Hyaluronic Acid and Its Key Role in the Body

Our body naturally contains approximately 15 grams of Hyaluronic acid (HA) distributed throughout the organism: skin, joints, scalp, eyes, soft tissues and synovial fluid. Due to its chemical structure, HA can retain large amounts of water, but its cycle is very short, with approximately one-third of the hyaluronic acids in our body being renewed daily. In every part of the body, HA has different functions related to its molecular weight (MW): High MW HA has greater water-retention function, while low MW HA increases biological activities and plays the role of a signaling molecule. The functional roles of HA in skin include: 1- Hydration and water retention, 2- Maintaining skin viscoelasticity and tonicity by forming a hydrogel in the extracellular matrix, 3- Enhancing cell proliferation and communication through CD44 receptors, 4- Facilitating cellular mobility and vitality through nutrient transport.

Aging Processes and Dermal Fillers

With chronological aging, the metabolic efficiency of skin cells decreases, reducing their ability to produce the main components of the extracellular matrix. Due to its high degradability rate, HA is among the best matrix polymers for eliminating deep lines and wrinkles, the first signs of aging. At the same time, the antioxidant defenses of aging cells significantly decrease, making them more susceptible to free radicals. In parallel, extrinsic aging is driven by daily exposure to a series of environmental aggressors: UV, blue light, pollution, chemicals or repeated mechanical stresses. All these factors lead to the production of Reactive Oxygen Species (ROS), damage to cellular components and promote excessive expression of matrix metalloproteinases (MMP) by encouraging the degradation of extracellular matrix fibers (such as collagen). Most aesthetic dermal fillers are based on HA because it is a natural skin component with high volumizing filler properties (water-binding capacity). However, the use of these dermal fillers requires local injections with possible complications and, despite their cost, cannot restore the skin's natural protection. For this reason, it is of great importance to protect the skin and its structure throughout life and, at the same time, provide an alternative to regain the main characteristics of the skin as much as possible and eliminate wrinkles.

Cosmetic Alternative to Dermal Fillers: PrimalHyal™ Ultrafiller

To meet this unmet need, Active Beauty experts designed PrimalHyal™ Ultrafiller, a new generation topical HA that optimizes the bioavailability of a specific HA through complete acetylation. PrimalHyal™ Ultrafiller acts like a filler by penetrating deeply into the skin and rapidly reducing wrinkles. It also stimulates skin epidermis and dermis metabolism: 1- Protects the extracellular matrix by reducing collagenase production and collagen degradation, even under photopollution. 2- Restores antioxidant defenses through the cytosol pathway, helping the skin fight free radicals. Biological Activity Deeper Skin Penetration and Long-Term Persistence 1. Deep Skin Penetration Skin explants from a 37-year-old Caucasian donor were treated regionally for 8 hours with 1% standard HA (PrimalHyal™ Ultrafiller with similar MW range, but non-acetylated) or PrimalHyal™ Ultrafiller and analyzed with Raman spectroscopy to evaluate product penetration. Results: Standard HA penetrates an average skin depth between 20 and 50μm. PrimalHyal™ Ultrafiller penetrates much deeper, with most of the signal around 100μm in the skin.

2. Biological Longevity

The resistance of standard HA and PrimalHyal™ Ultrafiller to biological degradation was analyzed by incubation with hyaluronidase for 16 hours and HPLC analysis was used to estimate degradation level (MW reduction). Results: PrimalHyal™ Ultrafiller shows high resistance to biological degradation and shows only 7% degradation. Standard HA is almost completely degraded under these conditions (92%). The half-life of PrimalHyal™ Ultrafiller is estimated to be 13 times longer than standard HA. **p<0.01 Student's t-test ***p<0.001 Student's t-test

Dermis Active Protection: Anti-Wrinkle Activity

Fibroblasts from a 52-year-old donor were pre-incubated for 2 hours with 0.1% PrimalHyal™ Ultrafiller and standard HA and exposed or not exposed to oxidative stress induced by H2O2 (200μM). MMP-1 and MMP-3 production was evaluated by Luminex 48 hours after oxidative stress, and collagen I degradation was measured by fluorescence analysis using DQ-collagen I. Results: PrimalHyal™ Ultrafiller inhibits MMP-1 and MMP-3 collagenase production by up to 40% under oxidative stress conditions. It also significantly reduces collagen I degradation, decreasing oxidative stress by 42%. Standard HA shows no effectiveness in reducing collagenases. Clinical Tests Medium and Long-Term Anti-Aging Activity 1. Nasolabial Wrinkle Reduction (1 Month) A double-blind test evaluation was conducted on 20 volunteers (aged 35 to 70, average 56 years) with wrinkles in the nasolabial region. Volunteers applied a similar cream containing 0.1% PrimalHyal™ Ultrafiller or placebo (inactive) to both sides of their face twice daily (morning and evening) for 28 days. VISIA® analysis was performed after D0 and D28 to evaluate the number and area of wrinkles. Results: In 1 month, PrimalHyal™ Ultrafiller reduces nasolabial wrinkle count by 9% and nasolabial wrinkle area by 13%.

2. Improvement of Skin Texture (2 Months)

A double-blind clinical evaluation test was conducted on 30 volunteers (aged 50 to 70, average 57 years) with facial wrinkles. Volunteers applied a cream containing 0.1% PrimalHyal™ Ultrafiller or a similar placebo cream (inactive) twice daily (morning and evening) for 56 days. VISIA® analysis was performed after D0 and D56 to evaluate skin texture, and volunteers were asked to evaluate the product's effectiveness on skin characteristics. References :1. Kanda, N., and S. Watanabe. 2007. Histamine enhances the production of human þ-defensin-2 in human keratinocytes. Am. J. Physiol. 293: C1916 –C1923. 2. Braff, M. H., and R. L. Gallo. 2006. Antimicrobial peptides: an essential com- ponent of the skin defensive barrier. Curr. Top. Microbiol. Immnunol. 306: 91–110.   Damla Yaman Sales Specialist Cosmer Kimya