CN105147710A - Hypoglycemic agent as well as preparation method and application thereof - Google Patents
Hypoglycemic agent as well as preparation method and application thereof Download PDFInfo
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- CN105147710A CN105147710A CN201510578171.7A CN201510578171A CN105147710A CN 105147710 A CN105147710 A CN 105147710A CN 201510578171 A CN201510578171 A CN 201510578171A CN 105147710 A CN105147710 A CN 105147710A
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- Prior art keywords
- methanol
- triterpene saponin
- pyrocincholicacid
- compound
- extract
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Abstract
Pyrocincholic acid type triterpenoid saponin in metadina trichotoma refers to the triterpenoid saponin and the other three derivatives with same framework structures, wherein the framework of the triterpenoid saponin contains pyrocincholic acid, a C-3 site of the pyrocincholic acid is connected with a beta-D-quinovose based 1' site by virtue of oxygen atoms, and a C-28 site carboxyl is connected with a beta-D-glucose based 1'' site by virtue of oxygen atoms. Preferably, the triterpenoid saponin is a compound shown by a formula (I), wherein R1=beta-D-quinovopyranosyl, and R2=beta-D-glucose. The triterpenoid saponin compounds 1-4 are novel plant-origin type-2 dibetes resistant hypoglycemic agents. The invention further provides a pharmaceutical composition, which takes a metadina trichotoma triterpenoid saponin extract containing pyrocincholic acid and a monomeric compound of the extract as active ingredients, preparation methods of the pharmaceutical composition and the extract and applications of the pharmaceutical composition and the extract in preparation of the hypoglycemic agent.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, particularly, the pharmaceutical composition that to relate to pyrocincholicacid type triterpene saponin or yellow Populus deltoides triterpene saponin extract in the yellow Populus deltoides of a class be effective ingredient, its preparation method and preparing the application in hypoglycemic drug, and the application in the hypoglycemic medicine of the anti-type-II diabetes of preparation.
Background technology
The chronic metabolic disease of type-II diabetes to be a kind of with hyperglycemia be feature, sickness rate continues to increase in the world at present, has become the noninfectious of the third-largest serious threat health of people and life after cardiovascular and cerebrovascular disease and malignant tumor.According to the data display of international diabetes association, within 2011, global diabetics sum is up to 3.66 hundred million, estimates that this numeral will reach 5.52 hundred million to the year two thousand thirty, and about has 90-95% to belong to type Ⅱdiabetes mellitus in diabetics.Along with the increase of living standard raising, aged tendency of population and fat incidence rate, onset diabetes rate raises rapidly and has rejuvenation trend.The persistent high blood sugar of diabetes and long-term metabolic are disorderly etc. can cause body tissue's organ, particularly eye, kidney, cardiovascular and neural infringement and dysfunction thereof and exhaustion.(Weilletal.,2004)。At present, the anti-type-II diabetes hypoglycemic drug used clinically mainly contains insulin sensitivity enhancing class (as biguanides and thiazolidinediones), Drugs Promoting Insulin Secretion sulphanylureas (as glimepiride etc.), alpha-glucosidase inhibitor (as acarbose and voglibose etc.), exendin-4 (as Exenatide etc.), DPP-4 inhibitor (as sitagliptin etc.).These medicines are substantially all chemical synthetic drug, although this its use achieves good curative effect, the concentration of glucose in blood can be made obviously to decline, all can not control blood sugar concentration very well after life-time service.In addition, these medicines also have certain side effect, and as Liver and kidney toxicity, edema, diarrhoea etc., therefore in the patient of hepatic insufficiency, its application is subject to a definite limitation, and some patients can not its treatment of withstand long term exposure.Therefore, the research and development of novel blood sugar lowing medicine are the emphasis of type II diabetes resisting drug research always.Natural product is that the Nature selects optimised compound through long-term evolution, is also the main source of mankind's disease preventing and treating medicine, has structure-rich, determined curative effect, safety and low toxicity and without according to advantages such as patience.In the micromolecule new chemical entities (NCE) that decades go on the market in the past, nearly 60% is directly or indirectly derive from natural product, and natural product remains the important source of medicine or lead compound research and development.So find that from plant anti-type-II diabetes hypoglycemic drug has very important academic significance and good application prospect more safely and effectively.
Type 2 diabetes mellitus is a kind of metabolic synthetic disease, and it is formed with the life style of modern's high glucose and high fat and hypomotility closely related.The selective destruction of streptozotocin (STZ) beta Cell of islet to mice, the STZ of injection low dosage can induce it to produce type-II diabetes.Mice high-calorie feed raises certain hour and fasting, by a certain amount of lumbar injection STZ, animal model of diabetes mellitus type II can be prepared, and have that overweight, impaired glucose tolerance, blood fat raise, serum insulin raises by the model that this method is prepared and combination rate of insulin receptor reduces the feature of companion's insulin resistant, be similar to the Clinical symptoms of Patients with NIDDM.The diabetes mice of STZ induction because of its cycle shorter, method is easy, is that research human type II diabetes treats the ideal model of new drug.
Yellow Populus deltoides is that the yellow Populus deltoides of Rubiaceae belongs to autogenus plant, and it is few that pyrocincholicacid type triterpene saponin exists kind in this plant, is only therefrom separated at present and obtains 4.Such triterpene saponin is separated with without the reasons such as uv absorption are more difficult because its content is lower.In prior art, be separated triterpene saponin composition and published following method from this plant: yellow 9 kilograms, Populus deltoides drying and crushing bark, with methanol room temperature lixiviate three times, concentrating under reduced pressure, obtains methanol extract 1668 grams.Methanol extract is dissolved in respectively with petroleum ether after hot water, and methanol and n-butanol extraction, obtain 19 grams of petroleum ether, 85 grams of chloroforms, 780 grams of n-butyl alcohol and 884 grams of moisture section positions.Chloroform segmentation position is through silica gel column chromatography (1.7kgSiO
2; CHCl
3/ MeOH/H
2o gradient elution), obtain Fr.1-8, Fr.7 is through silicagel column and RP-C18 post chromatography (SiO repeatedly
2: CHCl
3/ CH
3oH/H
2o8:2:0.2; Rp-18:CH
3oH/H
2o7.5:2.5) compound 1 (22mg) is obtained. n-butyl alcohol is through silica gel column chromatography (3.5kgSiO
2; CHCl
3/ MeOH/H
2o gradient elution), obtain 1-7. segmentation position, 7 segmentation positions 3 through silicagel column and RP-C18 post chromatography (SiO repeatedly
2: CHCl
3/ CH
3oH/H
2o8:2:0.2; Rp-18:CH
3oH/H
2o7:3) obtain compound 2 (36mg) and 3 (29mg), segmentation position 4 is through silicagel column and RP-C18 post chromatography (SiO repeatedly
2: CHCl
3/ CH
3oH/H
2o7:3:0.3; Rp-18:CH
3oH/H
2o6.5:3.5) compound 4 (35mg) is obtained.See: Zhang, Y.M.; Tan, N.H.; Huang, H.Q.; Zeng, G.Z., TriterpernoidsaponinsfromMetadinatrichotoma.Z.Naturforsc h2007,62b, 745-748.Its shortcoming is that this method uses yellow Populus deltoides bark part, larger to the destruction of resource, the content of compound (1), (2), (3), (4) is low, purification procedures is more, and in being separated, repeatedly use the mixed solvent system of organic solvent and water, this mixed solvent recovered temperature is high, is unfavorable for the recycling of solvent, is unfavorable for industrial mass production.
In prior art there are no pyrocincholicacid type triterpene saponin in yellow Populus deltoides, yellow Populus deltoides triterpene saponin extract as the report of anti-type-II diabetes hypoglycemic drug.
Summary of the invention
For prior art above shortcomings part, the object of the present invention is to provide a class pyrocincholicacid type triterpene saponin, and triterpene saponin componds and the salt of pharmacologically allowing thereof, or yellow Populus deltoides triterpene saponin extract is the hypoglycemic pharmaceutical composition of anti-type-II diabetes of active component, their preparation method, and the application in the anti-type-II diabetes hypoglycemic drug of preparation.The triterpene saponin componds with anti-type-II diabetes hypoglycemic activity that the present invention relates to is its hypoglycemic activity of Late Cambrian, prepare method controllability and the favorable reproducibility of this compounds, sample loss is few, cost is lower, easy to operate, more easily separatedly can obtain this class pyrocincholicacid triterpene saponin, solvent can be recycled repeatedly, is also applicable to commercial production.
In order to realize above-mentioned purpose of the present invention, the invention provides following technical scheme:
Pharmaceutical composition, Pyrocincholicacid type triterpene saponin componds wherein containing treatment effective dose, or its salt of pharmacologically allowing and pharmaceutically acceptable carrier, described Pyrocincholicacid type triterpene saponin componds refers to that skeleton contains a pyrocincholicacid, the C-3 position of pyrocincholicacid is connected by oxygen atom with 1 ' position of a β-D-quinovose base, and C-28 position carboxyl and 1 of a β-D-Glucose base " triterpene saponin that is connected by oxygen atom of position and other three derivants with framing structure.
Pharmaceutical composition, pyrocincholicacid triterpene saponin compound 1-4 wherein containing treatment effective dose, or its salt of pharmacologically allowing and pharmaceutically acceptable carrier, described pyrocincholicacid triterpene saponin compound 1-4 is the compound with following structural formula: pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1), pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4)
In formula, R
1=β-D-quinovose base or β-D-Glucose-(1 → 4)-β-D-quinovose base; R
2=β-D-Glucose base or β-D-Glucose-(1 → 6)-β-D-Glucose base,
The present invention provides the hypoglycemic drug that the salt of pharmacologically allowing with pyrocincholicacid type triterpene saponin componds or its is effective ingredient simultaneously, described Pyrocincholicacid type triterpene saponin refers to that skeleton contains a pyrocincholicacid, the C-3 position of pyrocincholicacid is connected by oxygen atom with 1 ' position of a β-D-quinovose base, and C-28 position carboxyl and 1 of a β-D-Glucose base " triterpene saponin that is connected by oxygen atom of position and other three derivants with framing structure.
The hypoglycemic drug of the anti-type-II diabetes that the salt of pharmacologically allowing with pyrocincholicacid triterpene saponin compound 1-4 or its is effective ingredient, described pyrocincholicacid triterpene saponin compound 1-4 is the compound with following structural formula: pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1), pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4)
In formula, R
1=β-D-quinovose base or β-D-Glucose-(1 → 4)-β-D-quinovose base; R
2=β-D-Glucose base or β-D-Glucose-(1 → 6)-β-D-Glucose base,
The present invention also provides the method for the above-mentioned pharmaceutical composition of preparation and medicine, gets yellow Populus deltoides branch and leaf, after drying, pulverizing, fully extracts with 90% methanol room temperature merceration; Methanol extract is added water after suspendible, fully extract with chloroform and n-butyl alcohol successively; N-butanol fraction uses silica gel, the various chromatographic column separation and purification of SephadexLH-20, RP-18 repeatedly, TLC detection method again in conjunction with triterpene saponin obtains pyrocincholicacid type triterpene saponin compound, then obtains described pharmaceutical composition and described medicine by traditional drug formulations preparation method.
And the pharmaceutical composition described in preparation or the method for medicine, get yellow Populus deltoides branch and leaf, drying, shatter after, extract 3 times with 90% methanol room temperature merceration, the time is respectively each 7,3,3 days, and extracting solution obtains methanol extract through concentrating under reduced pressure; Added water by methanol extract after suspendible, fully extract with chloroform and n-butyl alcohol successively, equal-volume respectively extracts three times, and recycling design obtains chloroform portion, n-butanol fraction and water section; By n-butanol fraction through silica gel column chromatography, with the chloroform/methanol gradient elution of 100:0,15:1,9:1,6:1,2:1,0:100, thin layer chromatography, contain the part of triterpene saponin in conjunction with triterpene saponin TLC detection method 9:1 and 6:1 merged wherein; Each following step all must carry out separation and purification in conjunction with triterpene saponin TLC detection method, extractum after merging is again through silica gel column chromatography, first remove non-triterpene saponin part with the chloroform/methanol isocratic elution of 15:1, again with the chloroform/methanol isocratic elution of 80:10, merge into three component Fr.1-Fr.5 according to the difference of triterpene saponin point; Fr.1 component is through SephadexLH-20 gel filtration chromatography, and the chloroform/methanol eluting of 1:1, merges and obtain three subfraction Fr.1-1 – Fr.1-3; Fr.1-2 is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 40:60, then obtain compound pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1) with the methanol/water eluting of 55:45; Fr.2 component is through SephadexLH-20 gel filtration chromatography, with 1:1 chloroform/methanol be eluant removing pigment, the triterpene saponin that enrichment obtains is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 38:62, gained triterpene saponin is finally by silica gel column chromatography, with the chloroform/methanol isocratic elution of 80:10, through TLC combining data detection, after evaporated under reduced pressure, obtain compound pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2); Fr.3 component is through SephadexLH-20 gel filtration chromatography, the chloroform/methanol eluting of 1:1, merge and obtain three subfraction Fr.3-1 – Fr.3-3, Fr.3-2 is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 35:65, then obtain compound pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3) with the methanol/water eluting of 46:54; Fr.4 component is through MCI column chromatography, with impurity such as the methanol/water eluting of 20:80 removing pigments, triterpene saponin part Fr.4-2 is obtained again with 50:50 methanol/water eluting, Fr.4-2, again through anti-phase RP-18 column chromatography, obtains compound pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) with the methanol/water eluting of 32:68; And then obtain described pharmaceutical composition and described medicine by the conventional method preparing medicine.
The present invention still further provides the application in the anti-type-II diabetes hypoglycemic drug of preparation of described pharmaceutical composition or active component pyrocincholicacid type triterpene saponin componds wherein or its salt of pharmacologically allowing.
And, described pharmaceutical composition or the application of active component pyrocincholicacid triterpene saponin compound 1-4 wherein in the anti-type-II diabetes hypoglycemic drug of preparation.
Again, the invention provides the yellow Populus deltoides triterpene saponin extract containing treatment effective dose, with the pharmaceutical composition of pharmaceutically acceptable carrier, described yellow Populus deltoides triterpene saponin extract is obtained by following method, use 90% methanol, abundant lixiviate goes out the extractum containing yellow Populus deltoides triterpene and saponins compound thereof, above-mentioned triterpene and saponins compound thereof are enriched to n-Butanol soluble position by recycling organic solvent extraction technology, then adsorption chromatography is carried out with forward chromatographic column, with chloroform/methanol system gradient elution, separation and concentration obtains containing the less yellow Populus deltoides triterpene saponin extract (chloroform/methanol 9:1 to chloroform/methanol 6:1 position) of pigment, this extract contains the pyrocincholicacid triterpene saponin compound 1-4 being not less than 23.8%.
And, the application of yellow Populus deltoides triterpene saponin extract in the anti-type-II diabetes hypoglycemic drug of preparation, described yellow Populus deltoides triterpene saponin extract is obtained by following method, use 90% methanol, abundant lixiviate goes out the extractum containing yellow Populus deltoides triterpene and saponins compound thereof, above-mentioned triterpene and saponins compound thereof are enriched to n-Butanol soluble position by recycling organic solvent extraction technology, then adsorption chromatography is carried out with forward chromatographic column, with chloroform/methanol system gradient elution, separation and concentration obtains containing the less yellow Populus deltoides triterpene saponin extract (chloroform/methanol 9:1 to chloroform/methanol 6:1 position) of pigment, this extract contains the pyrocincholicacid triterpene saponin compound 1-4 being not less than 23.8%.
The present invention carries out the triterpene saponin chemical constitution study of system to the yellow Populus deltoides of the yellow Populus deltoides platymiscium of Rubiaceae, utilize multiple separation and purification means, comprise positive reversed-phase silica gel column chromatography, SephadexLH-20 gel chromatography, MCI and RP-C18 etc., therefrom obtain a series of pyrocincholicacid triterpene saponin.Afterwards, to triterpene saponin composition pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1), pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) detects its hypoglycemic activity on mice hyperglycemia In vivo model, find pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1), pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) demonstrates the hypoglycemic activity being better than positive control drug metformin (with concentration administration) in vivo, for the anti-type-II diabetes hypoglycemic activity compound in novel plant source, can be used for the hypoglycemic drug preparing anti-type-II diabetes.
Pyrocincholicacid type triterpene saponin or its salt of pharmacologically allowing in described yellow Populus deltoides of the present invention, can enumerate such as with the mineral acids such as hydrochloric acid, nitric acid, sulphuric acid, phosphoric acid, hydrobromic acid, or the organic acid such as maleic acid, fumaric acid, tartaric acid, lactic acid, citric acid, acetic acid, methanesulfonic acid, p-benzene methanesulfonic acid, adipic acid, Palmic acid, tannin, lithium, the alkali metal such as sodium, potassium, the alkaline-earth metal such as calcium, magnesium, the salt that the basic amino acids such as lysine become.
The pharmaceutical composition for the treatment of type-II diabetes relevant disease of the present invention or medicine, the pharmaceutical dosage form prepared by pyrocincholicacid type triterpene saponin compound in yellow Populus deltoides or yellow Populus deltoides triterpene saponin extract and pharmaceutically acceptable carrier comprises tablet, capsule, oral liquid, injection, injection lyophilized preparation or injectable powder etc.Preparation due to pharmaceutical dosage forms such as tablet, capsule, oral liquid, injection, injection lyophilized preparation or injectable powder is the Conventional wisdom of this area, therefore, the various pharmaceutical dosage forms prepared by pyrocincholicacid type triterpene saponin and respective carrier in yellow Populus deltoides also can be realized by those skilled in the art.
Above described pharmaceutically acceptable carrier refers to the pharmaceutical carrier of pharmaceutical field routine, such as: diluent, excipient are as water etc., and filler is as starch, sucrose etc.; Adhesive is as cellulose derivative, alginate, gelatin and polyvinylpyrrolidone; Wetting agent is as glycerol; Disintegrating agent is as agar, calcium carbonate and sodium bicarbonate; Absorption enhancer is as quaternary ammonium compound; Surfactant is as hexadecanol; Absorption carrier is as Kaolin and soap clay; Lubricant is as Pulvis Talci, calcium stearate and magnesium stearate and Polyethylene Glycol etc.Other adjuvant can also be added in addition in the composition as flavouring agent, sweeting agent etc.
Extract of the present invention or compound can in the form of compositions by oral, snuffing enters, the mode of rectum or parenteral is applied to the patient needing this treatment.For time oral, conventional solid preparation can be made into as tablet, powder, granule, capsule etc., make liquid preparation if water or oil-suspending agent or other liquid preparations are as syrup, elixir etc.; During for parenteral, the solution of injection, water or oleaginous suspension etc. can be made into.The various dosage forms of pharmaceutical composition of the present invention can be prepared according to the conventional production process of pharmaceutical field.Such as make active component mix with one or more carriers, be then made into required dosage form.
It is the active component of 0.1% ~ 99.5% that pharmaceutical composition of the present invention preferably contains weight ratio, and most preferably containing weight ratio is the active component of 0.5% ~ 95%.
The amount of application of extract of the present invention or compound can according to the age of route of administration, patient, body weight, the change such as type and the order of severity of disease for the treatment of, and its daily dose can be 0.01 ~ 10mg/kg body weight, preferably 0.1 ~ 5mg/kg body weight.Can use by one or many.
In the yellow Populus deltoides triterpene saponin extract of the present invention and yellow Populus deltoides, the superiority of pyrocincholicacid type triterpene saponin extracting method is, what plant sample was chosen is branch and leaf parts, abundant raw material and be beneficial to protection and the sustainable use of plant resources, extraction and isolation thinking has novelty, chromatographic techniques is successfully utilized to be separated with pyrocincholicacid type triterpene saponin in yellow Populus deltoides by other micromolecule, the pyrocincholicacid type triterpene saponin comparatively concentrated, recycling forward and oppositely Column chromatography techniques etc. are separated the pyrocincholicacid type triterpene saponin obtaining purification.Put it briefly, main chemical compositions because of yellow Populus deltoides also has the triterpene saponin of other type, in the separation process of pyrocincholicacid type triterpene saponin, the triterpene saponin compound of other a large amount of types is had to disturb, especially Usu acid type triterpene saponin, usually mixed in together not easily separated with pyrocincholicacid type triterpene saponin.
First the present invention utilizes 90% methanol, abundant lixiviate goes out triterpene and saponins compound thereof, triterpene saponin is enriched to n-Butanol soluble position by recycling organic solvent extraction technology, then adsorption chromatography is carried out with forward chromatographic column, with chloroform/methanol system gradient elution, success separation and concentration obtains containing less yellow Populus deltoides triterpene saponin part (chloroform/methanol 9:1 to the chloroform/methanol 6:1 position of pigment, namely yellow Populus deltoides triterpene saponin extract), comprise the multiple separation means such as forward silica gel and reverse RP-18 in conjunction with various chromatographic material again and comprise recrystallization etc., separation and purification is to pyrocincholicacid type triterpene saponin sterling.Secondly, only utilize the chromatographic material of laboratory or industrial routine, comprise positive reverse phase silica gel, SephadexLH-20 etc., special chromatographic material need not be used as aminopropyl bonded silica gel, also avoid using the chromatographic materials such as active carbon that adsorptivity is stronger and aluminium oxide; Finally, in yellow Populus deltoides pyrocincholicacid type triterpene saponin separation process in must in conjunction with the TLC detection method of pyrocincholicacid type triterpene saponin.In a word, extraction separation method controllability of the present invention and favorable reproducibility, sample loss is few, and cost is lower, easy to operate, separablely obtains micro-pyrocincholicacid type triterpene saponin, and solvent can be recycled repeatedly, is also applicable to commercial production.
Accompanying drawing illustrates:
Fig. 1 is the preparation method flow chart of pyrocincholicacid type triterpene saponin extract and compound in yellow Populus deltoides of the present invention;
Fig. 2 is pyrocincholicacid type triterpene saponin compound structural formula in yellow Populus deltoides of the present invention.
Detailed description of the invention:
Below in conjunction with accompanying drawing, further illustrate essentiality content of the present invention with embodiments of the invention, but do not limit the present invention with this.Essence according to the present invention all belongs to scope of the present invention to the improvement that the present invention carries out.
Embodiment 1:
Pyrocincholicacid type triterpene saponin pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1) in yellow Populus deltoides triterpene saponin extract and yellow Populus deltoides, pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), the preparation of pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) and Structural Identification:
Get yellow Populus deltoides branch and leaf part 20kg, drying, shatter after, extract 3 times with 90% methanol room temperature merceration, the time is respectively each 7,3,3 days, and extracting solution obtains methanol extract through concentrating under reduced pressure; Added water by methanol extract after suspendible, fully extract with chloroform and n-butyl alcohol successively, equal-volume respectively extracts three times, and recycling design obtains chloroform portion, n-butanol fraction and water section; By n-butanol fraction through silica gel column chromatography, with 100:0,15:1,9:1, the chloroform/methanol gradient elution of 6:1,2:1,0:100, thin layer chromatography, merges part (the namely of the present invention yellow Populus deltoides triterpene saponin extract) 15.7g of 9:1 and 6:1 two wherein containing pyrocincholicacid type triterpene saponin in conjunction with triterpene saponin TLC detection method; Each following step all must carry out separation and purification in conjunction with triterpene saponin TLC detection method; Extractum after merging, again through silica gel column chromatography, first removes non-triterpene saponin part with the chloroform/methanol isocratic elution of 15:1, then with the chloroform/methanol isocratic elution of 80:10, merges into three component Fr.1-Fr.5 according to the difference of triterpene saponin point.
Fr.1 component is through SephadexLH-20 gel filtration chromatography, and the chloroform/methanol eluting of 1:1, merges and obtain three subfraction Fr.1-1 – Fr.1-3; Fr.1-2 is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 40:60, then obtain compound pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1) 720mg with the methanol/water eluting of 55:45.
Fr.2 component, through SephadexLH-20 gel filtration chromatography, is that eluant removes the element that discolors by 1:1 chloroform/methanol; The triterpene saponin that enrichment obtains, again through anti-phase RP-18 column chromatography, first removes impurity with the methanol/water eluting of 38:62; Gained triterpene saponin is finally by silica gel column chromatography, with the chloroform/methanol isocratic elution of 80:10, through TLC combining data detection, after evaporated under reduced pressure, obtain compound pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2) 1.15g.
Fr.3 component is through SephadexLH-20 gel filtration chromatography, and the chloroform/methanol eluting of 1:1, merges and obtain three subfraction Fr.3-1 – Fr.3-3; Fr.3-2 is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 35:65, then obtain compound pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3) 1.02g with the methanol/water eluting of 46:54.
Fr.4 component is through MCI column chromatography, with impurity such as the methanol/water eluting of 20:80 removing pigments, triterpene saponin part Fr.4-2 is obtained again with 50:50 methanol/water eluting, Fr.4-2, again through anti-phase RP-18 column chromatography, obtains compound pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) 854mg with the methanol/water eluting of 32:68.
In formula, R
1=β-D-quinovose base or β-D-Glucose-(1 → 4)-β-D-quinovose base; R
2=β-D-Glucose base or β-D-Glucose-(1 → 6)-β-D-Glucose base.
The Structural Identification data of Pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1) are:
Pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1): white powder, C
41h
66o
12, ESI-MS:749 [M-H]
-;
1hNMR (500MHz, Pyr-d
5) δ: 6.32 (1H, d, J=7.2Hz, H-1 "), 4.86 (1H, d, J=7.2Hz, H-1 '), 3.26 (1H, dd, J
1=11.2, J
2=4.3Hz, H-3), 1.65 (1H, d, J=5.0Hz, H-6 '), 1.19 (3H, s, H-23), 1.12 (3H, s, H-26), 0.90 (3H, s, H-24), 0.88 (3H, s, H-29), 0.85 (3H, s, H-30), 0.77 (3H, s, H-25).
13CNMR(125MHz,Pyr-d
5)δ:38.5(C-1)，26.9(C-2)，90.0(C-3)，39.7(C-4)，55.8(C-5)，18.9(C-6)，39.6(C-7)，38.1(C-8)，56.5(C-9)，37.2(C-10)，18.1(C-11)，32.1(C-12)，130.3(C-13)，136.9(C-14)，21.0(C-15)，23.6(C-16)，45.8(C-17)，39.6(C-18)，41.5(C-19)，30.6(C-20)，34.3(C-21)，31.7(C-22)，28.2(C-23)，16.7(C-24)，16.7(C-25)，20.8(C-26)，176.9(C-28)，32.4(C-29)，25.0(C-30)，106.8(C-1′)，76.0(C-2′)，78.4(C-3′)，77.0(C-4′)，72.8(C-5′)，18.9(C-6′),95.7(C-1″)，74.3(C-2″)，79.4(C-3″)，71.2(C-4″)，78.9(C-5″)，62.3(C-6″)。
The Structural Identification data of Pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2) are:
Pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), white powder, C
47h
76o
17, ESI-MS:911 [M-H]
-;
1hNMR (500MHz, Pyr-d
5) δ: 6.24 (1H, d, J=8.2Hz, H-1 "), 4.85 (1H, d, J=7.7Hz; H-1 '), 4.71 (1H, d, J=5.3Hz, H-1 " '), 4.60 (1H, d, J=8.0Hz, H-1 "), 3.28 (1H, dd, J
1=10.9, J
2=4.1Hz, H-3), 1.65 (1H, d, J=6.0Hz, H-6 '), 1.33 (3H, s, H-23), 1.15 (3H, s, H-26), 0.96 (3H, s, H-24), 0.88 (3H, s, H-29), 0.87 (3H, s, H-30), 0.77 (3H, s, H-25).
13CNMR(125MHz,Pyr-d
5)δ:38.7(C-1)，27.0(C-2)，89.1(C-3)，39.7(C-4)，56.0(C-5)，18.9(C-6)，39.8(C-7)，38.2(C-8)，56.7(C-9)，37.2(C-10)，18.2(C-11)，32.2(C-12)，130.4(C-13)，137.1(C-14)，21.1(C-15)，23.9(C-16)，45.8(C-17)，39.7(C-18)，41.6(C-19)，30.7(C-20)，34.5(C-21)，31.8(C-22)，28.3(C-23)，16.8(C-24)，16.8(C-25)，21.0(C-26)，176.9(C-28)，32.3(C-29)，25.0(C-30)，106.8(C-1′)，76.1(C-2′)，78.0(C-3′)，77.0(C-4′)，72.8(C-5′)，18.9(C-6′),95.7(C-1″)，75.3(C-2″)，78.8(C-3″)，71.7(C-4″)，78.5(C-5″)，69.6(C-6″),105.3(C-1″′)，74.1(C-2″′)，78.5(C-3″′)，71.1(C-4″′)，78.5(C-5″′)，62.8(C-6″′)。
The Structural Identification data of Pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3) are:
Pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), white powder, C
47h
76o
17, ESI-MS:911 [M-H]
-;
1hNMR (500MHz, Pyr-d
5) δ: 6.31 (1H, d, J=8.1Hz, H-1 " '), 5.37 (1H, d, J=7.5Hz, H-1 "), 4.80 (1H, d, J=7.6Hz, H-1 '), 3.29 (1H, dd, J
1=11.0, J
2=4.4Hz, H-3), 1.58 (1H, d, J=6.6Hz, H-6 '), 1.29 (3H, s, H-23), 1.12 (3H, s, H-26), 1.08 (3H, s, H-24), 0.90 (3H, s, H-29), 0.88 (3H, s, H-30), 0.80 (3H, s, H-25).
13CNMR(125MHz,Pyr-d
5)δ:38.4(C-1)，26.8(C-2)，89.3(C-3)，39.8(C-4)，55.9(C-5)，18.7(C-6)，39.8(C-7)，38.1(C-8)，56.5(C-9)，37.3(C-10)，18.1(C-11)，32.2(C-12)，130.3(C-13)，137.0(C-14)，21.1(C-15)，23.8(C-16)，45.8(C-17)，39.6(C-18)，41.6(C-19)，30.7(C-20)，34.4(C-21)，31.7(C-22)，28.2(C-23)，16.7(C-24)，16.7(C-25)，20.9(C-26)，176.7(C-28)，32.4(C-29)，25.0(C-30)，105.0(C-1′)，76.5(C-2′)，78.0(C-3′)，83.7(C-4′)，71.8(C-5′)，18.6(C-6′),106.0(C-1″)，75.3(C-2″)，78.6(C-3″)，71.3(C-4″)，78.3(C-5″)，62.8(C-6″),95.8(C-1″′)，74.3(C-2″′)，79.3(C-3″′)，71.7(C-4″′)，78.9(C-5″′)，62.4(C-6″′)。
The Structural Identification data of Pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) are:
Pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4), white powder, C
53h
86o
22, ESI-MS:1073 [M-H]
-;
1hNMR (500MHz, Pyr-d
5) δ: 6.22 (1H, d, J=8.1Hz, H-1 " '), 5.37 (1H, d, J=7.5Hz; H-1 "), 5.00 (1H, d, J=7.6Hz, H-1 " "), 4.80 (1H, d, J=7.60Hz, H-1 '), 3.28 (1H, dd, J
1=10.9, J
2=3.9Hz, H-3), 1.59 (1H, d, J=5.6Hz, H-6 '), 1.27 (3H, s, H-23), 1.12 (3H, s, H-26), 1.06 (3H, s, H-24), 0.88 (3H, s, H-29), 0.86 (3H, s, H-30), 0.80 (3H, s, H-25).
13CNMR(125MHz,Pyr-d
5)δ:38.6(C-1)，27.0(C-2)，89.3(C-3)，39.8(C-4)，56.0(C-5)，19.1(C-6)，39.8(C-7)，38.2(C-8)，56.7(C-9)，37.3(C-10)，18.2(C-11)，32.2(C-12)，130.4(C-13)，137.1(C-14)，21.1(C-15)，24.6(C-16)，45.8(C-17)，39.6(C-18)，41.6(C-19)，30.7(C-20)，34.6(C-21)，31.4(C-22)，28.3(C-23)，16.6(C-24)，16.8(C-25)，21.0(C-26)，176.9(C-28)，32.5(C-29)，25.1(C-30)，105.0(C-1′)，76.7(C-2′)，78.0(C-3′)，83.6(C-4′)，72.6(C-5′)，18.7(C-6′),106.0(C-1″)，75.2(C-2″)，78.8(C-3″)，71.1(C-4″)，78.5(C-5″)，62.8(C-6″),95.7(C-1″′)，74.1(C-2″′)，78.5(C-3″′)，71.7(C-4″′)，78.5(C-5″′)，69.6(C-6″′),105.3(C-1″″)，75.2(C-2″″)，78.3(C-3″″)，71.8(C-4″″)，78.0(C-5″″)，62.8(C-6″″)。
Embodiment 2:
Pyrocincholicacid type triterpene saponin compound pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1) in the yellow Populus deltoides triterpene saponin extract of the present invention and yellow Populus deltoides, pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) (hereinafter referred to as compound 1-4) has therapeutical effect to the mice type-II diabetes hyperglycemia that streptozotocin (STZ) is induced.Experimental principle, method and result are as follows:
Experimental principle: the selective destruction of streptozotocin (STZ) beta Cell of islet to mice, it is made to produce diabetes. mice high-calorie feed raises certain hour and fasting 12h, by 100mg/kg body weight lumbar injection STZ, animal model of diabetes mellitus type II can be prepared, and have that overweight, impaired glucose tolerance, blood fat raise, serum insulin raises by the model that this method is prepared and combination rate of insulin receptor reduces the feature of companion's insulin resistant, be similar to the Clinical symptoms of Patients with NIDDM.The diabetes mice of STZ induction because of its cycle shorter, method is easy, is that research human type II diabetes treats the ideal model of new drug.
Experimental technique: get 6 ~ 8 week age, the ICR male mice of 25-30g, high glucose and high fat forage feed 4 weeks, fasting 12h, with 1mL disposable sterilized injector, by 100mg/kg, (solvent is citric acid-sodium citrate buffer, PH-4.5) body weight lumbar injection STZ, detects fasting fasting blood sugar overnight after 3 days, it is then modeling success mice that blood glucose value is more than or equal to 11.1mmol/ml.From modeling same day, every day according to 50mg/kg bodyweight p gastric infusion once, continued ten days, until experiment terminates.The same day was measured mice fasting glucose, empty body weight in modeling.After experiment terminates, detect fasted mice fasting blood sugar overnight and body weight.
Experimental result:
Yellow Populus deltoides triterpene saponin extract and compound 1-4 all significantly can reduce the fasting glucose of the diabetic mice of STZ induction, and lose weight (table 1).
Table 1. compound 1-4 is to the hypoglycemic activity of the hyperglycemia mice that STZ induces
Experimental result shows, yellow Populus deltoides triterpene saponin extract and compound 1-4 all significantly can reduce the fasting glucose of the diabetic mice of STZ induction, its fasting glucose reducing the hyperglycemia mice of STZ induction can reach 36.61 to 41.12%, and its blood sugar decreasing effect is obviously better than positive control medicine metformin group (19.11%); And yellow Populus deltoides triterpene saponin extract and compound 1-4 also significantly can reduce the empty body weight of the diabetic mice of STZ induction, its empty body weight reducing the hyperglycemia mice of STZ induction can reach 10.12 to 11.93%, and it reduces body weight effect and is better than positive control medicine metformin group (10.15%); Prove a kind of hypoglycemic medicine that can become treatment type-II diabetes containing the yellow Populus deltoides triterpene saponin extract of compound (1)-(4) and compound (1)-(4).
Embodiment 3:
Embodiment 1 gained compound 1-4, adds the ethanol solution of sulfuric acid of 4%, PH=4, filters, dry, makes sulphate cpd 1-4.
Embodiment 4:
Embodiment 1 gained compound 1-4, adds the hydrochloric acid solution of 4%, PH=4, filters, dry, makes hydrochloride compound 1-4.
Embodiment 5:
Embodiment 1 gained compound 1-4, adds the tartaric acid solution of 4%, PH=4, filters, dry, makes tartrate compound 1-4.
Embodiment 6:
Embodiment 1 gained compound 1-4, adds the citric acid solution of 4%, PH=4, filters, dry, makes citrate compound 1-4.
Embodiment 7:
Tablet: by the salt 10mg of embodiment 1 gained compound 1-4 or embodiment 4-6 gained, lactose 180mg, starch 55mg, magnesium stearate 5mg, newborn sugar and starch mix, with water evenly moistening, the mixture after moistening to be sieved and dry, after sieve, add magnesium stearate, then by mixture tabletting, the heavy 250mg of every sheet, compounds content is 10mg.
Embodiment 8:
Ampulla: by the salt 2mg of embodiment 1 gained compound 1-4 or embodiment 4-6 gained, sodium chloride 10mg, is dissolved in appropriate water for injection, filters gained solution, aseptically loads in ampoule bottle.
Embodiment 9:
Injection lyophilized preparation: the salt 10mg of embodiment 1 gained compound 1-4 or embodiment 4-6 gained, sodium bicarbonate 2mg, mannitol 252mg.
Preparation method: by sodium bicarbonate, mannitol, be dissolved in water for injection, adds activated carbon adsorption 30min depyrogenation, cross and filter active carbon, in filtrate, add compound or its salt, supersound process makes dissolving, PH is regulated to be 5.0-7.0 with 1N hydrochloric acid, microporous filter membrane filters, and injects with water, subpackage, lyophilization, top plug, rolls lid, to obtain final product.
Embodiment 10:
Capsule: the salt 10mg of embodiment 1 gained compound 1-4 or embodiment 4-6 gained, lactose 187mg, magnesium stearate 3mg; Preparation method: compound or its salt and cosolvent are mixed, sieve, Homogeneous phase mixing, loads hard gelatin capsule the mixture obtained, and the heavy 200mg of each capsule, active component content is 10mg.
Claims (10)
1. pharmaceutical composition, Pyrocincholicacid type triterpene saponin componds wherein containing treatment effective dose, or its salt of pharmacologically allowing and pharmaceutically acceptable carrier, described Pyrocincholicacid type triterpene saponin componds refers to that skeleton contains a pyrocincholicacid, the C-3 position of pyrocincholicacid is connected by oxygen atom with 1 ' position of a β-D-quinovose base, and C-28 position carboxyl and 1 of a β-D-Glucose base " triterpene saponin that is connected by oxygen atom of position and other three derivants with framing structure.
2. pharmaceutical composition, pyrocincholicacid triterpene saponin compound 1-4 wherein containing treatment effective dose, or its salt of pharmacologically allowing and pharmaceutically acceptable carrier, described pyrocincholicacid triterpene saponin compound 1-4 is the compound with following structural formula: pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1), pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4)
In formula, R
1=β-D-quinovose base or β-D-Glucose-(1 → 4)-β-D-quinovose base; R
2=β-D-Glucose base or β-D-Glucose-(1 → 6)-β-D-Glucose base,
。
3. the hypoglycemic drug that the salt of pharmacologically allowing with pyrocincholicacid type triterpene saponin componds or its is effective ingredient, described Pyrocincholicacid type triterpene saponin refers to that skeleton contains a pyrocincholicacid, the C-3 position of pyrocincholicacid is connected by oxygen atom with 1 ' position of a β-D-quinovose base, and C-28 position carboxyl and 1 of a β-D-Glucose base " triterpene saponin that is connected by oxygen atom of position and other three derivants with framing structure.
4. the hypoglycemic drug of the anti-type-II diabetes that the salt of pharmacologically allowing with pyrocincholicacid triterpene saponin compound 1-4 or its is effective ingredient, described pyrocincholicacid triterpene saponin compound 1-4 is the compound with following structural formula: pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1), pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3), pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4)
In formula, R
1=β-D-quinovose base or β-D-Glucose-(1 → 4)-β-D-quinovose base; R
2=β-D-Glucose base or β-D-Glucose-(1 → 6)-β-D-Glucose base,
。
5. prepare the method for the pharmaceutical composition of claim 1 or the medicine of preparation claim 3, get yellow Populus deltoides branch and leaf, after drying, pulverizing, fully extract with 90% methanol room temperature merceration; Methanol extract is added water after suspendible, fully extract with chloroform and n-butyl alcohol successively; N-butanol fraction uses silica gel, the various chromatographic column separation and purification of SephadexLH-20, RP-18 repeatedly, TLC detection method again in conjunction with triterpene saponin obtains pyrocincholicacid type triterpene saponin compound, then obtains described pharmaceutical composition and described medicine by traditional drug formulations preparation method.
6. prepare pharmaceutical composition according to claim 2 or prepare the method for medicine according to claim 4, get yellow Populus deltoides branch and leaf, drying, shatter after, extract 3 times with 90% methanol room temperature merceration, time is respectively each 7,3,3 days, and extracting solution obtains methanol extract through concentrating under reduced pressure; Added water by methanol extract after suspendible, fully extract with chloroform and n-butyl alcohol successively, equal-volume respectively extracts three times, and recycling design obtains chloroform portion, n-butanol fraction and water section; By n-butanol fraction through silica gel column chromatography, with the chloroform/methanol gradient elution of 100:0,15:1,9:1,6:1,2:1,0:100, thin layer chromatography, contain the part of triterpene saponin in conjunction with triterpene saponin TLC detection method 9:1 and 6:1 merged wherein; Each following step all must carry out separation and purification in conjunction with triterpene saponin TLC detection method, extractum after merging is again through silica gel column chromatography, first remove non-triterpene saponin part with the chloroform/methanol isocratic elution of 15:1, again with the chloroform/methanol isocratic elution of 80:10, merge into three component Fr.1-Fr.5 according to the difference of triterpene saponin point; Fr.1 component is through SephadexLH-20 gel filtration chromatography, and the chloroform/methanol eluting of 1:1, merges and obtain three subfraction Fr.1-1 – Fr.1-3; Fr.1-2 is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 40:60, then obtain compound pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (1) with the methanol/water eluting of 55:45; Fr.2 component is through SephadexLH-20 gel filtration chromatography, with 1:1 chloroform/methanol be eluant removing pigment, the triterpene saponin that enrichment obtains is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 38:62, gained triterpene saponin is finally by silica gel column chromatography, with the chloroform/methanol isocratic elution of 80:10, through TLC combining data detection, after evaporated under reduced pressure, obtain compound pyrocincholicacid3 β-O-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2); Fr.3 component is through SephadexLH-20 gel filtration chromatography, the chloroform/methanol eluting of 1:1, merge and obtain three subfraction Fr.3-1 – Fr.3-3, Fr.3-2 is again through anti-phase RP-18 column chromatography, first remove impurity with the methanol/water eluting of 35:65, then obtain compound pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranoside (3) with the methanol/water eluting of 46:54; Fr.4 component is through MCI column chromatography, with impurity such as the methanol/water eluting of 20:80 removing pigments, triterpene saponin part Fr.4-2 is obtained again with 50:50 methanol/water eluting, Fr.4-2, again through anti-phase RP-18 column chromatography, obtains compound pyrocincholicacid3 β-O-β-D-glucopyranosyl-(1 → 4)-β-D-quinovopyranosyl-28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (4) with the methanol/water eluting of 32:68; And then obtain described pharmaceutical composition and described medicine by the conventional method preparing medicine.
7. the pharmaceutical composition described in claim 1 or active component pyrocincholicacid type triterpene saponin componds wherein or the application of its salt of pharmacologically allowing in the anti-type-II diabetes hypoglycemic drug of preparation.
8. the pharmaceutical composition described in claim 2 or the application of active component pyrocincholicacid triterpene saponin compound 1-4 wherein in the anti-type-II diabetes hypoglycemic drug of preparation.
9. pharmaceutical composition, yellow Populus deltoides triterpene saponin extract wherein containing treatment effective dose, with pharmaceutically acceptable carrier, described yellow Populus deltoides triterpene saponin extract is obtained by following method, use 90% methanol, abundant lixiviate goes out the extractum containing yellow Populus deltoides triterpene and saponins compound thereof, above-mentioned triterpene and saponins compound thereof are enriched to n-Butanol soluble position by recycling organic solvent extraction technology, then adsorption chromatography is carried out with forward chromatographic column, with chloroform/methanol system gradient elution, separation and concentration obtains containing the less chloroform/methanol 9:1-6:1 position of pigment, i.e. yellow Populus deltoides triterpene saponin extract, this extract contains the pyrocincholicacid triterpene saponin compound 1-4 being not less than 23.8%.
10. the application of yellow Populus deltoides triterpene saponin extract in the anti-type-II diabetes hypoglycemic drug of preparation, described yellow Populus deltoides triterpene saponin extract is obtained by following method, use 90% methanol, abundant lixiviate goes out the extractum containing yellow Populus deltoides triterpene and saponins compound thereof, above-mentioned triterpene and saponins compound thereof are enriched to n-Butanol soluble position by recycling organic solvent extraction technology, then adsorption chromatography is carried out with forward chromatographic column, with chloroform/methanol system gradient elution, separation and concentration obtains containing the less chloroform/methanol 9:1-6:1 position of pigment, i.e. yellow Populus deltoides triterpene saponin extract, this extract contains the pyrocincholicacid triterpene saponin compound 1-4 being not less than 23.8%.
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