Hyaluronan was first isolated from the vitreous of bovine eyes in 1934. The substance was found to contain two sugar molecules (disaccharide), one of which was uronic acid. As a result, it was called 'hyaluronic acid' [from hyaloid (vitreous) + uronic acid]. However, under normal physiological conditions (pH = 7.4) hyaluronic acid is not present in the acid form, but exists as a polyconjugated salt known as hyaluronate. In addition, because the most abundant ion in tissue is sodium, hyaluronic acid is most frequently present as sodium hyaluronate. Thus in 1996, in agreement with modern nomenclature of polysaccharides, the name hyaluronan (HA) was proposed. All of these terms are currently used, but vary depending on the therapeutic area.
The first commercial use of hyaluronan was in 1942 by Dr Balazs, who went on to become the leading expert on hyaluronan and made the majority of discoveries concerning the molecule during the next 50 years. Hyaluronan was first marketed for human use in the early 1980s. Healon® (Upjohn-Pharmacia) was introduced for use in the ophthalmic field as a viscous injectable gel into the anterior chamber, to protect eye tissues such as the corneal endothelium during surgery. Since then, hyaluronan has been used in many other indications, including joint disorders, tissue augmentation and characterisation of sperm. Hyaluronan derivatives with long, tailor-made forms were introduced in the nineties, further increasing the potential applications of the natural molecule.
Depending on the condition of use, field of application and claims made, hyaluronan can be considered as either:
- A medical device whose activity relies primarily on a mechanical effect due to its viscoelastic properties.
- A drug exerting a long-term pharmacological effect.
Although some hyaluronan products are registered as drugs, the majority are classed as medical devices.
HYALURONAN IN THE BODY
Hyaluronan exists naturally in almost all vertebrate connective tissues and is a universal component of the extracellular space (where it is released just after its synthesis).
Hyaluronan is found in a number of body tissues:
The eye. High concentrations are found in the vitreous body, where it gives volume and shape to the eyes. It is also found in the connective tissue of the trabecular chamber angle and plays a role in controlling aqueous flow in the trabecular meshwork.
Small amounts can be found in aqueous humour. Hyaluronan also covers the endothelium: human corneal endothelial cells retain specific binding sites for hyaluronan. The normal human eye has a hyaluronan concentration of 1.4 mg/l, which covers the corneal endothelium in a thin, uninterrupted coating.
Skin (where it creates volume - without hyaluronan, the skin would appear dry, withered and wrinkled).
Cartilage (as a structural component).
Synovial fluid (where it acts as a lubricant and shock absorber).
The umbilical cord (where its function is to ensure that the contact between the mother and the foetus is never broken).
The blood (in small amounts)
- Blood vessels
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