Hyaluronic Acid and it is Key Role in Organism

30 Haziran 2020

Our body naturally contains an average of 15 grams of hyaluronic acid (HA), found in every part of our organism: Skin, joints, scalp, eyes, soft tissues, and synovial fluid. Due to it is chemical nature, HA can hold up a great quantity of water, but it is turnover time is very short, with approximately a third of our body HA renewed everyday. In each body location, HA serves different functions, correlated to its molecular weight (MW): igh MW HA has more of a water retention function, while lower MW HA enhances biological activities, and plays a role of signal molecule. These physiological roles of HA in skin include:

1- Moisturising and holding water,
2- Maintaining skin viscoelasticity and tonicity by creating a hydrogel in the extracellular matrix,
3- Improving cell multiplication and communication through CD44 receptors,
4- Facilitating cellular mobility and viability by transportation of nutrients.

Ageing Processes and Dermal Fillers

Upon chronological ageing, the metabolic efficiency of skin cells decreases, lowering their capability to produce major constituents of the extracellular matrix. Due to it is high degradation rate, HA is among the first matrix polymer to disappear, leading to the first signs of ageing (fine lines, wrinkles). Meanwhile, antioxidant defences of ageing cells are strongly reduced, making them more sensitive to free radicals.

In parallel, extrinsic ageing is driven by daily expositions to a set of environmental aggressions: UV, blue light, pollution, chemicals or repeated mechanical stresses.

All of these factors result in the production of Reactive Oxygen Species (ROS), damaging cells components and inducing an overexpression of matrix metalloproteinases (MMP), fostering the degradation of extracellular matrix fibres (such as collagen).

A majority of aesthetic dermal fillers is based on HA, as it is a native component of skin with high volume filling properties (water binding capacities). However the use of these dermal fillers requires local injections with possible complications, and despite their cost, they cannot restore skin natural protection.

It was therefore crucial to find an alternative to protect the skin and its constituents along our lifetime, but also to restore some of its key properties when possible, and get rid of our wrinkles.

PrimalHyal™ Ultrafiller, the Cosmetic Alternative to Dermal Fillers

To answer this unmet need, Active Beauty experts have designed PrimalHyal™ Ultrafiller, a new generation of topical HA, by optimising the bioavailability of a specific MW of HA, thanks to its full acetylation. PrimalHyal™ Ultrafiller behaves as a filler by penetrating deeply into the skin, quickly reducing wrinkles. It also stimulates skin epidermis and dermis metabolisms to: 1- Protect the extracellular matrix by decreasing collagenases production and collagen degradation, even under photo-pollution, 2- Restore the antioxidant defences through the sequestosome pathway, helping skin to fight against free radicals.

Biological Activity

Deeper Skin Penetration and Long-Lastingness
1. Deeper Skin Penetration

Skin explants from a Caucasian 37 years old donor were topically treated for 8 hours with 1% of standard HA (same range of MW than PrimalHyal™ Ultrafiller, but non-acetylated) or PrimalHyal™ Ultrafiller, and analysed by Raman spectroscopy to assess products penetration.

Results: The standard HA shows an average skin penetration from 20 to 50μm. PrimalHyal™ Ultrafiller penetrates much deeper, with most of the signal around 100μm in the skin.


2. Biological Long-Lastingness

The resistance of standard HA and PrimalHyal™ Ultrafiller to biological degradation was analysed by incubating them 16 hours with hyaluronidase, and HPLC analysis was used to estimate the level of degradation (reduction of MW).

Results: PrimalHyal™ Ultrafiller shows a high resistance to biological degradation with only 7% of degradation. Standard HA is almost entirely degraded in these conditions (92%). PrimalHyal™ Ultrafiller half life is estimated to be 13 times longer than standard HA.


Dermis Active Protection: Anti-Ageing Activity Fibroblasts from a 52 years old donor were pre-incubated with 0.1% of PrimalHyal™ Ultrafiller or standard HA for 2 hours and then exposed or not to an oxidative stress induced by H2O2 (200μM). MMP-1 and MMP-3 production was assessed 48 hours after the oxidative stress by Luminex and Collagen I degradation was measured by fluorescence analysis using DQ-collagen I.

Results: PrimalHyal™ Ultrafiller significantly inhibits MMP-1 and MMP-3 collagenases production in oxidative stress conditions, down to -40%. It also significantly decreases the degradation of collagen I, down to -42% under oxidative stress.


The standard HA shows no activity to reduce collagenases.

Clinical Tests
Mid and Long-Term Anti-Ageing Activity
1. Nasogenian Wrinkles Reduction (1 Month)

A double blind clinical evaluation was carried out on 20 volunteers (women from 35 to 70, 56 years old in average) having wrinkles in the nasolabial area. Volunteers applied either a cream containing 0.1% of PrimalHyal™ Ultrafiller or the same cream without the active (placebo) on each side of their face for 28 days, twice a day (morning and evening). VISIA® analysis was performed after D0 and D28 to assess wrinkles number and area.

Results: In 1 month, PrimalHyal™ Ultrafiller significantly decreases down to -9% the number of nasogenian wrinkles, and down to -13% the nasogenian wrinkles area.

Skin Texture 

2. Improvement of Skin Texture (2 Months)

A double blind clinical evaluation was carried out on 30 volunteers (women from 50 to 70, 57 years old in average) having wrinkles on the face. Volunteers applied either a cream containing 0.1% of PrimalHyal™ Ultrafiller or the same cream without the active (placebo) on each side of their face for 56 days, twice a day(morning and evening). VISIA® analysis was performed after D0 and D56 to assess skin texture, and volunteers were asked to assess the product efficacy on their skin properties.

Results: PrimalHyal™ Ultrafiller enables a significant 9% improvement of skin texture in 2 months, while bringing noticeable skin benefits to volunteers.


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

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