CN116270616A - Carquinostatin A化合物在制备治疗炎症性肠病的药物中的应用 - Google Patents
Carquinostatin A化合物在制备治疗炎症性肠病的药物中的应用 Download PDFInfo
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Abstract
Description
技术领域
本发明属于医药技术领域,具体的说,涉及一种Carquinostatin A化合物在制备治疗炎症性肠病的药物中的应用。
背景技术
炎症性肠病(Inflammatory bowel disease,IBD)是一类由遗传、免疫、感染、环境及饮食习惯等多种因素所致的特异性自身免疫反应,包括溃疡性结肠炎(ulcerativecolitis,UC)和克罗恩病(Crohn’s disease,CD),其主要特征是肠道炎症和上皮损伤。UC局限于结肠,而CD的特征是从口腔到肛门的胃肠道不连续地受累,导致狭窄、脓肿、穿透邻近器官或肛周皮肤的瘘管。近30年间,中国IBD的患病人数增加了54.3%,患病率上升了34.5%,已成为威胁公众健康的一大疾病。
一般认为免疫异常激活是触发IBD的关键因素之一,目前临床治疗靶点大多基于免疫抑制。免疫系统根据介导炎症的功能分为促炎和抗炎两类,如巨噬细胞分为促炎M1型和抗炎M2型,主要根据细胞表面标志物的表达水平和分泌的细胞因子共同决定其功能。研究发现IBD患者表现出固有细胞因子的升高,如IL-6、IL-1β、IL-18等,这些炎症因子的释放,可是肠道组织和巨噬细胞中caspase-1活性增加,从而触发细胞焦亡。
IBD目前主要的治疗药物有5-氨基水杨酸、糖皮质激素、免疫抑制剂和生物制剂。全球范围内,治疗IBD药物品种匮缺,创新药物研究进展缓慢,仅有的5类治疗药物总体临床缓解率都不超过50%。目前主流的治疗药物包括常规治疗(氨基水杨酸盐、糖皮质激素、免疫抑制剂、抗生素)和生物制剂(抗TNFα单克隆抗体)。常规治疗中,氨基水杨酸盐用于轻中度IBD的活动期和维持治疗,糖皮质激素用于中重度IBD的活动期治疗,由于常引起严重不良反应故不适于维持治疗;免疫抑制剂用于中重度IBD的活动期和维持治疗,抗TNFα用于激素和免疫抑制剂无效者。从安全性上看,现有IBD治疗药物可导致一系列感染、肿瘤、血液系统、自身免疫性不良反应;从疗效上看,常规治疗虽能改善症状,但复发率高且对重症患者疗效不佳;抗TNF-α使用者中,约30%无应答,应答者中每年10%患者失效。多种新型生物制剂的涌现为IBD的治疗提供了新的选择,如新型抗TNF-α、黏附因子抑制剂、S1P受体调节剂、Janus激酶抑制剂和MAPK抑制剂等,安全性和有效性仍需扩大规模临床试验加以评估。总体而言,目前IBD治疗药物的临床缓解率都不超过50%。因此研发副作用小、靶点明确且疗效显著的新型小分子药物,仍是IBD创新药物研发的重要方向。
发明内容
本发明的目的是提供一种CarquinostatinA化合物在制备治疗炎症性肠病的药物中的应用。
为了实现上述目的,本发明采用的技术方案如下:
本发明的第一方面提供了一种CarquinostatinA化合物或其药用盐在制备治疗炎症性肠病的药物中的应用。
所述Carquinostatin A(CQS)化合物的结构(Swithching Prenyl DonorSpecificities in Squalene Synthase-Like Aromatic Prenyltransferases fromBacterial Carbazole Alkaloid Biosynthesis.Yaoyao Shen,Liu Zhang,MingYang,TingShi,Yongzhen Li,Lei Li,YiYu,Hai Deng,Hou-Wen Lin,andYongjun Zhou.ACS ChemBiol.2023,18(1):123-133.)如下所示:
所述治疗炎症性肠病的药物是以Carquinostatin A化合物作为唯一活性成分,或CarquinostatinA化合物与药学上允许的至少一种辅料构成药物组合物。
所述CarquinostatinA化合物可以制成药物制剂。
所述药物制剂的剂型选自液体药剂、片剂或胶囊剂。
所述药物制剂的给药方式为口服、静脉注射、腹腔注射或灌肠。
本发明分别从整体动物和细胞实验证实,CarquinostatinA化合物能够有效治疗炎症性肠病,具体如下:从动物实验中可以得出,CarquinostatinA化合物对以DSS诱导的炎症性肠病模型有显著的治疗作用,能够有效减缓小鼠体重的下降和小鼠结肠的缩短;有效减少炎症细胞的浸润,降低肠道损伤,对上皮粘膜屏障具有显著的保护作用,增加肠道中杯状细胞的表达,促进杯状细胞MUC2、Cldn2、Ocln紧密连接蛋白基因的表达;对血清和肠道中释放的炎症因子TNFα、IL-6具有显著的抑制作用,从而减轻或减缓IBD的病程;Carquinostatin A化合物对小鼠肝、肺、肾等器官没有显著影响,说明该化合物无显著毒性。从细胞学实验中可以得出,Carquinostatin A化合物抑制LPS诱导RAW264.7小鼠巨噬细胞中NF-κB、MAPKs、PI3K/AKT等信号通路,从而抑制炎症因子的释放;此外,CarquinostatinA化合物对LPS诱导的“Caco-2/THP-1”共培养体外肠炎模型有显著抑制作用,能够有效降低细胞中LDH的释放,减缓细胞损伤,同时还能够有效抑制细胞上清中炎症因子的表达,说明CarquinostatinA化合物能够通过降低炎症因子的表达,从而减缓体外IBD模型的损伤。这些结果证明,CarquinostatinA化合物确实能够有效治疗IBD,因此可用来制备治疗IBD或其他炎症免疫疾病的药物。
由于采用上述技术方案,本发明具有以下优点和有益效果:
本发明的CarquinostatinA化合物作为小分子化合物对炎症性肠病具有显著的治疗作用,具有毒性低,疗效显著的特征。因此,CarquinostatinA化合物可作为炎症性肠病这一重大疾病的先导化合物,具有重要的开发前景和临床应用价值,也为进一步探究IBD发病的机制,提供了科学依据。
附图说明
图1是CarquinostatinA化合物减缓DSS诱导IBD的小鼠体重降低示意图。
图2是CarquinostatinA化合物抑制DSS诱导IBD的小鼠结肠缩短示意图。
图3是CarquinostatinA化合物改善DSS诱导IBD的小鼠肠道屏障功能示意图。
图4是CarquinostatinA化合物抑制DSS诱导IBD的小鼠中炎症因子的释放示意图。
图5是CarquinostatinA化合物抑制DSS诱导IBD的小鼠结肠焦亡示意图。
图6是CarquinostatinA化合物对DSS诱导IBD的小鼠各器官均无显著毒性示意图。
图7是CarquinostatinA化合物对LPS刺激RAW264.7小鼠的巨噬细胞保护作用示意图。
图8是Carquinostatin A化合物抑制LPS刺激RAW264.7小鼠的巨噬细胞释放的炎症因子示意图。
图9是CarquinostatinA化合物抑制PI3K/AKT、MAPK、NF-κB信号通路示意图。
图10是CarquinostatinA化合物抑制LPS诱导的“Caco-2/THP-1”体外共培养肠炎模型释放的LDH和炎症因子示意图。
具体实施方式
为了更清楚地说明本发明,下面结合优选实施例对本发明做进一步的说明。本领域技术人员应当理解,下面所具体描述的内容是说明性的而非限制性的,不应以此限制本发明的保护范围。
实施例1
CarquinostatinA(CQS)化合物对DSS诱导的IBD模型的作用
材料:化合物CarquinostatinA(CQS)来源于上海交通大学医学院附属仁济医院药剂科;C57BL/6购于昇敞生物科技有限公司;葡聚糖硫酸钠购于美国MP生物科技有限公司;丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肌酐等检测试剂盒购于南京建成生物工程研究所;mouse inflammation cytometric bead array assay购于R&D systems。
实验方法:
1、建立葡聚糖硫酸钠(DSS)诱导的IBD模型:根据The TLR9 Agonist CobitolimodInduces IL10-Producing Wound Healing Macrophages and Regulatory T cells inUlcerative Colitis.J Crohns Colitis.2020.14(4):508-524和Hepatic cytochromeP4508B1 and cholic acid potentiate intestinal epithelial injury incolitis bysuppressing intestinal stem cell renewal.Cell Stem Cell.202229(9):1366-1381,将40只雄性C57BL/6小鼠随机分为5组:对照组(NC组)、2.5%DSS组、100mg/kg 5-氨基水杨酸组(5-ASA组)、化合物CQS低剂量组(2mg/kg)和化合物CQS高剂量组(20mg/kg),每组8只。让小鼠自由饮用2.5%的DSS溶液7天(造模期),正常饮水3天(恢复期)。在小鼠建模第2、4、6天,经腹腔注射分别给予2mg/kg CQS、20mg/kg CQS、生理盐水,灌胃给予5-氨基水杨酸。每天测量小鼠体重,记录粪便性状和出血情况。
2、建立IBD模型后相关各项指标:在建模后第10天,将小鼠处死,眼眶取血,检测血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)、肌酐(Cr)表达水平,检测血清中炎症因子TNFα、IL-6的释放;分离肝、肾、肺、脾组织标本,采用苏木精-伊红染色分析组织病理变化;分离小鼠结肠组织,测量小鼠结肠长度,采用PAS染色法(PeriodicAcid-Schiffstain)、阿利新蓝染色法(Alcian blue stain)分析肠道内杯状细胞的数量,通过RT-PCR检测小鼠肠道内炎症因子TNFα、IL-6、IL-1β和连接相关蛋白的表达。
结果显示:
1、化合物CQS对DSS诱导的IBD小鼠体重的影响,结果如图1所示,图1是CarquinostatinA化合物减缓DSS诱导IBD的小鼠体重降低示意图。在DSS诱导后,与NC组相比,2.5%DSS组小鼠体重显著降低,而化合物CQS高剂量组则能够有效减缓小鼠体重降低,但化合物CQS低剂量组和5-ASA组则没有显著疗效,说明化合物CQS高剂量组能够有效减缓DSS诱导IBD小鼠体重降低。
2、化合物CQS对DSS诱导的IBD小鼠结肠长度的影响,结果如图2所示,图2是CarquinostatinA化合物抑制DSS诱导IBD的小鼠结肠缩短示意图。在DSS诱导后,与NC组相比,2.5%DSS组小鼠结肠长度显著缩短,而化合物CQS高剂量组则能够有效抑制IBD小鼠结肠长度的缩短,但化合物CQS低剂量组和5-ASA组无有效作用,说明化合物CQS高剂量组能够有效抑制DSS诱导IBD小鼠结肠长度的缩短。
3、化合物CQS改善DSS诱导的IBD小鼠肠道屏障功能,结果如图3所示,图3是CarquinostatinA化合物改善DSS诱导IBD的小鼠肠道屏障功能示意图。从HE染色上分析,与NC组相比,2.5%DSS组小鼠结肠组织出现明显的炎症浸润、充血,而5-ASA组、化合物CQS低剂量组和化合物CQS高剂量组均能明显改善DSS诱导IBD小鼠引起的病理改变,炎性浸润程度缩小,组织结构相对完整;通过PAS染色法和阿利新蓝染色法分析结肠上皮中分泌粘蛋白的杯状细胞情况,结果显示DSS降低结肠上皮粘膜厚度,显著减少杯状细胞的数量,5-ASA组、化合物CQS低剂量组和化合物CQS高剂量组均可将这些抑制作用减缓至正常水平(图3中A所示);同时通过RT-PCR检测杯状细胞分泌的MUC2、Cldn2、Ocln紧密连接蛋白基因的表达,紧密连接是正常上皮细胞与细胞黏附的重要功能组成部分,通过机械的方式连接细胞,形成上皮屏障,阻止细胞间的大分子运输,维持上皮细胞极性。与NC组相比,2.5%DSS组显著降低MUC2(图3中B左图)、Cldn2(图3中B中图)、Ocln(图3中B右图)紧密连接蛋白基因的表达,而化合物CQS低剂量组、化合物CQS高剂量组、5-ASA组则可以有效增加因DSS而造成的紧密连接蛋白基因表达的降低(图3中B所示)。结果说明化合物CQS有效改善DSS对小鼠肠道屏障功能的损伤。
4、化合物CQS抑制DSS诱导的IBD小鼠体内炎症因子的释放,结果如图4所示,图4是CarquinostatinA化合物抑制DSS诱导IBD的小鼠中炎症因子的释放示意图。在DSS造模10天后,眼眶取血,采用ELISA法检测小鼠血清中TNFα和IL-6的水平变化,结果显示,与NC组对比,2.5%DSS组血清中促炎介质TNFα和IL-6的水平显著升高,化合物CQS低剂量组和化合物CQS高剂量组均能够有效降低TNFα和IL-6的水平(图4中A所示),5-ASA组则能够有效降低TNFα的表达;同样,提取小鼠结肠RNA,通过RT-PCR检测小鼠结肠中炎症介质TNFα和IL-6的表达,结果显示,化合物CQS低剂量组和化合物CQS高剂量组对TNFα和IL-6的表达显著低于2.5%DSS组(图4中B所示)。结果表明,化合物CQS能够有效降低DSS诱导IBD小鼠中炎症TNFα和IL-6的水平,从而抑制炎症反应。
5、化合物CQS抑制DSS诱导IBD小鼠结肠的焦亡,结果如图5所示,图5是CarquinostatinA化合物抑制DSS诱导IBD的小鼠结肠焦亡示意图。细胞焦亡是一种最近发现的细胞程序性死亡方式,表现为细胞不断胀大直至细胞膜破裂,导致细胞内容物的释放进而激活强烈的炎症反应。当细胞在感受到微生物感染或其他伤害信号时,会组装成一个包含NLRP3的炎性小体,招募并活化Caspase1,活化的Caspase-1通过切割Gasdermin-D而诱发细胞焦亡的,释放大量的炎症因子IL-1β和IL-18。提取小鼠结肠RNA,通过RT-PCR检测小鼠结肠中IL-1β、Caspase1、NLRP3表达,结果显示,2.5%DSS组能够显著促进小鼠结肠中IL-1β(图5中左图)、Caspase1(图5中中图)、NLRP3(图5中右图)表达,而化合物CQS低剂量组和化合物CQS高剂量组则能够有效抑制IL-1β、Caspase1、NLRP3的表达,从而说明化合物CQS能够有效抑制小鼠结肠的焦亡。
6、化合物CQS对DSS诱导IBD小鼠各器官无显著毒性,结果如图6所示,图6是CarquinostatinA化合物对DSS诱导IBD的小鼠各器官均无显著毒性示意图。检测小鼠血清中肌酐(Cr)、谷草转氨酶(AST)、谷丙转氨酶(ALT)表达水平,结果显示,化合物CQS对Cr、AST、ALT无显著影响(图6中A所示);通过HE染色同样证实化合物CQS对肝、肾、肺、脾等器官无显著损伤(图6中B所示)。
CarquinostatinA(CQS)作为小分子化合物,其毒性低,对肺、肝、肾、脾无显著毒性;从体内实验证实能够有效保护肠道粘膜,降低炎症因子对肠道的损伤,避免因DSS刺激造成的结肠缩短,减缓体重的降低,对炎症性肠病具有显著的治疗作用。
实施例2
CarquinostatinA(CQS)化合物对以LPS刺激小鼠巨噬细胞RAW264.7为模型所产生炎症因子及信号通路的作用
材料:小鼠巨噬细胞RAW264.7购于中国科学院细胞库;LPS购于sigma;CCK8试剂、凋亡检测试剂盒购于同仁化学;LDH细胞毒性检测试剂盒购于Promega;抗体pAKT、AKT、pGSK3β、GSK3、pJNK、JNK、pERK、ERK、pP38、P38、pP65、P65、IκB、GAPDH均购于cell signaltechnology。
实验方法:
1、检测化合物CQS对LPS刺激RAW264.7小鼠巨噬细胞的活性影响:1)将RAW264.7细胞按5*103个/ml铺于96孔板中,过夜,分别加入不同浓度的化合物CQS(剂量分别为0,3.125,6.25,12.5,25,50,100μM),24小时后,通过CCK8检测化合物CQS对细胞生长影响;2)将RAW264.7细胞按5*105个/ml铺于12孔板中,过夜,加入不同浓度的化合物CQS(剂量分别为5,10,20μM),培养2小时后,加入LPS(终浓度)1μg/ml,继续培养24小时,通过LDH检测化合物CQS对LPS刺激造成细胞损伤的影响;3)将RAW264.7细胞按5*105个/ml铺于12孔板中,过夜,加入不同浓度的化合物CQS(剂量分别为5,10,20μM),培养2小时后,加入LPS(终浓度)1μg/ml,继续培养24小时,通过流式细胞检测化合物CQS对细胞凋亡的影响。
2、检测化合物CQS对LPS刺激RAW264.7小鼠巨噬细胞炎症因子的影响:将RAW264.7细胞按5*105个/ml铺于12孔板中,过夜,加入不同浓度的化合物CQS(剂量分别为5,10,20μM),培养2小时后,加入LPS(终浓度)1μg/ml,继续培养24小时,通过ELISA和RT-PCR检测化合物CQS对LPS刺激RAW264.7小鼠巨噬细胞炎症因子TNFα、IL-6、NO的影响。
3、检测化合物CQS对LPS刺激RAW264.7小鼠巨噬细胞信号通路的影响:将RAW264.7细胞按1*106个/ml铺于6孔板中,过夜,加入不同浓度的化合物CQS(剂量分别为5,10,20μM),培养2小时后,加入LPS(终浓度)1μg/ml,刺激30分钟后,提取蛋白,通过Western blot检测炎症相关信号通路。
结果显示:
1、化合物CQS对LPS刺激RAW264.7小鼠巨噬细胞的活性影响,结果如图7所示,图7是CarquinostatinA化合物对LPS刺激RAW264.7小鼠的巨噬细胞保护作用示意图。通过CCK8检测发现化合物CQS对RAW264.7小鼠巨噬细胞无显著毒性(图7中A所示);通过LDH检测发现化合物CQS能够有效减缓LPS刺激RAW264.7细胞所造成的损伤,具有保护细胞的作用(图7中B所示);通过流式检测发现化合物CQS对细胞凋亡无影响(图7中C所示)。这些结果证实化合物CQS对RAW264.7小鼠巨噬细胞无细胞毒性,且可减缓LPS刺激RAW264.7细胞所造成的损伤,具有保护细胞的作用。
2、化合物CQS对LPS刺激RAW264.7小鼠巨噬细胞释放炎症因子和NO的作用,结果如图8所示,图8是CarquinostatinA化合物抑制LPS刺激RAW264.7小鼠的巨噬细胞释放的炎症因子示意图。LPS刺激24小时后,RAW264.7细胞释放大量的炎症因子TNFα(图8A中的左图)、IL-6(图8A中的中图)和NO(图8A中的右图),而化合物CQS则能够剂量依赖性的降低炎症因子的释放(图8中A所示);同样,通过RT-PCR检测化合物CQS对RAW264.7细胞中炎症因子表达的影响,结果显示,化合物CQS能够有效降低因LPS刺激而升高的炎症因子TNFα(图8B中的左图)、IL-6(图8B中的中图)、NO表达(图8B中的右图)。说明化合物CQS具有显著的抗炎活性,能够有效抑制因LPS刺激而升高的TNFα、IL-6、NO的表达。
3、化合物CQS对LPS刺激RAW264.7小鼠巨噬细胞信号通路的影响,结果如图9所示,图9是Carquinostatin A化合物抑制PI3K/AKT、MAPK、NF-κB信号通路示意图。通过Westernblot证实,在PI3K/AKT信号通路中,化合物CQS能够有效抑制因LPS刺激而磷酸化的AKT、GSK3β(图9中A所示);在MAPK信号通路中,LPS使JNK、ERK、p38的磷酸化水平显著增加,化合物CQS则能够有效抑制因LPS刺激而活化的MAPK信号通路(图9中B所示);在NF-κB通路中,LPS促进p65磷酸化水平升高,使IκB表达降低,化合物CQS则剂量依赖性的抑制LPS的作用(图9中C所示)。这些结果证实化合物CQS能够通过抑制NF-κB、MAPK、PI3K/AKT信号通路来抑制炎症反应。
通过体外实验证实,CQS可通过调控NF-κB、MAPKs、PI3K/AKT信号通路来抑制炎症因子TNFα、IL-6、NO的表达,从而发挥抗炎作用。
实施例3
CarquinostatinA(CQS)化合物对LPS刺激“Caco-2/THP-1”体外共培养肠炎模型所产生炎症因子的作用
材料:Caco-2细胞和THP-1细胞购于中国科学院细胞库。
实验方法:
1、化合物CQS对LPS刺激“Caco-2/THP-1”体外共培养肠炎模型所产生LDH和炎症因子的作用:将Caco-2细胞按5*104个/孔加入Transwell(0.4μM)小室的上室,连续培养2周;另外将THP-1细胞按3*105个/孔加入12孔板中,加入200nM PMA刺激48小时,换液;将铺有Caco-2细胞的小室,置入放有THP-1细胞的十二孔板中,构建“Caco-2/THP-1共培养”体外肠炎模型;下室加入化合物CQS,浓度为5,10,20μM,培养2小时;加入LPS刺激24小时,通过LDH试剂盒检测上室中LDH的表达;通过ELISA检测下室中炎症因子IL-6和TNFα表达。
结果显示:
1、化合物CQS对LPS刺激“Caco-2/THP-1”体外共培养肠炎模型所产生LDH和炎症因子的作用:结果如图10所示,图10是Carquinostatin A化合物抑制LPS诱导的“Caco-2/THP-1”体外共培养肠炎模型释放的LDH和炎症因子示意图。通过构建的“Caco-2/THP-1”体外共培养肠炎模型证实化合物CQS能够有效减缓细胞损伤,降低LDH的释放(图10中A所示),对炎症因子TNFα(图10B中的左图)、IL-6(图10B中的右图)也具有显著抑制作用。说明化合物CQS能够通过降低LDH释放,减少细胞损伤;通过抑制TNFα、IL-6表达,减少炎症损伤,从而减缓体外IBD模型的损伤。
通过体外“Caco-2/THP-1”共培养肠炎模型证实,CarquinostatinA化合物(CQS)能够有效降低LDH的释放,减少TNFα、IL-6的表达,从而有效减缓体外IBD模型损伤,达到IBD治疗目的。
本发明的Carquinostatin A化合物(CQS)能够有效治疗小鼠的炎症性肠病,减缓小鼠体重下降;抑制小鼠结肠缩短;改善IBD小鼠肠道屏障功能,缩小肠道炎性浸润程度,抑制杯状细胞数量减少,促进杯状细胞分泌MUC2、Cldn2、Ocln,维持组织结构相对完整;抑制结肠内IL-1β、Caspase1、NLRP3的表达,减少小鼠结肠的焦亡;有效降低IBD小鼠中炎症TNFα和IL-6的水平,从而有效减轻或减缓炎症性肠病的发病进程;并且对DSS诱导IBD小鼠各器官无显著毒性。在体外实验中,从LPS刺激RAW264.7细胞中证实CarquinostatinA化合物(CQS)通过调节NF-κB、MAPKs、PI3K/Akt信号通路,抑制炎症因子的产生;此外,从LPS刺激“Caco-2/THP-1”体外共培养肠炎模型证实化合物CQS能够有效减缓细胞损伤,降低LDH的释放,对炎症因子也具有显著抑制作用。说明化合物CQS能够通过降低炎症因子的表达,从而减缓体外IBD模型的损伤。
以上所述仅是本发明的较佳实施例而已,并非对本发明作任何形式上的限制,虽然本发明已以较佳实施例揭露如上,然而并非用以限定本发明,任何熟悉本专利的技术人员在不脱离本发明技术方案范围内,当可利用上述提示的技术内容作出些许更动或修饰为等同变化的等效实施例,但凡是未脱离本发明技术方案的内容,依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰,均仍属于本发明方案的范围内。
Claims (5)
2.根据权利要求1所述的CarquinostatinA化合物或其药用盐在制备治疗炎症性肠病的药物中的应用,其特征在于,所述治疗炎症性肠病的药物是以CarquinostatinA化合物作为唯一活性成分,或CarquinostatinA化合物与药学上允许的至少一种辅料构成药物组合物。
3.根据权利要求1所述的CarquinostatinA化合物或其药用盐在制备治疗炎症性肠病的药物中的应用,其特征在于,所述CarquinostatinA化合物可以制成药物制剂。
4.根据权利要求1所述的CarquinostatinA化合物或其药用盐在制备治疗炎症性肠病的药物中的应用,其特征在于,所述药物制剂的剂型选自液体药剂、片剂或胶囊剂。
5.根据权利要求1所述的CarquinostatinA化合物或其药用盐在制备治疗炎症性肠病的药物中的应用,其特征在于,所述药物制剂的给药方式为口服、静脉注射、腹腔注射或灌肠。
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