LG Science Park R&D Center of LG Household & Healthcare (LG H&H), Seoul, Republic of Korea.
Skin Res Technol. 2023 Jul;29(7):e13406. doi: 10.1111/srt.13406.
Salicylic acid has been used as an anti-acne agent with its comedolytic property and antimicrobial activity. However, there is a limit to use for leave-on cosmetics because of the transient skin irritation and low efficacy at neutral pH condition. We prepared a salicylic acid-based ionic pair with -carnitine (we named, IP-BHA) overcoming the limitation of salicylic acid. We examined the effect of IP-BHA as well as the combination effect with magnolol, a bioactive organic lignan, in order to clarify their efficacy as anti-acne agents.
After verifying the structure of IP-BHA, we confirmed anti-acne activities including the regulation of exfoliation, lipogenesis, bacterial growth, and inflammation with IP-BHA and/or magnolol.
The antibacterial activity of IP-BHA and magnolol was evaluated by determining the minimum antibacterial inhibitory concentration. Magnolol showed strong activity against Cutibacterium acnes, which was better than a medical antibiotic acne drug, clindamycin. The combined application with IP-BHA was more effective in antibacterial activity by 2.5 times. It was confirmed that testosterone-induced lipogenesis was significantly inhibited by treatment with IP-BHA and magnolol, while single treatment had no significant inhibitory effect. Interestingly, MMP-1 and VEGF were induced by C. acnes lysate in human keratinocytes. We found that these inflammatory molecules were completely inhibited by combined application of IP-BHA and magnolol. Through ex vivo test, the dose-dependent exfoliation effect of IP-BHA was confirmed at pH 5.5, and the synergic exfoliation effect was shown in the combined application of IP-BHA and magnolol. When topically applied, the emulsion containing IP-BHA and magnolol relieved the sodium dodecyl sulfate-induced erythema and improved inflamed acne with papule and pustule.
Our data demonstrate that the ionic paired salicylic acid with -carnitine can overcome the limitations of salicylic acid at low concentration and natural skin pH. Based on the dual administration effects, we suggest that IP-BHA and magnolol may be the potential agent for acne by improving inflammatory skin condition.
水杨酸具有溶粉刺和抗菌活性，已被用作一种治疗痤疮的药物。然而，由于其在中性 pH 条件下具有短暂的皮肤刺激性和低功效，因此其在驻留型化妆品中的应用存在局限性。我们制备了一种基于水杨酸的离子对与 - 肉碱（我们命名为 IP-BHA），以克服水杨酸的局限性。我们研究了 IP-BHA 以及与生物活性有机木质素厚朴酚的联合作用，以阐明它们作为治疗痤疮药物的功效。
在验证了 IP-BHA 的结构后，我们通过使用 IP-BHA 和/或厚朴酚来确定其对脱屑、脂肪生成、细菌生长和炎症的调节作用，以确认其抗痤疮活性。
通过测定最小抑菌浓度评估了 IP-BHA 和厚朴酚的抗菌活性。厚朴酚对痤疮丙酸杆菌具有很强的活性，优于医学抗生素痤疮药物克林霉素。与 IP-BHA 联合应用的抗菌活性提高了 2.5 倍。结果证实，IP-BHA 和厚朴酚处理可显著抑制睾酮诱导的脂肪生成，而单独处理则无明显抑制作用。有趣的是，C. acnes 裂解物可诱导人角质形成细胞中 MMP-1 和 VEGF 的表达。我们发现，这些炎症分子完全被 IP-BHA 和厚朴酚的联合应用所抑制。通过离体试验，在 pH5.5 下证实了 IP-BHA 的剂量依赖性脱屑作用，并显示了 IP-BHA 和厚朴酚联合应用的协同脱屑作用。当局部应用时，含有 IP-BHA 和厚朴酚的乳液可缓解十二烷基硫酸钠诱导的红斑，并改善伴有丘疹和脓疱的炎性痤疮。
我们的数据表明，与 - 肉碱形成离子对的水杨酸可以克服低浓度和天然皮肤 pH 下水杨酸的局限性。基于双重给药作用，我们认为 IP-BHA 和厚朴酚可能通过改善炎症性皮肤状况成为治疗痤疮的潜在药物。
