2-phenyl-benzimidazolesulfonic acids as UV-B filters

Details 2-phenyl-benzimidazolesulfonic acids as UV-B filters 2-phenyl-benzimidazolesulfonic acids as UV-B filters

2001-11-21

2002-08-27

Stockton, Laura L. (Department: 1626)

Drug, bio-affecting and body treating compositions

Topical sun or radiation screening, or tanning preparations

C548S310100, C548S310700, C514S395000, C514S060000

Reexamination Certificate

active

06440401

ABSTRACT:

The present invention relates to a 2-phenyl-benzimidazolesulfonic acids, to the use thereof as a UV filter, to cosmetic preparations which comprise these compounds, and to a preparation process for the compounds.
A suntan of the skin to whatever degree is regarded in today's society as attractive and as an expression of vigor and health. As well as this desired effect of the sun on the skin, however, a number of undesired secondary effects arise, such as sunburn or premature skin aging and the development of wrinkles. A number of performance UV filters have been developed which, applied to the skin in the form of creams, lotions or gels, can effectively delay the development of sunburn even when the incidence of solar rays is relatively high.
The UV filter present in the pharmaceutical or cosmetic formulation forms a film or a layer on the surface of the skin and does not penetrate into deeper skin layers with other substances present in the formulation. Known UV filters or sun protection agents thus act only by absorbing certain regions of sunlight; meaning that this radiation cannot penetrate into deeper layers of the skin.
As is known, the most hazardous part of solar radiation is formed by the ultraviolet rays having a wavelength of less than 400 nm. The lower limit of the ultraviolet rays which reach the surface of the earth is limited by the absorption in the ozone layer to about 280 nm or above. The sun protection filters which are currently customary in cosmetics absorb in a wavelength range from 280 to 400 nm. This range includes UV-B rays having a wavelength between 280 and 320 nm, which play a decisive role in the formation of a solar erythema, and UV-A rays, having a wavelength between 320 and 400 nm, which tan the skin but also age it, and favor the triggering of an erythematous reaction or can exacerbate this reaction in certain people or even trigger phototoxic or photoallergic and irritative reactions.
The object of skin care cosmetics is to obtain the impression of a youthful skin. In principle, there are various ways of achieving this object. For example, existing skin damage, such as irregular pigmentation or the development of wrinkles can be smoothed out by covering powders or creams. Another approach is to protect the skin against environmental influences which lead to permanent damage and thus aging of the skin.
The idea is therefore to intervene in a preventative manner and thus to delay the aging process. One example of this is the UV filters already mentioned which, as a result of absorption of certain wavelength regions, prevent or at least reduce skin damage. Depending on the position of their absorption maxima, UV absorbers for cosmetic and dermatological preparations are divided into UV-A and UV-B absorbers. UV-A absorbers usually also absorb in the UV-B region and are thus alternatively referred to as broad-band absorbers or broad-band filters. However, particularly in avoiding skin damage as a result of the formation of solar erythemas, the UV-B filters are of particular importance, since formulations based on broad-band filters alone offer inadequate protection or prevent entirely the desired tanning of the skin. For this reason, there is a continuous need for substances having an absorption maximum in the UV-B region which can be incorporated easily into cosmetic formulations.
Of decisive importance for the formulation is the solubility of the filter substances in the oil and water phases since it is necessary, particularly for establishing a high protection factor, to incorporate filters into all phases of a formulation. The oil-soluble UV-B filters include isooctyl methoxycinnamate, isoamyl methoxycinnamate and methylbenzylidenecamphor. Examples of water-soluble UV filters are, in particular, the salts of 2-phenylbenzimidazole-5-sulfonic acid, the use of which as UV ray filter has already been described in German Reichspatent No. 676 103.
However, a disadvantage of these water-soluble UV-B filters is that formulation is only possible in an alkaline medium since the sulfonic acid precipitates out at a pH below 7.
There is thus also a need for water-soluble UV-B filters which are highly suitable for the formulation of cosmetic formulations.
It has now surprisingly been found that certain 2-phenylbenzimidazolesulfonic acids and salts thereof can be readily incorporated into cosmetic formulations, while avoiding the above-mentioned problems.
The present invention accordingly firstly provides 2-phenylbenzimidazolesulfonic acids of the formula I
in which n is 0, 1 or 2 and m is 2 or 3. R1, R2, R3, R4 and R5 are each a radical from the group H, C
1-8
-alkyl, C
1-8
-alkoxy, hydroxyl, sulfate, nitro, F, Cl, Br or I radicals, and R
6
is a C
1-8
-alkyl or C
1-8
-alkoxy radical.
For the purposes of the present invention, 2-phenyl-benzimidazolesulfonic acids are here in principle also understood as meaning the salts of these acids. The salts are preferably the alkali metal salts, and in particular the sodium or potassium salts, or the ammonium salts, in particular the triethanolammonium salts of the corresponding sulfonic acids.
In a preferred 2-phenylbenzimidazolesulfonic acid according to formula I, m=2 and n=0 or n=1, preferably at least 4 radicals from the group R1, R2, R3, R4 and R5 are H, and particularly preferably even all radicals R1-R5 are H. According to the invention, particular preference is accordingly given to 2-phenylbenzimidiazole-4,6-disulfonic acid which, as shown in formula Ia, is usually in betaine form.
The 2-phenylbenzimidazolesulfonic acid according to the invention can be obtained by any desired preparation process suitable for this purpose. Processes which have proven particularly suitable and economical are those in which an ortho-phenylenediamine or a derivative thereof is reacted with an arylcarboxylic acid or an arylcarboxylic acid derivative.
The present invention thus secondly provides a process for the preparation of the abovedescribed 2-phenylbenzimidazolesulfonic acids, in which an o-phenylenediamine according to formula II
is reacted with a second compound according to formula III
where R1, R2, R3, R4 and R5, in each case independently of one another, are a radical from the group of H, C
1-8
-alkyl, C
1-8
-alkoxy, hydroxyl, nitro, F, Cl, Br or I radicals, and X is chosen from the radicals —COOH, —COCl, —COBr, —CN or —COOR, where R is a C
1-20
-alkyl radical.
In a preferred embodiment of the process, sulfuric acid, in particular 96% sulfuric acid, is used as solvent. Here, even the sulfuric acid on its own effects sulfonation of the benzimidazole at a suitable temperature. Thus, international application WO 93/15061 has already described a process in which monosulfonated products are obtained by reaction in sulfuric acid.
However, in the process for the preparation of polysulfonated benzimidazoles, it is preferred if an activated sulfuric acid is used, activation preferably being carried out by chlorosulfonic acid or sulfur trioxide. Sulfuric acid alone typically is not strong enough to act as a reagent for this process because it is believed that water forms during the reaction and dilutes the sulfuric acid. Activation of the acid improved the reactivity of the acid in the process.
The use of chlorosulfonic acid for the preparation of bisbenzimidazoloylsulfonic acids has already been described in European patent application EP-A-669 323. However, there are no indications that it is also possible to use chlorosulfonic acid to prepare the compounds according to the invention in the specification.
If the activation is carried out using sulfur trioxide, use is preferably made of the “fuming” sulfuric acid called oleum, which is a solution of sulfur trioxide in concentrated sulfuric acid. The use of sulfur trioxide (oleum) for the activation of the sulfuric acid has various advantages compared with the use of chlorosulfonic acid:
gas (HCl) is not evolved during the reaction, meaning that pressure regulation is not necessary,
accordingly, the collection and disposal of the aggressive gas (HCl)

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