Field of Invention
The present invention relates to a novel composition, comprising amino acid or its
derivative, urea and or its derivative along with polyols and or its derivatives for
improving/repairing human skin conditions related to dryness and ageing.
Background and Prior Art
Water content of the epidermis plays vital roles in maintaining the water balance in the
body as well as the appearance, physical and biological properties of the skin (Harding,
Watkinson et al. 2000; Dykes 2002; Sagiv and Marcus 2003; Rawlings, Canestrari et al.
2004; Rawlings and Harding 2004; Shwayder 2004; Lebwohl and Herrmann 2005;
Rawlings and Matts 2005; Wilson and Nix 2005; 2007; Short, Chan et al. 2007; Lynde
2008). The skin is characterized as dry, when the total water content of stratum corneum
(SC) is <10%, where the SC becomes dysfunctional and brittle. There are several
factors and processes that determine the water homeostasis in skin, e.g. functional
barrier quality, water uptake into the epidermis, concentration of water-retaining
humectants, and environmental humidity. Disturbances in any sort in these
factors/processes lead to dry skin related disorder (Lin, Duan et al. 1995; Katagiri, Sato
et al. 2003; Rawlings 2003; Shwayder 2004; McLean and Irvine 2007; Barco and
Gimenez-Arnau 2008)(e.g. contact dermatitis, ichthyosis, psoriasis, dry skin and atopic
dermatitis).
One of the factors that are responsible for maintaining age related dryness and
moisturization of skin is the natural moisturizing factors, the major components of which
are amino acids and urea. Skin with inadequate amount of natural moisturizing factors
becomes dry, loses its integrity, resulting in an increase in skin pH. The moisturization
efficacy of the conventional moisturizing agents (e.g. glycerol, water, etc) is limited to
imparting short-term benefits.
Being a major part of natural moisturizing factors, amino acids act as potent moisturizing
agents in skin care formulations. (Progress in Dermatology, November 1994, Vol 103,
No. 5., 731-740, Stratum Corneum Moisturisation at the molecular level, A. W. Rawlings
et al,; JOURNAL OF COSMETIC DERMATOLOGY, 2007 June, 6(2)75-82 Skin
Hydration: A Review On Its Molecular Mechanisms. Verdier-Sevrain, Sylvie MD; Bonte,
Frederic). US4724140A1 teaches use of a-amino acid sulphoxides for improving skin
texture and claimed that these molecules can act as active hydrating actives.
US5002680A teaches that natural amino acids can be used as non-occlusive
moisturizing active for skin. In US5204099A amino acid copolymer is used as hydrating
agent. US2006275238A1 teaches use of anionic polyamino acid as one of the ingredient
in moisturizing formulation. The use of a combination of arginine, urea and glycerol for
hydration and combating skin dryness is mentioned. The inventor having prior
knowledge have gone ahead and developed a formulation that moisturizes the skin
using copolymers.
Thus there is need to develop composition to improve the skin conditions, especially skin
dryness related problems (e.g. age related drying, buffer skin pH, maintain NMF levels,
reduce flaking etc). Also there is a need for continual improvement in the time duration
to which that these benefits (like long term moisturisation) can be delivered to the
consumer.
Prior art does not teach the unique combination and the levels of these actives that have
surprisingly shown sustained moisturisation leading to a formulation that is superior to
the marketed products for the same.
Objects of the Invention
Thus an object of the present invention is to provide a composition comprising amino
acid and or amino acid derivatives, urea and or its derivatives and polyols and or its
derivatives that will deliver long-term moisturization.
A further object is to provide a process of preparation of composition comprising amino
acid and or amino acid derivatives, urea and or its derivatives and polyols and or its
derivatives.
Summary of The Invention
Thus according to one aspect there is provided a moisturizing composition comprising
amino acid and/or amino acid derivatives in an amount of 0.01 to 10%, urea and/ or its
derivatives in an amount of 0.01% to 4% and polyols and or its derivatives in an amount
of 0.01 %to10%.
According to another aspect there is provided a process for preparing a moisturizing
composition comprising amino acid and/or amino acid derivatives in an amount of 0.01%
to 10%, urea and/ or its derivatives in an amount of 0.01% to 4% and polyols and or its
derivatives in an amount of 0.01 % to 10% said process comprising steps of preparation
of water phase containing moisturizing actives and preparation of oil phase and finally
mixing of both the phases for producing the formulations. There is no limitation in the
number of phases, the process of the preparation holds good in multiphasic systems too.
Detailed Description of The Invention.
The present invention discloses a moisturizing composition such that it provides
moisturizing effect for over 12 hrs after single application. This is brought about by the
synergistic effect of the composition such that the effect of the individual components is
surpassed in the composition comprising the same.
The present invention, which deals with a novel way of improving the skin conditions,
especially associated with problems directly linked with skin dryness (e.g. age related
drying, skin pH, NMF levels, flaking etc). It improves age related drying of skin.
It also improves skin rheology (e. g. elasticity etc)
The novel combination of actives have been arrived at by extensive study of amino
acids/derivatives solutions for the selection of the right amino acids that would lead to
sustained moisturisation over a period of 3 hours and then subsequently a design of
experiment was carried out for finding out the right levels of urea or its derivative along
with other known moisturising agents. These combinations gave an extent of
moisturisation that was surprisingly and significantly superior to their individual
contributions.
The present invention can be used in any form of personal care (such as but not limited
to creams, lotions, gels, shampoos, soaps, wipes, face wash, serum) formulations.
The amino acid used is selected from the 20 naturally/unnaturally occurring amino acids
as well as the derivatives thereof and combination thereof. Within the scope of the
disclosure it should be appreciated that naturally occurring amino acids are L prefixed
whereas unnatural amino acids are D prefixed. The amino acids used in this disclosure
are both from L and D groups. The preferred amino acids are proline, pyrollidone
carboxylic acid, leucine, isoleucine etc. The preferred range of the amino acid in the
present invention is 0.01% to 9%, and most preferably 0.01% to 7%.
The derivatives of urea are selected from N, N' substituted urea, most preferably
hydroxyetyl urea. The preferred amount of urea and/or its derivatives present is 0.01% to
4%
The polyols are selected from alkyl polyols, preferably glycerol. The preferred range of
the polyols and or its derivatives in the present invention is 0.01% to 10%, and most
preferably 0.01% to 5%.
The moisture content of skin was measured with the Corneometer, which is well-
established device throughout the world for assessing in vivo stratum corneum hydration
by capacitance measurement. The instrument is based on the measurement of the
dielectric constant of the water and measured in the superficial layers of the stratum
corneum as deep as ~10 urn to ensure that the measurement is not influenced by
capillary blood vessels.
The percent improvement of skin moisturization over baseline (I) was calculated based
on the following equation (1).

Where, R0 and Rt are respectively the Corneometer values at time t=0 and at time t. UT0
and UTt are respectively the Corneometer reading for the untreated area (Baseline) at
time t = 0 and at time t.
The active components (amino acids/derivatives, urea/derivatives, polyols/glycerol) were
weighed and dissolved in water.
The invention is now described by way of non-limiting illustrative examples and figures
Brief Description of The Accompanying Drawings
Figure 1 Moisturization efficacy (% improvement) of the individual components in PR-32
(Proline (1), PCA (2), Urea (3), Hdroxyethyl urea (4), protein hydrolysate (5) and glycerol
(6)) and their mixture (M). The solutions were applied on the volar forearm and
Corneometer was used for measuring the moisture content in the skin for a duration of
three hours.
Figure 2 Synergistic moisturization efficacy (% improvement) of the individual
components in PR-32 (Proline, PCA, Urea, Hdroxyethyl urea, protein hydrolysate,
glycerol) vs mixture of Proline, PCA and Urea (M). The % improvement of individual
components were summed up and then plotted against % improvement obtained for the
mixture of the individual components (M). 20mL of the solution was applied on the volar
fore arm and Corneometer was used for measuring the moisture content in the skin for
duration of three hours.
Example 1
A composition is prepared with single amino acid. The active components (amino
acids/derivatives, urea/derivatives, polyols/glycerol) were weighed and dissolved in
water. The working of the amino acid in the composition is then tested in comparative
manner. The result is provided below in Table 1
Table 1 Moisturization efficacy of the individual amino acids

Conclusion: Proline, PCA Alanine and Serine showed significant moisturization on a 3
hour time period. Of the three amino acids, Proline, PCA and Serine were used for
further study of binary components
Example 2
Formulations are prepared with combination of two amino acids and their results are
assessed to evaluate the synergistic effect. The results are provided in Table 2 below
Table 2 Moisturization efficacies of binary mixtures of amino acids

Conclusion: Proline+PCA, Proline+Urea and PCA+Urea show higher efficacy in 3-hour
moisturization
So, a combination of Proline, PCA and Urea was taken as the combination for further
study
Example 3
A mixture was prepared with Proline, PCA (pyrollidone carboxylic acid) and urea in the
ratio of 85:10:1 (w/w/w). This process was carried out to compare the moisturizing
efficacy of the amino acids and urea as single component and multi component systems.
The mentioned ingredients in the specified proportion as multi component shows higher
efficacy than the mere addition of the single component hydration efficacy of the
individual ingredient. The method of preparation has been described in Example 1.
A baseline comparative formulation is prepared without the said combination of proline,
PCA and urea
The result is depicted in Table 3 below
Table 3. Moisturization efficacy of ternary mixture

It is evident from above that on a 3 hour time period the improvement caused by the
composition comprising proline, PCA and urea is about 60% while within 5 minutes the
improvement is 120% over the baseline composition. This clearly shows that the active
composition of present invention with proline, PCA and urea provides significant
improvement in moisturizing effect compared with that of baseline composition.
In Figures 1 and 2, effect of glycerol (Polyol) has been mentioned. Amino
acids/derivatives or polyols or urea/derivatives alone cannot provide sustained skin
hydration as observed in our study. Present study provids selection of chemicals based
on, but not limited to, their molecular weight, hydrogen bonding capacity and partition
inside the skin. Without the study it is not possible to arrive such combinations for
sustained skin hydration. A mere combination by trial and error method spans to a wide
response space.
Example 4
To determine the optimal combination of ingredients having a skin moisturization benefit
for up to three hours, a design of experiment (DOE) based approach was used based on
the moisturization data for the individual ingredients. The response surface method was
used for creating a predictive model of the relationship between the factors and
response based on predetermined factors responsible for achieving a desired response.
The response surface designs are used only when there is a clear knowledge about
factors that are used for the study and the main objective of which is to find out better
operating setting or compositions for the given factors to achieve a given response.
Based on the design of experiment, 35 prototypes (P's) were prepared using different
compositions of active ingredients (obtained from DOE) and a base formulation without
using any additional moisturizing actives. A sample formulation, which has been used in
subsequent study, has been given in Table 4.
An in-vivo hydration study of 35 prototypes (Ps) was carried out. This study comprised of
checking the Corneometer values of 5 panelists over the duration of 3 hours for each
prototype. The inclusion criterion for this study was that the initial Corneometer reading
on volar forearm within 28-36. In the subsequent part P should be considered as
synonymous to different formulations/prototypes.
Table 4: One of the sample compositions (P-32) obtained from DOE

Example 5
Demonstration of synergy by one of the composition obtained from DOE.
The aqueous composition of P-32 was used for demonstrating the existence of
synergistic effects of combined ingredients. Here, the moisturization efficacy of individual
components and their mixture were measured using Corneometer. The results are
presented in Table 5 and Figure 2.
Table 5: The synergistic effects of different components used in P-32

From teh experimental result it is clear that mixing of all the ingredients has surprisingly
synergistic effect on the skin hydration. Multi-components mixture provides 40%
improvement over baseline after three hours, whereas the mathematical addition of
%improvement of moisturization for individual components gave -10.4% improvement
over baseline after three hours.
Example 6
The synergistic effect of proline, PCA, urea, hydroxyethyl urea and polyols was studied
and the experimental data is presented in Figurel.
The results clearly demonstrate the synergistic effect of the combination of actives that is
significantly superior to the mathematical addition of the moisturizing efficacies of
individual components.
Example 7
The effect of the P 32 was compared with a current market product. Four panelists were
chosen randomly with the inclusion criteria of Corneometer readings 28-36 and for each
group and the results were analyzed. The results are provided in Table 6
Table 6: % Improvement in skin moisturization (based on Corneometer reading)
during 12 hours for P-32, Market product and untreated

Conclusion: For one-hour time, P-32 shows 82% improvement over baseline as
compared to 53.2% of market product
On a 12-hour time line, P-32 shows 25% improvement over baseline, whereas market
product shows 1 % improvement
Example 8
Preparation of moisturizing cream
• Mixture 1 (Water phase preparation)
¦ 1 gm Brij721®, 0.375 gm sodium salt of ethylene diamine tetra
acetic acid (EDTA) and 0.375 UltrezIO® were added in 31.6 gm
water and heated with occasional stirring upto 75°C, when it forms
a homogenous mixture. The mixture containing the moisturizing
actives (as provided in the Table 5) was added to the water phase
at 60°C. Temperature was measured using a thermometer.
• Mixture 2 (Oil phase preparation)
¦ 1 gm Brij72®, 3 gm LLP, 0.75 gm Cetyl Alcohol, 1 gm
ArlamolHD®, 1.5 gm DC 245®, 0.02 gm Propyl paraben and 0.08
gm Methyl paraben were weighed in a beaker and heated to 75°C
with occasional stirring, where it forms a clear solution.
Temperature was measured using a thermometer
Mixture 2 (Oil phase) was added in mixture 1 (water phase) under
homogenized condition at 5000rpm in a homogenizer. The
homogenization was continued till the temperature of mixture attained
30°C. The obtained mixture was stored in sealed container.
Example 9.
Method of evaluation
¦ Five panelist were selected randomly, who has initial Corneometer
reading on volar forearm within 28-36
¦ Sites were marked and 0.02 ml of the above test samples were
applied and rubbed till no residue left (20- 40 rubs).
¦ Corneometer measurement were carried out after designated
period of times
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We claim:
1. A moisturizing composition comprising amino acid and/or amino acid derivatives
in an amount of 0.01 to 10%, urea and/ or its derivatives in an amount of 0.01%
to 4% and polyols and/or its derivatives in an amount of 0.01 %to 10%.
2. Composition as claimed in claim 1 wherein amino acid and/or its derivative is
selected from pyrollidone carboxylic acid, alanine, arginine, aspartic acid, cystein,
glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine,
phenylalanine, serine, proline, threonine, tyrosine and valine.
3. Composition as claimed in any one of claim 1 or 2 wherein amino acid and/or its
derivatives are present in amount of 6 %.
4. Composition as claimed in claim 1 wherein urea and or its derivative is present in
amount of 2 %.
5. Composition as claimed in claim 1 wherein polyol and/or its derivatives is
selected from alkyl/cyclic polyols e.g glycerol, trehalose etc
6. Composition as claimed in claim 1 wherein polyol and/or its derivatives is present
in amount of 2 %
7. A process for preparing a moisturizing composition comprising amino acid and/or
amino acid derivatives in an amount of 0.01 % to 20 %, urea and/ or its
derivatives in an amount of 0.01 % to 4 % and polyols and or its derivatives in an
amount of 0.01 % to 10 %, said process comprising steps of as provide in
example 8.

A moisturizing composition comprising amino acid and/or amino acid derivatives in an amount of 0.01 to 10%, urea and/ or its derivatives in an amount of 0.01% to 4% and polyols and/or its derivatives in an amount of 0.01 %to 10%. The composition delivers long-term moisturization benefits