae extract, 80 mg of the Radix Notoginseng extract, 60 mg of the Radix Astragali extract, obtained from the present example 1, and 25 mg of Borneol were sufficiently mixed. Then, the mixture was allowed to lyophilize to obtain the composition of the invention.

Example 6 75 mg of the Radix Salviae Miltiorrhizae extract, 135 mg of the Radix Notoginseng extract, 82 mg of the Radix Astragali extract, obtained from the present example 1, and 38 mg of Borneol were sufficiently mixed. Then, the mixture was allowed to lyophilize to obtain the composition of the invention.

Example 7 230 mg of the extract of Radix Salviae Miltiorrhizae, 75 mg of the extract of Radix Notoginseng, 17 mg of the extract of Radix Astragali, obtained from the present example 1, and 8 mg of Borneol were sufficiently mixed.

Then, the mixture was allowed to lyophilize to obtain the composition of the invention.

Example 8 17 mg of Radix Salviae extract Miltiorrhizae, 70 mg of the Radix Notoginseng extract, 230 mg of the Radix Astragali extract, obtained from the present example 1, and 13 mg of Borneol were sufficiently mixed.

Then, the mixture was allowed to lyophilize to obtain the composition of the invention.

Example 9 55 mg of Radix Salviae extract Miltiorrhizae, 160 mg of the Radix Notoginseng extract, 63 mg of the Radix Astragali extract, obtained from the present example 1, and 48 mg of Borneol were sufficiently mixed. Then, the mixture was allowed to lyophilize to obtain the composition of the invention.

Example 10 96 mg of the Radix Salviae Miltiorrhizae extract, 136 mg of the Radix Notoginseng extract, 70 mg of the Radix Astragali extract, obtained from the present example 1, and 28 mg of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 400 mg of polyethylene glycol -6000 and merged. Then, the mixture was allowed to cool and the composition of the invention was obtained.

Example 11 70 mg of Radix Salviae Miltiorrhizae extract, 150 mg of Radix Notoginseng extract, 90 mg of Radix Astragali extract, obtained from the present example 1, and 20 mg of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 400 mg of polyethylene glycol -6000 and were poured. Then, the mixture was allowed to cool and the composition of the invention was obtained.

Example 12 165 mg of Radix Salviae extract Miltiorrhizae, 80 mg of the Radix Notoginseng extract, 60 mg of the Radix Astragali extract, obtained from the present example 1 and 25 mg of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 400 mg of polyethylene glycol-6000 and poured. Then, the mixture was allowed to cool and the composition of the invention was obtained.

Example 13 75 mg of the Radix Salviae Miltiorrhizae extract, 135 mg of the Radix Notoginseng extract, 82 mg of the Radix Astragali extract, obtained from the present example 1, and 38 mg of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 400 mg of polyethylene glycol -6000 and were poured. Then, the mixture was allowed to cool and the composition of the invention was obtained.

EXAMPLE 14 230 mg of the Radix Salviae Miltiorrhizae extract, 75 mg of the Radix Notoginseng extract, 17 mg of the Radix Astragali extract, obtained from the present example 1, and 8 mg of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 400 mg of polyethylene glycol -6000 and were poured. Then, the mixture was allowed to cool and the composition of the invention was obtained.

Example 15 17 mg of the Radix Salviae Miltiorrhizae extract, 70 mg of the Radix Notoginseng extract, 230 mg of the Radix Astragali extract, obtained from the present example 1, and 13 mg of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 400 mg of polyethylene glycol -6000 and were poured. Then, the mixture was allowed to cool and the composition of the invention was obtained.

Example 16 55 mg of the Radix Salviae Miltiorrhizae extract, 160 mg of the Radix Notoginseng extract, 63 mg of the Radix Astragali extract, obtained from the present example 1, and 48 mg of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 400 mg of polyethylene glycol -6000 and were poured. Then, the mixture was allowed to cool and the composition of the invention was obtained.

Example 17 75 g of the extract of Radix Salviae Miltiorrhizae, 135 g of the Radix Notoginseng extract, 96 g of the extract of Radix Astragali, obtained from the present example 1, and 25 g of Borneol, 90 g of mannitol, 15 g of calcium disodium eluate and 15 ml of distilled water were sufficiently mixed. Then, the mixture was allowed to lyophilize and was divided into 1000 aliquots.

Example 18 67 g of the extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1352985A, example 1), 180 g of the extract of Radix Notoginseng (example 1 of the invention), 67 g of the extract of Radix Astragali (example 1 of the invention) and 16 g of Borneol were sufficiently mixed with 40 g of microcrystalline cellulose. A solution of povidone 3% -ethanol was added to soften the mixture. The mixture was then passed through a # 18 sieve to form granules and dried at 60 ° C for 30-45 minutes. The granules obtained in this way were then cut out and 4 g of talc were added and mixed thoroughly. The formed granules were poured into capsules.

Example 19 50 g of Radix Salviae Miltiorrhizae extract (prepared according to the method of water extraction and alcohol precipitation Guo Ying et al., The Journal of Yunnan University of Traditional Medicine, 2001, 24 (4): 6), 210 g of Radix Notoginseng extract (Qian Tian Xiang et al., Foreign Medical Sciences, Plant Medicine Section, 1997, 12 (4)), 50 g of Radix Astragali extract (example 1 of the invention) and 20 g of Borneol were dissolved individually with a small amount of physiological saline. Then an appropriate amount of Tween 80m was added. Each mixture was finely milled and decolorized after adding physiological saline. The solution was filtered under reduced pressure until it became clear and transparent. The filtrate was collected in a container containing physiological saline. The container was sealed and sterilized by boiling water. The three classes of clear solutions were then mixed and the acidity adjusted to 5. An appropriate volume of physiological saline was added. The filtration process was repeated to obtain a clear and transparent solution. The desired injection was obtained.

Example 20 60 g of the Radix Salviae Miltiorrhizae extract (Chinese Patent Application CN1384090A, example 1), 80 g of the Radix Notoginseng extract (Tang Di Guang, The Journal of Traditional Chinese Patent Medicine, 1990, 12 (8): 5 ), 165 g of the Radix Astragali extract (example 1 of the invention) and 25 g of Borneol were sufficiently mixed with 40 g of microcrystalline cellulose. A solution of povidone 3% -ethanol was added to soften the mixture. The mixture was then passed through a # 18 screen and dried at 60 ° C for 30-45 minutes to provide granules, 4 g of talc were added and mixed thoroughly. The formed granules were compressed into tablets.

Eg 21 90 g of extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1384090A, example 1), 150 g of the Radix Notoginseng extract (example 1 of the invention), 82 g of the extract of Radix Astragali (example 1 of the invention) and 8 g of Borneol were sufficiently mixed with g of microcrystalline cellulose. A solution of povidone 3% -ethanol was added to soften the mixture. The mixture was passed through a # 18 sieve to form a granular material and dried at 60 ° C for 30-45 minutes. The granules obtained in this way were cut and then 4 g of talc were added and mixed thoroughly.

EXAMPLE 22 85 g of the extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1384090A, example 1), 135 g of the Radix Notoginseng extract (example 1 of the invention), 80 g of the Radix Astragali extract (Teng Xing Long et al., Hei Long Jiang Medical Journal, 2002, 15 ( 5): 340) and 30 g of Borneol were sufficiently mixed with 700 g of polyethylene glycol-6000 and poured. They were then poured into selected liquid paraffin pills at low temperature and the liquid paraffin was removed at low temperature.

EXAMPLE 23 17 g of the extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1384090A, example 1), 280 g of Radix Notoginseng extract (example 1 of the invention), 17 g of Radix Astragali extract (example 1 of the invention), (Extraction: Yu Hao et al., West China Journal of Pharmaceutical Sciences, 1993, 8 (3): 163); Refinement: Teng Xing Long and collaborators Hei Long Jiang Medical Journal, 2002, 15 (5): 340) and 16 g of Borneol were sufficiently mixed with 700 g of polyethylene glycol-6000 and poured. They were then poured into selected liquid paraffin pills at low temperature and the liquid paraffin was removed at low temperature.

Example 24 67 g of the extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1352985A, example 1), 180 g of the Radix Notoginseng extract (example 1 of the invention), 67 g of the extract of Radix Astragali (example 1 of the invention) and 16 g of oil of Lignum Dalbergiae Odoriferae are they mixed sufficiently with 40 g of microcrystalline cellulose. A solution of povidone 3% ~ ethanol was added to soften the mixture. The mixture was passed through a # 18 sieve to form granules and dried at 60 ° C for 30-45 minutes. After trimming them, 4 g of talc were added and mixed thoroughly. The formed granules were poured into capsules.

Example 25 60 g of the extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1384090A, example 1), 80 g of Radix Notoginseng extract (Tang Di Guang, The Journal of Traditional Chinese Patent Medicine, 1990, 12 (8): 5), 165 g of Radix Astragali extract ( Example 1 of the invention) and 25 g of Lignum Dalbergxae Odoriferae oil were sufficiently mixed with 40 g of microcrystalline cellulose. A solution of povidone 3% -ethanol was added to soften the mixture. The mixture was passed through a # 18 screen to form the granular material and dried at 60 ° C for 30-45 minutes. After trimming it, 4 g of talc were added and mixed thoroughly. The formed granules were compressed into tablets.

EXAMPLE 26 90 g of the extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1384090A, example 1), 150 g of the Radix Notoginseng extract (example 1 of the invention), 82 g of the extract of Radix Astragali (example 1 of the invention) and 8 g of oil of Lignum Dalbergiae Odoriferae are they mixed sufficiently with 40 g of microcrystalline cellulose. A solution of povidone 3% -ethanol was added to soften the mixture. The mixture was passed through a # 18 sieve to form a granular material and dried at 60 ° C for 30-45 minutes. After trimming it, 4 g of talc were added and mixed thoroughly. The granules obtained in this manner were cut out and packed.

Example 27 85 g of the Radix Salviae Miltiorrhizae extract (Chinese Patent Application CN1384090A, example 1), 135 g of the Radix Notoginseng extract (example 1 of the invention), 80 g of the Radix Astragali extract (Teng Xing Long et al. Hei Long Jiang Medical Journal, 2002, 15 (5): 340) and 30 g of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 700 g of polyethylene glycol-6000 and poured. They were then poured into selected liquid paraffin pills at low temperature and the liquid paraffin was removed at low temperature.

Example 28 17 g of the extract of Radix Salviae Miltiorrhizae (Chinese Patent Application CN1384090A, example 1), 280 g of the Radix Notoginseng extract (example 1 of the invention), 17 g of the extract of Radix Astragali (example 1 of the invention, Extraction: Yu Hao et al., West China Journal of Pharmaceutical Sciences, 1993, 8 (3) -163); Refinement: Teng Xing Long et al., Hei Long Jiang Medical Journal, 2002, 15 (5): 340) and 16 g of Lignum Dalbergiae Odoriferae oil were sufficiently mixed with 700 g of polyethylene glycol-6000 and poured. They were then poured into selected liquid paraffin pills at low temperature and the liquid paraffin was removed at low temperature.

Experiment 1 - Effects of the Present Pharmaceutical Compositions on Cerebral Ischemia Located in Rats 1. Materials a. Animals: Male Sprague-Dawley rats (SD), weighing 180-200 grams, SCXK Quality Control Certificate number (Beijing) 2002-0003, provided by Beijing Weitong Lihua Experimental Animal Technology Co., Limited. b. Drugs and Chemical Substances Tested: Drugs Tested: The Composition Obtained in the Present Example 1 and Example 2; the extract of Radix Salviae Miltiorrhizae in the present example 1; he .

Radix Notoginseng extract in the present example 1; the extract of Radix Astragali in the present example 1; Lignum oil Dalbergiae Odoriferae and Borneol, XUESAITONG (Trade Name) was purchased from the market, made by Qunming Pharmaceutical Co., Limited, lot number 20020922.03. Chemical Agent: 2, 3, 5-triphenyltetrazolium chloride (TTC), light yellowish powder, product of Beijing Mashi Fine Chemical Co., Limited, lot number 011102. c. Experimental Instruments: XTT stereomicroscope, product of Yunnan Optical Instrument Factory: electronic analytical e Model AEG-220, product of Japan Shimadzu Corporation; 307-6 desktop dental instrument board 307-6, product of Shanghai Dental Medical Instrument Factory; HZQ-C air bath vibrator, product of Harbin Dongming Medical Instrument Factory. 2. Methods and Results a. The group and the administration of the research products: the animals were grouped randomly by weight. The animals in all groups were administered the investigational products tested by the sublingual vein 30 minutes after the operation. The investigational products tested were also administered by an intraperitoneal injection at 2 hours and 23 hours after the operation. All products were diluted with physiological saline to a desired concentration. The amount of the injection was 0.4 ml per 100 g of body weight, b. The intermediate cerebral artery embolism model: the rats were anesthetized by administering a 10% chloral hydrate solution (350 mg / kg) intraperitoneally and fixed on the right lateral position. A 1.5 cm long curved incision was made from the midpoint between the outer corner of the left eye and the left external auditory canal. The temporalis muscle was cut and removed, the temporal bone was exposed and, under a stereoscopic microscope, a window was opened in the 2.5 mm diameter bone in the position that is over the zygomatic bone joint and the flat temporal bone and It is only 1 mm from the end of the mouth of the joint. The wastes were removed and the intermediate cerebral artery (which was located between the olfactory fasciculus and the inferior cerebral vein) was exposed; a small piece of plastic film was placed to protect the surrounding area of the blood vessel. A small piece of quantitative filter paper soaked with 10 μl of iron chloride was placed (III) 50% on this segment of the middle cerebral artery, 30 minutes later, the filter paper was taken and the topical tissues were washed with physiological saline, the incision was sutured in layers. The rats were returned to the cage and recovered under normal living conditions. The room temperature was controlled at 24 ° C. Criteria for the Registration of Neurological Symptoms Behavioral evaluations were conducted 24 hours after the operation. The registration criteria were as follows: (1). The flexing condition of the forelimbs was observed after raising the rats by their tails; it would register as 0 points if both front limbs extended forward symmetrically; 1 point if there was shoulder flexion, flexion of the elbows, and / or intorsion of the shoulders on the front limb on the opposite side of the operation. (2) . The rat was placed on the flat surface, both shoulders were pushed to the opposite sides and resistance was verified. It would register as 0 points if the resistance was equal and strong on both sides; 1 point if the resistance on the opposite side of the operation decreases. (3). The front limbs of the rat were placed on a metal mesh and muscle tension was observed. It would register as 0 points if the muscular tension on both sides was equal and strong; 1 point if the muscular tension of the front limb on the opposite side of the operation decreases. (4) . It would register as 1 point if the rat continuously rotated to the opposite side of the operation after it was lifted by its tail. Based on the above registration criteria, the complete record is 4 points. The higher the registry, the more severe the behavioral disability, the determination of the degree of cerebral infarction. The rats were decapitated after the behavioral evaluations were completed. The brains were collected. The olfactory bulb, the cerebellum and the lower brainstem were discarded, the rest of the brain was sagittally cut into 5 slices. The 5 brain slices were immersed in TTC dye solution (each 5 ml of dye solution contained 1.5 ml of 4% TTC, 0.1 ml of 1 M K2HP04, then distilled water was added to the mark), incubated at 37 ° C. ° C in the dark for 30 minutes, the brain slices were placed in a 10% formaldehyde solution and stored 24 hours in the dark. By staining, the non-ischemic area was pink-red, but the ischemic area was white. The white tissues of the brain slices were carefully cut and weighed. The percentage by weight of the infarcted tissues in the whole brain and the damaged side of the brain were considered as the degree of infarction of the brain. e. Results: Table 1 The Effects of the Present Pharmaceutical Compositions and Extracts on Neurological Symptoms in Rats (MCAO) (X ± s) Dosage Number Registration Group Registration (mg / kg body symptom symptoms weight) Neurological neurological animals after 6 hours after 24 hours Pharmaceutical composition of the present example 1 ## && amp; «** ## && amp; « (Extract of Radix Salviae 5 + 10 + 5 + 2 10 1.22 + .0.41 * 1.07 ± 0.59 Miltiorrhizae + Radix Notoginseng Extract + Radix Astragali + Borneol Extract) Pharmaceutical composition of the present example 2 (Extract of Radix Salviae 5 + 10 + 5 + 2 10 1.32 + 0.45 ** ## &&@ 1.13 + 0.56 ** ** & Miltiorrhizae + Radix Notoginseng Extract + Radix Astragali Extract + Lignum Dalbergiae Odoriferae Oil) Salvianolic Acids + 6 + 12 + 2 10 1.68 ± 0.43 ** ## & 1.61 + 0.63 * Radix Notoginseng Saponins + Borneol Salvianolic Acids + 6.7 + 13.3 10 2.14 ± 0.60 ** # 2.14 ± 0.59 ** # Radix Notoginseng Saponins Salvianolic Acids 20 10 2.95 + 0.67 * 2.57 + 0.42 * Radix Saponins 20 10 2.65 + 0.32 * 2.52 + 0.51 * Notoginseng XUESAITONG 20 10 2.65 ± 0.37 * 2.56 ± 0.54 * Control Group 10 3.22 + 0.42 3.04 + 0.53 Note: * P < 0.05, ** P < 0.01, compared to the control group; # P < 0.05, ## P < 0.01, in comparison with the group of Salvianolic Acids or the group of Saponins of Radix Notoginseng; & P < 0.05, & P < 0.01, compared to the group of Salvianolic Acids + Saponins of Radix Notoginseng; @ P < 0.05 compared to the group of Salvianolic Acids + Radix Saponins' otoginseng + Borneol. MCAO - Occlusion of Intermediate Cerebral Artery.

Table 2 The Effects of the Present Pharmaceutical Compositions and Extracts on the Area of Cerebral Infarction in Rats (MCAO) (X ± s) Dosage Number Infarction Cerebral Infarction / Side Groups (brain mg / kg of brain weight / brain damaged) body) Complete animals (%) (%) Pharmaceutical composition of the present example 1 ## && amp; © (Radix Salviae Extract 5 + 10 + 5 + 2 10 1.28 + 0.74 ** m & & ® 2.57 + 1.41" Miltiorrhizae + Radix Extract Notoginseng + Extract Radix Astragali + Borneol) Pharmaceutical composition of the present example 2 (Extract of Radix Salviae Miltiorrhizae + Radix Extract 5 + 10 + 5 + 2 10 1.34 ± 0.69 ** ## & & amp; 2.61 + 1.50 ** ## && amp; Notoginseng + Extract Radix Astragali + Oil of Lignum Dalbergiae Odoriferae) Salvianolic acids + 6 + 12 + 2 t ## & fc. ## & 10 1.66 + 0.69 * 3.37 + 1.30"Radix Notoginseng Saponins + Borneol Salvianolic Acids + 6.7 + 13.3 10 2.32 + 0.84 * 4.61 + 1.80 * Radix Notoglnseng Saponins Salvianolic Acids 20 10 3.21 ± 0.86 * 6.41 ± 1.76 * Radix Notoglnseng Saponins 20 10 3.02 + 1.21 *, 5.99 + 2.33 * XUESAIXONG 20 10 2.99 + 1.11 * 5.98 ± 2.23 * Control Group 10 4.33 + 0.81 8.69 + 1.59 Note: * P < 0.05, ** P < 0.01, compared to the control group; # P < 0.05, ## P < 0.01, in comparison with the group of Salvianolic Acids or the group of Saponins of Radix Notoginseng; & P < 0.05, & P < 0.01, compared to the group of Salvianolic Acids + Saponins of Radix Notoginseng; @ P < 0.05 compared to the group of Salvianolic Acids + Radix Notoginseng Saponins + Borneol.

The results in Tables 1 and 2 show that all drugs tested have significant anti-cerebral ischemia effects. Of all the drugs, the composition of the present example 1 (Radix Salviae Miltiorrhizae extract, Radix extract Notoginseng, extract of Radix Astragali and Borneol) and the composition of the present example 2 (Radix extract Salviae Miltiorrhizae, Radix Notoginseng extract, Radix Astragali extract and Lignum Dalbergiae oil Odoriferae) achieve significant therapeutic effects.

Only the administration of salvianolic acids and saponins of Radix Notoginseng has similar effects to the administration of XUESAITONG [Trade Name, positive control drug]; the therapeutic effects of the administration of the combination of salvianolic acids plus saponins of Radix Notoginseng plus Borneol is better than that of the administration of salvianolic acids plus saponins of Radix Notoginseng or salvianolic acids only or saponins of Radix Notoginseng only or XUESAITONG. { Trade Name) but is worse than that of the pharmaceutical composition of the present example 1 and the pharmaceutical composition of the present example 2. By using the model of experimental cardiac infarction in rats and the extracorporeal perfusion method, the present invention compares the anti-inflammatory effects. Myocardial ischemia of the pharmaceutical composition of the present invention, salvianolic acids plus Radix Notoginseng saponins plus Borneol or Lignum Dalbergiae Odoriferae oil, salvianolic acids plus Radix Notoginseng saponins, salvianolic acids and Radix Notoginseng saponins. The results show that the pharmaceutical composition of the present invention has significant anti-ischemic myocardial effects. Its therapeutic effects are better than those of the application of only salixolic acids or saponins of Radix Notoginseng, stronger than those of the administration of salvianolic acids plus saponins of Radix Notoginseng and better than those of salvianolic acids plus saponins of Radix Notoginseng plus Borneol or oil of Lignum Dalbergiae Odoriferae. The results indicate that the pharmaceutical composition of the present invention, ie the extract of Radix Salviae Miltiorrhizae plus Radix Notoginseng extract plus extract of Radix Astragali and Borneol or extract of Radix Salviae Miltiorrhizae plus Radix Notoginseng plus extract of Radix Astragali and Lignum oil Dalbergiae Odoriferae, the four have strong synergistic actions.

Experiment 2 Studies on the anti-myocardial ischemia effects of the present compositions. 1. The group and the administration of the research products: 70 male Wistar rats, weighing 250.8 ± 24.6 grams, were randomly divided into seven drug groups by weight: physiological saline as control, XUESAITONG, salvianolic acids, saponins from Radix Notoginseng, salvianolic acids plus saponins of Radix Notoginseng, the pharmaceutical compositions of the present example 1 and the pharmaceutical compositions of the present example 2.

All drugs tested were diluted with physiological saline at the desired concentrations; the drugs tested were administered in 4 ml / kg via a vein injection in the tail. 2. Method a. Model of experimental myocardial infarction in rats: Rats were anesthetized with sodium pentobarbital (45 m9 / kg) via an intraperitoneal injection, fixed in the supine position and inserted with a tracheal tube, a longitudinal incision of 2 centimeters was made along the left side of the sternum. After opening the thoracic cavity, the third and fourth ribs were cut in their cartilage section near the sternum, breathing was maintained in an artificial respiration apparatus (ventilation volume 2 ml / 100 g, 50 times / minute). The pericardial membrane was opened and the heart was exposed, the cord was placed under the coronary artery, descending, left of the heart for ligature, the standard lead II electrocardiogram was recorded. It was stabilized for 10 minutes, then the coronary artery was ligated, descending, left of the heart and the thoracic cavity closed. The secreted substances were sucked into the larynx with a syringe and the rats were made to return to autonomous breathing. 15 minutes after the ligation of the coronary artery, the drugs under test were administered via a vein.

The heart was obtained 4 hours after the ligation of the coronary artery and the section of the heart was cut under the ligature line and cut into 5 slices, the heart slices were stained with nitro-tetrazolium blue (NBT). The percentage of myocardial infarction area over the area of the ventricles as well as the total heart was calculated and analyzed with a statistical method (t-test). b. Prefused, Isolated Heart Experiment (Langendorff): Referred to in "Experimental Methodology of Pharmacology" (edited by Shuyun Xu et al., People Health Press, third edition, January 2002). 3. Results a. The effect in the area of myocardial infarction in rats, see Table 3.

Table 3 The Effects of the Present Pharmaceutical Compositions and Extracts on the Area of Myocardial Infarction in Rats (MCAO) (X ± s) Dosage Number Area of Infarction / Area Area of Infarction / Groups (mg / kg body weight of the Ventricle (%) Full Body Heart) Animals (%) Pharmaceutical composition of the present example 1 5 + 10 + 5 + 2 10 ## & & © 12.53 ± 4.57 **** & & ® 10.96 + 3.35 * (Radix Salviae Miltiorrhizae Extract + Radix Notoginseng Extract + Radix Astragali + Borneol Extract) Pharmaceutical Composition of the present Example 2 (Extract of Radix Salviae Miltiorrhizae + Radix Extract 5 + 10 + 5 + 2 10 12.62 + 4.49 ** * &; & ® 11.01 + 3.42 ***** 8® Notoginseng + Radix Astragali Extract + Lignum Oil Dalbergiae Odoriferae) Salvianolic Acids + 6 + 12 + 2 10 16.72 + 6.43 ***** 13.15 + 4.16 **** & Radix Saponins Notoginseng + Borneol Salvianolic Acids + 6.7 + 13.3 10 ** # 20.51 + 6.58 ** # 14.03 + 5.18 ' Radix Saponins Notoginseng Salvianolic Acids 20 10 24.08 + 8.56 * 18. 1 ± 4.49 * Radix Notoginseng Saponins 20 10 25.97 + 4.65 * 21.03 + 3.82 * XUESAIXONG 20 10 25.02 + 5.72 * 19.64 ± 4.71 * Control Group 10 33.67 ± 7.85 26.48 + 5.11 Note: * P < 0.05, ** P < 0.01, compared to the control group; * P < 0.05, # P < 0.01, in comparison with the group of Salvianolic Acids or the group of Saponins of Radix Notoginseng; & P < 0.05, &S; P < 0.01, compared to the group of Salvianolic Acids + Saponins of Radix Notoginseng; @ P < 0.05 compared to the group of Salvianolic Acids + Radix Notoginseng Saponins + Borneol. b. Effect on the flow volume in the coronary artery and the heart rate in the isolated guinea-pig heart, see Table 4.

Table 4 The Effects of the Present Compositions Pharmaceuticals and Extracts on the Volume of Flow in the Coronary Artery and the Heart Rate in the Isolated Heart of Guinea Pig (X ± s) Dosage Number Increase of Value Decrease of the Groups (mg / kg of weight of the Volume of Value of the body) Animals Flow of the Artery Coronary Heart Rate (ml / min) (beats / min) Pharmaceutical Composition of the present Example 1 (Extract of Radix Salviae 5 + 10 + 5 + 2 10 16.67 + 1.74 * t & amp; # 40 + 14 ** & # Miltiorrhizae + Radix Notoginseng Extract + Radix Astragali + Borneol Extract) Pharmaceutical Composition of the present Example 2 (Extract of Radix Salviae 5 + 10 + 5 + 2 10 16.76 + 1.68 ** & & # 41 + 15 ** & & # Miltiorrhizae + Radix Notoginseng Extract + Radix Astragali Extract + Lignum Oil Dalbergiae Odoriferae) Salvianolic Acids + 6+ 12 + 2 10 14.85 + 1.76 ** & 32 + 12 * Radix Saponins Notoginseng + Borneol Salvianolic Acids + Saponins 6.7 + 13.3 10 11.34 ± 2.24 * 21 + 9 * of Radix Notoginseng Salvianolic Acids 20 10 7.91 ± 1.36 9 + 4 Radix Notoginseng saponins 20 10 8.88 ± 1.51 10 + 5 XUESAITONG 20 10 8.82 ± 1.11 10 + 4 Note: * P < 0.05, ** P < 0.01, compared to the control group; group of Salvianolic Acids or the group of Saponins of Radix Notoginseng or XUESAITONG; & P < 0.05, & P < 0.01, compared to the group of Salvianolic Acids + Saponins of Radix Notoginseng; P < 0.05 compared to the group of Salvianolic Acids + Radix Notoginseng Saponins + Borneol.

The results of Tables 3 and 4 show that all drugs tested have significant anti-myocardial ischemia effects. Of all the drugs, the composition of the present example 1 (Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract, Radix Astragali extract and Borneol) and the pharmaceutical composition of the present example 2 (Radix Salviae Miltiorrhizae extract, Radix Notoginseng extract, extract of Radix Astragali and Lignum oil Dalbergiae Odoriferae) have shown the best therapeutic effects. Only the administration of salvianolic acids or saponins of Radix Notoginseng has similar effects to the administration of XUESAITONG (positive control drug); the therapeutic effects of the administration of the combination of salvianolic acids plus saponins of Radix Notoginseng plus Borneol are better than those of the administration of salvianolic acids plus saponins of Radix Notoginseng or salvianolic acids only or saponins of Radix Notoginseng only or XUESAITONG only, but are worse than those of the pharmaceutical composition of the present example 1 and the pharmaceutical composition of the present example 2.

Claims (10)

1. A pharmaceutical composition, characterized in that it comprises extract of Radix Salviae Miltiorrhizae; Radix Notoginseng extract; extract of Radix Astragali and Borneol or oil of Lignum Dalbergiae Odoriferae.

2. The composition according to claim 1, characterized in that it comprises 5.0% -70.0% extract of Radix Salviae Miltiorrhizae; 10.0% - 85.0% Radix Notoginseng extract; 5% - 70.0% of extract of Radix Astragali and 1.0% - 15.0% of Borneol or oil of Lignum Dalbergiae Odoriferae.

3. The composition according to claim 2, characterized in that it comprises 15.0% -50.0% extract of Radix Salviae Miltiorrhizae; 25.0% -65.0% Radix Notoginseng extract; 15.0% - 50.0% of extract of Radix Astragali and 2.0% - 12.0% of Borneol or oil of Lignum Dalbergiae Odoriferae. The composition according to claim 3, characterized in that it comprises 20.0% - 30.0% extract of Radix Salviae Míltiorrhizae; 30.0% -55.0% Radix Notoginseng extract; 20.0% - 30.0% of extract of Radix Astragali and 4.0% - 10.0% of Borneol or oil of Lignum Dalbergiae Odoriferae. 5. The composition according to claim 4, characterized in that it comprises 23% extract of Radix Salviae Miltiorrhizae; 45.0% Radix Notoginseng extract; 23% Radix Astragali extract and 9% Borneol or Lignum Dalbergiae Odoriferae oil. 6. The composition according to claims 1, 2, 3, 4 or 5, characterized in that the extract of Radix Salviae Miltiorrhizae comprises 45% -70% of the salvianolic acid B, 2% -10% of the salvianolic acid E, 4% - 20% of rosmarinic acid, 1% - 10% of lithospermic acid and more than 70% of salvianolic acids; wherein the Radix Notoginseng extract comprises 2% -10% of notoginsenoside Rl, 2% -6% of ginsenoside Re, 15% -40% of ginsenoside Rgl, 15% -40% of ginsenoside Rbl, 5% -12% of ginsenoside Rd and more than 70% of Radix Notoginseng saponins; the extract of Radix Astragali comprises 5% - 15% of astragaloside 1 and more than 70% of saponins of Radix Astragali The composition according to claim 6, characterized in that the Radix Salviae Miltiorrhizae extract comprises more than 80% salvianolic acids; the Radix Notoginseng extract comprises more than 80% of Radix Notoginseng saponins and the extract of Radix Astragali comprises more than 80% of saponins from Radix Astragali. The composition according to claims 1, 2, 3, 4 or 5, characterized in that it is an injection, tablets, sustained release tablets, drop pills, granules, powders for injection, capsules or microgranules. 9. The composition according to claim 8, characterized in that it is an injection or a powder for injection. The use of the composition according to any of claims 1 to 9, wherein it is for the treatment of cardiovascular and cerebrovascular diseases.