CN105566251A - Novel leucothoe alkane type diterpene compound and preparation method and medical application thereof - Google Patents
Novel leucothoe alkane type diterpene compound and preparation method and medical application thereof Download PDFInfo
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Abstract
The invention discloses a novel leucothoe alkane type diterpene compound and a preparation method and medical application thereof. The leucothoe alkane type diterpene compound is reported for the first time, is of a novel structure, and can be extracted from a dry whole herb of sculellaria barbata and obtained after separation and purification. It is proved through the research that the compound can effectively restrain growth and proliferation of HepG2 cells, the restraining effect and the concentration of the compound (I) are in a certain dosage effect tendency, and the compound can be developed into medicine for treating liver cancer.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, be specifically related to be separated a kind of black laurel alkane type diterpenoid with Hepatoma therapy effect obtained and preparation method thereof from the dry herb of Herba Scutellariae Barbatae.
Background technology
Herba Scutellariae Barbatae Scutellariabarbata, have another name called and head grass, narrow leaf Indian Skullcap Herb, for Labiatae Scutellaria per nnial herb, be often born in the moist ground such as pond, the edge of a field, mountain stream, Zhejiang, Jiangsu, Anhui, Henan, Sichuan, Guangdong, Fujian, Shaanxi etc. are economized all has distribution.Herba Scutellariae Barbatae is cold in nature, and taste is pungent, bitter, and have the effects such as clearing heat and detoxicating, loose stasis of blood hemostasis, inducing diuresis to remove edema, being used for the treatment of furuncle swelling toxin, swelling and pain in the throat, traumatic pain, oedema, jaundice, snake bite and insect sting etc., is conventional herbal medicine among the people.
The chemical constitution study of Herba Scutellariae Barbatae is published in " the Herba Scutellariae Barbatae chemical constitution study bulletin " of " herbal medicine " entirely first appeared in Wang Zhao in 1981, so far researchist goes out hundreds of monomeric compound by modern plants chemical research technology isolation identification from Herba Scutellariae Barbatae, mainly flavonoid and diterpenes, also has the compositions such as alkaloid, steroidal, phenols, tannin and polysaccharide.Flavonoid compound is one of main component of Herba Scutellariae Barbatae, and structure contains the broad varietys such as flavones, flavanone, flavanonol, cinnamophenone.Diterpene is the another kind of main chemical compositions of Herba Scutellariae Barbatae, is also current research emphasis.Structure is mainly neo clerodane diterpenoids, comprises Herba Scutellariae Barbatae diterpene (scutellone) class, Herba Scutellariae Barbatae lactone (scuterivulactone) class, Herba Scutellariae Barbatae alkaloid (Scutebarbatine) class and rivularin (barbatin) class etc.Activity experiment shows, and Diterpenoid Alkaloids has good cytotoxicity, effectively can suppress the growth of various human tumour cell.
Modern pharmacology activity research shows, Herba Scutellariae Barbatae has good anti-tumor activity, is therefore widely used in the assisting therapy of the malignant tumours such as primary hepatocarcinoma, lung cancer, cervical cancer as antitumor and anti-inflammatory drug.Wherein scutellarin, wogonin, apigenin, luteolin etc. have good antibacterial, anti-oxidant and anti-tumor activity.In addition, Herba Scutellariae Barbatae also blocks the keeping of human body to tumour cell by Tumor suppression vasculogenesis, thus reaches the object of inhibition tumor cell propagation and transfer.Except above-mentioned activity, Herba Scutellariae Barbatae also have protect the liver, antiviral and diuresis and stone expeling isoreactivity.
Summary of the invention
The object of this invention is to provide and a kind ofly from the dry herb of Herba Scutellariae Barbatae, be separated a kind of black laurel alkane type diterpenoid with Hepatoma therapy effect obtained and preparation method thereof.
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 herb of Herba Scutellariae Barbatae is pulverized by (a), extract with 75 ~ 85% 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; Acetic acid ethyl ester extract macroporous resin removal of impurities in (b) step (a), first use 10% ethanol elution, 6 column volumes, then use 75% ethanol elution, 8 column volumes, collect 75% ethanol eluate, concentrating under reduced pressure obtains 75% ethanol elution thing medicinal extract; C in () step (b), 75% ethanol elution medicinal extract purification on normal-phase silica gel is separated, obtain 5 components successively with the methylene chloride-methanol gradient elution that volume ratio is 90:1,65:1,30:1,15:1 and 1:1; 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 25:1,15:1 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 70%, collect 8 ~ 10 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I).
Further, described macroporous resin is AB-8 type macroporous adsorbent resin.
Further, described alcohol heat reflux extracts the alcohol concn adopted is 80%.
A kind of pharmaceutical composition, the described compound (I) wherein containing treatment significant quantity and pharmaceutically acceptable carrier.
Described compound (I) is preparing the application in Hepatoma therapy medicine.
Described pharmaceutical composition is preparing the application in Hepatoma therapy medicine.
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 the theoretical ECD value of compound (I) compares with experiment ECD value;
Fig. 3 is the impact (n=3) of compound (I) on HepG2 and L02 cell proliferation.
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.
Embodiment 1: compound (I) is separated preparation and structural identification
Reagent source: ethanol, sherwood oil, ethyl acetate, propyl carbinol, methylene dichloride are analytical pure, purchased from Shanghai Ling Feng chemical reagent company limited, methyl alcohol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Preparation method: the dry herb (8kg) of Herba Scutellariae Barbatae is pulverized by (a), (25L × 3 time) are extracted with 80% alcohol heat reflux, united extraction liquid, be concentrated into without alcohol taste (3L), use sherwood oil (3L × 3 time), ethyl acetate (3L × 3 time) and water saturated propyl carbinol (3L × 3 time) to extract successively, obtain petroleum ether extract, acetic acid ethyl ester extract (351g) and n-butyl alcohol extract respectively; Acetic acid ethyl ester extract AB-8 type macroporous resin removal of impurities in (b) step (a), first use 10% ethanol elution, 6 column volumes, use 75% ethanol elution, 8 column volumes again, collect 75% ethanol eluate, concentrating under reduced pressure obtains 75% ethanol elution thing medicinal extract (133g); C in () step (b), 75% ethanol elution medicinal extract purification on normal-phase silica gel is separated, successively with volume ratio be 90:1 (8 column volumes), the methylene chloride-methanol gradient elution of 65:1 (8 column volumes), 30:1 (6 column volumes), 15:1 (8 column volumes) and 1:1 (5 column volumes) obtains 5 components; D component 4 (31g) is separated further by purification on normal-phase silica gel in () step (c), successively with volume ratio be 25:1 (8 column volumes), the methylene chloride-methanol gradient elution of 15:1 (10 column volumes) and 5:1 (6 column volumes) obtains 3 components; E in () step (d), component 2 (17g) reverse phase silica gel of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 70%, collect 8-10 column volume elutriant, elutriant concentrating under reduced pressure obtains pure compound (I) (31mg).
Structural identification: colourless needles (methyl alcohol), fusing point 239 ~ 240 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 (2.71, t, J=9.3), H-2 (2.17, m), H-2 (1.79, dd, J=14.6, 9.3), H-3 (3.64, d, J=4.6), H-6 (2.27, d, J=10.0), H-7 (1.75, d, J=14.4), H-7 (2.36, dd, J=14.4, 10.0), H-9 (2.19, m), H-11 (1.48, m), H-11 (1.77, m), H-12 (1.97, m), H-12 (1.75, m), H-13 (2.11, t, J=3.0), H-14 (5.16, s), H-15 (1.87, s), H-15 (1.86, s), H-17 (1.28, s), H-18 (0.92, s), H-19 (1.12, s), H-20 (5.22, s), H-20 (5.14, s), 16-OAc (2.05, s), carbon-13 nmr spectra data δ
c(ppm, DMSO-d
6, 100MHz): 58.8 (CH, 1-C), 36.3 (CH
2, 2-C), 84.4 (CH, 3-C), 51.1 (C, 4-C), 76.7 (C, 5-C), 53.1 (CH, 6-C), 40.5 (CH
2, 7-C), 50.1 (C, 8-C), 58.2 (CH, 9-C), 153.3 (C, 10-C), 26.4 (CH
2, 11-C), 27.8 (CH
2, 12-C), 54.3 (CH, 13-C), 82.0 (CH, 14-C), 56.2 (CH
2, 15-C), 79.9 (C, 16-C), 24.4 (CH
3, 17-C), 22.7 (CH
3, 18-C), 20.1 (CH
3, 19-C), 112.1 (CH
2, 20-C), 172.6 (C, 16-OAC), 21.3 (CH
3, 16-OAC), carbon atom mark is see Fig. 1.Infrared spectra shows that this compound contains hydroxyl (3435cm
-1) and ester carbonyl group (1716cm
-1).
1hNMR composes display three methyl (δ H1.28, s, H
3-17; 1.12, s, H
3-19; 0.92, s, H
3-18) a, ethanoyl (δ H2.05, s), two rings outer olefinic protons (δ H5.22, s, H-20a; 5.14, s, H-20b), an acidylate is containing oxygen methine protons (δ H5.16, s, H-14), and two containing oxygen methine protons (δ H3.64, d, J=4.6Hz, H-3; 2.27, d, J=10.0Hz, H-6), and a methine protons (δ H2.71, t, J=9.3Hz, H-1).
13cNMR and DEPT spectrum shows 22 carbon signals, ester carbonyl group (δ C172.6 ,-an OCOCH
3), exocyclic double bond (δ C153.3, C-10; 112.1, C-20), four quaternary carbons comprise two containing oxygen quaternary carbon (δ C76.7, C-5; 79.9, C-16; 51.1, C-4; 50.1, C-8), six methynes contain oxygen methyne (δ C84.4, C-3 comprising three; 82.0, C-14; 58.8, C-1; 58.2, C-9; 54.3, C-13; 53.1, C-6), five methylene radical (δ C56.2, C-15; 40.5, C-7; 36.3, C-2; 27.8, C-12; 26.4, C-11), and four methyl (δ C24.4, C-17; 22.7, C-18; 21.3 ,-OCOCH
3; 20.1, C-19).Containing oxygen carbon signal (δ C76.7 and 53.1) and Hydrogen Proton signal (δ H2.27, d, J=10.0Hz), two show that this compound contains 5,6-epoxide groups.In HMBC spectrum, with the dependency of ester carbonyl group (δ C172.6), H-13 (δ H2.11, t, J=3.0Hz) shows that C-13 (δ C54.3) position is connected with an acetoxyl group.H-9 is beta comfiguration usually in black laurel alkane type diterpene-kind compound.In NOESY spectrum, the dependency of H-1 and H-9 β shows that H-1 is beta comfiguration.H-2 α/H-20a/H
3the dependency of-18/H-6/H-3 shows that ring A with B is that cis is connected, and H-3 and H-6 is α configuration.It is that cis is connected that the dependency of H-7 α and H-14, H-20b and H-11 α indicates ring B with C, and H-14 is α configuration.It is H-9 β and H-15 β in being composed by NOESY that the cis of ring C with D is connected, and H-13 β and H
3the dependency of-17 is determined.Therefore, H
3-17 is beta comfiguration.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
HepG2 human hepatoma cell strain is purchased from Chinese Academy of Sciences's biological chemistry and Institute of Cell Biology.L02 normal liver cell strain presented by Zhong Shan hospital of Fudan University liver cancer research.Compound (I) is made by oneself, and HPLC normalization method purity is greater than 98%.RPMI-1640 substratum, pancreatin are purchased from Gibco company.Standard calf serum is purchased from Biowest company.3-(4,5-dimethylthiazole-2)-2,5-diphenyltetrazolium bromide bromine salt (MTT), dimethyl sulfoxide (DMSO) (DMSO), trypan blue (TrypanBLue), dichlorofluorescein diacetate (DCFH-DA) is all purchased from Shanghai Chemical Reagent Co., Ltd., Sinopharm Group.Other common agents are analytical pure.
Microbalance (Switzerland plum Teller-Tuo benefit, METTLRERAE2000).Common desktop whizzer (Anting Scientific Instrument Factory, Shanghai).Digital display electric heating constant-temperature water-bath tank (Shanghai leap medical machinery factory, HH.W21.600S).Carbon dioxide cell incubator (FormaScientific company of the U.S.).High speed freezing centrifuge (Thermo company of the U.S., IECMICROMAXRF).Ultramicron ultraviolet spectrophotometer (ThermoHsher company of the U.S., NanoDrop-1000).Ultraviolet imagery system (Shanhai Furi Science and Technology Co., Ltd., FR-200A).Enzyme-linked immunosorbent assay instrument, spectrophotofluorometer (HitachiF2500).
Two, test method
1, cell cultures
Cell routine is inoculated in the RPMI-1640 substratum containing 10% (volume fraction) calf serum, is placed in 37 DEG C, 5%CO
2cultivate in the incubator of concentration.
2, compound (I) intervenes the configuration of nutrient solution
45.44mg compound (I) be dissolved in the obtained storing solution of 10mL dimethyl sulfoxide (DMSO) (DMSO) and dilute 2 times, 4 times respectively, obtaining compound (I) the application liquid of 2mmol/L, 4mmol/L and 8mmol/L respectively.Before carrying out cell intervention, 50 μ L application liquid are fully mixed with 4950 μ L cellar culture liquid (calf serum containing 10% volume fraction), obtains compound (I) and intervene nutrient solution (20 μm of ol/L, 40 μm of ol/L, 80 μm of ol/L).
3, mtt assay detects cell survival rate
The vegetative period cell of taking the logarithm is inoculated in 96 well culture plates, every hole 200 μ L (5 × 10
3cell).Cultivate 12h after cell attachment, discard original fluid, compound (I) nutrient solution adding 200 μ L different concns (mixes with cellar culture liquid with 1% volume fraction after DMSO dissolved compound (I), compound (I) final concentration is made to be 20 μm of ol/L, 40 μm of ol/L, 80 μm of ol/L), often organize 6 parallel holes.Establish 6 solvent (DMSO) control wells simultaneously.Cultivate 24h, 48h, 72h, within every 24 hours, change compound (I) and intervene nutrient solution.Intervene after terminating, suck nutrient solution, add 20 μ LMTT solution to each hole, 37 DEG C hatch 4h after suck each hole supernatant liquor, add 150 μ LDMSO, put low speed concussion 10min on shaking table, after abundant dissolving to be crystallized, with DMSO zeroing, measure each hole absorbancy with enzyme-linked immunosorbent assay instrument at 490nm place, calculate cell survival rate (survivalrate, SR).SR=experimental group A
490/ control group A
490× 100%
4, trypan blue Ran Se Measuring determines survivaling cell number
By equal amts (2 × 10
6) cell be inoculated in Tissue Culture Flask, cultivate for some time after cell attachment, discard nutrient solution, after washing twice, cell with PBS, the compound (I) adding 5mL intervenes nutrient solution (20 μm of ol/L, 40 μm of ol/L, 80 μm of ol/L).Often organize three bottles of cells, set up three bottles of solvent (DMSO) contrasts simultaneously.After cultivating 48h, use 0.25% trypsin digestion cell, collecting cell suspension, determination of trypan blue staining cell count.
5, DCFH-DA method measures ROS activity in cell
By equal amts (2 × 10
6) cell be inoculated in Tissue Culture Flask, cultivate for some time after cell attachment, suck original fluid, add 5mL compound (I) and intervene nutrient solution, after continuing to cultivate 48h, discard nutrient solution, trypsin digestion cell, collecting cell suspension is in 1.5mLEP pipe, the centrifugal 5min of 1500rpm, abandons supernatant, in precipitation, add 1mLDCFH-DA, piping and druming mixing, hatch 30min for 37 DEG C, add PBS termination reaction, centrifugal collecting precipitation is also dissolved in 1mLPBS, blow and beat uniformly cell suspension, burn light spectrophotometric determination fluorescent value with Hitachi-F2500.Excitation wavelength 488nm, emission wavelength 525nm.
Three, result and conclusion
1, Growth of Cells survival rate
HepG2 cell is after compound (I) intervention cultivates 24h, 48h, 72h, the cell survival rate of basic, normal, high dosage group is all remarkable in solvent control group (P<0.05), and the degree that declines of cell survival rate and compound (I) are intervened between concentration and be there is doses effect trend (table 1
ap<0.05VS control group;
bp<0.05VS low dose group;
cdosage group in P<0.05VS).Under same compound (I) intervenes concentration, cell survival rate presents downward trend along with the increase of intervention time.And under equal conditions, L02 Human normal hepatocyte is after compound (I) is intervened, cell survival rate is without noticeable change (table 2).Trypan Blue cell counts consistent with MTT (Fig. 3,
ap<0.05VS control group;
bp<0.05VS low dose group;
cdosage group in P<0.05VS).
2, in cell, ROS is active
HepG2 human liver cancer cell is after different concns compound (I) is intervened, and compared with control group, intracellular ROS level significantly declines (P<0.05).The results are shown in Table 3 (
ap<0.05VS control group;
bp<0.05VS low dose group).
Conclusion, the compound (I) of different concns is adopted to carry out intervention process to human liver cancer cell HepG2, show through MTT colorimetric and Trypan Blue cell counting, compound (I) effectively can suppress the growing multiplication of HepG2 cell, the survival rate of intervention group cell comparatively control group significantly reduces, and reduction degree and compound (I) concentration present certain dosage effect trend, simultaneously under same compound (I) concentration, cell survival rate presents the trend continuing to reduce along with the increase of intervention time.Meanwhile, compound (I) intervention of same dose does not produce restraining effect to L02 normal liver cell.
Table 1 compound (I) is on the impact (x ± s, n=6) of HepG2 Growth of Cells survival rate
Table 2 compound (I) is on the impact (x ± s, n=6) of L02 Growth of Cells survival rate
Table 3 compound (I) is on the impact (x ± s, n=6) of HepG2 cell ROS level
Group | Dosage (μm ol/L) | ROS(Fluounit/mgprot) |
Control group | 0 | 4189±204 |
Low dosage | 20 | 3215±151 a |
Middle dosage | 40 | 3080±196 a |
High dosage | 80 | 2831±212 ab |
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 1:9 in itself and excipient weight.
Embodiment 4
Prepared by 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 herb of Herba Scutellariae Barbatae is pulverized by (a), extract with 75 ~ 85% 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; Acetic acid ethyl ester extract macroporous resin removal of impurities in (b) step (a), first use 10% ethanol elution, 6 column volumes, then use 75% ethanol elution, 8 column volumes, collect 75% ethanol eluate, concentrating under reduced pressure obtains 75% ethanol elution thing medicinal extract; C in () step (b), 75% ethanol elution medicinal extract purification on normal-phase silica gel is separated, obtain 5 components successively with the methylene chloride-methanol gradient elution that volume ratio is 90:1,65:1,30:1,15:1 and 1:1; 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 25:1,15:1 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 70%, collect 8 ~ 10 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: described macroporous resin is AB-8 type macroporous adsorbent resin.
4. the preparation method of compound according to claim 2 (I), is characterized in that: it is 80% that described alcohol heat reflux extracts the alcohol concn adopted.
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. compound according to claim 1 (I) is preparing the application in Hepatoma therapy medicine.
7. pharmaceutical composition according to claim 5 is preparing the application in Hepatoma therapy medicine.
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CN105153084A (en) * | 2015-09-13 | 2015-12-16 | 金丽秋 | Novel diterpene compound as well as preparation method and medicinal application thereof |
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