Simmons Peter A, Vehige Joseph G
Allergan plc, Irvine, CA, USA.
Clin Ophthalmol. 2017 Sep 12;11:1637-1642. doi: 10.2147/OPTH.S135550. eCollection 2017.
Artificial tear formulations typically contain a water-soluble polymer to enhance residence time, moisture retention, and binding to the mucin coat of the ocular surface, which facilitate corneal healing. This study investigated the potential advantages of combining carboxymethylcellulose (CMC) and hyaluronic acid (HA) polymers in a single formulation.
Individual CMC and HA solutions were prepared and tested for bulk viscosity in comparison to a solution that combined CMC and HA. Rheometry determined the differences between solutions at increasing shear rates, simulating eye movement and blinking.
The bulk viscosity of the individual 0.5% CMC and 0.1% HA solutions was 2.5 and 5.7 cP, respectively. The viscosity of the combined solution (13.1 cP) was 60% higher than predicted by additive effects. Rheometry revealed shear rates between 10/second (open eye) and 10,000/second (blinking eye). At these rates, viscosity ranged from 2.7 to 3.5 cP for 0.5% CMC, 2.8 to 6.8 cP for 0.1% HA, and 5.2 to 15.3 cP for the 0.5% CMC-0.1% HA combination. Low-shear viscosity of the CMC-HA combination increased 48% over the sum of the individual solutions, but high-shear viscosity remained virtually unchanged. Data from CMC and HA solutions at higher concentrations were consistent with these results.
Combining CMC and HA polymers produced a synergistic increase in low-shear viscosity (which cannot be fully explained by simple molecular entanglement), while the high-shear viscoelasticity of the combined solution remained unaffected. These data suggest that CMC-HA combinations have properties that may be used to formulate artificial tears that optimize ocular retention (through higher low-shear viscosity), while minimizing blur and stickiness during blinking (through lower high-shear viscosity).
人工泪液制剂通常含有一种水溶性聚合物,以延长停留时间、保持水分并与眼表的黏蛋白层结合,从而促进角膜愈合。本研究调查了在单一制剂中联合使用羧甲基纤维素(CMC)和透明质酸(HA)聚合物的潜在优势。
制备了单独的CMC和HA溶液,并与将CMC和HA混合的溶液进行了总体粘度测试。流变学测定了在增加剪切速率时各溶液之间的差异,模拟了眼球运动和眨眼。
单独的0.5% CMC溶液和0.1% HA溶液的总体粘度分别为2.5和5.7厘泊。混合溶液的粘度(13.1厘泊)比加和效应预测的高60%。流变学显示剪切速率介于10/秒(睁眼)和10000/秒(眨眼)之间。在这些速率下,0.5% CMC的粘度范围为2.7至3.5厘泊,0.1% HA的粘度范围为2.8至6.8厘泊,0.5% CMC - 0.1% HA混合物的粘度范围为5.2至15.3厘泊。CMC - HA混合物的低剪切粘度比各单独溶液的总和增加了48%,但高剪切粘度几乎保持不变。更高浓度的CMC和HA溶液的数据与这些结果一致。
联合使用CMC和HA聚合物可使低剪切粘度协同增加(这不能完全由简单的分子缠结来解释),而混合溶液的高剪切粘弹性不受影响。这些数据表明,CMC - HA混合物具有一些特性,可用于配制人工泪液,通过更高的低剪切粘度优化眼部滞留,同时通过更低的高剪切粘度使眨眼期间的模糊和粘性最小化。