The document describes a moisturizing composition comprising amino acids, urea, and polyols. It provides examples testing different combinations of these ingredients. Example 3 shows that a combination of proline, PCA, and urea provides significantly higher moisturization over 3 hours compared to the individual components alone or a baseline formulation. A design of experiment approach was used to determine optimal ingredient combinations and levels for prolonged moisturization of up to 3 hours.
The Fit for Passkeys for Employee and Consumer Sign-ins: FIDO Paris Seminar.pptx
Skin moisturizer
1. ~L_
FORM2
THE PATENTS ACT, 1970
(39 of 1970)
j
&
The Patents Rules, 2003
COMPLETE SPECIFIC ATION
(See sectIOn 10; rule 13)
1 Title of the inventIOn - AMINO ACID MOISTURISER
-
2 Apphcant(s)
---
(a) NAME ITe LIMITED
(b) NATIONALITY An Indian Company
(c) ADDRESS 37, J L Nehru Road,
Kolkata - 700 071,
State of West Bengal,
India
3 PREAMBLE TO THE DESCRIPTION
The 1olloVlng specification particularly describes the IIwentlOn and the manner III vvhlch It IS to be
performed
2. 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, Saglv and Marcus 2003, Rawlings, Canestrarl 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 IScharacterized 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
barner 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, Kataglrl, Sato
et al 2003, Rawlings 2003, Shwayder 2004, McLean and Irvine 2007, Barco and
'"
Glmenez-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
mOlstUriZatlon of skin ISthe 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 mOlstUriZatlon
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 MOlsturlsatlon at the molecular level, A W Rawlings
et al" JOURNAL OF COSMETIC DERMATOLOGY, 2007 June, 6(2) 75-82 Skin
2
3. Hydration A Review On Its Molecular Mechanisms Verdler-Sevraln, Sylvie MO, Bonte,
Frederic) US4724140A1 teaches use of a-amino aCid sulphoxldes 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 US2006275238A 1 teaches use of aniOniCpolyamlno 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
c.- - -- - -~--~ ~---~- ----
knowledge have gone ahead and developed a formulation that mOistUrizes the skin
uSing copolymers
Thus there ISneed 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 ISa need for continual Improvement In the time duration
to which that these benefits (like long term mOlstUriSatlon) 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 mOlstUrisatlon leading to a formulation that IS superior to
the marketed products for the same
Oblects 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 mOlstUriZatlon
A further object ISto prOVidea process of preparation of composition comprising amino
aCid and or amino aCid derivatives, urea and or ItS derivatives and polyols and or ItS
derivatives
3
4. 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 ItSderivatives In an amount
of 001 %to 10%
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%
, 0
to 10%, urea and/ or ItSderivatives 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 011 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 elastlcltyetc)
The novel combination of actives have been arnved at by extensive study of amino
aCids/derivatives solutions for the selection of the right amino aCids that would lead to
sustained mOlstUriSatlon over a period of 3 hours and then subsequently a design of
experiment was carned out for finding out the right levels of urea or ItS derivative along
With other known mOlsturlslng agents These combinations gave an extent of
mOlstUriSatlon that was surprisingly and significantly superior to their Individual
contributions
4
5. 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 ISselected from the 20 naturally/unnaturally occurnng amino aCids
as well as the derivatives thereof and combination thereof Within the scope of the
disclosure It should be appreciated that naturally occurnng amino aCids are L prefixed
whereas unnatural amino aCids are 0 prefixed The amino aCids used In this disclosure
are both from Land 0 groups The preferred amino aCids are proline, pyroliidone
carboxylic aCid, leucine, Isoleucine etc The preferred range of the amino aCid In the
present invention IS0 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 ItSderivatives present IS0 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 VIVOstratum 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 IJm to ensure that the measurement IS not Influenced by
capillary blood vessels
The percent Improvement of skin mOlsturlzatlon over baseline (I) was calculated based
on the follOWingequation (1)
J=(Rt-~)XI00{UTo) (1)
Ra UJ;
Where, Rc and RI are respectively the Corneometer values at time t=O and at time t UTo
and UTI are respectively the Corneometer reading for the untreated area (Baseline) at
time t = 0 and at time t
5
6. The active components (amino aCids/derivatives, urea/derivatives, polyols/glycerol) were
weighed and dissolved In water
The invention ISnow described by way of non-limiting Illustrative examples and figures
Brief Description of The Accompanying Drawings
Figure 1 MOlstUriZatlonefficacy (% 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 mOlstUriZatlon 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 ISprovided below In Table 1
Table 1 MOlstUriZatlonefficacy of the Individual amino aCids
IAmlno Corneometer Reading
IAclds/urea/polyols Baseline 5mms 1 hr 3 hrs
Serine (10%) 307 31 ~ 363 304
6
7. Alanine (10%) 292 328 373 326
Proline (10%) 289 407 469 401
Ornithine (10%) 256 249 285 256
Histidine (10%) 247 262 303 273
Glycine (10%) 271 291 31 7 281
Cltrullne (10%) 280 289 307 264
PCA (10%) 289 386 326 309
Urea (2%) 369 502 468 467
Glycerol (5 %) 253 472 431 422
Urea denvatlve (2 %) 298 472 420 41 0
Conclusion Proline, PCA Alanine and Senne showed significant mOlstunzatlon on a 3
hour time penod Of the three amino aCids, Proline, PCA and Senne 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 MOlstunzatlon efficacies of binary mixtures of amino aCids
% Improvement
NMF Combination (10%) 5 mlns 1 hour 3 hours
Senne+Prohne (1 1) 336 63 123
Senne+PCA (1 1) 159 09 00
Senne+Urea (1 1) 203 150 89
Prollne+PCA (1 1) 150 340 372
Prollne+Urea (1 1) 868 334 392
PCA+Urea (1 1) 462 193 271
7
8. Conclusion Prollne+PCA, Prollne+Urea and PCA+Urea show higher efficacy In 3-hour
mOlstUriZatlon
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 (pyroilidone carboxylic aCid) and urea In the
ratio of 85 10 1 (w/w/w) This process was carned 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 ISdepicted In Table 3 below
Table 3 MOlsturlzatlon efficacy of ternary mixture
% Improvement over Mean %Imp over
Time baseline baseline
5 mlns 130 121 139 130
1 hour 400 449 425 425
3 hours 61 8 51 3 655 595
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
8
9. 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 provlds 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 mOlstUrizatlon benefit
for up to three hours, a deSign of experiment (DOE) based approach was used based on
the mOlstUriZatlon 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 tn-vIVO hydration study of 35 prototypes (Ps) was carned 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
Proline 240
Actives % CompOSition In sample Formulation (P-32)
9
10. PCA 1 60
Urea 1 00
Hydroxyethyl urea 1 00
Protein hydrolysate 360
Glycerol 200
Cream base 884
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 mOlstunzatlon 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
% Improvement over baseline
Component Time
SL no
10 mms 1 hr 3 hrs
Proline 24% 1 161 6 1 -3 1
PCA 16% 2 84 -139 -7 2
Urea 1% 3 149 -8 7 -5 6
HEU 1% 4 143 23 -0 3
Hydrolysate 3 6% 5 13 1 -2 5 -1 8
Glycenn 2% 6 223 127 76
Multi (1+2+3+4+5+6) Mixture M 858 766 408
Mathematical Addition of Individual componen 892 -3 9 -104
10
11. From teh expenmental result It IS clear that mixing of all the ingredients has surpnslngly
synergistic effect on the skin hydration Multi-components mixture provides 40%
Improvement over baseline after three hours, whereas the mathematical addition of
%Improvement of mOlstunzatlon for Individual components gave -104% Improvement
over baseline after three hours
Example 6
The synergistic effect of proline, PCA, urea, hydroxyethyl urea and polyols was studied
and the expenmental data ISpresented In Flgure1
The results clearly demonstrate the synergistic effect of the combinatIOn of actives that IS
significantly supenor to the mathematical addition of the mOlstunzlng 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 cntena of Corneometer readings 28-3~ and for each
group and the results were analyzed The results are proVided In Table 6
Table 6 % Improvement In skin mOistUriZatlon (based on Corneometer reading)
during 12 hours for P-32, Market product and untreated
% Improvement
3
Time 1 hour hours 6 hours 8 hours 10 hours 12 hours
P-32 823 655 399 333 329 250
Current Market
product 532 530 239 86 105 1 0
Untreated 28 22 48 83 25 108
ConclUSion For one-hour time, P-32 shows 82% Improvement over baseline as
compared to 53 2% of market product
11
12. 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 BrlJ721®, 0375 gm sodium salt of ethylene dlamlne tetra
acetic aCid (EDTA) and 0375 Ultrez10® 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 (all phase preparation)
.. 1 gm BrlJ72®, 3 gm LLP, 075 gm Cetyl Alcohol, 1 gm
ArlamoIHD®, 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 (all 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
12
13. References
Harding, C R, S Long, et al (2003) "The cornified cell envelope an Important marker
of stratum corneum maturation In healthy and dry skin" International Journal of cosmetic
sCience 25(4) 157-167
Dykes, P J (2002) "What are meters measuring?" International Journal of cosmetic
sCience 24(4) 241-245
Saglv, A E and Y Marcus (2003) "The connection between In Vitro water uptake and In
VIVOskin mOlstUriZatlon " Skin research and technology official Journal of International
Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital
Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 9(4) 306-311
Rawlings, A V , 0 A Canestrarl, et al (2004) "Moisturizer technology versus clinical
performance" Dermatologlc therapy 17(1) 49-56
Rawlings, A V and C R Harding (2004) "MolstUriZatlon and skin barrier function"
Dermatologlc therapy 17(1) 43-48
Shwayder, T (2004) "Disorders of keratinization diagnosIs and management"
American Journal of clinical dermatology 5(1) 17-29
Lebwohl, M and L G Herrmann (2005) "Impaired skin barrier function In dermatologlc
disease and repair With mOlstUriZatlon" CUtiS,cutaneous mediCine for the practitioner
76(6 Suppl) 7-12
Rawlings, A V and P J Matts (2005) "Stratum corneum mOlstUrizatlon at the
molecular level an update In relation to the dry skin cycle" The Journal of Investigative
dermatology 124(6) 1099-1110
13
14. Wilson, D and D NIx (2005) "Evaluation of a once-dally mOlstunzer used to treat
xerosIs In long-term care patients" Ostomy/wound management 51(11) 52-60
Short, R W, J L Chan, et al (2007) "Effects of mOlstunzatlon on epidermal
homeostasIs and differentiation" Clinical and expenmental dermatology 32(1) 88-90
Lynde, C (2008) "Molstunzers for the treatment of Inflammatory skin conditions"
Journal of drugs In dermatology JDD 7(11) 1038-1043
Lln, S -Y , K -J Duan, et al (1995) "Direct or Indirect skin IIpld-ordenng effect of
pyrrolldone carboxylate sodium after topical treatment with "Biomedical Matenals &
Englneenng 5(1) 9-20
Kataglrl, C ,J Sato, et al (2003) "Changes In environmental humidity affect the water-
holding property of the stratum corneum and ItSfree amino aCid "Journal of
Dermatological SCience 31(1) 29-35
Rawlings, A V (2003) "Trends In stratum corneum research and the management of
dry skin conditions" International Journal of cosmetic sCience 25(1-2) 63-95
McLean, W H I and A D Irvine (2007) "Disorders of keratlnlSatlon from rare to
common genetic diseases of skin and other epithelial tissues" The Ulster Medical
Journal 76(2) 72-82
Barco, D and A Glmenez-Arnau (2008) "XerosIs una dlsfunclon de la barrera
epldermlca " Actas Dermoslfillograficas 99(9) 671-682
14