CN104974125B - Brown pore fungi lactone, its preparation method and its pharmaceutical composition and application - Google Patents
Brown pore fungi lactone, its preparation method and its pharmaceutical composition and application Download PDFInfo
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- CN104974125B CN104974125B CN201410132369.8A CN201410132369A CN104974125B CN 104974125 B CN104974125 B CN 104974125B CN 201410132369 A CN201410132369 A CN 201410132369A CN 104974125 B CN104974125 B CN 104974125B
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- phaeoporlactone
- lactone
- pore fungi
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种从褐孔菌属真菌斜生褐孔菌中提取出的新化合物褐孔菌内酯（Phaeoporlactone）、其制备方法、包含该化合物的药物组合物及其在预防和/或治疗肿瘤及蛋白酪氨酸激酶（protein tyrosine kinase，PTKs）相关疾病中的应用。褐孔菌内酯（Phaeoporlactone）具有抑制活性的作用；具有抑制人肝癌细胞Bel‑7402生长的作用。褐孔菌内酯（Phaeoporlactone）可预防、缓解和/或治疗PTKs活性异常升高相关疾病如肿瘤、经皮腔内血管成形术（Percutaneous transluminal coronary intervention，PCI）术后再狭窄、动脉粥样硬化、高血压、多发性硬化症、糖尿病视网膜病变、子宫内膜异位症、牛皮癣等皮肤病和哮喘等疾病。 The invention discloses a new compound Phaeoporlactone (Phaeoporlactone) extracted from Phaeoporus fungus Phaeoporactone, a preparation method thereof, a pharmaceutical composition containing the compound and its application in prevention and/or Application in the treatment of tumors and protein tyrosine kinases (PTKs) related diseases. Phaeoporlactone has inhibitory activity; it can inhibit the growth of human hepatoma cell Bel-7402. Phaeoporlactone can prevent, alleviate and/or treat diseases related to abnormally elevated activity of PTKs such as tumors, restenosis after percutaneous transluminal coronary intervention (PCI), and atherosclerosis , hypertension, multiple sclerosis, diabetic retinopathy, endometriosis, psoriasis and other skin diseases and asthma and other diseases.
Description
Technical field
The invention belongs to field of medicaments, tiltedly give birth to more particularly to one from brown hole Pseudomonas fungi extracted in brown pore fungi it is new
The brown pore fungi lactone (Phaeoporlactone) of compound, preparation method, the pharmaceutical composition comprising the compound and its pre-
Anti- and/or treatment tumour and the abnormal application increased in related disease of PTKs activity.
Background technique
Tiltedly give birth to brown pore fungi [Phaeoporus obliquus (Pers.:Fr.) J.Schrotet. or Inonotus
Obliquus (Pers.:Fr.) Pilat or Polyporus obliquus Pers.:Fr.], be agaric guiding principle, rust leather hole Zoopagales,
Hymenochaetaceae, brown hole Pseudomonas fungi, former name Inonotus obliquus.Brown pore fungi is tiltedly given birth to anti-diabetic, anticancer, prevention and treatment AIDS
Disease improves the effects of immune.
Tyrosine phosphorylation plays an important role in many cell regulation process, is mainly reflected in the work of T cell and B cell
Change, the reaction to external irritant, mitosis, blood vessel hyperplasia, neurotransmitter conduction, the growth of cell cycle control, transcription are adjusted
Section, glucose uptake, tumour occur and the processes such as cell differentiation, formation and apoptosis.Tyrosine protein kinase (Protein
Tyrosine kinases, PTKs) dysfunction may cause many diseases.PTKs activity has become measure of cell proliferation at present
One of mark of canceration.In view of important function of the PTKs in tumor cells aetology, people attempt to press down using PTKs inhibitor
Growth of tumour cell processed and some proliferative diseases, such as PCI postoperative restenosis, atherosclerosis, hypertension, multiple sclerosis
The diseases such as the skin diseases such as disease, diabetic retinopathy, endometriosis, psoriasis and asthma.
Two generation drugs can be divided into from broadly antineoplastic.First on behalf of traditional cellulotoxic chemotherapeutics, such as platinum class and
Anti-metabolism anticarcinogen；Second typically refers to specifically on behalf of molecular targeted therapy, this kind of drugs to one or more
The drug that tumor correlated albumen is regulated and controled.Operation, chemotherapy, radiotherapy are the main means of current treatment tumour, but respectively have drawback,
Mainly toxic side effect is larger.Anti-tumor drug researches and develops facing challenges at present, first is that a variety of anti-tumor drugs far can not expire
Sufficient clinical demand is badly in need of developing more new drugs；Second is that toxic side effect is big, poor selectivity, therapeutic effect is undesirable；Third is that targeting
For anti-tumor drug there is also resistance problems, the Drug-resistant sex expression that curative effect is more obvious is more prominent；Fourth is that prolonged application targets
Influence of the anti-tumor drug to body can not be ignored.Therefore novel efficient, less toxic, highly selective antitumor of the exploitation third generation
New drug is still an important research topic, has important innovative significance.
Summary of the invention
Present invention solves the technical problem that being on the one hand to provide a kind of brown pore fungi lactone of noval chemical compound
(Phaeoporlactone), structure is as shown in the formula (I):
Another aspect provides the methods of the brown pore fungi lactone (Phaeoporlactone) of prepare compound.
An additional aspect of the present invention is related to a kind of pharmaceutical composition comprising the brown pore fungi lactone of compound
(Phaeoporlactone) and pharmaceutically acceptable carrier.
Another aspect of the invention is related to brown pore fungi lactone (Phaeoporlactone) prevention of compound and/or treatment egg
The application of white tyrosine kinase (PTKs) related disease, protein tyrosine kinase (PTKs) related disease are including but not limited to swollen
Tumor, PCI postoperative restenosis, atherosclerosis, hypertension, multiple sclerosis, diabetic retinopathy, endometrium are different
Application in the disease medicaments such as skin diseases and asthma such as position disease, psoriasis.Especially in preparation prevention and/or the medicine for the treatment of liver cancer
Application in object.
To solve technical problem of the invention, the present invention adopts the following technical scheme:
A kind of preparation method of the brown pore fungi lactone (Phaeoporlactone) of noval chemical compound, it is characterised in that including following
Step:
(1) take it is a certain amount of tiltedly give birth to brown pore fungi medicinal material, with 95% ethyl alcohol extract three times, obtain medicinal extract；
(2) ethanol extract in step (1) is suspended in water, is first extracted with chloroform, be then extracted with ethyl acetate, finally
With extracting n-butyl alcohol, final rough segmentation is at four parts such as chloroform, ethyl acetate, n-butanol, water；
(3) ethyl acetate extraction part is concentrated under reduced pressure, and is separated through silica gel column chromatography, use chloroform-acetone and chloroform-
Methanol system carries out gradient elution, and every 500ml is a fraction, and detection, collection obtain brown pore fungi lactone (Phaeoporlactone)
Crude product, then purify to obtain brown pore fungi lactone (Phaeoporlactone) sterling of compound through preparative HPLC.
Wherein the separation condition of preparative HPLC is methanol-water-formic acid (30:70:1, V:V:V), flow velocity in step (3)
8ml/min, 227nm wavelength detecting take 500 μ L sample introductions, in tRIt is pure that=20min obtains brown pore fungi lactone (Phaeoporlactone)
Product.
Identified, the structure of the brown pore fungi lactone (Phaeoporlactone) of obtained noval chemical compound is as shown in the formula (I)
It is tested and is found by pharmacological activity, compound of formula I of the invention has and protein tyrosine kinase PTKs is inhibited to make
With.It can be applied to preparation prevention and/or the abnormal drug for increasing related disease for the treatment of PTKs activity.The PTKs related disease
Including but now schedule tumour, PCI postoperative restenosis, atherosclerosis, hypertension, multiple sclerosis, diabetes view
The diseases such as the skin diseases such as film lesion, endometriosis, psoriasis and asthma.According to can to antitumor relevant pharmacological evaluation
Know, the brown pore fungi lactone (Phaeoporlactone) of noval chemical compound has preferable antitumor pharmacological action, especially inhibition people liver
The growth of cancer cell.
Advantageous effects:
A) brown pore fungi lactone (Phaeoporlactone) is the monomeric compound that fungi tiltedly gives birth to extracting and developing in brown pore fungi,
Have the advantages that preparation process is simple.
B) its raw material can cultivate, have good applicating and exploitation prospect.
C) protein tyrosine kinase (PTKs) related disease includes but is not limited to tumour, PCI postoperative restenosis, artery congee
Skin diseases and the heavy breathings such as sample hardening, hypertension, multiple sclerosis, diabetic retinopathy, endometriosis, psoriasis
Application in the disease medicaments such as asthma.Application especially in the drug of preparation prevention and/or treatment liver cancer.
The invention further relates to the medicines of a kind of the formula (I) compound containing medicine effective dose and pharmaceutically acceptable carrier
Compositions.
According to an embodiment of the invention, formula (I) compound further include its pharmaceutically acceptable salt, hydrate, ester with
And pro-drug.
The invention further relates to containing as the formula (I) compound and customary pharmaceutical excipients of active ingredient or the medicine of adjuvant
Compositions.Usual formula (I) compound accounts for the 0.1~95% of pharmaceutical composition total weight.The formula (I) compound in unit dosage form
General content is 0.1 to 100mg.
Pharmaceutical composition of the present invention can be prepared according to method well known in the art.When for this purpose, if needed
It wants, can be made by formula (I) compound of the invention in conjunction with one or more solids or liquid pharmaceutical excipients and/or adjuvant
It can be used as administration form or dosage form appropriate that people's medicine or veterinary drug use.
Formula (I) compound of the invention can be administered, administration route in a unit containing its pharmaceutical composition
It can be enteron aisle or non-bowel, such as take orally, muscle, subcutaneous, nasal cavity, oral mucosa, eye, lung, skin, vagina, peritonaeum, rectum,
It is preferred that being administered orally.
Formula (I) compound of the invention or the administration route containing its pharmaceutical composition can be drug administration by injection.Injection packet
Include intravenous injection, intramuscular injection, subcutaneous injection, intracutaneous injection, intraperitoneal injection and acupoint injection therapy etc..
Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (including
True solution and colloidal solution), emulsion (including oil-in-water type, water-in-oil type and emulsion), suspension, injection (including liquid drugs injection,
Powder-injection and infusion), eye drops, nasal drop, lotion and liniment etc..Solid dosage forms can be tablet (including ordinary tablet, enteric
Piece, lozenge, dispersible tablet, chewable tablets, effervescent tablet, oral disnitegration tablet), capsule (including hard capsule, soft capsule, capsulae enterosolubilis),
Granule, powder, pellet, dripping pill, suppository, film, patch, the agent of gas (powder) mist, spray etc.；Semisolid dosage form can be ointment
Agent, gelling agent, paste etc..
Formula (I) compound of the invention can be made ordinary preparation, be also possible to sustained release preparation, controlled release preparation, targeting system
Agent and various particulate delivery systems.
In order to which tablet is made in unit dosage forms for administration, various excipient well known in the art can be widely used, including dilute
Release agent, binder, wetting agent, disintegrating agent, lubricant, glidant.Diluent can be starch, dextrin, sucrose, glucose, cream
Sugar, mannitol, sorbierite, xylitol, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate, calcium carbonate etc.；Wetting agent can be water, second
Alcohol, isopropanol etc.；Adhesive can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, Arabic gum
Slurry, gelatine size, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, card
Wave nurse, polyethylene adjoin pyrrolidone, two propyl alcohol of poly- second etc.；It is fine that disintegrating agent can be dried starch, microcrystalline cellulose, low substituted hydroxy-propyl
Dimension element, crosslinked polyethylene adjoin pyrrolidone, croscarmellose sodium, sodium carboxymethyl starch, sodium bicarbonate and citric acid, carbonic acid
Calcium, polyoxyethylene sorbitol aliphatic ester, dodecyl sodium sulfate；Lubricant and glidant can be talcum powder, titanium dioxide
Silicon, stearate, tartaric acid, atoleine, polyethylene glycol etc..
Tablet can also be further made to coating tablet, such as sugar coated tablet, thin membrane coated tablet, enteric coated tablets or double
Synusia and multilayer tablet.
In order to which pill is made in administration unit, various carriers well known in the art can be widely used.Example about carrier
Son is, such as diluent and absorbent, as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, polyvinylpyrrolidone,
Gelucire 44/14, kaolin, talcum powder etc.；Adhesive, as Arabic gum, yellow Bodhisattva's glue, gelatin, ethyl alcohol, honey,
Liquid sugar, rice paste or batter etc.；Disintegrating agent, such as agar powder, dry starch, alginate, dodecyl sodium sulfate, Methyl cellulose
Element, ethyl cellulose etc..
In order to which suppository is made in administration unit, various carriers well known in the art can be widely used.Example about carrier
Son is, such as ester, gelatin, semi-synthetic glyceride of polyethylene glycol, lecithin, cocoa butter, higher alcohol, higher alcohol etc..
In order to which capsule is made in administration unit, formula (I) compound is mixed with above-mentioned various carriers, and will thus obtain
Mixture be placed in hard gelatine capsule or soft capsule.Micro-capsule can also be made in effective component formula (I) compound of the invention
Agent is suspended in aqueous medium and forms suspension, also can be fitted into hard capsule or be made injection application.
For example, injection preparation is made in formula (I) compound, such as solution, suspension solution, emulsion, freeze-dried powder
Agent, this preparation can be aqueous or non-aqueous, can contain acceptable carrier in a kind of and/or a variety of pharmacodynamics, diluent, viscous
Mixture, lubricant, preservative, surfactant or dispersing agent.If diluent can be selected from water, ethyl alcohol, polyethylene glycol, l, 3- the third two
Alcohol, the isooctadecanol of ethoxylation, polyoxygenated isooctadecanol, Polyoxyethylene Sorbitol Fatty Acid Esters etc..In addition, in order to prepare
Isotonic injection can add suitable sodium chloride, glucose or glycerol into injection preparation, further, it is also possible to add often
Cosolvent, buffer, pH adjusting agent of rule etc..These auxiliary materials are commonly used in the art.
In addition, if desired, can also be added into pharmaceutical preparation colorant, preservative, fragrance, corrigent, sweetener or
Other materials.
To reach medication purpose, enhance therapeutic effect, formula (I) compound of the invention or pharmaceutical composition can use any public affairs
The medication administration known.
The dosage of pharmaceutical composition of the invention depends on many factors, such as to be prevented or be treated the property of disease
Gender, age, weight, personality and the individual reaction of matter and severity, patient or animal, administration route, administration number of times, treatment
Purpose, therefore therapeutic dose of the invention can have large-scale variation.In general, the use agent of Chinese pharmacology ingredient of the present invention
Amount is well known to those skilled in the art.It can practical medicine contained in preparation last in pharmaceutical composition according to the present invention
Object quantity is subject to adjustment appropriate, to reach the requirement of its therapeutically effective amount, completes prophylactic or therapeutic purposes of the invention.Formula
(I) the daily Suitable dosage ranges of compound: the dosage of formula (I) compound of the invention is 0.001~100mg/kg weight,
Above-mentioned dosage with single dose form or can be divided into several, such as two, three or four dosage forms for administration, this depends on administration doctor
Raw clinical experience and include dosage regimen with other treatment means.Accumulated dose needed for each is treated can be divided into repeatedly
Or it is administered by dose.Formula (I) compound of the invention or pharmaceutical composition can individually be taken, or with other treatment drug or
Symptomatic drugs, which merge, to be used and adjusts dosage.
Specific embodiment
The following examples and pharmacological activity experiment are for further illustrating the present invention, but this does not imply that the present invention
Any restrictions.
One, the preparation of brown pore fungi lactone (Phaeoporlactone)
Embodiment 1 is from tiltedly giving birth to the method extracted in brown pore fungi and separate brown pore fungi lactone (Phaeoporlactone):
Brown pore fungi medicinal material 22kg is tiltedly given birth to, is extracted three times with 95% ethyl alcohol, obtains medicinal extract 710g, takes 700g ethanol extract mixed
It is suspended from water, is first extracted with chloroform, is then extracted with ethyl acetate, finally uses extracting n-butyl alcohol, rough segmentation is at chloroform (424g), acetic acid
Four parts such as ethyl ester (51g), n-butanol (152g), water (67g).Ethyl acetate extraction part 50g is taken, it is more through silica gel column chromatography
Secondary separation, chloroform-acetone and chloroform-methanol system gradient elution, every 500ml are a fraction, are obtained in brown pore fungi in the 18th part
Ester (Phaeoporlactone) crude product, then through preparative HPLC purifying (30% methanol-water, the inspection of flow velocity 8ml/min, 227nm wavelength
Survey), 500 μ L sample introductions are taken, obtain brown pore fungi lactone (Phaeoporlactone) the sterling 52mg of compound in tR=20min, for Huang
Brown powder.
Brown pore fungi lactone (Phaeoporlactone) physicochemical property of compound and spectral data are as follows:
Fusing point: 132-133 DEG C；
(-) ESIMS:m/z179 [M-H]-, 359 [2M-H]-；Molecular formula: C9H8O4；
cm-1: 3349,3245,1730,1646,1616,1596,1522,1477,1347,1300,1264,1217,
1182,1165,1089,1060,998,955,877,818,677,578；
UV: λmax206,227,267,307nm；
1H-NMR(500MHz, C5D5N): δ 8.11(1H, s, H-8), 7.00(1H, s, H-5), 4.36(1H, t, J=6.0Hz,
H-3), 2.77(1H, t, J=6.0Hz, H-4)；
13C-NMR(125MHz, C5D5N): δ 165.2(C-1), 67.4(C-2), 27.3(C-4), 114.4(C-5) and, 146.5
(C-6), 153.2(C-7), 116.9(C-8), 133.4(C-9) and, 16.7(C-10).
Two, pharmacological activity is tested
The brown pore fungi lactone (Phaeoporlactone) of experimental example 1 is tested in protein tyrosine kinase inhibitor screening model
Using Enzyme-linked Immunosorbent Assay method, tyrosine kinase is separated and extracted from rat cerebral tissue, uses poly-Glu-
Tyr (PGT) is used as substrate, is coated with microwell plate.The tyrosine residue of PGT can by PTKs phosphorylation, then with HRP mark phosphoric acid
Change monoclonal antibody specific as probe, is specifically bound with the tyrosine residue of phosphorylation, by colour developing, measure its extinction
Degree, to react the activity of PTKs.
1) in rat cerebral tissue PTK extraction；
2) ELISA Plate is coated with；
3) ptk inhibitor screens: ELISA Plate, 37 DEG C of incubations first are added in compound and PTK crude extract；Kinase buffer is added
The diluted ATP of liquid, 37 DEG C of incubations；Remove reaction solution in plate, washing；Antibody complex, 37 DEG C of incubations are added；Remove antibody in plate
Compound, washing；TMB developing solution room temperature is added to be protected from light；Terminate liquid is added, surveys OD value in 450nm.
Inhibiting rate %=(normal-OD sample of OD)/(normal-OD blank of OD) * 100%
The brown pore fungi lactone of table 1 is in protein tyrosine kinase inhibitor screening model experimental result
In the experiment of protein tyrosine kinase inhibitor screening model, the compounds of this invention is in 10 μ g/ml dosage to egg
White tyrosine kinase has good inhibiting effect.Inhibiting rate reaches 73.59%, IC50Value is 4.989 μ g/ml.
The brown pore fungi lactone (Phaeoporlactone) of experimental example 2 presses down external Bel-7402 human liver cancer growth of tumour cell
System experiment
Tetrazole [MTT, 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl-tetrazolium
Bromide] it is a kind of dyestuff that can receive hydrogen atom.Dehydrogenase relevant to NADP can incite somebody to action in the cell in living cells mitochondria
The MTT of yellow is converted to the formazon of insoluble bluish violet, and dead cell is then without this function.Formazon is dissolved with DMSO
Afterwards, OD value is measured with microplate reader under certain wavelength, can quantitatively measures the survival rate of cell, can be obtained by calculating
Growth of tumour cell inhibiting rate.
The attached tumor cells of logarithmic growth phase are selected, are cultivated after pancreatin digestion with the RPMI1640 containing 10% fetal calf serum
Liquid is seeded in 96 well culture plates, 4000, every hole cell, and 37 DEG C, 5%CO2Culture is for 24 hours.The sample of experimental group addition various concentration
Product and positive control drug 5-Fu, control group then change the culture solution containing isometric solvent, and 37 DEG C, 5%CO2Cultivate 3d.It discards supernatant
The serum-free medium of the 0.5mg/ml MTT of 100 μ l Fresh is added in liquid, every hole, and 37 DEG C are continued to cultivate 4h.It is careful to abandon
Clearly, and addition 100 μ l DMSO dissolution MTT formazon precipitating measures in microplate reader after being mixed with miniature ultrasonic oscillator
OD value at wavelength 570nm.Growth of tumour cell inhibiting rate (%)=(ODControl-ODExperiment)/(ODControl-ODBlank)*100%
The brown pore fungi lactone of table 2 is to external Bel-7402 human liver cancer growth of tumour cell inhibition assay result
In to external Bel-7402 human liver cancer growth of tumour cell Inhibition test, what positive control drug was selected is 5- fluorine urine
Pyrimidine (5-Fu), the compounds of this invention in 5 μ g/ml concentration with positive control drug IC50Value is suitable.
Claims (7)
1. the brown pore fungi lactone of Formulas I compound represented
2. the preparation method of compound as described in claim 1 comprising following steps:
(1) take it is a certain amount of tiltedly give birth to brown pore fungi medicinal material, with 95% ethyl alcohol extract three times, solvent is recovered under reduced pressure, obtain ethyl alcohol leaching
Cream；
(2) ethanol extract in step (1) is suspended in water, is first extracted with chloroform, is then extracted with ethyl acetate, finally with just
Butanol, before immunoassay, final rough segmentation is at four chloroform, ethyl acetate, n-butanol, water parts；
(3) ethyl acetate extraction part is concentrated under reduced pressure, and through silica gel column chromatography separating for several times, uses chloroform-acetone and chloroform-
Methanol system carries out gradient elution, and every 500ml is a fraction, and detection, collection obtain brown pore fungi lactone (Phaeoporlactone)
Crude product, then purify to obtain brown pore fungi lactone (Phaeoporlactone) sterling of compound through preparative HPLC；
Wherein the separation condition of preparative HPLC is methanol-water-formic acid volume ratio 30:70:1, flow velocity 8ml/min in step (3),
227nm wavelength detecting takes 500 μ L sample introductions, in tR=20min obtains brown pore fungi lactone (Phaeoporlactone) sterling.
3. a kind of pharmaceutical composition, it includes compound of formula I as described in claim 1 and pharmaceutically acceptable carriers.
4. the dosage form of pharmaceutical composition according to claim 3, described pharmaceutical composition is selected from tablet, capsule, granule, mouth
Take liquid, dripping pill, pellet or injection.
5. application of the compound described in claim 1 in the drug of the related disease of preparation treatment albumen tyrosine kinase.
6. application according to claim 5, which is characterized in that the related disease of the protein tyrosine kinase be selected from tumour,
PCI postoperative restenosis, atherosclerosis, hypertension, multiple sclerosis, diabetic retinopathy, mullerianosis
Disease, psoriasis and asthma.
7. application according to claim 6, which is characterized in that the tumour is selected from liver cancer.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006046071A1 (en) * | 2004-10-29 | 2006-05-04 | Nipri Limited | Compounds and compositions useful in the treatment of neoplasia |
| CN101391958A (en) * | 2008-11-10 | 2009-03-25 | 马宏达 | Extraction method of medicinal fungus inonotus obliquus component |
-
2014
- 2014-04-03 CN CN201410132369.8A patent/CN104974125B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006046071A1 (en) * | 2004-10-29 | 2006-05-04 | Nipri Limited | Compounds and compositions useful in the treatment of neoplasia |
| CN101391958A (en) * | 2008-11-10 | 2009-03-25 | 马宏达 | Extraction method of medicinal fungus inonotus obliquus component |
Non-Patent Citations (2)
| Title |
|---|
| Total synthesis and cytotoxic activity of stellatin;Aamer Saeed et al;《ournal of Asian Natural Products Research》;20110128;第13卷(第2期);第97-104页 * |
| 桦褐孔菌的化学成分研究;赵芬琴等;《时珍国医国药》;20061231;第17卷(第7期);第1178-1181页 * |
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