Azeco Cosmeceuticals

2. Azepur99® as a cosmetic ingredient

2.1 Compliance of Azepur99® with the 1223/2009 EC regulations In consideration of the used process and raw materials, and of the done analytical evaluation on the finished product, Azepur99® does not contain any substance classified as CMR (Carcinogenic, Mutagenic and Reprotoxic substances 1a, 1b, 2) according to the 1272/2008 EC regulation. In addition, it has vegetal (synthetically modified) origin, and does not contain any animal or cell culture derived materials, it is not produced using, or does not come into contact with animal origin materials at any stage of the manufacturing steps. Moreover, no animal origin materials are used for other products in direct contact with production equipment used to manufacture Azepur99®. This high pure grade of Azelaic acid is then TSE (Transmissible Spongiform Encephalopathy) / BSE (Bovine Spongiform Encephalopa- thy) free. The starting vegetable used oil is a highly refined oil (Highly refined oils are intended to signify refined, bleached, deodorized (RBD) oils). These oils described in studies as “highly refined” do not demonstrate a significant hazard to allergic individuals, as shown in studies using the “gold standard” for food allergy diagnosis, the double-blind placebo-controlled food challenge any ingredient deri- ved from such highly refined oil.” This is due to the very low content of residual proteins of these oils. Azepur99® does not contain any ingredient classified as nanomaterial or nanoparticles as defined in the Article 2 of Regulation No 1223/2009 and/or in the Commission recommendation of 18 October 2011 (2011/696/EU) and/or in the French decree 2011/0673 and it has not been tested on animals for cosmetics purposes. 2.2 Azelaic acid in skin care products Azelaic acid is a naturally occurring straight-chained saturated dicarboxylic acid present in rye, wheat, and barley. A single mechanism of action has not been identified to explain the effects of azelaic acid on the skin. It helps scavenge reactive oxygen species, redu - ces expression of kallikrein-5 (KLK-5) and pro-inflammatory cathelicidins such as LL-37, as well as inhibits toll-like receptor 2 (TLR-2) (1,2). In fact, azelaic acid has been demonstrated to be effective for the treatment of rosacea. It is available as a 20% cream or a 15% hydrogel. It reduces inflammatory lesions and erythema in rosacea patients and also inhibits neutrophilic ROS (Reactive Oxygen Spe - cies). In the neutrophil system azelaic acid inhibits the ROS formation in a dose-dependent manner, markedly decreasing the number of free radicals. Azelaic acid is probably the only non-pharmaceutical ingredient that has been demonstrated to exhibit good activity for the treatment of rosacea, without side effects. In addition, it inhibits the pigment producing enzyme tyrosinase (3), has comedoly- tic properties, and may reduce epidermal hyperkeratinization. It has been shown to be effective in the treatment of hyperpigmen- tary disorders such as chloasma and lentigo maligna, and to have a cytotoxic effect on the human malignant melanocyte (4). While treating cases of chloasma with topical application of an azelaic acid cream, it was observed, and confirmed by patients, that lesions of acne within the areas being treated showed significant improvement. This acid is then used to treat bacterial-related acne breakouts by attacking the infected pores to help in reducing inflammation and lowering the production of keratin which creates clumps of dead skin cells that trap sebum in skin pores causing more breakouts. With that said, as azelaic acid was more commonly used to treat acne related problems, doctors noticed it had side effects to it which were related to skin lightening. Hyperpigmentation is a skin disturbance affecting many people all over the world. In 1978, the tyrosi- nase-inhibiting activity of certain lipid fractions, mainly C9–C11 dicarboxylic acids, was demonstrated for the first time in vitro.

Mussenberg 1 • 6049 GZ Roermond • The Netherlands

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