CN111298122B - Pharmaceutical composition for treating small cell lung cancer and application thereof - Google Patents
Pharmaceutical composition for treating small cell lung cancer and application thereof Download PDFInfo
- Publication number
- CN111298122B CN111298122B CN201911231857.3A CN201911231857A CN111298122B CN 111298122 B CN111298122 B CN 111298122B CN 201911231857 A CN201911231857 A CN 201911231857A CN 111298122 B CN111298122 B CN 111298122B
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- lung cancer
- small cell
- cell lung
- administration group
- 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
- 206010041067 Small cell lung cancer Diseases 0.000 title claims abstract description 30
- 208000000587 small cell lung carcinoma Diseases 0.000 title claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 239000003112 inhibitor Substances 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical group C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 claims description 12
- 229960004090 maprotiline Drugs 0.000 claims description 12
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 7
- 229960004316 cisplatin Drugs 0.000 claims description 7
- YDDMIZRDDREKEP-HWTBNCOESA-N lurbinectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1NC1=CC=C(C=C13)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 YDDMIZRDDREKEP-HWTBNCOESA-N 0.000 claims description 6
- 229950000680 lurbinectedin Drugs 0.000 claims description 5
- 229940079593 drug Drugs 0.000 abstract description 6
- 210000004027 cell Anatomy 0.000 description 12
- 238000000034 method Methods 0.000 description 8
- 239000000935 antidepressant agent Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 230000002195 synergetic effect Effects 0.000 description 6
- 229940005513 antidepressants Drugs 0.000 description 5
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 229960004801 imipramine Drugs 0.000 description 4
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 4
- 108010009460 RNA Polymerase II Proteins 0.000 description 3
- 102000009572 RNA Polymerase II Human genes 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 229960004688 venlafaxine Drugs 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- 108091007743 BRCA1/2 Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108010013845 RNA Polymerase I Proteins 0.000 description 1
- 102000017143 RNA Polymerase I Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229960003955 mianserin Drugs 0.000 description 1
- 108091064355 mitochondrial RNA Proteins 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229940127221 norepinephrine reuptake inhibitor Drugs 0.000 description 1
- 229940000673 orphan drug Drugs 0.000 description 1
- 239000002859 orphan drug Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 238000011127 radiochemotherapy Methods 0.000 description 1
- 229960003770 reboxetine Drugs 0.000 description 1
- CBQGYUDMJHNJBX-RTBURBONSA-N reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical class C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a pharmaceutical composition for treating small cell lung cancer and application thereof, belonging to the field of medicines. Which include lurbinedin and selective NA reuptake inhibitors. The mass ratio of the lurbinectin to the selective NA reuptake inhibitor in the pharmaceutical composition is 1: 0.01-1.
Description
Technical Field
The invention relates to a pharmaceutical composition for treating small cell lung cancer and application thereof, belonging to the field of medicines.
Background
Lung cancer is the first malignant tumor with global morbidity and mortality. In recent years, the incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is classified into non-small cell lung cancer (NSCLC) and Small Cell Lung Cancer (SCLC), with SCLC accounting for about 15-20% of all lung cancers.
SCLC is a systemic disease with a poor prognosis with a 5-year survival rate of less than 5%. At present, the first-line treatment of SCLC generally adopts operation and is mainly assisted by chemotherapy or radiotherapy. The chemotherapy drugs mainly comprise etoposide and cisplatin and irinotecan and cisplatin, and except chemotherapy, patients in a limited period are improved in survival by using a chest radiotherapy department. Survival can also be significantly improved by subjecting patients in a limited period of time to a Prophylactic (PCI) therapy directed at chemotherapy to achieve complete or partial remission.
Unlike NSCLC, SCLC has few new breakthroughs beyond existing chemoradiotherapy treatment methods, and especially has far inferior effect on SCLC compared to NSCLC in terms of targeted drugs and immunotherapy.
Recently, the U.S. Food and Drug Administration (FDA) awards a lurbinactedin (PM1183) orphan drug designation, which has been shown based on studies to have an Objective Remission Rate (ORR) of 39.3% in patients with advanced Small Cell Lung Cancer (SCLC) after chemotherapy, and a median Overall Survival (OS) of 11.8 months in patients. This brings new therapeutic promise to SCLC patients.
lurbinectin is an ecteinascidin derivative which is independently developed by PharmaMar, is an inhibitor of RNA polymerase II, can selectively inhibit a trans-activated RNA polymerase II-mediated transcription process, has no influence on the activities of RNA polymerase I and mitochondrial RNA polymerase, and also has no influence on the normal transcription process of mRNA. RNA polymerase II is often over-activated in the transcription process of tumor cells, and lubrinectedin can distort and die the tumor cells in the mitosis process and finally reduce the cell proliferation. In some types of tumors, tumor cells, which are particularly sensitive to lurbinedin, rely on a high-speed running transcriptional process to support their proliferation. The tumors comprise small cell lung cancer, BRCA1/2 mutant breast cancer, platinum drug-resistant ovarian cancer, sarcoma caused by chromosome translocation and the like.
However, in clinical application, the lurkinectin is found to have a relatively obvious bone marrow suppression effect, so that the search for a lower drug administration amount is the key for drug development around the lurkinectin.
Disclosure of Invention
In a first aspect of the invention, a pharmaceutical composition for the treatment of a tumor comprises a lurbinedin and a selective NA reuptake inhibitor.
In one embodiment of the invention, the mass ratio of lurbinedin to selective NA reuptake inhibitor in the pharmaceutical composition is 1: 0.01-1.
In another embodiment of the invention, the mass ratio of lurbinedin to selective NA reuptake inhibitor in said pharmaceutical composition is 1: 0.01-0.2. In a preferred embodiment, the mass ratio of lurbinedin to selective NA reuptake inhibitor in the pharmaceutical composition is 1: 0.05.
In the present invention, the selective NA reuptake inhibitor is selected from one or more of maprotiline, mianserin and reboxetine.
In yet another embodiment of the invention, the pharmaceutical composition further comprises one or more of etoposide, cisplatin and irinotecan. The mass ratio of the lurbinedin to the selective NA reuptake inhibitor to the cisplatin is 1:0.01-0.2: 0.1-0.5; preferably 1:0.05: 0.3.
The second aspect of the invention provides the application of the pharmaceutical composition in preparing a medicament for treating tumors.
In one embodiment, the tumor is selected from small cell lung cancer, breast cancer, or ovarian cancer. Further, the tumor is preferably small cell lung cancer.
Selective NA reuptake inhibitors can block Norepinephrine (NA) reuptake by the central presynaptic membrane, but cannot block the reuptake effect of 5-hydroxytryptamine (5-HT). Is generally used for treating depression clinically. The invention unexpectedly discovers that when the compound is used together with lurbinedin, the compound generates an obvious synergistic effect on the aspect of treating the small cell lung cancer, and can play a certain role in relieving the mental stress of a patient while realizing the treatment of the cancer.
Detailed Description
The invention may be further understood by reference to the following examples, which illustrate some methods of making or using. However, it is to be understood that these examples do not limit the present invention. Variations of the invention, now known or further developed, are considered to fall within the scope of the invention as described herein and claimed below.
Example 1 screening of Lurbinectedin in combination with antidepressants on a cell model of SCLC
Preparing a cell suspension from small cell lung cancer cell line H446 cells in a logarithmic growth phase by using an RPMI1640 culture medium; cells were diluted to a density of 4X 104Per ml; then, 96-well plates were inoculated, and 200ul of cell suspension was added per well and cultured in an incubator. After 24h of incubation, a grouping experiment was performed:
administration group 1 was supplemented with 5. mu.g/ml of lurbinactedin (final concentration);
dosing group 2 added maprotiline at 0.5ug/ml (final concentration);
in the administration group 3, imipramine (final concentration) was added at 0.5 ug/ml;
the administration group 4 was supplemented with 0.5ug/ml of cloxetine (final concentration);
in the administration group 5, 0.5ug/ml of venlafaxine (final concentration) was added;
dosing group 6 added 5ug/ml lurbinedin +0.5ug/ml maprotiline (final concentration);
in the administration group 7, 5ug/ml of lurbinectin +0.5ug/ml of imipramine (final concentration) was added;
dosing group 8 added 5ug/ml lurbinedin +0.5ug/ml chloricetin (final concentration);
administration group 9 was supplemented with 5ug/ml lurbinedin +0.5ug/ml venlafaxine (final concentration).
The control group was given the same amount of medium, cultured for 24h, and the proliferation inhibition rate of each group of cells was measured by MTT method, the proliferation inhibition rate being (control OD value-administration OD value)/control OD value × 100%
The specific results are as follows:
proliferation inhibition ratio (%) | |
Administration group 1 | 45.3±1.9 |
Administration group 2 | 3.9±0.7 |
Administration group 3 | 11.2±2.4 |
Administration group 4 | 8.6±1.8 |
Administration group 5 | 5.7±1.1 |
Administration group 6 | 67.1±2.2 |
Administration group 7 | 56.5±1.6 |
Administration group 8 | 49.8±1.4 |
Administration group 9 | 51.7±2.1 |
To screen whether there is a synergistic effect of lurbinactin and an antidepressant in treating SCLC. We screened representative drugs of different antidepressant mechanism pathways, such as the selective NA reuptake inhibitor maprotiline, the tricyclic antidepressant imipramine, the selective 5-HT reuptake inhibitor (SSRI) cloxetine, and the 5-hydroxytryptamine-norepinephrine reuptake inhibitor vindolac, at the same weight ratio. From the results, only imipramine in the antidepressant medicaments has certain effect of inhibiting the proliferation of SCLC cells, and other antidepressant medicaments have no obvious inhibition effect on small cell lung cancer cells when being singly administered. After the antidepressant drug and the lurbinedin are combined, the maprotiline has obvious synergistic effect, and the combination effect of other antidepressant drugs is poor.
Example 2 weight ratio screening of Lurbinectedin in combination with maprotiline on a cell model of SCLC
The test method is the same as that in example 1, the related medicaments with different dosages are added into each group, and the specific results are as follows:
from the results, the lurbinedin and the maprotiline can generate obvious synergistic effect under different weight ratios, wherein the synergistic effect is most obvious when the ratio is 1: 0.05. In addition, we repeated the above experiments in other small cell lung cancer cell lines H20 and H69, which gave results consistent with those in the H446 cell line, which also fully demonstrates the certainty that lurbinedin and maprotiline produce synergistic effects in treating SCLC.
EXAMPLE 3 Effect of pharmaceutical compositions on mouse Small cell Lung cancer model
Collecting about 20g of C57BL mice, half of each, randomly grouping after feeding for 24H, wherein the mice in the model group and the administration group are subcutaneously inoculated with small cell lung cancer cells H4462X 106In each control group, an equal amount of physiological saline was injected. Administration was started one day after lung cancer cell inoculation, and the control group and the model group were injected with physiological saline, and the administration schedule of the administration group was as follows:
administration group 1: intraperitoneal injection of 2.5mg/kg lurbinedin is carried out once a day;
administration group 2: intraperitoneal injection of 0.125mg/kg maprotiline is carried out once a day;
administration group 3: intraperitoneal injection of 0.75mg/kg cisplatin is carried out once a day;
administration group 4: intraperitoneal injection of 2.5mg/kg lurbinedin and 0.125mg/kg maprotiline is carried out once a day;
administration group 5: intraperitoneal injection of 2.5mg/kg lurbinedin, 0.125mg/kg maprotiline and 0.75mg/kg cis-platinum is carried out once a day;
mice were sacrificed 14 days after continuous administration, tumor bodies of each group of tumor-bearing mice were removed, and tumor growth inhibition rates were calculated after weighing, the inhibition rates being (average tumor weight in model group-average tumor weight in administration group)/average tumor weight in model group × 100%
The results are as follows:
tumor weight (g) | Inhibition ratio (%) | |
Model set | 3.31±0.54 | |
Administration group 1 | 2.44±0.37** | 26.4 |
Administration group 2 | 3.14±0.43 | 5.1 |
Administration group 3 | 2.91±0.49* | 11.9 |
Administration group 4 | 1.71±0.33** | 48.7 |
Administration group 5 | 1.35±0.36** | 59.3 |
This summary merely illustrates some embodiments which are claimed, wherein one or more of the features recited in the claims can be combined with any one or more of the embodiments, and such combined embodiments are also within the scope of the present disclosure as if they were specifically recited in the disclosure.
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911231857.3A CN111298122B (en) | 2019-12-04 | 2019-12-04 | Pharmaceutical composition for treating small cell lung cancer and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911231857.3A CN111298122B (en) | 2019-12-04 | 2019-12-04 | Pharmaceutical composition for treating small cell lung cancer and application thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111298122A CN111298122A (en) | 2020-06-19 |
CN111298122B true CN111298122B (en) | 2021-12-21 |
Family
ID=71159689
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911231857.3A Active CN111298122B (en) | 2019-12-04 | 2019-12-04 | Pharmaceutical composition for treating small cell lung cancer and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111298122B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP4578447A1 (en) | 2023-12-27 | 2025-07-02 | Fundação D. Anna de Sommer Champalimaud e Dr. Carlos Montez Champalimaud - Centro De Investigação Da Fundação Champalimaud | Ercc1-xpf complex inhibitor compounds for use in the treatment of cancer |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL293128A (en) | 2019-11-21 | 2022-07-01 | Pharma Mar Sa | Methods for the treatment of small cell lung cancer using lorbinactadine formulations |
TWI855149B (en) * | 2020-09-04 | 2024-09-11 | 西班牙商瑪製藥股份有限公司 | Lurbinectedin combinations |
CN113713111A (en) * | 2021-10-20 | 2021-11-30 | 南华大学附属第一医院 | Medicine composition for treating small cell lung cancer and overcoming chemotherapy resistance of small cell lung cancer |
CN117838853A (en) * | 2023-09-21 | 2024-04-09 | 中国人民解放军海军军医大学 | Application of maprotiline combined with CTLA4 antibody in the preparation of anti-tumor drugs |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103282037A (en) * | 2010-11-12 | 2013-09-04 | 法马马有限公司 | Combination therapy with an antitumor alkaloid |
-
2019
- 2019-12-04 CN CN201911231857.3A patent/CN111298122B/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103282037A (en) * | 2010-11-12 | 2013-09-04 | 法马马有限公司 | Combination therapy with an antitumor alkaloid |
Non-Patent Citations (3)
Title |
---|
PM01183 inhibits myeloid-derived suppressor;Hiromasa Kuroda等;《Immunotherapy》;20170907;805-817 * |
去甲肾上腺素对人肺癌细胞株H460增殖、迁移和侵袭能力的影响;龙晓莉等;《中国临床药理学与治疗学》;20141130;1217-1221 * |
抑郁发生与肺癌患者生存结局关系的研究进展;李慧媛等;《中南大学学报(医学版)》;20190615;685-691 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP4578447A1 (en) | 2023-12-27 | 2025-07-02 | Fundação D. Anna de Sommer Champalimaud e Dr. Carlos Montez Champalimaud - Centro De Investigação Da Fundação Champalimaud | Ercc1-xpf complex inhibitor compounds for use in the treatment of cancer |
Also Published As
Publication number | Publication date |
---|---|
CN111298122A (en) | 2020-06-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111298122B (en) | Pharmaceutical composition for treating small cell lung cancer and application thereof | |
US12178792B2 (en) | Pharmaceutical composition and use thereof in preparing drug for treating tumor multi-drug resistance | |
JP2017513869A (en) | Application of cyclic dinucleotide cGAMP in antitumor | |
WO2022188491A1 (en) | Tumor chemotherapy pharmaceutical composition | |
TWI547277B (en) | Honokiol for the treatment or prevention of bladder cancer growth and metastasis and improve the cachexia new use | |
CN111558044B (en) | Pharmaceutical composition containing sunitinib, and preparation and application thereof | |
CN104758292B (en) | PD-0332991 is preparing the purposes of prevention drug-resistant tumor drug | |
CN103239464B (en) | Application of icarisid II in preparation of sensitizer for chemotherapic medicine | |
CN112089710B (en) | Application of 4-hydroxyisoleucine in preparation of antitumor drugs | |
CN107583054A (en) | Cryptotanshinone pharmaceutical composition and its application in treatment chronic myelocytic leukemia medicine is prepared | |
CN101152192B (en) | Application of 1,3-di-O-galloyl 1-4,6-(S)-HHDP-β-D-glucopyranose in the preparation of antitumor drugs | |
CN105476996A (en) | Application of curcumin and afatinib for combined treatment of non-small cell lung cancer | |
CN101940569A (en) | Pharmaceutical composition containing sorafenib, artemisinin and artemisinin derivatives and application of pharmaceutical composition in preparation of drugs for treating cancers | |
CN104490942B (en) | Application of Phellinus Phellinus as Drug for Treating Tumor | |
CN114177299B (en) | Antitumor pharmaceutical composition containing EZH2 inhibitor and SCD1 inhibitor and application thereof | |
WO2018125950A1 (en) | A combination therapy for treating cancer | |
CN113663081A (en) | Application of Melaleuca and PD-1/PD-L1 inhibitors in the preparation of liver cancer drugs | |
CN101199534B (en) | Anti-tumor function of raw panoxadiol derivative | |
CN107441076B (en) | Combined medicine for treating cancer | |
CN101152193A (en) | Application of 1,3,4-tri-O-galloyl-6-O-caffeoyl-β-D-glucopyranose in the preparation of antitumor drugs | |
CN112043717B (en) | Pharmaceutical composition for treating lung cancer and preparation thereof | |
CN111632149B (en) | Pharmaceutical composition for treating lung cancer and preparation thereof | |
CN117085135B (en) | Use of squalene epoxidase inhibitors in the preparation of drugs for treating endometrial cancer | |
CN107243079A (en) | A kind of pharmaceutical composition containing Rhein and its application in antineoplastic is prepared | |
Zhang et al. | Efficacy of Apatinib Combined with Etoposide for Maintenance Therapy in Extensive Stage Small Cell Lung Cancer |
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 |