CN105418727A - Novel ursanes diterpenoid compound and preparation method and medical application thereof - Google Patents
Novel ursanes diterpenoid compound and preparation method and medical application thereof Download PDFInfo
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Abstract
The invention discloses a novel ursanes diterpenoid compound and a preparation method and medical application thereof and belongs to the technical field of medicine. The compound is reported for the first time, is novel in structure and can be obtained by extracting, separating and purifying the dry overground part of salvia chinensis. It is proved by in-vitro tests that after the compound acts on Molt4 cells, remarkable cycle retardation and apoptosis of the cells can be induced, and the cell cycle is made to stay in the S period, so that apoptosis is induced, and cell proliferation is inhibited. The compound (I) has potential application value on the aspect of treating acute T lymphocytic leukemia and can be used for being developed into medicine for treating the acute T lymphocytic leukemia.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, be specifically related to from the dry aerial parts of Herba Salviae Chinensis, be separated a kind of Ursane diterpene-kind compound obtained, containing its pharmaceutical composition and its preparation method and application.
Background technology
Herba Salviae Chinensis system Lamiaceae Salvia belongs to the dry aerial parts of Salvia chinensis Salviachinensisbenth, also name salvia chinensis, five phoenixes flower, the little red sage root, below the moon red, black sand-grass, black face wind, Rsdix Wisterinae Venustae, stone great river, mountain seam take, Zi Danhua, red ginseng, field celery, HUOXUECAO, be distributed widely in the ground such as Jiangsu, Anhui, Jiangxi, Hubei, Hunan, Guangdong, Guangxi, Sichuan, Yunnan.It is cool in nature, mildly bitter flavor, pungent, flat, returns stomach, liver, lung channel, has the functions such as clearing heat and detoxicating, blood circulation promoting regulates qi pain relieving, among the peoplely cures mainly the diseases such as the cancer of the esophagus, asthma due to excessive phlegm, hepatitis, red and white leukorrhea, carbuncle are swollen, scrofula.Successive dynasties ancient books and records are all on the books to its effect, think its " main ostalgia, strong wind carbuncle swells " (Compendium of Material Medica), " control scrofula " (" Jiangsu medicinal material will "), " control the cancer of the esophagus, phlegm and retained fluid is panted " (" Suzhou this product medicinal material "), " promoting blood circulation and removing blood stasis, hemostasis, removing toxic substances, detumescence " (" Zhejiang conventional herbal medicine among the people "), " promoting blood circulation and hemostasis, clearing heat and detoxicating " (" Anhui Chinese materia medica "), " control icterohepatitis, under humid tropics, dysmenorrhoea, bacillary dysentery, control facioplegia outward, mazoitis, furuncle, wound etc. " (" Zhejiang medicinal plant will ").
Up to the present, from Herba Salviae Chinensis, isolated chemical composition has reached kind more than 30, mainly comprises polyose, terpene, sterols, Polyphenols etc.
Herba Salviae Chinensis has anti-inflammatory, the effect such as anti-oxidant and antitumor." Chinese medicine voluminous dictionary ", " national herbal medicine compilation " all describe Herba Salviae Chinensis, Radix Oryzae Glutinosae etc. and share as side, are used for the treatment of acute hepatitis, chronic hepatitis and all achieve significant curative effect.Herba Salviae Chinensis is widely used in clinical as conventional " Chinese herbal medicine for preventing ".Herba Salviae Chinensis have also been obtained widespread use in gynecopathy therapeutic, except clearing heat and promoting diuresis, also has effect that is promoting blood circulation and removing blood stasis, softening and resolving hard mass.Because of its mild in medicine property and, not dryly not tremble with fear, therefore be widely used in because of diseases such as blood-head, damp and hot caused uterine bleeding, preceeded menorrhea pelvic inflammatory disease, endometriosis, hysteromyoma, ovarian cysts, dysmenorrhoeas, evident in efficacy.In addition, " Zhejiang common herbal medicine among the people " records salvia chinensis root 9 ~ 12g, and sheep breast block root 30g, is used for the treatment of tuberculous lymphadenitis, evident in efficacy.It is swollen etc. that this product is used for the treatment of facioplegia, mazoitis, sore by " Zhejiang pharmaceutical botany ".
Summary of the invention
The object of this invention is to provide and a kind ofly from the dry aerial parts of Herba Salviae Chinensis, be separated a kind of Ursane diterpene-kind compound obtained, containing its pharmaceutical composition and its preparation method and application.
Above-mentioned purpose of the present invention is achieved by technical scheme below:
There is the compound (I) of following structural formula:
The preparation method of described compound (I), comprise following operation steps: the dry aerial parts of Herba Salviae Chinensis are pulverized by (a), extract with 80 ~ 90% alcohol heat reflux, united extraction liquid, be concentrated into without alcohol taste, use sherwood oil, ethyl acetate and water saturated n-butanol extraction successively, obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract respectively; B in () step (a), the removal of impurities of thing macroporous resin got by propyl carbinol, first use 5% ethanol elution, 6 column volumes, then use 75% ethanol elution, 8 column volumes, collect 75% elutriant, concentrating under reduced pressure obtains 75% ethanol elution enriched material; C in () step (b), 75% ethanol elution enriched material purification on normal-phase silica gel is separated, obtain 4 components successively with the methylene chloride-methanol gradient elution that volume ratio is 65:1,30:1,15:1 and 8:1; D in () step (c), component 4 is separated further by purification on normal-phase silica gel, obtain 3 components successively with the methylene chloride-methanol gradient elution that volume ratio is 15:1,8:1 and 5:1; E in () step (d), component 2 reverse phase silica gel of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 75%, collect 8 ~ 12 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I).
Further, in step (a), extract with 85% alcohol heat reflux, united extraction liquid.
Further, described macroporous resin is AB-8 type macroporous adsorbent resin.
Pharmaceutical composition, the described compound (I) wherein containing treatment significant quantity and pharmaceutically acceptable carrier.
The application of described compound (I) in the medicine of preparation treatment Pancytopenia.
The application of described pharmaceutical composition in the medicine of preparation treatment Pancytopenia.
When the compounds of this invention is used as medicine, directly can uses, or use with the form of pharmaceutical composition.
This pharmaceutical composition contains the compounds of this invention (I) for the treatment of significant quantity, and all the other are acceptable on pharmacology, nontoxic to humans and animals and pharmaceutically acceptable carrier of inertia and/or vehicle.
Described pharmaceutically acceptable carrier or vehicle are that one or more are selected from solid, semisolid and liquid diluent, filler and pharmaceutical preparation assistant agent.Pharmaceutical composition of the present invention is used with the form of per weight dose.Medicine of the present invention is applied to by form that is oral or injection the patient needing treatment.For time oral, tablet, slow releasing tablet, controlled release tablet, capsule, dripping pill, micropill, suspensoid, emulsion, powder or granule, oral liquid etc. can be made into; During for injecting, can be made into water-based or oily solution, aseptic powder injection, liposome or the emulsion etc. of sterilizing.
Accompanying drawing explanation
Fig. 1 is compound (I) structural formula;
Fig. 2 is that compound (I) calculates ECD and experiment ECD figure.
Embodiment
Further illustrate essentiality content of the present invention below in conjunction with embodiment, but do not limit scope with this.Although be explained in detail the present invention with reference to preferred embodiment, those of ordinary skill in the art should be appreciated that and can modify to technical scheme of the present invention or equivalent replacement, and does not depart from essence and the scope of technical solution of the present invention.
Main raw, reagent source and instrument type:
Ethanol, sherwood oil, ethyl acetate, propyl carbinol, methylene dichloride are analytical pure, and purchased from Shanghai Ling Feng chemical reagent company limited, methyl alcohol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Embodiment 1: compound (I) is separated preparation and structural identification
A the dry aerial parts (8kg) of Herba Salviae Chinensis are pulverized by (), (30L × 3 time) are extracted with 85% alcohol heat reflux, united extraction liquid, be concentrated into without alcohol taste (6L), use sherwood oil (6L × 3 time), ethyl acetate (6L × 3 time) and water saturated propyl carbinol (6L × 3 time) to extract successively, obtain petroleum ether extract, acetic acid ethyl ester extract (375g) and n-butyl alcohol extract respectively; Acetic acid ethyl ester extract AB-8 macroporous resin removal of impurities in (b) step (a), first use 5% ethanol elution, 6 column volumes, use 75% ethanol elution, 8 column volumes again, collect 75% elutriant, concentrating under reduced pressure obtains 75% ethanol elution enriched material (129g); C in () step (b), 75% ethanol elution enriched material purification on normal-phase silica gel is separated, successively with volume ratio be 65:1 (8 column volumes), the methylene chloride-methanol gradient elution of 30:1 (8 column volumes), 15:1 (8 column volumes) and 8:1 (10 column volumes) obtains 4 components; D component 4 (27g) is separated further by purification on normal-phase silica gel in () step (c), successively with volume ratio be 12:1 (8 column volumes), the methylene chloride-methanol gradient elution of 8:1 (10 column volumes) and 5:1 (8 column volumes) obtains 3 components; E in () step (d), component 2 (15g) reverse phase silica gel of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 75%, collect 8 ~ 12 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I) (40mg).
Structural identification: white crystals (methyl alcohol), fusing point 326 DEG C; HR-ESIMS shows [M+Na]
+for m/z399.2120, can obtain molecular formula in conjunction with nuclear-magnetism feature is C
22h
32o
5, degree of unsaturation is 7.Hydrogen nuclear magnetic resonance modal data δ
h(ppm, DMSO-d
6, 400MHz): H-1 (2.41, d), H-1 (2.17, d), H-3 (4.15, s), H-5 (1.23, m), H-6 (1.24, m), H-6 (1.42, m), H-7 (1.53, m), H-7 (1.37, m), H-9 (2.14, br, s), H-11 (5.71, dd, J=10.2, 2.0), H-12 (6.08, dd, J=10.2, 3.0), H-15 (1.30, m), H-15 (1.19, m), H-16 (2.25, ddd, J=14.2, 5.2, 2.2), H-19 (4.64, s), H-21 (1.53, m), H-21 (1.32, m), H-22 (1.55, m), H-22 (1.74, m), H-23 (0.97, s), H-24 (0.83, s), H-25 (0.95, s), H-26 (0.73, s), H-27 (0.98, s), H-29 (1.01, s), H-30 (0.91, s), carbon-13 nmr spectra data δ
c(ppm, DMSO-d
6, 100MHz): 51.6 (CH
2, 1-C), 210.7 (C, 2-C), 82.8 (CH, 3-C), 45.1 (C, 4-C), 47.3 (CH, 5-C), 17.6 (CH
2, 6-C), 32.5 (CH
2, 7-C), 40.4 (C, 8-C), 52.4 (CH, 9-C), 37.8 (C, 10-C), 129.1 (CH, 11-C), 122.9 (CH, 12-C), 134.5 (C, 13-C), 40.8 (C, 14-C), 25.2 (CH
2, 15-C), 23.9 (CH
2, 16-C), 43.7 (C, 17-C), 132.6 (C, 18-C), 84.7 (CH, 19-C), 35.4 (C, 20-C), 32.3 (CH
2, 21-C), 34.2 (CH
2, 22-C), 27.8 (CH
3, 23-C), 21.1 (CH
3, 24-C), 19.0 (CH
3, 25-C), 17.1 (CH
3, 26-C), 19.2 (CH
3, 27-C), 177.7 (C, 28-C), 27.6 (CH
3, 29-C), 22.8 (CH
3, 30-C), carbon atom mark is see Fig. 1.Infrared spectra shows that this compound contains hydroxyl (3358cm
-1) and gamma lactone carbonyl (1778cm
-1).
1h-NMR modal data shows seven methyl signals [δ H0.73 (Me-26), 0.83 (Me-24), 0.91 (Me-30), 0.95 (Me-25), 0.97 (Me-23), 0.98 (Me-27) and 1.01 (Me-29)], two containing oxygen methine signals [δ H4.15 (s, H-3), 4.64 (s, H-19)] and two olefinic proton [δ H5.71 (dd, J=10.2,2.0Hz, H-11) and 6.08 (dd, J=10.2,3.0Hz, H-12)].
13cNMR and DEPT composes display 30 resonance carbon signal, comprising two containing oxygen methyne [δ C82.8 (C-3) and 84.7 (C-19)], four olefinic carbon [δ 122.9 (C-12), 129.1 (C-11), 132.6 (C-18) and 134.5 (C-13)] and two carbonyl carbon [δ C177.7 (C-28) and 210.7 (C-2)].An ester carbonyl group signal [δ C177.7 (C-28)] and two carbon signals [δ C43.7 (C-17) and 84.7 (C-19)] illustrate that this compound exists a gamma lactone structure.H in HMBC spectrum
2-22 and C-28, H-19 and C-18, and the connection of 28,19-these functional groups of the relevance verification of Me-29 and C-19.In addition, the chemical shift (δ C82.8) of C-3 shows existence hydroxyl.Above-mentioned data show that this compound is Ursane diterpene compound.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and NOESY spectrum, and document is about correlation type nuclear magnetic data, can substantially determine this compound as shown in Figure 1, steric configuration is determined further by ECD test, theoretical value and experimental value basically identical (Fig. 2).
Embodiment 2: compound (I) pharmacological action is tested
One, material and instrument
Pancytopenia Molt4 cell is so kind as to give by hemopathy institute of Ji'nan University; Chronic myeloid leukemia cell K562 cell is so kind as to give by Biochemistry and Molecular Biology teaching and research room by Ji'nan University.Compound (I) is self-control, and HPLC normalization method purity is greater than 98%, dissolves be mixed with 5.5 μ g/mL solution for standby with DMSO analytical pure.DMEM/F12 medium powder, hydroxyethyl piperazine ethanesulfonic acid (HEPES), the blue reagent of tetraphenyl nitrogen (MTT) are purchased from Gibeo company of the U.S..New-born calf serum (NewbomCalfSerum) is purchased from Hangzhou China folium ilicis chinensis company.Penicillin (Penicillin), Streptomycin sulphate (Streptomycin) are purchased from China of North China drugmaker.Iodate third eyelash (PT) is purchased from Sigma Co., USA.The two transfection reagent box of PI-AnnexinV is purchased from Bao Sai biotech company of BeiJing, China.ROS high-quality fluorimetric reagent box is purchased from Chinese green skies biotechnology research institute.Rhodamine123 is purchased from MolecularProbes company of the U.S..
CO
2incubator (U.S. ThermoForma), Bechtop (Chinese Suzhou purifying apparatus factory), pressure steam sterilization boiler (LDZX40BI) (Chinese Shanghai Shen An medical apparatus and instruments factory), TGL-16G type table model high speed centrifuge (Chinese Shanghai An Ting scientific instrument factory), MA260S type electronic analytical balance (Chinese Shanghai second balance equipment factory), automatic dual pure water distiller (Chinese Shanghai glassware one factory), SterivexTM, 0.22 μm of Millex Syringe Filters (Millipore company of the U.S.), XDS-1B optics inverted microscope (Chongqing in China optical instrument factory), full-automatic microplate reader (BIO-RID company of the U.S.), FACSCalibur flow cytometer (BDFACSAria company of the U.S.).QL-901 type vortex mixer (kylin medical apparatus factory of Jiangsu Haimen City).
Two, test method
1, cell cultures
People's Pancytopenia cell Molt4 cell culture system: DMEM/F12 nutrient solution containing 10% new-born calf serum, is put 37 DEG C, volume fraction is 5%CO
2incubator, every 2-3 days Secondary Culture.Select logarithmic phase, the cell of 0.2% trypan blue exclusion rate >95% tests.
2, mtt assay detects cell proliferation inhibition rate
3 × 10
4mLMolt4 cell is inoculated in 96 well culture plates, and final volume is 200 μ L/ holes, and often group establishes 5 multiple holes, and compound (I) establishes five concentration to be respectively 2.5 μ g/mL, 5 μ g/mL, 10 μ g/mL, 15 μ g//mL, 20 μ g//mL.Put 37 DEG C, 5%CO
2after cultivating 48h, 72h in incubator, every hole adds MTT solution (5mg/mL PBS<ph=7.4 joins) 20 μ L, continues to hatch 4 hours, stops cultivating, centrifugal, culture supernatant in hole is abandoned in careful suction, and every hole adds 150 μ LDMSO, vibrates 10 minutes, crystallisate is fully melted, microplate reader detects light absorption value (measuring wavelength 570nm, reference wavelength 690nm), calculates each group of proliferation inhibition rate.Each experiment repetition 3 times, gets its average.Proliferation inhibition rate (%)=(1-A experimental group/A control group) × 100%.
3, the mono-dye of PI detects the cell cycle
2 × l0
5/ mLMolt4 cell is inoculated in 12 well culture plates, every hole 1800 μ L, and compound (I) establishes three concentration to be respectively 5 μ g/mL, 10 μ g/mL15 μ g/mL, final volume 2500 μ L, if 3 multiple holes.Put 37 DEG C, 5%CO
2collecting cell after 48h is cultivated in incubator, the 0.01mol/LPBS washed cell of precooling 2 times, be that 70% ethanol 4 DEG C fixedly spends the night by volume fraction, centrifugally remove supernatant, add PI staining fluid (containing RNA enzyme), final concentration 50 μ g/mL, lucifuge dyeing 30min, flow cytometer analysis of cells DNA content after 300 order nylon net filters, each sample stochastic analysis 12000 cells, obtain each group of cell growth cycle ratio, U.S. BDFACSortCellQuest software analysis result.
4, the two dye of AnnexinV-PI measures apoptosis ratio
Cell process and adding method thereof are all the same, and after cultivating 48h, adjustment cell concn is 5 × 106/mL, get lmL cell for each group, precooling 0.01mol/LPBS washs 3 times, exhausts supernatant, adds the binding buffer liquid that 200 μ L test kits provide, re-suspended cell, add 10 μ LAnnexinV-FITC and 5 μ L respectively, mix gently, 4 DEG C of lucifuge reaction 30min, add 300 μ L binding buffer liquid again, flow cytometer detects.The cell mass (i.e. LR cell mass) of AnnexinV-FITC+, PI-is viable apoptotic cell.
5, statistical study
With mean scholar standard deviation
represent, the process of application SPSS13.0 statistical software, adopts the one-way analysis of variance (one-wayANOVA) of completely randomized design to analyze the significance of group difference.
Three, result and conclusion
1, compound (I) is to the inhibited proliferation of Molt4 cell
Compound (I) all has obvious inhibited proliferation in different time points to Molt4 cell.DMSO (0.5%) group is 5.2% ± 0.8%, 6.40% ± 0.9% at the proliferation inhibition rate of 48h, 72h respectively.The proliferation inhibition rate of different concns compound (I) treatment group all has statistical significance (P<0.01) compared with DMSO group.Under same concentrations condition, comparatively 48h is high for the proliferation inhibition rate of 72h.Compound (I) is to the IC of Molt4 cell 48h, 72h
5019.4 ± 0.2 μ g/mL, 15.7 ± 0.1 μ g/mL respectively.The compound (I) of different concns all shows certain proliferation inhibiting effect, and there is the time, dosage relies relation.The results are shown in Table for 1 (note: * mark compares with Control group, P<0.01).
2, compound (I) is on the impact of Molt4 cell cycle
After compound (I) effect Molt4 cell 48h, blank group G1 phase cell proportion is 37.5% ± 0.2%, S phase cell proportion is 50.6% ± 0.1%, G2 phase cell proportion is 11.7% ± 0.1%, DMSO group G1 phase cell proportion is 39.6% ± 0.1%, S phase cell proportion is 51.6% ± 0.2%, G2 phase cell proportion is 8.7% ± 0.2%.Shared by compound (I) medicine 20 μ g/mL, 25 μ g/mL treatment group G1 phases, cell proportion is respectively 4.1% ± 0.1%, 65.8% ± 0.1%, ratio increase shared by S phase cell is respectively 85.1% ± 0.3%, 87.1% ± 0.25 (P<0.01), G2 phase cell proportion is respectively 10.7% ± 0.2%, 7.0% ± 0.1%, the result display G1 phase have significant difference (P<0.05) to illustrate compound (I) retardance Molt4 cell is in the cycle S phase.The results are shown in Table for 2 (note: * mark compares with Control group, P<0.01).
3, the early apoptosis rate after compound (I) effect Molt4 cell
After compound (I) effect Molt4 cell 48h, AlmexinV/PI two dye flow cytomery early apoptosis rate.Early apoptosis rate 7.0% scholar 0.3% of blank group early apoptosis of cells rate 6.6% ± 0.4%, DMSO control group, not statistically significant (p>0.05) compared with blank.Compound (I) 10 μ g/mL group, 15 μ g/mL group early apoptosis rates are 9.5% ± 0.3%, 15.0% ± 0.5% respectively, have statistical significance (P<0.05) compared with blank.The results are shown in Table for 3 (note: * mark compares with Control group, P<0.05).
Conclusion, we can induce its significant Cycle Arrest and apoptosis after finding compound (I) effect Molt4 cell under study for action, and make cell cycle arrest in the S phase, thus cell death inducing, antiproliferative effect.Compound (I) has potential using value in treatment Pancytopenia.
Table 1 compound (I) to the inhibited proliferation of Molt4 cell (%,
n=3)
| Group | 48h inhibiting rate (%) | 72h inhibiting rate (%) |
| DMSO | 5.2±0.8 | 6.4±0.9 |
| Compound (I) 2.5 μ g/mL | 6.3±1.3 | 8.4±1.1 |
| Compound (I) 5 μ g/mL | 10.5±2.4 | 11.6±2.5 |
| Compound (I) 10 μ g/mL | 18.6±1.6 * | 26.9±2.7 * |
| Compound (I) 15 μ g/mL | 33.4±2.7 * | 49.4±2.2 * |
| Compound (I) 20 μ g/mL | 53.2±4.4 * | 65.4±1.6 * |
Table 2 each group cell cycle per-cent (%,
n=3)
Table 3 compound (I) on the apoptotic impact of Molt4 (%,
n=3)
| Group | Apoptosis rate |
| Control | 6.6±0.2 |
| DMSO | 7.0±0.4 |
| Compound (I) 10 μ g/mL | 9.5±0.3 * |
| Compound (I) 15 μ g/mL | 15.0±0.3 * |
Embodiment 3
The preparation of tablet: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, vehicle is added, pelletizing press sheet than the ratio for 1:7 in itself and excipient weight.
Embodiment 4
The preparation of oral liquid: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, oral liquid method for making makes oral liquid routinely.
Embodiment 5
The preparation of capsule or granule: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, add vehicle in itself and excipient weight than the ratio for 1:9, make capsule or granule.
Embodiment 6
The preparation of injection liquid: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, inject with water routinely, essence filter, injection liquid is made in embedding sterilizing.
Embodiment 7
The preparation of aseptic powder injection: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, be dissolved in sterile water for injection, stirring makes molten, filter with aseptic suction funnel, aseptic essence filter again, be sub-packed in ampoule, after frozen drying, aseptic sealing by fusing obtains powder injection.
The effect of above-described embodiment is essentiality content of the present invention is described, but does not limit protection scope of the present invention with this.Those of ordinary skill in the art should be appreciated that and can modify to technical scheme of the present invention or equivalent replacement, and does not depart from essence and the protection domain of technical solution of the present invention.
Claims (7)
1. there is the compound (I) of following structural formula:
2. the preparation method of compound according to claim 1 (I), it is characterized in that comprising following operation steps: the dry aerial parts of Herba Salviae Chinensis are pulverized by (a), extract with 80 ~ 90% alcohol heat reflux, united extraction liquid, be concentrated into without alcohol taste, use sherwood oil, ethyl acetate and water saturated n-butanol extraction successively, obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract respectively; B in () step (a), the removal of impurities of thing macroporous resin got by propyl carbinol, first use 5% ethanol elution, 6 column volumes, then use 75% ethanol elution, 8 column volumes, collect 75% elutriant, concentrating under reduced pressure obtains 75% ethanol elution enriched material; C in () step (b), 75% ethanol elution enriched material purification on normal-phase silica gel is separated, obtain 4 components successively with the methylene chloride-methanol gradient elution that volume ratio is 65:1,30:1,15:1 and 8:1; D in () step (c), component 4 is separated further by purification on normal-phase silica gel, obtain 3 components successively with the methylene chloride-methanol gradient elution that volume ratio is 15:1,8:1 and 5:1; E in () step (d), component 2 reverse phase silica gel of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 75%, collect 8 ~ 12 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I).
3. the preparation method of compound according to claim 2 (I), is characterized in that: in step (a), extracts, united extraction liquid with 85% alcohol heat reflux.
4. the preparation method of compound according to claim 2 (I), is characterized in that: described macroporous resin is AB-8 type macroporous adsorbent resin.
5. a pharmaceutical composition, is characterized in that: the compound according to claim 1 (I) wherein containing treatment significant quantity and pharmaceutically acceptable carrier.
6. the application of compound according to claim 1 (I) in the medicine of preparation treatment Pancytopenia.
7. the application of pharmaceutical composition according to claim 5 in the medicine of preparation treatment Pancytopenia.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106432391A (en) * | 2016-09-09 | 2017-02-22 | 中国科学院西北高原生物研究所 | Novel steroid compound as well as preparation method and application thereof, and drug compound and application thereof |
| CN107540641A (en) * | 2016-06-29 | 2018-01-05 | 彭朗 | A kind of new organic esterses and preparation method thereof and medical usage |
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