CN106924235A - Application of the usnic acid in antineoplastic sensitizer is prepared - Google Patents

Application of the usnic acid in antineoplastic sensitizer is prepared Download PDF

Info

Publication number
CN106924235A
CN106924235A CN201511012980.8A CN201511012980A CN106924235A CN 106924235 A CN106924235 A CN 106924235A CN 201511012980 A CN201511012980 A CN 201511012980A CN 106924235 A CN106924235 A CN 106924235A
Authority
CN
China
Prior art keywords
antineoplastic
usnic acid
cell
application
cancer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201511012980.8A
Other languages
Chinese (zh)
Inventor
余龙
朱恒锐
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fudan University
Original Assignee
Fudan University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fudan University filed Critical Fudan University
Priority to CN201511012980.8A priority Critical patent/CN106924235A/en
Publication of CN106924235A publication Critical patent/CN106924235A/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention belongs to cell biology and field of medicaments, it is related to application of the usnic acid in antineoplastic sensitizer is prepared.Usnic acid is natural products, the effect with reversing multiple medicine resistance of tumor cells, can be as the reversal agent of tumor multi-medicine drug-resistant；Usnic acid also has increases the effect of tumor multi-medicine drug-resistant cells against neoplastic drug susceptibility, can be used as chemotherapeutic sensitizer.Present invention also offers the method that the pharmaceutical composition that antineoplastic and usnic acid are used in combination suppresses tumor multi-medicine drug-resistant cell propagation.Micromolecular compound usnic acid in the present invention is developed as new antineoplastic or its auxiliary element, and substantially, environmental protection will provide a kind of new approach and means to tumor killing effect to treat and curing tumour.

Description

Application of the usnic acid in antineoplastic sensitizer is prepared
Technical field
The invention belongs to cell biology and field of medicaments, specifically, the present invention relates to the new application of usnic acid.This hair It is bright to further relate to corresponding pharmaceutical composition and its application process.
Background technology
Tumour is body under the effect of various carcinogenic factors, and some cell of local organization loses right on gene level The normal regulation of its growth, the abnormality for causing its clonal abnormality hyperplasia and being formed.The neoplastic disease number of cases of China is quite huge Greatly, there is data to show and account for the 55% of whole world case load.
Influence of the benign tumour to body is smaller, is mainly shown as local compression and obstructive symptom.Malignant tumour is due to dividing Change immature, growth very fast, infiltration destroys the 26S Proteasome Structure and Function of organ, and can shift, thus serious on body influence.Dislike Property tumour can have heating, intractable pain in addition to it can cause local compression and the obstructive symptom similar to above-mentioned benign tumour, also, Late period may occur in which seriously become thin, the state of weak, anaemia and cachexia.
The traditional Chinese medical science thinks that the cause of cancer is equilibrium between yin and yang in human body first, and histocyte is long-term in different carcinogenic factors Under effect, cell mutation and cause.Cancerous tissue is also a part for human body in fact, only in this imbalance between YIN and YANG of people, five Raw gram of row multiplies on the premise of insult changes, and the immunosurveillance system of human body can just lose monitoring to it, develop as one pleases.Chinese herbal medicine Can with recuperating qi-blood, adjustment equilibrium between yin and yang, maintain normal vital signs and save one's life；To train correction gas, produce antibody, cleaning " Malicious source " and effect a permanent cure.Thus, Chinese herbal medicine extract turns into treatment one important directions of tumour.
Usnic acid, alias:Lichenic acid.Plant origin:Usneaceae（Usneaceae）Plant sunglo Usnea diffracta Vain. thallus is dried with sunglo Usnea longissima Ach. long.
Property：Oblique quadratic prism shape crystallization (acetone) of yellow.
Fusing point：204℃.
Optical activity：+ 509.4 ° (c=0.697, chloroform).
Solubility (g/100ml water) at 25 DEG C：<0.01, acetone 0.77, ethyl acetate 0.88, ethanol 0.02, alditol 7.32, sugar alcohol 1.21.Chemically synthesis or biosynthesis is obtained.
CAS : 125-46-2
Molecular formula： C18H16O7
Molecular weight： 344.32
Alias：Usnic acid；(+)-Usnic acid; (+)-Usnein; (+)-Usniacin;
D-2,6-Diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H, 9bH)- Dibenzofurandione;
Structural formula：
Proterties：Yellow crystalline powder.
Fusing point： 192-204 ℃
Optical activity： [α]D20 +495° ~ 497° (C=1, in CHCl3)
Stability：Stablize under normal circumstances.
Usnic acid is a kind of broad-spectrum antibiotic, has powerful inhibitory action to most gram-positive bacteriums, can also be pressed down The growth of tulase processed.If shared with a small amount of streptomysin, its effect for suppressing tulase can be greatly reinforced, toxicity very little.Pine Trailing plants acid also has inhibitory action to protozoon, Trichomonas vaginalis.There is the work for promoting liver regeneration to the feeding rats usnic acid of partially hepatectomized With.Clinically there is certain curative effect to antimalarial.Wound, burn and skin disease, cervicitis, fissure of nipple, prevention perineum are broken Splitting etc. has certain curative effect.Lichenic acid comes from natural sunglo.For stopping blooding, antibacterial, anti-inflammatory, wound healing, except dental plaque, enhancing Body immunity, disease of being burst to oral cavity and vaginitis have preferable curative effect.Frequently as toothpaste and the additive of cosmetics.Additionally, loose Trailing plants acid is alternatively arranged as the raw material of antibiotic " the pyrrole food in one's mouth ".
Usnic acid is natural products, and bioavilability is high, Nature comparison is stable, with Clinical practice value.With people To going deep into for its chemistry and biology research, its molecular mechanism of action will progressively clearly, and this will further promote suchization The modifying for chemical structure and structure activity study of compound, and it is favorably improved its medical value.
The content of the invention
It is an object of the invention to provide the new medicinal usage of usnic acid.
It is an object of the invention to provide a kind of antineoplastic sensitizer.
On the one hand, the application the invention provides usnic acid in antineoplastic sensitizer is prepared.Wherein, usnic acid English full name is usnic acid, and its structure is as shown in Figure 1.
Described tumour includes carcinoma of mouth, breast cancer, liver cancer, lung cancer, cervical carcinoma, colon cancer or cancer of pancreas.
Described antineoplastic is vincristine, daunorubicin, taxol or 5 FU 5 fluorouracil.
Usnic acid can be as tumor multi-drug resistance reversal agents.
On the other hand, the invention provides a kind of antineoplastic pharmaceutical compositions, described antineoplastic pharmaceutical compositions have Effect composition is antineoplastic and usnic acid.
Described antineoplastic is CCSA or cell cycle nonspecific agent (CCNSA).
Described antineoplastic is vincristine, daunorubicin, taxol or 5 FU 5 fluorouracil.
Present invention also offers a kind of method for suppressing tumor cell in vitro growing multiplication, i.e., in the culture medium of tumour cell It is middle to add usnic acid and antineoplastic.
Wherein, the final concentration of 1-100 μm of ol/L of usnic acid is added.
Described tumour includes carcinoma of mouth, breast cancer, liver cancer, lung cancer, cervical carcinoma or cancer of pancreas.
When implementing the above method, usnic acid is first added, be subsequently adding antineoplastic.Can also add simultaneously usnic acid and Antineoplastic.
The invention provides the new application of usnic acid, i.e. its application in antineoplastic sensitizer is prepared.Usnic acid It is natural products, the effect with reversing multiple medicine resistance of tumor cells can be as the reversal agent of tumor multi-medicine drug-resistant；Usnic acid Also having increases the effect of tumor multi-medicine drug-resistant cells against neoplastic drug susceptibility, can be used as chemotherapeutic sensitizer.This Micromolecular compound usnic acid in invention is developed as new antineoplastic or its auxiliary element, and tumor killing effect is bright Aobvious, environmental protection will provide a kind of new approach and means to treat and curing tumour.
Brief description of the drawings
Fig. 1 is the structure of usnic acid.
Specific embodiment
The invention provides a kind of antineoplastic, the active component of described antineoplastic is usnic acid.Described Tumour can be HCC, stomach cancer cell, cervical cancer cell or blood cell.
Micromolecular compound of the invention can be prepared using various conventional preparation methods.For example, using artificial chemistry The method of synthesis.
Using micromolecular compound of the present invention, by various conventional screening assays, can filter out and occur mutually with usnic acid The material of effect, such as acceptor, inhibitor or antagonist.
The present invention and its inhibitor, antagonist etc., when (administration) is administered in treatment, it is possible to provide different effects. Generally, these materials can be formulated in nontoxic, inert and pharmaceutically acceptable aqueous carrier medium, wherein pH is usual About 5-8, preferably pH be about 6-8, pH value can be varied from the property for being formulated material and illness to be treated. The pharmaceutical composition for preparing can be administered by conventional route, including（But it is not limited to）：Intramuscular, intraperitoneal, Subcutaneous, intracutaneous or local administration.
By taking usnic acid of the invention as an example, it can be combined with suitable pharmaceutically acceptable carrier.This kind of medicine Composition contains the compound and pharmaceutically acceptable carrier or excipient of therapeutically effective amount.This kind of carrier includes（But not It is limited to）：Salt solution, buffer solution, glucose, water, glycerine, ethanol, and combinations thereof.Pharmaceutical preparation should match with administering mode.This The usnic acid of invention can be made into injection form, and such as aqueous solution with physiological saline or containing glucose and other assistant agents leads to Conventional method is crossed to be prepared.The pharmaceutical composition of such as tablet and capsule etc, can be prepared by conventional method.Medicine Composition such as injection, solution, tablet and capsule are preferably aseptically manufactured.The dosage of active component is therapeutically effective amount, Such as daily mg/kg body weight of about 1 microgram/kg body weight-about 5.Additionally, usnic acid of the invention can also be with other treatment Agent is used together.Certainly, specific dosage is also contemplated that the factors such as method of administration, patient health situation, and these are all skilled practitioners Within the scope of technical ability.
Experimental technique：
1. cell recovery
1) cryopreservation tube is taken out from liquid nitrogen container, in direct plungeing into 37 DEG C of warm water, and shake makes it melt as early as possible frequently.
2) take out cryopreservation tube from 37 DEG C of water-baths, with suction pipe suction out cell suspension, injection centrifuge tube and addition more than 10 times Nutrient solution, low-speed centrifugal after mixing, abandons supernatant, repeats and is washed once with nutrient solution.
3) after suitably being diluted with nutrient solution, inoculated and cultured bottle is placed on 37 DEG C of incubator quiescent cultures, and next day changes culture Liquid, continues to cultivate.Passed on when culture is to finite concentration.MCF-7 cell culture is in the RPMI 1640 containing 10% hyclone In culture medium, KB and KB/VCR cell culture is trained in the MEM containing 10% hyclone, 2mM glutamine and 1mM Sodium Pyruvates Support in base, MCF-7/ADR cell culture is in the MEM containing 10% hyclone, 0.01mg/ml insulin and 1mM Sodium Pyruvates In culture medium.Penicillin containing 100U/ml and 100 μ g/ml streptomysins in culture medium.
2. passage culture
The situation of daily observation of cell growth, passes on when when cell, length is converged to about 90% in blake bottle, is about passed every 2-4 days In generation, is once.One bottle passes on into three bottles, or 25 cm2Pass in 75 cm2Blake bottle in.Method：
1) with 1 × phosphate buffer washed cell once.
2) digestion of 2-3ml pancreatin digestive juice is added, several minutes in 37 DEG C of incubators are placed in.Tissue Culture Flask is patted with hand, Make cell separation.
3) terminate pancreatin with the suitable culture medium of the Gibico hyclones containing 10-15% to digest.Cell is sub-packed in newly Blake bottle in, continue cultivate.
When suspension cell is passed on, centrifugation in centrifuge tube is collected directly from, abandons old culture medium.General one bottle passes on into three bottles Ratio is sub-packed in new blake bottle, adds fresh culture to continue to cultivate.
3. cell cryopreservation
1) the cell Trypsin Induced of culture to exponential phase is taken, is collected in centrifuge tube and is counted, be centrifuged.
2) reject trypsase and old nutrient solution, what addition had been configured freezes nutrient solution (containing 10% DMSO, 40% DMEM and 50% Gibico hyclones), the ultimate density of cell is 0.5- 1 × 10 in frozen stock solution7/ml.Gently blown with suction pipe Beating makes cell uniform, is then distributed into aseptic cryopreservation tube, often pipe -1.5ml of Jia 1.
3) cryopreservation tube is put into freezing storing box and puts -80 DEG C of quick-frozen, preservations in immigration liquid nitrogen container after 5 hours.
4. experiment material
Medicine prepares：
Usnic acid is dissolved in DMSO (dimethyl sulfoxide (DMSO)), and the mother liquor for being configured to 100mM or 50mM is standby.
Vincristine (VCR) and adriamycin (ADR) are purchased from Roche chemical company, and purity is both greater than 99%.
Cell derived:
Human oral cancer cell line KB and its drug-resistant cell strain KB/VCR are provided by Chinese Academy of Sciences's medicine, Breast cancer lines MCF- 7 and its drug-resistant cell strain MCF-7/ADR is purchased from company of Nanjing Keygen Biotech.
Kit:
CCK-8 kits are purchased from colleague company.
CCK-8 is tested
KB and KB/VCR cells and MCF-7 and MCF-7/ADR cells are all inoculated into 96 orifice plates according to the density in 3500/ hole, The ADR of various concentrations after 24 h, VCR, usnic acid and VCR and usnic acid one are reinstated after the α-MEM containing 10% hyclone prepare It is added in each hole.After cultivating 48 h, nutrient solution is discarded, culture medium and 10 μ Ls of the 90 μ L without serum are added per hole CCK-8 reagents.After 37 DEG C of 2 h of reaction, ELIASA reads the light absorption value of 450 nm wavelength（OD450）.By being calculated medication Cell growth fraction of the group relative to control group.Blank group only adds culture medium to be not added with cell, and control group is same with medicine to add The DMSO of volume, cell survival rate=（Experimental group OD450- blank groups OD450）/（Control group OD450- blank groups OD450）.It is logical Cross IC50Value calculates resistance multiple again（Resistance Fold, RF）.
The IC of RF=drug-resistant cell strain50The IC of value/parental cell strain50Value.Each concentration sets 3 repeating holes, real Test repetition 3 times.
All mdr cells grow 3 days before tying up to Cell suppression test in without pharmaceutical culture medium.Each numerical value is 3 Independent experiment result, IC50Represented in " means standard deviation " form.VCR, vincristine；ADR, daunorubicin；RF, resistance times Number.
Embodiment 1
Experimental result：
KB/VCR and MCF-7/ADR are two kinds of conventional multidrug resistance cell strains, and in the present embodiment, both cells are also showed Go out the characteristic of MDR.As shown in table 1, KB/VCR cells are respectively relative to KB cells to the resistance multiple of VCR and ADR 81.9 times and 94.4 times, and MCF-7/ADR cells are respectively 38.1 times compared to the resistance multiple to VCR and ADR with MCF-7 cells With 20.9 times, display experiment mdr cell used has multidrug resistance, and MDR activity similar to the result of document report.
Half-inhibition concentration IC of the usnic acid to parental cell strain KB and MCF-750Respectively 98.3 μ Μ and 87.9 μ Μ, To the IC of drug-resistant cell strain KB/VCR and MCF-7/ADR50Respectively 116.3 μ Μ and 125.3 μ Μ, between the two without conspicuousness Difference, multidrug resistance cell strain KB/VCR and MCF-7/ADR do not show the crossing drug resistant to compound usnic acid, illustrate pine Trailing plants acid can escape the multidrug resistance of mdr cell.Under the concentration of below 20 μ Μ, cell growth is without obvious for usnic acid Suppression, the propagation of cell can be suppressed under the concentration higher than 100 μ Μ.
Conclusion：Usnic acid can overcome the drug resistance of drug-resistant cell strain, and drug-resistant cell strain is basic to the sensitiveness of usnic acid It is identical.
Embodiment 2：CCK-8 methods detect reverse effect of the usnic acid to tumor cell multidrug resistance activity
KB/VCR, MCF-7/ADR and HCT-8/VCR cell are inoculated into 96 orifice plates according to the density in 3500/ hole, after 24 h not Reinstated with the VCR and usnic acid one of the VCR of concentration, and various concentrations and be added to after the α-MEM containing 10% hyclone are prepared respectively In individual hole.After cultivating 48 h, discard nutrient solution, with method in embodiment 1, with CCK-8 kits survey drug-resistant cell strain and its Parental cell plots curve to the activity of VCR and VCR+ usnic acids.Each concentration sets 3 repeating holes, and experiment is repeated 3 times.
Experimental result：
KB/VCR cells are 81.9 times to the resistance multiple of VCR, and MCF-7/ADR is 20.9 times to the resistance multiple of ADR.Work as addition After 20 μM of usnic acid, ADR is set to increased 1.23 times to the sensitiveness of mdr cell MCF-7/ADR, and KB/VCR cells pair The sensitiveness increase of VCR is not notable.Usnic acid can reverse multiple drug resistance of tumor cell to the drug resistance of chemotherapeutics.And this Plant effect and show unobvious in parental cell.
Conclusion：
Usnic acid can be with the drug resistance of reverse multiple drug resistance of tumor cell MCF-7/ADR, can be as the enhanced sensitivity of antineoplastic Agent, or it is made pharmaceutical composition with antineoplastic.
The all documents referred in the present invention are all incorporated as reference in this application, independent just as each document It is incorporated as with reference to such.In addition, it is to be understood that after above-mentioned instruction content of the invention has been read, those skilled in the art can Made various changes or modifications with to the present invention, these equivalent form of values equally fall within the model that the application appended claims are limited Enclose.

Claims (10)

1. application of the usnic acid in antineoplastic is prepared, described application is that usnic acid is preparing antineoplastic sensitizer In application.
2. application as claimed in claim 1, it is characterised in that usnic acid is tumor multi-drug resistance reversal agents.
3. application as claimed in claim 1, it is characterised in that described tumour includes carcinoma of mouth, nasopharyngeal carcinoma, breast cancer, liver Cancer, lung cancer, cervical carcinoma, colon cancer or cancer of pancreas.
4. application as claimed in claim 1, it is characterised in that described antineoplastic is vincristine, daunorubicin, purple China fir alcohol or 5 FU 5 fluorouracil.
5. a kind of antineoplastic pharmaceutical compositions, it is characterised in that the active ingredient of described antineoplastic pharmaceutical compositions is anti-swollen Tumor medicine and usnic acid.
6. antineoplastic pharmaceutical compositions as claimed in claim 5, it is characterised in that described antineoplastic is the cell cycle Specific drug or cell cycle nonspecific agent (CCNSA).
7. antineoplastic pharmaceutical compositions as claimed in claim 5, it is characterised in that described antineoplastic is new Changchun Alkali, daunorubicin, taxol or 5 FU 5 fluorouracil.
8. it is a kind of suppress tumor cell in vitro growing multiplication method, it is characterised in that in the culture medium of tumour cell add Usnic acid and antineoplastic.
9. method as claimed in claim 8, it is characterised in that described tumour includes carcinoma of mouth, breast cancer, nasopharyngeal carcinoma, liver Cancer, lung cancer, cervical carcinoma or cancer of pancreas.
10. method as claimed in claim 8, it is characterised in that first add usnic acid, be subsequently adding antineoplastic.
CN201511012980.8A 2015-12-31 2015-12-31 Application of the usnic acid in antineoplastic sensitizer is prepared Pending CN106924235A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201511012980.8A CN106924235A (en) 2015-12-31 2015-12-31 Application of the usnic acid in antineoplastic sensitizer is prepared

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201511012980.8A CN106924235A (en) 2015-12-31 2015-12-31 Application of the usnic acid in antineoplastic sensitizer is prepared

Publications (1)

Publication Number Publication Date
CN106924235A true CN106924235A (en) 2017-07-07

Family

ID=59457910

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201511012980.8A Pending CN106924235A (en) 2015-12-31 2015-12-31 Application of the usnic acid in antineoplastic sensitizer is prepared

Country Status (1)

Country Link
CN (1) CN106924235A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110734429A (en) * 2019-11-22 2020-01-31 昆明医科大学 Usnea nicotinamide compound and preparation method and application thereof
CN110840877A (en) * 2019-11-29 2020-02-28 广东药科大学 Application of dextro-lichenin alone or in combination with taxol in preparing medicine for treating and resisting lung squamous carcinoma

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110734429A (en) * 2019-11-22 2020-01-31 昆明医科大学 Usnea nicotinamide compound and preparation method and application thereof
CN110734429B (en) * 2019-11-22 2022-05-03 昆明医科大学 Usnea nicotinamide compound and preparation method and application thereof
CN110840877A (en) * 2019-11-29 2020-02-28 广东药科大学 Application of dextro-lichenin alone or in combination with taxol in preparing medicine for treating and resisting lung squamous carcinoma
CN110840877B (en) * 2019-11-29 2021-05-14 广东药科大学 Application of dextro-lichenin alone or in combination with taxol in preparing medicine for treating and resisting lung squamous carcinoma

Similar Documents

Publication Publication Date Title
CN102526073A (en) Application of mogrol H9 for preparing antitumor drugs
CN106937953A (en) Application of the oxymatrine in antineoplastic sensitizer is prepared
CN106924235A (en) Application of the usnic acid in antineoplastic sensitizer is prepared
CN106924236A (en) Application of the rcumenol in antineoplastic sensitizer is prepared
CN103127049A (en) Application of usnic acid in manufacturing antitumor drugs
CN106924253A (en) Application of 8- the third dicyan jamaicins in antineoplastic sensitizer is prepared
CN106924252A (en) Application of the 8- diethyl malonates jamaicin in antineoplastic sensitizer is prepared
CN106924225A (en) Application of the magnolol in antineoplastic sensitizer is prepared
CN106890189A (en) Application of the chonglou saponin in antineoplastic sensitizer is prepared
CN106902101A (en) Application of the thelephora ganbajun in antineoplastic sensitizer is prepared
CN106852926A (en) Application of the triterpene glucoside unit in antineoplastic sensitizer is prepared
CN106913566A (en) Applications of the silver wire grass alcohol M in antineoplastic sensitizer is prepared
CN106806362A (en) Application of the dehydrogenation rush diphenol in antineoplastic sensitizer is prepared
CN106924243A (en) Application of the fraxinellone in antineoplastic sensitizer is prepared
CN104873493B (en) Application of the 2 hydroxyl eupatolides in antineoplastic is prepared
CN103417536B (en) The application in antitumor drug prepared by harmol
CN104887690B (en) Application of the chonglou saponin in antitumor drug is prepared
CN102697757A (en) Application of p-hydroxy benzylidene acetone in preparation of drugs for preventing and/or treating encephalopathy
CN106937950A (en) Application of the psoromic acid in antineoplastic sensitizer is prepared
CN106924244A (en) Application of the isosteviol lactams in antineoplastic sensitizer is prepared
CN106913568A (en) Application of the 13- acetyl shizukaol C in antineoplastic sensitizer is prepared
CN106937949A (en) Applications of the chloranthalactone C in antineoplastic sensitizer is prepared
CN106913877A (en) Application of the magnolol in antineoplastic sensitizer is prepared
CN112891341A (en) Application of GL-V9 and anthracycline antibiotics in preparation of leukemia treatment drug
CN106913562A (en) Application of the squamatic acid in antineoplastic sensitizer is prepared

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20170707