CN114831980B - Wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs - Google Patents
Wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs Download PDFInfo
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- CN114831980B CN114831980B CN202210524940.5A CN202210524940A CN114831980B CN 114831980 B CN114831980 B CN 114831980B CN 202210524940 A CN202210524940 A CN 202210524940A CN 114831980 B CN114831980 B CN 114831980B
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- FXNFHKRTJBSTCS-UHFFFAOYSA-N Baicalein Natural products C=1C(=O)C=2C(O)=C(O)C(O)=CC=2OC=1C1=CC=CC=C1 FXNFHKRTJBSTCS-UHFFFAOYSA-N 0.000 title claims abstract description 24
- XLTFNNCXVBYBSX-UHFFFAOYSA-N wogonin Chemical compound COC1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=CC=C1 XLTFNNCXVBYBSX-UHFFFAOYSA-N 0.000 title claims abstract description 23
- HIMJIPRMECETLJ-UHFFFAOYSA-N Wogonin Natural products COc1cc(O)c(O)c2C(=O)C=C(Oc12)c3ccccc3 HIMJIPRMECETLJ-UHFFFAOYSA-N 0.000 title claims abstract description 21
- UDFLTIRFTXWNJO-UHFFFAOYSA-N baicalein Chemical compound O1C2=CC(=O)C(O)=C(O)C2=C(O)C=C1C1=CC=CC=C1 UDFLTIRFTXWNJO-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 229940015301 baicalein Drugs 0.000 title claims abstract description 21
- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 20
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims abstract description 16
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 239000003560 cancer drug Substances 0.000 title abstract description 5
- 239000003814 drug Substances 0.000 claims description 23
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 6
- 230000002195 synergetic effect Effects 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000035755 proliferation Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000002609 medium Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 238000005138 cryopreservation Methods 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 241000050051 Chelone glabra Species 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- -1 flavonoid compound Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
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- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000007640 basal medium Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 230000007760 free radical scavenging Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
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- 239000004576 sand Substances 0.000 description 1
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- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000009441 vascular protection Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs. The invention discovers that the wogonin and the baicalein have obvious synergistic activity of inhibiting the proliferation of colorectal cancer cells, and have the unexpected technical effect of 1+1 & gt2, and the wogonin and the baicalein composition has the prospect of developing anti-colorectal cancer drugs.
Description
Technical Field
The invention belongs to the field of medicines, and in particular relates to a wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer medicines.
Background
Colorectal cancer (CRC) is one of the highest incidence and mortality cancers in the world, the fourth largest cancer type in the world. Epidemiological data statistics show that 94 tens of thousands of CRC193 (with a ratio of about 10% and third) and 94 tens of thousands of CRC193 (with a ratio of about 9.4% and second) are newly diagnosed worldwide in 2020, and the trend of rapid growth and younger is that the disease is seriously threatened for human health. Surgical treatment remains the most effective treatment at present, but there is still a risk of recurrence and metastasis. Radiotherapy and chemotherapy can be used as adjuvant therapy for operation to reduce local recurrence rate, but can cause adverse reaction such as emesis, enteritis, alopecia, anorexia, leucopenia, and immunity deterioration. Although clinical treatment schemes of colon cancer are continuously perfected, the 5-year survival rate of comprehensive treatment such as chemotherapy, radiotherapy and the like mainly used for operation is still not more than 40%.
Wogonin (wogonin) is one of the main active ingredients of the traditional Chinese herbal medicine radix scutellariae, is a flavonoid compound derived from natural plants separated from radix scutellariae, and has various pharmacological effects of anti-inflammatory, antiallergic, antiviral, anticonvulsant, vascular protection, antithrombotic and antitumor. Baicalein (baicalein) is a flavonoid monomer compound separated from the dry root of the traditional Chinese medicine baical skullcap root, and is a main pharmacodynamic substance basis of the baical skullcap root, and is called 5,6, 7-trihydroxyflavone. Baicalein has been reported to have antiviral, antibacterial, antiallergic, free radical scavenging, cancer treatment and immunomodulating functions.
At present, no research shows that the wogonin and the baicalein have synergistic anti-colon cancer activity at home and abroad, and no report that the wogonin and the baicalein are combined for preparing anti-colorectal cancer drugs exists.
Disclosure of Invention
The invention aims to provide a wogonin and baicalein composition and application thereof in preparing anti-colorectal cancer medicines.
The above object of the present invention is achieved by the following technical scheme:
Use of a composition consisting of wogonin and baicalein for the preparation of an anti-colorectal cancer medicament.
Preferably, the ratio of wogonin to baicalein in the composition is 1:0.5625-1:18.
More preferably, the medicine takes the composition as an active ingredient for resisting colorectal cancer, also contains a pharmaceutically acceptable carrier or auxiliary material, and is prepared into a pharmaceutically acceptable dosage form.
More preferably, the carrier or adjuvant is a solid, liquid or semi-solid.
More preferably, the dosage forms include tablets, capsules, pills, transdermal microneedle formulations, and injections.
The beneficial effects are that:
the invention discovers that the wogonin and the baicalein have obvious synergistic effect on the aspect of resisting colon cancer, and the unexpected technical effect of 1+1 & gt2 is generated, and the wogonin and the baicalein composition has the prospect of developing anti-colorectal cancer medicaments.
Detailed Description
The following describes the essential aspects of the present invention in detail with reference to examples, but is not intended to limit the scope of the present invention.
1. Experimental materials
Reagent: DMSO (Sigma-Aldrich, USA); penicillin-streptomycin (Hyclone, usa); 0.5% pancreatin-EDTA solution (Boshide, boshide bioengineering Co., ltd.); PBS solution (Hyclone, usa); FBS (Gibco, USA); DMEM medium (Gibco, usa), MTT (Jiangsu keyi biotechnology, inc.).
Consumable: 100mm cell culture dishes, cell cryopreservation tubes, 96 well plates (Corning, USA), 15ml/50ml centrifuge tubes (Guangzhou Jiete Biofiltration Co., ltd.).
Medicament: wogonin (CAS: 632-85-9) was purchased from duremia biotechnology limited, purity: 99 percent; baicalein (CAS: 491-67-8) was purchased from Chengdoremia Biotechnology Co., ltd., purity: 98%.
And (3) cells: human colon cancer cell HCT116 (purchased from the south tokyo, biotech limited).
2. Experimental method
1. HCT116 cell culture
HCT116 cells were cultured in high-sugar medium containing 10% fbs and 1% penicillin-streptomycin and 89% dmem.
1.1 Cell resuscitation: HCT116 cells frozen in liquid nitrogen are taken to a constant temperature water bath kettle with the temperature of 37 ℃, and are rapidly warmed and melted by shaking, and are rapidly transferred to a centrifuge tube containing 10mL of culture medium, and are centrifuged at 1000rpm for 5min. The supernatant was discarded, 2mL of medium was added to resuspend the cells, transferred to a 100mm dish containing 8mL of medium, and the medium was placed in a constant temperature cell incubator at 37℃with 5% CO 2 after shaking.
1.2 Passage of cells: when the healing rate of HCT116 cells was 80-90%, the medium was discarded, washed twice with PBS, 1mL of 0.25% trypsin solution (containing EDTA) was added, and digested at 37℃for 1min. When the cells were in the form of sand particles, 2mL of complete medium was rapidly added to terminate digestion, and gently blown, the cell suspension was collected into a 15mL centrifuge tube, centrifuged at 1000rpm for 5min, and the same procedure as described above for "cell resuscitation" was followed.
1.3 Cryopreservation of cells: after the cells were centrifuged by digestion, the supernatant was discarded, and the cells were resuspended in 1mL of cell cryopreservation solution (100. Mu.L DMSO+900. Mu.L FBS), and transferred to a cryopreservation tube after being blown and mixed. Storing at 4 deg.C for 0.5 hr, storing at-20 deg.C for 2 hr, storing at-80 deg.C overnight, and transferring into liquid nitrogen for long-term storage.
2. MTT cell proliferation assay
Taking HCT116 cells in logarithmic growth phase, digesting the HCT116 cells with pancreatin, collecting the cells, inoculating the cells into a 96-well plate according to the density of 3 multiplied by 10 3 cells/well, and singly administering wogonin with different concentrations into a wogonin group, wherein the concentrations of the combined drugs are set to be crossed with each other; the solvent is a basal medium. After cells were seeded in 96-well plates and incubated overnight at 5% CO 2, 37 ℃, the blank and control groups were changed for fresh medium, the dosing group was changed for fresh drug-containing medium, and incubation was continued for 48 hours in an incubator at 5% CO 2, 37 ℃. Then, 20. Mu.L of 5mg/mL MTT solution was added to each well, and the mixture was further incubated in an incubator at 37℃in 5% CO 2 for 4 hours, after which the solution in the well was aspirated, reconstituted with 150mL DMSO, and placed on a microplate shaker and shaken at 300rpm for 10 minutes. The absorbance value of each well was measured at a wavelength of 570 nm. Cell growth inhibition (%) = [1- (OD dosing group-OD blank)/(OD control group-OD blank) ]x100%.
3. Evaluation index of drug synergy
The evaluation method of the synergy of the medicines adopts a method of average Q value of Jinzheng (Jinzheng. Addition in combined medication [ J ]. Chinese pharmacology report, 1980) which is accepted in the field. I.e. q=m AB/(MA+MB-MA*MB). The numerator in the formula represents the "actually measured combination effect", and the denominator is the "expected combination effect", wherein M A、MB and M AB respectively represent the inhibition rate of drug A, the inhibition rate of drug B, and the inhibition rate of the combination of the two drugs at the current dosage. The drug synergy index Q is defined as follows: when the Q value is less than 0.85, the two drugs are considered to have antagonistic effects; when the Q value is between 0.85 and 1.15, the two medicines are considered to be independent of each other and are added; when the Q value is greater than 1.15, the two drugs are considered to have a synergistic effect.
3. Experimental results
The results of the inhibition rate and Q value calculations of HCT116 cells by different monomers or combinations thereof in the intervention culture are shown in the following table. The result shows that the wogonin and the baicalein have obvious synergistic effect on the inhibition activity of HCT116 cells.
In conclusion, the wogonin and baicalein composition has the prospect of being developed into anti-colorectal cancer medicines.
The above-described embodiments serve to describe the substance of the present invention in detail, but those skilled in the art should understand that the scope of the present invention should not be limited to this specific embodiment.
Claims (4)
1. Use of a composition consisting of wogonin and baicalein in a mass ratio of wogonin to baicalein of 1:0.28125, 1:0.5625, 1:1.125, 1:2.25, 1:4.5 or 1:9 for the preparation of an anti-colorectal cancer medicament.
2. Use according to claim 1, characterized in that: the medicine takes the composition as an active ingredient for resisting colorectal cancer, also contains a pharmaceutically acceptable carrier or auxiliary material, and is prepared into a pharmaceutically acceptable dosage form.
3. Use according to claim 2, characterized in that: the carrier or the auxiliary material is solid, liquid or semisolid.
4. Use according to claim 2, characterized in that: the dosage forms include tablets, capsules, pills, transdermal microneedle formulations and injections.
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CN202210524940.5A CN114831980B (en) | 2022-05-13 | 2022-05-13 | Wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs |
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CN202210524940.5A CN114831980B (en) | 2022-05-13 | 2022-05-13 | Wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs |
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CN114831980B true CN114831980B (en) | 2024-05-28 |
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Non-Patent Citations (2)
Title |
---|
CHUNHAO YU 等.Pretreatment of baicalin and wogonoside with glycoside hydrolase: A promising approach to enhance anticancer potential.《ONCOLOGY REPORTS》.2013,第30卷第2411-2418页. * |
SO-JUNG KIM 等.Antitumor actions of baicalein and wogonin in HT-29 human colorectal cancer cells.《MOLECULAR MEDICINE REPORTS》.2012,第6卷第1443-1449页. * |
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