CN101559066A - Application of 2'-O-beta-L-galactopyranosyl orientin and composition in preparing medicaments for resisting myocardial ischemia - Google Patents
Application of 2'-O-beta-L-galactopyranosyl orientin and composition in preparing medicaments for resisting myocardial ischemia Download PDFInfo
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- CN101559066A CN101559066A CNA2009100669240A CN200910066924A CN101559066A CN 101559066 A CN101559066 A CN 101559066A CN A2009100669240 A CNA2009100669240 A CN A2009100669240A CN 200910066924 A CN200910066924 A CN 200910066924A CN 101559066 A CN101559066 A CN 101559066A
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- orientin
- galactoside
- ethanol
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- methanol
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- 235000014655 lactic acid Nutrition 0.000 description 1
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- 210000000867 larynx Anatomy 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
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- 208000010125 myocardial infarction Diseases 0.000 description 1
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
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- DJSISFGPUUYILV-ZFORQUDYSA-N scutellarin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC(O)=CC=1)O2 DJSISFGPUUYILV-ZFORQUDYSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses novel application of composition with the content of flavone C-glycoside 2'-O-beta-L-galactopyranosyl orientin and 2'-O-beta-L-galactopyranosyl orientin between 30 and 90 percent in preparing medicaments for resisting angiocardiopathy such as myocardial ischemia and the like, and also describes a single component of the 2'-O-beta-L-galactopyranosyl orientin, a method for preparing the composition, and a medicinal preparation.
Description
Technical field
The invention relates to the new medical use of orientin-2 " O-β-L-galactoside reaches and mainly contains orientin-2 "-O-β-L-galactoside compositions, the application of orientin-2 " O-β-L-galactoside and mainly contain orientin-2 "-O-β-L-galactoside compositions in the cardiovascular disease medicine that preparation is caused by myocardial ischemia etc. specifically, also relate to the extraction separation and the pharmaceutical preparation of this medicine, the invention belongs to medical technical field.
Background technology
Flos Trollii claims " nasturtium ", " nonirrigated farmland lotus ", " golden Hibisci Mutabilis ", " globe-flower ", " golden pimple " etc. again, is the dried floral of ranunculaceae plant Flos Trollii (Trollius chinensis Bge.).Totally 25 kinds of Flos Trollii platymisciums, medicinal gold Flos Nelumbinis have Flos Trollii asiatici (Trollius asiaticus L.) and short lobe Flos Trollii (Trollius ledebouri Reichb.), and longpetal globeflower flower (TroUiusmacropetalus Fr.Schmidt).The Flos Trollii beginning is stated from Qing Dynasty's supplementary Amplifications of the Compendium of Materia Medica that ZHAO Xue-Min is shown.In addition, all on the books in the books such as " groupoid side's spectrum ", " Zhiwu Mingshi Tukao ".Call its " bitter in the mouth, cold in nature, nontoxic " in the supplementary Amplifications of the Compendium of Materia Medica, can " it is swollen to control aphtha, larynx, the superficial heat gingival atrophy, ear is painful, ophthalmalgia ", the effect of " make eye bright, separate the haze miasma " had.The aboundresources of Flos Trollii has antibiotic, antivirus action, is widely used in treatment respiratory tract and intestinal infection etc. (contemporary Chinese Chinese medicine, 2007 9 volume 3 phase 29-32 pages or leaves).Flos Trollii mainly is that the carbon glycosides flavone that contains is a big feature.Reported that in research in the past reports such as Zhao Yimin extract chromocor compound with organic reagent and are used for diseases (CN1872084) such as rheumatic arthritis or rheumatoid arthritis; High spring equality report, Flos Trollii prepares Chinese globe flower injection (CN1876031) with water decoction-alcohol sedimentation, the isolating method of macroporous resin; Cai Jinna etc. have reported the preparation method (CN101234147) of total flavones of tropaeolum for injections, are with water extraction or ethanol extraction, concentrate, and separate through macroporous resin, polyamide then; Reports such as Fan Guorong will be lacked lobe Flos Trollii ethanol extraction, concentrate, and concentrated solution is crossed macroporous adsorbent resin, uses ethanol elution, with high-speed countercurrent chromatography (HSCCC) and preparative liquid chromatography purification, obtain highly purified orientin, apigenin-8-C-glucoside (CN1660864);
Fu XiaochunDeng reported the orientin that extracts from Folium Bambusae have anti thrombotic action research (China Dispensary, 2006,17 17 phases of volume, 1292-1294);
Fu XiaochunDeng the orientin that from Folium Bambusae, extracts have to the influence of dog experimental myocardial infarction (
Medicine is led Newspaper, 2006,25 7 phases of volume, 621-623);
Fu XiaochunDeng from Folium Bambusae, extract the protective effect of orientin to anoxia-reoxygenation myocardial cell (
Shenyang Pharmaceutical University's journal, 2005,22 1 phases of volume, 45-48).Yang Yaxin etc. have reported Flos Trollii 70% ethanol extraction, use n-butanol extraction, then with Sephadex LH-20 post separate orientin-2 " (Heilungkiang medicine; 2006; 19 (2) 93-94), but clearly will not imitate for O-β-L-galactoside, orientin.Up to the present " O-β-L-galactoside and compositions have function of resisting myocardial ischemia also not have bibliographical information orientin-2.We are on the basis to searching document and patent, to orientin-" O-β-L-galactoside and compositions have been carried out the experiment that resists myocardial ischemia, and have good pharmacological action.
Before finishing, the present invention finds no and closes orientin-2 that " O-β-L-galactoside and compositions be as the report that resists myocardial ischemia, and the compositions of also not finding orientin-2 " O-β-L-galactoside and mainly contain orientin-2 "-O-β-L-galactoside is used for the treatment of the clinicing aspect of the cardiovascular disease that is caused by myocardial ischemia etc. and uses.
Characteristics of the present invention are that extracting solution does not concentrate after Flos Trollii is with ethanol or methanol extraction and directly go up macroporous resin or polyamide column, and are simple to operate, and solved concentrated back effective ingredient and partly separate out, and the solution muddiness is unfavorable for the problem of upper prop.After reclaiming solvent.Can obtain high-load through macroporous resin column purification, silica gel purification again and must contain orientin-2 " the compositions of O-β-L-galactoside; Whole production technology is only used ethanol, does not use inflammable and explosive and toxic solvent, and production technology is simple, with short production cycle, and safe, free from environmental pollution, cost is low, and the yield height is particularly suitable for the industrialization mass production.
Orientin-2 " O-β-L-galactoside structural formula
Summary of the invention
The present invention studies have shown that by further animal experiment orientin-2 " O-β-L-galactoside reaches and mainly contains orientin-2 "-O-β-L-galactoside compositions has the effect that resists myocardial ischemia.Orientin-2 " O-β-L-galactoside reaches and mainly contains orientin-2 "-O-β-L-galactoside compositions has the new purposes in the medicine of preparation myocardial ischemia.Before the present patent application, find no the report that has the application of the cardiovascular disease that prevention and treatment cause by myocardial ischemia etc. about orientin-2 " O-β-L-galactoside and mainly contain orientin-2 "-O-β-L-galactoside compositions.
One of purpose of the present invention is an orientin-2, and " O-β-L-galactoside and compositions main component are carbon glycosides flavone, and carbon glycosides flavone Stability Analysis of Structures is difficult for being degraded, and can go deep into diseased region, directly brings into play drug effect; Hydrophilic strengthens, and the dissolution height helps the exploitation of medicine.Carbon glycosides flavone belongs to the current research forward position.Application in treatment myocardial ischemia heart disease is a main innovate point of the present invention.Had report can treat myocardial ischemia be mainly compound Chinese medicinal preparation and chemical drugs.Mainly containing of single effective site treatment myocardial ischemia: Radix Astragali total flavones, tea polyphenols, salvianolic acid and TANSHINONES, Radix Scutellariae total flavones, breviscapine, schisandrol soluble components, Fructus Hippophae flavone, icariin and total flavones, Folium Ginkgo total flavones etc.Be not used for the treatment of the report of myocardial ischemia disease so see carbon glycoside flavone component.
Two of the object of the invention has provided and mainly contained orientin-2 " O-β-L-galactoside compositions extraction separation method; mostly the method for disclosed in the past extraction Flos Trollii is defat with petroleum ether and removes oil-soluble impurities such as chlorophyll or only limit to breadboard the separation, is not suitable for industrialization production.Or with water extraction, concentrating the back has very big difference with macroporous resin or polyamide separation with the present invention.The present invention has adopted the method purification of ethanol extraction and macroporous resin or polyamide column chromatography to contain orientin-2 " O-β-L-galactoside compositions, workable, be fit to commercial production.The present invention has adopted the extracting solution of ethanol or methanol extraction Flos Trollii without concentrating first, direct adsorption and purification on macroporous resin or polyamide column, having solved the concentrated rear section of ethanol or methanol extract liquid effective ingredient separates out, the medicinal liquid muddiness is unfavorable for the problem of adsorption and purification on macroporous resin or polyamide column.The thick compositions of extracting through the alcohol dissolving of excessive concentrations, adds activated carbon decolorizing again, directly passes through the silica gel edulcoration purification, organic reagent eluting of no use, and workable, this is another innovative point of the present invention.
Three of the object of the invention is to utilize C-18 anti-phase (normal pressure or mesolow) column separating purification orientin-2 " O-β-L-galactoside monomer component." O-β-L-galactoside purity height (content 98%) is owing to adopt normal pressure or the mesolow detached dowel; can follow the specification according to needs design post; " the O-β-L-galactoside that can prepare high-purity orientin-2 in a large number for this method isolating orientin-2, detached dowel can use repeatedly, easy to operate, before the present patent application, do not see useful this method separation and purification orientin-2 " report of O-β-L-galactoside.The invention also discloses this compositions except that orientin-2 " O-β-L-galactoside; also contain orientin-2 " O-β-arabinose, orientin, apigenin-8-C-glucoside etc., with the total flavones of tropaeolum of bibliographical information preparation tangible difference is arranged, in the compositions of our preparation orientin-2 " O-β-L-galactoside is a main active.
Four of purpose of the present invention provides the pharmaceutical preparation of orientin-2 " O-β-L-galactoside reaches and mainly contains orientin-2 "-O-β-L-galactoside compositions.Mainly be oral formulations, mainly be selected from tablet, capsule, pill, granule, suspensoid, drop pill, any in the oral formulations.
Five of the object of the invention provide the orientin-2 that medicine preferably contains 1%-99% " O-β-L-galactoside and mainly contain orientin-2 " but-O-β-L-galactoside compositions and the pharmaceutical excipient of 99%-1% or the medicine of other prescription.The medicine of other compatibility in the medicine of the present invention, refer to that orientin-2 with effective dose " O-β-L-galactoside and mainly contain orientin-2 "-O-β-L-galactoside compositions is certain medicine material, again compatibility other allow the Chinese medicine or the chemical drugs that share.
Orientin-2 " content of O-β-L-galactoside, total flavones of tropaeolum is measured by the following method:
1, " O-β-L-galactoside utilizes high effective liquid chromatography for measuring to orientin-2: be filler with the octadecylsilane chemically bonded silica; With acetonitrile-0.35% phosphate aqueous solution (13: 87) is mobile phase; The detection wavelength is 345nm.Number of theoretical plate is by orientin-2, and " O-β-L-galactoside peak calculates and is not less than 3000.
The preparation precision of reference substance solution takes by weighing orientin-2, and " O-β-L-galactoside reference substance puts in the volumetric flask, makes orientin-2 with 60% dissolve with methanol, and " O-β-L-galactoside concentration is the reference substance solution of 0.04mg/ml.
Compositions 5mg is got in the preparation of need testing solution, and accurate the title decides, and puts in the 50ml measuring bottle, adds 60% methanol 40ml, and ultrasonic 30min is placed to room temperature, and 60% methanol constant volume shakes up to scale, as need testing solution.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of assay method inject chromatograph of liquid, measure, promptly.
2, total flavones of tropaeolum utilizes the ultraviolet colorimetric method for determining:
The preparation precision of reference substance solution takes by weighing the orientin reference substance, makes the reference substance solution of 0.01mg/ml with dissolve with ethanol.
Compositions 5mg is got in the preparation of need testing solution, and accurate the title decides, and puts in the 100ml measuring bottle, adds ethanol 80ml, and ultrasonic 30min is placed to room temperature, and ethanol is settled to scale, shakes up, and precision is measured 2ml, puts in the 10ml measuring bottle, adds ethanol to scale, as need testing solution.
Algoscopy is got reference substance solution, need testing solution, blank respectively.According to spectrophotography (" an appendix V of Chinese pharmacopoeia version in 2005 B), measure trap respectively at wavelength 345nm place, calculate.
Contain total flavones in the compositions and be not less than 80% in orientin.
Orientin-2 " O-β-L-galactoside reaches and mainly contains orientin-2 "-O-β-L-galactoside compositions has function of resisting myocardial ischemia, is confirmed by following pharmacodynamics test example.
1, " O-β-L-galactoside and compositions cause the Electrocardiographic influence of acute myocardial ischemia rat to pituitrin (Pit) to orientin-2
Get 80 of health, screening electrocardiogram normal rats, be divided into 8 groups at random, 10 every group, male and female half and half, according to table 1 grouping, each organizes equal gastric infusion, and every day, gastric infusion was 1 time, successive administration 7d, the normal control group is given the equivalent normal saline.50min behind the last medicine, each group is all in sublingual vein injection Pit 1U/kg, inject to finish in 10 seconds, and the electrocardiogram of record 20min is measured the variation to ST section in the pituitrin 30 seconds and T ripple.The results are shown in Table 1.
" O-β-L-galactoside and compositions cause the Electrocardiographic influence of acute myocardial ischemia rat to pituitrin to table 1 orientin-2
Compare with matched group:
*P＜0.05,
*P＜0.01,
* *P＜0.001
After matched group was given pituitrin, ECG ST section and T ripple were all obviously raised, and show that pituitrin can bring out the Electrocardiographic change of Acute Myocardial Ischemia in Rats.Compare with matched group, " the high, medium and low dosage group of O-β-L-galactoside and compositions improves significantly to bring out the Electrocardiographic variation of Acute Myocardial Ischemia in Rats to pituitrin orientin-2.
2, " O-β-L-galactoside and compositions are to the influence of MDA content in LDH, CPK and the cardiac muscular tissue in the myocardial ischemia mice serum due to the isoproterenol for orientin-2
Get 90 of mices, female, body weight 20 ± 2g, divide equally 9 groups by body weight, in the 7th day, press dosage shown in the table 2, every day gastric infusion once, 1st, give consubstantiality hydrops 10ml/kg for 2 groups, after administration 4-6 days, the 1st group of subcutaneous injection normal saline 10ml/kg, 2-8 group subcutaneous injection isoproterenol 4mg/kg, 24h after last is given isoproterenol, after the socket of the eye vein is got blood, measure lactic acid dehydrogenase (LDH) and creatine phosphokinase (CPK) content in the mice serum, the muscular tissue of coring is surveyed malonaldehyde (MDA) content.The results are shown in Table 2
" O-β-L-galactoside and compositions are to the influence of LDH and CPK in the myocardial ischemia mice serum due to the isoproterenol for table 2 orientin-2
Compare with model control group:
*P＜0.05,
*P＜0.01,
* *P＜0.001
The result shows, orientin-2, and " O-β-L-galactoside and compositions can obviously reduce because the activity of LDH and CPK in the myocardial ischemia mice serum due to the isoproterenol, and mda content in the cardiac muscular tissue, and there were significant differences.
3, " O-β-L-galactoside and compositions are to the influence of the weary oxygen of myocardial ischemia mouse anti due to the isoproterenol for orientin-2
Get 90 of male mices, divide equally 9 groups by body weight, pressed the gastric infusion of dosage shown in the table 3 in 7 days, be administered once every day, and after the last administration 30 minutes, subcutaneous injection (except first group) isoproterenol 5ml/kg did anti-weary oxygen experiment after 15 minutes.The results are shown in Table 3.
" O-β-L-galactoside and compositions are to the influence of the weary oxygen of myocardial ischemia mouse anti due to the isoproterenol for table 3 orientin-2
Compare with model control group:
*P＜0.05,
*P＜0.01,
* *P＜0.001
The result shows, orientin-2 " O-β-L-galactoside and compositions can obviously prolong myocardial ischemia mouse diing time due to the isoproterenol, and significant difference is arranged,
4, " O-β-L-galactoside and compositions are to the influence of the weary oxygen of myocardial ischemia mouse anti due to the sodium nitrite for orientin-2
Get 90 of female mices, divide equally 9 groups by body weight, in 7 days, press the gastric infusion of dosage shown in the table 9, after the last administration 30 minutes, except that matched group, all the other respectively organized equal lumbar injection 0.25% sodium nitrite 10ml/kg, behind the 15min mice is put into the 125ml wide mouthed bottle of dress sodica calx 5g, one every bottle, seal, observation and record stop as the hypoxia death time with mouse breathing.The result shows, orientin-2, and " O-β-L-galactoside and compositions do not have influence to myocardial ischemia mouse diing time due to the sodium nitrite, see Table 4.
" O-β-L-galactoside and compositions are to the influence of the weary oxygen of myocardial ischemia mouse anti due to the nitrous acid for table 4 orientin-2
5, " O-β-L-galactoside and compositions are to the influence of rat acute blood stasis model hemorheology index for orientin-2
Get 90 of rats, be divided into 9 groups at random, 10 every group, male and female half and half are divided into groups according to table 5.Continuous irrigation stomach 7d, last administration the previous day, except that the normal control group, each organizes rat skin lower injection adrenalin hydrochloride 0.8mg/kg twice, 6h at interval, inject 3h first after, rat is placed 0～2 ℃ of frozen water moderate stimulation 5min.After water 18h is can't help in fasting, last administration 1 time, 1h behind the medicine, with chloral hydrate anesthesia, abdominal aortic blood, anticoagulant heparin, blood viscosity instrumentation packed cell volume, whole blood specific viscosity (high shear rate 120/s, low shear rate 30/s), blood plasma specific viscosity.The results are shown in Table 5.
" O-β-L-galactoside and compositions are to the influence of rat acute blood stasis model hemorheology index for table 5 orientin-2
Compare with the normal control group:
△ △P＜0.01; Compare with model group:
*P＜0.05,
*P＜0.01
Compare with the normal control group, model group rat whole blood specific viscosity, blood plasma specific viscosity are apparently higher than normal group, show that stimulation can cause the Blood stasis model to epinephrine with frozen water, show the aspects such as sticking, coagulate of blood, " O-β-L-galactoside and compositions group and FUFANG DANSHEN PIAN group rat whole blood specific viscosity and blood plasma specific viscosity significantly descend orientin-2, and " O-β-L-galactoside and compositions group and FUFANG DANSHEN PIAN group can be improved hemorheology to show orientin-2.
6, " O-β-L-galactoside and compositions are to the influence of clotting time of mice for orientin-2
Get 50 of mices, be divided into five groups at random, dosage sees Table 6, and every day 1 time, continuous irrigation stomach 15 days behind the last medicine 1 hour, adopts slide method to measure clotting time.Experimental result proves: orientin-2, and " O-β-L-galactoside and compositions can make clotting time of mice prolong, and be remarkable with normal control group comparing difference.The results are shown in Table 6.
" O-β-L-galactoside and compositions are to clotting time of mice for table 6 orientin-2
Compare with matched group:
*P＜0.05,
*P＜0.01,
The present invention executes example by following experiment to be achieved.
Embodiment 1Contain orientin-2 " the extraction preparation of O-β-L-galactoside compositions:
Globeflower medicinal materials was with 50% alcohol reflux 3 times, each 2 hours.Filter, filtrate is directly passed through AB-8 macroporous resin column adsorption and purification, and extremely pure content is less than 10% for effluent and 50% ethanol elution recovery ethanol, and concentrated solution is through AB-8 macroporous resin column adsorption and purification.Wash with water earlier, reuse 50% ethanol elution is collected 50% ethanol elution, reclaim solvent to doing, with 85% ethanol heating for dissolving, add 1% medical active carbon, stir, filter, filtrate is directly passed through silica gel purification, and uses 85% ethanol elution, collects effluent and eluent, reclaim solvent to doing, " the O-β-L-galactoside compositions that must contain orientin-2." O-β-L-galactoside content is 51.3% to orientin in this compositions-2, and orientin content is 24.6%, and apigenin-8-C-glucoside content is 5.8%.
Embodiment 2Contain orientin-2 " the extraction preparation of O-β-L-galactoside compositions:
Globeflower medicinal materials was with 40% alcohol reflux 3 times, each 2 hours.Filter, filtrate is directly passed through polyamide post adsorption and purification, and extremely pure content is less than 10% for effluent and 40% ethanol elution recovery ethanol, and concentrated solution is through AB-8 macroporous resin column adsorption and purification.Wash with water earlier, reuse 50% ethanol elution is collected 50% ethanol elution, reclaim solvent to doing, with 90% ethanol heating for dissolving, add 1.5% medical active carbon, stir, filter, filtrate is directly passed through silica gel purification, and uses 90% ethanol elution, collects effluent and eluent, reclaim solvent to doing, " the O-β-L-galactoside compositions that must contain orientin-2." O-β-L-galactoside content is 52.6% to orientin in this compositions-2, and orientin content is 22.8%, and apigenin-8-C-glucoside content is 6.4%.
Embodiment 3Orientin-2 " preparation of O-β-L-galactoside:
" O-β-L-galactoside compositions goes up separation and purification at C-18 reversed-phase column (normal pressure); containing water-acetonitrile with 20% is eluant, collects orientin 2, and " O-β-L-galactoside flow point, thin layer identify that the back merges will to contain orientin-2, recrystallization gets orientin-2 " O-β-L-galactoside crystallization.Content is 98.5%.
Embodiment 4(capsule)
Orientin-2 " O-β-L-galactoside or composition material 100g, medical starch is an amount of, and mix homogeneously is granulated, drying, granulate, the capsule of packing into No. 1 is made 1000, promptly.Orientin-2 " each 2 of O-β-L-galactoside, every day 2 times.Each 3 of compositions, every day 2 times.
Embodiment 5(tablet)
Orientin-2 " O-β-L-galactoside or composition material 100g, medical starch is an amount of, and dextrin is an amount of, and mix homogeneously is granulated, drying, granulate, drying, the adding lubricant is an amount of, and tabletting is made 1000, promptly.Orientin-2 " each 2 of O-β-L-galactoside, every day 2 times.Each 3 of compositions, every day 2 times.
Embodiment 6(drop pill)
Take by weighing the 30g Macrogol 4000, in water-bath, melt, " O-β-L-galactoside or composition material 20g stir, in the impouring insulating tube; regulate thermostat; medicinal liquid is splashed in the liquid paraffin that cooled off under 80-90 ℃, after dripping off, will blot paraffin oil on the pill impouring filter paper; make 1000, promptly to add orientin-2.Orientin-2 " each 10 of O-β-L-galactoside, every day 2 times.Each 15 of compositions, every day 2 times.
Embodiment 7(granule)
" mix homogeneously is used an amount of alcohol granulation to orientin-2 for O-β-L-galactoside or composition material 100g, Icing Sugar 400g, and drying, granulate, packing are made 500 bags, promptly.Orientin-2 " each 1 bag of O-β-L-galactoside, every day 2 times.Each 1.5 bags of compositions, every day 2 times.
Claims (10)
1, orientin-2 " O-β-L-galactoside reaches and mainly contains orientin-the 2 "-application of O-β-L-galactoside compositions in the preparation medicaments for resisting myocardial ischemia.
2, the described purposes of claim 1 is characterised in that orientin in the compositions-2, and " O-β-L-galactoside content reaches 30-90%, contain orientin-2 in addition " O-β-arabinose, orientin, apigenin-8-C-glucoside.
3, " O-β-L-galactoside and compositions are to extract to obtain from the dried floral of Ranunculaceae Flos Trollii platymiscium Flos Trollii Trollius chinensisBunge, short lobe Flos Trollii Trollius ledebouri Reichb. and longpetal globeflower flower Trollius macropetalusFr.Schmidt to claim 1 described orientin-2.
4, claim 1 is described mainly contains orientin-2, and " O-β-L-galactoside preparation method of composition is: medical material extracts 2-3 time with aquiferous ethanol or the methanol of 30-95%, the ethanol of preferred 40-65% or methanol eddy, 1-3 hour at every turn.Extracting solution is directly through macroporous resin column or polyamide column adsorption and purification, with an ethanol or the methanol-eluted fractions 1-2 retention volume of 40-65%, effluent and eluent reclaim ethanol extremely pure content less than 10%.Through the macroporous resin column adsorption and purification, wash with water earlier, reuse 20-80% ethanol or methanol, preferred 50% ethanol or methanol-eluted fractions are collected 20-80% ethanol or meoh eluate, reclaim solvent to doing.With 60-95% ethanol or methanol heating for dissolving, preferred 85% ethanol or methanol, the medical active carbon that adds 0.3-3.0% filters, and filtrate is directly passed through silica gel purification, and with 60-95% ethanol or methanol, preferred 85% ethanol or methanol, eluting is collected effluent and eluent, reclaim solvent to doing, " the O-β-L-galactoside compositions that must contain orientin-2.
5, the method for described macroporous resin of claim 4 and polyamide column adsorption and purification is characterized in that with the extracting solution of ethanol or methanol extraction Flos Trollii without concentrating, directly on macroporous resin column or the polyamide column adsorption and purification.The described macroporous resin of claim 4 is D101, D201, AB-8, preferred D101 and AB-8 resin.
6, the ethanol of compositions usefulness 60-95% according to claim 4 or dissolve with methanol, filtration, go up separation and purification at C-18 reversed-phase column (normal pressure or mesolow), containing water-acetonitrile with 10-40% is eluant, " O-β-L-galactoside flow point; merge after thin layer is identified; recrystallization gets orientin-2 " O-β-L-galactoside crystal to collect orientin-2.Content is more than 95%.
7, application according to claim 1 is characterized in that: the orientin-2 that contains dose therapeutically effective " O-β-L-galactoside and compositions and one or more pharmaceutically acceptable pharmaceutical excipients, or can with the orientin-2 " preparation that the other medicines of O-β-L-galactoside and compositions prescription are made.
8, pharmaceutical preparation according to claim 7 is characterized in that preferably containing the orientin-2 of 1%-99% " but-pharmaceutical excipient of O-β-L-galactoside and compositions and 99%-1% or the medicine of other prescription make the dosage form of oral formulations.
9, pharmaceutical preparation according to claim 8 is characterized in that said oral formulations is selected from any in the middle of the tablet, pill, capsule, soft capsule, granule, suspensoid, drop pill, oral liquid.
10, the described pharmaceutical excipient of claim 9 comprises filler, disintegrating agent etc., and filler is selected from starch, lactose, microcrystalline Cellulose, dextrin, calcium phosphate etc.; Disintegrating agent is selected from carboxymethyl starch sodium, hyprolose, polyvinylpolypyrrolidone; Also optional adhesive, wetting agent and the lubricant of adding.
Priority Applications (1)
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940585A (en) * | 2010-08-25 | 2011-01-12 | 赵全成 | Composite using orientin-2'-O-beta-L-galactoside as main component and application thereof |
| CN102579474A (en) * | 2012-03-06 | 2012-07-18 | 赵全成 | Combination with orientin-2''-O-beta-L-galactoside as main ingredient and use of combination |
| CN102670634A (en) * | 2011-03-09 | 2012-09-19 | 苏州世林医药技术发展有限公司 | C-glycosylflavones composition, preparation method and application thereof |
| CN108484700A (en) * | 2018-04-04 | 2018-09-04 | 新疆维吾尔自治区药物研究所 | Orientin 2 ' '-O- β-L- galactosides and its preparation method and application |
-
2009
- 2009-05-08 CN CN2009100669240A patent/CN101559066B/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940585A (en) * | 2010-08-25 | 2011-01-12 | 赵全成 | Composite using orientin-2'-O-beta-L-galactoside as main component and application thereof |
| CN102670634A (en) * | 2011-03-09 | 2012-09-19 | 苏州世林医药技术发展有限公司 | C-glycosylflavones composition, preparation method and application thereof |
| CN102579474A (en) * | 2012-03-06 | 2012-07-18 | 赵全成 | Combination with orientin-2''-O-beta-L-galactoside as main ingredient and use of combination |
| CN108484700A (en) * | 2018-04-04 | 2018-09-04 | 新疆维吾尔自治区药物研究所 | Orientin 2 ' '-O- β-L- galactosides and its preparation method and application |
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| Publication number | Publication date |
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| CN101559066B (en) | 2012-01-25 |
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