CN116059244B - 铂纳米线作为活性成分在治疗皮肤疾病中的应用 - Google Patents
铂纳米线作为活性成分在治疗皮肤疾病中的应用 Download PDFInfo
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Abstract
本发明公开了铂纳米线作为活性成分在治疗皮肤疾病中的应用，属于药物领域，具体为铂纳米线作为活性成分在制备外用皮肤疾病药物中的应用，尤其用于治疗玫瑰痤疮和银屑病。本发明所述药物由活性成份铂纳米线和必要药用辅料组成，证实了铂纳米线(PtNWs)相比铂纳米颗粒具有更高的表面应变和表面低配位结构，使其在催化反应中展现出极高的质量活性，也在炎症性皮肤病模型的治疗中表现出了更好的疗效。
Description
技术领域
本发明涉及药物领域，具体为铂纳米线作为活性成分在制备外用皮肤疾病药物中的应用，尤其用于治疗玫瑰痤疮和银屑病。
背景技术
玫瑰痤疮是一种常见的多发于面部的炎症性疾病，临床表现为红斑，丘疹，脓疱，毛细血管扩张和反复潮红，目前用于玫瑰痤疮的临床用药主要针对的是抗炎或抗血管生成。尽管玫瑰痤疮不会危及到生命，但因其发病部位在面部，且反复发作，给患者的身心健康和生活质量造成很大的影响。银屑病俗称牛皮藓，病因复杂且没有明确的发病机制和治疗方案。临床表现为红斑，鳞屑，是一种全身性慢病炎症皮肤病。目前主要是外用糖皮质激素或免疫抑制剂，内服甲氨蝶呤或其他免疫抑制剂以及物理疗法对症治疗，但停药后病情加重且耐受性较差。玫瑰痤疮和银屑病都属于炎症性皮肤病，炎症反应中产生的活性氧(ROS)过量时会加重局部组织损伤并导致慢性炎症。现有的药物抗氧化性能差、副作用大、治疗效果欠佳，从而限制了其用于治疗活性氧相关的炎性疾病的临床应用。
通常，细胞会通过酶(如，过氧化物歧化酶superoxide dismutase等)的作用来减少R活性氧对细胞的损伤，从而起到保护的作用。但是天然酶来源有限，提纯困难，价格昂贵。同时，天然酶容易受到多种物理、化学因素的影响而失去活性，使其应用受到了极大的限制。纳米人工模拟酶具有催化效率高、稳定、经济和规模化制备的特点。铂属的纳米粒子由于具有较大的比表面积而被开发出来，以提高铂属的催化活性。在纳米材料中，铂纳米颗粒(Pt NPs)已经被公认为是一种高度理想的催化剂，具有类过氧化酶、氧化酶、超氧化物歧化酶、过氧化氢酶等活性。这些催化剂可能作为抗氧化剂发挥作用，减少活体中的ROS。本发明证实了铂纳米线(Pt NWs)相比铂纳米颗粒具有更高的表面应变和表面低配位结构，使其在催化反应中展现出极高的质量活性，也在炎症性皮肤病模型的治疗中表现出了更好的疗效。
发明内容
本发明的目的在于提供一种铂纳米线作为活性成分在制备外用皮肤疾病药物中的应用，尤其用于玫瑰痤疮和银屑病。
为实现上述目的，本发明提供如下技术方案：
本发明所述的外用药物由活性成份铂纳米线和必要药用辅料组成；
为了达到较佳的治疗效果，所述的外用药物由0.1～1％活性成份铂纳米线和99～99.9％必要药用辅料组成；
为了使治疗效果达到更佳效果，所述的外用药物由0.2-0.8％活性成份铂纳米线和99.2～99.8％必要药用辅料组成。
为了使治疗效果达到最佳效果，所述的外用药物由0.5％活性成份铂纳米线和99.5％必要药用辅料组成。
本发明所述的外用药物是外用制剂；所述的外用制剂是搽剂、乳膏剂、喷雾剂、凝胶剂和洗剂等任何一种外用剂型。即本发明药物的活性成分可以加入制备不同剂型时所需的各种常规辅料，如润滑剂、粘合剂等，并以常规的制剂方法制备成任何一种常用外用剂型，如散剂、洗剂、软膏剂、喷雾剂、凝胶剂和乳膏剂等。
优选的，所述外用制剂是乳膏剂。
本发明的另一目的旨在提供一种制备治疗玫瑰痤疮或银屑病药用乳膏剂的方法，本发明所涉及的乳膏剂的制备方法如下：
称取铂纳米线溶于水中，然后加入聚丙烯酸酯交联聚合物-6，充分混匀，制成0.1～1％铂纳米线乳膏，于2～8℃保存。
最优选的，本发明所述乳膏剂是由下述方法制备的：
称取铂纳米线2.5g溶于纯水500ml中，再加入1000g聚丙烯酸酯交联聚合物-6，室温下充分混匀，制成铂纳米线乳膏1000支，于2～8℃保存。
附图说明
图1为本发明试验例1中铂纳米线和铂纳米颗粒的结构和尺寸；
图2为本发明试验例2中铂纳米线和铂纳米颗粒的类酶活性；
图3为本发明试验例3中铂纳米线和铂纳米颗粒在细胞水平的抗氧化能力；
图4为本发明试验例3中铂纳米线和铂纳米颗粒在细胞水平的抗炎和抗趋化能力；
图5为本发明试验例4中铂纳米线和铂纳米颗粒缓解玫瑰痤疮样小鼠表型；
图6为本发明试验例4中铂纳米线和铂纳米颗粒缓解银屑病样小鼠表型；
具体实施方式
为详细说明本发明的技术内容、所实现目的及效果，以下结合实施方式并配合附图予以说明。
试验例1、本发明中铂纳米线的结构和尺寸
图1A所示为Pt NPs的结构表征图，图1C所示为Pt NWs的结构表征图。我们用软件对颗粒的直径进行统计，选取了约200个颗粒，得出图B和D的粒径直方分布图。Pt NPs的平均粒径约为3.16nm，Pt NWs的直径约为2.67nm。
试验例2、本发明中铂纳米线和铂纳米颗粒的类酶活性
首先通过典型的过氧化物酶(POD)活性检测催化体系研究了Pt NWs的类POD活性，其中0.5mM的3,3二甲基联苯胺杂质(TMB)和5mM H2O2被用作底物。测量了加入不同浓度的Pt NWs和Pt NPs时的吸收光谱。如图2A所示，通过引入Pt NPs和Pt NWs使溶液变成蓝色，且加入Pt NWs的溶液颜色更蓝。这说明TMB的氧化归因于Pt NWs的催化作用。此外，从吸收光谱可得知，Pt NWs的吸收峰更高，这也说明Pt NWs的POD样活性更强。
然后比较分别添加Pt NWs和Pt NPs时，过氧化氢在520nm处的吸光度下降来确定过氧化氢酶(CAT)样活性【碧云天试剂盒S0051】。Pt NWs对于过氧化氢的清除率明显高于PtNPs，表明Pt NWs过氧化氢酶的活性比Pt NPs高，见图2B。
采用经典的WST-8显色法【碧云天试剂盒S0101S】测定了Pt NWs的超氧化物歧化酶(SOD)样活性。560nm处的吸光度随浓度的变化而变化，图2C给出了定量的单位活性，表明同一浓度下Pt NWs的SOD样活性约为Pt NPs的3倍甚至更高。
根据经典的谷胱甘肽还原酶偶联反应机制，通过检测还原酶在340nm处的吸光度的变化，研究了Pt NWs的谷胱甘肽过氧化物酶(GPx)样活性【碧云天试剂盒S0058】与Pt NPs相比，Pt NWs的GPx样活性显著增强，其吸光度随着时间的变化而降低。定量统计显示，PtNWs的GPx样活性约是PtNPs的三倍，见图2D。
最后使用1,1-二苯基-2-苦基肼(DPPH)测试了Pt NWs清除自由基的能力【索莱宝试剂盒BC4750】。测定515nm处的吸光度，根据计算得出剩余DPPH的量。如图2E所示，Pt NWs随着浓度的递增，清除自由基的能力变强，并且在选定的浓度范围内其清除自由基能力都远胜于Pt NPs。
试验例3、本发明细胞实验
一、实验方法
抗氧化能力检测：Pt NWs和Pt NPs与HaCaT细胞共孵育12个小时后，用1mM过氧化氢处理细胞，在6小时后用Dihydroethidium(超氧化物阴离子荧光探针)【碧云天试剂S0063】测定细胞内超氧化物阴离子的变化。
抗炎和抗趋化因子能力检测：用100ng/ml TNF-α处理HaCat细胞12小时后收集细胞提取RNA，进行实时荧光定量PCR检测细胞内炎症因子和趋化因子(TNF-α、IL-6、IL-8、CCL2、CCL20)的改变。
一、实验结果
如图3-4所示
图3为细胞水平的抗氧化能力，结果表明H2O2处理增加了细胞内超氧化物阴离子，但与单纯H2O2诱导组相比，Pt NWs处理组显著降低了超氧化物阴离子的产生。。
图4为细胞水平的抗炎和抗趋化因子能力，Pt NWs预处理组可以明显减轻TNF-α诱导的HaCat细胞中的炎症因子和趋化因子的表达，且效果比Pt NPs诱导组好。
试验例4、本发明在治疗改善玫瑰痤疮样及银屑病表型的动物的应用
一、实验方法
购买7周龄BALB/C雌鼠，小鼠背部皮肤剃毛，连续5天，在小鼠的背部涂抹0.5％PtNWs乳膏，早晚各一次，一日两次，于第3-4日早晚各一次皮内注射LL37以诱导玫瑰痤疮样表型，同时应用0.5％Pt NWs乳膏涂抹，早晚各一次，一日两次。同时加入Pt NPs乳膏组做对照。
Pt NWs改善玫瑰痤疮样表型的动物模型构建进行之后进行Pt NWs改善银屑病样表型的动物模型构建，即购买7周龄BALB/C雌鼠，连续9天，在Balb/c小鼠的耳部涂抹0.5％Pt NWs乳膏，早晚各一次，一日两次，于第3-8天在小鼠耳部涂抹咪喹莫特乳膏以诱导银屑病样表型，同时应用0.5％铂纳米线乳膏涂抹，早晚各一次，一日两次。同时加入Pt NPs乳膏组做对照。
造模结束后剪取小鼠皮损，分为两部分，分别进行福尔马林固定48h后，梯度脱水石蜡包埋，切成5μm厚，切片用苏木精和伊红(H&E)染色，并在标准光学显微镜下观察它们的组织形态学；液氮速冻，使用TRIzol试剂(Invitrogen Life Technologies，USA)皮损组织中分离总RNA，将1μg RNA转录成cDNA，q-PCR检测炎症因子和趋化因子的的mRNA水平。
二、试验结果
结果如图5-6所示。
图5为Pt NWs缓解玫瑰痤疮样小鼠表型，图5A为小鼠背部剃毛后，Pt NWs乳膏预涂抹三天，然后皮内注射LL37，诱导玫瑰痤疮样红斑表型，同时涂抹Pt NPs乳膏；图5B为玫瑰痤疮皮损处皮肤H&E染色分析；图5C为q-PCR法检测小鼠皮损中炎症因子和趋化因子的的mRNA水平。
图6为Pt NWs缓解银屑病样小鼠表型，图6A为Pt NWs乳膏预涂抹小鼠耳部3天，然后将IMQ涂抹至小鼠耳部，诱导银屑病样表型，同时涂抹Pt NPs乳膏；图6B银屑病皮损处皮肤H&E染色分析；图6C q-PCR法检测小鼠皮损中炎症因子和趋化因子的mRNA水平。
由图5可知，Pt NWs显著减弱了LL37诱导的玫瑰痤疮样红斑，组织学分析显示，PtNWs乳膏治疗改善了玫瑰痤疮样皮损中的炎症细胞浸润；大量研究表明，玫瑰痤疮中促炎细胞因子及趋化因子显著上调，但这在小鼠背部皮损中可被Pt NWs乳膏治疗所抑制，且其效果要比Pt NPs乳膏效果好，因此，这些结果表明Pt NWs改善了LL37诱导的小鼠玫瑰痤疮样炎症表型。
同样，由图6可知，咪喹莫特造模小鼠的银屑病样皮损从第3天开始出现，第7天最严重，包括红斑、皮肤增厚和脱屑，H&E染色显示IMQ处理小鼠的典型组织学变化，特征为角化不全、基层细胞增多和炎性细胞浸润，相比之下，在铂纳米乳膏治疗小鼠中，这些症状得到缓解，RT-PCR结果显示，在IMQ诱导的银屑病小鼠中，炎症及趋化因子的表达显著升高，而铂纳米乳膏显著减缓了这些因子的表达，且Pt NWs乳膏效果要比Pt NPs乳膏效果好。
综上所述，本发明的药物具有治疗玫瑰痤疮及银屑病的效果。
试验例4、本发明临床试验
为了验证本发明药物在制备治疗玫瑰痤疮药物的应用，本发明人在中南大学湘雅附属医院进行临床小试，具体情况如下：
一、病例选择
被两位临床医生诊断为红斑毛细血管扩张型和丘疹脓疱型玫瑰痤疮患者(红斑评分为3分及以上)，并自愿签署知情同意书。
二、病例概况
此次临床试验均按以下诊断标准进行病症选择，共选择120例患者，年龄为18～65岁，平均35岁，男女不限。
诊断标准：
1、在门诊被临床医生诊断为玫瑰痤疮红斑毛细血管扩张型和丘疹脓疱型患者；
2、年龄在18-65岁；
2、近期无妊娠计划者；
3、近两周内未予以局部外用治疗患者或4周内使用普通药物全身治疗或半年内使用异维A酸治疗；
4、无鼻部增生肥大的玫瑰痤疮患者。
三、资料均衡性检验
将上述病例随机分为2组，即治疗组和对照组。每组各60例。男女不限，试验组及对照组的年龄、病情程度大致匹配，具有可比性。
四、研究方法
随机、对照研究。并按下述疗效标准进行统计研究结果。
疗效标准：
疗效标准：
1、显效：持续性红斑，丘疹脓疱，刺痛和灼热感大部分消退，消退率>75％，症状明显减轻；
2、有效：持续性红斑，丘疹脓疱，刺痛和灼热感大部分消退，消退率25-75％，症状有所改善；
3、无效：皮损消退不明显或者加重，消退率＜25％，症状未见变化。
五、治疗方法
治疗组患者给予本发明乳膏剂(实施例3)，每天2次，每次适量，涂抹于患处，4周为1个疗程。对照组患者给予空白乳膏，即不含有Pt NWs的聚丙烯酸酯交联聚合物-6制成的乳膏，每天2次，每次适量，外涂患处，4周为1个疗程。治疗期间两组患者均不再使用其他任何药物。
六、结果
2、治疗组与对照组临床疗效比较情况见表一。
表一、治疗组与对照组临床疗效比较表
(P<0.01，差异有非常显著性)
从上表可以看出，本发明的有效率达95％，对照组的有效率10％，说明本发明有效率明显高于对照组，且效果显著。
2、不良反应情况
治疗组中尚未发现有明显不良反应者，对照组中7例出现不同程度的发红、脱屑或皮肤不适。
经临床验证，本发明的药物在治疗痤疮方面有显著疗效。
实施例1、本发明乳膏剂
称取铂纳米线0.5g溶于纯水500ml中，再加入1000g聚丙烯酸酯交联聚合物-6，室温下充分混匀，制成铂纳米线乳膏1000支，于2～8℃保存。
实施例2、本发明乳膏剂
称取铂纳米线5g溶于纯水500ml中，再加入1000g聚丙烯酸酯交联聚合物-6，室温下充分混匀，制成铂纳米线乳膏100支，于2～8℃保存。
实施例3、本发明乳膏剂
称取铂纳米线2.5g溶于纯水500ml中，再加入1000g聚丙烯酸酯交联聚合物-6，室温下充分混匀，制成铂纳米线乳膏1000支，于2～8℃保存。
Claims (2)
1.一种铂纳米线作为活性成分在制备外用皮肤疾病药物中的应用，其特征在于所述药物由活性成分铂纳米线和必要药用辅料组成；所述铂纳米线直径为2.67纳米；所述皮肤疾病为玫瑰痤疮；所述外用药物的剂型为乳膏剂，由下述方法制备的：称取铂纳米线溶于水中，然后加入聚丙烯酸酯交联聚合物-6，充分混匀，制成0.1～1% 铂纳米线乳膏，于2～8℃保存。
2.根据权利要求1所述的应用，其特征在于，所述乳膏剂是由下述方法制备的：称取铂纳米线 2.5g溶于纯水500ml中，再加入1000g聚丙烯酸酯交联聚合物-6，室温下充分混匀，制成铂纳米线乳膏1000支，于2～8℃保存。
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20020051824A1 (en) * | 2000-07-27 | 2002-05-02 | Burrell Robert Edward | Treatment of hyperproliferative skin disorders and diseases |
| US20020192298A1 (en) * | 2001-04-23 | 2002-12-19 | Burrell Robert Edward | Treatment of acne |
| CN108430431A (zh) * | 2015-11-13 | 2018-08-21 | 丝芭霞公司 | 用等离子体纳米粒子处理皮肤状况的方法 |
| CN115317511A (zh) * | 2022-08-17 | 2022-11-11 | 中南大学湘雅医院 | 一种用于治疗皮肤疾病的金纳米颗粒组合物及其制备方法 |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020051824A1 (en) * | 2000-07-27 | 2002-05-02 | Burrell Robert Edward | Treatment of hyperproliferative skin disorders and diseases |
| US20020192298A1 (en) * | 2001-04-23 | 2002-12-19 | Burrell Robert Edward | Treatment of acne |
| CN108430431A (zh) * | 2015-11-13 | 2018-08-21 | 丝芭霞公司 | 用等离子体纳米粒子处理皮肤状况的方法 |
| CN115317511A (zh) * | 2022-08-17 | 2022-11-11 | 中南大学湘雅医院 | 一种用于治疗皮肤疾病的金纳米颗粒组合物及其制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| 玫瑰痤疮发病机制研究进展;袁新 等;《中国皮肤性病学杂志》;20210831;第35卷(第8期);第943-948页 * |
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