CN107951871A - The new application of glycosyl modified polyphenolic substance - Google Patents
The new application of glycosyl modified polyphenolic substance Download PDFInfo
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- CN107951871A CN107951871A CN201711247696.8A CN201711247696A CN107951871A CN 107951871 A CN107951871 A CN 107951871A CN 201711247696 A CN201711247696 A CN 201711247696A CN 107951871 A CN107951871 A CN 107951871A
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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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
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Abstract
The invention discloses glycosyl modified polyphenolic substance as rescue paraquat poisoning and the purposes for the treatment of pulmonary fibrosis medicine.The glycosyl modified polyphenolic substance has following structures：
Description
Technical field
The invention belongs to drug field, and in particular to glycosyl modified polyphenolic substance for treating paraquat poisoning and pulmonary fibrosis
Purposes, more particularly to xylose modification pyrogallic acid prepare rescue paraquat poisoning medicine and treatment pulmonary fibrosis medicine
Application in thing.
Background technology
Paraquat, main component 1,1 '-dimethyl -4,4 '-dichloro, two pyridine, is a kind of quick steriland herbicide,
It has people and animals stronger toxicity [1].[2] according to the literature, the paraquat stoste 7-8ml that oral concentration is 20% can be caused
Extremely, case fatality rate is up to 60%~88%, and there are acute lung injury and interstitial lung fibrosis, prognosis by the overwhelming majority in survivor
It is poor.In addition, paraquat poisoning can also the device such as impair cardiac, liver, kidney, adrenal gland, central nervous system, skeletal muscle and spleen
Official, even results in multiple organ dysfunction syndrome (Multiple Organ Disfunction Syndrome, MODS) [3].
In recent years, numerous studies show that the mechanism of paraquat poisoning includes the generation of excessive oxygen radical, inflammatory factor
Release, the reduction of pulmonary surfactant or unbalance and coup injury DNA and inducing cell apoptosis etc.[4].At present, paraquat
Poisoning there is no the antidote of special efficacy, clinically it is main using suit the medicine to the illness the treatment means such as support, hemoperfusion and blood purification come
Improve early symptom, but unsatisfactory curative effect[5].Due to lacking effective treatment means, paraquat poisoning becomes seriously affects the people
The internal medicine Severe acute disease of life and health, its extent of injury greatly exceed Tetramine and organic phosphorus pesticide poisoning[6].Therefore, seek
Effective medicine is looked for become one of the research hotspot in paraquat poisoning field.
Idiopathic pulmonary fibrosis (IPF) is a kind of agnogenic chronic interstitial pulmonary disease, it is with the increasing at age
Long, incidence gradually rises, and has the characteristics that lethality height, poor prognosis, and the median survival interval of patient is only 3 years, clinical table
It is now pulmonary ventilation function decline, interstitial lung inflammatory cell infiltration, alveolar septum are broadening, bronchus chamber collapse and pulmonary insufficiency
Deng[7].At present, the pathogenesis of idiopathic pulmonary fibrosis is not fully understood, and clinically lacks effective treatment means, only with
Glucocorticoid carries out symptomatic treatment, but its therapeutic effect is not good enough, and long-time service side effect is larger[8].2014, U.S. FDA
Ratify pirfenidone and Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, but both medicines can only delay the hair of disease
Exhibition, can not fundamentally treat the disease[9].Therefore, the new drug for finding effective treatment idiopathic pulmonary fibrosis is to grind at present
The hot spot and difficult point studied carefully.
Glycosyl modified polyphenolic substance is this laboratory using xylose and a structure of pyrogallic acid reaction generation
Brand-new micromolecular compound, early-stage study show that such compound has anti-oxidant, weight-reducing and blood fat reducing function well, I
Applied for corresponding patent of invention[10-11].This patent we use it for acute paraquat poisoned and bleomycin induction
The treatment of pulmonary fibrosis, the glycosyl modified polyphenolic substance of the results show have the chmice acute injury of lungs caused by paraquat obvious
Protective effect, mechanism forms with reducing oxygen radical, mitigates oxidative stress and inflammatory reaction, raise GSH and lung group in serum
The content of middle SOD is knitted, the content for reducing MDA and HYP in lung tissue is related；Glycosyl modified polyphenolic substance can effectively press down at the same time
The mouse pulmonary fibrosis of bleomycin induction processed, mechanism is with reducing TGF-β 1, IL-6, α-SMA, P-smad2, I type in lung tissue
The expression of collagen and III Collagen Type VI, raises the content of GSH and SOD in serum, and the content for reducing HYP in lung tissue is related.With reference to
Document
[1]Gawarammana I B,Buckley N A.Medical management of paraquat
ingestion[J].Br J Clin Pharmacol,2011,72(5):745-757.
[2] Xu Lingjie, Wang Zhong paraquats cause acute lung injury Recent Advances in Mechanism [J] clinical emergency magazines, 2013,14
(4)：186-189.
[3]Dinis-Oliveira R J,Duarte J A,Sánchez-Navarro A,et al.Paraquat
poisonings:mechanisms of lung toxicity,clinical features,and treatment[J]
.Crit Rev Toxicol,2008,38(1):13-71.
[4] in Pi Lijuan, Zhu Wei, the mechanism of action of Li Shusheng paraquat poisoning lung injuries and treatment new development [J]
Section's Severe acute disease magazine, 2013,19 (4)：236-238.
[5] Li Xiaoli, Gong Yuan, Zhang Hao, wait the effect of endoxan is to paraquat poisoning cause acute lung injury and security
Analyze [J] China general family medicine, 2013,16 (32)：3124-3125.
[6] Zhang Zhengwei, eastwards, Ruan Yanjun, waits experiment [J] of " Xuebijing Injection " in Treating acute paraquat poisoneds malicious to villous themeda
Magazine of science, 2007,21 (2)：105-108.
[7] Chen Shengmin, Li Peng, Huang Ning, waits angiotensin converting enzyme inhibitors big to bleomycin inducing lung fibrosis
Influence [J] Xinxiang College of Medical Science journal that mouse lung function changes, 2013,30 (12)：937-941.
[8] Huang Cheng is bright, Wang Wenjun, Zhu Huilan, waits andrographolides to cause lung fibrosis in rats lung tissue hydroxyl to bleomycin
Treasure's traditional Chinese medical science traditional Chinese medicines during influence [J] that proline and PDGF are expressed, 2012,23 (4)：904-907.
[9]Karimi-Shah B A,Chowdhury B A.Forced vital capacity in idiopathic
pulmonary fibrosis--FDAreview of pirfenidone and nintedanib[J].N Engl J Med,
2015,372(13):1189-1191.
[10] the handsome of Liu Tianjun, Yang Shu, the Yang Xiao a kind of preparation method and purposes of glycosyl modified polyphenol compound:In
State, 2012105195079 [P] .2012-12-6.
[11] Liu Tianjun, Yang Xiaojiao, big vast pavilion, a kind of oral drug preparations containing glycosyl modified polyphenolic substance of Yang Shu
And purposes:China, 2013103895061 [P] .2013-12-11.
The content of the invention
It is an object of the invention to overcome the deficiencies of the prior art and provide glycosyl modified polyphenolic substance as the grass of rescue hundred
The purposes of withered poisoning medicine.
Second object of the present invention is to provide purposes of the glycosyl modified polyphenolic substance as treatment pulmonary fibrosis medicine.
The purpose of the present invention is achieved through the following technical solutions：
Glycosyl modified polyphenolic substance is preparing the application of rescue paraquat poisoning medicine, glycosyl modified more phenolate
Compound has following structures：
R=H or CH3。
Glycosyl modified polyphenolic substance is preparing the application for the treatment of pulmonary fibrosis medicine, the glycosyl modified polyphenol chemical combination
Thing has following structures：
R=H or CH3。
Experiment proves：The glycosyl modified polyphenolic substance of the present invention has good antioxidation and lung safeguard function,
Cause injury of lungs that there is significant protective effect to paraquat, mechanism is formed with reducing oxygen radical, mitigates oxidative stress and inflammation
Disease is reacted, and raises the content of SOD in GSH and lung tissue in serum, and the content for reducing MDA and HYP in lung tissue is related；The present invention
Glycosyl modified polyphenolic substance can also effectively suppress bleomycin induction mouse pulmonary fibrosis, mechanism with reduce lung tissue
The expression of middle TGF-β 1, IL-6, α-SMA, P-smad2, Type I collagen and III Collagen Type VI, raises the content of GSH and SOD in serum,
The content for reducing HYP in lung tissue is related.
Brief description of the drawings
Fig. 1 is that the existence after the glycosyl modified polyphenolic substance of the embodiment of the present invention 3 treats paraquat poisoning mouse is bent
Line.
Fig. 2 is the average body after the glycosyl modified polyphenolic substance of the embodiment of the present invention 3 treats paraquat poisoning mouse
Weight.
Fig. 3 is the lung tissue after the glycosyl modified polyphenolic substance of the embodiment of the present invention 3 treats paraquat poisoning mouse
HE colored graphs (× 200).
Fig. 4 is the lung tissue after the glycosyl modified polyphenolic substance of the embodiment of the present invention 3 treats paraquat poisoning mouse
Masson dyes (× 200).
Fig. 5 is the serum paddy after the glycosyl modified polyphenolic substance of the embodiment of the present invention 3 treats paraquat poisoning mouse
The sweet peptide of Guang and lung tissue mda content.
Fig. 6 is the lung tissue after the glycosyl modified polyphenolic substance of the embodiment of the present invention 3 treats paraquat poisoning mouse
Superoxide dismutase and hydroxyproline content.
Fig. 7 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Lung tissue HE colored graphs (× 200) afterwards.
Fig. 8 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Lung tissue HE dyeing pulmonary alveolitis classifications afterwards.
Fig. 9 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Lung tissue Masson colored graphs (× 200) afterwards.
Figure 10 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Lung tissue Masson dyeing pulmonary fibrosis classifications afterwards.
Figure 11 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Afterwards in lung tissue IL-6mRNA expression.
Figure 12 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Afterwards in lung tissue TGF-β 1mRNA expression.
Figure 13 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Afterwards in lung tissue Type I collagen mRNA expression.
Figure 14 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Afterwards in lung tissue III collagen mRNA expression.
Figure 15 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
HYP contents in GSH contents and lung tissue in mice serum afterwards.
Figure 16 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
1 content of SOD and TGF-β in mice serum afterwards.
Figure 17 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Afterwards in mouse lung tissue α-SMA albumen immunohistochemistry figure (× 200).
Figure 18 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Afterwards in mouse lung tissue 1 albumen of TGF-β immunohistochemistry figure (× 200).
Figure 19 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 4 treats bleomycin inducing lung fibrosis mouse
Afterwards in mouse lung tissue P-smad2 albumen immunohistochemistry figure (× 200).
Figure 20 is that the mouse after the glycosyl modified polyphenolic substance of the embodiment of the present invention 5 treats paraquat poisoning mouse gives birth to
Deposit rate.
Figure 21 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 6 treats bleomycin inducing lung fibrosis mouse
Lung tissue HE colored graphs (× 200) afterwards.
Figure 22 is that the glycosyl modified polyphenolic substance of the embodiment of the present invention 6 treats bleomycin inducing lung fibrosis mouse
Lung tissue Masson colored graphs (× 200) afterwards.
Embodiment
Below by embodiment, the invention will be further described, its purpose, which is only that, is better understood from present disclosure
The protection domain being not intended to limit the present invention：
The preparation (R=H) of 1 glycosyl modified polyphenolic substance of embodiment
1.8D- xyloses are taken, 9.4g pyrogallic acids are heated to 130 DEG C of meltings, stirring reaction 24h, and purifies and separates obtain
Glycosyl modified polyphenolic substance 4.0g (R=H), yield 87.0%.
Preparation (the R=CH of 2 glycosyl modified polyphenolic substance of embodiment3)
Glycosyl modified polyphenolic substance 3.8g (R=H) prepared by Example 1, adds 20ml ethanol, adds anhydrous carbon
Sour potassium 1.4g and iodomethane 8.6g, 60 DEG C of stirring reaction 5h, purifies and separates obtain glycosyl modified polyphenolic substance 4.0g (R=
CH3), yield 86.4%.
Embodiment 3
The glycosyl modified polyphenolic substance for treating acute paraquat poisoned of the gained of the embodiment of the present invention 1 causes mouse injury of lungs
Experiments in vivo process, includes the following steps：
42 Kunming mouses are randomly divided into blank control group, model group (paraquat 300mg/kg), positive controls (hundred
The withered 300mg/kg+ vitamin C 100mg/kg of grass), low dose therapy group (the glycosyl modified polyphenol chemical combination of paraquat group 300mg/kg+
Thing 200mg/kg), middle dosage treatment group (the glycosyl modified polyphenolic substance 400mg/kg of paraquat group 300mg/kg+), high dose
Treatment group (the glycosyl modified polyphenolic substance 800mg/kg of paraquat group 300mg/kg+).Paraquat stoste adds distilled water to dilute, mouth
Gavage contamination is taken, vitamin C injection is injected intraperitoneally in positive controls when after contamination 24 is small, and treatment group is when after contamination 24 is small
The glycosyl modified polyphenolic substance normal saline solution of oral administration gavage corresponding dosage, blank control group and model group oral administration gavage phase
The physiological saline of same volume.By daily single, continuous 14 days.
It is prepared by serum：Mouse orbit takes blood, and room temperature blood natural coagulation 20min, centrifugation 20min (3000rpm/min), is received
Collect supernatant, -80 DEG C of preservations.
It is prepared by lung homogenate：After the right lung homogenate of mouse, 1600g centrifugation 10min, collect supernatant.
Mouse lung tissue HE is dyed and Masson dyeing：After winning animal lungs, general condition, 10% neutral formalin are observed
It is fixed, embedding, section.HE is dyed：Carry out conventional haematoxylin and eosin stains 10min；Masson is dyed：Ponceaux is acid multiple
Red liquid dyes 10min, is developed a film quarter with 2% glacial acetic acid aqueous solution, 1% phosphomolybdic acid aqueous solution differentiation 5min, without washing directly
5min, the pathomorphism of light Microscopic observation lung tissue are contaminated with aniline blue.
Serum glutathione GSH Activity determinations and lung tissue malonaldehyde MDA Activity determinations：Serum and lung homogenate are taken,
Absorbance measurement is carried out in strict accordance with method as defined in kit, by formula scales into GSH and MDA concentration.
Lung tissue superoxide dismutase SOD and hydroxyproline HYP Activity determinations：Lung homogenate is taken, in strict accordance with examination
Method as defined in agent box carries out absorbance measurement, by formula scales into SOD and HYP concentration.
Statistical method：Data are analyzed using 21.0 softwares of SPSS, and data are represented with ± s, and comparison among groups uses
One-way analysis of variance, inspection level α=0.05, P<0.05 is statistically significant for difference.
The glycosyl modified polyphenolic substance for treating acute paraquat poisoned of the gained of the embodiment of the present invention 1 causes mouse injury of lungs
Experiments in vivo is as a result, including following content：
Mouse survival rate and food-intake observation：Model group occurs dead, the only survival 1 at the tenth day for first day in contamination
Animal；Each treatment group's survival rate is significantly increased, especially high-dose therapy group (glycosyl modified polyphenolic substance 800mg/kg)
Animal survives 4, and weight is significantly higher than model group, illustrates that glycosyl modified polyphenolic substance can rescue acute hundred grass of high concentration
Withered poisoning is (see Fig. 1-2).
Om observation HE is dyed：Model group mouse lung tissue loses normal configuration, and alveolar wall collapses, and has exudation in alveolar space
Thing, telangiectasis, hyperemia；Each treatment group mouse injury of lungs pathological change is obvious compared with model group to be mitigated, and with sugar
Base modifies the increase of polyphenolic substance concentration, and pathological change is gradually reduced；High-dose therapy group mouse alveolar wall collapses obvious few
In positive controls (see Fig. 3).Masson is dyed：Model group mouse lung tissue alveolar spaces are broadening, and extracellular matrix is also obvious
Hyperplasia, has and largely contaminates green collagen fiber hyperplasia deposition, form extensive fibrosis；And each treatment group's mouse pulmonary fibrosis degree
Significantly mitigate compared with model group；High-dose therapy group mouse lung tissue Collagen fiber deposition is less than positive controls (see Fig. 4).
Influence of the glycosyl modified polyphenolic substance to paraquat poisoning mice serum GSH and lung tissue MDA contents：Model group
Mice serum GSH contents significantly reduce (P compared with blank control group<0.001), model group mouse lung tissue MDA contents and sky
White control group, which is compared, dramatically increases (P<0.001)；Treatment group's mice serum GSH contents are bright compared with model group/positive controls
Aobvious rise (P<0.05), treatment group's mouse lung tissue MDA contents significantly reduce (P compared with model group/positive controls<
0.01).The above results prove that glycosyl modified polyphenolic substance can effectively mitigate mouse paraquat poisoning body oxidative stress
Level, reduces damage of the oxygen radical to body (see Fig. 5).
Influence of the glycosyl modified polyphenolic substance to paraquat poisoning mouse lung tissue SOD and HYP content：Model group mouse
Lung tissue SOD contents significantly reduce (P compared with blank control group<0.001), HYP contents significantly increase compared with blank control group
Add (P<0.01)；Treatment group's mouse lung tissue SOD contents significantly raised (P compared with model group/positive controls<0.001),
HYP contents significantly reduce (P compared with model group/positive controls<0.05).The above results prove glycosyl modified polyphenolic substance
Mouse paraquat poisoning body oxidative stress can effectively be mitigated, reduce damage of the oxygen radical to body (see Fig. 6).
Embodiment 4
The glycosyl modified polyphenolic substance for treating bleomycin inducing mouse pulmonary fibrosis of the gained of the embodiment of the present invention 1
Body experimentation, includes the following steps：
Packet and 60 Kunming mouses of modeling are randomly divided into blank control group, model group, positive controls (pirfenidone
80mg/kg), low dose therapy group (glycosyl modified polyphenolic substance 75mg/kg), (the glycosyl modified more phenolate of middle dosage treatment group
Compound 150mg/kg), high-dose therapy group (glycosyl modified polyphenolic substance 300mg/kg), every group 10.Blank control group gas
0.9% sodium chloride injection is instilled in pipe, remaining each group mouse transtracheal gives bleomycin solution 5mg/kg, establishes lung fiber
Change model.Second day after modeling, positive controls oral administration gavage pirfenidone (50mg/kg/ days), treatment group's oral administration gavage is corresponding
The physiology of the glycosyl modified polyphenolic substance normal saline solution of dosage, blank control group and model group oral administration gavage same volume
Brine.By daily single, continuous 21 days.
Sample is obtained put to death animal materials with the 21st day after analysis treatment.Eyeball takes blood, leaves and takes serum and detects；De- neck
Put to death it is quick open mouse thoracic cavity, cut the middle lobe of right lung, 4% neutral formalin is fixed, and observes pulmonary morphology, HE dyeing and
Masson coloring pathological sections, as a result carry out alveolar inflammation scoring, remaining -80 DEG C of lung tissue, which freezes, does index of correlation measure.
HE is dyed：Blank control group mouse lung tissue is clear in structure, and alveolar is complete, and lung interval has no and substantially thickens, anhydrous
Swollen, inflammation and fibrosis performance, alveolar space is interior to ooze out without obvious oedema；Model group mouse lung tissue alveolar structure destroys completely to disappear
Lose, inflammatory cell infiltration, fibr tissue is distributed in bar rope, patch shape；The lung tissue inflammatory cell infiltration area of each treatment group mouse
Domain is significantly reduced compared with model group, and lung tissue structure is substantially complete compared with model group, and pulmonary alveolitis degree and pulmonary fibrosis degree are compared with model
The different degrees of reduction of group (see Fig. 7).
Pulmonary alveolitis degree evaluation pulmonary alveolitis is classified：0 grade, no pulmonary alveolitis；1 grade, slight pulmonary alveolitis, alveolar septa is because of cellular infiltration
Broadening, extent of disease is confined to less than the 20% of full lung；2 grades, moderate pulmonary alveolitis, extent of disease accounts for the 20-50% of full lung；3 grades,
Severe pulmonary alveolitis, is distributed in diffusivity, and extent of disease is more than 50% (see Fig. 8).
Masson is dyed (see Fig. 9) and pulmonary fibrosis degree evaluation (see Figure 10).
Westernblot methods detect the relative expression quantity of lung tissue IL-6, TGF-β 1, Type I collagen and III collagen mRNA,
The result is shown in Figure 1 1-14.
Elisa methods detection Serum glutathione GSH, superoxide dismutase SOD, people shift chemotactic growth factor TGF-β 1
With the content of lung tissue hydroxyproline HYP：Serum is taken, absorbance measurement is carried out in strict accordance with method as defined in kit, by public affairs
Formula is converted into GSH, SOD, TGF-β 1 and HYP concentration, the result is shown in Figure 1 5-16.
α-smooth muscle actin α-SMA, people shift chemotactic growth factor TGF-β 1 in Immunohistochemical Method detection lung tissue
With the expression quantity of P-smad2 albumen, the result is shown in Figure 1 7-19, table 1-3.
1 mouse lung tissue α-SMA protein expressions of table (n=5,)
Compared with blank control group,*P<0.05；Compared with model group,#P<0.05；F=18.201
2 mouse lung tissue TGF-β of table, 1 protein expression (n=5,)
Compared with blank control group,*P<0.05；Compared with model group,#P<0.05；F=10.211
3 mouse lung tissue P-smad2 protein expressions of table (n=5,)
Compared with blank control group,*P<0.05；Compared with model group,#P<0.05；F=18.054
Embodiment 5
The glycosyl modified polyphenolic substance for treating acute paraquat poisoned of the gained of the embodiment of the present invention 2 causes mouse injury of lungs
Experiments in vivo process, includes the following steps：
60 random blank control groups of Kunming mouse, model group (paraquat 300mg/kg), positive controls (paraquat
300mg/kg+ pirfenidone 50mg/kg), low dose therapy group (the glycosyl modified polyphenolic substances of paraquat group 300mg/kg+
200mg/kg), middle dosage treatment group (the glycosyl modified polyphenolic substance 400mg/kg of paraquat group 300mg/kg+), high dose is controlled
Treatment group (the glycosyl modified polyphenolic substance 800mg/kg of paraquat group 300mg/kg+).Paraquat stoste adds distilled water to dilute, and takes orally
Gavage is contaminated, and positive controls oral administration gavage pirfenidone, treatment group when after contamination 24 is small take orally filling when after contamination 24 is small
The glycosyl modified polyphenolic substance normal saline solution of stomach corresponding dosage, blank control group and model group oral administration gavage same volume
Physiological saline.By daily single, continuous 14 days.
Mouse survival rate：There is death in first day in contamination in model group, and only survived 2 animals at the 14th day；Each treatment
Group survival rate is significantly increased, and especially middle high-dose therapy group is survived 6, illustrates that glycosyl modified polyphenolic substance can rescue
High concentration acute paraquat poisoned (see Figure 20).
Embodiment 6
The glycosyl modified polyphenolic substance for treating bleomycin inducing mouse pulmonary fibrosis of the gained of the embodiment of the present invention 2
Body experimentation, includes the following steps：
Packet and 60 Kunming mouses of modeling are randomly divided into blank control group, model group, positive controls (pirfenidone
50mg/kg), low dose therapy group (glycosyl modified polyphenolic substance 75mg/kg), (the glycosyl modified more phenolate of middle dosage treatment group
Compound 150mg/kg), high-dose therapy group (glycosyl modified polyphenolic substance 300mg/kg), every group 10.Blank control group gas
0.9% sodium chloride injection is instilled in pipe, remaining each group mouse transtracheal gives bleomycin solution 5mg/kg, establishes lung fiber
Change model.Second day after modeling, positive controls oral administration gavage pirfenidone (50mg/kg/ days), treatment group's oral administration gavage is corresponding
The physiology of the glycosyl modified polyphenolic substance normal saline solution of dosage, blank control group and model group oral administration gavage same volume
Brine.By daily single, continuous 21 days.
Animal materials are put to death within the 21st day after treatment, it is quick to open mouse thoracic cavity, cut middle lobe of right lung, 4% neutral formalin
It is fixed, observe pulmonary morphology, HE dyeing and Masson coloring pathological sections (see Figure 21-22).
Claims (2)
1. glycosyl modified polyphenolic substance is preparing the application of rescue paraquat poisoning medicine, the glycosyl modified polyphenol chemical combination
Thing has following structures：
R=H or CH3。
2. glycosyl modified polyphenolic substance is preparing the application for the treatment of pulmonary fibrosis medicine, the glycosyl modified polyphenolic substance
With following structures：
R=H or CH3。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110585180A (en) * | 2019-09-25 | 2019-12-20 | 中国热带农业科学院环境与植物保护研究所 | Specific antidote for treating paraquat acute poisoning |
| CN110818638A (en) * | 2019-09-20 | 2020-02-21 | 东南大学 | Nitroxide free radical and preparation method and application thereof |
| CN112294779A (en) * | 2020-11-05 | 2021-02-02 | 中国医学科学院生物医学工程研究所 | New use of glycosyl modified polyphenol compound for preventing and treating acute kidney injury |
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| CN110818638B (en) * | 2019-09-20 | 2022-12-27 | 东南大学 | Nitroxide free radical and preparation method and application thereof |
| CN110585180A (en) * | 2019-09-25 | 2019-12-20 | 中国热带农业科学院环境与植物保护研究所 | Specific antidote for treating paraquat acute poisoning |
| WO2021057721A1 (en) * | 2019-09-25 | 2021-04-01 | 中国热带农业科学院环境与植物保护研究所 | Specific antidotal drug for treating paraquat acute poisoning |
| JP2022549000A (en) * | 2019-09-25 | 2022-11-22 | 中国熱帯農業科学院環境与植物保護研究所 | A specific antidote for the treatment of acute paraquat poisoning |
| CN112294779A (en) * | 2020-11-05 | 2021-02-02 | 中国医学科学院生物医学工程研究所 | New use of glycosyl modified polyphenol compound for preventing and treating acute kidney injury |
| CN112294779B (en) * | 2020-11-05 | 2022-11-29 | 天津海润家和创新医药研究有限责任公司 | New use of glycosyl modified polyphenol compound for preventing and treating acute kidney injury |
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