CN107970237A - Imrecoxib is preparing the application in treating pulmonary fibrosis medicine - Google Patents
Imrecoxib is preparing the application in treating pulmonary fibrosis medicine Download PDFInfo
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- CN107970237A CN107970237A CN201711313962.2A CN201711313962A CN107970237A CN 107970237 A CN107970237 A CN 107970237A CN 201711313962 A CN201711313962 A CN 201711313962A CN 107970237 A CN107970237 A CN 107970237A
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- imrecoxib
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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Abstract
The present invention provides a kind of imrecoxib to prepare the application in treating pulmonary fibrosis medicine, belongs to pharmaceutical technology field, and imrecoxib is preparing the application in treating pulmonary fibrosis medicine.The dosage of the imrecoxib is 100mg/kg.Present invention also offers a kind of pharmaceutical composition, imrecoxib and imrecoxib pharmaceutically acceptable salt, ester, hydrate or combinations thereof and auxiliary material are included.The present invention provides a kind of new application of imrecoxib, i.e. imrecoxib is preparing the application in treating pulmonary fibrosis medicine.Imrecoxib has the effect of good to pulmonary fibrosis in the present invention, has no adverse reaction, and can slow down the mouse pulmonary fibrosis of bleomycin induced, and good application prospect is provided to treat, alleviating or improving pulmonary fibrosis disease.
Description
Technical field
The present invention relates to a kind of new application of imrecoxib, and in particular to imrecoxib is preparing treatment pulmonary fibrosis medicine
In application.
Background technology
Internal organs fibrosis is that fibrous connective tissue increases in organ-tissue as caused by a variety of acute and chronic lesions and essence is thin
The pathological change of born of the same parents' reduction, is the common pathological characters of a variety of chronic diseases.Fibrosis continuing advances can cause organ structure to break
Bad and hypofunction, Organ Failure caused by substantial viscera fibrosis (such as the heart, liver, lung, kidney etc.) is that patient disables, is dead
The main reason for.Prove according to the related statistics in the U.S., in the patient of all kinds of Died Of Diseases of developed country, can return close to 45%
In tissue fibers proliferative disease.Pulmonary fibrosis is internal organs fibrosis important component, it is because of chronic, repeatability and multifocal
Pulmonary parenchyma injury and trigger, maintained and promoted by abnormal epithelio-mesenchymal interaction, so as to cause alveolar and interstitial lung to go out
Now different degrees of inflammation and fibrosis, and then cause lung structure destruction and respiratory failure, so also referred to as interstitial lung disease
(interstitial lung disease, ILD) or diffusivity substance lung disease (diffuse parenchymal lung
Disease, DPLD).
Idiopathic pulmonary fibrosis (Idiopathic pulmonary fibrosis, IPF) belongs to interstitial lung disease
(ILDs) idiopathic interstitial pneumonia in family (IIP) group.IPF is a kind of agnogenic most common and most serious
Chronic inflammation interstitial lung disease, clinical signs are had difficulty in breathing with irritation dry cough, the normal continuing advances of the state of an illness for progressive,
Median survival interval is about 2.8 years, and for 5 years survival rates less than 50%, patient dies of respiratory failure and secondary pulmonary infection more.The world is each
Ground has been reported that its incidence is mostly middle-aged and elderly people, often in continuous ascendant trend and without obvious geographical and race differential in recent years
Fell ill at 50~70 years old, children's morbidity is rare.In view of substantial amounts of clinical setting, the illness rate and incidence of IPF are difficult estimation,
There is the probability of 15-250 in 100000, it is different according to country, age, gender, there are 34000 new cases every year.At present
Lung transplantation is can uniquely to extend the treatment means of pulmonary fibrosis patients life cycle, U.S. FDA have approved within 2014 Nintedanib and
Treatment of the pirfenidone applied to IPF patient, domestic in approval pirfenidone listing in 2014, being that the current country is the only approved controls
Treat the medicine of IPF.Although these medicines can delay decline in pulmonary function speed, reverse disease progress, and suitable one are unable to
Some patientss are not good enough to therapeutic response, its specific pharmacological mechanism is not yet fully apparent from.Therefore the occurrence and development of pulmonary fibrosis are illustrated
Mechanism, explores new potential drug target, and the effect of developing for pulmonary fibrosis confirms, is comparatively safe, reasonable price
Medicine has important social effect and medical significance.
Imrecoxib is the non-steroid anti-inflammatory drug of domestic approval listing in 2011, for treating the pain of relief from osteoarthritis
Pain symptom, analgesic activity is played by suppressing epoxidase (COX).Imrecoxib substantial selectivity suppresses induction type epoxidase COX-
2, so as to suppress the generation of inflammatory prostaglandin, suppress inflammatory reaction, it is very low to structural epoxy enzyme COX-1 inhibitory action, because
This is smaller to the interference of normal Physiological protection function, low to body side effect.Research shows that imrecoxib is combined with chemotherapeutic Lip river uncle
The growth and transfer of non-small cell lung tumor in mouse model can effectively be suppressed.So far, it there is no imrecoxib can
Slow down the relevant report of pulmonary fibrosis.The structural formula of imrecoxib is as follows：
The content of the invention
In view of this, the present invention is intended to provide a kind of new application of imrecoxib, i.e. imrecoxib are preparing treatment lung fibre
Tie up the application in chemical drug thing.
Further, imrecoxib is preparing the application in treating idiopathic pulmonary fibrosis medicine.
Further, the dosage of the imrecoxib is 100mg/kg.
It is pharmaceutically acceptable comprising imrecoxib and imrecoxib present invention also offers a kind of pharmaceutical composition
Salt, ester, hydrate or combinations thereof and auxiliary material.
Further, described pharmaceutical composition be selected from tablet, capsule, pill, suppository, aerosol, oral liquid,
Granule, powder, injection, syrup, vina, tincture, distillate medicinal water, film or combinations thereof.
Further, the administering mode of described pharmaceutical composition include oral, injection, implantation, external application, spraying, suction or
Combinations thereof.
Further, described pharmaceutical composition is prepared using routine or special preparation technique.
Imrecoxib is given present invention also offers the method for the treatment of pulmonary fibrosis disease, including to pulmonary fibrosis patients.
Said medicine group is given present invention also offers the method for the treatment of pulmonary fibrosis disease, including to pulmonary fibrosis patients
Compound.
Relative to the prior art, the present invention has the advantage that：
The present invention provides a kind of new application of imrecoxib, i.e., imrecoxib is in treatment pulmonary fibrosis medicine is prepared
Using.Imrecoxib has the effect of good to pulmonary fibrosis in the present invention, has no adverse reaction, and can slow down the small of bleomycin induced
Mouse pulmonary fibrosis, good application prospect is provided to treat, alleviating or improving pulmonary fibrosis disease.
Brief description of the drawings
Fig. 1 has to go up to a certain degree for imrecoxib administration group mouse weight.
Fig. 2 is mouse lung collagen content after imrecoxib reduction bleomycin induced.
Fig. 3 is mouse pulmonary fibrosis area after imrecoxib reduction bleomycin induced.
Embodiment
With reference to specific embodiment, the present invention is further explained.It is to be understood that these embodiments are merely to illustrate the present invention
Rather than limit the scope of the invention.
Embodiment：Imrecoxib slows down the mouse pulmonary fibrosis of bleomycin induced
Prepared by pulmonary fibrosis animal model refers to male C57BL/6J, (week old 8-10 weeks) wild-type mice, with 10% water
Close chloral and give mouse peritoneal injecting anesthetic, the invasive injection 2U/Kg bleomycin of tracheal strips by 0.5ml/100g.Specific embodiment party
Formula is as follows：Weigh after anesthetized mice record, mouse is fixed on operation console, 70% alcohol disinfecting of neck, with scalpel small
Mouse neck vertically scratches about 1cm long wounds, tracheae is exposed using microforceps chorista, by syringe transtracheal cartilage interannular
Gap enters tracheae towards heart terminal spine, and the bleomycin physiology that volume is adapted with its weight is then slowly injected into by the metering of 2U/kg
Saline solution, immediately by the upright simultaneously left rotation and right rotation of animal, makes liquid be uniformly distributed in intrapulmonary.Blank control group injection same volume
Physiological saline (0.9%Nacl).
Imrecoxib treatment refers to, when bleomycin is handled the 7-14 days, give mouse 100mg/kg by gavage daily
Imrecoxib, using coordinative solvent sodium carboxymethylcellulose (CMC-Na) as control, bleomycin detects lung glue after handling 14 days
Former content and the fibrosis order of severity.
Lung collagen detection is hydroxyproline content measure, refers to inject the 14th day in bleomycin and puts to death mouse, point
From mouse right lung, 5ml amperes of bottles are put into, 120 DEG C of oven for drying, adjust PH to 6.5-8.0 after hydrochloric acid hydrolysis, filter residue, add
It is 10ml to enter PBS adjustment cumulative volumes, takes 50 μ L samples, adds 350 μ L deionized waters, adds 200 μ L toluene-sodium-sulfonchloramides (Chloramine
T) solution is incubated at room temperature 20 minutes, is added 200 μ L perchloric acid (perchloric acid) and is incubated at room temperature 5 minutes, adds 200 μ L
65 DEG C of paradime thylaminobenzaldehyde (P-DMAB) is incubated 20 minutes.Take the extinction of 200 μ L determination sample 570nm into 96 orifice plates
Value, standard curve is drawn using standard items reading, and then it is dense according to formula obtained by standard curve to try to achieve institute's sample hydroxyproline
Spend Cs.The amount W of hydroxyproline contained by whole right lungs is scaled as follows:W=Cs × 8 (institute's sample extension rate) × 10
(population of samples product).
After bleomycin (2U/Kg) processing mouse inducing lung fibrosis occurs, gavage gives mouse 100mg/kg Ai Rui former times
Cloth or corresponding solvent C MC-Na, mouse take lung tissue to observe the fibrosis order of severity, make after bleomycin is handled 14 days
Mould contrast agents are physiological saline.Weight starts slowly to go up (Fig. 1) after imrecoxib group mouse self administration of medication, and with giving CMC-
The mouse of Na is compared, and hydroxyproline content substantially reduces (table 1, Fig. 2) in the lung tissue of imrecoxib group mouse, this explanation Ai Rui
Former times cloth can mitigate the collagen content that bleomycin is induced.Cut into slices to mouse lung tissue and carry out H＆E dyeing, find imrecoxib
The mouse pulmonary fibrosis degree of group is less than CMC-Na groups mouse (Fig. 3 A).The quantitative statistics of fibrosis are carried out to lung tissue section,
It was found that imrecoxib administration group mouse pulmonary fibrosis area is significantly lower than CMC-Na groups mouse (table 2, Fig. 3 B).
Fig. 1：Mouse weight gos up after weight record shows imrecoxib administration.
Fig. 2：Collage synthesis in the lung tissue of Hydroxyproline assay verification imrecoxib suppression bleomycin induced.*, p<
0.05, i.e., statistically there is significant difference.
Fig. 3 A：H＆E dyeing verification imrecoxibs suppress the progressive lung fibrosis of bleomycin induced.Scale:100
μm；Fig. 3 B:Lung tissue section carries out fibrosis area percentage statistics, and verification imrecoxib suppresses the lung group of bleomycin induced
Textured fiber.
1 imrecoxib of table suppresses the hydroxyproline content (microgram/right lung) of bleomycin induced
2 imrecoxib of table suppresses the pulmonary fibrosis (percentage) of bleomycin induced
| Sodium carboxymethylcellulose group | Imrecoxib group |
| 24.64±2.55 | 8.49±1.56 |
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
With within principle, any modification, equivalent replacement, improvement and so on, should all be included in the protection scope of the present invention god.
Claims (9)
1. imrecoxib is preparing the application in treating pulmonary fibrosis medicine.
2. purposes according to claim 1, it is characterised in that：Imrecoxib is preparing treatment idiopathic pulmonary fibrosis medicine
In application.
3. purposes according to claim 1, it is characterised in that：The dosage of the imrecoxib is 100mg/kg.
A kind of 4. pharmaceutical composition, it is characterised in that：Comprising imrecoxib and imrecoxib pharmaceutically acceptable salt, ester,
Hydrate or combinations thereof and auxiliary material.
5. pharmaceutical composition according to claim 4, it is characterised in that：Described pharmaceutical composition be selected from tablet, capsule,
Pill, suppository, aerosol, oral liquid, granule, powder, injection, syrup, vina, tincture, distillate medicinal water, film or
Combinations thereof.
6. pharmaceutical composition according to claim 4, it is characterised in that：The administering mode of described pharmaceutical composition includes mouth
Clothes, injection, implantation, external application, spraying, suction or combinations thereof.
7. pharmaceutical composition according to claim 4, it is characterised in that：Described pharmaceutical composition is using conventional or special
What preparation process was prepared.
A kind of 8. method for treating pulmonary fibrosis disease, it is characterised in that：Including giving imrecoxib to pulmonary fibrosis patients.
A kind of 9. method for treating pulmonary fibrosis disease, it is characterised in that：Including giving claim 4-7 to pulmonary fibrosis patients
Any one of them pharmaceutical composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711313962.2A CN107970237A (en) | 2017-12-12 | 2017-12-12 | Imrecoxib is preparing the application in treating pulmonary fibrosis medicine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711313962.2A CN107970237A (en) | 2017-12-12 | 2017-12-12 | Imrecoxib is preparing the application in treating pulmonary fibrosis medicine |
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| CN107970237A true CN107970237A (en) | 2018-05-01 |
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| CN201711313962.2A Pending CN107970237A (en) | 2017-12-12 | 2017-12-12 | Imrecoxib is preparing the application in treating pulmonary fibrosis medicine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368106A (en) * | 2020-02-25 | 2021-09-10 | 中国医学科学院药物研究所 | Application of Iguratimod in preparation of medicine for preventing and treating idiopathic pulmonary fibrosis |
-
2017
- 2017-12-12 CN CN201711313962.2A patent/CN107970237A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368106A (en) * | 2020-02-25 | 2021-09-10 | 中国医学科学院药物研究所 | Application of Iguratimod in preparation of medicine for preventing and treating idiopathic pulmonary fibrosis |
| CN113368106B (en) * | 2020-02-25 | 2023-09-29 | 渐宽(苏州)生物科技有限公司 | Use of etomod in medicine for preventing and treating idiopathic pulmonary fibrosis |
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Application publication date: 20180501 |