Use of cyclic organic amines in dermatological compositions

The use of cyclic organic amines, as free radicals deactivators, in the preparation of cosmetic and dermatological compositions.

The present invention relates to the use, as agents useful in cosmetics and 
dermatology, of the compounds of formula I 
##STR1## 
wherein R is selected from hydrogen, C.sub.1 -C.sub.12 alkyl, benzyl, 
C.sub.2 -C.sub.4 hydroxyalkyl, the group of formula II 
EQU --(CH.sub.2 -CH.sub.2 -O).sub.m --H (II) 
wherein m is an integer from 2 to 20; 
X is selected from oxygen, --NR.sub.1 -- in which R.sub.1 is hydrogen, 
C.sub.1 -C.sub.12 alkyl, the group of formula II, C.sub.5 -C.sub.6 
cycloalkyl; 
n is an integer from 1 to 4; 
A is an alkyl residue with a valence from 1 to 4, a mono- or polyacyl group 
deriving from carbonic acid or from an organic mono or polycarboxylic 
acid, a carbamoyl or dicarbamoyl group deriving from a mono or 
diisocyanate, a group of formula III or IV 
##STR2## 
wherein R is as defined above, R.sub.2 and R.sub.3 can be the same or 
different and they are a group of formula V 
##STR3## 
the group --OR.sub.1 ; --NRR.sub.1, wherein X, R and R.sub.1 are as 
defined above. 
Examples of an alkyl residue with valence from 1 to 4 are: 
valence 1=straight or branched C.sub.1 -C.sub.18 alkyl; 
valence 2=straight or branched C.sub.2 -C.sub.12 alkylene; such as 
##STR4## 
It is now believed that the cause of most of the alterations which lead to 
ageing of the skin are to be attributed to the action of endogenic and 
exogenic free radicals. On this point, dermatology has in recent years 
increasingly concerned itself with the processes and causes which lead to 
the formation of these highly reactive chemical groups, with their toxic 
effects and with possible defence mechanisms. 
Apart from some chemical agents such as pharmaceuticals, physical factors, 
such as heat, light, UV radiation, supersonic waves and ionising radiation 
lead to the formation of free radicals. 
Owing to their high reactivity, free radicals are capable of reacting 
easily with other neighbouring molecules, to generate further free 
radicals; a chain reaction thus takes place and continues to generate 
radicals until it is interrupted by combination with a chemical group 
which effects the formation of a stable molecule. 
This mechanism explains the destructive action of free radicals: in fact, 
they can bind to the elements of the cell, such as the nucleus, the 
proteins and particularly the membrane; consequently, alterations which 
disturb the normal metabolism appear in the cells. 
The adverse action of free radicals on the skin tissue consists in an 
attack on the cell membranes, which causes a degradation of the fibres in 
the connective tissue, such as collagen and elastin, which are responsible 
for the "tautness" and softness of young skin; the consequence is ageing 
of the skin, which manifests itself in the appearance of dryness, scaling 
and wrinkles. 
In nature, there are scavengers or deactivators of free radicals; these are 
enzymes present in skin tissue, such as superoxide dismutase or catalase. 
These are not always sufficient for total blocking of the free radicals 
present, which can then exert their devastating action on the skin tissue, 
which thus ages, losing its smooth and soft appearance. 
A few substances have been proposed as free radical deactivators against 
skin ageing, such as, for example, vitamin E, 
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, 13-cis-retinoic 
acid and 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline. However, these 
have not proved to be very effective. 
Among the compounds of formula I, preferably used are the following: 
4-acetoxy-2,2,6,6-tetramethylpiperidine 
4-lauryloxy-2,2,6,6-tetramethylpiperidine 
4-stearyloxy-2,2,6,6-tetramethylpiperidine 
4-benzoyloxy-1,2,2,6,6-pentamethylpiperidine 
4-p-chlorobenzoyloxy-2,2,6,6-tetramethylpiperidine 
4-(or-toluyloxy)-1-(2-hydroxyethyl)-2,2,6,6-tetramethylpiperidine 
4-isonicotinyloxy-2,2,6,6-tetramethylpiperidine 
4-methoxy-2,2,6,6-tetramethylpiperidine 
4-dodecyloxy-2,2,6,6-tetramethylpiperidine 
4-benzyloxy-2,2,6,6-tetramethylpiperidine 
4-propylcarbamoyloxy-2,2,6,6-tetramethylpiperidine 
4-phenylcarbamoyloxy-1,2,2,6,6-pentamethylpiperidine 
4-acetamido-1-(2-hydroxypropyl)-2,2,6,6-tetramethylpiperidine 
4-stearamido-2,2,6,6-tetramethylpiperidine 
4-(p-tert-butylbenzamido)-1,2,2,6,6-pentamethylpiperidine 
4-acrylamido-2,2,6,6-tetramethylpiperidine 
4-cyclohexylamino-2,2,6,6-tetramethylpiperidine 
4-octylamino-1,2,2,6,6-pentamethylpiperidine 
1-propyl-3-(2,2,6,6-tetramethyl-4-piperidinyl)urea 
1-phenyl-3-(1-benzyl-2,2,6,6-tetramethyl-4-piperidinyl)urea 
N,N-bis-(1,2,2,6,6-pentamethyl-4-piperidinyl)methylamine 
bis-(2,2,6,6-tetramethyl-4-piperidinyl)carbonate 
bis-(2,2,6,6-tetramethyl-4-piperidinyl)sebacate 
bis-(1,2,2,6,6-pentamethyl-4-piperidinyl)oxalate 
bis-(2,2,6,6-tetramethyl-4-piperidinyl)adipate 
bis-(1-hydroxyethyl-2,2,6,6-tetramethyl-4-piperidinyl)terephthalate 
1,2-bis-(2,2,6,6-tetramethyl-4-piperidinyloxy)ethane 
bis-(2,2,6,6-tetramethyl-4-piperidinyl)-hexamethylene-1,6-dicarbamate 
N,N'-bis-(2,2,6,6-tetramethyl-4-piperidinyl)sebacamide 
1,3-bis-(1,2,2,6,6-pentamethyl-4-piperidinyl)urea 
2-butylamino-4,6-bis-[(2',2',6',6'-tetramethylpiperidinyl-4')-butylamino]-1 
,3,5-triazine 
2-tert-octylamino-4,6-bis-[2',2',6',6'-tetramethylpiperidinyl-4'-amino]-1,3 
,5-triazine 
2-methoxy-4,6-bis-[1',2',2',6',6'-pentamethylpiperidinyl-4'-oxy]-1,3,5-tri 
azine 
2,4-bis-[2',2',4',4-tetramethylpiperidinyl-4-oxy]-6-[(2",2",6",6"-tetrameth 
ylpiperidinyl-4")-butylamino]-1,3,5-triazine 
tris-(2,2,6,6-tetramethyl-4-piperidinyl)-benzene-1,3,5-tricarboxylate 
N,N',N"-tris-(1,2,2,6,6-pentamethyl-4-piperidinyl)-benzene- 
1,3,5-tricarbonamide 
2,4,6-tris-[(2',2',6',6'-tetramethylpiperidinyl-4')butylamino)]-1,3,5-triaz 
ine 
2,4,6-tris-(1',2',2',6',6'-pentamethylpiperidinyl-4'-oxy)-1,3,5-triazine 
tetra-(2,2,6,6-tetramethyl-4'-piperidinyl)-benzene-1,2,4,5-tetracarboxylate 
tetra-(2',2',6',6'-tetramethyl-4-piperidinyl)-butane-1,2,3,4-tetracarboxyla 
te. 
The dermatological compositions for the treatment of the skin can be in 
form of lotions, ointments, creams, emulsions, gels, oils, which are used 
as moisturizing, tonifying, detergent agents both for day and night uses. 
Preferably, these preparations are emulsions of the oil-in-water kind, and 
they can contain preservatives, emulsifiers, thickening agents, 
antioxidants, emollients, solvents, UV absorbents, perfumes, dyes or other 
substances generally used in dermatological compositions. 
Generally the compositions, according to the present invention, can contain 
from 0.05 up to 10% and preferably from 0.1 to 5% of the free radical 
deactivators of formula I. 
Of course the compounds of formula I can be contained in the compositions 
of the invention also together with other radical deactivators, such as 
vitamin E, or other active principles useful for the treatment of the skin 
.

The following examples illustrate the invention. 
EXAMPLE 1 
Moisturizing Cream 
A solution of 0.3 g of 4-benzoyloxy-2,2,6,6-tetramethylpiperidine in 6 g of 
polyethylene glycol 400 is prepared heating to 60.degree. C; the resulting 
solution is added with 0.15 g of methyl paraben (methyl p-hydroxybenzoate) 
and 0.05 g of propyl paraben. Separately, a mixture of 15 g of vaseline 
and 8 g of glyceryl monostearate is prepared and added to the above 
obtained solution, at 80.degree. C. After that, the oily phase is added 
with 70.5 g of water pre-heated at 80.degree. C., under strong stirring, 
so as to obtain an emulsion, keeping stirring until temperature is 
decreased to 30.degree. C. 
EXAMPLE 2 
Lipophilic Gel 
6 g of high-melting paraffin and 3.6 g of sorbitan tristearate (Span 
65.sup.R) are melted together and heated to 100.degree. C., the melted 
mixture is added, under slow stirring, to 80.3 g of vaseline oil 
pre-heated to 100.degree. C., then it is quickly cooled to 50.degree. C. 
to obtain a gel. This gel is added with a solution of 0.1 g of 
4-stearamido-2,2,6,6-tetramethylpiperidine in 10 g of polyethylene glycol 
400 previously prepared, mixing until homogeneity. 
EXAMPLE 3 
Sun Cream 
A mixture of 10 g of cyclodimeticon/dimeticon copolymer (Dow Corning 
Q2-3225 C), 10 g of cyclometicon (Dow Corning 344), 0.5 g of polysorbate 
20 (Tween 20.sup.R), 3 g of 2-hydroxy-4-methoxybenzophenone, 5 g of 
2-ethylhexyl p-dimethylaminobenzoate and 0.2 g of 2,4,6 
-tris-(2',2',6',6'-tetramethylpiperidinyl-4'-butylamino)-1,3,5-triazine is 
prepared. This mixture is added to a solution prepared previously, 
consisting of 0.2 g of 
1,1'-methylene-bis-3-(3-hydroxymethyl-2,4-dioxy-imidazolidinyl)urea, 0.05 
g of methyl paraben and 71.05 g of water. 
EXAMPLE 4 
Face Make-up 
A mixture is prepared, heating to 75.degree. C. 78.4 g of water, 4.5 g of 
glycerin, 0.6 g of 2-pyrrolidone-5-carboxylic acid and 0.2 g of methyl 
paraben. This mixture is added to a second mixture, previously prepared, 
consisting of 3 g of octyl palmitate, 1 g of dimeticon, 4.5 g of 
polysorbate 60 (Tween 60.sup.R), 0.1 g of propyl paraben, 7.5 g of 
glyceryl monostearate and 0.2 g of 
bis-(1,2,2,6,6-pentamethyl-4-piperidinyl)-adipate. 
EXAMPLE 5 
Ointment 
A mixture of 0.1 g of 1,3-bis-(1,2,2,6,6-pentamethyl-4-piperidinyl)urea, 5 
g of C.sub.12 -C.sub.15 alcohols benzoate and 0.5 g of titanium dioxide is 
prepared. The resulting dispersion is subsequently added to 4.4 g of 
vaseline oil gelled with polyethylene glycol 6000, stirring to 
homogeneity.