CN100389785C - Pedunculate herpetospermum seed extract, its dripping pill and their preparing method and application - Google Patents
Pedunculate herpetospermum seed extract, its dripping pill and their preparing method and application Download PDFInfo
- Publication number
- CN100389785C CN100389785C CNB2006100731163A CN200610073116A CN100389785C CN 100389785 C CN100389785 C CN 100389785C CN B2006100731163 A CNB2006100731163 A CN B2006100731163A CN 200610073116 A CN200610073116 A CN 200610073116A CN 100389785 C CN100389785 C CN 100389785C
- Authority
- CN
- China
- Prior art keywords
- extract
- preparation
- drop pill
- caudigerum wall
- herpetospermum caudigerum
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to the technical fields of a semen herpetospermi extract product and a drop pill dosage form thereof and a preparation method of the extract product and a dripping pill and application, which belongs to the technical field of the invention of a traditional Chinese medicine preparation. China is a region with high pathogenesis rate of viral hepatites, chronic hepatitis b is not easily controlled because of rapid development of illness state, semen herpetospermi is a choice medicine for treating hepatoses in Tibetan medicine, and because the prescription amount is small, and the preparation process of the Tibetan medicine falls behind, the medicine absorption is greatly influenced. An effective fraction which is semen herpetospermi lignan and an administration dose of the semen herpetospermi lignan are determined by pharmacodynamics research. In the present invention, raw medicinal materials containing the semen herpetospermi lignan, which resist hepatitis viruses and resist tumors, are extracted from the semen herpetospermi by a modern extraction process and a modern preparation process, and the semen herpetospermi lignan raw medicinal material-drop pill preparation is prepared.
Description
Technical field
The invention belongs to Chinese medicine preparation invention technical field, be specifically related to the preparation method and the applied technical field of Herpetospermum caudigerum Wall. Extract and drops thereof and extract and drop pill.
Background technology
China is the viral hepatitis district occurred frequently, and chronic hepatitis B wherein particularly causes concern because of its state of an illness develops gradually, wayward, poor prognosis, pathogeny are complicated.It is hepatitis b virus carriers that there are nearly 1.3 hundred million people in the present whole nation, 5,000 ten thousand people suffer from chronic hepatitis, die from about 230,000 people of patient (investigation statistics data of in December, 2002 health ministry show: hepatitis still is the infectious disease kind that China's M ﹠ M all ranks first) of hepatitis every year, add sick kind of viral hepatitis that other known and unknown due to illness malicious alienation causes, cause the sickness rate of population of China higher, hazardness is bigger.According to incompletely statistics, China is directly used in the medical expense of hepatitis control every year above 1,000 hundred million yuans, therefore, the treatment of chronic hepatitis B still is one of difficult problem in the current hepatopathy field, though interferon in vogue both at home and abroad, nucleoside medicine treatment have certain curative effect, prospect allows of no optimist.At present, viral hepatitis treatment does not still have essence to be broken through, and its overall number of patients still has continuous ascendant trend, and the problem of hepatitis chronicity is still unresolved.Because domestic perinatal stage and childhood infection proportion height, Hepatitis B virus vaccine lower in some areas popularity, original HBV carries reasons such as crowd's radix is huge, in present and even following many decades, the chronic hepatitis that hepatitis B virus etc. cause will be one of disease of serious harm China people ' s health.
Herpetospermum caudigerum Wall. is one of choice drug of treatment hepatopathy in the Tibetan medicine, in being used for the treatment of the Tibetan medicine prescribed preparation of hepatopathy, is arranged over half being used as medicine.But because recipe quantity is less than normal, and Tibetan medicinal preparation technology is backward, influences the absorption of medicine greatly.We determine that by pharmacodynamic study effective site is Fructus Herpetospermi pedunculosi total lignans and dosage thereof, adopt modern technology to be developed into drops.According to its function and take dosage form, the called after liver can drop pill, has advantages such as drug dose is little, curative effect is high, release is fast, oral easy absorption.
Summary of the invention
At above defective, need a kind of steady quality, dose controlled on the market, consumption is little, curative effect is high, release is fast, oral easy absorption, and be suitable for the drop pill that contains the Herpetospermum caudigerum Wall. effective component extracts of large-scale production.
One object of the present invention is to disclose Herpetospermum caudigerum Wall. Extract and dropping pill formulation thereof.
Another object of the present invention has been to disclose the preparation method of Herpetospermum caudigerum Wall. Extract and dropping pill formulation thereof.
For achieving the above object, the present invention has adopted following technical scheme:
1, Herpetospermum caudigerum Wall. Extract is the preparation of Fructus Herpetospermi pedunculosi total lignans's crude drug:
1), the Herpetospermum caudigerum Wall. dry product is ground into coarse powder, according to the Pharmacopoeia of the People's Republic of China (one one, version in 2005), coarse powder is meant that all the powder by No. four sieves of standard is no more than 40% powder;
2), coarse powder is decocted extraction with 80% ethanol of 5～10 times of coarse powder amounts, extract twice, each 2 hours, collecting decoction;
3), decoction liquor adopts the sheet frame suction method to carry out sucking filtration, filtrate is evaporated to every 1ml medicinal liquid and is equivalent to the 2g crude drug under 40 ℃～100 ℃; Regulate concentrated solution pH value to 9～11 with NaOH, behind the resolution of precipitate, regulate pH value to 2～3 with HCl, centrifugal, abandon supernatant; It with boiling range 60～90 ℃ petroleum ether washing and precipitating thing, 40 ℃～100 ℃ following low-temperature reduced-pressure dryings, dry thing is ground into fine powder, cross 100 mesh sieves, obtain containing 2.0～7.9% PED I, 2.0～7.5% PED II, 1.5～7.0% herpetal, 1.5～15.3% herpetin, 5.0～39.6% herpetrione, the Herpetospermum caudigerum Wall. Extract of 4.3～28.7%herpetetrone is Fructus Herpetospermi pedunculosi total lignans's crude drug.
2, the qualitative and quantitative assay of main effective ingredient in Fructus Herpetospermi pedunculosi total lignans's crude drug:
2.1 the qualitative investigation of main effective ingredient in Fructus Herpetospermi pedunculosi total lignans's crude drug:
(1), compound H erpetrione (PED X), its structural formula is:
Mass spectral analysis [M+H]
+=553, obtaining molecular weight is 552.
The peak position ownership:
13Chemical shift δ=198.423 present the response signal of a carbonyl unsaturated carbon among the C, 151.641,147.969,147.694,147.322,145.887,142.999 be shown as six fragrant carbonyls that are connected with oxygen atom, 132.731,132.002,128.785,123.258 show and have four non-oxygen substituted aroma carbonaceous in the molecule.123.079,118.660,117.216,114.680,114.389,111.406,109.579,108.024 show that six not substituted aroma carbon are arranged in the molecule.
13The C spectrum shows the existence of oxolane and oxolane ring in 85.984,85.841,71.204,71.162,54.979,54.637 displacements, in addition, chemical shift comprises three methoxy groups in 53.972,53.841,53.739 corresponding signal prompting molecular structure.
13C NMR spectrum and known references (Kaouadji M, Favre BJ.Herpetrione, atrimeric lignoide isolated from Herpetospermum caudigerumWall[J] .Tetrahedron Lett, 1983,24 (52): the herpetrione structure of report is corresponding 5881-5884), simultaneously
1The peak position ownership of H NMR can be confirmed above-mentioned deduction.
(2), compound H erpetetrone:
Mass spectral analysis [M+Na] +=753, obtaining molecular weight is 730.
The peak position ownership:
13The peak position ownership of C: the response signal of a carbonyl unsaturated carbon appears in δ=198.369,147.999,147.721,146.212,144.085,143.023,134.503,133.165 be shown as seven aromatic carbons that are connected with oxygen atom, 123.330,118.316,117.230,114.936,114.772,114.647,111.227,110.703,109.172,108.006 show the existence of ten unsubstituted aromatic carbons.87.798 the response signal of position is because of being subjected to the influence of space structure, connecting the displacement of the carbon of phenyl on the oxolane.In addition, 86.230,85.952,71.332,71.157,55.413,55.163 chemical shift then common witness the existence of oxolane and oxolane ring, 63.436, there are the secondary carbon of two methylols in 62.771 promptings, have four methyl carbon in 54.987,54.836,54.068,53.913 prompting structures.
13The deduction and known references (the Kaouadji M of C NMR spectrum, Favre BJ, Sarrazin.Herpetetrone, another tetrameric lignoid fromHerpetospermum caudigerum seeds[J] .J.Nat.Prod., 1987,50 (6): the herpetetrone structure of report is corresponding 1089-1093.), simultaneously
1The peak position ownership of H NMR can be confirmed above-mentioned deduction.
(3), Compound P ED I:
Mass spectral analysis [M+Na]
+=397, obtaining molecular weight is 374.
The peak position ownership:
13The C peak position belongs to as shown in the figure: wherein NMR displacement δ 2.759 (d), 2.407 (d), 4.003,3.801 (dd), 4.804 (d) of chemical shift 44.006,54.112,73.611,84.312 and the top H that connects respectively thereof prove the existence of oxolane ring.33.928 and 2.739,2.515 (dd), 60.579 and 3.843,3.672 (dd) then show the existence that comprises the secondary carbon-based group that two chemical environments differ in the molecule jointly.116.176, the chemical shift at 116.014,115.824,114.436,111.943,111.607 places shows in the molecular structure and contains 6 unsubstituted aromatic carbons that fragrant hydrogen proton has been given corresponding proof respectively at the signal peak of 6.838 (dd), 6.933 (dd), 6.803 (d), 6.815 (d), 6.965 (d), 6.962 (d).
1All the other peak position ownership of H NMR have also been confirmed above-mentioned deduction.According to above-mentioned deduction and to each relevant analysis of composing, obtain said structure, called after: 3-methylol, 2-(3-methoxyl group, 4-hydroxy benzenes), 4-(3, the 4-dimethoxy benzene) oxolane.
(4), Compound P ED II:
Mass spectral analysis [M+K]
+=429, obtaining molecular weight is 390.
The peak position ownership:
13The C peak position belongs to as shown above: the wherein existence of chemical shift 55.261,55.366,89.045,89.187 proof oxolane rings, simultaneously, above-mentioned data combination
1The data of H NMR show that there are four symmetric relatively replacements in the oxolane ring in this molecular structure.63.853 with 3.845,3.660 (dd), and 63.357 and 3.840,3.650 (dd) molecular structure in show two symmetric secondary carbon-based groups of existence in the molecular structure.116.086, the chemical shift at 115.807,111.885,111.011,110.600,105.335 places shows in the molecular structure and contains 6 unsubstituted aromatic carbons.
1The peak position ownership of H NMR can be confirmed above-mentioned deduction.According to above-mentioned deduction and to each relevant analysis of composing, obtain said structure, called after: 3,4-dihydroxymethyl, 2-(3-methoxyl group, 4-hydroxy benzenes), 5-(3, the 4-dimethoxy benzene) oxolane.
(5), compound H erpetal (PED XI):
Mass spectral analysis [M+H]
+=355, obtaining molecular weight is 354.
By fragment ion is analyzed, in this mass spectrum, the listed very high fragment ion of relative abundance below also existing is a typical fragment ion in the contained lignan component in this crude drug, and this is also for determining that this chemical compound provides evidence for Herpetal:
297 C
17H
13O
5 +
151 C
10H
15O
+
137 C
9H
13O
+
2.2 the quantitative study of each composition in Fructus Herpetospermi pedunculosi total lignans's crude drug:
1) instrument and material
1.1) material: crude drug self-control (lot number 030512).PED I, PED II, herpetal, herpetrione, herpetin, herpetetrone are laboratory self-control (purity is all above 98%).Acetonitrile is a chromatographic grade, and water is redistilled water, and all the other reagent are analytical pure.
1.2) instrument: high performance liquid chromatograph (being furnished with the DAD detector, the Agilent-1100 type U.S.); Chromatographic column (ODS post, Kromasil 250 * 4.6mm, 5 μ m Sweden; Normal phase column, Alltech 250 * 4.6mm, Apollo Silica, 5 μ m); Microsyringe (25 μ l, the Hamilton U.S.); Microanalytical balance (Mettler AE163 Switzerland) etc.
2) method and result
2.1) preparation of reference substance solution: precision takes by weighing above-mentioned six kinds of reference substances, and each is an amount of, accurately claims surely, puts respectively in the 25ml measuring bottle, add methanol 20ml ultrasonic dissolution, put coldly, add methanol and be diluted to scale, shake up, be mixed with the reference substance solution that concentration is 0.2mg/ml respectively, store for future use.
2.2) preparation of need testing solution: get the crude drug 12mg of Fructus Herpetospermi pedunculosi total lignans, accurately claim surely, add methanol 20ml, claim decide weight, supersound process 30min weighs after the cooling again, adds methanol and supplies bodies lost weight, filtration.Accurately measure in subsequent filtrate 5ml to the 10ml measuring bottle, add methanol constant volume, shake up, make the sample need testing solution to scale.
2.3) chromatographic condition
2.3.1) reversed phase chromatography condition chromatographic column: Kromasil, 5 μ m C18 posts (250 * 4.6mm); Mobile phase: acetonitrile-0.05% phosphoric acid water (20: 80); Detect wavelength: 280nm; Flow velocity: 1ml/min; Column temperature: room temperature;
2.3.2) normal-phase chromatography condition chromatographic column: Alltech, Apollo Silica, 5 μ m (250 * 4.6mm); Mobile phase: cyclohexane extraction-methylene chloride-methanol (42.5: 42.5: 5); Detect wavelength: 280nm; Flow velocity: 1ml/min; Column temperature: room temperature;
2.4) measurement result
2.4.1) the reversed-phase HPLC measurement result of 10 batches of ripple rib crude drug
2.4.2) the positive HPLC measurement result of 10 batches of ripple rib crude drug
It is as follows to draw in the extract main content of effective by above result: PED I content range 2.0～7.9%, PED II content range 2.0～7.5%, herpetal content range 1.5～7.0%, herpetin content range 1.5～15.3%, herpetrione content range 5.0～39.6%, herpetetrone content range 4.3～28.7%; Also contain a spot of following composition coniferylalcohol, herpetriol, herpetetrol, herpetradione, herpepentol, herpetone, herpetfluorenone, herpetenol in the extract.
3, the preparation process of the dropping pill formulation of Herpetospermum caudigerum Wall. Extract is as follows:
1), to take by weighing mass percent be 70% pharmaceutic adjuvant, heating and melting;
2), to get mass percent be 30% Herpetospermum caudigerum Wall. Extract, adds in the pharmaceutic adjuvant of molten condition, stirs fusion;
3), with step 2) in medicinal liquid add drop pill machine liquid storage tank, selecting a kind of in dimethicone and/or the liquid paraffin is liquid coolant, and the liquid coolant height is 60～120cm, and temperature is 6～30 ℃, dripping speed is 40 droplets/minute, is prepared with the liquid coolant on filter paper flush away drop pill surface.
Described pharmaceutic adjuvant is selected from one or more the arbitrary proportion combination in pEG4000, PEG6000, PVP, poloxamer188 and the carbamide.
Among the preparation technology of above-mentioned drop pill, the DWJ series automatization drop pill machine that uses Yantai Yintai Kangdaer Pharmaceutical Co., Ltd to produce.
Owing to adopted technique scheme, obtained Fructus Herpetospermi pedunculosi total lignans's crude drug and drop pill thereof, have and extract and preparation process is stable, quality controllable, the recipe quantity consumption is little, the curative effect advantages of higher.
The specific embodiment
Below specify the beneficial effect that medicine of the present invention has by testing example, the pharmacodynamics test and the clinical trial of medicine under test example comprises.
Test example 1 pharmacodynamics test
1. instrument, reagent and animal
1.1 medicine and reagent
Fructus Herpetospermi pedunculosi total lignans's crude drug, laboratory self-control (lot number 030512).Bifendate, Beijing XieHe medicine Factory (lot number 030109).Lamivudine, the plain one-tenth of Britain Ge Lan health company limited produces (lot number: 00212008).Glutamate pyruvate transaminase (GPT), glutamic oxaloacetic transaminase, GOT (GOT) are measured test kit, are the safe clinical reagent company limited of Beijing northization product.Total protein (TP), albumin (ALB) are measured test kit, are Beijing Zhongsheng Biological Engineering High Technology Company's product.Cyclophosphamide (Cy) injectable powder, Hengrui Medicine Co., Ltd., Jiangsu Prov. produces, lot number: 01060821.D-galactosamine (D-GalN), α-ANIT (ANIT) analytical pure, chemical defence institute of the Chinese People's Liberation Army provides.Bacillus calmette-guerin vaccine (BCG), Beijing Biological Product Inst. produces, lot number: 010910.Lipopolysaccharide (LPS), Sigma company product, lot number: L2688.Phytohaemagglutinin (PHA), Sigma company product, lot number: L8754.Eagles MEM dry powder, G-418 (Geneticin), yeast t-RNA, E.C. 3.4.21.64, U.S. GIBCO company product.Hyclone, U.S. Hyclone Lab company product.L-glutaminate, the import packing of Jing Ke chemical reagents corporation.HBsAg, HBeAg solid phase ria-determination box, Beifang Inst. of Immune Reagents, Chinese Isotopes Co.'s product.Kanamycin, North China Pharmaceutical Factory's product.Other reagent is commercially available analytical pure.The Wistar rat, body weight 190-210g, male and female half and half are by Chinese biological goods calibratings institute animal center (the animal quality certification number: SCXK11-00-0010) provide; Kunming mouse, body weight 18-22g, male and female half and half are by Military Medical Science Institute's animal center (the animal quality certification number: medical officer moves word BDW95001) and Chinese biological goods calibrating institute animal center (the animal quality certification number: SCXK11-00-0010) provide; 1 age in days Beijing duck, 80-100g, planting institute animal feeding field by Beijing medical courses in general institute medicine provides.The zoopery condition: two grade standards, the quality certification number: medical officer moves word B98006.BS-224 biochemical analysis analyzer.
2.1 anti-hepatitis virus test
Adopt anti-dhbv dna test, to carry out the evaluation of hepatitis virus resisting pharmacodynamics primary dcreening operation with Herpetospermum caudigerum Wall. total lignans crude drug.With DHBVDNA is observation index, analyzes the drug action of various dose under same level, and has carried out the repeated authentication test.By crude drug, respectively with 0.15g/kg day, 0.3g/kg day, 0.45g/kg day three dosage infect the age in days duckling of DHBVDNA, 3 days (P3) gets blood after 5 days (T5), 10 days (T10), drug withdrawal after the administration, adopt the dot blot hybridization method to measure DHBVDNA level in the serum, judge the inhibitory action of medicine DHBVDNA.The results are shown in Table 1,2:
Table 1 crude drug in the duck body to the suppression ratio (the 1st batch) of DHBVDNA
Table 2 crude drug in the duck body to the suppression ratio (the 2nd batch) of DHBVDNA
The pharmacodynamic result of table 1 and table 2 proves: the anti-dhbv dna effect of crude drug is remarkable.
2.2 the liver protecting and ALT lowering experiment
2.2.1 carbon tetrachloride is caused the influence of rat chronic hepatic injury
Get the Wistar rat, be divided into 6 groups at random by body weight, 10 every group, normal control group, liver injury model group, three dosage groups of crude drug basic, normal, high (0.008g, 0.016g, 0.032g/kg).Except that the normal control group, each treated animal lumbar injection 10%CCl
4Vegetable oil 0.5ml/100g body weight, weekly twice, totally 12 weeks, normal control group ip normal saline.Modeling is ig every day be administered once (0.5ml/100g body weight, normal control group ig is with the distilled water of volume) simultaneously.Before experiment finished, femoral artery blood was got in animal fasting 12 hours, with 3000 rev/mins centrifugal 10 minutes, separation of serum is measured GPT, GOT, TP, ALB, with sacrifice of animal, get hepatic tissue and make hydroxyproline determination after the blood sampling, calculate liver collagen content (the results are shown in Table 3,4).
Table 3 pair carbon tetrachloride causes the influence (n=10) of rat chronic hepatic injury
Compare #p＜0.05, ##p＜0.01 with normal group; Compare * p＜0.05, * * p＜0.01 with model group
The influence of table 4. pair rats'liver collagen content (X ± SD)
Compare * p＜0.05, * * p＜0.01 with model group
Table 3,4 results show that crude drug can suppress multiple injection CCl
4The rat blood serum transaminase's who causes rising, total protein and albumin reduce, and reduce the liver collagen content.
2.3 influence to the mouse immune liver damage
60 of healthy mices are divided into six groups at random, three dosage groups of normal control group, model group, bifendate group (0.029g/kg), crude drug (0.012,0.023,0.046g/kg), 10 every group, mice ig administration 2 times/day, totally 10 days.Except that the normal control group, every caudal vein is injected 0.25%BCG 2.5mg before the administration, every Mus tail vein injection LPS 2.5 μ g attack again after 10 days, and the eyeball rear vein beard is got blood and is surveyed Serum ALT, AST after 12 hours.
The influence of table 5 pair mouse immune liver damage (X ± SD)
Compare with the normal control group,
*P＜0.01; Compare * p＜0.05, * * p＜0.01 with model group
Table 5 is the result show, crude drug has the obvious suppression effect to the rising of immunologic liver injury mice serum transaminase due to the BCG+LPS, has compared significant difference with model group.
2.4 antitumor action
Method respectively with human hepatoma cell strain BEL-7402, BEL-7404, and human colon cancer cell strain HCT be object of study, to contain the culture medium and the cell co-cultivation of different diluted concentration ripple rib crude drug, adopt the inhibitory action of mtt assay detection of drugs effect to cancerous cell.Target cell is adjusted to 1 * 105/mL with complete culture solution, be inoculated in respectively in 96 well culture plates, every hole 100 μ L, add different pastille serum of 100 μ L and blank serum then respectively, cumulative volume 200 μ L, establish 7 parallel holes for every group, after under 37 ℃, 5%CO2, saturated humidity condition, cultivating 48h, every hole adds 5mL MTT 10 μ L, carry out chromogenic reaction after continuing to cultivate 4h, add 20% dimethyl sulfoxide, 100 μ L cessation reactions, concussion 10min, at DG3022-A type enzyme-linked immunosorbent assay instrument, wavelength 570nm surveys absorbance (A) value.The cytotoxic activity computing formula is:
The results are shown in Table 6.
The suppression ratio (%) of table 6. pair growth of tumour cell
The result shows: ripple rib crude drug is respectively 1.45,1.68 to 50% suppression ratio of BEL-7402, BEL-7404, is 2.36 to 50% suppression ratio of HCT, illustrates that ripple rib crude drug of the present invention has the obvious suppression effect to the different carcinoma cell in-vitro growth.
The clinical trial of test example 2 medicinal dropping ball agent treatment chronic viral hepatitis Bs of the present invention
1 data and method
1.1 this group of data case is HBeAg and/or the male chronic hepatitis patient of HBV DNA.Clinical being divided into: treatment group (liver energy drop pill group) 30 examples (go into group 36 examples altogether, 6 examples come off naturally because of therapy discontinued).Wherein male 20 examples, women 10 examples; Age (19～55) year, average (28.6 ± 8.67) year; Equal positive person's 30 examples of HBeAg and HBVDNA; Diagnostic criteria according to chronic hepatitis B in " viral hepatitis is prevented and treated scheme " of Chinese Medical Association's the tenth national viral hepatitis academic conference discussion revision in JIUYUE, 2000 Xi'an
[1]Matched group (lamivudine group) 28 examples.Wherein male 22 examples, women 6 examples; Age (20～58) year, average (31.34 ± 9.26) year; Equal positive person's 28 examples of HBeAg and HBVDNA.Two groups of patients in aspect data such as sex, age, the course of disease and the state of an illness relatively have harmony and comparability.
1.2 that method adopts is open, counter point at random.The treatment group gives liver can drop pill.Prescription is formed: ripple rib crude drug 12g PEG400020g PEG60008g makes 1000.Usage: 12/time, 3 times/day.Matched group gives lamivudine, and is every day 1 time, oral.Two groups are 3 months a course of treatment.Treatment group and matched group are all used basic medicine (comprising vitamins and general liver-protecting medicine), but do not use other antiviral agents and immunomodulator.Two groups respectively at before the treatment, treatment back every month, detect serum glutamic pyruvic transminase (ALT), glutamic oxaloacetic transaminase, GOT (AST), bilirubin (BIL) when treatment finishes, adopt the ELISA method to detect 7 indexs of hepatitis B virus, fluorescence quantitative PCR method detects HBVDNA; And detect blood, routine urinalysis, renal function." viral hepatitis traditional Chinese medical science curative effect determinate standard (try) " judgement curative effect of formulating according to internal medicine hepatopathy Professional Committee of Chinese Chinese medicine association.
The statistical method enumeration data is used the x of SAS6.12
2Testing procedure.
2, result
2.1 the treatment group that influences to serum HBeAg is treated positive 30 examples of preceding HBeAg, treatment back 9 routine the moon change, and negative conversion rate is 30.00%; Positive 28 examples of HBeAg before matched group (lamivudine) treatment are treated cloudy commentaries on classics of back 6 examples, and negative conversion rate is that 21.4%, two group of HBeAg negative conversion rate compares P＞0.05, difference not statistically significant.
2.2 the treatment group that influences to serum HBV DNA is treated positive 30 examples of preceding HBVDNA, treatment back 16 routine the moon change negative conversion rate 53.33%; Positive 28 examples of HBV.DNA before matched group (lamivudine) treatment, treatment back 19 examples are cloudy changes negative conversion rate 67.86%.Two groups of HBVDNA negative conversion rates compare P＞0.05, difference not statistically significant.(seeing Table 6).
Hbv replication index positive rate situation of change relatively before and after the table 6 liang group treatment
2.3 unusual 30 examples of ALT before the multiple reason condition treatment group treatment of liver function before and after the treatment, multiple normal 23 examples in treatment back, the ALT normalization rate is 76.67%.Unusual 28 examples of ALT before the treatment of control group, multiple normal 21 examples in treatment back, treatment back ALT normalization rate is 75.00%.Two groups of ALT normalization rates compare P＞0.05, difference not statistically significant (seeing Table 7).
Unusual 29 examples of AST before the treatment of treatment group, multiple normal 28 examples in treatment back, the AST normalization rate is 96.55%.Unusual 25 examples of AST before the treatment of control group, multiple normal 12 examples in treatment back, treatment back AST normalization rate is 48.0%.Two groups of AST normalization rates compare, P＜0.01, and difference has statistical significance (seeing Table 7).
The multiple reason condition of liver function relatively before and after the table 7 liang group treatment
3, untoward reaction and processing treatment group have no adverse reaction substantially in therapeutic process or are very slight, and slight loose stool appears in rarely seen 3 routine patients, need not special handling, spontaneous remission.Blood WBC, BUN, Cr all do not have significant difference before and after the treatment.Stomach discomfort after taking medicine in various degree appears in 4 examples in matched group 28 examples all gives alleviating after the anti symptom treatment.
Specify the preparation process of medicine of the present invention by the following examples.
Embodiment 1 Herpetospermum caudigerum Wall. Extract is the preparation of crude drug:
Embodiment 1-1
Herpetospermum caudigerum Wall. Extract, its preparation method is as follows:
1), the Herpetospermum caudigerum Wall. dry product is ground into coarse powder;
2), coarse powder is decocted extraction with 80% ethanol of 6 times of coarse powder amounts, extract 2 times, each 2 hours, collecting decoction;
3), decoction liquor adopts the sheet frame suction method to carry out sucking filtration, filtrate is evaporated to every 1ml medicinal liquid and equals the 2g crude drug under 40 ℃; Regulate the concentrated solution pH value to pH=10 with NaOH, behind the resolution of precipitate, regulate pH value to pH=2 with HCl, centrifugal, abandon supernatant; With boiling range is 60 ℃ petroleum ether washing and precipitating thing, 40 ℃ of following low-temperature reduced-pressure dryings, dry thing is ground into fine powder, crosses 100 mesh sieves, obtains Herpetospermum caudigerum Wall. Extract.
Embodiment 1-2
The preparation method of Herpetospermum caudigerum Wall. Extract, its step and raw material such as embodiment 1-1 are in step 2) in coarse powder is decocted extraction with 80% ethanol of 8 times of coarse powder amounts; In step 3), make filtrate at 50 ℃ of following concentrating under reduced pressure; Regulate the concentrated solution pH value to pH=10.5 with NaOH, behind the resolution of precipitate, regulate pH value to pH=2.5 with HCl, centrifugal, abandon supernatant; With boiling range is 70 ℃ petroleum ether washing and precipitating thing, 50 ℃ of following low-temperature reduced-pressure dryings, dry thing is ground into fine powder, crosses 100 mesh sieves, obtains Herpetospermum caudigerum Wall. Extract.
Embodiment 1-3
The preparation method of Herpetospermum caudigerum Wall. Extract, its step and raw material such as embodiment 1-1 are in step 2) in coarse powder is decocted extraction with 80% ethanol of 10 times of coarse powder amounts; In step 3), make filtrate at 60 ℃ of following concentrating under reduced pressure; Regulate the concentrated solution pH value to pH=11 with NaOH, behind the resolution of precipitate, regulate pH value to pH=3 with HCl, centrifugal, abandon supernatant; With boiling range is 90 ℃ petroleum ether washing and precipitating thing, 60 ℃ of following low-temperature reduced-pressure dryings, dry thing is ground into fine powder, crosses 100 mesh sieves, obtains Herpetospermum caudigerum Wall. Extract.
The preparation of the dropping pill formulation of embodiment 2 Herpetospermum caudigerum Wall. Extracts:
Embodiment 2-1
The preparation of the dropping pill formulation of Herpetospermum caudigerum Wall. Extract may further comprise the steps:
1), to take by weighing mass percent be 10% pharmaceutic adjuvant PVP, heating and melting;
2), to get mass percent be 90% Herpetospermum caudigerum Wall. Extract, adds among the pharmaceutic adjuvant PVP of molten condition, stirs fusion;
3), with step 2) in medicinal liquid add drop pill machine liquid storage tank, selections dimethicone is a liquid coolant, the liquid coolant height is 60cm, temperature is 6 ℃, a speed is 40 droplets/minute, is prepared with the liquid coolant on filter paper flush away drop pill surface.
Embodiment 2-2
The preparation of the dropping pill formulation of Herpetospermum caudigerum Wall. Extract may further comprise the steps:
1), to take by weighing mass percent be 50% pharmaceutic adjuvant poloxamer188, heating and melting;
2), to get mass percent be 50% Herpetospermum caudigerum Wall. Extract, adds among the pharmaceutic adjuvant poloxamer188 of molten condition, stirs fusion;
3), with step 2) in medicinal liquid add drop pill machine liquid storage tank, selections dimethicone is a liquid coolant, the liquid coolant height is 90cm, temperature is 18 ℃, a speed is 40 droplets/minute, is prepared with the liquid coolant on filter paper flush away drop pill surface.
Embodiment 2-3
The preparation of the dropping pill formulation of Herpetospermum caudigerum Wall. Extract may further comprise the steps:
1), take by weighing 90% pharmaceutic adjuvant, this pharmaceutic adjuvant is PEG4000 and PEG6000 by mass ratio is to mix at 5: 2, with the pharmaceutic adjuvant heating and melting;
2), to get mass percent be 10% Herpetospermum caudigerum Wall. Extract, adds in the pharmaceutic adjuvant of molten condition, stirs fusion;
3), with step 2) in medicinal liquid add drop pill machine liquid storage tank, selections liquid paraffin is a liquid coolant, the liquid coolant height is 120cm, temperature is 30 ℃, a speed is 40 droplets/minute, is prepared with the liquid coolant on filter paper flush away drop pill surface.
Claims (7)
1. the preparation method of a Herpetospermum caudigerum Wall. Extract, it comprises following steps:
1), the Herpetospermum caudigerum Wall. dry product is ground into coarse powder;
2), coarse powder is decocted extraction with 80% ethanol of 5～10 times of coarse powder amounts, extract 2 times, each 2 hours, collecting decoction;
3), decoction liquor adopts the sheet frame suction method to carry out sucking filtration, filtrate is evaporated to every 1ml medicinal liquid and is equivalent to the 2g crude drug under 40 ℃～100 ℃; Regulate concentrated solution pH value to 9～11 with NaOH, behind the resolution of precipitate, regulate pH value to 2～3 with HCl, centrifugal, abandon supernatant; With petroleum ether washing and precipitating thing, 40 ℃～100 ℃ following low-temperature reduced-pressure dryings, dry thing is ground into fine powder, cross 100 mesh sieves, obtain Herpetospermum caudigerum Wall. Extract.
2. with the Herpetospermum caudigerum Wall. Extract of the described method of claim 1 preparation, it is characterized in that: described extract can extract acquisition with following method: with the Herpetospermum caudigerum Wall. coarse powder with 80% ethanol extraction of 5～10 times of coarse powder amounts 2 times, each 2 hours, collecting decoction; Decoction liquor is carried out sucking filtration, and filtrate is evaporated to every 1ml medicinal liquid and is equivalent to the 2g crude drug under 40 ℃～100 ℃; Regulate concentrated solution pH value to 9～11 with NaOH, behind the resolution of precipitate, regulate pH value to 2～3 with HCl, centrifugal, abandon supernatant; With petroleum ether washing and precipitating thing, 40 ℃～100 ℃ following low-temperature reduced-pressure dryings, dry thing is ground into fine powder, cross 100 mesh sieves, obtain containing 2.0～7.9% PEDI, 2.0～7.5% PED II, 1.5～7.0% herpetal, 1.5～15.3% herpetin, 5.0～39.6% herpetrione, the Herpetospermum caudigerum Wall. Extract of 4.3～28.7% herpetetrone.
3. the application of the described Herpetospermum caudigerum Wall. Extract of claim 2 in preparation anti-hepatitis virus medicament, medicines resistant to liver cancer, resistive connection bowelcancer medicine and the liver protecting and ALT lowering medicine.
4. the drop pill of the described Herpetospermum caudigerum Wall. Extract of claim 2 is characterized in that: described drop pill is that 10～90% Herpetospermum caudigerum Wall. Extract and 90～10% pharmaceutic adjuvant are formed by mass percent.
5. the described drop pill of claim 4 is characterized in that: described pharmaceutic adjuvant is selected from one or more the combination in PEG4000, PEG6000, PVP, poloxamer188 and the carbamide.
6. the preparation method of the described drop pill of claim 4, it is characterized in that: it may further comprise the steps:
1), takes by weighing the pharmaceutic adjuvant of described mass percent, heating and melting;
2), take by weighing the Herpetospermum caudigerum Wall. Extract of described mass percent, add in the pharmaceutic adjuvant of molten condition, stir fusion;
3), with step 2) in medicinal liquid add drop pill machine liquid storage tank, selecting a kind of in dimethicone and/or the liquid paraffin is liquid coolant, and the liquid coolant height is 60～120cm, and temperature is 6～30 ℃, dripping speed is 40 droplets/minute, is prepared with the liquid coolant on filter paper flush away drop pill surface.
7. the application of the described drop pill of claim 4 in preparation anti-hepatitis virus medicament, medicines resistant to liver cancer, resistive connection bowelcancer medicine and the liver protecting and ALT lowering medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100731163A CN100389785C (en) | 2006-04-04 | 2006-04-04 | Pedunculate herpetospermum seed extract, its dripping pill and their preparing method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100731163A CN100389785C (en) | 2006-04-04 | 2006-04-04 | Pedunculate herpetospermum seed extract, its dripping pill and their preparing method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1857367A CN1857367A (en) | 2006-11-08 |
| CN100389785C true CN100389785C (en) | 2008-05-28 |
Family
ID=37296355
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100731163A Expired - Fee Related CN100389785C (en) | 2006-04-04 | 2006-04-04 | Pedunculate herpetospermum seed extract, its dripping pill and their preparing method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100389785C (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102000136B (en) * | 2010-11-25 | 2012-04-18 | 西南大学 | Method for extracting components having antibacterial activity from fruit of pedunculate herpetospermum |
| CN102138525B (en) * | 2011-03-07 | 2012-07-18 | 西藏自治区高原生物研究所 | Tissue culture method of pedunculate herpetospermum fruit plant |
| CN102140101B (en) * | 2011-03-24 | 2013-04-10 | 中国人民解放军第三〇二医院 | Method for preparing Herperione, application thereof, capsule thereof, preparation method and application of capsule |
| CN104274551A (en) * | 2014-09-23 | 2015-01-14 | 苏州市天灵中药饮片有限公司 | Potentilla anserine and herpetospermum seed chewable tablet and preparation method thereof |
| CN104274550A (en) * | 2014-09-23 | 2015-01-14 | 苏州市天灵中药饮片有限公司 | Potentilla anserine-herpetospermum seed liver protecting effervescent tablet and preparation method thereof |
| CN105434503B (en) * | 2015-12-31 | 2020-11-27 | 成都中医药大学 | Liver-protecting pharmaceutical composition and preparation method and application thereof |
| WO2019213807A1 (en) * | 2018-05-07 | 2019-11-14 | 袁海龙 | Lignan active ingredient composition of herpetospermum caudigerum wall and preparation method therefor and application and dosage form thereof |
| CN112778432B (en) * | 2021-02-01 | 2022-04-22 | 西藏天虹科技股份有限责任公司 | Method for extracting herpetospermum pedunculosum seed polysaccharide |
| CN113116880B (en) * | 2021-05-25 | 2022-11-11 | 西南大学 | Application of herpetospermum elegans extract in preparation of medicine for treating non-alcoholic fatty liver disease |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1486691A (en) * | 2003-05-29 | 2004-04-07 | 中国人民解放军第三○二医院 | Bolengsu compound and its prepn, medicine composition and use |
-
2006
- 2006-04-04 CN CNB2006100731163A patent/CN100389785C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1486691A (en) * | 2003-05-29 | 2004-04-07 | 中国人民解放军第三○二医院 | Bolengsu compound and its prepn, medicine composition and use |
Non-Patent Citations (2)
| Title |
|---|
| 波棱素一种新的生物活性木脂素. 袁海龙.Journal of Chinese Phamaceutical Sciences,Vol.14 No.3. 2005 |
| 波棱素一种新的生物活性木脂素. 袁海龙.Journal of Chinese Phamaceutical Sciences,Vol.14 No.3. 2005 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1857367A (en) | 2006-11-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100389785C (en) | Pedunculate herpetospermum seed extract, its dripping pill and their preparing method and application | |
| CN103823034B (en) | A kind of honeysuckle reference extract and preparation method thereof | |
| CN102266318A (en) | Application of caffeoylquinic acid and derivatives thereof in preparing anticomplementary medicines | |
| CN101979366A (en) | Diarylheptanoid compounds in curcuma zedoary and medicinal application thereof | |
| CN101380318A (en) | Use of isochlorogenic acid compound and different combinations in hepatitis treatment | |
| CN101002849B (en) | Traditional Chinese medicine extractive or tablet for treating hepatitis, and its preparing method | |
| CN102140101B (en) | Method for preparing Herperione, application thereof, capsule thereof, preparation method and application of capsule | |
| CN103784427B (en) | Containing the pharmaceutical composition of eudesmane type sesquiterpene and the application in pharmacy thereof | |
| CN100544727C (en) | The pharmaceutical composition of treatment hepatitis B | |
| CN111150740A (en) | Lipid-lowering active ingredient and lipid-lowering composition in panax japonicus and application of lipid-lowering active ingredient and lipid-lowering composition | |
| CN1118471C (en) | Medicine containing tan matter caesalpinia extract | |
| CN112062738B (en) | Artemisinol A-B, pharmaceutical composition thereof, and preparation method and application thereof | |
| CN102818867A (en) | Quality control method for ribonucleic acid II for injection | |
| CN1264502C (en) | Injection of still-freeze drying powder for restoring consciousness and new preparation method | |
| CN107485615A (en) | Purposes of the Ligustrum robust glycosides C and combinations thereof in treatment hyperlipidemia and slimming medicine is prepared | |
| Liu et al. | Preparation and characterization of silymarin synchronized and sustained release dropping pill | |
| CN105535050A (en) | Radix angelica sinensis antitumor medicine | |
| CN105524077B (en) | Bilobalide K crystalline substance K-type and preparation method and its composition and purposes | |
| CN100516078C (en) | Adefovir dipivoxil CHARIOTEER crystallographic form and preparation method thereof | |
| CN102988486A (en) | New application of cinnamon oil and cinnamaldehyde serving as main component thereof in lung cancer resistance | |
| CN103191105A (en) | Application of furocoumarin compounds in preparation of anti-hepatitis B virus (HBV) medicaments | |
| CN108569953B (en) | Oriental wormwood triperydyl alcohol compound, pharmaceutical composition and application thereof | |
| CN100503592C (en) | Anti-AIDS virus active substance desmosdumotin D and desmosdumotin and its analogue | |
| CN101293833A (en) | 5-oxygen-substituted benzene alkene propionyl quinic acid compounds and medicine uses thereof | |
| CN110652509A (en) | Application of diaryl butyrolactone lignan compound in preparing anti-hepatic fibrosis medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080528 Termination date: 20110404 |