Cosmetic composition for the simultaneous treatment of the surface and deep layers of the skin, its use

A composition comprising a first dispersion of lipid vesicles capable of entering the deep layers of the skin and containing at least one first active substance capable of treating these deep layers, and a second dispersion of lipid vesicles capable of entering the surface layers of the skin and containing at least one second active substance, different from the first active substance, capable of treating these surface layers is found effective for anti-age, anti-wrinkle, depigmenting, nutrient, slimming, hydrating, anti-ache, antimycotic, anti-dermic and anti-psoriatic treatment.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to a composition for the cosmetic or 
dermatological treatment of imperfections or disorders of the skin, 
including the scalp. It relates more particularly to a composition of this 
type including at least one active substance conveyed by at least two 
separate types of lipid vesicles. 
The invention also relates to a use of this composition for the cosmetic 
treatment of the skin, to the use of this composition for the preparation 
of an ointment intended for the dermatological treatment of the skin and 
to a process of cosmetic treatment of the skin. 
2. Discussion of the Background 
Many examples are known of cosmetic or dermatological compositions intended 
for the treatment of the skin, which have one or a number of active 
substances that are suitable for the treatment of the skin, encapsulated 
in lipid vesicles or spherules (also called liposomes). 
Lipid vesicles or spherules are intended to mean particles made up of a 
membrane consisting of one or a number of concentric leaflets, these 
leaflets comprising one or more bimolecular layers of amphophilic lipids 
encapsulating an aqueous phase. The aqueous phase may contain 
water-soluble active substances and the bimolecular layers of amphophilic 
lipids may contain lipophilic active substances. 
These spherules generally have a mean diameter of between 10 and 5,000 
nanometres. 
Among the many published documents relating to this matter, it is possible 
to mention French Certificate of Addition 2408387, which describes a 
composition based on aqueous dispersions of ionic or nonionic lipid 
spherules encapsulating at least one active substance. More precisely, 
this document describes compositions containing at least two dispersions 
of spherules containing different active substances, with the aim of 
obtaining a mixed system. That is to say, a system where a first 
dispersion of spherules containing a first class of active substance is 
used in combination with a second dispersion of spherules containing 
another class of active substance, which enables both categories of 
substances to act simultaneously at the time of the treatment and possibly 
to obtain a synergistic effect that would not be produced if these two 
classes of substances were made to act successively and separately. 
The inventors have has now developed a cosmetic or dermatological 
composition permitting the simultaneous action of two different active 
substances and, furthermore, enabling these active substances to act in 
different regions of the skin, that is to say in the surface layers and in 
the deep layers of the skin, thereby very markedly enhancing the 
effectiveness of these compositions and the complementary or synergistic 
effect of the active substances used. 
The inventors have also developed a cosmetic or dermatological composition 
enabling the same active substance to act simultaneously in the surface 
layers and in the deep layers of the skin, ensuring a more complete and 
therefore more effective treatment of the disorder from which it suffers. 
Now, there are many situations in which skin disorders involve both a 
threat to the surface layers of the skin and accompanying change in the 
deeper layers of the latter. 
It is well known that the skin consists of surface layers, the stratum 
corneum, and of deep layers, the living epidermis and the dermis. However, 
in the prior art it was not known to deliver such an active substance 
specifically into the surface layers and, simultaneously, the same or some 
other active substance into the deep layers. 
SUMMARY OF THE INVENTION 
The subject of the present invention is a cosmetic or dermatological 
composition for the simultaneous treatment of the surface and deep layers 
of the skin comprising 
i) a first dispersion of lipid vesicles capable of entering the deep layers 
of the skin and containing at least one active substance capable of 
treating these deep layers; and 
ii) a second dispersion of lipid vesicles capable of entering the surface 
layers of the skin and containing at least one active substance capable of 
treating these surface layers, 
wherein when said active substance contained in said first dispersion and 
said active substance contained in said second dispersion provide 
different effects, 
a) the vesicles of the first dispersion are not based on hydrogenated egg 
lecithin, cholesterol and dicetyl phosphate when the vesicles of the 
second dispersion are based on soya lecithin, cholesterol and dicetyl 
phosphate, or 
b) the vesicles of the first dispersion are not based on diglycerol oleate, 
cholesterol and dicetyl phosphate when the vesicles of the second 
dispersion are based on triglyceryl cetyl ether, cholesterol and dicetyl 
phosphate. 
According to a particular embodiment, the active substances present in the 
first vesicle dispersion and in the second are the same.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The Applicant has employed a means for sorting the vesicles, enabling a 
person skilled in the art to select easily the lipid vesicles capable of 
conveying the active substance into the deep layers of the skin, which are 
called depth vesicles, and those capable of conveying the active substance 
into the surface layers of the skin, called surface vesicles. 
This sorting is performed on the basis of the diffusion constant D of a 
probe introduced into the vesicles. This probe is ASL 
[N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidyl) 
-N-dimethyl-N-hydroxyethylammonium iodide] of formula: 
##STR1## 
The vesicles for which the diffusion constant D of the probe in the stratum 
corneum is &gt;1.times.10.sup.-7 cm.sup.2 s.sup.-1 are the vesicles capable 
of entering the deep layers of skin. 
The vesicles for which the diffusion constant D of the probe in the stratum 
corneum is &lt;1.times.10.sup.-7 cm.sup.2 s.sup.-1 are the vesicles capable 
of conveying the active substance into the surface layers of the skin. 
The vesicles of the first category, called depth vesicles, are generally in 
a fluid state at ambient temperature (around 20.degree. C.) and those of 
the second category, called surface vesicles, are generally in a gelled 
state at ambient temperature. The means for recognizing the state of the 
vesicles consists in determining the phase transition temperature 
(lameliar fluid-gel) of the main lipid of which their membrane consists, 
by differential thermal analysis (DTA). 
Other characteristics of these vesicles relate to their ability to deliver 
the active substance more or less in depth in the skin. This is 
particularly the case with the encapsulation ratio. 
Glucose is a marker traditionally employed for this type of determination 
(cf. especially "Liposomes, a practical approach" by R.R.C. New, IRL Press 
(1990), p. 125-136). 
The encapsulation ratio is expressed as the volume of glucose solution 
encapsulated in the vesicles, measured in .mu.l in relation to the unit 
weight (mg) of the lipids of which the membrane consists. This 
encapsulation ratio is determined immediately after the stage of 
separation of the free glucose and of the encapsulated glucose (T.sub.o) 
and twenty four hours after this separation (T.sub.24 hours). 
The difference between these 2 successive determinations illustrates the 
permeability of the vesicles for the encapsulated glucose, and this can 
also be called their encapsulation potential. 
The first category of vesicles (delivering the active substance into the 
deep layers of the skin) has a high potential for encapsulation of the 
water soluble small molecules traditionally modelled by glucose, this 
encapsulation potential being maintained for at least 24 hours. The second 
category of vesicles (delivering the active substance into the surface 
layers of the skin) does not retain glucose in the encapsulated state for 
the same time. 
The main lipids constituting the vesicles of the first category (active 
substance delivered in depth) include at least one linear and saturated 
fatty chain of length ranging from 16 to 30 carbon atoms, such as 
hydrogenated phospholipids (from plants or from egg), saturated synthetic 
phospholipids such as dipalmitoylphosphatidylcholine, or the alkyl ethers 
or alkyl esters of polyols containing one, two or three fatty chains per 
molecule. These lipids are employed by themselves or mixed. 
The main lipids constituting the vesicles of the second category (active 
substance delivered at the surface) are chosen in particular from the 
group including ionic lipids such as especially the plant- or egg-based 
natural phospholipids containing unsaturated fatty chains of 16 to 30 
carbon atoms, nonionic lipids such as the alkyl ethers or alkyl esters of 
polyols containing one or several fatty chains per molecule, including at 
least one fatty chain of length shorter than 16 carbon atoms, such an 
lauryl polyglyceryl-6-cetearyl glycol ether, described in detail in Patent 
Application FR 92-09603 filed by L'Oreal. 
It is possible, in a known manner, to incorporate into the lipid phase 
constituting the lipid membrane of the vesicles at least one additive 
chosen from the group consisting of sterols (phytosterols, cholesterols, 
polyoxyethylenated phytosterols), long-chain alcohols, diols and triols 
(phytanetriol), long-chain amines and their quarternary ammonium 
derivatives, phosphoric esters of fatty alcohols and their alkali metal 
salts (Na, K) such as dicetyl phosphate, sodium dicetyl phosphate, alkyl 
sulphates (sodium cetyl sulphate), alkali metal salts of cholesterol 
sulphate or of cholesterol phosphate, the sodium salt of phosphatidic 
acid, lipoaminoacids and their salts such as sodium acylglutamates. 
As an example of vesicles of the first category (delivering the active 
substance into the deep layers of the skin) there may be mentioned the 
vesicles obtained from the following lipids (CTFA name): 
A/cholesterol/casein lipoamino acid, especially in a weight ratio of 
45/45/10 (where A is a triglyceryl cetyl ether marketed by the Chimex 
company under the name CHIMEXANE NL); 
B/cholesterol/dicetyl phosphate, especially in a weight ratio of 60/35/5 
(where B is a mixture of triglyceryl mono-, di-and tricetyl ethers 
marketed by the Chimex company under the name CHIMEXANE NT); 
Span 40 (from ICI) or sorbitan palmitate/cholesterol/sodium acylglutamate 
(sold by the Ajinomoto company under the name HS 11), especially in a 
weight ratio of 47.5/47.5/5; 
PEG 8 stearate/cholesterol/sodium acylglutamate, especially with a weight 
ratio of 47.5/47.5/5 (where PEG 8 stearate is polyethylene glycol 
containing 8 ethylene oxide units marketed by the Unichema company under 
the name STEARATE PEG 400); 
PEG 8 stearate/cholesterol/phytanetriol/sodium acylglutamate, especially 
with a weight ratio of 47.5/20/27.5/5; 
Hydrogenated lecithin/phytosterol polyoxyethylenated with 5 ethylene oxide 
units, especially in a weight ratio of 60/40; 
Methyl glucose distearate polyoxyethylenated with 20 ethylene oxide 
units/cholesterol/sodium acylglutamate, especially in a weight ratio of 
45/45/10 (the distearate being, for example, sold under the name GLUCAM E 
9 20 distearate by Amerchol); 
A/cholesterol/dicetyl phosphate especially with a weight ratio of 
47.5/47.5/5 (where A is a triglyceryl cetyl ether marketed by the Chimex 
company under the name CHIMEXANE NL); 
Diglyceryl distearate (for example that sold by Nihon under the name EMALEX 
DS G2)/cholesterol/sodium acylglutamate, in a weight ratio of 45/45/10; 
Sucrose mono- and distearate (for example that sold by Grillo under the 
name GRILLOTEN PSE 141 G)/cholesterol/sodium acylglutamate, especially in 
a weight ratio of 45/45/10; 
Tetraglyceryl tristearate (for example that sold by Nikkol under the name 
TETRAGLYN 3S)/cholesterol/sodium acylglutamate, especially in a weight 
ratio of 45/45/10. 
The vesicles obtained from the following lipids may be mentioned an 
examples of vesicles of the second category (delivering the active 
substance into the surface layers of the skin): 
sunflower lecithin; 
NATIPIDE II (soya lecithin/ethanol/water in a weight ratio of 20/16/64, 
marketed by Nattermann); 
C (soya lecithin/cholesterol/propylene glycol in a weight ratio of 
60/20/20, marketed by Nattermann under the name NAT 50 PG); 
D/dimyristyl phosphate especially in a weight ratio of 95/5 (where D is a 
lauryl polyglyceryl-6-cetearyl glycol ether marketed by Chimex under the 
name CHIMEXANE NS). 
Table I below gives, for some vesicles obtained from the above lipids, the 
diffusion constant D of ASL in the stratum corneum and in the 
epidermis/dermis, as well as the glucose encapsulation ratio and the phase 
transition temperature of the main lipid constituting the membrane. The 
diffusion constant was measured for an encapsulated ASL concentration of 
0.35% by weight based on the total weight of the composition. 
TABLE I 
__________________________________________________________________________ 
Diffusion coefficient 
D in 10.sup.-7 cm.sup.2 s.sup.-1 
Degree of encapsulation 
Proportions 
in the in the of glucose in 
Phase transition 
Ref. 
LIPID SYSTEMS 
% by weight (mg) 
stratum corneum 
epidermis/dermis 
T.sub.o 
T.sub.24h 
temperature in 
.degree.C. 
__________________________________________________________________________ 
1st type = deep down 
1 A/cholesterol/casein 
45/45/10 42 5 7.5 6.8 50 
lipoamino acid 
(67.5/67.5/15) 
2 B/cholesterol/dicetyl 
60/35/5 58 2 11.1 11.1 54 
phosphate (90/52.5/7.5) 
3 Span 40/cholesterol/ 
47.5/47.5/5 
42 2 13.8 13.8 50 
sodium acylglutamate 
(71.25/71.25/7.5) 
4 PEG 8 stearate/ 
47.5/47.5/5 
42 2 14.4 14.4 55 
cholesterol/sodium 
(71.25/71.25/7.5) 
acylglutamate 
5 PEG 8 stearate/ 
47.5/20/27.5/5 
8.3 2.5 4.1 3.0 55 
cholesterol/phytanetriol/ 
(71.25/30/41.25/7.5) 
sodium acylglutamate 
6 Hydrogenated lecithin/ 
60/40 8 2 6.0 4.8 80 
polyoxyethylenated 
(90/60) 
phytosterol 
2nd type = surface 
7 Sunflower lecithin 
100 0.3 0.2 1.6 0 &lt;0 
(150) 
8 Natipide II (soya 
20/16/64 0.4 0.2 0.4 0 &lt;0 
lecithin/ethanol/water) 
(30/24/96) 
9 C (soya lecithin/ 
60/20/20 0.25 0.1 1.8 0 &lt;0 
sterols/propylene glycol) 
(90/30/30) 
10 D/dimyristyl phosphate 
95/5 0.3 0.2 2.0 0 14 
(142.5/7.5) 
__________________________________________________________________________ 
The measurement of the diffusion constant D is performed by a combination 
of two methods employing a paramagnetic probe, ASL: on the one hand, 
one-dimensional and periodic electron paramagnetic resonance (EPR) and, on 
the other hand, kinetic EPR imagery. These two methods are described in 
the following papers: "Evaluation of liposomes as drug carriers into the 
skin by one-dimensional EPR imaging" by V. Gabrijelcic et al., 
International Journal of Phamaceutics, 62 (1990) p. 75-79, Elsevier, and 
"Liposome entrapped molecules penetration into the skin measured by 
nitroxide reduction kinetic imaging" by V. Gabrijelcic et al., Periodicum 
Biologorum, vol. 93, No. 2, p. 245-246 (1991). 
The measurement of the encapsulation ratio is performed as described in 
"Liposomes, a practical approach" by R. R. C. New, IRL Press (1990), p. 
125-136, and that of the phase transition temperature as described above. 
The compositions which are the subject of the present invention find their 
application in a large number of cosmetic or dermatological treatments of 
the skin, including the scalp, such as, for example: hydration, nutrition, 
protection, firming-up, anti-aging, anti-wrinkle, slimming, 
depigmentation, anti-acne and the treatments of mycoses, of dermatitis and 
of psoriasis. 
Thus, another subject of the invention is a use of the composition defined 
above for the cosmetic treatment of the skin, of the face and/or of the 
body and for the preparation of an ointment intended for the treatment of 
skin diseases. A further subject of the invention is a process for 
cosmetic treatment of the skin, consisting in applying the above 
composition to the skin. 
The active substances encapsulated in the vesicles of first and second 
types, of course, on the intended application. 
A number of active substances are advantageously employed simultaneously in 
each type of vesicle which have the same function and/or which exert the 
same type of action on the skin, at the surface and in depth; the surface 
and depth active substances are therefore complementary. 
In particular, the active substances of the first and second type of 
vesicle are either anti-aging active substances or anti-wrinkle active 
substances or hydrating or moisturizing or slimming active substances, or 
depigmenting active substances or substances active against free radicals 
(radical oxygen species) or anti-irritation active substances or nutrient 
active substances or protective active substances or restructurizing 
active substances or firming-up active substances or anti-acne active 
substances or exfoliating active substances, or emollient active 
substances or else active substances treating skin diseases such as 
mycoses, dermatitis, psoriasis and the like. 
By way of example, in the case of hydration, surface vesicles are used in 
combination with one or a number of moisturizers (or hydrating agents) 
such as glycerine or urea and the depth vesicles in combination with one 
or a number of precursor agents for the biosynthesis of structural 
proteins, such as hydroxyproline, collagen peptides and the like. 
In the case of slimming, at least one keratolytic agent or an 
alpha-hydroxyacid such as salicylic acid or 5-n-octanoylsalicylic acid 
encapsulated in the surface vesicles is used for example in combination 
with at least one liporegulating agent such as caffeine, encapsulated in 
the depth vesicles. 
In the case of depigmentation, at least one keratolytic agent encapsulated 
in the surface vesicles is combined, for example, with at least one 
depigmenting agent such as especially a tyrosinase inhibitor (kosic acid), 
encapsulated in the depth vesicles. 
In the case where a protection is intended against damage by radical 
species or singlet oxygen, it is possible, for example, to use an agent 
against ROO.sup.. radicals (vitamin E) or against singlet oxygen for the 
surface treatment in combination with an agent against O.sub.2.sup.. free 
radicals (superoxide dismutase) and against OH.sup.. radicals (sugar, 
caffeine) for the depth treatment. 
Similarly, in the case of an anti-aging action, moisturizers (sodium 
lactate), sunscreens, alpha-hydroxyacids (fruit acids) or 
surface-restructuring agents, encapsulated in surface vesicles, may be 
used in combination with peptides (especially soya peptide extracts), 
enzymes for repairing the DNA, vascular protective agents or phospholipids 
extracted from the octopus, which are rich in oligoelements and in C20:4, 
20:5, 22:4, 22:5 and 22:6 polyunsaturated fatty acids, encapsulated in 
depth vesicles. 
If nutrition of the skin is intended, it is possible, for example, to use 
at least one active substance such as sugars or fatty acids for a surface 
action in combination with at least one active substance such as 
especially vitamins and amino acids for an action in depth. 
If the treatment of mycoses is envisaged, it is possible to use active 
substances for acting at the surface, such as, for example, exfoliants, in 
combination with anti-mycotic agents for acting in depth. The active 
substances may represent from 0.02 to 5% of the total weight of the 
composition. The compositions according to the invention may introduce all 
the galenic forms normally employed for a topical application, such as 
aqueous gels, emulsions, lotions, ointments, serums and more particularly 
oil droplets dispersed by the vesicles, as described in French Patents 
FR-A-2,485,921 and FR-A-2,490,504. 
In a known manner, in addition to the vesicles in the compositions of the 
invention it is possible to find a vegetable, mineral, silicone or 
synthetic oil dispersed in an aqueous phase and also hydrophilic adjuvants 
such as gelling agents, stabilizers, opacifiers, lipophilic adjuvants such 
as perfumes, pigments and fillers, as described in the above French 
patents. The dispersed oil may represent from 2% to 40% by weight based on 
the total weight of the composition, and the adjuvants may represent, in 
all, from 0.1% to 10% by weight. 
Another subject of the invention is the use of the composition defined 
above and a process for the anti-aging, anti-wrinkle, depigmenting, 
nutrient, slimming, hydrating and/or anti-acne treatment of the skin; this 
process consists in applying to the skin, locally or over the whole face 
and/or body, a composition as defined above. 
The invention also relates to the use of this composition for the 
preparation of an ointment intended for the treatments of skin diseases, 
such as the treatments of the skin against mycosis, dermatitis and 
psoriasis. 
The total weight of vesicle contained in the composition is preferably from 
1 to 90 wt. %, more preferably from 5 to 70 wt. %, most preferably from 5 
to 20 wt. % based on the total weight of the composition. 
The ratio of the amount of vesicles of the first dispersion type which are 
capable of penetrating into the deep layers to the second dispersion type 
which are capable of penetrating into the surface layers is preferably 
from 1:9 to 9:1, more preferably from 3:7 to 7:3, most preferably from 4:6 
to 6:4. 
Within the context of the following examples the term qs 100 g is an amount 
needed to bring the total amount of the composition to 100 g. 
Other characteristics and advantages of the invention will emerge better 
from the description which follows, given by way of illustration and 
without any limitation being implied. 
A) Preparation of lipid vesicles containing ASL 
The lipid constituents of the wall of the vesicles are weighed and 
dissolved in 10 ml of methanol. The alcoholic solution is then poured into 
a 50 ml ground-joint round bottom flask which is then placed on a rotary 
evaporator so that the content is thermostatted at a temperature of 
30.degree. C. The evaporation is continued until a dry film of lipids is 
deposited on the walls of the flask. 
3 ml of a 0.01 molar aqueous solution of ASL are then added to the flask, 
which is then shaken manually for approximately 10 minutes, either at 
ambient temperature (20.degree. C.) in the case of the vesicles of Table I 
which are given references 7 to 10, or at a temperature of 50.degree. C. 
in the case of the vesicles given references 1 to 6 in Table I. The 
mixture is then allowed to equilibrate at ambient temperature for 2 hours 
and the dispersion is then placed in a dialysis bag and in contact with 
500 ml of distilled water. The dialysis is performed overnight. After one 
night the water is changed and the dialysis is continued for 4 hours 
longer. 
A cotton thread 0.3 mm in thickness is then soaked in the vesicle 
dispersion and then placed in contact with a skin section originating from 
a porcine ear freshly recovered from a slaughterhouse intended for the 
supply of food. 
The ear sample is rinsed with water and cut into slices 1 mm in thickness, 
5 mm in width and 10 mm in length, and is then placed in a holding cell. 
Measurements of diffusion of ASL in the skin are performed within the 24 
hours following the sampling of skin. 
B) Preparation of the cosmetic composition 
1. Preparation of vesicles of first type (distributing in depth) 
The (depth) vesicles are prepared by a usual method for joint melting of 
the chosen membrane constituents (see Table I). Thus, the membrane 
constituent which has the lowest melting point T.sub.m is melted; the 
other membrane constituents are added and then homogenization is carried 
out with moderate stirring and, finally, partial hydration is carried out, 
the melting temperature T.sub.m defined above being maintained. 
An aqueous solution of at least one active substance for the treatment in 
depth is added to the paste obtained. A turbine is switched on for 1 h 30 
min in order to have good hydration, the temperature T.sub.m being 
maintained. One or a number of other active substances for the treatment 
in depth are added to the reaction mixture, which in homogenized and the 
temperature of the mixture is lowered to ambient temperature (20.degree. 
C). 
2. Preparation of vesicles of second type (distributing at the surface) 
An aqueous solution of one (or more) second active substance(s) for the 
surface treatment is introduced at ambient temperature (20.degree. C.) and 
using simple stirring, into the chosen mixture of constituents which are 
to form the membrane of the surface vesicles (see Table 1). Surface 
vesicles encapsulating the second surface active substance are thus 
obtained. 
3. Preparation of the "double liposomes" composition 
The fatty phase of the composition is added to the mixture containing the 
depth vesicles and is dispersed with stirring (at ambient temperature). 
The reaction mixture obtained is then mixed with that containing the 
surface vesicles. Adjuvants are then optionally added, such as 
stabilizers, a gelling agent which may be neutralized, if need be, with a 
base (triethanolamine or sodium hydroxide) and perfumes and the like. 
The product obtained is in the form of a soft and unctuous white cream 
which can be employed in the cosmetic and/or dermatological field 
depending on the nature of the chosen active (surface and depth) 
substances. 
Individual examples of cosmetic composition in accordance with the 
invention are given below. The compositions are given in % by weight. 
EXAMPLE I: Depigmenting, double liposomes cream 
______________________________________ 
Depth vesicles: 
A/cholesterol/dicetyl phoshate in a weight 
3% 
ratio of 47.5/47.5/5 
Kojic acid (active substance) 
0.5% 
Surface vesicles: 
D/dimyristyl phosphate in a weight ratio 
3% 
of 95/5 
Salicylic acid (active substance) 
0.3% 
fatty phase: 
Vegetable or mineral oils 
10% 
Silicone oil 5% 
Caffeic acid (active substance) 
0.7% 
aqueous phase: 
Glycerol 3% 
Carboxyvinyl polymer (gelling agent) 
0.4% 
Triethanolamine q.s. pH = 6 
Demineralized water q.s. 100% 
______________________________________ 
EXAMPLE 2: Depigmenting, double liposomes cream 
This cream differs from that of Example 1 in the use of 
5-n-octanoylsalicylic acid instead of salicylic acid as the active agent 
in the surface vesicle. 
EXAMPLE 3: Anti-wrinkle, double liposomes cream 
______________________________________ 
Depth vesicles: 
PEG 8 stearate/cholesterol/sodium 
3% 
acylglutamate in a weight ratio of 
47.5/47.5/5 
Soluble collagen (active substance) 
1% 
Soya hydrolysed protein (active substance) 
0.1% 
Surface vesicles: 
NAPITIDE II marketed by the Natterman 
3% 
company 
Tocopherol acetate (active substance) 
0.5% 
Glycerine (active substance) 
4.5% 
Sodium lactate (active substance) 
0.35% 
Fatty phase: 
Vegetable oils 13% 
Karite butter 4% 
Cyclomethicone 4.% 
Aqueous phase: 
Stabilizer 1.3% 
Perfume 0.4% 
Carboxyvinyl polymer (gelling agent) 
0.4% 
Sodium hydroxide q.s. pH = 6 
Water q.s. 100% 
______________________________________ 
Obviously, numerous modifications and variations of the present invention 
are possible in light of the above teachings. It is therefore to be 
understood that within the scope of the appended claims, the invention may 
be practiced otherwise than as specifically described herein. 
This application is based on French Patent Application 93/15863, filed with 
the French Patent Office on Dec. 30, 1993, the entire contents of which 
are hereby incorporated by reference.