CN109481436A - Application of the thromboxane A2 synthetase inhibitors ozagrel in preparation treatment caused by smoking lung-cancer medicament - Google Patents
Application of the thromboxane A2 synthetase inhibitors ozagrel in preparation treatment caused by smoking lung-cancer medicament Download PDFInfo
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- CN109481436A CN109481436A CN201910017008.1A CN201910017008A CN109481436A CN 109481436 A CN109481436 A CN 109481436A CN 201910017008 A CN201910017008 A CN 201910017008A CN 109481436 A CN109481436 A CN 109481436A
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- thromboxane
- ozagrel
- lung cancer
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- smoking
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The present invention provides a kind of application of thromboxane A2 synthetase inhibitors ozagrel in preparation treatment caused by smoking lung-cancer medicament, it was found that the potential novel targets for becoming treatment lung cancer of thromboxane A2 synzyme, ozagrel is by inhibiting thromboxane A2 synthase activity, it is horizontal to reduce thromboxane A2, to which the size due to caused by smoking lung cancer be obviously reduced, a new application approach is provided for ozagrel.
Description
Technical field
The invention belongs to medicine and hygiene fields, and in particular to thromboxane A2 synthetase inhibitors ozagrel is treated in preparation
Application in caused by smoking lung-cancer medicament.
Background technique
Lung cancer is the highest malignant tumour of morbidity and mortality in global range.China's lung cancer neopathy number in 2017 reaches
To 800,000, a quarter of nearly 700,000, the Zhan Suoyou number of cancer deaths of death toll, and this data is also with annual 26.9%
Speed increase, it is contemplated that be up to 1,000,000 people by 2025.Wherein 90% or more lung cancer is all related with smoking or secondhand smoke.
Although various countries take severe smoking ban measure in recent years, clinical treatment means also achieve significant progress, lung cancer it is dead
It dies rate still to remain high, 5 years survival rates of patient are still below 17%.The drug and new therapy target for finding high-efficiency low-toxicity, which become, to be mentioned
The top priority of high patients with lung cancer survival rate.
Ozagrel can selectively inhibit thromboxane A2 synthase activity, reduce thromboxane A2 synthesis.At present in clinic
On be only used for inhibit platelet aggregation and mitigate vasopasm, improve cerebral ischemia when microcirculation and energetic supersession barrier
Hinder.
Discovery clinical medicine ozagrel can effectively treat the lung cancer caused by smoking to inventor's research for the first time.
Summary of the invention
The invention discloses the potential target spots for becoming treatment lung cancer of thromboxane A2 synzyme, and therefore, selection can effectively press down
The drug ozagrel of thromboxane A2 synzyme processed carries out zoopery.It was found that ozagrel can significantly reduce due to smoking
The size of caused lung cancer provides a new application approach for ozagrel.
In order to achieve the above-mentioned object of the invention, The technical solution adopted by the invention is as follows:
Application of the thromboxane A2 synthetase inhibitors ozagrel in preparation treatment caused by smoking lung-cancer medicament.
Further, the caused by smoking lung cancer is the primary lung cancer that the carcinogenic substance NNK in tobacco causes.
Further, the drug is aqua, emulsion, paste, tablet or injection.
Further, the usage mode of the drug is injection or takes orally.
The beneficial effects of the present invention are:
Inventor has found the potential target spot for becoming treatment lung cancer of thromboxane A2 synzyme, and therefore, selection can effectively inhibit
The drug ozagrel of thromboxane A2 synzyme carries out zoopery.It was found that ozagrel can significantly reduce by the institute that smokes
The size for causing lung cancer, provides a new application approach for ozagrel.
Rat primary lung cancer model, disposable NNK are established using the carcinogenic substance NNK in A/J mouse and tobacco
After (100mg/kg) 34 weeks, the ozagrel of mouse 15,30,60mg/kg is given in a manner of stomach-filling respectively, is put to death after 6 weeks small
Mouse takes lung tissue detection number of tumors and tumor size, and detects the content of thromboxane B2 in lung tissue and serum.As a result, it has been found that:
Ozagrel can significantly reduce the lung cancer size caused by NNK, and cancer resistant effect and ozagrel concentration are positively correlated, and and mouse
Internal thromboxane B2 is horizontal negatively correlated.
Detailed description of the invention
Fig. 1 is experimental group and dosage.
Fig. 2 is the mouse lung tissue slice map of each experimental group.
Fig. 3 is that ozagrel reduces the horizontal related statistics knot of thromboxane B2 with it to the inhibiting effect of lung cancer caused by NNK
Fruit figure.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate this hair
It is bright, rather than limit the scope of the invention.Under the premise of without departing substantially from technical solution of the invention, the present invention is made
Those of ordinary skill in the art's any change easy to accomplish fall within scope of the presently claimed invention.
Embodiment 1
Rat primary lung cancer model, disposable NNK are established using the carcinogenic substance NNK in A/J mouse and tobacco
After (100mg/kg) 34 weeks, the ozagrel of mouse 15,30,60mg/kg is given in a manner of stomach-filling respectively, is put to death after 6 weeks small
Mouse takes lung tissue to detect number of tumors, and detects the content of thromboxane B2 in cancerous lung tissue.
Zoopery grouping such as Fig. 1.Fig. 1 is experimental group and dosage.Female 4 week old of A/J mouse, weight 18-
22g, is randomly divided into 6 groups, every group 10 by 60.By experiment the 1st day, model (NNK, NNK+Oz-L, NNK+Oz-M,
NNK+Oz-H) group mouse disposable celiac injects NNK, dosage 100mg/kg, blank control group (Control) and ozagrel
Control group (Oz-H) injects isometric physiological saline respectively.34th week, each administration group (NNK+Oz-L, NNK+Oz-M, NNK+Oz-
H the ozagrel of mouse 15,30,60mg/kg) is given in a manner of stomach-filling respectively, ozagrel control group is with 60mg/kg Austria bundle
Gray's stomach-filling, blank control group and NNK group give isometric physiological saline.Continuous gavage put to death mouse after 6 weeks.
Fig. 2 is the mouse lung tissue slice map of each experimental group.The mouse lung tissue after experiment is collected, formaldehyde is solid
It after fixed, embedding, through hematoxylin eosin staining, takes pictures under microscope, amplification factor is 100 times.
Fig. 3 is that ozagrel reduces the horizontal related statistics knot of thromboxane B2 with it to the inhibiting effect of lung cancer caused by NNK
Fruit figure.After putting to death mouse, lung tissue and blood plasma are collected.Record the number and size of lung tumors.With ELISA detection kit,
Detect the level of blood examination element B2 in mice plasma and lung tissue.Thromboxane A2 is unstable in vivo, and rapid metabolization becomes inactive
And stable thromboxane B2, therefore, detection thromboxane B2 level is considered as reflection thromboxane A2 indirect indexes.
As a result, it has been found that: ozagrel can significantly reduce lung tumors quantity (Fig. 2, the figure by NNK induced mice lung cancer
3A), it but cannot reduce by lung cancer caused by smoking incidence (Fig. 3 B)；The ozagrel of the various dose different degrees of drop of energy
Thromboxane B2 in low mouse lung tissue and serum is horizontal (Fig. 3 C, D), and the metabolism of stablizing that thromboxane B2 is thromboxane A2 produces
Object can directly reflect thromboxane A2 level.These results suggest that ozagrel inhibits thromboxane A2 in Mice Body to close by reducing
At enzymatic activity, thromboxane A2 synthesis level is reduced to inhibit caused by smoking lung cancer.The ozagrel of various dose is to smoking primer
Lung cancer have certain inhibiting effect, wherein 60mg/kg dosage group effect is the most significant.
Claims (4)
1. application of the thromboxane A2 synthetase inhibitors ozagrel in preparation treatment caused by smoking lung-cancer medicament.
2. thromboxane A2 synthetase inhibitors ozagrel according to claim 1 treats caused by smoking lung cancer drug in preparation
Application in object, it is characterised in that: the caused by smoking lung cancer is the primary lung cancer that the carcinogenic substance NNK in tobacco causes.
3. thromboxane A2 synthetase inhibitors ozagrel according to claim 1 treats caused by smoking lung cancer drug in preparation
Application in object, it is characterised in that: the drug is aqua, emulsion, paste, tablet or injection.
4. thromboxane A2 synthetase inhibitors ozagrel according to claim 1 treats caused by smoking lung cancer drug in preparation
Application in object, it is characterised in that: the usage mode of the drug is injection or takes orally.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810958931 | 2018-08-21 | ||
| CN2018109589310 | 2018-08-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109481436A true CN109481436A (en) | 2019-03-19 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910017008.1A Pending CN109481436A (en) | 2018-08-21 | 2019-01-08 | Application of the thromboxane A2 synthetase inhibitors ozagrel in preparation treatment caused by smoking lung-cancer medicament |
Country Status (1)
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| CN (1) | CN109481436A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101253167A (en) * | 2005-08-09 | 2008-08-27 | 诺华有限公司 | Substituted imidazole compounds as KSP inhibitors |
| WO2009089098A1 (en) * | 2008-01-03 | 2009-07-16 | Musc Foundation For Research Development | Methods for the treatment of cancers |
-
2019
- 2019-01-08 CN CN201910017008.1A patent/CN109481436A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101253167A (en) * | 2005-08-09 | 2008-08-27 | 诺华有限公司 | Substituted imidazole compounds as KSP inhibitors |
| WO2009089098A1 (en) * | 2008-01-03 | 2009-07-16 | Musc Foundation For Research Development | Methods for the treatment of cancers |
Non-Patent Citations (1)
| Title |
|---|
| LIU YI,ET AL.: "Tumorigenesis of smoking carcinogen 4-(methylnitrosamino)-1-(3-", 《CANCER LETTERS》 * |
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| PB01 | Publication | ||
| PB01 | Publication | ||
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| WD01 | Invention patent application deemed withdrawn after publication | ||
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Application publication date: 20190319 |