【 文献重点摘要 】

Purpose

Hyaluronic acid (HA) fillers can be reversed with hyaluronidase, but their dose responses are not well-characterized. We evaluated 12 fillers’ in vitro responses to varying doses of recombinant human hyaluronidase (RHH).

Methods

For the 12 HA gels, 0.2 mL aliquots were placed on six slides. Samples received no injection, saline injection, or RHH (2.5, 5, 10, or 20 units). The most resistant gels received 40 units of RHH on a seventh slide. Photos of gels were taken from bird’s-eye and lateral views with a ruler at multiple time points.

Results

Restylane-L and Restylane Lyft were the most easily dissolvable HA fillers. Both demon- strated a significant response to 2.5 units RHH/0.2 mL. Juvéderm Ultra, Belotero, Restylane Silk, and Restylane Defyne had moderate resistance to RHH. Restylane Refyne, Juvéderm Ultra Plus, Vollure, Versa, and Voluma were most resistant, requiring more than 20 units RHH/0.2 mL for complete dissolution. Volbella was moderately resistant up to 20 units RHH but demon- strated pronounced dissolution with 40 units RHH.

Conclusions

This study visually and objectively demonstrates the in vitro response of HA to dissolution by hyaluronidase. Fillers were categorized into least, moderate, and most resistant to RHH. Interesting findings include markedly different degrees of liquefaction for products used for similar indications (such as Restylane Lyft being more liquefied than Voluma), and Belotero easily flattening but retaining texture. Combined with in vivo data, this may help calculate hyaluronidase doses needed for controlled, partial reversal of commercially available HA gels.

KEYWORDS

Hyaluronic acid fillers; Hyaluronidase dosing; Hyaluronidase; Hyaluronic acid gel dissolution

目的

透明质酸(HA)填充物可被透明质酸酶逆转，但其量效关系尚不清楚。我们评估了12个填充物对不同剂量的重组人透明质酸酶(RHH)的体外反应。

方法

12种透明质酸凝胶剂，将0.2mL等量放在6张玻片上。样本不接受注射、生理盐水注射或RHH(2.5、5、10或20单位)。最具抵抗力的凝胶在第七张幻灯片上获得了40个单位的RHH。凝胶的照片是在多个时间点用尺子从鸟瞰和侧视拍摄的。

结果

Restylane-L和Restylane Lyft是最易溶解的HA填充剂。两者均显示对2.5单位RHH/0.2mL有显著反应。Juvéderm Ultra、Belotero、Restylane Silk和Restylane Defyne对RHH有中度抗性。Restylane Refyne、Juvéderm Ultra Plus、Vollure、Versa和Voluma的抗药性最强，需要超过20单位的RHH/0.2毫升才能完全溶解。Volbella对RHH有中等抗性，高达20单位RHH，但明显溶解，有40单位RHH。

结论

本研究直观、客观地证实了透明质酸酶体外溶解透明质酸的反应。填充物被分类为最不耐RHH、中等和最抗RHH。有趣的发现包括用于类似适应症的产品的液化程度明显不同(例如Restylane Lyft比Voluma更容易液化)，以及Belotero容易变平但保持质地。结合体内数据，这可能有助于计算可控制的、部分逆转市售透明质酸凝胶所需的透明质酸酶剂量。

关键词

透明质酸填充剂；透明质酸酶剂量；透明质酸酶；透明质酸凝胶溶解