Summary of the invention
The objective of the invention is to: little Chinese medicine preparation of a kind of good effect, taking convenience, the using dosage that can treat angina pectoris and preparation method thereof is provided.
The present invention is achieved in that according to components by weight percent and calculates, preparation of the present invention is soft capsule or the drop pill of being processed into by following materials of weight proportions, wherein: Fructus Choerospondiatis 240-720 part, Radix Salviae Miltiorrhizae 120-360 part, Flos Caryophylli 30-90 part, Borneolum Syntheticum 15-45 part, Concretio Silicea Bambusae 15-45 part.Particularly, it is soft capsule or the drop pill of being processed into by following materials of weight proportions, wherein: 480 parts of Fructus Choerospondiatis, 240 parts of Radix Salviae Miltiorrhizaes, 60 parts of Flos Caryophyllis, 30 parts of Borneolum Syntheticums, 30 parts of Concretio Silicea Bambusaes.
The preparation method of the Chinese medicine preparation of this treatment angina pectoris is: Fructus Choerospondiatis is used the 60-80% ethanol percolation, and percolate is concentrated into thick paste; Radix Salviae Miltiorrhizae carries out percolation with sour water earlier, and after filtrate was adsorbed with the low pole macroporous resin, sour water was washed the back and used ethanol elution, collects pure washing liquid; Radix Salviae Miltiorrhizae residue reuse 85-99% ethanol percolation behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; The Concretio Silicea Bambusae water extraction filters, and filtrate is concentrated into thick paste; Merge above medicinal liquid, concentrate, after the drying, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation, and is standby; The mixed extract that adds adjuvant, Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae at last, Flos Caryophylli volatile oil and Borneolum Syntheticum fine powder are made soft capsule or drop pill.
Said sour water refers to acidic aqueous solution, preferred 0.005-0.02mol/L HCl or H2SO4, preferred especially 0.01mol/L HCl.
The low pole macroporous resin can be with AB-8 or DA1 or D180 or DS-401 type macroporous resin, preferred AB-8 type resin.
Soft capsule of the present invention can prepare like this: Fructus Choerospondiatis carries out percolation with the 60-80% ethanol that 8-12 doubly measures, and collects percolate, is evaporated to thick paste; 0.005-0.02mol/L HCl or H2SO4 that Radix Salviae Miltiorrhizae is doubly measured with 10-14 earlier carry out percolation, collect percolate, and after filtrate was adsorbed with the low pole macroporous resin, sour water was used 3-6 column volume of 60-99% ethanol elution after washing 3-4 column volume, collects pure washing liquid; The 85-99% ethanol percolation that Radix Salviae Miltiorrhizae residue reuse 12-16 behind the water percolation doubly measures is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; Concretio Silicea Bambusae water extraction 1-3 time, each amount of water be the medical material amount 8-12 doubly, be 1-3 hour heat time heating time, filters, merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind the 50-70 ℃ of vacuum drying, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation, and is standby; It is an amount of to get the adjuvant soybean oil, adds 5% Cera Flava, after heating makes dissolving, adds the mixed extract of Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae, stirs evenly the back and adds Flos Caryophylli volatile oil and Borneolum Syntheticum fine powder, and colloid mill grinds well, and is pressed into soft capsule, promptly.Particularly, Fructus Choerospondiatis carries out percolation with 70% ethanol of 10 times of amounts, collects percolate, is evaporated to thick paste; Radix Salviae Miltiorrhizae earlier carries out percolation with the 0.01mol/L HCl of 12 times of amounts, the collection percolate, and after filtrate was adsorbed with the AB-8 resin, sour water was washed behind 4 column volumes with 3 column volumes of 95% ethanol elution, collects pure washing liquid.The 95%L alcohol percolation of the 14 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; Concretio Silicea Bambusae water extraction 2 times, each amount of water is 10 times of medical material amount, and be 2 hours heat time heating time, filters, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 60 ℃ of vacuum dryings, be ground into fine powder, standby.Flos Caryophylli is extracted volatile oil with vapor distillation, and is standby.It is an amount of to get the adjuvant soybean oil, adds 5% Cera Flava, after heating makes dissolving, adds the mixed extract of Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae, stirs evenly the back and adds Flos Caryophylli volatile oil and Borneolum Syntheticum fine powder, and colloid mill grinds well, and is pressed into soft capsule, promptly.
Drop pill of the present invention can prepare like this: Fructus Choerospondiatis carries out percolation with the 60-80% ethanol that 8-12 doubly measures, and collects percolate, is evaporated to thick paste; 0.005-0.02mol/L HCl or H2SO4 that Radix Salviae Miltiorrhizae is doubly measured with 10-14 earlier carry out percolation, collect percolate, and after filtrate was adsorbed with the low pole macroporous resin, sour water was used 3-6 column volume of 60-99% ethanol elution after washing 3-4 column volume, collects pure washing liquid; The 85-99% ethanol percolation that Radix Salviae Miltiorrhizae residue reuse 12-16 behind the water percolation doubly measures is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; Concretio Silicea Bambusae water extraction 1-3 time, each amount of water be the medical material amount 8-12 doubly, be 1-3 hour heat time heating time, filters, merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind the 50-70 ℃ of vacuum drying, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation, and is standby; With Macrogol 4000, put the mixed extract that adds Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae in the water-bath behind the heating and melting, stir evenly the back and add Flos Caryophylli volatile oil and Borneolum Syntheticum fine powder, stirring is transferred to reservoir, drips to make ball, promptly.Particularly, Fructus Choerospondiatis carries out percolation with 70% ethanol of 10 times of amounts, collects percolate, is evaporated to thick paste; Radix Salviae Miltiorrhizae earlier carries out percolation with the 0.01mol/L HCl of 12 times of amounts, the collection percolate, and after filtrate was adsorbed with the AB-8 resin, sour water was washed behind 4 column volumes with 3 column volumes of 95% ethanol elution, collects pure washing liquid.95% ethanol percolation of the 14 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; Concretio Silicea Bambusae water extraction 2 times, each amount of water is 10 times of medical material amount, and be 2 hours heat time heating time, filters, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 60 ℃ of vacuum dryings, be ground into fine powder, standby.Flos Caryophylli is extracted volatile oil with vapor distillation, and is standby.With Macrogol 4000, put the mixed extract that adds Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae in the water-bath behind the heating and melting, stir evenly the back and add Flos Caryophylli volatile oil and Borneolum Syntheticum fine powder, stirring is transferred to reservoir, airtight and in 70 ℃ of insulations, is coolant with the methyl-silicone oil, make drop pill, promptly.
For confirming that the product that obtains has effective therapeutic effect, we have carried out a series of experiments:
Be example now, illustrate that main pharmacodynamics is as follows with drop pill contrast capsule:
One, to the influence of coronary ligation Acute Myocardial Ischemia in Rats
1, test method
Get 60 of rats, divide 6 groups at random, promptly existing capsule (240mg/kg), drop pill high dose of the present invention (180mg/kg) group, middle dosage (90mg/kg) group, low dosage (45mg/kg) group, model group, Nifedipine group (6mg/kg), drop pill group successive administration of the present invention 7 days, model group gives the drop pill adjuvant with volume.Fasting is 16 hours after administration in the 6th day, after the administration in the 7th day 90 minutes, 20% crow is drawn dawn 1.2g/kg anesthesia, the record normal ECG, and 3~4 intercostals are opened breast from the left side, expose heart, find out arteria coronaria left anterior descending branch (LAD) in pulmonary conus and left room, wear one " 0 " number toe-in at distance starting point 2~3mm place and prick, send heart back to thoracic cavity, extrude thoracic cavity inner blood and gas, sew up thoracic wall immediately.Whole surgery was finished in 30 seconds.Record operation electrocardiogram after 5,15,30,45,60,90,120,150,180,210,240 minutes.Nifedipine group (6mg/kg) fasting 16 hours, administration in the 2nd day is after 90 minutes, and all the other steps are with above-mentioned.
Perform the operation after 360 minutes, abdominal aortic blood, get serum, to survey rat blood serum lactic acid dehydrogenase (LDH), creatine kinase (CK), aspartate amino transferase (AST) activity, measure CK, LDH, AST according to the detection kit description, opening breast cores dirty, remove the atrium, the ventricle crosscut is become 3~4, insert 0.25% chlorination nitro blue tetrazolium (NBT) solution of pH7.4, in 37 ℃ of dyeing, treat to take out immediately when the infarcted myocardium boundary line is known, separate infarcted myocardium and normal myocardium, weigh respectively, calculate infarcted myocardium and account for the percentage ratio of chamber muscle wet weight whole-heartedly.
2, result of the test
The result shows dosage group in drop pill high dose group of the present invention, the drop pill of the present invention, existing Capsules group LDH, CK, AST is active and model group compares, and obviously reduces (p<0.01); Drop pill small dose group LDH of the present invention, CK, AST activity compare with model group, there was no significant difference, but inhibition trend is arranged.Drop pill high dose group infarcted myocardium percentage rate of the present invention and model group relatively obviously reduce (p<0.01); Dosage group, existing Capsules group infarcted myocardium percentage rate and model group relatively obviously reduce (p<0.05) in the drop pill of the present invention.Dosage group LDH, CK, AST, infarcted myocardium percentage comparisons in existing Capsules group and the drop pill of the present invention, there was no significant difference the results are shown in Table 1.
Table 1 drop pill of the present invention is to the protective effect of rat acute myocardial infarction
Group |
Dosage |
LDH (U.L
-1)
|
CK (U.L
-1)
|
AST (U.L
-1)
|
Infarcted myocardium percentage rate (%) |
Dosage group drop pill low dose group of the present invention in the existing Capsules group drop pill high dose group of the present invention drop pill of the present invention of model group Nifedipine group |
---- 6mg/kg 240mg/kg 180mg/kg 90mg/kg 45mg/kg |
1043±209 472±125
** 570±84
** 547±98
** 574±101
** 829±213
|
1387±327 864±334** 995±269
** 862±287
** 996±242
** 1208±272
|
169±45 114±26
** 118±26
** 113±19
** 116±25
** 142±34
|
26.2±5.5 18.5±4.6
** 21.2±4.2
* 19.7±3.3
** 20.7±3.8
* 23.6±4.9
|
Annotate: with the model group ratio
*, P<0.05,
*, P<0.01
The result shows that drop pill high dose group electrocardiogram J point value of raising of the present invention compared with model group, obviously forced down (p<0.05) after ligation 0-90 minute; The dosage group J point value of raising compared with model group after ligation 15-60 minute in the drop pill of the present invention, obviously forced down (p<0.05); Existing Capsules group J point value of raising compared with model group after ligation 30-60 minute, obviously forced down (p<0.05); The dosage group J point value of raising compares in existing Capsules group and the drop pill of the present invention, and there was no significant difference the results are shown in Table 2.
Table 2 drop pill of the present invention is to the influence of rats with myocardial ischemia electrocardiogram J point
Group |
Move (mv) on the J point after the ligation |
5min |
15min |
30min |
45min |
60min |
90min |
120min |
150min |
180min |
210min |
240min |
Dosage drop pill low dosage of the present invention in the model group nifedipine capsule of the present invention drop pill high dose of the present invention drop pill of the present invention |
0.446± 0.180 0.294± 0.106
* 0.338± 0.071 0.318± 0.068
* 0.338± 0.137 0.346± 0.103
|
0.433± 0.132 0.298± 0.104
* 0.395± 0.131 0.325± 0.090
* 0.305± 0.081
* 0.350± 0.072
|
0.436± 0.096 0.295± 0.080
** 0.341± 0.058
* 0.329± 0.121
* 0.308± 0.152
* 0.353± 0.089
|
0.428± 0.073 0.288± 0.092
** 0.329± 0.042
** 0.308± 0.116
* 0.298± 0.126
* 0.375± 0.096
|
0.374± 0.081 0.284± 0.086
* 0.313± 0.042
* 0.299± 0.092
* 0.268± 0.10
* 0.335± 0.098
|
0.319± 0.073 0.254± 0.100 0.296± 0.040 0.248± 0.051
* 0.256± 0.090 0.331± 0.106
|
0.313± 0.060 0.258± 0.105 0.289± 0.069 0.290± 0.077 0.255± 0.082 0.345± 0.092 |
0.296± 0.064 0.236± 0.101 0.286± 0.088 0.296± 0.092 0.255± 0.141 0.335± 0.082 |
0.300± 0.079 0.240± 0.105 0.245± 0.086 0.289± 0.086 0.278± 0.113 0.331± 0.076 |
0.328± 0.079 0.253± 0.096 0.285± 0.067 0.279± 0.082 0.295± 0.108 0.318± 0.076 |
0.300 ± 0.079 0.243 ± 0.107 0.283 ± 0.065 0.271 ± 0.083 0.283 ± 0.107 0.315 soil 0.078 |
Annotate: with the model group ratio
*, P<0.05,
*, P<0.01
The result proves that drop pill of the present invention has the effect of anti-experimental character rat heart muscle ischemia.
Two, drop pill of the present invention is to the influence of clotting time of mice
1, test method
Get 50 of mices, divide 5 groups at random, promptly existing capsule (480mg/kg), drop pill high dose of the present invention (360mg/kg), middle dosage (180mg/kg), the blank group of low dosage (90mg/kg) group, fasting 16 hours, each treated animal is irritated the stomach relative medicine respectively, and blank group gives the drop pill adjuvant with volume, administration volume: 0.2ml/20g, after the administration 90 minutes, eye socket was got blood and is measured clotting time with slide method.Data are used
Expression, statistical procedures is carried out in the t check between group.
2, result of the test
The result shows that existing Capsules group, drop pill group height of the present invention, middle dosage compare with blank group, make the cruor time extending (P<0.01) of normal mouse; Drop pill low dosage of the present invention compares with blank group, also makes cruor time extending (P<0.05), the results are shown in Table 3.
Results suggest, drop pill of the present invention can be improved patient's blood clotting situation.
Table 3 drop pill of the present invention is to the influence of clotting time of mice
Group |
Dosage |
Clotting time (s) |
Dosage group drop pill low dose group of the present invention in the existing Capsules group drop pill high dose group of the present invention drop pill of the present invention of blank group |
--- 480mg/kg 360mg/kg 180mg/kg 90mg/kg |
114±42 164±22
** 171±27
** 167±23
** 147±22
* |
Annotate: with blank group ratio
*, P<0.05,
*, P<0.01
The soft capsule main pharmacodynamics is close with the drop pill experimental data, and conclusion is identical.
Among the present invention, we find to adopt common technology to be difficult to prescription provided by the invention is made desired dosage form, so for the technology and the adjuvant of two dosage forms, we do lot of experiments:
At the few characteristics of novel form drug loading, we change the extraction process of Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae three flavor medical materials, under the prerequisite that as far as possible fully ensures effective ingredient, have reduced the paste-forming rate of medical material.
Fructus Choerospondiatis: former capsule preparations has only carried out 60-80%, best 70% ethanol percolate extraction to part Fructus Choerospondiatis medical material (1/4 amount).Remainder is used as medicine with crude drug.Novel form has carried out ethanol percolate extraction to whole Fructus Choerospondiatis medical materials.
Radix Salviae Miltiorrhizae: former preparation carried out for three steps to Radix Salviae Miltiorrhizae and has extracted: 85-99%, best 95% alcohol reflux, 40-60%, best 50% alcohol reflux and water boiling and extraction.Novel form is with the water solublity salvianolic acid with Tanshinone I I
AFor the TANSHINONES of representative is extracted as target.After the sour water percolation is at first passed through in the extraction of water solublity salvianolic acid, again through the purification of low pole macroporous resin; The extracting method of TANSHINONES is the 85-99% ethanol percolation.
Concretio Silicea Bambusae: directly be used as medicine after Concretio Silicea Bambusae is pulverized by former dosage form and be used as medicine after changing into water boiling and extraction.
Specific as follows:
One, Fructus Choerospondiatis is extracted:
This test is determined the volume of percolate on the basis of former technology.
The extracting method of Fructus Choerospondiatis: Fructus Choerospondiatis is ground into coarse powder, and 70% alcoholic solution is an index with the extract yield of effective ingredient total flavones in the Fructus Choerospondiatis, determines the volume of percolate.
Content of total flavone is measured in table 4 percolate
Sample point (by the multiple record of suitable medical material amount) |
Absorbance (A) |
The amount of total flavones (mg) in the 5ml percolate |
2 times 4 times 6 times 8 times 9 times 10 times 11 times |
The too big absorption value of absorption value is too big by 0.402 0.196 0.087 0.011 0.007 |
----- ----- 1.160 0.561 0.244 0.023 0.011 |
Can find out that by above result of the test when percolate arrived 10 times of amounts, absorbance was less.On color, the eluent color is also very shallow, illustrates the extraction of Fructus Choerospondiatis complete substantially in addition.The volume of determining percolate is that the 8-12 of medical material amount doubly measures, best 10 times of amounts.
Two, the preparation of Radix Salviae Miltiorrhizae extract
Main effective ingredient in the Radix Salviae Miltiorrhizae comprises water miscible salvianolic acid and fat-soluble tanshinone, and wherein tanshinone is with Tanshinone I I
ABe representative, TANSHINONES and salvianolic acid by a large amount of experiments, at first extract salvianolic acid with the water as solvent percolation all to thermally labile, again with 85-99% ethanol percolate extraction TANSHINONES, the consumption of two kinds of solvents when solvent condition when determining the water percolation and percolation by testing.
(1) extraction of water-soluble phenolic acids material
1, water percolation solvent is selected
Radix Salviae Miltiorrhizae powder is broken into coarse powder, gets two parts, a copy of it adds deionized water, and another part adds 0.01mol/L HCl, draws filtrate, and standardize solution is made reference with water, measures its absorbance under 280nm.Measure as stated above once more after the filtrate ambient temperature overnight.
The light absorption value of extracting solution under 280nm when table 5 different solvents is handled Radix Salviae Miltiorrhizae
Solvent |
Extracting solution absorbance (280nm) |
The absorbance rate of change |
Detect after the supersound process |
Detect after the ambient temperature overnight |
Deionized water 0.01mol/L HCl 0.02mol/LH
2SO
4 |
0.842 0.865 0.851 |
0.706 0.853 0.783 |
-16.15% -1.39% -7.54% |
The light absorption value of extracting solution slightly raises when making solvent with sour water; The light absorption value that detects sour extract after spending the night under the room temperature is constant substantially, and the light absorption value of water extract then significantly reduces.This shows that acid condition not only can improve the extraction ratio of salvianolic acid, also has significant Stabilization to salvianolic acid.Therefore in this technical study, adopt 0.005-0.02mol/L HCl or H
2SO
4, preferred 0.01mol/L HCl makes the solvent extraction Radix Salviae Miltiorrhizae.
2, the consumption of solvent during the water percolation
Get the coarse powder of Radix Salviae Miltiorrhizae, 0.01mol/L HCl solution percolation, 2 times of amounts of every percolation medical material acidifying water is made reference with water after getting 200 times of effluent dilute with waters, measures its light absorption value under 280nm.
The light absorption value of effluent under 280nm when table 6 water percolation extracts salvianolic acid
Solvent load (doubly amount) |
2 |
4 |
6 |
8 |
10 |
12 |
14 |
16 |
18 |
Light absorption value (280nm) |
1.321 |
1.306 |
1.213 |
0.672 |
0.221 |
0.009 |
0.012 |
0.003 |
0.003 |
The result shows that through using 0.01mol/L HCl solution percolation, to 12 times of amounts of percolation, salvianolic acid extracts substantially fully.In this technology during acidifying water percolation salvianolic acid the acidifying water consumption be decided to be 10-14 and doubly measure best 12 times of amounts.
3, the technical study of purification by macroporous resin salvianolic acid
To some non-liposoluble ingredients that under 280nm, does not absorb, remove by means of the macroporous resin chromatographic technique.
The investigation of the screening of macroporous resin kind and maximum adsorption carrying capacity: directly get the sour water percolate of Radix Salviae Miltiorrhizae, the macroporous resin column of having handled well on continuing detects the light absorption value of effluent under 280nm, to effluent till under the 280nm obvious light absorption being arranged.Determine to be converted to the volume of upper prop solution the amount of Radix Salviae Miltiorrhizae raw medicinal herbs again, thereby to determine the maximum adsorption carrying capacity of macroporous resin by the volume of measuring effluent to salvianolic acid.
Three kinds of macroporous resins of table 7 are to the maximum adsorption carrying capacity measurement result of salvianolic acid
The resin model |
Resin polarity |
Maximum adsorption carrying capacity (gram Radix Salviae Miltiorrhizae/ml macroporous resin) |
AB-8 DM130 NKA |
The nonpolar middle polarity of low pole |
0.644 0.546 0.216 |
Conclusion: in the macroporous resin of three kinds of opposed polarities, with the AB-8 of low pole absorption carrying capacity maximum to salvianolic acid, so the selected low pole macroporous resin of this technology, again through test, as a result AB-8 or DA1 or D180 or DS-401 type resin all can, AB-8 type resin optimum.
Elution requirement is definite during AB-8 macroporous resin treatment salvianolic acid: the sour water percolate of Radix Salviae Miltiorrhizae is directly gone up the AB-8 macroporous resin.In whole chromatography process, transfer to 2~3 with hydrochloric acid.Preceding 4 column volumes of reuse sour water eluting behind the AB-8 macroporous resin on the sour water percolate of Radix Salviae Miltiorrhizae as a result, it is yellow that effluent is, but light absorption value is very low under 280nm, and this explanation part can directly not flow out with the impurity of resin-bonded; Use 6 column volumes of ethanol elution of 60% then, eluting goes out salvianolic acid substantially fully, and the ethanol elution with 95% then only needs 3 column volumes.Ethanol elution paste-forming rate difference with 60% and 95% is little, and is more suitable than 60% ethanol with 95% ethanol from shortening the operating time and being convenient to the angle consideration that ethanol reclaims, and therefore selects 60-99% ethanol, best 95%.
(2) extraction of fat-soluble TANSHINONES
Our selected 95% ethanol extracts the solvent of TANSHINONES from Radix Salviae Miltiorrhizae as percolation.Medicinal residues are used 95% ethanol percolation instead, and 2 times of amounts of every percolation ethanol is got effluent and diluted three times, detects the amount of tanshinone wherein.
The assay of tanshinone in effluent when table 8 95% alcohol percolation method extracts TANSHINONES
Solvent load (doubly amount) |
2 |
4 |
6 |
8 |
10 |
12 |
14 |
16 |
Tanshinone concentration (ug/ml) |
43.32 |
29.17 |
6.17 |
4.35 |
2.94 |
1.65 |
0.97 |
0.93 |
Conclusion (of pressure testing): find out from detecting data, 14 times of amounts of 95% ethanol percolation, the tanshinone content in the effluent is very low, and the 95% ethanol consumption that therefore percolation is extracted TANSHINONES is defined as 12-16 and doubly measures, and the best is 14 times of amounts.
Three, determining of Concretio Silicea Bambusae extraction process:
The extractum that decocting boils is subjected to the influence of factors such as amount of water, decocting time, decoction number of times.With the leaching rate is index, carries out three factors, and the orthogonal test of three levels is selected L for use
9(3
4) orthogonal test table, select the decocting extraction process and be: Concretio Silicea Bambusae water extraction 1-3 time, the 8-12 that each amount of water is the medical material amount doubly, be 1-3 hour heat time heating time.The best is: extract 2 times, each amount of water is 10 times of medical material amount, and be 2 hours heat time heating time.
Four, preparation of soft capsule
The adjuvant that can be used as diluent in the soft capsule has multiple, as vegetable oil, and PEG400 etc.Through experiment, we select soybean oil is adjuvant, and Cera Flava is a suspensoid, and with the Cera Flava of 3-6%, particularly 5% ratio is comparatively suitable.
Five, drop pill choice of base
Drop pill substrate commonly used have polyethylene glycol 6000, Macrogol 4000, etc., through repetition test, medicinal substances extract dispersion in Polyethylene Glycol-12000 is poor slightly, and dispersion is preferably arranged all in Polyethylene Glycol-4000 and 6000, but under similar circumstances at drug loading, with PEG-6000 is the medicinal liquid flowability of substrate and the dissolve scattered time limit of drop pill, all effective not as PEG-4000.Polyethylene Glycol-400 can increase the dispersion of extract in substrate, and the acceleration drop pill is molten to loose, but Polyethylene Glycol-400 room temperature is liquid down, drop pill hardness is reduced, so select PEG-4000 for use.
The specific embodiment
Embodiments of the invention 1: Fructus Choerospondiatis is used ethanol percolation for 600 parts, and percolate is concentrated into thick paste; 180 parts of elder generations of Radix Salviae Miltiorrhizae carry out percolation with sour water, and after filtrate was adsorbed with low pole macroporous resin resin, sour water was washed the back and used ethanol elution, collects pure washing liquid; Radix Salviae Miltiorrhizae residue reuse ethanol percolation behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; 20 parts of water extraction of Concretio Silicea Bambusae filter, and filtrate is concentrated into thick paste; Merge above medicinal liquid, concentrate, after the drying, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation for 45 parts, and is standby; The mixed extract that adds adjuvant, Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae at last, Flos Caryophylli volatile oil and 20 parts of Borneolum Syntheticum fine powders are made soft capsule or drop pill.
Embodiments of the invention 2: 70% ethanol of 10 times of amounts of 480 parts of usefulness of Fructus Choerospondiatis carries out percolation, collects percolate, is evaporated to thick paste; 240 parts of Radix Salviae Miltiorrhizaes carry out percolation with the 0.01mol/LHCl of 12 times of amounts earlier, the collection percolate, and after filtrate was adsorbed with the AB-8 resin, sour water was washed behind 4 column volumes with 3 column volumes of 95% ethanol elution, collects pure washing liquid.95% ethanol percolation of the 14 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; 30 parts of water extraction of Concretio Silicea Bambusae 2 times, each amount of water is 10 times of medical material amount, and be 2 hours heat time heating time, filters, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 60 ℃ of vacuum dryings, be ground into fine powder, standby.Flos Caryophylli is extracted volatile oil with vapor distillation for 60 parts, and is standby.It is an amount of to get the adjuvant soybean oil, adds the Cera Flava of 4-6%, after heating makes dissolving, adds the mixed extract of Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae, stirs evenly the back and adds Flos Caryophylli volatile oil and 30 parts of Borneolum Syntheticum fine powders, and colloid mill grinds well, and is pressed into soft capsule, promptly.Oral, one time 3,3 times on the one, warm water delivery service.
Embodiments of the invention 3: 75% ethanol of 9 times of amounts of 360 parts of usefulness of Fructus Choerospondiatis carries out percolation, collects percolate, is evaporated to thick paste; 330 parts of Radix Salviae Miltiorrhizaes carry out percolation with the 0.005mol/L HCl of 13 times of amounts earlier, the collection percolate, and after filtrate was adsorbed with the DAl resin, sour water was washed behind 3 column volumes with 5 column volumes of 70% ethanol elution, collects pure washing liquid; 95% ethanol percolation of the 15 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; 40 parts of water extraction of Concretio Silicea Bambusae 1 time, amount of water are 11 times of medical material amount, and be 2.5 hours heat time heating time, filter, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 55 ℃ of vacuum dryings, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation for 75 parts, and is standby; It is an amount of to get the adjuvant soybean oil, adds 4% Cera Flava, after heating makes dissolving, adds the mixed extract of Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae, stirs evenly the back and adds Flos Caryophylli volatile oil and 40 parts of Borneolum Syntheticum fine powders, and colloid mill grinds well, and is pressed into soft capsule, promptly.Oral, one time 3,3 times on the one, warm water delivery service.
Embodiments of the invention 4: 65% ethanol of 11 times of amounts of 300 parts of usefulness of Fructus Choerospondiatis carries out percolation, collects percolate, is evaporated to thick paste; 300 parts of Radix Salviae Miltiorrhizaes carry out percolation with the 0.02mol/L HCl of 11 times of amounts earlier, the collection percolate, and after filtrate was adsorbed with the D180 resin, sour water was washed behind 3 column volumes with 4 column volumes of 80% ethanol elution, collects pure washing liquid; 95% ethanol percolation of the 13 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; 43 parts of water extraction of Concretio Silicea Bambusae 3 times, each amount of water is 9 times of medical material amount, and be 1.5 hours heat time heating time, filters, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 65 ℃ of vacuum dryings, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation for 85 parts, and is standby; It is an amount of to get the adjuvant soybean oil, adds 6% Cera Flava, after heating makes dissolving, adds the mixed extract of Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae, stirs evenly the back and adds Flos Caryophylli volatile oil and 43 parts of Borneolum Syntheticum fine powders, and colloid mill grinds well, and is pressed into soft capsule, promptly.Oral, one time 3,3 times on the one, warm water delivery service.
Embodiments of the invention 5: 70% ethanol of 10 times of amounts of 480 parts of usefulness of Fructus Choerospondiatis carries out percolation, collects percolate, is evaporated to thick paste; 240 parts of Radix Salviae Miltiorrhizaes carry out percolation with the 0.01mol/LHCl of 12 times of amounts earlier, the collection percolate, and after filtrate was adsorbed with the AB-8 resin, sour water was washed behind 4 column volumes with 3 column volumes of 95% ethanol elution, collects pure washing liquid; 95% ethanol percolation of the 14 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; 30 parts of water extraction of Concretio Silicea Bambusae 2 times, each amount of water is 10 times of medical material amount, and be 2 hours heat time heating time, filters, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 60 ℃ of vacuum dryings, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation for 60 parts, and is standby; With Macrogol 4000, put the mixed extract that adds Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae in the water-bath behind the heating and melting, stir evenly the back and add Flos Caryophylli volatile oil and 30 parts of Borneolum Syntheticum fine powders, stirring is transferred to reservoir, airtight and in 70 ℃ of insulations, is coolant with the methyl-silicone oil, drip and make ball, promptly.Oral, one time 18,3 times on the one, warm water delivery service.
Embodiments of the invention 6: 80% ethanol of 8 times of amounts of 240 parts of usefulness of Fructus Choerospondiatis carries out percolation, collects percolate, is evaporated to thick paste; 120 parts of first 0.02mol/LH of Radix Salviae Miltiorrhizae with 10 times of amounts
2SO
4Carry out percolation, collect percolate, after filtrate was adsorbed with the DS-401 resin, sour water was washed behind 3 column volumes with 6 column volumes of 60% ethanol elution, collects pure washing liquid; 95% ethanol percolation of the 12 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; 15 parts of water extraction of Concretio Silicea Bambusae 3 times, each amount of water is 8 times of medical material amount, and be 1 hour heat time heating time, filters, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 50 ℃ of vacuum dryings, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation for 30 parts, and is standby; With Macrogol 4000, put the mixed extract that adds Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae in the water-bath behind the heating and melting, stir evenly the back and add Flos Caryophylli volatile oil and 15 parts of Borneolum Syntheticum fine powders, stirring is transferred to reservoir, drips to make ball, promptly.Oral, one time 18,3 times on the one, warm water delivery service.
Embodiments of the invention 7: 60% ethanol of 12 times of amounts of 720 parts of usefulness of Fructus Choerospondiatis carries out percolation, collects percolate, is evaporated to thick paste; 360 parts of first 0.005mol/L H of Radix Salviae Miltiorrhizae with 14 times of amounts
2SO
4Carry out percolation, collect percolate, after filtrate was adsorbed with the DAl resin, sour water was washed behind 4 column volumes with 3 column volumes of 99% ethanol elution, collects pure washing liquid; 95% ethanol percolation of the 16 times of amounts of Radix Salviae Miltiorrhizae residue reuse behind the water percolation is collected percolate, merges with above-mentioned eluent, is evaporated to thick paste; 45 parts of water extraction of Concretio Silicea Bambusae 1 time, amount of water are 12 times of medical material amount, and be 3 hours heat time heating time, filter, and merging filtrate is evaporated to thick paste; Merge above medicinal liquid, concentrate, behind 70 ℃ of vacuum dryings, be ground into fine powder, standby; Flos Caryophylli is extracted volatile oil with vapor distillation for 90 parts, and is standby; With Macrogol 4000, put the mixed extract that adds Fructus Choerospondiatis, Radix Salviae Miltiorrhizae, Concretio Silicea Bambusae in the water-bath behind the heating and melting, stir evenly the back and add Flos Caryophylli volatile oil and 45 parts of Borneolum Syntheticum fine powders, stirring is transferred to reservoir, drips to make ball, promptly.Oral, one time 18,3 times on the one, warm water delivery service.