CN101856603A - 透明质酸的纳米/微封装和释放 - Google Patents
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Abstract
本发明描述了在加工后期或有孔和无孔模板准备期(胶状粒子)通过包合或包封透明质酸的封装和控制方法，和随后的释放方法。这种封装方法是应用有机物的沉积或吸附比如聚合物；或无机物的沉积或吸附，比如粒子或纳米粒子；或合成物的沉积或吸附来形成有机物或有机-无机合成物，也就是混合纳米合成壳，纳米和微囊。通过这些方法，在各种应用中包括(但不限于)在活有机体或注射，通过自降解或外部作用来实现可控传输、控制和随后的释放，来使用被封装在纳米合成壳内或固定在模板内的透明质酸。
Description
发明的详细说明
使用大小从10纳米到1000纳米，1微米到1000微米，1毫米到10毫米的各种模板来封装透明质酸。模板可由纳米合成物材料合成，例如硅，碳酸钙，聚苯乙烯等。
模板准备，有孔模板和封装
可以选择商业购买或自制的有孔或无孔纳米合成物模板。有孔模板的合成可以通过在精确的搅拌下混合沉淀物来形成原料。这种情况下，有孔模板封装会有两种途径：
1，要被封装的透明质酸被吸附在模板孔内，随后被纳米合成壳覆盖。
2，在模板形成的同时加入透明质酸来完成封装。例如同氯化钙和碳酸钠一起沉淀形成含有透明质酸的碳酸钙粒子。混合速度，成分和要被封装的透明质酸的浓度制造出随后被混合有机-无机(聚合粒子或纳米粒子)封装壳覆盖的模板浓缩或模板固定的透明质酸。透明质酸的浓度由它的初始浓度控制，也可以加相对的量到沉淀形成的模板母体上。
模板可以被去除(例如碳酸钙可以在微酸性溶液中被溶解或通过钙的配位作用)，留下透明质酸自由漂浮在纳米囊和微囊内，或者保持完整。在后种情况下，可从生物可降解的或生物惰性的模板或有机-无机(聚合粒子和纳米粒子)覆盖模板上进行释放。所有情形下，被封装的透明质酸可以从纳米囊和微囊中按照要求的释放顺序或释放方案进行释放。
透明质酸仅仅只能并入壳内。例如：通过正电聚合物比如胶原质，聚精氨酸，透明质酸自己或其它物质一层一层地组合。透明质酸壳的降解和随后释放可以被壳降解过程诱导，比如由胶原酶降解在胶原质/透明质酸合成壳内的胶原质。
这类模板，混合有机-无机覆盖模板和纳米囊和微囊都可以用磁纳米粒子使其功能化，使所描述的传输媒介具有磁性反应能力，或者用其它纳米粒子实现透视显像或激活功能。金属纳米粒子(金，银粒子)放入混合壳会使这些囊具有光激发释放能力。
无孔模板的封装
为进行无孔模板封装，首先在模板周围形成纳米合成或混合纳米合成壳。然后，有两种情况：
1，要被封装的透明质酸直接被吸入模板，随后被纳米合成壳覆盖。然后去除或溶解模板来形成中空壳。
2，模板首先由纳米合成或混合纳米合成壳覆盖，然后下一步再封装。在这种方法中，模板首先被去除或溶解。在普通的或增强的渗透性下，要被封装的透明质酸渗透进入纳米合成壳内。然后降低渗透性或激烈降低来实现包合和封装。渗透性控制方法包括聚合属性，热处理，酸度，离子力，和外场。
纳米合成覆盖层
通过吸附，界面吸附，界面配位，表面诱导聚合和沉淀，或相关化合，来沉淀纳米合成或混合纳米合成壳(聚合粒子或纳米粒子)到模板上。纳米合成或混合纳米合成覆盖层是通过吸附被沉淀，吸附可以依靠盐，pH值等浓度来定。模板可从生物惰性材料，例如硅，或生物适合材料，例如碳酸钙中选择。生物可降解模板可被用来作为传输时的结构支持。有必要实现技术优势时，覆盖层和聚合覆盖层也可以通过喷雾来应用。
另外一种设想也可行，就是通过中心分解来去除模板。由于溶剂能够渗透纳米合成壳，这样就可以去除中心留下完整的纳米合成壳。纳米合成壳具有保护和释放控制功能。作为控制释放，纳米壳的厚度或外部刺激/场将确定时间间隔，在间隔中部分设定的封装透明质酸离开纳米囊或微囊。
纳米合成和/或聚合覆盖层也可以由被称为‘聪明的’生物可降解聚合物和纳米合成物组成。覆盖和覆盖层的厚度和组合条件来控制释放，释放是可以在特定的时间段进行调节的，比如小时，天，星期，月等。即时释放可以通过外场来实现。小分子的封装和纳米封装的纳米合成聚合覆盖层可以用不溶于水的/溶于水的聚合物，溶胶与凝胶覆盖物，化学交联，或油基覆盖物来增强。
纳米囊和微囊的改进
纳米和微合成囊的纳米合成壳可以用合适的制剂来改良以避免摄入。另一方面，纳米和微合成囊壳也可以被改良来诱导特定地点摄入。
进步说明
纳米合成覆盖物可以广泛应用聚合体，聚合合成物，有机纳米合成物，混合有机-无机纳米合成物等。可以用聚合物和化合物制作聚合纳米合成覆盖物，包括但不限于聚赖氨酸，聚精氨酸，聚谷氨酸，凝胶，胶原质，透明质酸自己，多聚糖，壳聚糖，葡聚糖，和它们的派生物。‘聪明的’生物可降解聚合覆盖物被用来应用于那些不需要外部释放操作和激活的。外场和外激活被应用于需要特定释放顺序的混合有机-无机纳米合成纳米囊和微囊。混合有机-无机合成物包含聚合物，有机成分，无机粒子和纳米粒子，例如贵金属，金属氧化物，磁性粒子等。有些应用中，封装透明质酸是自由的在纳米囊和微囊内。还有些应用中，封装透明质酸是模板固定在纳米囊和微囊内。在封装处理时纳米囊和微囊内是暴露在温和条件下，它的结构是不会被改变和受影响的。以上描述的步骤广泛应用于，但不限于，组织，皮肤，在活有机体等。封装环境可是是水，缓冲液，或各种溶剂。
Claims (11)
1.对透明质酸通过以下方式进行封装的方法
A、吸附进入多孔模板的孔内；
B、在多孔模板的形成时加入透明质酸；
C、吸附进入无孔模板内；
D、透明质酸渗透进入现有的纳米合成壳内以及包合；
E、或者直接将透明质酸封装进入纳米合成壳。
2.根据权利要求1中所述的方法，在最终使用前模板被去除或完整留下。
3.根据权利要求1中所述的方法，从中心分解去除模板。
4.根据权利要求1的方法，其中应用磁性，金属或荧光粒子，纳米粒子和染料来增加锁定，移动，激活，定位或显像功能。
5.根据权利要求1中所述的方法，模板被用来作为传输时的结构支持。
6.根据权利要求1方法，其中纳米合成壳提供控制释放功能。
7.根据权利要求1的方法，其中壳可以被改良用来诱导特定地点摄入。
8.根据权利要求1的方法，其中壳可以被改良用来诱导粘合或特定粘合到细胞和组织上。
9.根据权利要求1的方法，其中壳可以被改良用来防止纳米合成囊粘合到细胞和组织上。
10.根据权利要求1的方法，其中通过吸附或喷雾来沉淀纳米合成或混合纳米合成覆盖物。
11.根据权利要求10的方法，其中所述的用不溶水/溶水聚合物，油脂，溶胶凝胶覆盖物，或油基覆盖物增强覆盖层。
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| US16791709P | 2009-04-09 | 2009-04-09 | |
| US61167917 | 2009-04-09 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103764272A (zh) * | 2011-08-30 | 2014-04-30 | 哈佛学院院长等 | 壳包囊的体系和方法 |
| US9238206B2 (en) | 2011-05-23 | 2016-01-19 | President And Fellows Of Harvard College | Control of emulsions, including multiple emulsions |
| US10195571B2 (en) | 2011-07-06 | 2019-02-05 | President And Fellows Of Harvard College | Multiple emulsions and techniques for the formation of multiple emulsions |
| US10874997B2 (en) | 2009-09-02 | 2020-12-29 | President And Fellows Of Harvard College | Multiple emulsions created using jetting and other techniques |
-
2009
- 2009-06-04 CN CN200910143973A patent/CN101856603A/zh active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10874997B2 (en) | 2009-09-02 | 2020-12-29 | President And Fellows Of Harvard College | Multiple emulsions created using jetting and other techniques |
| US9238206B2 (en) | 2011-05-23 | 2016-01-19 | President And Fellows Of Harvard College | Control of emulsions, including multiple emulsions |
| US9573099B2 (en) | 2011-05-23 | 2017-02-21 | President And Fellows Of Harvard College | Control of emulsions, including multiple emulsions |
| US10195571B2 (en) | 2011-07-06 | 2019-02-05 | President And Fellows Of Harvard College | Multiple emulsions and techniques for the formation of multiple emulsions |
| CN103764272A (zh) * | 2011-08-30 | 2014-04-30 | 哈佛学院院长等 | 壳包囊的体系和方法 |
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