DE2519161A1 - ANTI-INFLAMMATORS FOR COSMETIC PREPARATIONS - Google Patents

Description

4 Düsseldorf, April 28, 1975 Henkel & CieGmbH

Patent department at Henkelstrasse 67

z-sü

Patent application

"Inflammation inhibitors for cosmetic preparations"

The invention relates to anti-inflammatory agents for cosmetic preparations, in particular for sun protection and sunburn control agents, based on cyclic acetals from aromatic aldehydes.

E3 it was found that cyclic acetals of the general formula

Ar-CH X,

in Ar for an aromatic radical of the general formula

in which R ^, Rp and R, independently of one another, are hydrogen Halogen atom, a nitro group, an alkyl radical with 1-4 C atoms, an alkoxy radical with 1-4 C atoms, a hydroxyl group

and two of the radicals together represent a methylenedioxy group or together with the 6-membered ring represent a naphthyl radical

and X is an alkylene radical of the general formula

609847/1017

Sheet 2 / to the patent application D 5 ± H l \

Henkel & Cie GmbH

Γ atentabttilung

CR _c

^l 8

C.
t

in the R ₁ . - R _{q is} a hydrogen atom, an alkyl radical with 1-6 C atoms, a hydroxyl group, a hydroxymethyl group or a phenyl radical

and η are the numbers 0, 1 or 2,

are outstandingly suitable as anti-inflammatory agents for cosmetic preparations.

The products are of particular importance as anti-inflammatory Agents in sunscreen or sunburn control agents. When used in means of preventing the Sunburns are the anti-inflammatory agents of the invention Products preferably in combination with conventional ultraviolet filter substances used.

The preparation of the cyclic acetals to be used as anti-inflammatory agents according to the invention can be carried out according to known methods Procedure. For example, they can be extracted from the corresponding aromatic aldehydes and diols gain azeotropic water separation, as described in the monograph Organikum, organic-chemical basic internship, VEB-Verlag der Wissenschaften (1968), p. 379 will. Another method is that the condensation of the aromatic aldehyde with the diol with trimethyl orthoformate or triethyl orthoformate as described by S.R. Sandler and W. Karo in Organic Functional Group Preparation Vol. 12, III, Academic Press, New York, London (1972), pp. 2-70 is pictured.

609847/1017

Henke} & Cie GmbH

Sheet -g for patent application D 51 Ij Ij patent department

As aromatic aldehydes which are used to prepare the cyclic acetals to be used according to the invention are for example benzaldehyde, α-, ß-naphthaldehyde, p-, m-, o-anisaldehyde, p-, m-, o-toluylaldehyde, salicylaldehyde, Vanillin, veratraldehyde, piperonal, p-isopropyl, p-ethyl, p-propyl, p-butyl, p-tert-butyl, p-pentyl, p-hexyl-, o-, m-, p-chlorine, p-, o-xthoxy-, p-butoxy-, p-phenyl-, m-, p-hydroxy-, o-, m-, p- Bromine, o-, m-, p-nitro, p-fluorine, 2.4-, 2.5-, 2.6-, 3.4-, 3,5-dichloro, 2.4-, 2.5-, 2.6-, 3.5-dimethoxy-, 2.4-, 3.4-, 3.5-dihydroxy-2.4-, 3.5-dimethyl-, 4-methoxy-2-methyl-, 3-chloro-4-methoxy-, 3.5-dimethoxy-4-hydroxy-, 2.4.5-trichloro-, 3.4.5-, 2.4.5-trihydroxy-, 2.4.5-, 2.4.6-, 3.4.5-trimethoxybenzaldehyde, Mesitylaldehyde, 2-hydroxy-1-naphthaldehyde to call.

As diols that are used to produce the according to the invention using cyclic acetals can be used, for example, xethylene glycol, 1,2-, 1,3-propylene glycol, 1.2-, 1.3-, 1.4-, 2.3-butylene glycol, 2-methyl-2.3-butylene glycol, Pinacol, hexane-1.2-, 1.3-, -2.4-diol, octane-1.2-diol, pentane-1.2-, -1.3-, -1.4-, -2.4-diol, 2-, 3-methyl-, 3.3-dimethyl-, 3.3-diethylpentane-2.4-diol, 2.2-dimethyl-, 2.2-diethyl-, 2-ethyl-2-methyl-, 2-methyl-2-propyl-, 2-ethyl-2-butyl-, 2-hydroxymethyl-2-methyl-propane-1,3-diol, Glycerine, 2.2.4-trimethylpentane-1.3-diol, 2-methyl-, 2-ethyl-, 2.2.-dimethylhexane-1,3-diol, 1-phenyl-, 1,2-diphenyl-ethylene glycol cite.

Compounds to be used according to the invention are, for example, 2- (o-tolyl) -4-isopropyl-5,5-dimethyl-1,3-dioxaiT, 2- (ra-tolyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (p-Tolyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (o, p-Dimethylphenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (p-isopropyl-phenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (p-isopropylphenyl) -4,5,6-trimethyl-1,3-dioxane, 2- (p-Isopropylphenyl) -4-methyl-1,3-dioxolane,

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Henkel & Cie GmbH

Sheet 4 for patent application D 5l4 4 patent department

2- (p-Hydroxyphenyl) «^ -isopropyl-S, 5-dimethyl-1,3-dioxane, 2- (p-hydroxyphenyl) -5 » 5-dimethyl-1,3-dioxane _s 2- (© -hydroxyphenyl ) ^ -isopropyl-S _s 5-dimethyl-1,3-dioxane ,. 2- (o-hydroxyphenyl) -4,5,6 ~ trimethyl-1,3-dioxane, 2- (-hydroxyphenyl) -4 _s 6-diirethyl-1,3-dioxane, 2- (p »methoxypheny 1) -1,7-dimethyll _s 3-dioxepane, 2- (p-methoxyphenyl) - ¹ i-propyl-5-ethyl-1,3-dioxane, 2- (p-methoxyphenyl) -4-propyl-5 _s 5- dimethyl-l, 3-dioxane, 2- (p-methoxyphenyl) -4-isopropyl-5 "5-dimethyl-1,3-dioxane, 2- (p-methoxyphenyl) -5-ethyl-5-butyl 1,3-dioxane, 2- (p-methoxyphenyl) -S-niethyl-S-isopropyl-1,3-dioxane, 2- (p-methoxyphenyl) -5,5-diethyl-1,3-dioxane, 2- (p-Methoxyphenyl) -5-ethyl-5-niethyl-1,3-dioxane, 2- (p-methoxyphenyl) -4,4,6-trimethyl-1,3-dioxane, 2- (p-methoxyphenyl) - M, 5,6-trimethyl-1,3-dioxane, 2- (p-methoxyphenyl) -5 > 5-dimethyll _s 3-dioxane, 2- (p-methoxyphenyl) -4,6-dimethy1-1,3- dioxane, 2- (p-methoxyphenyl) -4-phenyl-l, 3-dioxolane, 2- (p-methoxyphenyl) -4-ntethyl-l, 3-dioxane, 2- (p-methoxyphenyl) -l _s 3- dioxane, 2 »(p-methoxyphenyl) -4,4,5,5-tetramethyl-1,3-dioxolane, 2- (p-methoxyphenyl) -4 ₉ 5-dimethyl-1,3-dioxolane ₅ 2- (p Methoxyphenyl) -4-methyl-1,3-dioxolane, 2- (p-methoxyphenyl) -1,3- "d ioxolan _s 2- (la-methoxypheny 1) -4-isopropyl-5 ₉ 5-dimethyl-1 _s 3-dioxane, 2- (o-methoxyphenyl) -i-isopropyl-5 ₉ 5-dimethyl-1 j3-dioxane, 2- (δ, p-dimethoxyphenyl) -4-isopropyl-5 »5- dimethyl-1,3-dioxane, 2 - (- o, p-dimethoxyphenyl) -4,5,6-trimethyl-1,3-dioxane , 2- (m-hydroxyphenyl) -4-i opropyl-5,5-dimethyl-1,3-dioxane, 2- (p-hydroxy-m-methoxyphenyl) -4-isopropyl-5,5-dimethyl-1, 3-dioxane, 2- (p-hydroxy-m-methoxyphenyl) -4,4,6-trimethyl-1,3-dioxane, 2- (m, p-methylenedioxyphenyl) -4-isopropyl-5 » 5-dimethyl- 1,3-dioxane, 2- (m, p-methylenedioxyphenyD-4,4,6-trimethy1-1,3-dioxane, 2- (m, p-methylenedioxyphenyl) -4,5,6-trimethyl-l _s 3 -dioxane, 2- (m, p-methylenedioxyphenyl) -4,6-dimethyl-1,3-dioxane, 2- (m, p-methylenedioxyphenyl) -4-methyl-1,3-dioxolane, 2- (p- Chlorophenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (p-chlorophenyl) -4-methy1-1,3-dioxolane, 2- (p-nitropheny1) -4,7-dimethyl -l, 3-dioxepane, 2- (p-nitrophenyl) -5-ethyl-

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Henket & Cie GmbH

Leaf tour patent application D $ ± ki \ patent department

5-butyl-1,3-dioxane, 2- (p-nitrophenyl) -4-propyl-5,5-dimethyl-1,3-dioxane, 2- (p-nitrophenyl) -4-isopropy1-5,5- dimethyl-1,3-dioxane, 2- (p-nitrophenyl) -4,4,6-trimethyl-1 > 3-dioxane, 2- (p-nitrophenyl) -4,5,6-trimethy1-1,3- dioxane, 2- (p-nitrophenyl) -5,5-dimethyl-1,3-dioxane, 2- (p-nitrophenyl) -4,5-dimethyl-1,3-dioxolane, 2- (m-nitrophenyl) - 4-1SOPrOPyI-S, 5-dimethyl-1,3-dioxane, 2- (o-nitrophenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (a-naphthyl) -4 ~ isopropyl-5,5-dimethyl-1,3-dioxane, 2- (β-naphthyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (0-hydroxy-o-naphthyl) -4-isopropyl-5,5-diethyl-1,3-dioxane, 2- (p-tert-butylphenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (p-tert. Butylphenyl) -4-methy1-1,3-dioxolane, 2- (m-chlorophenyl) -4-isopropy1-5,5-dimethy1-1,3-dioxane, 2- (m-chlorophenyl) -4-methyl-1 , 3-dioxolane, 2- (p-Bi-phenylyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2 ~ (p-Bi-phenylyl) -4-methyl-1,3-dioxolane , 2- (2 *, 6'-dichlorophenyl) -4-isopropyl ~ 5 * 5-dimethyl-1,3-dioxane, 2- (2 *, 6 '= · dichlorophenyl) -4-methyl-1,3 - dioxolane, 2- (p-ethoxyphenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (p-ethoxyphenyl) -4-methyl-1,3-dioxolane, 2- (3 ' _J 4 ^l 5 ^l -trimethoxyphenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane, 2- (3 ', 4 ¹ ^ ¹ -trimethoxyphenyl) -4-mathyl-1,3-dioxolane, 2- Pheny1-4-isopropyl-5,5-dimethyl-1,3-dioxane.

The compounds to be used according to the invention are colorless to slightly yellowish, crystalline or liquid substances, which is characterized by a good anti-inflammatory effect with good physiological tolerance, in particular excellent skin tolerance.

When used in sunscreens that are used for contraception serve for sunburn, the cyclic acetals to be used according to the invention are preferably used in combination used with conventional ultraviolet filter substances, such as ethyl p-aminobenzoate, propyl ester,

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Henkel & Cie GmbH

Sheet | J for patent application D 51 ty ty Fatentabt ^ ilung

-butyl ester, isobutyl ester, monoglycerol ester, p-dimethylaminobenzoic acid ethyl ester, -amyl ester, p-diethylaminobenzoic acid ethyl ester, -amyl ester, salicylic acid menthyl ester, -homomentyl ester, -ethylene glycol ester, -glycerol ester, -2-ethylhexyl ester. butyl ester, -bornyl ester, -phenyl ester, triethanolammonium salt of salicylic acid, anthranil-boronyl ester, p-methoxycinnamic acid 3-ethoxyethyl ester, -2-ethylhexyl ester, p-acetamidocinnamic acid isopropyl ester, 2.2 ^I -dihydroxy-4,4'-benzyne 2-hydroxy-4-ethoxybenzophenone, ^ -hydroxy-ty-n-octoxy-benzophenone, 4-phenylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 4-phenylbenzophenone-2-carboxylic acid isooctyl ester, 7- Ethylamino-4-methylcoumarin, 7,8-dihydroxycoumarin, 6,7-dihydroxycoumarin, 7-hydroxycoumarin, 4-methyl-7-hydroxycoumarin, 2-phenylbenzimidazole-5-sulfonic acid, sodium 3,4-dimethoxyphenylglyoxylate, butylbenzalacetone, benzalacetone, 3-benzylidene-DjL-camphor, 3- (p-methylbenzylidene) -D, L-camphor and urocanic acid.

When used as anti-inflammatory substances, the cyclic acetals according to the invention can be converted into liquid, pasty or solid cosmetic preparations are incorporated, such as. B. aqueous solutions, aqueous suspensions, emulsions, Solutions in organic solvents, oils, ointments, creams, pens or powders. The preparations can be of the most varied Serve purposes as opposed to general skin waters with anti-inflammatory effects, aftershave, water, pencils, or lotions Insect bites, shaving powder, baby powder, creams or lotions, but especially as aqueous, emulsion-like, oily or pasty sunscreen or sunburn control preparations.

609847/1017

Hang! & Cie GmbH

Sheet ^ to patent application D 51 ^^ patent department

When used as anti-inflammatory substances, the cyclic acetals according to the invention are used in quantities from 0.01 to 10 percent by weight, preferably 0.5 to 5 percent by weight, based on the total batch of the cosmetic agent used. If the cyclic acetals according to the invention are used in sunscreens in Used in combination with UV filter substances, the amount of UV filter substances is 1 to 10 percent by weight, preferably 2 to 6 percent by weight, based on the total sunscreen agent.

The following examples are intended to explain the subject matter of the invention in more detail without, however, restricting it thereto.

609847/1017

Henkel & Cie GmbH

Sheet / to the patent application D tjltyty patent department

Examples

First, the preparation of the cyclic acetals to be used according to the invention will be described.

A) 2- (o-Tolyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane

A mixture of 24 g (0.2 mol) of o-toluylaldehyde, 29.2 g of 2,2,4-trimethylpentane-1,3-diol, 29.6 g of triethyl orthoformate and a spatula tip of p-toluenesulfonic acid was 16 Stirred at room temperature for hours. After the volatile constituents had been distilled off (up to a bottom temperature of 100 ° C.), the residue was taken up in ether, the solution was shaken out with sodium bicarbonate solution and water and dried over magnesium sulfate. After evaporation, the product was fractionally distilled through a column. 31 g (63 % of theory) of pure 2- (o-tolyl-4-isopropyl ~ 5,5-dimethyl-1,3-dioxane with a boiling point of 150 ° C./1.5 Torr with a refractive index n _{? 0} : 1.5053 received.

The products mentioned below were obtained analogously to the production method listed above.

B) 2- (m-Tolyl) -4-isopropyl-5 »5-dimethyl ~ l _? 3-'dioxane bp 98 ° C / _{0.1 Torr, n 2Q} : 1.4520

C) 2- (p-Tolyl) -4-isopropyl-5,5-dimethyl- 1,3-dioxane bp 92-93 ° C / _{0.15 Torr, n 2Q} : 1.5007

D) 2- (o, p-Dimethyl-phenyl) -4 ~ isopropyl-5,5-dimethyl-1,3-dioxane

Bp 100-1O2 ° C / 0.15 torr, n _2Q : 1.5055

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Henkel & Cie GmbH

Sheet M for patent application D 5144 patent department

E ₁ ) 2- (p-isopropyl-phenyl) -4-isopropy1-5 _; 5-dimethyl-1,3-dioxane bp 112 ° C / 0.01 torr, n _2Q : 1.4981

E2) 2- (p-13opropyl-phenyl) -4,5,6-trimethyl-1,3-dioxane

Bp. 156 ° C / 3, O Torr, n _{2 (J} : 1,5O4l

E. 2- (p-13opropyl-phenyl) -4-methy1-1,3-dioxolane bp 121 ° C / 2.4 Torr, n _2Q : 1.533

P ₁ ) 2- (p-Hydroxyphenyl) -H-isopropyl · ^ -5,5-dimethyl- · 1,3-dioxane
Mp. 87 - 90 ⁰ C

F ₂₎ 2 ~ (p ~ hydroxy ~ phenyl) -5 »5-dimethyl-l, 3-dioxan mp. 132-133 ⁰ C.

G ₁ ) 2- (o-Hydroxyphenyl) -4-JSOPrOPyI-S, 5- dimethyl-1,3-dioxane

Bp. 131-13 ¹ » ^O C / 0 _> 02 Torr, n _2Q : 1.5153

Gp) 2 - * (o-hydroxyphenyl ) -4 _> 5,6 ~ trimethyl- 1,3-dioxane

_2Q

Bp 114 ° C / O, O1 torr, n _2Q : 1.5202

G,) 2- (o-Hydroxyphenyl) ~ 4,6-dimethyl ~ 1,3-dioxane bp 112 ° C / 0.01 Torr, n _{2 ()} : 1,500

H ₁ ) 2 ~ (p-methoxy-phe n yl) -4,7-diinethyl - l ^ 3-dioxepane

Bp. 157-16O ° C / 3.0 O Torr, n _2Q : 1.508 H ₂ ) 2- (p-Methoxyphenyl) ~ 4-propyl-5-ethyl-1,3-dioxane

Bp 133-136 ° C / 0.15 torr, n _{2 (J} : 1,5102 H,) 2- (p-methoxyphenyl) -4-propyl-5 _f 5-dimethyl-1,3-dioxane

Bp 169-17O ° C / 3, O Torr, n _2Q : 1.5068

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Henkel & Cie GmbH

Sheet ^ Ozur patent application D 5144 patent department

Hj.) 2- (p-Methoxyphenyl) -4-JSQPrOPyI-S, 5-dimethy 1-1,3-dioxane

Bp 123 ° C / O, O3 torr; n _2Q : 1.5098 H _c ) 2- (p-methoxyphenyl) -5-ethyl-5-butyl-1,3-dioxane

D si a ■■ = - * *

Bp 146-148 ° C / _{0.15 torr, n 2O} : 1.5097 Hg) 2- (p-methoxyphenyl) -5-methy1-5-propyl-1,3-dioxane

Bp 180-182 ° C / 1.5 torr, m.p. 32 ° CH ₇ ) 2- (p-methoxyphenyl) -5,5-diethy1-1,3-dioxane

Bp. 187-188 ° C / 2.3 torr, n _2Q : 1.5172 Hq) 2- (p-methoxyphenyl) -5-ethyl-5-methy1-1,3-dioxane

Bp 170-172 ° C / 1.5 torr, m.p. 45 ° C H) 2- (p-methoxyphenyl) -4,4, G-trimethyl-1,3-dioxane

Bp. 149-152 ° C / 3, O Torr, n _2Q : 1.5127 ^H ifP 2- (p- Methoxy-phenyl) -4-phenyl-1,3-dioxorane

Bp. 180 ⁰ C / O, 6 Torr, mp. 62-64 ° C H ₁₁₎ 2- (p-methoxy-phenyl) -4,5,6-trimethyl-l, 3-dioxane

Bp. 10 3 ° C / 0.3 torr, n _2Q : 1.5164 H ₁₂ ) 2- (p-methoxyphenyl) -5,5-dimethyl-1,3-dioxane

Bp. 112-113 ° C / O, Ol Torr, m.p. 75-76 ° C H ₁ ,) 2- (p-methoxyphenyl) -4,6-dimethy1-1,3-dioxane

Sdp. 1O5 ° C / O, O2 Torr, mp. 53-56 ° C + 78-8O ⁰ C H ₁ J ₄₎ 2- (p-methoxy-phenyl) -4-methyl-1-1,3-dioxan bp. 158 ° C / 2.1 Torr, n _2Q : 1 _s 525O

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Hang! & Cie GmbH

Sheet yi for patent application D 5 ± l \ l \ patent department

< \\ * 251916 I.

H ₄ r-) 2- (p-methoxyphenyl) -1,3-dioxane

ip ^E * - ^c * -

Bp. 127-128 ° C / O, 9 Torr, η _{2 ()} : 1.5363, m.p. M6-48 ° C H ₁ ^) 2- (p-methoxyphenyl) -4, M, 5.5- tetramethyl1-1,3-dioxolane

.Sdp. 140 ° C / 2.5 Torr, n _2Q : 1.5098 H ₁₇ ) 2- (p ~ methoxy-phenyl) - ^ ^ -dimethyl-l ^ -dioxolane

Bp 90-92 ° C / _{0.110 torr, n 2Q} : 1.5150 Hg) 2 " (p- methoxyphenyl) -k- methylol, 3-dioxolane

Bp. 103-105 ° C / 0.15 torr, n _2Q : 1.5223 H ₁₉ ) 2- (p- methoxyphenyl) -1,3-dioxolane bp. 106 ° C / 0.6 torr, n _2Q : 1.5351

I) 2- (m-Methoxyphenyl) "4-isopropyl-5» 5-dimethyl-1,3-dioxane

Bp 177-178 ° C / 1.7 torr, n _2Q : 1.5075

J) 2- (o-Methoxyphenyl) -4 ~ isopropyl-5-5 "dimethyl-1,3 ~ diuxane

. B.p. 158 ° C / 2.5 Torr, P. 48-50 ⁰ C

K ₁ ) 2- (o, p-dimethoxyphenyl) -4-isopropyl-5 ^ 5-dimethyl - 1,3-dioxane

Bp 138 ° C / 0.2 torr, m.p. 57-59 ° CK ₂ ) 2- (o, p-dimethoxyphenyl) -4,5,6-trimethyl-1,3-dioxane

^v bp 133 ° C / _{0.2 torr, n 2 ()} : 1.5227

L) 2- (m-Hydroxyphenyl) -M-isopropyl-5,5-dimethyl-1,3-dioxane

Melting point 99 - 100 ⁰ C (recrystallized from ether / petroleum ether)

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Hang! & Cie GmbH

Sheet ^ E for patent application D 5144 patent department

- 41 <251916!

M ₁ ) 2- (p-Hydroxy-m-methoxyphenyl) -4-isopropyl-5T5-dimethyl -1,3-dioxane, bp 150 ° C / 0.3 Torr, m.p. 67-70 ° C

M ₂ ) 2- (p-Hydroxy-m-methoxyphenyl) -4 _y 4,6-trimethyl- Ij 3- dioxane

Bp 155 C / 1.2 Torr, n _2Q : 1.5279

N ₁ ) 2- (m, p-Methylenedioxy-phenyl) -4-isopropyl-5> 5-dimethyl-1,3-dioxane

Bp. 135 ° C / _{0.2 Torr, n 2Q} : 1.5183 N ₂ ) 2- (ιη, ρ-methylenedioxy-phenyl) -4,4,6-trimethyl-1,3-dioxane

Bp 167 ° C / 4 Torr, n _2Q : 1..5224
N,) 2- (m _> p-methylenedioxy-phenyl) -4,5,6-triethyl.1-1 _> 3-dioxane

Bp. 161 ° C / 2, O Torr, n _2Q : 1.5255 N _1. ) 2- (m, p ~ Methylenedioxy-phenyl) -4,6-dimethyl-1,3-dioxane

. B.p. 120 ⁰ C / 0.6 Torr, mp ¹ 5 "-. 57 ° C Nc) 2- (m, p-methylenedioxy-phenyl) -4-methy1-1,3-dioxolan

. Sdp L43 ° C / 2.6 torr, n _{2 ():} l, 5338 ^ ⁰ I 2- (p-chloro-phenyl) ~ 4-ieopropyl-5> 5 ~ dimethyl-l, 3-dioxane

Bp 160 ° C / 2, O Torr, n _2Q : 1.5126 O ₂ ) 2- (p-chloro-phenyl) -4-methyl-1,3-* dioxolane bp 121 ° C / 1.8 Torr , n _2Q : 1.5252

P ₁ ) 2- (p-nitro-phenyl) -4,7-dimethyl-1,3-dioxepane bp 170 ° C / 2.8 Torr, n _2Q : 1.5272

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Sheet yfzMX patent application D 5144 patent department

2513161

P ₂ ) 2- (p-nitrophenyl) -5-ethyl-5-butyl-1,3-dioxane

Bp 218 ° C / 4 torr, m.p. 40-47 ° CP,) 2- (p-nitrophenyl) -4-propyl-5,5-dimethyl-1,3-dioxane

Bp 188 ° C / 2.6 Torr, n _2Q : 1.5220 P _1. ) 2- (p-Nitro-phenyl) -4-isopropyl-5> 5-dimathy 1-1,3-dioxane

Bp 124 ° C / 0.12 torr, n _2Q : 1.5215 P ₅ ) 2- (p-nitro-phenyl) -4,4,6-trimethyl-1,3-dioxane

Bp 141-142 ° C / _{0.4 torr, n 2Q} : 1.5165 P ₆ ) 2- (p-nitro- phenyl ) -4, 5,6-trimethy1-1,3-dioxane

Bp 175-177 ° C / 2, O Torr, n _2Q : 1.5292 P ₇ ) 2- (p-nitrophenyl) -5,5-dimethyl-1,3-dioxane

Dioxolane 3-80 ⁰ C (from chloroform / petroleum ether) Pg) of 2- (p-nitro-ph en yl) -4,5-dimethyl-l, - mp 79th

Bp. 127 ° C / O, 1 Torr, mp. 48-52 ⁰ C

Q) 2- (m-Nitro-phenyl) -4-J3Opropyl-5,5-dimethyl-1,3-dioxane bp. 191 ° C / 3 Torr, n _{2 ()} : 1,5215

R) 2- (o-nitro-phsnyl) -4-isopropyl-5 _> 5-dimethyl-1,3-dioxane

Bp 180 ° C / 3 torr, n _2Q : 1.5195

. S) 2- (g-Maphthy1) -4-J3opropyl-5,5-dimethyl-l, 3-dioxan b.p. 205-208 ⁰ C / 2.5 torr, n _2Q: 1.5639, mp 35 ° C. "

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Henkel & Cie GmbH

Sheet ^ for patent application D 514 4 patent department

. T) 2- (B-naphthyl) -4-i3opropyl-5 "5-dimethyl-l, 3-dioxan b.p. 211 ^o C / 3.0 torr, n _20: 1.5613, m.p. 59-6l ° C.

U) 2- (B-Hydroxy-g-naphthyl) - ^ - isopropyl ^, 5-dimethyl-1,3-dioxane

Mp. 87 - 89 ⁰ C (from cyclohexane)

V ₁ ) 2- (p-biphenylyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane

Mp. 71-73 ° C (petroleum ether) V ₂ ) 2- (p-biphenylyl) -4-methyl-1,3-dioxolane

Bp 187 ° C / 3.1 torr, n _2Q : 1.5921

W ₁ ) 2- (p-tert-butyl-phenyl) -4-isopropyl-5,5-dimethyl-1,3-dioxa n

. B.p. 167 ⁰ C / 2.3 torr, n _2Q: 1.5004 W ₂₎ 2- (p-tert.butyl-phenyl) -4-methyl-l, 3-dioxolan

Bp 132 ° C / 2.5 torr, n _2Q : 1.5052 X ₁ ) 2- (m-chloro-phenyl) -4-propyl-5,5-dimethyl-1,3-dioxane

Bp. 156 ° C / 2.8 Torr, n _2Q : 1.5131 X ₂ ) 2- (m-chloro-phenyl) -4-methyl- 1,3-dioxolane bp. 110 ° C / 2.2 Torr, n _2Q : 1.5251

Y ₁₎ 2- (2 ', 6 ^{t-dichloro-phenyl)} _{-4-isopropyl-5>} 5-dimethyl-1,3-dioxane

Mp. 60-62 ⁰ C (from n-hexane)

Y ₂ ) 2- (2 ', 6'-dichloropheny1) -4-methyl-1,3-dioxolane bp 137 ° C / 2.7 Torr, n _2Q : 1 _S 5495

609847/1017

Hang! & C: e GmbH

Sheet ^ f for patent application D 51 ^ ¹ I Pa'.ant jbteilunc

Z ₁ ) 2 - »(p-Ethoxyphenyl) ^-1 t -isopropyl-5,5-dimethyl-1,3-dioxane

Sdp, l60-l6l | ⁰ C / 1,3-1,7 Torr, n _2Q : 1.5063 Z ₂ ) 2- (p-Xthoxyphenyl) - ^ - methyl-1,3-dioxolane bp. 137 ° C / 2 _S 2 Torr , n _2Q : 1.5165

AA ₁ ) 2- (3 ' , **' , 5 ^! -Trimethoxyphenyl) ^-1 t -isopropyl-5,5-dimethyl 1,3-dioxane

Bp 193 ° C / 1.8 torr, m.p. 65-69 ° C AA ₂ ) 2- (3 ^T , ^ ¹ , 5 ^f -trimethoxyphenyl) -4-methyl-1,3-dioxolane

^AB ) 2-phenyl-4-isopropyl-5,5-dimethy1-1.3-dioxane

Bp 165 ° C / 1.5 Torr, n _2Q : 1.5273

Bp 96 ° C / _{0.3 torr, n 2Q} : 1.5021

The following statements are intended to describe the anti-inflammatory properties of those to be used according to the invention Compounds and their suitability for cosmetic preparations, in particular sunscreen or sunburn control agents, point out.

In the investigations listed below, the cyclic acetals to be used according to the invention were used tested for their anti-inflammatory properties. Previously there was an exploratory study of her Toxicity carried out in order to be able to determine the test dosages for further investigations.

- 16 -

609847/1017

Henkt * & Die GmbH

Blatt ^ TO to the patent application D 51 ty 4 PatenttbteHunc.

2513161

The rat paw test, as described by P. Kemper in the journal "Arzneimittelforschung" 10 (1960), p. 777, was used as a test to assess the compounds with regard to their suitability for inhibiting the inflammation caused by sunburn. To produce the edema, 0.1 ml of 6 % dextran solution was injected into the right hind paw about 5 mm deep between the second and third toe of the test animals. While only the dextran solution was administered to the control animals, the test animals were injected or per os 30 minutes before their injection with the various test substances in the amount indicated in the table. The volume of the paws was determined with the electrical volume measuring device described in more detail by F. Kemper and G. Amelin in the "Zeitschrift für die Gesamt experimental Medizin" 131 (1959), page 07. The measurements were made 30 minutes before injections of the dextran solution, ie at the time of administration of the test substances to the test animals and 30 minutes after the injection of the dextran solution. For comparison, the left untreated paw was always measured at the times mentioned. From the values for the swelling in animals that had been treated with the test substance and in untreated animals 30 minutes after the dextran injection, the degree of inhibition of the edema was calculated as a percentage of the swelling that occurred in animals that had not received any test substance.

Another rat paw test was that of CH. Winter in the J. of pharmac. and experiment. Therap. Vol. 141 (1963) So-called amputation methodology described on page 369 used. In this procedure, the test animals are exposed 3 hours after the injection of the inflammatory substance The substance is killed and the paw weights are determined. In these studies, carrageenin is used as an inflammation-causing product. Inhibition of development of the edema of the rat paws by the test substance, the Is administered orally 1 hour before the inflammation is triggered,

- 17 609847/1017

Henke »6 _; Ce GmbH

Sheet yfixx patent application D 5-L ^ Patenttbhjilunc

serves as an indicator of the effect and is expressed as a percentage.

Based on general experience, the results of the rat paw tests can be used as a basis for the assessment a compound serve as a sunburn control agent. Furthermore, a UV text was carried out on hairless mice, which also allows a statement to be made about the usefulness of the substances as sunburn control agents. the hairless mice were irradiated on the back with a UV lamp from a distance of 60 cm for 30 minutes, whereby a Skin inflammation was triggered. In the laboratory animals the test substances were administered by interperitoneal injection or per os following the irradiation, while the control animals received no after-treatment. The dosage of the test substances was the same like in the rat paw test. The degree of edema formation was determined by measuring the thickness of the skin folds after 30 hours. From the comparison of the change in skin fold thickness through the irradiation in treated test animals with the change in the thickness of the skin folds in animals that are irradiated, but were not treated, the degree of percent inhibition of the erythema was determined in the subsequent Table is given.

The UV erythema test was carried out on guinea pigs as a further test. For this purpose, the backs of the test animals are used by shearing and treating with a depilatory cream freed from hair. The test animals are then 8 minutes irradiated and treated following the irradiation on the marked test fields with the test solutions or ointments. The second application takes place after 30 minutes, the third and the following treatments follow one after the other 60 minutes. After 6 hours from the irradiation, the animals are washed off, dried and assessed visually. The evaluation is repeated the next morning and the mean value for each substance is calculated from both evaluations. Be there as irradiated and untreated control points the two

- 18 609847/1017

Henke; & Cie GmbH

Sheet y & zu patent application D 51 ^ 4 patent ibfejiluna

^ 2519Ί61

Radiation spots chosen just behind the ears. Their reddening intensity is set equal to O. Disappearance of the redness in the treated areas is rated with plus points up to + 4 (no more stain recognizable) and intensification of the redness with minus points up to -4 (blistering). The sum of the evaluations from both evaluations, set in relation to the number of animals multiplied by 4 as the maximum achievable (= 100%) , gives the percentage inhibitory value of the substance. The inhibition values determined in this way are listed in the table below under the heading "UV erythema guinea pigs".

In the investigations carried out - as described above - for the individual substances the in values listed in the table below.

- 19 -

609847/1017

Tabel

CD CD CX)

Anti-inflammatory properties and Orientation
Toxicity LD ^ _n orienting toxicity inhibition Dextran edema inhibition
(*) UV edema
Hairless mouse UV erythema
Guinea pig C. Test sub
punch 50
(g / kg) Rat paw test 17th dose
po
(mg / kg) 30th 5? In vase
line
Inhibition (%)
and 30 h 5 * ig in Tink
door
Inhibition (%) A. 1.0 Carragenine edema 37 500 26th - ■ 48 B. 1.0 dose
po
(mg / kg) 12th 250 - - 40 C. 1.0 1,000 38 - 12th - 36 D. 1.0 500 37 500 22nd - 32 ^E l 1.0 1,000 500 - 50 /1 ^E 2
^E 3 1,000 13th 14th 40
33 O 0.75 1,000 19th 500 15th 38 P ₂ 1.13 25th 500 11 - 36 ^G l 1.0 500 23 1000 26th - 37 ^H 2 1.0 500 30th 500 29 - - ^H 3 1.0 1,000 15th
32 500 23
14th 30th 45 ^H 4
^H 5 1.0
1.0 1,000 40 1000
500 45 31 45 t
42: ^H 6 1.0 1,000 23 ' 1000 16 60 33 < W.
^H 7 1.0 1,000
1000 47 500 18th 27 45 < K ₉ 1.0 1,000 1,000 18th 1,000 1,000

Table 1 (port setting)

CT5 O CO CO

Anti-inflammatory Orientation
Toxicity LD _cn Properties and orienting toxicity inhibition
(*) Dextran edema - 500 - inhibition UV edema
Hairless mouse UV erythema
Guinea pig Test sub
punch (g / kg) Rat paw test 33 dose
po
mg / kg) 1,000 1,000 -
14th 5 / fig in vase
line
Inhibition ( %)
and 30 h 5 days in Tink
door
Inhibition ( %) ^H 10
^H ll 1.0 Carrageenin edema 20th 1,000 1,000 - 18th - 38
37 H ₁₂ 1.0 dose
po
mg / kg) 10 500 1,000 1,000 - - 36 ^H 13 1.0 1,000 44 1,000 - 36 - 41 ^- ^
^H l4 1.0 1,000 33 1,000 21 63 47 ^H l6 1.0 1,000 36 - 28 27 - H ₁₇ 1.0 1,000 44 - 26th - - ^H l8 1.0 1,000 26th - 17th 37 50 ^H 19 1.0 1,000 14th - 50 51 ^K l 1.0 1,000 14th - - 40 K ₂ 1.0 1,000 10 - - 47 ^M l 1.0 250 39 29 - 40 ^N l 1.0 500 - - 24 45 1.0 1,000 46 16 - 40 P ₁ 1.0 1,000 - - - 40 ^P 2 1.0 - 41 19th - 38 Q 1.0 1,000 12th - 28 38 T 1.0 - 30th 36 1,000 1,000

Ie GmbH

Sheet 9 ^ to patent application D 5144 Ha.entibteilunu

Below are some examples of the invention Cosmetic preparations containing substances listed.

1. To be used in the manufacture of a sun protection oil

20 g of 2- (o-tolyl) -4-isopropyl-5,5-dimethyl-1,3-dioxane 30 g of menthyl salicylate

suspended under heating in 100 ς paraffin oil

and then wii ingredients

and then at approx. 25 ° C, the following further ones are advised

300 g vegetable oil containing lecithin 400 g olive oil 100 g isopropyl myristinate 100 g purcellin oil

intimately mixed.

2. Be used to make a sunburn powder

40 g of 2- (p-isopropylphenyl) - ⁱ ! -Isopropyl-5,5-dimethyl-1,3-dioxane

intensively in a powder mixer

g rice starch g colloidal clay g lycopodium g talc

brought into homogeneous distribution.

3. To make an anti-inflammatory aftershave will

30 g of 2- (p-methoxyphenyl) -4-methyl-1,3-dioxolane

- 22 -

609847/101

Hey ike! . "iCie GmbH

Sheet 2 yiur patent application D 5 J. 1} 4 patent department

along with a solution of

5 g citric acid
30 g glycerine in
g Hammarnelis water

combined with a perfumed, 80% alcoholic preparation to a total of 1000 g.

4. Be used to make a sunscreen

^ O g glycerol monostearate
g beeswax
g mineral oil
50 grams of ceresin
50 g of an absorption base based on

Cholesterol, beeswax, stearyl alcohol and Vaeeline

30 g of 2- (p-methoxyphenyl) -l, 3-dioxolane 40 g benzyl salicylate

melted together at 65 ^{° C.} Into this warm mixture is a mixture of heated to the same temperature

2 * 17 g water
13 g borax
2 g of methyl p-oxybenzoate

incorporated with vigorous stirring and the obtained Cream will continue until it reaches room temperature touched.

- 23 -

609847/1017

Her; ko>. & C ': eGmbH

Biäitjj ^ for Pateotan avoidance D 5144 Patent jbteilur ^

5. To produce a sun protection emulsion, a mixture of

20 g glycerol monostearate 70 g stearic acid 30 g oleic acid 20 g cetyl alcohol 40 g 2- (o, p-dimethoxyphenyl) -4,5,6-trimethyl-

1,3-dioxane 40 g phenyl salicylate

a mixture of 800 g of water with vigorous stirring, 10 g glycerine and 9 g triethanolamine are added. The lotion obtained is then stirred while cold.

The above emulsion can also be used a propellant gas in the ratio of 80 parts lotion: 20 parts propellant gas in aerosol form.

Instead of the cyclic acetals used in the aforementioned formulations, the other cyclic acetals listed above can be used.

609847/1017

Claims (5)

Claims Use of cyclic acetals of the general formula Ar-CH X, in Ar for an aromatic radical of the general formula in which R ^ R ₂ and R, independently of one another, hydrogen, a halogen atom, a nitro group, an alkyl radical with 1 <- 4 carbon atoms, an alkoxy radical with 1-4 carbon atoms, a hydroxyl group and two of the radicals together represent a methylenedioxy group or together with the 6-membered ring represent a naphthyl radical and X is an alkylene radical of the general formula C ι R, \ ι / R t R, in which R _2. -Rq is a hydrogen atom, an alkyl radical with 1-6 C atoms, a hydroxyl group, a hydroxymethyl group or a phenyl radical - 25 - ^ 609847/101 Henke * ÄCle GmbH Sheet JiJ 'for patent application D 5144 PatertobtQiiunn and η are the numbers 0, 1 or 2 as an anti-inflammatory in cosmetic preparations. 2. Use of cyclic acetals according to claim 1 as Anti-inflammatory agents in sunscreens or sunburn control agents . 3. Use of cyclic acetals according to claim 1 and 2 in an amount of 0.01 to 10 percent by weight, preferably 0.5 to 5 percent by weight, based on the total preparation. 4. Use of cyclic acetals according to claims 1-3 as an anti-inflammatory in sunscreens in combination with common UV filter substances. 5. Use of cyclic acetals according to claim 4, wherein the amount of UV filter substance 1 to 10 percent by weight, is preferably 2 to 6 percent by weight, based on the total sunscreen. 609847/1017