CN109394749A - The new application of Nifuroxazide or its salt - Google Patents
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Abstract
The present invention relates to Nifuroxazide or the new applications of its salt, belong to field of medicaments.To be solved by this invention is the problem of the existing therapeutic agent unsatisfactory curative effect of pulmonary fibrosis, patient dependence difference, purposes of the technical solution there is provided Nifuroxazide or its salt in the drug of preparation treatment and/or prevention pulmonary fibrosis.The present invention confirms that Nifuroxazide has the function of significantly preventing and treating pulmonary fibrosis, and good security by external and experiment in vivo, is a kind of potential treatment drug for pulmonary fibrosis, has biggish clinical value.
Description
Technical field
The present invention relates to Nifuroxazide or the new applications of its salt, belong to field of medicaments.
Background technique
Pulmonary fibrosis (Lung Fibrosis) is with fibroblast proliferation and the aggregation of a large amount of extracellular matrixs and with inflammation
The terminal phase that damage, institutional framework destroy the major class lung disease being characterized changes, that is, normal alveolar tissue is damaged
Lead to textural anomaly by abnormal reparation afterwards (scar is formed).It seriously affects human body respiration function, shows as dry cough, progressive
It has difficulty in breathing (conscious gas is not enough), and with the exacerbation of the state of an illness and pulmonary lesion, breath function due constantly deteriorates.Lung fiber
Change is a kind of multiple and common disease, it can involve each age level.Currently, with factors such as pollution, environmental degradations
Aggravation, number of the infected have increased trend year by year.It is reported that 5 years survival rates of disease are only 50%, prognosis is similar to cancer.
Pulmonary fibrosis process includes the inflammatory damage of lung tissue, institutional framework destruction and then accumulates with pulmonary interstitial cells
The process of tissue reparation come.Many factors can cause pulmonary fibrosis, such as such as occupational dusts, radioactive substance and some drugs
Bleomycin (Bleomycin, BLM) etc..In addition there are the pulmonary fibrosis of a kind of unknown cause of disease, i.e. idiopathic pulmonary fibrosis
(idiopathic pulmonary fibrosis, IPF), although cause is different, development and the basic phase of final result of fibrosis
Seemingly.In the process, lung inflammation cell (predominantly mononuclear macrophage), alveolar epithelial cells, mast cell, endothelial cell and
Pulmonary interstitial cells (such as fibroblast, myofibroblast) pass through the bioactive substances such as secrete cytokines, inflammatory mediator,
Play direct or indirect effect；It is found on morphology, alveolar type II cells fibroblast, macrophage in fibrotic disease
And mast cell is in close contact each other.Therefore, participate in pulmonary fibrosis various kinds of cell together constitute one it is complicated
Pneumonocyte network, mutually influences.A large amount of result of study shows that pulmonary macrophage, alveolar epithelial cells and interstitial lung are thin
Born of the same parents may serve the most key in fibrosis starting and progression.
To the prophylactic treatment of pulmonary fibrosis, because pathogenesis is not yet completely apparent, modern medicine controls the disease
It treats mainly using glucocorticoid, immunosuppressor, antioxidant, cytokine antagonist etc., but sugared skin is used for a long time
Matter hormone, can produce very big hepatorenal damage, further endangers other organs of the mankind, can make human body immunity degradation, makes hidden
New infection is sent out or induced to the lesion hidden, or even a possibility that can increase respiratory failure, and serious secondary infection is
The lethal major reason of pulmonary fibrosis.Currently, clinically treatment is supported primarily directed to IPF complication, such as oxygen uptake, lung function
Energy rehabilitation training, Clinical Trials, lung transplantation technology and prevention gastroesophageal reflux may slow down pulmonary fibrosis progress.Drug is controlled
It treats mould including anticoagulant therapy, colchicin, cyclophosphamide, endothelin receptor antagonists, gamma interferon 1-b, methotrexate (MTX), ring spore
Element, penicillamine, N-acetylcystein and prednisone/imuran/N-acetylcystein combination therapy.Prednisone/sulphur
Azoles purine/N-acetylcystein is widely used in the treatment of IPF, but its safety and validity are still uncertain.Therefore,
Clinically it is badly in need of more drugs for safely and effectively treating pulmonary fibrosis.On pulmonary fibrosis disease incidence is high, the death rate is continuous
It rises, there is no ideal treatment method at present, so prevention and treatment pulmonary fibrosis in recent years becomes focus of attention, it is meant that need more
More drugs for being likely to become clinical treatment pulmonary fibrosis are developed.
Summary of the invention
The purpose of the present invention is to provide Nifuroxazides or its salt in the drug of preparation treatment and/or prevention pulmonary fibrosis
Purposes, to solve the problems, such as that the existing therapeutic agent unsatisfactory curative effect of pulmonary fibrosis, patient dependence are poor.
The present invention provides the purposes of Nifuroxazide or its salt in the drug of preparation treatment and/or prevention pulmonary fibrosis.
Further, Nifuroxazide or its salt are sole active agent in the drug.
Further, the pulmonary fibrosis is pulmonary fibrosis caused by bleomycin.
Further, the pulmonary fibrosis is pulmonary interstitial fibrosis.
Further, the drug is the drug for inhibiting proliferation of lung fibroblast.
Further, the drug is the drug for inhibiting lung's collagen fiber hyperplasia.
Further, the drug reduces the expression of Epithelial and stromal conversion GAP-associated protein GAP α-SMA, Vimentin, increases E-
The expression of Cadherin.
Further, the drug reduces the expression of P-Stat3, MMP9, FAK.
Further, the drug is that pharmaceutically acceptable auxiliary material is added using Nifuroxazide or its salt as active constituent
And/or the preparation that complementary ingredient is prepared.
Further, the drug is oral preparation, ejection preparation or aerosol agent.
The present invention provides the purposes of Nifuroxazide or its salt in the drug of preparation treatment and/or prevention pulmonary fibrosis.
Experiment in vitro show Nifuroxazide can by concentration and it is time dependent in a manner of inhibit mouse embryonic fibroblasts (NIH3T3),
The proliferation of pancreas cancer mankind's alveolar substrate epithelial cell (A549) and source of mouse lung fibroblast can significantly improve the stimulation of TGF-β 1
The expression variation of caused pancreas cancer mankind's alveolar substrate epithelial cell (A549) Epithelial and stromal conversion GAP-associated protein GAP, so that α-
The expression of SMA, Vimentin reduce, and the expression of E-Cadherin increases.Zoopery further proves that Nifuroxazide can be shown
The extent of disease for improving pulmonary fibrosis mice lung is write, pulmonary parenchyma structural damage is mitigated.Moreover, Nifuroxazide is to people's normal hepatocytes
The toxicity of cell is smaller, good security.In conclusion present invention finds Nifuroxazides to have potential prevention and treatment pulmonary fibrosis
Effect, there is significant clinical and social effect.
Detailed description of the invention
Fig. 1 is 1 Nifuroxazide of embodiment to mouse embryonic fibroblasts proliferation inhibition rate figure；
Fig. 2 is 1 Nifuroxazide of embodiment to pancreas cancer mankind's alveolar substrate epithelial cell proliferation inhibiting rate figure；
Fig. 3 is 1 Nifuroxazide of embodiment to source of mouse proliferation of lung fibroblast inhibiting rate figure；
Fig. 4 is the metamorphosis influence diagram that 1 Nifuroxazide of embodiment stimulates TGF-β 1 A549 cell；
Fig. 5 is that 1 Nifuroxazide of embodiment stimulates the Epithelial and stromal of A549 cell to convert the expression of GAP-associated protein GAP TGF-β 1
Influence diagram；
Fig. 6 is the HE colored graph that 2 Nifuroxazide of embodiment treats 28 days mouse lung Pathological morphologic changes；
Fig. 7 is that 2 Nifuroxazide of embodiment treats 28 days mouse lung tissue Masson Macchiavello's staining figures；
Fig. 8 is that 2 Nifuroxazide of embodiment treats 28 days influence diagrams to mouse lung tissue P-Stat3 expression；
Fig. 9 is that 2 Nifuroxazide of embodiment treats 28 days influence diagrams to mouse lung tissue MMP9 expression；
Figure 10 is that 2 Nifuroxazide of embodiment treats 28 days influence diagrams to mouse lung tissue FAK expression；
Figure 11 is 3 Nifuroxazide of embodiment to Human normal hepatocyte proliferation inhibition rate figure.
Specific embodiment
Raw material, equipment used in the specific embodiment of the invention are known product, are obtained by purchase commercial product.
The present invention provides purposes of the Nifuroxazide in the drug of preparation treatment and/or prevention pulmonary fibrosis.
Wherein, Nifuroxazide (alias nifuroxazide, English name Nifuroxazide, Nif), No. CAS: 965-52-6,
Structure is as follows:
In the prior art, Nifuroxazide is mainly used for preventing and treating bacillary dysentery, enteritis, with sulfamido, quinolone
Class drug and other antibiotic are without cross resistance.Then creatively discovery Nifuroxazide also has prevention and treatment pulmonary fibrosis to the present invention
Effect, and this purposes by establishing Evaluation in Vivo and in Vitro model validation Nifuroxazide has biggish clinical application valence
Value.
The cell experiment of 1 Nifuroxazide of embodiment inhibition pulmonary fibrosis
One, experimental principle
Mouse embryonic fibroblasts (NIH3T3), pancreas cancer mankind's alveolar substrate epithelial cell (A549), source of mouse lung is at fibre
The hyper-proliferative of dimension cell will cause the deposition of collagen, so, inhibit their proliferation that can inhibit collagen deposition.
A549 can accelerate its EMT to convert after being stimulated by TGF-β 1, and then accelerate the formation of pulmonary fibrosis, so, inhibit
EMT converts the formation that can reduce pulmonary fibrosis.
This experiment confirms that Nifuroxazide inhibits the effect of pulmonary fibrosis in terms of two above.
Two, experimental method
1, the culture of cell
Mouse embryonic fibroblasts (NIH3T3) high glucose medium of DMEM containing 10%FBS culture；Pancreas cancer mankind's alveolar
Substrate epithelial cell (A549) the 1640 culture medium cultures of 10%FBS；Source of mouse lung fibroblast is trained with the F-12 of 10%FBS
Support base culture.The above cell line is required to that the penicillin and streptomysin of 100U/mL is added in culture and experimentation, and culture exists
Environmental condition is 37 DEG C, in the incubator of 5%CO2.2, the extraction of source of mouse lung fibroblast
From 3 SD rats (180-220g, 8 week old, male) up to large purchase, raised after a week under conditions of SPF grades,
With 5mg/kg bleomycin from bronchus instillation modeling, lung fibroblast is extracted after 2 weeks.First by rat anesthesia (10% water
Close chloral), afterwards by taking out entire lung after abdominal aortic blood, is cleaned with Hanks liquid, get rid of fascia etc..Lung is shredded, is used
Trypsin digestion 45min containing EDTA.Supernatant is taken after taking out the sieve sieving with 70 μM, 1500r/5min centrifugation is gone
Reset and add 500r/5min after culture medium mixes to be centrifuged.It takes 1500r/min after supernatant to be centrifuged, removes supernatant, what is obtained is primary lung
Fibroblast.The third generation is taken to be tested to eighth generation.
3, influence of the mtt assay detection Nifuroxazide to three kinds of cell Proliferations
Three kinds of cells of exponential phase of growth are digested and collected respectively, spread 96 orifice plates, it is normal to cultivate.It chooses logarithmic phase and grows shape
The good cell of state is inoculated with 96 orifice plates, about 1500-2000, every hole cell, every 100 μ L of hole, 37 according to vitro growth rates
DEG C, 5%CO2 incubator culture.Inoculation second day, every hole are added the Nifuroxazide that 100 μ L were diluted with corresponding culture medium, make it
6 multiple holes are arranged in final concentration of 0 μ g/mL, 1.25 μ g/mL, 2.5 μ g/mL, 5 μ g/mL, 10 μ g/mL, 20 μ g/mL, same concentrations,
20 μ L of MTT storing liquid is added after 37 DEG C, 5%CO2 incubator cultivate 24,48,72h respectively, in every hole and is put into incubator culture
2-4h gently siphons away cell supernatant, and every hole is added the DMSO of 150 μ L, is placed on 150r/min on horizontal shaker and rocks 5min,
Microplate reader measures OD value at 570nm.Experiment in triplicate, arranges data, obtains growth inhibition ratio according to absorbance value, calculates
IC50 out.
4, the metamorphosis of pancreas cancer mankind's alveolar substrate epithelial cell (A549) after detection Nifuroxazide stimulates TGF-β 1
Influence
The cell of logarithmic growth phase is chosen, cell is collected in digestion, and supernatant is abandoned in centrifugation, is gently blown and beaten after fresh culture is added
It mixes, cell count is simultaneously uniformly inoculated into the 6 orifice plates for being covered with slide, every hole 2mL cell suspension, after cell density is to be inoculated with
48h control wells can cover with.After inoculation for 24 hours, with the culture medium starvation 6h of serum-free, addition contains the complete of 5ng/mL TGF-β 1
Fresh culture stimulates, and 20 μM of Nifuroxazides are added after 1h and continue to be put into incubator culture.After dosing for 24 hours, 6 orifice plates are taken out, are used
The metamorphosis of inverted microscope white-light visualization cell.
5, the EMT of pancreas cancer mankind's alveolar substrate epithelial cell (A549) converts egg after detection Nifuroxazide stimulates TGF-β 1
The influence of white expression
The cell of logarithmic growth phase carries out cell passage, and the cell density of passage is to grow to 80%- after control group 48h
90% is advisable, and is divided into 4 wares.After for 24 hours, with the culture medium starvation 6h of serum-free, addition contains the complete fresh of 5ng/mL TGF-β 1
Culture medium stimulates, and 20 μM of Nifuroxazides are added after 1h and continue to be put into incubator culture.After dosing for 24 hours, the culture dish of processing is taken out,
It is put on ice for 10min.Liquid is discarded supernatant, is gently washed twice with PBS, 1mL PBS is stayed, is collected with cell scapes thin in ware
Born of the same parents, 4 DEG C of 3000rpm/min are centrifuged 3min, as far as possible blot only supernatant, suitable RIPA lysate is added, is blown with liquid-transfering gun
Beat it is several under, come into full contact with lysate with cell, lytic cell is vortexed once every 10min, vortex 5-6 times, and use ultrasonic wave
Cell pulverization instrument ultrasound 2-3 times.After cell sufficiently cracks, 4 DEG C, 13000rpm/min is centrifuged 3-5min, takes supernatant, uses
Bradford method carries out protein quantification, and 5 × SDS sample-loading buffer is added, and heating 5-10min makes albuminous degeneration, is put into -20 DEG C of guarantors
It deposits.The step of according to PAGE gel kit, prepares 7.5%, 10% or 12.5% gel, and gel strength is according to purpose
The size of albumen determines.Every hole applied sample amount is 50 μ g, 80V electrophoresis 30min or so, switchs to 100V after sample enters separation gel
Electrophoresis 60min or so can stop electrophoresis when sample goes to separation gel bottom.It, will be with separation gel sizableness after electrophoresis
Pvdf membrane be put into methanol and impregnate 10s or so, film is put into transferring film buffer later.By gel and pvdf membrane according to (red
Face) sponge → 3 filter paper → pvdf membrane → gel → 3 filter paper → sponge (black flour) sequence be made transferring film " sandwich " knot
Structure excludes the bubble between each layer, and is rapidly inserted into transferring film folder, and voltage 100V carries out transferring film, and the transferring film time is by destination protein
Molecular size range determines.After transferring film, film is put into Block buffer, room temperature closes 1h.Film TBST after closing
Film washing liquid is washed five minutes, and primary antibody is then diluted to suitable concentration with primary antibody dilution according to antibody specification, film is put into
In primary antibody after dilution, 4 DEG C overnight.It takes the film out and is placed on horizontal shaker later, wash 5 times with TBST film washing liquid, every time
10min dilutes secondary antibody, 37 DEG C of incubation film 1h with confining liquid.Film is taken out, is washed 3-4 times in TBST, ten minutes every time, by developer solution
It drops evenly on pvdf membrane, is exposed in exposure instrument.
Three, experimental result
Nifuroxazide to mouse embryonic fibroblasts (NIH3T3), pancreas cancer mankind's alveolar substrate epithelial cell (A549) and
Experimental result is shown in Fig. 1~3 for the influence of source of mouse proliferation of lung fibroblast.It will be seen from figure 1 that Nifuroxazide can with concentration and when
Between the mode that relies on inhibit NIH3T3 cell Proliferation.Figure it is seen that Nifuroxazide can by concentration and it is time dependent in a manner of
Inhibit pancreas cancer mankind alveolar substrate epithelial cell (A549) proliferation.From figure 3, it can be seen that Nifuroxazide can with concentration and time according to
Bad mode inhibits source of mouse proliferation of lung fibroblast.
The influence of the metamorphosis of pancreas cancer mankind's alveolar substrate epithelial cell (A549) after Nifuroxazide stimulates TGF-β 1
Experimental result is shown in Fig. 4.From fig. 4, it can be seen that A549 cell is polygonal, and endochylema is full, there is born of the same parents in the stimulation of no TGF-β 1
Matter protrusion is in adherent growth, typical epithelial cell form.TGF-β 1 stimulates so that A549 form changes, and presentation is obvious
Interstitial cell form, cell obviously elongates, and becomes long shuttle-type from short fusiform, Cell tracking becomes loose.Nif medicine is being added
After object processing, A549 cell has restored epithelial cell form to a certain extent.
The EMT transforming protein of pancreas cancer mankind's alveolar substrate epithelial cell (A549) is expressed after Nifuroxazide stimulates TGF-β 1
Influence experimental result is shown in Fig. 5.From fig. 5, it can be seen that the stimulation of TGF-β 1 is so that pancreas cancer mankind's alveolar substrate epithelial cell
(A549) the expression variation of the GAP-associated protein GAP of Epithelial and stromal conversion, so that the expression of α-SMA, Vimentin increase, E-
The expression of Cadherin reduces, and Nifuroxazide can improve this variation.
2 Nifuroxazide of embodiment treats the zoopery of the pulmonary fibrosis of bleomycin induction
After bronchus instillation bleomycin, the multifocal necrosis of 1 type alveolar epithelial cells is oozed out with fibroid to be entered
Alveolar.The proliferation and metaplasia of 2 type epithelial cells in 2 to 2 weeks, the fibroblast tissue and interstitial fibers of Alveolar fibrin
Change.Endothelial cell becomes oedema and by big foam and following substrate UF membrane, observes capillary endothelium after 4 weeks
Blistering and interstitial edema.The consistent induction of variation similar with the pulmonary fibrosis of mankind's diffusivity or fibrosing alveolitis shows rich
The damage of bleomycin induction can provide suitable model to study this indefinite disease group.Based on this, C57 mouse is established
Bleomycin inducing lung fibrosis model (CNV) evaluation Nifuroxazide treats the effect of pulmonary fibrosis in vivo.
(1) it anaesthetizes: 10% chloraldurate, by mouse weight 5mL/kg intraperitoneal injection.
(2) Preparatory work of experiment: syringe, surgical instrument and suture, Iodophor, 3mg/kg bleomycin, physiological saline, alcohol
Cotton.
(3) experimental procedure and points for attention:
1) intraperitoneal injection of anesthesia mouse.
2) after mouse anesthesia success, its skin of neck is cut off with aseptic apparatus, exposes bronchus, pays attention to destroy small
Other vital tissues such as mouse blood vessel.
3) after finding its bronchus, 3mg/kg/10mL bleomycin is injected with syringe, is careful not to leak out, is slowly infused
It penetrates and slowly extracts needle point after all bleomycins again, then both hands lift mouse forelimb, uniformly rock up and down, make rich next mould
Element is evenly distributed on its lung.
4) then the skin of neck cut off is sutured with operation suture thread, and sprayed with iodophor disinfection.
5) after the completion of modeling, mouse is lain against in clean cage tool and is recovered, pay attention to warming, observation mouse heartbeat, breathing feelings
Condition prevents from suffocating.
(4) anti-fibrosis drug is assessed using bleomycin model
1) administration route: intraperitoneal injection, solvent group are to give the same dose of solvents after modeling, control group mice with
The physiological saline modeling of equal volume, gives the same dose of solvents.
2) administration time: modeling starts to be administered orally for 24 hours afterwards, and 25mg/kg/ pcs/day of Nifuroxazide, 50mg/kg/ pcs/day,
Successive administration 28 days.
3) evaluation index: after administration 28 days, observation mouse state takes lung tissue to be soaked in Fu Er after weighing and putting to death
In Malin.Afterwards simultaneously by lung tissue paraffin embedding, it is sliced.The histopathology structure of mouse is evaluated with HE dyeing and Masson dyeing
And collagen deposition；The P-Stat3 in lung tissue, the expression variation of MMP9, FAK are evaluated with immunofluorescence dyeing.Experimental result
See Fig. 6~10.
Fig. 6, HE coloration result are shown: control group mice lung tissue structure is completely clear, and alveolar wall, which has no, to be thickened, alveolar space
It is bright, it is intracavitary to have no obvious exudation, no inflammatory cell infiltration, no fibroblast proliferation.Solvent group mouse alveolar structure destroys,
Alveolar septum is broadening, and massive inflammatory cells infiltrated and fibroblast proliferation, pulmonary fibrosis are formed.Each dosage administration of Nifuroxazide
Group improves with solvent group comparable situation, and extent of disease significantly reduces, and pulmonary parenchyma structure is destroyed less.
Fig. 7, Masson (Macchiavello's staining) be as the result is shown: control group mice lung tissue structure is normal；Fibrosis solvent group is small
Mouse is visible around alveolar septum, alveolar wall and bronchioli terminales, respiratory bronchiole and bronchium tube wall
The blue collagenous fibres of a large amount of hyperplasia；Each administration group of Nifuroxazide degree of fibrosis compared with solvent group is light, collagen total content compared with
It is few, show that Nifuroxazide has mitigation collagen fiber hyperplasia, improves the effect of pulmonary interstitial fibrosis.
Showed by immune group result: Fig. 8 compared to control group, increases the expression of P-Stat3 after bleomycin induction
Add, gives the expression that can reduce P-Stat3 after Nifuroxazide.
Fig. 9, immunohistochemical staining as the result is shown: compared to control group, bleomycin induction after the expression of MMP9 is increased
Add, gives the expression that can reduce MMP9 after Nifuroxazide.
Figure 10, immunohistochemistry are shown: compared to control group, after bleomycin induction the expression of FAK being increased, given nitre
The expression of FAK can be reduced after the neat spy of furan.
The hepatotoxicity of 3 Nifuroxazide of embodiment is tested
1. the culture of cell
Human normal hepatocyte (LO2) all uses the culture of the high glucose medium of DMEM containing 10%FBS, in culture and experimentation
It is required to that the penicillin and streptomysin of 100U/mL is added, cultivating in environmental condition is 37 DEG C, in the incubator of 5%CO2.
The influence that 2.MTT method detection Nifuroxazide is proliferated Human normal hepatocyte (LO2)
The good cell of logarithmic phase growth conditions is chosen, is inoculated with 96 orifice plates, every hole about 1500- according to vitro growth rates
2000 cells, every 100 μ L of hole, in 37 DEG C, 5%CO2 incubator culture.100 μ L are added with corresponding training in inoculation second day, every hole
The Nifuroxazide that feeding base diluted makes its final concentration of 0 μ g/mL, 1.25 μ g/mL, 2.5 μ g/mL, 5 μ g/mL, 10 μ g/mL, 20 μ
G/mL, same concentrations are arranged 6 multiple holes and MTT are added in every hole after 37 DEG C, 5%CO2 incubator cultivate 24,48,72h respectively
20 μ L of storing liquid is put into incubator culture 2-4h, gently siphons away cell supernatant, and every hole is added the DMSO of 150 μ L, is placed on water
150r/min rocks 5min on yawing bed, and microplate reader measures OD value at 570nm.Experiment in triplicate, arranges data, according to suction
The growth inhibition ratio that shading value obtains, calculates IC50.
As a result as shown in figure 11, Nifuroxazide does not obviously press down the proliferation of Human normal hepatocyte under 10 μM of concentration
Production is used, and under 20 μM of concentration, there is certain inhibiting effect to Human normal hepatocyte, but with enumerated in embodiment 1 its
Its cell is compared, and toxicity may be significantly smaller.
Claims (10)
1. the purposes of Nifuroxazide or its salt in the drug of preparation treatment and/or prevention pulmonary fibrosis.
2. purposes as described in claim 1, it is characterized in that: Nifuroxazide or its salt are sole active agent in the drug.
3. purposes as claimed in claim 1 or 2, it is characterized in that: the pulmonary fibrosis is pulmonary fibrosis caused by bleomycin.
4. the purposes as described in claims 1 to 3 any one, it is characterized in that: the pulmonary fibrosis is pulmonary interstitial fibrosis.
5. the purposes as described in Claims 1 to 4 any one, it is characterized in that: the drug is that lung fibroblast is inhibited to increase
The drug grown.
6. the purposes as described in Claims 1 to 4 any one, it is characterized in that: the drug is that lung's collagenous fibres is inhibited to increase
Raw drug.
7. the purposes as described in claim 1~6 any one, it is characterized in that: the drug reduces Epithelial and stromal conversion correlation
The expression of protein alpha-SMA, Vimentin increase the expression of E-Cadherin.
8. the purposes as described in claim 1~6 any one, it is characterized in that: the drug reduces P-Stat3, MMP9, FAK
Expression.
9. the purposes as described in claim 1~8 any one, it is characterized in that: the drug is to be with Nifuroxazide or its salt
The preparation that pharmaceutically acceptable auxiliary material and/or complementary ingredient are prepared is added in active constituent.
10. purposes as claimed in claim 9, it is characterized in that: the drug is oral preparation, ejection preparation or aerosol agent.
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| CN111533733A (en) * | 2020-05-11 | 2020-08-14 | 河南省锐达医药科技有限公司 | Preparation method of novel nifuratel series derivatives |
| CN113336729A (en) * | 2021-05-31 | 2021-09-03 | 四川大学华西医院 | Nifuratel derivatives, and preparation method and application thereof |
| CN113336729B (en) * | 2021-05-31 | 2022-05-27 | 四川大学华西医院 | Nifuratel derivatives, and preparation method and application thereof |
| CN116270881A (en) * | 2022-06-07 | 2023-06-23 | 四川大学 | Traditional Chinese medicine composition for treating pneumoconiosis and preparation method thereof |
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Application publication date: 20190301 |