GB1591136A - Cosmetic formulations for protecting the skin against harmfull light - Google Patents

Abstract

Sunscreen compositions for the human skin contain 4-dialkylaminophthalic acid diesters of the formula I. The substituents in formula I have the meanings given in Patent Claim 1. The compounds of the formula I are non-toxic and very skin-compatible. They are not modified by UV radiation. <IMAGE>

Description

(54) COSMETIC FORMULATIONS FOR PROTECTING THE SKIN AGAINST HARMFUL LIGHT (71) We, BASF AKTIENGESELLSCHAFT, a German Joint Stock Company of 6700 Ludwigshafen, Federal Republic of Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following Statement: The present invention relates to cosmetic formulations for protecting human skin against harmful light and thus preventing or alleviating erythema.

It is known that light of 297 nm causes the most intense erythema reaction.

Continuing in the direction of shorter wavelengths, there is a minimum at about 280 nm, after which the erythema-inducing activity again rises at 250 nm. The relevant curve, called the ideal mean curve for erythema effectiveness, has a maximum at 297 nm. Since, however, wavelengths below 290 nm present in sunlight are totally absorbed by the layer of ozone in the stratosphere, it is only the region above 290 nm which decides the biological effects of sunlight. If the curve obtained, for example, with an artificial light source is compared with that of sunlight, the maximum is found to be shifted to 307 nm because of the very different intensity distribution of sunlight. Accordingly, it is a relatively narrow range of wavelengths (307 nm+lO nm) which is responsible for causing erythema.

A suitable active ingredient for protecting the skin against harmful light should therefore absorb strongly, in the ultraviolet, in the above region around 307 nm.

However, whether such an ultraviolet filter for human skin also constitutes a useful filter for protection against sunlight is decisively influenced by other factors, including the following: The material should be a very effective filter in the region responsible for erythema, but should be highly transparent to the energy responsible for bronzing.

It should exhibit near-ideal toleration by the skin and mucous membranes, and must be non-toxic. It must not be prone to oxidation and must not undergo discolorations or other changes when exposed to ultraviolet. It should be stable on storage and should have no intrinsic odor. It should be compatible with the cosmetic media employed, and, finally, should be industrially readily accessible.

The conventional ultraviolet filters frequently have the disadvantage that they are unstable on storage, and unstable to ultraviolet radiation or visible radiation and/or to air, and that they are converted to colored decomposition products which can soil clothing or even be harmful to the skin. Since protective sun agents are extensively used by persons who work in the open or pursue sports such as swimming and diving, the agents must not be very readily removable from the skin by water or perspiration.

There are relatively few compounds which more or less successfully meet the above requirements. For example, according to the literature, viz. Fette, Seifen, Anstrichmittel, 71 (1969), 46-48 or German Laid-Open Application DOS 2,032,914, only esters of p - amino - benzoic acid or esters of p - dimethylaminobenzoic acid with benzophenone derivatives, amongst many compounds investigated, exhibit a useful light-protection action.

Preparations which contain ethyl p - aminobenzoate as an ultraviolet filter have the disadvantage of discoloring in the presence of air and therefore causing undesirable soiling of clothing, and discoloration of the formulation employed. The lower esters of p - diethylaminobenzoic acid are less prone to such discoloration but are significantly soluble in water so that the agent, applied as a thin layer to the skin, is readily removed by perspiration or water and accordingly little protection against erythema is ensured.

According to German Published Application DAS 1,717,102, the disadvantage of excessive solubility in water can be circumvented by using esters of4 - dimethyl aminobenzoic acid with higher alcohols, of 5 to 18 carbon atoms. However, the properties of these compounds are also not entirely satisfactory and it is recommended to add stabilizers or antioxidant to protective sun agents which contain the higher alkyl esters of 4 - dimethylaminobenzoic acid.

We have found that compounds of the formula I

where R' and R2 are identical or different and each is alkyl of 1 to 18 carbon atoms and R3 and R4 are identical or different and each is alkyl of I to 12 carbon atoms, successfully meet the requirements for protective sun agents.

Accordingly, the present invention provides a cosmetic formulation for protecting the skin against harmful light and this preventing or alleviating erythema, the formulation being in a form suitable for application to the skin and containing from 0.1 to 10 per cent by weight of a diester of 4 - dialkylaminophthalic acid of the formula I defined above and a cosmetically acceptable diluent or carrier, with or without one or more cosmetically acceptable additives, but being free from ingredients harmful to the skin.

Examples of R1 and R2 are methyl, ethyl, propyl, isopropyl, n-butyl, sec.-butyl amyl, iso-amyl, n-hexyl n-heptyl, n-octyl, n-nonyl, n-decyl, lauryl, myristyl, palmityl and stearyl.

Examples of R3 and R4 are methyl, ethyl, sec.-butyl, n-amyl, iso-amyl, n-hexyl, 2-methylpentyl, n-heptyl, n-octyl, propyl, isopropyl, n-butyl, 2-ethylhexyl, n-nonyl, n-decyl and n-undecyl.

Preferred alkyl radicals R' and R2, from amongst the above, are those of I to 6 carbon atoms and those of 10 to 18 carbon atoms. R3 and R4 are preferably of I to 6 carbon atoms and especially of 1 to 4 carbon atoms.

Specific examples of compounds to be used according to the invention are: dimethyl 4 - dimethylamino - phthalate, diethyl 4 - dimethylamino - phthalate, dibutyl 4 - dimethylamino - phthalate, dimethyl 4 - diethylamino - phthalate, di n - hexyl 4 - dimethylamino - phthalate, di - n - octyl 4 - dimethylamino phthalate, di - n- decyl 4- dimethylamino - phthalate, dilauryl 4dimethylamino - phthalate, dimyristyl 4 - dimethylamino - phthalate, dipalmityl 4 - dimethylamino - phthalate, distearyl 4 - dimethylamino - phthalate, dimethyl 4 N - methyl - N - ethyl - aminophthalate, dimethyl 4 - N - butyl - N - methylaminophthalate, dimethyl 4 - N - butyl - N- ethylaminophthalate, dimethyl 4 - N - n - hexyl - N - methyl - aminophthalate, dimethyl 4 - N - (2 ethyl - hexyl) - N - methyl - aminophthalate, dimethyl 4 - N - n - decyl - N ethyl - aminophthalate, dimethyl 4 - N,N - dibutyl - aminophthalate, dibutyl 4 N- butyl - N- ethyl - aminophthalate, dibutyl 4 - N,N - dibutyl aminophthalate, di - n - decyl 4 - N,N - diethyl - aminophthalate and dibutyl 4 - N - (2 - ethylhexyl) - N - methyl - aminophthalate.

Among these, dimethyl 4- dimethylamino - phthalate, diethyl 4dimethylamino - phthalate, dimethyl 4 - diethylamino - phthalate, dibutyl 4 dimethylamino - phthalate, di - n - decyl 4 - dimethyl - aminophthalate, di - n stearyl 4- dimethylamino - phthalate and dimethyl 4- N- butyl - N ethylamino - phthalate are particularly preferred.

The diesters of formula I may be prepared in the form of cosmetic formulations by conventional methods. These formulations contain from 0.1 to 10, preferably from 3 to 7, per cent by weight of at least one diester of the formula I in a cosmetically acceptable carrier or diluent, which may be a conventional vehicle or diluent, or a mixture of such vehicles or diluents, with or without the addition of one or more cosmetically acceptable additives, which may be conventional cosmetic assistants. They must of course be free from ingredients capable of harming the skin when applied in the formulations.

Whether the final formulation is, for example, a solution, an oil, a cream, an ointment, a lotion, an emulsion or a powder depends on the nature of the vehicle or diluent.

Such formulations may be found, for example, in Fette and Seifen, 53 (1951), 694699, or Seifen, Ole, Fette, Wachse (1955), 147.

Examples of conventional cosmetic assistants which may be added are emulsifiers, e.g. fatty alcohol oxyethylates, sorbitan-fatty acid esters or lanolin derivatives, thickeners, e.g. carboxymethylcellulose or crosslinked polyacrylic acid, preservatives and perfumes.

Examples of bases for oils are vegetable oils, e.g. groundnut oil, olive oil, sesame oil, cottonseed oil, coconut oil, grapeseed oil or castor oil, and mineral oils e.g. petroleum jelly or especially liquid paraffin, synthetic fatty acid esters and glycerides.

Examples of ointment bases are petroleum jelly, lanolin, emulsifying aqueous wool fat alcohols (e.g. 'R'Eucerin) and polyethylene glycols.

Examples of bases for creams are glycerol, polysaccharides and tylose in the case of non-greasy creams, and cetyl alcohol, lanolin cream, cacao butter, beeswax, stearic acid, stearyl alcohol, glycerol monostearate and natural and mineral oils and fats in the case of creams based on fats and waxes.

Examples of bases for emulsions (which may be of the water-in-oil or oil-inwater type) are mixtures of glycol monostearate, a vegetable and/or mineral oil, e.g.

almond oil, paraffin oil and petroleum jelly, and water, or mixtures of ethyl alcohol, water, lanolin and tragacanth, or mixtures of ethyl alcohol, stearin and water, or tragacanth, glycerol, alcohol and water, or mixtures of stearic acid, paraffin oil, propyl or isopropyl alcohol and water.

Surprisingly, the compounds of the formula I exhibit absorption maxima at 3,060 A and 2,330 A and therefore come very close to the ideal mean curve for erythema effectiveness. The compounds are non-toxic and are very well tolerated by the skin, and cause no irritation even when repeatedly applied to the skin and mucous membranes. An advantage to be singled out particularly is that the compounds to be used according to the invention do not undergo any alteration or discoloration on exposure to ultraviolet, even in the presence of atmospheric oxygen, so that their formulations need not contain any stabilizers and antioxidants. The compounds of the formula I are virtually insoluble in water but are readily soluble in alcohol and oil, and consequently continue to adhere well when exposed to perspiration and water. They can readily be processed to give cosmetic formulations. Furthermore, they can be obtained economically and simply.

The diesters of 4-dialkylaminophthalic acids can be manufactured, for example, by reductive dimethylation of a corresponding diester of 4-nitrophthalic acid in accordance with German Laid-Open Application DOS 2,407,160, or by alkylation of a diester of 4-aminophthalic acid in accordance with German Patent 871,156.

Compounds of the formula I can be prepared by reductive dimethylation of a corresponding ester of 4-nitrophthalic acid, by reacting the latter with formaldehyde and hydrogen in the presence of a hydrogenating catalyst which contains one or more metals of atomic number from 24 to 29, and in the presence of a weak organic acid at from 35 to 1500C under a pressure of at least 40 atmospheres, or by alkylating a corresponding diester of 4-aminophthalic acid by means of a dialkyl sulfate or an alkyl halide, advantageously in the presence of a base. The reductive dimethylation process may advantageously be carried out under the following conditions: The formaldehyde may be used as a gas, as a solution in alcohol, e.g. ethanol, or, preferably, as an aqueous solution, advantageously of from 30 to 40 per cent strength by weight. The starting material can be reacted with the stoichiometric amount of formaldehyde or with an excess thereof, preferably using from 2 to 8, especially from 2 to 3, moles of formaldehyde per mole of starting material.

The reaction is carried out at from 35 to 1500C, preferably from 45 to 950C, in particular from 45 to 700 C, and under a pressure of at least 40, preferably from 50 to 250, advantageously from 70 to 150, especially from 70 to 110, atmospheres, continuously or batchwise. It is advantageous to use organic solvents which are inert under the reaction conditions, for example alkanols, especially of 1 to 4 carbon atoms, e.g. methanol, ethanol or isopropanol, glycols, e.g. methylene glycol, or mixtures of these, and the solvents are advantageously employed in amounts of from 200 to 1,000 /" by weight, especially from 200 to 400 /n by weight, based on the starting ester.

The reaction is carried out in the presence of weak organic acids, which in general have a dissociation constant of at least 1 1.5x 10-4, preferably from 1.5x 10-4 to 1x10-6, especially from 1.5x10-4 to 1x10-;. Preferred acids are aliphatic carboxylic acids of 3 to 10 carbon atoms, in particular appropriate unsubstituted or hydroxy-substituted or cyano-substituted alkane-carboxylic acids or alkenecarboxylic acids, advantageously monocarboxylic acids or dicarboxylic acids, e.g. propionic acid, butyric acid, acrylic acid, maleic acid, crotonic acid, isocrotonic acid, vinylacetic acid, succinic acid, isobutyric acid, angelica-acid, tiglic acid, levulic acid, glutaric acid, valeric acid, isovaleric acid, trimethylacetic acid, adipic acid, caproic acid, diethylacetic acid, enanthic acid and perargonic acid, but it is also possible to use formic acid, acetic acid lactic acid, cycloaliphatic carboxylic acids, e.g. cyclopropanecarboxylic acid, cyclobutanecarboxylic acid and cyclohexane carboxylic acid, uric acid, heterocyclic carboxylic acids, e.g. furan - 2 - carboxylic acid and aromatic or araliphatic carboxylic acids, e.g. benzoic acid, m - hydroxybenzoic acid, terephthalic acid, phenylacetic acid, p-toluic acid, p-methoxybenzoic acid, cinnamic acid, palmitic acid and cholic acid. The use of alkanecarboxylic acids of 3 to 8 carbon atoms, especially of propionic acid, is particularly advantageous. In general, amounts of from 0.1 to 0.5, preferably from 0.1 to 0.3, mole of acid per mole of starting ester may be used.

The hydrogenating catalysts are generally one or more metals of atomic number from 24 to 29, preferably cobalt, copper, manganese and/or nickel catalyst, e.g. sintered catalysts of these elements. The metals may also be present in the catalyst as their oxides and/or as mixtures with phosphoric acid. Advantageous catalysts of the above type contain from 3 to 300/, by weight of copper and/or cobalt, from 0.5 to l0V by weight of manganese and from 10 to 800/, by weight of nickel. In addition, from 0.1 to 50/, by weight of phosphoric acid, based on the amount of metal, may or may not be present.

The hydrogenating catalyst is as a rule used for the reaction in an amount of from 0.5 to 50, preferably from 2 to 30, 0/, by weight or, in the case of Raney nickel, preferably from 2 to 5 / by weight, based on the starting ester. It can be used as a mixture with a carrier suitable for the reaction, e.g. silicon dioxide, in which case the amount of catalyst is as a rule from 10 to 40 /, by weight of the mixture of catalyst and carrier. Examples of suitable catalyst mixtures are: a) 70.5V of Ni, 19.70/, of Co, 5.4( of Mn and 4.2 /n of phosphoric acid.

b) 15% of Ni, 6.1 /" of Cu, 1.4 / of Mn, 0.9 /n of phosphoric acid and SiO2.

c) 15 of Ni, 5.20/, of Cu, 1.3 /" of Mn on SiO2 The use of Raney nickel is particularly advantageous. As a rule, such amounts of hydrogen are introduced into the reaction mixture at the start and during the reaction that an appropriate reaction pressure, advantageously of from 40 to 150 atmospheres, is obtained at all times at the reaction temperature. Inert gases, e.g.

nitrogen, may also be used to set up the appropriate pressure. The residence times in the reaction space are as a rule from 15 to 600 minutes.

The reaction may be carried out as follows: the ester starting material and the formaldehyde, with or without solvent, is introduced into a reactor, the catalyst and the acid are added and the reaction space is flushed with nitrogen. Hydrogen is then forced in until the above reaction pressure is reached. The reaction mixture is then brought to the above temperature and is kept thereat, whilst passing in further hydrogen, until no more hydrogen is consumed by the reaction. The reaction mixture is then cooled and filtered. The end product is isolated from the filtrate by conventional methods e.g. by adding water, removing the organic lower phase from the two-phase mixture formed, and subjecting it to fractional distillation.

Dialkyl N,N - dialkylamino - phthalates of the formula I, where the radicals R3 or R4 are identical or different and are alkyl of more than one carbon atom may be prepared in accordance with one of the following processes: Alkylation of dialkyl 4 - amino - phthalates by means of a dialkyl sulfate, alkyl halide, chlorosulfonic acid ester, trialkyl phosphate or aromatic sulfonic acid alkyl ester. A general description of the method is given, for example, in Houben Weyl, Methoden der organ. Chemie, volume l l/l, pages 205-222 and 3443.

The dialkyl 4 - amino - phthalates are preferably prepared from the 4 - nitro compounds by catalytically reducing their solutions in alcohols with Raney nickel at 60---80"C and from 5 to 50 bars hydrogen pressure (cf. Houben-Weyl), volume l l/l, page 363). Alternatively, the amino compound is prepared from the nitro compound by Bechamp reduction, using the general method described in detail in HoubenWeyl, volume l l/l, pages 394406.

The dialkylation of the nitrogen is now carried out as follows: One mole of amino compound is treated with one mole of trialkyl phosphate or 2 moles of dialkyl sulfate at the boil for about two hours. In general, the reaction is complete after this time. The reaction mixture is cooled to 500C and sufficient aqueous concentrated ammonia is added, whilst stirring, to the viscous mixture in order to obtain a readily stirrable consistency. The mixture is then boiled for about 15 minutes and the crude dialkyl 4 - N,N - dialkylamino - phthalate which has separated out is isolated and purified by fractional distillation.

A further method of preparing 4 - dialkylamino - phthalic acid diesters also starts from the corresponding 4 - nitro compound, which is converted to the 4 N - monoalkylamino - phthalic acid compound by reductive alkylation with a higher aldehyde, e.g. acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, valeraldehyde, 2- methyl - pentanal or 2 - ethylhexanal. The monoalkylamino - phthalic acid diesters obtained are then converted to the dialkyl 4 - dialkylamino - phthalates by means of dialkyl sulfates, alkyl halides, alkyl chlorosulfonates, trialkyl phosphates or aromatic sulfonic acid alkyl esters. The equation below outlines the method of synthesis. Using this synthesis it is above all possible to obtain compounds where R3 and R4 are different.

The reductive alkylation is advantageously carried out with the following measures: The aldehyde is in most cases employed undiluted, or as a solution in alcohol, e.g. methanol, or as an aqueous solution. The starting material is reacted with the aldehyde in the stoichiometric amount or in excess, preferably in a ratio of from 1 to 1.5, especially from 1 to 1.2, moles of aldehyde per mole of starting material.

In other respects, the reaction conditions, the method of carrying out the redaction, and the working up correspond to what has been described for the reductive dimethylation.

The reaction may be carried out as follows: the starting ester and the aldehyde, with or without the solvent, are introduced into a reactor, the catalyst and the acid are added and the reaction space is flushed with nitrogen. Hydrogen is then forced in until the above reaction pressure is reached. The reaction mixture is then brought to the above temperature and is kept thereat, whilst passing in further hydrogen, until no more hydrogen is taken up. The reaction mixture is then cooled and filtered. The end product is isolated from the filtrate by conventional methods, for example by adding water, isolating the organic phase from the two-phase mixture formed, and subjecting it to fractional distillation.

The further alkylation of the alkyl 4 - monoalkylamino - phthalate thus obtained, using dialkyl sulfate, alkyl halide, alkyl chlorosulfonate, trialkyl phosphate or an aromatic sulfonic acid alkyl ester is carried out in accordance with the general description in Houben-Weyl, Methoden der organ, Chemie, volume 11/1, pages 205-222 and 3443.

For example, a suitable method is to stir the dialkyl 4 - monoalkylaminophthalate with a stoichiometric amount of alkyl bromide, alkyl iodide, dialkyl sulfate or alkyl toluenesulfonate or with about 0.5 mole of trialkyl phosphate per mole of alkylamino compound at from 25 to 500 in the case of alkyl bromides and alkyl iodides and at from 100 to 2000 in the case of dialkyl sulfates, alkyl toluenesulfonates or trialkyl phosphates, until no further monoalkylamino compound is detectable. The cooled mixture is then stirred into excess concentrated aqueous ammonia solution at room temperature, the batch is boiled for about 30 minutes and the amine which has separated out is then isolated. As a rule, the crude dialkyl N,N - dialkylaminophthalate is purified by fractional distillation under reduced pressure.

The following Examples I to 6 illustrate the manufacture of the active ingredients.

EXAMPLE I Dimethyl 4 - dimethylamino - phthalate 90 parts of dimethyl 4-nitrophthalate are suspended in 580 parts of methanol and are hydrogenated, after adding 90 parts of aqueous 40 percent strength formaldehyde solution, 18 parts of propionic acid and 9 parts of Raney nickel, at 60"C and 100 bars hydrogen pressure. After the hydrogen uptake has ceased, the catalyst is filtered off and the methanolic solution is diluted with 2,000 parts of water. Dimethyl 4 - dimethylamino - phthalate separates out initially as an oil, which is isolated and crystallizes to give colorless crystals. 75 parts of dimethyl 4 dimethylamino - phthalate of melting point 54--57"C, corresponding to a yield of 85% of theory, are obtained.

EXAMPLE 2 Diethyl 4-dimethylamino-phthalate 64 parts of diethyl 4 - nitrophthalate are dissolved in 560 parts of methanol and are hydrogenated, after adding 90 parts of aqueous 40 percent strength formaldehyde solution, 18 parts of propionic acid and 9 parts of Raney nickel, at 60"C and 100 atmospheres hydrogen pressure. After the hydrogen uptake has ceased, the catalyst is filtered off and the methanolic solution is diluted with 2,000 parts of water. The ester, which initially separates out as an oil, crystallizes after separating off the water phase. 55 parts of dimethyl 4 - dimethylamino - phthalate of melting point 62--64"C are obtained, corresponding to a yield of 86 /" of theory.

EXAMPLE 3 Dimethyl 4-diethylamino-phthalate 108 parts of diethyl sulfate are heated to 600 and 105 parts of dimethyl 4 aminophthalate are then run in over about 60 minutes, at a rate such that the temperature does not rise above 850C. 63 parts of dry calcium hydroxide are then introduced into the reaction mixture, whilst stirring, and the temperature is then raised to 1150C and is kept at this level for 45 minutes so that the water formed during the reaction can evaporate off. The temperature is then raised to 1400C and kept thereat for 5 hours. The viscous reaction mixture is cooled and stirred into 1,000 parts of aqueous 25% strength by weight ammonia. Stirring is continued for 30 minutes at 40--500C, 300 parts of chloroform are added and the mixture is stirred for about 15 minutes longer. The lower layer, containing the chloroform is separated from the upper layer, i.e. the aqueous layer. After distilling off the chloroform, an oily residue, which is crude dimethyl 4- dimethylamino phthalate, remains. This is purified by distillation under reduced pressure. 104 parts of a colorless oil which boils at 183--1850C/0.3 bar are obtained, corresponding to a yield of 78 , of theory.

EXAMPLE 4 Dibutyl 4-dimethylamino-phthalate 140 parts of dibutyl 4 - nitrophthalate are dissolved in 100 parts of methanol and are hydrogenated, after adding 120 parts of aqueous 30% strength formaldehyde solution, 19 parts of propionic acid and 10 parts of Raney nickel, at 70"C and 100 atmospheres hydrogen pressure. After the hydrogen uptake has ceased, the catalyst is filtered off and the methanolic solution is diluted with 6,000 parts of water. The ester, which separates out as an oil, is isolated, washed with water and dried. 119 parts of dibutyl 4 - dimethylamino - phthalate of refractive index nod8=1.5367 are obtained, corresponding to a yield of 85 /" of theory.

Ajax=308 nm and 232.8 nm.

EXAMPLE 5 Dimethyl 4-N-n-butyl-N-ethylamino-phthalate 90 parts of dimethyl 4-nitrophthalale are suspended in 700 parts of methanol and are hydrogenated, after adding 40 parts of n - butyraldehyde, 6 parts of propionic acid and 10 parts of Raney nickel, at 600C and 100 bars hydrogen pressure. After the hydrogen uptake has ceased, the catalyst is filtered off and the methanolic solution is diluted with 2,500 parts of water. Dimethyl 4 - n - butylamino - phthalate separates out as an oil, and is separated from the aqueousmethanolic phase. 95 parts of crude dimethyl 4 - n - butylamino - phthalate are obtained and are processed further without purification.

60 parts of ethyl bromide are added to 95 parts of crude dimethyl 4 - n - butylamino - phthalate and the mixture is boiled under reflux for 6 hours. The excess ethyl bromide is then distilled off, 600 parts of aqueous ammonia of about 25 per cent strength by weight are added to the reaction mixture which remains, the batch is then stirred for 30 minutes at 500 C, 300 parts of chloroform are added and the mixture is stirred for a further 15 minutes. The lower layer of chloroform is separated from the aqueous layer and the chloroform is evaporated off. 100 parts of an oily residue, which is crude dimethyl 4 - N - n - butyl - N - ethylamino phthalate, remain. This material is purified by distillation under reduced pressure.

82 parts of a colorless oil boiling at 198--2020C/0.1 bar are obtained, corresponding to a yield of 74 /,, of theory based on dimethyl 4 - nitrophthalate employed.

EXAMPLE 6 Di-n-decyl 4-dimethylamino-phthalate 98 parts of di - n - decyl 4 - nitro - phthalate are suspended in 1,000 parts of methanol and are hydrogenated, after adding 50 parts of aqueous 40% strength formaldehyde solution, 10 parts of propionic acid and 10 parts of Raney nickel, at 600 and 100 atmospheres hydrogen pressure. After the hydrogen uptake has ceased, the catalyst is filtered off and the methanolic solution is diluted with 3,000 parts of water. Di-n-decyl 4-dimethylamino-phthalate separates out as an oil. 400 parts of chloroform are added, the mixture is stirred for 15 minutes and the chloroform layer is separated off. After evaporating off the chloroform, 88 parts of di-n-decyl 4-dimethylamino - phthalate of melting point 36--39"C are obtained, corresponding to a yield of 90% of theory.

Examples of Formulations EXAMPLE 7 Protective sun cream, oil-in-water type Glycerol monostearate 6.0 Cetyl alcohdl 6.0 Oxyethylated fatty alcohol, e.g.

Cremophor A 25 2.0 Oxyethylated fatty alcohol, e.g.

*Cremophor A 6 2.0 Paraffin oil 10.0 Isopropyl myristate 5.0 Silicone oil 350 1.0 Dimethyl 4-dimethylamino-phthalate 3.0 1,2-Propylene glycol 3.0 Perfume oil 0.2 Water 61.6 *("Cremophor" is a Registered Trade Mark) EXAMPLE 8 Protective sun emulsion, oil-in-water type Glycerol monostearate 4.0 Cetyl alcohol 1.0 Cremophor A 25 1.5 Cremophor A 6 1.5 Mixture of triglycerides of saturated vegetable fatty acids, e.g.

*Miglyol 812 5.0 Paraffin oil 5.0 Diethyl 4-dimethylamino-phthalate 5.0 Preservative 0.2 Perfume oil 0.2 Water 79.6 *("Miglyol" is a Registered Trade Mark) EXAMPLE 9 Protective sun emulsion, oil-in-water type Glycerol monostearate 5.0 Cremophor A 25 2.5 Cremophor A 6 1.5 Sesame oil 10.0 Olive oil 5.0 Dibutyl 4-dimethylamino-phthalate 4.0 Aqueous sorbitol solution, e.g.

Karion F 3.0 Preservative 0.2 Perfume oil 0.2 Water 70.6 EXAMPLE 10 Soft Protective sun cream, water-in-oil type *Vaseline 25.0 Cholesterol 0.5 Micro-crystalline wax 0.5 Cetyl alcohol 0,5 Oleyl diglycerol ether, e.g.

Cremophor WO CE 5070 2.0 Dimethyl 4-N-n-butyl-N-ethylamino- phthalate 6.0 Glycerol 3.0 Magnesium sulfate heptahydrate 0.5 Preservative 0.2 Perfume oil 0.3 Water 67.5 *("Vaseline" is a Registered Trade Mark) EXAMPLE 11 Protective sun emulsion, water-in-oil type Vaseline 20.0 Paraffin oil 15.0 Fatty acid ester, e.g. *Cetiol SN 10.0 Carnauba wax 2.0 Cremophor WO CE 5070 5.0 Dibutyl 4-dimethylamino-phthalate 3.0 Glycerol 2.0 Preservative 0.2 Perfume oil 0.3 Water 45.5 *("Cetiol" is a Registered Trade Mark) EXAMPLE 12 Protective sun foam (Aerosol), oil-in-water type Stearic acid 3.5 Cetyl alcohol 1.5 Miglyol 812 5.0 Paraffin oil 5.0 Cremophor A 25 1.5 Di-n-decyl 4-dimethylamino-phthalate 7.0 Diethanolamine 0.5 Preservative 0.1 Perfume oil 0.2 Water 73.4 Contents of aerosol container: 90% by weight of active compound formulation and 10% by weight of propellant 12 (dichloro-difluoromethane) and propellant 114 (dichlorotetrafluoroethane) in the ratio of 40:60.

EXAMPLE 13 Protective sun foam (Aerosol), oil-in-water type Cremophor A 6 1.5 Cremophor A 25 1.5 Cetyl alcohol 2.0 Paraffin oil 4.0 Miglyol 812 2.0 Silicone oil 350 1.0 Dimethyl 4-dimethylaino-phthalate 4.0 Glycerol 6.0 Film-forming agent and foam stabilizer, e.g.

*Luviskol VA 64 1.0 Water 81.0 *("Luviskol" is a Registered Trade Mark) Contents of aerosol container: 90 /n by weight of active compound formulation and 10% by weight of propellant 12 (dichlorodifluoromethane) and propellant 114 (dichlorotetrafluoroethane) in the ratio of 40:60.

Epicutaneous test of dimethyl dimethylaminophthalate: A 10% strength solution in paraffin oil was used for this test. The formulation was applied to the back of 50 test persons, using a standard commercial test plaster.

After 24 hours, the plasters were removed and the reactions were assessed semiquantitatively in the conventional manner. A second determination was carried out after a further 24 hours. In no case was a positive or doubtful reaction found in the tests carried out, so that there is no indication that the compound might cause a primary irritative action or might cause sensitization. Accordingly, the tested substance is outstandingly well tolerated by the skin.

WHAT WE CLAIM IS: -1. A cosmetic formulation for protecting the skin against harmful light and thus preventing or alleviating erythema, the formulation being in a form suitable for application to the skin and containing from 0.1 to 10 per cent by weight of a 4 dialkylaminophthalic acid diester of the general formula:

in which R' and R2 are, each independently, an alkyl group containing from 1 to 18 carbon atoms and in which R3 and R4 are, each independently, an alkyl group of 1 to 12 carbon atoms, and a cosmetically acceptable carrier or diluent, with or without one or more cosmetically acceptable additives, but being free from ingredients harmful to the skin.

2. A formulation as claimed in claim 1 wherein the diester is one having formula I in which R3 and R4 contain from 1 to 6 carbon atoms.

3. A formulation as claimed in claim I or 2 wherein the diester is one having formula I in which R1 and R2 are methyl or ethyl.

4. A formulation as claimed in claim 1 or 2 wherein the diester is one having formula I in which R1 and R2 contain from 3 to 6 carbon atoms.

5. A formulation as claimed in claim 1 or 2 wherein the diester is one having formula I in which R' and R2 contain from 10 to 18 carbon atoms.

6. A formulation as claimed in any of claims 3 to 5 wherein the diester is one having formula I in which R3 and R4 contain from 1 to 4 carbon atoms.

7. A formulation as claimed in claim 6 wherein the diester is one having formula I in which R3 and R4 are methyl.

8. A formulation as claimed in claim 7 wherein the diester is one having the formula I in which R' and R2 have 4 carbon atoms.

9. A formulation as claimed in claim 1 wherein the diester is one spccifically mentioned herein.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (24)

1. **WARNING** start of CLMS field may overlap end of DESC **.

   EXAMPLE 13 Protective sun foam (Aerosol), oil-in-water type Cremophor A 6 1.5 Cremophor A 25 1.5 Cetyl alcohol 2.0 Paraffin oil 4.0 Miglyol 812 2.0 Silicone oil 350 1.0 Dimethyl 4-dimethylaino-phthalate 4.0 Glycerol 6.0 Film-forming agent and foam stabilizer, e.g.

   *Luviskol VA 64 1.0 Water 81.0 *("Luviskol" is a Registered Trade Mark) Contents of aerosol container: 90 /n by weight of active compound formulation and 10% by weight of propellant 12 (dichlorodifluoromethane) and propellant 114 (dichlorotetrafluoroethane) in the ratio of 40:60.

   Epicutaneous test of dimethyl dimethylaminophthalate: A 10% strength solution in paraffin oil was used for this test. The formulation was applied to the back of 50 test persons, using a standard commercial test plaster.

   After 24 hours, the plasters were removed and the reactions were assessed semiquantitatively in the conventional manner. A second determination was carried out after a further 24 hours. In no case was a positive or doubtful reaction found in the tests carried out, so that there is no indication that the compound might cause a primary irritative action or might cause sensitization. Accordingly, the tested substance is outstandingly well tolerated by the skin.

   WHAT WE CLAIM IS: -1. A cosmetic formulation for protecting the skin against harmful light and thus preventing or alleviating erythema, the formulation being in a form suitable for application to the skin and containing from 0.1 to 10 per cent by weight of a 4 dialkylaminophthalic acid diester of the general formula:

   in which R' and R2 are, each independently, an alkyl group containing from 1 to 18 carbon atoms and in which R3 and R4 are, each independently, an alkyl group of 1 to 12 carbon atoms, and a cosmetically acceptable carrier or diluent, with or without one or more cosmetically acceptable additives, but being free from ingredients harmful to the skin.
2. 2. A formulation as claimed in claim 1 wherein the diester is one having formula I in which R3 and R4 contain from 1 to 6 carbon atoms.
3. 3. A formulation as claimed in claim I or 2 wherein the diester is one having formula I in which R1 and R2 are methyl or ethyl.
4. 4. A formulation as claimed in claim 1 or 2 wherein the diester is one having formula I in which R1 and R2 contain from 3 to 6 carbon atoms.
5. 5. A formulation as claimed in claim 1 or 2 wherein the diester is one having formula I in which R' and R2 contain from 10 to 18 carbon atoms.
6. 6. A formulation as claimed in any of claims 3 to 5 wherein the diester is one having formula I in which R3 and R4 contain from 1 to 4 carbon atoms.
7. 7. A formulation as claimed in claim 6 wherein the diester is one having formula I in which R3 and R4 are methyl.
8. 8. A formulation as claimed in claim 7 wherein the diester is one having the formula I in which R' and R2 have 4 carbon atoms.
9. 9. A formulation as claimed in claim 1 wherein the diester is one spccifically mentioned herein.
10. 10. A formulation as claimed in claim 1 wherein the diester is dimethyl 4

    dimethylamino - phthalate, diethyl 4 - dimethylamino - phthalate, dimethyl 4 diethylamino - phthalate, dibutyl 4 - dimethylamino - phthalate, or di - n decyl 4 - dimethylamino - phthalate.
11. I I. A formulation as claimed in any preceding claim which is in the form of a cream, an ointment, a lotion or a powder.
12. 12. A formulation as claimed in any of claims I to 10 in the form of an oil-inwater or water-in-oil emulsion.
13. 13. A formulation as claimed in any of claims I to 10 in the form of an oil.
14. 14. A formulation as claimed in any of claims I to 10 in the form of a solution containing an alcohol as solvent.
15. 15. A formulation as claimed in claim 13 which comprises the diester and a mineral oil or vegetable oil.
16. 16. A formulation as claimed in claim 15 wherein the mineral oil is liquid paraffin, a synthetic fatty acid ester, a glyceride or petroleum jelly.
17. 17. A formulation as claimed in claim 15 wherein the vegetable oil is groundnut oil, olive oil, sesame oil, cottonseed oil, coconut oil, grapeseed oil or castor oil.
18. 18. A formulation as claimed in claim 11 which is in the form of an ointment comprising the diester and petroleum jelly, lanolin or an emulsifing aqueous wool fat alcohol.
19. 19. A formulation as claimed in claim 11 which is in the form of a cream comprising the diester and glycerol, a polysaccharide, tylose, cetyl alcohol, lanolin cream, cacao butter, beeswax, stearic acid, stearyl alcohol, glycerol monostearate, a natural or mineral oil or a fat.
20. 20. A formulation as claimed in claim 12 which is in the form of an emulsion comprising a mixture of glycol monostearate, a vegetable or mineral oil and water, a mixture of ethyl alcohol, water, lanolin and tragacanth, a mixture of ethyl alcohol, stearin and water, a mixture of tragacanth, glycerol, alcohol and water or a mixture of stearic acid, paraffin oil, water and propyl and/or isopropyl alcohol.
21. 21. A formulation as claimed in any preceding claim wherein the diester is present in an amount of from 3% to 7% by weight.
22. 22. A formulation as claimed in claim 1 and substantially as hereinbefore described in any one of Examples 7 to 13.
23. 23. A method of protecting the skin against harmful light which comprises applying to the surface of the skin a diester of formula I defined in claim 1.
24. 24. A method as claimed in claim 23 wherein the diester is applied in the form of a composition as claimed in any one of claims 1 to 22.