CN110755479B - 一种用于治疗关节炎的外用凝胶贴 - Google Patents
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Abstract
本发明公开了一种用于治疗关节炎的外用凝胶贴，它是在现有关节风痛丸的基础上改剂型而来。本发明通过将现有的治疗关节炎的口服中药改剂型为外用凝胶贴，避免了肝脏的首过效应和药物对胃肠道的不良反应，同时还减少用药的个体差异，提高了患病部位的血药浓度，从而能更迅速、准确地发挥疗效，与现有药物相比，本发明还具有使用方便、依从性高等优点。
Description
技术领域
本发明属于制药领域，具体涉及一种用于治疗关节炎的外用凝胶贴。
背景技术
CN1823910A公开了一种用于风湿性筋骨酸痛、关节痛、四肢麻木的中药制剂，它是在“关节风痛丸”的基础上改剂型而来，“关节风痛丸”收载于中药部颁标准，标准号WS3-B-1126-92，它由豨莶草、狗脊、伸筋草、秦艽等10味中药材制成。部颁标准上的制备方法是将豨莶草、秦艽、独活用70％乙醇渗漏提取；五加皮、防己粉碎成细粉；鸡血藤、狗脊、桑枝、老鹳草、伸筋草加水煎煮提取，制成丸剂。
现有的剂型均为口服制剂，临床应用中，该药物具有很强的止痛、抗炎、抗肿胀活性，但也容易引起恶心、呕吐、腹痛腹泻等明显的胃肠道不良反应。
外用药物通过透皮吸收发挥作用，避免了药物在胃肠道的吸收、降解，因此可明显减轻药物副作用，另外，外用药物避免了肝脏的首过效应，可直接作用于患处，能提高患病部位的血药浓度，减少用药的个体差异，而且外用药还具有使用方便、依从性高等优点，是治疗风湿、类风湿关节炎的理想剂型。
发明内容
本发明的目的是针对现有口服中成药副作用大，服用不方便等问题，提供一种用于治疗关节炎的外用凝胶贴。
上述目的是通过以下技术方案实现的：
一种用于治疗关节炎的外用凝胶贴，它由以下重量份数的中药材制成：豨莶草100-200份、狗脊50-150份、伸筋草50-150份、秦艽50-150份、鸡血藤50-100份、防己50-150份、老鹳草50-100份、桑枝50-150份、五加皮20-80份、独活20-80份。
优选地，所述中药材的重量份数是：豨莶草138份、狗脊104份、伸筋草104份、秦艽104份、鸡血藤70份、防己104份、老鹳草70份、桑枝104份、五加皮52份、独活52份。
优选地，所述制备方法包括以下步骤：
1)以上药材，先加水蒸馏5-10小时，收集挥发油备用，然后继续加水煎煮提取1-4次，合并提取液并浓缩成相对密度为1.10～1.25的稠膏，冷至室温，加乙醇使含醇量达30-80％，搅匀后静置沉降，取上清液并浓缩至相对密度为1.35～1.40的稠膏；
2)将挥发油、稠膏和辅料混匀，制成凝胶基质，将凝胶基质摊涂于裱背材料上，即得凝胶贴。
进一步优选地，所述含醇量为70％，指重量含量。
进一步优选地，所述辅料由以下重量配比的成分组成：聚丙烯酸钠(骨架材料)100-500份、聚乙烯吡咯烷酮(凝胶材料)10-50份、交联聚维酮(凝胶材料)10-50份、氢氧化铝(交联剂)10-50份、枸橼酸(交联剂)10-50份、甘油(保湿剂)1000-2000份、山梨醇(保湿剂)10-50份、丙二醇(促渗剂)100-500份、月桂氮卓酮(促渗剂)100-200份、乙二胺四乙酸二钠(螯合剂)5-20份、羟苯乙酯(防腐剂)5-20份、薄荷脑(芳香剂、促渗剂)10-50份、纯化水(溶剂)2000-5000份。
进一步优选地，所述辅料由以下重量配比的成分组成：聚丙烯酸钠300份、聚乙烯吡咯烷酮30份、交联聚维酮30份、氢氧化铝30份、枸橼酸20份、甘油1000份、山梨醇30份、丙二醇300份、月桂氮卓酮150份、乙二胺四乙酸二钠15份、羟苯乙酯15份、薄荷脑30份、纯化水2500份。
进一步优选地，所述凝胶基质的制备方法是：将聚丙烯酸钠、交联聚维酮、氢氧化铝、甘油、丙二醇、月桂氮卓酮、羟苯乙酯、薄荷脑和步骤1)收集的挥发油搅拌混匀；将聚乙烯吡咯烷酮、枸橼酸、山梨醇、乙二胺四乙酸二钠、纯化水和步骤1)得到的稠膏搅拌混匀；然后再一起搅拌均质，制成凝胶基质。
本发明的有益效果是：
1)本发明将现有的治疗关节炎的口服中药改剂型为外用凝胶贴，避免了肝脏的首过效应和药物对胃肠道的不良反应，同时还减少用药的个体差异，提高了患病部位的血药浓度，从而能更迅速、准确地发挥疗效，与现有药物相比，本发明还具有使用方便、依从性高等优点。
2)本发明还具有很好的透皮吸收效果以及很高的镇痛药理活性，其镇痛作用接近于扶他林乳膏，能很好地缓解关节炎临床症状。
附图说明
图1是凝胶贴体外透皮吸收的累积透过量-时间曲线。
具体实施方式
以下通过实施例对本发明进行详细说明。
实施例1
处方：
豨莶草138g、狗脊104g、伸筋草104g、秦艽104g、鸡血藤70g、防己104g、老鹳草70g、桑枝104g、五加皮52g、独活52g。
制备方法：
1)以上药材，先加水蒸馏6小时，收集挥发油备用，然后继续加水煎煮提取3次，每次1小时，合并两次提取液并浓缩成相对密度为1.20(冷测)的稠膏，冷至室温，加乙醇使含醇量达40％(重量)，搅匀后静置沉降，取上清液并浓缩至相对密度为1.35(冷测)的稠膏。
2)制备凝胶基质，辅料如下：
聚丙烯酸钠200g、聚乙烯吡咯烷酮50g、交联聚维酮50g、氢氧化铝20g、枸橼酸30g、甘油1500g、山梨醇50g、丙二醇500g、月桂氮卓酮100g、乙二胺四乙酸二钠5g、羟苯乙酯5g、薄荷脑20g、纯化水2000g。
将聚丙烯酸钠、交联聚维酮、氢氧化铝、甘油、丙二醇、月桂氮卓酮、羟苯乙酯、薄荷脑和步骤1)收集的挥发油搅拌混匀；将聚乙烯吡咯烷酮、枸橼酸、山梨醇、乙二胺四乙酸二钠、纯化水和步骤1)得到的稠膏搅拌混匀；然后再一起搅拌均质，制成凝胶基质。
3)将凝胶基质摊涂于裱背材料上，即得凝胶贴。
实施例2
处方与实施例1相同。
制法：
1)以上药材，先加水蒸馏8小时，收集挥发油备用，然后继续加水煎煮提取2次，每次2小时，合并两次提取液并浓缩成相对密度为1.15(冷测)的稠膏，冷至室温，加乙醇使含醇量达70％(重量)，搅匀后静置沉降，取上清液并浓缩至相对密度为1.35(冷测)的稠膏。
2)制备凝胶基质，辅料如下：
聚丙烯酸钠300g、聚乙烯吡咯烷酮30g、交联聚维酮30g、氢氧化铝30g、枸橼酸20g、甘油1000g、山梨醇30g、丙二醇300g、月桂氮卓酮150g、乙二胺四乙酸二钠15g、羟苯乙酯15g、薄荷脑30g、纯化水2500g。
将聚丙烯酸钠、交联聚维酮、氢氧化铝、甘油、丙二醇、月桂氮卓酮、羟苯乙酯、薄荷脑和步骤1)收集的挥发油搅拌混匀；将聚乙烯吡咯烷酮、枸橼酸、山梨醇、乙二胺四乙酸二钠、纯化水和步骤1)得到的稠膏搅拌混匀；然后再一起搅拌均质，制成凝胶基质。
3)将凝胶基质摊涂于裱背材料上，即得凝胶贴。
实施例3
处方与实施例1相同。
制法：
1)以上药材，先加水蒸馏10小时，收集挥发油备用，然后继续加水煎煮提取4次，第一次1.5小时，第二次1小时，第三次和第四次各0.5小时，合并两次提取液并浓缩成相对密度为1.10(冷测)的稠膏，冷至室温，加乙醇使含醇量达55％(重量)，搅匀后静置沉降，取上清液并浓缩至相对密度为1.35(冷测)的稠膏。
2)制备凝胶基质，辅料如下：
聚丙烯酸钠450g、聚乙烯吡咯烷酮15g、交联聚维酮15g、氢氧化铝40g、枸橼酸40g、甘油1200g、山梨醇15g、丙二醇150g、月桂氮卓酮180g、乙二胺四乙酸二钠20g、羟苯乙酯15g、薄荷脑40g、纯化水2300g。
将聚丙烯酸钠、交联聚维酮、氢氧化铝、甘油、丙二醇、月桂氮卓酮、羟苯乙酯、薄荷脑和步骤1)收集的挥发油搅拌混匀；将聚乙烯吡咯烷酮、枸橼酸、山梨醇、乙二胺四乙酸二钠、纯化水和步骤1)得到的稠膏搅拌混匀；然后再一起搅拌均质，制成凝胶基质。
3)将凝胶基质摊涂于裱背材料上，即得凝胶贴。
对比例
参照CN1823910A的方法对中药材进行提取，即，豨莶草、秦艽、独活用70％乙醇渗漏提取；五加皮、防己用70％乙醇回流提取；鸡血藤、狗脊、桑枝、老鹳草、伸筋草加水煎煮提取，提取液浓缩后再用95％乙醇醇沉。将各部分的提取液浓缩成稠膏后加入实施例1中的辅料制成凝胶贴。
试验例
1.体外透皮吸收实验
以小鼠离体腹部皮肤为渗透屏障，采用Franz扩散池，将处理好的大鼠皮肤固定于扩散池的两室之间，精密称取实施例1～3和对比例制备的凝胶基质1g于供给室，生理盐水为接收介质。分别于1、2、4、6、8、12h取样，测定接收液中的防己碱含量，并计算累积透过率，结果见表1。
防己碱HPLC色谱条件如下：固定相为Agilent XDB-C18(5μm，4.6×250mm)，流动相为乙腈-甲醇-水-冰乙酸(35：34：30：1)，检测波长280nm，流速1.0mL/min，柱温30℃，进样量20μL。
表1凝胶贴体外透皮吸收的累积透过率(％)
累积透过量-时间曲线结果见图1，结果显示，本发明制备的凝胶贴具有较好的透皮吸收效果，12小时的累积透过率可达30％以上。
2.本发明药物对乙酸刺激所致小鼠疼痛的影响
关节风痛丸含有多种解毒镇痛类药物，能明显改善关节炎的疼痛症状，因此选择小鼠疼痛模型评价外用制剂对疗效的影响。
SPF级昆明小鼠60只，雌雄各半，体重20-24g，随机分为6组，分别为空白对照组、扶他林乳膏组、实施例1、2、3药物组和对比例药物组，每组10只。剃去各组小鼠背部毛3cm×3cm，然后6％硫化钠溶液进行脱毛处理，脱毛后扶他林乳膏组去毛区皮肤给药扶他林0.5g/kg，实施例1、2、3药物组和对比例药物组去毛区皮肤贴凝胶贴一片(3cm×3cm，相当于2.35g生药材/kg)，空白对照组贴不含药物的凝胶贴，每天换药一次，连续7天。末次给药后，参照徐淑云《药理实验方法学》小鼠醋酸扭体法建立小鼠疼痛模型，各组小鼠腹腔注射0.6％醋酸0.2mL。
开始计时，记录注射冰醋酸后30min内小鼠出现扭体反应的潜伏期和扭体次数，结果见表2。
表2各组小鼠的扭体潜伏期和次数
与扶他林乳膏组相比，＊P＜0.05，＊＊P＜0.01。
从以上结果可以看出，与空白对照组相比，扶他林乳膏组和各药物组都能显著延长小鼠模型的扭体潜伏期、减少扭体次数，说明都有镇痛作用，但是与扶他林乳膏组相比，仅实施例2无论是潜伏期还是扭体次数都没有显著差异(P>0.05)，说明实施例2的镇痛作用最接近于扶他林乳膏，而对比例与扶他林乳膏组相比二者都具有极显著差异(P＜0.01)，说明对比例的镇痛作用最差。
Claims (2)
1.一种用于治疗关节炎的外用凝胶贴，其特征在于由以下重量份数的中药材制成：豨莶草138份、狗脊104份、伸筋草104份、秦艽104份、鸡血藤70份、防己104份、老鹳草70份、桑枝104份、五加皮52份、独活52份，
制备方法包括以下步骤：
1)以上药材，先加水蒸馏8小时，收集挥发油备用，然后继续加水煎煮提取2次，每次2小时，合并提取液并浓缩成相对密度为1.15的稠膏，冷至室温，加乙醇使含醇量达70％，搅匀后静置沉降，取上清液并浓缩至相对密度为1.35的稠膏；
2)将挥发油、稠膏和辅料混匀，制成凝胶基质，将凝胶基质摊涂于裱背材料上，即得凝胶贴，
所述辅料由以下重量配比的成分组成：聚丙烯酸钠300份、聚乙烯吡咯烷酮30份、交联聚维酮30份、氢氧化铝30份、枸橼酸20份、甘油1000份、山梨醇30份、丙二醇300份、月桂氮卓酮150份、乙二胺四乙酸二钠15份、羟苯乙酯15份、薄荷脑30份、纯化水2500份。
2.如权利要求1所述用于治疗关节炎的外用凝胶贴，其特征在于所述凝胶基质的制备方法是：将聚丙烯酸钠、交联聚维酮、氢氧化铝、甘油、丙二醇、月桂氮卓酮、羟苯乙酯、薄荷脑和步骤1)收集的挥发油搅拌混匀；将聚乙烯吡咯烷酮、枸橼酸、山梨醇、乙二胺四乙酸二钠、纯化水和步骤1)得到的稠膏搅拌混匀；然后再一起搅拌均质，制成凝胶基质。
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| CN102772590A (zh) * | 2012-07-23 | 2012-11-14 | 广东省中医院 | 一种中药组合物及凝胶膏剂和制备方法 |
| CN109966366A (zh) * | 2019-05-17 | 2019-07-05 | 上海市光华中西医结合医院(上海市光华医院) | 一种清热消肿止痛的凝胶贴膏及其制备方法 |
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| CN102772590A (zh) * | 2012-07-23 | 2012-11-14 | 广东省中医院 | 一种中药组合物及凝胶膏剂和制备方法 |
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