CN105797163B - 一种用于治疗视网膜疾病的药物及其制备方法 - Google Patents
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Abstract
本发明一种用于治疗视网膜疾病的药物，含有A2AR 拮抗剂SCH 442416，在所述的拮抗剂SCH 442416的外部包裹有聚酰胺‑胺。本发明还提供了上述的一种用于治疗视网膜疾病的药物的制备方法，先称取SCH442416，将SCH442416溶解于有机溶剂中；再称取聚酰胺‑胺，将聚酰胺‑胺溶解于缓冲液中；将SCH442416有机溶液加入到聚酰胺‑胺的缓冲液中，采用进行超声乳化，再采用旋转蒸发除去有机溶剂制得聚酰胺‑胺包裹的SCH442416纳米颗粒。本发明所述的PAMAM纳米包裹SCH 442416滴眼液纳米粒粒径为169.2nm，具有良好的生物相容性，包裹率高，且易分解。
Description
技术领域：
本发明属于生物医药领域，尤其涉及一种滴眼液，具体来说是一种用于治疗视网膜疾病的药物及其制备方法。
背景技术：
在2010年国际防盲协会第八次大会上，已将视网膜疾病作为视力障碍和致盲的主要原因之一。据统计，在全球，糖尿病性视网膜病变、老年黄斑变性、视网膜脱离等视网膜疾病的致盲率约占15-20％。多种视网膜疾病的终点是多种病理状态(视网膜缺血、缺氧、血-视网膜屏障的破坏、高眼压)，视网膜组织水肿，视网膜神经节细胞的损伤、凋亡。
视网膜组织对低氧非常敏感，多种视网膜疾病(青光眼、黄斑变性、视网膜中央静脉阻塞、糖尿病性视网膜病变等)的病程发生发展过程中均有缺血缺氧的表现。研究发现：在病理状态下(低氧，高眼压，炎症等)，视网膜组织内谷氨酸浓度显著增加，产生细胞毒性作用，从而引神经细胞损伤、坏死。而视网膜上的Müller细胞则应急激活，细胞增大伸长，进入视神经纤维层，包裹RGCs胞体；并释放一些神经营养因子，如睫状神经生长因子、血管内皮生长因子等，激活其下游靶点，从而保护视网膜各类细胞免受或减轻损伤。
腺苷A2A受体已被证实能够影响诸如缺氧性、缺血性、感染性以及变态反应性疾病等一系列疾病的发病过程。在中枢神经系统，A2AR高表达于胶质细胞、巨噬细胞及神经元。近几年来，A2AR拮抗剂在CNS疾病(帕金森病、阿尔茨海默病等)中的神经保护作用得到广泛关注。目前研究认为其作用在于：A2AR拮抗剂可抑制胶质细胞对谷氨酸的释放，调整k+的浓度，水的转运的方面从而保护神经元。我们实验也发现A2AR拮抗剂(SCH 442416＝＝＝2-(2-以呋喃)-7-【3-(4-甲氧基苯基丙酮)丙基】-7H-吡唑【4,3-e】【1,2,4】三唑【1,5-c】嘧啶-5-胺)可上调Müller细胞上谷氨酰胺合成酶、谷氨酸转运体、水通道蛋白-4、内流性K+通道4.1等蛋白的表达，从而保护视网膜神经节细胞，其结构式如下所示：
目前治疗视网膜疾病采用的治疗手段是：玻璃体切割术，眼底激光光凝术、玻璃体腔注药术。这些治疗手段均存在不同程度的手术风险和术后并发症。因此，我们拟采用眼部滴眼液的方式治疗视网膜疾病。总所周知，眼部滴眼液由于眨眼，眼球运动，角膜的屏障作用，不利于药物进入眼内。
发明内容：
本发明的目的在于提供一种用于治疗视网膜疾病的药物及其制备方法，所述的这种用于治疗视网膜疾病的药物及其制备方法解决了现有技术中的治疗视网膜疾病的眼部滴眼液中的有效成分难以进入眼睛中的有效部位，治疗效果不佳的技术问题。
本发明提供了一种用于治疗视网膜疾病的药物，含有A2AR拮抗剂SCH 442416，在所述的拮抗剂SCH 442416的外部包裹有聚酰胺-胺。
本发明还提供了上述用于治疗视网膜疾病的药物的制备方法，包括如下步骤：
1)称取SCH442416，将SCH442416溶解于有机溶剂中，在有机溶剂中，所述的SCH442416的浓度为40～60μg/ml；
2)称取聚酰胺-胺，将聚酰胺-胺溶解于缓冲液中；
3)在聚酰胺-胺的缓冲液中加入步骤1)的SCH442416有机溶液，其中，聚酰胺-胺和SCH442416有机溶液的质量体积比为5mg:0.50～1.0ml；
4)将步骤3)获得的溶液采用探头超声仪进行超声乳化；
5)将步骤4)获得的均一稳定的乳剂转入一个容器中，旋转蒸发除去有机溶剂制得聚酰胺-胺包裹的SCH442416纳米颗粒。
进一步的，步骤5)中，采用旋转蒸发仪蒸发除去有机溶剂，参数为：水浴温度28～32℃、真空度0.07～0.08MPa。
进一步的，所述的探头超声仪的超声参数为超声处理5s、停2s、进行40次、功率200W。
进一步的，所述的SCH442416的浓度为50μg/ml。
进一步的，所述的缓冲液为PBS溶液。
进一步的，所述的有机溶剂为二氯甲烷。
进一步的，聚酰胺-胺和SCH442416有机溶液的质量体积比为5mg:0.75ml。
纳米颗粒是直径在1-1000nm间的多聚胶体颗粒，以大分子多聚体为载体，药物可通过溶解、嵌入、包裹或吸附等方式与之结合。纳米载药系统的胶体性质有助于延长药物在眼部的停留时间，具有增加角膜通透性、增加药物眼内吸收、缓释增效的特点。本发明采用的聚酰胺-胺[Poly(amidoamine)PAMAM]是树状大分子，它的特点是：精确的分子结构、分子本身具有纳米尺寸、分子内存在空腔、良好的相容性、低的熔体粘度和溶液粘度。
本发明所述的PAMAM纳米包裹SCH 442416滴眼液纳米粒粒径为169.2nm，具有良好的生物相容性，无毒性，并包裹率高，且易分解。本发明的制备方法简单，快速，可望大规模实际应用。
本发明与现有技术相对比，其效果是积极和明显的。本发明使用PAMAM包裹SCH442416制备成滴眼液治疗视网膜疾病，提高了眼部药物的生物利用度，为新的眼部用药研发提供新的思路。
附图说明：
图1是显示了本发明的用于治疗视网膜疾病的药物的粒径分布图。
图2是显示了本发明的用于治疗视网膜疾病的药物的释放图。横坐标为释放时间(min)，纵坐标为释放百分率。
具体实施方式：
实施例1一种用于治疗视网膜疾病的药物的制备方法
(1)称取PAMAM 5mg，用2ml PBS溶液(pH7.4)溶解后，加入0.75mL SCH442416二氯甲烷溶液(50μg/ml)；
(2)采用探头超声仪进行超声乳化，超声参数：超5s、停2s、40次、功率200W；
(3)将制得的均一稳定的乳剂转入圆底烧瓶中，旋转蒸发除去有机溶剂制得PAMAM纳米粒，参数：水浴温度30±2℃、真空度0.07～0.08MPa。
实施例2包封率测定
将样品溶液置于透析袋(截留分子量3500)中，100ml PBS溶液(pH7.4)中透析处理5min，测定透析液中药物含量。
透析液中未检测出SCH442416，包封率为100％。
实施例3粒径测定
采用Malvern粒度分析仪测定PAMAM纳米粒的粒径，如图1所示，载药PAMAM纳米粒的粒径为169.2nm。
实施例4释放考察
(1)采用实施例的方法制备PAMAM纳米粒溶液1ml，取0.2ml置于10ml容量瓶中，加甲醇溶解定容；
(2)取0.8ml置于透析袋(截留分子量3500)中，80ml PBS溶液(pH7.4)室温条件下透析考察药物释放，分别于0.25、0.5、0.75、1、1.5、2、2.5、3、3.5、4、5、8、10h取样20μl进行HPLC分析，测定释放百分率。发现10h累积释放55.6％的药物(如图2所示)。
Claims (7)
1.一种用于治疗视网膜疾病的药物的制备方法，其特征在于：包括如下步骤：
1）称取SCH442416，将SCH442416溶解于有机溶剂中，在有机溶剂中，所述的SCH442416的浓度为40~60μg/ml；
2）称取聚酰胺-胺，将聚酰胺-胺溶解于缓冲液中；
3）在聚酰胺-胺的缓冲液中加入步骤1）的SCH442416有机溶液，其中，所述的聚酰胺-胺和SCH442416有机溶液的质量体积比为5mg:0.50~1.0ml；
4）将步骤3）获得的溶液采用探头超声仪进行超声乳化，
5）将步骤4）获得的均一稳定的乳剂转入一个容器中，旋转蒸发除去有机溶剂制得聚酰胺-胺包裹的SCH442416纳米颗粒。
2.如权利要求1所述的一种用于治疗视网膜疾病的药物的制备方法，其特征在于：步骤5）中，采用旋转蒸发仪蒸发除去有机溶剂的参数为：水浴温度28~32℃、真空度0.07~0.08MPa。
3.如权利要求1所述的一种用于治疗视网膜疾病的药物的制备方法，其特征在于：所述的探头超声仪的超声参数为超声处理5 s、停2 s、进行40次、功率200W。
4.如权利要求1所述的一种用于治疗视网膜疾病的药物的制备方法，其特征在于：所述的SCH442416的浓度为50μg/ml。
5.如权利要求1所述的一种用于治疗视网膜疾病的药物的制备方法，其特征在于：所述的缓冲液为PBS溶液。
6.如权利要求1所述的一种用于治疗视网膜疾病的药物的制备方法，其特征在于：所述的有机溶剂为二氯甲烷。
7.如权利要求1所述的一种用于治疗视网膜疾病的药物的制备方法，其特征在于：步骤3）中，所述的聚酰胺-胺和SCH442416有机溶液的质量体积比为5mg:0.75ml。
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| CN102429870A (zh) * | 2011-12-21 | 2012-05-02 | 中国药科大学 | 一种喜树碱类药物的新型肿瘤靶向树状聚合物纳米载体 |
| CN103990145A (zh) * | 2014-06-17 | 2014-08-20 | 福州大学 | 具有肿瘤靶向的叶酸-pamam-熊果酸纳米药物及其制备方法 |
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| US20120134979A1 (en) * | 2010-11-22 | 2012-05-31 | Yang Xia | Methods and compositions for the treatment of sickle cell disease |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102429870A (zh) * | 2011-12-21 | 2012-05-02 | 中国药科大学 | 一种喜树碱类药物的新型肿瘤靶向树状聚合物纳米载体 |
| CN103990145A (zh) * | 2014-06-17 | 2014-08-20 | 福州大学 | 具有肿瘤靶向的叶酸-pamam-熊果酸纳米药物及其制备方法 |
Non-Patent Citations (5)
| Title |
|---|
| Advances in Combination Therapies Based on Nanoparticles for Efficacious Cancer Treatment: An Analytical Report;Serge Mignani等;《Biomacromolecules》;20141126;第16卷(第1期);第4页左栏第17-28行，第4页右栏倒数第6行至第5页左栏第21行 * |
| Molecular modeling of a PAMAM-CGS21680 dendrimer bound to an A2A adenosine receptor homodimer;Andrei A. Ivanov等;《Bioorganic & Medicinal Chemistry Letters》;20080628;第18卷;第4312-4315页 * |
| Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold;T. Santhosh Kumar等;《Bioorganic & Medicinal Chemistry Letters》;20110501;第21卷(第9期);摘要部分第1-2行，示意图3，第2743页右栏第8-9行 * |
| The Effect of A2A Receptor Antagonist (SCH 442416) on the mRNA Expression of Kir 2.1 and Kir 4.1 Channels in Rat Retinal Müller Cells Under Hypoxic Conditions in Vitro;Xiaoli Kang等;《Adv Clin Exp Med》;20131231;第22卷(第6期);摘要部分第11-13行 * |
| 腺苷及其衍生物在眼科应用的研究进展;于军等;《中华实验眼科杂志》;20110930;第29卷(第9期);第857-860页 * |
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