United States Patent  7,485,315

L'Oreal S.A. (Paris, FR)

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Compositions comprising a compound of low solubility and a lipophilic amino acid derivative, uses thereof and process for dissolving a compound of low solubility

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.