GlypureTM GL is a new active ingredient developed by Chemours as an alternative to glycolic acid for anti-aging benefits. It delivers glycolic acid to the skin in situ by generating it from its cyclic diester form, glycolide, which penetrates the skin more efficiently than glycolic acid and has a lower irritation potential. Studies show GlypureTM GL reduces wrinkles, improves skin elasticity and water content. Formulations developed include anhydrous solid stick and gel formats. Human studies demonstrate GlypureTM GL reduces wrinkles within 2 weeks with low irritation. It is a novel technology that can deliver glycolic acid's benefits more efficiently and gently than acidic AHAs.

1. Glypure™ GL:
A New Anti-Aging Active Ingredient
Meeting the Needs of Today’s
Consumer
The Chemours Company
Presented by Jeff Horsager at 2016 In-Cosmetics Global Paris:
https://www.in-cosmetics.com/archive/2016/innovation-presentations-
2016/is-Tuesday-12-April-2016/

2. What’s Critical for Consumers
in Today’s Market?
• More youthful looking skin
• Fast acting with long lasting effects
• And, of course, gentleness on the skin

3. Glycolic Acid – A Known Active

4. Glypure™ Cosmetic Grade Glycolic Acid
Glycolic acid is a well known, proven skin rejuvenation ingredient.
Products formulated with glycolic acid
demonstrate:
• Minimization of fine lines and wrinkles
• Improved skin elasticity
• More even skin tone
• Skin moisturization
New products continue to be introduced that realize the many
benefits of glycolic acid.

5. The Downsides to Glycolic Acid and
Other Alpha Hydroxy Acids (AHAs)…
Acidity
To see faster results, more acid and/or lower pH is
needed. It is the fully protonated acid that penetrates the
skin. But this increases the chance of skin irritation.
Perception
Many preconceived views exist based upon early use
patterns of AHA’s when technology was first introduced.
Namely, more must be better! Which resulted in irritation
cases and more negative reactions.
Sensitivity
Certain skin types have a higher level of sensitivity to
AHAs.

6. Glypure™ GL: A new active ingredient
Over two years of research have demonstrated
that Glypure™ GL is an active ingredient that:
➢ Delivers the benefits of an AHA without
applying acid to the skin
➢ Generates glycolic acid in situ upon
exposure to moisture in the skin
➢ More efficient in delivering active ingredient
➢ Offers lower irritation potential than AHAs
➢ Patent pending application

7. ➢Clear evidence of wrinkle reduction
10-person, 4-week study completed by AMA
Laboratories
Glypure™ GL: Current State of Development

8. 0
0.5
1
1.5
2
2.5
3
3.5
Baseline Week 1 Week 2 Week 4
3.23
0.00%
2.91
-9.80%
2.61
-19.08% 2.24
-30.55%
[SEr]
Study Time Points
Roughness Reduction [SEr] via Visioscan
➢ Decrease of fine lines and wrinkles
Glypure™ GL Development Results -
10-person, 4-week study recently completed

9. 80.000
90.000
100.000
110.000
120.000
130.000
140.000
150.000
160.000
170.000
Baseline Week 1 Week 2 Week 4
141.4
0.00%
158.33
11.98%
161.53
14.24%
168.73
19.33%
[RelativeNovameterUnits]
Study Time Points
Electroconductivity via Novameter
➢ Skin water content improvement
Glypure™ GL Development Results -
10-person, 4-week study recently completed

10. 0.290
0.295
0.300
0.305
0.310
0.315
0.320
Baseline Week 1 Week 2 Week 4
0.3017
0.00%
0.3039
0.71%
0.3046
0.95%
0.3152
4.48%
[R7]
Study Time Points
Skin Elasticity via Cutometer (R7)
➢ Elasticity improvement
Glypure™ GL Development Results -
10-person, 4-week study recently completed

11. Latest Research Results: Cumulative Irritation Study
August 5, 2020Title of Presentation 11
0
50
100
150
200
250
300
350
400
0 2 4 6 8 10 12 14 16
SummationScoreofPanelists
Time (Evaulation Days)
Summation of Panelists Scores vs Time
10% Glycolic Acid
10% Glypure™ GL
5% Glypure™ GL

12. Glypure™ GL – The New Active

13. Glypure™ GL – the Chemistry
Glypure™ GL is the cyclic diester of glycolic acid called glycolide. Glycolide is
formed by the dehydration reaction of two glycolic acid molecules into a ring
structure.
Equally important is the delivery technology to get the molecule in its cyclic
state into the stratum corneum for maximum efficiency and benefit.
H2O
HO OH
H2O
HO
OH
HO
OH

14. Glypure™ GL – Stages of Development

15. * indicates solvents that fall in the Hansen solubility
area highlighted above.
Solvents
Dimethylacetamide*
Acetonitrile*
Dimethyl isosorbide*
Dimethylformamide*
Ethyl Acetate
1-Butanol
1-Octanol
Isopropyl Palmitate
Ethanol
Methanol (Dried)
Benzyl Alcohol
DPM
Ethyl lactate
Ethanol
1.3 Propanediol
Tetrahydrofuran
Dimethicone
Stage 1. Determining the solubility and stability of
Glypure™ GL in various solvents.

16. O
O
O
O
H2O
HO
O
O
OH
O
HO
OH
O
G
F
A
B
D
E J
K
Stage 2. Measuring Glypure™ GL vs Glycolic Acid
Determining the stability of Glypure™ GL via 14C NMR Spectroscopy

17. Stage 3. Determining Glypure™ GL Stability Over Time
Demonstrated stability in dried DMI over several weeks.

18. ➢ Goal: Demonstrate ability to measure Glypure GL vs. glycolic acid in skin
systems
➢ TRI Princeton contracted to do a series of analytical and skin penetration
studies
➢ Study validated:
➢ ability to discern Glypure GL from glycolic acid (via ATR-FTIR)
➢ water vapor alone was enough to drive ring opening action
100% humidity 75% humidity 1 week after
75% humidity Pure component Glycolide
Shift demonstrating conversion of
glycolide to glycolic acid
Stage 4. Measuring Glypure™ GL Conversion to
Glycolic Acid (ATR-FTIR Fingerprint)
1766 cm-1
Glycolide
Measurement

19. Three means of Glypure™ GL control:
1. Concentration of Glypure™ GL
2. Choice of Solvent
3. Concentration of DMI
➢ Next step: ex vivo swine skin penetration studies.
➢ ATR-FTIR analysis via tape strips
Stage 5. Control of Glypure™ GL Skin Penetration

20. ➢ At equal concentrations glycolide penetrates the skin to a higher degree
than glycolic acid. (V = 10% glycolic acid, Z = 10% Glypure™ GL).
Sample
L
V
W
Z
Composition
66% Petroleum Jelly 32% Mineral Oil 2% Glycolide
90% DMI 10% Glycolic Acid
66% Petroleum Jelly 32% Mineral Oil 2% Lactide
90% DMI 10% Glycolide
Stage 5. Glypure™ GL vs Glycolic Acid

21. Standard industry desquamation testing carried out by
TRI Princeton.
Stage 6. Demonstration of Desquamation Properties
Sample
Preparation

22. Stage 6. Demonstration of Desquamation Properties
Desquamation
Experiment
Each desquamation
tapes were analyzed
at 4 different areas.
Examples of images
from desquamation
tapes.
After previous time periods the samples were removed from the desiccator and dried
at room temperature during 45 minutes before desquamation experiments.
Each groups were analyzed with 3 desquamation tapes
Dry Samples

23. 0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
1% 2.50% 5% 7.50% 10% 1% 2.50% 5% 7.50% 10%
control DMI Glycolide * Glycolic Acid *
24 hours
24 hours
Stage 6. Demonstration of Desquamation Properties
After 24 hours, Glypure™ GL had a peak effect at 5%
concentration vs glycolic acid peak effect at 7.5%
concentration.

24. Challenge: Develop a user friendly, anhydrous
formulation.
Two test formulations developed:
➢ Solid stick product. Much like a lipstick or chap stick
type product.
➢ A viscous gel formula dispensed via an airless pump
sprayer
Stage 7. Glypure™ GL Formulation Development

25. Stage 7. Glypure™ GL Formulation Development
Formulation #: 14G-15 (Stick)
Date: 1/5/2015
A1 Polyester-4 LexFeel 700 Inolex 52.50
A2 Propylene Glycol Dibenzoate Lexfeel Shine Inolex 5.00
A3 Caprylic/Caprylic Triglyceride Protachem CTG Protameen 8.00
A4 Oleyl Lactate Pelemol OL Phoenix Chemical 4.00
A5 Tocopheryl Acetate Tocopheryl Acetate NF Ruger 0.50
A6 Dimethicone DC 200/20 cst Dow Corning 1.00
A7 C18-36 Acid Triglyceride Syncrowax HGL-C Croda 12.00
A8 C18-36 Acid Glycol Ester Syncrowax ERL-C Croda 3.00
B1 Dimethyl Isosorbide Arlasolve DMI-LQ-(AP) Croda 10.00
B2 Glycolide Glypure™ GL Chemours 4.00
Total: 100.00
Chemours Formulation w/Glypure™ GL
Raw
Material Ingredient Trade Name(s) Supplier Wt %
"Night Stick"
Manufacturing Procedure
NOTE: All equipment must be cleaned, sanitized and abolutely dry. Any moisture intoduced into the
manufacturing process may destabilize the Glypure™ GL.
1. To the main vessel equipped with a prop mixer, add raw materials of Phase A (A1 thru A8).
2. Heat to 68°- 74°C and mix until items A7 & A8 are completely soluble. The mix should be
clear amber.
3. At 68°-74°C, add B1 and B2 and mix until the Glyp[ure™ GL is completely soluble.
4. Cool to 64°-68°C and pour into appropriate molds or components. (Processing thru a cooling
tunnel helps reduce/minimize cavitation during cooling.

26. Stage 7. Glypure™ GL Formulation Development
Formulation #: 14G-18 (Gel)
Date: 1/5/2015
A1 Dimethyl Isosorbide Arlasolve DMI-LQ-(AP) Croda 8.00
A2 Diisocetyl Dodecanedioate Liquiwax DICDD Croda 2.00
A3 Oleyl Lactate Pelemol OL Phoenix Chemical 5.00
A4 Glycolide Glypure™ GL Chemours 2.50
B1 Lauryl PEG/PPG 18/18-Methicone DC 5200 Formulation Aid Dow Corning 1.00
B2 Cyclopentasiloxane (and) Cyclohexasiloxane DC 345 Dow Corning 5.00
C1 Ethylene Brassylate Ethylene Glycol Brassylate TCI America 0.30
C2 Cyclopentasiloxane (and) Dimethicone DC 9546 Dow Corning 76.20
Crosspolymer (and) Dimethicone/
Vinyl Dimethicone Crosspolymer (and)
Dimethiconol
Total: 100.00
Chemours Formulations w/Glypure™ GL
Ingredient Trade Name(s) Supplier Wt %
Raw
Material
Manufacturing Procedure
NOTE: All equipment must be cleaned, sanitized and abolutely dry. Any moisture intoduced into the
manufacturing process may destabilize the Glypure™ GL.
1. To the main vessel equipped with an anchor or counter rotating blade equipped with side-
scrapers,
add raw materials A1 - A4.
2. Heat to 28°- 40°C and mix until item A4 is completely soluble. The mix should be clear.
3. Add items B1 and B2 and mix until a uniform opaque dispersion is observed.
4. Add items C1 and C2 and mix until completely uniform.
5. Cool to ambient temperature.

27. EpiDerm™ testing indicated Glypure™ GL formulations (5%
and 15%) were non-corrosive.
Human Repeat Insult Patch Testing (HRIPT) completed on
formulation indicating low irritation potential (AMA
Laboratories; New City, NY).
Stage 8. Glypure™ GL Human Panel Studies

28. Performed first human subject trials at AMA Laboratories to
look for wrinkle reduction on human subjects.
Study Background:
➢ Apply Glypure GL using solid stick formulation (4% active)
➢ Directed to use twice per day to maximize short term effect.
➢ Measured: baseline, 1 week and 2 week results
Stage 9. 2-Week Scouting Trial

29. ➢Clear evidence of wrinkle reduction
10-person, 4-week study completed by AMA Laboratories
➢ Directed to use stick formulation, once per day at night.
Glypure™ GL: Current State of Development

30. 0
0.5
1
1.5
2
2.5
3
3.5
Baseline Week 1 Week 2 Week 4
3.23
0.00%
2.91
-9.80%
2.61
-19.08% 2.24
-30.55%
[SEr]
Study Time Points
Roughness Reduction [SEr] via Visioscan
➢ Decrease of fine lines and wrinkles
Glypure™ GL Development Results -
10-person, 4-week study recently completed

31. 80.000
90.000
100.000
110.000
120.000
130.000
140.000
150.000
160.000
170.000
Baseline Week 1 Week 2 Week 4
141.4
0.00%
158.33
11.98%
161.53
14.24%
168.73
19.33%
[RelativeNovameterUnits]
Study Time Points
Electroconductivity via Novameter
➢ Skin water content improvement
Glypure™ GL Development Results -
10-person, 4-week study recently completed

32. 0.290
0.295
0.300
0.305
0.310
0.315
0.320
Baseline Week 1 Week 2 Week 4
0.3017
0.00%
0.3039
0.71%
0.3046
0.95%
0.3152
4.48%
[R7]
Study Time Points
Skin Elasticity via Cutometer (R7)
➢ Elasticity improvement
Glypure™ GL Development Results -
10-person, 4-week study recently completed

33. Latest Research Results: Cumulative Irritation Study
August 5, 2020Title of Presentation 33
0
50
100
150
200
250
300
350
400
0 2 4 6 8 10 12 14 16
SummationScoreofPanelists
Time (Evaulation Days)
Summation of Panelists Scores vs Time
10% Glycolic Acid
10% Glypure™ GL
5% Glypure™ GL

34. ➢ Novel technology to efficiently deliver a proactive form of
glycolic acid to the stratum corneum.
➢ No or very low acid content providing lower irritation
potential.
➢ Formulation will deliver the active ingredient more efficiently
than applying AHA directly on to skin.
➢ Multiple means of controlling degree of penetration.
➢ Two patent applications have been submitted. Patent
pending applications instruct how to deliver glycolide in an
anhydrous solvent system for the benefit in skin care
formulations.
Glypure™ GL: A New Skin Care Active Ingredient Meeting the
Needs of the Modern Consumer

35. Thank You You!
April 14, 2015
Glypure™ GL:
A New Anti-Aging Active Ingredient Meeting the
Needs of Today’s Consumer
35