DE202012006657U1 - Sun protection indicator - Google Patents

Abstract

Sun protection indicator characterized by the fact that it contains a photochemical dye.

Description

The invention relates to a sunscreen indicator which indicates the decreasing effect of sunscreen on the skin using a chemical process. The basis for this invention is the use of UV-active carbonyl compounds for the indication of radiation with a wavelength of 280-400 nm (UV A / B radiation) by optical change of the substance (color change or fluorescence). In practice, this can be achieved by photochemical dyes, which are based on the principle of light-induced structural changes of chemical substances, ie, for example, a "cis-trans isomerization".

Such an isomerization is based on the sun protection indicator for which protection of utility patents is sought. This is a substance (eg cream) in which the above-mentioned photochemical dyes are incorporated. This cream should be applied to the skin at certain points, for example at a point on the arm that is strongly exposed to the sun's rays, and covered with sunscreen. The application in the form of a pattern (cross, circle, etc.) is conceivable here. The sunscreen protects the skin from UV radiation. However, after some time, after its effects, so penetrates UV radiation to the skin and damaging them. In order to determine when this is the case and thus a renewed creaming or ending the sunbathing is necessary, the indicator should give a 'warning' by changing its color.

The effect of sunscreen can be reduced by various processes. These include, for example, the removal by water (sweat, swimming, etc.), by friction or the inclusion of sunscreen through the skin. Many users can not estimate the extent to which sunscreen is removed from or absorbed by the skin, and are therefore often unsure about how long the applied protection is effective. Furthermore, too small an amount of sunscreen is often applied. This also leads to a faster loss of effect than expected by the user.

Excessive exposure of the skin to UV radiation, however, can lead to skin aging (such as skin cancer), in addition to faster skin aging. This utility model protection relates to a sunscreen indicator in which a photochemical dye (here a UV-active carbonyl compound) is introduced. This is applied directly to the skin and indicated by optical change, the decrease in the effect of the sunscreen, to make the user this loss of effect clear. The direct application of photochemical dyes, for example, UV-active carbonyl compounds in a sunscreen indicator, to illustrate the loss of sunscreen effect on the skin is a novel invention.

An already known method is the UV indication using plastic tapes in which a UV-indexing substance is incorporated and which are attached to clothing or on the skin. These are then covered with sunscreen when creaming. However, in contrast to the indicator described in this application, these plastic tapes are not skin-like and therefore have a different behavior in the detachment of the sunscreen than in direct application to the skin. This can lead to a falsification of the result. Furthermore, both sunscreens and the indicator described are partially UV-transparent and thus allow both a degree of tanning of the skin. This is not guaranteed by plastic tapes, in which the indicator is introduced, since they keep the UV radiation to 100%. Thus, the skin at the location of the tape remains untanned. Another disadvantage of UV indicators that are not applied directly to the skin, is that they can fall off especially during sports activities and thus have no more benefit. In addition, such bands are often perceived as disturbing and unpleasant.

A patent of L'Oreal SA (Pub. EP 0 847 751 B1 ) protects the application of inorganic (mineral) photochromic compounds, characterized in that the compound is an aluminosilicate with at least one dopant which changes under the influence of UV radiation. However, the UV-active carbonyl compounds used in the sun protection indicator described herein are not covered by the patent protected materials and also the principle of the sunscreen indicator is not mentioned or protected in any way.

Another already known method is the use of photochromic dyes for the indication of UV radiation (see patent application publication no. US2002 / 0022008 A1 the Procter & Gamble Company). Unlike this method, the sun protection indicator presented here does not photochromic but a photochemical substance used. The significant difference between these two groups of substances is that the reaction of photochromic dyes with UV radiation is reversible in the absence or absence of this type of radiation, that is, the color of the substance may decrease again or disappear completely. The change in color of photochemical dyes, however, is not reversible by changing the light composition (see Photochromism Molecules and Systems, Heinz Dürr, Elsevier, 1990 ). This is the great advantage of the described invention. Photochromic dyes have a chemical equilibrium between the starting material and the differently colored end product. In the substances used in already known processes, this balance is shifted by an increase in incident UV radiation and the associated decrease in the proportion of visible light to the end product. If the proportion of UV radiation decreases, the color is more similar to the original substance. So, if the user drifts from a sunny spot into the shade, where the proportion of UV radiation is much lower, the photochromic substance returns almost to the color of the original substance due to the reversibility of its color change. However, even in the shade there is still a certain amount of UV radiation that damages the skin after a while. However, this is relatively low compared to the amount of visible light. Thus, the color of the UV indicator is almost that of the starting substance and thus the danger is almost invisible to the user. In the case of photochemical dyes whose reaction is not reversible, the change in color persists even with a reduction in the proportion of UV radiation. Thus, it can not lead to a falsification of the result both in the application in sunny and shady places. Furthermore, the composition of the UV indicator in the Procter & Gamble patent does not allow this product to be removed from the skin by water or soap. It is only a replacement with the help of alcohol, nail polish remover or similar substances possible. This is a problem especially when applied to skin irritated by UV radiation. All the substances used in our product are predominantly greasy and only sparingly soluble in water due to their long alkyl radical. Therefore, contact with water does not cause the indicator to come off. Thus, the result is not distorted by sweating, swimming, etc. However, it is possible to remove the described indicator with soap from the skin. Soap is a surfactant that allows the formation of a removable dispersion of water and indicator.

One issue that arises when using the sunscreen indicator directly on the skin is the toxicity of the substance used. Therefore, it makes sense to use a substance that already exists in the human organism.

An example of such a substance is the aldehyde 11-cis-retinal, which plays a significant role in human vision. This substance can by a of Babak Borhan, Maria L. Souto, Joann M. Um, Bishan Zhou and Koji Nakanishi (see Chem. Eur. J. 1999, 5, No. 4 ) are synthesized efficiently and in an amount sufficient for commercial use. As shown in material 1, the β-ionone (CAS: 79-77-6) is converted by a chemical process into 11-cis-retinol and in a further step tetrapropylammonium perruthenate (CAS: 114615-82-6) (TPAP ) with N-methylmorpholine-N-oxide (CAS: 7529-22-8) to the final product 11-cis-retinal.

The 11-cis-retinal used as a dye is also known as vitamin A and as such has even positive effects on the health of the skin. Thus, for example, it leads to a thickening of the epidermis, an improvement in cell division, an increase in skin metabolism and can even reduce the depth of wrinkles in skin damaged by UV radiation (Die 5-Minuten Kosmetik, Jean Pütz / Christine Niklas, 1990). These positive effects do not affect most of the substances used to date as a sunscreen indicator.

In order to prevent further oxidation of the 11-cis-retinal in the air, stable derivatives of this substance, so-called ketimines or aldimines, should be used. These are obtained, for example, by the reaction with hydroxylamine (H ₃ NO) (M2) or its derivatives in an acidic solution. The thus-synthesized stable derivatives of the colorless 11-cis-retinal absorb light of wavelength between 280-400 nm, being converted into all-trans-retinal (yellow, absorption range: about 500 nm), the other by its other absorption range of a different color and can therefore be used as a basis for the sun protection indicator (M3).

Furthermore, contrast enhancement on the skin is conceivable by conversion of the yellow all-trans retinal into bisretinyl hydrazine (orange) (M4) or retinaliminium trifluoroacetate (red) (M5). However, these materials are only examples of contrast enhancement that can generally be achieved by systems with a push-pull effect, extension of the Pi system, or chaining of multiple molecules.

In order to make the fat-soluble derivatives of the 11-cis-retinol usable as a sunscreen indicator, they should be incorporated into one or more glycerol esters or triacylglycerols and the cream thus obtained can be filled, for example, in a rotating sleeve housing. Such a mixture for the filling of a rotary sleeve housing (content: about 5 g raw mass), for example, from castor oil (3.3 g), cocoa butter (0.667 g), lanolin (0.667 g), white beeswax (0.667 g) and carnauba wax (0.333 g). Irradiation with UV radiation leads to a clearly visible color change from almost colorless to yellow to orange, possibly even dark red. Both concentration and color, however, depend on the basic substance used.

Since it may already come to the color change when applying the sunscreen before the sunscreen was applied over this product can be added to this product a small amount of sunscreen with low sun protection factor to prevent this effect largely.

material Notes

M1: synthetic method 11-cis-retinal

β-Ionone: CAS (79-77-6)

diethyl (3-trimethylsilyl-2-propynyl) phosphonates:

Synthesis: Source: A.W. Gibson, G.R. Humphrey, D.J. Kennedy, S.H.B. Wright, Synthesis 1991, 414 ± 416.

• 1) To a stirred solution of NaN (SiMe ₃ ) ₂ dissolved in THF (1 M, 10 mL, 10 mmol) at a temperature of -10 ° C is added diethyl phosphonate (1.38 g, 10 mmol) in THF (3 mL).
• 2) The solution is then stirred for 15 minutes at -10 ° C and then admixed with 3-bromo-1-trimethylsilylprop-1-yne (1.91 g, 10 mmol) in THF (3 mL). The temperature of -10 ° C is maintained
• 3) The mixture is stirred at -10 ° C for 1 hour.
• 4) The mixture is then diluted with water (15 mL) and then extracted with EtOAc (2 x 15 mL).
• 5) The extract is washed with HCl (2 M, 25 mL), then with water (20 mL) and then dried with sodium sulfate.
• 6) The solution is then separated by evaporation and the resulting oil distilled to give a mobile phase (1.9 g, 77%).

Vinyl iodide 9:

Synthesis: Source: F. Sato, Y. Kobayashi, Org. Synth. 1990, 69, 106. Isobutylmagnesium chloride is dissolved in ether (320 mL, 0.75 M, 240 mmol)

• 7) The solution is immersed in an ice-water bath (0 ° C) and stirred with the addition of titanocene dichloride (1.3 g, 5.2 mmol) for 10 minutes.
• 8) To this mixture is added dropwise 2-octyn-1-ol (13.2 g, 105 mmol) dissolved in 30 mL of ether (20 min at 0 ° C).
• 9) Solution is stirred at room temperature for an additional 4 hours.
• 10) Control successful implementation by TCL analysis. If this does not provide the desired result, a further addition of titanocene dichloride must take place at 0 ° C.
• 11) Subsequently, the reaction is stopped by squeezing with I ₂ (13.325 g, -78 ° C).
• 12) Thereafter, the primary alcohol is protected by the addition of tert-butyldimethylsilyl chloride.
• 13) The organic layers are then separated and the liquid phase extracted with 150 mL of ethyl acetate.
• 14) Dry the substance with magnesium sulfate.
• 15) Purification by conducting a column chromatography (silica gel, 100-200 mesh) → (225 g, 60 × 210 mm) (benzene-ethyl acetate → 1: 1) (Yield = 60%)

Zinc dust:

Synthesis: Source: W. Boland, N. Schroer, C. Sieler, M. Feigel, Helv. Chim. Acta 1987, 70, 1025 ± 1040.

• 1) Argon is passed through a suspension of 10 g zinc dust with 60 mL water and 1 g Cu (OAc) ₂ for 15 minutes.
• 2) Add a little water and stir for an additional 15 minutes.
• 3) Thereafter, 1 g of AgNO _{3 is} added, causing an exothermic reaction. Continue stirring the suspension for 30 minutes.
• 4) Separation of the metal by the "suction filtration" method. Then carefully wash the metal 2 times with 30 mL water, MeOH, acetone and Et ₂ O.
• 5) The Et ₂ O-moist zinc dust is immediately transferred to a MeOH-water solution (1: 1 → 20 mL each) and is ready for use. Synthesis of the 11-cis-Retinal
  

Section 1: Source: Babak Borhan, Maria L. Souto, Joann M. Um, Bishan Zhou, and Koji Nakanishi, Chem. Eur. J. 1999, 5, no. 4

• 1) Diethyl (3-trimethylsilyl-2-propynyl) phosphonate (2.3 g, 10.5 mmol) is dissolved in 50 mL THF at 0 ° C and treated under an argon atmosphere with nBuLi (10.5 mmol) to give a red solution arises.
• 2) The ice bath is removed and the mixture worked for 15 minutes at room temperature.
• 3) Thereafter, the β-ionone (1.7 g, 5.28 mmol) dissolved in 5 mL of THF is added.
• 4) Additional stirring of the mixture for 3 hours.
• 5) Stop the reaction by adding ammonium chloride and extracting the mixture with diethyl ether (2 times).
• 6) Wash the organic phases with NaCl and then dry with waterless sodium sulfate.
• 7) To obtain the product 7a, the mixture is purified by column chromatography (hexane / ethyl acetate → 4: 1) → (2.14 g, 97% conversion; 5: 1 E: Z at C9).

Section 2: Source: Babak Borhan, Maria L. Souto, Joann M. Um, Bishan Zhou, and Koji Nakanishi, Chem. Eur. J. 1999, 5, no. 4

• 1) The resulting product is dissolved with (1.7 g, 4.1 mmol) THF (20 mL) and washed with
  
  Scheme 5. Synthesis of 11-cis-retinoids. Oxidation of 13a → 14a was accomplished with TPAP / NMO, oxidation of 13b → 14b used MnO ₂ . Tetrabutylammonium fluoride (16.4 mL, 1 M in THF; 16.35 mmol). This removes the protection group (TMS).
• 2) Stir the mixture at room temperature for 2 hours.
• 3) Termination of the reaction by addition of ammonium chloride and extraction of the mixture with diethyl ether (2 times).
• 4) Washing the organic phases with NaCl and then drying with waterless sodium sulfate.
• 5) To obtain the product 8a, the mixture is purified by column chromatography (hexane / ethyl acetate → 3: 1) → (929 mg, 98%).

Section 3: Source: Babak Borhan, Maria L. Souto, Joann M. Um, Bishan Zhou, and Koji Nakanishi, Chem. Eur. J. 1999, 5, no. 4

• 1) Dissolve the previously prepared vinyl iodide 9 (268 mg, 0.86 mmol) in 3 mL of propane-1-amine.
• 2) Tetrakis (triphenylphosphine) palladium (8.2 mg, 0.007 mmol) is added.
• 3) The resulting solution is stirred at room temperature for about 5 minutes.
• 4) Then add CuI (1.4 mg, 0.007 mmol).
• 5) After 5 minutes, add acetylene 8a (165 mg, 0.70 mmol) to the solution and stir at room temperature for about 3.5 hours.
• 6) The reaction is stopped by solvent removal (by pressure reduction).
• 7) The residue is dissolved in Et ₂ O, extracted with ammonium chloride, washed with NaCl and dried with water-free sodium sulfate.
• 8) The product 10a (271 mg, 91%) is purified by column chromatography (EtOAc / hexanes → 1:19).

Section 4: Source: Babak Borhan, Maria L. Souto, Joann M. Um, Bishan Zhou, and Koji Nakanishi, Chem. Eur. J. 1999, 5, no. 4

• 1) The resulting product 10a (170 mg, 4.1 mmol) is dissolved in THF (2 mL) and treated with tetrabutylammonium fluoride (1.64 mL, 1 M in THF: 1.635 mmol). This removes the protecting group (TBS).
• 2) Transfer the previously activated zinc dust to the reaction solvent consisting of water (2 mL) and iPrOH (2 mL).
• 3) A solution of the enzyme 11a (168 mg, 0.05 mmol) in the solvent iPrOH (24 ml) is added to the activated zinc and the solution is stirred at room temperature for 21 hours.
• 4) The zinc is filtered through diatomaceous earth (Et ₂ O and water).
• 5) The separated organic phases are washed with NaCl and dried with waterless sodium sulfate.
• 6) Removal of the solvent (reduction in pressure) gives the product 13a (142.8 mg, 85%) (13: 1 → Z: E at the 11th carbon atom).

M2: Synthesis of Oximes (Organic Chemistry, K. Peter / C. Vollhardt, WILEY-VHC Textbook of Organic Chemistry, Hans Beyer, S. Hirzel Verlag Stuttgart):

M3: Absorption change 11-cis-retinal - all-trans-retinal:

Absorption change trans-cis-retinal

Graph M3 shows that the targeted excitation of 11-cis-retinal at a wavelength of 365 nm after 3 minutes results in a chemical equilibrium between the visible all-trans retinal (about 390 nm) and the invisible 11-cis Retinal (about 275 nm) sets. By further excitation in the wavelength range of 365 nm, the desired isomerization to colored substance (all-trans retinal) occurs. The yield is very low. This can be maximized by the direct synthesis of 11-cis-retinal described above.

M4: Absorption change in bis-vinyl-hydrazine:

Bis-vinyl-hydrazine exposure with 365 nm LEDs

At baseline (0 min), two peaks are initially visible. This suggests that many isomers have already been formed due to the synthesis of bis-vinyl-hydrazine. This can be avoided by the synthesis of the 11-cis retinal by the method described above followed by hydrazine. If the bis-vinyl-hydrazine is then irradiated with radiation of 365 nm, the formation of a colored substance (about 440 nm) can be recognized.

M5: Absorption change in retinaliminium trifluoroacetate:

Retinaliminium Trifluoroacetate Exposure with 365 nm LEDs

In the graphic M5 it becomes apparent that by targeted excitation at a wavelength of 365 nm after 3 minutes, a chemical equilibrium between visible (about 450 nm) and invisible (about 350 nm) substance is established. By further excitation of the wavelength range of 365 nm, the desired isomerization to the colored substance occurs.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• EP 0847751 B1 [0006]
• US 2002/0022008 A1 [0007]

Cited non-patent literature

• Photochromism Molecules and Systems, Heinz Durr, Elsevier, 1990 [0007]
• Babak Borhan, Maria L. Souto, Joann M. Um, Bishan Zhou and Koji Nakanishi (see Chem. Eur. J. 1999, 5, No. 4 [0009]

Claims (10)

Sunscreen indicator , which is characterized in that it contains a photochemical dye. This photochemical dye is characterized according to claim 1 in that it consists of a UV-active carbonyl compound. The durability of this photochemical dye according to claim 1 and 2 can be extended by formation of oxime derivatives. The dye according to claim 1 to 3 changes its optical properties by light of wavelength between 280-400 nm (UV A / B radiation). The optical change of claim 4 is irreversible in the dyes used according to claim 1 to 4. The used fabric according to claim 1 to 4 is removable by means of surfactants and water from the skin. The possible contrast enhancement of the dye according to claim 1 to 6 on the skin by systems with a push-pull effect, the extension of the Pi system or the linking of several molecules. The dye according to claim 1 to 7 introduced into one or more glycerol esters or triacylglycerols. The dye of claim 1 to 7 applied directly to the skin. The indicator of claims 1 to 8 in the form of a lotion, a cream, a balsam, a pen or a stamp with ink pad.