CN111714451B - 一种预防瘢痕产生的抗血管生成胶束及其制备方法 - Google Patents
一种预防瘢痕产生的抗血管生成胶束及其制备方法 Download PDFInfo
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Abstract
本发明涉及一种预防瘢痕产生的抗血管生成胶束及其制备方法，属于药物制剂技术领域。该胶束按重量百分比计，包括如下组份：聚β‑熊果苷8‑15％，皮肤外用制剂中可接受的辅料4‑22％，余量为水。该胶束中加入了聚β‑熊果苷，该物质具有高抗氧化活性，能够使得ROS失活，使得VEGF的mRNA表达及蛋白分泌无法正常进行，从而抑制伤口愈合过程中多余血管的生长，进而起到预防瘢痕的作用。另外，通过加入活性成分，将进一步提升该胶束预防瘢痕的能力。该胶束组分简单且对组织具有较好的生物相容性，其制备方法简单，易操作，适合扩大化生产。
Description
技术领域
本发明属于药物制剂技术领域，具体涉及一种预防瘢痕产生的抗血管生成胶束及其制备方法。
背景技术
瘢痕(scar)是各种创伤后所引起的正常皮肤组织的外观形态和组织病理学改变的统称，它是人体创伤修复过程中必然的产物。瘢痕生长超过一定的限度，就会发生各种并发症，诸如外形的破坏及功能活动障碍等，给患者带来巨大的肉体痛苦和精神痛苦，尤其是烧伤、烫伤、严重外伤后遗留的瘢痕。
正常的创面愈合过程是由一系列生理生化变化和细胞、细胞因子、细胞外基质等共同参与，并相互调节的网络调控过程，多种病理、生理条件均可影响和改变这一正常的生理愈合过程，瘢痕的过度增生即是病理性愈合的结果。
大量研究指出，瘢痕组织内纤维细胞的过度繁殖，并伴有大量胶原在组织内沉积，由于胶原形态大，排列方向呈极性，胶原蛋白生物合成中，关键酶的活性明显增强，但其基质降解减少，所以瘢痕的形成可能与胶原的合成、降低失衡有关，即瘢痕疙瘩形成主要是由于成纤维细胞的增生和凋亡之间的平衡失调，受多种因素影响。
目前，治疗瘢痕主要采用手术、放疗和药物治疗，无特效治疗方法。其中，减少胶原形成促进其凋亡是药物治疗的主要途径。血液循环是组织、器官和细胞行使正常生理功能以及从病理状态恢复的基础，也影响皮肤伤口的愈合以及瘢痕的重塑。先前的研究表明，瘢痕疙瘩浸润性生长和其胶原表达与血供及微循环改变关系密切，抗血管生成治疗可能是很有前途的治疗方法。
发明内容
有鉴于此，本发明的目的之一在于提供一种预防瘢痕产生的抗血管生成胶束；目的之二在于提供一种预防瘢痕产生的抗血管生成胶束的制备方法。
为达到上述目的，本发明提供如下技术方案：
1、一种预防瘢痕产生的抗血管生成胶束，按重量百分比计，所述胶束包括如下组份：聚β-熊果苷8-15％，皮肤外用制剂中可接受的辅料4-22％，余量为水。
优选地，按重量百分比计，所述胶束还包括活性成分0.1-3％。
优选地，所述活性成分为依沙吖啶、依托度酸、酮洛芬、普拉洛芬、氟比洛芬、美洛昔康、阿克他利、舒林酸、塞来昔布、噻洛芬酸、替诺昔康、萘普生、吡罗昔康、联苯乙酸、阿西美辛、安吡昔康、氨芬酸、布洛芬、扎托洛芬、双氯芬酸、吲哚美辛、莫苯唑酸、洛索洛芬、氯苯扎利或氯诺昔康中的至少一种。
优选地，所述聚β-熊果苷的制备方法如下：
在氧气气氛中，向Tris-HCl缓冲液中加入β-熊果苷和氯化亚铜-四甲基乙二胺，于60-80℃下反应1-2d后渗析纯化12-24h，最后冷冻干燥即可。
优选地，所述Tris-HCl缓冲液的浓度为0.05mol/L，pH值为7-9；所述β-熊果苷和氯化亚铜-四甲基乙二胺的质量比为1:3-7。
优选地，所述辅料包括保湿剂、增稠剂和防腐剂；所述保湿剂占所述胶束总重量的3-10％，所述增稠剂占所述胶束总重量的0.1-2％，所述防腐剂占所述胶束总重量的1-10％。
优选地，所述保湿剂为1,3-丁二醇、1,3-丙二醇、乳酸钠、甘油、羟乙基脲、透明质酸钠、甲壳素、甲壳素衍生物或植物多糖提取物中的至少一种；所述增稠剂为聚丙烯酸酯交联聚合物-6、丙烯酸羟乙酯/丙烯酰二甲基牛磺酸钠共聚物、聚丙烯酸钠、聚丙烯酸类聚合物、黄原胶或羟乙基纤维素中的至少一种；所述防腐剂为苯氧基乙醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯或山梨醇中的至少一种。
2、所述的一种预防瘢痕产生的抗血管生成胶束的制备方法，所述方法如下：
将聚β-熊果苷、活性成分和皮肤外用制剂中可接受的辅料溶于有机相中，然后在冰浴、搅拌条件下以10-30滴/min的速度滴加水相，继续搅拌12-24h后透析6-12h，冷冻干燥后溶于水，即可。
优选地，所述有机相和水相的体积比为1:10-15。
优选地，所述有机相为二甲基亚砜；所述水相为水。
优选地，所述冷冻干燥后溶于水具体为：对冷冻干燥后的产物中各组分含量进行测试，然后根据对胶束中各组分含量的实际需求设定所述产物和水的用量，将所述产物溶于水，即可。
本发明的有益效果在于：本发明提供了一种预防瘢痕产生的抗血管生成胶束及其制备方法，该胶束中加入了聚β-熊果苷，由于邻接效应以及共轭体系，使得β-熊果苷上的酚羟基的氢氧键离解键能降低，苯环上羟基(-OH)上的H原子容易从分子上脱落下来，其抗氧化活性增大，使得聚β-熊果苷具有高抗氧化活性，与过氧自由基(ROO·)、烷氧自由基(RO·)、羟自由基(·OH)等结合使之失去活性。ROS激活STAT3转录调控VEGF，促进VEGF的mRNA表达及蛋白分泌，进而促进血管生成，此时具有高抗氧化活性的聚β-熊果苷通过上述作用，能够使得ROS失活，使得VEGF的mRNA表达及蛋白分泌无法正常进行，从而抑制伤口愈合过程中多余血管的生长，进而起到预防瘢痕的作用。另外，通过加入活性成分，将进一步提升该胶束预防瘢痕的能力。该胶束组分简单且对组织具有较好的生物相容性，其制备方法简单，易操作，适合扩大化生产。
本发明的其他优点、目标和特征在某种程度上将在随后的说明书中进行阐述，并且在某种程度上，基于对下文的考察研究对本领域技术人员而言将是显而易见的，或者可以从本发明的实践中得到教导。本发明的目标和其他优点可以通过下面的说明书来实现和获得。
具体实施方式
以下通过特定的具体实例说明本发明的实施方式，本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用，本说明书中的各项细节也可以基于不同观点与应用，在没有背离本发明的精神下进行各种修饰或改变。
实施例1
一种预防瘢痕产生的抗血管生成胶束，按重量百分比计，该胶束包括如下组份：聚β-熊果苷10％，活性成分(氯苯扎利)1％，皮肤外用制剂中可接受的辅料(保湿剂[1,3-丁二醇]5％、增稠剂[黄原胶]0.1％、防腐剂[对羟基苯甲酸丙酯]1％)6.1％，余量为纯化水。该胶束按如下方法制备：
(1)在氧气气氛中，向浓度为0.05mol/L，pH值为8的Tris-HCl缓冲液中加入β-熊果苷和氯化亚铜-四甲基乙二胺，于60℃下反应2d后渗析纯化18h，最后冷冻干燥，制得聚β-熊果苷，其中，β-熊果苷和氯化亚铜-四甲基乙二胺的质量比为1:5；
(2)将步骤(1)中制备的聚β-熊果苷、活性成分(氯苯扎利)和皮肤外用制剂中可接受的辅料(保湿剂[1,3-丁二醇]、增稠剂[黄原胶]、防腐剂[对羟基苯甲酸丙酯])溶于二甲基亚砜中，然后在冰浴、搅拌条件下以10滴/min的速度滴加纯化水，二甲基亚砜与滴加的纯化水的体积比1:10，继续搅拌12h后以截留分子量为5000的透析袋透析12h，冷冻干燥，对冷冻干燥后的产物中各组分含量进行测试，然后根据该胶束中各组分的重量百分比设定该产物和纯化水的用量，将该产物溶于纯化水，即可。
实施例2
一种预防瘢痕产生的抗血管生成胶束，按重量百分比计，该胶束包括如下组份：聚β-熊果苷15％，活性成分(普拉洛芬)3％，皮肤外用制剂中可接受的辅料(保湿剂[透明质酸钠]3％、增稠剂[聚丙烯酸钠]1％、防腐剂[苯氧基乙醇]2％)6％，余量为纯化水。该胶束按如下方法制备：
(1)在氧气气氛中，向浓度为0.05mol/L，pH值为7的Tris-HCl缓冲液中加入β-熊果苷和氯化亚铜-四甲基乙二胺，于80℃下反应1d后渗析纯化24h，最后冷冻干燥，制得聚β-熊果苷，其中，β-熊果苷和氯化亚铜-四甲基乙二胺的质量比为1:7；
(2)将步骤(1)中制备的聚β-熊果苷、活性成分(普拉洛芬)和皮肤外用制剂中可接受的辅料(保湿剂[透明质酸钠]、增稠剂[聚丙烯酸钠]、防腐剂[苯氧基乙醇])溶于二甲基亚砜中，然后在冰浴、搅拌条件下以30滴/min的速度滴加纯化水，二甲基亚砜与滴加的纯化水的体积比1:15，继续搅拌24h后以截留分子量为5000的透析袋透析6h，冷冻干燥，对冷冻干燥后的产物中各组分含量进行测试，然后根据该胶束中各组分的重量百分比设定该产物和纯化水的用量，将该产物溶于纯化水，即可。
实施例3
一种预防瘢痕产生的抗血管生成胶束，按重量百分比计，该胶束包括如下组份：聚β-熊果苷8％，活性成分(布洛芬)0.1％，皮肤外用制剂中可接受的辅料(保湿剂[甘油]10％、增稠剂[羟乙基纤维素]2％、防腐剂[山梨醇]1％)13％，余量为纯化水。该胶束按如下方法制备：
(1)在氧气气氛中，向浓度为0.05mol/L，pH值为9的Tris-HCl缓冲液中加入β-熊果苷和氯化亚铜-四甲基乙二胺，于70℃下反应1.5d后渗析纯化12h，最后冷冻干燥，制得聚β-熊果苷，其中，β-熊果苷和氯化亚铜-四甲基乙二胺的质量比为1:3；
(2)将步骤(1)中制备的聚β-熊果苷、活性成分(布洛芬)和皮肤外用制剂中可接受的辅料(保湿剂[甘油]、增稠剂[羟乙基纤维素]、防腐剂[山梨醇])溶于二甲基亚砜中，然后在冰浴、搅拌条件下以20滴/min的速度滴加纯化水，二甲基亚砜与滴加的纯化水的体积比1:12，继续搅拌18h后以截留分子量为5000的透析袋透析8h，冷冻干燥，对冷冻干燥后的产物中各组分含量进行测试，然后根据该胶束中各组分的重量百分比设定该产物和纯化水的用量，将该产物溶于纯化水，即可。
对比实施例
按重量百分比计，将β-熊果苷10％，活性成分(氯苯扎利)1％，皮肤外用制剂中可接受的辅料(保湿剂[1,3-丁二醇]5％、增稠剂[黄原胶]0.1％、防腐剂[对羟基苯甲酸丙酯]1％)6.1％加入纯化水中，混匀制得β-熊果苷溶液。
实施例4
胶束的包封率和载药量测定
将实施例1至实施例3中冷冻干燥后所得的产物分别用二甲基亚砜复溶，采用紫外可见分光光度法测定各胶束中活性物质的吸光度，利用活性物质的标准曲线回归方程计算相应活性物质的含量，并按照下列公式计算包封率(encapsulation efficacy，EE)和载药量(loading capacity，LC)，结果见表1。
表1包封率和载药量测定结果
由表1可知，实施例1至实施例3中胶束中活性物质包封率依次为73.7±1.9％、69.87±2.1％和71.9±1.2％，载药量依次为25.7±0.8％、23.7±0.6％和27.1±0.4％，表明本发明中胶束的包封率和载药量较好，且较高的载药量是保证疗效的关键。
实施例5
胶束粒径及电位测定
将实施例1至实施例3中制备的胶束溶液分别置于特定的比色皿中，利用纳米粒度及电位分析仪测定胶束的粒径、粒径分散系数(PDI)和Zeta电位，温度设定为室温25℃，测试角度为90°，测试结果见表2。
表2粒径、粒径分散系数(PDI)和Zeta电位测定结果
由表2可知，实施例1至实施例3中胶束粒径分布均匀、分散性良好，各胶束均带负电荷，说明具有较好的稳定性。
实施例6
胶束抗氧性能测定
DPPH自由基在517nm波长附近有最大吸收峰，当DPPH自由基与抗氧化剂反应后，517nm波长处的吸收值降低，其降低的程度与接收的电子(抗氧化剂清除自由基活性)呈定量关系，反应进程很容易通过分光光度计监测。
分别取3mL实施例1中胶束溶液和对比实施例中β-熊果苷溶液，首先测量两种溶液未加DPPH时在517nm处的波长，然后测试各加入0.5μg DPPH后在517nm处的波长，计算DPPH消除率，测定结果见表3，DPPH自由基清除计算公式为：
式中：A对照组为未加DPPH溶液自由基吸光度
A样品为加入DPPH溶液自由基吸光度。
表3 DPPH消除率测定结果
由表3可知，实施例1的胶束溶液中DPPH自由基消除率近50％，而对比实施例的β-熊果苷溶液中DPPH自由基消除率近17％，说明聚β-熊果苷相较于β-熊果苷具有更好的抗氧化性。
实施例7
胶束对瘢痕微血管数量和成纤维细胞增生和凋亡测定
30只裸鼠背部用75％乙醇消毒，于右侧肩胛骨处作一0.5cm切口，潜行分离形成皮下腔隙，瘢痕组织去表皮后切成5mm×5mm×8mm大小，植入皮下腔隙中，切口外用红素眼膏后裸露，术后裸鼠转入各自笼内饲养，20d后观察有6只移植物表面色白，移植物和皮肤粘连不可靠被别除，其余24只瘢痕疙瘩表面皮肤色泽红润，瘢痕组织位置固定与周围皮肤紧密粘连，有血管自周围深入生长，表明瘢痕疙瘩完全成活，即疤痕裸鼠模型制作成功，将24只疤痕裸鼠模型分成3组，每组8只，分别标记为实施例1组、对比实施例组、空白对照组。三组于术后21、23、25、27d在瘢痕疙瘩周围皮下分别注射实施例1中胶束溶液0.4mg/0.2mL；对比实施例中胶束溶液0.4mg/0.2mL、浓度为0.9％的氯化钠溶液0.2mL。每天测试瘢痕周围微血管数量(MVC)、成纤维细胞增殖指数(PI)、成纤维细胞凋亡指数(AI)，结果显示第10天后实施例1组中瘢痕周围微血管数量(MVC)减少，和空白对照组相比差异有统计学意义；成纤维细胞增殖指数(PI)和空白对照组相比明显减少(P<0.05)，成纤维细胞凋亡指数(AI)和空白对照组相比明显增加(P<0.05)；实施例1组与对比实施例组对比，明显抑制微血管生长，成纤维细胞增殖指数降低，促进成纤维细胞凋亡，结合实施例6说明本发明中聚β-熊果苷比β-熊果苷具有更强的抗氧化性和抑制血管增生、纤维细胞增生的能力，增加成纤维细胞凋亡，有效预防瘢痕形成。第10天各组瘢痕周围微血管数量(MVC)、成纤维细胞增殖指数(PI)、成纤维细胞凋亡指数(AI)测定数据见表4。
表4各组疤痕微血管数量和成纤维细胞增生和凋亡测定结果
最后说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本技术方案的宗旨和范围，其均应涵盖在本发明的权利要求范围当中。
Claims (1)
1.一种预防瘢痕产生的抗血管生成胶束，其特征在于，按重量百分比计，该胶束包括如下组份：聚β-熊果苷8％，活性成分布洛芬0.1％，皮肤外用制剂中可接受的辅料保湿剂共13％，余量为纯化水；其中，可接受的辅料保湿剂由甘油10％、增稠剂羟乙基纤维素2％和防腐剂山梨醇1％组成；
所述胶束按如下方法制备：
(1)在氧气气氛中，向浓度为0.05mol/L，pH值为9的Tris-HCl缓冲液中加入β-熊果苷和氯化亚铜-四甲基乙二胺，于70℃下反应1.5d后渗析纯化12h，最后冷冻干燥，制得聚β-熊果苷，其中，β-熊果苷和氯化亚铜-四甲基乙二胺的质量比为1:3；
(2)将步骤(1)中制备的聚β-熊果苷、活性成分布洛芬和所述由甘油、增稠剂羟乙基纤维素和防腐剂山梨醇组成的皮肤外用制剂中可接受的辅料保湿剂溶于二甲基亚砜中，然后在冰浴、搅拌条件下以20滴/min的速度滴加纯化水，二甲基亚砜与滴加的纯化水的体积比1:12，继续搅拌18h后以截留分子量为5000的透析袋透析8h，冷冻干燥，对冷冻干燥后的产物中各组分含量进行测试，然后根据该胶束中各组分的重量百分比设定该产物和纯化水的用量，将该产物溶于纯化水，即得所述抗血管生成胶束；
所述胶束中活性物质包封率为71.9±1.2％，载药量为27.1±0.4％。
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| CN1481233A (zh) * | 2001-01-10 | 2004-03-10 | ���ʺ� | 包含熊果苷和葡糖苷酶作为活性成分的增白皮肤组合物 |
| JP2005213198A (ja) * | 2004-01-29 | 2005-08-11 | Iwase Cosfa Kk | 皮膚外用剤 |
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| JP2005213198A (ja) * | 2004-01-29 | 2005-08-11 | Iwase Cosfa Kk | 皮膚外用剤 |
Non-Patent Citations (3)
| Title |
|---|
| Enhanced antimicrobial activities of polymerized arbutin and its derivatives prepared by oxidative polymerization of arbutin;Rika Kajiwara et al.;《Reactive and Functional Polymers》;20190218;第138卷;第39-45页 * |
| Preparation of glycoside polymer micelles with antioxidant polyphenolic cores using alkylated poly(arbutin)s;Ayaka Seto et al.;《RSC Adv.》;20190308;第9卷;第7777页式1，第7778页左栏第2-3段，第7783页右栏第2、4段 * |
| Water-soluble polyphenol synthesis via oxidative coupling polymerisation of b-arbutin with copper catalyst in alkaline media;Maria Hashimoto et al.;《European Polymer Journal》;20160530;第81卷;摘要及第2.5、3.1节 * |
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