Dermatological Product

Abstract

The present invention discloses a composition comprising sugar alcohols or a combination of sugar alcohols and a Tetraselmis extract or either of the former together with niacinamide for treating or preventing dysfunctions of the human hair or skin or as a skin or hair care product.

Claims

1. A composition comprising: a sugar alcohol and a Tetraselmis extract, wherein the total sugar alcohol content is in an amount of ≥16 wt. % in the overall composition, calculated based on the extract dry weight, and wherein the Tetraselmis extract comprises the following based on the extract dry weight: a) total minerals ≥10 wt. % of the total Tetraselmis extract composition, b) total galactose ≥3 wt. % of the total Tetraselmis extract composition, c) total glucose ≥2 wt. % of the total Tetraselmis extract composition, d) total amino acids ≥3 wt. % of the total Tetraselmis extract composition, e) total nitrogen ≥2 wt. % of the total Tetraselmis extract composition.

2. A composition according to claim 1, wherein the sugar alcohol is selected from one or more of: C4, C5, C6, C7 sugar alcohols and disaccharide sugar alcohols.

3. A composition according to claim 1, wherein the sugar alcohol is selected from one or more of: threitol (C4 sugar alcohol), erythritol (C4 sugar alcohol), ribitol (C5 sugar alcohol), arabitol (C5 sugar alcohol), xylitol (C5 sugar alcohol), sorbitol (C6 sugar alcohol), mannitol (C6 sugar alcohol), dulcitol (galactitol) (C6 sugar alcohol), inositol (cyclic C6 sugar alcohol), volemitol (C7 sugar alcohol), lactitol (4-O-β-D-galactopyranolsyl-D-glucitol; disaccharide sugar alcohol), maltitol (4-O-α-glucopyranosyl-D-sorbitol; disaccharide sugar alcohol) and their respective enantiomers.

4. A combination composition according to claim 1 further comprising niacinamide.

5. Combination composition according to claim 4, wherein the weight ratio range of sugar alcohol and Tetraselmis extract together in relation to niacinamide is 1:10000 to 1:1, calculated based on the extract dry weight.

6. A concentrate comprising: a) 0.5 to 80 wt. % of the composition or the combination composition according to claim 1, calculated based on extract dry weight, b) 0.5 to 90 wt. % water, c) 0.5 to 90 wt. % carrier, d) optionally 0.1 to 5 wt. % of one or more preservative or preservative system, wherein the ratio of the total sugar alcohol content to the sugar alcohol content in the Tetraselmis extract based on the extract dry weight is ≥1.1:1.

7. Liquid concentrate comprising: a) 0.5 to 10 wt. % of the composition according to claim 1, calculated based on the extract dry weight, b) 1 to 70 wt. % water, c) 0.5 to 85 wt. % liquid carrier, preferably glycerin, d) optionally 0.1 to 5 wt. % of one or more preservative or preservative system, wherein the ratio of the total sugar alcohol content to the sugar alcohol content in the Tetraselmis extract based on the extract dry weight is ≥1.1:1.

8. Solid concentrate comprising: a) 1 to 10 wt. % of the composition according to claim 1, calculated based on the extract dry weight, b) 0.5 to 10 wt. % water, c) 50 to 98 wt. % solid carrier, preferably maltodextrin, wherein the ratio of the total sugar alcohol content to the sugar alcohol content in the Tetraselmis extract based on the extract dry weight is ≥1.1:1.

9. A method of using a pharmaceutical composition comprising the composition according to claim 1 for treating or preventing dysfunctions of human hair and/or skin, seborrhoeic dermatitis, acne vulgaris, wound healing, tissue regeneration, postinflammatory hyperpigmentation, inflammatory related diseases, dandruff or Pityriasis versicolor.

10. A method of using a pharmaceutical product comprising one or more sugar alcohols and niacinamide for treating or preventing dysfunctions of human hair and/or skin, seborrhoeic dermatitis, acne vulgaris, wound healing, tissue regeneration, postinflammatory hyperpigmentation, inflammatory related diseases, dandruff or Pityriasis versicolor.

11. The method according to claim 10, wherein the sugar alcohol, is in an amount of 0.0001 to 5 wt. % in the total pharmaceutical product.

12. A method of treating a skin disease comprising applying a dermatological or therapeutic product comprising a composition according to claim 1, and optionally further comprising auxiliary substances, to the skin of a subject.

13. A cosmetic composition comprising a composition according to claim 1, the cosmetic composition or cosmetic product further optionally comprising auxiliary substances and/or perfumes, wherein the cosmetic composition or cosmetic product is a skin and/or hair care product.

14. Dermatological or therapeutic product according to claim 12, wherein the amount of the composition according to claim 1 in the product is 0.0001 to 10 wt. % in the total dermatological or therapeutic product.

15. Cosmetic composition or cosmetic product according to claim 13, wherein the amount of the composition according to claim 1, is 0.0001 to 10 wt. % in the total cosmetic composition or cosmetic product.

16. A method of using a cosmetic composition according to claim 13, for application on, caring, cleansing or protecting the skin, or for reduction of sebum.

17. A method of using a pharmaceutical composition according to claim 9 for: a) the stimulation of cutaneous junctions. b) stimulation of cutaneous antimicrobial peptides, c) reduction of COX-2 gene expression and prostaglandin mediated effects, d) reduction of post-inflammatory hyperpigmentation, e) stimulation of filaggrin.

18. A method of using a cosmetic composition according to claim 13 for: a) for improvement of epidermal integrity of the skin, b) for prevention of external stimuli such as air pollution or particulate matter, c) for prevention of skin barrier dysfunction.

19. Use-Gf-A method of using a pharmaceutical composition according to claim 9, wherein the composition further comprises additional sebum reducing and/or anti-acne agents.

20. A method of using a Pharmaceutical composition according to claim 9, wherein the composition further comprise one or more of the following: anti-acne agents, anti-dandruff agents, anti-inflammatory agents, TRPV1 antagonists, anti-itch agents, anti-microbial agents, especially anti-propioni-bacterium acnes, anti-Malassezia agents.

21. (canceled)

22. A method of using a cosmetic composition or cosmetic product according to claim 16, wherein the composition further comprises one or more of the following: anti-acne agents, anti-dandruff agents, anti-inflammatory agents, TRPV1 antagonists, anti-itch agents, anti-microbial agents, especially anti-propioni-bacterium acnes, anti-Malassezia agents.

23. Liquid formulation comprising a) 0.5 to 25 wt. %, preferably 1 to 20 wt. %, sugar alcohol; b) optionally 1 to 35 wt. %, preferably 2 bis 20 wt. %, niacinamide; c) 5 to 55 wt. %, preferably 10 to 50 wt. %, liquid carrier; and d) optionally 0.1 to 5 wt. % of one or more preservative or preservative system.

24. Liquid formulation according to claim 23, wherein the sugar alcohol is selected from the group consisting of mannitol, sorbitol, xylitol, erythritol, maltitol, inositol and mixtures thereof and the liquid carrier is selected from the group consisting of glycerin, 1,3-butylene glycol, 1,3-propanediol, 1,2-pentanediol and mixtures thereof.

25. A method of using a liquid formulation according to claim 23 for treating or preventing dysfunctions of human hair and/or skin, seborrhoeic dermatitis, acne vulgaris, wound healing, tissue regeneration, postinflammatory hyperpigmentation, inflammatory related diseases, dandruff or Pityriasis versicolor.

Description

EXPERIMENTAL SECTION

Example 1: Preparation of a Tetraselmis suecica Extract

[0178] 3 g freeze-dried Tetraselmis suecica biomass and 30 g of water were mixed and stirred for 2 hours at 80° C. The liquid extract was separated from the biomass, 30 g of water was added to the extracted biomass and the mixture was stirred for another 2 hours at 80° C. The liquid was separated from the biomass by centrifugation, both extract solutions were combined, and the water was removed by freeze-drying. The extractions were performed with 3 different biomass batches.

[0179] For comparison, an aqueous extract according to the description in US2010143267 A1 was prepared from the same 3 biomass batches and water was removed by freeze-drying.

TABLE-US-00001 TABLE 1 Tetraselmis suecica extract obtained by extraction at room temperature and at 80° C. Condition of extraction Mean yield Appearance 80° C. 38.4 ± 0.2% Beige greenish solid Room temperature 40.0 ± 0.9% Intensive dark green solid (18 to 23° C.)

[0180] Extraction upon heating gives a well comparable, very slightly lower, high extraction yield when compared to extraction at room temperature, but it surprisingly gives a much lighter colored extract which is especially advantageous for the use as cosmetic ingredient as consumers prefer low colored products. Heat treatment furthermore has the additional advantage that enzymes in the biomass are inactivated which is especially advantageous when using viable or non-inactivated biomass. Additionally, microbiological contamination by bacteria, fungi or yeasts, which is especially challenging for extractions with water or extractant systems with high water content at low temperatures is prevented by extracting at higher temperatures (>50° C.).

TABLE-US-00002 TABLE 2 Composition of Tetraselmis suecica extracts obtained by extraction at 80° C. and at Room temperature Mean content Mean content [wt.-%] [wt.-%] (Extract obtained at (Extract obtained Room temperature Substance class at 80° C.) (18 to 23° C.)) Sum of minerals 20.3 ± 0.6  21.4 ± 0.8  Containing but not limited to: Sodium Na.sup.+ 5.7 ± 0.2 5.7 ± 0.3 Potassium K.sup.+ 3.6 ± 0.1 3.6 ± 0.2 Magnesium Mg.sup.2+ 0.7 ± 0.1 0.7 ± 0.0 Calcium Ca.sup.2+ 0.8 ± 0.1 0.9 ± 0.0 Chloride Cl.sup.− 6.9 ± 0.2 7.1 ± 0.2 Sulfate SO.sub.4.sup.2− 2.1 ± 0.1 2.6 ± 0.1 Phosphate PO.sub.4.sup.3− 0.4 ± 0.2 0.9 ± 0.4 Mannitol 11.8 ± 0.9  11.6 ± 0.7  Total galactose 9.7 ± 0.7 7.8 ± 0.4 (free and bound)* Total glucose 7.0 ± 0.8 3.5 ± 0.0 (free and bound)* Sum of amino acids 8.4 ± 0.8 9.2 ± 0.7 Containing but not limited to: Glutamic acid 2.88 ± 0.30 2.77 ± 0.27 Alanine 1.11 ± 0.08 1.10 ± 0.10 Arginine 0.80 ± 0.30 0.17 ± 0.02 Ornithine 0.54 ± 0.28 1.26 ± 0.17 Citruline 0.53 ± 0.23 0.74 ± 0.03 Asparagine 0.39 ± 0.04 0.19 ± 0.02 Taurine 0.39 ± 0.04 0.35 ± 0.04 Lysine 0.37 ± 0.04 0.49 ± 0.02 Aspartic acid 0.27 ± 0.10 0.76 ± 0.03 Proline 0.14 ± 0.02 0.18 ± 0.02 Glutamine 0.12 ± 0.06 0.07 ± 0.02 Total Nitrogen** 4.22 ± 0.17 4.91 ± 0.16 *determined after hydrolysis and derivatization by GC **determined by nitrogen analyzer

Example 2: Preparation of a Liquid Version of Sugar Alcohol with Tetraselmis suecica Extract

[0181] To 4.6 g Tetraselmis suecica extract dry matter, obtained by extraction at 80° C. according to Example 1, 97 g water, 46 g glycerin, 18 wt. % mannitol, 0.5% sodium benzoate and 0.2% potassium sorbate (both based on the total weight of the liquid mixture) were added, and the pH of the mixture was adjusted with help of lactic acid to 4.5 giving a beige to light brownish solution.

Example 3: Effect of Tetraselmis suecica Extract (Dried) on the Total Lipid Content of Ex Vivo Human Sebaceous Glands

[0182] Organ culture of human sebaceous glands micro-dissected from human skin explants was performed to evaluate the modulatory activity of Tetraselmis suecica extract prepared according to the description given in Example 1 on the sebum level. The extract is employed in the dried form.

[0183] After removal of the epidermis of the full thickness skin sample, the sebaceous glands were carefully removed using micro-scissors and scalpel. The micro-dissected sebaceous glands were then pooled in groups of 8 and cultured up to day 6 in a 24 well plate immersed in 500 μl of modified Williams'E medium. After 24 hours of acclimation the culture medium was changed and substituted with the medium containing the extract to be tested. The medium was renewed at day 3 and 5 of culture. At day 6 the glands were collected and used for the quantification of lipids and proteins. In order to make the estimated productivity of the glands comparable, which are variable in biomass, their total sebum content was estimated and divided by the proteins extracted from the gland tissue, obtaining the ratio between the produced sebum and the tissue proteins (i.e. mg of lipids/mg of proteins).

[0184] To do so, each sebaceous glands group was homogenized in 100 μl of isopropyl alcohol to extract lipids and let the proteins undissolved. After centrifugation the supernatant containing the extracted sebum was collected and analyzed. The remaining pellet was dried using a vacuum dry evaporator and then minced in presence of 50 μl of protein lysis buffer. After an appropriate incubation time, this extractive mixture was centrifuged, and the supernatant was collected and analyzed. The lipids dissolved in isopropyl alcohol and the proteins dissolved in the lysis buffer were quantified by infrared spectroscopy using a Direct Detect IR Spectrometer (Millipore). The total lipid amount was obtained by normalizing the quantified lipids upon the quantified proteins (i.e. mg of lipids/mg of proteins). The amounts of normalized lipids, i.e. the sebum produced by each group of sebaceous glands, obtained from the treated groups was compared to that of the untreated control group and the modulatory activity was calculated in percentage. As positive control, a 5 μM Capsaicin treatment was included in the experimental design. Capsaicin is an active component of chili peppers suitable to inhibit sebogenesis [T6th et al., J. Invest. Derm. (2009), 129: 329-339]. For statistical analysis, differences among groups were evaluated by one-way anova with permutation test followed by Dunnett's permutation test.

[0185] To better understand the response to the extract, a viability test was performed in parallel at day 1 and day 6 of organ culture. Resazurin was added to the wells (1:11) and let incubate for 2 hours. At the end of the incubation an aliquot of the medium was read with a fluorometer (excitation: 560 nm, emission: 590 nm). The medium was then replaced with normal medium for 2 hours in order to eliminate residual resazurin. After this the medium was replaced again with medium containing the test samples. The viability in each well was measured as the difference in percentage between day 6 and day 1.

[0186] To evaluate donor responsiveness and interindividual variability the extract was tested on sebaceous glands obtained from skin samples of three different donors.

TABLE-US-00003 TABLE 3 Effect of Tetraselmis suecica water-extract (dried) on lipids and viability of micro-dissected human sebaceous glands In the present cell tests, ex vivo and in vitro, and generally for biological tests, the dried form of the Tetraselmis extract is employed to avoid side effects resulting from solvents, glycerin or the preservative system. Donor Donor Donor Parameter Test sample 1 2 3 Reduction 5 μM (= 1.5 ppm) 11 28 14 of lipids at Capsaicin day 6 versus 0.3 ppm extract 19 33 18 untreated [%]* (extraction at 80° C.) Viability [%] Untreated 93 100 81 5 μM (1.5 ppm) 92 99 85 Capsaicin 0.3 ppm extract 108 101 83 (extraction at 80° C.) *All results were statistically significant versus untreated with p < 0.01

[0187] The results show that Tetraselmis suecica water extract (dried) obtained by extraction at 80° C. is surprisingly a highly effective reducer of the normalized total lipids, i.e. sebum content of human sebaceous glands without affecting their viability. It is more effective than the positive control capsaicin and this even at a 5-fold lower concentration. Furthermore, the sebaceous glands obtained from all three donors responded to the extract (donor responsiveness: 100%).

[0188] Similar effects were also achieved in comparing the mannitol and Tetraselmis extract combination as prepared according to Example 2. The combination of mannitol with Tetraselmis suecica water extract (dried) is a particularly highly effective reducer of the normalized total lipids, i.e. sebum content of human sebaceous glands without affecting their viability. It is more effective than the positive control capsaicin. Moreover, the further addition of niacinamide shows good skin moisturizing effects.

Example 4: Effect of Mannitol (Alone) on the Total Lipid Content of Ex Vivo Human Sebaceous Glands

[0189] The Organ culture of human sebaceous glands micro-dissected from human skin explants was performed to evaluate the modulatory activity of mannitol on the sebum level.

[0190] After removal of the epidermis of the full thickness skin sample, the sebaceous glands were carefully removed using micro-scissors and scalpel. The micro-dissected sebaceous glands were then pooled in groups of 8 and cultured up to day 6 in a 24 well plate immersed in 500 μl of modified Williams'E medium. After 24 hours of acclimation the culture medium was changed and substituted with the medium containing the sample to be tested. The medium was renewed at day 3 and 5 of culture. At day 6 the glands were collected and used for the quantification of lipids and proteins. In order to make the estimated productivity of the glands comparable, which are variable in biomass, their total sebum content was estimated and divided by the proteins extracted from the gland tissue, obtaining the ratio between the produced sebum and the tissue proteins (i.e. mg of lipids/mg of proteins).

[0191] To do so, each sebaceous glands group was homogenized in 100 μl of isopropyl alcohol to extract lipids and let the proteins undissolved. After centrifugation the supernatant containing the extracted sebum was collected and analyzed. The remaining pellet was dried using a vacuum dry evaporator and then minced in presence of 50 μl of protein lysis buffer. After an appropriate incubation time, this extractive mixture was centrifuged, and the supernatant was collected and analyzed. The lipids dissolved in isopropyl alcohol and the proteins dissolved in the lysis buffer were quantified by infrared spectroscopy using a Direct Detect IR Spectrometer (Millipore). The total lipid amount was obtained by normalizing the quantified lipids upon the quantified proteins (i.e. mg of lipids/mg of proteins). The amounts of normalized lipids, i.e. the sebum produced by each group of sebaceous glands, obtained from the treated groups was compared to that of the untreated control group and the modulatory activity was calculated in percentage. As positive control, a 5 μM Capsaicin treatment was included in the experimental design. Capsaicin is an active component of chili peppers suitable to inhibit sebogenesis [T6th et al., J. Invest. Derm. (2009), 129: 329-339]. For statistical analysis, differences among groups were evaluated by one-way anova with permutation test followed by Dunnett's permutation test.

[0192] To better understand the response to the extract, a viability test was performed in parallel at day 1 and day 6 of organ culture. Resazurin was added to the wells (1:11) and let incubate for 2 hours. At the end of the incubation an aliquot of the medium was read with a fluorometer (excitation: 560 nm, emission: 590 nm). The medium was then replaced with normal medium for 2 hours in order to eliminate residual resazurin. After this the medium was replaced again with medium containing the test samples. The viability in each well was measured as the difference in percentage between day 6 and day 1.

TABLE-US-00004 TABLE 4 Effect of mannitol on lipids and viability of micro-dissected human sebaceous glands Total lipid reduction Parameter Test sample [%] Reduction of lipids at day 6 5 μM (1.5 ppm) −25 versus untreated [%]* Capsaicin 0.03 ppm mannitol** −17 Viability [%] Untreated 84 5 μM (1.5 ppm) Capsaicin 82 0.03 ppm mannitol 81 *All results were statistically significant versus untreated with p < 0.01 **D-Mannitol, Sigma-Aldrich M4125 (≥98%)

[0193] The results clearly show that mannitol surprisingly significantly reduces the lipid content of ex vivo human sebaceous glands.

[0194] According to Example 1, Tetraselmis suecica water extract (dried) contains 11.8±0.9 wt. % of mannitol. The extract reduced the total lipid content at 0.3 ppm significantly and was always more effective than 5 μM capsaicin when tested in three separate experiments (Example 3).

[0195] The 0.03 ppm mannitol corresponds to the mannitol content in 0.3 ppm Tetraselmis suecica water extract (dried). The 0.03 ppm mannitol significantly reduced the sebum content but less effectively than 5 μM capsaicin, thus, indicating that mannitol is part of the active principles/ingredients of Tetraselmis suecica extract but is not solely responsible for the observed sebum reducing effect of the extract. Other extract constituents enhance the observed sebum reducing efficacy of the extract in an additive or synergistic manner.

Example 5: Effect of Mannitol on the Gene Expression of Claudin 7

[0196] Neonatale humane epidermal keratinocytes (nHEK) were cultivated in EpiLife medium (Gibco) including HKGS-Kit (Gibco) at 5% C02 at 37° C. according to the supplier instructions.

[0197] The cells were treated for 24 hours with Tetraselmis suecica water extract obtained according to Example 1 by extracting at 80° C. at 0.025% or medium as vehicle control. Genomic target expression levels in extract treated cells were measured by RT-qPCR comparing to medium treatment.

[0198] RNA isolation took place using RNeasy® Mini Kit, Qiagen. Total RNA concentrations were measured using pCuvetteG 1.0 and BioPhotometer, Eppendorf by measuring the absorption at 260 nm. Purity control values, like E260/280 and E 260/230 were calculated simultaneously. Reverse transcription was done using high capacity RNA-to-cDNA Kit, Applied Biosystems, according to the supplier instructions. Samples were treated in the PCR Thermocycler, Biometra.

[0199] For the fast real-time PCR, cDNA was diluted with RNase-free water and TaqMan™ Fast Universal PCR Master Mix, Applied biosystems. Quantitaive Real-Time PCR was done using StepOne Plus Fast Real Time PCR Instrument, Applied biosystems. Analysis was done with StepOne-Software and 2-ΔCT Method (normalized to endogenous control HTRP1 expression).

[0200] For upregulations RQ values ≥2.0 and for downregulations RQ values <0.5 are considered to be relevant.

TABLE-US-00005 TABLE 5 Effect of mannitol on claudin 7 RQ value 0.025% Tetraselmis extract (containing ca. 0.002% Gene Relevance 0.002% Mannitol) Mannitol CLDN1 [Claudin 1] Tight junctions 4.0 0.5 CLDN7 [Claudin 7] Tight junctions 2.0 2.0 OCLN [Occludin] Tight junctions 4.0 1.0 CGN [Cingulin] Tight junctions 4.0 1.0

[0201] The results show that mannitol alone or also the combination of Tetraselmis extract containing mannitol surprisingly upregulate the claudin 7 gene involved in tight junctions.

[0202] Furthermore, other genes, such as claudin 1, occludin or cingulin, also involved in tight junctions are synergistically upregulated by the combination of Tetraselmis extract containing mannitol. Therefore, a differentiation of the effect by treatment with Tetraselmis extract and by the treatment with mannitol is shown.

Example 6: Effect of Erythritol, Xylitol and Sorbitol on the Total Lipid Content of Ex Vivo Human Sebaceous Glands

[0203] Organ culture of human sebaceous glands micro-dissected from human skin explants was performed as described in Example 4 to evaluate the modulatory activity of erythritol (C4 sugar alcohol), xylitol (C5 sugar alcohol) and sorbitol (C6 sugar alcohol) on the sebum level. 5 μM Capsaicin was tested in parallel as reference/positive control.

TABLE-US-00006 TABLE 6 Effect of erythritol, xylitol and sorbitol on lipids and viability of micro-dissected human sebaceous glands Parameter Test sample Results Reduction of lipids 5 μM (1.5 ppm) Capsaicin −21 at day 6 versus 0.05 ppm erythritol** −26 untreated [%]* 0.5 ppm erythritol** −36 0.05 ppm xylitol*** −23 0.5 ppm xylitol*** −46 0.05 ppm sorbitol**** −16 0.5 ppm sorbitol**** −40 Viability [%] Untreated 89 5 μM (1.5 ppm) Capsaicin 89 0.05 ppm erythritol** 82 0.5 ppm erythritol** 77 0.05 ppm xylitol*** 86 0.5 ppm xylitol*** 80 0.05 ppm sorbitol**** 80 0.5 ppm sorbitol**** 78 *All results were statistically significant versus untreated with p < 0.01 **meso-Erythritol, Sigma E7500 (≥99%), CAS number 149-32-6 ***Xylitol, Sigma X3375 (≥99%), CAS number 87-99-0 ****D-Sorbitol, Aldrich 240850 (99%), CAS number: 50-70-4

[0204] The results clearly show that erythritol, xylitol and sorbitol surprisingly significantly reduces the lipid content of ex vivo human sebaceous glands. All three sugar alcohols are more active than the positive control/reference capsaicin.

[0205] None of the test samples has relevantly impacted sebaceous glands viability.

Example 7: Effect of Threitol, Inositol, Lactitol, and Maltitol on the Total Lipid Content of Ex Vivo Human Sebaceous Glands

[0206] Organ culture of human sebaceous glands micro-dissected from human skin explants was performed as described in example 4 to evaluate the modulatory activity of threitol, inositol, lactiol and maltitol on the sebum level. 5 μM Capsaicin was tested in parallel as reference/positive control.

TABLE-US-00007 TABLE 7 Effect of threitol, inositol, lactitol and maltitol on lipids and viability of micro-dissected human sebaceous glands Parameter Test sample Results Reduction of lipids 5 μM (1.5 ppm) −20 at day 6 versus Capsaicin untreated [%]* 0.05 ppm threitol ** −31 0.5 ppm threitol ** −47 0.05 ppm inositol *** −32 0.5 ppm inositol *** −10 0.05 ppm lactitol **** −22 0.5 ppm lactitol **** −22 0.05 ppm maltitol ***** −44 0.5 ppm maltitol ***** −39 Viability [%] Untreated 92 5 μM (1.5 ppm) Capsaicin 91 0.05 ppm threitol ** 84 0.5 ppm threitol ** 82 0.05 ppm inositol *** 91 0.5 ppm inositol *** 97 0.05 ppm lactitol **** 99 0.5 ppm lactitol **** 100 0.05 ppm maltitol ***** 79 0.5 ppm maltitol ***** 80 *All results were statistically significant versus untreated with p < 0.01 ** D-Threitol, Aldrich 377619 (99%), CAS number 2418-52-2 *** myo-Inosiitol, Sigma I5125 (≥99%), CAS number 87-89-8 **** Lactitol, Sigma-Aldrich 19346 (≥98%), CAS number 585-86-4 ***** Maltitol, Sigma M8892 (≥98%), CAS number 585-88-6

[0207] The results clearly show that threitol, inositol, lactitol and maltitol surprisingly significantly reduce the lipid content of ex vivo human sebaceous glands. All four sugar alcohols are more active than the positive control/reference capsaicin.

[0208] None of the test samples has relevantly impacted sebaceous glands viability.

Example 8: Synergistic Effect of Sugar Alcohol and Niacinamide on the Total Lipid Content of Ex Vivo Human Sebaceous Glands

[0209] The same experimental set-up as described in Example 4 was used to evaluate the combination of the sugar alcohol sorbitol and niacinamide for synergistic activity. 5 μM Capsaicin was tested in parallel as reference/positive control.

[0210] Kull's equation for calculation of the synergism index SI was used:

SI=C×D/A+C×E/B

With

[0211] A=lipid reduction by sorbitol at concentration x
B=lipid reduction by niacinamide at concentration y
C=lipid reduction by the combination of sorbitol at concentration x/2 and niacinamide at concentration y/2
D=Factor for sorbitol=>0.5 (due to half concentration tested in the combination)
E=Factor for niacinamide=>0.5 (due to half concentration tested in the combination)

[0212] A SI=1 is obtained for additive activity of the two combined components, whereas a SI<1 proves antagonistic activity (observed efficacy is lower than additive) and SI>1 proves synergistic activity (observed efficacy is higher than additive). Results of this experiment are summarized in Table 8.

TABLE-US-00008 TABLE 8 Effect of sorbitol and niacinamide on the total lipid content of ex vivo human sebaceous glands Lipid reduction Parameter Test sample [%] Reduction of lipids 5 μM (1.5 ppm) capsaicin  13* at day 6 versus 0.5 ppm sorbitol**  11* untreated [%]* 0.5 ppm niacinamide***  2 0.25 ppm sorbitol +  15* 0.25 ppm niacinamide Viability [%] Untreated 99 5 μM (1.5 ppm) capsaicin 95 0.5 ppm sorbitol 95 0.5 ppm niacinamide 100  0.25 ppm sorbitol + 98 0.25 ppm niacinamide *Results were statistically significant versus untreated with p < 0.01 **D-Sorbitol, Aldrich 240850 (99%), CAS number: 50-70-4 ***Niacinamide, Nutrilo GmbH (≥99% by HPLC), CAS number: 98-92-0

SI=15×0.5/11+15×0.5/2=4.43

[0213] The obtained SI of 4.43 clearly proves that a combination of a sugar alcohol and niacinamide surprisingly exhibits a highly synergistic reduction of the total lipids content, i.e. sebum level of human sebaceous glands.

[0214] Niacinamide alone did not show a relevant lipid reducing activity when tested on ex vivo sebaceous glands. Sorbitol exhibited efficacy in the expected range when compared to capsaicin. The combination of both let to an unexpected intensively boosted efficacy.

[0215] Cosmetic ingredients ideally possess no own color and odor and thereby have no own impact on the visual appearance and smell of the final cosmetic formulation. Sugar alcohols and niacinamide are both colorless and odorless compounds; furthermore both are readily water soluble and allow thus broad application in all different kind of cosmetic formulations.

[0216] Additionally, sugar alcohols and niacinamide are solids available typically in powder form. To make a synergistic combination even more easily to formulate typical cosmetic formulations, they can be used in a liquid carrier system. To prepare liquid combinations, the solid ingredients, i.e. sugar alcohols and niacinamide, are dissolved under stirring at ambient temperature (20-30° C.) in the liquid carrier system giving a colorless solution.

TABLE-US-00009 TABLE 9 Formulations containing sugar alcohols and niacinamide in liquid form Amount wt.-% Ingredient 1 2 3 4 5 6 7 8 Mannitol 5 1 5 Sorbitol 20 5 Xylitol 3 5 Erythritol 20 Maltitol 15 Inositol 1 Niacinamide 5 5 1.5 2 10 30 20 5 Glycerin 35 25 50 1,3-Butylene glycol 25 1,3-Propanediol 20 30 1,2-Pentanediol 10 10 10 Water Ad 100

[0217] The liquid formulations can further comprise 0.1 to 5 wt. % of one or more preservative(s) or a preservative system.

[0218] The liquid formulations comprising one or more sugar alcohol(s) or a combination of one or more sugar alcohol(s) and niacinamide are used in the preparation of the pharmaceutical or cosmetic products or the dermatological or therapeutic products according to the present invention.

Example 9: Formulation Examples

[0219] In formulations 1 to 22 the following two perfume oils PFO1 and PFO2 were each used as fragrance (DPG=dipropylene glycol).

TABLE-US-00010 TABLE 10 Perfume oil PFO1 with rose smell (amounts in parts b.w.) Component Amount Acetophenone, 10% in DPG 10.00 n-Undecanal 5.00 Aldehyde C14, so-called (peach aldehyde) 15.00 Allylamyl glycolate, 10% in DPG 20.00 Amyl salicylate 25.00 Benzyl acetate 60.00 Citronellol 80.00 d-Limonene 50.00 Decenol trans-9 15.00 Dihydromyrcenol 50.00 Dimethylbenzylcarbinyl acetate 30.00 Diphenyloxide 5.00 Eucalyptol 10.00 Geraniol 40.00 Nerol 20.00 Geranium oil 15.00 Hexenol cis-3, 10% in DPG 5.00 Hexenyl salicylate cis-3 20.00 Indole, 10% in DPG 10.00 Alpha-ionone 15.00 Beta-ionone 5.00 Lilial ® (2-methyl-3-(4-tert-butyl-phenyl)propanal) 60.00 Linalool 40.00 Methylphenyl acetate 10.00 Phenylethyl alcohol 275.00 Styrolyl acetate 20.00 Terpineol 30.00 Tetrahydrolinalool 50.00 Cinnamyl alcohol 10.00 Total: 1,000.00

TABLE-US-00011 TABLE 11 Perfume oil PFO2 with white blossom and musk smell (amounts in parts b.w.) Component Amount Benzyl acetate 60.00 Citronellyl acetate 60.00 Cyclamenaldehyde (2-methyl-3-(4-isopropylphenyl)propanal 20.00 Dipropylene glycol (DPG) 60.00 Ethyllinalool 40.00 Floral (2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol) 30.00 Globanone ® [(E/Z)-8-cyclohexadecen-1-one] 180.00 Hedione ® (methyldihydrojasmonate) 140.00 Hexenyl salicylate, cis-3 10.00 Vertocitral (2,4-dimethyl-3-cyclohexenecarboxaldehyde) 5.00 Hydratropaaldehyde, 10% in DPG 5.00 Isodamascone (1-(2,4,4-trimethyl-2-cyclohexen-1-yl)-2- 5.00 buten-1-one, 10% in DPG Isomuscone (cyclohexadecanone) 40.00 Jacinthaflor (2-methyl-4-phenyl-1,3-dioxolane) 10.00 Cis-jasmone, 10% in DPG 20.00 Linalool 50.00 Linalyl acetate 30.00 Methyl benzoate, 10% in DPG 25.00 para-Methyl cresol, 10% in DPG 10.00 Nerol 20.00 Phenylpropylaldehyde 5.00 2-Phenylethyl alcohol 82.00 Tetrahydrogeraniol 13.00 2,2-Dimethyl-3-cyclohexyl-1-propanol 80.00 Total: 1,000.00

TABLE-US-00012 TABLE 12 Cosmetic formulations 1 to 11 (amounts in parts b.w.) Ingredients 1 2 3 4 5 6 7 8 9 10 11 Mannitol 0.3 0.1 0.7 Sorbitol 1 0.5 0.1 Xylitol 0.2 1 Lactitol 0.1 Maltitol 0.5 Erythritol 0.4 Inositol 0.3 Threitol 0.05 Actipone Alpha-Pulp 0.1 1 Aqua, Butylene Glycol, Malic Acid, Actinidia Chinensis Fruit Extract, Citrus Aurantium Dulcis Juice, Citrus Paradisi Juice, Pyrus Malus Juice, Trideceth-9, Prunus Amydalus Dulcis Seed Extract Allantoin 0.1 Allantoin Aloe Vera Gel Conc. 10:1 0.2 Aloe Barbadensis (Aloe) Leaf Juice Aluminium Stearate 1.2 Aluminium Stearate Asebiol 3 Water, Pyridoxine HCL, Niacinamide, Glycerin, Panthenol, Hydrolyzed Yeast Protein, Threonine, Allantoin, Biotin Beta-Arbutin 1 Arbutin Arlypon ® F 2 Laureth-2 Asensa ® SC 220 2 Polyethylene Azelaic acid 0.5 Azelaic acid Biotive L-Arginine 0.6 Arginine Biotive Troxerutin 0.5 Troxerutin (-)-alpha-Bisabolol 0.1 Bisabolol Carbopol Aqua SF-1 Polymer 5 Acrylates Copolymer Carbopol ® Ultrez-10 0.2 0.2 0.2 0.3 Carbomer Citric acid 10% in water 0.2 0.5 Citric acid, water Colour 0.04 Crinipan ® AD 0.3 Climbazole Cutina ® AGS 1.5 Glycol Distearate Cutina ® PES 2 Pentaerythrityl Distearate D-Panthenol 0.5 Panthenol Dehyton K 8 8 Cocamidopropyl Betaine Dow Corning 200 (100 cs) 2 2 0.5 Silicone Fluid Dimethicone Dracorin ® CE 5 2.5 Glyceryl Stearate Citrate Dracorin GOC 2, 5 Glyceryl Oleate Citrate, Caprylic/Capric Triglyceride Dragocalm ® 1 Water (Aqua), Glycerin, Avena Sativa (Oat) Kernel Extract Dragoderm ® 0.5 Glycerin, Triticum Vulgare (Wheat) Gluten, Water (Aqua) Dragosan ® W/O P 8 Sorbitan Isostearate, Hydrogenated Castor Oil, Ceresin, Beeswax (Cera Alba) Dragosantol ® 100 0.2 Bisabolol Dragosine ® 0.2 0.2 Carnosine Dragoxat ® 89 5 7 1 5 Ethylhexyl Isononanoate Disodium EDTA 0.1 0.1 0.1 0, 1 0.1 0.05 0.05 Disodium EDTA Emulsiphos ® 2 1.5 Potassium Cetyl Phosphate, Hydrogenated Palm Glycerides Estearina L2SM GS 2 Stearic Acid, Palmitic Acid Ethanol 2 Ethanol Extrapone ® Aloe vera 1 Water (Aqua), Aloe Barbadensis, Propylene Glycol, Alcohol Extrapone Eucalyptus 1 Aqua, Propylene Glycol, Eucalyptus Globulus Leaf Extract Extrapone Iris B Aqua, Propylene Glycol, PEG-40 Hydrogeanted Castor Oil, 0.5 Trideceth-9, Bisabolol, Iris Germanica Root Extract Extrapone ® Witch Hazel Propylene Glycol, Hamamelis Virginiana (Witch Hazel) Water, Water 1 (Aqua), Hamamelis Virginiana (Witch Hazel) Extract Food Color Brown E172+E171 Powder Titanium Dioxides (Cl77891), Iron Oxides (Cl77492), Iron Oxides 2 1.5 (Cl77491), Iron Oxides (Cl77499) Food Color Titanium Dioxide Powder E171 3 Titanium Dioxides (Cl77891) Frescolat ® MGA 0.5 Menthone Glycerin Acetal Frescolat ® ML 0.3 0.2 0.3 Menthyl Lactate Frescolat Plus 0.2 Menthol, Menthyl Lactate Frescolat ® X-Cool 0.2 Menthyl Ethylamido Oxalate Genapol ® LRO Liquid 37 Sodium Laureth Sulfate Glycerin 3 3 4.5 3 1.5 3 Glycerin Hydrolite ® 5 3 2 Pentylene Glycol Hydroviton-24 ® Water (Aqua), Pentylene Glycol, Glycerin, Lactic Acid, Sodium 1 Lactate, Serine, Urea, Sorbitol, Sodium Chloride, Allantoin Hydroviton ® Plus 2290 Water (Aqua), Pentylene Glycol, Glycerin, Fructose, Urea, Citric 2 acid, Sodium Hydroxide, Maltose, Sodium PCA, Sodium Chloride, Sodium Lactate, Trehalose, Allantoin, Sodium Hyaluronate, Glucose Isoadipate 2 2 Diisopropyl Adipate Isodragol ® 1 Triisononanoin Jojoba Oil 0.3 Simmondsia Chinensis (Jojoba) Seed Oil Kaolin 10 Kaolin Keltrol ® CG-RD 0.2 0.1 0.3 0.2 0.3 1.2 Xanthan Gum Kojic acid 0.5 Kojic Acid KP-545 1 Cyclopentasiloxane Acrylates/Dimethicone Copolymer Lanette ® 16 1.5 2 Cetyl Alcohol Lanette ® 22 3 Behenyl Alcohol Lanette ® O 5 2 Cetearyl Alcohol Magnesium Sulfate 0.7 Magnesium Sulfate Mineral Oil 5 Paraffinum Liquidum Neo Heliopan ® 303 4 10 Octocrylene Neo Heliopan ® 357 2 4 2 Butylmethoxydibenzoyl-methane Neo Heliopan ® AP 15% Lösung, neutralisiert mit L-Arginin 6.7 Aqua, Disodium Phenyl Dibenzimidazole Tetrasulfonate, Arginin Neo Heliopan ® AV 7.5 Ethylhexyl Methoxycinnamate Neo Heliopan ® BB 3 Benzophenone-3 Neo Heliopan ® E 1000 1 Isoamyl p.Methoxycinnamate Neo Heliopan ® HMS 7 10 Homosalate Neo Heliopan ® OS 3 5 5 Ethylhexyl Salicylate Neo Heliopan ® Hydro 20% Lösung, neutralisiert mit Biotive 10 3.5 Arginine Aqua, Phenylbenzimidazole, Sulphonic Acid, Arginin Neo-PCL Water Soluble N 1.5 2 Trideceth-9, PEG-5 Ethylhexanoate, Water (Aqua) Neutral oil 2 Caprylic/Capric Triglyceride Niacinamide 2 0.5 0.3 Niacinamide Ozokerite Wax 2389 2 Ozokerite Parfume oil PFO1 or PFO2 0.05 0.3 1 0.3 0.3 0.5 0.3 0.1 0.5 Parfum Passion Fruit Oil 1 Refined Passiflora Edulis seed oil PCL-Liquid 100 3 2 5 Cetearyl Ethylhexanoate PCL-Solid 1 2 Stearyl Heptanoate, Stearyl Caprylate Pemulen ® TR-2 0.6 0.15 Acrylates/C10-30 Alkyl Acrylate Crosspolymer Phenethyl Alcohol 0.2 Phenethyl Alcohol Phytoconcentrole ® 1 Shea Butter, Glycine Soja (Soybean) Oil, Butyrospermum Parkii (Shea Butter) Plantacare PS 10 5 Sodium Laureth Sulfate, Lauryl Glucoside Polymer JR 400 0.4 Sodium Laureth Sulfate, Lauryl Glucoside Retinol 0.1 Retinol Salicylic acid 0.5 0.3 Salicylic Acid Sodium Ascorbyl Phosphate 1 Sodium Ascorbyl Phosphate Sodium Chloride 0.1 Sodium Chloride Sodium Hydroxide 10% Solution 1 0.5 2 0.2 1.9 1.1 Sodium Hydroxide 10% Solution Softisan 100 6 Hydrogenated Coco-Glycerides Solubilizer PEG-40 Hydrogenated Castor Oil, Trideceth-9, Propylene Glycol, 3 Water (Aqua) Sulfetal LA 12 Ammonium Lauryl Sulfate SymCalmin ® 1 0.1 0.5 Butylene Glycol, Pentylene Glycol, Hydroxyphenyl Propamidobenzoic Acid SymClariol ® 0.1 1 0.2 0.38 Decylene Glycol SymDecanox HA 1 2 Caprylic/Capric Triglyceride, Hydroxymethoxyphenyl Decanone Symdiol ® 68 1 0.5 0.5 0.5 0.8 1,2-Hexanediol, Caprylyl Glycol SymFinity ® 1298 0.05 Echinacea Purpurea Extract SymGlucan ® 1 2 Water (Aqua), Glycerin, Beta-Glucan SymHair ® Force 1631 2 Pentylene Glycol, Isochrysis galbana Extract SymHelios ® 1031 0.3 Benzylidene Dimethoxydimethylindanone SymLift 2 Water, Trehalose, Glycerin, Pentylene glycol, beta-Glucan, Hordeum Vulgare Seed Extract, Sodium Hyaluronate, 1,2-Hexanediol, Caprylyl glycol, Sodium Benzoate, Maltodextrin SymMatrix 0.2 Maltodextrin, Rubus Fruticosus (Blackberry) Leaf Extract SymMollient S 1 Cetearyl Nonanoate SymMollient ® W/S 1 2 1.5 2 Trideceth-9, PEG-5 Isononanoate, Water (Aqua) SymOcide ® C 0.1 o-Cymen-5-ol SymOcide ® PC 1 Phenoxyethanol, Caprylyl Glycol, SymOcide ® PH 1 Phenoxyethanol, Hydroxyacetophenone, Caprylyl Glycol, Water (Aqua) SymOcide ® PS 0.8 0.8 Phenoxyethanol, Decylene Glycol, 1,2-Hexanediol SymOcide ® PT 0.8 Phenoxyethanol, Tropolone SymPeptide ® 225 1 Glycerin, Water (Aqua), Myristoyl Pentapeptide-11 SymRelief ® 100 0.1 Bisabolol, Zingiber Officinale (Ginger) Root Extract SymRelief ® S 0.1 Bisabolol, Hydroxymethoxyphenyl Decanone SymRepair ® 100 1 Hexyldecanol, Bisabolol, Cetylhydroxyproline Palmitamide, Stearic Acid, Brassica Campestris (Rapeseed) Sterols SymSave ® H 0.5 0.5 0.5 0.5 Hydoxyacetophenone SymSitive ® 1609 1 0.5 Pentylene Glycol, 4-t-Butylcyclohexanol SymVital ® AgeRepair 3040 0.1 Zingiber Officinale (Ginger) Root Extract SymWhite ® 377 0.5 Phenylethyl Resorcinol Tetraselmis suecica extract 2.5% in glycerin/water 1 2 Water, Glycerin, Tetraselmis suecica extract Tetraselmis suecica extract spray-dried containing 95% 0.25 maltodextrin, 5% extract matter Maltodextrin, Tetraselmis suecica extract Vitacel CS 20 FC 3 Cellulose Vitamin A Palmitate 0.1 Retinyl Palmitate Vitamin E Acetate 0.5 0.2 0.5 0.25 Tocopheryl Acetate Willow bark extract 0.1 Salix Alba Extract Xiameter PMX-345 6 Cyclopentasiloxane, Cyclohexasiloxane Zetesol LA-2 26 Ammonium Laureth Sulfate Water Ad to 100  1 = Skin calming balm for sensitive oily skin  2 = Tinted Face Balm, SPF 15  3 = Rinse-off purifying mask for greasy skin  4 = Night cream W/O  5 = Facial Cleansing gel  6 = Face tonic for oily skin  7 = Anti-dandruff hair shampoo for greasy hair  8 = Sunscreen fluid for acne prone skin, SPF 30  9 = Skin lightening day care fluid O/W for impure oily skin 10 = Anti-acne skin cream 11 = 3 in 1 Skin purifying Wash + Scrub + Mask

TABLE-US-00013 TABLE 13 Cosmetic formulations 12 to 22 (amounts in parts b.w.) Ingredients 12 13 14 15 16 17 18 19 20 21 22 Mannitol 0.5 0.05 Sorbitol 0.3 Xylitol 0.3 0.5 0.2 0.1 Lactitol 0.5 Maltitol Erythritol 0.1 0.2 Inositol 0.4 Threitol 0.1 Actipone ® White Tea GW 1 Aqua, Glycerin, Camellia Sinensis Leaf Extract Actipone ® Witch Hazel 3 1 Hamamelis Virginiana Bark/Leaf/Twig Extract, Alcohol, Hamamelis Virginiana Water Actipone ® Black Currant GW 1 Aqua, Glycerin, Ribes Nigrum Juice Amisoft ® CS-11/CS-11(F) 0.5 Sodium Cocoyl Glutamate Andiroba Oil, refined 0.3 Carapa Guaianensis Seed Oil Aristoflex ® AVC 0.5 Ammonium Acryloyoldimethyltaurate/VP Copolymer 5-Alpha-Avocuta 1 Butyl Avocadate Beeswax 5 Cera Alba Butylene Glycol 0.5 5 Butylene Glycol Candelilla Wax 15 Euphorbia Cera (Candelilla) Wax Carnauba Wax 5 Cera Carnaubae depurata Carbopol ® Aqua SF-1 Polymer 10 Acrylates Copolymer CeramideBio 0.5 Cetylhydroxyproline Palmitamide Citric acid 10% in water 0.5 0.2 Citric acid, water Crinipan ® AD 0.2 Climbazole Disodium EDTA 0.1 0.05 0.1 0.1 Disodium EDTA Dow Corning 345 Fluid 5 Cyclomethicone Dow Corning 556 Fluid 4 Phenyl Trimethicone Dow Corning 2502 Fluid 5 Cetyl Dimethicone D-Panthenol 75 L 0.3 Panthenol Dracorin GOC 2.5 Glyceryl Oleate Citrate, Caprylic/Capric Triglyceride Dragoxat ® 89 5 20 2 Ethylhexyl lsononanoate Emulsiphos ® 2 Potassium Cetyl Phosphate, Hydrogenated Palm Glycerides Ethanol 5 5 10 Alcohol, Aqua Evermat 3 Enantia chlorantha bark extract Extrapone ® Strawberry B Aqua, Propylene Glycol, Citric Acid, Trideceth-9, Bisabolol, Fragaria 1 Ananassa Fruit Extract Extrapone ® Tiger Grass Aqua, Glycerin, PEG-40 Hydrogenated Castor Oil, Trideceth-9, 5 1 Centella Asiatica Extract Flowerconcentrole ® Frangipani Pentylene Glycol, Bisabolol, Plumeria Acutifolia Flower 2 Extract L Frescolat ® ML 0.3 0.3 0.3 0.5 Menthyl Lactate Glycerin 3 3 3 5 1 Glycerin Green Pigment 0.85 Cl77288, Triethoxycaprylylsilane Hexylene Glycol 25 Hexylene Glycol Hispagel ® 200 1 1 Glycerin, Glyceryl Polyacrylate Hydrolite ® 5 1.5 3 1 4 5 7 Pentylene Glycol Hydrolite ® 6 0.5 1,2-Hexanediol Hydromoist ® L 1 Aqua, Hydrolyzed Lupine Seed Extract Hydroviton ® Plus 2290 1 1 Water (Aqua), Pentylene Glycol, Glycerin, Fructose, Urea, Citric acid, Sodium Hydroxide, Maltose, Sodium PCA, Sodium Chloride, Sodium Lactate, Trehalose, Allantoin, Sodium Hyaluronate, Glucose Icroquat Behenyl TMS-50 2 Behentrimonium Methosulfate, Cetyl Alcohol, Butylene Glycol Isoadipate 12.7 Diisopropyl Adipate Isodragol ® 8 Triisononanoin Isopropyl Myristate 2 Isopropyl Myristate Jaguar ® Excel 0.1 Guar Hydroxypropyltrimonium Chloride Jojoba Oil 8 0.5 Simmondsia Chinensis (Jojoba) Seed Oil Keltrol ® CG-T 0.1 0.2 0.3 Xanthan Gum Lactic acid 0.2 Lactic acid Lanette ® 16 1 1 3 Cetyl Alcohol Lanette ® 18 4 Stearyl Alcohol Lanette ® 22 2 Behenyl Alcohol Lanette ® O 1 4.5 Cetearyl Alcohol Medialan ® LD 10 Sodium Lauroyl Sarcosinate Mineral Oil 1 Paraffinum Liquidum Miniporyl ® 1 Isopentyldiol, Trifolium Pratense (Clover) Flower Extract Neo-PCL Water Soluble N 1.5 Trideceth-9, PEG-5 Ethylhexanoate, Aqua Niacinamide 0.5 0.3 0.5 0.4 Niacinamide Parfume oil PFO1 or PFO2 0.5 0.3 1 0.5 0.3 0.1 0.5 Parfum PCL-Liquid 100 5 2 Cetearyl Ethylhexanoate PCL-Solid 3 Stearyl Heptanoate, Stearyl Caprylate Pemulen TR-2 Polymeric Emusifier 0.3 Acrylates/C10-30 Alkyl Acrylate Crosspolymer Plantacare ® 2000 UP 15 Decyl Glucoside Potassium Sorbate 0.2 Potassium sorbate Propylene Glycol 2 5 Propylene Glycol Retinopeptide 189 1 Glycerin, Pentylene Glycol, Aqua, Myristoyl Nonapeptide-3 Salicylic Acid 0.3 0.1 0.3 0.2 Salicylic Acid Shea Butter (Organic) 20 Butyrospermum Parkii (Shea) Butter Sodium Benzoate 0.2 Sodium Benzoate Sodium Chloride 6 Sodium Chloride Sodium Hydroxide 10% solution 2.43 2 0.58 0.46 Sodium Hydroxide, water Softigen ® 767 3 PEG-6, Caprylic/Capric Glycerides Solubilizer 1.2 2 PEG-40 Hydrogenated Castor Oil, Trideceth-9, Propylene Glycol, Water (Aqua) SymCalmin ® 0.5 Butylene Glycol, Pentylene Glycol, Hydroxyphenyl Propamidobenzoic Acid SymClariol ® 0.3 0.5 0.3 Decylene Glycol SymDecanox HA 2 0.5 Caprylic/Capric Triglyceride, Hydroxymethoxyphenyl Decanone Symdiol ® 68 0.5 0.8 0.5 0.5 0.5 1,2-Hexanediol, Caprylyl Glycol SymHair ® Restore 0.5 1 Glycerin, Triticum Vulgare Protein, Aqua SymHair ® Shield 0.5 Pentylene Glycol, Aqua, Glycerin, Triticum Vulgare Bran Extract, 1,2-Hexanediol, Caprylyl Glycol SymMatrix 0.3 Maltodextrin, Rubus Fruticosus (Blackberry) Leaf Extract SymMollient ® S 2 2 Cetearyl Nonanoate SymMollient ® W/S 2 1.5 2 3 Trideceth-9, PEG-5 Isononanoate, Water (Aqua) SymOcide ® PS 1 0.8 Phenoxyethanol, Decylene Glycol, 1,2-Hexanediol SymRelief ® S 0.1 Bisabolol, Hydroxymethoxyphenyl Decanone SymSave ® H 0.5 0.5 0.5 0.5 Hydoxyacetophenone SymSitive ® 1609 1 Pentylene Glycol, 4-t-Butylcyclohexanol SymSol ® PF-3 Aqua, Pentylene Glycol, Sodium Lauryl Sulfoacetate, Sodium 1.5 3 1.2 Oleoyl Sarcosinate, Sodium Chloride, Sodium Oleate SymVital ® AgeRepair 3040 0.2 Zingiber Officinale (Ginger) Root Extract Tetraselmis suecica extract 2.5% in glycerin/water 1 Water, Glycerin, Tetraselmis suecica extract Tetraselmis suecica extract spray-dried containing 95% 0.25 maltodextrin, 5% extract matter Maltodextrin, Tetraselmis suecica extract White Pigment 7 Cl77891, Ricinus (Castor) Seed oil Witch Hazel-Distillate 1 Hamamelis Virginiana (Witch Hazel) Water, Water (Aqua), Alcohol Xiameter ® PMX-200 Silicone Fluid 100 cs 1 0.5 Dimethicone Xiameter ® XM OFX-0193 Fluid 1 1 PEG-12 Dimethicone Yellow Pigment 0.15 Cl77492, Triethoxycaprylylsilane Water Ad 100 Aqua 12 = Pore Refining Fluid 13 = Make-Up Remover Wipes Solution for impure skin 14 = Anti-acne Cleansing Mousse 15 = 3-Phases Clear Make-up Remover Lotion for oily skin 16 = Eau micellaire 17 = Purifying / Anti-Imperfections Cocktail 18 = Tightening Serum for young skin 19 = Concealer Stick 20 = Hair Mask 21 = Aqueous-based Hair & Scalp Serum 22 = Hair Conditioner