CN106943392A - 一种用于治疗小儿疝气的药物组合物及其用途 - Google Patents
一种用于治疗小儿疝气的药物组合物及其用途 Download PDFInfo
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Abstract
本发明涉及一种用于治疗小儿疝气的药物组合物及其用途,所述药物组合物包括对羟基苯乙腈、原花青素、绿原酸、局部麻醉剂和药学上可接受的辅料,本发明药物组合物通过局部涂抹或疝囊内部注射方式施用后可刺激疝环的非细菌性的炎性反应,促进成纤维细胞的增殖,诱导疝环周围组织的纤维化,促进组织修复,使疝环逐渐缩小,直至闭合。本发明药物组合物局部使用,安全有效,无需手术,可避免手术所带来的痛苦。
Description
技术领域
本发明属于药物领域,具体地,涉及一种治疗小儿疝气的药物组合物及其用途。
背景技术
小儿疝气为小儿常见病之一,主要包括腹股沟斜疝、脐疝等,疝气的形成与正常组织强度弱、腹内压力增高等因素有有关,若得不到及时、有效的治疗,将逐渐增大,可造成肠坏死等,严重者可危及患儿生命。小儿疝气的形成有先天因素和后天因素,先天性因素主要为先天性的生理缺陷,后天性缺陷包括后天营养不良,小孩突发性的大哭导致腹腔压力突然增大,腹腔内容物突破薄弱环节向外突出而形成各种类型的疝,对儿童的生长发育造成严重的影响。
患儿年龄在一岁之内时,疝气还有自愈的可能,当患儿年龄超过一岁时一般很难自愈,需要及时进行治疗,目前临床上治疗疝气的方法主要包括:
手术疗法:其为通过手术方法,在患儿全身麻醉后,高位结扎疝囊,阻止疝内容物脱出,加强精索前壁或后壁的修补,增强腹壁张力及强度。手术治疗目前为治疗小儿疝气最有效的治疗方法之一,但其也存在诸多弊端:(1)手术造成伤口及后期可能存在的伤口感染给患儿带来很大的痛苦;(2)存在反复的可能;(3)需要对患儿进行全身麻醉,存在术后躁动等不良反应。
疝气带:该方法对新生婴儿有一定的疗效,但对1岁以上的患儿疗效很差,对2岁以上患儿几乎无效。
药物治疗:目前针对小儿疝气的药物治疗多采取防风、麻黄、山楂、当归等药物组方,治疗效果差。目前也存在通过局部注射硬化剂的方式治疗小儿疝气的方法,治疗效果也不理想,且副作用多。
为了克服现有小儿疝气治疗方法的各种弊端,本发明致力于开发一种安全有效的治疗小儿疝气的药物组合物。
发明内容
本发明的一个目的是提供一种治疗小儿疝气的药物组合物,所述药物组合物包括对羟基苯乙腈、原花青素、绿原酸、局部麻醉剂和药学上可接受的辅料。
优选的,所述治疗小儿疝气的药物组合物中对羟基苯乙腈、原花青素、绿原酸、局部麻醉剂的重量比为1-5:5-10:1-5:0.5-2,优选的为2-3:6-8:1-2:0.5-1,更优选的为3:8:1:0.5。
优选的,所述局部麻醉剂选自:利多卡因、普鲁卡因、布比卡因或罗哌卡因,更优选的为利多卡因。
本发明提供一种治疗小儿疝气的药物组合物,所述药物组合物包含对羟基苯乙腈3份、原花青素8份、绿原酸1份、利多卡因0.5份和药学上可接受的辅料。
本发明治疗小儿疝气的药物组合物适于局部使用或疝囊内注射使用,适宜的局部制剂包括软膏剂、喷雾剂等,优选的为软膏剂,适于的注射制剂为注射液或冻干粉针剂。本发明治疗小儿疝气的药物组合物可以使用本领域常规的制剂方法制备成相应的剂型
优选的,本发明的局部制剂中还包含促渗剂,更优选的,所述促渗剂为尿素。
本发明所述治疗小儿疝气的药物组合物中活性成分对羟基苯乙腈、原花青素、绿原酸和局部麻醉剂的含量可以为药物组合物总重量的1-90%,优选的为5-30%,更优选的为10-20%,最优选的为15%。
本发明的再一个目的是提供对羟基苯乙腈、原花青素、绿原酸与局部麻醉剂的组合在制备治疗小儿疝气药物组合物的用途。
优选的,所述局部麻醉剂选自:利多卡因、普鲁卡因、布比卡因或罗哌卡因,更优选的为利多卡因。
所述治疗小儿疝气的药物组合物中对羟基苯乙腈、原花青素、绿原酸、局部麻醉剂的重量比为1-5:5-10:1-5:0.5-2,优选的为2-3:6-8:1-2:0.5-1,更优选的为3:8:1:0.5。
有益效果
本发明治疗小儿疝气的药物组合物,无需手术即可以有效治疗小儿疝气,安全有效,患儿无痛苦,本申请药物组合物通过局部涂抹或疝囊内部注射方式施用后可刺激疝环的非细菌性的炎性反应,促进成纤维细胞的增殖,诱导疝环周围组织的纤维化,促进组织修复,使疝环逐渐缩小,直至闭合,从而有效治疗小儿疝气。
具体实施方式
在下文中更详细地描述了本发明以有助于对本发明的理解。
应当理解的是,在说明书和权利要求书中使用的术语或词语不应当理解为具有在字典中限定的含义,而应理解为在以下原则的基础上具有与其在本发明上下文中的含义一致的含义:术语的概念可以适当地由发明人为了对本发明的最佳说明而限定。
实施例1:一种治疗小儿疝气的软膏剂
对羟基苯乙腈 30g;
原花青素 80g;
绿原酸 10g;
利多卡因 5g;
尿素 15g;
尼泊金甲酯 5g;
凡士林 855g;
所述治疗小儿疝气的软膏剂,通过以下步骤进行制备:
(1)按照配方量称取对羟基苯乙腈、原花青素、绿原酸、利多卡因、尿素、尼泊金甲酯和凡士林;
(2)将羟基苯乙腈、原花青素、绿原酸、利多卡因、尿素、尼泊金甲酯与200g凡士林加入配料罐后搅拌均匀;
(3)添加剩余凡士林后搅拌均匀,灭菌后灌装,即得本发明治疗小儿疝气的软膏剂。
效果例1:对大鼠腹壁切口疝的影响
1.1实验药物
(1)实施例1治疗小儿疝气的软膏剂。
1.2实验方法
4周龄雄性SD大鼠15只,体重75±5g。
适应性饲养2天后,大鼠自由进水,但禁食12h,以3%戊巴比妥腹腔注射麻醉后固定于手术台上,以大鼠下腹部为中心线划取3×3cm区域进行脱毛,并先后使用碘酒、75%酒精消毒,于脱毛区域沿大鼠腹部正中纵向切开皮肤,长度约3cm,钝性分离肌肉组织后,切除2×2cm的全部腹壁组织,然后缝合皮肤,伤口每日消毒,7日后选取形成疝囊的大鼠10只,随机分为两组,具体为空白组与实施例1组,测量每组大鼠疝囊长度与宽度。每天两次与疝囊及周围皮肤涂抹实验药物,其中空白组涂抹与实施例1软膏剂相同,但不包含对羟基苯乙腈、原花青素、绿原酸、利多卡因的软膏。连续给药30天,末次给药3h后,再次麻醉大鼠,测量疝囊长度与宽度,暴露疝环,测量每组大鼠疝环内径,具体实验结果见表1。
1.3试验结果
表1、对大鼠腹壁切口疝的影响
注:与空白组比较:**P<0.01。
大鼠腹壁切口疝的实验结果显示了空白组大鼠随着体重的增大,饲养30天后,疝囊大小明显增大,而使用本发明实施例1软膏的大鼠,在体重明显增加的情况下,疝囊大小不仅未增大,其疝囊大小相对于给药前均出现了一定程度的缩小,且施用本发明实施例1组软膏剂后,大鼠腹壁切口疝的疝环直径也明显小于空白组,从而表明本发明实施例1的软膏剂具有治疗疝气的优异效果。
效果例2:对小鼠皮肤成纤维细胞(3T6)增殖的影响
2.1实验药物
按照3:8:1:0.5的比例称取对羟基苯乙腈、原花青素、绿原酸、利多卡因,使用PBS溶液分别配制成高剂量组100μg/mL、中剂量组50μg/mL的药液
2.2实验方法
取对数生长期的3T6细胞,按照1×104/mL浓度接种于96孔板中,共80孔,每孔200μL,每孔加入DEME培养基200μL,将96孔板置于37℃、5%CO2的细胞培养箱中培养24h。24h后96孔板分为4组,分别为空白组、高剂量组、中剂量组和低剂量组,每组20孔,每孔添加实验药物100μL,其中空白组添加PBS缓冲液。培养24小时后使用MTT法,于490nm测量各孔吸光度值,计算测定实验药物对3T6细胞增殖的影响,计算促增殖率,实验结果见表2,其中
促增殖率=(实验组OD-空白组OD)/实验组OD×100%。
2.3试验结果
表2、实验药物对4-氨基吡啶致小鼠瘙痒的影响
注:与空白组比较:*P<0.05;**P<0.01。
对比例1为:按照8:1:0.5的比例称取对原花青素、绿原酸、利多卡因,使用PBS溶液分别配制成100μg/mL的药液
对比例2为:按照3:8:0.5的比例称取对羟基苯乙腈、原花青素、利多卡因,使用PBS溶液分别配制成100μg/mL的药液
表2实验结果显示了高、中剂量的本发明药物组合物均显示出一定的小鼠皮肤成纤维细胞促进增殖的效果,该实验结果揭示了本发明药物组合物治疗小儿疝气的效果可能与其促进成纤维细胞增殖,诱导组织纤维化,增强组织张力与强度的效果有关。
Claims (10)
1.一种用于治疗小儿疝气的药物组合物,其特征在于,所述药物组合物包括对羟基苯乙腈、原花青素、绿原酸、局部麻醉剂和药学上可接受的辅料。
2.根据权利要求1所述的治疗小儿疝气的药物组合物,其特征在于,所述对羟基苯乙腈、原花青素、绿原酸、局部麻醉剂的重量比为1-5:5-10:1-5:0.5-2,优选的为2-3:6-8:1-2:0.5-1,更优选的为3:8:1:0.5。
3.根据权利要求1或2所述的治疗小儿疝气的药物组合物,其特征在于,所述局部麻醉剂选自:利多卡因、普鲁卡因、布比卡因或罗哌卡因,更优选的为利多卡因。
4.根据权利要求1-3任一项所述的治疗小儿疝气的药物组合物,其特征在于,所述药物组合物包含对羟基苯乙腈3份、原花青素8份、绿原酸1份、利多卡因0.5份和药学上可接受的辅料。
5.根据权利要求1-4任一项所述的治疗小儿疝气的药物组合物,其特征在于,所述药物组合物为局部制剂或注射制剂。
6.根据权利要求5所述的治疗小儿疝气的药物组合物,其特征在于,所述局部制剂选自软膏剂、喷雾剂,优选的为软膏剂,所述注射制剂为注射液或冻干粉针剂。
7.根据权利要求5或6所述的治疗小儿疝气的药物组合物,其特征在于,所述局部制剂中还包含促渗剂、防腐剂,优选的,所述促渗剂为尿素,所述防腐剂为尼泊金酯。
8.根据权利要求1-7任一项所述的治疗小儿疝气的药物组合物,其特征在于,所述药物组合物中活性成分对羟基苯乙腈、原花青素、绿原酸和局部麻醉剂的含量为药物组合物总重量的1-90%,优选的为5-30%,更优选的为10-20%,最优选的为15%。
9.对羟基苯乙腈、原花青素、绿原酸与局部麻醉剂的组合在制备治疗小儿疝气药物组合物的用途。
10.根据权利要求9所述的用途,其特征在于,所述局部麻醉剂选自:利多卡因、普鲁卡因、布比卡因或罗哌卡因,更优选的为利多卡因。
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