Yarrow fresh-plant pressed juice concentrate, production, and use

Abstract

The present invention relates to a yarrow fresh plant press juice concentrate and a gentle method for its manufacture. The yarrow fresh plant press juice concentrate is used in cosmetic compositions, pharmaceutical compositions, food compositions or food supplements. This invention also relates to new aspects of the use of yarrow. The invention provides the use of yarrow to stimulate the expression of heat shock proteins and/or antimicrobial peptides in skin cells. It also describes the use of yarrow to increase the thermal tolerance of the skin.

Claims

1. A spray dried yarrow fresh plant press juice concentrate comprising: 10 to 50 wt. % of yarrow fresh plant press juice dry residue, 0 to 10 wt. % of water, 50 to 90 wt. % of carrier(s) chosen from maltodextrin, dextrin, cyclodextrin, and mixtures thereof, and one or more dicaffeoylquinic acid(s); wherein the percent by weight is based on the total weight of the spray dried yarrow fresh plant press juice concentrate.

2. The spray dried yarrow fresh plant press juice concentrate according to claim 1, wherein the yarrow fresh plant press juice concentrate further comprises preservatives and/or stabilizers.

3. A method for manufacturing the spray dried yarrow fresh plant press juice concentrate of claim 1 comprising: mixing yarrow fresh plant press juice with carrier(s) chosen from maltodextrin, dextrin, cyclodextrin, and mixtures thereof, and spray drying the mixture of yarrow fresh plant press juice and carrier(s).

4. The method according to claim 3, wherein the spray drying is performed at a temperature of 200 to 400° C.

5. A cosmetic composition comprising the spray dried yarrow fresh plant press juice concentrate according to claim 1.

6. A pharmaceutical composition, food composition, or food supplement comprising the spray dried yarrow fresh plant press juice concentrate according to claim 1.

7. A cosmetic composition according to claim 5, further comprising: 0.01 to 10 wt. % of a skin soothing agent and/or an antioxidant.

8. A pharmaceutical composition according to claim 6, further comprising: 0.01 to 10 wt. % of a skin soothing agent and/or an antioxidant.

9. A method for treating skin and/or hair comprising topically applying to the skin and/or hair the spray dried yarrow fresh plant press juice concentrate according to claim 1.

10. The method according to claim 9, wherein the method comprises stimulating the expression of heat shock proteins (HSP) in skin cells of the skin.

11. The method according to claim 9, wherein the method increases the thermal tolerance of the skin.

12. A method for treating skin and/or hair comprising topically applying to the skin and/or hair the cosmetic composition according to claim 5.

13. The method of claim 12, wherein the cosmetic composition comprises 0.0001 to 10 wt. % of the spray dried yarrow fresh plant press juice concentrate, based on the total weight of the cosmetic composition.

14. The spray dried yarrow fresh plant press juice concentrate according to claim 1, wherein the one or more dicaffeoylquinic acid(s) is/are chosen from 1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid.

Description

EXAMPLES

(1) All specifications given in the examples in % refer to specifications in wt.-% unless explicitly stated otherwise.

Example 1: Manufacturing of a Yarrow Fresh Plant Press Juice Concentrate by Freeze Drying

(2) 100 ml yarrow (Achillea millefolium) fresh plant press juice (company Schoenenberger), produced from the flowering herb cultivated in Germany, is frozen and subsequently freeze-dried. 5.3 g dry juice 1a is obtained as a brown-green solid and the composition is analysed:

(3) TABLE-US-00001 TABLE 1 Substance class Content [wt.-%] Total polyphenols (photometric, Folin-Denis method as 16.4 catechin equivalents) Containing Sum of monocaffeoylquinic acids (chlorogenic acid, neo- 10.5 and cryptochlorogenic acid, HPLC)* Sum of dicaffeoylquinic acids (1,5-, 3,4-, 3,5- and 4,5- 5.3 dicaffeoylquinic acid, HPLC)* Rutin (HPLC) 0.3 Total proteins (Nitrogen analyser) 3.3 Sum of amino acids (HPLC) 1.0 Potassium K.sup.+ (IC) 10.2 Calcium Ca.sup.2+ (IC) 0.7 Magnesium Mg.sup.2+ (IC) 0.4 Sodium Na.sup.+ (IC) 0.04 Water (Karl Fischer) 7.5 *Quantified as chlorogenic acid

(4) Three further batches of yarrow (Achillea millefolium) fresh plant press juice (company Schoenenberger) of 100 ml each are frozen and subsequently freeze-dried. The obtained dry juices 1b-1d are weighed and analysed for the sum of mono- and dicaffeoylquinic acids and rutin:

(5) TABLE-US-00002 TABLE 2 Substance class 1a 1b 1b 1d Average Yield of freeze-dried yarrow 5.3 4.5 4.9 4.1 4.7 ± 0.4 fresh plant press juice Content [wt.-%] Sum of monocaffeoylquinic 10.5 8.9 11.4 7.7 9.6 ± 1.3 acids (chlorogenic acid, neo- and cryptochlorogenic acid, HPLC)* Sum of dicaffeoylquinic acids 5.3 3.9 5.7 3.1 4.5 ± 1.0 (1,5-, 3,4-, 3,5- and 4,5- dicaffeoylquinic acid, HPLC)* Rutin (HPLC) 0.3 0.4 0.3 0.1 0.3 ± 0.1 Water (Karl Fischer) 7.5 n.d. n.d. 5.6 6.6 ± 1.0 *Quantified as chlorogenic acid n.d. = not determined

(6) The results show that the 4 batches of yarrow (Achillea millefolium) fresh plant press juice (company Schoenenberger) contain on average 4.7±0.4 dry residue.

(7) The freeze-dried yarrow fresh plant press juice concentrates contain on average only 6.6±1.0% water, 9.6±1.3% sum of monocaffeoylquinic acids, 4.5±1.0% sum of dicaffeoylquinic acids and 0.3±0.1% rutin.

Example 2: Manufacturing of a Yarrow Fresh Plant Press Juice Concentrate by Spray Drying

(8) 1 l yarrow fresh plant press juice (company Schoenenberger, dry matter content 5.3%) is mixed with 150 g maltodextrin DE 17-20 and spray dried. Obtained is a beige, free-flowing powder consisting of 75% maltodextrin and 25% yarrow dry fresh plant press juice. The spray-dried concentrate is analysed for the sum of mono- and dicaffeoylquinic acids and rutin:

(9) TABLE-US-00003 TABLE 3 Substance class Content [wt.-%] Sum of monocaffeoylquinic acids (chlorogenic acid, 2.9 neo- and cryptochlorogenic acid, HPLC)* Sum of dicaffeoylquinic acids (1,5-, 3,4-, 3,5- and 1.4 3,4-dicaffeoylquinic acid, HPLC)* Rutin (HPLC) 0.1 Water (Karl Fischer) 3.9 *Quantified as chlorogenic acid

(10) The analytical results show that the ingredients remain unchanged during spray drying and no degradation takes place.

Example 3: Effect of Yarrow Fresh Plant Press Juice Concentrate on the Gene Expression of Heat Shock Proteins in Skin Cells

(11) Neonatal human epidermal keratinocytes (nHEKs) are seeded in microtiter plates with 6 wells in a density of 0.2×10.sup.6 cells/cavity and cultured in EpiLife medium. After an incubation period of 24 hours, the yarrow fresh plant press juice concentrate from example 1 is applied in a concentration of 0.005 wt.-% in EpiLife and incubated for 24 hours.

(12) The isolation and purification of the mRNA takes place with the aid of the RNeasy® Mini Kit from the company Qiagen. Elution of the mRNA from the column takes place with 50 μl RNase free water. The quantification and determination of the purity of the isolated RNA takes place spectrophotometrically. The purity is assessed by the ratios of the extinctions E260/E280 and E260/E230. The transcription of RNA into cDNA takes place according to the manufacturer's instructions (RNA-to-cDNA Kit, Applied Biosystems). The amount transcribed is 0.5-1 μg per 6-well. The transcribed samples are immediately processed in the PCR or stored at −20° C. until the experiment is continued.

(13) TABLE-US-00004 TABLE 4 Transcription conditions for the reverse transcription Duration Step [min] Temp. [C. °] Number of cycles Reverse transcription 60 37 Enzyme inactivation 5 95 Holding a temperature until the device 4 until the device is is stopped stopped

(14) The qRT-PCR takes place in the next step. For qRT-PCR, the cDNA is thawed and mixed with the TaqMan® Fast Universal PCR Master Mix (2×) (Life Technologies). The TaqMan® plate with 96 wells (Life Technologies, Darmstadt) can be individually equipped with the desired primers. Into each well of the 96 well array plate a volume of 10 μL of sample is pipetted and the wells are carefully airtightly sealed with an adhesive film (MicroAmp®) and centrifuged. Gene expression analysis takes place in the StepOne Plus Fast Real-Time PCR Instrument (Applied Biosystems). After the heating phase, the device automatically runs through the cycles shown in table 5 one after the other.

(15) TABLE-US-00005 TABLE 5 The set PCR cycles Number Step Duration [sec] Temp. [C. °] of cycles Initial cDNA denaturation 20 95 1 cDNA denaturation 3 95 40 Annealing and elongation 30 60 40

(16) The measured values are exported and evaluated in MS Office Excel. The relative gene expression is calculated according to the ΔΔCT method. In the first step of the calculation, the ΔCT value is calculated for each sample by subtracting the CT value of the reference gene (gene HRPT) from the CT value of the gene to be examined.
ΔCTvalue.sub.target gene=CTvalue.sub.target gene−CTvalue.sub.reference gene (HTRP gene)

(17) After standardisation, the ΔCT value of the control sample (untreated) is subtracted from the ΔCT value of the treated sample (PS applied).
ΔΔCTvalue.sub.target gene=ΔCTvalue.sub.treated−ΔCTvalue.sub.control

(18) In the last step, the relative expression difference (relative quantification value (RQ value)) between the stimulated sample (PS applied) and control is calculated. Relative gene expression (RQ value)=2.sup.−ΔΔCT

(19) An RQ value of >2.5 is considered a relevant induction of a gene.

(20) TABLE-US-00006 TABLE 6 Results Cell type NHEK Test concentration 0.005% RQ values HPRT1 (housekeeping gene) 1.0 HSPB2 .fwdarw. HSP27 8.0 ASPA1L .fwdarw. HSP70 No relevant induction

(21) The results show that yarrow fresh plant press juice very effectively upregulates the gene expression of heat shock protein HSP27 at a very low test concentration, but has no effect on HSP70.

Example 4: Effect of Yarrow Fresh Plant Press Juice Concentrate on the Gene Expression of AMPs in Skin Cells

(22) HaCaT cells are seeded in microtiter plates with 6 wells in a density of 0.5×10.sup.6 cells/well and cultured in EpiLife medium.

(23) After an incubation period of 2 days, the yarrow fresh plant press juice concentrate from example 1 is applied in a concentration of 0.005 wt.-% in EpiLife and incubated for 24 hours.

(24) The isolation and purification of the mRNA takes place with the aid of the RNeasy® Mini Kit from the company Qiagen. Elution of the mRNA from the column takes place with 50 μl RNase free water. The quantification and determination of the purity of the isolated RNA takes place spectrophotometrically. The purity is assessed by the ratios of the extinctions E260/E280 and E260/E230.

(25) The transcription of the RNA into cDNA takes place according to the manufacturer's instructions (RNA-to-cDNA Kit, Applied Biosystems). The amount transcribed is 0.5-1 μg per 6-well. The transcribed samples are immediately processed in the PCR or stored at −20° C. until the experiment is continued.

(26) TABLE-US-00007 TABLE 7 Transcription conditions for the reverse transcription Duration Step [min] Temp. [C. °] Number of cycles Reverse transcription 60 37 Enzyme inactivation 5 95 Holding a temperature until the device 4 until the device is is stopped stopped

(27) The qRT-PCR takes place in the next step. For the qRT-PCR, the cDNA is thawed and mixed with the TaqMan® Fast Universal PCR Master Mix (2×) (Life Technologies). The TaqMan® plate with 96 wells (Life Technologies, Darmstadt) can be individually equipped with the desired primers. Into each well of the 96 well array plate a volume of 10 μL of sample is pipetted and the wells are carefully airtightly sealed with an adhesive film (MicroAmp®) and centrifuged again for one minute. Gene expression analysis takes place in the StepOne Plus Fast Real-Time PCR Instrument (Applied Biosystems). After the heating phase, the device automatically runs through the cycles shown in Table 8 one after the other.

(28) TABLE-US-00008 TABLE 8 The set PCR cycles Number Step Duration [sec] Temp. [C. °] of cycles Initial cDNA denaturation 20 95 1 cDNA denaturation 3 95 40 Annealing and elongation 30 60 40

(29) The measured values are exported and evaluated using MS Office Excel. The relative gene expression is calculated according to the ΔΔCT method. In the first step of the calculation, the ΔCT value is calculated for each sample by subtracting the CT value of the reference gene (gene HRPT) from the CT value of the gene to be examined.
ΔCTvalue.sub.target gene=CTvalue.sub.target gene−CTvalue.sub.reference gene (HTRP gene)

(30) After standardization, the ΔCT value of the control sample (untreated) is subtracted from the ΔCT value of the treated sample (PS applied).
ΔΔCTvalue.sub.target gene=ΔCTvalue.sub.treated−ΔCTvalue.sub.control

(31) In the last step, the relative expression difference (relative quantification value (RQ value)) between stimulated sample (PS applied) and control is calculated.

(32) Relative gene expression (RQ value)=2.sup.−ΔΔCT

(33) An RQ value of >2.5 is considered a relevant induction of a gene.

(34) TABLE-US-00009 TABLE 9 Results Cell type HaCaT Test concentration 0.005% RQ values HPRT1 (housekeeping gene) 1.0 DEFB1 .fwdarw. beta-defensin 1 9.1 S100A8 .fwdarw. calgranulin A 2.7

(35) The results show that yarrow fresh plant press juice very effectively upregulates the gene expression of the antimicrobial peptides beta-defensin 1 and S100 calcium binding protein A8 at very low test concentrations.

Example 5: Formulation examples

(36) 1=Soothing balm for the skin

(37) 2=Tinted anti-aging balm, SPF 15

(38) 3=After-sun moisturizing spray O/W

(39) 4=Night cream W/O

(40) 5=Facial cleansing gel

(41) 6=After-shave hydrogel

(42) 7=Anti-dandruff hair shampoo

(43) 8=Antiperspirant pump spray

(44) 9=Day care fluid for skin lightening O/W

(45) 10=Cream to restore the barrier function O/W

(46) 11=Sun protection lotion SPF 24 (UVA/UVB balance)

(47) In the formulation examples 1-11, the two perfume oils PFO1 and PFO2 described below are used as fragrances, respectively (DPG=dipropylene glycol).

(48) TABLE-US-00010 TABLE 10 Perfume oil PFO1 with rose scent Component Amount (in wt.-%) Acetophenone, 10% in DPG 10 n-Undecanal 5 Aldehyde C14 (so-called peach aldehyde) 15 Allylamylglycolate, 10% in DPG 20 Amylsalicylate 25 Benzyl acetate 60 Citronellol 80 d-Limonene 50 trans-9 Decenol 15 Dihydromyrcenol 50 Dimethylbenzylcarbinyl acetate 30 Diphenyl oxide 5 Eucalyptol 10 Geraniol 40 Nerol 20 Geranium oil 15 cis-3 Hexenol, 10% in DPG 5 cis-3 Hexenyl salicylate 20 Indol, 10% in DPG 10 Alpha ionone 15 Beta ionone 5 Lilial ® (2-Methyl-3-(4-tert-butyl- 60 phenyl)propanal) Linalool 40 Methylphenyl acetate 10 Phenylethyl alcohol 275 Styrolyl acetate 20 Terpineol 30 Tetrahydrolinalool 50 Cinnamyl alcohol 10 Total 1000

(49) TABLE-US-00011 TABLE 11 Perfume oil PFO2 with white flowers and musk scent Amount Component (in wt.-%) Benzyl acetate 60 Citronellyl acetate 60 Cyclamen aldehyde (2-methyl-3-(4- 20 isopropylphenyl)propanal Dipropylene glycol (DPG) 60 Ethyllinalool 40 Florol (2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol) 30 Globanone ® [(E/Z)-8-cyclohexadecen-1-one] 180 Hedione ® (Methyldihydrojasmonate) 140 Hexenylsalicylate, cis-3 10 Vertocitral (2,4-dimethyl-3- 5 cyclohexenecarboxaldehyde) Hydratropa aldehyde, 10% in DPG 5 Isodamascone (1-(2,4,4-trimethyl-2-cyclohexen-1-yl)- 5 2-buten-1-one), 10% in DPG Isomuscone (cyclohexadecanone) 40 Jacinthaflor (2-methyl-4-phenyl-1,3-dioxolane) 10 Cis-jasmone, 10% in DPG 20 Linalool 50 Linalyl acetate 30 Methyl benzoate, 10% in DPG 25 para-Methylcresol, 10% in DPG 10 Nerol 20 Phenylpropyl aldehyde 5 2-Phenylethyl alcohol 82 Tetrahydrogeraniol 13 2,2-Dimethyl-3-cyclohexyl-1-propanol 80 Total: 1000

(50) TABLE-US-00012 TABLE 12 Cosmetic formulations (quantities in wt.-%) Components 1 2 3 4 5 6 7 8 9 10 11 Spray-dried yarrow fresh plant press 1.2 0.5 0.1 0.3 0.02 juice concentrate containing 75% maltodextrin Maltodextrin, Achillea millefolium extract Yarrow fresh plant press juice 2.5 1 0.02 concentrate, 10% dry residue Achillea millefolium extract, Glycerin Freeze-dried yarrow fresh plant press 0.01 0.002 0.05 juice concentrate Achillea millefolium extract Actipone © Laminaria Saccharina 0.3 Glycerin, Water (Aqua), Laminaria saccharina extract Allantoin 0.1 0.1 Allantoin Aloe Vera Gel Conc. 10:1 1 Aloe barbadensis (Aloe) leaf juice Aluminium Stearate 1.2 Aluminium stearate Beta arbutin 1 Arbutin Arlypon ® F 2 Laureth-2 Avocado Oil 3 Persea gratissima (avocado) oil Betulin 90% 0.1 Betulin Biotive L-Arginine 0.6 0.5 Arginine Biotive Troxerutin 0.5 0.5 Troxerutin (−)-alpha-Bisabolol 0.1 Bisabolol Carbopol Aqua SF-1 Polymer 5 Acrylates copolymer Carbopol ® Ultrez-10 0.2 0.4 0.2 Carbomer CeramideBIO ® 0.5 Cetylhydroxyproline palmitamide Citric acid 10% in water 0.2 0.5 Covi-Ox ® T-70 0.1 Tocopherol Crinipan ® AD 0.3 Climbazole Cutina ® PES 2 Pentaerythrityl distearate D-Panthenol 1 1 0.5 0.5 Panthenol Dehyton K 8 8 Cocamidopropyl betaine Dermacryl ® AQF Acrylates 2 Copolymer Dow Corning 200(100 cs) 2 2 0.5 0.5 Silicone fluid dimethicone Dow Corning 246 Fluid 2 3 Cyclohexasiloxane, Cyclopentasiloxane Dracorin ® CE 1.5 Glyceryl stearate citrate Dracorin ® GMS 2 Glyceryl stearate Dracorin ® GOC 2 Glyceryl oleate citrate, Caprylic/Capric triglyceride Dragocalm ® 1 Water (aqua), Glycerin, Avena sativa (oat) kernel extract Dragocid ® Liquid 0.8 Phenoxyethanol, Methyl paraben, Ethyl paraben, Butyl paraben, Propyl paraben, Isobutyl paraben 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 Carnosine Dragoxat ® 89 5 7 2 2 Ethylhexyl Isononanoate Disodium EDTA 0.1 0.1 0.1 0.1 Emulsiphos ® 2 1.5 2 2 Potassium cetyl phosphates, Hydrogenated palm glycerides Ethanol 5 8 Extrapone ® Aloe vera 2 Water (aqua), Aloe barbadensis, Propylene glycol, Alcohol Extrapone ® Witch Hazel 1 Propylene glycol, Hamamelis virginiana (Witch Hazel) Water, Water (Aqua), Hamamelis virginiana (Witch Hazel) extract Extrapone ® Rosemary 0.3 Glycerin, Water (aqua), Rosmarinus officinalis (rosemary) leaf extract Extrapone ® Seaweed Water 0.5 (Aqua), Butylene glycol, Fucus vesiculosus extract Farnesol DT 0.2 Phenoxyethanol, Farnesol, Bisabolol Food coloring brown 2 E172 + E171 Powder Frescolat ® MGA 0.1 Menthone glycerin acetal Frescolat ® ML 0.5 0.3 0.2 Menthyl lactate Frescolat ® X-Cool 0.2 Menthyl ethylamido oxalate Genapol ® LRO Liquid 37 Sodium laureth sulphate Givobio ® GZN 0.5 Zinc gluconate Glycerin 1.5 4 3 3.5 3 3 Hydrolite ® 5 3 5 2 5 5 2 Pentylene glycol Hydroviton-24 ® 1 Water (aqua), Pentylene glycol, Glycerin, Lactic acid, Sodium lactate, Serine, Urea, Sorbitol, Sodium chloride, Allantoin Hydroviton ® Plus 2290 1 2 Water (aqua), Pentylene glycol, Glycerin, Fructose, Urea, Citric acid, Sodium hydroxide, Maltose, Sodium PCA, Sodium chloride, Sodium lactate, Trehalose, Allantoin, Sodium hyaluronate, Glucose Isoadipate 2 Diisopropyl adipate Isodragol ® 1 3 2 Triisononanoin Jojoba Oil 2 Simmondsia Chinensis (Jojoba) Seed Oil Potassium sorbate 0.1 Keltrol ® CG-RD 0.2 0.2 0.4 Xanthan gum Kojic acid 0.5 Kojic acid Lanette ® 16 1.5 1 Cetyl alcohol Lanette ® O 2 0.5 Cetearyl alcohol Lara Care ® A-200 0.3 Galactoarabinan Locron ® L 16 Aluminium chlorohydrate Magnesium sulphate 0.7 Mineral oil 8 Sodium ascorbyl phosphate 1 Sodium chloride 0.1 Sodium hydroxide 10% in water 1 2 0.7 0.2 0.3 Neo Heliopan ® 303 4 10 Octocrylene Neo Heliopan ® 357 2 2 3 Butylmethoxydibenzoyl methane Neo Heliopan ® AP, 6.7 6.7 15% solution, neutralized with L-Arginine Aqua, Disodium phenyl dibenzimidazole tetrasulfonate, Arginine Neo Heliopan ® AV 7.5 Ethylhexyl methoxycinnamate Neo Heliopan ® BB 3 Benzophenone-3 Neo Heliopan ® E 1000 1 Isoamyl p. methoxycinnamate Neo Heliopan ® HMS 10 5 Homosalate Neo Heliopan ® OS 3 5 Ethylhexyl salicylate Neo Heliopan ® Hydro, 10 10 20% solution, neutralized with biotive arginine Aqua, Phenylbenzimidazole, Sulphonic acid, Arginine Neo-PCL Water Soluble N 1 1.5 2 Trideceth-9, PEG-5 Ethylhexanoate, Water (aqua) Neutral Oil 5 10 Caprylic/Capric Triglyceride Niacinamide 1 Ozokerite Wax 2389 2 Ozokerite Perfume oil PFO1 or PFO2 0.05 0.3 0.25 0.3 0.1 0.5 0.7 0.3 0.1 0.2 Perfume PCL-Liquid 100 3 2 4 5 Cetearyl ethylhexanoate PCL-Solid 1 0.5 Stearyl heptanoate, Stearyl caprylate Pemulen ® TR-2 0.6 0.25 Acrylates/C10-30 Alkyl acrylate crosspolymer Phenethyl alcohol 0.2 Phenoxyethanol 0.2 Phytoconcentrole ® 1 Shea butter Glycine soy (soybean) oil, Butyrospermum parkii (shea butter) Polymer JR 400 0.4 Polyquaternium-10 Propylene glycol-1,2 5 3 Propylene glycol Silcare Silicone 41M65 Stearyl 1 dimethicone Solubilizer 3 PEG-40 Hydrogenated castor oil, Trideceth-9, Propylene glycol, Water (Aqua) Suletal LA 12 Ammonium lauryl sulphate SymCalmin ® 1 0.1 0.1 Butylene glycol, Pentylene glycol, Hydroxyphenyl propamidobenzoic acid SymClariol ® 0.5 1 0.3 Decylene glycol SymDecanox HA 2 Caprylic/Capric Triglyceride, Hydroxymethoxyphenyl decanone SymDeo ® B125 0.2 2-Methyl 5-cyclohexylpentanol SymDeo ® MPP 0.5 Dimethyl phenyl 2-butanol Symdiol ® 68 1 0.5 0.3 1.2-Hexanediol, Caprylyl glycol SymFinity ® 1298 0.05 Echinacea purpurea extract SymGlucan ® 1 5 2 Water (Aqua), Glycerin, Beta-glucan SymHair ® Force 1631 2 Pentylene glycol, Isochrysis galbana extract SymHelios ® 1031 0.5 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 0.1 0.3 Maltodextrin, Rubus fruticosus (Blackberry) leaf extract SymMollient ® W/S 2 2 Trideceth-9, PEG-5 Isononanoate, Water (Aqua) SymOcide ® C 0.1 o-Cymen-5-ol SymOcide ® PH 1.0 Phenoxyethanol, Hydroxyacetophenone, Caprylyl glycol, Water (Aqua) SymOcide ® PS 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 0.2 Bisabolol, Zingiber officinale (Ginger) root extract SymRelief S 0.1 Bisabolol, Hydroxymethoxyphenyl Decanone SymRepair ® 100 1 3 Hexyldecanol, Bisabolol, Cetylydroxyproline Palmitamide, Stearic acid, Brassica campestris (rapeseed) sterols SymSave ® H 0.5 0.8 0.5 0.5 Hydoxyacetophenone SymSol ® PF-3 1.3 Water (Aqua), Pentylene glycol, Sodium lauryl sulfoacetate, Sodium oleoyl sarcosinate, Sodium chloride, Disodium sulfoacetate, Sodium oleate, Sodium sulfate SymSitive ® 1609 Pentylene 0.5 0.5 glycol, 4-t-Butylcyclohexanol SymVital ® AgeRepair 3040 0.1 Zingiber officinale (ginger) root extract SymWhite ® 377 0.5 Phenylethyl resorcinol Tamasterol ® 0.3 Phytosterols Tapioca Pure 5 Tapioca starch Tegosoft ® PC 31 0.3 Polyglyceryl-3 caprate Triethanolamin 0.3 Vitamin A Palmitate 0.1 Retinyl Palmitate Vitamin E Acetate 0.5 0.2 0.3 0.5 Tocopheryl Acetate Zetesol LA-2 26 Ammonium laureth sulfate Water Ad 100

(51) TABLE-US-00013 TABLE 13 Gel toothpaste Component I (%) II (%) III (%) Sodium carboxymethylcellulose 0.40 0.40 0.40 Sorbitol 70%, in water 72.00 72.00 72.00 Polyethylene glycol (PEG) 1500 3.00 3.00 3.00 Sodium saccharinate 0.07 0.07 0.07 Sodium fluoride 0.24 0.24 0.24 p-Hydroxybenzoic acid (PHB) 0.15 0.15 ethyl ester SymDiol 68 0.5 SymSave H 0.25 Peppermint aroma 1.00 1.00 1.00 Spray-dried yarrow fresh plant 0.5 0.1 press juice concentrate containing 75% maltodextrin Yarrow fresh plant press juice 1 concentrate, 10% dry residue in glycerin/water Abrasive silica 11.00 11.00 11.00 Thickening silica 6.00 6.00 6.00 Sodium dodecyl sulphate (SDS) 1.40 1.40 1.40 Dist. water ad 100.00 ad 100.00 ad 100.00

(52) TABLE-US-00014 TABLE 14 Ready-to-use mouthwash with fluoride Component I (%) II (%) III (%) Ethanol 7.00 7.00 Glycerin 12.00 12.00 Sodium fluoride 0.05 0.05 0.18 Pluronic F-127 ® (BASF, surface 1.40 1.40 active substance) Sodium phosphate buffer pH 7.0 1.10 1.10 Sorbic acid 0.20 0.20 Sodium saccharinate 0.10 0.10 0.10 Cinnamon/menthol aroma 0.15 0.15 0.15 Spray-dried yarrow fresh plant 0.05 0.8 press juice concentrate containing 75% maltodextrin Yarrow fresh plant press juice 0.5 concentrate, 10% dry residue in glycerin/water Dye 0.01 0.01 0.01 Sorbitol 70% 10 Cremophor RH455 1.8 SymDiol 68 0.5 SymSave H 0.2 Dist. water ad 100.00 ad 100.00 ad 100.00