CN109091482A - 一种用于丘疹性荨麻疹的膏剂 - Google Patents
一种用于丘疹性荨麻疹的膏剂 Download PDFInfo
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- CN109091482A CN109091482A CN201811251953.XA CN201811251953A CN109091482A CN 109091482 A CN109091482 A CN 109091482A CN 201811251953 A CN201811251953 A CN 201811251953A CN 109091482 A CN109091482 A CN 109091482A
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- papular urticaria
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- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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Abstract
一种用于丘疹性荨麻疹的膏剂，包括作为活性成分的丁酸氢化可的松，还包括作为活性成分的丹皮酚，按重量份计，所述膏剂包括丁酸氢化可的松1.5份、丹皮酚23份、乳膏基质1005‑1070.5份；所述乳膏基质包括：甘油60‑65份、丙二醇20‑30份、凡士林145‑155份、十八醇95‑105份、液态石蜡95‑105份、平平加O20‑30份、枸橼酸1.5‑4.5份、枸橼酸钠0.5‑1份、纯化水568‑574.5份。本发明中丹皮酚的加入减少了丁酸氢化可的松的副作用，减少皮肤刺激性，止痒、止痛、消肿效果显著；明显改善色素沉着，同时丹皮酚的特殊气味具有驱蚊驱虫的效果，减少二次叮咬过敏；所制得的膏剂不含防腐剂，但防腐效果依然符合标准。
Description
技术领域
本发明涉及一种治疗丘疹性荨麻疹的膏剂，具体涉及一种含有丁酸氢化可的松和丹皮酚的膏剂。
背景技术
丘疹性荨麻疹是一个以症状特点而命名的疾病，又称荨麻疹苔藓、婴儿苔藓，是与昆虫叮咬有关的迟发性过敏反应性皮肤病，多见于婴幼儿及儿童，好发于四肢和躯干部，春、夏、秋季多见，本病其特征为圆形、椭圆形或纺锤形的红色风团样丘疹，顶端有水疱或大疱以及吸血昆虫叮咬的小窝痕，周围无红晕，数目不定，散在分布，也可群集但不融合，因剧痒搔抓而皮肤破伤继发脓疱疮、疖等感染性皮肤病。病因与臭虫、跳蚤、虱、螨、蚊、狗疥虫、米恙虫、鸡刺皮螨、蠓虫叮咬外因性过敏反应以及食物、药物过敏反应有关，主要是节肢动物叮咬皮肤后注入唾液，使该物质过敏的儿童产生本病。目前多以1％薄荷炉甘石洗剂和皮质类固醇霜止痒消炎治疗，治疗时效长、治愈率低、经常反复发作，同时1％薄荷炉甘石洗剂对皮肤有刺激性作用。
丁酸化可的松是一种的中效甾体糖皮质激素，可抑制局部血管扩张，能降低毛细血管的通透性，抑制淋巴因子所引起的炎症反应，抑制皮肤迟发性变态反应，具有抗炎、抗过敏、免疫抑制等作用，对非感染引起的皮肤病具有显著的抗炎作用。外用主要用于过敏性皮炎、脂溢性皮炎、湿疹、慢性单纯性苔藓等皮肤病。目前市场上流通的丁酸氢化可的松软膏或乳膏剂，大多为单方制剂，其中丁酸氢化可的松的含量一般为0.1％，虽然有效，但是单独应用甾体糖皮质激素的缺点在于副作用较多，例如皮肤变薄、肌萎缩、痤疮、多毛、色素沉着等，其中色素沉着的副作用影响最为棘手，通常需要1-2年的时间才能代谢吸收掉。
现有专利CN105687207A涉及一种以丁酸氢化可的松等为活性成分的膏剂，包括作为活性成分的丁酸氢化可的松，还包括作为活性成分的薄荷脑、樟脑或冰片三者中任意组分，乳膏基质余量。降低了丁酸氢化可的松的副作用，减少皮肤刺激性，止痒、止痛、消肿效果提高，改善患者用药的顺应性。该发明是利用薄荷脑、樟脑或冰片消炎止痛的功能，以减少丁酸氢化可的松的用药量，来达到降低副作用的效果。现有专利CN1883444A公开了丹皮酚在制备皮肤美白及祛斑化妆品或皮肤美白及治疗色素沉着性疾病药物上的应用，具体公开了丹皮酚的质量浓度为0.1％-20％，优选为5％-10％，丹皮酚既可以直接抑制酪氨酸酶活性，同时可以抑制其转运过程。现在急需提供一种皮肤用组合物，既能减少丁酸氢化可的松的副作用，同时针对性解决色素沉着的问题。
发明内容
本发明的目的是解决现有技术中存在的问题，提供一种降低丁酸氢化可的松的副作用，减少皮肤刺激性，止痒、止痛、消肿效果显著，明显改善色素沉着副作用的用于丘疹性荨麻疹的膏剂。
为实现上述目的，本发明采用如下技术方案：一种用于丘疹性荨麻疹的膏剂，包括作为活性成分的丁酸氢化可的松，还包括作为活性成分的丹皮酚。
进一步地，按重量份数计，所述的膏剂包括：丁酸氢化可的松1-2份、丹皮酚20-26份、乳膏基质1005-1070.5份。
进一步地，所述的膏剂包括：丁酸氢化可的松1.5份、丹皮酚23份、乳膏基质1005-1070.5份。
进一步地，所述乳膏基质按重量份计包括：甘油60-65份、丙二醇20-30份、凡士林145-155份、十八醇95-105份、液态石蜡95-105份、平平加O20-30份、枸橼酸1.5-4.5份、枸橼酸钠0.5-1份、纯化水568-574.5份。
优选为，所述乳膏基质按重量份计包括：甘油63-65份、丙二醇25-30份、凡士林150-155份、十八醇100-105份、液态石蜡100-105份、平平加O25-30份、枸橼酸2-4.5份、枸橼酸钠0.7-1份、纯化水570-574.5份。
进一步优选为，所述乳膏基质按重量份计包括：甘油63份、丙二醇25份、凡士林150份、十八醇100份、液态石蜡100份、平平加O25份、枸橼酸2份、枸橼酸钠0.7份、纯化水570份。
制备如上所述的用于皮炎、湿疹的膏剂的方法，包括以下步骤：
(1)油相配制：将十八醇、凡士林、液状石蜡混合，加热熔融成液状；
(2)水相配制：将甘油、平平加O、丙二醇、枸橼酸、枸橼酸钠、纯化水混合后加热；
(3)合相：将步骤(1)配制的油相缓缓加入步骤(2)配制的水相中，加入同时搅拌，再加入溶有丹皮酚的溶液，继续搅拌，加入丁酸氢化可的松粉末，继续搅拌至凝，即得。
进一步地，所述步骤(1)和(2)中，加热至75-85℃。
进一步地，所述步骤(3)中待温度降至60-65℃，加入溶有丹皮酚的溶液。
进一步地，所述步骤(3)中待温度降至55-60℃，加入丁酸氢化可的松粉末。
本发明具有以下有益效果：
一、丹皮酚的加入减少了丁酸氢化可的松的副作用，减少皮肤刺激性，止痒、止痛、消肿效果显著。
二、明显改善色素沉着，同时丹皮酚的特殊气味具有驱蚊驱虫的效果，减少二次叮咬过敏。
三、所制得的膏剂不含防腐剂，但防腐效果依然符合标准。
具体实施例
下面对本发明做进一步详述：以下实施例用于进一步描述本发明，但不作为对本发明的限制。本领域的技术人员应理解，对本发明的技术特征所作的等同替换或相应的改进，仍属于本发明的保护范围之内。
实施例1
一种用于丘疹性荨麻疹的膏剂，按重量份数计，包括丁酸氢化可的松1份、丹皮酚20份、甘油60份、丙二醇20份、凡士林145份、十八醇95份、液态石蜡95份、平平加O20份、枸橼酸1.5份、枸橼酸钠0.5份、纯化水568份。
按以上配比精准测量，膏剂制备方法如下：(1)油相配制：将十八醇、凡士林、液状石蜡混合，加热熔融成液状，温度保持在75℃；(2)水相配制：将甘油、平平加O、丙二醇、枸橼酸、枸橼酸钠、纯化水混合后加热，温度保持在75℃；(3)合相：将步骤(1)配制的油相缓缓加入步骤(2)配制的水相中，加入同时搅拌，温度降到60℃时，再加入溶有丹皮酚的溶液，继续搅拌，温度降到55℃时加入丁酸氢化可的松粉末，继续搅拌至凝，即得。
实施例2
一种用于丘疹性荨麻疹的膏剂，按重量份数计，包括丁酸氢化可的松1.5份、丹皮酚23份、甘油63份、丙二醇25份、凡士林150份、十八醇100份、液态石蜡100份、平平加O25份、枸橼酸2份、枸橼酸钠0.7份、纯化水570份。
按以上配比精准测量，膏剂制备方法如下：(1)油相配制：将十八醇、凡士林、液状石蜡混合，加热熔融成液状，温度保持在85℃；(2)水相配制：将甘油、平平加O、丙二醇、枸橼酸、枸橼酸钠、纯化水混合后加热，温度保持在85℃；(3)合相：将步骤(1)配制的油相缓缓加入步骤(2)配制的水相中，加入同时搅拌，温度降到65℃时，再加入溶有丹皮酚的溶液，继续搅拌，温度降到60℃时加入丁酸氢化可的松粉末，继续搅拌至凝，即得。
实施例3
一种用于丘疹性荨麻疹的膏剂，按重量份数计，包括丁酸氢化可的松2份、丹皮酚26份、甘油65份、丙二醇30份、凡士林155份、十八醇105份、液态石蜡105份、平平加O30份、枸橼酸4.5份、枸橼酸钠1份、纯化水574.5份。
按以上配比精准测量，膏剂制备方法如下：(1)油相配制：将十八醇、凡士林、液状石蜡混合，加热熔融成液状，温度保持在80℃；(2)水相配制：将甘油、平平加O、丙二醇、枸橼酸、枸橼酸钠、纯化水混合后加热，温度保持在80℃；(3)合相：将步骤(1)配制的油相缓缓加入步骤(2)配制的水相中，加入同时搅拌，温度降到63℃时，再加入溶有丹皮酚的溶液，继续搅拌，温度降到57℃时加入丁酸氢化可的松粉末，继续搅拌至凝，即得。
对比例1
该对比例1与实施例2的区别在于，将所述膏剂中还包括防腐剂羟苯乙酯1.5份，制备方法中在所述步骤(1)中加入羟苯乙酯。
对比例2
该对比例2与实施例2的区别在于，除去所述膏剂中的丹皮酚23份，制备方法中省略步骤(3)中加入丹皮酚的步骤。
实验例1：稳定性试验
取来自实施例1-3和对比例1制得的乳膏剂，按照《中国药典》2010年版二部附录200-201页稳定性加速试验方法进行考察。
检测仪器：日本岛津LC—IOA高效液相色谱仪；SPD-l0A紫外检测器。
色谱条件：色谱柱，岛津CIS-ODS柱(150mm×4.6mm，5μm)；流动相，甲醇：水：乙醚(62：38：2)；流速1.0ml/min；进样量，20μL；柱温，室温；检测波长，UV240nm。理论塔板数按丁酸氢化可的松计算应不低于2000。丁酸氢化可的松的峰与相邻杂质峰的分离度符合要求。
对照品溶液的制备，精密称取丁酸氢化可的松对照品(含量测定用，中国生物制品检定所提供)12.0mg，用流动相溶解，并定容至100m1，摇匀。即是浓度为每1ml约含0.120mg的溶液。
样品溶液的制备：取样品乳膏约3.0g。精密称定，置50ml量瓶中。加甲醇适量，置80℃水溶中，加热使溶解，放冷至室温，加甲醇稀释至刻度，摇匀。置冰浴中冷却2h。取出后迅速滤过，弃去初滤液，取续滤液作为样品溶液。
样品测定：取对照品溶液和供试品溶液各20μL进样，读取峰面积值，按外标法计算含量。
稳定性考查按照中国药典2005版附录176页中药物制剂稳定性试验指导原则公开方法进行加速稳定性试验(40℃±2℃，相对湿度75％±5％)下的稳定性试验。
表1 实施例1-3和对比例1加速稳定性考察结果(n＝20，平均±s)
由上表中实施例1-3制得的膏剂和对比例1-2制得的膏剂稳定性数据对比可以发现：经过6个月的加速稳定性实验后，本发明实施例提供的膏剂的有效成分含量均高于对比例2膏剂；采用实施例2中的比例制得的膏剂中有效成分含量稍稍优于实施例3，说明实施例2为最优比例和最优制备方法；实施例2膏剂中有效成分含量略高于添加了防腐剂的对比例1，远高于省略了丹皮酚组分的对比例2，说明丹皮酚在该膏剂中的防腐效果显著；按本发明方案制得的乳膏在加速稳定性考察中，均没有发生分层、变色现象。
实验例2：皮肤急性毒性试验
一组对照组涂赋形剂(空白基质)2g，四组试验组涂来至实施例3制得的乳膏剂(完整皮肤组和破损皮肤组，各高低两个剂量)。低剂量组用量1g，高剂量组用量3g，每组家兔四只。受试药物均匀涂于脱毛区，并用无刺激纱布加以覆盖。给受试药物24小时后，用温水除去残留的受试物，去除受试物1、24、48小时至第七日，观察完毕，取赋形剂组、完整皮肤高剂量组和破损皮肤高剂量组家兔各2只，耳静脉注射空气处死，剪取受试部位皮肤约2×2cm，置10％甲醛溶液中保存，送病理组织学检查。检查结论：本试验无动物死亡。对照组和试验组无明显差别，给药组家兔摄食、体重、皮肤毛发、眼和粘膜的变化、呼吸、中枢神经系统、四肢活动等均正常，脱皮区皮肤正常，无中毒表现。提示该制剂皮肤急性毒性很小，临床用药安全。
实验例3：皮肤刺激性试验
实验分为两组，为完整皮肤组和破损皮肤组，每组3只。左侧去毛区涂来至实施例3制得的乳膏剂1g,右侧涂赋形剂1g，并用无刺激纱布加以覆盖。给受试药物24小时后，用温水除去残留的受试物，去除受试物1、24、48小时肉眼观察涂抹部位有无红斑和水肿等。实验至第48小时观察完毕，取完整皮肤组家兔2只，耳静脉注射空气处死，剪取受试部位皮肤约2×2cm，置10％甲醛保存，送病理组织学检查；破损皮肤组因是与皮肤急性毒性实验共用三只家兔，故待给药后第七日再取样送病理组织学检查。检查结论：给药完整皮肤组、破损皮肤组和赋形剂组对皮肤刺激的总平均分值均在0-0.49范围内，属于无刺激性；病理组织学检查结果可见，对照组和试验组无明显差别；给药组家兔摄食、体重、皮肤毛发、眼和粘膜的变化、呼吸、中枢神经系统、四肢活动等均正常，脱皮区皮肤正常。提示该制剂皮肤刺激性很小，临床用药安全。
Claims (10)
1.一种用于丘疹性荨麻疹的膏剂，包括作为活性成分的丁酸氢化可的松，还包括作为活性成分的丹皮酚。
2.根据权利要求1所述的用于丘疹性荨麻疹的膏剂，其特征在于，按重量份数计，所述的膏剂包括：丁酸氢化可的松1-2份、丹皮酚20-26份、乳膏基质1005-1070.5份。
3.根据权利要求2所述的用于丘疹性荨麻疹的膏剂，其特征在于，按重量分计，所述的膏剂包括：丁酸氢化可的松1.5份、丹皮酚23份、乳膏基质1005-1070.5份。
4.根据权利要求2所述的用于丘疹性荨麻疹的膏剂，其特征在于，所述乳膏基质按重量份计包括：甘油60-65份、丙二醇20-30份、凡士林145-155份、十八醇95-105份、液态石蜡95-105份、平平加O20-30份、枸橼酸1.5-4.5份、枸橼酸钠0.5-1份、纯化水568-574.5份。
5.根据权利要求4所述的用于丘疹性荨麻疹的膏剂，其特征在于，所述乳膏基质按重量份计包括：甘油63-65份、丙二醇25-30份、凡士林150-155份、十八醇100-105份、液态石蜡100-105份、平平加O25-30份、枸橼酸2-4.5份、枸橼酸钠0.7-1份、纯化水570-574.5份。
6.根据权利要求4所述的用于丘疹性荨麻疹的膏剂，其特征在于，所述乳膏基质按重量份计包括：甘油63份、丙二醇25份、凡士150份、十八醇100份、液态石蜡100份、平平加O25份、枸橼酸2份、枸橼酸钠0.7份、纯化水570份。
7.制备权利要求4-6任意一项所述的用于丘疹性荨麻疹膏剂的方法，包括以下步骤：
(1)油相配制：将十八醇、凡士林、液状石蜡混合，加热熔融成液状；
(2)水相配制：将甘油、平平加O、丙二醇、枸橼酸、枸橼酸钠、纯化水混合后加热；
(3)合相：将步骤(1)配制的油相缓缓加入步骤(2)配制的水相中，加入同时搅拌，再加入溶有丹皮酚的溶液，继续搅拌，加入丁酸氢化可的松粉末，继续搅拌至凝，即得。
8.根据权利要求7所述的制备方法，其特征在于，所述步骤(1)和(2)中，加热至75-85℃。
9.根据权利要求7所述的制备方法，其特征在于，所述步骤(3)中：步骤(1)配制的油相缓缓加入步骤(2)配制的水相后，待温度降至60-65℃，再加入溶有丹皮酚的溶液。
10.根据权利要求7所述的制备方法，其特征在于，所述步骤(3)中：加入溶有丹皮酚的溶液后，待温度降至55-60℃，加入丁酸氢化可的松粉末。
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| CN104095869A (zh) * | 2014-07-28 | 2014-10-15 | 王卫武 | 一种治疗丘疹性荨麻疹的乳膏及其制备方法 |
| CN105748436A (zh) * | 2014-12-15 | 2016-07-13 | 安徽中医药大学 | 一种外用丹皮酚泡囊乳膏及其制备方法 |
| CN106924177A (zh) * | 2017-03-21 | 2017-07-07 | 西安培华学院 | 一种外用丹皮酚纳米缓释温度敏感型原位凝胶及其制备方法 |
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| CN104095869A (zh) * | 2014-07-28 | 2014-10-15 | 王卫武 | 一种治疗丘疹性荨麻疹的乳膏及其制备方法 |
| CN105748436A (zh) * | 2014-12-15 | 2016-07-13 | 安徽中医药大学 | 一种外用丹皮酚泡囊乳膏及其制备方法 |
| CN106924177A (zh) * | 2017-03-21 | 2017-07-07 | 西安培华学院 | 一种外用丹皮酚纳米缓释温度敏感型原位凝胶及其制备方法 |
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| 王忠友: "《丹皮酚软膏联合丁酸氢化可的松软膏治疗婴儿头面部湿疹的疗效观察》", 《临床合理用药》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114504548A (zh) * | 2020-11-16 | 2022-05-17 | 湖北舒邦药业有限公司 | 软膏剂及其制备方法 |
| CN114504548B (zh) * | 2020-11-16 | 2023-08-22 | 湖北舒邦药业有限公司 | 软膏剂及其制备方法 |
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