CN102408466B - New Salicomia europaea saponin and preparation method and applications thereof - Google Patents
New Salicomia europaea saponin and preparation method and applications thereof Download PDFInfo
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- CN102408466B CN102408466B CN201110434057.9A CN201110434057A CN102408466B CN 102408466 B CN102408466 B CN 102408466B CN 201110434057 A CN201110434057 A CN 201110434057A CN 102408466 B CN102408466 B CN 102408466B
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- 229930182490 saponin Natural products 0.000 title claims abstract description 24
- 239000001397 quillaja saponaria molina bark Substances 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 150000007949 saponins Chemical class 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- -1 oleanolic acid saponin compound Chemical class 0.000 claims abstract description 11
- 229940124599 anti-inflammatory drug Drugs 0.000 claims abstract description 7
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 claims abstract description 5
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229940100243 oleanolic acid Drugs 0.000 claims abstract description 5
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 claims abstract description 5
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Abstract
The invention relates to the field of the natural pharmaceutical chemistry and discloses a chemical structure of a new oleanolic acid saponin compound which is extracted and separated from Salicomia europaea. The invention also discloses a preparation method of the compound and applications of the compound in the medical field, in particular applications of the compound in the field of inhibiting the activity of phospholipase A2 (PLA2) and preparing anti-inflammatory drugs.
Description
One, technical field:
The present invention relates to natural medicine field, be specifically related to extract the new saponin(e of one that separation obtains, its preparation method, and this saponin(e inhibition of phospholipase A from medicinal plant salicornia europaeal
2(PLA
2) active and in the purposes of preparing in anti-inflammatory drug.
Two, technical background:
Salicornia europaeal (Salicornia europaea Linn.) is Chenopodiaceae (Chenopodiaceae) salicornia europaeal platymiscium, mainly be distributed in saltings, seashore is taken up in salt lake, " China book on Chinese herbal medicine " records the effect of flat liver, diuresis, step-down, is among the peoplely commonly used to cure mainly hypertension and headache.In salicornia europaeal platymiscium, be rich in saponin component, its aglycon is mainly Oleanolic Acid aglycon.In the separation of the Chinese Academy of Sciences of Jiangsu Province medicinal plants study development centre saponin component in to salicornia europaeal, obtain a saponin compound, the clear and definite structure of this compound, pharmacologically active and purposes.
Phospholipase A2 (PLA
2) be present in various organisms. its physiological function is specificity hydrolytic phosphatide Sn-2 fat key, makes it to be decomposed into lipid acid and lysophospholipid.If lipid acid is arachidonic acid (arachidonic acid), be decomposed into respectively prostaglandin(PG) (prostaglandins) and leukotriene (leukotrienes) by cyclooxygenase (cyclooxygenase) and 5-lipoxygenase (lipoxygenase), prostaglandin(PG) is the precursor of inflammation, and leukotriene plays an important role in the pathogeny that causes asthma; The platelet activation factor (platelet-activating factor) that lysophospholipid is metabolized to is also the important medium that causes inflammation.PLA
2if in the biosynthetic key position of inflammation regulatory factor. can effectively suppress PLA
2activity, with the biosynthesizing of closely-related three regulatory factors of inflammatory process all by suppressed.Efficient single-minded PLA
2inhibitor likely develops into novel NSAID (non-steroidal anti-inflammatory drug).
Three, summary of the invention:
Technical problem
One of object of the present invention is to provide a kind of saponin compound (3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester) and preparation method thereof and this new compound is being prepared PLA
2the new purposes of inhibitor and anti-inflammatory drug.According to the present invention, this new compound can be prepared into medicine, for the preparation of PLA
2the treatment of the relative disease such as inhibitor and inflammation.
Technical scheme
The invention provides a kind of saponin compound and tool preparation method.This saponin compound that extraction in salicornia europaeal, separation, purifying obtain, called after 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester.
3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester, chemical name is: 3 β, 29-dihydroxyl volatile oil-12-alkene-28-carboxylic acid 28-O-β-D-Glucose ester,
Chemical structural formula is:
The preparation method of above-mentioned salicornia europaeal saponin compound, it is characterized in that: take the fresh herb of salicornia europaeal as raw material, through water or organic solvent or mixed solvent extraction, aqueous extract is directly crossed macroporous resin adsorption, after organic solvent or mixed solvent extracting solution are concentrated, be dissolved in water through macroporous resin adsorption or n-butanol extraction, macroporous resin adsorption thing or n-butyl alcohol extract obtain through column chromatography for separation again.Wherein, macroporous resin comprises D101, AB-5 or HP-20; Column chromatography is selected from one or more in silica gel, gel, aluminum oxide, polymeric amide, ODS and MCI with carrier; Organic solvent comprises methyl alcohol, ethanol or propyl carbinol; Extract temperature lower than 100 ℃.
The invention provides 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester and medically acceptable pharmaceutical excipient composition pharmaceutical composition and preparation thereof.As, tablet, pill, paste, capsule, oral liquid, granule and injection liquid powder injection or liquid drugs injection liquid.
The invention provides salicornia europaeal saponin compound and prepare PLA
2the application of inhibitor and anti-inflammatory drug.In vitro, the IC of 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
50value and indoles PLA
2the IC of inhibitor
50close, in body, experiment shows 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester 20mgkg
-1and 40mgkg
-1two dosage groups can be passed through PLA
2active remarkable restraining effect, thereby the content of minimizing inflammatory mediator PGE, prompting 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester is similar to PLA
2the effect of inhibitor; In addition 40mgkg,
-1and 80mgkg
-1two dosage group p-Xylol induced mice ear swellings have obvious restraining effect.
Beneficial effect
The invention discloses the chemical structure of extracting a kind of oleanolic acid saponin class new compound separating from salicornia europaeal, and this compounds process for production thereof and the purposes in field of medicaments, especially preparing Phospholipase A2 (PLA
2) purposes of inhibitor and anti-inflammatory drug.In view of PLA
2the research of inhibitor can be research PLA
2mechanism in cell and molecular level complexity provides strong means, also open up wide treatment prospect for the treatment of clinical anti-inflammatory and various autoimmune disease, the present invention is of great practical significance for the saponins compound in abundant exploitation salicornia europaeal simultaneously.
Evidence, in vitro, the IC of 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
50value and indoles PLA
2the IC of inhibitor
50close, in body, experiment shows 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester 20mgkg
-1and 40mgkg
-1two dosage groups can be passed through PLA
2active remarkable restraining effect, thereby the content of minimizing inflammatory mediator PGE, prompting 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester is similar to PLA
2the effect of inhibitor; In addition 40mgkg,
-1and 80mgkg
-1two dosage group p-Xylol induced mice ear swellings have obvious restraining effect, illustrate that 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester can be used for PLA
2the exploitation of inhibitor and anti-inflammatory drug.
Four, accompanying drawing explanation:
Can be used as annex material with figure below reports.
The ESI-MS spectrum of Fig. 1 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
The HR-MS spectrum of Fig. 2 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
Fig. 3 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
1h-NMR spectrum
Fig. 4 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
13c-NMR spectrum
The COSY spectrum of Fig. 5 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
The HMQC spectrum of Fig. 6 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
The HMBC spectrum of Fig. 7 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
The ROESY spectrum of Fig. 8 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
The extraction of Fig. 9 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester separates
The structural formula of Figure 10 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester
Five, embodiment:
In conjunction with embodiment, the invention will be further described, but content of the present invention is not restricted to cited embodiment.This saponins new compound that the present invention's extraction in salicornia europaeal, separation, purifying obtain, called after 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester.
1. extract and separate
Present inventor concentrates to obtain medicinal extract at this institute pilot plant with 90% alcohol reflux by salicornia europaeal herb, gets medicinal extract successively with sherwood oil, ethyl acetate extraction.Obtain sherwood oil portion, ethyl acetate portion and propyl carbinol portion.
Propyl carbinol portion adsorbs with macroporous resin, then with water-ethanol system segment wash-out, merges the component that contains saponin(e, obtains salicornia europaeal total saponins.Gained salicornia europaeal total saponins carries out silica gel column chromatography, and moving phase is followed successively by chloroform-methanol (10: 1,4: 1,2: 1,1: 1), methyl alcohol.Wherein chloroform-methanol (4: 1) part is through reversed-phase column separation and gel column purifying obtain monomeric compound 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester repeatedly.
2. Structural Identification
White amorphous powder, is soluble in methyl alcohol.The TLC vitriol oil-Vanillin displaing amaranth, after placing, color goes down.Molish reaction and Liebermann-Burchard reaction are all positive, and this compound of deducibility is triterpene saponin componds.
(c?0.11,MeOH)。The data that show according to Low Resolution Mass Spectra, m/z 673.30 ([M+K]
+), 657.30 ([M+Na]
+), 669.25 ([M+Cl]
-), 67930 ([M+HCOO]
-), 633.25 ([M-H]
-) show that its molecular weight is 634, in conjunction with
1the hydrogen signal of H-NMR and
13the carbon signal quantity of C-NMR, deduction molecular formula is C
36h
58o
9, degree of unsaturation is 8.This molecular formula is by high resolution mass spectrum (HR-ESI-MS), m/z 657.3991 ([M+Na]
+) (calculated value is 657.3979), further evidence.
1h-NMR (C
5d
5n, 500MHz, δ, ppm) 6 angular methyl(group) (δ 0.91,1.01 of demonstration, 1.08,1.13,1.20 and 1.25), an alkene hydrogen proton (δ 5.48,, and sugared anomeric proton signal (δ 6.33, d, J=8.1Hz) t-like).
13c-NMR (C
5d
5n, 125MHz, δ, ppm) show that the carbon signal of connection hydroxyl is δ
c78.1 (C-3-OH) and a hydroxy methylene are δ
c73.7, and this hydroxy methylene carbon signal shows and δ on hsqc spectrum
hthe unimodal of two hydrogen on 3.54 is correlated with.Relevant with H-23 (δ 1.20) according to H-H COSY and ROESY spectrum H-3 (δ 3.40), prove that the α position of the upper hydrogen proton of C-3 is orientated, therefore infer that 3 upper hydroxyls are β position orientation.Except E ring and sugared part, above
1h-NMR and
13the spectral data of C-NMR and Oleanolic Acid coincide.
In HMBC spectrogram, observe δ
hunimodal and the four carbon atom δ of two hydrogen of 3.54
c19.7,28.9 (C-21), 36.4 (C-20), 41.0 (C-19) intersects, and shows that C-29 or C-30 are oxidized.With the comparison of document nuclear magnetic data, infer C-29 (δ
c73.7) oxidized.
δ in ROESY spectrum
h1.08 and 3.32 (H-18, β-axial) intersects, and proves that 30 carbon are β positions, and therefore C-29 is positioned at α position.
13c-NMR shows δ 95.8 (Glc-1), 74.2 (Glc-2), 79.0 (Glc-3), 71.2 (Glc-4), 79.3 (Glc-5), 62.3 (Glc-6), may be Glucopyranose glycosyls.The monose that hydrolysis generates detects as Glucopyranose through TLC, infers that it is D-Glucopyranose again by its optical value, by the coupling constant J=8.1Hz of glucose terminal hydrogen, therefore infers and has connected β-D-Glucopyranose, the H (δ of sugared end group in HMBC spectrum
h6.33) and aglycon C-28 (δ
c176.5) relevant, show that glucose link position is triterpene aglycon C-28 position.
Comprehensive above analysis, new saponin(e structure is decided to be 3 β, 29-dihydroxyl volatile oil-12-alkene-28-carboxylic acid 28-O-β-D-Glucose ester.
The structure of the new saponin(e of Fig. 1 is relevant with ROESY with main HMBC (H → C)
Nuclear magnetic resonance data (δ, ppm, 0=TMS, the C of the new saponin(e of table 1
5d
5n)
New compound of the present invention can be made conventional pharmaceutical dosage form as active constituents of medicine, as, tablet, pill, paste, capsule, oral liquid, granule and injection liquid powder injection or liquid drugs injection liquid.
3. vitro inhibition PLA
2effect
Take SIBLINKS analogue as substrate, with Lp-PLA
2(the PLA extracting in cobra-venom
2) as lytic enzyme, indoles PLA
2inhibitor 5-methoxyl group-1-benzyl-1H-indole-3-acetamide is contrast, measures the maximum speed of reaction of hydrolysis by microplate reader colorimetric system, suppresses active qualitative, quantitative comparison, the results are shown in Table 2.
Table 2 is to PLA
2the predictor of restraining effect and SCORE
Show the IC of 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester from the result of table 2
50value and indoles PLA
2the IC of inhibitor
50close, measured value of experiment and SCORE predictor are corresponding relation, and prompting 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester is similar to PLA
2the effect of inhibitor.
4. anti-inflammatory action
(1) impact on Mice Auricle dimethylbenzene inflammation
To 60 random point 5 groups of male mices, 1. 2. 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester I (20mgkg of control group
-1), II (40mgkg
-1), III (80mgkg
-1) three 3. indomethacin group (8mgkg of dosage group
-1), each physiological saline of organizing gastric infusion or giving equivalent, every day 1 time, continuously 3d, 30min after last administration, the interior outside of every mouse auris dextra exterior feature is dripped and is coated with 20 μ l caused by dimethylbenzene xylene inflammation, and left ear in contrast, causes the de-cervical vertebra of scorching rear 30min and puts to death mouse, lay auricle respectively at left and right ear same area with diameter 7mm punch tool, weigh, with left and right auricle weight difference value representation swelling, the results are shown in Table 3.
The impact of table 3 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester p-Xylol induced mice auricle inflammation ear swelling degree (
n=15)
With model group comparison
*p < 0.05,
*p < 0.01
Experimental result shows, 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester 40mgkg
-1and 80mgkg
-1two dosage group p-Xylol induced mice ear swellings have obvious restraining effect, and prompting 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester has certain anti-inflammatory action.
(2) on Carrageenan is prepared the impact of rat Air-vesicle Synovitis inflammatory model
Get healthy SD male white rat, be divided at random 6 groups: 1. normal group; 2. model group; 3. 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester I (10mgkg
-1), II (20mgkg
-1), III (40mgkg
-1) three dosage; 4. Dexamethasone group (0.15mgkg
-1).Each treated animal ether is slightly anaesthetized, center, back s.c sterile air 20ml, and 3d supplements injection air 10ml and maintains air bag swelling, 6d gas intracapsular injection carrageenin 50mrkg
-1cause inflammation, Normal group is with method injecting normal saline isometric(al).Each treated animal in 3d start gastric infusion 1. 2. group give isometric(al) physiological saline, 6d cause scorching before 30min again administration be administered once.Cause animal i.p vetanarcol 25mgkg after scorching 6h
-1anesthesia, gas intracapsular injection is aseptic without calcium magnesium Hank ' s balanced salt solution (HBSS) 4ml lavation, collects irrigating solution, carries out the mensuration of leukocyte count and protein content in irrigating solution; Adopt Determining Micro Acid titration measuring PLA
2active; The content of exempting from method mensuration PGE is put in employing, the results are shown in Table 4.
Table 4 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester is to leukocyte count, protein and PGE content and PLA in rat Air-vesicle Synovitis irrigating solution
2active impact (
n=8)
With model group comparison
*p < 0.05,
*p < 0.01
On the basis of Mice Auricle inflammation test, carried out again rat Air-vesicle Synovitis disease test, result with tested last time basically identically, 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester can reduce leukocytic oozing out and the content of protein in perfusate; Meanwhile, 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester 20mgkg
-1and 40mgkg
-1two dosage groups can be passed through PLA
2active remarkable restraining effect, thereby the content of minimizing inflammatory mediator PGE, this experimental result and its vitro inhibition PLA
2effect is consistent, illustrates that 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester can be used for PLA
2the exploitation of inhibitor and anti-medicament for the eyes thing.
In conjunction with embodiment, the invention will be further described, but content of the present invention is not restricted to cited embodiment.
The fresh herb 50Kg of salicornia europaeal, with 90% alcohol reflux three times, 200 liters of consumptions, each 3 days, the concentrated concentrated solution being merged into without alcohol taste, obtained total medicinal extract.Use successively again sherwood oil, ethyl acetate, n-butanol extraction.N-butyl alcohol extract obtains respectively 1 gram of 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester after column chromatography for separation.(seeing accompanying drawing 9)
Salicornia europaeal herb 10Kg, water heating is extracted three times, water consumption is 20 liters, extraction time is 1 hour, extracting temperature is 70 ℃, and extracting solution is through macroporous resin (D101, AB-5, HP-20 etc.) absorption, water, after 30% alcohol flushing, use 70% ethanol elution, 70% ethanol eluate decompression and solvent recovery obtains saponin(e mixture.Mixture after column chromatography (silica gel column chromatography: chloroform-methanol system, RP-C18 column chromatography: water-methanol system) separates, obtains respectively 0.2 gram of 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester again.
Salicornia europaeal herb 10Kg, with methyl alcohol cold soaking extraction three times, methanol usage is 20 liters, and extraction time is 1 day, and extracting solution adsorbs through macroporous resin (D101, AB-5, HP-20 etc.).Water, uses 70% ethanol elution after 30% alcohol flushing, 70% ethanol eluate decompression and solvent recovery obtains saponin(e mixture.Mixture after column chromatography (silica gel column chromatography: chloroform-methanol system, RP-C18 column chromatography: water-methanol system) separates, obtains respectively 0.25 gram of 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester again.
Get 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester compound 100mg and starch 50mg that embodiment 1 makes, dextrin 50mg mixes, and makees wetting agent with appropriate 30% ethanol, makes softwood, and ordinary method is granulated, and adds appropriate Magnesium Stearate mixing, makes tablet.
Get 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester compound 50mg and starch 70mg, dextrin 10mg, Icing Sugar 10mg mixes, and makees wetting agent with appropriate 30% ethanol, makes softwood, and ordinary method granulation, packs in hard capsule.
Get 3BETA,29-dihydroxy-olean-12-en-28-oic acid 28-O-BETA-D-glucopyranosyl ester compound 80mg and Vltra tears K15M 120mg, ethyl cellulose 45cps40mg, lactose 40mg mixes, appropriate with 10% V-Pyrol RC k30 ethanolic soln, make softwood, ordinary method is granulated, and packs into and in hard capsule, makes slow releasing capsule.
Claims (6)
2. the method for preparing compound described in claim 1, is characterized in that take salicornia europaeal as raw material, extracts through the mixing solutions of water, methyl alcohol, ethanol or methanol-water, alcohol-water; Aqueous extract is directly crossed macroporous resin adsorption, and macroporous resin adsorption was dissolved in water after the extracting solution of the mixing solutions of methyl alcohol, ethanol or methanol-water, alcohol-water is concentrated; Macroporous resin adsorption thing obtains through column chromatography for separation.
3. preparation method according to claim 2, is characterized in that described macroporous resin is the one in D101, AB-8, HP-20; Column chromatography is selected from one or more in silica gel, gel, aluminum oxide, polymeric amide, ODS and MCI with carrier.
4. the pharmaceutical preparation of compound claimed in claim 1 and medically acceptable pharmaceutical excipient composition.
5. preparation according to claim 4, is characterized in that formulation is tablet, capsule and injection.
6. compound claimed in claim 1 is in the purposes of preparing in anti-inflammatory drug.
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