Patent Description:
With the improvement of living standards, worldwide population aging and younger onset population, the patients with cerebral and cardiovascular diseases are increased year by year. It has become the second large disease that does harm to human health. Angina pectoris is a clinical syndrome which is characterized in chest pain and chest discomfort, caused by myocardial temporary ischemia and hypoxia. Coronary heart disease (CHD) angina pectoris means the pectoris induced by myocardial ischemia and hypoxia that is caused by coronary arteriosclerosis or spasm, accounting for about <NUM>% of the patients with angina pectoris.

Now, the methods for treating angina pectoris are dominated by dilating vessels, reducing blood viscosity and inhibiting platelets aggregation as well as anticoagulation. Traditionally, the chemicals include the nitrate, nitrite, β-receptor blocker and calcium antagonist. However, due to the stronger toxicity and side effect, these drugs are not suitable to use for long time. In addition, most of them focus on symptomatic treatment with no more effect on disease progress. Occassionally, symptoms occur after administrating the nitroglycerin, for example the head pain, head throbbing, speed-up heartbeat and even syncope (see <NPL>). Recently, the nitroglycerin was reported to have problems of inducing severe hypotension (see <NPL>, <NPL>) and of being prone to producing tolorance (see <NPL>). Hence, this hindered its application in clinic.

Althought a lot of traditional Chinese medicines have been used for treating angina pectoris, the pill, powder, ointment, Dan and decoction had become acient history, which is seldom used by modern people. Now, there are common compound Salvia tablet and capsule commercially available. Because the production processes for the tablet and capsule are outdated, the content of active ingredients is low with no quality control indices. Both are absorbed into blood via the gastrointestinal tract after oral administration. Due to the hepatic first pass effect, they have low bioavailability and slow absorption, and are not competent to the first aid for the patients with angina pectoris.

Drop pill is a traditional preparation for traditional Chinese medicine. It has the following merits: reduced volatility of drug, increased drug stability, high bioavailability, quickened onset of effect, prolonged action in topical administration, shortened production cycle, dust pollution-free, and easily carried on.

However, the preparation method of traditional drop pill is to melt a medicine liquid and drop it into immiscible cooling medium to give the drop pill. Because the drop pill is formed by the factors of downwards gravity, surface tension of medicine liquid and internal stress, the unit drug loading capacity is small (usually, the drug loading capacity of API is about <NUM> %. ) and the amount of matrix very large. This does not meet the requirement of international market that the maximum daily dose of PEG matrix should not exceed <NUM>. Moreover, it is difficult to prepare the traditional drop pill with diameter of less than <NUM>, so the patients have to take a lot of hard-to-swallow pills each time, which will not satisfy the fast-paced trend of morden life, and be prone to the problems of inaccurate dose. Thus, it is generally unacceptable by the international consumers. In addition, there are a number of shortcomings in the preparation of traditional drop pill, e.g. the low dropping rate, poor roundness and large variation on the pill weight and particle size, as well as small unit drug loading capacity and large amount of matrix (due to sufficient medium to ensure dropping effect). Because the cooling liquid has been used for solidifying the drop pill, the neccecary step is needed in the sequent process to remove the cooling liquid, and the remaining cooling liquid may pose the problem of residual organic solvent. Besides, drying methods for the tradiational drop pill have the defects of prolonged time, slow speed, uneven drying and easily leading to evaporation of volatile oil and precipitation of Borneol that is included in the products.

As a result of this, how to find a production process for preparing micro drop pills, regular drop pills and drop pill capsules that achieves high production rate, reduces amount of matrix and increases drug-loading capacity is an important subject in need of development and exploration of the modern formulation technique for drop pill. Examples may be found in <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT> or <CIT>.

Compound Salvia Drop Pill (CSDP) is a traditional Chinese medicine developed by Tasly Pharmaceutical Co. , Ltd, which is proven to have the effects of activating blood by removing stasis as well as stopping pain by regulating Qi, used for treating chest distress and angina pectoris. The main ingredients of CSDP include Salvia Militiorrhiza, Panax Notoginseng and Borneol. Its pharmacological effects include increasing coronary blood flow, protecting ischemia myocardium by strengthening hypoxia tolerance, anti-platelet aggregation, preventing thrombosis and improving microcirculation etc. Although the preparation of CSDP is known as a very mature technique in the prior art, there are still a lot of problems faced during preparation process, e.g. large amount of matrix and small drug-loading capacity.

The objective of present invention is to provide a preparation method for a compound Salvia micro drop pill, wherein said micro drop pill comprises a traditional Chinese medicine composition and a drop pill matrix in a ratio of <NUM>:<NUM>~<NUM>:<NUM> by weight. The traditional Chinese medicine composition is useful for treating acute myocardial infarction and acute myocardial ischemia. Said composition is composed of following materials by weight percentage: <NUM>%~<NUM>% of Salvia Militiorrhiza and Panax Notoginseng extract and <NUM>%~<NUM>% of borneol. Wherein, the Salvia Militiorrhiza and Panax Notoginseng extract comprises following ingredients by weight parts:
Danshensu : Salvianolic acid T : protocatechuic aldehyde : Salvianolic acid D : rosmarinic acid : Salvianolic acid B : Salvianolic acid A : Panax Notoginseng Saponin R1 : Ginsenoside Rg1 : Ginsenoside Re : Ginsenoside Rb1 : Ginsenoside Rd : dihydrotanshinone I : tanshinone I : cryptotanshinone : tanshinone IIA= (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>).

Said drop pill matrix includes one or more of PEG, sorbitol, xylitol, lactitol, maltose, starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), Arabic gum, alginate, dextrin, cyclodextrin, agar and lactose.

Said micro drop pill means a smaller-sized drop pill than the traditional drop pill. In particular, said micro drop pill has the particle size of <NUM>~<NUM>.

An objective of present invention is to provide a compound Salvia micro drop pill (CSMDP). In said micro drop pill, the weight ratio of medicine to matrix is <NUM>:<NUM>~<NUM>:<NUM>, and particle size <NUM>~<NUM>. The preparation method for preparing said micro drop pill comprises the steps as follows:.

In particular, the present invention comprises technical solutions as follows:.

The traditional Chinese medicine composition which is used for preparing a compound Salvia micor drop pill is composed of following materials by weight percentage: <NUM>%~<NUM>% of Salvia Militiorrhiza and Panax Notoginseng extract and <NUM>%~<NUM>% of borneol. The Salvia Militiorrhiza and Panax Notoginseng extract comprises following ingredients by weight percentage:
Danshensu : Salvianolic acid T : protocatechuic aldehyde : Salvianolic acid D : rosmarinic acid : Salvianolic acid B : Salvianolic acid A : Panax Notoginseng Saponin R1 : Ginsenoside Rg1 : Ginsenoside Re : Ginsenoside Rb1 : Ginsenoside Rd : dihydrotanshinone I : tanshinone I : cryptotanshinone : tanshinone IIA= (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>).

Preferably, said composition is composed of following materials by weight percentage: <NUM>%~<NUM>% of Salvia Militiorrhiza and Panax Notoginseng extract and <NUM>%~<NUM>% of borneol.

More preferably, said composition is composed of following materials by weight percentage: <NUM>%~<NUM>% of Salvia Militiorrhiza and Panax Notoginseng extract and <NUM>. <NUM>%~<NUM>% of borneol.

Preferably, the Salvia Militiorrhiza and Panax Notoginseng extract comprises following ingredients by weight parts:
Danshensu : Salvianolic acid T : protocatechuic aldehyde : Salvianolic acid D : rosmarinic acid : Salvianolic acid B : Salvianolic acid A : Panax Notoginseng Saponin R1 : Ginsenoside Rg1 : Ginsenoside Re : Ginsenoside Rb1 : Ginsenoside Rd : dihydrotanshinone I : tanshinone I : cryptotanshinone : tanshinone IIA= (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>).

More preferably, the Salvia Militiorrhiza and Panax Notoginseng extract comprises following ingredients by weight parts:
Danshensu : Salvianolic acid T : protocatechuic aldehyde : Salvianolic acid D : rosmarinic acid : Salvianolic acid B : Salvianolic acid A : Panax Notoginseng Saponin R1 : Ginsenoside Rg1 : Ginsenoside Re : Ginsenoside Rb1 : Ginsenoside Rd : dihydrotanshinone I : tanshinone I : cryptotanshinone : tanshinone IIA= (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>): (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>).

Further preferably, the Salvia Militiorrhiza and Panax Notoginseng extract comprises following ingredients by weight parts:
Danshensu : Salvianolic acid T : protocatechuic aldehyde : Salvianolic acid D : rosmarinic acid : Salvianolic acid B : Salvianolic acid A : Panax Notoginseng Saponin R1 : Ginsenoside Rg1 : Ginsenoside Re : Ginsenoside Rb1 : Ginsenoside Rd : dihydrotanshinone I : tanshinone I : cryptotanshinone : tanshinone IIA=<NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM> : <NUM>.

In an embodiment of this invention, aforesaid traditional Chinese medicine composition is prepared by extracting Salvia Militiorrhiza and Panax Notoginseng to give the extract, adding the borneol into the extract and mixing to have the product.

Preferably, the traditional Chinese medicine is prepared by the following method:.

Wherein, Salvia Militiorrhiza and Panax Notoginseng may be decocted with water under alkaline condition either alone, or in combination.

Preferably, the Salvia Militiorrhiza and Panax Notoginseng extract is prepared by following method:.

Further preferably, the Salvia Militiorrhiza and Panax Notoginseng extract is prepared by following method:.

Wherein, said alkaline water solution includes, but not limited to, one or more of sodium bicarbonate, sodium carbonate, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium hydroxide, potassium hydroxide and magnesium hydroxide with the pH value of <NUM>~<NUM>; the concentration of the alkaline water solution is <NUM>~<NUM>. 5wt%, preferably <NUM>~3wt%, ensuring that Danshensu and salvainolic acid T can be extracted totally.

More preferably, the Salvia Militiorrhiza and Panax Notoginseng extract is prepared by following method:.

Wherein, in step (<NUM>), <NUM> times of water means that the water is <NUM> times of total crude medicine in weight. Similarly, in step (<NUM>), <NUM> times of water means that the water is <NUM> times of total residue in weight. Said macroporous resin is nonpolar resin, for example HPD-<NUM>, HPD-<NUM>, HPD-<NUM>, preferable the HPD-<NUM>.

In an embodiment of this invention, said traditional Chinese medicine composition is prepared by following crude medicine by weight parts: Salvia Militiorrhiza <NUM>~<NUM> parts, Panax Notoginseng <NUM>~<NUM> parts and Borneol <NUM>~<NUM> parts.

Preferably, said traditional Chinese medicine composition is prepared by following crude medicine by weight parts: Salvia Militiorrhiza <NUM>~<NUM> parts, Panax Notoginseng <NUM>~<NUM> parts and Borneol <NUM>~<NUM> parts.

Most preferably, said traditional Chinese medicine composition is prepared by following crude medicine by weight parts: Salvia Militiorrhiza <NUM>~<NUM> parts, Panax Notoginseng <NUM>~<NUM> parts and Borneol <NUM>~<NUM> parts.

In an embodiment of this invention, said traditional Chinese medicine composition is either extract or powder.

In an embodiment of this invention, during the process for detecting the bioactive ingredients of Salvia Militiorrhiza and Panax Notoginseng extract, it is first time to discover bioactive ingredients in aforesaid ratio by weight, and first time to separate and obtain new compound of salvianolic acid T.

The structure of new compound of salvianolic acid was identified in its physicochemical properties, high resolution mass spectrum (QFT-ESI), electrospray ionization mass spectrum (ESI-MS), <NUM>H-NMR, <NUM>C-NMR, DEPT, COSY, HMBC, HMQC and CD spectra (<FIG>).

The structure of the new compound of salvianolic acid is represented by the general formula (I) as follows,
<CHM>.

<NUM>H-NMR shows <NUM> signal of methenyl proton attached to oxygen at δ <NUM> (<NUM>, dd, <NUM>, <NUM>); <NUM> signals of aromatic proton at δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, s), δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, d, <NUM>), δ <NUM> (<NUM>, dd, <NUM>, <NUM>), δ <NUM> (<NUM>, s); <NUM> signals of aliphatic proton at δ <NUM> (<NUM>, ddd, <NUM>, <NUM>, <NUM>).

Carbon-<NUM> nuclear magnetic resonance <NUM>C-NMR spectrum shows <NUM> carbon signals, including <NUM> aliphatic carbon signal at δ <NUM>, <NUM> signal of methenyl carbon attached to oxygen at δ <NUM>, <NUM> signals of carbonyl carbon at δ <NUM>, δ <NUM>, δ <NUM> and <NUM> signals of double-bond carbon at δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>, δ <NUM>.

Said compound of the present invention has <NUM> isomers with optical rotation respectively at -<NUM>° and <NUM>°. Compound with C-<NUM>' absolute configuration set as SIR-configuration is obtained through molecular optimum design and calculated by BPV86 method having TD-SCF with (2d, p) basis sets to read comparison between result and experimental CD spectrum of the compound. It is inferred by the substantially matched CD spectra that the absolute configuration of C-<NUM>' in <NUM> isomoers of the compound of the present invention are S configuration and R configuration (see <FIG>). The spectrum by HMBC of the compound in the present invention is presented as follows:
<CHM>.

Said salvianolic acid T is prepared by the following method:.

In an embodiment of this invention, a compound Salvia micro drop pill (CSMDP) is provided and said CSMDP is prepared with traditional Chinese medicine composition and the micro drop pill matrix in a ratio of <NUM>:<NUM>~<NUM>:<NUM> by weight, preferably prepared with traditional Chinese medicine composition and the micro drop pill matrix in a ratio of <NUM>:<NUM>~<NUM>:<NUM> by weight, most preferably in a ratio of <NUM>:(<NUM>~<NUM>).

In an embodiment of this invention, the preparation method for preparing CSMDP comprises following steps:.

Preferably, the preparation method for preparing CSMDP comprises following steps:.

Wherein, in step (<NUM>), said drop pill matrix includes one or more of PEG, sorbitol, xylitol, lactitol, maltose, starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), Arabic gum, alginate, dextrin, cyclodextrin and agar, preferably the solid PEG, e.g. PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, PEG-<NUM> and PEG-<NUM>, more preferably one or more of the PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, PEG-<NUM>, most preferably the PEG-<NUM>, PEG-<NUM>, or the combination of PEG-<NUM> and PEG-<NUM>. In step (<NUM>), homogenization may enhance content uniformity, and RSD is improved from previous <NUM>% to <NUM>%.

Preferably, in step (<NUM>), said ratio of medicine to drop pill matrix is <NUM>:<NUM>~<NUM>:<NUM> by weight, mixing homogeneously <NUM>~5000rpm for <NUM>~<NUM> and melting homogeneously at <NUM>~9000rpm for <NUM>~<NUM>, and during the metling process the temperature is kept at <NUM>~<NUM>; most preferably, said ratio of medicine to the matrix is <NUM>: (<NUM>~<NUM>) by weight, mixing homogeneously <NUM>~4000rpm for <NUM>~<NUM> and melting homogeneously at <NUM>~6000rpm for <NUM>~<NUM>, and during the metling process the temperature is kept at <NUM>~<NUM>.

In step (<NUM>), preferably, said temperature of dripper is at <NUM>~<NUM>, preferably <NUM>~<NUM>; the vibration frequency at <NUM>~<NUM>, preferably <NUM>~<NUM>, more preferably <NUM>~<NUM>, more preferably <NUM>~<NUM>, most preferably <NUM>; acceleration at <NUM>~<NUM> preferably <NUM>; dropping pressure at <NUM>~<NUM> Bar, preferably <NUM> Bar; dropping rate is <NUM>~<NUM>/h, preferably <NUM>~<NUM>/h, further preferably <NUM>~<NUM>/h.

In step (<NUM>), said condensation by cooling gas means that the falling drops are cooled by using low-temperature condensate trap to make solidification. Said temperature of cooling gas is -<NUM>~-<NUM>, most preferably -<NUM>~-<NUM>; said cooling gas is air, nitrogen or inert gas; said particle size of micro drop pill is <NUM>~<NUM>.

Further, said method may additionally comprise step (<NUM>) of drying step: fluidized-bed drying equipment is preferred at -<NUM>~<NUM>, preferably drying at -<NUM>~<NUM> for <NUM>~<NUM> hours to obtain the blank drop pill. Especially, fluidized-bed drying the low-temperature drop pill from step (<NUM>) is performed at <NUM>~<NUM>, preferably <NUM>~<NUM> for <NUM>~<NUM> hours, preferably <NUM>~<NUM> hours, most preferably <NUM> hours, to obtain the blank drop pill.

In step (<NUM>), gradient-rising temperature drying method is preferred, including steps of: fluidizing at -<NUM>~<NUM>, drying at <NUM>~<NUM> for <NUM>~<NUM>, drying at <NUM>~<NUM> for <NUM>~<NUM>, drying at <NUM>~<NUM> for <NUM>~<NUM>; preferably fluidizing at <NUM>~<NUM>, drying at <NUM> for <NUM>, drying at <NUM> for <NUM>, drying at <NUM> for <NUM>~<NUM>. In this step, the drop pills are in state of fluidization, not only solving the problems of drop pill adhesion, but also enhancing the efficiency and productivity up to <NUM>/h.

In step (<NUM>), by screening through a large number of the drying methods, the inventors found that: in step (<NUM>), the blank pill is dried by one of following drying methods: the low-humidity airing method, coating pot drying method, vacuum oven drying method, hot-air blasting drying method, track microwave heating drying method, fluidization drying coating method. In terms of yield and productivity, the coating pot drying method, track microwave heating drying method and fluidization drying coating method are preferred. In terms of the industrialization, the fluidization bed drying method is preferred, and the fluidization drying coating method is more preferred. Advantages and disadvantages of various drying methods are shown in Table <NUM>.

Further, said preparation method for micro drop pill may additionally comprise step (<NUM>) of coating: coating the blank pill obtained from step (<NUM>) in a state of fluidization at <NUM>~<NUM>; the concentration of coating liquid is at <NUM>~<NUM> wt%, preferably <NUM>~20wt%; the coating material is selected from shellac, CAP (cellulose acetate phthalate), methyl acrylate, methyl methacrylate or opadry; the ratio of coating material to the blank pill is <NUM>:<NUM>~<NUM>:<NUM>, preferably <NUM>:<NUM>~<NUM>:<NUM>.

In order to better implement the preparation method for micro drop pill, preferably, said method may additionally comprise a premixing step before step (<NUM>): adding the medicine powder or extract with water, strirring over <NUM> at <NUM>~<NUM> to obtain the premixed material, ensuring the homogenization of water. This step may remedy the defects brought about by inputted dried powder.

In an embodiment of this invention, said micro drop pills prepared by the method may be either packaged directly, or prepared into capsule after loading into capsule shell. After preparation of capsule, the weighing step for capsule may be additionally employed one by one. High-speed weighing for the loaded capsule one-by-one before packaging is employed so as to eliminate possibly substandard capsules.

Said method is characterized in that: it is the first time to creatively combine the techniques of vibration dropping and air cooling with the fluidization drying coating method to apply to the formulation of drop pill and drop pill capsule. Hence, both producing rate and forming quality of the drop pill are increased, further simplifying the production process. The advantages of the present invention are presented as follows:.

Comparison of the physico-chemical parameters between the micro drop pill of the present invention (CSMDP prepared by the method of Example <NUM>) and traditional drop pill was presented in Table <NUM>.

The following examples are offered for purposes of elaborating explanation of the present invention only and are not intended to limit the scope of the invention in any way.

In following Examples, each ingredient of the traditional Chinese medicine was determined by following method, including the Danshensu, Salvianolic acid T, protocatechuic aldehyde, Salvianolic acid D, rosmarinic acid, Salvianolic acid B, Salvianolic acid A, dihydrotanshinone I, tanshinone I, cryptotanshinone, tanshinone IIA, Panax Notoginseng Saponin R1, Ginsenoside Rg1, Ginsenoside Re, Ginsenoside Rb1 and Ginsenoside Rd.

Preparation of reference solution: a certain amount of reference substances, including the Danshensu, Salvianolic acid T, protocatechuic aldehyde, Salvianolic acid D, rosmarinic acid, Salvianolic acid B, Salvianolic acid A, dihydrotanshinone I, tanshinone I, cryptotanshinone, tanshinone IIA, were weighed accurately, transferred to <NUM> volumetric flask and diluted with methanol to the scale, which was continued to be diluted as required, shaked well and flitered through <NUM> membrane to give the reference solution respectively as follows: Danshensu at <NUM>/ml, Salvianolic acid T at <NUM>/ml, protocatechuic aldehyde at <NUM>/ml, Salvianolic acid D at <NUM>/ml, rosmarinic acid at <NUM>/ml, Salvianolic acid B at <NUM>/ml, Salvianolic acid A at <NUM>/ml, dihydrotanshinone I at <NUM>/ml, tanshinone I at <NUM>/ml, cryptotanshinone at <NUM>/ml, tanshinone IIA at <NUM>/ml.

Preparation of tested solution: <NUM> of Salvia Militiorrhiza and Panax Notoginseng extract was weighed accurately, transferred to <NUM> volumetric flask, dissolved with purified water, diluted to scale and filtered through <NUM> membrane to give the tested solution.

Method: 10µl of reference and tested solutions were respectively absorbed with precision and injected into HPLC to assay.

The eluting condition was presented in following Table <NUM>.

Wherein, the retention time of Danshensu, Salvianolic acid T, protocatechuic aldehyde, Salvianolic acid D, rosmarinic acid, Salvianolic acid B, Salvianolic acid A, dihydrotanshinone I, tanshinone I, cryptotanshinone and tanshinone IIA under wavelength of <NUM> was presented in <FIG> and Table <NUM>.

Preparation of reference solution: a certain amount of reference substances, including the Panax Notoginseng Saponin R1, Ginsenoside Rg1, Ginsenoside Re, Ginsenoside Rb1 and Ginsenoside Rd, were weighed accurately, into which methanol was added to give the reference solution, respectively containing <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> per ml.

Preparation of tested solution: <NUM> of Salvia Militiorrhiza and Panax Notoginseng extract was weighed accurately, dissolved with <NUM>% ammonia solution (<NUM>) and passed through D101 macro porous column (inner diameter: <NUM> and height: <NUM>), which was eluted firstly with <NUM> water, <NUM> methanol (<NUM>%) and <NUM> methanol to collect the methanol solution in <NUM> volumetric flask, shake well to give the tested solution.

Chromatographic condition and system suitability test: octadecylsilane bonded silica gel was used as bulking agent; acetonitrile was used as mobile phase "A" and water as mobile phase "B". According to following Table <NUM>, a gradient elution method was used, and flow rate was at <NUM>/min, detective wavelength at <NUM>, column temperature at <NUM> and recording time <NUM>.

Measurement: 10µl of reference and tested solutions were respectively absorbed with precision and injected into HPLC to assay under aforesaid conditions. The retention time of each ingredient was presented in <FIG>.

<NUM> of crude medicine of Salvia Militiorrhiza was cut into the pieces of <NUM>~<NUM> in length and <NUM> of crude medicine of Panax Notoginseng ground into particles of <NUM>. Sodium bicarbonate accounting for <NUM>~3wt% of total crude medicine was weighed and charged into an extracting tank together with Salvia Militiorrhiza and Panax Notoginseng and <NUM> times of water was added to heat and keep boiling for <NUM> and filtered to give the filtrate I and residue I. Resultant residue I was extracted for <NUM>nd time by adding with <NUM> times of water to heat and keep boiling for <NUM> and filtered to give the filtrate II and residue II. The filtrates I and II were concentrated to a relative density of <NUM>~<NUM> (<NUM>±<NUM>) or a relative sugar degree of <NUM>~<NUM>% to give the concentrated liquid. The liquid was delivered to the alcohol precipitation tank, into which a proper amount of ethanol was poured to make final ethanol content of <NUM>~<NUM>% and allowed to stand still for <NUM> hours to precipitate completely. The supernatant was separated and the deposit eliminated. The supernatant was concentrated to give the extract, which was dried to obtain extract I.

The residue II was extracted with ethanol for <NUM> times, <NUM> hours for each time and filtered. The ethanol was recovered to give the extract II. Resultant extract II was dissolved with <NUM>% ethanol, eluted with HPD-<NUM> macroporous resin column and allowed to stand still for <NUM> hours for full absorption by resin. The resin column was desorbed by elution with <NUM>% ethanol until the eluent was colorless; the eluent was collected and the ethanol was recovered to give the extract III. The extract I and extract III were mixed uniformly to give the Salvia Militiorrhiza and Panax Notoginseng extract.

By aforesaid method, the Salvia Militiorrhiza and Panax Notoginseng extract was determined and the concentration of ingredients was presented as follows: the Danshensu at <NUM>/g, Salvianolic acid T at <NUM>/g, protocatechuic aldehyde at <NUM>/g, Salvianolic acid D at <NUM>/g, rosmarinic acid at <NUM>/g, Salvianolic acid B at <NUM>/g, Salvianolic acid A at <NUM>/g, Panax Notoginseng Saponin R1 at <NUM>/g, Ginsenoside Rg1 at <NUM>/g, Ginsenoside Re at <NUM>/g, Ginsenoside Rb1 at <NUM>/g and Ginsenoside Rd at <NUM>/g, dihydrotanshinone I at <NUM>/g, tanshinone I <NUM>/g, cryptotanshinone at <NUM>/g, tanshinone IIA at <NUM>/g.

<NUM> of the Salvia Militiorrhiza and Panax Notoginseng extract was added with <NUM> of borneol to give the traditional Chinese medicine.

<NUM> of Salvia Militiorrhiza and Panax Notoginseng extract obtained from Example <NUM> and <NUM> of borneol was mixed uniformly to give the traditional Chinese medicine composition.

<NUM> of crude medicine of Salvia Militiorrhiza and <NUM> of Panax Notoginseng were decocted with water under alkaline condition for <NUM> times (pH=<NUM>), <NUM> hour each time and filtered to give the filtrate I and residue I. Resultant residue I was decocted with water for <NUM> times, <NUM> hour each time and filtered to give the filtrate II and residue II. The filtrate I and filtrate II were combined and concentrated under reduced pressure to give the concentrated liquid. The concentrated liquid was added into the alcohol precipitation tank with addition of a proper amount of ethanol to make final ethanol content of <NUM>% and allowed to stand still. The supernatant was taken and concentrated to obtain the extract I.

The residue II was extracted with ethanol for <NUM> hour, <NUM> time and filtered. The ethanol was recovered to give the extract II. Resultant extract II was dissolved with <NUM>% ethanol, eluted with HPD-<NUM> macroporous resin column and allowed to stand still for <NUM> hours for full absorption by resin. The resin column was desorbed by elution with <NUM>% ethanol until the eluent was colorless; the eluent was collected and the ethanol was recovered to give the extract III. The extract I and extract III were mixed uniformly to give the Salvia Militiorrhiza and Panax Notoginseng extract.

<NUM> of the Salvia Militiorrhiza and Panax Notoginseng extract was mixed uniformly with <NUM> of borneol to give the traditional Chinese medicine. By aforesaid method, the Salvia Militiorrhiza and Panax Notoginseng extract was determined to contain: the Danshensu at <NUM>, Salvianolic acid T at <NUM>, protocatechuic aldehyde at <NUM>, Salvianolic acid D at <NUM>, rosmarinic acid at <NUM>, Salvianolic acid B at <NUM>, Salvianolic acid A at <NUM>, Panax Notoginseng Saponin R1 at <NUM>, Ginsenoside Rg1 at <NUM>, Ginsenoside Re at <NUM>, Ginsenoside Rb1 at <NUM> and Ginsenoside Rd at <NUM>, dihydrotanshinone I at <NUM>, tanshinone I <NUM>, cryptotanshinone at <NUM>, tanshinone IIA at <NUM>.

<NUM> of crude medicine of Salvia Militiorrhiza and <NUM> of Panax Notoginseng were decocted with water under alkaline condition for <NUM> times (pH=<NUM>), <NUM> hours each time and filtered to give the filtrate I and residue I. Resultant residue I was decocted with water for <NUM> times, <NUM> hours each time and filtered to give the filtrate II and residue II. The filtrate I and filtrate II were combined and concentrated. The concentrated liquid was added with ethanol to make final ethanol content of <NUM>% and allowed to stand still. The supernatant was filtered and the ethanol was recovered to obtain the extract I.

The residue II was extracted with ethanol for <NUM> times, <NUM> hour for each time and filtered. The ethanol was recovered to give the extract II. Resultant extract II was dissolved with <NUM>% ethanol, eluted with HPD-<NUM> macroporous resin column and allowed to stand still for <NUM> hours for full absorption by resin. The resin column was desorbed by elution with <NUM>% ethanol until the eluent was colorless; the eluent was collected and the ethanol was recovered to give the extract III. The extract I and extract III were mixed uniformly to give the Salvia Militiorrhiza and Panax Notoginseng extract.

<NUM> of the Salvia Militiorrhiza and Panax Notoginseng extract was mixed uniformly with <NUM> of borneol to give the traditional Chinese medicine. By aforesaid method, the Salvia Militiorrhiza and Panax Notoginseng extract contained the Danshensu, Salvianolic acid T, protocatechuic aldehyde, Salvianolic acid D, rosmarinic acid, Salvianolic acid B, Salvianolic acid A, Panax Notoginseng Saponin R1, Ginsenoside Rg1, Ginsenoside Re, Ginsenoside Rb1, Ginsenoside Rd, dihydrotanshinone I, tanshinone I, cryptotanshinone and tanshinone IIA respectively at <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> and <NUM>.

<NUM> of crude medicine of Salvia Militiorrhiza and <NUM> of Panax Notoginseng were decocted with water under alkaline condition for <NUM> times (pH=<NUM>), <NUM> hours each time and filtered to give the filtrate I and residue I. Resultant residue I was decocted with water for <NUM> times, <NUM> hours each time and filtered to give the filtrate II and residue II. The filtrate I and filtrate II were combined and concentrated. The concentrated liquid was added with ethanol to make final ethanol concentration of <NUM>% and allowed to stand still. The supernatant was filtered and the ethanol was recovered to obtain the extract I.

The residue II was extracted with ethanol for <NUM> hours, <NUM> stime and filtered. The ethanol was recovered to give the extract II. Resultant extract II was dissolved with <NUM>% ethanol, eluted with HPD-<NUM> macroporous resin column and allowed to stand still for <NUM> hours for full absorption by resin. The resin column was desorbed by elution with <NUM>% ethanol until the eluent was colorless; the eluent was collected and the ethanol was recovered to give the extract III. The extract I and extract III were mixed uniformly to give the Salvia Militiorrhiza and Panax Notoginseng extract.

<NUM> of crude medicine of Salvia Militiorrhiza was cut into the pieces of <NUM>~<NUM> in length and <NUM> of crude medicine of Panax Notoginseng ground into particles. Sodium bicarbonate accounting for 3wt% of total crude medicine was weighed and charged into an extracting tank together with Salvia Militiorrhiza and Panax Notoginseng and <NUM> times of water was added to heat and keep boiling for <NUM> and filtered to give the filtrate I and residue I. Resultant residue I was extracted for <NUM>nd time by adding with <NUM> times of water to heat and keep boiling for <NUM> and filtered to give the filtrate II and residue II. The filtrates I and II were combined and concentrated under reduced pressure to a relative density of <NUM>-<NUM> (<NUM>±<NUM>) or a relative sugar degree of <NUM>% to give the concentrated liquid. The liquid was delivered to the alcohol precipitation tank, into which a proper amount of ethanol was poured to make final ethanol content of <NUM>% and allowed to stand still for <NUM> hours to precipitate completely. The supernatant was separated and the deposit was eliminated. The supernatant was concentrated to give the extract I.

By aforesaid method, the Salvia Militiorrhiza and Panax Notoginseng extract contained the Danshensu, Salvianolic acid T, protocatechuic aldehyde, Salvianolic acid D, rosmarinic acid, Salvianolic acid B, Salvianolic acid A, Panax Notoginseng Saponin R1, Ginsenoside Rg1, Ginsenoside Re, Ginsenoside Rb1, Ginsenoside Rd dihydrotanshinone I, tanshinone I, cryptotanshinone and tanshinone IIA respectively at <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g, <NUM>/g.

<NUM> of crude medicine of Salvia Militiorrhiza was cut into the pieces of <NUM>~<NUM> in length and <NUM> of crude medicine of Panax Notoginseng ground into particles. Sodium bicarbonate accounting for <NUM>. 5wt% of total crude medicine was weighed and charged into an extracting tank together with Salvia Militiorrhiza and Panax Notoginseng and <NUM> times of water was added to heat and keep boiling for <NUM> and filtered to give the filtrate I and residue I. Resultant residue I was extracted for <NUM>nd time by adding with <NUM> times of water to heat and keep boiling for <NUM> and filtered to give the filtrate II and residue II. The filtrates I and II were combined and concentrated under reduced pressure to a relative density of <NUM>-<NUM> (<NUM>±<NUM>) or a relative sugar degree of <NUM>% to give the concentrated liquid. The liquid was delivered to the alcohol precipitation tank, into which a proper amount of ethanol was poured to make final ethanol content of <NUM>% and allowed to stand still for <NUM> hours to precipitate completely. The supernatant was separated and the deposit was eliminated. The supernatant was concentrated to give the extract I.

<NUM> of the Salvia Militiorrhiza and Panax Notoginseng extract was mixed uniformly with <NUM> of borneol to give the traditional Chinese medicine.

<NUM> of traditional Chinese medicine composition prepared by any one method of Examples <NUM>~<NUM> was mixed uniformly with <NUM> of PEG-<NUM>, molten by heating and delivered to the dropping machine to acquire medicine drops by means of dropping the medicine solution into liquid paraffin at <NUM>~<NUM>. Residual liquid paraffin was removed to give <NUM> micro drop pills.

<NUM> of traditional Chinese medicine composition prepared by any one method of Examples <NUM>~<NUM>, <NUM> of glucose, <NUM> of sodium thiosulphate and <NUM> of distilled water were mixed uniformly to give <NUM> injectable lyophilized powders by lyophilizing.

<NUM> of traditional Chinese medicine composition prepared by any one method of Examples <NUM>~<NUM>, <NUM> of mannitol, <NUM> of EDTA calcium disodium and <NUM> of distilled water were mixed uniformly to give <NUM> injectable lyophilized powders by lyophilizing.

<NUM> of traditional Chinese medicine composition prepared by any one method of Examples <NUM>~<NUM>, <NUM> of starch and <NUM> of sucrose were mixed uniformly to give the tablets by compression after granulating.

<NUM> of traditional Chinese medicine composition prepared by any one method of Examples <NUM>~<NUM>, <NUM> of starch and <NUM> of sucrose were mixed uniformly to give the capsules by filling into capsules.

<NUM> of traditional Chinese medicine composition prepared by the method of Example <NUM> and <NUM> of PEG-<NUM> were prepared.

Wherein, during the process of dropping, formation of drop pill was measured visually by using stroboscopic illumination to perform real-time monitoring and adjustment. In order to improve the uniformity and roundness of the drop pills, the step of screening and regulating might be added.

Except that the ratio of traditional Chinese medicine composition to PEG-<NUM> was <NUM>:<NUM>, the CSMDP was prepared by the method of Example <NUM>.

Following materials were taken: <NUM> of traditional Chinese medicine composition prepared by Example <NUM> and <NUM> of a mixture of cyclodextrin and agar (<NUM>:<NUM>). CSMDP was prepared according to the following method:.

Following materials were taken: <NUM> of traditional Chinese medicine composition prepared by Example <NUM> and <NUM> of a mixture of Arabic gum and lactose (<NUM>:<NUM>). CSMDP was prepared according to the following method:.

Following materials were taken: <NUM> of traditional Chinese medicine composition prepared by Example <NUM> and <NUM> of lactitol. CSMDP was prepared according to the following method:.

Following materials were taken: <NUM> of traditional Chinese medicine composition and <NUM> of PEG-<NUM>. CSMDP was prepared according to the following method:
Said traditional Chinese medicine composition powder was added with water and stirred at <NUM> for <NUM> or more to obtain the pre-mixed traditional Chinese medicine composition.

Following materials were taken: <NUM> of traditional Chinese medicine composition and <NUM> of a mixture of PEG-<NUM> : PEG-<NUM> (<NUM>:<NUM>). CSMDP was prepared according to the following method:
Said traditional Chinese medicine composition powder was added with water and stirred at <NUM> for <NUM> or more to obtain the pre-mixed traditional Chinese medicine composition.

Following materials were taken: <NUM> of traditional Chinese medicine composition prepared by Example <NUM>, <NUM> of borneol and <NUM> of xylitol as drop pill matrix.

Following materials were taken: <NUM> of traditional Chinese medicine composition prepared by Example <NUM>, <NUM> of borneol and <NUM> of a mixture of PEG-<NUM> and PEG-<NUM> as drop pill matrix.

Following materials were taken: <NUM> of traditional Chinese medicine composition prepared by Example <NUM>, <NUM> of borneol and <NUM> of PEG-<NUM> as drop pill matrix.

As found in the study by the inventors, compared with existing CSDP, the CSMDP prepared by the methods disclosed in the Examples <NUM>~<NUM> had the merits of good efficacy, high bioavailablility, reduced administration dose and good compliance to the patients.

Salvia Militiorrhiza was transferred to an herbal decocting pot, into which <NUM> times of <NUM>% (w/v) sodium bicarbonate aqueous solution based on the amount of Salvia Militiorrhiza was added, decocted for <NUM> and filtered to give the filtrate. The filtrate was concentrated to obtain the aqueous extract with relative density of <NUM> (<NUM>).

The aqueous extract was added with <NUM>% (v/v) ethanol to make the final ethanol content as <NUM>% (v/v) (<NUM>) and allowed to stand still for <NUM> to give the supernatant. The supernatant was concentrated under reduced pressure to obtain the ethanol-precipitated extract with a relative density of <NUM> (<NUM>).

The ethanol-precipitated extract was dissolved with water, passed through AB-<NUM> macroporous resin column and eluted with aqueous hydrochloric acid solution (pH=<NUM>) until the eluent was nearly colorless. Later, <NUM> times of <NUM>% (v/v) ethanol based on the column volume was used to elute the column and the eluent was concentrated to give the extract with no smell of alcohol.

The extract obtained from previous step was dissolved with mobile phase (acetonitrile : water : formic acid=<NUM>:<NUM>:<NUM> by volume) and purified with NOVASEP LC80-<NUM> dynamic axial high-pressure preparative LC. C18 reverse-phase chromatographic column (<NUM>, YMC Inc. ) was used as stationary phase to carry out the isocratic elution with the mobile phase of acetonitrile : water : formic acid=<NUM>:<NUM>:<NUM> by volume. The flow rate was at <NUM>/min and detective wavelength at <NUM>. The process of elution was monitored by using HPLC to collect the fraction between <NUM>~<NUM> and concentrate to dry with the rotary evaporator to obtain salvianolic acid T.

Afore-obtained salvianolic acid T was dissolved with mobile phase (acetonitrile : water : formic aicd=<NUM>:<NUM>:<NUM> by volume) and Waters Prep <NUM> preparative LC was used to carry out chiral isomer separation. The chromatographic column was CHIRALCEL® OD-RH reverse-phase chiral column (<NUM>×<NUM>, <NUM>) and the mobile phase of acetonitrile : water : formic acid=<NUM>:<NUM>:<NUM> by volume was used to perform isocratic elution. The flow rate was at <NUM>/min and detective wavelength at <NUM>. The process of elution was monitored by using HPLC to collect the fraction of (S)-salvianolic acid T between retention time of <NUM>~<NUM> and (R)-salvianolic acid T between retention time of <NUM>~<NUM>. The eluent was concentrated with rotary evaporator at <NUM> and lyophilized to obtain the pure product of (S)- and (R)-salvianolic acid T.

By using a high-resolution mass spectrometry, a quasi-molecular ion peak of (S)-salvianolic acid T was at m/z <NUM> and (R)-salvianolic acid T at m/z <NUM>.

NMR data assignments for (S)-salvianolic acid T and (R)-salvianolic acid T were seen in the following tables.

In order to better prove the merits of the present invention, the trial was presented as follows:.

SD male rats, weighing <NUM>, were purchased from Beijing Weitonglihua Experimental Animal Co. , Ltd, with certification No.: SCXK (JING) <NUM>-<NUM>.

Rabbits, male, weighing <NUM>~<NUM>, were purchased from Qinglongshan Animal Reproduction Plant, Jiangning Country, Nanjing with certification No.: SCXK (SU) <NUM>-<NUM>.

The Salvia Militiorrhiza and Panax Notoginseng extracts were divided into two types, which were prepared by the method of Example <NUM>, Extract A (with borneol) and Extract B (without borneol). Chloral hydrate and triphenyl tetrazolium chloride (TTC) were used.

Aspirin enteric-coated tablet was purchased from Baijingyu Pharmaceutical Inc, Nangjing. Batch number was <NUM>.

Arachidonic acid (AA) was provided by Sigma Inc in specification of <NUM>/bottle, and batch number was <NUM>.

Monosodium adenosine diphosphate (ADP) was provided by Shanghai Boao Biotech Inc (Imported). Batch number was <NUM>.

Collegan was provided by Sigma Inc in specification of <NUM>/bottle, and batch number was <NUM>.

<NUM> rats were randomly divided into groups according to the body weight: the blank group, model group, group A (with borneol) and group B (without borneol); <NUM> rats in each group.

After grouping, all animals were administrated intragastrically for <NUM> week, which was seen in Table <NUM>. On <NUM>th day, the animals were anesthetized by intraperitoneal injection of <NUM>% chloral hydrate (<NUM>/kg) and fixed on a small plate in a supine position. Conductors were inserted under the skin of right forelimb and both hind limbs, which was connected with the MedLab-U/8c bio-signal collecting-processing system to record the ECG of rats. Hair on front wall of left chest was clipped. Oral tracheal cannula was performed and the animal respirator was connected at respiratory frequency of <NUM> breaths/min, tidal volume <NUM>/<NUM> and I:E=<NUM>:<NUM>. Chest on left front chest lateral side was incised to cut <NUM>rd rib and the pericardium carefully lifted with forceps to tear apart. Left coronary vein trunk pass between the lower edge of left atrial appendage and pulmonary artery cone was observed in most of animals, accompanied with LAD. Medical suture (<NUM>-<NUM>) was used to ligate LAD and a small amount of myocardial tissue <NUM>~<NUM> from the low edge of left atrial appendage inside the interventricular sulcus in the vincity of left coronary vein trunk. Chest was closed layer by layer. The tracheal tube was detubated until the respiration was recovered in rats.

Testing index: after <NUM> ligation, the animals were euthanized. The hearts were taken out and washed with <NUM>% sodium chloride injection to absorb the water. Along the coronary sulcus, the atrium was cut to weigh wet ventricular mass. The heart was sliced into <NUM> thickness of myocardial sections in parallel from the apex to the base portion along ventricular ditch. Obtained myocardium was placed in TTC colorant to dye for <NUM> on <NUM> thermal water bath. Normal myocardium was dyed red and infarcted area white. Wet mass in each section of infarcted area was weighed to calculate the myocardial infarction rate (MIR).

The rabbits were randomly grouped into <NUM> groups: the model group was given with distilled water, the aspirin group (<NUM>/ml), Exatract A groups of low dose and high dose at <NUM> and <NUM>/kg (respectively <NUM>~<NUM> times of clinic equivalent dosage), intragastrically administrated, once a day for <NUM> consecutive days. The volume of medicine administrated was <NUM>/kg body weight. <NUM> after intragastric administration on <NUM>th day, the aminals were anesthetized locally, blooded through carotid artery, anticoagulated with sodium citrate (<NUM>%) <NUM>:<NUM> and centrifugated at 1000r/min for <NUM>. Platelet-rich plasma (PRP) was taken and the remain centrifugated at 3000r/min to take platelet-poor plasma (PPP. Aggregation was induced by ADP (final concentration 3µg/ml), AA (final concentration 80µg/ml) and collegan (5µg/ml). STEELIEX platelet aggregation & coagulation factor analyzer was used to measure the maximum platelet aggregation rate and to calculate inhibition rate according to following formula.

The results were in Table <NUM>. <NUM> days after pre-administration, compared with the model group (<NUM>±<NUM>), the weights of myocardial infarction in group A and group B (<NUM>±<NUM>, <NUM>±<NUM>) were decreased obviously, having statistical significance. According to the results of inter-group comparison, the ratio of myocardial infarction in group A was much less than that in group B, having significant difference between two groups (p<<NUM>).

As shown in Table <NUM>, Extract A was proven to have inhibitory effect on ADP-induced platelet aggregation in rabbits, which, compared with the blank group, had a significant difference. Compared with the aspirin group, no significant difference was found in the group A in inhibiting ADP-induced platelet aggregation.

As shown in Table <NUM>, Extract A was proven to have inhibitory effect on AA-induced platelet aggregation in rabbits, which, compared with the blank group, had a significant difference. Compared with the aspirin group, no significant difference was found in the group A in inhibiting AA-induced platelet aggregation.

As shown in Table <NUM>, Extract A was proven to have inhibitory effect on collegan-induced platelet aggregation in rabbits, which, compared with the blank group, had a significant difference. Compared with the aspirin group, no significant difference was found in the group A in inhibiting collegan-induced platelet aggregation.

As shown in the results, administration of Salvia Militiorrhiza and Panax Notoginseng extract for <NUM> consecutive days could take effect of antimyocardial infarction in ligated rats.

In Group A, the Salvia Militiorrhiza and Panax Notoginseng extract with borneol was administrated for <NUM> consecutive days. Obviously, the myocardial infarction rate was less than that in Group B (without borneol) and had significantly inhibitory effect on ADP, AA or collegan induced platelet aggregation in rabbits.

The preliminary conclusion showed that addition of borneol might strengthen the efficacy of anti-myocardial infarction.

CSMDP was prepared by the method of Preparative Example <NUM> of CSMDP.

CSDP, used as compared drug, was commercially available in China, prepared by Tianjin Tasly Pharmaceutical Co.

Anesthesia was performed by chloral hydrate and triphenyl tetrazolium chloride (TTC).

Apparatus: MedLab-U/8c bio-signal collecting-processing system, purchased from Nanjin Meiyi Inc.

Grouping: rats were randomly divided into groups according to the body weight: S group (the sham operation group), M group (the model group), Y group (the positive group, Metoprolol Tartrate, Lot No. <NUM>), F group (the CSMDP group in the present invention) and G group (the CSDP group commercially available in China, batch number: <NUM> <NUM>); <NUM> rats in each group.

After grouping, the animals were administrated intragastrically for <NUM> days, which was seen in Table <NUM>. On <NUM>th day, the rats were anesthetized by intraperitoneal injection of <NUM>% chloral hydrate (<NUM>/kg) and fixed on a small wood plate in a supine position. Pins were inserted under the skin of right forelimb and both hind limbs, which was connected with the MedLab-U/8c bio-signal collecting-processing system to record the ECG of rats. Hair on front wall of left chest was clipped. Oral tracheal cannula was performed and the animal respirator was connected at respiratory frequency of <NUM> breaths/min, tidal volume <NUM>/<NUM> and I:E=<NUM>:<NUM>. Chest on left front chest lateral side was incised to cut <NUM>rd rib and the pericardium carefully lifted with forceps to tear apart. Left coronary vein trunk pass between the lower edge of left atrial appendage and pulmonary artery cone was observed in most of animals, accompanied with LAD. Medical suture (<NUM>-<NUM>) was used to ligate LAD and a small amount of myocardial tissue <NUM>~<NUM> from the low edge of left atrial appendage inside the interventricular sulcus in the vincity of left coronary vein trunk. The rats with elevated J point by <NUM>. 1mV in ECG and pale LVAW (left ventricular anterior wall) represented the successful modeling. Chest was closed layer by layer. The tracheal tube was detubated until the respiration was recovered in rats. ECG was recorded continuously for <NUM> hours. Rats were anesthetized, heart taken out, sliced and dyed to calculate myocardial infarction rate (MIR). The serum was for later use.

The results were in Table <NUM>. As shown in Table <NUM>, <NUM> days after pre-administration, MIR in M group was significantly higher than that in S group, suggesting the successful modeling. MIR in G group and F group were respectively <NUM>% and <NUM>%, significantly lower than that in M group (<NUM>%), having a significant difference (p<<NUM>). It was indicated that both samples had a certain effect against acute myocaudial infarction. However, there was no significantly statistical difference (p><NUM>) in comparison to those in G group and F group.

As shown in Table <NUM>, the descending order of heart rate in each group was F group, G group, M group, Y group and S group within observation time and <NUM>~<NUM> hour after ligation. <NUM> hour later, the heart rate in each group was decreased. Within observation time, the variation of heart rate in Y group and S group was relatively stable. There was no significant difference on heart rate in rats among groups.

Claim 1:
A preparation method for the micro drop pill, comprising the following steps:
(<NUM>) Material melting step: charging traditional Chinese medicine composition and drop pill matrix into a homogenizer, mixing homogenously at <NUM>~5000rpm for <NUM>~<NUM>, melting homogenously at <NUM>~10000rpm for <NUM>~<NUM>; during the metling process, the temperature is kept at <NUM>~<NUM> to obtain the molten medicine liquid; the ratio of the medicine to the micro drop pill matrix is <NUM>:<NUM>~<NUM>:<NUM> by weight;
(<NUM>) Dropping step: delivering the molten medicine liquid to a dripper, and acquiring medicine drops from the dripper by means of vibration dropping at a vibration frequency of <NUM>~<NUM> under a dropping pressure of <NUM>~<NUM> Bar, with an acceleration at <NUM>~<NUM>; and the temperature of the dripper is at <NUM>~<NUM>; the dropping rate is matched with the melting rate in step (<NUM>); and
(<NUM>) Condensation step: cooling the medicine drops with cooling gas rapidly to solidify and obtaining solid drop pill having a particle size of <NUM>~<NUM>; the temperature of the cooling gas is -<NUM> to -<NUM>,
wherein the traditional Chinese medicine composition composed of the following materials by weight percentage: <NUM>%~<NUM>% of Salvia Militiorrhiza and Panax Notoginseng extract and <NUM>%~<NUM>% of borneol, wherein the Salvia Militiorrhiza and Panax Notoginseng extract comprises the following ingredients by weight percentage:
Danshensu : Salvianolic acid T : protocatechuic aldehyde : Salvianolic acid D : rosmarinic acid : Salvianolic acid B : Salvianolic acid A : Panax Notoginseng Saponin R1 : Ginsenoside Rg1 : Ginsenoside Re : Ginsenoside Rb1 : Ginsenoside Rd : dihydrotanshinone I : tanshinone I : cryptotanshinone : tanshinone IIA= (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>) : (<NUM>~<NUM>), and said drop pill matrix includes one or more of PEG, sorbitol, xylitol, lactitol, maltose, starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), Arabic gum, alginate, dextrin, cyclodextrin, agar and lactose,
wherein said compound Salvia micro drop pill is prepared with the traditional Chinese medicine composition and drop pill matrix in a ratio of <NUM>:<NUM>~<NUM>:<NUM> by weight.