CN1309372C - Preparation of granular powder for treating hepatitis and quality control method - Google Patents
Preparation of granular powder for treating hepatitis and quality control method Download PDFInfo
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- CN1309372C CN1309372C CNB200410078096XA CN200410078096A CN1309372C CN 1309372 C CN1309372 C CN 1309372C CN B200410078096X A CNB200410078096X A CN B200410078096XA CN 200410078096 A CN200410078096 A CN 200410078096A CN 1309372 C CN1309372 C CN 1309372C
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- weight portion
- methanol
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- 238000003908 quality control method Methods 0.000 title claims abstract description 12
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 72
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Abstract
The present invention relates to a method for preparing a traditional Chinese medicine granule preparation and a quality control method, wherein the traditional Chinese medicine granule preparation has the effects of clearing away heat, promoting diuresis, reinforcing the spleen, nourishing blood, benefiting qi and relieving the depressed liver, and is mainly used for treating chronic hepatitis, early-stage liver cirrhosis, fatty liver and toxic hepatitis. The preparation is prepared from 16 kinds of traditional Chinese medicine as raw material medicine, such as virgate wormwood herb, etc., and contains 200 parts of beta-cyclodextrin by weight. In a preparation process, methods of spray-drying and dry type granulation are used so as to reserve effective components to a maximum degree, so the stability of the medicine is obviously improved. The quality control method of the preparation comprises the thin layer identification of Chinese angelica, white peony alba, red sage root, milkvetch root and licorice, and the detection of the content of paeoniflorin, wherein octadecylsilane chemically bonded silica is used as filler on chromatographic columns, and methanol and 0.05% of trifluoroacetic acid liquid with the volume ratio of 28: 72 are used as mobile phases; a detecting wavelength is 230 nanometers, a flow velocity is 1.0 ml/min, and column temperature is 30 DEG C; each bag of the preparation contains no less than 8.0 mg of white peony alba according to the content of paeoniflorin.
Description
(technical field)
The present invention relates to a kind of preparation method and method of quality control for the treatment of the granule of hepatitis, this granule is a kind of clearing away heat-damp and promoting diuresis that has, and spleen reinforcing is nourished blood, the effect of QI invigorating resolving depression is used for the treatment of chronic hepatitis, early stage liver cirrhosis, fatty liver, the medicine of toxic hepatitis belongs to the field of Chinese medicines.
(background technology)
China is the hotspot of viral hepatitis, and according to the report of infectious disease of health and epidemic prevention department, the annual morbidity of China's viral hepatitis is 95/10000ths, and its sickness rate occupies the 3rd in Notifiable disease, is only second to infectious diarrhea and influenza; And hepatitis also need be taken hepatic for a long time.Take the modern chemistry medicine for a long time has the side effect of impairing the liver more, and Chinese medicine is characteristic with many active component, many target spots drug effect, and treatment is characteristics with the ill physiological function of conditioning, and can be for taking for a long time.Therefore, develop the Chinese medicine traditional advantage, the exploitation preparation stabilization, drug safety, dosage is accurate, quality controllable, the reliable Chinese medicine preparation of curative effect is significant.
Chinese medicine QINGGAN TANGJIANG (" second in People's Republic of China's national drug standards Chinese traditional patent formulation preparation ", the committee of pharmacopeia chief editor of Ministry of Health of the People's Republic of China, on December 31st, 1991) be a kind of chronic hepatitis that is used for the treatment of, early stage liver cirrhosis, fatty liver, the Chinese medicine patent medicine preparation of toxic hepatitis, by main material medicine Artemisia anethoicles Mattf, Radix Isatidis, Radix Angelicae Sinensis, the Radix Paeoniae Alba, Radix Salviae Miltiorrhizae, Radix Curcumae, the Radix Astragali, Radix Codonopsis, Rhizoma Alismatis, Rhizoma Polygonati, Radix Rehmanniae, Rhizoma Dioscoreae, Fructus Crataegi, Massa Medicata Fermentata, Radix Gentianae Macrophyllae, Radix Glycyrrhizae is made, in the side with the Herba Artemisiae Scopariae clearing away heat-damp and promoting diuresis, the Radix Codonopsis strengthening QI of middle-JIAO, the Radix Astragali, the Rhizoma Dioscoreae air making-up and spleen enlivening, the Radix Salviae Miltiorrhizae nourshing blood and promoting blood circulation is principal agent altogether; Radix Angelicae Sinensis, the Radix Paeoniae Alba, the Radix Rehmanniae, Rhizoma Polygonati YIN nourishing (blood) nourishing the liver, Fructus Crataegi, Massa Medicata Fermentata invigorating the spleen and regulating the stomach; The Radix Isatidis heat-clearing and toxic substances removing, the Radix Gentianae Macrophyllae removing obstruction in the collateral to relieve pain, the Radix Curcumae stasis of blood liver heat removing of living be adjuvant drug altogether, the Rhizoma Alismatis dampness removing, Radix Glycyrrhizae with in, be messenger drug altogether.Modern scientific research shows that the effective ingredient of Herba Artemisiae Scopariae is a chlorogenic acid, chlorogenic acid have protect the liver, the effect of function of gallbladder promoting, antiviral [Hu Runsheng. Herba Artemisiae Scopariae effective ingredient and kind, collection period and medicinal part relation.Chinese patent medicine; 1998; 20 (5): 47]; ferulic acid has antibiotic; antiviral effect [Ou Shiyi; Bao Huiyan; Lan Zhidong. the Advance on Pharmacological Activities of ferulic acid and derivant thereof. Chinese crude drug; 2001; 24 (3): 220], glycyrrhizic acid can direct anti-HBV and improve hepatic insufficiency [the public health of Rhizoma Atractylodis macrocephalae. glycyrrhizic acid function of resisting hepatitis B virus mechanism. and Chinese medicine pharmaceutical journal (day), 1995; 12 (1): 24]; in the Radix Angelicae Sinensis water soluble ingredient Radix Angelicae Sinensis have liver-protective effect [Wang Hui, Peng Renxiu. angelicin is to the protective effect of carbon tetrachloride hepatic injury. Hubei medical college journal, 1992; 13 (2): 117]; peoniflorin in the Radix Paeoniae Alba also has hepatoprotective effect [icariin; peoniflorin. Chinese agriculture guide to investment, 2001, (12): 31～32].
At present, " QINGGAN TANGJIANG " is liquid preparation, its preparation process falls behind, in order to improve the dissolubility of acid effective ingredient, medicinal liquid needs adjust pH to 8, but under the condition of higher pH value, heating can make a large amount of Polyphenols compositions (as chlorogenic acid, ferulic acid etc.) destroy when concentrating, and glycoside effective ingredient basic hydrolysis such as peoniflorin is destroyed, make its content descend at double (referring to embodiment four tables 3); Its dosage form falls behind, wherein stability of drug is poor, the long-time storage can produce precipitation and turbidity, effective ingredient such as the multiple volatile oil component of poorly water-soluble, ligustilide, TANSHINONES, catalpol, 23-alisol acetyl B, table alisol are separated out, ferulic acid in the liquid preparation, ligustilide are also unstable in aqueous solution simultaneously, easily decomposition and inversion; No strict quality method in " QINGGAN TANGJIANG " can't be guaranteed the curative effect of its preparation.Therefore, " QINGGAN TANGJIANG " preparation does not meet reliable, the quality controllable requirement of modern medicines curative effect.So content of the present invention just provides novel form of a kind of " QINGGAN TANGJIANG " and preparation method thereof and method of quality control.
One of purpose of the present invention provides the preparation technology of a kind of Chinese medicine " strong liver granule ", this technology has been avoided the operation of adjust pH to 8 in the former technology, main effective ingredient such as chlorogenic acid, ferulic acid, peoniflorin is kept substantially, significantly improved content of effective; The present invention adds beta-schardinger dextrin-again disperses liposoluble constituent, play the hydrotropy effect, thereby minimizing loss of active ingredients, better keep its effective ingredient, the suspension type granule of making makes the multiple volatile oil component of poor solubility, ligustilide, TANSHINONES, catalpol, 23-alisol acetyl B, effective ingredient such as table alisol are hybrid state by hydrotropy or with adjuvant, kept effective ingredient to greatest extent, and the ferulic acid in the preparation, ligustilide is unstable in aqueous solution, by making particulate solid preparation, effective ingredient is significantly improved than former dosage form, thereby improved our curative effect greatly; Two of the object of the invention has provided the quality control method of this " strong liver granule ", by thin layer discriminating, assay, has controlled the quality of medicine preferably, reaches the quality controllable purpose of modern medicines.
(summary of the invention)
The present invention's " strong liver granule " is made by 250 weight portion Herba Artemisiae Scopariaes, 125 weight portion Radix Isatidis, 125 weight portion Radix Angelicae Sinensis, the 125 weight portion Radix Paeoniae Albas, 250 weight portion Radix Salviae Miltiorrhizaes, 125 weight portion Radix Curcumaes, the 250 weight portion Radixs Astragali, 125 weight portion Radix Codonopsis, 125 weight portion Rhizoma Alismatis, 125 weight portion Rhizoma Polygonatis, 125 weight portion Radix Rehmanniae, 125 weight portion Rhizoma Dioscoreaes, 100 weight portion Fructus Crataegis, 100 weight portion Massa Medicata Fermentatas, 100 weight portion Radix Gentianae Macrophyllae, 100 weight portion licorice raw material medicines, medicament also contains beta-schardinger dextrin-200 weight portions, forming agent dextrin 267 weight portions.
The preparation method of this Chinese medicine " strong liver granule " is as follows:
Take by weighing 250 weight portion Herba Artemisiae Scopariaes, 125 weight portion Radix Isatidis, 125 weight portion Radix Angelicae Sinensis, the 125 weight portion Radix Paeoniae Albas, 250 weight portion Radix Salviae Miltiorrhizaes, 125 weight portion Radix Curcumaes, the 250 weight portion Radixs Astragali, 125 weight portion Radix Codonopsis, 125 weight portion Rhizoma Alismatis, 125 weight portion Rhizoma Polygonatis, 125 weight portion Radix Rehmanniae, 125 weight portion Rhizoma Dioscoreaes, 100 weight portion Fructus Crataegis, 100 weight portion Massa Medicata Fermentatas, 100 weight portion Radix Gentianae Macrophyllae, 100 weight portion Radix Glycyrrhizaes, standby;
More than ten Six-elements, decoct with water merging filtrate three times, filtrate is concentrated into relative density 1.12 (50 ℃), adds beta-schardinger dextrin-200 weight portions, makes it dissolving, fully stir spray drying (170 ℃ of hot-air inlet temperature, 80 ℃ of leaving air temps) while hot, spray powder add-on type agent dextrin 267 weight portions add correctives stevioside 5 weight portions, fully mix thoroughly, material is compressing dry granulation, granulation under 60 ℃ of temperature, granulate, packing promptly gets product (5g/ bag).
The discrimination method of the strong liver granule of the present invention, concrete steps are:
A. get this product 10g, add water 20ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, gets supernatant, evaporate to dryness adds water 20ml and makes dissolving, uses ethyl acetate extraction 2 times, each 20ml, combined ethyl acetate liquid volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, adds 10ml ethyl acetate supersound extraction 30min, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; Draw need testing solution 15 μ l, control medicinal material solution 5 μ l, putting respectively on same silica gel g thin-layer plate, is that petroleum ether (30～60 ℃)-ethyl acetate system of 9: 1 is developing solvent with volume ratio, launches, take out, dry, put (365nm) observation under the uviol lamp, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
B. get this product 15g, add water 60ml, heating makes dissolving, on the AB-8 macroporous resin (the macroporous resin consumption is 40ml, wet method upper prop, internal diameter 15-20mm) handled well, 40% ethanol 80ml eluting is collected eluent, evaporate to dryness, add the 15ml water dissolution, on the polyamide column handled well (the polyamide consumption is 20ml, the wet method upper prop, internal diameter 15-20mm), collect effluent, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Other gets the peoniflorin reference substance, uses dissolve with methanol, makes every 1ml and contains the 1mg reference substance solution; Draw above-mentioned test sample liquid 10 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with volume ratio is 40: 5: 10: chloroform-ethyl acetate of 0.2-methanol-formic acid is developing solvent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, about 5 minutes of 105 ℃ of bakings.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
C. get this product 15g, add water 30ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, gets supernatant, and evaporate to dryness adds water 30ml and makes dissolving, and with extracted with diethyl ether 2 times, each 20ml merges ether solution, volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Radix Salviae Miltiorrhizae control medicinal material powder 1g, and the 5ml that adds diethyl ether puts in the tool plug test tube, and jolting was placed 1 hour, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, makes control medicinal material solution; Draw above-mentioned test sample liquid 15 μ l, reference substance solution 3 μ l put respectively on same silica gel g thin-layer plate, are that ethyl acetate-toluene system of 1: 9 is developing solvent with volume ratio, launch, and take out, and dry; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
D. get this product 25g, add water 50ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, get supernatant, evaporate to dryness adds water 50ml and makes dissolving, puts in the separatory funnel, it is inferior to give a baby a bath on the third day after its birth with ether, and each 40ml discards ether solution, the water saturated n-butanol extraction of reuse 5 times, each 30ml merges n-butyl alcohol liquid, with 1% potassium hydroxide washed twice, each 60ml discards washing liquid, and the reuse n-butyl alcohol is saturated is washed to neutrality, extracting solution is put evaporate to dryness in the water-bath, and residue adds methanol 2ml makes dissolving, as need testing solution; Other gets the astragaloside reference substance, adds methanol and makes the reference substance solution that every 1ml contains 1mg; Other gets the astragaloside reference substance, adds methanol and makes the reference substance solution that every 1ml contains 1mg; Draw above-mentioned test sample liquid 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with volume ratio is that lower floor's solution system that chloroform-methanol-water of 65: 35: 10 is placed below 10 ℃ is developing solvent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, about 5 minutes of 105 ℃ of bakings; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E. get this product 15g, add water 60ml, heating makes dissolving, is added on the D that has handled well
101On the type macroporous resin column (the macroporous resin consumption is 40ml, wet method upper prop, internal diameter 15-20mm), use the 60ml70% ethanol elution, collect eluent, put evaporate to dryness in the water-bath, residue adds water 30ml dissolving, on the polyamide column handled well (the polyamide consumption is 30ml, the wet method upper prop, internal diameter 15-20mm), use the 60ml70% ethanol elution, collect eluent, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Extracting liquorice control medicinal material powder 0.5g adds 30ml water-saturated n-butanol supersound extraction 20 minutes in addition, filters, and filtrate evaporate to dryness, residue add 1ml methanol makes dissolving, as Radix Glycyrrhizae control medicinal material solution; Drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is that methylene chloride-methanol-water body of 40: 10: 1 is developing solvent with volume ratio, launch, take out, dry up, spray is with 10% ethanol solution of sulfuric acid, and putting 105 ℃, to be heated to the speckle colour developing clear; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
The content assaying method of the strong liver granule of the present invention, concrete steps are:
The selection of assay index and method:
Contain multiple glycosides compound in the Radix Paeoniae Alba, peoniflorin is its main effective ingredient, and stable in properties can be accurately quantitative, so it is decided to be the index components that this formulation content is measured.The paeoniflorin content assay method of bibliographical information has thin layer chromatography scanning, high performance liquid chromatography etc.We have adopted the HPLC method to measure paeoniflorin content in the preparation, have set up quality of the pharmaceutical preparations control method.
The chromatographic column octadecylsilane chemically bonded silica is a filler.Compare the anti-phase C that Huaiyin Han Bang scientific ﹠ technical corporation produces
18Post: Kromasil C
18The anti-phase C of (4.6 * 250mm, 5 μ m) and Huaiyin Han Bang scientific ﹠ technical corporation
18Post: Lichrospher C
18(4.6 * 250mm, 5 μ m), the result shows that the chromatographic column of two different models all can reach good separation, but with Kromasil C
18Chromatographic column is better, so select for use.Pump: Waters510 pump.Detector: Waters486 UV-detector.Mobile phase: with multiple ratio (20: 80,25: 75,30: 70 etc.) methanol-0.05% trifluoroacetic acid water system is that mobile phase is carried out chromatography, and the result is methanol with mobile phase: 0.05% trifluoroacetic acid water=(28: 72) (V/V) or methanol: 0.05% acetic acid water=(28: 72) (V/V) or methanol: 0.05% phosphoric acid water=(28: 72) are (V/V) for well.Measure wavelength: according to the ultraviolet spectra of peoniflorin, its maximum absorption wavelength is 230nm, determines at 230nm so it is measured wavelength.Flow velocity 1.0ml/min.Column temperature: 30 ℃.Number of theoretical plate calculates by the peoniflorin peak should be not less than 3000.
The present invention has measured the content of paeoniflorin of protection hepatocyte injury in the Radix Paeoniae Alba, and Radix Angelicae Sinensis, the Radix Paeoniae Alba, Radix Salviae Miltiorrhizae, the Radix Astragali, Radix Glycyrrhizae have been carried out the thin layer discriminating.The establishment of preparation quality control method has improved the quality control of medicine, has guaranteed preparation homogeneity and effectiveness.
(specific embodiment)
The preparation of embodiment the last one liver granule
Take by weighing raw material 250g Herba Artemisiae Scopariae, 125g Radix Isatidis, 125g Radix Angelicae Sinensis, the 125g Radix Paeoniae Alba, 250g Radix Salviae Miltiorrhizae, 125g Radix Curcumae, the 250g Radix Astragali, 125g Radix Codonopsis, 125g Rhizoma Alismatis, 125g Rhizoma Polygonati, 125g Radix Rehmanniae, 125g Rhizoma Dioscoreae, 100g Fructus Crataegi, 100g Massa Medicata Fermentata, 100g Radix Gentianae Macrophyllae, 100g Radix Glycyrrhizae.
More than ten Six-elements, decoct with water merging filtrate three times, filtrate is concentrated into about 1.12 (50 ℃) of relative density, adds beta-schardinger dextrin-200g, stirs, spray drying (170 ℃ of hot-air inlet temperature, 80 ℃ of leaving air temps) gets spray powder, add 267g dextrin and 5g stevioside, mixing, material is dry granulation under 60 ℃ of temperature, granulate, get brown particle 1000g, with aluminum-plastic composite membrane packing (5.0g/ bag), promptly.
Embodiment two outlet and inlet temperature are to the influence of spray drying powder
The spray drying condition is very important to the reservation and the grain forming of effective ingredient.Reservation of effective ingredient for the benefit of and granule Cheng Li compare as table 1 inlet temperature, leaving air temp.
Table 1 outlet and inlet temperature is to the influence of spray drying powder
| Inlet temperature (℃) | Leaving air temp (℃) | Peoniflorin retention rate (%) | Chlorogenic acid retention rate (%) | Ferulic acid retention rate (%) | Water content (%) | To the influence of granulating |
| 190 180 180 170 170 | 90 80 70 80 70 | 92.84 96.34 96.03 97.89 98.11 | 88.75 90.96 90.32 91.05 92.84 | 87.04 89.52 90.17 90.95 92.16 | 2.8 3.6 3.8 3.4 5.3 | Poor slightly very good better flowability is relatively poor |
The granulation result of the test shows, the water content of this preparation semi-finished product fine silt is at 3.0～5.0% o'clock, and directly dry type makes granularity, granule that hardness is suitable; Water content is higher than at 5.0% o'clock, and mobility of particle is relatively poor, and the back moisture of granulating is difficult to be controlled in 5%; Water content was less than 3.0% o'clock, and particulate fine powder is many slightly, and productive rate can descend.Therefore should control spray-dired inlet temperature is 170-180 ℃, leaving air temp 70-80 ℃.Consider from the angle of the retention rate of each effective ingredient again, select the high spray drying condition of retention rate, so the selection inlet temperature is 170 ℃, 80 ℃ of leaving air temps.
Embodiment three beta-schardinger dextrin-s disperse the selection of hydrotropy condition
Owing to contain the relatively poor active component of multiple water-soluble among the we,, make its active component better obtain keeping so adopt beta-schardinger dextrin-to make its better dispersion.In order to select the dispersive optimum condition of beta-schardinger dextrin-, three comparative tests have been carried out.Take by weighing 250g Herba Artemisiae Scopariae, 125g Radix Isatidis, 125g Radix Angelicae Sinensis, the 125g Radix Paeoniae Alba, 250g Radix Salviae Miltiorrhizae, 125g Radix Curcumae, the 250g Radix Astragali, 125g Radix Codonopsis, 125g Rhizoma Alismatis, 125g Rhizoma Polygonati, 125g Radix Rehmanniae, 125g Rhizoma Dioscoreae, 100g Fructus Crataegi, 100g Massa Medicata Fermentata, 100g Radix Gentianae Macrophyllae, 100g Radix Glycyrrhizae, decoct with water three times, filtrate is concentrated into relative density 1.12 (50 ℃), with three parts of concentrated solution div in par aeq, add not commensurability beta-schardinger dextrin-respectively, test after fully stirring evenly while hot.As investigating index, investigate its influence with TANSHINONES, 23-alisol acetyl B, the results are shown in Table 2 the retention rate of TANSHINONES, 23-alisol acetyl B.
Table 2 beta-schardinger dextrin-consumption is to the influence of composition retention rate
The result shows, solubilization-aid effect was undesirable when the beta-schardinger dextrin-consumption was 60g, when increasing to 90g, the retention rate of index components TANSHINONES, 23-alisol acetyl B is higher, when increasing to 120g again as the beta-schardinger dextrin-consumption, the retention rate difference of index components is very little during with 90g, is 90-120g so select the consumption of beta-schardinger dextrin-, and the best is 90g.
The research of the active constituent content of embodiment top four glycogen slurry, strong liver granule
The QINGGAN TANGJIANG of former explained hereafter and the strong liver granule of new technology preparation active constituent content contrast test, experimental result such as table 3 have been carried out.
The effective ingredient contrast test of table 3 QINGGAN TANGJIANG, strong liver granule
From the above, the strong particulate chlorogenic acid contents of liver improves 2 times than QINGGAN TANGJIANG, and the strong particulate content of ferulic acid of liver improves 1 times than QINGGAN TANGJIANG, and the strong particulate glycyrrhizic acid of liver, content of paeoniflorin all improve than QINGGAN TANGJIANG.
Embodiment five QINGGAN TANGJIANG, strong liver granule are to the protective effect of experimental liver poisoning mice
Get 50 of mices, male and female half and half, body weight 18～24g is divided into 5 groups at random, 10 every group.Positive controls ip liver-protecting tablet 50mg/kg, QINGGAN TANGJIANG (10ml/ props up) ip3.33ml/kg, strong liver granule (5g/ bag) ip1.7g/kg, the crude drug consumption of every QINGGAN TANGJIANG is identical with the every bag strong particulate crude drug consumption of liver, so QINGGAN TANGJIANG ip3.33ml/kg is identical with the consumption of strong liver granule ip1.7g/kg.Every day 1 time, successive administration 7 days, after the last administration, normal solvent group ip equivalent solvent, all the other respectively organize ip0.1% CCL
4Vegetable oil 5ml/kg, or to sulfo-second phthalein amine (TAA) 40mg/kg, fasting 16h post-tensioning neck is put to death animal, and the eye socket blood sampling is got liver and is prepared homogenate for test.
Table 4 QINGGAN TANGJIANG, strong liver granule are to CCL
4The influence of poisoning mice ALT, TBIL
(x±s)
| Group | ALT(U/dL) | TBIL(umol/L) |
| According to group model group CCL 4Positive drug group+CCL 4QINGGAN TANGJIANG group+CCL 4Strong liver groups of grains+CCL 4 | 33±13 874±221*** 286±168***△△ 579±257** 281±209***△△ | 9.34±1.89 11.44±2.43 10.54±2.28 11.13±2.56 10.61±2.99 |
Compare with model group, * * P＜0.05, * * * P＜0.01, with QINGGAN TANGJIANG group ratio, △ △ * * P＜0.05 (down together).
Table 5 QINGGAN TANGJIANG, strong liver granule are to the influence of TAA poisoning mice ALT, AST
(x±s)
| Group | ALT(U/dL) | AST(umol/L) |
| According to group model group TAA positive drug group+strong liver groups of grains+TAA of TAA QINGGAN TANGJIANG group+TAA | 68±23 700±231 300±64***△△ 426±147*** 263±91***△△△ | 153±25 325±53 210±66*** 237±41*** 213±34*** |
By table 4, table 5 as seen, strong liver granule improves 1 times to the inhibition degree of the rising of experimental poisoning mice Serum ALT than QINGGAN TANGJIANG, and experimental poisoning mice serum T BIL, AST are also decreased than QINGGAN TANGJIANG.
The thin layer of embodiment the last six liver granule Radix Angelicae Sinensis is differentiated
Get this product 10g, add water 20ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, gets supernatant, evaporate to dryness adds water 20ml and makes dissolving, uses ethyl acetate extraction 2 times, each 20ml, combined ethyl acetate liquid volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution.Other gets Radix Angelicae Sinensis control medicinal material 1g, adds 10ml ethyl acetate supersound extraction 30min, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution.Test according to thin layer chromatography (appendix VI B), draw need testing solution 15 μ l, control medicinal material solution 5 μ l put respectively on same silica gel g thin-layer plate, with petroleum ether (30～60 ℃)-ethyl acetate (9: 1) is developing solvent, launch, take out, dry, put (365nm) observation under the uviol lamp, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.
The thin layer of embodiment the last the seven liver granule Radix Paeoniae Alba is differentiated
Get this product 15g, add water 60ml, heating makes dissolving, on the AB-8 macroporous resin (the macroporous resin consumption is 40ml, wet method upper prop, internal diameter 15-20mm) handled well, 40% ethanol 80ml eluting is collected eluent, evaporate to dryness, add the 15ml water dissolution, on the polyamide column handled well (the polyamide consumption is 20ml, the wet method upper prop, internal diameter 15-20mm), collect effluent, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution.Other gets the peoniflorin reference substance, uses dissolve with methanol, makes every 1ml and contains the 1mg reference substance solution.According to thin layer chromatography (" 2000 editions one appendix VI B of Chinese pharmacopoeia) test, draw above-mentioned test sample liquid 10 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with chloroform-ethyl acetate-methanol-formic acid (40: 5: 10: 0.2) be developing solvent, launch, take out, dry, spray ethanol solution of sulfuric acid, about 5 minutes of 105 ℃ of bakings with 10%.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The thin layer of embodiment top eight liver granule Radix Salviae Miltiorrhizae is differentiated
Get this product 15g, add water 30ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, gets supernatant, and evaporate to dryness adds water 30ml and makes dissolving, and with extracted with diethyl ether 2 times, each 20ml merges ether solution, volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution.Other gets Radix Salviae Miltiorrhizae control medicinal material powder 1g, and the 5ml that adds diethyl ether puts in the tool plug test tube, and jolting was placed 1 hour, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, makes control medicinal material solution.According to thin layer chromatography (" 2000 editions one appendix VI B of Chinese pharmacopoeia) test, draw above-mentioned test sample liquid 15 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with ethyl acetate-toluene (1: 9) is developing solvent, launch, take out, dry.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
The thin layer of embodiment the last the nine liver granule Radix Astragali is differentiated
Get this product 25g, add water 50ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, get supernatant, evaporate to dryness adds water 50ml and makes dissolving, puts in the separatory funnel, it is inferior to give a baby a bath on the third day after its birth with ether, and each 40ml discards ether solution, the water saturated n-butanol extraction of reuse 5 times, each 30ml merges n-butyl alcohol liquid, with 1% potassium hydroxide washed twice, each 60ml discards washing liquid, and the reuse n-butyl alcohol is saturated is washed to neutrality, extracting solution is put evaporate to dryness in the water-bath, and residue adds methanol 2ml makes dissolving, as need testing solution.Other gets the astragaloside reference substance, adds methanol and makes the reference substance solution that every 1ml contains 1mg.Other gets the astragaloside reference substance, adds methanol and makes the reference substance solution that every 1ml contains 1mg.According to thin layer chromatography (" 2000 editions one appendix VI B of Chinese pharmacopoeia) test, draw above-mentioned test sample liquid 10 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, lower floor's solution of placing below 10 ℃ with chloroform-methanol-water (65: 35: 10) is developing solvent, launches, take out, dry, spray ethanol solution of sulfuric acid, about 5 minutes of 105 ℃ of bakings with 10%.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.
The thin layer of embodiment top ten liver granule Radix Glycyrrhizae is differentiated
Get this product 15g, add water 30ml, heating makes dissolving, is added on the D that has handled well
101On the type macroporous resin column (the macroporous resin consumption is 40ml, wet method upper prop, internal diameter 15-20mm), use the 80ml70% ethanol elution, collect eluent, put evaporate to dryness in the water-bath, residue adds water 30ml dissolving, on the polyamide column handled well (the polyamide consumption is 30ml, the wet method upper prop, internal diameter 15-20mm), use the 60ml70% ethanol elution, collect eluent, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution.Extracting liquorice control medicinal material powder 0.5g adds 30ml water-saturated n-butanol supersound extraction 20 minutes in addition, filters, and filtrate evaporate to dryness, residue add 1ml methanol makes dissolving, as Radix Glycyrrhizae control medicinal material solution.According to thin layer chromatography (" 2000 editions one appendix VI B of Chinese pharmacopoeia) test, draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with methylene chloride-methanol-water (40: 10: 1) is developing solvent, launch, take out, dry up, spray then with 10% ethanol solution of sulfuric acid, putting 105 ℃, to be heated to speckle colour developing clear.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
Embodiment ten the last one liver granule content of paeoniflorin are measured
This preparation is measured according to high performance liquid chromatography (" 2000 editions one appendix VI D of Chinese pharmacopoeia).
Chromatographic condition and system suitability test: use Waters510 pump and Waters486 UV-detector; Methanol-0.05% trifluoroacetic acid water=28: 72 (V/V) is mobile phase; The detection wavelength is 230nm; Flow velocity 1.0ml/min; Column temperature is 30 ℃.Number of theoretical plate calculates by the peoniflorin peak should be not less than 3000.
Wherein mobile phase also: methanol-0.05% acetic acid water=28: 72 (V/V) methanol-0.05% phosphoric acid water=28: 72 (V/V).
The preparation of reference substance solution: precision takes by weighing in 70 ℃ of peoniflorin reference substances that are dried to constant weight an amount of, makes the solution that every 1ml contains the 0.164mg peoniflorin with mobile phase, promptly;
The preparation of need testing solution: get in this product 1.5g to 25ml measuring bottle, add mobile phase 20ml, weigh, supersound extraction 30min, weight is supplied in cooling, shakes up, and leaves standstill, and gets clear liquid, and is centrifugal, gets supernatant, promptly;
Measure: accurate respectively reference substance solution and each 10 μ l of need testing solution of drawing, inject chromatograph of liquid, measure, calculate with external standard method, that is, this product contains Radix Paeoniae for every bag and is no less than 8.0mg in peoniflorin.
This strong liver granule adopts said method to carry out quality control, promptly Radix Angelicae Sinensis, the Radix Paeoniae Alba, Radix Salviae Miltiorrhizae, the Radix Astragali and Radix Glycyrrhizae are carried out thin layer respectively and differentiate and measure content of paeoniflorin, compare with QINGGAN TANGJIANG, the invention provides quality standard, control the quality of product effectively, guaranteed the curative effect of medicine.
Description of drawings
Fig. 1: lack Radix Paeoniae negative sample HPLC figure
Fig. 2: peoniflorin reference substance HPLC figure
Fig. 3: strong liver particulate samples HPLC figure (No. 5 peaks are the peoniflorin peak)
Claims (6)
1. granule for the treatment of hepatitis, by 250 weight portion Herba Artemisiae Scopariaes, 125 weight portion Radix Isatidis, 125 weight portion Radix Angelicae Sinensis, the 125 weight portion Radix Paeoniae Albas, 250 weight portion Radix Salviae Miltiorrhizaes, 125 weight portion Radix Curcumaes, the 250 weight portion Radixs Astragali, 125 weight portion Radix Codonopsis, 125 weight portion Rhizoma Alismatis, 125 weight portion Rhizoma Polygonatis, 125 weight portion Radix Rehmanniae, 125 weight portion Rhizoma Dioscoreaes, 100 weight portion Fructus Crataegis, 100 weight portion Massa Medicata Fermentatas, 100 weight portion Radix Gentianae Macrophyllae, 100 weight portion licorice raw material medicines are made, it is characterized in that: contain beta-schardinger dextrin-200 weight portions, forming agent dextrin 267 weight portions contain correctives stevioside 5 weight portions.
2. the preparation method of the granule of treatment hepatitis according to claim 1 is as follows by concrete steps:
It is standby to take by weighing Herba Artemisiae Scopariae, Radix Isatidis, Radix Angelicae Sinensis, the Radix Paeoniae Alba, Radix Salviae Miltiorrhizae, Radix Curcumae, the Radix Astragali, Radix Codonopsis, Rhizoma Alismatis, Rhizoma Polygonati, Radix Rehmanniae, Rhizoma Dioscoreae, Fructus Crataegi, Massa Medicata Fermentata, Radix Gentianae Macrophyllae, Radix Glycyrrhizae; More than ten Six-elements, decoct with water three times, medicinal liquid filters, the relative density that filtrate is concentrated to 50 ℃ of mensuration is 1.12; Add beta-schardinger dextrin-200 weight portions, make it dissolving, fully stir while hot, spray drying, 170 ℃ of hot-air inlet temperature, 80 ℃ of leaving air temps, spray powder add-on type agent dextrin 267 weight portions, add correctives stevioside 5 weight portions, fully mix thoroughly, material is compressing dry granulation, granulation under 60 ℃ of temperature, granulate, packing promptly gets product.
3. the method for quality control of the granule of the described treatment hepatitis of claim 1 is characterized in that the thin layer discrimination method has following several in this method of quality control:
A. the discriminating of Radix Angelicae Sinensis
Get this product 10g, add water 20ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, gets supernatant, evaporate to dryness adds water 20ml and makes dissolving, uses ethyl acetate extraction 2 times, each 20ml, combined ethyl acetate liquid volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Radix Angelicae Sinensis control medicinal material 1g, adds 10ml ethyl acetate supersound extraction 30min, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, in contrast medical material solution; Draw need testing solution 15 μ l, control medicinal material solution 5 μ l put respectively on same silica gel g thin-layer plate, with volume ratio is that 9: 1 petroleum ether-ethyl acetate system is developing solvent, the boiling spread of petroleum ether is 30～60 ℃, launches, and takes out, dry, put under the uviol lamp and observe, wavelength is 365nm, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;
B. the discriminating of the Radix Paeoniae Alba
Get this product 15g, add water 60ml, heating makes dissolving, on the AB-8 macroporous resin handled well, the macroporous resin consumption is 40ml, wet method upper prop, internal diameter 15-20mm, 40% ethanol 80ml eluting is collected eluent, evaporate to dryness, add the 15ml water dissolution, on the polyamide column handled well, the polyamide consumption is 20ml, the wet method upper prop, internal diameter 15-20mm collects effluent, evaporate to dryness, residue add methanol 1ml makes dissolving, as need testing solution; Other gets the peoniflorin reference substance, uses dissolve with methanol, makes every 1ml and contains the 1mg reference substance solution; Draw above-mentioned test sample liquid 10 μ l, reference substance solution 5 μ l, put respectively in same be on the silica gel g thin-layer plate of binding agent with the sodium carboxymethyl cellulose, with volume ratio is 40: 5: 10: chloroform-ethyl acetate of 0.2-methanol-formic acid is developing solvent, launch, take out, dry, spray is with 10% stream acid alcoholic solution, 105 ℃ of bakings 5 minutes.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
C. the discriminating of Radix Salviae Miltiorrhizae
Get this product 15g, add water 30ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, gets supernatant, and evaporate to dryness adds water 30ml and makes dissolving, and with extracted with diethyl ether 2 times, each 20ml merges ether solution, volatilizes, and residue adds ethyl acetate 1ml makes dissolving, as need testing solution; Other gets Radix Salviae Miltiorrhizae control medicinal material powder 1g, and the 5ml that adds diethyl ether puts in the tool plug test tube, and jolting was placed 1 hour, filters, and filtrate volatilizes, and residue adds ethyl acetate 1ml makes dissolving, makes control medicinal material solution; Draw above-mentioned test sample liquid 15 μ 1, reference substance solution 5 μ l put respectively on same silica gel g thin-layer plate, are that ethyl acetate-toluene system of 1: 9 is developing solvent with volume ratio, launch, and take out, and dry; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color;
D. the discriminating of the Radix Astragali
Get this product 25g, add water 50ml, heating makes dissolving, adds alcohol and makes and contain alcohol amount and reach 70%, get supernatant, evaporate to dryness adds water 50ml and makes dissolving, puts in the separatory funnel, it is inferior to give a baby a bath on the third day after its birth with ether, and each 40ml discards ether solution, the water saturated n-butanol extraction of reuse 5 times, each 30ml merges n-butyl alcohol liquid, with 1% potassium hydroxide washed twice, each 60ml discards washing liquid, and the reuse n-butyl alcohol is saturated is washed to neutrality, extracting solution is put evaporate to dryness in the water-bath, and residue adds methanol 2ml makes dissolving, as need testing solution; Other gets the astragaloside reference substance, adds methanol and makes the reference substance solution that every 1ml contains 1mg; Draw above-mentioned test sample liquid 10 μ l, reference substance solution 5 μ l, put respectively on same silica gel g thin-layer plate, with volume ratio is that lower floor's solution system that chloroform-methanol-water of 65: 35: 10 is placed below 10 ℃ is developing solvent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, 105 ℃ of bakings 5 minutes; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;
E. the discriminating of Radix Glycyrrhizae
Get this product 15g, add water 60ml, heating makes dissolving, is added on the D that has handled well
101On the type macroporous resin column, the macroporous resin consumption is 40ml, the wet method upper prop, internal diameter 15-20mm uses the 80ml70% ethanol elution, collects eluent, put evaporate to dryness in the water-bath, residue adds water 30ml dissolving, on the polyamide column handled well, the polyamide consumption is 30ml, wet method upper prop, internal diameter 15-20mm, use the 60ml70% ethanol elution, collect eluent, evaporate to dryness, residue adds methanol 1ml makes dissolving, as need testing solution; Extracting liquorice control medicinal material powder 0.5g adds 30ml water-saturated n-butanol supersound extraction 20 minutes in addition, filters, and filtrate evaporate to dryness, residue add 1ml methanol makes dissolving, as Radix Glycyrrhizae control medicinal material solution; Drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is that methylene chloride-methanol-water body of 40: 10: 1 is developing solvent with volume ratio, launch, take out, dry up, spray is with 10% ethanol solution of sulfuric acid, and putting 105 ℃, to be heated to the speckle colour developing clear; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the speckle of same color.
4. the paeoniflorin content assay method of the granule of treatment hepatitis according to claim 1:
Get in preparation 1.5g to the 25ml measuring bottle, add mobile phase 20ml, weigh supersound extraction 30min, cooling, supply weight, shake up, leave standstill, get clear liquid, centrifugal, get supernatant, as need testing solution, the peoniflorin liquid of preparing with mobile phase is contrast, the chromatographic column octadecylsilane chemically bonded silica is a filler, use Waters510 pump and Waters486 UV-detector, volume ratio 28: 72 methanol-0.05% trifluoroacetic acid water is mobile phase, and the detection wavelength is 230nm, flow velocity 1.0ml/min, 30 ℃ of column temperatures.
5. the paeoniflorin content assay method of the granule of treatment hepatitis according to claim 4 is characterized in that: volume ratio 28: 72 methanol-0.05% acetic acid water is mobile phase.
6. the paeoniflorin content assay method of the granule of treatment hepatitis according to claim 4 is characterized in that: volume ratio 28: 72 methanol-0.05% phosphoric acid water is a mobile phase.
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| CN108578445A (en) * | 2018-03-23 | 2018-09-28 | 广西中医药大学 | Cortex Ilicis Rotundae extract and its preparation and the application for treating hepatitis |
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| CN103341088B (en) * | 2013-07-23 | 2015-03-11 | 乐山安婷生物技术有限公司 | Medicine for treating blood sugar type fatty liver |
| CN104857348B (en) * | 2015-06-01 | 2016-03-02 | 李玮 | A kind of preparation method for the treatment of the medicine of early stage liver cirrhosis |
| CN104996862A (en) * | 2015-06-17 | 2015-10-28 | 蚌埠市天星树脂有限责任公司 | Resin for active compound extraction for hepatitis alleviating medicine and preparation method of resin |
| CN110988248B (en) * | 2019-12-23 | 2021-06-18 | 河北中医学院 | Rapid thin-layer identification method for radix puerariae intestine clearing granules |
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