CN102872155A - Application of flavonoid glycoside compound on medicine for treating cerebral apoplexy - Google Patents
Application of flavonoid glycoside compound on medicine for treating cerebral apoplexy Download PDFInfo
- Publication number
- CN102872155A CN102872155A CN2012104255481A CN201210425548A CN102872155A CN 102872155 A CN102872155 A CN 102872155A CN 2012104255481 A CN2012104255481 A CN 2012104255481A CN 201210425548 A CN201210425548 A CN 201210425548A CN 102872155 A CN102872155 A CN 102872155A
- Authority
- CN
- China
- Prior art keywords
- formula
- flavonoid glycoside
- compound
- glycoside compound
- group
- 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.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an application of a flavonoid glycoside compound on a medicine for treating cerebral apoplexy. A compound with a structure represented by a formula I is apigenin-7-O-beta-D-(6''-p-coumaroyl)-glucopy ranoside. The pharmacological test results prove that the compound has an obvious protection effect on ischemic injury caused by a middle cerebral artery occlusion (MACO) model and is free from toxic and side effects. The application of the flavonoid glycoside compound on the medicine for treating the cerebral apoplexy provided by the invention can provide a lead compound for preparing new medicines for protecting cerebral ischemic injury, so that the flavonoid glycoside compound can be a new medicine for treating the cerebral apoplexy.
Description
Technical field
The present invention relates to medical technical field; the application that is a kind of flavonoid glycoside compound in preparation treatment apoplexy medicine, specifically a kind of flavonoid glycoside compound apigenin-7-O-beta-D-(6 "-p-coumaric acyl)-pyranglucoside (apigenin-7-O-β-D-(6 " p-coumaroyl)-glucopyranoside) application in preparation treatment ischemia apoplexy medicine.
Background technology
Apoplexy (apoplexy) is the second largest cause of the death of China, and its high disability rate, case fatality rate and relapse rate have a strong impact on patient's life quality, and threat to life is healthy, causes great burden to family and society.At present for ischemia apoplexy, except the t-PA thromboembolism treatment, clinically there is no effective medicine or measure, but thromboembolism treatment there is again strict time window restriction, only has the only a few patient can access effective thromboembolism treatment.Therefore in the urgent need to development of new curing apoplexy medicine safely and efficiently.
Flavonoid glycoside compound is a class natural product that distributes in plant and very extensively exist, and many and sugar is combined into glycoside in plant.Pharmaceutical research shows that this compounds has the effects such as antioxidation, anti-inflammation, antitumor, also has significant curative effect aspect the cardiovascular and cerebrovascular diseases such as prevention and treatment coronary heart disease, hypertension and arteriosclerosis simultaneously.In recent years, the new cardiovascular medicament of separating natural flavonoid glycoside compound research and development becomes the focus that researcher is paid close attention to from traditional medicinal plants.
Apigenin-7-O-beta-D-(6 "-the p-coumaric acyl)-pyranglucoside (apigenin-7-O-β-D-(6 " p-coumaroyl)-glu copyranoside) belong to flavonoid glycoside compound, can from the plants such as Ranunculaceae Herba Clematidis tanguticae, Labiatae Herba Pogostemonis and Radix Lamiophlomidis Rotatae, extract.Ranunculaceae Actions of Clematis Species Herba Clematidis tanguticae (Clematis tangutica), the another name Clematistangutica (Maxim.) Korsh., the Tibetan medicine name claims again Ye Mangnabu, leaf Mongolian.Mainly be distributed in Qinghai-xizang Plateau Region, according to " Jingzhubencao " and the record such as " Tibetan medicine will " ancient books and records, its property is hot, sweet, warm, cold relieving, and the hypertrophy stomach-fire, the logical stasis of blood of invigorating blood circulation, broken painful abdominal mass tumor is gathered.In addition, Herba Clematidis tanguticae as the principal agent of compound preparation Yixinkangtai capsule evident in efficacy aspect the treatment cardiovascular and cerebrovascular disease.The inventor obtains flavonoid glycoside compound APG from the Herba Clematidis tanguticae separation first, though existing bibliographical information is crossed its structure and (is seen for details: Itokawa H, Suto K, et al.Studies on a novel p-coumaroyl glucoside of Apigenin and on other flavonoids isolated from Patchouli (Labiatae) .Chem Pharm Bull, 1981,29 (1): 254 ~ 256 and Zhang Aijun, Ren Fengxia, Deng. the research of Tibet medicine lamivphlomis root chemical constituent, Chinese Pharmaceutical Journal, 2011,46 (2): 102 ~ 104).But take a broad view of domestic and foreign literature, be showed no the application of this chemical compound aspect the treatment ischemic brain injury.
Summary of the invention
Purpose of the present invention provides the application of a kind of flavonoid glycoside compound in preparation treatment apoplexy medicine.This chemical compound has significant protective effect for line bolt method being caused the ischemia injury that middle cerebral artery thromboembolism (MCAO) model causes, and has no toxic and side effects.The present invention can be the drug provision lead compound of the new protection cerebral ischemia of development, can become new treatment apoplexy medicine.
The object of the present invention is achieved like this, a kind of flavonoid glycoside compound, and chemical structural formula is as follows:
Formula I
The chemical name of above-mentioned formula Ι structure is that ((6 " p-coumaroyl)-glucopyranoside) are flavonoid glycoside compound to apigenin-7-O-β-D-to apigenin-7-O-beta-D-(6 "-p-coumaric acyl)-pyranglucoside; hereinafter to be referred as APG, it is characterized in that: the application of formula Ι compd A PG in preparation treatment ischemia apoplexy medicine.
Described formula Ι compd A PG can use separately or prepare into clinically operable injection or powder or pill or capsule or tablet or microcapsule or soft capsule or membrane or unguentum or tincture or granule or aerosol with other drug.
Described ischemia apoplexy is Focal Cerebral Infarction.
Described flavone compound extracts separation from Herba Clematidis tanguticae, it is concrete, and to extract separating step as follows: take the Herba Clematidis tanguticae herb as raw material, raw material after crushed, volume ratio adds 3～5 times of 70% ethanol by weight, heating and refluxing extraction 3 times, each 2 ~ 4 hours; Extracting liquid filtering also merges, concentrate drying gets total extract, extract is scattered in the water of 4 times of volume ratios by weight, with with the isopyknic petroleum ether extraction of water 3 times, water after the extraction is used and the isopyknic n-butanol extraction of water 4 times again, merge butanol extraction liquid, decompression and solvent recovery obtains n-butanol portion; N-butanol portion is through silica gel column chromatography, chloroform-methanol-water mixed solution take volume ratio as 20:1:0.1 ~ 6:3:0.3 is eluant, gradient elution, thin layer chromatography detects, collection contains stream part of formula I chemical compound, through Sephadex LH-20 gel filtration chromatography, remove impurity with volume ratio 1:1 chloroform-methanol, get formula I compd A PG sterling.
Characteristics of the present invention are: the active drug that lacks clinically at present the treatment ischemia apoplexy.Compd A PG of the present invention is fat-soluble flavonoid glycoside compound, molecular weight is little, can pass through blood brain barrier, has good treatment ischemic brain injury effect, and have no toxic and side effects, show that it can be further used as new treatment apoplexy medicine and research and develop.
The specific embodiment
Now in conjunction with the embodiments the present invention is elaborated, but scope of the present invention and unrestricted.
Embodiment 1: the extraction of chemical compound with separate 1
The Herba Clematidis tanguticae herb that picks up from the Tibetan Autonomous Prefecture of Huangnan, Qinghai Province is raw material, dries in the shade, and after crushed, gets 4 kilograms of coarse powder, adds 12 liters of heating and refluxing extraction of 70% ethanol, extracts altogether each 2 hours 3 times.Extracting liquid filtering also merges, and concentrate drying gets total extract 985.6 grams.Extract is scattered in 4 premium on currency, uses petroleum ether extraction 3 times, and each 4 liters, the water after the extraction is used n-butanol extraction 4 times again, and each 4 liters, merge butanol extraction liquid, reclaim solvent, obtain n-butanol extraction position 168 grams.Through silica gel column chromatography (thin layer chromatography silica gel H, Haiyang Chemical Plant, Qingdao), the chloroform-methanol-water mixed solution take volume ratio as 20:1:0.1 ~ 6:3:0.3 is eluant, gradient elution with the n-butanol extraction position.Be one by 200 milliliters and flow a part collection, and detect with thin layer chromatography that (it is chloroform-methanol-subsurface layer of 7:3:1 that volume ratio is adopted in developing solvent, developer is volume ratio 1:4 sulphuric acid-alcoholic solution, develop the color in 105 ℃ of heating after spraying developer), collect the 24th ~ 38 stream part that contains as shown in the formula I compd A PG.Get 2.8 gram crude products behind the evaporated under reduced pressure solvent, the chloroform-methanol dissolving of volume ratio 1:1, through SephadexLH-20 sephadex column (GE-Healthcare company) chromatograph, the chloroform-methanol eluting of volume ratio 1:1, merge the 12nd ~ 18 stream part that contains as shown in the formula the I chemical compound, obtain behind the evaporated under reduced pressure solvent as shown in the formula I compd A PG sterling 1.2 grams.
Formula I
Its chemical name of said structure formula is that apigenin-7-O-beta-D-(6 "-p-coumaric acyl)-((6 " p-coumaroyl)-glucopyranoside) for apigenin-7-O-β-D-for pyranglucoside; the flavonoid glycoside compound that from Herba Clematidis tanguticae, separates, referred to as APG.
Embodiment 2: the extraction of chemical compound with separate 2
The Herba Clematidis tanguticae herb that picks up from the Tibetan Autonomous Prefecture of Huangnan, Qinghai Province is raw material, dries in the shade, and after crushed, gets 1 kilogram of coarse powder, adds 5 liters of heating and refluxing extraction of 70% ethanol, extracts altogether each 4 hours 3 times.Extracting liquid filtering also merges, and concentrate drying gets total extract 256.8 grams.Extract is scattered in 1 premium on currency, uses petroleum ether extraction 3 times, and each 1 liter, the water after the extraction is used n-butanol extraction 4 times again, and each 1 liter, merge butanol extraction liquid, reclaim solvent, obtain n-butanol extraction position 46 grams.Through silica gel column chromatography (thin layer chromatography silica gel H, Haiyang Chemical Plant, Qingdao), the chloroform-methanol-water mixed solution take volume ratio as 20:1:0.1 ~ 6:3:0.3 is eluant, gradient elution with the n-butanol extraction position.Be one by 200 milliliters and flow a part collection, and detect with thin layer chromatography that (it is chloroform-methanol-subsurface layer of 7:3:1 that volume ratio is adopted in developing solvent, developer is volume ratio 1:4 sulphuric acid-alcoholic solution, develop the color in 105 ℃ of heating after spraying developer), collect the 24th ~ 38 stream part that contains as shown in the formula I compd A PG.Get 0.8 gram crude product behind the evaporated under reduced pressure solvent, the chloroform-methanol dissolving of volume ratio 1:1, through SephadexLH-20 sephadex column (GE-Healthcare company) chromatograph, the chloroform-methanol eluting of volume ratio 1:1, merge the 12nd ~ 18 stream part that contains as shown in the formula the I chemical compound, obtain embodiment 1 formula I compd A PG sterling 0.35 gram behind the evaporated under reduced pressure solvent.
The Structural Identification of chemical compound
The formula I compd A PG of embodiment 1 and embodiment 2 is yellow unformed powder, the lower displaing yellow fluorescence of uviol lamp (365nm), and hydrochloric acid-magnesium powder and Molish reaction all are positive, ESI-MS provides quasi-molecular ion peak m/z 601[M+Na]
+(positive mode), in conjunction with
1H-NMR (500MHz, DMSO-d
6) and
13C-NMR (125MHz, DMSO-d
6) spectral data (Table 1) determines that its molecular formula is C
30H
26O
13
1δ 6.49 (1H, d, J=1.8Hz, H-6) and δ 6.82 (1H, d, J=1.8Hz, H-8) are the hydrogen proton signal of 6,8 interdigit idols in the H-NMR spectrum; There are one group of AA ' BB ' Coupling System in 4 aromatic ring hydrogen proton signal δ 7.95 (2H, d, J=8.7Hz, H-2 ', 6 ') and δ 6.93 (2H, d, J=8.7Hz, H-3 ', 5 ') prompting chemical compound; Other 4 aromatic ring hydrogen proton signal δ 7.38 (2H; d; J=8.5Hz, H-5 " ', 9 " ') and δ 6.68 (2H; d; J=8.5Hz, H-6 " ', 8 " ') there is other one group of AA ' BB ' Coupling System in prompting; therefore infer that chemical compound also has 11 except the flavone parent nucleus; the structure fragment of 4 substituted benzene rings, and in conjunction with δ 6.34 (1H, d; J=15.9Hz; H-2 " ') and δ 7.50 (1H, d, J=15.9Hz; H-3 " ') provide the hydrogen proton signal of 1 unsaturated trans double bond structure, infer in the chemical compound to have hydroxyl cinnamyl structure.5.18 (1H, d, J=7.4Hz, H-1 ") be the terminal hydrogen proton signal of glucose, and be beta comfiguration.
13C-NMR spectrum (table 1) and DEPT (135 °) spectrum provides 30 carbon, comprises 12 quaternary carbons, 17 methines, 1 methylene.Wherein contain 2 carbonyl carbon signal C-4 (δ 182), C-1 " ' (δ 166.4).1 two replaces double key carbon signal C-2 " ' (δ 113.7), C-3 " ' (δ 144.9).The end group carbon signal C-1 of glucose sugar " (δ 99.5).Comprehensive above the analysis, with document contrast (Itokawa H, Suto K, et al.Studies on a novel p-coumaroyl glucoside of Apigenin and on other flavonoids isolated from Patchouli (Labiatae) .Chem.Pharm.Bull.1981,29 (1): 254-256).The structure of authenticating compound 1 is apigenin-7-O-beta-D-(6 "-p-coumaric acyl)-pyranglucoside (apigenin-7-O-β-D-(6 " p-cou maroyl)-glucopyranoside).
Table 1 compd A PG's
13C nuclear magnetic resonance data (mensuration solvent: deuterated dimethyl sulfoxide)
Embodiment 3: compd A PG is to the protective effect of cerebral ischemia/reperfusion injury of rats
Test objective: observe compd A PG to the impact of middle cerebral artery thromboembolism (MCAO) rat behavior scoring and brain infarction area, estimate APG to the protective effect of cerebral ischemia.
Laboratory animal: 60 of male Sprague Dawley (SD) rats, body weight 250-280g.Ad lib and drinking-water, 25 ± 2 ℃.
Formula 1 compd A PG among reagent reagent: the embodiment 1,2,3,5-triphenyltetrazolium chloride (TTC, the SigmaAldrich company U.S.), dimethyl sulfoxide (DMSO, the SigmaAldrich company U.S.).
The animal grouping
Be divided into immediately 6 groups, 8 every group
(1) sham operated rats: 0.9% sodium chloride injection
(2) model group: 0.9% sodium chloride injection
(3) model+DMSO group: 20%DMSO sodium chloride solution
(4) low dose group: 25mg/kg
(5) dosage group: 50mg/kg in
(6) high dose group: 100mg/kg
Experimental technique:
60 of male Sprague Dawley (SD) rats, body weight 250 – 280g.Provided by The Fourth Military Medical University zoopery center.Be divided at random sham operated rats, model group, model+DMSO group, APG organizes high, medium and low dosage group, 8 every group.A Sham group ligation common carotid artery, the inside and outside tremulous pulse of neck are declined the lambda line bolt; Each group is all in pouring at once intraperitoneal administration again.The high, medium and low dosage group of APG according to 25,50, the administration of 100mg/kg peritoneal injection.Sham operated rats, model group and model+DMSO group injection equivalent solvent.
The MCAO modelling is with reference to working specification (Wang Q before, Xiong LZ et al.Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system.Stroke 200940 (6): 2157-64), with 10% chloral hydrate intraperitoneal injection of anesthesia, 350mg/kg.Adopt the standby intraluminal middle cerebral artery occlusion in rats resistance of line bolt legal system closed model (middle cerebral artery occlusion, MCAO), get the neck median incision, expose right carotid, external carotid artery and internal carotid artery, ligation common carotid artery, external carotid artery, 5mm cuts a kerf in common carotid artery bifurcated below, inserts line bolt (Beijing Sha Dong), degree of depth 18mm, and obvious resistance sense is arranged.Rat ischemia is pulled out the line bolt after 2 hours.Adopt laser Doppler flowmetry (PefiFlux 5000PerimedAB company, Sweden) monitor cerebral blood flow, probe is fixed in 2mm behind the bregma, and the other 2mm that opens of center line reduces take the middle cerebral artery Cerebral Blood Flow Following and to surpass 80% sign that is successfully prepared as the MCAO model.Monitoring anus temperature is kept rat temperature at 37.0 ℃～37.5 ℃ in the operation process.
The neuroethology scoring
After animal is clear-headed, put back to raising, free diet.Adopted single blind method to carry out behavioristics's scoring in rear 24 hours in pouring into again, standards of grading are improvement Garcia standards of grading: comprise six of autonomic activities, quadriplegia, climbing, limb motion, somesthesia and neural reflexs, every minute 0,1,2,3 minutes, total points 18 minutes, mark is lower to show that damage is more serious.
Infarct size is measured in TTC dyeing: cerebral tissue was got in execution after scoring was finished, and put and put into the section of brain groove in the brine ice after 2 minutes, began forward every 2mm coronalplane from the lambdoid suture crotch and cut a slice, totally 6.At 37 ℃, dyed among the 2%TTC 15 minutes, 4% paraformaldehyde is fixed 24 hours, the rear calculating infarct size of taking pictures, white is the infarction part, redness is the normal structure part, use Photoshop CS2 and record pixel value, infarct volume=(left side normal structure-right side normal structure)/left side normal structure.
Statistical analysis:
All data all adopt SPSS13.0 statistics software to analyze, and measurement data represents that with mean ± standard deviation enumeration data represents with median ± range interquartile, relatively adopts one factor analysis of variance between group, and P＜0.05 is thought significant difference.
Result of the test:
Table 1, APG are on the impact (n=8) of the scoring of MCAO rat neuroethology and cerebral infarction rate
Compare * P＜005 with model group; Compare with the 25mg group,
#P＜005
Compare with model group, 25mg group, 50mg group, the scoring of 100mg group behavioristics obviously improve; Infarct size obviously dwindles.Compare with the 25mg group, 50mg group and the scoring of 100mg group neuroethology improve; Infarct size reduces.Prompting APG has therapeutical effect to the cerebral ischemia reperfusion injury of rat, and certain dose dependent is arranged.The 50mg group has no notable difference with the 100mg group.
Embodiment 4: compd A PG is to the protective effect of Cerebral Ischemia-reperfusion in Mice damage
Test objective: observe compd A PG to the impact of the scoring of middle cerebral artery thromboembolism (MCAO) mice behavior and brain infarction area, estimate APG to the protective effect of mouse brain ischemic injuries.
Laboratory animal: 60 of male C57/6J mices, body weight 25-30g.Ad lib and drinking-water, 25 ± 2 ℃.
Formula 1 compd A PG among reagent reagent: the embodiment 1,2,3,5 – triphenyltetrazolium chlorides (TTC, the Sigma Aldrich company U.S.), dimethyl sulfoxide (DMSO, the SigmaAldrich company U.S.).
The animal grouping
Be divided into immediately 6 groups, 8 every group
(1) sham operated rats: 0.9% sodium chloride injection
(2) model group: 0.9% sodium chloride injection
(3) model+DMSO group: 20%DMSO sodium chloride solution
(4) low dose group: 25mg/kg
(5) dosage group: 50mg/kg in
(6) high dose group: 100mg/kg
Experimental technique:
60 of male C57/6J mices, body weight 25 – 30g.Provided by The Fourth Military Medical University zoopery center.Be divided at random sham operated rats, model group, model+DMSO group, APG organizes high, medium and low dosage group, 8 every group.A Sham group ligation common carotid artery, the inside and outside tremulous pulse of neck are declined the lambda line bolt; Each group is all in pouring at once intraperitoneal administration again.The high, medium and low dosage group of APG according to 25,50, the administration of 100mg/kg peritoneal injection.Sham operated rats, model group and model+DMSO group injection equivalent solvent.
The MCAO modelling is with reference to working specification (Wang Q before, Xiong, LZ et al.Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system.Stroke 2009,40 (6): 2157-64), with 10% chloral hydrate intraperitoneal injection of anesthesia, 350mg/kg.Adopt the standby intraluminal middle cerebral artery occlusion in rats resistance of line bolt legal system closed model (middle cerebral artery occlusion, MCAO), get the neck median incision, expose right carotid, external carotid artery and internal carotid artery, ligation common carotid artery, external carotid artery, 2mm cuts a kerf in common carotid artery bifurcated below, inserts line bolt (Beijing Sha Dong), degree of depth 9mm, and obvious resistance sense is arranged.The mice ischemia is pulled out the line bolt after 1 hour.Adopt laser Doppler flowmetry (PefiFlux 5000PerimedAB company, Sweden) monitor cerebral blood flow, probe is fixed in 1mm behind the bregma, and the other 1mm that opens of center line reduces take the middle cerebral artery Cerebral Blood Flow Following and to surpass 80% sign that is successfully prepared as the MCAO model.Monitoring anus temperature is kept mouse temperature at 37.0 ℃～37.5 ℃ in the operation process.
The neuroethology scoring
After animal is clear-headed, put back to raising, free diet.Adopted single blind method to carry out behavioristics's scoring in rear 24 hours in pouring into again, standards of grading are improvement Garcia standards of grading: comprise six of autonomic activities, quadriplegia, climbing, limb motion, somesthesia and neural reflexs, every minute 0,1,2,3 minutes, total points 18 minutes, mark is lower to show that damage is more serious.
Infarct size is measured in TTC dyeing: cerebral tissue was got in execution after scoring was finished, and put and put into the section of brain groove in the brine ice after 2 minutes, began forward every 1mm coronalplane from the lambdoid suture crotch and cut a slice, totally 6.At 37 ℃, dyed among the 2%TTC 15 minutes, 4% paraformaldehyde is fixed 24 hours, the rear calculating infarct size of taking pictures, white is the infarction part, redness is the normal structure part, use Photoshop CS2 and record pixel value, infarct volume=(left side normal structure-right side normal structure)/left side normal structure.
Statistical analysis:
All data all adopt SPSS13.0 statistics software to analyze, and measurement data represents that with mean ± standard deviation enumeration data represents with median ± range interquartile, relatively adopts one factor analysis of variance between group, and P＜0.05 is thought significant difference.
Result of the test:
Table 2, APG are on the impact (n=8) of the scoring of MCAO mice neuroethology and cerebral infarction rate
Compare * P＜005, * * P＜001 with model group; Compare with the 25mg group,
#P＜005 is compared with model group, and 50mg group, the scoring of 100mg group behavioristics obviously improve; 25mg group, 50mg group, 100mg group infarct size obviously dwindle.Compare with the 25mg group, 50mg group and the scoring of 100mg group neuroethology improve; 50mg and 100mg group infarct size reduce.Prompting APG has therapeutical effect to the cerebral ischemia reperfusion injury of mice, and certain dose dependent is arranged.Possible 50mg dosage is more effective to the Cerebral Ischemia-reperfusion in Mice damage.As seen, embodiment 1 formula Ι compd A PG can be used for preparing the medicine in the treatment ischemia apoplexy medicine.Described ischemia apoplexy is Focal Cerebral Infarction.
The preparation of medicine
The injection prescription: 2mg APG, the 50mmol/L phosphate buffer, pH 7.0, cumulative volume 1mL.Method for making: get embodiment 1 formula I compd A PG 10mg, add 50mmol/L phosphate buffer (pH 7.0) 5mL, fully dissolving under aseptic condition is filtered through G3 and G6 glass sand filter respectively, and embedding was sterilized 30 minutes, and got 5 for 100 ℃ in the 1mL ampoule.
Oral formulations prescription: 5 milligrams of APG, 50 milligrams of mannitol, 100 milligrams of soluble starches.Method for making: get 5 milligrams of embodiment 1 formula I compd A PG, add 50 milligrams of mannitol and 100 milligrams of soluble starches, fully granulate behind the mixing, made granule packaging namely gets granule; Made granule is loaded in the hungry area softgel shell, namely gets capsule; Made granule direct compression, film coating namely gets tablet.
When clinical practice, with the preparation process of routine, described formula Ι compd A PG can use separately or prepare into clinically operable injection or powder or pill or capsule or tablet or microcapsule or soft capsule or membrane or unguentum or tincture or granule or aerosol with other drug.
The part that present embodiment is not described in detail and english abbreviation belong to the common practise of the industry, can search on the net, here not one by one narration.
Claims (4)
1. flavonoid glycoside compound, chemical structural formula is as follows:
Formula Ι
The chemical name of above-mentioned formula Ι structure is that ((6 " p-coumaroyl)-glucopyranoside) are flavonoid glycoside compound to apigenin-7-O-β-D-to apigenin-7-O-beta-D-(6 "-p-coumaric acyl)-pyranglucoside; hereinafter to be referred as APG, it is characterized in that: the application of formula Ι compd A PG in preparation treatment ischemia apoplexy medicine.
2. a kind of flavonoid glycoside compound claimed in claim 1, it is characterized in that: described formula Ι compd A PG can use separately or prepare into clinically operable injection or powder or pill or capsule or tablet or microcapsule or soft capsule or membrane or unguentum or tincture or granule or aerosol with other drug.
3. a kind of flavonoid glycoside compound claimed in claim 1, it is characterized in that: described ischemia apoplexy is Focal Cerebral Infarction.
4. a kind of flavonoid glycoside compound claimed in claim 1, it is characterized in that: described flavone compound extracts separation from Herba Clematidis tanguticae, its concrete extraction separating step is as follows: take the Herba Clematidis tanguticae herb as raw material, raw material after crushed, volume ratio adds 3～5 times of 70% ethanol by weight, heating and refluxing extraction 3 times, each 2 ~ 4 hours; Extracting liquid filtering also merges, concentrate drying gets total extract, extract is scattered in the water of 4 times of volume ratios by weight, with with the isopyknic petroleum ether extraction of water 3 times, water after the extraction is used and the isopyknic n-butanol extraction of water 4 times again, merge butanol extraction liquid, decompression and solvent recovery obtains n-butanol portion; N-butanol portion is through silica gel column chromatography, chloroform-methanol-water mixed solution take volume ratio as 20:1:0.1 ~ 6:3:0.3 is eluant, gradient elution, thin layer chromatography detects, collection contains stream part of formula I chemical compound, through the SephadexLH-20 gel filtration chromatography, remove impurity with volume ratio 1:1 chloroform-methanol, get formula I compd A PG sterling.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210425548.1A CN102872155B (en) | 2012-10-30 | 2012-10-30 | Application of flavonoid glycoside compound on medicine for treating cerebral apoplexy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210425548.1A CN102872155B (en) | 2012-10-30 | 2012-10-30 | Application of flavonoid glycoside compound on medicine for treating cerebral apoplexy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102872155A true CN102872155A (en) | 2013-01-16 |
| CN102872155B CN102872155B (en) | 2014-04-02 |
Family
ID=47473826
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210425548.1A Expired - Fee Related CN102872155B (en) | 2012-10-30 | 2012-10-30 | Application of flavonoid glycoside compound on medicine for treating cerebral apoplexy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102872155B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823197A (en) * | 2017-11-01 | 2018-03-23 | 中国医学科学院阜外医院 | Application of the apiolin in hemorrhagic cerebrovascular disease and ICVD medicine caused by prevention and treatment hypertension is prepared |
| CN109053836A (en) * | 2018-08-14 | 2018-12-21 | 南京中医药大学 | Luteolin 7-O- succinyl glucoside and apiolin -7-O- succinyl glucoside and its application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1668287A (en) * | 2001-09-06 | 2005-09-14 | 赛诺克思公司 | Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto |
-
2012
- 2012-10-30 CN CN201210425548.1A patent/CN102872155B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1668287A (en) * | 2001-09-06 | 2005-09-14 | 赛诺克思公司 | Inhibition by 3-deoxyflavonoids of t-lymphocyte activation and therapies related thereto |
Non-Patent Citations (3)
| Title |
|---|
| CHANDRASHEKHAR S.PATIL ET.AL: "Protective Effect of Flavonoids against Aging- and Lipopolysaccharide-Induced Cognitive Impairment in Mice", 《PHARMACOLOGY》 * |
| HIDEJI ITOKAWA ET.AL: "Studies on a novel p-coumaroyl glucoside of Apigenin and on other flavonoids isolated from Patchouli(Labiatae)", 《CHEM PHARM BULL》 * |
| 张爱军 等: "藏药独一味化学成分的研究", 《中国药学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823197A (en) * | 2017-11-01 | 2018-03-23 | 中国医学科学院阜外医院 | Application of the apiolin in hemorrhagic cerebrovascular disease and ICVD medicine caused by prevention and treatment hypertension is prepared |
| CN109053836A (en) * | 2018-08-14 | 2018-12-21 | 南京中医药大学 | Luteolin 7-O- succinyl glucoside and apiolin -7-O- succinyl glucoside and its application |
| CN109053836B (en) * | 2018-08-14 | 2021-12-03 | 南京中医药大学 | Luteolin 7-O-succinyl glucoside and apigenin-7-O-succinyl glucoside and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102872155B (en) | 2014-04-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102068535A (en) | Immature bitter orange or bitter orange total flavonoids extract prepared by ethanol reflux and extraction and application thereof | |
| CN102872155B (en) | Application of flavonoid glycoside compound on medicine for treating cerebral apoplexy | |
| CN101612183B (en) | Glaucescent fissistigma root saponin extract, pharmaceutical composition and preparation method and application thereof | |
| CN100509009C (en) | Chinese medicinal preparation for treating heart cerebrovascular disease and ischemic apoplexia and making method thereof | |
| CN101974011B (en) | New compound methyl brevicate with medical activity | |
| WO2022151978A1 (en) | Drug for treating urolithiasis-related disease, and preparation method therefor | |
| CN109810153B (en) | Preparation method and analgesic application of aromatic substituted glucose compound and pharmaceutical composition thereof | |
| CN102048874B (en) | General flavone extractive of immature bitter orange or bitter orange extracted through water decoction and use of general flavone extractive | |
| CN101538297A (en) | Preparation method of high-purity monomer flavone and general flavone contained in capsella bursa-pastoris and application of general flavone | |
| CN101974012B (en) | Novel compound ethyl brevicate with pharmaceutical activity | |
| CN102058833B (en) | Traditional Chinese medicine composition-type spray or aerosol and preparation method thereof | |
| CN102406735A (en) | Immature bitter orange or bitter orange total flavonoid extract decocted and extracted by water and its purpose | |
| CN101357213B (en) | Compound cantharis liquid formulation and preparation method thereof | |
| CN1919244B (en) | Chinese traditional medicine for treating cardiovascular disease | |
| CN111943919A (en) | Pheracimin C as phloroglucinol compound and preparation method and application thereof | |
| CN101974010B (en) | New compound erigeron breviscapus acid with officinal activity | |
| CN104523819B (en) | A kind of false indigo extract and preparation method thereof | |
| CN109091602A (en) | Semen allii tuberosi effective component, extracting method and its application in terms of liver injury medicament is protected in preparation | |
| CN102988342B (en) | Application of cyclo-icaritin aglycone in preparation of anti-inflammatory and antimicrobial medicaments | |
| CN115429790B (en) | Application of isoflavone compound in preparing medicament for preventing or treating alcoholic liver injury or dispelling alcohol effect and protecting liver | |
| CN102397374B (en) | Immature bitter orange or bitter orange general flavone extract extracted in decoction way through water and application thereof | |
| CN102058835B (en) | Chinese medicine composition drop for reducing blood pressure and clearing heat and resisting inflammation and preparation method thereof | |
| CN100421685C (en) | Chinese material medica preparation in use for treating infection of influenza virus, and preparation method | |
| CN108530505A (en) | A kind of flavonoid glycoside compound and its preparation method and application | |
| CN104257679B (en) | Application of flavonoid glycoside compounds in preparing drugs for treating ischemic heart disease and complication thereof |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140402 Termination date: 20211030 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |