CN116747263A - 一种治疗复发性口腔溃疡的中药组合物、中药制剂及其制备方法 - Google Patents
一种治疗复发性口腔溃疡的中药组合物、中药制剂及其制备方法 Download PDFInfo
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Abstract
本发明提出一种治疗复发性口腔溃疡的中药组合物、中药制剂及其制备方法,属于中药技术领域。针对现有技术中的口腔溃疡药物不能缓解口腔溃疡的疼痛或者阵痛效果不理想的问题,本发明的中药组合物包括青黛、黄柏、蟾酥、草乌、五倍子、儿茶、冰片、琥珀、龙骨、甘草,通过加入青黛、黄柏等清热泻火成分,有效清除脾胃积热、心火炽盛、阴虚火旺之病症根源,促进溃疡粘膜修复;加入蟾酥、草乌等消肿止痛成分,迅速缓解患部疼痛;加入琥珀、龙骨等镇静安神成分,有效缓解口腔溃疡引起的烦躁、失眠等。本发明利用各味中药材之间的协同作用及配伍机理,制成兼具促溃疡愈合和迅速镇痛双重作用的中药组合物,能够达到标本兼治,治疗效果好且复发率低。
Description
技术领域
本发明涉及中药技术领域,特别涉及一种治疗复发性口腔溃疡的中药组合物、中药制剂及其制备方法。
背景技术
复发性口腔溃疡(RAU)为临床最常见的口腔黏膜疾病,一般人群的患病率高达20%,主要表现为口腔粘膜反复出现孤立的、圆形或椭圆形的溃疡,溃疡表浅,呈淡黄色,或白色,边缘整齐,周围绕以红晕,可单发或多发。发病不受年龄限制,以青年为多,女性略多于男性,一年四季均能发生,冬春季较多。具有自愈性、高发病率、高复发率等特点。发病时灼痛难忍,严重影响患者日常生活,长期反复发作将直接影响机体免疫功能,还可能有诱发癌变的危险。
目前,RAU的病因和发病机制仍不清楚,尚无特效疗法。临床上常采用糖皮质激素类药物治疗,但此类药物对溃疡修复无明显直接作用,且长期使用副作用较大。对于重型RAU,多采用局部注射肾上腺皮质激素治疗,疗效显著,但该方法易造成局部周围组织的损伤,患者对局部注射激素具有恐惧感,易产生心理负担,远程患者复诊困难,应用受局限。
采用中草药及其方剂治疗复发性口腔溃疡,主要是通过改善微循环、补充微量元素或调节机体免疫功能,从而达到治疗目的。但目前市售的中药制剂普遍存在指标不治本、治疗时间长等缺陷,而且西瓜霜、冰硼散等药物虽然有一定的镇痛效果,但刚刚涂布到溃疡粘膜时常伴随几十秒的灼痛感,灼痛过后才能短暂地缓解疼痛。
近年来,用中药材治疗口腔溃疡的配方越来越多,如专利号为CN109620923B、名称为一种治疗复发性口腔溃疡的中药组合物及其应用的中国发明专利,公开了以生黄芪、石膏、知母、生地、土茯苓、人中白、胡黄连、淡竹叶、拳参、赤芍、丹皮、碧玉散制成的中药组合物,此现有技术中各味原料药来源广泛、其制备方法简单、成本低廉。但上述现有技术的配方却没有侧重于缓解口腔溃疡带来的疼痛或者阵痛效果不理想,因此,亟需研制一种兼具促溃疡愈合和迅速镇痛双重作用的全新中药制剂以解决现有难题就显得尤为必要。
发明内容
本发明的目的是为了克服现有技术中对口腔溃疡的治疗药物的不足和缺陷,提供一种配伍简单、兼具促溃疡愈合和迅速镇痛双重作用的中药组合物,以解决上述现有技术中存在的技术问题。
为了实现上述目的,本发明是通过以下技术方案予以实现的:
本发明的中药组合物是参考我国传统医学体系组成的临床经验方,选用《千金要方·口疮》中记载的青黛、黄柏两味药材为主进行组方。
青黛:咸、寒,归肝、肺、胃经,具有清热解毒,凉血散肿等功效。临床多用于斑疹吐帆,惊痈抽搐,咳嗽咯血,痒腮肿痛等症。
黄柏:苦、寒,归肾经。具有清热燥湿、泻火除蒸,解毒疗疮等功效。
蟾酥:辛、温,归心经。主要用于痈疽疔疮,消肿定痛。
草乌:辛、苦、热,归心、肝、肾、脾经。具有祛风除湿,温经止痛等功效,可用于寒疝作痛及麻醉止痛。
五倍子:酸、涩、寒,归肺、大肠、肾经,主要用于收湿敛疮,镇痛止血。
儿茶:苦、涩、微寒,归肺、心经。具有止血生肌,收湿敛疮,消肿止痛等功效,可用于外伤出血,疮疡不敛,湿疹、湿疮,肺热咳嗽。
冰片:辛、苦、微寒,归心、脾、肺经。可清热止痛,防腐生肌。
琥珀:甘、平,归心、肝、脾、肺、膀胱经。具有镇静安神、散瘀止血等功效,可用于痈疽疮毒、跌打创伤等症状。
龙骨:甘、涩、平,归心、肝、肾经。可镇静安神,收敛固脱,生肌敛疮,止血。
甘草:甘、平,归心、肺、脾、胃经。具有补脾益气,清热解毒,祛痰止咳,缓急止痛,调和诸药等功效。
青黛泻火解毒,黄柏清热燥湿,两药合用,是为君,协同作用清除脾胃积热、心火炽盛、阴虚火旺之病症根源,平火生阴,修复粘膜;蟾酥消肿定痛,草乌温经止痛,五倍子止血生肌,儿茶收湿敛疮,冰片清热止痛,五药合用,是为臣,协助君药消炎止痛,泻火除蒸;同时,佐以琥珀和龙骨,镇静安神、散瘀杀菌;再使以甘草,调和诸药,消除口腔溃疡之标象,诸药合用,共同达到镇痛、消炎、抑菌、止血以及促进溃疡愈合的治疗目的。
基于以上各味中药材的药性机理,本发明公开的一方面是提供了一种治疗复发性口腔溃疡的中药组合物,中药组合物由以下重量份的中药材组成:青黛20~40份、黄柏2~15份、蟾酥15~35份、草乌15~35份、五倍子15~35份、儿茶5~25份、冰片5~25份、琥珀5~25份、龙骨5~25份、甘草2~15份。
优选地,中药组合物由以下重量份的中药材组成:青黛25~35份、黄柏5~12份、蟾酥20~30份、草乌20~30份、五倍子20~30份、儿茶10~20份、冰片10~20份、琥珀10~20份、龙骨10~20份、甘草5~12份。
优选地,中药组合物由以下重量份的中药材组成:青黛32份、黄柏8份、蟾酥24份、草乌24份、五倍子24份、儿茶16份、冰片16份、琥珀16份、龙骨16份、甘草8份。
优选地,中药组合物的粒径≤150μm。
本发明公开的另一方面是提供一种治疗复发性口腔溃疡的中药制剂,中药制剂由上述中药组合物制备而成,或以上述中药组合物为基础添加药学上可接受的辅料制备而成。
本发明的中药组合物根据需要可以加入一些药学上可接受的辅料,采用药剂学常规技术制备中药制剂,包括外用剂型和内服剂型,在原料药基础上加入增稠剂、保湿剂、成膜剂等各种常规辅料,如甘油、液体石蜡、卡波姆、聚乙烯醇等,制成外用制剂,如散剂、喷剂、软膏剂、凝胶剂、膜剂、酊剂、漱口水、漱口片等;还可以在原料药的基础上加入稀释剂、崩解剂、润滑剂等各种常规辅料,如微晶纤维素、乳糖、交联聚维酮、硬脂酸镁等,制成内服制剂,如口服液、汤剂、胶囊剂、颗粒剂、冲剂、片剂、丸剂等。
优选地,为了使该药的各原料更好的发挥药效,减少毒副反应,将原料药制成散剂或喷剂外用,但是这些不能用于限制本发明的保护范围。
本发明公开的又一方面是提供一种治疗复发性口腔溃疡的中药制剂的制备方法,每种中药组合物的药物活性物质是通过传统制药工艺加工制成的,如以下加工方法:
S1:分别按重量份称取青黛、黄柏、蟾酥、草乌、五倍子、儿茶、冰片、琥珀、龙骨、甘草,经粉碎后过六号筛,得到每种中药成分的细粉;
S2:将上述细粉按照等量递增法充分混合;
S3:将混合后的粉末过五号筛五遍,振摇混匀后即得中药粉末,
需要时加入上述辅料,按照药剂学的常规技术制成中药剂型。
或以下方法制得:
S1:分别按重量份称取青黛、黄柏、蟾酥、草乌、五倍子、儿茶、冰片、琥珀、龙骨、甘草,置于容器中;
S2:向容器中加3-8倍重量的水煎3次,每次2小时,得到提取液;
S3:将提取液滤过,浓缩成浸膏;
以上述浸膏为活性成分,需要时加入上述辅料,按照药剂学的常规技术制成中药剂型。
或以下方法制得:
S1:分别按重量份称取青黛、黄柏、蟾酥、草乌、五倍子、儿茶、冰片、琥珀、龙骨、甘草,置于容器中;
S2:向容器中加3-8倍重量的乙醇回流提取3次,每次1小时,分取提取液;
S3:将提取液滤过,溶液蒸馏出乙醇,浓缩成浸膏;
以上述浸膏为活性成分,需要时加入上述辅料,按照药剂学的常规技术制成中药剂型。
本发明与现有技术相比,具有如下的有益效果:
1、通过加入青黛、黄柏等清热泻火的功能成分,能够有效清除脾胃积热、心火炽盛、阴虚火旺之病症根源,促进溃疡粘膜修复;通过加入蟾酥、草乌等消肿止痛的功能成分,能够迅速缓解患部疼痛;通过加入琥珀、龙骨等镇静安神的功能成分,能够有效缓解口腔溃疡引起的烦躁、失眠等不良感受。
2、本发明的中药组合物中的草乌具有表面麻醉效果,可快速阻断神经末梢的痛觉传导,能够有效解决现有口腔溃疡治疗药物镇痛效果不理想的问题,试验证实本发明的中药组合物镇痛效果优于西瓜霜,而且患者使用该中药组合物后,约5s后口腔溃疡特有的疼痛感消失,相比现有市售药物西瓜霜、冰硼散在接触溃疡面时短暂引发的灼痛,本发明的中药组合物在使用过程中无任何不适感,疼痛缓解率高达100%,因此能够显著改善患者的生活质量。
3、本发明的各味中药材来源广泛,价格低廉,配伍和制备工艺简单,解决了现有同类药物配伍复杂、治疗效果不理想的问题;同时中药组合物辩证准确且完整,各成分协同作用,标本兼治,本发明的中药制剂对复发性口腔溃疡治疗效果良好,且复发率低。
附图说明
为了更清楚地说明本发明实施例的技术方案,下面将对实施例中所需要使用的附图作简单地介绍。
图1为本发明的各组大鼠的体质量变化(x±s,n=6);
图2为本发明的各组大鼠口腔溃疡愈合情况观察;
图3为本发明的各组大鼠口腔溃疡组织病理学观察(×100);
图4为本发明的各组大鼠口腔溃疡组织中bFGF、IL-2、IL-6和TNF-α的含量变化(x±s,n=3;与正常组相比,*P<0.05;与模型组相比,#P<0.05);
图5为本发明的各组大鼠口腔溃疡组织中IL-2的含量变化(x±s,n=3;与正常组相比,*P<0.05;与模型组相比,#P<0.05);
图6为本发明的各组大鼠口腔溃疡组织中IL-6的含量变化(x±s,n=3;与正常组相比,*P<0.05;与模型组相比,#P<0.05);
图7为本发明的各组大鼠口腔溃疡组织中TNF-α的含量变化(x±s,n=3;与正常组相比,*P<0.05;与模型组相比,#P<0.05);
图8为本发明的大鼠穿环及开口行为训练图片;
图9为本发明的各组大鼠机械刺激所致疼痛阈值(x±s,n=3;与正常组相比,*P<0.05;与模型组相比,#P<0.05)。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚,下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明的一部分实施例,而不是全部的实施例。
参照图1-9,本发明提供一种治疗复发性口腔溃疡的中药组合物、中药制剂及其制备方法,
中药组合物由以下重量份的中药材组成:青黛20~40份、黄柏2~15份、蟾酥15~35份、草乌15~35份、五倍子15~35份、儿茶5~25份、冰片5~25份、琥珀5~25份、龙骨5~25份、甘草2~15份。
优选地,中药组合物由以下重量份的中药材组成:青黛25~35份、黄柏5~12份、蟾酥20~30份、草乌20~30份、五倍子20~30份、儿茶10~20份、冰片10~20份、琥珀10~20份、龙骨10~20份、甘草5~12份。
优选地,中药组合物由以下重量份的中药材组成:青黛32份、黄柏8份、蟾酥24份、草乌24份、五倍子24份、儿茶16份、冰片16份、琥珀16份、龙骨16份、甘草8份。
优选地,中药组合物的粒径≤150μm。
本发明公开的另一方面是提供一种治疗复发性口腔溃疡的中药制剂,中药制剂由上述中药组合物制备而成,或以上述中药组合物为基础添加药学上可接受的辅料制备而成。
本发明的中药组合物根据需要可以加入一些药物可接受的辅料,采用药剂学常规技术制备中药制剂,中药制剂包括外用剂型和内服剂型,在原料药基础上加入增稠剂、保湿剂、成膜剂等各种常规辅料,如甘油、液体石蜡、卡波姆、聚乙烯醇等,制成外用制剂,如散剂、喷剂、软膏剂、凝胶剂、膜剂、酊剂、漱口水、漱口片等;还可以在原料药的基础上加入稀释剂、崩解剂、润滑剂等各种常规辅料,如微晶纤维素、乳糖、交联聚维酮、硬脂酸镁等,制成内服制剂,如口服液、汤剂、胶囊剂、颗粒剂、冲剂、片剂、丸剂等。
优选地,为了使该药的各原料更好的发挥药效,减少毒副反应,将原料药制成散剂或喷剂外用,但是这些不能用于限制本发明的保护范围。
本发明公开的又一方面是提供一种治疗复发性口腔溃疡的中药制剂的制备方法,每种中药组合物的药物活性物质是通过传统制药工艺加工制成的,如以下加工方法:
S1:分别取上述每种中药材粉碎后过六号筛,得到每种中药材的细粉;
S2:按重量份配比,照等量递增法充分混合;
S3:将混合后的粉末过五号筛五遍,振摇混匀后即得。
或以下方法制得:
S1:分别称取上述每种中药材置于容器中;
S2:向容器中加3-8倍重量的水煎3次,每次2小时,得到提取液;
S3:滤过,浓缩成浸膏;
S4:以上述浸膏为活性成分,需要时加入上述辅料,按照药剂学的常规技术制成中药制剂。
或以下方法制得:
S1:分别称取上述每种中药材置于容器中;
S2:向容器中加3-8倍重量的乙醇回流提取3次,每次1小时,分取提取液;
S3:滤过,滤过,溶液蒸馏出乙醇,浓缩成浸膏;
S4:以上述浸膏为活性成分,需要时加入上述辅料,按照药剂学的常规技术制成中药制剂。
具体地,通过以下几个实施例具体描述本发明的技术方案,但以下实施例不应理解为对本发明所要保护范围的限制,对于本领域的技术人员来说,在以下说明及思路的基础上还可以做出其它不同形式的变化或变动,这里无需也无法对所有的实施方式予以穷举。
实施例1:散剂的制备
按重量份计,青黛32份、黄柏8份、蟾酥24份、草乌24份、五倍子24份、儿茶16份、冰片16份、琥珀16份、龙骨16份、甘草8份;取各中药材分别粉碎后过六号筛,得到各中药材的细粉,按重量份配比照等量递增法充分混合,将混合后的粉末过五号筛五遍,振摇混匀,即得散剂。
实施例2:片剂的制备
按重量份计,青黛30份、黄柏10份、蟾酥22份、草乌26份、五倍子22份、儿茶18份、冰片14份、琥珀18份、龙骨14份、甘草10份;取各中药材分别粉碎后过六号筛,得到各中药材的细粉,按重量份配比照等量递增法充分混合,加入赋形剂微晶纤维素、交联聚维酮、硬脂酸镁混匀,粉末直接压片法制成漱口片,即得。
实施例3:软膏剂的制备
按重量份计,青黛35份、黄柏5份、蟾酥28份、草乌20份、五倍子28份、儿茶12份、冰片20份、琥珀12份、龙骨18份、甘草6份。加3-8倍重量的乙醇回流提取3次,每次1小时,分取提取液,滤过,溶液蒸馏出乙醇,浓缩成浸膏,加入赋形剂凡士林,搅拌均匀制成软膏剂,分装,即得。
实施例4:颗粒剂的制备
按重量份计,青黛28份、黄柏12份、蟾酥20份、草乌28份、五倍子20份、儿茶20份、冰片12份、琥珀20份、龙骨12份、甘草12份。取各中药材,加3-8倍重量的水煎3次,每次2小时,得到提取液,滤过,浓缩成浸膏,加入赋形剂糊精适量,混匀,制成颗粒剂,分装,即得。
实施例5:丸剂的制备
按重量份计,青黛24份、黄柏12份、蟾酥26份、草乌22份、五倍子26份、儿茶14份、冰片18份、琥珀14份、龙骨18份、甘草10份。取各中药材,加3-8倍重量的水煎3次,每次2小时,得到提取液,滤过,浓缩成浸膏,加入赋形剂淀粉,搅拌均匀制成丸剂,分装,即得。
实施例6:试验验证
取实施例1作为受试药进行药效学试验验证,选用市售药西瓜霜作为阳性对照,试验结果如下:
1、对大鼠口腔溃疡的促愈合作用的试验验证
1.1口腔溃疡模型的建立
选用健康雄性SD大鼠108只,将大鼠随机分为6组,即正常组、模型组、阳性药桂林西瓜霜组、受试药低、中、高剂量组,每组18只。放在昼夜交替,温湿度分别为(24±2℃和40~70%)的房间适应性饲养三天,正常饮食。用舒泰50(0.75g/kg)和盐酸赛拉嗪(0.01g/kg)腹腔注射麻醉,将50%冰醋酸浸润的直径为5mm的脱脂棉球紧贴于大鼠下唇口角黏膜处,持续按压60s后迅速移除棉球并用5mL生理盐水冲洗,建立口腔溃疡模型(正常组用生理盐水代替冰醋酸,其它操作步骤一样)。24h后,观察局部黏膜的炎症情况,如果观察到红肿假膜则表明溃疡形成。
1.2给药方法
造模成功当日开始给药,阳性组按2次/天(相当于0.50g/kg)撒布给药,受试药低、中、高剂量组分别按1、2、3次/天(相当于0.25、0.50、0.75g/kg)撒布给药,连续给药4天,正常组、模型组不作任何处理。用药后2h内禁食禁水,其余时间自由进食进水。
1.3大体观察
造模成功后观察动物外观、精神及一般状况的变化。结果显示,正常组大鼠反应灵敏,背毛光泽,二便和活动正常;模型组大鼠反应迟钝,口唇边潮湿,流口水,毛发粗糙分叉,大便偏稀;阳性组和受试药组大鼠反应灵敏,背毛光泽,活动正常。
1.4体质量变化
造模成功后记录大鼠体质量变化,结果如图1。
试验第2日,与正常组比较,模型组、阳性组和受试药各剂量组体质量变化均显著下降(P<0.05),说明冰醋酸处理使大鼠产生疼痛与不适导致了大鼠体质量下降;
试验第3日,与模型组比较,阳性组和受试药各剂量组体质量变化均显著升高(P<0.05),说明给予适量药物处理能够缓解大鼠口腔不适,减少大鼠的体质量下降;
试验第5日,与模型组相比,受试药高剂量组大鼠体质量变化显著升高(P<0.05),与正常组相比差异无统计学意义;
试验第7日,与模型组相比,受试药中剂量组大鼠体质量变化显著升高(P<0.05),与正常组相比差异无统计学意义。
结果提示,受试药处理能够加快大鼠体质量的恢复。
1.5溃疡创面愈合情况观察
造模成功后观察大鼠溃疡创面愈合情况,结果如图2。
正常组大鼠各时间点口腔黏膜表面光滑,无水肿,无充血现象(图2A,B,C)。
试验第3日,模型组、阳性组和受试药各剂量组造模区黏膜水肿,形成黄白色假膜(图2D,G,J,M,P);
试验第6日,模型组黄白色假膜还未脱落,局部充血严重(图2E);阳性组和受试药低、中剂量组黄白色假膜变薄并部分脱落(图2H,K,N);受试药高剂量组黄白色假膜已完全脱落,肿胀程度减轻,组织周围充血减轻(图2Q);
试验第9日,模型组黄白色假膜还未完全脱落,与第6天相比有明显的好转(图2F);阳性组和受试药各剂量组假膜完全脱落,溃疡基本愈合,肿胀现象消失,周围组织充血消失,外观同正常组没有明显差异(图2I,L,O,R)。
结果表明,受试药处理能够明显加速口腔溃疡的愈合,同时验证口腔溃疡具有自愈性。
1.6溃疡组织病理学观察
各组于试验开始后第3、6、9日各随机选取3只大鼠处死取得黏膜标本后,将黏膜标本用生理盐水冲洗干净后立即放入4%多聚甲醛溶液进行固定,用石蜡对组织进行包埋后,连续5μm切片,HE染色,然后在光学显微镜下观察分析,结果如图3。正常组大鼠口腔黏膜上皮完整连续,固有层无血管充血及大量炎性细胞浸润等病理改变(图3A,B,C)。
试验第3日,模型组、阳性组和受试药各剂量组黏膜上皮结构被破坏消失,表面有纤维性渗出,细胞出现空泡变性,溃疡部位有密集的炎性细胞浸润,以中性粒细胞和淋巴细胞为主(图3D,G,J,M,P)。
试验第6日,模型组上皮呈现修复反应,但炎性细胞浸润明显,大多为淋巴细胞(图3E);阳性组和受试药低、中剂量组有新的肉芽组织产生,上皮细胞层次增多,但仍有炎性细胞浸润(图3H,K);受试药高剂量组基底层逐渐修复,炎性细胞浸润明显减少,粘膜组织结构趋于完整(图3N)。
试验第9日,模型组黏膜上皮初步修复,但是厚度不一,层次紊乱(图3F);阳性组和受试药各剂量组黏膜上皮完全愈合,厚度均匀,层次分明,与正常组无明显差异(图3I,L,O,R)。
结果表明,受试药处理能够明显加速口腔溃疡的愈合,同时验证口腔溃疡具有自愈性。
1.7溃疡局部组织中炎性因子bFGF、IL-2、IL-6和TNF-α含量测定
各组于试验开始后第3、6、9日各随机选取3只动物处死。正常组切取正常黏膜,其余各组切取溃疡组织黏膜,用预冷的生理盐水冲洗组织以去除残留血液,用眼科小剪将黏膜剪碎,操作应在冰水浴中进行,置于EP管中称重后用移液枪加入NP-40裂解液,裂解液的体积是黏膜重量的10倍,将EP管置于盛有冰水的烧杯中,用细胞超微粉碎机对黏膜进行充分粉碎。将粉碎得到的组织匀浆置于高速离心机中,于4℃、5000r/min离心20min后用移液枪移取上清液分装保存于-20℃冰箱中备用,按ELISA试剂盒说明书操作进行上清液中bFGF、IL-2、IL-6和TNF-α含量的测定,结果如图4-7。
试验第3日,与正常组相比,模型组、阳性组和受试药各剂量组口腔溃疡组织中bFGF和IL-2的含量显著下降(P<0.05),IL-6和TNF-α的含量显著增加(P<0.05),说明造模成功。
试验第6日,与模型组相比,阳性组和受试药各剂量组bFGF和IL-2的含量显著增加(P<0.05),IL-6和TNF-α的含量显著下降(P<0.05)。
试验第9日,与正常组相比,阳性组和受试药各剂量组口腔溃疡组织中bFGF、IL-2、IL-6和TNF-α的含量差异无统计学意义,与模型组相比,bFGF和IL-2的含量仍显著增加(P<0.05),IL-6和TNF-α的含量仍显著下降(P<0.05)。
2、对大鼠口腔溃疡的镇痛作用的试验验证
2.1机械刺激测量疼痛阈值模型的建立
选用健康雄性SD大鼠18只,将大鼠随机分为6组,即正常组、模型组、阳性药桂林西瓜霜组、受试药低、中、高剂量组,每组3只。放在昼夜交替,温湿度分别为(24±2℃和40~70%)的房间适应性饲养三天,正常饮食。为了稳定的暴露大鼠口腔黏膜的穹窿区域,用舒泰50(0.75g/kg)和盐酸赛拉嗪(0.01g/kg)腹腔注射麻醉,然后给大鼠穿环,大鼠穿环以后先适应一周,待一周行为稳定后增加一个6g的重物使其能够稳定暴露黏膜,将大鼠放置在手工制作的黑色塑料盒中每天10分钟,连续训练两周后,按照上述“1.1”及“1.2”方法进行口腔溃疡造模及给药,穿环及开口行为训练情况如图8。
2.2VonFrey法测定大鼠疼痛阈值
使用一组VonFrey丝(0.02、0.04、0.07、0.16、0.4、0.6、1、2、4和6g)刺激口腔黏膜测量疼痛阈值。为了防止损伤黏膜最大使用6g的VonFrey丝进行测量,于试验第1日即造模当日,试验第2、5、9日末次给药后进行测量。在测试前,将大鼠置于自制的塑料盒中10min,待大鼠行为稳定后采用VonFrey丝刺激稳定暴露的口腔溃疡区黏膜,并将大鼠有挣扎和企图逃脱的行为定义为阳性反应。发现有阳性行为时选用小一个型号的针再试,测量5次出现3次阳性行为就定义为机械阈值,每次测量之间相隔至少30s,结果如图9,试验第2、5、9日,与正常组和模型组比较,受试药各剂量组机械刺激所致疼痛阈值均显著升高(P<0.05),且优于阳性组。说明适量受试药处理能够明显缓解冰醋酸诱发的大鼠口腔溃疡区疼痛。
经过上述试验结果可得出,本发明提出的中药组合物可明显加快大鼠口腔溃疡的愈合,减轻炎症反应并缓解疼痛程度,且与阳性药物西瓜霜相比,本发明的中药组合物具有更优的镇痛效果。
以上所述仅是本发明的优选实施方式,应当指出,对于本领域的普通技术人员来说,在不脱离本发明原理及未付出创造性劳动的前提下,还可以作出若干改进、润饰和替换,这些改进、润饰和替换也包括在本发明的保护范围内。
Claims (10)
1.一种治疗复发性口腔溃疡的中药组合物,其特征在于,中药组合物由以下重量份的中药材组成:青黛20~40份、黄柏2~15份、蟾酥15~35份、草乌15~35份、五倍子15~35份、儿茶5~25份、冰片5~25份、琥珀5~25份、龙骨5~25份、甘草2~15份。
2.根据权利要求1所述的一种治疗复发性口腔溃疡的中药组合物,其特征在于,中药组合物由以下重量份的中药材组成:青黛25~35份、黄柏5~12份、蟾酥20~30份、草乌20~30份、五倍子20~30份、儿茶10~20份、冰片10~20份、琥珀10~20份、龙骨10~20份、甘草5~12份。
3.根据权利要求2所述的一种治疗复发性口腔溃疡的中药组合物,其特征在于,中药组合物由以下重量份的中药材组成:青黛32份、黄柏8份、蟾酥24份、草乌24份、五倍子24份、儿茶16份、冰片16份、琥珀16份、龙骨16份、甘草8份。
4.根据权利要求1-3任一项所述的一种治疗复发性口腔溃疡的中药组合物,其特征在于,中药组合物的粒径≤150μm。
5.一种由权利要求1-3任一项所述中药组合物或在中药组合物中添加药学上可接受的辅料制备而成的中药制剂。
6.根据权利要求5所述的一种治疗复发性口腔溃疡的中药制剂,其特征在于,包括外用剂型和内服剂型,其中:
外用剂型为散剂、喷剂、软膏剂、凝胶剂、膜剂、酊剂、漱口水、漱口片中的一种;
内服剂型为口服液、汤剂、胶囊剂、颗粒剂、冲剂、片剂、丸剂中的一种。
7.根据权利要求5所述的一种治疗复发性口腔溃疡的中药制剂,其特征在于,药学上可接受的辅料包括增稠剂、保湿剂、成膜剂、稀释剂、崩解剂、润滑剂、着色剂、甜味剂、粘合剂、或抗氧化剂中的一种或多种。
8.一种治疗复发性口腔溃疡的中药粉末的制备方法,其特征在于,至少包括以下步骤:
S1:分别按重量份称取青黛、黄柏、蟾酥、草乌、五倍子、儿茶、冰片、琥珀、龙骨、甘草,经粉碎后过六号筛,得到每种中药成分的细粉;
S2:将上述细粉按照等量递增法充分混合;
S3:将混合后的粉末过五号筛五遍,振摇混匀后即得。
9.一种治疗复发性口腔溃疡的中药浸膏的制备方法,其特征在于,至少包括以下步骤:
S1:分别按重量份称取青黛、黄柏、蟾酥、草乌、五倍子、儿茶、冰片、琥珀、龙骨、甘草,置于容器中;
S2:向容器中加3-8倍重量的水煎3次,每次2小时,得到提取液;
S3:将提取液滤过,浓缩成浸膏。
10.一种治疗复发性口腔溃疡的中药浸膏的制备方法,其特征在于,至少包括以下步骤:
S1:分别按重量份称取青黛、黄柏、蟾酥、草乌、五倍子、儿茶、冰片、琥珀、龙骨、甘草,置于容器中;
S2:向容器中加3-8倍重量的乙醇回流提取3次,每次1小时,分取提取液;
S3:将提取液滤过,溶液蒸馏出乙醇,浓缩成浸膏。
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