Indolin derivatives as sun protection agents

Details Indolin derivatives as sun protection agents Indolin derivatives as sun protection agents

2001-03-29

2002-03-19

Dodson, Shelley A. (Department: 1624)

Drug, bio-affecting and body treating compositions

Topical sun or radiation screening, or tanning preparations

C424S060000, C424S400000, C424S401000, C514S245000, C514S419000

Reexamination Certificate

active

06358496

ABSTRACT:

The present invention relates to indoline derivatives and to the use of those compounds as light-protective agents.
Indoline compounds are known from dye chemistry, where they are used as intermediates or starting materials. Indoxyl, for example, occurs as an intermediate in industrial indigo synthesis. Trimethyl-2-methyleneindoline (Fischer base) is used as starting compound in the preparation of polymethine dyes.
It has been found, surprisingly, that certain indoline derivatives are also suitable as light-protective agents.
The present invention accordingly relates to the use of indoline derivatives of formula
wherein
R
1
is hydrogen; C
1
-C
5
alkoxy; C
1
-C
18
alkoxy; or halogen;
R
2
is C
1
-C
8
alkyl; C
5
-C
7
cycloalkyl; C
6
-C
10
aryl;
R
3
is C
1
-C
18
alkyl; or a radical of formula (1a)
R
4
is hydrogen; or a radical of formula (1b)
R
5
is a radical of formula (1c)
 C
1
-C
18
alkoxy; or a radical of formula
R
6
and R
7
are each independently of the other hydrogen; or C
1
-C
5
alkyl;
R
8
is hydrogen; C
1
-C
5
alkyl; C
5
-C
7
cycloalkyl; phenyl; phenyl-C
1
-C
3
alkyl;
R
9
is C
1
-C
18
alkyl;
X is halogen; a radical of formula (1e)
n is 0; or 1,
as light-protective agents.
C
1
-C
18
Alkyl denotes straight-chain or branched alkyl radicals, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, amyl, isoamyl or tert-amyl, hexyl, heptyl, octyl, isooctyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl.
C
1
-C
18
Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, amyloxy, isoamyloxy or tert-amyloxy, hexyloxy, heptyloxy, octyloxy, isooctyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tetradecyloxy, pentadecyloxy, hexadecyloxy, heptadecyloxy or octadecyloxy.
Halogen is fluorine or bromine, and especially chlorine.
C
5
-C
7
Cycloalkyl is, for example, cyclopentyl, cycloheptyl and especially cyclohexyl.
C
6
-C
10
Aryl is phenyl or naphthyl.
Preference is given according to the invention to the use of compounds of formula (1) wherein
R
5
is a radical of formula (1g)
 and
R
8
is hydrogen; C
1
-C
5
alkyl; or phenyl, especially hydrogen or methyl.
Also of interest are compounds of formula (1) wherein
R
5
is C
1
-C
18
alkoxy, and especially a radical of formula
Also of interest are compounds of formula (1) wherein
R
5
is a radical of formula
 and
R
8
is hydrogen; or methyl.
Of special interest are also compounds of formula (1) wherein R
3
is C
3
-C
18
isoalkyl.
Exemplary compounds used in accordance with the invention correspond to formulae
Some of the compounds of formulae (1) to (11) are known compounds while some are new compounds.
The new compounds correspond to formula
wherein
R
1
is hydrogen; C
1
-C
5
alkyl; C
1
-C
5
alkoxy; or halogen;
R
2
is C
1
-C
5
alkyl; C
5
-C
7
cycloalkyl; C
6
-C
10
aryl;
R
3
is C
1
-C
5
alkyl or a radical of formula (1a)
R
4
is hydrogen; or a radical of formula (1b)
R
5
is C
5
-C
18
alkoxy; a radical of formula (1b); or a radical of formula
R
9
is C
1
-C
18
alkyl; or
R
4
and R
5
denote a radical of formula (1b).
The indoline derivatives used in accordance with the invention are prepared in a manner known per se by means of condensation of the indoline compound (Fischer base) of formula
with the appropriate acid chloride or a CH acid compound to form the compound of formula (1).
The reaction is usually carried out at temperatures of from 20 to 110° C. in the presence of an inert solvent, for example petroleum ether, toluene, xylene, a mixture of xylene isomers, or of a halogenated hydrocarbon, for example CH
2
Cl
2
. The reaction can, however, also be performed without solvents. The reaction time is usually a few minutes and may last for up to a few hours.
The compounds of formula (1) are especially suitable as UV filters, that is to say for protecting ultraviolet-sensitive organic materials, especially the skin and hair of humans and animals, against the damaging action of UV radiation. The compounds are accordingly suitable as light-protective agents in cosmetic, pharmaceutical and veterinary-medicinal compositions. The compounds can be used both in dissolved form and in the micronised state.
The invention relates also to a cosmetic composition comprising a compound of formula (1).
For cosmetic use, these light-protective agents, unless they are water-soluble, usually have an average particle size in the range from 0.02 to 2, preferably from 0.05 to 1.5, and very especially from 0.1 to 1.0, m. The insoluble light-protective agents in accordance with the invention can be brought to the desired particle size by customary methods, e.g. grinding with, for example, a jet, ball, vibration or hammer mill. Preference is given to performing the grinding in the presence of from 0.1 to 30% by weight, preferably from 0.5 to 15% by weight, based on the UV absorber, of a grinding aid, for example an alkylated vinylpyrrolidone polymer, a vinylpyrrolidone-vinyl acetate copolymer, an acyl glutamate, an alkyl polyglucoside or, especially, a phospholipid.
The light-protective agents can also be used dry in powder form. For that purpose, the light-protective agents are subjected to known grinding processes such as vacuum atomisation, countercurrent spray-drying etc. Such powders have a particle size of from 0.1 nm to 2 &mgr;m. To avoid agglomeration processes, the light-protective agents can be coated, before the pulverisation process, with a surface-active compound, for example an anionic, non-ionic or amphoteric surfactant, for example with phospholipids or known polymers, such as PVP, acrylates etc.
The cosmetic composition, in addition to comprising the UV absorber according to the invention, may also comprise one or more further UV-protective substances of the following classes of substance;
1. p-aminobenzoic acid derivatives, e.g. 4-dimethylaminobenzoic acid 2-ethylhexyl ester;
2. salicylic acid derivatives, e.g. salicylic acid 2-ethylhexyl ester;
3. benzophenone derivatives, e.g. 2-hydroxy-4-methoxybenzophenone and the 5-sulfonic acid derivative thereof;
4. dibenzoylmethane derivatives, e.g. 1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione;
5. diphenyl acrylates, e.g. 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate and 3-(benzo-furanyl)-2-cyanoacrylate;
6. 3-imidazol-4-yl-acrylic acid and esters;
7. benzofuran derivatives, especially 2-(p-aminophenyl)benzofuran derivatives, described in EP-A-582 189, U.S. Pat. Nos. 5,338,539, 5,518,713 and EP-A-613 893;
8. polymeric UV absorbers, e.g. the benzylidene malonate derivatives described in EP-A-709 080;
9. cinnamic acid derivatives, e.g. the 4-methoxycinnamic acid 2-ethylhexyl ester and isoamyl ester or cinnamic acid derivatives disclosed in U.S. Pat. No. 5,601,811 and WO 97/00851;
10. camphor derivatives, e.g. 3-(4′-methyl)benzylidene-bornan-2-one, 3-benzylidene-bornan-2-one, N-[2(and 4)-2-oxyborn-3-ylidene-methyl)-benzyl]acrylamide polymer, 3-(4′-trimethylammonium)-benzylidene-bornan-2-one methyl sulfate, 3,3′-(1,4-phenylenedimethine)-bis(7,7-dimethyl-2-oxo-bicyclo[2.2.1 ]heptane-1-methanesulfonic acid) and salts, 3-(4′-sulfo)benzylidene-bornan-2-one and salts;
11. trianilino-s-triazine derivatives, e.g. 2,4,6-trianiline-(p-carbo-2′-ethyl-1′-oxy)-1,3,5-triazine and the UV absorbers disclosed in U.S. Pat. No. 5,332,568, EP-A-517 104, EP-A-507 691, WO 93/17002 and EP-A-570 838;
12. 2-hydroxyphenylbenzotriazole derivatives;
13. 2-phenylbenzimidazole-5-sulfonic acid and salts thereof;
14. menthyl-o-aminobenzoate;
15. inorganic micropigments, for example TiO
2
(variously encapsulated);
16. N-substituted benzimidazoles, as described in EP-A-0 843 995;
17. hydroxyphenylbenzotriazoles and derivatives, especially siloxane derivatives;
18. siloxanes of oxanilide derivatives, as described in EP-A-0 712 856.
The UV absorbers described in “Sunscreens”, Eds. N. J. Lowe, N. A. Shaath, Marcel Dekker, Inc., New York and Basle or in Cosmetics & Toiletries (107), 50ff (1992) can also be used as additional UV-

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