广东省化妆品学会 2019-01-01 22:06:46


Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors



Melanogenesis is a process to synthesize melanin, which is a primary responsible for the pigmentation of human skin, eye and hair. Although numerous enzymatic catalyzed and chemical reactions are involved in melanogenesis process, the enzymes such as tyrosinase and tyrosinase-related protein-1 (TRP-1) and TRP-2 played a major role in melanin synthesis. Specifically, tyrosinase is a key enzyme, which catalyzes a rate- limiting step of the melanin synthesis, and the downregulation of tyrosinase is the most prominent approach for the development of melanogenesis inhibitors. Therefore, numerous inhibitors that target tyrosinase have been developed in recent years. The review focuses on the recent discovery of tyrosinase inhibitors that are directly involved in the inhibition of tyrosinase catalytic activity and functionality from all sources, including laboratory synthetic methods, natural products, virtual screening and structure-based molecular docking studies.



Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe



Lightening skin tone is an ancient and well-documented practice, and remains common practice among many cultures. Whitening agents such as corticosteroids, tretinoin and hydroquinone are medically applied to effectively lighten the skin tone of hyperpigmented lesions. However, when these agents are used cosmetically, they are associated with a variety of side-effect. Alternative agents, such as arbutin and its derivatives kojic acid and nicotinamide have been subsequently developed for cosmetic purposes. Unfortunately, some cosmetics contain whitening agents that are banned for use in cosmetic products. This article provides an overview of the mode of action and potential side-effects of cosmetic legal and illegal whitening agents, and the pattern of use of these types of products. Finally, an EU analysis of the health prob- lems due to the presence of illegal products on the market is summarized.



Hexamidine salts – applications in skin health and personal care products



Hexamidine (HEX) has been used as a preservative in topical prepa- rations since the 1950s. A number of studies also indicate that the molecule plays a beneficial role in skin homoeostasis. In this review, we describe the physicochemical properties of hexamidine diisethionate (HEX D) and the corresponding hydrochloride salt (HEX H). The biocidal and protease inhibition properties of HEX are outlined as well as the effects of HEX on lipid processing enzymes, corneocyte maturity, stratum corneum thickness and transepider- mal water loss (TEWL). Skin permeation properties of HEX D and HEX H are summarized, and formulation approaches for effective dermal targeting of HEX are discussed.

摘要:己脒定从1950开始就一直当防腐剂使用。许多研究表明己脒定在皮肤平衡方面也有重要的作用。这篇文章主要讨论己脒定二盐 (HEX D)和己脒定二盐酸盐(HEX H)的物理化学性质。己脒定抑制微生物和蛋白酶方面特性以及对油脂加工酶、角质细胞成熟度、角质层厚度、经皮失水值(TEWL)的作用效果 。总而言之:HEX系列对真皮的渗透吸收和皮肤的屏障功能有作用。

文中主要从:HEX D和HEX H的物理化学特性分析两者的区别;己脒定作为抗微生物制剂的应用;酶抑制剂; 与皮肤的生理学信息;


Polar extracts from the berry-like fruits of Hypericum androsaemum L. as a promising ingredient in skin care formulations



Ethnopharmacological relevance: The top flowering aerial parts of the Hypericum species are traditionally used to prepare ointments to heal cuts and burns. Sometimes even the fruits are used for these purposes. Hypericum androsaemum L., commonly known as tutsan or shrubby St. John's Wort, is a Mediterranean medicinal plant which has been traditionally used to prepare an ointment for treating cuts and wounds.

Aim of the study: To evaluate the extracts obtained from H. androsaemum red berries as functional ingredients for skin care formulations.Materials and methods: The methanolic extract was obtained by Soxhlet extraction while the aqueous extract was prepared by decoction; their composition was determined by HPLC analysis. Their biological activities were measured in terms of proliferation and migration of human fibroblasts, inhibition of collagenase activity, and immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their photostability by UV spectroscopy and their protective effects against APPH-induced hemolysis in red blood cells (RBC).

Results: The polar extracts contained significant amounts of shikimic (108,143.7–115,901.3 mg/kg) and chlorogenic acids (45,781.1–57,002.7 mg/kg). The main components of these extracts made an important contribution to a significant increase in human fibroblast migration. Both extracts were also active as collagenase inhibitors, with the aqueous one showing a greater inhibitory capacity (IC50 value of 88.1 μg/ mL), similar to that of chlorogenic acid. The kinetic parameters determined for the enzymatic reaction revealed for both aqueous extract and chlorogenic acid an uncompetitive mechanism of inhibition. The methanolic extract showed important effects on PBMCs by modulating IL-6. Both extracts proved to be photostable in the UVA/B range and protected RBC against peroxidation at low concentrations.

Conclusions: H. androsaemum red berries were proven to contain phytochemicals that improve skin regeneration, hence potentially employable in skin care formulations.



结果:甲醇提取物包含重要的莽草酸(108.1-115.9g/kg)和绿原酸(45.781-57.0g/kg)。这些提取物的成份对人体成纤维细胞的增加有重要的作用,而且这两类提取物具有胶原酶抑制作用的功能。水提取物具有更好的抑制能力(IC5088.1μg /ml),类似于绿原酸。其酶反应动力学参数表明水溶性提取物和绿原酸是非竞争性抑制机制。甲醇提取物通过调节IL-6,对人体外周血单核细胞有重要影响。实验证明这两种提取物都具有一定的UVA/UVB耐光性,并且在低浓度下能防止氧化,保护红细胞。



Introduction to skin aging



Cutaneous science has seen considerable development in the last 25 years, in part due to the Omics revolution, and the appreciation that this organ is hardwired into the body’s key neuro-immuno-endocrine axes. Moreover, there is greater appreciation of how stratification of skin disorders will permit more targeted and more effective treatments. Against this has been how the remarkable extension in the average human life-span, though in the West at least, this parallels worrying increases in lifestyle-associated conditions like diabetes, skin cancer etc. These demographic trends bring greater urgency to finding clinical solutions for numerous age-related deficits in skin function caused by extrinsic and intrinsic factors. Mechanisms for aging skin include the actions of reactive oxygen species (ROS), mtDNA mutations, and telomere shortening, as well as hormonal changes.

We have also significantly improved our understanding of how to harness the skin’s considerable regenerative capacity e.g., via its remarkable investment of stem cell subpopulations. In this way we hope to develop new strategies to selectively target the skin’s capacity to undergo optimal wound repair and regeneration. Here, the unsung hero of the skin regenerative power may be the humble hair follicle, replete with its compliment of epithelial, mesenchymal, neural and other stem cells. This review introduces the topic of human skin aging, with a focus on how maintenance of function in this complex multi-cell type organ is key for retaining quality of life into old age.

摘要:由于组织时代的兴起,皮肤科学的发展已经有近25年的历史,人体器官的发展与人体关键的神经-免疫-内分泌系统息息相关。而且,皮肤紊乱需要更具针对性更有效的治疗方式。至少在西方国家,如何提升人的平均寿命和解决糖尿病、皮肤癌等一样重要。大量统计数据显示,对内外因素导致的与老化相关方面的皮肤功能缺陷,急需找到关键的解决办法。皮肤老化的机理包括:活性氧活跃度、mtDNA(线粒体脱氧核糖核酸) 突变、端粒变短、荷尔蒙变化等有关。



3-(3,4,5-Trimethoxybenzylidene)-2,4-pentanedione: Design of a novel photostabilizer with in vivo SPF boosting properties and its use in developing broad-spectrum sunscreen formulations


OBJECTIVE: The study concerned the synthesis of a novel photo- stabilizer based on benzylidenepentanedione chemistry and the evaluation of its potential in developing a broad-spectrum sun- screen formulation containing avobenzone.

METHODS: 3-(3,4,5-Trimethoxybenzylidene)-2-4-pentanedione (TMBP) was synthesized through a condensation reaction and incorporated into a sunscreen formulation containing, inter alia, avobenzone. The SPF, critical wavelength and in vitro photostability of the product were measured. The photostability was compared with that afforded by current avobenzone photostabilizers, namely octocrylene, ethylhexylmethoxycrylene and diethylhexylsyringylidenemalonate. The photostability of TMBP either alone or in the presence of avobenzone in a methanolic solution was also evaluated by UV spectrophotometric and HPLC analyses. The optical prop- erties of TMBP were estimated experimentally and supported by time- dependent density functional theory (TD-DFT) calculations.

RESULTS: The ability of TMBP to stabilize avobenzone under ultravi- olet (UV) light exposure was shown both in formulated products and in solution. A comparative stability study incorporating various com- binations of avobenzone, TMBP (vs. three commercial photostabiliz- ers) and UVB sunscreens clearly showed TMBP to be a very effective stabilizer. The photostabilizing effect of TMBP arises from triplet-state energy transfer from avobenzone to TMBP and through light-induced reactions that preserve the main chromophores. Interestingly, a 50% in vivo SPF boosting was observed when TMBP was used with organic and inorganic sunscreens when alone it has no contribution to SPF. TMBP-containing sunscreen formulations clearly showed a critical wavelength of well over 370 nm and can thus be categorized as broad-spectrum sunscreens.

CONCLUSION: We were able to design a very effective photostabi- lizer, trimethoxybenzylidene pentanedione (INCI name), based on benzylidenepentanedione chemistry. TMBP is very efficient in stabiliz- ing avobenzone in formulated products and boosts in vivo SPF by >50% for organic and inorganic sunscreens, and the formulations have critical wavelengths of> 370 nm. These efficacious properties make it a promising additive for inclusion in broad-spectrum photo- protective products.


方法: 3-(3,4,5-三甲氧基苯亚基)-2,4-戊二酮(TMBP)是通过合成方法而得到,可在防晒产品中与阿伏苯宗复配。与阿伏苯宗等对比,通过测定波长和体外光稳定性,UV和HPLC分析,TMBP的光学特性,含时密度泛函理论计算其稳定性。