Hyaluronic acid and new cooperative hybrid complexes

On several occasions over the years, Arturo Licenziati summarised his entrepreneurial vision as follows: “We cannot compete with the big players: this focus on addressing the real needs of doctors and patients is the only way for a small company to grow”.

Thanks to its properties, hyaluronic acid (HA) can be used in various medical and cosmetic fields. Its diverse applications depend on molecular weight and degree of purity.

For years, extraction from animal tissues was the primary method of producing hyaluronic acid. In 1989, Shiseido was the first company to develop and patent its fermentative production.

To produce hyaluronic acid through bio-fermentation, various bacteria are used, and the most important steps to obtain a product with a high degree of purity are extraction and purification.

In 2011, Arturo Licenziati launched a new entrepreneurial initiative with Altergon Italia, developing and patenting an innovative biotechnological fermentation process for the production of hyaluronic acid with a high degree of purity.
The patent recognised the originality of the production process for injectable pharmaceutical-grade hyaluronic acid. Altergon is now among the world’s leading companies in the production of injectable-grade hyaluronic acid.

Although many hyaluronic acid-based products are available on the market, in recent years, IBSA has developed several innovations in collaboration with the Università Vanvitelli in Naples (Prof. De Rosa and Prof. Schiraldi).
Among these, the new hybrid cooperative complexes of high and low molecular weight hyaluronic acid (H-HA and L-HA) and hyaluronic acid and non-sulphated biotech sodium chondroitin (SC) stand out. These were developed at the biotechnological laboratories of IBSA’s site at Qingdao Huashan Biochemicals (IBSA China).

IBSA’s portfolio of hyaluronic acid-based products includes a range of preparations developed for intra-articular use, aesthetic medicine treatments, wound healing, and uro-gynaecological solutions. 

High and low molecular weight hyaluronic acid (HA-HL) hybrid complexes

Through NAHYCO technology (i.e. sodium hyaluronate hybrid complex, a unique patented thermal process carried out at the Lodi site), high and low molecular weight hyaluronic acids are mixed to produce a hybrid cooperative complex, where short and long chains are linked by hydrogen bonds without the use of chemical cross-linking agents.

Thanks to this innovative treatment:

• a high concentration of hyaluronic acid can be achieved, without compromising the ease and safety of the procedure (i.e. the injection);
• resistance to the degradation operated by hyaluronidases can be improved, since the hyaluronidase enzyme is unable to recognise the conformation of these complexes. 

Moreover, the tolerability of the hybrid complex is ensured by the absence of chemical modifications that could increase the risk of reactions. Excessive cross-linking, in fact, makes the polymer less hydrophilic, promoting localised reactions such as pain and swelling. Cross-linking could also increase the product’s immunogenicity, making it less similar to natural hyaluronic acid. 

Cooperative hybrid complexes of sodium hyaluronate and sodium chondroitin biotech

The technological excipient used by IBSA to regulate the viscosity of high-weight, high-concentration hyaluronic acid solutions is biotechnological (biotech) or non-sulphated chondroitin (SC).
IBSA can produce non-sulphated chondroitin through a patented biotechnological fermentation process. The use of non-sulphated chondroitin allows for a higher concentration of glycosaminoglycans without a significant increase in viscosity.