CN103585150A - Nitrosporeusines A在治疗鼻炎药物中的应用 - Google Patents
Nitrosporeusines A在治疗鼻炎药物中的应用 Download PDFInfo
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- CN103585150A CN103585150A CN201310636243.XA CN201310636243A CN103585150A CN 103585150 A CN103585150 A CN 103585150A CN 201310636243 A CN201310636243 A CN 201310636243A CN 103585150 A CN103585150 A CN 103585150A
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- 229930191006 nitrosporeusine Natural products 0.000 title claims abstract description 25
- 206010039083 rhinitis Diseases 0.000 title claims abstract description 23
- 239000003814 drug Substances 0.000 title claims abstract description 14
- 229940079593 drug Drugs 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 5
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 abstract description 4
- 206010061218 Inflammation Diseases 0.000 abstract description 2
- 229960001193 diclofenac sodium Drugs 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 abstract 1
- 229960000351 terfenadine Drugs 0.000 abstract 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 12
- 108010058846 Ovalbumin Proteins 0.000 description 8
- 229940092253 ovalbumin Drugs 0.000 description 8
- 229960001340 histamine Drugs 0.000 description 6
- 210000001331 nose Anatomy 0.000 description 6
- 206010039085 Rhinitis allergic Diseases 0.000 description 3
- 241001137869 Streptomyces nitrosporeus Species 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 201000010105 allergic rhinitis Diseases 0.000 description 3
- 210000003928 nasal cavity Anatomy 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 1
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Abstract
一种治疗免疫性炎症的Nitrosporeusines A，用于制备治疗免疫性炎症药物，尤其适用于制备治疗鼻炎的药物，用特非那丁及双氯灭痛作为对照，Nitrosporeusines A疗效明确，属于首次公开，由于骨架类型属于全新的骨架类型，而且其治疗鼻炎活性强，具备突出的实质性特点，同时用于鼻炎的防治显然具有显著的进步。
Description
技术领域
本发明涉及化合物Nitrosporeusines A的新用途，尤其涉及Nitrosporeusines A在制备治疗鼻炎药物中的应用。
背景技术
鼻炎为临床常见病和多发病，鼻炎的发生主要与过敏反应有关，属于免疫性炎症的范畴。目前，治疗鼻炎主要采用特非那丁等抗组胺药物或曲尼司特、酮替芬等抗过敏药物，这些药物对鼻炎的慢性化和反复发作疗效较差或无效。因此，成分明确、质量可控且安全高效的小分子化合物在研制鼻炎治疗药物方面，具有潜在的价值。
本发明涉及的化合物Nitrosporeusines A是一个2013年发表（Aigang Yang，et al.,Nitrosporeusines A and B,Unprecedented Thioester-Bearing Alkaloids from the ArcticStreptomyces nitrosporeus.Organic Letters，2013，15(20):5366–5369.）的新化合物，该化合物拥有全新的骨架类型，发现其能抗H1N1（Aigang Yang，et al.,Nitrosporeusines A and B,Unprecedented Thioester-Bearing Alkaloids from the ArcticStreptomyces nitrosporeus.Organic Letters，2013，15(20):5366–5369.），本发明涉及的Nitrosporeusines A在制备治疗鼻炎药物中的用途属于首次公开。
发明内容
本发明的目的在于根据现有Nitrosporeusines A研究中未发现其具有抗鼻炎活性的报道的现状，提供了Nitrosporeusines A在制备抗鼻炎药物中的应用。
所述化合物Nitrosporeusines A,结构如式（Ⅰ）所示：
式（Ⅰ）
Nitrosporeusines A10，20mg/kg口服给药，对抗原（卵白蛋白）和组胺所致大鼠搔抓鼻部、打喷嚏反应及鼻腔血管通透性升高具有抑制作用，因此，可用于制备治疗鼻炎的药物。
Nitrosporeusines A在制备治疗鼻炎药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其治疗鼻炎活性强，具备突出的实质性特点，同时用于鼻炎的防治显然具有显著的进步。
具体实施方式
以下通过实施例对本发明作进一步详细的说明，但本发明的保护范围不受具体实施例的任何限制，而是由权利要求加以限定。
本发明所涉及化合物Nitrosporeusines A的制备方法参见文献（Aigang Yang，et al.,Nitrosporeusines A and B,Unprecedented Thioester-Bearing Alkaloids from the ArcticStreptomyces nitrosporeus.Organic Letters，2013，15(20):5366–5369.），按照上述方法制备化合物Nitrosporeusines A。
实施例1：本发明所涉及化合物Nitrosporeusines A片剂的制备：
取5克化合物Nitrosporeusines A,加入糊精195克，混匀，常规压片制成1000片。
实施例2：本发明所涉及化合物Nitrosporeusines A胶囊剂的制备：
取5克化合物Nitrosporeusines A，加入淀粉195克，混匀，装胶囊制成1000粒。
下面通过药效学实验来进一步说明其药物活性。
实验例1、本发明Nitrosporeusines A对卵白蛋白引起大鼠过敏性鼻炎的影响
雄性SD大鼠，体重180～220g，腹腔注射卵白蛋白1mg及氢氧化铝凝胶10mg，其后隔日注射1次，共7次。从第14天始，每日在大鼠两侧鼻腔内滴入1mg/ml卵白蛋白生理盐水溶液10ul，共7次。末次滴注后立刻观察30分钟内大鼠打喷嚏及擦鼻的次数，试验药物于卵白蛋白末次滴注前1小时口服给予。
表1本发明Nitrosporeusines A对卵白蛋白引起大鼠过敏性鼻炎的影响（x±SD）
与对照组比较，**P<0.01*P<0.05
由表1可见，Nitrosporeusines A（10，20mg/kg）明显抑制卵白蛋白所致过敏性鼻炎大鼠的喷嚏和搔抓鼻部反应。特非那丁10mg/kg亦呈现显著的抑制作用。
实验例2、本发明Nitrosporeusines A对组胺引起的大鼠鼻炎的影响
雄性SD大鼠，体重180～220g，口服给予试验药物后1小时，两侧鼻腔内滴入1M组胺生理盐水溶液10ul，观察30分钟内大鼠打喷嚏及擦鼻的次数。
表2本发明Nitrosporeusines A对组胺引起大鼠鼻炎的影响（x±SD）
与对照组比较，**P<0.01*P<0.05
由表2可见，本发明Nitrosporeusines A（10,20mg/kg）明显减少组胺所致鼻炎大鼠的喷嚏次数，对搔抓鼻部反应呈抑制趋势。特非那丁10mg/kg则呈显著的抑制作用。
结论：Nitrosporeusines A口服给药，对抗原（卵白蛋白）和组胺所致大鼠搔抓鼻部、打喷嚏反应具有抑制作用，因此，可用于制备治疗鼻炎的药物。
Claims (1)
1.Nitrosporeusines A在治疗鼻炎药物中的应用，所述化合物NitrosporeusinesA结构如式（Ⅰ）所示：
式（Ⅰ）。
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| 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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Non-Patent Citations (2)
| Title |
|---|
| AIGANG YANG,ET AL.: "Nitrosporeusines A and B, Unprecedented Thioester-Bearing Alkaloids from the Arctic Streptomyces nitrosporeus", 《ORGANIC LETTERS》 * |
| 郭明荣等: "山莨菪碱临床应用进展", 《基层医学论坛》 * |
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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