CN103665088B - Antitumoral compounds extracted from Resina garciniae and preparation method thereof and purposes - Google Patents
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Abstract
The present invention relates to antitumoral compounds of extraction and preparation method thereof and purposes from Resina garciniae.Described compound preparation method is: (1) takes Resina garciniae medical material ethyl acetate and extracts, and extract separates through silica gel column chromatography, and petroleum ether ethyl acetate gradient obtains 11 components A～K；(2) discard oil component and gamlogic acid component, then analyze through HPLC PDA MS deduplication, obtain emphasis component I；(3) component I separates through silica gel column chromatography again, and chloroform methanol gradient elution obtains flow point I 2；(4) take I 2 to separate through silica gel chromatography, chloroform methanol gradient elution, obtain Arius and divide I 2A；(5) the inverted RP of I 2A 18 separate, acetonitrile water gradient elution, obtain the compounds of this invention.Compound of the present invention can be used for the treatment of tumor.
Description
Technical field
The present invention relates to pharmaceutical technology field, from Chinese crude drug Resina garciniae, extract the compound of separation, system particularly to a kind of
The method of standby described compound, comprise the medical composition of described compound, and use described compound to prepare antitumor drug
Purposes.
Background technology
Resina garciniae is the glue that the trunk of Garcinia maingayii Resina garciniae (Garcinia hanburyi Hook f.) is flowed out after hurting
Shape resin, has another name called sea rattan, beautiful Huang, the moon yellow, cured Huang etc..Originate in Southeast Asia, China some areas such as Yunnan, Guangxi, Guangdong etc.
There is introducing and planting.
Resina garciniae begins to be loaded in " Haiyao Bencao, Oversea Materia Medica ", and it is cold in nature, sour in the mouth, puckery, pungent, poisonous, has removing blood stasis eliminating stagnation, detoxifies, stops blooding, kills
Effect of worm, the traditional Chinese medical science is used for controlling swollen ulcer drug, stubborn dermatitis malignant boil, bleeding due to trauma, ulcerative gingivitis decayed tooth, burn.
At present, reported be divided into from Resina garciniae from identify more than 20 compounds, be mostly the ton ketone containing bridged ring
(xanthone) compounds, i.e. gambogic acid, Mo Lilin class, guttiferin class, and Resina garciniae aldehyde, betulic acid etc. multipleization
Compound.
Modern pharmacology research shows, Resina garciniae extract has the antibacterial activity of wide spectrum, to staphylococcus aureus, green pus
Bacillus etc. have stronger bacteriostasis.And, pharmacological evaluation and clinical experience prove, it has antitumor action, it is possible to effectively press down
Tumor proliferation processed, has significant curative effect to kinds of tumors.
Inventor extracts from Resina garciniae and obtains having bioactive the compounds of this invention, has more compared with gamlogic acid
Superior anti-tumor activity.
Summary of the invention
The invention provides a kind of extract from Resina garciniae separate there is bioactive formula (1) compound, and provide
The preparation method of this compound and the purposes of preparation tumor.
Formula (1) compound has a following formula:
Present invention also offers the preparation method of this formula (1) compound, concretely comprise the following steps:
(1) taking Resina garciniae medical material ethyl acetate to extract, extract separates through silica gel column chromatography, petroleum ether-ethyl acetate ladder
Degree eluting, obtains 11 components A～K；
(2) discard oil component and gamlogic acid component, analyze through HPLC-PDA-MS, obtain emphasis component I；
(3) component I separates through silica gel column chromatography again, chloroform-methanol gradient elution, and every 30ml collects a flow point, merges
6th part to the 10th part eluent, flow velocity is 2mL/min, obtains flow point I-2；
(4) taking I-2 to separate through silica gel chromatography, chloroform-methanol gradient elution, every 8ml collects a flow point, merges the 2nd part
To the 6th part of eluent, flow velocity is 2mL/min, obtains Arius and divides I-2A；
(5) I-2A inverted RP-18 separation, acetonitrile-water gradient, obtain formula (1) compound.
Preferably, in step (1) petroleum ether-ethyl acetate by volume 50～0: 1 ratio carry out gradient elution；
It is furthermore preferred that petroleum ether-ethyl acetate is divided into six gradients to carry out eluting, respectively 50: 1,10: 1,5: 1,2: 1,
1: 1,0: 1.
Preferably, in step (3) chloroform-methanol by volume 50～10: 1 ratio carry out gradient elution；
Preferably, in step (4) chloroform-methanol by volume 30～10: 1 ratio carry out gradient elution；
It is furthermore preferred that chloroform-methanol is divided into three gradients to carry out eluting, respectively 30: 1,20: 1,10: 1.
Preferably, in step (5) acetonitrile-water by volume 50～80: 50～20 ratio carry out gradient elution；
It is furthermore preferred that acetonitrile-water is divided into four gradients to carry out eluting, respectively 50: 50,60: 40,70: 30,80: 20.
Inventor by physicochemical property and the Modern spectroscopy section of learning to do (1H-NMR (Fig. 2),13C-NMR (Fig. 3), HR-ESI-MS
、1H-1H COSY and HSQC) compound of isolated has been carried out Structural Identification, it was demonstrated that and it is structure change as shown in formula (1)
Compound.
In one aspect, formula (1) compound of the present invention may be used for treating tumor disease.Inventor finds of the present inventionization
Compound has the inhibitory activity of wide spectrum to tumor cell.Described tumor disease includes the group selected from consisting of: nasopharyngeal carcinoma, breast
Adenocarcinoma, mice sarcoma cell and cancer of pancreas.
Another aspect, present invention also offers the pharmaceutical composition for the treatment of tumor disease, and it comprises therapeutically effective amount
Formula (1) compound, and at least one is selected from following pharmaceutically acceptable non-active ingredient: pharmaceutically acceptable
Diluent, pharmaceutically acceptable excipient and pharmaceutically acceptable supporting agent.
Accompanying drawing explanation
Fig. 1 is formula (1) structural formula of compound；
Fig. 2 is formula (1) compound1H-NMR composes；
Fig. 3 is formula (1) compound13C-NMR composes.
Detailed description of the invention
Compound
Formula (1) compound has a structure that
Medical composition/composite
Be suitable for administration routes include, but is not limited to per os, intravenous, rectum, aerosol, parenteral, eye, pulmonary,
Through mucous membrane, percutaneous, vagina, ear, per nasal, intramuscular injection, subcutaneous injection and topical administration.It addition, the most for example, non-warp
Intestinal transmission includes intramuscular, subcutaneous, intravenous, intramedullary injection, and sheath indoor interior, direct, intraperitoneal, lymph is interior and intranasal is noted
Penetrate.
In certain embodiments, compound as herein described with local rather than systemic manner administration.In other embodiments
In, compound as herein described is quickly to discharge formulation, to extend release formulation or middle release composite shape
Formula provides.In other embodiments, compound as herein described is local administration.
In certain embodiments, compound as herein described is formulated for medical composition.In a particular embodiment, medicine
Compositions in the usual way, uses one or more physiologically acceptable supporting agents to allocate, and described physiologically can accept
Supporting agent comprise excipient and auxiliary agent, its preparation contributing to reactive compound is processed as can be used for pharmacy.Suitably composite
Depend on selected dosing way.
Medical composition refers to the mixture of formula (1) compound and other chemical constituent, described chemical constituent as supporting agent,
Stabilizer, diluent, dispersant, suspending agent, thickening agent and/or excipient.In certain embodiments, medical composition contributes to
To mammal administration compound.
In certain embodiments, compound as herein described is formulated for oral administration.Compound as herein described with
Peroral dosage form allocate, the most for example, described peroral dosage form include tablet, powder, pill, sugar-coated ingot, capsule, liquid, gel,
Syrup, elixir, serosity, suspension and the like.
In certain embodiments, described medical composition be tablet, capsule, powder ampoule agent for injection, injection, drop pill and
Slow releasing tablet.
In one embodiment, formula (1) compound is allocated in aqueous solution.In a particular embodiment, the most for example,
Aqueous solution is selected from physiological compatibility buffer, such as Han Shi liquid (Hank ' s solution), ringer's solution (Ringer ' s
Or normal saline buffer solution solution).
In other embodiments, formula (1) compound is formulated offers medicine for through mucous membrane.In a particular embodiment, through mucous membrane
Composite includes the penetrating agent being suitable to be intended to permeability barrier.
Formulated in the other embodiments of other parenteral injection at compound as herein described, suitable composite bag
Include aqueous or non-aqueous solution.
In certain embodiments, by mixing one or more solid excipients and one or more this paper institutes
The compound stated, optionally grinds gained mixture and adds applicable auxiliary agent post-treatment granulate mixture when necessary to obtain sheet
Agent or pill obtain the pharmaceutical preparation used for per os.Specifically, suitable vehicle is filler, such as sugar, including breast
Sugar, sucrose, mannitol or sorbitol；Cellulose preparation, such as corn starch, wheaten starch, rice starch, potato starch, bright
Glue, tragacanth, methylcellulose, microcrystalline Cellulose, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose；Or other material, as
Polyvinylpyrrolidone (PVP or polyvidone) or calcium phosphate.In a particular embodiment, disintegrating agent is optionally added.Only citing comes
Saying, disintegrating agent includes cross-linking sodium carboxymethyl cellulose, polyvinyl pyrrole a heatable brick bed ketone, agar or alginic acid or its salt, such as sodium alginate.
Peroral dosage form also includes inserting capsule with gelatin is made, and by gelatin and plasticizer (such as glycerol or mountain
Pears alcohol) soft seal capsule made.In a particular embodiment, coordinate insert capsule contain active component and one or more
The mixture of filler.The most for example, filler includes lactose, such as binding agents such as starch and/or such as Talcum or magnesium stearate
Deng lubricant, and the stabilizer optionally employed.In other embodiments, soft capsule contains one or more dissolvings or suspends
Reactive compound in suitable liquid.The most for example, appropriate liquid includes one or more fatty oils, liquid paraffin
Or liquid polyethylene glycol.Additionally, optionally add stabilizer.
In other embodiments, formula (1) compound is local administration.Can local administration compositions include solution, suspension
Liquid, lotion, gel, paste, swab, balsam, cream or ointment.
In other embodiments, formula (1) compound is formulated for inhalation dosing.Be suitable to the various forms bag of inhalation dosing
Include (but not limited to) aerosol, spraying or powder.
In order to make those skilled in the art be more fully understood that technical scheme, below in conjunction with specific embodiment pair
The present invention is described in further detail.There is provided described example to be for illustration purposes only, and be not intended to limit right provided herein
The scope of claim.
The preparation method of embodiment 1 formula (1) compound
(1) extracting Resina garciniae medical material (weight ratio of ethyl acetate and Resina garciniae is 15: 1) by ethyl acetate, extract is through silica gel
Pillar layer separation, six gradient elutions of petroleum ether-ethyl acetate (50: 1,10: 1,5: 1,2: 1,1: 1,0: 1), flow velocity is 2mL/
Min, every 30ml collect once, and every 7 parts of merging obtain 11 components A～K；
(2) after discarding oil component A and B and gamlogic acid component D and E, then analyze through HPLC-PDA-MS, obtain emphasis group
Divide I；
(3) component I separates through silica gel column chromatography again, chloroform-methanol (50: 1～10: 1) gradient elution, and every 30ml collects one
Individual flow point, merges the 6th part to the 10th part, and flow velocity is 2mL/min, obtains flow point I-2；
(4) take I-2 through through silica gel chromatography separate, chloroform-methanol (30: 1,20: 1,10: 1) eluting, every 8ml collect successively,
Merging the 2nd part to the 6th part, flow velocity is 2mL/min, obtains Arius and divides I-2A；
(5) the inverted RP-18 of 1-2A separates, acetonitrile-water (50～80: 50～20) gradient elution, obtain formula
(1) compound.
The Structural Identification of embodiment 2 formula (1) compound
This compound is white amorphous powder,(c0.21, MeOH)；1H and13CNMR data are shown in Table 1；
IR(KBr)vmax3429,2947,1720,1695,1642,1365,1252,1142,1080,1047cm-1；HR-TOF-MS shows
Quasi-molecular ion peak m/z711.4090 [M+Na]+(cald for C39H60O10Na, 711.4084).
The nuclear magnetic data of table 1 formula (1) compound (1H (500MHz, C5D5N),13C (100MHz, C5D5N)NMR)
Embodiment 3
Formula (1) compound inhibitory action to people's transplantable lung cancer
1. materials and methods
1.1 tested material
Formula (1) compound: 10mg/ml, purity 98.5%, lot number 20100121, by Chinese Academy of Sciences's Shanghai drug research
Prepared.
Vinorelbine tartrate injection (Gai Nuo): Jiangsu Haosen Pharmaceutical Co., Ltd, lot number 100301.
Normal saline: Shandong Lukang Cisen Pharmaceutical Co., Ltd, lot number 1004234202.
Gamlogic acid: 10mg/ml, purity 98% (detecting through HPLC), lot number 20100819, Jiangsu Kang Yuan Pharmaceutical share have
Prepared by limit company.
1.2 transplanted tumor
People's pulmonary carcinoma NCI-H460 Nude Mice, is inoculated in nude mouse by people's pulmonary carcinoma NCI-H460 cell strain subcutaneous and build
Vertical.Cell inoculum concentration is 3 × 106, inoculation uses after passing for 3 generations after forming transplanted tumor again in nude mice.
1.3 animal
Female BAl BIc/c nude mouse, age in days 35-40 days, body weight 18-22g, zoopery section of hospital general of Nanjing Military Command carry
Supply.Every treated animal number is negative control group 12, administration group 6.
1.4 test method
The tumor tissue taking growth animated period cuts into 1.5mm3Left and right, aseptically, is inoculated in axil on the right side of nude mouse
Nest is subcutaneous.Nude Mice vernier caliper measurement transplanted tumor diameter, treats that tumor growth is to 100～300mm3After by animal with
Machine is grouped.Use the method measuring tumor footpath, dynamically observe the effect of tested drugs against tumor.The pendulous frequency of diameter of tumor is every
Week 3 times, measure every time and the most also need to claim Mus weight.Formula (1) compound intravenously administrable, dosage divides and is 12mg/kg, 6mg/
Kg, 3mg/kg, give three times weekly.Lid promise intravenously administrable 10mg/kg, gives twice weekly, each 0.2ml, and negative control group is simultaneously
To normal saline.
1.5 Testing index and computational methods
(1) gross tumor volume (tumor volume, TV), computing formula is:
Wherein a, b represent length and width respectively.
(2) relative tumour volume (relative tumor volume, RTV), computing formula is:
RTV=TVt/TV0
Wherein TV0For (d during sub-cage administration0) gross tumor volume, TVtGross tumor volume during for measuring each time.
(3) Relative tumor rate of increase T/C (%), computing formula is:
T/C (%)=TRTv/CRTV×100
TRTV: treatment group RTV；CRTV: negative control group RTV.
Result of the test is using Relative tumor rate of increase T/C (%) as the evaluation index of anti-tumor activity.
1.6 statistical method
Experimental data represents with meansigma methods and standard deviation, and statistical method uses t-inspection.
2. result
Formula (1) compound the results are shown in Table 2 to the experimental treatment of people's pulmonary carcinoma NCI-H460.
Formula (1) compound high dose group intravenously administrable has preferable growth inhibited to people's pulmonary carcinoma NCI-H460 mice-transplanted tumor
Effect, best T/C (%) is 62.33；
People's pulmonary carcinoma NCI-H460 Nude Mice is had certain growth inhibited to make by middle dosage group intravenously administrable 6mg/kg
With, best T/C (%) is 69.91；
Low dose group intravenously administrable 3mg/kg has certain growth inhibited effect to people's pulmonary carcinoma NCI-H460 mice-transplanted tumor,
Preferably T/C (%) is respectively 70.05；
Lid promise intravenously administrable 10mg/kg has certain growth inhibited effect to people's pulmonary carcinoma NCI-H460 Nude Mice,
Preferably T/C (%) is 56.69；
People's pulmonary carcinoma NCI-H460 Nude Mice is had certain growth inhibited to make by gamlogic acid intravenously administrable 12mg/kg
With, best T/C (%) is 70.55.
The experimental therapy of people's pulmonary carcinoma NCI-H460 Nude Mice during table 2 formula (1) compound
The RTV of d1 sub-cage administration time P administration group contrasts *: P ＜ 0.05**:P ＜ 0.01 with the RTV of blank group
The extracorporeal anti-tumor function of embodiment 4 the compounds of this invention
1. experiment material
1.1 cell strain
CNE: human nasopharyngeal carcinoma cell line, purchased from Chinese Academy of Sciences's cell bank；
Bcap-37: Breast cancer lines, purchased from Chinese Academy of Sciences's cell bank；
S180: mice sarcoma cell strain, purchased from Chinese Academy of Sciences's cell bank；
Bxpc-3: human pancreas cancer cell strain, purchased from Chinese Academy of Sciences's cell bank；
MCF-7: Breast cancer lines, purchased from Chinese Academy of Sciences's cell bank.
1.2 tested materials and reagent
Formula (1) compound: purity 98.5%, lot number 20100121, Shanghai Pharmaceutical Inst., Chinese Academy of Sciences prepare；
0.25% trypsin-EDTA: GIBCO company of the U.S.；
MTT solution: purchased from this hundred remittances bio tech ltd, Beijing；
PBS: Ji Nuo biological medicine technology company limited；
Dimethyl sulfoxide (DMSO): analytical pure.
1.3 experimental technique
1.3.1 Cell culture invitro
Cell Soviet Union of often restoring to norm is placed in incubator at 37 DEG C, 5%CO2And cultivate under the conditions of saturated humidity, treat cell
When growing to exponential phase of growth, pass on 0.25% trypsin-DTA digestion method.Absorb old culture fluid in bottle, wash away with PBS
Residual culture fluid, then in bottle, add appropriate Digestive system (0.25% trypsin-EDTA), make Digestive system submergence all cells table
Face, puts in 37 DEG C of incubators and hatches (time is depending on different cells), put and observe under microscope, finds that kytoplasm bounces back, carefully
After intercellular space increases, adding the complete culture solution containing serum immediately and terminate digestion, centrifugal (1000rpm, 5min) removes supernatant afterwards
Liquid, counts with after culture fluid re-suspended cell, with cell number 3 × 105～5 × 105Cells/mL is seeded in new culture bottle, puts
Cultivating with above-mentioned condition of culture in incubator, 2～3d pass on once.
1.3.2MTT method detection
When cell grows to exponential phase of growth, with 0.25% trypsin-DTA digestion, it is centrifuged (1000rpm, 5min), carefully
Born of the same parents' precipitation complete medium adjusts cell number to be 2 × 104～3 × 104Cells/mL, 96 holes cultivate the every holes of version inoculate 190 μ L,
37 DEG C, 5%CO2And cultivate under the conditions of saturated humidity, add formula (1) compound after 24h, making cumulative volume is 200 μ L, if 6 are multiple
Hole, control wells adds PBS solution, continues to cultivate 48h, and adding 20 μ L concentration is the MTT of 5mg/mL, is placed in CO2Incubator 37
DEG C hatching, discard culture fluid after 4h, every hole adds 150 μ LDMSO, and vibrate 10min, puts in enzyme micro-plate reader and detects, measures each hole
OD value, calculate suppression ratio.Formula (1) compound IC to subject cell strain50Weight back by probit with SPSS11.5 software
Method is returned to calculate.
Suppression ratio computing formula:
2. experimental result
Experimental result shows (such as table 3), and formula (1) compound all has inhibitory action to each tested tumor cell, its small mouse
Euphorbia egg decoctum cell strain is the highest to the sensitivity of medicine.
Table 3 formula (1) compound IC to each subject cell strain50
The preparation of embodiment 5 tablet
According to the operational approach of conventional tablet, mixed above uniformly, wet granulation, be eventually adding magnesium stearate mix homogeneously
It is pressed into tablet, totally 50, every 500mg.
The preparation of embodiment 6 capsule
According to the operational approach of conventional capsule, mixed above uniformly, wet granulation, fill becomes capsule, totally 90, every
300mg。
The preparation of embodiment 7 drop pill
Formula (1) compound 10.0g
Polyethylene glycol 6000 25.0g
Formula (1) compound is pulverized 100 mesh sieves, was uniformly added in molten polyethylene glycol 6000 substrate, stir 30
Minute to uniformly, with dimethicone 100 as coolant, 15-4 DEG C of gradient cooling, dripping pelletization, centrifugal segregation surface cools down
Agent, obtains drop pill 1000 ball.
The preparation of embodiment 8 powder ampoule agent for injection
Formula (1) compound 1.0g
Hydrochloric acid is appropriate
Mannitol 50.0g
Carrying out according to the operation of conventional freeze-dried powder, formula (1) compound adds 800ml water for injection and dissolves, and adds mannitol,
It is settled to 1000ml, between regulation pH value to 5.0-6.5, aseptic filtration, lyophilization and get final product.
The preparation of embodiment 9 injection
Formula (1) compound is dissolved in dehydrated alcohol, adds 20% polyoxyl castor oil mixing, be evaporated under reduced pressure and remove second
Alcohol, adds appropriate water for injection and is mixed into clear transparent solutions, and through filtering with microporous membrane, coating-dividing sealing, flowing steam sterilization is i.e.
?.
The preparation of embodiment 10 slow releasing tablet
Formula (1) compound and polyvidone being dissolved in a small amount of ethanol, ethanol is evaporated under reduced pressure, 100 mesh sieves crossed by gained solid；Will
Above-mentioned solid and lactose, hypromellose cross 60 mesh sieve mixings, add 3% hydroxypropyl methylcellulose (E5) aqueous solution and make in right amount
Soft material, crosses 20 mesh sieves and pelletizes, forced air drying.Dry granule crosses 20 mesh sieve granulate, adds the Pulvis Talci of recipe quantity, mixing, and tabletting is i.e.
?.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For Yuan, under the premise without departing from the principles of the invention, it is also possible to make some improvements and modifications, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (13)
1. formula (1) compound:
2. a medical composition, it comprises the compound according to claim 1 of therapeutically effective amount, and at least one
Pharmaceutically acceptable non-active ingredient selected from following: pharmaceutically acceptable diluent, pharmaceutically acceptable
Excipient and pharmaceutically acceptable supporting agent.
Medical composition the most according to claim 2, wherein said medical composition is tablet, capsule, injection, drop pill
Agent.
4., according to the arbitrary described compound of claims 1 to 3 or the purposes of medical composition, it is used for treating swollen for preparation
The medicine of tumor disease.
Purposes the most according to claim 4, described tumor disease is selected from the group of consisting of: nasopharyngeal carcinoma, breast carcinoma, pancreas
Adenocarcinoma.
6. the method preparing compound according to claim 1, it comprises the following steps:
(1) taking Resina garciniae medical material ethyl acetate to extract, extract separates through silica gel column chromatography, and petroleum ether-ethyl acetate gradient is washed
De-, obtain 11 components A～K；
(2) discard oil component and gamlogic acid component, analyze through HPLC-PDA-MS, obtain emphasis component I；
(3) component I separates through silica gel column chromatography again, and chloroform-methanol gradient elution, every 30mL collects a flow point, merges the 6th part
To the 10th part of eluent, flow velocity is 2mL/min, obtains flow point I-2；
(4) taking I-2 to separate through silica gel chromatography, chloroform-methanol gradient elution, every 8mL collects a flow point, merges the 2nd part to the 6th
Part eluent, flow velocity is 2mL/min, obtains Arius and divides I-2A；
(5) I-2A inverted RP-18 separation, acetonitrile-water gradient, obtain formula (1) compound.
Method the most according to claim 6, petroleum ether-ethyl acetate by volume 50～0: 1 in wherein said step (1)
Ratio carry out gradient elution.
Method the most according to claim 7, wherein said petroleum ether-ethyl acetate is divided into six gradients to carry out eluting, point
It is not 50: 1,10: 1,5: 1,2: 1,1: 1,0: 1.
Method the most according to claim 6, in wherein said step (3) chloroform-methanol by volume 50～10: 1 ratio
Example carries out gradient elution.
Method the most according to claim 6, in wherein said step (4) chloroform-methanol by volume 30～10: 1 ratio
Example carries out gradient elution.
11. methods as claimed in claim 10, wherein chloroform-methanol is divided into three gradients to carry out eluting, and respectively 30: 1,20
∶1、10∶1。
12. methods as claimed in claim 6, acetonitrile-water by volume 50～80: 50～20 in wherein said step (5)
Ratio carries out gradient elution.
13. methods according to claim 12, wherein said acetonitrile-water is divided into four gradients to carry out eluting, and respectively 50:
50,60: 40,70: 30,80: 20.
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| CN101607978A (en) * | 2008-06-20 | 2009-12-23 | 秦继红 | Two new compounds, its preparation method and pharmaceutical uses in the gamboge |
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