Hepran sulfate is a relatively new ingredient in skin care formulas. Yet, it promises so many beneficial effects on the skin that Dr. Leslie Baumann said that it is time to add hepran sulfate to the list of tried-and-true skin care actives like hyaluronic acid, collagen and elastin (MDedge.dermatology Journal, Jan.26, 2017). It is also dynamic and multifunctional star ingredient in Senté’s Dermal Repair Cream.

Controlling this molecule is the key to determining skin health. Hepran sulfate (HS) is a naturally-occurring component of your skin that is essential to maintaining skin health. Like hyaluronic acid, hepran sulfate belongs to the glycosaminoglycan (GAGs) family of naturally-occurring water-binding molecules found throughout the body. Hyaluronic acid is an atypical GAG, unique by virtue of being non-sulfated, of large molecular size. GAGs are complex sugars that act as natural hydrators. They are long linear polysaccharides comprised of repeating disaccharide units and are ubiquitous within the skin. They are present intracellularly on the cell surface. Hepran sulfate is present in all layers of the skin and can interact with extracellular matrix molecules; collagen types 3, 4 and 5; growth factors and cytokines; and within the extracellular matrix (ECM).

Anti-Aging Beauty Benefits

The anti-aging ingredients market is expected to top $1.3 billion this year and grow 7.2% a year to reach $2.3 billion by 2030. The antiaging ingredients comprise of standard moisturizing constituents consisting of peptides, retinoic acid, retinol, hyaluronic acid, hydroxy acids, sunscreen and antioxidant ingredients. This column will briefly review the role of hepran sulfate in skincare. HS is another one of these important hydrators produced by skin. It contributes to skin firmness, elasticity and clarity. It sends signals to other cells to produce more anti-aging compounds including collagen and hyaluronic acid.

Hepran sulfate surrounds and protects the growth factors, bringing them to the cells, so that the growth factors bind the proper receptor sites and tell the cells to make collagen. Ultimately this helps to increase firmness and promote a more youthful complexion.

Most consumers know hyaluronic acid is capable of holding a great deal of water. This property makes it a popular addition in countless skincare products as well as injectable fillers. However, despite hyaluronic acid’s fame, it actually has far less biological activity than another GAG—hepran sulfate. GAGs are emerging as an essential target for reversing skin aging. At one time, they were considered inert molecules restricted in their functioning as mere space fillers during orientation and organization of extra cellular matrix. Recent studies revealed their importance in regulating inflammation, wound healing, and tissue repair.

A damaged skin barrier can be difficult to treat as it is often characterized by multiple skin conditions. Most notably, a damaged skin barrier can be dry, flaky, irritated, itchy and inflammed. According to the Journal of Clinical Cosmetic and Investigational Dermatology, GAGs play a significant role in regulating cell production and inflammatory processes in the skin. With age, our levels of hepran sulfate decline, which leads to destructive dehydration resulting in chronic skin inflammation. This inflammation is responsible for facial redness and visible signs of aging among other skin concerns such as skin sags, disorganized collagen and slow-healing wounds. Replenishing this molecule is likely to have myriad benefits for aging skin.

Despite all of these attributes, only Senté utilizes hepran sulfate in its products. As more information on HS becomes available, more anti-aging products may begin including this novel moisturizing agent to help plump and smooth skin.

Where You’ll Find It

Endogenous HS is too large and highly polar; therefore, it is unable to penetrate the skin, preventing most skincare brands from effectively adding HS into their products in topical form. Senté patented the cosmetic analog of HS called HSA modified to low molecular weight hepran sulfate (LMW-HS), which is bio-engineered to a size, shape and charge that is optimal for topical use. According to Senté Chairman Faheem Hasnain, their proprietary, low molecular weight HS is key to successful formulation. Three Senté skincare products are formulated with the patented Hepran Sulfate Analog (HSA) technology. HSA is clinically proven to diminish the appearance of wrinkles and improve skin texture. It has been scientifically proven to absorb throughout the epidermis and penetrate into the dermis very effectively, reducing redness and improving appearance of fine lines.

HSA formulations are well tolerated by sensitive skin including aging skin and rosacea. Not only does HSA hold on to water, but it also helps skin rebuild its protective barrier to minimize moisture loss. HSA is a repairing molecule which is readily absorbed. The molecule mimics the effects of hepran sulfate, providing a natural boost to skin’s immune response to inflammation and promoting repair from within. Hepran sulfate has been formulated with a number of other synergistic factors that have the ability to maximize the effect of HS. HSA+Retinol strengthens the skin barrier and improves tolerability when paired with prescription retinoids and retinol products. HSA+ pigmentation correcting ingredients, helps prevent inflammation-induced pigmentation. HSA+ in-office treatments are recommended for use with peels.

Clinical Studies

At the 2018 AAD Annual Meeting, Amy Taub MD said that growth factors had become controversial, being blamed for causing cancer. They have been viewed as ineffective because these molecular weight proteins cannot get past the stratum corneum. She suggested three alternatives to growth factors namely: hepran sulfate, tripeptide palmitoyl and defensin. HS is much smaller than growth factors and plays a role in skin healing. According to Senté’s Hasnain, clinical trials were carried out to test product efficacy. Each study recruited 30-60 subjects to assess the formulation, pre-clinical safety and absorption of the ingredient, together with the whitening, hydrative and anti-wrinkle properties.

Senté products target all skin types and were launched in the US via dermatologist and estheticians, with plans to evaluate its launch in markets worldwide in the future. The LMW-HS based formula improved photodamaged skin, indicating its therapeutic potential (Journal Cosmetic Dermatology, Vol. 19, issue 8, Aug. 2020, pages 1851-1856). One study with an HS analog demonstrated that the formulation penetrates into skin, enhancing hydration, reducing transepidermal water loss and improving the appearance of wrinkles and skin tone.1 One study published by the Journal of Drugs in Dermatology showed that topical application of HS improved skin hydration within eight weeks of use. In this study, researchers looked at the role of HS in repair of aging skin. They concluded that HS reduces the appearance of wrinkles as well as discoloration in skin in just a few weeks. The Journal of Pathology explored the role between HS and wound healing in the skin. It was concluded that HS directly impacts the inflammation and cell growth associated with wound healing.

Baumann has been using Senté Dermal Repair Cream on her rosacea patients without any problems. She suggests HS analogs represent a good option for patients who cannot tolerate retinoids. In 2015, Gallo et. al. reported that 15 patients using a HS analog formulation in an 8-week study displayed improvements in various skin metrics, including hydration, firmness, elasticity, barrier function and the appearance of fine lines and wrinkles. The investigators concluded that photodamaged skin may benefit from the use of novel topically-applied products containing low-molecular-weight HS (J Drugs Dermatol. 2015 Jul: 14(7): 669-74).

Remarks

HS is proving to be a very promising topical ingredient with many different uses in skincare. In addition to its role as an antiaging and moisturizing agent, it could also be used to aid in wound healing, to reduce redness and protect against pathogens. HS analog formulations are well tolerated by people with sensitive skin. While more research is needed, current clinical testing evidence suggests that HS analogs may prove to be acceptable. 

References:

1. R. Gallo, V. Bucay, J. Drugs Dermatology, 2015 14(7): 669-674.

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Navin Geria
Chief Scientific Officer
Ayurderm Technologies, LLC
navin@ayurderm.com
 
Navin Geria, former Pfizer Research Fellow is a cosmetic and pharmaceutical product development chemist and the chief scientific officer of AyurDerm Technologies LLC, which provides Ayurvedic, natural and cosmeceutical custom formulation development and consulting services to the spa-wellness-dermatology industries. He has launched dozens of cosmeceutical and ayurvedic anti-aging products. Geria has more than 30 years of experience in the personal care industry and was previously with Clairol, Warner-Lambert, Schick-Energizer, Bristol-Myers and Spa Dermaceuticals. He has nearly 20 US patents and has been published extensively. Geria edited the Handbook of Skin-Aging Theories for Cosmetic Formulation Development focus book published in April 2016 by Harry’s Cosmeticology. He is a speaker, moderator and chairman at cosmetic industry events.