CN103585147A - Application of Nitrosporeusines A in preparation of oral ulcer treatment or prevention medicines - Google Patents
Application of Nitrosporeusines A in preparation of oral ulcer treatment or prevention medicines Download PDFInfo
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- CN103585147A CN103585147A CN201310613245.7A CN201310613245A CN103585147A CN 103585147 A CN103585147 A CN 103585147A CN 201310613245 A CN201310613245 A CN 201310613245A CN 103585147 A CN103585147 A CN 103585147A
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- Prior art keywords
- nitrosporeusines
- day
- preparation
- treatment
- ulcer
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- 229930191006 nitrosporeusine Natural products 0.000 title claims abstract description 30
- 238000011282 treatment Methods 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 208000007117 Oral Ulcer Diseases 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 208000002399 aphthous stomatitis Diseases 0.000 title abstract description 8
- 229940079593 drug Drugs 0.000 title abstract description 4
- 230000002265 prevention Effects 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 12
- 208000020670 canker sore Diseases 0.000 claims description 9
- 230000000694 effects Effects 0.000 abstract description 4
- 208000025865 Ulcer Diseases 0.000 description 14
- 231100000397 ulcer Toxicity 0.000 description 14
- 230000035876 healing Effects 0.000 description 10
- 230000003203 everyday effect Effects 0.000 description 6
- 241000700159 Rattus Species 0.000 description 4
- 239000006189 buccal tablet Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 241001137869 Streptomyces nitrosporeus Species 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 229940046011 buccal tablet Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 206010028034 Mouth ulceration Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 244000241235 Citrullus lanatus Species 0.000 description 1
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 240000001624 Espostoa lanata Species 0.000 description 1
- 235000009161 Espostoa lanata Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000001354 calcination Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an application of Nitrosporeusines A in the preparation of oral ulcer treatment or prevention medicines for the first time. The Nitrosporeusines A has a brand new skeleton type, has a strong treatment activity against oral ulcers, has protruding substantive features, and has an obvious substantial advantage in the treatment of the oral ulcers.
Description
Technical field
The present invention relates to the new purposes of compound N itrosporeusines A, relate in particular to the application of Nitrosporeusines A in preparation treatment or preventing canker sore medicine.
Background technology
Recurrent oral ulceration is modal disease in diseases of oral mucosa.The first place of prevalence office diseases of oral mucosa.Sircus(1975) investigate 1587 people, prevalence is 20%.As can be seen here, oral ulcer patient is a very huge colony.The cause of disease of recurrent oral ulceration is complicated, still indefinite so far, may infect with viral infection, antibacterial and the factor such as the endocrine regulation of body, immune dysfunction relevant.The primary treatment measure of oral ulcer comprises topical therapeutic and whole body therapeutic, and because topical therapeutic toxic and side effects is lower, the people who has therefore obtained people can.Although the buccal tablets that the part occurring is in recent years used carries, easy to use, mouthfeel and compliance are better, and as lysozyme buccal tablet, watermelon crystal buccal tablet, cydiodine etc., these medicines emphasize particularly on different fields at aspects such as sterilization, antiinflammatory, pain relievings.
The compound N itrosporeusines A the present invention relates to is one and within 2013, delivers (Aigang Yang, et al., Nitrosporeusines A and B, Unprecedented Thioester-Bearing Alkaloids from the Arctic Streptomyces nitrosporeus.Organic Letters, 2013, 15 (20): 5366 – 5369.) noval chemical compound, this compound has brand-new framework types, current purposes finds that it can resist H1N1(Aigang Yang, et al., Nitrosporeusines A and B, Unprecedented Thioester-Bearing Alkaloids from the Arctic Streptomyces nitrosporeus.Organic Letters, 2013, 15 (20): 5366 – 5369.), the purposes of the Nitrosporeusines A the present invention relates in preparation treatment or preventing canker sore medicine belongs to open first.
Summary of the invention
The object of the invention is to, according to not finding that it has the present situation of the report for the treatment of or preventing canker sore in existing Nitrosporeusines A research, provides the application of Nitrosporeusines A in preparation treatment or preventing canker sore medicine.
Described compound N itrosporeusines A structure is as shown in formula I:
Formula I
The purposes of the Nitrosporeusines A the present invention relates in preparation treatment or preventing canker sore medicine belongs to open first, because framework types belongs to brand-new framework types, and its treatment or preventing canker sore are active strong, possess outstanding substantive distinguishing features, be used for the treatment of or preventing canker sore obviously has significant progress simultaneously.
The specific embodiment
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subject to any restriction of specific embodiment, but be limited by claim.
The preparation method of compound N itrosporeusines A involved in the present invention is referring to document (Aigang Yang, et al., Nitrosporeusines A and B, Unprecedented Thioester-Bearing Alkaloids from the Arctic Streptomyces nitrosporeus.Organic Letters, 2013,15 (20): 5366 – 5369.), prepare according to the method described above compound N itrosporeusines A.
Embodiment 1: the preparation of compound N itrosporeusines A tablet involved in the present invention:
Get 5 and digest compound Nitrosporeusines A and add 195 grams, dextrin, mix, conventional tabletting is made 1000.
Embodiment 2: the preparation of compound N itrosporeusines A capsule involved in the present invention:
Get 5 and digest compound Nitrosporeusines A and add 195 grams of starch, mix, encapsulatedly make 1000.
Below by pharmacodynamic experiment, further illustrate its pharmaceutically active.
The experimental study of test example 1:Nitrosporeusines A anti-oral ulcer
1, test objective: whether manufacture oral ulcer model with phenol, give the Nitrosporeusines A of the certain number of times of oral ulcer rat model every day, observing Nitrosporeusines A has the effect that reduces ulcer.
2, tested medicine and reagent
Cydiodine (Beijing Sihuan Medicine Science and Technology Co., Ltd); Phenol
Animal: Wistar rat, male, body weight 240～280g, Nanjing Medical University's Experimental Animal Center.
3, test method
Get 50 of rats, male, body weight 240～280g, 10% chloral hydrate anesthesia, dosage: 0.35ml/100g, after anesthesia by the plastic dropper of 90% phenol cotton balls (internal diameter: 3mm) lower end is flat on the cheek film at the about 1mm of rats with left bicker place, calcination 30min, is shown in the white infringement that this locates about 3mm.Grouping immediately after 24 hours,, divides 5 groups, i.e. model group (4 times/day of adjuvants, containing medicine) by 10 every group; Nitrosporeusines A high dose group (4 times/day, 0.5mg/ time); Dosage in Nitrosporeusines A (4 times/day, 0.1mg/ time); Nitrosporeusines A low dose group (4 times/day, 0.02mg/ time); Positive controls: cydiodine group (4 times/day, 0.5mg/ time).Nitrosporeusines A and cydiodine buccal tablet be pulverize before use, and administration be take flap coverage as degree.Successive administration 5 days, after the front and each administration of administration, observe ulcer area size (in the diameter of ulcer) and ulcer healing situation (being considered as healing without macroscopic ulcer) next day, and first administration to last administration is recorded as respectively 1,2,3,4,5,6 day.Ulcer area size is checked with t, and ulcer healing rate is checked with X2.
4, result of the test
Ulcer area comparison (table 1): Nitrosporeusines A high dose group and model group comparison, from administration, within the 3rd day, play off-test, relatively there is significant difference corresponding every day; Cydiodine group and model group comparison, play off-test on the 3rd day from administration, relatively has significant difference corresponding every day; Dosage group and model group comparison in Nitrosporeusines A, play off-test on the 3rd day from administration, relatively has significant difference corresponding every day; Nitrosporeusines A low dose group and model group comparison, play off-test on the 5th day from administration, relatively has significant difference corresponding every day; Dosage group and the comparison of cydiodine group in Nitrosporeusines A, play off-test on the 1st day from administration, relatively has significant difference corresponding every day.
The impact of table 1 on rat ulcer area
Note: with model group comparison, * p<0.05, * p<0.01.
Healing rate (table 2): model group and Nitrosporeusines A low dose group play off-test on the 1st day from administration, ulcer is healing not; And Nitrosporeusines A high dose group was from administration the 4th day, just there is ulcer healing, to off-test, reach 90%; Cydiodine group, from administration the 4th day, has ulcer healing, to off-test, reaches 60%; In Nitrosporeusines A, dosage group, from administration the 5th day, has ulcer healing, to off-test, reaches 40%.
The impact of table 2 on rat ulcer healing time
Note: with model group comparison, * p<0.05, * p<0.01.
5, conclusion
Nitrosporeusines A has the effect of obvious promotion oral ulcer healing.
Claims (1)
- The application of 1.Nitrosporeusines A in treatment or preventing canker sore medicine, described compound N itrosporeusines A structure is as shown in formula I:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310613245.7A CN103585147B (en) | 2013-11-27 | 2013-11-27 | Application of Nitrosporeusines A in preparation of oral ulcer treatment or prevention medicines |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310613245.7A CN103585147B (en) | 2013-11-27 | 2013-11-27 | Application of Nitrosporeusines A in preparation of oral ulcer treatment or prevention medicines |
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| Publication Number | Publication Date |
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| CN103585147A true CN103585147A (en) | 2014-02-19 |
| CN103585147B CN103585147B (en) | 2015-04-22 |
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| CN201310613245.7A Active CN103585147B (en) | 2013-11-27 | 2013-11-27 | Application of Nitrosporeusines A in preparation of oral ulcer treatment or prevention medicines |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016051425A1 (en) | 2014-10-01 | 2016-04-07 | Council Of Scientific & Industrial Research | Benzenecarbothioccyclopenta[c] pyrrole-1,3-dione compounds and process for synthesis thereof |
-
2013
- 2013-11-27 CN CN201310613245.7A patent/CN103585147B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| AIGANG YANG,ET AL.: "Nitrosporeusines A and B, Unprecedented Thioester-Bearing Alkaloids from the Arctic Streptomyces nitrosporeus", 《ORGANIC LETTERS》 * |
| 柳正东: "山莨菪碱治疗复发性口腔溃疡的疗效观察", 《中国厂矿医学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016051425A1 (en) | 2014-10-01 | 2016-04-07 | Council Of Scientific & Industrial Research | Benzenecarbothioccyclopenta[c] pyrrole-1,3-dione compounds and process for synthesis thereof |
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| Publication number | Publication date |
|---|---|
| CN103585147B (en) | 2015-04-22 |
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Inventor after: Cao Fengxia Inventor after: Zhong Yun Inventor after: Li Xiaoxia Inventor before: Chen Bin |
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| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: CHEN BIN TO: CAO FENGXIA ZHONG YUN LI XIAOXIA |
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Effective date of registration: 20151231 Address after: 048100, Yangcheng County, Shanxi City, Jincheng Province Water Town Village Ya rock bottom No. 74 Patentee after: SHANXI REALLY TECHNOLOGY CO., LTD. Address before: 315700 Xiangshan, Zhejiang, Dandong street, Xiangshan Port Road, No. 79, No. Patentee before: Chen Bin |