CN116850236B - 一种治疗银屑病的外用中药组合物及其制剂与应用 - Google Patents
一种治疗银屑病的外用中药组合物及其制剂与应用 Download PDFInfo
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Abstract
本发明公开了一种治疗银屑病的外用中药组合物及其制剂与应用。所述外用中药组合物由以下重量份的原料制成:黄柏5~20份,龙血竭1~8份,火把花根5~20份,滇王不留行5~25份,马齿苋5~20份,冰片1~8份。所述中药组合物的药物制剂为软膏、搽剂、洗剂、喷剂、凝胶剂、乳膏剂和油剂中的任意一种。所述中药组合物的应用为在制备治疗银屑病药物中的应用。本发明中药组合物通过干预T细胞亚群CD4+T细胞的增值,可减少Th17亚细胞的分化,抑制IL‑1β、IL‑6、IL‑8、IL‑17A、IL‑22、IL‑23等相关炎症因子的表达,减轻银屑病样小鼠皮损症状,改善炎症和自身免疫反应。本发明中药组合物配伍精当,临床适用性强,接受度高。小鼠实验及临床实验疗效均优于阳性药卡泊三醇软膏,且不良反应发生率低。
Description
技术领域
本发明属于中药技术领域,具体涉及一种治疗银屑病的外用中药组合物及其制剂与应用。
背景技术
银屑病俗称牛皮癣,是一种慢性炎症性皮肤病,病程较长,有易复发倾向,有的病例几乎终生不愈。临床表现以红斑,鳞屑为主,全身均可发病,以头皮,四肢伸侧较为常见。银屑病在世界范围内均有发病,发病人群占全球人口的2~3%,并呈一定的上升趋势,病情反复发作,极难根治,轻者影响患者的身心健康和学习工作。然而银屑病发病时常伴有不同程度的瘙痒,较多患者在感染后因无法得到妥善的医治使得病情加重甚至死亡。目前已经成为世界范围内重大疑难病之一,这使得价格低廉、安全有效的药物研发迫在眉睫。
银屑病的病因复杂多样,发病机制目前尚不明确。中医认为银屑病发病有内外因之分,外因如外感风、寒、湿、热等邪气导致皮肤失养而发病;内外因如风湿毒气袭表,血分热燥,血燥难荣或素体血虚,外感风燥之邪,合而致病。近现代医家多从血分认识,有血热、血虚、血瘀、血燥之分,依据各医家对银屑病病机的认识,治疗应采取清热、活血、化瘀、解毒等方法,为银屑病的中医诊疗提供了理论依据。
现代医学认为银屑病与遗传、免疫、感染等因素有关,对其机制的研究主要集中于免疫系统,其发病机制与T细胞相关。参与其中的T细胞主要包含了辅助性T细胞1(Th1)、辅助性T细胞17(Th17)等,它们可分泌肿瘤坏死因子-α(TNF-α)、干扰素γ(IFN-γ)以及白介素17(IL-17)等细胞因子,进而参与银屑病的发生发展。目前西医治疗银屑病大多从发病机制入手,多选用一些具有免疫抑制、消炎、抑制角质细胞增生作用的药物,比如阿维A胶囊、醋酸泼尼松片、环孢素A、氨甲喋呤片、复方甘草酸苷片、卡泊三醇软膏、生物制剂等。虽然这些药物能帮助患者缓解其症状,但较难根治,且治疗费用相对较高,而具有中医特色的中药组合物,在银屑病的治疗中有疗效确切、副作用小、治疗后复发率低、费用较低等优势,使得中药在银屑病中的治疗地位日益突出。
发明内容
本发明的第一目的在于提供一种治疗血热、血瘀、血燥型银屑病的外用中药组合物,进一步的目的在于提供该外用中药组合物的药物制剂与应用。
本发明的第一目的是这样实现的,一种治疗银屑病的外用中药组合物,由以下重量份的原料制成:黄柏5~20份,龙血竭1~8份,火把花根5~20份,滇王不留行5~25份,马齿苋5~20份,冰片1~8份。
本发明的第二目的是这样实现的,所述中药组合物的药物制剂为软膏、搽剂、洗剂、喷剂、凝胶剂、乳膏剂和油剂中的任意一种。
所述中药组合物的应用为在制备治疗银屑病药物中的应用。
黄柏为芸香科植物黄檗(Phellodendron amurenseRupr.)的干燥树皮。剥取树皮,除去粗皮,晒干。苦,寒。归肾、膀胱经。
龙血竭为百合科植物剑叶龙血树[Dracaena cochinchinensis(Lour.)S.C.Chen]的含脂木材提取得到的树脂。甘、咸,温。归心、肝、肾经。
火把花根为卫矛科植物火把花根[Tripterygium hypoglaucum(Levl.) Hutch.]的干燥根。辛、苦、温,归肝、肾经。
马齿苋为马齿苋科植物马齿苋(Portulaca oleraceaL.)的干燥地上部分。酸,寒。归肝、大肠经。
滇王不留行为锦葵科植物拔毒散(Sida szechuensisMatsuda)干燥地上部分。苦,寒,归肝经。
冰片为樟科植物樟[Cinnamomumcamphora(L.)Presl]的新鲜枝、叶经提取加工制成,或合成。辛、苦,凉。归心、脾、肺经。
本发明依据中医君臣佐使的组方原则进行配伍,组方中黄柏,龙血竭为君药;火把花根和马齿苋同为臣药;滇王不留行是方中佐助药;冰片为使药,具有引经作用。本中药组合物中的黄柏,具有清热燥湿,解毒疗疮的作用,对于血热及血热后期的血燥型银屑病有显著疗效,龙血竭有活血散瘀功效,活血之效可防止血与热致瘀,两药共奏清热,活血,化瘀之功效,为君药;马齿苋能清热解毒,凉血之效兼能清血分之热,火把花根具有祛风除湿,止痛之效,用于治疗血热导致的皮痹瘙痒,二者同为臣药;滇王不留行有活血散瘀的作用,助君药加强活血散瘀之效,为佐药;冰片,清热止痛,具有引经作用,引上述诸药直达病位,冰片止痛作用能缓解血热,血瘀所致疼痛。全方共奏清热解毒,活血散瘀的功效,可用于治疗血热、血燥及血瘀型银屑病。
本发明的有益效果为:
1、经实验证明,本发明中药组合物通过干预T细胞亚群CD4+T细胞的增值,可减少Th17亚细胞的分化,抑制IL-1β、IL-6、IL-8、IL-17A、IL-22、IL-23等相关炎症因子的表达,减轻银屑病样小鼠皮损症状,改善炎症和自身免疫反应。
2、本发明中药组合物配伍精当,临床适用性强,接受度高。本发明中药组合物为外用涂抹给药,小鼠实验及临床实验疗效均显著优于阳性药卡泊三醇软膏,相对于现有技术的龙血竭胶囊和火把花根片口服给药,外用给药可避免药物进入全身血液循环,同等剂量下可有效减缓不良反应(如胃肠道反应、过敏反应、对肝功的影响、对血液系统的影响等)发生。另外,采用本发明中药组合物治疗银屑病的临床实验中仅见1例病症瘙痒感觉轻微增加,不良反应发生率也低于上述口服给药治疗方法。
附图说明
图1为不同实验组连续造模给药后皮损状态结果图;
图2为不同实验组对小鼠银屑病皮损PASI评分图;
图3为不同实验组对银屑病样小鼠脾指数的影响;
图4为HE染色后不同实验组对银屑病样小鼠皮肤组织病理学结果图;
图5为不同实验组对银屑病样小鼠血清中IL-1β、IL-6、IL-8、IL-17A、IL-22、IL-23等炎症因子表达水平的影响。
具体实施方式
下面结合实施例对本发明作进一步的说明,但不以任何方式对本发明加以限制,基于本发明教导所作的任何变换或替换,均属于本发明的保护范围。
本发明一种治疗银屑病的外用中药组合物,由以下重量份的原料制成:黄柏5~20份,龙血竭1~8份,火把花根5~20份,滇王不留行5~25份,马齿苋5~20份,冰片1~8份。
本发明还提供了一种基于所述中药组合物的药物制剂,所述药物制剂为软膏、搽剂、洗剂、喷剂、凝胶剂、乳膏剂和油剂中的任意一种。
所述软膏由下列工艺制备:
1)取液状石蜡60~90份,黄凡士林160~190份,黄柏5~20份,龙血竭1~8份,火把花根5~20份,滇王不留行5~25份,马齿苋5~20份,冰片1~8份。将液状石蜡和黄凡士林加热至110~130℃。将中药组合物中黄柏、火把花根、马齿苋、滇王不留行四味药加入炸15分钟,滤过,滤液冷却至60~70℃;
2)将龙血竭和冰片分别研细过120目筛,加入龙血竭粉和冰片粉1倍重量份的95%乙醇研磨溶解。溶解后的乙醇溶液和上述滤液混合,不断搅拌至均匀,待近凝固前再次搅拌均匀,分装,即得。
所述搽剂由下列工艺制备:
1)将黄柏、火把花根、滇王不留行、马齿苋粉粹后过100目筛,混合均匀,用20~30%乙醇回流或渗漉提取,过滤,合并滤液,浓缩至适量;
2)龙血竭和冰片用适量95%乙醇搅拌溶解后与步骤1)得到的浓缩滤液合并,加20~30%乙醇使成200ml,搅拌均匀,分装,即得。
所述洗剂由下列工艺制备:
1)将黄柏、火把花根、滇王不留行、马齿苋四味加水煎煮两次,每次60分钟,过滤,合并滤液,浓缩至适量;
2)将龙血竭和冰片加入适量95%乙醇搅拌溶解后加入至步骤1)得到的浓缩滤液中,补液至200ml,加入0.1~0.3份苯甲酸和0.1~0.2份羟苯乙酯,搅匀,分装,即得。
所述喷剂由下列工艺制备:
1)将黄柏、火把花根、马齿苋、滇王不留行粉碎成粗粉,按渗漉法用20~30%乙醇渗漉2次,每次3h以上,收集渗漉液,滤过,浓缩至适量;
2)龙血竭和冰片用95%乙醇溶解后加入步骤1)得到的浓缩渗漉液中,混合均匀,加入加入0.1~0.3份苯甲酸和0.1~0.2份羟苯乙酯,搅匀,密闭,静置24h,分装,即得。
所述凝胶剂由下列工艺制备:
1)取2~3份卡波姆用80~120份甘油室温溶胀24h;
2)将龙血竭和冰片用95%乙醇溶解,黄柏、火把花根、马齿苋、滇王不留行粉碎成粗粉后混匀,用20~30%乙醇作溶剂渗漉,收集渗漉液,滤过,浓缩至适量,备用;
3)将渗漉液浓缩液和龙血竭和冰片的乙醇溶液加入用甘油溶胀的卡波姆中,搅拌均匀,分装,即得。
所述乳膏剂由下列工艺制备:
1)冰片与龙血竭研磨成细粉,龙血竭用适量乙酸乙酯溶解;
2)取70~90份硬脂酸、40~60份单硬脂酸甘油酯水浴加热熔融,保温,加入10~30份司盘60与0.3~0.5份羟苯乙酯使溶解,加入冰片细粉用乙酸乙酯溶解的龙血竭得到溶液I;
3)称取20~40 份聚山梨酯80用蒸馏水溶解得到溶液Ⅱ;
4)将黄柏、火把花根、马齿苋、滇王不留行四味药材粉碎成粗粉后混匀,用20~30%乙醇作溶剂渗漉,收集渗漉液,滤过,浓缩至相对密度为1.3~1.35的稠膏,稠膏用溶液Ⅱ搅拌溶解,再缓缓加入溶液Ⅰ,边加边搅拌至冷凝,分装,即得。
所述油剂由下列工艺制备:将黄柏、龙血竭、火把花根、滇王不留行、马齿苋、冰片六味中药粉碎成细粉。用麻油调和均匀,分装,即得。
本发明还提供了所述的中药组合物在制备治疗银屑病药物中的应用。
实施例1
组方:黄柏5g,龙血竭1g,火把花根5g,滇王不留行5g,马齿苋5g,冰片1g;将组方中各药味按组方量称量,取液状石蜡40g,黄凡士林90g,加热至110℃。将组方中黄柏、火把花根、马齿苋、滇王不留行四味药加入炸15分钟,滤过,滤液冷却至60℃;将龙血竭和冰片分别研细过120目筛,加入4ml 95%乙醇研磨溶解。溶解后的乙醇溶液和上述滤液混合,不断搅拌至均匀,待近凝固前再次搅拌均匀,分装,即得软膏。
实施例2
组方:黄柏0g,龙血竭8g,火把花根20g,滇王不留行25g,马齿苋20g,冰片8g;将组方中各药味按组方量称量,取液状石蜡100g,黄凡士林210g,加热至30℃。将组方中黄柏、火把花根、马齿苋、滇王不留行四味药加入炸15分钟,滤过,滤液冷却至70℃;将龙血竭和冰片分别研细过120目筛,加入22ml 95%乙醇研磨溶解。溶解后的乙醇溶液和上述滤液混合,不断搅拌至均匀,待近凝固前再次搅拌均匀,分装,即得软膏。
实施例3
组方:黄柏12g,龙血竭5g,火把花根12g,滇王不留行15g,马齿苋12g,冰片5g;将组方中各药味按组方量称量,取液状石蜡81g,黄凡士林190g,加热至120℃。将组方中黄柏、火把花根、马齿苋、滇王不留行四味药加入炸15分钟,滤过,滤液冷却至65℃;将龙血竭和冰片分别研细过120目筛,加入14ml 95%乙醇研磨溶解。溶解后的乙醇溶液和上述滤液混合,不断搅拌至均匀,待近凝固前再次搅拌均匀,分装,即得软膏。
实施例4
组方:黄柏20g,龙血竭1g,火把花根20g,滇王不留行20,马齿苋12g,冰片1g;将组方中各药味按组方量称量,将黄柏、火把花根、滇王不留行、马齿苋粉粹后过100目筛,混合,用30%乙醇回流或渗漉提取,过滤,合并滤液,浓缩至相对密度为1.25的稠膏;龙血竭和冰片用适量95%乙醇搅拌溶解后与浓缩滤液合并,加30%乙醇使成200ml,搅拌均匀,分装,即得搽剂。
实施例5
组方:黄柏5g,龙血竭1g,火把花根5g,滇王不留行5g,马齿苋5g,冰片1g;将组方中各药味按组方量称量,将黄柏、火把花根、滇王不留行、马齿苋四味加水煎煮两次,每次60分钟,过滤,合并滤液,浓缩至适量;将龙血竭和冰片加入适量95%乙醇搅拌溶解后加入至浓缩滤液中,补液至200ml,加入0.2g苯甲酸和0.1g羟苯乙酯,搅匀,分装,即得洗剂。
实施例6
组方:黄柏20g,龙血竭5g,火把花根12g,滇王不留行5g,马齿苋12g,冰片5g;将组方中各药味按组方量称量,将黄柏、火把花根、马齿苋、滇王不留行粉碎成粗粉,按渗漉法用20%乙醇渗漉2次,每次3h以上,收集渗漉液,滤过,浓缩至适量;龙血竭和冰片用95%乙醇溶解后加入浓缩渗漉液中,混合均匀,加入0.2g苯甲酸和0.1g羟苯乙酯,搅匀,密闭,静置24h,分装,即得喷剂。
实施例7
组方:黄柏12g,龙血竭5g,火把花根5g,滇王不留行12g,马齿苋5g,冰片1g;将组方中各药味按组方量称量,取2~3g卡波姆用80~120g甘油室温溶胀24h;将龙血竭和冰片用95%乙醇溶解,黄柏、火把花根、马齿苋、滇王不留行粉碎成粗粉后混匀,用20~30%乙醇作溶剂渗漉,收集渗漉液,滤过,浓缩至适量,备用;将渗漉液浓缩液和龙血竭和冰片的乙醇溶液加入用甘油溶胀的卡波姆中,搅拌均匀,分装,即得凝胶剂。
实施例8
组方:黄柏20g,龙血竭5g,火把花根12g,滇王不留行5g,马齿苋20g,冰片5g;将组方中各药味按组方量称量,冰片与龙血竭研磨成细粉,龙血竭用适量乙酸乙酯溶解;
取70~90g硬脂酸、40~60g单硬脂酸甘油酯水浴加热熔融,保温,加入10-30g司盘60与0.3-0.5g羟苯乙酯使溶解,加入冰片细粉及用乙酸乙酯溶解的龙血竭得到溶液I;称取20g聚山梨酯80用蒸馏水溶解得到溶液Ⅱ;将黄柏、火把花根、马齿苋、滇王不留行四味药材粉碎成粗粉后混匀,用20~30%乙醇作溶剂渗漉,收集渗漉液,滤过,浓缩至相对密度为1.3~1.35的稠膏,稠膏用溶液Ⅱ搅拌溶解,再缓缓加入溶液Ⅰ,边加边搅拌至冷凝,分装,即得乳膏剂。
实施例9
组方:黄柏20g,龙血竭1g,火把花根5g,滇王不留行5g,马齿苋12g,冰片1g;将组方中各药味按组方量称量,碎成细粉。用麻油调和均匀,分装,即得油剂。
下面通过药效学实验,以该中药组合物制成软膏给药,评价本发明中药组合物对小鼠银屑病模型的治疗效果。
实验例1
一、实验方法
脾脏是最重要的免疫器官之一,研究发现,银屑病样小鼠较正常小鼠的脾指数高,本发明中药组合物的药效学实验中计算脾指数,可在一定程度上反映机体免疫功能的强弱;PASI评分是临床和药理实验中监测和评价银屑病严重程度和改善程度的重要指标;苏木精-伊红(HE)染色可以观察背部皮损组织病理变化,评价银屑病的发病情况;现有研究认为,银屑病是一种免疫介导的炎症性皮肤病,IL-1β、IL-6、IL-8、IL-17A、IL-22、IL-23等炎症因子在银屑病发生发展过程中发挥重要作用,故采用酶联免疫吸附法(ELISA)检测血清中抗炎因子的表达水平。本实验通过咪喹莫特诱导银屑病动物模型,给予不同剂量实施例1制备的中药组合物软膏进行干预,运用H&E染色、酶联免疫吸附实验法等多种药理学、免疫学的技术方法研究该中药组合物干预银屑病的作用及疗效。
1、药物与试剂: 5%咪喹莫特软膏(造模),卡泊三醇软膏(阳性组给药),凡士林(正常组给药),实施例1制备的中药组合物软膏(实验组给药)。
2、实验分组:昆明种小鼠,将小鼠适应性喂养一周后,按体重随机分为6组,每组10只。分别为正常对照组,模型组(5%咪喹莫特乳膏),阳性组(卡泊三醇软膏),中药组合物高、中、低剂量组。
3、造模:除去小鼠背部毛发使得皮肤裸露约 2cm × 3 cm 大小区域。鼠脱毛后正常组涂抹凡士林62.5 mg/d/(2×3 cm2),相同剂量的5 %咪喹莫特乳膏涂于造模组小鼠背部62.5 mg/d/(2×3 cm2),持续造模5天。
4、给药:造模开始之日起,每日按上述分组给药,凡士林62.5 mg/只作为正常、模型组涂抹药物,阳性药组(卡泊三醇,62.5 mg/只)作为阳性对照药物,实验组给药按中药组合物高、中、低剂量组分别180mg/只、120mg/只、60mg/只,实验过程中观察小鼠的一般生理状态(毛色、精神状态、摄食量、粪便等),每日测量小鼠体重及PASI评分。
参考临床银屑病的面积与严重性指数PASI评分标准(如表1),每日由专人定时盲选并观察各组小鼠皮损的变化情况,尽量减少实验误差。根据PASI评分标准(红斑,0-4;鳞屑,0-4;皮肤增厚程度,0-4)每日评出实验动物背部银屑病样变化总积分(鳞屑+红斑+皮损增厚,0-12),统计分析后绘制银屑病评分趋势图以观察小鼠皮损动态变化情况。
表1 临床银屑病的面积与严重性指数评分标准
5、续造模及给药5天后,眼球取血,处死小鼠,拍照取材,采集血液样本。处后进行相应指标的测定。
(1)造模及给药5天后记录小鼠体重,剖取各组小鼠脾脏,处理后称重,记录各组小鼠脾脏重量(mg),并计算小鼠脾脏指数[脾质量/体质量(mg /g × 10)]。
(2)小鼠背部皮损处皮肤处理后,进行苏木精和伊红(HE)染色以观察组织病理变化,在显微镜下观察(皮层厚度、炎性浸润)并进行图像采集。
(3)在免疫学反应原理的基础上通过酶联免疫吸附试验(ELISA法)检测所有组别小鼠背部皮损处炎症因子IL-1β、IL-6、IL-8、IL-17A、IL-22及IL-23的水平。
二、结果分析
(1)如图1所示,通过肉眼观察,正常组小鼠皮肤始终保持光滑,表皮没有干燥鳞屑、红斑等现象;造模组于第2-3天开始出现皮损,背部出现红色斑点,随着造模时间的延长,红斑逐渐从点扩大到片状,背部由轻微鳞屑到片状再到鳞屑成层,造模及给药6天后银屑病样模型形成;与模型组及阳性组相比,本发明中药组合物中、高剂量组银屑病皮损程度较轻,且小鼠鳞屑薄、少,鳞屑成层现象不明显。根据这些结果可以初步判断本发明中药组合物能够缓解银屑病样小鼠的皮损症状,且中、高剂量组效果明显。
(2)本实验通过银屑病面积与严重性指数(PASI评分)来比较给药组和模型组小鼠背部皮肤皮损的严重程度。正常组红斑、鳞屑、皮损增厚三者评分之和始终为0;模型组小鼠造模第3天皮肤逐渐出现银屑病样皮损:背部红斑,鳞屑,皮肤增厚,且随时间增加,严重程度逐渐增重,面积逐渐增大。第 3至第 6天 PASI 评分在红斑、鳞屑、皮损增厚及总分中均明显高于正常组,提示模型建造成功。阳性组及中药组合物高、中、低剂量组小鼠与模型组小鼠同期相比较,皮肤红斑、鳞屑、皮损增厚情况减轻,在第3天此三项及总分较模型组降低,见表2。在第 6天,中药组合物高、中剂量组皮损颜色减淡,鳞屑减少,皮损厚度减轻,PASI 评分均明显降低,见图1、2。以上结果表明,中药组合物低、中、高剂量组和阳性组可以不同程度地改善小鼠皮肤的红斑、鳞屑、增厚情况。
表2 PASI日评分平均值汇总表
(3)如表3和图3所示,模型组与正常组相比较,脾脏指数极有显著性差异(P<0.001),阳性组和本发明中药组合物中、高剂量组与模型组相比较均极有显著性差异(P<0.001)。表明和“中药组合物”对免疫功能具有调节作用,极有显著性调节作用的是中、高剂量组。
表3不同实验组脾指数
(4)通过HE染色对银屑病样小鼠皮损组织进行病理学分析(如图4):正常组细胞形态正常,表皮较薄,无炎性浸润现象,模型组与之相反;与模型组相比,经阳性药和本发明中药组合物干预治疗的银屑病小鼠在皮损厚度、炎性浸润方面均有改善。由此说明本发明中药组合物能够抑制银屑病样小鼠皮损处的炎性细胞浸润,并降低疾病的严重程度。抑制作用中、高剂量组优于低剂量组。
(5)如图5所示,正常组与模型组相比较,相关炎症因子表达均极有显著性上升(P<0.001),阳性组与模型组相比较,阳性组给药后IL-8、IL-17A炎症因子表达极有显著性下降(P<0.001), IL-6、IL-22炎症因子表达有显著性下降(P<0.01),而本发明中药组合物高、中、低剂量组与模型组相比较,本发明中药组合物中、高剂量组对抑制血清中IL-1β、IL-6、IL-8、IL-17A、IL-22、IL-23等炎症因子的表达均极有显著性下降(P<0.001)。这表明本发明中药组合物对银屑病炎症的发生发挥了改善作用。
实验例2 临床药效实验
一、实验方法
本临床试验为考察本发明中药组合物对血热证寻常型银屑病的治疗效果。实验方法如下:
诊断标准:患者于昆明市中医医院门诊确诊为银屑病且为血热证所致。诊断标准参照《临床皮肤病学》和《临床诊疗指南—皮肤病与性病分册》中寻常型银屑病的诊断标准进行诊断。辨证标准参照《中医皮肤性病学》。主症:①皮损鲜红;②新出皮疹不断增多或迅速扩大;③原有皮损肥厚浸润或浸渍。次症:①心烦易怒;②小便黄;③咽部充血、扁桃体肿大;④舌质红或绛;⑤脉弦或数。
分组、治疗。将自愿者随机分配为对照组和治疗组,每组各60人,且两组的年龄、病程、性别无显著性差异。治疗组,取实施例1制备的中药组合物软膏,外涂,薄涂,每日早晚各2次。对照组,取卡泊三醇软膏,外涂,每日早晚2次,治疗8周后判定疗效。
疗效评定。参照研究文献进行PASI、DLQI评分,依次判定疗效。
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表4 疗效分级标准表
二、试验结果分析
1、疗效分析
治疗组总有效率为68.3%,高于对照组的55.0%。其中治疗组痊愈13例,显效28例,好转14例。结果见表5。
表5 疗效分析结果
2、PASI评分分析
治疗前,治疗组为11.35±1.92分,与对照品组11.23±1.87分比较无统计学意义。治疗后,治疗组为4.26±1.23分,PASI评分优于对照品组的5.35±1.14分,比较有统计学意义。结果见表6。
表6 PASI评分结果
3、DLQI评分分析
治疗前,治疗组为12.02±2.21分,与对照品组11.95±2.01分比较无统计学意义。治疗后,治疗组为5.31±1.40分,DLQI评分优于对照品组的7.90±2.61分,比较有统计学意义。结果见表7。
表7 DLQI评分结果
4、不良反应
治疗组和对照组均未出现严重不良反应,治疗组1例出现病症瘙痒感觉轻微增加,未影响继续治疗,治疗8周后查肝肾功,两组患者均未见异常。
综上可知,本发明中药组合物对于银屑病的治疗总体优于阳性药卡泊三醇软膏。
Claims (10)
1.一种治疗银屑病的外用中药组合物,其特征在于,由以下重量份的原料制成:黄柏5~20份,龙血竭1~8份,火把花根5~20份,滇王不留行5~25份,马齿苋5~20份,冰片1~8份。
2.一种基于权利要求1所述中药组合物的药物制剂,其特征在于,所述药物制剂为软膏、搽剂、洗剂、喷剂、凝胶剂、乳膏剂和油剂中的任意一种。
3.根据权利要求2所述的药物制剂,其特征在于,所述软膏由下列工艺制备:
1)取液状石蜡60~90份,黄凡士林160~190份,黄柏5~20份,龙血竭1~8份,火把花根5~20份,滇王不留行5~25份,马齿苋5~20份,冰片1~8份;
将液状石蜡和黄凡士林加热至110~130℃;
将中药组合物中黄柏、火把花根、马齿苋、滇王不留行四味药加入炸15分钟,滤过,滤液冷却至60~70℃;
2)将龙血竭和冰片分别研细过120目筛,加入龙血竭粉和冰片粉1倍重量份的95%乙醇研磨溶解;
溶解后的乙醇溶液和上述滤液混合,不断搅拌至均匀,待近凝固前再次搅拌均匀,分装,即得。
4.根据权利要求2所述的药物制剂,其特征在于,搽剂由下列工艺制备:
1)将黄柏、火把花根、滇王不留行、马齿苋粉粹后过100目筛,混合均匀,用20~30%乙醇回流或渗漉提取,过滤,合并滤液,浓缩至适量;
2)龙血竭和冰片用适量95%乙醇搅拌溶解后与步骤1)得到的浓缩滤液合并,加20~30%乙醇使成200ml,搅拌均匀,分装,即得。
5.根据权利要求2所述的药物制剂,其特征在于,洗剂由下列工艺制备:
1)将黄柏、火把花根、滇王不留行、马齿苋四味加水煎煮两次,每次60分钟,过滤,合并滤液,浓缩至适量;
2)将龙血竭和冰片加入适量95%乙醇搅拌溶解后加入至步骤1)得到的浓缩滤液中,补液至200ml,加入0.1~0.3份苯甲酸和0.1~0.2份羟苯乙酯,搅匀,分装,即得。
6.根据权利要求2所述的药物制剂,其特征在于,所述喷剂由下列工艺制备:
1)将黄柏、火把花根、马齿苋、滇王不留行粉碎成粗粉,按渗漉法用20~30%乙醇渗漉2次,每次3h以上,收集渗漉液,滤过,浓缩至适量;
2)龙血竭和冰片用95%乙醇溶解后加入步骤1)得到的浓缩渗漉液中,混合均匀,加入加入0.1~0.3份苯甲酸和0.1~0.2份羟苯乙酯,搅匀,密闭,静置24h,分装,即得。
7.根据权利要求2所述的药物制剂,其特征在于,所述凝胶剂由下列工艺制备:
1)取2~3份卡波姆用80~120份甘油室温溶胀24h;
2)将龙血竭和冰片用95%乙醇溶解,黄柏、火把花根、马齿苋、滇王不留行粉碎成粗粉后混匀,用20~30%乙醇作溶剂渗漉,收集渗漉液,滤过,浓缩至适量,备用;
3)将渗漉液浓缩液和龙血竭和冰片的乙醇溶液加入用甘油溶胀的卡波姆中,搅拌均匀,分装,即得。
8.根据权利要求2所述的药物制剂,其特征在于,所述乳膏剂由下列工艺制备:
1)冰片与龙血竭研磨成细粉,龙血竭用适量乙酸乙酯溶解;
2)取70~90份硬脂酸、40~60份单硬脂酸甘油酯水浴加热熔融,保温,加入10~30份司盘60与0.3~0.5份羟苯乙酯使溶解,加入冰片细粉用乙酸乙酯溶解的龙血竭得到溶液I;
3)称取20~40 份聚山梨酯80用蒸馏水溶解得到溶液Ⅱ;
4)将黄柏、火把花根、马齿苋、滇王不留行四味药材粉碎成粗粉后混匀,用20~30%乙醇作溶剂渗漉,收集渗漉液,滤过,浓缩至相对密度为1.3~1.35的稠膏,稠膏用溶液Ⅱ搅拌溶解,再缓缓加入溶液Ⅰ,边加边搅拌至冷凝,分装,即得。
9.根据权利要求2所述的药物制剂,其特征在于,所述油剂由下列工艺制备:将黄柏、龙血竭、火把花根、滇王不留行、马齿苋、冰片六味中药粉碎成细粉;
用麻油调和均匀,分装,即得。
10.权利要求1所述的中药组合物在制备治疗银屑病药物中的应用。
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