CN106880624A - Purposes of the kutkin nitrone in preventing and treating asthmatic medicament is prepared - Google Patents
Purposes of the kutkin nitrone in preventing and treating asthmatic medicament is prepared Download PDFInfo
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Abstract
The invention belongs to pharmaceutical technology field, purposes of the kutkin nitrone in preventing and treating asthmatic medicament is prepared is specifically disclosed.The present invention sets up the mouse asthmatic animal model of OVA inductions, by Integral animal experiment and isolated tracheal test etc. research method to the anti-inflammatory of kutkin nitrone, anti-oxidant studied with the effect of diastole tracheae.Result of the test confirms that kutkin nitrone can be obviously improved the lung tissue inflammation and its caused lung injury of asthma mice, suppress the generation of inflammatory cytokine, reduce lung it is wet/dry weight ratio and lung permeation index.Superoxide dismutase and the level of glutathione in lung homogenate are improved, the level of lipid peroxidation product MDA is reduced, improves lung's oxidative stress status.Isolated tracheal smooth muscle tension force is reduced, improves tracheospasm.Kutkin nitrone of the invention can prepare the pharmaceutical composition for preventing and treating asthma with pharmaceutically acceptable carrier or excipient as active component.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to kutkin nitrone is in preventing and treating asthmatic medicament is prepared
Purposes.
Background technology
Asthma (asthma) is a kind of chronic airway inflammation worked with various kinds of cell and cellular factor, is one
Kind by foreign protein sensitization and excite produce allergic inflammation disease, common sympton mainly have asthma, shortness of breath,
Uncomfortable in chest, cough etc., main Clinical symptoms includes reversible airflow obstruction, lung and bronchial reaction high
Property, airway inflammation.The pathogenesis of asthma is complex, and the response of helper T lymphocyte, airway inflammation are thin
The secretion of intracellular cytokine, various triggering factors, inherent cause, oxidative stress etc. are participated.Asthma
Shape is general to be broken out and aggravates at night or morning, and patient can be fallen ill within a few minutes, and trouble is had a strong impact on during breaking-out
The quality of life of person.Patient is in asthma attack, it may appear that be short of breath, and breathing is there is also when serious tired
Hardly possible, hypoxemia etc..The incidence of disease of asthmatic patient is gradually increasing, and the quantity in the whole world is more than 300,000,000.
The clinical application for the treatment of asthma at present mainly has inhaled glucocorticoid, β2Receptor stimulating agent, white three
Alkene conditioning agent etc..These medicines only improve SOA, it is impossible to cure, and long-term taking there is also pair
Effect.Although as inhaled glucocorticoid has anti-inflammatory and immunosuppressive action, can only be entered with low dose
Row long-term treatment, long-term use occurs water-sodium retention, withdrawal reaction easily occurs after being discontinued.β2Receive
Body activator can alleviate asthma with oedema under relaxing smooth muscle, reduction vasopermeability, mitigation airway mucus
Symptom, but this class medicine does not suppress the effect of inflammation in air flue, and for a long time, single application β2Acceptor swashs
Dynamic agent can cause cell membrane β2, there is resistance phenomenon in the downward of acceptor.Leukotriene modifer effect is not as good as sugar skin
Matter hormone, clinically many and glucocorticoid carries out drug combination.
In recent years, the active component kutkin for being extracted from Chinese medicine Radix picrorrhizae is increasingly becoming respiratory disorder curative
One focus of thing research.Kutkin (Apocynin), chemical entitled 3- methoxyl groups -4- hydroxy-acetophenones,
Molecular formula is C9H10O3, structure is as follows
Kutkin is a very effective antioxidant and antiinflammatory, energy Selective depression human neutrophils' grain
Cytoactive oxygen (ROS) discharges.Kutkin can be isolated from the root of Chinese medicine Radix picrorrhizae, and it is also wide
It is general to be present in various plants.Research finds that kutkin is related to oxidativestress damage and inflammation anti-in many
Therapeutic action, such as asthma, ALI, arthritis, ischemia apoplexy are played in the disease answered.
Chinese herbal medicine Radix picrorrhizae has been used for the treatment of asthma and injury of lungs in one's early years, and research finds that its active ingredient is recklessly yellow
Lian Suke suppresses the inflammation factor that the human respiratory epithelial cell of TNF-α induction is produced, anti-so as to play
Inflammation effect (Houser KR, Johnson DK, Ishmael FT.Anti-inflammatory effects of
methoxyphenolic compounds on human airway cells[J].Journal of inflammation.
2012,9:6.).To the patients with mild asthma of ozone exposure, suction gives kutkin and can obviously relieve air flue pair
The high response of methacholine and its caused airway constriction (Peters EA, Hiltermann JT, Stolk J.
Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in
asthmatics[J].Free radical biology&medicine.2001,31(11):1442-1447.).In people's II types
In alveolar epithelial cells (A549), kutkin can be by increasing the activity of GC-syn
And increasing the synthesis of glutathion inside cell, this effect partial ground is relevant with the activation of transcription factor AP -1
(Lapperre TS,Jimenez LA,Antonicelli F,Drost EM,Hiemstra PS,Stolk J,MacNee
W,Rahman I.Apocynin increases glutathione synthesis and activates AP-1in
alveolar epithelial cells[J].FEBS letters.1999,443(2):235-239.).Kutkin can also mitigate
The lipopolysaccharide-induced injury of lungs in body lung perfusion model of rat, and its caused inflammatory reaction, apoptosis and core because
The rise of sub- NF- κ B and activation (Chian CF, Chiang CH, Yuan-Jung C, Chuang CH, Liu SL,
Yi-Han J,Zhang HB,Ryu JH.Apocynin attenuates lipopolysaccharide-induced lung
injury in an isolated and perfused rat lung model[J].Shock.2012,38(2):196-202.)。
Research also found that kutkin can dose-dependently mitigate the arthritic symptom of BALB/c mouse, rise
To edema is improved, suppress TNF-α, the generation of the pro-inflammatory cytokine such as IL-1 β, T cell mediation immune response with
And reduce the effect such as vasopermeability (Pandey A, Kour K, Bani S, Suri KA, Satti NK, Sharma P,
Qazi GN.Amelioration of adjuvant induced arthritis by apocynin.Phytotherapy
Research,2009,23(10):1462-1468.).Intraperitoneal injection kutkin can effectively reduce what line brush was caused
Infarct rate (Tang LL, Ye K, Yang XF, Zheng JS.Apocynin after SD rat cerebral ischemias
attenuates cerebral infarction after transient focal ischaemia in rats.Journal of
International Medical Research.2007,35(4):517-522.)。
Kutkin can be by blocking the subunit of nadph oxidase, and specificity suppresses nadph oxidase
Activity, and then suppress its generation superoxide anion, so as to play scavenging activated oxygen, suppress body ROS and produce
Raw effect.This oxidative stress status that can improve relevant disease and inflammatory reaction etc., show certain controlling
Treatment is acted on, but the therapeutic effect of kutkin generally has certain limitation.
Those skilled in the art are devoted to the structural modification and activity research of kutkin always, and design synthesizes
Some Kutkin derivativess, the Patent No. ZL200610037302.1 (derivatives and its system of kutkin
Preparation Method and application) and Patent No. 201010185981.3 (Kutkin derivativess and its preparation and application)
Patent in design synthesized some Kutkin derivativess.
The N- tert-butyl groups-α-phenyinitrone (N-tert-Butyl- α-Phenylnitrone, PBN) is one effective
Free radical scavenger and antioxidant, are often used to modify other compounds to strengthen its antioxygenic property, institute
The derivatization product of acquisition can typically keep original effect of parent, and the anti-oxidant work of parent can be strengthened again
Property.
To sum up, existing asthma medications have much room for improvement in place of still having some deficits, and asthma is main with chronic inflammation
One of therapeutic purpose, inflammation is closely related with oxidative stress, and many researchs are found asthma and controlled from anti-oxidant angle
Treat medicine.The active ingredient kutkin of Chinese medicine Radix picrorrhizae not only has antioxidation activity while having anti-inflammatory to make
With, but its drug effect has much room for improvement.
The content of the invention
The purpose of the present invention is directed to the weak point that existing treatment asthmatic medicament is present, there is provided a kind of Radix picrorrhizae
Purposes of the plain nitrone in preventing and treating asthmatic medicament is prepared.Kutkin raw material is easy to get, abundance, with nitrone
The kutkin nitrone that coupling is obtained shows anti-oxidant and anti-inflammatory double action, with the preventing and treating of significant asthma
Effect.
The object of the invention is achieved through the following technical solutions：
Purposes of the kutkin nitrone of structure shown in formula (I) in preventing and treating asthmatic medicament is prepared,
The medicine is, with kutkin nitrone as active component, to add pharmaceutically acceptable carrier or figuration
The medicament that agent is prepared from.
The compound of this seminar design synthesis is by screening active ingredients, it was demonstrated that the life of kutkin nitrone derivative
Thing activity is better than parent compound kutkin.Therefore, primary study kutkin nitrone derivative of the present invention
Therapeutic action to asthma.Found by studying, inflammatory cell in kutkin nitrone reduction bronchoalveolar lavage fluid
Quantity, inflammatory cytokine increases in suppressing bronchoalveolar lavage fluid, improves lung tissue inflammation；Lung can be reduced to lead to
Saturating index, reduce lung tissue it is wet/dry weight ratio；The infiltration of inflammatory cell in lung tissue can be reduced, makes alveolar structure
It has been recovered that, oedema situation mitigates, and can improve the Pathologic changes of lung injury caused by asthma；Can improve
Superoxide dismutase activity and glutathione content in lung homogenate, and mda content is reduced, improve
Lung tissue oxidative stress status；Tracheal smooth muscle tension force can be also reduced, there is obvious diastole to tracheal smooth muscle
Effect, can alleviate tracheospasm.
, by setting up the BALB/c mouse asthmatic model that ovalbumin (OVA) is induced, observation is recklessly for the present invention
Berberine nitrone is to inflammatory cell, the cell factor in mouse asthma bronchoalveolar lavage fluid (BALF), the penetrating finger of lung
Number (LPI), lung is wet/dry weight ratio, lung tissue superoxide dismutase (SOD) activity, glutathione (GSH)
With the influence of MDA (MDA) level；Using HE dyeing observation kutkin nitrones to mouse asthma lung
The influence of institutional framework and histological scores；And investigate the BALB/c heavy breathings that kutkin nitrone is induced OVA
Breathe heavily the influence of model mice tracheal smooth muscle tension force.In terms of anti-inflammatory, anti-oxidant and improvement airway tone etc. altogether
The purposes in preventing and treating asthmatic medicament is being prepared with kutkin nitrone is proved.
Test result indicate that, kutkin nitrone can reduce inflammatory cell quantity and cell factor in bronchoalveolar lavage fluid
Level, reduce lung permeability, reduce lung it is wet/dry weight ratio, significantly improve the pathological state of mouse asthma.Recklessly
Berberine nitrone can improve superoxide dismutase activity and glutathione content in lung homogenate, and reduce
Mda content, improves the oxidative stress status of lung tissue.Isolated tracheal smooth muscle tension force experimental result shows,
The isolated tracheal smooth muscle of the mouse asthma that kutkin nitrone is induced OVA has obvious diastole to act on, can
Alleviate tracheospasm.After to the section HE dyeing of each group mouse lung tissue, observation finds kutkin nitrone pair
The asthmatic mouse inflammatory cell infiltration of OVA inductions improves significantly with structural damage tool.With
Upper result shows that kutkin nitrone has preferable therapeutic action to asthma, in terms of anti-oxidant and anti-inflammatory
Reach and approached even more excellent effect with positive control drug dexamethasone (2mg/kg), had to isolated tracheal
There is obvious diastole to act on, can reach the 62% of positive control drug isoprel (2mg/kg) effect.
Compared with prior art, the present invention has advantages below and beneficial effect：
In view of the weak point that existing asthma medications are present, and kutkin and nitrone are in anti-inflammatory, anti-
Activity in terms of oxidation and treating asthma, the present invention discloses and nitrone modification is spread out to resulting on kutkin
It is biological --- purposes of the kutkin nitrone in preventing and treating asthmatic medicament is prepared.By by nitrone and kutkin
Structure combines, and makes disclosed kutkin nitrone while having the structure of kutkin and nitrone base,
Further enhanced so as to playing anti-inflammatory, the antioxidation of kutkin simultaneously, and being closed by nitrone base junction
Antioxidation.Purposes of the disclosed kutkin nitrone in preventing and treating asthmatic medicament is prepared, from asthma
Basic symptom --- the treatment of long-term chronic inflammation is started with, and is expected to obtain the asthma medications of the advantage of having more,
Make up the deficiency of existing medicine.
The present invention, to the evaluating drug effect of asthma, is disclosed kutkin nitrone and existed by open kutkin nitrone
The purposes in preventing and treating asthmatic medicament is prepared, it is found that it while have anti-inflammatory, antioxidation, can mitigate tracheae
Spasticity, and curative effect is better than parent compound kutkin, in some anti-oxidant and anti-inflammatory indexs, connects
Closely it is even more than positive control medicine dexamethasone.
Brief description of the drawings
Inflammatory cell quantity in the asthma mice bronchoalveolar lavage fluid that Fig. 1 kutkins nitrone is induced OVA
Influence (n=11；###P<0.001, model group is compared with control group；**P<0.01, * * * P<0.001, control
Treatment group is compared with model group).
TNF in the asthma mice bronchoalveolar lavage fluid that Fig. 2 kutkins nitrone is induced OVA
α, IL-4, the influence (n=11 of the content of interleukin-11 3；###P<0.001, model group and control group phase
Than；***P<0.001, treatment group is compared with model group).
Asthma mice lung that Fig. 3 kutkins nitrone is induced OVA is wet/dry weight ratio, lung permeation index
Influence (n=11；###P<0.001, model group is compared with control group；**P<0.01, * * * P<0.001,
Treatment group is compared with model group).
The change of asthma mice pathologic state colony and pathology that Fig. 4 kutkins nitrone is induced OVA
Influence (HE, × 20 times of scoring；N=5；##P<0.01, model group is compared with control group；*P<0.05,
**P<0.01, treatment group is compared with model group).
It is asthma mice lung homogenate GSH-PX activity that Fig. 5 kutkins nitrone is induced OVA, super
Influence (the n=11 of superoxide dismutase, MDA level；###P<0.001, model group is compared with control group；
**P<0.01, * * * P<0.001, treatment group is compared with model group).
Diastole effect (the n=of the asthma mice isolated tracheal that Fig. 6 kutkins nitrone is induced OVA
11；###P<0.001, model group is compared with control group；***P<0.001, treatment group is compared with model group).
Specific embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiment party of the invention
Formula not limited to this.
Embodiment 1
Female BAl BIc/c mouse, body weight 20-25g, 6-8 week old, is randomly divided into Normal group, OVA
Model group, kutkin (Apo) group, kutkin nitrone (AN-1) basic, normal, high dosage group, sun
Property agent dexamethasone (Dex) group, every group 11.23 ± 2 DEG C are placed in, lighting hours is 12h/ days rings
In border, animal adapts to environment and starts experiment after one week.Daystart is tested, in addition to Normal group, respectively
The group equal intraperitoneal injection of animal contains the μ g of ovalbumin (OVA) 10, the phosphate buffer of aluminium hydroxide 1mg
(PBS) 200 μ l, interval once continues 3 weeks in 7 days, and Normal group is replaced with isometric PBS.The
21 days start, and in addition to Normal group, each group mouse are placed in transparent airtight container, give exciting liquid (to contain
Having the PBS of 20g/L OVA) atomization excites, and once a day, a 30min continues 3 days, normal right
Exciting liquid is replaced with PBS according to group.1 hour before each exciting step, each group is given in intraperitoneal injection mode
Medicine.Positive drug group gives dexamethasone (2mg/kg), and kutkin group gives kutkin 27mg/kg,
The basic, normal, high dosage group of kutkin nitrone give respectively kutkin nitrone 21.5mg/kg, 43mg/kg,
86mg/kg, Normal group and model group give the PBS of equal volume, continue 3 days.To each group mouse lung
Inflammatory cell is counted in bubble irrigating solution (BALF), using inflammatory cell in ELISA method detection BALF
The content of the factor, determine lung tissue it is wet/dry weight ratio, lung permeation index (LPI), lung tissue section is carried out
Histopathological examination, to evaluate therapeutic action of the kutkin nitrone to asthma induced mice lung tissue inflammation.
Kutkin nitrone can significantly improve lung tissue inflammation, and specific experiment result is as follows：
(1) on the basis of Normal group mouse, eosinophil in model group mouse asthma BALF,
Neutrophil leucocyte and lymphocyte these three inflammatory cell quantity increase severely.Described kutkin nitrone is to asthma
The inflammatory cell quantity of mouse BALF increases has obvious inhibitory action, as a result as shown in Figure 1.With model
Group is compared, and positive drug group mouse inflammatory cell quantity is substantially reduced, and the asthma treated through kutkin nitrone is small
Inflammatory cell quantity is in different degrees of decline with doses change in mouse BALF, and it is poor that effect is respectively provided with pole conspicuousness
Different (P ＜ 0.001).The effect of kutkin nitrone group is better than parent compound kutkin group.
(2) compared with Normal group mouse, the tumor necrosis factor α in model group mouse asthma BALF
(TNF-α), IL-4 (IL-4), the content of interleukin-11 3 (IL-13) substantially increase.Positive drug
TNF-α, IL-4, IL-13 level value in group and kutkin nitrone treatment group mouse asthma BALF compared with
Model group is decreased obviously, and has pole significant difference (P ＜ 0.001).Kutkin nitrone reduces mouse lung group
The effect of the tissue inflammation factor is significantly better than kutkin (P ＜ 0.01 or 0.001)), and middle and high dosage group
Effect there was no significant difference with positive drug dexamethasone effect, as a result as shown in Figure 2.
(3) kutkin nitrone each group mouse lung it is wet/dry weight ratio measurement result shows, model group mouse it is wet
/ dry weight ratio is significantly increased compared with Normal group.After being treated through kutkin nitrone, mouse lung is wet/dry weight ratio
It is obviously reduced compared with model group, illustrates that lung tissue water content reduces, oedema degree mitigates, as a result as shown in Figure 3.
There was no significant difference with parent compound for kutkin nitrone effect, and three effects and positive drug of dosage group
Also there was no significant difference for thing group.
(4) model group lung permeation index is greatly increased, and is 4.9 times of Normal group.Compared with model group,
Positive drug group lung permeation index reduces 43%, and kutkin nitrone treatment group LPI reduces 17%-33%.Institute
The kutkin nitrone stated can well reduce lung permeation index at high doses, reduce blood vessel caused by OVA
Permeability increase, as a result as shown in Figure 3.Kutkin nitrone high dose group has extremely aobvious compared with model group
Sex differernce (P ＜ 0.01) is write, there was no significant difference with positive drug group.
(5) histopathological examination result shows that the lung tissue of Normal group has no inflammatory cell, alveolar knot
Structure is normal, and a large amount of cell infiltrations, alveolar bleeding, alveolar wall thickening, knot occurs in model group mouse lung tissue
Structure is destroyed, tunica mucosa bronchiorum oedema.After intervening through kutkin, kutkin nitrone and dexamethasone,
Inflammatory conditions make moderate progress, and alveolar structure has recovered, oedema situation mitigate, and degree of alleviation according to
Kutkin group<Kutkin nitrone low dose group<Kutkin nitrone middle dose group<Kutkin nitrone is high
Dosage group<Sequentially, histological scores also taper off trend positive drug Dexamethasone group, as a result see figure
4.Compared with model group, the histological scores of the middle and high dosage group of kutkin nitrone significantly reduce (P<0.01
Or 0.001).The histological scores of kutkin nitrone group are significantly lower than parent compound group (P<0.05),
There was no significant difference with positive drug group for the effect of its high dose group improvement pathologic change.
Embodiment 2
Female BAl BIc/c mouse, body weight 20-25g, 6-8 week old, is randomly divided into Normal group, OVA
Model group, kutkin (Apo) group, kutkin nitrone (AN-1) basic, normal, high dosage group, sun
Property agent dexamethasone (Dex) group, every group 11.23 ± 2 DEG C are placed in, lighting hours is 12h/ days environment
In, animal adapts to environment and starts experiment after one week.Daystart is tested, in addition to Normal group, each group
The equal intraperitoneal injection of animal contains the μ g of ovalbumin (OVA) 10, the phosphate buffer of aluminium hydroxide 1mg
(PBS) 200 μ l, interval once continues 3 weeks in 7 days, and Normal group is replaced with isometric PBS.The
21 days start, and in addition to Normal group, each group mouse are placed in transparent airtight container, give exciting liquid (to contain
Having the PBS of 20g/L OVA) atomization excites, and once a day, a 30min continues 3 days, normal right
Exciting liquid is replaced with PBS according to group.1 hour before each exciting step, each group is given in intraperitoneal injection mode
Medicine.Positive drug group gives dexamethasone (2mg/kg), and kutkin group gives kutkin 27mg/kg,
The basic, normal, high dosage group of kutkin nitrone give respectively kutkin nitrone 21.5mg/kg, 43mg/kg,
86mg/kg, Normal group and model group give the PBS of equal volume, continue 3 days.Examined using kit
Survey the water of superoxide dismutase (SOD), glutathione (GSH) and MDA (MDA) in lung tissue
It is flat, to evaluate the therapeutic action of the oxidative damage that kutkin nitrone causes to asthma.
Compare with Normal group, under SOD, GSH activity are notable in the homogenate of asthmatic model group mouse lung tissue
Drop, MDA levels increase.Compared with model group, positive drug group SOD in Mice rises with GSH levels,
MDA levels decline, and the mouse asthma SOD activity and GSH levels treated through kutkin nitrone are improved,
The reduction of MDA levels, there is pole significant difference (P<0.001).Result is pointed out, kutkin nitrone energy
The decline and the rising of MDA levels of GSH, SOD level in asthma mice lung tissue are reversed, effectively
Improve mouse lung internal oxidition stress effect, to increase the curative effect to asthma, as a result as shown in Figure 5.Radix picrorrhizae
The effect that plain nitrone increases GSH and SOD is substantially better than parent compound (P<0.01)；And each dosage group
Effect is significantly better than positive control medicine (P<0.001).Kutkin nitrone reduction MDA ability with
There was no significant difference for parent compound；Low, middle dose group effect is weaker than positive control medicine, during high dose
There was no significant difference with positive control medicine.
Embodiment 3
Female BAl BIc/c mouse, body weight 20-25g, 6-8 week old, is randomly divided into Normal group, OVA
Model group, kutkin (Apo) group, kutkin nitrone (AN-1) basic, normal, high dosage group, sun
Property medicine isoprel group, every group 11.It is placed in 23 ± 2 DEG C, during lighting hours is 12h/ days environment,
Animal adapts to environment and starts experiment after one week.Daystart is tested, in addition to Normal group, each group animal
Equal intraperitoneal injection contains the phosphate buffer (PBS) of the μ g of ovalbumin (OVA) 10, aluminium hydroxide 1mg
200 μ l, interval once continues 3 weeks in 7 days, and Normal group is replaced with isometric PBS.Open within 21st day
Begin, in addition to Normal group, each group mouse is placed in transparent airtight container, give exciting liquid (to contain 20g/L
The PBS of OVA) atomization excite, once a day, a 30min continues 3 days, and Normal group is with PBS
Instead of exciting liquid.1 hour before each exciting step, each group is administered in intraperitoneal injection mode.Positive drug
Thing group gives isoprel (2mg/kg), and kutkin group gives kutkin 27mg/kg, Radix picrorrhizae
The plain basic, normal, high dosage group of nitrone gives kutkin nitrone 21.5mg/kg, 43mg/kg, 86mg/kg respectively,
Normal group and model group give the PBS of equal volume, continue 3 days.Peel off tracheae and determine isolated tracheal
The tension force of smooth muscle, investigates the influence that various drug therapies are shunk to mouse asthma isolated tracheal smooth muscle.
Isolated trachea chain is placed in and is connected with 95%O2, 5%CO2Ke-Heng Shi nutrient solutions in, be fixed on bath
Between Muscle tensility transducer, after isolated trachea chain balance after, add OVA stimulate, model group mouse from
Body tracheal smooth muscle tension force mean value is 3.401 ± 0.096g, with Normal group (3.176 ± 0.072g) phase
Than significantly raising (P ＜ 0.001).Compared with model group, the basic, normal, high dosage group of kutkin nitrone is in vitro
The smooth muscle tension of tracheae is substantially reduced, and tension force mean value is below 2.5g, and high dose group tension force is most as little as
2.312±0.096g.Described kutkin nitrone can be obviously reduced isolated tracheal tension force, mitigate tracheae convulsion
Contraction, alleviates SOA, as a result sees Fig. 6.The effect of kutkin nitrone is poor without conspicuousness with parent compound
Different, the effect of three dosage is below positive drug isoprel (1.659 ± 0.032g).
Above-described embodiment is the present invention preferably implementation method, but embodiments of the present invention do not receive above-mentioned reality
Apply the limitation of example, it is other it is any without departing from the change made under Spirit Essence of the invention and principle, modification,
Substitute, combine, simplify, should be equivalent substitute mode, be included within protection scope of the present invention.
Claims (2)
1. kutkin nitrone of the structure as shown in formula (I) prepare preventing and treating asthmatic medicament in purposes,
2. purposes according to claim 1, it is characterised in that the medicine is with kutkin nitrone
It is active component, adds the medicament that pharmaceutically acceptable carrier or excipient are prepared from.
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| CN201510955782.9A CN106880624A (en) | 2015-12-16 | 2015-12-16 | Purposes of the kutkin nitrone in preventing and treating asthmatic medicament is prepared |
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| CN111714476A (en) * | 2019-03-21 | 2020-09-29 | 暨南大学 | Application of kutkin dimer analogue derivative in preparation of medicine or health-care product for preventing and treating Parkinson's disease |
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| CN102260239A (en) * | 2010-05-28 | 2011-11-30 | 暨南大学新药研究所 | Kutkin derivatives, and preparation and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102260239A (en) * | 2010-05-28 | 2011-11-30 | 暨南大学新药研究所 | Kutkin derivatives, and preparation and application thereof |
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| J. STEFANSKA等: "Apocynin reduces reactive oxygen species concentrations in exhaled breath condensate in asthmatics", 《EXPERIMENTAL LUNG RESEARCH》 * |
| LIPENG XU等: "Protective effects of apocynin nitrone on acute lung injury induced by lipopolysaccharide in rats", 《INTERNATIONAL IMMUNOPHARMACOLOGY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111714476A (en) * | 2019-03-21 | 2020-09-29 | 暨南大学 | Application of kutkin dimer analogue derivative in preparation of medicine or health-care product for preventing and treating Parkinson's disease |
| CN111714476B (en) * | 2019-03-21 | 2021-09-21 | 暨南大学 | Application of kutkin dimer analogue derivative in preparation of medicine for preventing and treating Parkinson's disease |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114917212A (en) | 2022-08-19 |
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