CN116808049A - 一种治疗前列腺炎的药用组合物及其制备方法与应用 - Google Patents
一种治疗前列腺炎的药用组合物及其制备方法与应用 Download PDFInfo
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Abstract
本发明提供了一种治疗前列腺炎的药用组合物及其制备方法与应用,属于药物技术领域。本发明提供的治疗前列腺炎的药用组合物包括左氧氟沙星、吲哚美辛和氯硝西泮,各组分的重量比为:左氧氟沙星250份,吲哚美辛25份,氯硝西泮2.5份。本发明还提供了由上述组合物制备成的药物剂型,其包含药学上可接受任一辅料,以及上述组合物的应用。本发明提供的药物组合物融合了抗生素、非甾体类抗炎药物和精神类药物,从抗菌、抗炎、缓解焦虑和局部神经紧张等多个维度进行干预,起到了明显的协同作用,其针对前列腺炎的治疗效果显著,治疗周期缩短;同时本发明的给药方式采用纳肛治疗,针对性强,前列腺局部药物浓度较高,给药便捷,适合临床推广使用。
Description
技术领域
本发明属于药物技术领域,具体涉及一种治疗前列腺炎的药用组合物及其制备方法与应用。
背景技术
慢性前列腺炎(chronic prostatitis,CP)或是慢性盆腔疼痛综合征(chronicpelvic pain syndrome,CPPS)是困扰男性的常见健康问题。该病的发病率高,成年男性发病率为10%,中亚人群更高,约有70%的男性曾经有过慢性前列腺炎/慢性盆腔疼痛综合征的病史,同时该病表现出年轻化的趋势。
慢性前列腺炎/慢性盆腔疼痛综合征的症状复杂多样,发病机制尚不明确。临床表现主要有尿道刺激征,尿频、尿急、尿道灼痛,尿混浊或大便后尿道口有白色液体流出,长期反复的盆腔周围疼痛不适,排尿异常,可伴有心因性性功能障碍和精神心理疾病,更容易出现抑郁症状,严重影响生活质量。
既往关于CP/CPPS发病机制的报道多集中在病原微生物、尿液反流和氧化应激等影响前列腺微环境的局部病因上。随着医学模式的变化和复杂系统医学的发展,CP/CPPS被发现受病变器官外的因素所调控如全身免疫和内分泌因素,以及毗邻的肠道和腰椎间盘等因素影响。但总体上,CP/CPPS机制复杂并且并无能够很好针对病因治疗的相关药物。
尽管CP/CPPS的病因目前尚未阐明,但现有的观点是:其是一种涉及躯体和精神因素的复杂疾病,治疗上需要运用多学科的综合方法,包括手术,药物,理疗,心理治疗,饮食疗法等,治疗的目标是缓解疼痛,改善功能和消除心理障碍,但病程长者治疗效果不佳。
针对CP/CPPS的既往规范治疗方案主要包括:α受体阻断剂,抗生素,植物制剂等,但其疗效因人而异。由于该病的病因复杂,单一用药往往难以取得理想效果,因此多种药物的联合使用是目前临床上通用的方案,但总体疗效仍然差强人意。许多医生在诊治CP/CPPS过程中感到很棘手,普遍对该病缺乏自信心和准确诊断的能力,最终导致不能合理治疗,造成巨大的医疗和人力资源的浪费。同时该类患者常伴有性功能障碍或其他难以启齿的不适症状,患者就医依从性较差,一次治疗后效果不佳,导致患者对医生的治疗计划使用信心。
现有虽然有开发出针对慢性前列腺炎或是慢性盆腔疼痛综合征的复合药物,但其疗效仍然不佳,新的药物制剂有待进一步开发。
因此,针对于CP/CPPS患病人群基数大,无特效药,市场鱼龙混杂的特点,如果能够提供一种可显著改善慢性前列腺炎症状的正规药物,将蕴含巨大的市场潜力。
发明内容
本发明就是为了解决上述技术问题,从而提供一种治疗前列腺炎的药用组合物及其制备方法与应用。本发明的技术目的在于,为现有慢性前列腺炎/慢性盆腔疼痛综合征的治疗提供一种有效的复方药物,能够显著提升现有药物的治疗效果,并缩短药物治疗时间。
本发明提供了一种治疗前列腺炎的药用组合物,包括左氧氟沙星、吲哚美辛和氯硝西泮。
本发明的药用组合物中,各组分的重量份为:
左氧氟沙星250份,吲哚美辛25份,氯硝西泮2.5份。
左氧氟沙星属于第三代喹诺酮类抗生素,主要治疗革兰氏阴性细菌引起上、下呼吸道感染以及泌尿生殖系统感染,还有皮肤软组织感染等。
吲哚美辛是环氧化酶的非选择性抑制剂,可以抑制前列腺素E的合成,显著降低患者的炎症性疼痛,可抑制白细胞的运动,减少其在炎症部位的浸润和释放致痛物质,从而减轻前列腺局部的炎症反应,消除水肿,解除局部肌肉痉挛,可减少缓激肽的生成,抑制红细胞和血小板的聚集而发挥止痛和抗炎作用。
氯硝西泮是苯二氮类镇静安眠药,具有中枢性肌松作用,对于缓解盆底肌肉痉挛疼痛有较好疗效,同时可以缓解局部坠胀及疼痛不适症状,进而缓解患者的焦虑症状。
由于单一药物在治疗前列腺炎的效果并不佳,后续科研人员展开了对药物联用的研究。高为和汪玉宝于2007年发表了对于采用吲哚美辛栓与曲唑酮用于联合治疗CAP/CAPPS的研究成果,结果显示:在治疗4周后无效例有9例,显效例为7例,好转例有44例;治疗8周后无效例为4例,好转例有48例,显效例为8例。上述两种药物的联用虽表现出一定的协同效果,但治疗效果仍然有待提升,治疗周期也较长。
刘晓艳于2011年发表了宁泌泰联合特拉唑嗪或吲哚美辛栓治疗Ⅲ型前列腺炎的疗效的文章,其对120例病患给予口服宁泌泰胶囊(每次4粒,每天3次)联合特拉唑嗪片(每次2mg,每晚睡前服1次)或吲哚美辛栓(每次1枚,每晚1次)塞肛治疗,疗程为1个月,结果显示:宁泌泰联合特拉唑嗪组总有效率为88.71%,宁泌泰联合吲哚美辛组总有效率为87.93%。虽然表现出一定的联合用药效果,但其疗效仍有待提高,治疗周期有待缩短。
侯贺胜等在《用吲哚美辛栓联合左氧氟沙星治疗慢性前列腺炎的疗效观察》报道了对于慢性前列腺炎患者采用左氧氟沙星和吲哚美辛栓的联合治疗方案,经过4周的治疗,治疗结果为显效者有8例,有效者有25例,无效者有12例,治疗总有效率为71.2%。该研究表明两种药物之间产生了协同治疗效果,但其疗效仍有待进一步提高。
上述研究表明,现有对于治疗前列腺炎的药物联用报道较少,其疗效仍然有待提升,治疗周期较长。目前并无理论支撑如何寻找到其它的联合药物,来显著提升药用组合物的疗效和缩短治疗周期。
然而,本发明人意外发现,采用左氧氟沙星、吲哚美辛和氯硝西泮进行联合用药,所得到的药物组合物在治疗前列腺炎方面产生了显著的协同增效作用,其相比于三种药物的单一用药,以及左氧氟沙星和吲哚美辛的双药联合,治疗效果得到了明显提升。同时本发明的组合物还显著缩短了用药周期,仅用药21天后,炎症表现就大大减轻,表现出了明显的治疗效果。
本发明提供的上述药用组合物融合了抗生素、非甾体类抗炎药物和精神类药物,从抗菌、抗炎、缓解焦虑和局部神经紧张等多个维度进行干预,起到了明显的协同作用。同时本发明的给药方式采用纳肛治疗,针对性强,前列腺局部药物浓度较高,给药便捷。
本发明还提供了一种用于治疗前列腺炎的药物制剂,其包含本发明所述的药用组合物。
本发明的药物制剂为药学上任一可以接受的剂型,包括胶囊、片剂、丸剂、栓剂、水剂或注射制剂等。
本发明还提供了一种用于治疗前列腺炎的复合栓剂,其包含上述药用组合物,以及药学上任一可接受的辅料。
本发明的复合栓剂,可以采用的辅料为法国嘉法狮公司的半合成硬脂AM,辅料的添加量为722.5份。
本发明的又一目的是提供上述用于治疗前列腺炎的药物制剂的制备方法,包括以下步骤:
(1)按照重量份比取相应药物,将其研磨成粉,混合均匀;
(2)向步骤(1)的混合物中添加辅料,制备成相应剂型。
本发明还提供了用于治疗前列腺炎的复合栓剂的制备方法,其包括以下步骤:
(1)将辅料基质进行水浴熔化,然后加入研磨后的药粉混匀,磁力搅拌器混合均匀;
(2)将步骤(1)所得混合物灌模,冷却定型,削平后脱模,即得复合栓剂。
本发明的又一目的是提供如上所述的药用组合物的应用,其是将该药用组合物制备成用于治疗前列腺炎的药物。
具体的,本发明中所述的前列腺炎包括慢性前列腺炎或慢性盆腔疼痛综合征。
本发明的有益效果如下:
与现有的治疗药剂相比,本发明提供的药用组合物中包含的三种药物之间产生了协同增效作用,使得针对前列腺炎的治疗效果得到了明显提升,且能够缩短用药周期,患者炎症表现大大减轻,为现有治疗前列腺炎提供了一种很好的正规治疗方案。同时,本发明采用纳肛治疗,针对性强,前列腺局部药物浓度较高,给药便捷,适合临床推广使用。
附图说明
图1为各处理组术后21天的前列腺指数结果;
图2为各处理组在术前、术后7天和术后21天的炎症因子表达水平;图1和图2中各柱形图从左到右依次代表假手术组、空白组、安慰剂组、单药组(左氧氟沙星)、单药组(吲哚美辛)、单药组(氯硝西泮)、双药组(左氧氟沙星+吲哚美辛)、复合剂型组(左氧氟沙星+氯硝西泮+吲哚美辛);
图3为各处理组术后21天的标本病理结果。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合实施例对本发明进行具体描述,有必要指出的是,以下实施例仅仅用于对本发明进行解释和说明,并不用于限定本发明。本领域技术人员根据上述发明内容所做出的一些非本质的改进和调整,仍属于本发明的保护范围。
实施例1
(一)复合栓剂的药物组成:
每粒栓剂含盐酸左氧氟沙星250mg,吲哚美辛25mg,氯硝西泮2.5mg,辅料为法国嘉法狮公司的半合成硬脂AM。辅料的添加量比为722.5mg。
(二)动物模型:
构建前列腺炎大鼠动物模型,向雄性SD大鼠腹腔注射10%水合氯醛,一至两分钟后,将其平卧于超净台上,于阴茎根部上方2~3cm进行以下处理:(A)做1~2cm横行切口,逐层切开皮肤筋膜,到达肌肉组织是上皮肌肉向下切一小口,出现踏空感后,使用止血钳进入腹腔钝性分离机组织提起膀胱其后方找到颜色较深的前列腺两侧叶;(B)向两侧分别注射3%卡拉胶50微升;(C)注射完成后将膀胱和前列腺回纳腹腔逐层缝合切口;(D)建模一周后,各组大鼠进行测控实验,评估建模效果。
(三)分组设计和给药方法:
取9周龄雄性SD大鼠40只,随机分为8组,每组5只,分别为:假手术组(仅剖腹分离前列腺,前列腺不注射卡拉胶,后重新关腹),空白组(不予任何药物干预),安慰剂组(使用辅料基质相同,但仅含淀粉的栓剂),单药组(左氧氟沙星),单药组(氯硝西泮),单药组(吲哚美辛),双药组(左氧氟沙星+吲哚美辛),复方剂型组(左氧氟沙星+氯硝西泮+吲哚美辛)。给药方式为术后第一天开始每天一次,纳肛1粒(纳肛前禁食4小时排空肠道),持续至术后21天。
(四)数据收集方法:
(1)术后21天取样测量前列腺指数,前列腺指数=前列腺湿重mg/体重×100%。
(2)炎性因子浓度,收集各组大鼠外周血100μl,分离血清,Elisa检测法IL-1a、IL-6表达水平。实验前基础值和实验后不同时间点及终点(术前、7d、21d)。
(3)前列腺病理:术后21天取样做前列腺病理切片(HE染色)。
(五)实验结果统计分析:
1、前列腺指数:与安慰剂组相比较,单药组除氯硝西泮组之外均有差异,以复合剂型组差异最为显著,如图1所示,复合剂型组的前列腺指数最低。
2、炎性因子表达水平:与安慰剂组相比较,单药组均有差异,以复合剂型组差异最为显著,如图2所示,复合剂型组的炎性因子表达水平最低。
3、标本病理:假手术组前列腺组织腺体完整,无炎症细胞浸润,各组模型组可见不等量的组织变性,前列腺腺体水肿或增生,间质内炎性细胞浸润,以空白组和安慰剂组最为显著,单药组相对下降,以复合剂型组炎症表现最轻,如图3所示。
上述实验结果表明,本发明提供的复合剂型组在对前列腺炎的治疗方面产生了明显的协同作用,且复合剂型组比联合用药组的治疗效果更优,协同作用明显提升。
Claims (10)
1.一种用于治疗前列腺炎的药用组合物,其特征在于,所述药用组合物包括左氧氟沙星、吲哚美辛和氯硝西泮。
2.根据权利要求1所述的药用组合物,其特征在于,所述药用组合物按重量份计,包括以下组分:
左氧氟沙星250份,吲哚美辛25份,氯硝西泮2.5份。
3.一种用于治疗前列腺炎的药物制剂,其特征在于,包含权利要求1或2所述的药用组合物。
4.根据权利要求3所述的药物制剂,其特征在于,为药学上任一可以接受的剂型,包括胶囊、片剂、丸剂、栓剂、水剂或注射制剂。
5.一种用于治疗前列腺炎的复合栓剂,其特征在于,包含权利要求1或2所述的药用组合物,以及药学上任一可接受的辅料。
6.根据权利要求5所述的复合栓剂,其特征在于,所述辅料为法国嘉法狮公司的半合成硬脂AM,辅料的添加量为722.5份。
7.一种如权利要求3或4所述用于治疗前列腺炎的药物制剂的制备方法,其特征在于,包括以下步骤:
(1)按照重量份比取相应药物,将其研磨成粉,混合均匀;
(2)向步骤(1)的混合物中添加辅料,制备成相应剂型。
8.一种如权利要求5或6所述用于治疗前列腺炎的复合栓剂的制备方法,其特征在于,包括以下步骤:
(1)将辅料基质进行水浴熔化,然后加入研磨后的药粉混匀,磁力搅拌器混合均匀;
(2)将步骤(1)所得混合物灌模,冷却定型,削平后脱模,即得复合栓剂。
9.如权利要求1或2所述的药用组合物的应用,其特征在于,是将该药用组合物制备成用于治疗前列腺炎的药物。
10.根据权利要求9所述的应用,其特征在于,所述前列腺炎包括慢性前列腺炎或慢性盆腔疼痛综合征。
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