CN1253170C - Chinese medicine preparation for treating hepatitis and its preparing and detecting method - Google Patents
Chinese medicine preparation for treating hepatitis and its preparing and detecting method Download PDFInfo
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- CN1253170C CN1253170C CN 200410073956 CN200410073956A CN1253170C CN 1253170 C CN1253170 C CN 1253170C CN 200410073956 CN200410073956 CN 200410073956 CN 200410073956 A CN200410073956 A CN 200410073956A CN 1253170 C CN1253170 C CN 1253170C
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Abstract
The present invention discloses a new traditional Chinese medicine preparation for treating hepatitis and a preparing method thereof. The preparation is in a solid form and is prepared by processing baicalin, honeysuckle extract, gardenia extract and capillary artemisia extract as raw material by means of different physical methods or chemical methods. With the advantage of unique formula, the present invention has obvious effects for clinically treating hepatitis.
Description
Technical field
The present invention relates to a kind of Chinese medicine preparation for the treatment of hepatitis, is raw material with the Chinese crude drug specifically, and the Chinese patent medicine that is prepared from relates to the preparation method of this medicine simultaneously.
Background technology
Hepatitis is a kind of global commonly encountered diseases, and China belongs to popular " severely afflicated area ", and compatriots' health in the serious threat of all kinds hepatitis.Western countries are at most with the hepatitis C, the main popular hepatitis B of China.It is predicted and China surface antigen positive person promptly infect the hepatitis B person has more than 100,000,000 people, and 3,000 ten thousand people are arranged approximately by the undesired patient of liver function that hepatitis B causes.In addition, chronic viral hepatitis also with the substantial connection that has of primary hepatocarcinoma, most hepatocarcinoma patients have the chronic hepatitis medical history.Therefore the treatment of chronic hepatitis has become a significant problem that presses for solution.The types of drugs that is used at present chronic hepatitis treatment both at home and abroad is a lot of, and conclusion is got up, and Western medicine can be divided into two classes substantially:
(1) antiviral agents
Antiviral agents mainly contains interferon and several nucleoside analog.Interferon is about 30%～50% to B-mode and therapy for hepatitis C effective percentage, and is good slightly to therapy for hepatitis C effect comparison hepatitis B.But most patients can recur in about 6 months to 1 year after drug withdrawal.And expenses for medicine is quite expensive, and a patient needs the tens thousand of units of RMB with the import interferon, with homemade interferon also more than 10,000 yuan.Interferon needs intramuscular injection, and the side reaction of influenza-like symptom is arranged after part patient's medication.Some nucleoside analog such as lamivudine (lamivudin), famciclovir (famciclovir) have certain therapeutic effect to hepatitis virus, and very fast knock-on is a rebound phenomenon after the drug withdrawal but also exist.Drug price is also expensive, and part patient's virus has variation, and more refractory is treated, and side reaction is arranged.
(2) immunomodulator
Immunomodulator has transfer factor, interleukin II, thymosin, 17-hydroxy-11-dehydrocorticosterone etc.The case of this class Drug therapy chronic hepatitis is few, and curative effect waits certainly, and expenses for medicine is expensive, and side reaction is arranged.
Chinese medicine preparation should play an important role in treatment hepatitis, and the wide world is arranged.
Summary of the invention
The objective of the invention is to provide a kind of Chinese medicine preparation of effective treatment hepatitis, another object of the present invention provides the preparation detection method of this Chinese medicine preparation.
For achieving the above object, we have adopted following technical scheme:
Preparation of the present invention is made by following raw material:
Baicalin 40-90 weight portion Flos Lonicerae extract (in chlorogenic acid) 6-20 weight portion
Fructus Gardeniae extract 5-15 weight portion Herba Artemisiae Scopariae extract 12-30 weight portion.
The raw material optimal proportion of making preparation of the present invention is:
Baicalin 66.7 weight portion Flos Lonicerae extracts (in chlorogenic acid) 13.3 weight portions
Fructus Gardeniae extract 10.7 weight portion Herba Artemisiae Scopariae extract 20 weight portions.
Preparation of the present invention can add suitable adjuvant make receptible all the solid preparation types of clinical institute as: granule, tablet, pill, capsule, drop pill etc. are preferably granule.
Mainly containing effective component content in the granule of the present invention is:
Contain in every gram granule: baicalin 10-200mg,
Contain in every gram granule: chlorogenic acid 4-25mg
Contain in every gram granule: jasminoidin 0.5-5mg.
The assay method of above-mentioned effective ingredient in granule of the present invention is:
(1) assay method of baicalin:
Chromatographic condition and system suitability test octadecyl silane are packing material
With 47: 53: 0.2 methanol-water-phosphoric acid of ratio is mobile phase
Detect wavelength 280nm
The preparation precision of reference substance solution takes by weighing the about 10mg of the baicalin that is dried to constant weight, puts in the 10ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 0.5g, puts in the 50ml measuring bottle, add 50% methanol 35ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, adds 50% methanol to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add 50% methanol, shake up to scale, with microvoid filter membrane (0.45 μ m), filter, promptly;
Accurate respectively reference substance solution and the need testing solution 10 μ l of drawing of algoscopy;
(2) assay method of chlorogenic acid:
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica;
With ratio is that 10: 90 acetonitrile-0.4% phosphoric acid solution is a mobile phase
The detection wavelength is 327nm
It is an amount of that the preparation precision of reference substance solution takes by weighing the chlorogenic acid reference substance, adds methanol and make the solution that every 1ml contains 0.05mg, shakes up, promptly;
This product is got in the preparation of need testing solution, and porphyrize gets that about 0.5g is accurate to be claimed surely, puts in the tool plug conical flask, adds 50% methanol 50ml, claims decide weight, and ultrasonic 30min is put coldly, and weight decided in title again.Supply with 50% methanol and to subtract weight loss, shake up, filter, get that filtrate is an amount of to be added brown measuring bottle and promptly get for test agent solution;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly;
(3) assay method of jasminoidin:
The chromatographic condition octadecylsilane chemically bonded silica is a filler
With ratio is that 10: 90 acetonitrile-0.05% trifluoroacetic acid water is mobile phase;
The detection wavelength is 239nm
The preparation precision of reference substance solution takes by weighing in 60 ℃ of jasminoidin reference substances that are dried to constant weight an amount of, makes the solution that every 1ml contains 1.0mg with mobile phase, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 3g, put in the tool plug conical flask, add 50% methanol 20ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, add 50% methanol to scale, shake up, filter, evaporate to dryness with the mobile phase dissolving, is put in the 2ml measuring bottle, add mobile phase and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, and calculate with external standard method, promptly.
The preparation method of granule of the present invention is:
The particulate preparation method of the present invention: will pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, adding cane sugar powder and dextrin or lactose are an amount of, mixing, and it is an amount of to add ethanol, granulate, drying, promptly;
The preparation method of Flos Lonicerae extract: extracting honeysuckle, with 30% alcohol reflux secondary, each 1 hour, merge extractive liquid, filters, and filtrate recycling ethanol extremely every 1ml contains crude drug 2g, add ethanol and make and contain alcohol amount and reach 75%, left standstill 24 hours, filter, filtrate recycling ethanol extremely every 1ml contains crude drug 4g, adds water to 8 times of amounts, cold preservation 48 hours, filter, filtrate is concentrated into the thick paste shape, vacuum drying, promptly;
The preparation method of Fructus Gardeniae extract: get Fructus Gardeniae, be ground into coarse powder, decoct with water three times, first and second time 1 hour, 0.5 hour for the third time, collecting decoction, filter, filtrate is concentrated into every 1ml and contains crude drug 1g, adds ethanol and makes and contain alcohol amount and reach 70%, cold preservation 24 hours, filter, filtrate recycling ethanol contains crude drug 3g to every 1ml, adds ethanol again and makes and contain the alcohol amount and reach 85%, cold preservation 24 hours, filter, filtrate recycling ethanol adds the about 5 times of amounts of water, cold preservation 48 hours to every 1ml water content crude drug 5g, filter, filtrate is concentrated into the thick paste shape, vacuum drying, promptly;
The preparation method of baicalin: Radix Scutellariae is cataclasm, decocts with water secondary, each 1 hour, merging filtrate, filtrate transfers pH value to 1.0-2.0 with hydrochloric acid (2mol/L), at 80 ℃ of insulation 30min, leave standstill 24h, filter, precipitation adds 8 times of water gagings, stir, transfer pH value to 7.0 with 40% sodium hydroxide solution, and add equivalent ethanol, stirring makes dissolving, filters, and filtrate is transferred PH to 2.0 with hydrochloric acid (2mol/L), 60 ℃ of insulation 30min leave standstill 12h, filter, precipitation is washed till PH to 4.0 with ethanol, adds 10 times of water gagings, stirs, transfer PH to 6.0 with 40% sodium hydroxide solution, add 0.5% active carbon, fully stir, 50 ℃ of insulation 30min add 1 times of amount ethanol and stir, and filter immediately, filtrate is transferred PH to 2.0 with hydrochloric acid (2mol/L), and 60 ℃ of insulation 30min leave standstill 12h, filter, after precipitation is washed with small amount of ethanol, in dry below 60 ℃, promptly.
Drug therapy hepatitis of the present invention has better curative effect.For showing the therapeutical effect of medicine of the present invention to hepatitis, we have done a large amount of experimentatioies, below experimental example be used to further specify the present invention.
Preparation of the present invention protects the liver the pharmacodynamic study of jaundice eliminating
Summary gives mice preparation 1.8g/kg of the present invention, 3.6g/kg ig the acute liver damage that D-Gal causes is had significant protective effect; Give rat 1.5g/kg, 3.0g/kg ig, acute liver damage due to the carbon tetrachloride is also shown tangible alt-reducing and liver-protecting effect; In addition this product to isothiocyanic acid-1-how the mice serum bilirubin due to the fat have tangible reduction effect.
Test material
1 test drug:
Preparation of the present invention, southern Shandong pharmaceutical factory in Shandong provides.Be compound Chinese medicinal preparation, be made into desired concn by water during experiment.Potenlin, Jiangsu Qidong City pharmaceutical factory
2 experimental animals: Kunming mouse, Wistar rat provide by Shandong Medical University's medical experiment animal center.
3 main agents:
D-Gal (D-GalN), U.S. Sigma company product, the supply of Beijing chemical reagents corporation.Carbon tetrachloride, Beijing chemical general factory product.
Isothiocyanic acid-1-is fat how, Tong County, Beijing Fine Chemical Works product of cultivating people of ability.
Glutamic oxaloacetic transaminase, GOT (AST), glutamate pyruvate transaminase (ALT) test kit, Shanghai Biological Products Inst., Ministry of Public Health provides.The determination of bilirubin medicine box, Shanghai Rongsheng Bioisystech Co., Ltd provides.
Test method and result
1. to the protective effect of D-Gal induced mice acute liver damage
(1)
Select 66 of 18-20g mices, male and female half and half.Be divided into five groups at random by the sex body weight, 10 of normal control groups, all the other every group each 14, be respectively normal control group (the normal raising), model control group (5% starch 0.2ml/10g), granule small dose group of the present invention (9% aqueous suspensions 0.2ml/10g, 1.8g/kg), heavy dose of group (18% aqueous suspensions 0.2ml/10g, 3.6g/kg), (get 6ml adds water and causes 15ml the potenlin group, 0.15ml/10g, be equivalent to 3.6g/kg).Administering mode is the filling stomach, successive administration 3 days, every day 1 time.In fasting 4h, 2h after the last administration gives 8% D-Gal 0.1ml/10g.ip, is equivalent to 800mg/kg except that the normal control group.The injection back 2h give food again.In giving D-Gal 24h, behind the fasting 8h, extract each mice right eye ball and get blood, 3000r/min, centrifugalize serum carries out each specimen AST by test kit description requirement Lai Shi colorimetry, and ALT measures and standard curve is drawn.Organize a statistical by the t check.Result such as table 1:
Table 1 preparation of the present invention is to the protective effect of D-Gal mouse liver injury
| Group | ALT (nmol/s.L) | P | AST (nmol/s.L) | P |
| Normal group model control group 1.8g/kg of the present invention 3.6g/kg positive controls of the present invention | 176.17±14.51 432.09±27.54 367.96±39.37 336.65±75.91 382.06±42.06 | ＜0.001 ＜0.001 ＜0.001 ＜0.01 | 159.93±36.49 408.39± 175.14 239.56± 130.39 224.81± 146.16 256.09±129.7 | ＜0.001 ＜0.05 ＜0.01 ＜0.05 |
Annotate: model group is compared with the normal control group, and medication group and model group are relatively
Experimental result explanation preparation of the present invention is to the caused mice serum AST of D-Gal, and the rising of ALT has tangible reduction effect, and its effect strengthens to a certain extent than positive control.
After mice is got blood, dissect and get mouse liver, with carrying out pathological examination behind 10% the formaldehyde fixed 24h.Check substantially: the normal control group, color is brown red, the matter medium hardness; Model control group, surface color is dark red, dark brown, matter is softer.Positive drug group and the large and small dosage group of preparation of the present invention color, quality are between two matched groups.
Microscopy: compare with the normal control group, the pathological changes of model control group mainly shows as the lobules of liver structural fuzzy, the blood sinus dilatation and congestion, and hepatocyte is granular degeneration, acidophilia's degeneration and necrosis.There is cell infiltration around the necrotic area and portal area, each medication group has similar morphology performance, but lesion degree is lighter, for ease of comparing, with degeneration necrosis and cell infiltration is main morphological indexes, sxemiquantitative is observed and is listed in the table below, and calculates the class index that each is organized with grade preface value method, is the significance test that reference frame (class index is 0) is carried out group difference with the model control group.
Table 2 preparation of the present invention is to the morphology influence of the acute mouse liver injury of D-GalN
| n | Degeneration necrosis | M | Cell infiltration | M | |||||||
| - | + | ++ | +++ | - | + | ++ | +++ | ||||
| The heavy dose of low dose of the present invention of normal group model group oral liquid the present invention | 10 14 14 14 14 | 7 1 2 3 3 | 3 1 6 5 6 | 0 8 5 4 5 | 0 4 1 2 0 | 10.33 ** 6.57 5.88 7.50 * | 6 0 2 3 3 | 4 4 8 7 6 | 0 8 2 3 3 | 0 2 2 1 1 | 12.4 ** 5.71 6.71 5.14 |
Compare with model control group
*P＜0.05
*P＜0.01 (, only doing pathologic finding) so number of animals is more than the biochemical analysis number because part mice serum malsegregation is not done biochemical measurement
Attached: semi-quantitative standards
(1) degeneration necrosis:
"-" is normal
1/5 of "+" extent of disease＜full lobule
1/2 of " ++ " extent of disease＜full lobule
1/2 of " +++" extent of disease＞full lobule
(2) cell infiltration:
"-" is normal
"+" inflammatory cell is dispersed in, and is rare
" ++ " inflammatory cell is in a certain local the gathering in groups
" +++" inflammatory cell fills the air distribution
Histopathologic examination's impression: comparing the model control group appearance with the normal control group is the acute liver damage performance of characteristics with the degeneration of hepatocyte diffusivity, necrosis, cell infiltration.Compare with model group, each medication group pathological changes is lighter relatively, wherein heavy dose of group difference significance.
(histology pictures is seen below, and all photo object lens magnifications are 20 *
2. carbon tetrachloride is caused the protective effect of rat acute hepatic injury:
Select 50 of 180-200g rats, male and female half and half, be divided into normal control group, model group (20% starch 1ml/100g ig), the heavy dose of group of preparation of the present invention (20% preparation suspension 1ml/100g of the present invention at random, 2g/kgig), small dose group (10% preparation suspension 1ml/100g of the present invention, 1g/kg ig), positive controls (potenlin).Except that the normal control group, each organized the rat successive administration three days, in fasting 5.5h, gave 25%CCl respectively behind the last administration 2h
4Peanut oil solution 0.2ml/100g ip.Give rats eating behind the carbon tetrachloride.After giving 24 hours fasting 12h of carbon tetrachloride, jugular vein is got each rat serum, and the centrifugal 10min separation of serum of 3000r/min is pressed ALT, and AST measures description, carries out Serum ALT, the AST determination of activity, and result such as table 3:
Table 3 preparation of the present invention is to the influence of carbon tetrachloride rat acute hepatic injury
| Group | n | AST(nmol/s.L) | P | ALT(nmol/s.L) | P |
| Normal control group model matched group high dose low dosage positive control | 10 10 10 10 10 | 201.53±31.45 399.59±42.44 342.23±58.68 363.43±38.82 352.23±58.68 | ＜0.001 ＜0.05 ＜0.05 ＜0.05 | 169.8±25.76 392.0±84.24 316.56±44.36 335.6±32.93 331.91±29.49 | ＜0.001 ＜0.01 ＜0.05 ＜0.05 |
Annotate: model group and normal group ratio, other groups all compare with model group
Cut open the belly behind the rat extracting blood, get liver, carry out pathological examination with 10% formaldehyde fixed.The result:
Normal control group color is brown red, and clear-cut margin, tangent plane are fine and smooth.Model control group color is by comparison omited sallow, and volume is fuller, and the edge is blunt, and granular sensation is arranged, and all the other each medication group color quality fall between.
Microscopy: with the contrast of normal control group, the general swelling of model group hepatocyte, sinus hepaticus narrows down, and liver cell lesion is the heaviest around the central vein, shows as vacuolar degeneration, and round cell soaks into and hepatic necrosis, and similar pathological changes is arranged the medication group but degree is lighter.For ease of relatively, be main morphological indexes with the hepatocellular degeneration necrosis, sxemiquantitative is observed and is seen attached list.And, be the significance comparison that reference frame (M=0) is carried out group difference with the model control group with each class index (M) of organizing of grade preface value method calculating.See Table 4.(histology pictures is seen below, all look after object lens magnification and be 20 *)
Table 4 preparation of the present invention is to the morphology influence of rat carbon tetrachloride hepatic injury
| n | The degeneration necrosis degree | M | T | P | ||||
| - | + | ++ | +++ | |||||
| The heavy dose of low dose of the present invention of normal control model contrast positive control the present invention | 10 10 9 9 9 | 8 0 1 0 1 | 2 1 1 3 1 | 0 3 4 6 4 | 0 6 3 1 4 | 9.8 3.56 5.89 2.56 | 4.1 1.34 2.22 0.96 | ＜0.05 ＞0.05 ＜0.05 ＞0.05 |
Attached: the semi-quantitative assessment standard
"-" is normal
"+" pathological changes is dispersed in generation, and degree is lighter
" ++ " pathological changes is assembled around central vein, scope＜1/4 lobules of liver
" +++" pathological changes increases the weight of, and expanded range surpasses 1/4 lobules of liver
By table 4 as seen, each medication group M value all is following value, illustrates that its morphological indexes all is better than model control group, and wherein heavy dose of group of effect is the most remarkable.
3. to the how influence of fat mice serum content of bilirubin of isothiocyanic acid-1-
The 24-28g mice, the male and female dual-purpose, the grouping administration is with 1, successive administration 3 days, fasting 4h, 1h after the last administration gives 0.3% isothiocyanic acid-1-how fat peanut oil solution, and 0.2ml/10g ig closes 60mg/kg.Give isothiocyanic acid-1-how behind the fat 4h, mice is feeding once more, rechallenge behind the 24h gives isothiocyanic acid-1-how fat the 3rd day, fasting 5h, each Mus of 3h is plucked the right eye ball and gets blood 3000r/min after the administration, centrifugal 10 minutes, separation of serum was by the requirement of test kit description, carry out total bilirubin and conjugated bilirubin and measure, the mensuration wavelength is 600nm.The result organizes a significant difference relatively by t check, as table 5:
Table 5 pair isothiocyanic acid mice serum total bilirubin, the influence of conjugated bilirubin content
| Group | Dosage | n | Total bilirubin | Red in conjunction with gallbladder | ||
| (nmol/L) | P | Plain (nmol/L) | P | |||
| Normal control group model matched group small dose group of the present invention | -- -- 1.8g/kg | 12 12 12 | 1.88±3.99 40.95±17.92 14.55±9.94 | ＜0.001 ＜0.001 | 2.15±1.53 9.73±5.37 4.19±1.39 | ＜0.001 ＜0.001 |
| The heavy dose of group of the present invention positive controls | 3.6g/kg 1.5ml/kg | 12 12 | 10.41±5.46 18.73±3.7 | ＜0.01 ＜0.001 | 3.47±2.28 5.47±1.48 | ＜0.001 ＜0.01 |
Annotate model group and compare with the normal control group, other group is compared with model control group
Brief summary
By pharmacodynamics test preparation of the present invention as can be known to D-Gal; the big mice acute liver damage that carbon tetrachloride causes all has significant protective effect; not only obviously reduce Serum ALT and AST; and hepatic tissue also there is significant protective effect; alleviate the hepar damnification degree; isothiocyanic acid is caused the high bilirubin of mice serum tangible reduction effect, confirms that this product has tangible reducing enzyme and treating jaundice hepatoprotective effect, and these effects meet with its attending effectiveness.
Following embodiment is further openly the present invention, need to prove that these embodiment only for optimal way of the present invention, do not limit the scope of protection of present invention.
Embodiment 1
Baicalin 66.7 weight portion Flos Lonicerae extracts (in chlorogenic acid) 13.3 weight portions
Fructus Gardeniae extract 10.7 weight portion Herba Artemisiae Scopariae extract 20 weight portions
To pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, adding cane sugar powder and dextrin are an amount of, mixing, and it is an amount of to add ethanol, granulate, drying, promptly.
Assay:
(1) assay method of baicalin:
Chromatographic condition and system suitability test octadecyl silane are packing material
With 47: 53: 0.2 methanol-water-phosphoric acid of ratio is mobile phase
Detect wavelength 280nm
The preparation precision of reference substance solution takes by weighing the about 10mg of the baicalin that is dried to constant weight, puts in the 10ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 0.5g, puts in the 50ml measuring bottle, add 50% methanol 35ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, adds 50% methanol to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add 50% methanol, shake up to scale, with microvoid filter membrane (0.45 μ m), filter, promptly;
Accurate respectively reference substance solution and the need testing solution 10 μ l of drawing of algoscopy;
(2) assay method of chlorogenic acid:
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica;
With ratio is that 10: 90 acetonitrile-0.4% phosphoric acid solution is a mobile phase
The detection wavelength is 327nm
It is an amount of that the preparation precision of reference substance solution takes by weighing the chlorogenic acid reference substance, adds methanol and make the solution that every 1ml contains 0.05mg, shakes up, promptly;
This product is got in the preparation of need testing solution, and porphyrize gets that about 0.5g is accurate to be claimed surely, puts in the tool plug conical flask, adds 50% methanol 50ml, claims decide weight, and ultrasonic 30min is put coldly, and weight decided in title again.Supply with 50% methanol and to subtract weight loss, shake up, filter, get that filtrate is an amount of to be added brown measuring bottle and promptly get for test agent solution;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid,
Measure, promptly;
(3) assay method of jasminoidin:
The chromatographic condition octadecylsilane chemically bonded silica is a filler
With ratio is that 10: 90 acetonitrile-0.05% trifluoroacetic acid water is mobile phase;
The detection wavelength is 239nm
The preparation precision of reference substance solution takes by weighing in 60 ℃ of jasminoidin reference substances that are dried to constant weight an amount of, makes the solution that every 1ml contains 1.0mg with mobile phase, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 3g, put in the tool plug conical flask, add 50% methanol 20ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, add 50% methanol to scale, shake up, filter, evaporate to dryness with the mobile phase dissolving, is put in the 2ml measuring bottle, add mobile phase and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, and calculate with external standard method, promptly.
Result: contain in every gram granule: baicalin 60mg, contain: chlorogenic acid 13.3mg, contain: jasminoidin 1.4mg.
Embodiment 2
Baicalin 40 weight portion Flos Lonicerae extracts (in chlorogenic acid) 20 weight portions
Fructus Gardeniae extract 15 weight portion Herba Artemisiae Scopariae extract 30 weight portions.
To pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, adding cane sugar powder and dextrin are an amount of, mixing, and it is an amount of to add ethanol, granulate, drying, promptly;
Assay:
(1) assay method of baicalin:
Chromatographic condition and system suitability test octadecyl silane are packing material
With 47: 53: 0.2 methanol-water-phosphoric acid of ratio is mobile phase
Detect wavelength 280nm
The preparation precision of reference substance solution takes by weighing the about 10mg of the baicalin that is dried to constant weight, puts in the 10ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 0.5g, puts in the 50ml measuring bottle, add 50% methanol 35ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, adds 50% methanol to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add 50% methanol, shake up to scale, with microvoid filter membrane (0.45 μ m), filter, promptly;
Accurate respectively reference substance solution and the need testing solution 10 μ l of drawing of algoscopy;
(2) assay method of chlorogenic acid:
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica;
With ratio is that 10: 90 acetonitrile-0.4% phosphoric acid solution is a mobile phase
The detection wavelength is 327nm
It is an amount of that the preparation precision of reference substance solution takes by weighing the chlorogenic acid reference substance, adds methanol and make the solution that every 1ml contains 0.05mg, shakes up, promptly;
This product is got in the preparation of need testing solution, and porphyrize gets that about 0.5g is accurate to be claimed surely, puts in the tool plug conical flask, adds 50% methanol 50ml, claims decide weight, and ultrasonic 30min is put coldly, and weight decided in title again.Supply with 50% methanol and to subtract weight loss, shake up, filter, get that filtrate is an amount of to be added brown measuring bottle and promptly get for test agent solution;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid,
Measure, promptly;
(3) assay method of jasminoidin:
The chromatographic condition octadecylsilane chemically bonded silica is a filler
With ratio is that 10: 90 acetonitrile-0.05% trifluoroacetic acid water is mobile phase;
The detection wavelength is 239nm
The preparation precision of reference substance solution takes by weighing in 60 ℃ of jasminoidin reference substances that are dried to constant weight an amount of, makes the solution that every 1ml contains 1.0mg with mobile phase, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 3g, put in the tool plug conical flask, add 50% methanol 20ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, add 50% methanol to scale, shake up, filter, evaporate to dryness with the mobile phase dissolving, is put in the 2ml measuring bottle, add mobile phase and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, and calculate with external standard method, promptly
Result: contain in every gram granule: baicalin 10mg, contain: chlorogenic acid 25mg, contain: jasminoidin 0.5mg.
Embodiment 3
Baicalin 90 weight portion Flos Lonicerae extracts (in chlorogenic acid) 6 weight portions
Fructus Gardeniae extract 15 weight portion Herba Artemisiae Scopariae extract 30 weight portions.
To pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, add lactose, sweeting agent is an amount of, mixing, dry granulation, packing, promptly;
Content assaying method is the same:
Measurement result: contain in every gram granule: baicalin 200mg, contain: chlorogenic acid 4mg, contain: jasminoidin 5mg.
Embodiment 4
Baicalin 90 weight portion Flos Lonicerae extracts (in chlorogenic acid) 20 weight portions
Fructus Gardeniae extract 5 weight portion Herba Artemisiae Scopariae extract 30 weight portions.
To pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, the agent of adding dextrin flavor is an amount of, and the ethanol system soft material with 70% is granulated, drying, and tabletting, promptly;
Content assaying method is the same:
Measurement result: contain in every gram granule: baicalin 100mg, contain: chlorogenic acid 25mg, contain: jasminoidin 0.5mg.
Embodiment 5
Baicalin 90 weight portion Flos Lonicerae extracts (in chlorogenic acid) 20 weight portions
Fructus Gardeniae extract 15 weight portion Herba Artemisiae Scopariae extract 12 weight portions.
To pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, the agent of adding dextrin flavor is an amount of, and the ethanol system soft material with 70% is granulated, and drying is encapsulated, promptly;
Assay:
(1) assay method of baicalin:
Chromatographic condition and system suitability test octadecyl silane are packing material
With 47: 53: 0.2 methanol-water-phosphoric acid of ratio is mobile phase
Detect wavelength 280nm
The preparation precision of reference substance solution takes by weighing the about 10mg of the baicalin that is dried to constant weight, puts in the 10ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, promptly;
This product content is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 0.5g, puts in the 50ml measuring bottle, add 50% methanol 35ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, adds 50% methanol to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add 50% methanol, shake up to scale, with microvoid filter membrane (0.45 μ m), filter, promptly;
Accurate respectively reference substance solution and the need testing solution 10 μ l of drawing of algoscopy;
(2) assay method of chlorogenic acid:
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica;
With ratio is that 10: 90 acetonitrile-0.4% phosphoric acid solution is a mobile phase
The detection wavelength is 327nm
It is an amount of that the preparation precision of reference substance solution takes by weighing the chlorogenic acid reference substance, adds methanol and make the solution that every 1ml contains 0.05mg, shakes up, promptly;
This product content is got in the preparation of need testing solution, and porphyrize gets that about 0.5g is accurate to be claimed surely, puts in the tool plug conical flask, adds 50% methanol 50ml, claims decide weight, and ultrasonic 30min is put coldly, and weight decided in title again.Supply with 50% methanol and to subtract weight loss, shake up, filter, get that filtrate is an amount of to be added brown measuring bottle and promptly get for test agent solution;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid,
Measure, promptly;
(3) assay method of jasminoidin:
The chromatographic condition octadecylsilane chemically bonded silica is a filler
With ratio is that 10: 90 acetonitrile-0.05% trifluoroacetic acid water is mobile phase;
The detection wavelength is 239nm
The preparation precision of reference substance solution takes by weighing in 60 ℃ of jasminoidin reference substances that are dried to constant weight an amount of, makes the solution that every 1ml contains 1.0mg with mobile phase, promptly;
This product content is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 3g, put in the tool plug conical flask, add 50% methanol 20ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, add 50% methanol to scale, shake up, filter, evaporate to dryness with the mobile phase dissolving, is put in the 2ml measuring bottle, add mobile phase and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, and calculate with external standard method, promptly
Measurement result: contain in every gram granule: baicalin 150mg, contain: chlorogenic acid 25mg, contain: jasminoidin 5mg.
Embodiment 6
Baicalin 66.7 weight portion Flos Lonicerae extracts (in chlorogenic acid) 13.3 weight portions
Fructus Gardeniae extract 10.7 weight portion Herba Artemisiae Scopariae extract 20 weight portions.
To pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, mixing, the taking polyethylene glycol heating and melting adds medicated powder in addition, drips and makes ball, and packing promptly gets drop pill.
Content assaying method: with embodiment 1.
Measurement result: contain in every gram granule: baicalin 20mg, contain: chlorogenic acid 4mg, contain: jasminoidin 0.5mg.
Embodiment 7
Baicalin 66.7 weight portion Flos Lonicerae extracts (in chlorogenic acid) 13.3 weight portions
Fructus Gardeniae extract 10.7 weight portion Herba Artemisiae Scopariae extract 20 weight portions.
To pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, mixing, it is an amount of that other gets dextrin, adds medicated powder, mixing, the general ball of making, packing promptly gets pill.
Content assaying method: with embodiment 1.
Measurement result: contain in every gram granule: baicalin 40mg, contain: chlorogenic acid 8mg, contain: jasminoidin 2mg.
The preparation method of Flos Lonicerae extract: extracting honeysuckle, with 30% alcohol reflux secondary, each 1 hour, merge extractive liquid, filters, and filtrate recycling ethanol extremely every 1ml contains crude drug 2g, add ethanol and make and contain alcohol amount and reach 75%, left standstill 24 hours, filter, filtrate recycling ethanol extremely every 1ml contains crude drug 4g, adds water to doubly amount, cold preservation 48 hours, filter, filtrate is concentrated into the thick paste shape, vacuum drying, promptly;
The preparation method of Fructus Gardeniae extract: get Fructus Gardeniae, be ground into coarse powder, decoct with water three times, first and second time 1 hour, 0.5 hour for the third time, collecting decoction, filter, filtrate is concentrated into every 1ml and contains crude drug 1g, adds ethanol and makes and contain alcohol amount and reach 70%, cold preservation 24 hours, filter, filtrate recycling ethanol contains crude drug 3g to every 1ml, adds ethanol again and makes and contain the alcohol amount and reach 85%, cold preservation 24 hours, filter, filtrate recycling ethanol adds the about 5 times of amounts of water, cold preservation 48 hours to every 1ml water content crude drug 5g, filter, filtrate is concentrated into the thick paste shape, vacuum drying, promptly;
The preparation method of baicalin: Radix Scutellariae is cataclasm, decocts with water secondary, each 1 hour, merging filtrate, filtrate transfers pH value to 1.0-2.0 with hydrochloric acid (2mol/L), at 80 ℃ of insulation 30min, leave standstill 24h, filter, precipitation adds 8 times of water gagings, stir, transfer pH value to 7.0 with 40% sodium hydroxide solution, and add equivalent ethanol, stirring makes dissolving, filters, and filtrate is transferred PH to 2.0 with hydrochloric acid (2mol/L), 60 ℃ of insulation 30min leave standstill 12h, filter, precipitation is washed till PH to 4.0 with ethanol, adds 10 times of water gagings, stirs, transfer PH to 6.0 with 40% sodium hydroxide solution, add 0.5% active carbon, fully stir, 50 ℃ of insulation 30min add 1 times of amount ethanol and stir, and filter immediately, filtrate is transferred PH to 2.0 with hydrochloric acid (2mol/L), and 60 ℃ of insulation 30min leave standstill 12h, filter, after precipitation is washed with small amount of ethanol, in dry below 60 ℃, promptly.
Claims (5)
1, a kind of Chinese medicine granules for the treatment of hepatitis is characterized in that it is made by following raw material:
Baicalin 40-90 weight portion Flos Lonicerae extract (in chlorogenic acid) 6-20 weight portion
Fructus Gardeniae extract 5-15 weight portion Herba Artemisiae Scopariae extract 12-30 weight portion.
And its preparation method is:
Preparation method of the present invention: will pulverize with Flos Lonicerae extract, Fructus Gardeniae extract, baicalin, Herba Artemisiae Scopariae extract, adding cane sugar powder and dextrin or lactose are an amount of, mixing, and it is an amount of to add ethanol, granulate, drying, promptly;
The preparation method of Flos Lonicerae extract: extracting honeysuckle, with 30% alcohol reflux secondary, each 1 hour, merge extractive liquid, filters, and filtrate recycling ethanol extremely every 1ml contains crude drug 2g, add ethanol and make and contain alcohol amount and reach 75%, left standstill 24 hours, filter, filtrate recycling ethanol extremely every 1ml contains crude drug 4g, adds water to 8 times of amounts, cold preservation 48 hours, filter, filtrate is concentrated into the thick paste shape, vacuum drying, promptly;
The preparation method of Fructus Gardeniae extract: get Fructus Gardeniae, be ground into coarse powder, decoct with water three times, first and second time 1 hour, 0.5 hour for the third time, collecting decoction, filter, filtrate is concentrated into every 1ml and contains crude drug 1g, adds ethanol and makes and contain alcohol amount and reach 70%, cold preservation 24 hours, filter, filtrate recycling ethanol contains crude drug 3g to every 1ml, adds ethanol again and makes and contain the alcohol amount and reach 85%, cold preservation 24 hours, filter, filtrate recycling ethanol adds the about 5 times of amounts of water, cold preservation 48 hours to every 1ml water content crude drug 5g, filter, filtrate is concentrated into the thick paste shape, vacuum drying, promptly;
The preparation method of baicalin: Radix Scutellariae is cataclasm, decocts with water secondary, each 1 hour, merging filtrate, filtrate transfers pH value to 1.0-2.0 with the hydrochloric acid of 2mol/L, at 80 ℃ of insulation 30min, leave standstill 24h, filter, precipitation adds 8 times of water gagings, stir, transfer pH value to 7.0 with 40% sodium hydroxide solution, and add equivalent ethanol, stirring makes dissolving, filters, and filtrate is transferred PH to 2.0 with the hydrochloric acid of 2mol/L, 60 ℃ of insulation 30min leave standstill 12h, filter, precipitation is washed till PH to 4.0 with ethanol, adds 10 times of water gagings, stirs, transfer PH to 6.0 with 40% sodium hydroxide solution, add 0.5% active carbon, fully stir, 50 ℃ of insulation 30min add 1 times of amount ethanol and stir, and filter immediately, filtrate is transferred PH to 2.0 with the hydrochloric acid of 2mol/L, and 60 ℃ of insulation 30min leave standstill 12h, filter, after precipitation is washed with small amount of ethanol, in dry below 60 ℃, promptly.
2, the assay method of the effective ingredient of granule as claimed in claim 1 is characterized in that:
(1) assay method of baicalin:
Chromatographic condition and system suitability test octadecyl silane are packing material
With 47: 53: 0.2 methanol-water-phosphoric acid of ratio is mobile phase
Detect wavelength 280nm
The preparation precision of reference substance solution takes by weighing the about 10mg of the baicalin that is dried to constant weight, puts in the 10ml measuring bottle, adds dissolve with methanol and is diluted to scale, shakes up, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 0.5g, puts in the 50ml measuring bottle, add 50% methanol 35ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, adds 50% methanol to scale, shake up, filter, precision is measured subsequent filtrate 1ml, put in the 10ml measuring bottle, add 50% methanol, shake up to scale, with microvoid filter membrane (0.45 μ m), filter, promptly;
Accurate respectively reference substance solution and the need testing solution 10 μ l of drawing of algoscopy;
(2) assay method of chlorogenic acid:
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica;
With ratio is that 10: 90 acetonitrile-0.4% phosphoric acid solution is a mobile phase
The detection wavelength is 327nm
It is an amount of that the preparation precision of reference substance solution takes by weighing the chlorogenic acid reference substance, adds methanol and make the solution that every 1ml contains 0.05mg, shakes up, promptly;
This product is got in the preparation of need testing solution, and porphyrize gets that about 0.5g is accurate to be claimed surely, puts in the tool plug conical flask, adds 50% methanol 50ml, claims decide weight, and ultrasonic 30min is put coldly, and weight decided in title again.Supply with 50% methanol and to subtract weight loss, shake up, filter, get that filtrate is an amount of to be added brown measuring bottle and promptly get for test agent solution;
Accurate respectively reference substance solution and each the 20 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly; (3) assay method of jasminoidin:
The chromatographic condition octadecylsilane chemically bonded silica is a filler
With ratio is that 10: 90 acetonitrile-0.05% trifluoroacetic acid water is mobile phase;
The detection wavelength is 239nm
The preparation precision of reference substance solution takes by weighing in 60 ℃ of jasminoidin reference substances that are dried to constant weight an amount of, makes the solution that every 1ml contains 1.0mg with mobile phase, promptly;
This product is got in the preparation of need testing solution, porphyrize, and it is fixed to get the accurate title of about 3g, put in the tool plug conical flask, add 50% methanol 20ml, heating is 20 minutes in hot water, jolting constantly, supersound process 20 minutes is put and is chilled to room temperature, add 50% methanol to scale, shake up, filter, evaporate to dryness with the mobile phase dissolving, is put in the 2ml measuring bottle, add mobile phase and be diluted to scale, shake up, promptly;
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, and calculate with external standard method, promptly.
3, granule as claimed in claim 1 is characterized in that containing in every gram granule: baicalin 10-200mg.
4, granule as claimed in claim 1 is characterized in that containing in every gram granule: chlorogenic acid 4-25mg.
5, granule as claimed in claim 1 is characterized in that containing in every gram granule: jasminoidin 0.5-5mg.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410073956 CN1253170C (en) | 2004-09-17 | 2004-09-17 | Chinese medicine preparation for treating hepatitis and its preparing and detecting method |
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| CN 200410073956 CN1253170C (en) | 2004-09-17 | 2004-09-17 | Chinese medicine preparation for treating hepatitis and its preparing and detecting method |
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| CN100341536C (en) * | 2005-07-06 | 2007-10-10 | 鲁南制药集团股份有限公司 | Yinzhihuang dispersion tablet of oriental wormwood, cape jasmine and baicalin, and its preparing and detecting method |
| CN100352468C (en) * | 2005-07-06 | 2007-12-05 | 鲁南制药集团股份有限公司 | Yinzhihuang tablet of oriental wormwood, cape jasmine and baicalin, and its preparing and detecting method |
| CN102675387B (en) * | 2011-03-18 | 2015-02-18 | 四川济生堂药业有限公司 | Method for extracting baicalin from scutellaria baicalensis |
| CN111617127A (en) * | 2020-06-24 | 2020-09-04 | 鲁南制药集团股份有限公司 | A pharmaceutical composition for treating icterohepatitis with syndrome of dampness-heat in liver and gallbladder, and its preparation method |
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Effective date of registration: 20161223 Address after: 276005 Hongqi Road, Shandong, Linyi, No. 209 Patentee after: Lunan Hope Pharmaceutical Co., Ltd. Address before: 276005 Hongqi Road, Shandong, Linyi, No. 209 Patentee before: Lunan Pharmaceutical Group Co., Ltd. |