An Evolution of Hyaluronic Acid Technology.

The Next Generation of HA Technology for Dermal Fillers.

Not all Hyaluronic llers are alike.

The world of dermal llers is continuously evolving. New formulas are regularly being introduced, surrounded by a profusion of information and claims. In order to make an informed decision about what will be best for your patient, and your business, it is essential to understand the distinctions between the variety of options.

Hyaluronic Acid. The building blocks of todays dermal llers.

Hyaluronic acid (HA) has been widely used in medicine providing lubrication to joints, and more recently, giving volume to the skin as a dermal ller. HA is a biocompatible polymer with a high molecular weight and long safety record. Hyaluronic acid is highly soluble in its natural state and has a rapid turnover through enzymatic and free radical metabolization. For effective and lasting use, all dermal llers have HA modied through cross-linking, connecting the HA molecules to form a water-insoluble polymer hydrogel network more resistant to degradation.

Where does your HA come from? Medical HA has two sources:

Avian.
Developed from rooster combs, may have a high avian protein content (leading to allergic reactions in some patients).

Bacterial Fermentation (synthesized).

A very pure form of HA created by the fermentation of the staphylococcus equine bacterium. Non-animal based.

Particulate vs. Non-Particulate: Whats the difference?

Particulate and non-particulate HA-based llers behave very differently, so it is essential to understand the distinctions. While all HA llers (particulate and non-particulate) use a single cross-link ether bond to stabilize their HA, there are some key differences.

Non-Particulate HA Fillers
Non-Particulate (gel) HA llers are a fairly recent introduction, some claiming to be variously, multi-cross linked, double cross- linked, or monophasic gels. These HA gels are all single cross-linked with an ether bond in a two-stage process (not two different types of bonds):

rst stage bonds long HA chains with BDDE

second stage bonds shorter HA chains to the network also with BDDE

This creates a network of combined short and long HA chains that is a homogeneous mass, resulting in a weaker network. However, because these gels are non-particulate, they must depend on HA concentration or cross-link density for duration, rather than particle size.

Cover images represent (left to right) syrup-like HA, high concentration HA particles with low HA concentration - heavily cross-linked HA molecules, and high concentration HA particles with high HA concentration - minimally modied HA molecules.

Particulate HA Fillers
Particulate HA llers are more common, and depend on three factors for duration:
Cross-linking

A brief history of Hyaluronic Acid

1934
Karl Meyer and John Palmer isolate a previous unknown chemical substance from the vitreous body of cows eyes. The substance contained uronic acid, so they propose the name hyaluronic acid from hyaloid (vitreous) + uronic acid.

by ether linkages. Some use DVS, most use BDDE, but all use a single

cross-link ether bond.

Particle

size. All single cross-linked HA llers

depend on particle size to differentiate between ne line and deeper dermis treatments. Because of their greater surface
The smaller Puragen particles pass through the needle whole and emerge intact Larger particle HA ller particles are distorted & sheared as they pass through the needle.

1942
The rst commercial use of Hyaluronic Acid. Endre Balazs applies for a patent to use it as a substitute for egg white in bakery products. He goes on to become a leading expert on HA, making the majority of discoveries concerning HA during the next 50 years.

area, smaller particles have a shorter duration, requiring more frequent treatments to maintain correction.

1964
TC Laurent created the rst cross-linked HA

The

Difference.

using Bis-epoxide as a cross-linking agent.

1980 and 1990s

The use of HA in medicine is extended to a number of areas, including treatment of joint pain due to arthritis, use in fertility clinics, aiding eye surgeons with cataract operations, and tissue augmentation.

DXL (double cross-linked hyaluronic acid) is the result of a revolutionary process that
stabilizes extremely pure HA chains using a two-stage cross-linking process with two separate types of bonds. Only DXL uses 1,2,7,8-diepoxyoctane to create both ether and ester bonds. A slightly hydrophobic nature results, which increases the gel network physical bonding. DXL HA has a high stability against heat, which supports shelf life. Combined with the additional ester bonds, this molecular conguration greatly slows the degradation rate of the DXL network by reducing the diffusion rate of the enzyme Hyaluronidase into the matrix.

1996
Restylane is launched by Q-Med in Sweden, introducing the rst generation of HA dermal llers used for cosmetic use.

2000
Dr. Xiaobin Zhao les for a patent for the Preparation of Multiple Cross-linked HA, the technology behind DXL.

Double X-Linking Technology:

LEA Derm introduces the Juvederm range of products, the rst homogeneous gels.

2004
After a decade of development and testing, Mentor receives CE marking for Puragen with DXL, the rst double crosslinked form of HA, ushering in the era of 4th generation HA technology.

2005
Mentor corporation launches the sale of
Single cross-linked llers are held together with single hydrophilic ether-type bonds. When using Puragen, the double cross-linkage between both hydrophilic ether and hydrophobic ester bonds results in more stable molecules with greater resistance to biodegradation.

Puragen internationally.

A new standard for HA.

Double bonded hyaluronic acid enables the production of very small particles with the durability of large particle products. Injections are equally suitable for delicate or deep lines and wrinkles. Aesthetic results can be extremely precise. The HA concentration is 2%, which allows for Puragen to be administered with a ne needle designed for precise injection control. Most importantly, small particle benets are now complemented by large particle resilience, extending product duration in the body. Clinical trials indicate as much as 6 months efcacy.

Unmatched Benets.
DXL is a proprietary technology of the Puragen brand hyaluronic llers, and represents the most advanced HA technology on the market.
Regardless of claims, there is no other hyaluronic ller that features both ether and ester bonds. Consequently, only DXL offers this unique combination of benets:

Versatility: One HA ller can meet the need for mulitple

uses. Small particle HA with the duration of large particle single cross-linked HA, eliminates the need to stock multiple llers for different areas.

Duration: Small particle efcacy meets large particle

longevity. Smooth contours and durability.

Brought to you by Mentor, an international leader in the medical aesthetic eld.

Mentor is a medical-device company trusted by aesthetic surgeons around the world for its high quality products and exceptional customer service. For more than 20 years, we have been dedicated to developing and delivering products that give patients the power to transform their lives. Our standards of quality are considered the highest in the industry. And we will continue this history of excellence throughout our development of facial aesthetics products. For more information about Mentor and Puragen, please visit www.mentorcorp.com.

Mentor Benelux B.V. Tel: +31 71 524 99 15 Mentor Deutschland GmbH Tel: +49 8116 00500 Mentor Medical Systems France, S.A. Tel: +33 1 46 01 30 54 Mentor Medical Systems Iberica, S.L. Tel: +34 91 562 2700 Mentor Medical Italia, S.r.l. Tel: +39 0 2 880 7761 Mentor Medical Systems Ltd., U.K. Tel: +1635 511800 Mentor Medical Systems Canada, Inc., Tel: +1 905 725 7763
January 2006 Mentor 0601013