Tetrahexyldecyl Ascorbate and Ascorbyl
Tetraisopalmitate: Are they Identical
Vitamin C Tetra Esters? Not Really!
Ratan K Chaudhuri, William Swindell & Krzysztof Bojanowski
Sytheon, 10 Waterview Blvd., Suite 105, Parsippany, NJ 07054
Background
Longstanding challenges of topical L-Ascorbic Acid (AA, Vitamin C) have been related to skin-penetration and the stability of AA as an active ingredient. AA is water-soluble hydrophilic
anion with a high polarity which is repelled by the stratum corneum and can only penetrate skin under acidic condition (pH <3.5). Moreover, upon exposure to ambient air and UV light,
AA undergoes oxidation to dehydro-L-ascorbic acid in a reaction facilitated by elevated temperatures and in the presence of high pH, metal ions and dissolved oxygen. Additionally, AA
can react with singlet oxygen to generate more persistent reactive oxygen species, such as H2O2 , consequently AA may function as a pro-oxidant in certain circumstances.
What is the Real Active?
Confusion about the Structure!
One of the most popular oil-soluble derivatives of AA today is
tetrahexyldecyl ascorbate (THDC, VitaSynol® C), prepared by
esterifying AA with 2-hexyldecanoic acid. As an oil-soluble derivative,
THDC not only improves chemical stability, but its lipophilic
nature facilitates delivery into the epidermis and dermis where it
undergoes intracellular enzymatic conversion to free ascorbic acid
(AA). Importantly, free AA must be released by THDC before its skin
benefits can be realized. Thus, THDC is a precursor of AA.
It is well over 25 years, THDC (CAS # 183476-82-6) and Ascorbyl Tetraisopalmitate (CAS
#327594-27-4) were construed as being equivalent structures, in fact, they represent two
different chemistries with different CAS#s.
Tetrahexyldecyl Ascorbate
Ascorbyl Tetraisopalmitate
Structural Problem Resolved
While both are esters of ascorbic acid, THDC comes from reaction with 2-hexyldecanoic
acid whereas Ascorbyl Tetraisopalmitates derives from reaction with isopalmitic acid
(14-methylpentadecanoic acid). Two different fatty acids that when esterified with ascorbic
acid yield two unique products. This misnomer was finally corrected by Sytheon working in
close collaboration with the Personal Care Product Council (PCPC) and the Chemical Abstract
Services (CAS #provider).
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Skin Benefits Enhanced by Combining THDC with Acetyl Zingerone (AZ)
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Our research (International J Molecular Sciences, 22: 8756, 2021) provides new insights into the effects of THDC in human skin model and
how these effects can be modulated through combination with Synoxyl® AZ as a stabilizing antioxidant. Some benefits are given below:
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OCH3
Synoxyl® AZ
Inhibition of THDC Degradation (Solution) & Cell Viability (Keratinocytes)
Figure 1:
THDC degredation & its stabilization with
AZ under singlet oxygen
Figure 7: Production of Collagen I with THDC and THDC+AZ in fibroblasts
Figure 2:
Comparative H2O2 neutralizing activity of THDC+AZ and THDC
n CTL
Concentration (µg/mL)
FC (THDC/CTL)
1.29
1
0.76
Type I IFN genes
1.15
0.87
HHLA-C
HLA-A
XRCC5
PIN1
HLA-B
ITFITM1
YTHDF2
IFNAR1
IFI35
HERC5
IFNAR2
HLA-F
SAMHD1
NMI
IFIT2
NFKB2
IRF1
POLR2F
0.66
SOD2
PRMT1
RCC1
CARHSP1
SNRPD3
GSPT1
EBNA1BP2
EIF4A1
AKR1B10
YARS
CFB
PTGES
GNA15
RAC2
DNMT1
MCL1
FC (THDC/CTL)
n THDC • THDC+AZ
100
B
C
MMP7 Expression
MMP1 Expression
93.4
200
112.7
100
74.1
76
Concentration (µg/mL)
Figure 6:
THDC+AZ Opposes expression response of
THDC on Type I IFN genes
USS-increased genes
50
*P < 0.05
1.15
1
0.87
1.41
1
0.71
0.71
0.50
0.35
0.25
CTL
1.00
THDC + AZ Opposes Expression Responses of THDC on Proinflammatory Genes
n THDC • THDC+AZ
127.1
104.9
25
Figures 8A-8C: Down regulation of MMP expressions by THDC and THDC+AZ in EpidermFT
0.76
Figure 5:
THDC+AZ Opposes expression response of
THDC on "Unhealthy Skin Signature" Genes
112.4
98
200
102.3
THDC + AZ Significantly Inhibits MMP Expression & Activities
A
400
200
100
400
200
0
n THDC+AZ
200
40
0
n THDC
57
60
*
H2O2(+)
80
20
100
Concentration (µg/mL)
H2O2-treated cells (3 hrs)
H2O2(-)
Vaibility (%)
89.3
*
20
H2O2(+)
150
MMP14 Expression
n CTL
100
*P < 0.05
112
40
*
62.1
55.6
*
100
Figure 4:
Effects of THDC with and without AZ on viability of
KCs exposed to H2O2 stress — long-term
120
62.4
82.7
60
50
Concentration (µg/mL)
n THDC+AZ
100
80
100
0
H2O2-treated cells (0.5 hrs)
H2O2(-)
Vaibility (%)
120
98.6
10
Figure 3:
Effects of THDC with and without AZ on viability of
KCs exposed to H2O2 stress ­­­— short-term
n THDC
60
0
0.1
Time (Minutes)
n CTL
50
8
*P < 0.05
20
83.5
6
0.3
100
4
• 0%
2
• 0%
0
• 0%
20
• 2.4%
40
0.5
100
100
H2O2 Neutralization
75%
77%
78%
79%
81%
.07
• 6.4%
THDC remaining (%)
60
n THDC+AZ
*
CTL
— THDC+AZ (62.6) — THDC (849.6)
• THDC
Degradation with singlet oxygen
80
n THDC
*
Collagen I (%) (Media)
n THDC+AZ
THDC + AZ Augments Production of Collagen 1 Protein
THDC
0.93
THDC+AZ
0.78
CTL
1.00
THDC
1.41
THDC+AZ
0.55
CTL
1.00
THDC
0.93
THDC+AZ
0.26
Inhibition (IC50 values) of MMP Enzyme Activities by THDC + AZ vs THDC
Table 1: Inhibition (IC50 values) of MMP enzyme activities by THDC vs THDC+AZ
IC50 Values in mg/ml
Matrix
Metalloproteases
Functions (Visse & Nagase, Circulation Res, 92:827–839, 2003)
MMP-1
THDC
THDC+AZ
Ability to cleave interstitial collagens I, II, and III; Can also digest several other ECM and non-ECM molecules.
572.68
2.56
MMP-2
Digests type I, II, and III collagens and the denatured collagens & gelatins
914.66
0.87
MMP-3
Besides digesting ECM components, MMP-3 activates a number of pro-MMPs.
3.07
0.78
MMP-12
Besides elastin, it digests a number of other proteins.
0.48
0.41
Significance of Combining THDC with Acetyl Zingerone
Combination with AZ as a stabilizing antioxidant, THDC’s degradation can be slowed and levels of AA released can be increased, leading to activation of differentiation pathways favorable
to barrier function development (not discussed), overall increase in collagen production, repression of pro-inflammatory biomarkers and inhibition of MMP enzymes. The synergies observed
here emphasize the need to combine THDC with stabilizing antioxidants such as AZ as co-ingredients in all topical formulations
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