CN103638009B - Artoxanthochromane在治疗抗结核菌药物中的应用 - Google Patents
Artoxanthochromane在治疗抗结核菌药物中的应用 Download PDFInfo
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Abstract
本发明公开了Artoxanthochromane在制备抗结核菌药物中的应用，药理实验发现Artoxanthochromane具有显著抑制结核菌的活性，具有很好的应用前景,由于属于全新的骨架类型，而且其对于结核菌抑制活性强，具备突出的实质性特点，同时用于结核菌感染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Artoxanthochromane的新用途，尤其涉及Artoxanthochromane在制备治疗抗结核菌药物中的应用。
背景技术
近年来全球结核病的发病呈增高趋势，然而由于结核病患者的治疗管理尚不十分规范，不规则化疗，滥用抗结核药物，使结核病耐药情况日益严重，且耐药性的变化更趋向于多种药物同时耐药，这给结核病的防治工作造成极大困难。因此寻找新的抗结核药物，尤其是抗多药耐药性的抗结核药物对保护人民身体健康，具有重要意义。
本发明涉及的化合物Artoxanthochromane是一个2013年发表（Horng-HueyKo，etal.,ANovelMonoterpeneStilbeneAdductwitha4,4-Dimethyl-2,3-diphenylchromaneSkeletonfromArtocarpusxanthocarpus.chemistry&biodiversity,2013(10):1269-1275.）的新化合物，该化合物拥有全新的骨架类型，目前的用途发现其能清除氧自由基（Horng-HueyKo，etal.,ANovelMonoterpeneStilbeneAdductwitha4,4-Dimethyl-2,3-diphenylchromaneSkeletonfromArtocarpusxanthocarpus.chemistry&biodiversity,2013(10):1269-1275.），本发明涉及的Artoxanthochromane在制备治疗抗结核菌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Artoxanthochromane研究中未发现其具有抗抗结核菌活性的报道的现状，提供了Artoxanthochromane在制备抗抗结核菌药物中的应用。
所述化合物Artoxanthochromane结构如式（Ⅰ）所示：
发明人先用卡介苗做应试菌株，采用纸片扩散法对Artoxanthochromane的抗结核菌活性进行初步试验，根据初步试验的结果，本发明再用固体培养基稀释法测定了该化合物对卡介苗、结核分枝杆菌标准株H37Rv株和耐多药结核分枝杆菌（MDRMTB）三种结核菌的最小抑菌浓度，实验结果证实Artoxanthochromane具有很强的抗结核菌和抗耐药性结核菌活性，可作为治疗结核菌感染疾病的先导化合物，也可用于制备治疗结核病药物。
本发明涉及的Artoxanthochromane在制备治疗抗结核菌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，而且其对于结核菌抑制活性强，具备突出的实质性特点，同时用于结核菌感染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Artoxanthochromane的制备方法参见文献（Horng-HueyKo，etal.,ANovelMonoterpeneStilbeneAdductwitha4,4-Dimethyl-2,3-diphenylchromaneSkeletonfromArtocarpusxanthocarpus.chemistry&biodiversity,2013(10):1269-1275.），按照上述方法制备化合物Artoxanthochromane。
实施例1：本发明所涉及化合物Artoxanthochromane片剂的制备：
取5克化合物Artoxanthochromane，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Artoxanthochromane胶囊剂的制备：
取5克化合物Artoxanthochromane，加入淀粉180克，混匀，装胶囊制成1000粒。
实验例1：固体培养基稀释法测定Artoxanthochromane抗卡介苗（BCG）绝对浓度
从斜面上刮取卡介苗培养物，加入到3mlMiddlebrook7H9肉汤培养基中，加入少量玻璃珠，旋紧试管盖，于漩涡振荡器上剧烈振动研磨，与标准麦氏比浊管（MacFarlandNo.1）比浊，即配成1mg/ml的卡介苗（BCG）菌悬液。
将Artoxanthochromane用DMSO配成高浓度的原液，用含5%的吐温-80无菌超纯水稀释原液至所需浓度，将稀释好的Artoxanthochromane按所需剂量加入到4mlMiddlebrook7H11琼脂培养基（该培养基已经121℃高压蒸汽灭菌15分钟、冷却至50～55℃），混匀，制成含Artoxanthochromane，浓度分别为6.0ug/ml，4.0ug/ml，3.0ug/ml，2.0ug/ml，1.5ug/ml，1.0ug/ml，0.75ug/ml，0.5ug/ml等浓度的斜面培养基。
将浓度为1mg/ml的卡介苗（BCG）菌悬液用接种环蘸取数环，分别接种于含Artoxanthochromane系列浓度的培养基和空白对照培养基斜面上，置于37℃培养4～8周，观察实验结果，结果如表1所示。
本实施例中所用Middlebrook7H9肉汤培养基和Middlebrook7H11琼脂培养基为本领域技术人员进行结核菌培养时的常用培养基，其配方采用常规配方即可。
实验例2固体培养基稀释法测定Artoxanthochromane抗结核分枝杆菌标准株H37Rv株绝对浓度
从斜面上刮取结核分枝杆菌标准株H37Rv株培养物，加入到3mlMiddlebrook7H9肉汤培养基中，加入少量玻璃珠，旋紧试管盖，于漩涡振荡器上剧烈振动研磨，与标准麦氏比浊管（MacFarlandNo.1）比浊，即配成1mg/ml的H37Rv株菌悬液。
将Artoxanthochromane分别用DMSO配成高浓度的原液，用含5%的吐温-80无菌超纯水稀释原液至所需浓度，将稀释好的Artoxanthochromane按所需剂量加入到4mlMiddlebrook7H11琼脂培养基（该培养基已经121℃高压蒸汽灭菌15分钟、冷却至50～55℃），混匀，制成含Artoxanthochromane，浓度分别为6.0ug/ml，4.0ug/ml，3.0ug/ml，2.0ug/ml，1.5ug/ml，1.0ug/ml，0.75ug/ml，0.5ug/ml等浓度的斜面培养基。
将浓度为1mg/ml的H37Rv株菌悬液用接种环蘸取数环，分别接种于含Artoxanthochromane系列浓度的培养基和空白对照培养基斜面上，置于37℃培养4～8周，观察实验结果，结果如表1所示。
实验例3固体培养基稀释法测定Artoxanthochromane抗结核分支杆菌临床分离耐ISREMTB株绝对浓度
从斜面上刮取结核分枝杆菌临床分离耐ISREMTB株（耐异烟肼、链霉素、利福平、乙胺丁醇结核分枝杆菌临床分离柱）培养物，加入到3mlMiddlebrook7H9肉汤培养基中，加入少量玻璃珠，旋紧试管盖，于漩涡振荡器上剧烈振动研磨，与标准麦氏比浊管（MacFarlandNo.1）比浊，即配成1mg/ml的菌悬液。
将Artoxanthochromane分别用DMSO配成高浓度的原液，用含5%的吐温-80无菌超纯水稀释原液至所需浓度，将稀释好的Artoxanthochromane按所需剂量加入到4mlMiddlebrook7H11琼脂培养基（该培养基已经121℃高压蒸汽灭菌15分钟、冷却至50～55℃），混匀，制成含Artoxanthochromane，浓度分别为6.0ug/ml，4.0ug/ml，3.0ug/ml，2.0ug/ml，1.5ug/ml，1.0ug/ml，0.75ug/ml，0.5ug/ml等浓度的斜面培养基。
将浓度为1mg/ml的结核分枝杆菌临床分离耐ISREMTB株菌悬液用接种环蘸取数环，分别接种于含Artoxanthochromane系列浓度的培养基和空白对照培养基斜面上，置于37℃培养4～8周，观察实验结果，结果如表1所示。
表1固体培养基稀释法测定Artoxanthochromane抗结核菌绝对浓度结果
结论：Artoxanthochromane具有很强的抗结核菌和抗耐药性结核菌活性，可作为治疗结核菌感染疾病的先导化合物，也可用于制备治疗结核病药物。
Claims (1)
1.Artoxanthochromane在制备抗结核菌药物中的应用，所述化合物Artoxanthochromane结构如式(Ⅰ)所示：
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Non-Patent Citations (3)
| Title |
|---|
| Horng-Huey Ko等.a novel monoterpene-stilbene adduct with a 4,4-dimethyl-2,3-diphenylchromane skeleton from artocarpus xanthocarpus.《Chemistry & Biodiversity》.2013,第10卷(第7期),1269-1275. * |
| N-乙酰半胱氨酸辅助治疗肺结核患者氧化/抗氧化失衡的影响;梁清涛 等;《临床肺科杂志》;20130228;第18卷(第2期);306-307 * |
| U.B.Jagtap等.Artocarpus: A review of its traditional uses, phytochemistry and pharmacology.《Journal of ethnopharmacology》.2010,第129卷142-166. * |
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