CN108853114A - Application in the drug of nifurtimox metastatic encephaloma derived from preparation treating cancer - Google Patents
Application in the drug of nifurtimox metastatic encephaloma derived from preparation treating cancer Download PDFInfo
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Abstract
The present invention provides the applications in a kind of drug of nifurtimox metastatic encephaloma derived from preparation treating cancer, the cancer is preferably lung cancer, breast cancer or cutaneum carcinoma, the nifurtimox is a kind of drug of anti parasitic disease, and the metastatic encephaloma of the cancer is the tumour that the Malignant tumor of bonal metastasis at other positions of body occurs to encephalic, such tumour consequence is serious, lethality is high, but the related drugs of clinical treatment metastatic encephaloma are few, therefore the present invention provides the applications in a kind of drug of nifurtimox metastatic encephaloma derived from preparation treating cancer, greatly solve this technical problem.
Description
Technical field
The present invention relates to the applications in a kind of drug of nifurtimox metastatic encephaloma derived from preparation treating cancer, belong to
Drug field.
Technical background
Metastatic cerebral tumor is usually cancer, especially lung cancer, breast cancer or the most common feature of cutaneum carcinoma.
The ratio of melanoma brain metastes reaches 40%.Brain metastes are advanced non-small cell lung cancer (NSCLC) and breast cancer
The main reason of death.The medicament selection for treating this kind of patient at present is limited, especially after brain metastes occur.
Primary lung cancer is one of most common malignant tumour in China, the most common DISTANT METASTASES IN position of lung cancer first is that brain
Portion.In whole metastatic encephalomas, male is with lung cancer arrangement first, followed by malignant mela noma；Women is also to be arranged with lung cancer
First, followed by breast cancer.Brain is common one of the DISTANT METASTASES IN position of lung cancer, and brain metastes are the main originals for leading to treatment failure
Cause.With the rising of lung cancer morbidity rate, the systematic treating of use, the optimization of advanced image documentation equipment extends total life cycle, lung
The incidence of cancer brain metastes, which is presented, obviously increases trend.Small Cell Lung Cancer (small cell lung cancer, SCLC) first visit
The incidence of brain metastes can reach 80% after being 10%, 2 years, non-small cell lung cancer (non-smallcell lung cancer,
NSCLC) the incidence of brain metastes about 20%, postmortem 40%.
Breast cancer
There is 15-25% patient with breast cancer to have found that central nervous system shifts, and incidence is constantly increasing.In addition,
The prognosis of these patients is poor, and annual rate of depositing is 20%.
Melanoma
Brain metastes are the major clinical challenges that melanoma patients face, this is accounted in metastasis melanin tumor patient
60%.This can generate serious clinical symptoms, and influence overall survival prognosis.Brain metastes (BM) are melanoma patients treatment faces
The challenge faced.There is 60% metastasis melanin tumor patient that this threat to life and serious shadow can occur in its pathological process
Ring the complication of quality of life.Compared with other common metastatic encephalomas such as lung cancer and breast cancer, melanoma metastasis to brain
Risk it is especially high.Median survival interval after brain metastes confirmation is generally within the scope of 3.4 to 13.2 months.
Brain metastes patient's nature median survival interval about 1 month.In this section in patient, the only feasible surgery hand of sub-fraction
Art cuts off metastatic lesion.In the patient that not can be carried out operation, the median survival interval of simple hormone therapy is 1~2 month.
At present still without ratifying the molecular targeted therapy dedicated for NSCLC brain metastes.
The difficulty of brain tumor treatment is that drug needs to can be only achieved therapentic part across blood-brain barrier.Blood-brain barrier
(blood-brain barrier；BBB) be positioned at blood and brain, spinal cord nerve cell between barrier, structure basis is brain
It is continuous type with the capillary in spinal cord, endothelial cell has close connection closing, makes macromolecular without fenestra between endothelial cell
Substance cannot pass through, but water and certain ions can pass through；Complete and continuous capillary basement membrane；Capillary basement membrane has outside
The cutose that astroglia protrusion is formed.Blood-brain barrier is the successful principal element of influence maincenter medicament research and development, several
The macromolecular drug and small-molecule drug greater than 98% for blocking 100%.Act on medicine for central nervous system needs gram
Blood-brain barrier is taken, only reaches enough exposed amounts, competence exertion therapeutic effect in cental system.
A kind of drug of brain metastes derived from treating cancer is clinically needed, which there should be broad-spectrum anti-tumor work
With easily propagating through blood-brain barrier, metastatic encephaloma therapeutic agent curative for effect and of reasonable cost.
Nifurtimox is approved only for treatment trypanosomiasis at present；It is (a kind of once to carry out a treatment neuroblastoma
Out- cranial neoplasms) clinical test, in terms of oncotherapy not yet approval listing, there is no at present people to its brain caused by cancer turn
The effect for moving tumor field is studied.
Nifurtimox (nifurtimox, Bay 2502) is a kind of nitro-aromatics, molecular formula C10H13N3O5S,
Trade name Lampit.Molecular weight is 287.3, and structural formula is shown in Formulas I,
Present nifurtimox is applied in the treatment of South American trypanosomiasis and neuroblastoma.
Disclose the purposes of nifurtimox in cancer treatment for the first time in patent application CN200780017695.2.This
Application relates generally to application of the nifurtimox in terms of neuroblastoma treatment.Neuroblastoma (neuroblastoma,
NB) originating from stomodaeal nervous system by adrenal medella or vertebra, the most common cranium outer solid tumor childhood being.But this applies
Any substantive research contents of nifurtimox treatment intracranial tumors is not disclosed.
In patent application CN201410487143.X, inventor discloses a kind of suitable child patient administration, and significant
Improve the nifurtimox dry suspensoid agent of bioavilability, and preparation method thereof.
In conclusion new tumor therapeutic agent emerges one after another although as the progress of technology.But for brain tumor or
Metastatic encephaloma lacks the factors, still limited success such as sensibility due to blood-brain barrier and to chemicotherapy.Many emerging targetings
Drug still leaves a question open for the effect of metastatic encephaloma although achieving huge progress to the treatment of periphery primary tumor.
Its bigger value may be embodied in the primary tumor for inhibiting periphery, reduce or reduce brain metastes；Once brain occurs to turn
It moves, effect declines to a great extent, and more situations is that it needs further to be confirmed to the effect of intracranial tumors.In addition, these are new out
An existing targeted drug beneficiary group of mean people, medical expense is high, such as the CAR-T cell therapy that Novartis is newly developed, and medical expense is high
Up to 3,000,000 yuan, this is unreachable for Most patients.Therefore, there is broad-spectrum anti-tumor effect, easily propagate through blood
, there is huge demand always in brain barrier, metastatic encephaloma therapeutic agent curative for effect and of reasonable cost, such as Temozolomide,
It is simultaneously also the direction that pharmaceuticals industry is made great efforts.
Summary of the invention
In view of the above technical problems, a kind of nifurtimox metastatic encephaloma derived from preparation treating cancer is inventor provided
Drug in application.
Inventor gives Primary Stage Data and data summarizes, and finds the drug of this anti parasitic disease of nifurtimox at other
Have the function for the treatment of cancer in patent, but be directed to the metastatic encephaloma field that cancer is caused, based between various cancers
Otherness, there has been no being applied researches show that nifurtimox causes the drug in metastatic encephaloma to have in treatment preparation cancer, therefore
The application of the drug in this respect belongs to technological gap.
Metastatic encephaloma field caused by cancer and cancer belongs to pathogenesis and is related, but the disease neck to differ from one another
Domain, for decades, only a kind of standard regimens, i.e. radiotherapy+Temozolomide go through to be applied to brain derived from treating cancer
Metastatic tumor clinically there is no effective therapeutic agent.
And in view of the above technical problems, inventor provide a kind of nifurtimox brain metastes derived from preparation treating cancer
Application in the drug of tumor.
One aspect of the present invention provide mammal (preferably people) of the treatment with metastatic encephaloma derived from cancer by
The method of examination person.This method includes applying nifurtimox compound to the subject with the effective quantity for the treatment of cancer.In any reality
It applies in scheme, subject can not need other indications treated with nifurtimox, i.e. subject does not need additionally to suffer from
Chagas disease or such as some other indication as caused by microorganism infection.This method can also additionally include with chemotherapy,
Operation and/or radiation therapy treatment subject.
The present invention further provides a kind of above-mentioned applications, wherein the cancer is basal-cell carcinoma, cutaneum carcinoma, mammary gland
Cancer, cholangiocarcinoma, bladder cancer, osteocarcinoma, the cancer of the brain or CNS cancer, breast cancer, choriocarcinoma, colon and the carcinoma of the rectum, connective tissue cancer, food
Pipe cancer, cancer eye, fibroma, head and neck cancer, epithelial neoplasm, kidney, laryngocarcinoma, leukaemia, liver cancer, lymthoma, carcinoma of mouth, ovary
Cancer, cancer of pancreas, prostate cancer, rhabdomyosarcoma, cutaneum carcinoma, gastric cancer, carcinoma of testis, thyroid cancer or uterine cancer.
Wherein further preferably, the cancer is that the cancer is cutaneum carcinoma, lung cancer or breast cancer.
Further, the administration route of the drug is the form of oral, intrathecal, encephalic or intramuscular administration.
In a very specific aspect, the composition includes pharmaceutical unit dosage forms, contains and effectively treats above-mentioned phase
Close the Nitrofuran compound of the dosage for the metastatic encephaloma that cancer extends, preferably nifurtimox.
Therapeutic combination of the invention can oral, sublingual, buccally, intranasal, intravenous, intramuscular, intrathecal, encephalic, peritonaeum
Interior, subcutaneous, intradermal, part, rectum, vagina, intrasynovial or intravitreal administration.
The dosage form of the drug is tablet, injection, dry suspensoid agent, powder, emulsion or pill.
The administration route of the drug is for oral, intrathecal, intravenous or intramuscular administration；It is preferred that oral administration formula.
The active drug dosage containing nifurtimox drug is 50-200mg/Kg.
Beneficial effects of the present invention：
The nifurtimox can be applied in the drug of metastatic encephaloma derived from preparation treating cancer, and the effect is visible
The biochemical test part of specific embodiment, nifurtimox for source of people tumour cell growth inhibition effect, and for people
Brain metastasis tumor, human breast cancer cell, Humanmachine tumour have significant inhibiting effect, and tumour can be improved in the drug
Susceptibility of the cell in chemotherapy, is conducive to tumour and further controls.
The present invention will be further described for following embodiment, but the protection model that the embodiment is not intended to limit the invention
It encloses.
Specific embodiment
For nifurtimox compound to treat effective and physiologically acceptable amount application, which is that subject physiologically can
Tolerance, required or enough amounts of realizing desired beneficial organism effect institute, the beneficial biological effect in this case can
Metastatic encephaloma derived from enough treating cancers.It can be for example beneficial to measure by measuring the physiological effect for the treatment of after administering the treatment
Biological effect.Biological beneficial effect can be improvement or completely eliminate general as being treated metastatic encephaloma this field caused by cancer
Logical technical staff can empirically determined specific nifurtimox compound or combined effective quantity, without excessive experiment.
It can cook up by being selected in multiple compounds and weight factor in conjunction with introduction provided herein and not cause great poison
Property however be capable of the effective preventative or therapeutic treatment regime of the specific subject of fully effective treatment, the weight factor is such as
Effect, relative bioavailability, patient's weight, the seriousness of adverse side effect and preferred mode of administration.
Biochemical embodiment 1
Mtt assay measures nifurtimox to the growth inhibition effect of source of people tumour cell
The purpose of this test is to measure cell survival rate using mtt assay, observes nifurtimox in cellular level to a variety of people
The growth inhibition effect of source tumour cell and normal cell, explore its in vitro level on whether have inhibit growth of tumour cell
Effect, action intensity and to sensibility of different type tumour cell etc., for mechanism of action, the safety for exploring tested material
Evaluation and the selection of the dosage regimen in clinical test, tumor kind etc. provide reference information.
Cell strain：People's bone spinal nerve blastoma SH-SY5Y, human neuroblastoma people neuroblast SK-N-SH, people
Brain glioblastoma cell Hs683, neuroglia cell of human oncocyte U251, human brain astrocytes blastoma U87MG, SHG44 cells are thin
Born of the same parents SF126, Non-small cell lung carcinoma cell H460, human liver cancer cell Bel7402, human breast cancer cell line Bcap-37, human gastric cancer are thin
Born of the same parents BGC823, human oral cavity epithelial cancer cell KB, people's immortalized keratinocytes strain HaCaT, human liver cancer cell HepG2, people's kidney
Cancer cell Ketr-3.
Above-mentioned cell is commercial commercial product.
Testing program：The above-mentioned tumour cell for collecting logarithmic growth phase, is configured to certain density single cell suspension, according to
The difference of vitro growth rates, is generally inoculated in 96 orifice plates by 1000-3000/hole, and 100 μ L of cell suspension is added in every hole.Training
After supporting for 24 hours, it is separately added into nifurtimox containing various concentration or positive control drug (Japanese yew liquor-saturated or Temozolomide), continues to cultivate.
After 48~72 hours, the culture solution containing medical fluid is discarded, MTT working solution is added by 0.5mg/ml and (weighs thiazolyl blue MTT 0.05
Gram, it is dissolved in the phosphate buffer (PBS) of 100ml, with 0.22 μm of membrane filtration to remove the bacterium in solution, puts 4 DEG C and be protected from light
Save), every 150 μ L of hole after being incubated for 4h, discards MTT working solution, and 180 μ L of DMSO is added to dissolve MTT and forms formazan
(fomazan) particle.After slight concussion, absorbance OD (545 or 570) value, reference wavelength 450nm, examination are measured with microplate reader
It tests and is repeated 3 times.
Testing index：IC of the nifurtimox to kinds of tumor cells and normal cell50.Experimental result is shown in Table 1.
Half-inhibitory concentration of 1 nifurtimox of table to different cell strains
Note：/ indicate without this data
Above-mentioned data illustrate that nifurtimox has growth inhibition effect for different types of cancer cell, and growth inhibition is made
With effect directly proportional to concentration is used.
Biochemical embodiment 2
Therapeutic effect of the nifurtimox to nu/nu nude mouse lotus human lung cancer metastatic encephaloma H460
Experiment purpose evaluates the nifurtimox (Nifurtimox) of various concentration to nu/nu nude mouse lotus human lung cancer brain metastes
The therapeutic effect of tumor H460.
Experimental material tumor cell line：Human lung cancer H460 cell strain.
Experimental animal：It grows up Nu/Nu nude mice (Beijing Vital River Experimental Animals Technology Co., Ltd.), 18~20g is female
Property.Animal subject raises 5, every cage in sterile independent air-feeding IVC cage.Padding is60The corncob padding of Co radiosterilization,
Partial size 4-6mm.Raise the disinfection feed to prepare exclusively for mouse, free drinking pure water.Temperature is maintained in zoopery room
25 DEG C or so, relative humidity is maintained at 40-70%, daily illumination 12 hours.
Experimental program：Cell is cultivated, by the slow-virus infection H460 comprising pCDH-luc2-GFP plasmid of logarithmic growth phase
Cell (H460-luc2-GFP cell) collected by trypsinisation, and resuspension is washed with PBS, then press PBS:Metrigel=2:1
Ratio, be added Metrigel (U.S. company BD, lot number：4335005), final concentration of cells is made to reach 2 × 107A cell/ml
Suspension.After nude mice anesthesia is fixed, with micro syringe in nude mice cranium brain under slightly biased right side puncture injection, every nude mice injection
20 μ l cell suspensions, i.e., 4 × 105A cell.Biodiversity resources mode is selected, luminous signal in nude mouse is detected.Operation is made
After mould three days, mice with tumor is subjected to IVIS Spectrum CT living imaging, the luminous intensity pair in result is analyzed according to software
Mice with tumor is grouped at random, and is administered.
Experimental result
Tumour multiplication rate and medication effect are calculated using knubble biological luminous intensity.With (Day when experimental group
1) tumour luminous intensity is compared, and after 11 days (Day 11), the tumour luminous intensity of nude mice of control group increases about 2125 times；Sun
Property medicine Temozolomide 30mg/kg treatment group, tumour luminous intensity increase 217 times；Test drug nifurtimox 50mg/kg,
100mg/kg and 200mg/kg treatment group, tumour luminous intensity increase 199 times, 98 times and 63 times respectively, show apparent
Dose-effect relationship.The tumour multiplication rate of each treatment group compared with the control group, significantly reduces (P<0.001).To test knot
When beam (Day 11), the bioluminescence Strength co-mputation tumour inhibiting rate of each group tumor bearing nude mice, positive drug Temozolomide 30mg/kg treatment
The tumour inhibiting rate of group is 83.1%, the tumour inhibiting rate point of test drug nifurtimox 50mg/kg, 100mg/kg and 200mg/kg treatment group
It Wei 84.8%, 95.8% and 98.0%.Therefore the nifurtimox of various concentration is for nu/nu nude mouse lotus human lung cancer brain metastes
Tumor H460 has high inhibition effect.Experimental result is shown in Table 2.
Therapeutic effect of 2 nifurtimox of table to nu/nu nude mouse lotus human lung cancer metastatic encephaloma H460
Compared with the control group, * P<0.05, * * P<0.01, * * * P<0.001；Compared with Temozolomide group,###P<
0.001；Compared with nifurtimox 50mg/kg group,&&P<0.01 (One-way ANOVA and the Tukey ' s compared two-by-two are examined)
Biochemical embodiment 3
Growth inhibition effect of the nifurtimox to the nude mice metastatic encephaloma of human breast cancer cell line Bcap-37
This test of experiment purpose selection human breast cancer cell line Bcap-37 cell strain establishes nude mice metastatic encephaloma model, observes nitre
Furan is not taken charge of to its growth inhibition effect, provides reference for clinical application.
Experimental material
Test sample
Title：Nifurtimox (English name：Nifurtimox).
Experimental system
1, strain：Nu/Nu nude mice (Beijing Vital River Experimental Animals Technology Co., Ltd.).
2, tumor strain：Human breast cancer cell line Bcap-37.
Tumor model building and detection method
Experimental design foundation：Using standard：According to《Cell toxicant series antineoplastic medicament non-clinical study technological guidance's principle》
Carry out experimental design.
The foundation of nude mice intracranial transplantation tumor model：The human breast cancer cell line Bcap-37 of logarithmic growth phase is collected under aseptic condition,
With serum free medium (wisent；Cell density 001-081-CL) is adjusted to 1x 108A/mL, is prepared into cell suspension, sets
It is saved backup in ice water.After nude mice 0.5% yellow Jackets (50mg/kg) intraperitoneal injection of anesthesia, prone position, iodophor disinfection
Skin of head appears skull in mouse overhead midsection about 1.0cm skin, before bregma at 0.5mm, middle line right side 1.5mm
Drilling, drilling use aseptic injection syringe needle (0.7 × 30).Nude mice is fixed on stereotaxic apparatus, spare cell suspension
It is packed into microsyringe, 15 μ L of injection and skin suture notch.
Experimental result
After nifurtimox is administered, tumor bearing nude mice scan image is analyzed using Image J software, test result
As shown in table 3.The result shows that the middle and high dosage group of nifurtimox (100,150mg/kg) exists to the growth inhibition ratio of MCF-7 cell
50% or more, it is for statistical analysis through SPSS 13.0, compared with negative control group, the middle and high dosage group of nifurtimox and TMZ group
Gross tumor volume all has significant difference (P<0.05).Experimental result is shown in Table 3.
Growth inhibition effect test result of 3. nifurtimox of table to human breast cancer cell line Bcap-37 metastatic encephaloma
Compared with negative control group, * P<0.05
Conclusion：Nifurtimox has apparent growth inhibition effect to the nude mice metastatic encephaloma of human breast cancer cell line Bcap-37.
Biochemical embodiment 4
Therapeutic effect of the nifurtimox to Humanmachine tumour SK-MEL-3 metastatic encephaloma
Therapeutic effect of the experiment purpose preliminary assessment nifurtimox to Humanmachine tumour SK-MEL-3 metastatic encephaloma.
Experimental material tumor cell line：Humanmachine tumour SK-MEL-3.
Experimental animal：It grows up Nu/Nu nude mice (Beijing Vital River Experimental Animals Technology Co., Ltd.), 18~20g is female
Property.
Tumor model building and detection method
Experimental design foundation：Using standard：According to《Cell toxicant series antineoplastic medicament non-clinical study technological guidance's principle》
Carry out experimental design.
The foundation of nude mice intracranial transplantation tumor model：The Humanmachine tumour SK-MEL- of logarithmic growth phase is collected under aseptic condition
3, with serum free medium (wisent；Cell density 001-081-CL) is adjusted to 1x 108A/mL, prepares cell suspension, sets
It is saved backup in ice water.After nude mice 0.5% yellow Jackets (50mg/kg) intraperitoneal injection of anesthesia, prone position, iodophor disinfection
Skin of head appears skull in mouse overhead midsection about 1.0cm skin, before bregma at 0.5mm, middle line right side 1.5mm
Drilling, drilling use aseptic injection syringe needle (0.7 × 30).Nude mice is fixed on stereotaxic apparatus, spare cell suspension
It is packed into microsyringe, 15 μ L of injection and skin suture notch.
Experimental result
After nifurtimox is administered, tumor bearing nude mice scan image is analyzed using Image J software, test result
As shown in table 4.The result shows that the middle and high dosage group of nifurtimox (100,150mg/kg) is to the growth inhibition of SK-MEL-3 cell
Rate is for statistical analysis through SPSS 13.0 50% or more, compared with negative control group, the middle and high dosage group of nifurtimox and
TMZ group gross tumor volume all has significant difference (P<0.05).Experimental result is shown in Table 4.
Growth inhibition effect test result of 4. nifurtimox of table to Humanmachine tumour SK-MEL-3 metastatic encephaloma
Compared with negative control group, * P<0.05
Conclusion：Nifurtimox makees the nude mice metastatic encephaloma of Humanmachine tumour SK-MEL-3 with apparent growth inhibition
With.
Biochemical embodiment 5
The synergistic effect of nifurtimox and radiotherapy
Experiment purpose evaluates the synergistic effect of nifurtimox and radiotherapy in human glioma model.
Experimental material tumor cell line：Human glioma cell U87MG-mCherry-luc.
Experimental animal：It grows up Nu/Nu nude mice (Beijing Vital River Experimental Animals Technology Co., Ltd.), 18~20g is female
Property.
Experimental design foundation：According to《Cell toxicant series antineoplastic medicament non-clinical study technological guidance's principle》Experiment is carried out to set
Meter.
Tumor model building and detection method
Experimental program：Cell is cultivated, the human glioma cell U87MG-mCherry-luc of logarithmic growth phase (is come from
Shanghai Ke Yuandi Biotechnology Co., Ltd) collected by trypsinisation is used, and resuspension is washed with PBS, then press PBS:Metrigel=
2:Metrigel (U.S. company BD, lot number is added in 1 ratio：4335005), final concentration of cells is made to reach 2 × 107A cell/
Ml suspension.After nude mice anesthesia is fixed, with micro syringe in nude mice cranium brain under slightly biased right side puncture injection, every nude mice note
Penetrate 20 μ l cell suspensions, i.e., 4 × 105A cell.Biodiversity resources mode is selected, luminous signal in nude mouse is detected.Operation
After modeling three days, mice with tumor is subjected to IVIS Spectrum CT living imaging, the luminous intensity in result is analyzed according to software
Mice with tumor is grouped at random, and administration or x-ray bombardment knurl (conventional fractionation irradiation).
Experimental result is shown in Table 5.
Tumour multiplication rate and medication effect are calculated using knubble biological luminous intensity.With tumour when experimental group
Luminous intensity is compared, and after 14 days, the tumour luminous intensity of nude mice of control group increases about 2114 times；Positive drug Temozolomide
30mg/kg treatment group, tumour luminous intensity increase 315 times；Test drug nifurtimox 50mg/kg treatment group, tumour strong light
411 times of degree；The luminous intensity of x-ray bombardment group increases 675 times；And nifurtimox+x-ray bombardment group is that luminous intensity only increases
85 times are grown.This joint group has excellent tolerance simultaneously, there is no animal dead, and with comparatively ideal brain weight/
Body mass index.
The tumour multiplication rate of each treatment group compared with the control group, significantly reduces.At the end of experiment (the 15th day), respectively
The bioluminescence Strength co-mputation tumour inhibiting rate of group tumor bearing nude mice, the tumour inhibiting rate of positive drug Temozolomide 30mg/kg treatment group are
The tumour inhibiting rate of 82.2%, test drug nifurtimox 50mg/kg treatment group is 79.4% and 50mg/kg nifurtimox+X ray photograph
It penetrates group and has then reached strongest tumour inhibiting rate 94.8%.Therefore nifurtimox and radiotherapy have the inhibiting effect of human glioma cell
There is significant synergistic effect.
Po is oral.
Test result associated with 5 nifurtimox of table and radiotherapy
Compared with the control group, * P<0.05, * * P<0.01, * * * P<0.001
In addition, including people's bone spinal nerve blastoma SH-SY5Y, human lung cancer H460 cell strain, human breast cancer cell
In other vivo tumor models of MCF-7 and Humanmachine tumour SK-MEL-3, it has been found that nifurtimox and radiotherapy are different degrees of
Synergistic effect.These data show that nifurtimox is a kind of potent radiotherapeutic sensitizer.
Gy is X-ray radiation dosage unit.
The summary opinion of biochemical embodiment 1-5 is：Nifurtimox all has high inhibition growth for various tumour cells,
And there is apparent suppression for human lung cancer metastatic encephaloma H460, human breast cancer cell line Bcap-37 and Humanmachine tumour SK-MEL-3
Production is used, and illustrates that nifurtimox has significant tumor-inhibiting action in metastatic encephaloma field, can be applied to preparation treatment kinds cancer
Among the drug of derivative metastatic encephaloma, and in 50-200mg/kg, there is apparent inhibitory effect.In addition, nifurtimox is also
Tumour can be enhanced to the sensibility of radiotherapy, enhance the effect of other drugs or treatment means.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as, it is noted that for those skilled in the art,
Without departing from the inventive concept of the premise, several deformations and transformation can also be made, these belong to protection model of the invention
It encloses, therefore, the scope of protection of the patent of the present invention is determined by the appended claims.
Claims (7)
1. the application in a kind of drug of nifurtimox metastatic encephaloma derived from preparation treating cancer.
2. applying according to claim 1, which is characterized in that the cancer is basal-cell carcinoma, cutaneum carcinoma, breast cancer, gallbladder
Pipe cancer, bladder cancer, osteocarcinoma, the cancer of the brain or CNS cancer, breast cancer, choriocarcinoma, colon and the carcinoma of the rectum, connective tissue cancer, the cancer of the esophagus,
Cancer eye, fibroma, head and neck cancer, epithelial neoplasm, kidney, laryngocarcinoma, leukaemia, liver cancer, lymthoma, carcinoma of mouth, oophoroma, pancreas
Gland cancer, prostate cancer, rhabdomyosarcoma, cutaneum carcinoma, gastric cancer, carcinoma of testis, thyroid cancer or uterine cancer.
3. applying according to claim 2, which is characterized in that the cancer is cutaneum carcinoma, lung cancer or breast cancer.
4. applying according to claim 3, which is characterized in that the cutaneum carcinoma includes melanoma.
5. applying according to claim 1, which is characterized in that the administration route of the drug is oral, intrathecal, encephalic or flesh
The form of interior administration.
6. applying according to claim 1, which is characterized in that the dosage form of the drug be tablet, injection, dry suspensoid agent,
Powder, emulsion or pill.
7. applying according to claim 1, which is characterized in that the nifurtimox is shown in the structure of Formulas I, and molecular formula is
C10H13N3O5The compound of S or its derivative salt
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810275954.1A CN108853114B (en) | 2018-03-30 | 2018-03-30 | Application of nifurolimus in preparation of medicine for treating cancer-derived brain metastasis tumor |
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| CN114377018A (en) * | 2020-10-21 | 2022-04-22 | 中国医学科学院药物研究所 | Application of nifurolimus in preparation of anti-influenza virus medicine |
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| CN114377018A (en) * | 2020-10-21 | 2022-04-22 | 中国医学科学院药物研究所 | Application of nifurolimus in preparation of anti-influenza virus medicine |
| CN114377018B (en) * | 2020-10-21 | 2024-02-06 | 中国医学科学院药物研究所 | Application of nifuraolimus in preparation of anti-influenza virus drugs |
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