BMG PHARMA / SCIENCE & TECH

HYALUROMIMETHIC® TECHNOLOGY

Hyaluromimethic® reshapes the hyaluronan approach.

Hyaluromimethic® technology is an innovative and patented technology platform by BMG Pharma and it represents an exclusive covalent modification of the hyaluronic acid molecule in its hydroxylic residues with functional, biologically active and bio-tolerable molecules.
Its use has made it possible to create a wide range of biomaterials that explode the positive characteristics of the original molecule.

To increase the biological benefits of sodium hyaluronate (HA), BMG Pharma has functionalized and esterificated on its hydroxylic groups this biocompatible and biologically active polysaccharide with other biocompatible, safe, biological active, endogenous and already involved in the natural biological process ones, , maintaining the hydrophilic function of the molecule intact (the carboxylic group).

The result is a modulable technological platform and a new recombined form of HA that considers:

Hyaluromimetic® technological platform

The Hyaluromimethic® Technology platform is suitable for the development of products with different formulations (both topical and injectable) for several applications in many therapeutic areas.

A synthetic pathway has been developed to obtain several chemical derivatizations of HA; the method involves common reagents and mild reaction conditions in organic media and it allows to obtain both linear and cross-linked hyaluronan derivates.

Sodium Hyaluronate Butyrate (SHB)

Sodium Hyaluronate and Butyric Acid are two molecules which have been condensed at level of hydroxylic functions present on the polysaccharide backbone through an esterification reaction with the aim to obtain an amphipathic system with unique biological properties.

In fact, Hyaluronan Sodium Butyrate has biological characteristics that are not achievable by the simple mixing of the constituents.
The enhanced enzymatic resistance (which confers a long-lasting activity), the cytokines expression regulations and the improvement of collagen productions make this product an important tool in the development of new generation of cosmeceuticals and an active ingredient in different classes of medical devices; furthermore, there is a change in the interaction with neutrophils, which are involved in the first stages of the inflammatory process, with an overall effect in modulation and reduction of inflammatory processes.
In short, resulting unique combination performs a synergistic strengthening action that improves some HA features:
- the moisturizing effect;
- anti-irritative activity;
- the lipophilicity;
- the interaction with lipidic moiety of the dermis.
The total biocompatibility of SHB is an additional value in developing innovative tools with a broad range of applications in the field of medical devices.

Bibliography

  • "Chemical Coupling of Butyric Acid and Hyaluronan: an Innovative Epigenetic Agent"
    (Marco Bosco, A. Sechi, Rita Gianni, Matteo Fabbian, Luca Stucchi, E. Marsich, P. Sacco)
    SIGEA Srl, AREA Science Park
  • "Esters of hyaluronan with Butyric Acid Downregulate ROS Production by Human Neutrophils" (E. Decleva, R. Gianni, E. Marsich, R. Menegazzi, P Sacco, A. Sechi, L. Stucchi)

Sodium Hyaluronate Butyrate Formiate (SHBF)

Sodium Hyaluronate Butyrate Formed is a biomaterial characterized by specific balance between hydrophilic and lipophilic components.

The addition of Formiate to the SHB helps to improve its lipophilic function that manages to enhance the affinity of interaction with the components of the Extracellular Matrix. The advantage that follows is an even more pronounced film-forming and moisturizing effect that allows you to maintain the physiological state of the skin layer.
Its primary areas of application are dermatology and skin care.

Sodium Hyaluronate Lipoate (SHL)

Alpha-lipoic acid, also called thioctic acid, is an essential co-factor in several multi-enzyme complexes at the mitochondrial level, in the metabolism of carbohydrates and proteins and in the conversion of energy into ATP.

Being a relatively small molecule, lipoic acid is easily absorbed and transported across cell membranes, acting as a carrier of electrons and acetyl groups. It was shown that have a direct antioxidant effect due to the neutralization of reactive oxygen species that are destructive to DNA, proteins and lipids of cells.
Hyaluronate lipoate is a powerful molecule capable to combine the advantages of the hyaluronic acid molecule with the lipoic acid, namely neutralizing free radicals and achieving a deep moisturizing effect.
The addition of lipoate brings some additional advantages over the basic SH molecules: - viscosity enhancement - antioxidant activity - tissue regeneration - water retention
The main fields of application concern hair care and ophthalmology.

Sodium Hyaluronate Lipoate in Silver Complex (SHLS)

Using the affinity of lipoic acid with metals, a complex between Sodium Hyaluronate Lipoate and Silver has been developed.

SHLS in solution, create a 3D network with viscoelastic properties and, thanks to the actions known in the silver bibliography, he exercises antimicrobial activity; already at very low concentrations of silver ions it reduces bacterial growth on the biofilm without cytotoxic effects.
The rheological profile and the antimicrobial activity are the key factors for a broad range of applications as medical devices with barrier effect against bacteria and biofilm growth.
Moreover, alpha-lipoic Acid is a natural molecule which acts as an essential cofactor for many enzymatic reactions. It is a potent performance that prevents the symptoms of Vitamin C and E deficiency.
The chemical affinity of the components and their balance brings to products with tailored characteristic, improving the possible applications  customized, improving the possible applications.
In summary, lipoate, hyaluronate and silver synergize and offer numerous benefits:
- neutralization of free radicals
- enhancement of film-forming properties and barrier function
- improvement of resistance to enzymatic degradation
- activation against Gram-positive and Gram-negative bacteria and biofilm growth reduction three-dimensional network

Bibliography

  • "HYALURONAN LIPOATE SILVER COMPLEX: STRUCTURE AND BIOLOGICAL ACTIVITY" M. Borgogna, M. Fabbiam *, F. Picotti *, P. Sacco and L. Stucchi
SHLF (Sodium Hyaluronate Lipoate Formate) & SHLFZ (Sodium Hyaluronate Lipoate Formate & Zinc Gluconate)

The covalent binding on hydroxylic groups of the HA with formate and lipoate impacts significantly both on the physical and chemical behaviors of the native molecule and the final adding of Zinc Gluconate allows to stabilize the solution in a new form of gel.

SHLFZ technology offers numerous advantages and represents a source of biomaterials for many therapeutic applications, thanks to unique properties compared to all current hyaluronic acid technologies on the market:
- 3D matrix long lasting resistant to enzymatic degradation
- strong elasticity independent to the concentration
- amphiphilicity
– performances performance even at very very low dosages
- completely biocompatible, reversible and not recognizable as a foreign product
- Zinc gluconate protected and with enhanced biological activity
- BDDE-free
Thanks to the possibility of combining filling, elastic and regenerative properties, the first focus of BMG Pharma is the development of a portfolio for aesthetic medicine and intra-articular injectables.

Bibliography

  • "Chemical Coupling of Butyric Acid and Hyaluronan: an Innovative Epigenetic Agent" (Marco Bosco, A. Sechi, Rita Gianni, Matteo Fabian, Luca Stucchi, E.Marsich, P.Sacco) SIGEA srl, AREA Science Park
  • "Esters of hyaluronan with Butyric Acid Downregulate ROS Production by Human Neutrophils" (E. Decleva, R. Gianni, E. Marsich, R. Menegazzi, P. Sacco, A. Sechi, L. Stucchi)