Hyaluronic acid in cosmetics.

A review of its chemistry and biochemistry

I must admit that hyaluronic acid (HA), frequently called hyaluronan, has been of limited interest to me for many years. However, nearly one year ago I read an advertisement by a major cosmetic company with some significant claims for skin benefits attributable to the presence of "Bio-Hyaluronic Serum." I really do not know what this substance is, but I assumed that it had to have some relationship to HA.

Hyaluronic acid - biochemically identified as a glycosaminoglycan (GAG) - was isolated approximately 60 years ago from vitreous humor. Its name reflects its transparent glassy nature (the Greek word for glass is hyalos). Since its original isolation. HA has been found at differing levels in a variety of animal tissues (Table 1-1).

The long-lasting interest in HA's use in skin-care products started after the observation that the level of HA in skin decreases with age.[6,27] A report by Ghersetich not only demonstrates that actinically or chronologically aged skin contains less HA than younger skin, but also asserts that this alteration in HA levels plays an important role in the pathophysiology of aged skin.[6] Balazs and Band summarized this and earlier observations in some detail?

The widely reported[14] reduction in levels of HA in the dermis of the aged is one way to rationalize all types of measures to increase HA levels. In fact, the GAGs of older skin may differ from the GAGs of younger skin in terms of both quantity and quality (structure). These subtle chemical alterations become apparent during precipitation with ethanol-water mixtures containing varying amounts of ethanol.[13]

 
Table 1-1. Hyaluronic acid content (mg/ml) in selected animal 
tissues 
 
Animal tissue                     Hyaluronic acid 
 
Rooster comb                           7-8 
Human umbilical cord                    4 
Human dermis                           0.2 
Human serum              [less than or equal to]0.0001 
Rabbit brain                           0.065 

Of course, the cosmetic industry welcomed scientific speculation on the benefits of HA for skin care. Suppliers and finished-product houses completed this preliminary assessment by providing more convincing evidence. The information on product usage for HA or HA salts in the International Cosmetic Ingredient Handbook suggests that HA enjoys wide use in cosmetic skin-care products.[9]

In this current review, I attempt to present documentation for in vivo efficacy of HA's topical use in cosmetics. Information on this subject is remarkably limited.

Chemical Description

Hyaluronic acid is a linear polysaccharide and, at physiological pH, the carboxyl groups are almost completely ionized. Since the nature of the neutralizing cation is not defined, the term "hyaluronan" has been adopted to describe HA in its native state. HA apparently is not linked covalently to a protein and facetiously has been dubbed an "honorary proteoglycan."[12]

Structure: The structure of HA [ILLUSTRATION FOR FIGURE 1-1 OMITTED] consists of repeating disaccharide units linked to each other [Beta]1,3. This disaccharide consists of glucuronic acid (GlcUA) linked [Beta]1,3 to N-acetylglucosamine (GlcNAc). GlcUA, which bears some resemblance to AHAs, is a strong acid and in vivo is likely to be almost completely neutralized.

HA is a linear polymer of very high molecular weight (HMW) ranging up to 4-5 x [10.sup.6] Daltons (Da). Hydrogen bonding is evidently parallel to the polymeric chain with little cross linking to adjacent chains. Some researchers have reported that UV irradiation in the presence of oxygen effects changes in HA's viscoelastic properties.[10]

Secondary structure: The secondary structure of HA depends on the formation of H-bonds. Scott suggested H-bonding between the 4-OH group of glucosamine and the acetal O of glucuronic acid and of a water …