CN101164566A - Peony leaves total glycoside extract, its preparation method and application - Google Patents
Peony leaves total glycoside extract, its preparation method and application Download PDFInfo
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Abstract
The present invention provides a moutan leaf total glucoside extract which is separated from new medicinal portion of moutan leaf and is purified and its preparation method. In the concrete, the total glucoside content in the described moutan leaf total glucoside extract is 50%-95%, in which the paeoniflorin content is 45%-95%. Said invention also provides the application of moutan leaf total glucoside extract in preparation of medicines for curing diabetes and coronary heart disease.
Description
Technical field
The invention belongs to new Chinese medicine research and development field.Relate to a kind of from the new medicinal part of Chinese crude drug, the separation and obtain effective site, and its preparation method and medical usage are provided.
Background technology
Paeonia suffruticosa is not only ornamental plant, and it can also be as medicinal.Version in 2005 " Chinese pharmacopoeia is recorded Cortex Moutan (also claiming Cortex Moutan) and is used as legal Chinese crude drug.Cortex Moutan is the dry root bark of Ranunculaceae Paeonia plant Paeonia suffruticosa (Paeonina suffruticosa Andr.).At present, a lot of about the chemical constituent of Cortex Moutan and effective site research thereof.According to bibliographical information, mainly contain paeonol, paeonolide, paeonolide, the new glycoside of paeonol, paeoniflorin, hydroxypaeoniflorin, benzoylpaeoniflorin, benzoyl hydroxypaeoniflorin, gallic acid, volatile oil, inorganic elements etc. in the Cortex Moutan.Modern pharmacological research shows, Cortex Moutan has antitumor, antiinflammatory, antibiotic, blood sugar lowering, blood pressure lowering, resists myocardial ischemia, arrhythmia, antithrombotic and effects such as arteriosclerosis, immunomodulating (" Cortex Moutan Pharmacological action study progress " " Chinese new medicine " rolled up the 8th phase p110-111 in 2004 the 3rd).Its effective site Cortex Moutan polysaccharide has hypoglycemic activity, and the Cortex Moutan total glycosides has treatment hepatitis B, immunomodulating, antiphlogistic effect.Cycle is grown (3 years) but Cortex Moutan is gathered, get its root simultaneously, plant can't survive, therefore from rationally utilizing herb resource, its chemical constituent is studied, clear and definite effective site as medicinal in other position of considering whether to develop medical material, finding new medical usage, is the direction that medical research staff makes great efforts to study.
Leaf of paeonia suffruticosa ardr. is the dried leaves of Ranunculaceae Paeonia plant Paeonia suffruticosa (Paeonia suffruticosa Andr.), according to the literature, contains glycoside in the leaf of paeonia suffruticosa ardr., phenols, phenolic acids, tannin, flavone, chemical constituents such as saccharide.At present, to the chemical constituent of leaf of paeonia suffruticosa ardr. and pharmacology activity research thereof seldom, and do not see bibliographical information about extraction separation effective site from leaf of paeonia suffruticosa ardr..
Summary of the invention
One of the technical problem to be solved in the present invention provides a kind of peony leaves total glycoside extract, and active component wherein is the effective site that comes from the leaf of paeonia suffruticosa ardr. a---peony leaves total glycoside.
Having the present invention further provides with above-mentioned peony leaves total glycoside is active component, is used for the treatment of the pure Chinese medicine pharmaceutical preparation and the related dose forms of diabetes, coronary heart disease.
Another technical problem that the present invention will solve provides the preparation method of the peony leaves total glycoside extract that is used for the treatment of diabetes, coronary heart disease.
For solving the problems of the technologies described above, the present invention has studied and defined following technical scheme.
The used leaf of paeonia suffruticosa ardr. of the present invention is the dried leaves of ranunculaceae peony Paeonia suffruticosa Andr..The inventor is raw material through years of researches with leaf of paeonia suffruticosa ardr., through solvent extraction, macroporous resin adsorption, solvent elution, eluent concentrate drying, obtains peony leaves total glycoside extract, and wherein containing the peony leaves total glycoside percentage by weight is 50%～95%.Mainly contain peoniflorin, Hydroxy peoniflorin, benzoylpaeoniflorin, benzoyl Hydroxy peoniflorin etc. in this extract.Wherein the percentage by weight of peoniflorin is 45%～95%.
The embodiment of comparative optimization of the present invention, peony leaves total glycoside prepares by following method:
(1) with the leaf of paeonia suffruticosa ardr. is raw material, water or aqueous ethanol extraction;
(2) concentrated extracting solution, to relative density be 1.20 extractum, add water and make the extractum dissolving, centrifugal, supernatant;
(3) supernatant is by macroporous adsorptive resins, water, the remove impurity of aquiferous ethanol eluting successively;
(4) with ethanol or aquiferous ethanol eluting, collect eluent, the eluent concentrate drying gets peony leaves total glycoside extract.
Extracting the concentration of alcohol of selecting for use in the preparation method of the present invention is X, and 0＜X≤95% is preferably 50≤X≤95%; Extracting method can be that percolation extracts or reflux, extract,, should keep bigger ratio between ethanol and the raw material, extracts fully guaranteeing, can use the solvent extraction 2～3 times of 8～16 times of medical material weight.
Described adsorbent resin can be the resin of framework material in styrene, divinylbenzene, acrylate or the methacrylate any one or a few, specifically can comprise ZTC-1, D101, AB-8 or DM301 type resin.Be preferably the ZTC-1 resin.
Earlier with 4～10 times of water to resin volume (V/W), the aquiferous ethanol of 2～5 times of resin volumes of reuse (V/W), concentration of alcohol are X, 5≤X≤20% in the process of described remove impurity.The impurity that is not adsorbed in the flush away post uses this method can remove impurity effectively.
The used concentration of ethanol of eluting is X in the described preparation method, 20≤X≤95%; Be preferably 20≤X≤40%.And determine that with 4～12 times of aquiferous ethanol eluting the eluent concentrate drying gets peony leaves total glycoside extract to resin volume (V/W).
In the process of remove impurity and desorbing, can monitor remove impurity or eluting consumption of ethanol by detecting in the eluent content of peony leaves total glycoside at any time, the time of control remove impurity or eluting.The content assaying method of peony leaves total glycoside can be measured by method well known in the art, and the present invention provides a cover feasible high-performance liquid chromatogram determination method at this.Specific as follows:
1, the preparation precision of reference substance solution takes by weighing benzoic acid reference substance 9.53mg, places the 100ml measuring bottle,, shakes up to scale with methanol constant volume, gets reference substance storing solution (0.0953mg/ml).The above-mentioned solution of accurate again absorption 1ml is put in the 10ml measuring bottle,, shakes up to scale with methanol constant volume, promptly gets reference substance solution (9.53 μ g/ml).
2, the preparation of need testing solution is got the about 20mg of test sample with the dry test sample that gets of the eluent of Fractional Collections, and accurate the title decides, to the 10mL measuring bottle, add an amount of supersound process of 5% sodium hydroxide solution (power 250W, frequency 33KHZ) and made dissolving in 10 minutes, take out, put to room temperature, fixed with 5% sodium hydroxide solution to scale, shake up, filter, precision is measured subsequent filtrate 1mL, to 10mL tool plug test tube, boiling water bath hydrolysis 2 hours, take out, put, quantitatively be transferred in the 50mL measuring bottle to room temperature, transfer pH=6 with dilute hydrochloric acid, thin up shakes up to scale, filters with microporous filter membrane (0.22um), get subsequent filtrate, promptly.
3, accurate respectively reference substance solution and each the 10 μ L of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Advantage of the present invention: the invention discloses the new medicinal part of Paeonia suffruticosa, i.e. leaf of paeonia suffruticosa ardr., and be raw material with it, extraction separation has obtained its effective site, i.e. peony leaves total glycoside extract first.Because adopted the resin technology in the modernization of Chinese medicine technology, technology is simple, has removed a large amount of impurity, the content height of active component.
Peony leaves total glycoside extract described in the present invention can use separately or use with pharmaceutical compositions.Pharmaceutical composition can be that peony leaves total glycoside extract and pharmaceutic adjuvant are formed, and also can be that peony leaves total glycoside extract and other medicines are formed.
According to technical scheme of the present invention, this pharmaceutical composition can exist with the form of oral formulations or injection preparation, and wherein oral formulations comprises capsule, soft capsule, granule, oral liquid, tablet, drop pill etc.Injection type is injectable powder or injection.Used adjuvant comprises: conventional adjuvants such as starch, sucrose, lactose, Icing Sugar, glucose, mannitol, xylitol, Polyethylene Glycol, isopropyl alcohol, soil temperature-80, glycerol, propylene glycol, microcrystalline Cellulose sodium, dextrin, cyclodextrin, sodium chloride, vitamin C, cysteine, citric acid, sodium thiosulfate, sodium sulfite, stearate and gelatin, preparation later stage preparation technology and equipment all belong to the routine techniques of pharmaceutical field, the present invention does not limit this, so will not describe in detail at this.
Observe by research, peony leaves total glycoside extract of the present invention has better therapeutic effect to diabetes, coronary heart disease, and suitable with the therapeutic effect of peoniflorin.For the ease of understanding the therapeutic effect of this extract, the inventor adopts the peony leaves total glycoside extract (total glycosides content is 85%) and the peoniflorin (content＞92%) of the preparation of embodiment 3 methods to carry out following pharmacodynamics test:
Test example 1 peony leaves total glycoside extract causes the therapeutical effect of rat experiment myocardial infarction to coronary ligation
144 of Wistar rats, body weight 260～280g, male and female dual-purpose.Be divided into 9 groups at random, 16 every group, be respectively: sham operated rats, model group, positive drug group (diltiazem hydrochloride 10mg/kg), peony leaves total glycoside extract low dose (10mg/kg), middle dosage (30mg/kg), heavy dose of (90mg/kg) group; Peoniflorin low dose (10mg/kg), middle dosage (30mg/kg), heavy dose of (90mg/kg) group.Lumbar injection urethane (1000mg/kg) anesthesia separates duodenum, and each organizes respectively the record standard II ECG1min that leads.The chest routine disinfection, left mid-clavicular line the 4th intercostal is opened breast, exposes heart, apart from the about 2mm of ramus descendens anterior arteriae coronariae sinistrae root place's ligation, sends heart back to, closes the thoracic cavity.Record II leads electrocardiogram behind the ligation arteria coronaria 15min, alarms with the ST section with the T wave height and raises sign into the ligation success, and record II leads electrocardiogram and is worth before as administration, and then through duodenal administration once, dosage is the same.5h after the ligation, abdominal aortic blood, stagnant blood is clear, in order to indexs such as thought-read flesh four enzymes.Put to death rat then, become 5 to place 0.1% NBT (with the 0.2mol/LTris liquid preparation of pH7.4～7.8) solution the heart crosscut, 37 ℃ of water-bath 3～5min, the dyestuff that flush away is unnecessary, infarcted region are not painted, and non-infarcted region is dyed by NBT and is hyacinthine, and take a picture, account for whole-heartedly with pattern analysis software comparison myocardial infarction area that the percentage ratio experimental result of area sees Table 1, table 2, table 3:
Annotate: this test is provided with in peony leaves total glycoside extract and the total glycosides that oral administration compares research under the monomer component peoniflorin Isodose.
Table 1 peony leaves total glycoside extract and peoniflorin to coronary ligation cause rat experiment myocardial infarction T ripple change absolute value influence (
Unit: mV, n=9)
Annotate: compare with sham operated rats,
▲ ▲P＜0.01,
▲ ▲ ▲P＜0.001; Compare with model group,
*P＜0.05 or
*P＜0.01
As seen from the above table, behind the coronary ligation, with sham operated rats relatively, model group 15min, 2h, 5h each point after 15min, administration after the ligation T ripple change absolute value that all significantly raises is learned by statistics and is handled difference and have highly significant (P＜0.01 or P＜0.001); Compare with model group, the peony leaves total glycoside extract small dose group all significantly reduces T ripple change absolute value at 2h after the administration and 5h, middle dosage group at 15min, 2h, 5h and heavy dose of group 15min, 2h, 5h after administration after the administration, learns processing difference by statistics and has significance (P＜0.05 or P＜0.01); Compare with model group, the peoniflorin small dose group all significantly reduces T ripple change absolute value at 2h after the administration and 5h, middle dosage group at 15min, 2h, 5h and heavy dose of group 15min, 2h, 5h after administration after the administration, learns processing difference by statistics and has significance (P＜0.05 or P＜0.01); The result shows that peoniflorin and peony leaves total glycoside extract all have tangible activity against myocardial ischemia.
Table 2 peony leaves total glycoside extract and peoniflorin to coronary ligation cause rat experiment myocardial infarction myocardium enzyme influence (
Unit: U/L)
Annotate: compare with sham operated rats,
▲ ▲P＜0.01 or
▲ ▲ ▲P＜0.001; Compare with model group,
*P＜0.05 or
*P＜0.01
AST: glutamate pyruvate transaminase CK-MB: the isozyme of creatine phosphokinase (CK)
CK: creatine phosphokinase LDH: lactic acid dehydrogenase
Serum cardiac muscle four enzymes can the reflecting myocardium cell the extent of damage, wherein CK-MB is the isozyme of creatine phosphokinase (CK), only has myocardial cell, when the myocardial cell damaged, CK-MB spills, and its activity in serum is increased, serum CK-MB activity is high more, and the reflecting myocardium damage is heavy more.As seen from the above table, behind the coronary ligation, with sham operated rats relatively, model group can significantly raise AST, CK-MB, CK, LDH value, difference has significance (P＜0.01 or P＜0.001); With model group relatively, in positive drug group, the peony leaves total glycoside extract in heavy dose of group and the peoniflorin heavy dose of group all can significantly reduce AST, CK, LDH, difference has significance (P＜0.05 or P＜0.01).And compare with model group, heavy dose of group of peony leaves total glycoside extract and the heavy dose of group of peoniflorin can significantly reduce CK-MB, and difference has significance (P＜0.05 or P＜0.01).
Coronary ligation is caused the rat heart muscle infarct size for table 3 peony leaves total glycoside extract and peoniflorin and infarcted region accounts for the influence of area % whole-heartedly (n=9)
Annotate: compare with model group,
*P＜0.05 or
*P＜0.01 or
* *P＜0.001
As seen from the above table, behind the coronary ligation, with model group relatively, the positive drug group can significantly be dwindled infarct size, infarcted region accounts for whole-heartedly that area % difference has significance (P＜0.001).With model group relatively, peony leaves total glycoside extract is little, in, heavy dose of group and peoniflorin is little, in, heavy dose of group can significantly dwindle infarct size, infarcted region accounts for whole-heartedly that area % difference has significance (P＜0.05 or P＜0.01).
In sum: experimental result shows, peony leaves total glycoside extract and peoniflorin to the influence of rat heart muscle infarct size due to the coronary ligation with to plasma A ST, CK, LDH, ECG T wave change absolute value to influence the result consistent, can obviously dwindle myocardial infarction area, reduce the release of AST, CK, LDH, reduce the ECG T wave change absolute value, point out it that rat experiment myocardial infarction is had therapeutical effect preferably.The pharmacological action that resists myocardial ischemia under peony leaves total glycoside extract and the peoniflorin Isodose is suitable substantially.
Test example 2 peony leaves total glycoside extracts and peoniflorin cause the therapeutical effect of experimental myocardial infarction dog to coronary ligation
54 of healthy adult hybrid dogs, body weight 12-17kg, male and female dual-purpose.Be divided into 9 groups at random, 6 every group, be respectively: sham operated rats (a not ligation of threading), model group, diltiazem group (5mg/kg), peony leaves total glycoside extract small dose group (5mg/kg), middle dosage group (15mg/kg) and heavy dose of group (45mg/kg); Peoniflorin small dose group 5mg/kg), middle dosage group (15mg/kg) and heavy dose of group (45mg/kg).Through 3% pentobarbital sodium 30mg/kg intravenous anesthesia.Back of the body position is fixing, and skin of neck cuts, and tracheal intubation connects electric pulmotor.Separate left carotid, measure blood pressure.Separate femoral vein, intubate is got blood usefulness in order to fluid infusion and vein.Cut down in xiphoid-process, separate duodenum, in order to administrable.The dog right arm reclining, the 4th intercostal is opened breast in the left side, exposes heart, does the pericardium art.Separate branch of coronary artery, in, 1/3 place's threading is in order to ligation down.Fixing multipoint mode epicardial lead mapping EECG, 12 of mapping points.Art finishes, and stablize behind the 15min record EECG and is worth before as ligation, gets blood from femoral vein simultaneously, in order to detecting the preceding every serological index of ligation.30min behind the ligation coronary artery, record EECG are worth before the administration after as ligation, and through duodenal administration, sham operated rats and model group wait the capacity sodium chloride injection.After the record administration 20,120,240, the ECG of 360min.And finishing to get blood in experiment, separation of serum is in order to surveying serum zymetology index; 360min puts to death animal and takes out heart rapidly after the administration.The even crosscut of left ventricle is become 5,5 myocardium specimen are placed 0.5% N-BT (with the 0.2mol/LTris liquid preparation of pH7.4-7.7) solution, 37 ℃ of water-bath 10min, the dyestuff that flush away is unnecessary, infarcted region is not painted, non-infarcted region is dyed by N-BT and is hyacinthine, account for the percentage ratio of left ventricle area with pattern analysis software comparison myocardial infarction area, respectively infarcted region is separated with non-infarcted region and weigh, relatively infarcted region accounts for the ratio (test is set the peoniflorin that has activity against myocardial ischemia equally and contrasted as pharmacodynamics) of ventricular weight.The results are shown in Table 4, table 5, table 6, table 7:
Table 4 peony leaves total glycoside extract and peoniflorin to the influence of experimental myocardial infarction dog ∑-ST (mV) (
N=6)
Annotate: compare with sham operated rats,
▲P＜0.05 or
▲ ▲P＜0.01; Compare with model group,
*P＜0.05 or
*P＜0.01 or
* *P＜0.001
With sham operated rats relatively, model group each time point ∑-ST after administration obviously raise (p＜0.01 or p＜0.001); The diltiazem group can obviously reduce the millivolt number that ∑-ST raises at 20～360min, has significance (p＜0.05 or p＜0.001) with the model group comparing difference; Each dosage group of peony leaves total glycoside extract and peoniflorin is the millivolt number that raises of in various degree reduction ∑-ST all, the peony leaves total glycoside extract small dose group is at 120min, dosage group in the peony leaves total glycoside extract, peoniflorin is little, middle dosage group is at 120～240min, has significance (p＜0.05 or p＜0.01) with the model group comparing difference, heavy dose of group of peony leaves total glycoside extract and the heavy dose of group effect of peoniflorin are remarkable, action time is also longer, at 20～360min, has significance (p＜0.05 or p＜0.01) with the model group comparing difference.
Table 5 peony leaves total glycoside extract and peoniflorin to the influence of experimental myocardial infarction dog N-ST (individual) (
N=6)
Annotate: compare with model group,
*P＜0.05 or
*P＜0.01 or
* *P＜0.001
Compare with model group, the diltiazem group can obviously reduce counting of N-ST, has significance (p＜0.05 or p＜0.01) in 20～360min difference.Each dosage group of peony leaves total glycoside extract and peoniflorin can obviously reduce counting of N-ST, peony leaves total glycoside extract and peoniflorin small dose group are at 120min, the dosage group is at 120～240min in the peony leaves total glycoside extract, in heavy dose of group of peony leaves total glycoside extract and the peoniflorin, heavy dose of group has significance (p＜0.05 or p＜0.01) at 20～360min with the model group comparing difference.
Table 6 peony leaves total glycoside extract and peoniflorin to the influence of experimental myocardial infarction dog myocardial infarction area (
N=6)
Annotate: compare with model group,
*P＜0.05 or
*P＜0.01
Compare with model group, each dosage group of peony leaves total glycoside extract and peoniflorin, diltiazem group are all obviously dwindled the area of myocardial infarction, difference has significance (p＜0.05 or p＜0.01 or p＜0.001), peony leaves total glycoside extract is little, in, heavy dose of group effect is obvious, and is suitable with each group effect of peoniflorin.
Table 7 peony leaves total glycoside extract and peoniflorin to the influence of experimental myocardial infarction dog myocardium enzyme (IU/L) (
N=6)
Annotate: compare with sham operated rats,
▲P＜0.05; Compare with model group,
*P＜0.05
Compare with sham operated rats, model group AST, CK after administration obviously raise, and difference has significance (p＜0.05); Compare with model group, diltiazem group CK after administration obviously reduces (p＜0.05), but AST and LDH are not had obvious influence, and each dosage group of peony leaves total glycoside extract and peoniflorin has the effect that reduces CK, and difference all has significance (p＜0.05).
By above two experiment confirms: peony leaves total glycoside extract has and significantly resists myocardial ischemia and the pharmacotoxicological effect of infarction, contrasted the drug effect of peoniflorin monomer and peony leaves total glycoside extract in the peony leaves total glycoside extract simultaneously by test, the result confirms that both have same activity against myocardial ischemia, consider that leaf of paeonia suffruticosa ardr. is new medicinal part, the extraction cost of peony leaves total glycoside extract is low than monomer component peoniflorin extraction cost, and the pharmacological action that both resist myocardial ischemia under the Isodose is suitable substantially, so think leaf of paeonia suffruticosa ardr. made full use of, extract wherein total glycosides composition, it is prepared into the new drug that resists myocardial ischemia, has very strong practical value.
Test example 3 peony leaves total glycoside extracts are to the blood sugar reducing function of model induced by alloxan hyperglycemia mice
Choose SPF level ICR mice, tail vein injection alloxan normal saline solution (65mg/kg) was surveyed fasting glucose after 72 hours, select blood glucose value greater than the mice of 11.1mmol/L as diabetes animal model.Be divided into dosage group (100mg/kg), the heavy dose of group of peoniflorin (200mg/kg) in model control group, insoral group (150mg/kg), peony leaves total glycoside extract small dose group (50mg/kg), middle dosage group (100mg/kg), heavy dose of group (200mg/kg), peoniflorin small dose group (50mg/kg), the peoniflorin at random according to blood glucose value, other establishes blank group (tail vein injection saline 0.1ml/10g), 12 every group.All by 0.2ml/10g volume gastric infusion, blank group and model control group give the equal-volume normal saline to each administration group, and every day 1 time, administration is 14 days altogether.After administration last administration in the 7th day 1 hour, get blood behind the socket of the eye and survey the mice fasting glucose; After the last administration in the 14th day 1 hour, pluck eyeball and get blood, survey the mice fasting glucose.The gained data with
Expression, the t check is relatively used in homogeneity of variance utilization F check between group.The results are shown in Table 8, table 9.
Table 8 peony leaves total glycoside extract and peoniflorin to the diabetic mice medicine of model induced by alloxan after 7 days, 14 days blood glucose values influence (
N=12)
Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001; Compare with the blank group,
▲ ▲ ▲P＜0.001.
As seen from the above table, before the administration model group and blank group relatively, blood glucose value obviously raise (P＜0.001); Each administration group and model group relatively, blood glucose value have no significant change (P＞0.05).Administration the 7th day, model group compares with blank group, and blood glucose value obviously raises, and handle difference by statistics significance (P＜0.001); Dosage group and model group compare in peony leaves total glycoside extract small dose group, peoniflorin small dose group, the peoniflorin, and blood glucose value all has reduction trend, but not statistically significant (P＞0.05); Dosage group, peony leaves total glycoside extract heavy dose group, peoniflorin heavy dose group compare with model group in the peony leaves total glycoside extract, and blood glucose value obviously reduces (P＜0.05～0.01), and the blood sugar lowering rate is difference 14.68%, 20.99% and 20.99%; Insoral group and model group compare, and blood glucose value obviously reduces (P＜0.01).
Administration the 14th day, model group and blank group relatively, blood glucose value obviously raise (P＜0.001); Peony leaves total glycoside extract is little, in, heavy dose of group and model group relatively, blood glucose value obviously reduces (P＜0.05～0.001), the blood sugar lowering rate is respectively 18.99%, 25.90% and 38.46%; The peoniflorin small dose group has reduction trend, and dosage group and heavy dose of group blood glucose value obviously reduce (P＜0.05～0.01) in the peoniflorin; Insoral group and model group compare, and blood glucose value obviously reduces (P＜0.001).
Table 9 peony leaves total glycoside extract to the diabetic mice medicine of model induced by alloxan after 7 days, 14 days body weight influence (
N=12)
Compare with the blank group,
▲P＜0.05,
▲ ▲P＜0.01.
As seen from the above table, before the administration model group and blank group relatively, body weight obviously descend (P＜0.01); Each administration group and model control group comparison body weight have no significant change (P＞0.05).Behind the medicine 7 days, 14 days, model group and blank group relatively, body weight obviously descend (P＜0.05); Each administration group and model group compare, the equal no significant difference of body weight (P＞0.05).
Paeonia suffruticosa is traditional medicinal plants, and the merit of clearing away heat and cooling blood, promoting blood circulation to remove blood stasis is arranged, and how to be used as medicine with root bark.Its effective site---the peony leaves total glycoside that the present invention extracts from leaf of paeonia suffruticosa ardr. shows that by test of pesticide effectiveness result it has obvious hypoglycemic activity, and effect is better than the main component peoniflorin of leaf of paeonia suffruticosa ardr..
The specific embodiment
Describe the enforcement of technical solution of the present invention by the following examples in detail, but should not limit practical range of the present invention with this.
Embodiment 1: the preferred for preparation method of peony leaves total glycoside extract
Get the leaf of paeonia suffruticosa ardr. medicinal powder, extract 3 times each 1 hour with 14 times of medical material amount 50% alcohol heating reflux.Filter, with 60 ℃ of decompression recycling ethanols of ethanol extract, extracting solution is concentrated into the extractum of relative density 1.20 (25 ℃ of mensuration), add 5 times of water (60 ℃) and make the extractum dissolving to medical material weight, centrifugal, supernatant is by the ZTC-1 resin column, with 4 times to the water of resin volume (V/W) and 5% ethanol of 5 times of resin volumes (V/W), the impurity that is not adsorbed in the flush away post is then with 6 times of 40% alcohol desorptions to resin volume (V/W).Collect stripping liquid, concentrating under reduced pressure, vacuum drying, peony leaves total glycoside extract, the content 75% of peony leaves total glycoside wherein, content of paeoniflorin is 69%.
Embodiment 2: the preferred for preparation method of peony leaves total glycoside extract
Get the leaf of paeonia suffruticosa ardr. medicinal powder, extract 2 times each 1 hour with 8 times of medical material amount 95% alcohol heating reflux.Filter, with 60 ℃ of decompression recycling ethanols of ethanol extract, extracting solution is concentrated into the extractum of relative density 1.20 (25 ℃ of mensuration), add 10 times of water (60 ℃) and make the extractum dissolving to medical material weight, centrifugal, supernatant is by the D101 resin column, with 6 times to the water of resin volume (V/W) and 10% ethanol of 2.5 times of resin volumes (V/W), the impurity that is not adsorbed in the flush away post is then with 10 times of 20% alcohol desorptions to resin volume (V/W).Collect stripping liquid, concentrating under reduced pressure, vacuum drying gets peony leaves total glycoside extract, and wherein the content of peony leaves total glycoside is 90%, and content of paeoniflorin is 85%.
Embodiment 3: the preferred for preparation method of peony leaves total glycoside extract
Get the leaf of paeonia suffruticosa ardr. medicinal powder, with 10 times of medical material amount 80% ethanol, percolation extracts.With 60 ℃ of decompression recycling ethanols of ethanol extract, extracting solution is concentrated into the extractum of relative density 1.20 (25 ℃ of mensuration), add 8 times of water (60 ℃) and make the extractum dissolving to medical material weight, centrifugal, supernatant is by the DM301 resin column, with 10 times to the water of resin volume (V/W) and 20% ethanol of 2 times of resin volumes (V/W), the impurity that is not adsorbed in the flush away post is then with 4 times of 60% alcohol desorptions to resin volume (V/W).Collect stripping liquid, concentrating under reduced pressure, vacuum drying gets peony leaves total glycoside extract, and wherein the content of peony leaves total glycoside is 85%, and content of paeoniflorin is 79%.
Embodiment 4: the preferred for preparation method of peony leaves total glycoside extract
Get the leaf of paeonia suffruticosa ardr. medicinal powder, with 16 times of medical material calorimetric water, percolation extracts.Extracting solution is concentrated into 10 times of medical material amounts, centrifugal, supernatant is by the AB-8 resin column, with 8 times to the water of resin volume (V/W) and 10% ethanol of 2.5 times of resin volumes (V/W), the impurity that is not adsorbed in the flush away post is then with 8 times of 30% alcohol desorptions to resin volume (V/W).Collect stripping liquid, concentrating under reduced pressure, vacuum drying gets peony leaves total glycoside extract, and wherein the content of peony leaves total glycoside is 70%, and content of paeoniflorin is 63%.
Embodiment 5: the preferred dosage form capsule of peony leaves total glycoside extract
Get the peony leaves total glycoside extract 100g of embodiment 4 methods preparation, 60 ℃ of dryings grind, and cross 80 mesh sieves, the medical starch 98g and the magnesium stearate 2g that added 80 mesh sieves, mix homogeneously is made soft material in right amount with 85% ethanol, crosses 30 mesh sieve system granules, oven dry, make moisture less than 5%, cross 40 orders and shine granulate, be sub-packed in No. 3 capsules.Every capsules contains peony leaves total glycoside extract 0.1g, uses aluminium plastic composite packaging, promptly.
Embodiment 6: the preferred dosage form tablet of peony leaves total glycoside extract
Get the peony leaves total glycoside extract 30g of embodiment 4 methods preparation, add starch 30g, microcrystalline Cellulose 10g granulates with 12 mesh sieves in right amount with 10% starch slurry, and dry below 55 ℃, dry granular adds magnesium stearate, granulate, and mixing, tabletting, promptly.
Embodiment 7: the preferred dosage form freeze-dried powder of peony leaves total glycoside extract
Get the peony leaves total glycoside extract 50g of embodiment 2 methods preparation, add an amount of water for injection, after the stirring and dissolving, ultrafiltration obtains apyrogenic clear liquor, adds the injection water to 1000ml, is packed as 1000, presses the lyophilizing of freeze-dried powder technology, makes freeze-dried powder.
Claims (19)
1. peony leaves total glycoside extract, the percentage by weight that it is characterized in that containing peony leaves total glycoside is 50%～95%.
2. peony leaves total glycoside extract according to claim 1 is characterized in that mainly containing in this extract peoniflorin, Hydroxy peoniflorin, benzoylpaeoniflorin, benzoyl Hydroxy peoniflorin.
3. peony leaves total glycoside extract according to claim 1 and 2, the percentage by weight that it is characterized in that containing peoniflorin is 45%～95%.
4. according to the preparation method of claim 1,2, the described peony leaves total glycoside extract of 3 arbitrary claim, it is characterized in that:
(1) with the leaf of paeonia suffruticosa ardr. is raw material, water or aqueous ethanol extraction;
(2) concentrated extracting solution, to relative density be 1.20 extractum, add water and make the extractum dissolving, centrifugal, supernatant;
(3) supernatant is by macroporous adsorptive resins, water, the remove impurity of aquiferous ethanol eluting successively;
(4) again with ethanol or aquiferous ethanol eluting, collect eluent, the eluent concentrate drying gets peony leaves total glycoside extract.
5. the preparation method of peony leaves total glycoside extract according to claim 4 is characterized in that being extracted as percolation and extracts or reflux, extract.
6. the preparation method of peony leaves total glycoside extract according to claim 4, it is characterized in that extracting used concentration of ethanol is X, 0＜X≤95%.
7. the preparation method of peony leaves total glycoside extract according to claim 6, it is characterized in that extracting used concentration of ethanol is X, 50≤X≤95%.
8. the preparation method of peony leaves total glycoside extract according to claim 4 is characterized in that described resin is that in styrene, divinylbenzene, acrylate or the methacrylate any one or a few is the resin of framework material.
9. the preparation method of peony leaves total glycoside extract according to claim 8 is characterized in that the adsorbent resin that is adopted can be ZTC-1, D101, AB-8 or DM301 type resin.
10. the preparation method of peony leaves total glycoside extract according to claim 4 is characterized in that the used concentration of ethanol of remove impurity is X, 5≤X≤20%.
11. the preparation method of peony leaves total glycoside extract according to claim 4 is characterized in that the used concentration of ethanol of eluting is X, 20≤X≤95%.
12. the preparation method of peony leaves total glycoside extract according to claim 11 is characterized in that the used concentration of ethanol of eluting is X, 20≤X≤40%.
13. contain the pharmaceutical composition of the described peony leaves total glycoside extract of the arbitrary claim of claim 1～12.
14. pharmaceutical composition according to claim 13 is characterized in that said composition can be that peony leaves total glycoside extract and other drug are formed.
15. pharmaceutical composition according to claim 13 is characterized in that said composition can be that peony leaves total glycoside extract and pharmaceutic adjuvant are formed.
16., it is characterized in that and to exist with oral formulations or ejection preparation form according to claim 13,14 or 15 described pharmaceutical compositions.
17. pharmaceutical composition according to claim 16 is characterized in that described oral formulations is capsule, soft capsule, granule, oral liquid, tablet, drop pill.
18. pharmaceutical composition according to claim 16 is characterized in that described ejection preparation is injectable powder or injection.
19. described peony leaves total glycoside extract of the arbitrary claim of claim 1～18 or the pharmaceutical composition application in preparation treatment diabetes, medicaments for coronary disease.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101574410B (en) * | 2008-05-05 | 2012-01-11 | 周亚伟 | Effective components of peony leaves as well as preparation method and application thereof |
| CN102335276A (en) * | 2011-10-10 | 2012-02-01 | 杨永庆 | Preparation method and application of tree peony extract and composition of tree peony extract |
| CN101558879B (en) * | 2009-02-23 | 2012-06-20 | 铜陵凯润牡丹生物医药科技有限公司 | Teabag containing paeoniifolia for calming and tranquilizing mind and manufacturing method thereof |
| CN101558880B (en) * | 2009-02-23 | 2012-09-26 | 铜陵凯润牡丹生物医药科技有限公司 | Teabag containing paeoniifolia for beautifying skin and manufacturing method thereof |
| CN103087128A (en) * | 2013-02-05 | 2013-05-08 | 菏泽尧舜牡丹生物科技有限公司 | Method for extracting paeoniflorin from peony seed meal |
| CN106063828A (en) * | 2016-06-20 | 2016-11-02 | 武汉市农业科学技术研究院林业果树科学研究所 | A kind of oil extracting method of Paeonia suffruticosa blade polyphenol |
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2006
- 2006-10-18 CN CN2006101505051A patent/CN101164566B/en active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101574410B (en) * | 2008-05-05 | 2012-01-11 | 周亚伟 | Effective components of peony leaves as well as preparation method and application thereof |
| CN101558879B (en) * | 2009-02-23 | 2012-06-20 | 铜陵凯润牡丹生物医药科技有限公司 | Teabag containing paeoniifolia for calming and tranquilizing mind and manufacturing method thereof |
| CN101558880B (en) * | 2009-02-23 | 2012-09-26 | 铜陵凯润牡丹生物医药科技有限公司 | Teabag containing paeoniifolia for beautifying skin and manufacturing method thereof |
| CN102335276A (en) * | 2011-10-10 | 2012-02-01 | 杨永庆 | Preparation method and application of tree peony extract and composition of tree peony extract |
| CN102335276B (en) * | 2011-10-10 | 2014-06-04 | 杨永庆 | Preparation method and application of tree peony extract and composition of tree peony extract |
| CN103087128A (en) * | 2013-02-05 | 2013-05-08 | 菏泽尧舜牡丹生物科技有限公司 | Method for extracting paeoniflorin from peony seed meal |
| CN103087128B (en) * | 2013-02-05 | 2015-09-02 | 菏泽尧舜牡丹生物科技有限公司 | A kind of method extracting peoniflorin from the peony seeds dregs of rice |
| CN106063828A (en) * | 2016-06-20 | 2016-11-02 | 武汉市农业科学技术研究院林业果树科学研究所 | A kind of oil extracting method of Paeonia suffruticosa blade polyphenol |
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|---|---|
| CN101164566B (en) | 2011-07-20 |
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