CN108853083A - The application of formononetin - Google Patents
The application of formononetin Download PDFInfo
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- CN108853083A CN108853083A CN201810959843.2A CN201810959843A CN108853083A CN 108853083 A CN108853083 A CN 108853083A CN 201810959843 A CN201810959843 A CN 201810959843A CN 108853083 A CN108853083 A CN 108853083A
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- formononetin
- pulmonary fibrosis
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- mouse
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
Abstract
The present invention provides application of the formononetin in the drug of preparation treatment pulmonary fibrosis.Invention provides a kind of new application of formononetin, i.e. application of the formononetin in preparation treatment pulmonary fibrosis disease drug.In the present invention, formononetin has good effect to pulmonary fibrosis, has no adverse reaction, and can slow down the mouse pulmonary fibrosis of bleomycin induced, provides good application prospect for treatment, alleviation or improvement pulmonary fibrosis disease.
Description
Technical field
The present invention relates to field of medicinal chemistry, in particular to the application containing formononetin.
Background technique
Internal organs fibrosis is that fibrous connective tissue increases in the 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.It is broken that fibrosis continuing advances can lead to organ structure
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.It proves 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, gone out so as to cause alveolar and interstitial lung
Now different degrees of inflammation and fibrosis, and then lead to 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 that progressive is had difficulty in breathing with irritation dry cough, the normal continuing advances of the state of an illness,
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 disease incidence is on the rise and without obvious geographical and race differential, the mostly middle-aged and the old in recent years, often
It fell ill at 50~70 years old, children's morbidity is rare.In view of a large amount of clinical setting, the illness rate and disease incidence of IPF is difficult to estimate,
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, have approved within U.S. FDA 2014 Nintedanib and
Pirfenidone is applied to the treatment of IPF patient, domestic to list in approval pirfenidone in 2014, and being that the current country is the only approved controls
Treat the drug of IPF.Although these drugs can delay decline in pulmonary function speed, it is unable to reverse disease progress, and suitable one
Some patientss are not good enough to therapeutic response, and 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, develop for pulmonary fibrosis curative effect confirmation, it is comparatively safe, reasonable price
Drug has important social effect and medical significance.
Formononetin is to be rich in a kind of phytoestrogen of natural plants red clover and traditional Chinese medicine Radix Astragali, it
With blood pressure lowering, adjust the pharmacotoxicological effects such as inflammatory reaction and lipid metabolism.Studies have shown that formononetin is to breast cancer, female
Sexual reproduction system malignant tumour, urological cancer etc. also have anticarcinogenic effect, and mechanism and formononetin are in Several Kinds of Malignancy
In have the effects that inhibit cell Proliferation, induce cell apoptosis, inhibits cell invasion shift effect it is related.So far, it there is no
Formononetin can slow down the relevant report of pulmonary fibrosis.
Summary of the invention
The purpose of the present invention is to provide application of the formononetin in the drug of preparation treatment pulmonary fibrosis.
According to an embodiment of the invention, providing a kind of formononetin answering in the drug of preparation treatment pulmonary fibrosis
It is with, wherein the molecular structural formula of the formononetin：
In above-mentioned application, application of the formononetin in the drug of preparation treatment idiopathic pulmonary fibrosis.
In above-mentioned application, effective therapeutic dose of the formononetin is 80-120mg/kg.
In above-mentioned application, the drug of the treatment pulmonary fibrosis include formononetin and formononetin pharmaceutically
Acceptable salt, ester, hydrate or their combination and auxiliary material.
In above-mentioned application, the dosage form of the drug of the treatment pulmonary fibrosis is selected from tablet, capsule, pill, suppository, gas
Mist agent, oral liquid, granule, powder, injection, syrup, vina, tincture, distillate medicinal water, film or their combination.
In above-mentioned application, the administration mode of the drug of the treatment pulmonary fibrosis include oral, injection, implantation, external application,
Spraying, sucking or their combination.
Invention provides a kind of new application of formononetin, i.e. formononetin treats pulmonary fibrosis disease medicine in preparation
Application in object.In the present invention, formononetin has good effect to pulmonary fibrosis, has no adverse reaction, and it is mould can to slow down rich Lay
The mouse pulmonary fibrosis of element induction provides good application prospect for treatment, alleviation or improvement pulmonary fibrosis disease.
The advantage for the treatment of pulmonary fibrosis medicine provided by the invention is：Formononetin can inhibit the lung fiber of body
Change horizontal, inhibition lung cells epimatrix over-deposit, there is good therapeutic effect to pulmonary fibrosis.In addition, the drug is suffered from
Person is not only acceptant, and small, cheap, from a wealth of sources, the easy acquisition of toxic side effect, is also convenient for understanding patient to drug
Reaction.
Detailed description of the invention
Fig. 1, which shows the mouse weight after different disposal is administered in physiological saline, bleomycin and formononetin, to be changed.
Fig. 2 shows mouse lung collagen content (*, p after formononetin reduction bleomycin induced lung fibrosis
<0.05, i.e., statistically there is significant difference).
Fig. 3 A shows the progressive lung fibrosis that H&E dyeing verifying formononetin inhibits bleomycin induced
(scale:100μm).
Fig. 3 B shows the fibrosis area percentage statistics of lung tissue section, and verifying formononetin inhibits bleomycin
The lung fibrosis of induction.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, those of ordinary skill in the art's every other embodiment obtained belong to what the present invention protected
Range.
The test material and its source that the present invention uses include：
(1) mouse
Male C57BL/6J, (week old 8-10 weeks) wild-type mice：The limited public affairs of tonneau China experimental animal technology are tieed up by Beijing
Department provides.
After animal reaches, animal is received in double corridor barrier environment Mice Residences by special messenger, is filled in《Experimental animal connects
Receive record sheet》(BG-017-V00), animal general condition is observed when reception, and randomly selects animal and weighs, really
It protects experimental animal and introduces standard and coincide substantially.Experimental animal uses credit number：SYXK (saliva) 2012-0003.
(2) test sample
Formononetin is purchased from the biotech inc Chengdu Pu Si, purity：99%.
Bleomycin is purchased from Nippon Kayaku K. K.
Sodium carboxymethylcellulose is purchased from Sangon Biotech (Shanghai) Co., Ltd..
Chloraldurate closes wound chemical reagent distribution centre purchased from Tianjin Bai Ou.
Hydrochloric acid is purchased from Yong Fei chemical reagent Co., Ltd.
Toluene-sodium-sulfonchloramide is purchased from source leaf biology Co., Ltd.
Perchloric acid is purchased from Tianjin Bo Hua chemical reagent Co., Ltd.
Paradime thylaminobenzaldehyde is purchased from ocean Science and Technology Ltd. of Beijing China.
The foundation of 1 mouse pulmonary fibrosis model of embodiment and pharmacodynamics test experience method and step：
1, the foundation of mouse pulmonary fibrosis model
36 mouse are randomly divided into three groups, blank control group (physiological saline group/Normal group), pulmonary fibrosis model
Group (bleomycin), formononetin group (formononetin is administered after modeling), every group 12.
The preparation of pulmonary fibrosis animal model refers to male C57BL/6J, (week old 8-10 weeks) wild-type mice, with 10% water
It closes chloral and gives mouse peritoneal injecting anesthetic by 0.5ml/100g, intratracheal invasive injection 2U/Kg bleomycin.Specific embodiment party
Formula is as follows：It weighs and records after anesthetized mice, mouse is fixed on station, 70% alcohol disinfecting of neck, with scalpel small
Mouse neck vertically scratches about 1cm long wound, using microforceps chorista exposure tracheae, 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 by the metering of 2U/kg
Saline solution, it is immediately that animal is upright and rotate left and right, it is uniformly distributed medical fluid in intrapulmonary.
The physiological saline (0.9%Nacl) of blank control group injection same volume.
2, the drug treatment of pulmonary fibrosis mice
Formononetin treatment refers to when bleomycin handles the 7-14 days (after modeling the 2nd week), passes through stomach-filling daily
Formononetin group mouse 100mg/kg formononetin is given, blank control group and pulmonary fibrosis model group stomach-filling are given identical
The coordinative solvent sodium carboxymethylcellulose (CMC-Na) of volume is as control.Bleomycin detects each group mouse lung after handling 14 days
Collagen content and pulmonary fibrosis severity.
Pharmacodynamics detection and experimental result and evaluation：
1, Lung collagen detects：
That is, hydroxyproline content measures, refers to and inject the 14th day execution mouse in bleomycin, separating mouse right lung is put
Enter 5ml amperes of bottles, 120 DEG C of baking oven drying adjust PH to 6.5-8.0 after hydrochloric acid hydrolysis, filter residue, it is overall that PBS adjustment is added
Product is 10ml, takes 50 μ L samples, and 350 μ L deionized waters are added, and 200 μ L toluene-sodium-sulfonchloramide (Chloramine T) solution room temperatures are added and incubate
It educates 20 minutes, 200 μ L perchloric acid (perchloric acid) is added and are incubated at room temperature 5 minutes, 200 μ L are added to Dimethylaminobenzene
65 DEG C of formaldehyde (P-DMAB) are incubated for 20 minutes.It takes 200 μ L to measure the light absorption value of sample 570nm into 96 orifice plates, utilizes standard items
Reading draws standard curve, and then acquires institute sample Hydroxyproline concentration Cs according to formula obtained by standard curve.By following public affairs
Formula is scaled amount W (μ g/ right lung)=Cs × 8 (institute's sample extension rate) × 10 (samples of hydroxyproline contained by whole right lungs
Total volume).
2, pulmonary fibrosis severity compares：
After bleomycin (2U/Kg) handles the generation of mouse inducing lung fibrosis, formononetin group is in bleomycin processing
Mouse 100mg/kg formononetin, while blank control group and pulmonary fibrosis model group are given by stomach-filling daily within 7-14 days
Stomach-filling gives the coordinative solvent sodium carboxymethylcellulose (CMC-Na) of same volume as control.Each group mouse is at bleomycin
Reason takes lung tissue to observe fibrosis severity after 14 days.
3, experimental result and evaluation：
The Mice Body after different disposal is administered in physiological saline, bleomycin and formononetin is shown with reference to Fig. 1, Fig. 1
Change again.It will be seen from figure 1 that compared to physiological saline group and bleomycin group, body after formononetin group mouse self administration of medication
It reopens and begins slowly to go up.
With reference to Fig. 2, Fig. 2 shows mouse lung collagen contents after formononetin reduction bleomycin induced.From Fig. 2
As can be seen that compared with the bleomycin group for the mouse for giving CMC-Na, hydroxyl dried meat ammonia in the lung tissue of formononetin group mouse
Acid content is substantially reduced, this illustrates that formononetin can reduce the collagen content that bleomycin is induced, and further relates to awns handle
Xanthin is able to suppress collage synthesis in the lung tissue of bleomycin induced.In addition, showing corresponding number in such as the following table 1
According to i.e. physiological saline group, bleomycin group, hydroxyproline content in formononetin group mouse.
The hydroxyproline content (microgram/right lung) of 1 formononetin of table inhibition bleomycin induced
| Physiological saline group | Bleomycin group | Formononetin group |
| 121.93±7.25 | 218.41±10.38 | 139.51±5.72 |
With reference to Fig. 3 A-3B, Fig. 3 A shows the progressive lung that H&E dyeing verifying formononetin inhibits bleomycin induced
Tissue fibrosis (scale:100μm).Fig. 3 B shows the fibrosis area percentage statistics of lung tissue section, verifies rest-harrow
The lung fibrosis of flavine inhibition bleomycin induced.By Fig. 3 A it is found that carrying out H&E dye by being sliced to mouse lung tissue
The mouse pulmonary fibrosis degree of color, discovery formononetin group is lower than the pulmonary fibrosis degree of bleomycin group mouse.By Fig. 3 B
It is found that carrying out the quantitative statistics of fibrosis to lung tissue section, discovery formononetin administration group mouse pulmonary fibrosis area is bright
It is aobvious to be lower than bleomycin group mouse pulmonary fibrosis area.Formononetin administration group mouse pulmonary fibrosis face has been shown in table 2
Product percentage and bleomycin group mouse pulmonary fibrosis area percentage.
The pulmonary fibrosis (percentage) of 2 formononetin of table inhibition bleomycin induced
| Bleomycin group | Formononetin group |
| 24.64±2.55 | 6.81±2.86 |
To which invention provides a kind of new application of formononetin, i.e. formononetin treats pulmonary fibrosis in preparation
Application in disease medicament.In the present invention, formononetin has good effect to pulmonary fibrosis, has no adverse reaction, and can slow down
The mouse pulmonary fibrosis of bleomycin induced provides good application prospect for treatment, alleviation or improvement pulmonary fibrosis disease.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (6)
1. application of the formononetin in the drug of preparation treatment pulmonary fibrosis, wherein the molecule knot of the formononetin
Structure formula is：
2. application according to claim 1, which is characterized in that the formononetin treats idiopathic lung fiber in preparation
Application in the drug of change.
3. application according to claim 1, which is characterized in that effective therapeutic dose of the formononetin is 80-
120mg/kg。
4. application according to any one of claim 1-3, which is characterized in that it is described treatment pulmonary fibrosis drug include
Formononetin and formononetin pharmaceutically acceptable salt, ester, hydrate or their combination and auxiliary material.
5. application according to claim 4, which is characterized in that the dosage form of the drug of the treatment pulmonary fibrosis is selected from piece
Agent, capsule, pill, suppository, aerosol, oral liquid, granule, powder, injection, syrup, vina, tincture,
Distillate medicinal water, film or their combination.
6. application according to claim 4, which is characterized in that the administration mode of drug of the treatment pulmonary fibrosis includes
Oral, injection, implantation, external application, spraying, sucking or their combination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810959843.2A CN108853083A (en) | 2018-08-21 | 2018-08-21 | The application of formononetin |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810959843.2A CN108853083A (en) | 2018-08-21 | 2018-08-21 | The application of formononetin |
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| CN108853083A true CN108853083A (en) | 2018-11-23 |
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| CN201810959843.2A Pending CN108853083A (en) | 2018-08-21 | 2018-08-21 | The application of formononetin |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109806255A (en) * | 2019-02-28 | 2019-05-28 | 天津国际生物医药联合研究院 | Diosmetin is in preparation for treating the application in pulmonary fibrosis disease drug |
| CN110090209A (en) * | 2019-06-11 | 2019-08-06 | 中日友好医院 | Application of the formoononetin in treatment nonalcoholic fatty liver |
| CN110141565A (en) * | 2019-05-10 | 2019-08-20 | 丽水市中心医院 | Application and treatment pulmonary hypertension drug of the formononetin in preparation treatment pulmonary hypertension drug |
| CN113975266A (en) * | 2021-12-17 | 2022-01-28 | 广州医科大学附属第五医院 | Application of formononetin in treating COPD |
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Patent Citations (2)
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| CN102048727A (en) * | 2011-01-11 | 2011-05-11 | 上海交通大学医学院 | Application of formononetin in preparing of medicament for restricting angiogenesis |
| CN104910122A (en) * | 2014-03-14 | 2015-09-16 | 滨州医学院 | Formononetin derivative, preparation method and application thereof |
Non-Patent Citations (2)
| Title |
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| HONGBO LI 等: "Feifukang ameliorates pulmonary fibrosis by inhibiting JAK-STAT signaling pathway", 《BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE》 * |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109806255A (en) * | 2019-02-28 | 2019-05-28 | 天津国际生物医药联合研究院 | Diosmetin is in preparation for treating the application in pulmonary fibrosis disease drug |
| CN110141565A (en) * | 2019-05-10 | 2019-08-20 | 丽水市中心医院 | Application and treatment pulmonary hypertension drug of the formononetin in preparation treatment pulmonary hypertension drug |
| CN110090209A (en) * | 2019-06-11 | 2019-08-06 | 中日友好医院 | Application of the formoononetin in treatment nonalcoholic fatty liver |
| CN113975266A (en) * | 2021-12-17 | 2022-01-28 | 广州医科大学附属第五医院 | Application of formononetin in treating COPD |
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Application publication date: 20181123 |