CN107056742A - A kind of pharmaceutical composition for treating asthma - Google Patents
A kind of pharmaceutical composition for treating asthma Download PDFInfo
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- CN107056742A CN107056742A CN201710261132.3A CN201710261132A CN107056742A CN 107056742 A CN107056742 A CN 107056742A CN 201710261132 A CN201710261132 A CN 201710261132A CN 107056742 A CN107056742 A CN 107056742A
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- halogen
- pharmaceutical composition
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/94—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
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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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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
In order to alleviate the Airway inflammatory response of asthmatic patient, the invention discloses a kind of pharmaceutical composition for treating asthma.The pharmaceutical composition is used as active component using the compound with following formula innovation structure：Medicine of the present invention has preferable effect in terms of mitigating airway of patient with asthma inflammatory reaction, suppressing asthma, improvement PFT, is expected to develop the medicine of the treatment asthma as clinical practice.
Description
Technical field
The present invention relates to field of medicaments, specifically, the present invention relates to a kind of pharmaceutical composition for treating asthma and change
Purposes of the compound in the medicine for preparing treatment asthma.
Background technology
Asthma is many cells in a kind of chronic airway inflammation disease, congenital immunity and acquired immune system,
Cause bronchial hyperresponsiveness together with epithelial cell, mucus produces surplus, and airway inflammation cellular infiltration, Airway Remodeling and air flue are narrow
It is narrow.The conventional method for treating asthma is to use glucocorticoid and bronchodilators, but the recurrence of patient does not have still
Have and preferably controlled, therefore in the urgent need to developing effective medicine.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition for treating asthma.
In order to realize the purpose of the present invention, the present invention provides a kind of pharmaceutical composition for treating asthma, the pharmaceutical composition
Active component is used as using the compound with following formula innovation structure：
Preferably, R1 represents hydrogen, halogen, hydroxyl, nitro, cyano group, C1-6 alkoxy carbonyl groups, amino, C1-6 alkyl aminos, two
(C1-6 alkyl) amino, C1-6 alkanoyls, phenyl, alkoxy, optionally by one-, two-or the C1-6 alkyl that replaces of three-halogen or
Optionally by one-, two-or the C1-6 alkoxies that replace of three-halogen.
Preferably, R2 represents hydrogen, halogen, hydroxyl, nitro, cyano group, amino, carboxyl, tetrazole radical, C1-6 alkoxies, C1-6
Alkoxy carbonyl group, C1-6 alkanoyls, C1-6 alkanoylaminos, optionally by one-, two-or the C1-6 alkane that replaces of three-halogen or hydroxyl
Base.
It is highly preferred that R1, R2 are while representation methoxy.
It is highly preferred that described pharmaceutical composition can also include one or more pharmaceutic adjuvants, diluent or carrier.
The present invention also provides purposes of the compound in the medicine for preparing treatment asthma, and the structural formula of the compound is：
Preferably, R1 represents hydrogen, halogen, hydroxyl, nitro, cyano group, C1-6 alkoxy carbonyl groups, amino, C1-6 alkyl aminos, two
(C1-6 alkyl) amino, C1-6 alkanoyls, phenyl, alkoxy, optionally by one-, two-or the C1-6 alkyl that replaces of three-halogen or
Optionally by one-, two-or the C1-6 alkoxies that replace of three-halogen.
Preferably, R2 represents hydrogen, halogen, hydroxyl, nitro, cyano group, amino, carboxyl, tetrazole radical, C1-6 alkoxies, C1-6
Alkoxy carbonyl group, C1-6 alkanoyls, C1-6 alkanoylaminos, optionally by one-, two-or the C1-6 alkane that replaces of three-halogen or hydroxyl
Base.
It is highly preferred that R1, R2 are while representation methoxy.
Medicine of the present invention has preferably in terms of mitigating airway of patient with asthma inflammatory reaction, suppressing asthma, improvement PFT
Effect, is expected to develop the medicine of the treatment asthma as clinical practice.
Brief description of the drawings
Fig. 1 is 4 groups of mouse lung tissue pathological characters (× 200).
Fig. 2 is the expression of IL-5 and IL-13 genes in 4 groups of mouse lung tissues.
Fig. 3 is the expression of PTEN and SIRT1 in 4 groups of mouse lung tissues.
A. Normal group；B. model control group；C. medicine group of the present invention；D. Dexamethasone group.
Embodiment
Asthmatic model is set up by embodiment to illustrate the action effect of medicine of the present invention.
The sign of the medicine of the present invention of experimental example 1
1H NMR(CDCl3)δ:7.24(1H,d),6.89(1H,d),4.44(1H,d),4.40(1H,d),4.36(1H,d),
3.89(3H,s),3.87(1H,d),3.31(3H,s),1.98(1H,m),1.74(1H,m),1.10(1H,m),1.04(1H,m)。
The effect of the drug therapy asthma of the present invention of experimental example 2
Packet and model are set up
All mouse are divided into Normal group, model control group, medicine group of the present invention and ground plug according to random digits table
The loose group of rice, every group 10.Sensitization liquid 0.2mL sensitization was injected intraperitoneally at the 1st and 14 day in remaining group in addition to normal group, the 14th, 25,
26th, give after yellow Jackets intraperitoneal injection of anesthesia within 27 days, give exciting liquid 0.05mL collunariums and excite.In the 28th~41 day model
Control group gives 0.9% sodium chloride solution 0.5mL gavages, and medicine group of the present invention gives the medicine 10mg/kg gavages of embodiment 1, ground
Sai meter Song groups intraperitoneal injection dexamethasone 0.5mL (1mg/kg).Normal group sensitization, excite, gavage intervene the stage with
0.9% sodium chloride solution is replaced.All mouse plucked eyeball after administration 24h in the 42nd day and take blood to put to death, and left and took right lung tissue, Gu
Due in 4% formalin.
Hematoxylin-eosin (HE) is dyed：Mouse lung tissue is taken, row HE is dyed after FFPE, section.Conventional dewaxing, Soviet Union
Another name for contaminates core, acidic alcohol differentiation, Yihong dye cytoplasm, dehydration, neutral gum mounting.
PAS dyes (periodic acid-schiff dyeing)：Take each group mouse lung tissue, routine paraffin wax section, dewaxing.Carry out PAS special
Different dyeing.
EUSA (ELISA) detection SERUM IgE (immunoglobulin)：Each group mice serum is collected by centrifugation,
Content in serum is detected according to ELISA kit specification.
Western blot detect mouse lung tissue PTEN, SIRT1 protein expression
Equal protein matter sample is taken to carry out polyacrylamide gel electrophoresis, then by Protein transfer to polyvinylidene fluoride film
On, TBST+5%BSA confining liquids closing 2h.By film respectively with 4 DEG C of PTEN and SIRT1 primary antibodies overnight incubation, then TBST washings 3
Secondary, each 10min adds the goat anti-rabbit igg secondary antibody of horseradish peroxidase-labeled afterwards, is incubated at room temperature 2h.Washed with TBST
Film 3 times, each 10min is eventually adding the colour developing of ECL luminescent solutions.
Changes in gene expression in realtime quantitative inspection (qPCR) detection each group mouse lung tissue
RNA extraction is using the RNeasy Plus Kit reagents of Qiagen companies, the progress of by specification operating method.
CDNA synthesis is carried out using the chain synthetic agent box of Invitrogen company Superscript III first, by specification operating method.
Quantitative fluorescent PCR reaction reagent uses Roche companies PCR master mix, and reaction condition is：94 DEG C of 10min, 94 DEG C of 30s,
60 DEG C of 1min, totally 40 circulations, the full-automatic quantitative real time PCR Instruments of ABI STEP one (American AB I companies), with GAPDH genes
It is used as internal reference.
Statistical method uses 16.0 editions statistics softwares of SPSS.Meet the measurement data of normal distribution with mean ± mark
It is accurate poorRepresent, mean compares using two independent samples t tests between group.With P<0.05 is that difference is statistically significant.
Pathologic feature
Normal group mouse lung tissue bronchium no inflammation cellular infiltration, air flue are without obvious mucilage secretion；Model pair
Dramatically increased according to group mouse lung tissue in obvious inflammatory cell infiltration, airway mucus secretion；Medicine group mouse lung tissue of the present invention
Inflammatory cell infiltration is relieved compared with model group, and airway mucus secretion is significantly reduced.See Fig. 1.
4 groups of mice serum IgE (immunoglobulin E) contents
Normal group, model control group, medicine group of the present invention and Dexamethasone group mice serum IgE contents are respectively
(0.22 ± 0.02), (6.79 ± 2.56), (3.10 ± 1.43), (2.32 ± 1.18) pg/mL.Compared with Normal group, mould
Type control group mice SERUM IgE content dramatically increases (t=3.331, P<0.01) mouse, and after pharmaceutical intervention of the present invention is given
The IgE contents of serum significantly reduce (t=2.806, P<0.05).
QPCR detects adjustment effect of the medicine of the present invention to mouse asthma IL-5 and IL-13
Forefathers' research shows that interleukins IL-5 and IL-13 and asthma are closely related.In 4 groups of mouse lung tissues
IL-5 and IL-13 changes in gene expression is shown in Fig. 2, as a result shows that medicine of the present invention reduces IL-5 and IL-13 expression
(t=2.569,2.788, P<0.05).
The change of PTEN and SIRTl expression in Western blot detection mouse lung tissues
PTEN genes are played an important role in inflammation of asthma mechanism, and SIRTl can drop as a kind of deacetylase
Low PTEN Acetylation Level, therefore inflammation of asthma level can be judged by internal PTEN and SIRTl expression.
In Fig. 3：The lung tissue PTEN and SIRT1 of model control group mouse expression quantity are substantially less than Normal group (t
=-2.491, P<0.05；T=-3.454, P<0.01), medicine group mouse lung tissue PTEN and SIRTl of the present invention expression quantity show
Write and be higher than model control group (t=-2.301, -2.586, P<0.05).
Claims (9)
1. a kind of pharmaceutical composition for treating asthma, it is characterised in that the pharmaceutical composition is with the change with following formula innovation structure
Compound is used as active component：
2. it is according to claim 1 treatment asthma pharmaceutical composition, it is characterised in that R1 represent hydrogen, halogen, hydroxyl,
Nitro, cyano group, C1-6 alkoxy carbonyl groups, amino, C1-6 alkyl aminos, two (C1-6 alkyl) amino, C1-6 alkanoyls, phenyl, alkane
Epoxide, optionally by one-, two-or the C1-6 alkyl that replaces of three-halogen or optionally by one-, two-or the C1-6 alkane that replaces of three-halogen
Epoxide.
3. it is according to claim 2 treatment asthma pharmaceutical composition, it is characterised in that R2 represent hydrogen, halogen, hydroxyl,
Nitro, cyano group, amino, carboxyl, tetrazole radical, C1-6 alkoxies, C1-6 alkoxy carbonyl groups, C1-6 alkanoyls, C1-6 alkanoylaminos,
Optionally by one-, two-or the C1-6 alkyl that replaces of three-halogen or hydroxyl.
4. the pharmaceutical composition for the treatment of asthma according to claim 3, it is characterised in that R1, R2 are while representation methoxy.
5. the pharmaceutical composition for the treatment of asthma according to claim 4, it is characterised in that described pharmaceutical composition can be with
Include one or more pharmaceutic adjuvants, diluent or carrier.
6. purposes of the compound in the medicine for preparing treatment asthma, it is characterised in that the structural formula of the compound is：
7. purposes according to claim 6, it is characterised in that R1 represents hydrogen, halogen, hydroxyl, nitro, cyano group, C1-6 alkane
Oxygen carbonyl, amino, C1-6 alkyl aminos, two (C1-6 alkyl) amino, C1-6 alkanoyls, phenyl, alkoxy, optionally by one-,
Two-or the substitution of three-halogen C1-6 alkyl or optionally by one-, two-or the C1-6 alkoxies that replace of three-halogen.
8. purposes according to claim 7, it is characterised in that R2 represents hydrogen, halogen, hydroxyl, nitro, cyano group, amino, carboxylic
Base, tetrazole radical, C1-6 alkoxies, C1-6 alkoxy carbonyl groups, C1-6 alkanoyls, C1-6 alkanoylaminos, optionally by one-, two-or
Three-halogen or the C1-6 alkyl of hydroxyl substitution.
9. purposes according to claim 8, it is characterised in that R1, R2 are while representation methoxy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710261132.3A CN107056742A (en) | 2017-04-20 | 2017-04-20 | A kind of pharmaceutical composition for treating asthma |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710261132.3A CN107056742A (en) | 2017-04-20 | 2017-04-20 | A kind of pharmaceutical composition for treating asthma |
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| CN107056742A true CN107056742A (en) | 2017-08-18 |
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| CN201710261132.3A Pending CN107056742A (en) | 2017-04-20 | 2017-04-20 | A kind of pharmaceutical composition for treating asthma |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013109735A1 (en) * | 2012-01-18 | 2013-07-25 | Zafgen, Inc. | Tricyclic sulfone compounds and methods of making and using same |
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2017
- 2017-04-20 CN CN201710261132.3A patent/CN107056742A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013109735A1 (en) * | 2012-01-18 | 2013-07-25 | Zafgen, Inc. | Tricyclic sulfone compounds and methods of making and using same |
Non-Patent Citations (2)
| Title |
|---|
| KEVIN K. ARIEN等: "Diaryltriazine non-nucleoside reverse transcriptase inhibitors are potent candidates for pre-exposure prophylaxis in the prevention of sexual HIV transmission", 《J ANTIMICROB CHEMOTHER》 * |
| 郑燕敏等: "抗哮喘药物现状和研发动态", 《上海医药》 * |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170818 |
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