Transcript Safety and Efficacy of Gluconolactone Regimen on Sensitive

AHCare
Efficacy Verification
© Cognis Corporation 2001
Proof of Principle
• AHCare complexes compared to AHA
formulations are:
– less irritating
– less stinging
– at minimum of equivalent efficacy
• Glycolic/Lactic acid complexed with
arginine
– additional work is ongoing with other
complexes
© Cognis Corporation 2001
Proof of Principle Studies
 Objective: Compare AHCare complexes to
AHAs partially neutralized with conventional
agents to determine irritation profiles.
 Method: 14 Day Cumulative Irritation Test on
Humans (n=24); 14 consecutive days including
weekends with occlusive patches. (Hill Top
Research)
 Comparison of test materials to 0.9% NaCl
(negative control) and 0.1% SLS (positive control)
© Cognis Corporation 2001
Proof of Principle Studies
 Test materials: Aqueous solutions of glycolic
acid partially neutralized to pH 3.5 using (1)
arginine (amphoteric), (2) NaOH (alkali), (3)
Ammonium Hydroxide
 Conclusion: solution partially neutralized with
arginine is more mild than the glycolic acid
solutions partially neutralized with either
sodium hydroxide or ammonium hydroxide
© Cognis Corporation 2001
Cumulative Irritation Study
Mean Irritation Scores
20% Glycolic Acid, pH 3.5
3
NH4OH
2.5
NaOH
2
Arginine
0.9% Saline
1.5
0.1 SLS
1
0.5
Statistical Differences, p<0.05:
NH4OH vs. Arginine: days 2-11 and overall
NaOH vs. Arginine: days 2-6, 8-10 and overall
13
Da
y
11
Da
y
9
Da
y
7
Da
y
5
Da
y
3
Da
y
Da
y
1
0
© Cognis Corporation 2001
Cumulative Irritation Study
20% Glycolic Acid Solutions, pH 3.5
4 days to moderate irritation vs. 11 days
3
Mean Scores
2.5
2
NH4OH
Arginine
1.5
1
n=24
0.5
0.9% Salin
0.1 SLS
0.2
0.5
0.1
0.5
0.4
1.2
0.6
1.4
0.6
1.7
0.5
1.9
0.4
1.9
0.3
2.1
0.3
2.2
0.4
2
0.5
2.3
0.5
2.4
0.6
2.1
0.8
2.3
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Days of Patching
Statistical Differences, p<0.05.
NH4OH vs. Arginine: days 2-11 and overall
© Cognis Corporation 2001
Proof of Principle Studies
 Objective: Compare Amphoteric AHA
complexes (AHCare) to AHAs partially
neutralized with conventional agents to
determine the stinging profile.
 Method: Method: Lactic Acid Sting Test;
n=20 female ‘stingers’; (CPTC)
 Application to nasolabial fold and cheek area
 Screened panelists using 10% unneutralized lactic
acid
© Cognis Corporation 2001
Proof of Principle Studies
 Test materials: Comparison of lactic acid
(20%, aq.) partially neutralized to pH 3.5 using
(1) arginine (amphoteric), (2) NaOH (alkali),
(3) Ammonium Hydroxide
 Negative control - water
 Conclusion: Solutions containing arginine
induced significantly less stinging than those
containing sodium hydroxide and ammonium
hydroxide
 Arginine containing solutions were equivalent to
the negative control solution (water)
© Cognis Corporation 2001
Facial Sting Study
20% Lactic Acid Partially Neutralized to pH=3.5
*
0.8
Sting Sensation Averages
0.9
0.8
*
0.7
0.7
*
0.6
n=21
0.5
0.5
Arginine
NH4OH
0.4
0.4
0.3
0.2
0.1
0.1
0.1
0
0
10 seconds
2 minutes
5 minutes
0
8 minutes
*Statistical Significance p<0.05
© Cognis Corporation 2001
Facial Sting Study
20% Lactic Acid Partially Neutralized to pH=3.5
Sting Sensation Averages
1
0.8
n=21
0.6
0.4
0.2
Arginine
Water
0.3
0.2
0.1 0.1
0.2
0.1
0.1
0
0
10 seconds 2 minutes
5 minutes
8 minutes
No significant differences
© Cognis Corporation 2001
Facial Sting Study
AHCare (Arginine)
10% Glycolic Acid Adjusted to pH=3.5
1.6
1.45
1.46
Sting Sensation Averages
1.4
1.2
1.06
1
0.8
0.66
0.62
0.6
0.4
AHC
NH4OH
0.47
0.39
0.26
0.2
0
10 seconds
2 minutes
5 minutes
8 minutes
© Cognis Corporation 2001
Proof of Principle Studies
 Objective: Compare the efficaciousness of
Amphoteric AHA (AHCare) complexes to
AHAs neutralized using conventional, nonamphoteric agents
 Method: Dansyl Chloride Cell Turnover;
product application twice daily
© Cognis Corporation 2001
Dansyl Chloride
Study # 2, n=5
Solutions = 10% Glycolic Acid, pH 3.5
5
Untreated
3
Arginine
Solution
2
1
NH4OH
Solution
Day 9
Day 8
Day 7
Day 5
Day 2
0
Day 0
Fluorescence Scores
4
© Cognis Corporation 2001
Dansyl Chloride
Study 3, n=6
Cream = 10% Glycolic Acid, pH 3.5
Untreated
4
10%
G1/Arginine
Cream
3
10%
G1/NH4OH
Cream
2
1
8% G1
Marketed
Cream
Day 4
Day 3
Day 2
0
Day 0
Fluorescence Scores
5
© Cognis Corporation 2001
Dansyl Chloride
Study 4a, n=5
Solutions = 10% Lactic Acid, pH 3.5
Untreated
4
3
Arginine
Solution
2
NH4OH
Solution
1
Day 8
Day 5
Day 3/4
0
Day 0
Fluorescence Scores
5
© Cognis Corporation 2001
AHCare L 65
Cell Turnover Study - CPT
Dansyl Chloride Cell Turnover Study
10%
Fluorescence Intensity (arb. units)
10% AHCare™ L 65
3.0
2.5
2.0
1.5
Lactic
AHCare
Control
1.0
0.5
0.0
0
AHCare.opj (G1)
2
4
6
8
10
12
14
Day
AHCare equivalent to Lactic Acid
AHCare, Lactic Acid outperform placebo, p<0.05
© Cognis Corporation 2001
Proof of Principle Studies
 Objective: Determine the regenerating and
revitalizing activities on human fibroblasts
cultured in vitro of AHCare G-60.
 Method: Human dermal fibroblasts were
incubated in a standard medium of cell culture
with fetal calf serum. After an incubation for 3
days, the medium was exchanged for a
standard medium with or without FCS but with
AHCare G-60 and re-incubated for 3 days.
© Cognis Corporation 2001
C
e
l
l
u
l
a
r
P
r
o
t
e
i
n
s
Cellular Protein Growth
AHCare G-60
125
100
118
100
101
Control
0.10%
75
50
25
0
0.30%
% AHCare G-60
© Cognis Corporation 2001
Summary
• Glycolic acid amphoteric complexes:
– prototypes showed comparable efficacy to NH4OH
(non-amphoteric) prototypes
– creams showed comparable efficacy to marketed nonamphoteric cream
• Lactic acid formulations
– amphoteric complex prototypes showed comparable
efficacy to NH4OH (non-amphoteric) prototypes
© Cognis Corporation 2001