CN108309997B - 一种治疗痛风性关节炎的外用凝胶制剂及其制备方法 - Google Patents
一种治疗痛风性关节炎的外用凝胶制剂及其制备方法 Download PDFInfo
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Abstract
本发明属于医药领域,具体涉及一种治疗痛风性关节炎的外用凝胶制剂及其制备方法。该外用凝胶制剂的有效成分为香芹酚、番泻苷B,二者重量份比为:香芹酚13~18重量份、番泻苷B 1~3重量份。本发明的外用凝胶制剂对痛风性关节炎具有良好的治疗作用,且安全性良好。
Description
技术领域
本发明属于医药领域,具体涉及一种治疗痛风性关节炎的外用凝胶制剂及其制备方法。
背景技术
痛风性关节炎是尿酸盐沉积于关节囊、滑囊、软骨、骨质和其他组织中而引起骨关节病损及炎性反。该病可能与遗传因素有关,多发于40岁以上男性。该病常表现为跖趾关节、踝关节等处红肿热痛反复发作,甚至活动障碍和关节畸形,迁延难愈。过去认为本病是欧美国家的常见病,但随着人民生活水平的提高,饮食结构的变化,我国发病率有上升的趋势。
痛风分为原发性和继发性两大类,原发性患者有不足1%为酶缺陷所,其余病因大都不明。继发性可由肾脏病、血液病及药物等引起。现代医学认为痛风发病的先决条件是高尿酸血症,血中尿酸浓度过高导致尿酸盐沉积在组织中造成痛风组织学改变,导致痛风性关节炎的发作。
目前痛风性关节炎常用的治疗药物:秋水仙碱、非甾体抗炎药、糖皮质激素等。其中秋水仙碱可缓解痛风性关节炎患者的疼痛,但其毒副作用较大,近几年其应用已经开始下降。非甾体抗炎药如双氯芬酸钠、吲哚美辛等等,为治痛风性关节炎的一线用药,可缓解患者疼痛,然而,其具有诸多毒性作用,如胃肠毒性,肾毒性以及胃肠道出血等。糖皮质激素如曲安奈德等也可缓解痛风性关节炎的症状,但易引起内分泌失常等问题。
香芹酚( Carvacrol) 也称为香荆芥酚,是一种单帖酚,广泛存在于各种天然植物中。最近研究结果表明其具有较强的抗氧化、抗炎特性。对痛风性关节炎具有一定的治疗作用(刘安宁,张高生,黄晶,王亮. 香芹酚对大鼠痛风性关节炎中血清炎性因子及软骨细胞凋亡的影响. 临床和实验医学杂志.2017;16(6):531.)。但香芹酚几乎不溶于水,口服生物利用度较低,外用需要进行一定比例的稀释方可避免皮肤刺激性。
发明内容
针对上述现有技术,本发明的目的之一是提供一种治疗痛风性关节炎的外用凝胶制剂。
为实现上述的目的,本发明采用的技术方案为:
一种治疗痛风性关节炎的外用凝胶制剂,由医药学上可接受的外用凝胶制剂辅料和以下原料中的至少一种制成:香芹酚、番泻苷B。
优选的,所述治疗痛风性关节炎的外用凝胶制剂由医药学上可接受的外用凝胶制剂辅料和香芹酚、番泻苷B制成,所述原料的重量份比为香芹酚 13~18重量份、番泻苷B 1~3重量份。
优选的,所述原料的重量份比为香芹酚14重量份、番泻苷B 3重量份。
优选的,所述原料的重量份比为香芹酚17重量份、番泻苷B 2重量份。
优选的,所述原料的重量份比为香芹酚18重量份、番泻苷B 1重量份。
优选的,所述医药学上可接受的外用凝胶制剂辅料包括卡泊姆940、无水乙醇、丙二醇、吐温-80、三乙醇胺、碳酸氢钠和水。
优选的,所述卡泊姆940的用量为香芹酚重量的5倍、无水乙醇的用量为香芹酚重量的35倍,丙二醇的用量为香芹酚重量的2倍、吐温-80的用量为香芹酚重量的1倍、三乙醇胺的用量为香芹酚重量的1倍、碳酸氢钠的用量为番泻苷B重量的50倍、水的用量为香芹酚重量的700倍。
本发明的另一方面提供了一种上述治疗痛风性关节炎的外用凝胶制剂的制备方法,包括如下步骤:
(1)取处方量卡泊姆940加水溶胀制成凝胶基质;
(2)取处方量无水乙醇、丙二醇、吐温-80和香芹酚混合搅拌均匀加入步骤(1)所得凝胶基质中搅拌均匀;
(3)取处方量碳酸氢钠用水配制成质量分数为2%的水溶液,加入处方量番泻苷B,搅拌均匀,加入步骤(2)所得载药凝胶基质中搅拌均匀;
(4)向步骤(3)所得混合物中加入处方量三乙醇胺和余量水,搅拌均匀,得外用凝胶制剂。
本发明技术方案所述的香芹酚,英文名为Carvacrol,CAS号为499-75-2;番泻苷B,英文名为Sennoside B,CAS号为128-57-4;二者均可从市场购得。本发明技术方案所述的卡泊姆940、无水乙醇、丙二醇、吐温-80、三乙醇胺、碳酸氢钠和水为常用的药用辅料,也可从市场购得。本发明技术方案所述的外用凝胶剂为膏状液体,涂抹后在皮肤表面形成凝胶层,附着于皮肤,使得凝胶中存在的药物缓慢向皮肤内释放,从而规避药物胃肠道给药的肝损伤、消化道刺激等不良作用。关于凝胶制备工艺可参见暨南大学出版社出版的薛巍、张渊明主编的《生物医用水凝胶》等公开文献。
申请人在研究中发现,香芹酚与番泻苷B制成外用凝胶制剂经皮给药对痛风性关节炎具有更好的治疗效果,且皮肤刺激性更低,有利于提高疗效和安全性。
具体实施方式
下面结合实施例对本发明作进一步的解释。应当理解的是,以下实施例仅用于解释本发明,而不是限制本发明的保护范围。
实施例1 治疗痛风性关节炎的外用凝胶制剂的制备
表1 治疗痛风性关节炎的外用凝胶制剂的组方
按照表1的组方进行制备,制备方法如下:
(1)取处方量卡泊姆940加水溶胀制成凝胶基质;
(2)取处方量无水乙醇、丙二醇、吐温-80和香芹酚混合搅拌均匀加入步骤(1)所得凝胶基质中搅拌均匀;
(3)取处方量碳酸氢钠用水配制成质量分数为2%的水溶液,加入处方量番泻苷B,搅拌均匀,加入步骤(2)所得载药凝胶基质中搅拌均匀;
(4)向步骤(3)所得混合物中加入处方量三乙醇胺和余量水,搅拌均匀,得外用凝胶制剂。
实施例2 外用凝胶制剂治疗痛风性关节炎的药效学研究及皮肤刺激性观察
一、实验药物及阳性对照药物
实验药物分别采用实施例1中组方1、2、3制备的凝胶。
阳性对照药物以香芹酚和番泻苷B单组份凝胶为对照。
1. 香芹酚阳性对照凝胶的制备:
组方: 香芹酚 18mg、卡泊姆940 90 mg、无水乙醇630mg、丙二醇36 mg、吐温-8018 mg、三乙醇胺18 mg、碳酸氢钠 50 mg、水12600 mg。
制备方法:
(1)取处方量卡泊姆940加水溶胀制成凝胶基质;
(2)取处方量无水乙醇、丙二醇、吐温-80和香芹酚混合搅拌均匀加入步骤(1)所得凝胶基质中搅拌均匀;
(3)取处方量碳酸氢钠用水配制成质量分数为2%的水溶液,搅拌均匀,加入步骤(2)所得载药凝胶基质中搅拌均匀;
(4)向步骤(3)所得混合物中加入处方量三乙醇胺和余量水,搅拌均匀,得外用凝胶制剂。
2.番泻苷B阳性对照凝胶的制备:
组方:番泻苷B 3mg、卡泊姆940 70 mg、无水乙醇490 mg、丙二醇28 mg、吐温-8014 mg、三乙醇胺 14 mg、碳酸氢钠150 mg、水9800 mg。
制备方法:
(1)取处方量卡泊姆940加水溶胀制成凝胶基质;
(2)取处方量无水乙醇、丙二醇、吐温-80混合搅拌均匀加入步骤(1)所得凝胶基质中搅拌均匀;
(3)取处方量碳酸氢钠用水配制成质量分数为2%的水溶液,加入处方量番泻苷B,搅拌均匀,加入步骤(2)所得混合物中搅拌均匀;
(4)向步骤(3)所得混合物中加入处方量三乙醇胺和余量水,搅拌均匀,得外用凝胶制剂。
二、痛风性关节炎大鼠模型的建立及给药
雄性SD大鼠36只,SPF级,体重180~220g。将大鼠随机分为6组,每组6只。大鼠麻醉后固定,碘伏消毒右后肢小腿踝关节,用6 号注射针在右后肢踝关节背后从45°方向插入至胫骨肌腱内侧,感觉有落空感后,注人50mg/ml尿酸钠溶液20 μL,以踝关节及足爪红肿为造模成功标准,制备痛风性关节炎模型。各组动物造模后当日开始给药,分别于造模前和末次给药当日采用缚线法测量右后肢小腿踝关节同一部位的周径,计算每只大鼠的关节肿胀度。关节肿胀度= (末次给药后周径-造模前周径) /造模前周径。并于实验期间观察各组大鼠背部给药区域皮肤症状,包括红斑、皮疹等。
大鼠关节肿胀度及给药局部症状观察完毕后,处死大鼠,以右后肢踝关节为中心上下各0. 5 cm 处剪断,取下受试关节及周围软组织,冰盘上切开踝关节囊,快速切取关节囊、滑膜等组织,称重,按重量比1:9比例加生理盐水稀释,匀浆,4℃条件下12000转/分钟离心30 min,取上清液,分装,-70 ℃冰箱保存待测。测定时采用市售大鼠IL-1β和TNF-αELISA试剂盒,按照说明书操作,测定关节浸液中IL-1β和TNF-α含量。
各组大鼠给药方式及给药剂量如下:大鼠造模后背部剃毛,剃毛面积约为2 cm×2cm,于背部剃毛区域涂抹给药。模型组涂抹蒸馏水;三个实验组分别涂抹实施例1中组方1、2、3制备的凝胶,两个阳性对照组分别涂抹香芹酚阳性对照凝胶和番泻苷B阳性对照凝胶。各凝胶组每次涂抹凝胶50mg,凝胶涂抹后单笼饲养。各组动物每日背部涂抹给药3次,连续给药7天。
给药部位观察发现,各组给药部位均未见红肿过敏等刺激现象,说明该剂量下所制备的载药凝胶皮肤刺激性极低。
各组大鼠关节肿胀度及关节浸液炎症因子水平测定结果见表2。
表2 各组大鼠关节肿胀度及关节浸液炎症因子水平测定结果
表2中:A表示与模型组相比 P<0.05;B表示与香芹酚组相比 P<0.05。组间比较采用单因素方差分析和post-hoc检验。
由表2可见,组方1、2、3及香芹酚组关节肿胀度及关节浸出液中IL-1β、TNF-α水平均显著低于模型组。番泻苷B组上述指标与模型组无显著差异。说明番泻苷B对痛风性关节炎大鼠的症状及细胞因子均无显著影响。
组方1、2、3组大鼠关节肿胀度及关节浸出液中IL-1β、TNF-α水平均显著低于香芹酚组,说明番泻苷B的加入提高了香芹酚对痛风性关节炎的疗效,其效果可能得益于番泻苷B的增效作用。
Claims (5)
1.一种外用凝胶制剂在制备痛风性关节炎治疗药物中的用途,其特征在于,所述外用凝胶制剂由医药学上可接受的外用凝胶制剂辅料和以下原料制成:香芹酚、番泻苷B;所述原料的重量份比为香芹酚13~18重量份、番泻苷B1~3重量份;所述医药学上可接受的外用凝胶制剂辅料包括卡泊姆940、无水乙醇、丙二醇、吐温-80、三乙醇胺、碳酸氢钠和水。
2.根据权利要求1所述的用途,其特征在于,所述原料的重量份比为香芹酚14重量份、番泻苷B 3重量份。
3.根据权利要求1所述的用途,其特征在于,所述原料的重量份比为香芹酚17重量份、番泻苷B 2重量份。
4.根据权利要求1所述的用途,其特征在于,所述原料的重量份比为香芹酚18重量份、番泻苷B1重量份。
5.根据权利要求1所述的用途,其特征在于,所述卡泊姆940的用量为香芹酚重量的5倍、无水乙醇的用量为香芹酚重量的35倍,丙二醇的用量为香芹酚重量的2倍、吐温-80的用量为香芹酚重量的1倍、三乙醇胺的用量为香芹酚重量的1倍、碳酸氢钠的用量为番泻苷B重量的50倍、水的用量为香芹酚重量的700倍;所述外用凝胶制剂的制备方法,包括如下步骤:
(1)取处方量卡泊姆940加水溶胀制成凝胶基质;
(2)取处方量无水乙醇、丙二醇、吐温-80和香芹酚混合搅拌均匀加入步骤(1)所得凝胶基质中搅拌均匀;
(3)取处方量碳酸氢钠用水配制成质量分数为2%的水溶液,加入处方量番泻苷B,搅拌均匀,加入步骤(2)所得载药凝胶基质中搅拌均匀;
(4)向步骤(3)所得混合物中加入处方量三乙醇胺和余量水,搅拌均匀,得外用凝胶制剂。
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---|
M.A.Botelho,et al.Protective Effect of Locally Applied Carvacrol Gel on Ligature-induced Periodontitis in Rats:A Tapping Mode AFM Study.《PHYTOTHERAPY RESEARCH》.2009,第1439-1448页. * |
Protective Effect of Locally Applied Carvacrol Gel on Ligature-induced Periodontitis in Rats:A Tapping Mode AFM Study;M.A.Botelho,et al;《PHYTOTHERAPY RESEARCH》;20091231;第1439-1448页 * |
清热利水解毒法治疗急性痛风性关节炎;邓伟等;《中药材》;20081031;第31卷(第10期);第1605-1606页 * |
香芹酚对大鼠痛风性关节炎中血清炎性因子及软骨细胞凋亡的影响;刘安宁等;《临床和实验医学杂志》;20170331;第16卷(第6期);第531-533页 * |
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