CN108938610B - For treating the pharmaceutical composition and its related preparations of oophoroma - Google Patents
For treating the pharmaceutical composition and its related preparations of oophoroma Download PDFInfo
- Publication number
- CN108938610B CN108938610B CN201811109716.XA CN201811109716A CN108938610B CN 108938610 B CN108938610 B CN 108938610B CN 201811109716 A CN201811109716 A CN 201811109716A CN 108938610 B CN108938610 B CN 108938610B
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- dihydromyricetin
- thymoquinone
- preparation
- composition according
- 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.)
- Active
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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The pharmaceutical composition comprising thymoquinone and dihydromyricetin that the present invention relates to a kind of, and its application in treatment of ovarian cancer；Belong to drug field.It includes thymoquinones and dihydromyricetin.The molar ratio of the thymoquinone and dihydromyricetin is 1:0.1-10.
Description
Technical field
The pharmaceutical composition comprising thymoquinone and dihydromyricetin that the present invention relates to a kind of, and its in treatment of ovarian cancer
Application；Belong to drug field.
Background technique
Oophoroma is the second largest common cancer of women.But due to the symptom for lacking specificity, oophoroma initial stage is difficult to diagnose,
Cause clinically diagnosed oophoroma be usually advanced stage and with extensive transfer, and poor prognosis.Therefore oophoroma, which becomes, causes
The highest gynecological cancer of dead rate.Currently, 5 year life cycle of the oophoroma of global range is only 25%-30%.There are about 90% ovaries
Cancer is Ovarian surface epithelium and Epithelium Cells source, and 80% epithelial ovarian cancer is serous papillary carcinoma.It is right
In most advanced ovarian cancers, clinically commonly uses platinum medicine and carry out chemotherapy, but drug resistance problems are difficult to overcome always, lead to curative effect
It is bad.In addition, therapeutic scheme clinically is mostly based on comprehensive cancer network (the National Comprehensive of US National
Cancer Network) the malignant tumour clinical practice guideline issued is designed, and basic research majority is directed to west
Square state's kin group, and the research for the especially our people of asian ancestry group more lacks.
Thymoquinone (Thymoquinone, TQ) is the primary bioactive components of Chinese medicine Oleum Nigellae, have it is anti-inflammatory,
Anti-oxidant and antitumor action.A large amount of document report shows that TQ can inhibit kinds cancer, including breast cancer, prostate cancer,
Oophoroma, liver cancer, cancer of pancreas, colorectal cancer etc..Early-stage study shows that TQ plays inhibition to multiple processes of cancer development and makees
With, including cell Proliferation, apoptosis, migration, invasion and angiogenesis.In addition, TQ can cooperate with enhancing conventional medicament to cancer cell
Inhibiting effect, however, the molecular mechanism of TQ antitumor action is not elucidated with yet, and it acts on the potential treatment of oophoroma
It is still not very clear.The chemical structural formula of the thymoquinone is as follows:
Dihydromyricetin (Dihydromyricetin, DHM) also known as ampelopsin (Ampelopsin).Extract from grape
In the leaf of snake section vitis spp vine tea, belong to flavone compound, molecular formula C15H12O8.Studies have shown that DHM is with more
Kind pharmacological activity includes anti-inflammatory, anti-oxidant, antibacterial, anti-hypertension and antithrombotic.DHM has potentially early-stage study as the result is shown
Anticancer activity, including breast cancer, liver cancer, colon cancer and lung cancer.But its activity and Mechanism Study in oophoroma more lacks,
In addition to this, DHM can also accelerating alcohol metabolism product acetaldehyde fast decoupled, to reduce damage of the alcohol to liver, separately
Outside, the liver protection effect that DHM has been demonstrated further includes improving serum lactic dehydrogenase (SLDH) vigor caused by stem cell loses to increase, and is inhibited
Liver property M cell collagen fiber is formed.The chemical structural formula of the dihydromyricetin is as follows:
Report in terms of combining dihydromyricetin treating cancer there has been no thymoquinone so far.
Summary of the invention
The first aspect of the present invention is to provide a kind of pharmaceutical composition, can be used for oncotherapy, and it includes thymoquinones
And dihydromyricetin.
In some embodiments, the molar ratio of the thymoquinone and dihydromyricetin is 1:0.1-10.
In other embodiments, the molar ratio of the thymoquinone and dihydromyricetin is 1:0.5-2.
In further carrying out scheme, described pharmaceutical composition also includes tumor chemotherapeutic drug, the chemotherapy of tumors medicine
Object is selected from, including but not limited to, cyclophosphamide (CTX), ifosfamide (IFO), methopterin (MTX), fluorouracil (5-
FU), mitomycin (MMC), adriamycin (ADM), vincristine (VCR) are eldisine (VDS), etoposide (VP-16), suitable
Platinum (DDP), carboplatin (CBP), interferon, taxol, Docetaxel, mesna etc..
In some embodiments, the molar ratio of the thymoquinone, dihydromyricetin and tumor chemotherapeutic drug is 1:
0.1-10:0.05-1.
In other embodiments, the molar ratio of the thymoquinone, dihydromyricetin and tumor chemotherapeutic drug is 1:
0.5-2:0.1-0.5.
The second aspect of the present invention is to provide the preparation comprising described pharmaceutical composition, by pharmaceutical composition and pharmaceutically
Acceptable carrier composition；The pharmaceutical preparation is oral preparation or injection.
In another embodiment, the pharmaceutically acceptable carrier is selected from starch, beta-cyclodextrin, carbomer, micro-
Crystalline cellulose, hydroxypropyl methyl cellulose, calcium carboxymethylcellulose, polyethylene glycol (PEG), sodium carboxymethylcellulose, methyl are fine
Tie up element, ethyl cellulose, mannitol, lauryl sodium sulfate, lactose, polyvinylpyrrolidone (PVP), crosslinked polyethylene pyrroles
Alkanone, ethyl-para-hydroxybenzoate, magnesium stearate, talcum powder, superfine silica gel powder, Aspartame, orange flavor, sodium bicarbonate, carbon
One or more of sour sodium.
The third aspect of the present invention is to provide application of the described pharmaceutical composition in preparation tumor.
In some embodiments, the tumour is oophoroma.
In above-mentioned medical usage, administration time and administration number of times for pharmaceutical composition of the present invention are needed according to disease
Depending on the specific diagnostic result of feelings, this is within the technical scope that those skilled in the art grasp.For example, will be to mouse or rat
Therapeutic scheme be applied on the person, all drugs to the effective dose of people can by the drug to the effective dose of mouse into
Row conversion, this is easy to accomplish for those of ordinary skill in the art.
The present invention can significantly be improved existing anti-with the pharmaceutical composition of thymoquinone joint dihydromyricetin
The curative effect of medication of oophoroma, Small side effects, dosage is low, and can play the liver-protective activity of DHM, can be outstanding as preparation cancer
It is the drug of oophoroma.Test proves that TQ combines DHM in the proliferation for inhibiting ovarian cancer cell, induces ovarian cellular apoptosis
And autophagy, apparent synergistic effect can all be played by reducing the horizontal aspect of ovarian cancer cell ROS, and this synergy is in addition chemotherapy
It is further strengthened after drug.
Specific embodiment
Also the present invention further can be understood by embodiment, wherein the embodiment illustrates some preparations or user
Method.It is to be appreciated, however, that these embodiments do not limit the present invention.The change of the invention of currently known or further exploitation
Change is considered within the scope of the invention described herein and claimed below.
In the present invention, the synergistic effect refers to the biological effect after said components combination, and based on individually making
It generates content required by given biological effect with expectation when single component to compare, the activity of composition is apparently higher than single group
The synergistic effect divided.
The reagents and materials used in the present invention are commercially available or can prepare by literature method.Tool is not specified in the following example
The experimental method of concrete conditions in the establishment of a specific crime, usually according to normal condition, or according to the normal condition proposed by manufacturer.
The influence that example 1 drug composition and monomer are proliferated ovarian cancer cell line
One, Ovarian Cancer Cells in vitro culture
1) cell origin
Abortion syndrome SKOV3 and HO-8910 cell is purchased from Shanghai Cell Bank of the Chinese Academy of Sciences.
2) cell culture and passage
SKOV3 and HO-8910 cell uses 1640 culture mediums (Gibico).10% fetal calf serum is added in cell culture
(fetalbovineserum, FBS, Gibco).Above-mentioned cell strain is cultivated in 37 DEG C, 5%CO2 incubator, is grown to cell
To when accounting for culture dish bottom 80-90%, digests and pass on using 0.25% pancreatin+EDTA.
Two, test method
Main experimental materials: thymoquinone (Thymoquinone, TQ, Sigma) is dissolved in methanol, is configured to 10mM concentration
Liquid, -20 DEG C, when use, is diluted to 10,20,40,80 and 100 μM respectively, i.e., with using.Dihydromyricetin
(Dihydromyrictin, DHM, Sigma) is dissolved in dimethyl sulfoxide (DMSO), is configured to 50mM concentrate, and -20 DEG C save,
1,50,100 and 200 μM is diluted to when use respectively, i.e., with i.e. use；Cis-platinum (cisplatium, Cis, Nuo Xin, the gloomy medicine of Jiangsu person of outstanding talent
Industry Group Co., Ltd) it is configured to 5mg/mL concentrate, 4 DEG C of preservations, when use, is diluted to 5 and 10mg/L respectively.Thiazolyl blue
(MTT, Sigma) is dissolved in PBS, final concentration of 5mg/mL, and 4 DEG C of preservations are prepared and used in latter week；Pancreatin (Gibco)；PBS；
6 orifice plates (Nunc).
Test method: it by cell dissociation, is centrifuged and is resuspended in corresponding culture solution, with 1 × 104The density in/hole is planted
In 96 orifice plates, 37 DEG C are placed in, 5%CO2After being cultivated for 24 hours in incubator, original fluid is removed, Fresh is added, containing being
The culture solution of column concentration compound continues to cultivate, and culture terminates culture afterwards for 24 hours, 20 μ LMTT is added to every hole, then be replaced in 37
DEG C, after cultivating 4h in 5%CO2 incubator, the culture solution containing MTT is carefully removed, every hole is added DMSO150 μ L, carefully rocks
The light absorption value in each hole is detected after mixing at microplate reader OD 490nm.Three repeating groups are arranged in each concentration.
Three, test result
1) influence to SKOV3 cell line proliferation is applied alone in thymoquinone or dihydromyricetin
2) influence of thymoquinone, dihydromyricetin and/or Cisplatin to SKOV3 cell line proliferation
According to non-patent literature Chou T C.Theoretical basis, experimental design, and
computerized simulation of synergism and antagonism in drug combination
Studies. [J] .Pharmacological Reviews, 2006,58 (3): the standard places proposed in 621-681. are specific
Whether there is collaboration, addition or antagonism, the multicomponent synergistic effect is calculated using following formula between compound component:
CI=A/Ae+B/Be+C/Ce
A, B and C refers to the dosage of three kinds of compound components in pharmaceutical composition, Ae、BeAnd CeRefer to individually using unification
The dosage of single component needed for polymer component reaches the inhibition efficiency of pharmaceutical composition, as CI (Combination Index)
When value is less than 1, and the smaller synergistic effect illustrated between component of CI value is stronger, illustrates that component has synergistic effect, CI value etc.
Illustrate that component has equivalent or antagonism in 1 or greater than 1 when.
It carries out related synergistic effect especially by Calcusyn V2.0 (BIOSOFT, MO, USA) to calculate, it has been determined that chemical combination
Synergistic effect whether is produced in terms for the treatment of oophoroma between object, concrete outcome is as follows:
| Thymoquinone | Dihydromyricetin | Inhibiting rate (%) | CI | |
| Group 1 | 20μM | - | 39.27±1.83 | - |
| Group 2 | - | 20μM | 10.74±1.59 | - |
| Group 3 | 20μM | 20μM | 64.82±1.94 | 0.422 |
| Group 4 | 20μM | 10μM | 42.61±1.67 | 0.426 |
| Group 5 | 10μM | 20μM | 36.29±1.71 | 0.484 |
3) influence to HO-8910 cell line proliferation is applied alone in thymoquinone or dihydromyricetin
| Dosage | Inhibiting rate (%) | |
| Thymoquinone | 10μM | -33.86±1.71 |
| 20μM | -22.08±1.11 | |
| 40μM | 19.72±0.99 | |
| 80μM | 45.64±2.38 | |
| Dihydromyricetin | 1μM | 7.09±0.31 |
| 10μM | 3.83±0.21 | |
| 50μM | 19.62±1.35 | |
| 100μM | 28.43±1.61 |
4) thymoquinone and dihydromyricetin are combined the influence to HO-8910 cell line proliferation
| Thymoquinone | Dihydromyricetin | Inhibiting rate (%) | CI | |
| Group 1 | 40μM | - | 43.41±5.04 | - |
| Group 2 | - | 40μM | 15.17±0.64 | - |
| Group 3 | 40μM | 40μM | 74.96±3.42 | 0.287 |
| Group 4 | 20μM | 40μM | 54.21±2.86 | 0.307 |
| Group 5 | 40μM | 20μM | 65.38±3.57 | 0.349 |
5) influence of thymoquinone, dihydromyricetin and cisplatin combined application to SKOV3 cell line proliferation
According to the combination for ovarian cancer cell of above-mentioned thymoquinone and dihydromyricetin as a result, we select thyme
The molar ratio 1:1 of quinone and dihydromyricetin, further investigates the effect of itself and Cisplatin, and concrete outcome is as follows:
6) influence of thymoquinone, dihydromyricetin and cisplatin combined application to HO-8910 cell line proliferation
The inducing action of 2 pharmaceutical composition of embodiment and monomer to ovarian cellular apoptosis
It is purchased from Chinese Academy of Sciences Shanghai cell institute using abortion syndrome, SKOV3 and HO-8910 cell uses 1640
Culture medium (Gibico).10% fetal calf serum (fetalbovineserum, FBS, Gibco) is added in cell culture.It is above-mentioned
Cell strain is at 37 DEG C, 5%CO2It cultivates in incubator, when cell grows to and accounts for culture dish bottom 80-90%, uses
0.25% pancreatin+EDTA is digested and is passed on.
Test method: by cell dissociation at cell suspension after, be laid in 60mm culture dish with suitable density, in 37 DEG C,
5%CO2It is incubated in incubator about for 24 hours, when cell grows to and accounts for culture dish bottom 50% or so, removes original fluid, be added
The culture solution containing 20 μM of TQ, 20 μM of DHM and/or 5mg/L cis-platinums of Fresh continues to cultivate.It is careful after culture for 24 hours to receive
Collect supernatant and use Accutase-Enzyme Cell Detachment Medium vitellophag, by cell suspension and supernatant
Liquid mixing centrifugation, the cells rinsed with PBS being collected into is primary, it is centrifuged and is resuspended to 1 × Binding Buffer, is adjusted thin
Born of the same parents' density is 1 × 106A/mL.100 μ L cell suspensions are drawn into loading pipe, 5 μ L AnnexinV-FITC and 5 μ L are added
Propidium Iodide (PI) is protected from light room temperature reaction 15min, then 400 1 × Binding of μ L is added into every pipe after mixing
Buffer uses flow cytomery Apoptosis situation.
Test result:
1) inducing action of the pharmaceutical composition to SKOV3 Apoptosis
| Thymoquinone | Dihydromyricetin | Cis-platinum | AnnexinV (%) | |
| Blank control group | - | - | - | 0.47±0.22 |
| Group 1 | 20μM | - | - | 30.19±1.49 |
| Group 2 | - | 20μM | - | 11.54±1.21 |
| Group 3 | - | - | 5mg | 48.42±1.73 |
| Group 4 | 20μM | 20μM | 5mg | 99.12±1.53 |
2) inducing action of the pharmaceutical composition to HO-8910 Apoptosis
| Thymoquinone | Dihydromyricetin | Cis-platinum | AnnexinV (%) | |
| Blank control group | - | - | - | 0.11±0.41 |
| Group 1 | 20μM | - | - | 19.51±2.14 |
| Group 2 | - | 20μM | - | 7.24±1.37 |
| Group 3 | - | - | 5mg | 17.63±1.53 |
| Group 4 | 20μM | 20μM | 5mg | 72.48±1.42 |
Thymoquinone and dihydromyricetin are inhibiting ovarian cancer cell line proliferation and induction to wither it can be seen from the above results
It dies aspect and produces apparent synergistic effect.Especially to the oophoroma HO-8910 cell in Asia women source, classic chemotherapy
Drug (such as cis-platinum), HO-8910 cell have apparent drug resistance to it, but press down after combining three to which create apparent
Production is used.
The content of present invention merely illustrates claimed some specific embodiments, one of them or more skill
Documented technical characteristic can be combined with arbitrary one or more technical solutions in art scheme, these are combined and obtain
Technical solution also in the application protection scope, the technical solution just as obtained from these are combined is disclosed in the present invention
It is specifically recorded in content the same.
Claims (9)
1. a kind of pharmaceutical composition, can be used for oncotherapy, it includes thymoquinones and dihydromyricetin.
2. pharmaceutical composition according to claim 1, which is characterized in that mole of the thymoquinone and dihydromyricetin
Than for 1:0.1-10.
3. pharmaceutical composition according to claim 1, which is characterized in that mole of the thymoquinone and dihydromyricetin
Than for 1:0.5-2.
4. pharmaceutical composition according to claim 1, which is characterized in that described pharmaceutical composition also includes chemotherapy of tumors medicine
Object, the tumor chemotherapeutic drug are selected from: cyclophosphamide, ifosfamide, methopterin, fluorouracil, mitomycin, Ah mould
Element, vincristine, eldisine, etoposide, cis-platinum, carboplatin, interferon, taxol, Docetaxel or mesna.
5. pharmaceutical composition according to claim 4, which is characterized in that the thymoquinone, dihydromyricetin and tumour
The molar ratio of chemotherapeutics is 1:0.1-10:0.05-1.
6. pharmaceutical composition according to claim 5, which is characterized in that the thymoquinone, dihydromyricetin and tumour
The molar ratio of chemotherapeutics is 1:0.5-2:0.1-0.5.
7. a kind of preparation comprising any one of claim 1-6 described pharmaceutical composition, by pharmaceutical composition and pharmaceutically may be used
The carrier of receiving forms；The pharmaceutical preparation is oral preparation or injection.
8. pharmaceutical preparation according to claim 7, which is characterized in that the pharmaceutically acceptable carrier be selected from starch,
Beta-cyclodextrin, carbomer, microcrystalline cellulose, hydroxypropyl methyl cellulose, calcium carboxymethylcellulose, polyethylene glycol (PEG), carboxylic first
Base sodium cellulosate, methylcellulose, ethyl cellulose, mannitol, lauryl sodium sulfate, lactose, polyvinylpyrrolidone
(PVP), crosslinked polyvinylpyrrolidone, ethyl-para-hydroxybenzoate, magnesium stearate, talcum powder, superfine silica gel powder, Aspartame,
One or more of orange flavor, sodium bicarbonate, sodium carbonate.
9. application of any one of the claim 1-6 described pharmaceutical composition in preparation treatment ovarian cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811109716.XA CN108938610B (en) | 2018-09-21 | 2018-09-21 | For treating the pharmaceutical composition and its related preparations of oophoroma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811109716.XA CN108938610B (en) | 2018-09-21 | 2018-09-21 | For treating the pharmaceutical composition and its related preparations of oophoroma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108938610A CN108938610A (en) | 2018-12-07 |
| CN108938610B true CN108938610B (en) | 2019-05-31 |
Family
ID=64471708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811109716.XA Active CN108938610B (en) | 2018-09-21 | 2018-09-21 | For treating the pharmaceutical composition and its related preparations of oophoroma |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108938610B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115607540A (en) * | 2022-10-24 | 2023-01-17 | 中国人民解放军空军军医大学 | Application of myricetin in preparation of CD147 inhibitor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101485655A (en) * | 2009-02-12 | 2009-07-22 | 华南理工大学 | Application of dihydromyricetin in preparing medicament for preventing and treating adverse reaction of tumor chemoradiotherapy |
| CN102631341A (en) * | 2011-02-12 | 2012-08-15 | 广东泰禾医药科技有限公司 | New application of ampelopsin sodium in treating bladder cancer |
| CN103288618A (en) * | 2013-06-05 | 2013-09-11 | 江苏昊华精细化工有限公司 | Synthesis method of thymoquinone serving as blood vessel inhibition medicament |
| CN108125946A (en) * | 2016-12-01 | 2018-06-08 | 国药集团健康产业研究院有限公司 | Application of the dihydromyricetin in terms of kidney medicine is prepared |
-
2018
- 2018-09-21 CN CN201811109716.XA patent/CN108938610B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101485655A (en) * | 2009-02-12 | 2009-07-22 | 华南理工大学 | Application of dihydromyricetin in preparing medicament for preventing and treating adverse reaction of tumor chemoradiotherapy |
| CN102631341A (en) * | 2011-02-12 | 2012-08-15 | 广东泰禾医药科技有限公司 | New application of ampelopsin sodium in treating bladder cancer |
| CN103288618A (en) * | 2013-06-05 | 2013-09-11 | 江苏昊华精细化工有限公司 | Synthesis method of thymoquinone serving as blood vessel inhibition medicament |
| CN108125946A (en) * | 2016-12-01 | 2018-06-08 | 国药集团健康产业研究院有限公司 | Application of the dihydromyricetin in terms of kidney medicine is prepared |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108938610A (en) | 2018-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2011270165B2 (en) | Antitumor agent using compounds having kinase inhibitory effect in combination | |
| CA2560058A1 (en) | A method for inhibiting cancer cell proliferation or increasing cancer cell apoptosis | |
| CN109908145B (en) | Pharmaceutical composition of fangchinoline-7-propionate and tyrosine kinase inhibitor | |
| CN108938610B (en) | For treating the pharmaceutical composition and its related preparations of oophoroma | |
| CN101972247A (en) | Medicinal application of 15-benzyl subunit-1 4-deoxy-11,12-dehydrogenation andrographolide derivative | |
| CN101312737A (en) | Parapoxviruses in combination with classical cytotoxic chemotherapeutic agents as biochemotherapy for the treatment of cancer | |
| EP3459537B1 (en) | Application of clofoctol for manufacturing pharmaceutical product for treating human neuroglioma | |
| CN109620836B (en) | Compound pharmaceutical composition with breast cancer resistance, application thereof and medicine based on composition | |
| CN101977612A (en) | The use of phenolic glycosides derivatives in the manufacture of compositions for treating cell proliferation diseases | |
| AU2014245146B2 (en) | Antitumor agent including irinotecan hydrochloride hydrate | |
| CN111588714B (en) | A pharmaceutical composition for treating lung cancer and preparation method thereof | |
| KR102205656B1 (en) | Pharmaceutical composition for preventing and treating cancer | |
| CN103826701A (en) | Combined pharmaceutical compositions for the treatment of tumours | |
| CN105251023A (en) | Application of AXL/c-Met inhibitor in preparation of drug for reversing renal cancer sunitinib drug resistance | |
| CN112336716A (en) | Application of vitamin C and disulfiram in preparation of anti-tumor combined medicine | |
| WO2011113300A1 (en) | Medicines for inhibiting toxicity or side effects caused by chemotherapeutic agents | |
| CN104906578A (en) | Application of proton pump inhibitor in preparation of medicine for treating hepatocellular carcinoma | |
| CN107661324B (en) | Application of the Propafenone in preparation treatment oesophagus cancer drug | |
| CN111544580B (en) | Anti-cancer pharmaceutical composition | |
| CN116687920A (en) | Application of marine bisindole compound combined with cytarabine (Ara-C) in preparation of drugs for treating Acute Myeloid Leukemia (AML) | |
| CN102526081A (en) | Medicinal composition capable of inhibiting proliferation of tumor cells | |
| CN110448555B (en) | Application of polycyclic compound in preparation of antitumor drug and antitumor drug | |
| KR102552913B1 (en) | Pharmaceutical composition for preventing and treating secondary cancer comprising aldehyde inhibitor and biguanide compounds | |
| CN108078991A (en) | Application of the Aurora A inhibitor in terms of inhibition tumor microenvironment drug is prepared | |
| CN110876800B (en) | Application of micafungin in preparation of antitumor drugs and antitumor drugs |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |