Patent Publication Number: US-2019175467-A1

Title: Composition for the treatment of acne

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a Continuation of U.S. Non-Provisional application Ser. No. 15/550,934, filed Aug. 14, 2017, which is a national stage application, filed under 35 U.S.C. § 371, of PCT/EP2016/000312, filed Feb. 23, 2016, which claims priority to European Patent Application No. EP15000576, filed Feb. 27, 2015. The disclosure of the priority applications are hereby incorporated in their entirety by reference. 
    
    
     The present invention describes a cosmetic or dermatological composition for use in the treatment of acne comprising a combination of vegetal extracts titrated in salicin and 1,2-alkanediols, preferably 1,2-decanediol and willow bark ( Salix alba ) extract. 
     Acne vulgaris is the most frequently diagnosed dermatosis in patients in the age between 11 and 30. It is believed that acne affects about 80% of persons in this age group or even, taking into account lesions of low intensity, 100% of young people. The aetiopathogenesis of acne is multifactorial. In all patients with acne, the following symptoms occur: excessive sebum production, excessive keratosis of excretory ducts and openings of sebaceous glands, development of bacterial flora and release of inflammatory mediators in the skin. 
     In 95% of the patients, lesions are situated on the face and on the upper parts of the trunk, occasionally on the other parts of the body, and due to this location and the chronic nature of the disease, the patients have serious psychological problems. 
     Excessive sebum production and accumulation and blocked sebaceous gland openings favour bacterial colonization. Microcomedones are inhabited mostly by  Propionibacterium acnes , a micro-organism mainly involved in the development of acne. Other bacteria are inter alia:  Staphylococcus epidermidis  and  Malasezzia furfur . Due to the presence of lipase, this microorganism hydrolyses sebum di- and triglycerides to free fatty acids. Free fatty acids, which arise during the hydrolysis process, have the irritating, proinflammatory effect and intensify follicular keratosis. Also hyaluronidase, proteases and neuraminidases, produced by  Propionibacterium acnes , have the pro-inflammatory effect. Moreover, this microorganism releases low-molecular chemotactic factors (peptides), attracting neutrocytes, and it activates both the alternative complement pathway and a classic immune response. The activator of the alternative complement pathway is the cell wall of  Propionibacterium  (B. Bergler-Czop, International Journal of Cosmetic Science, 2014, 36, 187-194). 
     Microorganisms like  Propionibacterium acnes  can prompt the secretion of a variety of cutaneous anti-microbial peptides (AMPs). The inflammatory effects of  P. acnes  do not require the organism to be alive or be present in its entirety. In vitro, supernatants containing either membranous peptidoglycans (PG) and lipopolysaccharides (LPS) or, cytosolic contents or membrane proteins were able to increase keratinocyte expression of TLR2 and TLR4. 
     It is well known that further cytokines play a significant role in acne inflammation.  Propionibacterium acnes  triggers the pro-inflammatory mediators through activation of Toll-like receptor 2 (TLR2). Among these mediators is IL-8 the expression of which is induced by  P. acnes.    
     Tumor necrosis factor-alpha (TNF-alpha) is another pro-inflammatory cytokine involved in acne pathogenesis (Archives of Dermatological Research 2008, Volume 300, No 7, pp 371-376). 
     The extract of white willow bark ( Salix alba ) contains salicin and its derivatives, which have been used for longer than a century as antipyretic agents and in the treatment of many rheumatic disorders. 
     Herbal medicinal products such as various formulations from the bark of  Salix  species are well recognised throughout Europe for treating inflammatory conditions and pains of different origin. 
       Salix  extracts have demonstrated analgesic, antiphlogistic and antipyretic effects in various animal models (Loniewski et al. 2002). 
     For example, dose-dependent effects have been reported in the hot-plate and carrageenan-induced paw edema tests in rats (established test procedures to demonstrate analgesic and anti-inflammatory effects, respectively) for a  Salix  extract containing 12% salicin (Loniewski et al. 2002). 
     Salicin has been known as a potent anti-inflammatory agent when taken orally. 
     It is believed that salicin may have anti-aging capabilities when applied topically to human skin. The data from a study show that topical application of a serum formulation containing 0.5% salicin offers wide-spectrum anti-aging benefits, targeting the major signs of visible human skin aging. Statistical improvements were indicated in structure-related signs of skin aging against baseline. These include wrinkles, fine lines, jaw-line contour, firmness, extensibility, and density. Statistical improvements were also seen in mottled pigmentation, uneven skin tone, radiance, hydration and tactile roughness against baseline. These results substantiate salicin&#39;s ability to improve the visible signs of aging, when applied topically to human skin in a product formulation. (Gopaul Remona et al., An evaluation of the effect of a topical product containing salicin on the visible signs of human skin aging Journal of Cosmetic Dermatology, 9, 196-201) 
     From prior art it has been known that salicin has may be useful as anti-irritative active compound in cosmetic and topical dermatological preparations (EP 0801946). 
     Salicin is also useful in combinations with additional herbal extracts. DE 10034328 discloses a cosmetic formulation for external application to skin, especially skin reddened by acne rosaceae, containing quercetin, rutin, salicin and escin in aqueous medium. 
     1,2-Alkanediols like 1,2-pentanediol (INCI: Pentylene Glycol), 1,2-hexane diol (INCI: 1,2-Hexanediol) and 1,2-octanediol (INCI: Caprylyl Glycol) as well as combinations thereof are multifunctional ingredients widely used in personal care products as moisturizers and antibacterial agents. It is well known to the person skilled in the art that these substances show specific antibacterial activity against  P. acnes.    
     WO 2011117126 describes a combination of 1,2-decanediol and licochalcone A and carnitine which is effective against  Propionibacterium acnes  ( P. acnes ) without irritating the skin. 
     EP 1731036 discloses mixtures containing different 1,2-alkanediols for acne treatment. 
     Conventional products for the treatment of oily and blemished skin, eg. aqueous/ethanolic and/or surfactant-containing cleaning products have the disadvantage to strain usually the skin to dry out and work only little skin caring. It is particularly disadvantageous that the body&#39;s reaction to the use of ethanol and/or detergents-containing solutions over a longer period of time may be an overproduction of sebum, which counteracts the primary therapeutic goal of sebum reduction in oily, blemished and acne prone skin. 
     For the topical treatment of acne there are acne agents, such as strong oxidizing agents, such as. benzoyl peroxide; alpha-hydroxy acids, such as salicylic acid and lactic acid; aliphatic dicarboxylic acids such as azelaic acid; retinoids such as tretionoin (synonym: all-trans-retinoic acid), all-trans-retinal and 13-cis-retinoic acid (isotretinoin); antiandrogens (5alpha-reductase) and antibiotics such as clindamycin, tetracycline and erythromycin. 
     Said substances usually have only a very moderate antimicrobial activity against  P. acnes  and have to be used in a relatively high concentration—benzoyl peroxide for example, with up to 5 wt.-%, and azelaic acid with up to 20 wt.-%—in cosmetic and dermatological formulations. 
     Due to the high dosage, however, the skin is extremely disadvantageous heavily overused, which is manifested particularly in very dry skin, which is often associated in part with severe skin irritation due to the strong reduction of the pH of the skin. 
     The effectiveness of the strong oxidizing agent such as benzoyl peroxide, the alpha hydroxy acids such as salicylic acid and lactic acid, and the aliphatic dicarboxylic acids such as azelaic acid is based on the inhibition of  P. acnes.    
     It is desirable to have a cosmetic or dermatological preparation to provide acne treatment that has an improved activity against  Propionibacterium acnes  ( P. acnes ) and improved inflammatory activity especially against inflamed comedones without severely irritating the skin. 
     The problem is solved by a cosmetic or dermatological composition comprising a combination of 1,2-decanediol and willow bark extract. This preparation surprisingly shows a synergistic antibacterial and anti-inflammatory effect compared to the single substances. 
    
    
     EXPERIMENTAL PART 
     Determination of MIC and MBC on Gram Positive Bacteria 
     Aim of the Test 
     The aim of the test was to determine the antimicrobial activity of one or more samples against a micro-organism. The values obtained must be considered characteristic of the test sample for a determined microbial species under determined test conditions. 
     Description of the Method 
     A series of test tubes was prepared containing the culture broth inoculated with the test micro-organism and the substance to be tested was introduced at decreasing scalar concentrations. 
     The cultures were incubated at the optimal temperature and under optimal growth conditions of the preselected micro-organism and for a sufficient period of time to demonstrate development. 
     The test tubes in which the microbial population developed were then determined by observing visually the turbidity that is indicative of growth. Test tubes in which the substance is present at a sufficient concentration to inhibit growth remain clear. When the nature itself of the sample prevents visual reading or if it is wished to determine whether the lack of development is due to a microbiostatic or microbicidal action, transfers are made to appropriate agar media for confirmation. 
     Criteria of Interpretation 
     The concentration of sample at which growth of the micro-organisms is inhibited is considered to be the Minimum Inhibitory Concentration (MIC), while that at which viable micro-organisms are no longer present is considered to be the Minimum Bactericidal Concentration (MBC) 
     A) Evaluation of the Antibacterial Activity of Different Substances Against  Staphylococcus  Species 
     A test to evaluate antibacterial activity against Gram positive bacteria was conducted evaluating the following substances: 
     Bakuchiol, Lactoferrin, Lauric acid, Resveratrol,  Salix alba  extract. 
     The antibacterial activity of these substances against  Staphylococcus aureus acnes  ATCC 25923 and  Staphylococcus epidermidis  ATCC 12228 was tested according to the above-described method. The results are shown in Table 1. 
     
       
         
           
               
               
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                   
                   
                 
                   Staphylococcus 
                 
               
               
                   
                 
                   Staphylococcus aureus 
                 
                 
                   epidermidis 
                 
               
               
                   
                 ATCC 25923 
                 ATCC 12228 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 MBC 
                   
                 MBC 
               
               
                   
                 MIC (μg/ml) 
                 (μg/ml) 
                 MIC (μg/ml) 
                 (μg/ml) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Bakuchiol 
                 6.25 
                 100 
                 6.25 
                 100 
               
               
                 Lactoferrin 
                 &gt;20000 
                 — 
                 &gt;20000 
                 — 
               
               
                 Lauric Acid 
                 250 
                 1.000 
                 500 
                 1000 
               
               
                 Resveratrol 
                 1000 
                 &gt;100000 
                 250 
                 &gt;100000 
               
               
                   Salix alba  extract 
                 30000 
                 100000 
                 30000 
                 100000 
               
               
                   
               
            
           
         
       
     
     Minimum Inhibition Concentration (MIC) and Minimum Bactericide Concentration (MBC) of different substances against  Staphylococcus aureus acnes  and  Staphylococcus epidermidis    
     The test showed poor activity of  Salix alba  extract against Gram positive bacteria with respect to other substances tested. 
     B) Evaluation of the Antibacterial Activity of Different Substances Against  P. acnes    
     In a further set of experiments we tested the antibacterial activity of  Salix alba  extract and 1,2-decanediol, a substance which is known to show antibacterial activity against  P. acnes , alone and in combination according to the above-described method. 
     The microbial strain used was  Propionibacterium acnes  ATCC 11827 titrated at a concentration of 2.6×104 cells per milliliter of medium. 
     The result is shown in Table 2. 
     
       
         
           
               
               
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                   
                 
                   Propionibacterium acnes 
                 
                   
               
            
           
           
               
               
               
            
               
                   
                 MIC (μg/ml) 
                 MBC (μg/ml) 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                   Salix alba  extract 
                 1560 
                 3120 
               
               
                   
                 1,2-decanediol 
                 620 
                 1250 
               
               
                   
                   Salix alba  extract + 
                 620 
                 620 
               
               
                   
                 1,2-decanediol 
                   
                   
               
               
                   
                 (1:1) 
                   
                   
               
               
                   
                 benzoyl peroxide 
                 480 
                 480 
               
               
                   
               
            
           
         
       
     
     Minimum Inhibition Concentration (MIC) and Minimum Bactericide Concentration (MBC) of 1,2-Decanediol and  Salix alba  extract against  Propionibacterium acnes    
       Salix alba  extract alone shows only poor antibacterial activity. 
     1,2-decanediol is known to be effective against  P. acnes.    
     The combination (1:1) of  Salix alba  extract and 1,2-decanediol surprisingly displayed a synergistic antibacterial effect against  P. acnes.    
     A combination of 1,2-decanediol and  Salix alba  extract is capable to obtain the same MIC of the double concentration of 1,2-decanediol and to improve dramatically its MBC. 
     The selected order degree of the association is in line with benzoyl peroxide that is commonly known as strong antibacterial agent against  P. acnes.    
     In Vitro Evaluation of the Anti-Inflammatory Activity of  Salix alba  Extract and 1,2-Decanediol 
     The aim of the test was the evaluation of the anti-inflammatory activity of  Salix alba  extract, 1,2-decanediol and their combination by means of the study of TNFalpha, IL1alpha, IL8 synthesis modulation in a biological experimental model (keratinocyte cell culture HaCat). 
     TNFalpha, IL1alpha, IL8 are inflammatory mediators related to the acneic process. 
     Keratinocyte cell culture were selected as experimental model on the base that the acneic process is performed inside the sebaceous glands follicle, a tissue composed by keratinocytes. 
     In order to stimulate the inflammatory process in our experimental model, lipopolysaccharides (LPS) were selected. LPS are pro-inflammatory mediators secreted by bacteria, e.g. by  P. acnes.    
     1,2-decanediol (SMAL) was emulsified with corn oil (37° C.) in mechanical agitation and addition of culture medium, starting from the following ratio: 0.05 g emulsified with 100 μl corn oil in a final volume of culture medium of 1 ml (37° C.). 
       Salix alba  extract (WMAL) was direct diluted in culture medium, starting from the following ratio: 0.05 g in 1 ml (37° C.); subsequent dilutions in culture medium (37° C.). 
     For the test execution, human keratinocytes (HaCat) were treated with LPS (Lipopolysaccharide from  Escherichia coli,  10 ng/ml) and with tested product at 3 concentrations, chosen among non-cytotoxic ones after a preliminary cytotoxicity test. 
     At the end of the monitored experimental period, cytokine levels were measured by means of ELISA assay. 
     Results were compared to negative control (cells not subjected to LPS, CTR−) and positive control (cells treated with LPS, CTR+). 
     A preliminary cytotoxicity test was performed on the two products by using a concentration range from 5.0% to 0.0012% (serial dilution 1:2). According to obtained results, the following concentrations were chosen for the analysis of the antinflammatory activity: 
     1,2-decanediol (SMAL): 0.002%
 
 Salix alba  extract (WMAL): 0.04%-0.02%-0.01%
 
     A second cytotoxicity test was performed on the mix of the two raw materials preliminary to the beginning of the test to verify the action synergism in the antinflammatory activity; tested concentrations were the following: 
     SMAL 0.002%+WMAL: 0.04%-0.02%-0.01% 
     Culture media of controls and cells treated with tested product were used for the dosage of pro-inflammatory cytokines TNFalpha, IL1alpha and IL8 by means of ELISA method. 
     Commercial ELISA kits were used for the determination of cytokine quantity. 
     The quantitative determination uses a calibration curve made-up of standard known and growing concentrations of standard cytokine. 
     The data obtained in the different experimental groups were subjected to statistical analysis and compared according to t-test. The variations are considered significant for p&lt;0.05. 
     In table 3 below the data obtained for each tested series are reported. 
     The results are expressed as cytokine released into the medium during the experimental period (mean value±dev.st.) and as mean % variation compared to the controls. 
     In order to compare the two different work sessions, the obtained data were normalized in a 0-100% scale, in which CTR− is 0 and CTR+ is 100%; all the other data were calculated in this interval. 
     On these data, statistical analysis by t-test was performed and variations are considered significant for p&lt;0.05. 
     On the base of the results obtained, it is observed that SMAL and WMAL are able to significantly reduce the LPS-induced release of the inflammation markers TNFalpha, IL1alpha and IL8, which are all related to acne. 
     For all substances analyzed, the substances WMAL and SMAL in combination show a synergistic effect. 
     
       
         
           
               
               
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                   
                 Normalized data 0-100% 
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                 T-test vs 
                 T-test vs 
               
               
                   
                   
                   
                 T-test vs 
                 CTR+ 
                 CTR+ 
               
               
                   
                   
                 dev std 
                 CTR+ 
                 +WMAL 
                 +SMAL 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 TNF-ALPHA 
                   
                   
                   
                   
                   
               
               
                 CTR− 
                 0 
                   
                   
                   
                   
               
               
                 CTR+ 
                 100.00% 
                 6.2% 
                   
                   
                   
               
               
                 WMAL 0.4% 
                 32.94% 
                 22.2% 
                 0.0545 
                   
                   
               
               
                 SMAL 0.02% 
                 18.45% 
                 3.9% 
                 0.0040 
                   
                   
               
               
                 WMAL 0.4% + 
                 −25.00% 
                 8.5% 
                 0.0042 
                 0.0751 
                 0.0224 
               
               
                 SMAL 0.02% 
                   
                   
                   
                   
                   
               
               
                 IL-8 
                   
                   
                   
                   
                   
               
               
                 CTR− 
                 0 
                   
                   
                   
                   
               
               
                 CTR+ 
                 100.00% 
                 9.4% 
                   
                   
                   
               
               
                 WMAL 0.4% 
                 17.77% 
                 0.4% 
                 0.0064 
                   
                   
               
               
                 SMAL 0.02% 
                 34.56% 
                 0.3% 
                 0.0101 
                   
                   
               
               
                 WMAL 0.4% + 
                 −13.76% 
                 2.9% 
                 0.0011 
                 0.0044 
                 0.0019 
               
               
                 SMAL 0.02% 
                   
                   
                   
                   
                   
               
               
                 IL-6 
                   
                   
                   
                   
                   
               
               
                 CTR− 
                 0 
                   
                   
                   
                   
               
               
                 CTR+ 
                 100.00% 
                 45.6% 
                   
                   
                   
               
               
                 WMAL 0.4% 
                 75.81% 
                 111.8% 
                 0.8035 
                   
                   
               
               
                 SMAL 0.02% 
                 61.69% 
                 106.6% 
                 0.6864 
                   
                   
               
               
                 WMAL 0.4% + 
                 −21.43% 
                 7.2% 
                 0.0017 
                 0.3444 
                 0.3861 
               
               
                 SMAL 0.02% 
               
               
                   
               
            
           
         
       
     
     Dosage of cytokine in cell culture CTR−, CTR+, treated with SMAL, WMAL and their associations. The results are expressed as mean value±dev.st. (expressed in ng/L) and as mean % variation compared to the controls. 
     Formulations can be of various nature both water-based, hydro-alcohol and anhydrous. Among the most commonly used include: surfactants systems (including even such as shampoo, bubble bath, shower gel, liquid soaps and solid soaps, micellar waters, liquid detergents), water-in-oil emulsions, oil-in-water emulsions, serums, gels, oils, aqueous solutions, hydroalcoholic solutions, anhydrous sticks, compact founding powders, lotions, milks, suncreams, after sun products and camouflage products (i.e. CC creams, BB creams). 
     It is optionally possible and advantageous to use the compositions according to the invention as a base for pharmaceutical formulations. 
     It is of course known to the person skilled in the art that cosmetic compositions are usually inconceivable without the customary auxiliaries and additives. Among these are included, for example, consistency-imparting agents, fillers, perfume, colorants, emulsifiers, additional active compounds such as vitamins or proteins, sunscreens, stabilisers, insect repellents, alcohol, water, salts, substances having proteolytic or keratolytic activity, thickeners, emollients, fatty acids, chelating agents, soothing agents, glycols, colorants, buffering substances. 
     The willow bark extract is prepared according to the Ph.Eur. monograph “Extracta”. Whole or fragmented dried bark of young branches or whole dried pieces of current year twigs of various species of genus  Salix  including  S. purpurea  L.,  S. saphnoides  Vill. And  S. fragilis  L. are extracted with water and/or ethanol. The total content of salicylic derivatives expressed in salicin has to be at least 5%; preferably between 10 and 20%. 
     The  Salix alba  extract according to the present invention has to be titrated to a total concentration of salicylic derivatives expressed as salicin not less than 20% (w/w). 
     The ratio between  Salix alba  extract and 1,2-decanediol is between 1:100 and 100:1, or between 1:50 and 50:1, or between 1:10 and 10:1, preferably 1:5 and 5:1; more preferably 1:1. 
     The overall amount of  Salix alba  extract in the formula is in a range between 0.001% and 10%, preferably between 0.01% (w/w) and 5% (w/w), more preferably between 0.3% (w/w) and 1% (w/w). 
     The overall amount of 1,2-decanediol in the formula is in a range between 0.001% (w/w) and 10% (w/w), preferably between 0.01% (w/w) and 5% (w/w), more preferably between 0.3 (w/w) and 1% (w/w). 
     EXAMPLES 
     The following examples shall not represent a restriction of the invention. 
     Example 1 
     Suncream 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Avobenzone 
                 0-5 
               
               
                   
                 Glycerol 
                 0-5.00 
               
               
                   
                 Panthenol 
                 0-1.00 
               
               
                   
                 Disodium EDTA 
                 0.10 
               
               
                   
                 Glyceryl Stearate, PEG-100 Stearate 
                 1-5.00 
               
               
                   
                 (50%:50%) (Arlacel 165V P) 
                   
               
               
                   
                 4-Methylbenzylidene Camphor 
                 1-4.00 
               
               
                   
                 
                   Citrus Aurantius Amara 
                 
                 0-1 
               
               
                   
                 Xanthan Gum 
                 0-1 
               
               
                   
                 Ascorbyl Tetraisopalmitate 
                 0.20 
               
               
                   
                 Polyacrylamide (45%), C13-14 
                 0-2.00 
               
               
                   
                 Isoparaffin (25%), Laureth-7 (8%), 
                   
               
               
                   
                 Aqua (22%) (Sepigel 305) 
                   
               
               
                   
                 Methylene Bis-Benzotriazolyl 
                 0-2.00 
               
               
                   
                 Tetramethylbutylphenol, Aqua, Decyl 
                   
               
               
                   
                 Glucoside, Propylene Glycol, Xanthan 
                   
               
               
                   
                 Gum (Tinosorb A2B) 
                   
               
               
                   
                 Ethylhexyl Methoxycinnamate 
                 0-8.00 
               
               
                   
                 Niacinamide 
                 0-1 
               
               
                   
                 Magnesium Aluminum Silicate 
                 0-0.50 
               
               
                   
                 Dicaprylyl Carbonate 
                 1-5.00 
               
               
                   
                 1,2-Hexanediol, Caprylyl Glycol 
                 0.50 
               
               
                   
                 (50%:50%) (Symdiol 68) 
                   
               
               
                   
                 Soy Isoflavones 
                 0.30 
               
               
                   
                 Ethylhexyl Triazone 
                 0-2.00 
               
               
                   
                 Titanium Dioxide (75%), Silica (10%), 
                 0-5 
               
               
                   
                 Dimethicone (15%) (Parsol TX) 
                   
               
               
                   
                 1,2-Decanediol 
                 0.30 
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.30 
               
               
                   
                 Tocopheryl Acetate 
                 0.50 
               
               
                   
                 Butylated hydroxytoluene 
                 0-0.05 
               
               
                   
                 Hydroxyacetophenone 
                 0-0.50 
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 2 
     Serum 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Sodium Hydroxide 
                 0-8 
               
               
                   
                 Glycolic Acid 
                 0-20.00 
               
               
                   
                 Lactic Acid 
                 0-3 
               
               
                   
                 Niacinamide 
                 1.00 
               
               
                   
                 Caprylyl Glycol 
                 0-5.00 
               
               
                   
                 Xanthan Gum 
                 0.10 
               
               
                   
                 Polyacrylate Crosspolymer-6 
                 2.20 
               
               
                   
                 Dicaprylyl Ether 
                 0-4.00 
               
               
                   
                 Salicylic Acid 
                 0-2 
               
               
                   
                 1,2-Decanediol 
                 1.00 
               
               
                   
                 Polyglyceryl-6 Stearate (85-98%), 
                 0-4 
               
               
                   
                 Polyglyceryl-6 Behenate (2-15%) 
                   
               
               
                   
                 (Tego Care PBS 6) 
                   
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.30 
               
               
                   
                 Aluminum Starch Octenylsuccinate 
                 0-2.00 
               
               
                   
                 Dipotassium Glycirrhyzinate 
                 0-2 
               
               
                   
                 Sodium Phytate, Aqua, Alcohol 
                 0.10 
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 3 
     Hydrating Cream 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Disodium EDTA 
                 0.10 
               
               
                   
                 Glycerol 
                 0-7.00 
               
               
                   
                 Sodium Hyaluronate 
                 0-1 
               
               
                   
                 Niacinamide 
                 1.00 
               
               
                   
                 Caprylyl Glycol 
                 0-2.00 
               
               
                   
                 Xanthan Gum 
                 0.10 
               
               
                   
                 Polyacrylate Crosspolymer-6 
                 0-3.00 
               
               
                   
                 Dicaprylyl Ether 
                 0-5.00 
               
               
                   
                 1,2-Decanediol 
                 0.30 
               
               
                   
                 Polyglyceryl-6 Stearate (85-98%), 
                 2.50 
               
               
                   
                 Polyglyceryl-6 Behenate (2-15%) 
                   
               
               
                   
                 (Tego Care PBS 6) 
                   
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.3 
               
               
                   
                 Lactic Acid 
                 0-1 
               
               
                   
                 Sodium Phytate (48-52%), Aqua (48-52%), 
                 0.05 
               
               
                   
                 Alcohol (1%) (Dermosoft PA 3) 
                   
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 4 
     Gel 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Disodium EDTA 
                 0.10 
               
               
                   
                 Glycerol 
                 0-3.00 
               
               
                   
                 Niacinamide 
                 1.00 
               
               
                   
                 Caprylyl Glycol 
                 0-2.00 
               
               
                   
                 Xanthan Gum 
                 0.20 
               
               
                   
                 Polyacrylate Crosspolymer-6 
                 0-3.0  
               
               
                   
                 1,2-Decanediol 
                 0.50 
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.50 
               
               
                   
                 Lactic Acid 
                 0.50 
               
               
                   
                 Sodium Phytate (48-52%), Aqua (48-52%), 
                 0.10 
               
               
                   
                 Alcohol (1%) (Dermosoft PA 3) 
                   
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 5 
     Liquid Detergent 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Disodium EDTA 
                 0.10 
               
               
                   
                 Glycerol 
                 0-4.00 
               
               
                   
                 Hydroxypropyl Guar 
                 0-1.0 
               
               
                   
                 Hydroxypropyltrimonium Chloride 
                   
               
               
                   
                 (Jaguar C162) 
                   
               
               
                   
                 Niacinamide 
                 0.30 
               
               
                   
                 Methylpropanediol (80%), Caprylyl 
                 0-5.0 
               
               
                   
                 Glycol (15%), Phenylpropanol (5%) 
                   
               
               
                   
                 (Dermosoft OMP) 
                   
               
               
                   
                 Xanthan Gum 
                 0.30 
               
               
                   
                 Sodium Cocoamphoacetate 
                 0-10.0 
               
               
                   
                 Disodium Laureth Sulfosuccinate 
                 0-10.0 
               
               
                   
                 1,2-Decanediol 
                 1.00 
               
               
                   
                 PEG-40 Hydrogenated Castor Oil 
                 1.00 
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.01 
               
               
                   
                 Lactic Acid 
                 1.00 
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 6 
     CC Cream 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 Aqua 
                 56.00 
               
               
                   
                 Glycerol 
                 2.00 
               
               
                   
                 Niacinamide 
                 0.50 
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.50 
               
               
                   
                 Magnesium Sulfate Heptahydrate 
                 0.50 
               
               
                   
                 Methylpropanediol (80%), Caprylyl 
                 2.00 
               
               
                   
                 Glycol (15%), Phenylpropanol (5%) 
                   
               
               
                   
                 (Dermosoft OMP) 
                   
               
               
                   
                 Cetyl Dimethicone 
                 2.00 
               
               
                   
                 Octyldodecanol 
                 10.00 
               
               
                   
                 Ethylhexyl Palmitate 
                 8.00 
               
               
                   
                 Dimethicone 
                 1.50 
               
               
                   
                 Hydrogenated Castor Oil 
                 1.50 
               
               
                   
                 1,2-Decanediol 
                 1.00 
               
               
                   
                 Cetyl PEG PPG-10/1 Dimethicone 
                 2.50 
               
               
                   
                 (Abil EM 90) 
                   
               
               
                   
                 Titanium dioxide 
                 5.00 
               
               
                   
                 Tocopheryl Acetate 
                 1.00 
               
               
                   
                 Mica (48-59%), Titanium Dioxide (41-52%) 
                 4.00 
               
               
                   
                 (Timica Terra White) 
                   
               
               
                   
                 Mica (44-54%), Iron Oxides (36-50%), 
                 2.00 
               
               
                   
                 Titanium Dioxide (2-8%) (Timica Terra 
                   
               
               
                   
                 Brown) 
                   
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 7 
     Moisturizing Cream 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Disodium EDTA 
                 0-0.10 
               
               
                   
                 Glycerin 
                 0-6.00 
               
               
                   
                 Niacinamide 
                 0-1.00 
               
               
                   
                 Sodium Phytate 
                 0-0.05 
               
               
                   
                 Sodium Hyaluronate 
                 0.2-0.9 
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.01-0.3 
               
               
                   
                 Caprylyl Glycol 
                 0.5-1.5 
               
               
                   
                 Xanthan Gum 
                 0-0.30 
               
               
                   
                 Polyacrilate Cosspolymer-6 
                 0-1.50 
               
               
                   
                 Dicaprylyl Ether 
                 1-5.00 
               
               
                   
                 1,2-Decanediol 
                 0-0.9 
               
               
                   
                 Polyglyceryl-6 Stearate (85-98%), 
                 2.50 
               
               
                   
                 Polyglyceryl-6 Behenate (2-15%) (Tego 
                   
               
               
                   
                 Care PBS 6) 
                   
               
               
                   
                 Aluminum Starch Octenylsuccinate 
                 0-2.00 
               
               
                   
                 Lactic Acid 
                 0-0.15 
               
               
                   
                 Demin. H 2 O 
                 ad 100 
               
               
                   
               
            
           
         
       
     
     Example 8 
     Detergent 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Glycerol 
                 0.1-2.00   
               
               
                   
                 Disodium EDTA 
                 0-0.10 
               
               
                   
                 Niacinamide 
                 0.1-0.90   
               
               
                   
                 Phytospingosine HCl 
                 0.01-0.1    
               
               
                   
                 1,2-Decanediol 
                 0.01-3    
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.01-0.9    
               
               
                   
                 PEG-40 Hydrogenated Castor Oil 
                 0-1.00 
               
               
                   
                 Polyquaternium-10 
                 0-1   
               
               
                   
                 Sodium Cocoamphoacetate 
                 1-6.00 
               
               
                   
                 Disodium Laureth Sulfosuccinate 
                 1-8.00 
               
               
                   
                 Methylpropanediol (80%), Caprylyl 
                 1-2.50 
               
               
                   
                 Glycol (15%), Phenylpropanol (5%) 
                   
               
               
                   
                 (Dermosoft OMP) 
                   
               
               
                   
                 Lactic Acid 
                 0.01-0.90   
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 9 
     Suncream 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Avobenzone 
                 0-5 
               
               
                   
                 Glycerol 
                 0-5.00 
               
               
                   
                 Panthenol 
                 0-1.00 
               
               
                   
                 Disodium EDTA 
                 0.10 
               
               
                   
                 Glyceryl Stearate, PEG-100 Stearate 
                 1-5.00 
               
               
                   
                 (50%:50%) (Arlacel 165V P) 
                   
               
               
                   
                 4-Methylbenzylidene Camphor 
                 1-4.00 
               
               
                   
                 
                   Citrus Aurantius Amara 
                 
                 0-1 
               
               
                   
                 Xanthan Gum 
                 0-1 
               
               
                   
                 Ascorbyl Tetraisopalmitate 
                 0.20 
               
               
                   
                 Polyacrylamide (45%), C13-14 
                 0-2.00 
               
               
                   
                 Isoparaffin (25%), Laureth-7 (8%), 
                   
               
               
                   
                 Aqua (22%) (Sepigel 305) 
                   
               
               
                   
                 Methylene Bis-Benzotriazolyl 
                 0-10.00 
               
               
                   
                 Tetramethylbutylphenol (46-55%), 
                   
               
               
                   
                 Aqua (33.9-47.7%), Decyl Glucoside 
                   
               
               
                   
                 (6-10%), Propylene Glycol 0.2-0.6%), 
                   
               
               
                   
                 Xanthan Gum (0.1-0.5%) (Tinosorb M) 
                   
               
               
                   
                 Ethylhexyl Methoxycinnamate 
                 0-8.00 
               
               
                   
                 Niacinamide 
                 0-1 
               
               
                   
                 Magnesium Aluminum Silicate 
                 0-0.50 
               
               
                   
                 Dicaprylyl Carbonate 
                 1-5.00 
               
               
                   
                 1,2-Hexanediol (and) Caprylyl Glycol 
                 0.50 
               
               
                   
                 (50%:50%) (Symdiol 68) 
                   
               
               
                   
                 Soy Isoflavones 
                 0.30 
               
               
                   
                 Ethylhexyl Triazone 
                 0-2.00 
               
               
                   
                 Titanium Dioxide (75%), Silica (10%), 
                 0-5 
               
               
                   
                 Dimethicone (15%) (Parsol TX) 
                   
               
               
                   
                 1,2-Decanediol 
                 0.30 
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.30 
               
               
                   
                 Tocopheryl Acetate 
                 0.50 
               
               
                   
                 Butylated hydroxytoluene 
                 0-0.05 
               
               
                   
                 Hydroxyacetophenone 
                 0-0.50 
               
               
                   
                 Demin. H 2 O 
                 ad 100.00 
               
               
                   
               
            
           
         
       
     
     Example 10 
     Suncream 2 
       
     
       
         
           
               
               
               
             
               
                   
               
               
                   
                 INCI NAME 
                 % (w/w) 
               
               
                   
               
             
            
               
                   
                 Avobenzone 
                 0-5 
               
               
                   
                 Glycerol 
                 0-5.00 
               
               
                   
                 Panthenol 
                 0-1.00 
               
               
                   
                 Disodium EDTA 
                 0.10 
               
               
                   
                 Glyceryl Stearate, PEG-100 Stearate 
                 1-5.00 
               
               
                   
                 (50%:50%) (Arlacel 165V P) 
                   
               
               
                   
                 4-Methylbenzylidene Camphor 
                 1-4.00 
               
               
                   
                 
                   Citrus Aurantius Amara 
                 
                 0-1 
               
               
                   
                 Xanthan Gum 
                 0-1 
               
               
                   
                 Ascorbyl Tetraisopalmitate 
                 0.20 
               
               
                   
                 Polyacrylamide (45%), C13-14 
                 0-2.00 
               
               
                   
                 Isoparaffin (25%), Laureth-7 (8%), 
                   
               
               
                   
                 Aqua (22%) (Sepigel 305) 
                   
               
               
                   
                 Aqua (37-46%), Tris-Biphenyl Triazine 
                 0-10.00 
               
               
                   
                 (47-53%), decyl glucoside (6.5-8.5%), 
                   
               
               
                   
                 disodium phosphate (0.2%-0.6%), 
                   
               
               
                   
                 butylene glycol (0.2%-0.6%), xanthan 
                   
               
               
                   
                 gum (0.1%-0.3%) (Tinosorb A2B) 
                   
               
               
                   
                 Ethylhexyl Methoxycinnamate 
                 0-8.00 
               
               
                   
                 Niacinamide 
                 0-1 
               
               
                   
                 Magnesium Aluminum Silicate 
                 0-0.50 
               
               
                   
                 Dicaprylyl Carbonate 
                 1-5.00 
               
               
                   
                 1,2-Hexanediol (and) Caprylyl Glycol 
                 0.50 
               
               
                   
                 (50%:50%) (Symdiol 68) 
                   
               
               
                   
                 Soy Isoflavones 
                 0.30 
               
               
                   
                 Ethylhexyl Triazone 
                 0-2.00 
               
               
                   
                 Titanium Dioxide (75%), Silica (10%), 
                 0-5 
               
               
                   
                 Dimethicone (15%) (Parsol TX) 
                   
               
               
                   
                 1,2-Decanediol 
                 0.30 
               
               
                   
                   Salix alba  (Willow) Bark Extract 
                 0.30 
               
               
                   
                 Tocopheryl Acetate 
                 0.50 
               
               
                   
                 Butylated hydroxytoluene 
                 0-0.05 
               
               
                   
                 Hydroxyacetophenone 
                 0-0.50 
               
               
                   
                 Demin. H 2 O 
                 ad 100.00