United States Patent 7,485,315
L'Oreal S.A. (Paris, FR)
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Summary
The invention relates to a process for dissolving at least one compound of low solubility in water, the said process comprising the essential step of mixing the compound of low solubility with at least one lipophilic amino acid derivative. The invention also relates to a cosmetic or dermatological composition comprising, in a physiologically acceptable medium, at least one compound of low solubility and at least one lipophilic amino acid derivative. Among the compounds of low solubility that are especially included are aminophenol derivatives, salicylic acid derivatives, 2-amino-4-alkylaminopyrimidine 3-oxide derivatives and DHEA, and also its chemical or metabolic derivatives and precursors.
The examples that follow
illustrate the invention without limiting its scope.
1--Simple Solubility
Protocol: The derivatives of low solubility in water are weighed out and placed
in a sealed pill bottle. The required amount of solvent is added. The
suspension is stirred (magnetic stirring) at 80o C. for not more than 1 hour.
The dissolution or non-dissolution of the active agent and the change over time
are reported in the table below.
The non-solubility of the active agent in the solvent is characterized
macroscopically by a precipitate or just a cloudy solution, and microscopically
by the presence of crystals.
The solvent used is isopropyl N-lauroylsarcosinate.
|
|
Solubility in Water at 25oC |
δa J1/2cm-3/2 |
|
N-ethoxycarbonyl para-aminophenol |
<1% |
16.1 |
|
N-cholesteryloxycarbonyl-para-aminophenol |
|
8.7 |
|
(3β, 5α, 25R)-3- hydroxyspirostan- 12- one (hecogenin acetate) |
|
6.7 |
|
5 -spirostene-3β-ol (diosgenin) |
|
8.6 |
|
5 -n-octanoyl-salicylic acid |
|
11.3 |
|
DHEA |
|
9.9 |
|
2-amino-4-dodecyl- aminopyrimidine 3-oxide |
|
8.9 |
Formulation Examples – Emulsions for Skin Care
|
|
N-cholesteryloxycarbonyl-para-aminophenol |
Phase |
|
|
|
Example |
Reference |
A |
|
Preserving agent |
0.2 |
0.2 |
|
|
Disodium EDTA |
0.15 |
0.15 |
|
|
Glycerol |
3 |
3 |
|
|
Water |
Qs 100 |
Qs 100 |
|
|
Glyceryl stearate and PEG-100 stearate |
0.3 |
0.3 |
B |
|
Cetyl alcohol |
0.4 |
0.4 |
|
|
Preserving agent |
0.1 |
0.1 |
|
|
Triclosan |
0.1 |
0.1 |
|
|
N-cholesterylcarbonyl-para- aminophenol |
0.5 |
0.5 |
C |
|
N- ethoxycarbonylparaaminophenol |
- |
- |
|
|
5-n-octanoyl salisylic acid |
- |
- |
|
|
Isopropyl lauroylsarcosinate |
10.0 |
- |
|
|
Crosslinked polymer (acrylates/ C10-C30 alkyl acrylate) |
0.5 |
0.5 |
D |
|
Cyclohexasiloxane |
5 |
5 |
|
|
Water |
10 |
10 |
E |
|
Alcohol |
5 |
5 |
|
|
Polyacrylamide and C13-C14 isoparaffin and laureth-7 |
1 |
1 |
F |
|
Triethanolamine |
1.03 |
1.03 |
G |
|
Water |
7 |
7 |
|
Formulation Procedure
Phase A
The mixture is heated to 85oC. Stirring is carried out to dissolve
the preserving agents. The temperature is then reduced to 75o C. to form the
emulsion.
Phase B
The mixture is heated to 75o C. and homogenized until fully dissolved.
Preparation of the emulsion: B is poured into A at 75o C. with stirring for 15
minutes.
Phase C
The mixture is homogenized until fully dissolved at 30o C. and is added to the
emulsion (A+B) at 60o C.
Phase D
The mixture is dispersed at room temperature and added to the emulsion (A+B+C)
at 60o C. The resulting mixture is homogenized.
Phases E, F and G
These phases are prepared at room temperature and are then added to the
emulsion (A+B+C+D) at 40o C., and the resulting mixture is homogenized with
stirring. The emulsion is allowed to cool to 25o C.
It was shown that the dissolution of the derivatives of low solubility with
amino acid esters may indeed be achieved in emulsion, so as to confirm that it
is possible to formulate stable cosmetic compositions containing such
derivatives.
The emulsions prepared above are oils in water with Simulsol 165 sold by the
company SEPPIC as surfactant, Simulsol 165 being a mixture of glyceryl stearate
and PEG-100 stearate.
The physicochemical stability of the emulsions is confirmed by macroscopic and
microscopic monitoring, and monitoring of the pH and the viscosity, after 24
hours.