CN100344321C - Medicinal composition, its preparation process and quality control method - Google Patents
Medicinal composition, its preparation process and quality control method Download PDFInfo
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Abstract
The present invention discloses a medicine composition for treating fatty liver and hyperlipemia, a preparation method thereof and a quality control method thereof. The traditional Chinese medicine composition is prepared from water plantain, trichosanthis, semen cassiae, rhubarb, radish seed, haw, red sage root, curcuma root and fleece-flower root, and can be prepared into various clinically acceptable preparations. The preparation method of the composition has the main steps: extracting the curcuma root in a steam distillation way; carrying out alcohol extraction to five medicinal herbs of the water plantain, the red sage root, the fleece-flower root, the rhubarb and the semen cassiae; simultaneously carrying out water decoction and extracting medicinal dregs after the alcohol extraction together with three medicinal herbs of the haw, the radish seed and the trichosanthis; combining the distilled extraction solution of the curcuma root with the extraction solution for decompression and concentration; combining, decompressing and drying the alcohol extract of the five medicine herbs with the extraction solution; adding auxiliary materials for preparing the preparation. The quality control method of the composition preparation comprises an identification method: a water plantain identification method or a haw pascal identification method. The content measurement of the quality control method is measured by the medicine composition preparation according to the oral dosage containing tanshinone IIA C19H18O3 which can not be less than 6.70 mg.
Description
Invention field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, method of quality control, particularly a kind of pharmaceutical composition for the treatment of fatty liver or hyperlipemia and preparation method thereof, method of quality control.
Background technology
Fatty liver can be an independently primary disease, but more is the performance of a certain systemic disease at liver, is the liver fat degeneration that is caused by the multiple disease and the cause of disease, and it is made a definite diagnosis depends on percutaneous transhepatic puncture biopsy or postmortem.The increase of intrahepatic deposition fat mainly is the increase of fatty acid and triglyceride, and cholesterol, cholesteryl ester and phospholipid etc. increase less, more definite fatty liver name, should comprise the character of the lipid material that deposits.Owing to most fatty livers is due to triglyceride deposits, so general alleged fatty liver belongs to the triglyceride fatty liver.A variety of causes causes the synthetic and excretory unbalance just easy generation TG of the interior triglyceride (TG) of liver to form fatty liver at intrahepatic deposition.Most applications is the reason of liver itself, and minority is the outer reason of liver.TG is determined by above-mentioned two kinds of balances at the thin actual concentrations that runs of liver.So the formation of fatty liver mainly ascribes following two aspects to: 1. synthetic lipid is too much in external lipid of hepatocyte or the liver, and the oxidized minimizing in liver of these lipids be liver can not be with the whole oxidations of these lipids, they synthesize TG again the most at last, cause the interior TG of liver and increase; 2. because of causing TG can not be assembled into very low density lipoprotein (VLDL), body malnutrition, poisoning, essential fatty acid shortage, choline or potein deficiency in time be secreted in the blood.Thus, TG's is synthetic uneven with the secretion generation in the liver, finally causes the generation of fatty liver.Usually said fatty liver mainly is meant by the chronic fatty liver due to the factors such as ethanol, nutrient imbalance.Because the improving constantly of living standard, the variation of dietary structure and relatively lagging behind of prevention and health care measure, the prevalence of China's fatty liver is remarkable increase trend, becomes one of modal disease in recent years.
Summary of the invention
The object of the invention is to disclose a kind of pharmaceutical composition, another object of the present invention is to disclose this preparation of drug combination method and method of quality control, and the 3rd purpose of the present invention is to disclose the application of this pharmaceutical composition in the medicine of treatment fatty liver or hyperlipemia.
The present invention is achieved through the following technical solutions
The crude drug composition and the proportioning of pharmaceutical composition of the present invention are as follows:
Rhizoma Alismatis 30-60 weight portion Fructus Trichosanthis 20-50 weight portion Semen Cassiae 20-50 weight portion
Radix Et Rhizoma Rhei 5-10 weight portion Semen Raphani 20-40 weight portion Fructus Crataegi 20-50 weight portion
Radix Salviae Miltiorrhizae 20-50 weight portion Radix Curcumae 20-40 weight portion Radix Polygoni Multiflori 20-50 weight portion
The optimum ratio of above-mentioned raw materials medicine is
Rhizoma Alismatis 40-50 weight portion Fructus Trichosanthis 30-40 weight portion Semen Cassiae 30-40 weight portion
Radix Et Rhizoma Rhei 7-9 weight portion Semen Raphani 20-30 weight portion Fructus Crataegi 30-40 weight portion
Radix Salviae Miltiorrhizae 30-40 weight portion Radix Curcumae 20-30 weight portion Radix Polygoni Multiflori 30-40 weight portion
The optimum ratio of above-mentioned raw materials medicine can also for:
Rhizoma Alismatis 46 weight portion Fructus Trichosanthis 31 weight portion Semen Cassiaes 31 weight portions
Radix Et Rhizoma Rhei 7.5 weight portion Semen Raphanis 23 weight portion Fructus Crataegis 31 weight portions
Radix Salviae Miltiorrhizae 31 weight portion Radix Curcumaes 23 weight portion Radix Polygoni Multiflori 31 weight portions
Press practice of pharmacy, the above-mentioned raw materials medicine can be prepared into various clinical acceptable forms, include but not limited to a kind of in the middle of the following dosage form: as solid preparations such as tablet, pill, capsule, granule, drop pill, soft capsule and suppository, freeze-dried powders, liquid preparations such as suspensoid, oral liquid, enema.
Preparation method comprises the steps:
Radix Curcumae adds 5-8 times of water gaging, soaks after 6-10 hour, and vapor distillation extracted volatile oil 1.5-6.5 hour, and aqueous solution after the distillation and medicinal residues device are in addition collected, and volatile oil and beta-schardinger dextrin-be weight ratio 1 by volume: 4-8 doubly measures and makes clathrate; Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, Semen Cassiae add 3-7,3-5,2-4 successively and doubly measure the 50-90% alcohol reflux 3 times, and each 1-2 hour, merge extractive liquid, filtered, filtrate recycling ethanol and relative density 1.30～1.35 when being evaporated to 80 ℃; Radix Curcumae medicinal residues behind medicinal residues and the distillating extracting oil merge, add Fructus Crataegi, Semen Raphani, Fructus Trichosanthis, adding 6-8 times of medical material water gaging decocted 1-2 hour, adding 4-6 times of medical material water gaging again decocts 1-2 time, each 1-2 hour, aqueous solution after collecting decoction and the distillation, filter, density 1.10～1.15 when filtrate decompression is concentrated into to 80 ℃ adds ethanol and makes determining alcohol reach 50-70%, fully stir, left standstill 20-30 hour, and filtered, filtrate recycling ethanol and relative density 1.30～1.35 when being evaporated to 80 ℃, with Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, the Semen Cassiae ethanol extract merges, 70-90 ℃ of drying under reduced pressure is ground into fine powder, with the Benexate Hydrochloride mixing of Radix Curcumae, encapsulated or add acceptable clinically any adjuvant, make acceptable clinically various oral formulations.
The method of quality control that this pharmaceutical composition is made medicament comprises discriminating and/or assay.
Discrimination method comprises in the following method a kind of and/or several in the method for quality control of this pharmaceutical composition
A, get this drug combination preparation day 2.32 times of taking doses, added the 40-60% alcohol reflux 1-1.5 hour, filter, filtrate is concentrated into 10ml, adds 10ml water and mixes, and extracts 2-3 time with the jolting of 30ml ethyl acetate at every turn, merge ethyl acetate extraction liquid, evaporate to dryness, residue add methanol 2-5ml makes dissolving, as need testing solution.Other gets Rhizoma Alismatis control medicinal material powder 5-8g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 13-15: 5-8: toluene-ethyl acetate-formic acid of 2 is developing solvent, launch, take out, dry, acetic anhydride-concentrated sulphuric acid-ethanol solution of spray 1-1.5: 1-1.5: 1-1.5, clear 105 ℃ of bakings to developing the color; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
B, get this drug combination preparation day 1.16 times of taking doses, add methanol 20-30ml, supersound process 10-20 minute, filter, filtrate evaporate to dryness, residue add 0.5-0.8% sodium hydroxide solution 20ml dissolving, transfer pH value to 1～2 with 10% sulphuric acid, transfer in the separatory funnel, use benzene extraction 2-3 time, each 20-25ml, merge extractive liquid,, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution, other gets Fructus Crataegi control medicinal material 2g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography.Draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 10-15: 4-6: 0.5-0.8 toluene-ethyl acetate-acetic acid is developing solvent, launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
C, get this drug combination preparation day 1.16 times of taking doses, add methanol 20-30ml, supersound process 10-20 minute, filter, filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution, other gets Radix Curcumae control medicinal material 2g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography.Draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 4-6: 1-3 petroleum ether-ethyl acetate is developing solvent, launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
Content assaying method in the method for quality control comprises the steps:
Chromatographic condition and system suitability test are filler with octadecylsilane key silica gel, and the methanol-water of 70-75: 25-30 is a mobile phase, and the detection wavelength is 270nm.Number of theoretical plate is pressed Tanshinone I I
AThe peak calculates, and should be not less than 2000;
The preparation precision of reference substance solution takes by weighing Tanshinone I I
AReference substance 5mg puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up; Precision is measured 2ml, puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up, and promptly gets to contain Tanshinone I I among every 1ml
A16 μ g;
The content 0.5g under the content uniformity item is got in the preparation of need testing solution, and accurate the title decides, and puts in the tool plug conical flask, the accurate 1-1.5 that adds: 1-1.5 methanol-dichloromethane 50ml, close plug claims to decide weight, supersound process 20-30 minute, put coldly, claim to decide weight again, use 1-1.5: 1-1.5 methanol-dichloromethane is supplied the weight that subtracts mistake, shake up, filter, discard filtrate just, get subsequent filtrate as need testing solution;
Algoscopy: precision is drawn reference substance solution 10～15 μ l and is supplied the brilliant solution 5 μ l of examination respectively, and the injection chromatograph of liquid is measured, and calculates, promptly;
This drug combination preparation per diem taking dose contains tanshinone C
19H
18O
3Meter must not be less than 6.70mg;
Wherein the day taking dose at the drug combination preparation of the present invention described in the method for quality control is equivalent to day take the about 30.72g of crude drug amount.
In the experiment of this preparation of drug combination technical study, concentration technology all adopts low, the fireballing concentrating under reduced pressure method of temperature; Before the precipitate with ethanol medicine is concentrated into relative density 1.10～1.15 (80 ℃), because it is big as the too small then consumption of relative density alcohol amount, the excessive medicinal ingredient that then easily causes of relative density is lost because of containing, so concentrated solution relative density before the precipitate with ethanol is decided to be 1.10～1.15 (80 ℃); For the concentrating degree before dry, the principle of assurance is the maximum relative density when concentrated solution can be emitted from concentration tank smoothly, is 1.30～1.35 (80 ℃) after measured; Consider that tanshinone very easily destroys when higher temperature, so being chosen in of drying means is no more than drying under 60 ℃ of control temperature; The broken flour extraction of dried cream powder reaches 96.27%; The selection of capsule 's content existence, the result shows, makes the equal good fluidity of particulate content and fine powder and nonhygroscopic; Process is to the extraction process screening study, extracting solution has been carried out purification process, in that to guarantee that former preparation is taken the crude drug amount constant, when effective component extraction rate improves, greatly reduce this preparation taking dose, simultaneously, with reference to the animal effective dose of pharmacodynamics test and the conversion result of human body effective dose, finally determine the clinical taking dose of this preparation; Determined the production technology of blood fat reducing liver-benefiting capsules, on this basis, carried out pilot plant test research, the every batch of inventory is 20 times of recipe quantity, and volatile oil must be measured average 44.6ml, the broken flour extraction 95.1% of dried cream powder, 98.6%, three batch of pilot scale sample size of yield rate measurement result tanshinone content 0.636mg/ grain, by above data as seen, this stable preparation process property is better, can be used as big working condition foundation.
In the assay test of this pharmaceutical composition, reference substance Tanshinone I I
A(C
19H
18O
3) purchase in Nat'l Pharmaceutical ﹠ Biological Products Control Institute; Measure wavelength selective 2 70nm for measuring wavelength; Linear relationship examination Tanshinone I I
AThe range of linearity: 0.0644 μ g～0.3220 μ g., result of the test Y=-797026.50+46075057.45X r=0.9997; The negative controls interference test, the chromatogram of negative controls is at Tanshinone I I as a result
AThe corresponding retention time of chromatographic peak place is noiseless, and the peak occurs; Stability test is the result show, need testing solution chromatographic peak area score value is basic no change in 8 hours, and need testing solution is stable in 8 hours; Precision test result RDS is 0.25%, shows that content assaying method precision is good; Reproducible test results RSD is 1.19%, shows that the content assaying method method is stable, and repeatability is better; Recovery test meansigma methods as a result is 99.35%, and RSD is 1.42, shows that content assaying method is feasible.
The compound Chinese medicinal preparation that nine herbal medicine compositionss of the present invention are made, have that dampness removing reduces phlegm, blood circulation promoting and blood stasis dispelling, be used for the treatment of hyperlipidemia (belong to expectorant turbid check the card person) clinically, laboratory observation the influence of blood fat reducing liver-benefiting capsules (capsule preparations of this pharmaceutical composition) to rat high blood lipid model, pigeon high blood lipid model, mice high blood lipid model, the result shows, the blood fat reducing liver-benefiting capsules can significantly reduce high blood lipid model animal serum T-CHO and TG content, adjust lipoprotein content, reduce the lipopexia amount in tissue and the liver; And can significantly improve animal SOD level, reduce MDA content, thereby improve cell membrane function; Simultaneously can obviously reduce hyperlipidemia model of a syndrome rat whole blood viscosity (high, medium and low cutting), plasma viscosity, the erythrocytic aggregation of inhibition, improve the blood flow recurrent state.Laboratory observation the influence of blood fat reducing liver-benefiting capsules to DL-second thiamine acid liver lipidosis model, the result shows that said preparation has good improvement effect to the liver lipidosis.Pathological research shows that blood fat reducing the liver benefiting capsule improves significantly to the liver fat degeneration of high blood lipid model animal.
Following experimental example is used to further specify but is not limited to the present invention.
Experimental example 1:
Use the optimization experiment that steam distillation extracts volatile oil technical conditions in the Radix Curcumae
Use steam distillation and extract operation, from prerun as can be known, Radix Curcumae volatile oil belongs to light oil, retortable extraction, and the principal element that the volatile oil effect is extracted in influence is a distillation time, has carried out following test on the trial test basis:
Get 2 parts of 500g Radix Curcumaes, put respectively in the volatile oil extractor, add 5～6 times of water of medical material amount, soak after 6 hours, make to begin distillation after fully soaking into, own backflow picks up counting when producing, and control identical back-flow velocity, the different volatile oil constantly of record are carried to such an extent that measure respectively, the results are shown in Table 1.
Table 1, preferred Radix Curcumae volatile oil extraction conditions be table as a result
| Distillation time (h) | 1.5 | 2.0 | 2.5 | 3.0 | 3.5 | 4.0 | 4.5 | 5.0 | 5.5 | 6.0 | 6.5 |
| Extracted amount (ml) | 2.80 | 3.25 | 3.75 | 4.05 | 4.25 | 4.50 | 4.75 | 4.75 | 4.75 | 4.75 | 4.75 |
Above result shows that the extraction conditions of volatile oil is that medical material adds 6 times of water gagings in the Radix Curcumae medical material, distillation extraction 5 hours.
Experimental example 2: ethanol is to the optimization experiment of liposoluble constituent extractive technique condition in the five kinds of Chinese medicine such as Rhizoma Alismatis
Three factors, i.e. A of extraction effect have been determined to influence: used concentration of alcohol; B: at every turn add amount of alcohol; C: each extraction time, and, determined three levels for each factor in conjunction with practical situation, see Table 2.
Four flavor alcohol reflux such as table 2, Rhizoma Alismatis, Radix Salviae Miltiorrhizae are investigated the factor level table
Using orthogonal test is index with general anthraquinone extracted amount (colorimetry) contained in Radix Et Rhizoma Rhei, Radix Polygoni Multiflori, the Semen Cassiae, presses L
9(3
4) orthogonal table tests.
The preparation of sample liquid: with recipe quantity 1/10 is a duplicate samples (Rhizoma Alismatis 46.5, Semen Cassiae 31.0g, Radix Salviae Miltiorrhizae 31.0g, Radix Et Rhizoma Rhei 7.8g, Radix Polygoni Multiflori 31.0g), adds alcohol reflux by table 3 condition, and extract reclaims ethanol to bone dry, weighs.Investigate the mensuration of index and see appendix 1.The results are shown in Table 3, variance analysis as a result sees Table 4.
Table 3, orthogonal experiments
| The gauge outfit design | A | B | C | Blank | Result of the test |
| Row number | 1 | 2 | 3 | 4 | General anthraquinone extracted amount (mg) |
| 1 2 3 4 5 6 7 8 9 | 1 1 1 2 2 2 3 3 3 | 1 2 3 1 2 3 1 2 3 | 1 2 3 2 3 1 3 1 2 | 1 2 3 3 1 2 2 3 1 | 623.09 762.45 672.34 773.68 772.18 739.68 603.33 692.26 734.57 |
| Ij IIj IIIj Ij2 IIj2 IIIj2 S.Sj | 2057.88 2285.54 2030.16 4234870.09 5223693.09 4121549.63 13090.71 | 2000.10 2226.89 2146.59 4000400.01 4959039.07 4607848.63 8815.68 | 2055.03 2270.70 2047.85 4223148.30 5156078.49 4193689.62 10691.91 | 2129.84 2105.46 2138.28 4536218.43 4432961.81 4572241.36 193.64 | CT＝G 2/n＝ 4513613.56 Q＝I j 2+II j 2+III j 2 S.S j＝Q/3-CT |
Table 4, variance analysis
| Soruces of variation | Sum of deviation square | Degree of freedom | Mean square | The F value | Significance |
| A B C blank | 13090.71 8815.68 10691.91 193.64 | 2 2 2 2 | 6545.36 4407.84 5345.96 96.82 | 67.60 45.53 55.22 | P＜0.05 P＜0.05 P＜0.05 |
F
0.10(2，2)＝9.0；F
0.05(2，2)＝19.0；F
0.01(2，2)＝99.0
Above-mentioned variance analysis (table 4) is the result show: factor A (concentration of alcohol), B (ethanol consumption), C (extraction time) are even significant difference (P＜0.05), in conjunction with the intuitive analysis result, determines that best alcohol extraction technology is A
2B
2C
2, that is: 70% alcohol heating reflux extracts three times, and each 1.5 hours, alcohol adding amount was respectively 6,4,3 times.
Experimental example 3: decocting method extraction conditions optimization experiment
Character according to its chemical constituent, adopt traditional decocting cooking method that Fructus Crataegi, Semen Raphani, Fructus Trichosanthis are extracted, lose for fear of composition simultaneously, to distill or Radix Curcumae, Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, the Semen Cassiae medicinal residues of alcohol extraction are blended into together and carry out water and carry, through prerun, determine to influence three factors, i.e. A of extraction effect: each amount of water during decoction; B: each decocting time; C: decoct number of times, and determined three levels for each factor, see Table 5 in conjunction with practical situation.
On the investigation index of orthogonal test is determined, carry the composition (once attempting with the extracted amount of representing the composition Fructus Crataegi total flavones in the Fructus Crataegi is index, but too much because of impurity, disturbs greatly, and abandons) that part can not be measured because of water, therefore be to investigate index with the paste volume, press L
9(3
4U) orthogonal table is tested, to investigate the influence of above three factor levels variation to result of the test.
The preparation of sample liquid: accurately take by weighing medical material (Rhizoma Alismatis 46.5g in prescription 1/10 ratio, Semen Cassiae 31.0g, Fructus Crataegi 31.0g, Radix Salviae Miltiorrhizae 31.0g, Radix Et Rhizoma Rhei 7.8g, Radix Curcumae 23.3g, Radix Polygoni Multiflori 31.0g, Semen Raphani 23.3g, Fructus Trichosanthis 31.0g), totally 9 parts, wherein Radix Curcumae is used above-mentioned preferred optimum process condition and carries volatile oil, with Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, after Semen Cassiae is pressed the optimum process condition extraction with ethanol, three flavor medical materials such as medicinal residues and Fructus Crataegi merge, decoct the extraction operation by the listed condition of table 6, decocting boils, filter, filtrate placement is spent the night, remove precipitation, get supernatant, be concentrated into 100ml (2.559g crude drug/ml) be sample liquid to make 9 duplicate samples liquid.
Investigate the mensuration (mensuration of paste-forming rate) of index
Accurate each sample liquid 30ml that draws, in the evaporating dish of constant weight, water bath method is according to the dry weight-loss method gravimetry extremely.
Table 5, decocting method extract medical material and investigate the factor level table.
Table 6, orthogonal experiments
| The gauge outfit design | A | B | C | Blank | Result of the test |
| Row number | 1 | 2 | 3 | 4 | Dried cream extracted amount (mg) |
| 1 2 3 4 5 6 7 8 9 | 1 1 1 2 2 2 3 3 3 | 1 2 3 1 2 3 1 2 3 | 1 2 3 2 3 1 3 1 2 | 1 2 3 3 1 2 2 3 1 | 9.29 12.93 13.74 18.79 18.18 19.80 19.80 18.18 22.42 |
| Ij IIj IIIj Ij2 IIj2 IIIj2 S.Sj | 35.96 56.77 60.40 1293.12 3222.83 3648.16 115.95 | 47.88 49.29 55.96 2292.49 2429.50 3131.52 12.42 | 47.27 54.14 51.72 2234.45 2931.14 2674.96 8.10 | 49.89 52.53 50.71 2489.01 2759.41 2571.50 1.22 | CT＝G 2/n＝180698.67 Q＝I j 2+II j 2+III j 2 S.S j＝Q/3-CT |
Table 7, variance analysis
| Soruces of variation | Sum of deviation square | Degree of freedom | Mean square | The F value | Significance |
| A B C D | 115.95 12.42 8.10 1.22 | 2 2 2 2 | 57.98 6.21 4.05 0.61 | 95.04 10.18 6.64 | P＜0.05 |
Above-mentioned The results of analysis of variance shows: factor A (extraction time) has significant difference (P＜0.05), factor B (extraction time), C (amount of water) there was no significant difference (P＞0.05), and analysis result determines that best water extraction process is A in view of the above
3B
3C
2, promptly water extraction is 3 times, and each 1.5 hours, amount of water was 6 times (consider the water absorption problem of medical material, should add 2 times of amounts of water when extracting for the first time) of medical material total amount.
Experimental example 4: beta-schardinger dextrin-inclusion Radix Curcumae volatile oil technology condition is selected test
According to the inclusion time in the experimental study beta-cyclo dextrin included compound volatile oil process, the inclusion temperature is little to the influence of inclusion rate, and its influence of the comparison of volatile oil and beta-schardinger dextrin-is bigger, therefore, with saturated water solution method, condition, has carried out selecting to test to the ratio of volatile oil with beta-schardinger dextrin-under 4 hours the condition of ultrasonic inclusion 40 ℃ of inclusion temperature routinely.
The inclusion rate of table 8, volatile oil and the not commensurability ratio of beta-schardinger dextrin-
| β-CD(g) | Volatile oil (ml) | Inclusion rate (%) |
| 40 60 80 | 10 10 10 | 71.3 75.6 82.2 |
Volatile oil: the ratio of beta-schardinger dextrin-is 1: 8 (ml: in the time of g), the inclusion complex yield is the highest, so production technology inclusion method method is: get the beta-schardinger dextrin-of 8 times of amounts of volatile oil volume, put in the tool plug triangular flask, adding water puts water-bath in right amount and makes dissolving, reduce to temperature when being 40 ℃, add the equal amount of mixture of volatile oil and dehydrated alcohol, ultrasonic enclose 40 minutes, putting refrigerator and cooled hid 24 hours, sucking filtration is drained, and 40 ℃ of dryings promptly got clathrate in 4 hours.
Experimental example 5: separating technology development test
Because in this operational process of craft, medicinal residues separate with extracting solution, the precipitation of precipitate with ethanol all belongs to crude separation with separating of pure liquid, so adopt filterable mode; The filtration method: decompression (or pressurization) filters; The selection of filter material: it is filter material that 200 order nylon screens are selected in the filtration of medicinal residues and extracting solution for use; The precipitation of precipitate with ethanol is separated with pure liquid, after choosing supernatant and isolating with the method for siphon, is that filter material separates with 200 order nylon cloths.In order further to remove invalid components, reduce taking dose, after being concentrated, decocting liquid carried out the ethanol precipitation processing, with the macromolecular protein in place to go, polysaccharide composition.Consider principle economic, practical and that reduce effective one-tenth loss as far as possible, adopt the low-concentration ethanol precipitate with ethanol, through testing the purification process of selecting 60% ethanol precipitate with ethanol for use.
Experimental example 6: discrimination method test
In the discrimination test of Rhizoma Alismatis, be control medicinal material, make the sample that does not contain Rhizoma Alismatis in prescription ratio and method for making in addition, make the negative need testing solution of Rhizoma Alismatis with method with the Rhizoma Alismatis.Be that thin layer chromatography is carried out in developing solvent with toluene-ethyl acetate-formic acid (14: 7: 2), benzene-ethyl acetate-formic acid (10: 8: 0.5) respectively, the result shows that the former is good, and favorable reproducibility is as technical scheme.
In the discrimination test of Fructus Crataegi, be control medicinal material, make the sample that does not contain Fructus Crataegi in prescription ratio and method for making in addition, make the negative need testing solution of Fructus Crataegi with method with the Fructus Crataegi.Be that thin layer chromatography is carried out in developing solvent with toluene-ethyl acetate-acetic acid (12: 5: 0.6), chloroform-methanol-water (7: 2.5: 0.25) respectively, the result shows that the former is good, and favorable reproducibility is as technical scheme.
In the discrimination test of Radix Curcumae, be control medicinal material, make the sample that does not contain Radix Curcumae in prescription ratio and method for making in addition, make the negative need testing solution of Radix Curcumae with method with the Radix Curcumae.Be that thin layer chromatography is carried out in developing solvent with petroleum ether-ethyl acetate (5: 2), petroleum ether-acetone (10: 4) respectively, the result shows that the former is good, and favorable reproducibility is as technical scheme.
Because of Semen Cassiae, Radix Et Rhizoma Rhei, Radix Polygoni Multiflori all contain identical identifiable composition (compositions such as emodin, chrysophanol, chrysophanic acid), the three does not have specific component, so can't carry out the qualitative identification test to Semen Cassiae, Radix Et Rhizoma Rhei, Radix Polygoni Multiflori.Get this medicament composition capsule agent content 5g and add methanol 20ml, supersound process 10min filters, the filtrate evaporate to dryness, residue adds water 10ml makes dissolving, adds hydrochloric acid 1ml again, puts and heats 30min in the water-bath, extract 2 times with the ether gradation cooling back, each 20ml merges ether solution, evaporate to dryness, residue adds chloroform 1ml makes dissolving, as need testing solution.Get Radix Et Rhizoma Rhei, Semen Cassiae, each 2g of Radix Polygoni Multiflori control medicinal material, shine medical material solution in pairs with legal system.Get emodin, chrysophanol reference substance, add methanol and make the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 5 μ l of above-mentioned three kinds of solution, put respectively on same silica gel g thin-layer plate, with petroleum ether (60～90 ℃)-Ethyl formate-formic acid (15: 5: 1) upper strata is developing solvent, launches, and takes out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with control medicinal material, the corresponding position of reference substance chromatograph on, the three all shows the fluorescence speckle of same color, therefore can't distinguish because of Semen Cassiae, Radix Et Rhizoma Rhei, Radix Polygoni Multiflori.
In addition Semen Raphani, Fructus Trichosanthis have been carried out the thin layer discriminating, other composition has interference, so exclude technical scheme.
Experimental example 7: assay test
Select the Tanshinone I I in the ministerial drug Radix Salviae Miltiorrhizae in this pharmaceutical composition
ABe the composition of control finished product inherent quality, adopt high performance liquid chromatography that the blood fat reducing liver-benefiting capsules has been carried out assay.
The sample treatment condition is selected before the high effective liquid chromatography for measuring, and methanol-dichloromethane of selecting methanol and 1: 1 respectively for use is as extracting the solvent processing sample, but the need testing solution impurity that methanol is handled is too much, and impurity peaks is to Tanshinone I I in high-efficient liquid phase chromatogram
AThe peak is influential, and with methanol-dichloromethane 1: 1 as the sample that extracts after the solvent processing, Tanshinone I I in high-efficient liquid phase chromatogram
AThe peak good separating effect, impurity peaks is to Tanshinone I I
AThe peak is noiseless.
Instrument and reagent: day island proper Tianjin LC-10ATVP high performance liquid chromatograph, reference substance Tanshinone I I
AProvided by the calibrating of Chinese biological goods, methanol is chromatographically pure.Water is two flowing water.Chromatographic condition and system suitability test: ODS (250 * 4.6mm; 5 μ) chromatographic column (Di Ma company); Mobile phase: methanol-water (85: 15); Flow velocity: 1ml/min detects wavelength: 270nm; Sensitivity: 0.01AUFS; Decay: 4; Column temperature: room temperature.Number of theoretical plate (n): by above-mentioned chromatographic condition, inject need testing solution 10 μ l, the record chromatogram is measured Tanshinone I I
ARetention time (the t at peak
R) and half-peak breadth (W
0.5h), n=5.54 (t
R/ W
0.5h)
2=5.54 * (21/0.9)
2=3016.Get five batch samples, measure its content according to content assaying method in the technical scheme.
Table 9, five batch sample assay results
| Lot number | 010501 | 010502 | 010503 | 010504 | 010505 |
| Radix Salviae Miltiorrhizae II AContent (mg/ grain) | 1.37 1.39 | 0.84 0.81 | 0.77 0.74 | 1.22 1.25 | 1.31 1.34 |
Experimental example 8: the capsule of compositions is to the influence test of hyperlipidemia model rat blood serum total cholesterol level, triglyceride
Tried 48 of rats, male and female half and half.Body weight 180～200g.After weighing in, animal is divided into normal control group, model group, positive drug group (Xuezhikang group), blood fat reducing liver-benefiting capsules (capsule of this pharmaceutical composition) 1,2,3 administration groups at random.Totally 6 groups.Every group 8.Except that the normal control group, all the other the five groups of every preparation hyperlipidemia of rat animal models.Prepare the 14th day beginning gastric infusion in model.Once a day.Each treated animal dosage is: 1 group of blood fat reducing liver-benefiting capsules: 2g/kg body weight (20% blood fat reducing liver-benefiting capsules 10ml/kg); 2 groups of blood fat reducing liver-benefiting capsules: 1g/kg body weight (10% blood fat reducing liver-benefiting capsules 10ml/kg); 3 groups of blood fat reducing liver-benefiting capsules: 0.5g/kg body weight (5% blood fat reducing liver-benefiting capsules 10ml/kg), positive controls: 0.25g/kg body weight (2.5% XUEZHIKANG JIAONANG 10ml/kg); Matched group and model group give isometric(al) distilled water 10ml/kg.
The result shows, compares with matched group, and model group animal total cholesterol level and content of triglyceride all obviously raise (P＜0.001), and the prompting rat gives high lipid food and can cause the animal lipid level obviously to raise.Each treated animal serum total cholesterol content observation of blood fat reducing liver-benefiting capsules administration shows that compare with model group, the serum total cholesterol content of administration high dose group and middle dosage treated animal significantly reduces, and low dose group and model group be unknown significance difference relatively.But still be higher than the concurrent control group.Each the group between content of triglyceride comparison shows that high dose group animal serum content of triglyceride is starkly lower than model group (P＜0.05), relatively do not have significant difference (P＞0.05) with positive controls.Middle dosage group and low dose group and model group be unknown significance difference (P＞0.05) relatively.The above results shows that the blood fat reducing liver-benefiting capsules raises to the animal lipid level due to the high fat diet certain inhibitory action.
Comparison (the X ± s) of rat blood serum T-CHOL, triglyceride level is respectively organized in table 10 experiment
| Group | The example number | Dosage | T-CHO(mmol/L) | TG(mmol/L) |
| Dosage group low dose group in the matched group model group positive controls high dose group | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.5g/kg 0.5g/kg | 2.860±0.549 6.026±1.298### 4.271±0.691***### 3.835±0.635***### 5.154±0.754*### 5.805±1.095### | 1.278±0.245 1.766±0.666### 1.330±0.319* 1.284±0.218* 1.655±0.317## 1.775±0.347### |
Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
Compare with matched group: ##P＜0.01, ###P＜0.001.
Experimental example 9: to the influence test of high blood lipid model rat blood serum HDL-C and LDL-C content
The HDL-C test result shows, control rats Serum HDL-C content is 2.589 ± 0.421g/L, and model group rat blood serum HDL-C content is 1.176 ± 0.416, and the two relatively has significant difference (P＜0.001), shows that hyperlipidemia rat blood serum HDL-C content obviously reduces.
Observe after the administration and show, blood fat reducing liver-benefiting capsules administration high dose group and positive control drug group rat blood serum HDL-C content is apparently higher than model group (P＜0.01), middle dosage group and low dose group rat blood serum HDL-C content and model group there was no significant difference (P＞0.05).The low density lipoprotein, LDL change-detection is the result show, model group animal serum LDL-C content shows that apparently higher than matched group high blood lipid model raises with the low-density lipoprotein white level.Compare with model group, the LDL-C content of the high, medium and low dosage treated animal of blood fat reducing liver-benefiting capsules all obviously reduces, and the blood fat reducing liver-benefiting capsules of prompting doses has certain regulating action to hyperlipidemia animal model animal fat Developmental and Metabolic Disorder.
The comparison of each treated animal Serum HDL-C of table 11 and LDL-C content (X ± s)
| Group | The example number | Dosage | HKL-C(g/L) | LDL-C(g/L) |
| 3 groups of 2 groups of blood fat reducing the liver benefiting of 1 group of blood fat reducing the liver benefiting of matched group model group positive controls blood fat reducing the liver benefiting | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.5g/kg 0.5g/kg | 2.525±0.395 1.178±0.468### 2.007±0.711*** 1.751±0.281***# 1.410±0.233### 1.170±0.283### | 2.131±0.533 4.362±1.212### 2.616±0.553** 2.294±0.426** 2.353±0.654** 3.189±0.891** |
Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
Compare with matched group: ###P＜0.001, ##＜0.01.
Experimental example 10: the blood fat reducing liver-benefiting capsules is to the influence test of high blood lipid model hemorheology of rat
Blood is the suspendible body of visible component-cell and blood plasma, is subjected to influence of various factors in it flows, and whole blood viscosity is mainly with packed cell volume, plasma viscosity, carefully erythrocyte aggregation is relevant with deformability.Different shear rates has tangible influence to blood viscosity, and the variation of shear rate mainly influences erythrocytic gathering, during low shear rate, arranges the growth aggregation because erythrocyte is the cash strings sample, and blood viscosity increases.When shear rate raise, aggregation can depolymerization be single erythrocyte again, viscosity degradation, and the visible reduction of assembling with shear rate raises, and erythrocytic gathering is that blood viscosity reduces the main cause that increases with shear rate.Plasma viscosity also is the key factor that influences whole blood viscosity.
This experimental observation the influence of blood fat reducing liver-benefiting capsules to the high blood lipid model hemorheology of rat, the result shows, the whole blood viscosity that blood fat reducing liver-benefiting capsules high dose group and middle dosage group can obviously reduce the high blood lipid model rat lowly cuts, height is cut reduces plasma viscosity.Reduce erythrocyte aggregation index, increase erythrocytic deformation index, packed cell volume and reduction whole blood viscosity are not seen tangible influence.Show that the blood fat reducing liver-benefiting capsules to improving blood circulation state, reduces the blood compendency, improve erythrocyte membrane function tool and have certain effect.
Comparison (the X ± s) of rat whole blood viscosity is respectively organized in table 12 experiment
| Group | The example number | Dosage | Whole blood viscosity (mpa.s) | ||
| Low 10 (l/s) that cut | In cut 40 (l/s) | Whole blood 120 (l/s) | |||
| 3 groups of 2 groups of blood fat reducing the liver benefiting of 1 group of blood fat reducing the liver benefiting of matched group model group positive controls blood fat reducing the liver benefiting | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.5g/kg 0.5g/kg | 13.57±0.925 17.86±4.035## 15.45±2.082* 13.88±2.865** 14.48±2.019** 17.80±4.143 | 7.45±0.418# 8.55±1.271* 8.06±0.812 7.43±0.498* 7.88±1.332 8.86±1.302 | 5.22±0.215### 5.97±0.395 5.48±0.286** 5.40±0.476** 5.45±0.400** 5.88±0.882 |
Compare * P＜0.05, * * P＜0.01, * * * P＜0.001 with matched group.Compare with matched group: ###P＜0.001, #P＜0.05.
Comparison (the X ± s) of rat reduction whole blood viscosity is respectively organized in table 13 experiment
| Group | The example number | Dosage | Whole blood reduced viscosity (mPa.s) | ||
| Low 10 (l/s) that cut | In cut 40 (l/s) | Height is cut 120 (l/s) | |||
| Dosage group low dose group in the matched group model group positive controls high dose group | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.5g/kg 0.5g/kg | 26.84±1.948 33.95±7.091 27.97±6.450 26.46±6.096* 27.81±6.315 29.98±8.312 | 12.910±0.660 13.99±1.985 12.36±1.740 12.46±1.484 12.55±1.536 12.80±2.440 | 8.17±0.411 8.090±0.871 6.930±0.697 8.07±0.839 7.82±0.890 7.08±1.593 |
Compare * P＜0.05, * * P＜0.01, * * * P＜0.001. with matched group
Compare with matched group: ###P＜0.001, #P＜0.05.
The comparison of each treated animal plasma viscosity of table 14 (X ± s)
| The example number | Dosage | Plasma viscosity (mPa.s) 120 (l/s) | |
| Dosage group low dose group in the matched group model group positive controls high dose group | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.5g/kg 0.5g/kg | 1.575±0.114*** 2.180±0.287 2.052±0.189 1.683±0.182*** 1.850±0.231* 2.180±0.392 |
Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
The comparison of each treated animal packed cell volume of table 15, erythrocyte aggregation index (X ± s)
| Group | The example number | Dosage | Packed cell volume (%) | Erythrocyte aggregation index |
| Dosage group low dose group in the matched group model group positive controls high dose group | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.5g/kg 0.5g/kg | 45.425±1.756 46.136±3.465 47.613±2.324 46.108±3.114 47.045±1.964 45.246±0.984 | 2.594±0.187 3.501±0.456 2.813±0.457*** 2.553±0.342*** 2.760±0.430** 3.055±0.736 |
Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
Compare with matched group: ###P＜0.001, ##P＜0.01.
Each treated animal erythrocyte rigidity index of table 16, deformation index and the exponential comparison of electrophoresis (X ± s)
| Group | The example number | Dosage | Deformation index | The electrophoresis index |
| Dosage group low dose group in the matched group model group positive controls high dose group | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.5g/kg 0.5g/kg | 0.858±0.027## 0.734±0.058 0.648±0.065 0.810±0065** 0.780±0.056** 0.624±0.099 | 5.919±0.457# 6.596±0.629 5.930±1.072 5.538±0.811 6.140±0.698 5.860±1.521 |
Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
Compare with matched group: ###P＜0.001, ##P＜0.01.
Experimental example 11: to the influence of high blood lipid model animal serum superoxide dismutase, mda content variation
Blood fat reducing liver-benefiting capsules administration 1,2,3 treated animal SOD content are all apparently higher than model group; show that the blood fat reducing liver-benefiting capsules has certain promotion to the liver SOD activity; MDA content is starkly lower than model group simultaneously; prompting blood fat reducing liver-benefiting capsules may be organized the vigor of superoxide dismutase by raising; suppress the generation of peroxide malonaldehyde, liver injury model animal liver cell, mitochondrion, microsome and biomembrane change the certain protection effect of playing.
The comparison of table 17 each treated animal SOD in serum of experiment and MDA content (X ± s)
| Group | The example number | Dosage | SOD(nM/ml) | MDA(nM/ml) |
| Dosage group low dose group in the matched group model group positive controls high dose group | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.0g/kg 0.5g/kg | 42.17±2.393### 36.57±3.339 42.76±2.498*** 41.051±4.683* 40.54±2.005* 42.93±2.211* | 6.003±1.372### 9.175±2.151 5.910±1.533*** 6.245±1.417*** 6.544±1.076*** 8.109±1.474 |
Compare * P＜0.05, * * P＜0.01, * * * P＜0.001. with model group
Compare with matched group: ###P＜0.001.
Experimental example 12: the blood fat reducing liver-benefiting capsules is to the influence of high blood lipid model animal abdominal cavity fat amount
With model group relatively, each treated animal intraperitoneal lipopexia amount of blood fat reducing liver-benefiting capsules administration obviously reduces, the abdominal cavity fat coefficient reduces, prompting blood fat reducing liver-benefiting capsules can suppress fat accumulating in vivo.
The comparison of each treated animal abdominal cavity fat weight of table 18 experiment (X ± s)
| Group | The example number | Dosage | Abdominal cavity fat coefficient (g/100g body weight) |
| Dosage group low dose group in the matched group model group positive controls high dose group | 8 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.0g/kg 0.5g/kg | 1.649±0.366# 2.394±0.729 2.289±0.414* 1.725±0.194** 2.077±0.277* 1.834±0.554* |
Compare * P＜0.05, * * P＜0.01, * * * P＜0.001. with model group
Compare with matched group: ###P＜0.001.
Experimental example 13: to the lipopectic pathological observation of bait high blood lipid model rat liver
Tried 40 of rats, male and female half and half.Body weight 180-200g.After weighing in, animal is divided into normal control group, model group, positive drug group, blood fat reducing liver-benefiting capsules 1,2 administration groups, totally 5 groups at random.Every group 8.The animal sub-cage rearing, 4 in every cage is freely drunk water high lipid food.The preparation of hyperlipidemia animal model: except that the normal control group, all the other five groups of rats give high lipid food every day on time.Gave high lipid food continuously 14 days, behind the model copy, the high lipid food amount subtracts 1/3.Continue to give high lipid food and finish to experiment, the normal control group gives the conventional granulates feedstuff.
Prepare the 14th day beginning gastric infusion in model.Once a day.Each treated animal dosage is: 1 group of blood fat reducing liver-benefiting capsules: 2g/kg body weight (20% blood fat reducing liver-benefiting capsules 10ml/kg); 2 groups of blood fat reducing liver-benefiting capsules: 1g/kg body weight (10% blood fat reducing liver-benefiting capsules 10ml/kg); Positive controls: 0.25g/kg body weight (2.5% XUEZHINING CHONGJI 10ml/kg); Matched group and model group give isometric(al) tap water 10ml/kg.
Animal subject was promptly tested the 28th day by behind the above-mentioned dosage successive administration 14 days, put to death rat, cut the abdominal cavity, got right lobe of liver, and 5% formalin is fixed, the routine pathology section, and mirror is observed the liver fat degeneration down, foam cell forms and the hepatic lesions situation.
The comparison of each treated animal liver fat denaturation degrees of table 19 (X ± s)
| Group | The example number | Dosage | Hepatocyte fat range degree |
| Matched group model group positive controls high dose group low dose group | 8 8 8 8 8 | ---- ---- 0.25g/kg 2.0g/kg 1.0g/kg | 1.0±0.4 3.6±0.5 2.1±0.7** 1.1±0.4*** 2.1±0.4*** |
Compare * P＜0.05, * * P＜0.01, * * * P＜0.001. with model group
The above results shows, model group hepatic cell fattydegeneration showed increased, and the foam cell of formation that has shows the high blood lipid model success.Positive controls, high dose and low dose group animal livers cytopathy degree obviously alleviate, wherein the most obvious with high dose, low dosage is similar to hepatocyte fat change effect to positive controls, results suggest, the blood fat reducing liver-benefiting capsules has the liver fat degeneration of high blood lipid model rat and significantly alleviates effect, and is wherein best with the high dose effect.
Experimental example 14: the blood fat reducing liver-benefiting capsules is to pigeon high blood lipid model T-CHO and TG content
Get 50 of pigeons, be used for high blood model replication of Model, other gets 10 and is made as the blank group.The serum total cholesterol monitoring shows that pigeon gives high fat bait 14 days, and moulding is respectively organized pigeon serum total cholesterol content all apparently higher than the blank group, shows by high fat bait and duplicates the pigeon high blood lipid model.
Above-mentioned pigeon reduces by half in the 15th day high fat bait of experiment, the treatment group gives blood fat reducing liver-benefiting capsules suspension, positive controls gives the Xuezhikang suspension, blank group and the model control group distilled water that deturs talis dosis, the medicine of giving through irritating the stomach administration, dosage is: blood fat reducing liver-benefiting capsules treatment high dose group; 1.5g/kg body weight (15% blood fat reducing liver-benefiting capsules 10ml/kg body weight).Middle dosage group is irritated stomach and is given blood fat reducing liver-benefiting capsules suspension 1g/kg body weight (10% blood fat reducing liver-benefiting capsules 10ml/kg body weight).Blood fat reducing liver-benefiting capsules low dose group is irritated stomach and is given blood fat reducing liver-benefiting capsules suspension 0.5g/kg body weight (5% blood fat reducing liver-benefiting capsules 10ml/kg body weight).Positive drug control group: irritate stomach and give XUEZHIKANG JIAONANG 0.2g/kg body weight (2% XUEZHIKANG JIAONANG 10ml/kg body weight).Model group: irritate stomach and give body weight with volume distilled water 10ml/kg.
Gavage continuously and be administered to the 28th day.Get serum, spectrophotometry serum total cholesterol, triglyceride, high density lipoprotein (HDL), low density lipoprotein, LDL (LDL-C).
The comparison of each treated animal serum T-CHO, TG content behind table 20 drug treatment (X ± s)
| Group | The example number | Dosage | T-COH(mmol/L) | TG(mmol/L) |
| Dosage group low dose group in the matched group model group positive controls high dose group | 10 10 10 10 10 10 | ---- ---- 0.2g/kg 1.5g/kg 1.0g/kg 0.5g/kg | 3.891±0.971 7.251±1.06### 4.331±0.801*** 4.063±1.016*** 4.680±1.030*** 4.965±1.203*** | 2.111±0.696 3.543±0.495### 2.856±0.651* 2.677±0.451** 2.703±0.583** 3.010±0.628 |
Compare with matched group: ###P＜0.001.
Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
The result shows, compares with matched group, and model group animal T-CHO and TG content are all kept higher level.Show that high fat bait can bring out animal hyperlipidemia card.Compare with model group, each treated animal change of serum C HO of blood fat reducing liver-benefiting capsules administration group all is starkly lower than model group, and the TG content and the model group of high dose group and middle dosage group more also have significant difference.The administration of prompting blood fat reducing liver-benefiting capsules high dose has certain inhibitory action to model group animal CHO and TG rising.
Experimental example 15: to the influence test of pigeon high blood lipid model Serum HDL-C, LDH-C content
The comparison of each treated animal Serum HDL-C, LDH-C content behind table 21 drug treatment (X ± s)
| Group | The example number | Dosage | HDL-C(g/L) | LDH-C(g/L) |
| Dosage group low dose group in the matched group model group positive controls high dose group | 10 10 10 10 10 10 | ---- ---- 0.2g/kg 1.5g/kg 1.0g/kg 0.5g/kg | 2.505±0.183 3.195±0.436## 3.811±0.533*** 4.737±0.704*** 4.678±1.063*** 3.689±0.625* | 1.849±0.449 3.661±0.558### 2.691±0.534*** 2.657±0.449*** 2.951±0.488** 2.979±0.519** |
Compare with matched group: ##P＜0.01, ###P＜0.001.
Compare with model group: * P＜0.05, * * P＜0.01, * * * P＜0.001.
Compare with matched group, the HDL-C of model group animal, LDH-C content all obviously raise.Administration group and model group are relatively, the high, medium and low dosage group of blood fat reducing liver-benefiting capsules pigeon high blood lipid model Serum HDL-C all obviously raises, LDH-C content all obviously descends, compare unknown significance difference with positive control drug, results suggest blood fat reducing liver-benefiting capsules has regulating action preferably to pigeon high blood lipid model serum lipoprotein.
Experimental example 16: to the influence test of ethionine (DL-E) animal pattern liver lipidosis amount
The comparison of TG and CHO content in each treated animal liver tissue homogenate liquid of table 22 (X ± s)
| Group | The example number | Dosage | TG content (mmlo/L) | T-CHO(U/L) |
| Dosage DL-E+ low dosage among the normal control group DL-E model group DL-E+ Xuezhikang DL-E+ high dose DL-E+ | 10 10 10 10 10 10 | ---- ---- 5.0g/kg 4g/kg 2g/kg 1g/kg | 2.06±0.32 3.82±0.59### 3.14±0.58* 2.90±0.37** 3.22±0.35* 3.54±0.51* | 3.46±0.42 6.01±1.02### 4.76±0.76*** 4.50±0.98*** 4.98±0.93* 5.57±1.01 |
Compare * P＜0.05, * * P＜0.01, * * * P＜0.001. with model group
Compare with matched group: ###P＜0.001, #P＜0.05.
Compare with matched group, the TG level obviously raises in the model group animal liver tissue homogenate, and prompting DL-E can bring out the animal livers lipopexia and cause fatty liver.Compare with model group, blood fat reducing liver-benefiting capsules administration 1,2,3 treated animal hepatic tissue TG content obviously descend; Cholesterol level, unknown significance difference between model group and administration group.Show that the blood fat reducing liver-benefiting capsules improves significantly to liver lipopexia due to the Dl-E, does not see tangible influence to cholesterol level.
The preparation of embodiment 1. tablets
Get Rhizoma Alismatis 32kg, Fructus Trichosanthis 45kg, Semen Cassiae 25kg, Radix Et Rhizoma Rhei 6kg, Semen Raphani 35kg, Fructus Crataegi 25kg, Radix Salviae Miltiorrhizae 25kg, Radix Curcumae 40kg, Radix Polygoni Multiflori 25kg, make tablet, every heavy 0.36g, Patients with Fatty Liver is oral, one time 4,3 times on the one.
Embodiment 2: the preparation of granule
Rhizoma Alismatis 50kg, Fructus Trichosanthis 40kg, Semen Cassiae 30kg, Radix Et Rhizoma Rhei 8kg, Semen Raphani 30kg, Fructus Crataegi 35kg, Radix Salviae Miltiorrhizae 35kg, Radix Curcumae 35kg, Radix Polygoni Multiflori 35kg make granule, and the hyperlipemia patient is oral, one time one bag, 3 times on the one.
Embodiment 3: the preparation of drop pill
Rhizoma Alismatis 55kg, Fructus Trichosanthis 30kg, Semen Cassiae 40kg, Radix Et Rhizoma Rhei 10kg, Semen Raphani 25kg, Fructus Crataegi 45kg, Radix Salviae Miltiorrhizae 45kg, Radix Curcumae 25kg, Radix Polygoni Multiflori 45kg make drop pill, and Patients with Fatty Liver is oral, one time 10,3 times on the one.
Embodiment 4: the preparation of oral liquid
Rhizoma Alismatis 46kg, Fructus Trichosanthis 31kg, Semen Cassiae 31kg, Radix Et Rhizoma Rhei 7.5kg, Semen Raphani 23kg, Fructus Crataegi 31kg, Radix Salviae Miltiorrhizae 31kg, Radix Curcumae 23kg, Radix Polygoni Multiflori 31kg make oral liquid, every bottle of 100ml.Hyperlipemia is oral, a 10ml, 3 times on the one.
Embodiment 5: the preparation of colloid solution
Rhizoma Alismatis 43kg, Fructus Trichosanthis 33kg, Semen Cassiae 36kg, Radix Et Rhizoma Rhei 7kg, Semen Raphani 26kg, Fructus Crataegi 33kg, Radix Salviae Miltiorrhizae 36kg, Radix Curcumae 23kg, Radix Polygoni Multiflori 36kg make colloid solution, and Patients with Fatty Liver is oral, a 10ml, 3 times on the one.
Embodiment 6: the preparation of oral liquid
Rhizoma Alismatis 46kg, Fructus Trichosanthis 36kg, Semen Cassiae 33kg, Radix Et Rhizoma Rhei 9kg, Semen Raphani 23kg, Fructus Crataegi 36kg, Radix Salviae Miltiorrhizae 33kg, Radix Curcumae 26kg, Radix Polygoni Multiflori 33kg make oral liquid, and hyperlipemia is taken, a 10ml, 3 times on the one.
Embodiment 7: the preparation of capsule
Rhizoma Alismatis 465g, Fructus Trichosanthis 310g, Semen Cassiae 310g, Radix Et Rhizoma Rhei 78g, Semen Raphani 233g, Fructus Crataegi 310g, Radix Salviae Miltiorrhizae 310g, Radix Curcumae 233g, Radix Polygoni Multiflori 310g, more than nine the flavor, Radix Curcumae adds 6 times of water gagings, vapor distillation extracted volatile oil 5 hours, aqueous solution after the distillation and medicinal residues device are in addition collected, and volatile oil is made clathrate with 8 times of amount beta-schardinger dextrin-s (polishing).Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, Semen Cassiae adds 6,4, measure 70% alcohol reflux 3 times for 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate recycling ethanol also is evaporated to relative density 1.30～1.35 (80 ℃), Radix Curcumae medicinal residues behind medicinal residues and the distillating extracting oil merge, and add Fructus Crataegi, Semen Raphani, Fructus Trichosanthis adds 6 times of medical material water gagings and decocts (adding 2 times of water gagings when decocting for the first time) 3 times, each 1.5 hours, aqueous solution after collecting decoction and the distillation filters, and filtrate decompression is concentrated into to density 1.10～1.15 (80 ℃), adding ethanol makes determining alcohol reach 60%, fully stir, left standstill 24 hours, filter, filtrate recycling ethanol also is evaporated to relative density 1.30～1.35 (80 ℃), with Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, the Semen Cassiae ethanol extract merges, and drying under reduced pressure (80 ℃) is ground into fine powder, Benexate Hydrochloride mixing with Radix Curcumae, incapsulate, make 1000, promptly.
Embodiment 8: the discriminating of compositions
(1) gets the preparation method gained capsule content 10g of this pharmaceutical composition by technical scheme, add 50% alcohol reflux 1 hour, filter, filtrate is concentrated into 10ml, adds 10ml water and mixes, and extracts (30,30ml) 2 times with the ethyl acetate jolting, merge ethyl acetate extraction liquid, evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution.Other gets Rhizoma Alismatis control medicinal material powder 6g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene-ethyl acetate-formic acid (14: 7: 2) is developing solvent, launch, take out, dry, spray acetic anhydride concentrated sulphuric acid alcoholic solution (acetic anhydride-concentrated sulphuric acid-dehydrated alcohol 1: 1: 1), clear 105 ℃ of bakings to developing the color.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
(2) get the preparation method gained capsule content 5g of this pharmaceutical composition, add methanol 20ml, supersound process 10 minutes by technical scheme, filter, filtrate evaporate to dryness, residue add 0.5% sodium hydroxide solution 20ml dissolving, transfer pH value to 1～2 with 10% sulphuric acid, transfer in the separatory funnel, use benzene extraction 2 times, each 20ml, merge extractive liquid,, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution, other gets Fructus Crataegi control medicinal material 2g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography.Drawing each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with toluene-ethyl acetate-acetic acid (12: 5: 0.6), launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
(3) get the preparation method gained capsule content 5g of this pharmaceutical composition, add methanol 20ml, supersound process 10 minutes by technical scheme, filter, filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution, other gets Radix Curcumae control medicinal material 2g, shines medical material solution in pairs with legal system.Test according to thin layer chromatography.Drawing each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with petroleum ether-ethyl acetate (5: 2), launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
Embodiment 9: the assay of compositions
Chromatographic condition and system suitability test: with octadecylsilane key silica gel is filler, and methanol-water (73: 27) is a mobile phase, and the detection wavelength is 270nm.Number of theoretical plate is pressed Tanshinone I I
AThe peak calculates, and should be not less than 2000.
The preparation of reference substance solution: precision takes by weighing Tanshinone I I
AReference substance 5mg puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up; Precision is measured 2ml, puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up, and promptly gets (to contain Tanshinone I I among every 1ml
A16 μ g).
The preparation of need testing solution: get this pharmaceutical composition under the content uniformity item by the preparation method gained capsule content 0.5g of technical scheme, accurately claim surely, put in the tool plug conical flask, accurate methanol-dichloromethane (1: 1) 50ml that adds, close plug claims to decide weight, supersound process 20 minutes, put coldly, claim again to decide weight, supply the weight that subtracts mistake with methanol-dichloromethane (1: 1), shake up, filter, discard filtrate just, get subsequent filtrate as need testing solution.
Algoscopy: precision is drawn reference substance solution 10～15 μ l and is supplied the brilliant solution 5 μ l of examination respectively, and the injection chromatograph of liquid is measured, and calculates, promptly.
Originally get this pharmaceutical composition and contain Tanshinone I I by every of the preparation method gained capsule of technical scheme
A(C
19H
18O
3) must not be less than 0.56mg.
Claims (15)
1, a kind of pharmaceutical composition for the treatment of fatty liver or hyperlipemia is characterized in that this pharmaceutical composition is to be made by following raw material medicaments in part by weight:
Rhizoma Alismatis 30-60 weight portion Fructus Trichosanthis 20-50 weight portion Semen Cassiae 20-50 weight portion
Radix Et Rhizoma Rhei 5-10 weight portion Semen Raphani 20-40 weight portion Fructus Crataegi 20-50 weight portion
Radix Salviae Miltiorrhizae 20-50 weight portion Radix Curcumae 20-40 weight portion Radix Polygoni Multiflori 20-50 weight portion.
2, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition is to be made by following raw material medicaments in part by weight:
Rhizoma Alismatis 40-50 weight portion Fructus Trichosanthis 30-40 weight portion Semen Cassiae 30-40 weight portion
Radix Et Rhizoma Rhei 7-9 weight portion Semen Raphani 20-30 weight portion Fructus Crataegi 30-40 weight portion
Radix Salviae Miltiorrhizae 30-40 weight portion Radix Curcumae 20-30 weight portion Radix Polygoni Multiflori 30-40 weight portion.
3, pharmaceutical composition as claimed in claim 1 is characterized in that this pharmaceutical composition is to be made by following raw material medicaments in part by weight:
Rhizoma Alismatis 46 weight portion Fructus Trichosanthis 31 weight portion Semen Cassiaes 31 weight portions
Radix Et Rhizoma Rhei 7.5 weight portion Semen Raphanis 23 weight portion Fructus Crataegis 31 weight portions
Radix Salviae Miltiorrhizae 31 weight portion Radix Curcumaes 23 weight portion Radix Polygoni Multiflori 31 weight portions.
4,, it is characterized in that said composition makes dosage form clinical or that pharmaceutically accept as claim 1,2 or 3 described pharmaceutical compositions.
5, the dosage form of pharmaceutical composition as claimed in claim 4 is characterized in that this dosage form is tablet, pill, capsule, granule, drop pill, soft capsule, suppository, freeze-dried powder, suspensoid, oral liquid or enema.
6, as claim 1,2 or 3 described preparation of drug combination methods, it is characterized in that this method may further comprise the steps:
Radix Curcumae adds 5-8 times of water gaging, soaks after 6-10 hour, and vapor distillation extracted volatile oil 1.5-6.5 hour, and aqueous solution after the distillation and medicinal residues device are in addition collected, and volatile oil and beta-schardinger dextrin-be weight ratio 1 by volume: 4-8 doubly measures and makes clathrate; Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, Semen Cassiae add 3-7,3-5,2-4 successively and doubly measure the 50-90% alcohol reflux 3 times, and each 1-2 hour, merge extractive liquid, filtered, filtrate recycling ethanol and relative density 1.30～1.35 when being evaporated to 80 ℃; Radix Curcumae medicinal residues behind medicinal residues and the distillating extracting oil merge, add Fructus Crataegi, Semen Raphani, Fructus Trichosanthis, adding 6-8 times of medical material water gaging decocted 1-2 hour, adding 4-6 times of medical material water gaging again decocts 1-2 time, each 1-2 hour, aqueous solution after collecting decoction and the distillation, filter, density 1.10～1.15 when filtrate decompression is concentrated into to 80 ℃ adds ethanol and makes determining alcohol reach 50-70%, fully stir, left standstill 20-30 hour, and filtered, filtrate recycling ethanol and relative density 1.30～1.35 when being evaporated to 80 ℃, with Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, the Semen Cassiae ethanol extract merges, 70-90 ℃ of drying under reduced pressure is ground into fine powder, with the Benexate Hydrochloride mixing of Radix Curcumae, the adjuvant encapsulated or adding is accepted is clinically made oral formulations.
7, preparation of drug combination method as claimed in claim 6 is characterized in that this method may further comprise the steps:
Radix Curcumae adds 6 times of water gagings, and vapor distillation extracted volatile oil 5 hours, and aqueous solution after the distillation and medicinal residues device are in addition collected, and volatile oil has polishing to make clathrate with 8 times of amount beta-schardinger dextrin-s; Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, Semen Cassiae adds 6,4, measure 70% alcohol reflux 3 times for 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate recycling ethanol and be 1.30～1.35 when being evaporated to 80 ℃ of relative densities, the Radix Curcumae medicinal residues behind medicinal residues and the distillating extracting oil merge, and add Fructus Crataegi, Semen Raphani, Fructus Trichosanthis, adding 8 times of medical material water gagings decocted 1.5 hours, add 6 times of medical material water gagings again and decoct 2 times, each 1.5 hours, the aqueous solution after collecting decoction and the distillation, filter, filtrate decompression be concentrated into to density be 1.10～1.15 80 ℃ the time, add ethanol and make determining alcohol reach 60%, fully stir, left standstill 24 hours, filter, filtrate recycling ethanol and to be evaporated to relative density be 1.30～1.35 in the time of 80 ℃ is with Rhizoma Alismatis, Radix Salviae Miltiorrhizae, Radix Polygoni Multiflori, Radix Et Rhizoma Rhei, the Semen Cassiae ethanol extract merges, at 80 ℃ of drying under reduced pressure, be ground into fine powder, the Benexate Hydrochloride mixing with Radix Curcumae incapsulates, the adjuvant encapsulated or adding is accepted is clinically made oral formulations.
8,, it is characterized in that discrimination method in this method comprises a kind of and/or several in the following discriminating as the method for quality control of claim 1,2 or 3 described pharmaceutical compositions:
A, get this drug combination preparation day 2.32 times of taking doses, added the 40-60% alcohol reflux 1-1.5 hour, filter, filtrate is concentrated into 10ml, adds 10ml water and mixes, and extracts 2-3 time with the jolting of 30ml ethyl acetate at every turn, merge ethyl acetate extraction liquid, evaporate to dryness, residue add methanol 2-5ml makes dissolving, as need testing solution; Other gets Rhizoma Alismatis control medicinal material powder 5-8g, shines medical material solution in pairs with legal system; Test according to thin layer chromatography, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 13-15: 5-8: toluene-ethyl acetate-formic acid of 2 is developing solvent, launch, take out, dry, acetic anhydride-concentrated sulphuric acid-ethanol solution of spray 1-1.5: 1-1.5: 1-1.5, clear 105 ℃ of bakings to developing the color; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
B, get this drug combination preparation day 1.16 times of taking doses, add methanol 20-30ml, supersound process 10-20 minute, filter, filtrate evaporate to dryness, residue add 0.5-0.8% sodium hydroxide solution 20ml dissolving, transfer pH value to 1～2 with 10% sulphuric acid, transfer in the separatory funnel, use benzene extraction 2-3 time, each 20-25ml, merge extractive liquid,, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution, other gets Fructus Crataegi control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to thin layer chromatography; Draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 10-15: 4-6: 0.5-0.8 toluene-ethyl acetate-acetic acid is developing solvent, launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C, get this drug combination preparation day 1.16 times of taking doses, add methanol 20-30ml, supersound process 10-20 minute, filter, filtrate evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution, other gets Radix Curcumae control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to thin layer chromatography; Draw each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with 4-6: 1-3 petroleum ether-ethyl acetate is developing solvent, launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
9, the method for quality control of pharmaceutical composition as claimed in claim 8 is characterized in that discrimination method in this method comprises a kind of and/or several in the following discriminating:
A, get this drug combination preparation day 2.32 times of taking doses, add 50% alcohol reflux 1 hour, filter, filtrate is concentrated into 10ml, adds 10ml water and mixes, and extracts 2-3 time with the jolting of 30ml ethyl acetate at every turn, merge ethyl acetate extraction liquid, evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets Rhizoma Alismatis control medicinal material powder 6g, shines medical material solution in pairs with legal system; According to the thin layer chromatography test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene-ethyl acetate-formic acid of 14: 7: 2 was developing solvent, launched, and took out, dry, spray acetic anhydride-concentrated sulphuric acid-ethanol solution of 1: 1: 1, clear 105 ℃ of bakings to developing the color; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
B, get this drug combination preparation day 1.16 times of taking doses, add methanol 20ml, supersound process 10 minutes, filter, filtrate evaporate to dryness, residue add 0.5% sodium hydroxide solution 20ml dissolving, transfer pH value to 1～2 with 10% sulphuric acid, transfer in the separatory funnel, use benzene extraction 2 times, each 20ml, merge extractive liquid,, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution, other gets Fructus Crataegi control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to thin layer chromatography; Drawing each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with 12: 5: 0.6 toluene-ethyl acetate-acetic acid, launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
C, get this drug combination preparation day 1.16 times of taking doses, add methanol 20ml, supersound process 10 minutes filters, and filtrate evaporate to dryness, residue add methanol lml makes dissolving, and as need testing solution, other gets Radix Curcumae control medicinal material 2g, shines medical material solution in pairs with legal system; Test according to thin layer chromatography; Drawing each 2 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developing solvent with 5: 2 petroleum ether-ethyl acetates, launches, and takes out, and dries, and spray is dried by the fire to clear spot at 105 ℃ with 5% phosphomolybdic acid ethanol solution; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
10,, it is characterized in that assay in this method is to comprise a kind of and/or several in the following assay method as the method for quality control of claim 1,2 or 3 described pharmaceutical compositions:
Chromatographic condition and system suitability test: with octadecylsilane key silica gel is filler, and the methanol-water of 70-75: 25-30 is a mobile phase, and the detection wavelength is 270nm; Number of theoretical plate is pressed Tanshinone I I
AThe peak calculates, and should be not less than 2000;
The preparation of reference substance solution: precision takes by weighing Tanshinone I I
AReference substance 5mg puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up; Precision is measured 2ml, puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up, and promptly gets to contain Tanshinone I I among every 1ml
A16 μ g;
The preparation of need testing solution: get the content 0.5g under the content uniformity item, the accurate title, decide, and puts in the tool plug conical flask, the accurate 1-1.5 that adds: 1-1.5 methanol-dichloromethane 50ml, close plug claims to decide weight, supersound process 20-30 minute, put coldly, claim to decide weight again, use 1-1.5: 1-1.5 methanol-dichloromethane is supplied the weight that subtracts mistake, shake up, filter, discard filtrate just, get subsequent filtrate as need testing solution;
Algoscopy: precision is drawn reference substance solution 10～15 μ l and is supplied the brilliant solution 5 μ l of examination respectively, and the injection chromatograph of liquid is measured, and calculates, promptly;
This drug combination preparation per diem taking dose contains tanshinone C
19H
18O
3Meter must not be less than 6.70mg.
11, the method for quality control of pharmaceutical composition as claimed in claim 10 is characterized in that assay in this method is to comprise a kind of and/or several in the following assay method:
Chromatographic condition and system suitability test: with octadecylsilane key silica gel is filler, and 73: 27 methanol-water is a mobile phase, and the detection wavelength is 270nm; Number of theoretical plate is pressed Tanshinone I I
AThe peak calculates, and should be not less than 2000;
The preparation of reference substance solution: precision takes by weighing Tanshinone I I
AReference substance 5mg puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up; Precision is measured 2ml, puts in the brown measuring bottle of 25ml, adds methanol to scale, shakes up, and promptly gets to contain Tanshinone I I among every 1ml
A16 μ g;
The preparation of need testing solution: get the content 0.5g under the content uniformity item, the accurate title, decide, and puts in the tool plug conical flask, 1: 1 methanol-dichloromethane 50ml of accurate adding, close plug claims to decide weight, supersound process 20 minutes, put coldly, claim again to decide weight, supply the weight that subtracts mistake with 1: 1 methanol-dichloromethane, shake up, filter, discard filtrate just, get subsequent filtrate as need testing solution;
Algoscopy: precision is drawn reference substance solution 10～15 μ l and is supplied the brilliant solution 5 μ l of examination respectively, and the injection chromatograph of liquid is measured, and calculates, promptly;
This drug combination preparation per diem taking dose contains tanshinone C
19H
18O
3Meter must not be less than 6.70mg.
12, as claim 1, the application of 2 or 3 described pharmaceutical compositions in the medicine of preparation treatment fatty liver.
13, as claim 1, the application of 2 or 3 described pharmaceutical compositions in the medicine of preparation treatment hyperlipidemia.
14, the application of pharmaceutical composition as claimed in claim 12, it is characterized in that described treatment fatty liver is meant improves the liver lipidosis or improves the liver fat degeneration.
15, the application of pharmaceutical composition as claimed in claim 13, it is characterized in that described treatment hyperlipidemia is meant reduction serum total cholesterol and content of triglyceride, adjust lipoprotein content, reduce lipopexia amount, raising superoxide dismutase level in tissue and the liver, reduce mda content, improve cell membrane function, reduce plasma viscosity, suppress erythrocytic aggregation or improve the blood flow recurrent state.
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| CN102139084B (en) * | 2011-04-01 | 2012-02-22 | 南京中医药大学 | Chinese medicinal composition for treating fatty liver and preparation method and application thereof |
| CN102228577B (en) * | 2011-06-14 | 2012-07-25 | 南京正宽医药科技有限公司 | Traditional Chinese medicine composition for treating hyperlipemia, and preparation method and application thereof |
| CN103033586A (en) * | 2011-09-30 | 2013-04-10 | 西安千禾药业有限责任公司 | Detection method of medicament for treating coronary disease and stenocardia |
| CN105999109A (en) * | 2016-07-19 | 2016-10-12 | 杜娜 | Traditional Chinese medicine composition for treating high blood lipid |
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| CN1478508A (en) * | 2002-12-31 | 2004-03-03 | 临沂新时代药业有限公司 | Chinese medicinal composition for treating fatty liver and its preparation method |
| CN1478497A (en) * | 2002-08-31 | 2004-03-03 | 邱学良 | Medicine for treating fatty liver |
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