Will the hyaluronic acid cross-linking agent BDDE remain in the body forever?

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Under the premise of achieving the same maintenance time and hardness, the less crosslinkers BDDE are used, the less the degree of modification of the gel, and the closer the hyaluronic acid is to the form and appearance of our own natural hyaluronic acid, so that the body's immune system can be more likely to avoid recognition, resulting in adverse reactions such as allergies.

What ingredients are contained in a hyaluronic acid filler for injection? The standard answer is: hyaluronic acid + crosslinker BDDE + physiological buffer.

Aqua Secret dermal hyaluronic acid dermax_副本

BDDE hydrolysis

Hydrolysis BDDE is a glycol-ether formed by hydrolysis of epoxy groups in BDDE or cross-linked BDDE. Hydrolyzed BDDE has been shown to be non-toxic and non-toxic. It is known that it is carried out by ether bond breaking of the cytochrome P450 family. These enzymes participate in the oxidative degradation of organic molecules and can catalyze the breakdown of ether bonds into alcohols. After degradation, two main products can appear: glycerol and butanediol.

The low concentration of BDDE-derived by-products in commercial fillers (20 mL/year) is a fraction of the safe thresholds for the BDDE metabolites butylene glycol (100 mg/kg/day) and glycerol (2,000 mg/kg/day). Therefore, similar to trace levels of unreacted BDDE, the presence of BDDE by-products in fillers is highly unlikely to cause toxicity (the claim that Juverdurm injects no more than 20ml a year has finally found its source).

About the existence form of BDDE

According to the state of BDDE in hyaluronic acid injection, it is divided into 4 types:

1. Fully reacted crosslinker 

Has been completely crosslinked with hyaluronic acid, that is, BDDE molecules that are crosslinked with hyaluronic acid at both ends

2. Pendant crosslinker

BDDE molecules crosslinked with hyaluronic acid at only one end

3 Deactivated crosslinker

BDDE molecules that react with water (hydrolyze to alcohol)

4 Residual crosslinker

BDDE molecules that are not crosslinked with hyaluronic acid or react with water

are in the basic conditions of crosslinking reactions (pH> 7) Most epoxy groups are "open", linked to HA by ether bonds, or hydrolyzed into alcohols. Since there are no reactive epoxy groups, any other chemical state of BDDE is highly unlikely to pose an additional risk of toxicity. So to make a simple elimination, since the BDDE crosslinked with hyaluronic acid no longer has an active epoxy group (ether bond formation), and the inactivated BDDE has reacted with water, then its toxicity may only exist in free BDDE.