HYALURONIC ACID

Hyaluronic acid is the main constituent of a family of polysaccharides which are similar in terms of structure and behaviour, and contain amino sugars better known as glycosaminoglycans.
In chemical terms, it is a non-branched linear polymer consisting of a disaccharide unit formed by glucuronic acid and N-acetylglucosamine, which is repeated in the molecule numerous times, reaching molecular weights of up to several million daltons.

HA is a polysaccharide highly soluble in water, and HA solutions exhibit viscoelastic, non-Newtonian behaviour: these properties depend on molecular weight (length of chain), concentration, and external environmental conditions such as pH. Its viscoelastic properties, together with the total absence of toxicity or immunogenicity, have led to its use in numerous industries, with applications ranging from the medical to cosmetic fields.

BRIEF HISTORY

Hyaluronic acid was discovered in 1934 by Karl Meyer and John Palmer, scientists at Columbia University, New York.
They isolated the substance from a cow’s eye and derived the name from hyalos (the Greek word for glass) and the uronic sugar found in the substance.
This marked the birth of one of nature’s most versatile and fascinating macromolecules. Today, this macromolecule is most frequently referred to as Hyaluronan, reflecting the fact that it exists in vivo as a polyanion and not in the protonated acid form.
The first industrial applications were performed in the ophthalmic field (Sweden), and in the dermatological field for burn damage (Italy).

Pharmaceutical companies, requiring industrial quantities of HA, opted to use a product of animal origin obtained from coxcombs. More recently, with the advent of biotechnology, the industry has obtained this substance from a specific bacterium (microbial production), leading to evident improvements in quality (no more risk of viral infection).
Today’s major medical applications:
Osteoarthritis: numerous clinical investigations have demonstrated the efficacy and safety of HA in the treatment of osteoarthritis of the knee and other large joints.

Ophthalmology: a field in which the purely physico-chemical properties of high-molecular-weight HA play a predominant role is ocular microsurgery. Specifically, it is extremely useful in anterior or posterior segment eye surgery: cataract extraction, with or without intraocular lens implantation, keratoplasty, trabeculectomy, and vitreous-retinal surgery.
Wound repair: many of the biological processes mediated by HA are central to the wound healing process. Following injury, wound healing relies on a series of tightly-regulated sequential events, e.g. inflammation, formation of granulation tissue, re-epithelialisation, and remodelling. HA is likely to have a multifaceted role in the mediation of these cellular
and matrix events.

Oral care: Ricerfarma is proud to be the first company ever to have thought of applying HA to the field of dentistry.
We hold the utility patent for a specific hyaluronic acid. This acid is particularly suitable to re-form the gingival tissues, to reduce oedema, and therefore regulate the return of the gum to the normal physiological state.

ORAL CARE APPLICATIONS

Hyaluronic acid (hyaluronan) is an indispensable component of intact, healthy gums and oral mucosal tissue.
It is distributed in a selective, specific manner and tends to concentrate particularly in those layers of the gingival epithelium closest to the surface, where it acts as a barrier imparting stability and elasticity to the periodontal connective tissue.

As hyaluronic acid (hyaluronan) is a purely physiological substance devoid of any toxic or unpleasant accompanying phenomena, it can be used without restriction by children, pregnant women, diabetics, vegetarians and the elderly.
In the case of inflammations and injuries, for example, hyaluronic acid is broken down and dissolved by the enzyme hyaluronidase. If oral hygiene is poor, hyaluronidase is produced and released by bacterial plaque.

The enzyme induces a loosening of the structure and a slackening of the tissue and facilitates fluid exchange between the tissue and the vascular system, causing mild oedemas to form.
The enzymatic breakdown (catabolisation) of hyaluronic acid by hyaluronidase significantly increases the permeability of tissue and capillaries with the consequence that toxins, drugs and bacteria can propagate more easily.
This in turn leads, amongst other things, to poor healing and tissue inflammation.

The Action
By normalising the natural cohesive structure of the connective tissue (macro-aggregation of the proteoglycans), hyaluronic acid accelerates the rate of tissue reconstruction. The weakening of the mucosal tissue due to the influence of bacterial hyaluronidase is thus reduced. A further biological function of hyaluronic acid in tissue regeneration is its ability to influence both the migration of fibroblasts and fibrogenesis, with the result that scar tissue formation and wound healing are promoted.

Hyaluronic acid possesses an extremely high capacity to bind water (up to 200 times its own volume); thanks to this property, HA produces an anti-oedematous effect. The molecular structure of hyaluronic acid or, more exactly, the molecular chains formed by the glycosaminoglycans, binds not only water, but also specific proteins and their tissue polysaccharides, by means of hydrogen bond bridges, to form a viscous macro-aggregate.

Hyaluronic acid combats the inflammation caused by hyaluronidase-producing bacteria by inactivating the enzyme.
Hyaluronic acid regulates cell permeability and reduces abnormally high capillary permeability.
This helps to prevent infestation by infectious micro-organisms, thus inhibiting tissue destruction.