Synergistic mixtures of aromatic alcohols and derivatives thereof and tropolone (derivatives)

Abstract

An antimicrobial mixture comprising or consisting of: one or more compounds of the formula (I) ##STR00001## their salts or solvates, wherein R.sup.1 and R.sup.2 in each case independently of one another are chosen from the group consisting of: H, OH, F, Cl, Br and I, and wherein X in each case denotes:
(CH.sub.2).sub.m where m=1, 2 or 3 or
OCH.sub.2.sub.n where n=1, 2 or 3 or
OCH.sub.2CH(R.sup.3) where R.sup.3=CH.sub.3 or CH.sub.2OH or
(CH.sub.2O.sub.pCH.sub.2 where p=1 or 2, wherein in the compound(s) of the formula I a primary alcohol function CH.sub.2OH is optionally replaced by a radical which is chosen from the group consisting of CH.sub.2OR.sup.4, COOH and COOR.sup.4 and/or a secondary alcohol function CHOH is optionally replaced by the radical CHOR.sup.4, wherein each R.sup.4 denotes an aliphatic or aromatic radical, independently of the meaning of further radicals, and one, two or more compounds chosen from the group consisting of the tropolones of the formula (II) ##STR00002## wherein the substituents R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 independently of one another have the following meaning: H; linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms; OH; OR.sup.10, wherein R.sup.10 is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms; COOH; COOR.sup.11, wherein R.sup.11 is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms; NO.sub.2, NH.sub.2, F, Cl, Br, I.

Claims

1. Antimicrobial mixture comprising: (a) phenoxyethanol ##STR00014## and (b) tropolone of the formula (II) ##STR00015## wherein the substituents R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 represent H, constituent (b) is present in an amount in the range of 0.001-10 wt. %, based on the amount of constituent (a), and compounds (a) and (b) are present in an amount such that an antimicrobial activity of said compounds (a) and (b) is synergistically intensified against Aspergillus niger as shown by a Kull value.

2. An antimicrobial mixture according to claim 1, wherein constituent (b) is present in an amount in the range of 0.5-4 wt. %, based on the amount of constituent (a).

3. An antimicrobial mixture according to claim 1, comprising one or more additional constituents (c) selected from the group consisting of (c) 2,4-hexadienoic acid (sorbic acid) and its salts, formaldehyde and paraformaldehyde, 2-hydroxybiphenyl ether and its salts, 2-zinc-sulfidopyridine N-oxide, inorganic sulfites and bisulfites, sodium iodate, chlorobutanolum, 4-ethylmercury-(II)5-amino-1,3-bis(2-hydroxybenzoic acid), its salts and esters, dehydracetic acid, formic acid, 1,6-bis(4-amidino-2-bromophenoxy)-n-hexane and its salts, the sodium salt of ethylmercury-(II)-thiosalicylic acid, phenylmercury and its salts, 10-undecylenic acid and its salts, 5-amino-1,3-bis(2-ethylhexyl)-5-methyl-hexahydropyrimidine, 5-bromo-5-nitro-1,3-dioxane, 2-bromo-2-nitro-1,3-propanediol, N-(4-chlorophenyl)-N-(3,4-dichlorophenyI)-urea, 4-chloro-m-cresol, 2,4,4-trichloro-2.sup.1-hydroxy-diphenyl ether, 4-chloro-3,5-dimethylphenol, 1,1-methylene-bis(3-(1-hydroxymethyl-2,4-dioximidazolidin-5-yl)urea), poly-(hexamethylenediguanide) hydrochloride, hexamethylenetetramine, 1-(3-chloroallyl)-3,5,7-triaza-1-azonia-adamantane chloride, 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-2-butanone, 1,3-bis(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidinedione, 1,2-dibromo-2,4-dicyanobutane, benzethonium chloride, 2,2-methylene-bis(6-bromo-4-chlorophenol), bromochlorophene, mixture of 5-chloro-2-methyl-3(2H)-isothiazolinone and 2-methyl-3(2H)-isothiazolinone with magnesium chloride and magnesium nitrate, 2-benzyl-4-chlorophenol, 3-(4-Chlorphenoxy)-1,2-propanediol (Chlorphenesin), 2-chloroacetamide, chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, N-alkyl(C12-C22)trimethyl-ammonium bromide and chloride, 4,4-dimethyl-1,3-oxazolidine, N-hydroxymethyl-N-(1,3-di(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl)-N-hydroxy-methylurea, 1,6-bis(4-amidino-phenoxy)-n-hexane and its salts, glutaraldehyde, 5-ethyl-1-aza-3,7-dioxabicyclo(3.3.0)octane, 3-(4-chlorophenoxy)-1,2-propanediol, hyamines, alkyl-(C.sub.8-C.sub.18)-dimethyl-benzyl-ammonium chloride, alkyl-(C.sub.8-C.sub.18)-dimethyl-benzylammonium bromide, alkyl-(C.sub.8-C.sub.18)-dimethyl-benzyl-ammonium saccharinate, benzyl hemiformal, 3-iodo-2-propynyl butylcarbamate, sodium hydroxymethyl-aminoacetate and sodium hydroxymethyl-aminoacetate, imidazolidinylurea, diazolidinylurea, sodium hydroxymethylglycinate, chlorphenesin, DMDM hydantoin, methylchloroisothiazolinone, methylisothiazolinones, branched or unbranched 1,2-alkanediols having 6 to 12 carbon atoms, triclosan, climbazole, octoxyglycerol (ethylhexyl glycerol), Octopirox (1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-aminoethanol), chitosan, totarol, farnesol, geranylacetol, glycerol monolaurate, arylalkyl alcohols (preferably 4-methyl-4-phenyl-2-pentanols, 2,2-dimethyl-3-phenylpropanol), essential oils with antimicrobial properties and isolates from essential oils with antimicrobial properties or single aroma chemicals with antimicrobial activity, and polyglycerol esters, preferably polyglyceryl 3-caprylates.

4. An antimicrobial mixture according to claim 1, wherein the amount of constituent (a) and/or the amount of constituent (b) in each case considered in itself is not antimicrobially active, but the total amount of constituent (a) and (b) is antimicrobially active.

5. A cosmetic or pharmaceutical formulation or foodstuff comprising the antimicrobial mixture according to claim 1.

6. A foodstuff according to claim 5, wherein the amount of constituent (a) and/or the amount of constituent (b) in each case considered in itself is not antimicrobially active, but the total amount of constituents (a) and (b) is antimicrobially active.

7. A method for the preservation or antimicrobial treatment of a perishable product, with the following step: bringing of the perishable product into contact with an antimicrobially active amount of the mixture according to claim 1.

8. A method for the cosmetic and/or therapeutic treatment of (i) microorganisms which cause body odour, (ii) microorganisms which cause acne and/or (iii) microorganisms which cause mycoses, comprising topical application of an antimicrobially active amount of the mixture according to claim 1.

9. An antimicrobial mixture according to claim 1, wherein the antimicrobial activity of said compounds (a) and (b) is synergistically intensified against the Aspergillus niger within two days.

10. An antimicrobial mixture according to claim 1, excluding antimicrobial mixtures comprising or consisting of (a) one or more branched or unbranched alkanediols having 6-12 carbon atoms, (b) tropolone, and (c) one or more preservatives selected from the group consisting of: benzoic acid, its esters and salts, salicylic acid and its salts, 2,4-dichlorobenzyl alcohol, 2-phenoxyethanol, benzyl alcohol, 1-phenoxy-propan-2-ol, 3-(4-chlorophenoxy)-1,2-propanediol and benzyl hemiformal.

Description

EXAMPLE 1

Comparison of Adequate Preservation of Cosmetic Formulations Comprising 2-phenoxyethanol (Product A, not According to the Invention), Tropolone (Product B, not According to the Invention) and a Mixture of 2-phenoxyethanol and tropolone (Product C, According to the Invention)

(1) Testing for adequate preservation was carried out in accordance with the European Pharmacopoeia.

(2) Testing thus comprises contamination of the formulation, if possible in its final condition, with a prescribed inoculum of suitable microorganisms, storage of the inoculated formulation at a certain temperature, removal of samples from the container at certain intervals of time and determination of the number of microorganisms in the samples removed in this way. The preserving properties are adequate if, under the conditions of the test, a clear reduction or, where appropriate, no increase in the germ count results in the inoculated formulations after the prescribed times at the prescribed temperatures. Experimental details of the test procedure are described in the European Pharmacopoeia (ISBN 3-7692-2768-9; Supplement 2001 to the 3rd Edition, page 421-422, chapter 5.1.3).

(3) Test Germs:

(4) The following microorganism strains were used for the tests for adequate preservation: A: Escherichia coli ATCC 8739 B: Pseudomonas aeruginosa ATCC 90270 C: Staphylococcus aureus ATCC 6538 D: Candida albicans ATCC 10231 E: Aspergillus niger ATCC 16404 The initial germ count (CFU/g; 0 value) was in the range of from 220,000 to 280,000 in the various test series.
Formulation:

(5) For the tests for adequate preservation, a defined amount of the active compound combination according to the invention (product C) was incorporated into an O/W emulsion. For comparison purposes, the comparison products (product A and B) were incorporated into separate O/W emulsions.

(6) TABLE-US-00001 TABLE 1 Formulations with products A, B and C: Wt. % Wt. % Wt. % with with with INCI name Manufacturer A B C Phase A Dracorin CE Glyceryl Stearate Symrise 4.0 4.0 4.0 614035 Citrate PCL Solid Stearyl Heptanoate, Symrise 3.0 3.0 3.0 660086 Stearyl Caprylate Paraffin oil E Paraffinum Liquidum Parafluid 7.0 7.0 7.0 Lanette 18 Stearyl Alcohol Cognis 1.5 1.5 1.5 Dracorin Glyceryl Stearate Symrise 1.5 1.5 1.5 GMS 647834 Dow Corning Dimethicone Dow Corning 2.0 2.0 2.0 200 fluid Phase B Water, Water (Aqua) to 100 to 100 to 100 demineralized Carbopol Carbomer Noveon 0.15 0.15 0.15 ETD 2050 Polymer 2-Phenoxy- Phenoxyethanol Symrise 1.0 0.5 ethanol Tropolone Symrise 0.01 0.005 Phase C Neutralizer Amino Dow/Angus 0.1 0.1 0.1 AMP-95 Methylpropanol Total: 100.0 100.0 100.0 pH: 5.5
Result:

(7) The results of the preservative stress tests for Aspergillus niger for the active compound combinations investigated, comprising the mixture according to the invention (product C) or the comparison systems (products A and B), clearly show a synergistic effect of the mixture according to the invention (product C). In the case of Aspergillus niger, a germ which is particularly problematic in respect of preservation of industrial products, it was possible to reduce the germ count to 0 within 7 days by using the mixture according to the invention. By using the mixture according to the invention (product C), it was already possible to reduce the number of colony-forming units from 220,000 to 200 after 2 days (Table 2). In contrast, the active compound contained in product A (2-phenoxyethanol) in a dosage of 1.0 wt. % for comparison purposes rendered possible no such significant reduction in the number of colony-forming units (CFU after 2 days: 113,000) in Aspergillus niger, which also applies to product B (tropolone, dosage: 0.01%; CFU after 2 days: 95,000). This test series thus shows by way of example that the active compound mixtures according to the invention have an action which is significantly improved synergistically compared with products A (2-phenoxyethanol) and B (tropolone).

(8) TABLE-US-00002 TABLE 2 Testing for adequate preservation for product A (comprising 1% phenoxyethanol), for product B (comprising 0.01% tropolone) and for product C (mixture according to the invention comprising 0.05% phenoxyethanol and 0.005% tropolone). C 0.5% phenoxyethanol A B and 1% 0.01% 0.005% phenoxyethanol tropolone tropolone CFU (colony-forming units) Aspergillus niger ATCC 16404 0 count 220,000 220,000 220,000 2 d 113,000 95,000 200 7 d <100 <100 0 14 d 0 0 0 28 d 0 0 0

(9) The calculation of the SI value for treatment of Aspergillus niger with a mixture of phenoxyethanol and tropolone after an incubation phase of 2 days is shown below by way of example (Table 3). The calculated SI of 0.0019 clearly shows that the mixture is a highly synergistic combination of active compounds. It was not possible to calculate the 7-day, 14-day and 28-day SI values, since after this incubation phase the germ counts either could not be determined precisely, as in the case of the individual substances (<100), or were 0 (compare Table 1). In these special cases, Kull's equation cannot be used; however, the synergism is also evident for product C in the 7-day values on the basis of the germ count of 0.

(10) TABLE-US-00003 TABLE 3 Calculation of the synergy index (SI) at the time 2 days with the aid of the CFU values for product A (phenoxyethanol; dosage: 1%), product B (tropolone; dosage: 0.01%) and for the synergistic mixture according to the invention (ratio of amounts of product A and product B: 1:1; w/w; dosage of phenoxyethanol: 0.5%; dosage of tropolone: 0.005%); test germ: Aspergillus niger) C 0.5% phenoxyethanol A B and 1% 0.01% 0.005% phenoxyethanol tropolone tropolone Aspergillus niger: 113,000 95,000 200 2 days [CFU/ml] Kull's equation: SI = C D/A + C E/B A: Germ count for 113,000 substance A B: Germ count for 95,000 substance B C: Germ count for 200 mixture A + B D: Content of A in C 0.5 E: Content of B in C 0.5 SI: Synergy index 0.0019 Literature: Synergy index: D. C. Steinberg; Cosmetics & Toiletries 115 (11); p. 5962 (2000) F. C. Kull et al.; Applied Microbiology 9; p. 538541 (1961)

(11) Outstanding results which confirm the superiority of product C according to the invention were likewise obtained in respect of the further test germs.

EXAMPLE 2

Comparison of Adequate Preservation of Cosmetic Formulations with a High Amount of Organic UV Filters and Having a SPF of Equal or Greater than 15

(12) Testing for adequate preservation against germs in sunscreen formulations:

(13) For the tests for adequate preservation, 1 wt. % of the respective active compound were incorporated into separate O/W emulsions: A2 is a comparison formulation and formulation C2 is according to the present invention.

(14) TABLE-US-00004 TABLE 4 Trade Name INCI A2 C2 Emulsiphos Potassium cetyl phosphate, 2.00 2.00 hydrogenated palm glycerides PCL Solid Stearyl heptanoate, stearyl caprylate 2.00 2.00 Lanette 16 Cetyl alcohol 1.50 1.50 Dragoxat 89 Ethylhexyl ethylisononanoate 2.00 2.00 Neutral Oil Caprylic/capric triglyceride 3.00 3.00 Tegosoft TN C1215 Alkyl benzoate 3.00 3.00 Neo Heliopan BB Benzophenone-3 6.00 6.00 Neo Heliopan HMS Homosalate 10.00 10.00 Neo Heliopan OS Ethylhexyl salicylate 5.00 5.00 Neo Heliopan 357 Butyl methoxy dibenzoylmethane 3.00 3.00 Neo Heliopan AV Ethylhexyl methoxycinnamate 7.50 7.50 Carbopol ETD 2050 Carbomer 0.20 0.20 Keltrol T Xanthan gum 0.20 0.20 Water Water (Aqua) 50.45 50.45 Glycerol Glycerine 3.00 3.00 AMP 2-Amino-2-methyl-1-propanol 0.15 0.15 Phenonip Phenoxyethanol (and) Methylparaben 1.00 (and) Butylparaben (and) Ethylparaben (and) Propylparaben SPT Phenoxyethanol, Tropolone 1.00 Phenonip (not according to the present invention) is a commercially available (Clariant, Nipa preservatives) and in cosmetic formulations widely used antimicrobial active mixture consisting of phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben and isobutylparaben. SPT is a mixture according to the present invention consisting of 99.0 wt. % phenoxyethanol (2-phenoxyethanol) and 1 wt. % tropolone.

(15) Testing for adequate preservation was carried out in accordance with the European Pharmacopoeia.

(16) Testing thus comprises contamination of the formulation, if possible in its final condition, with a prescribed inoculum of suitable microorganisms, storage of the inoculated formulation at a certain temperature, removal of samples from the container at certain intervals of time and determination of the number of microorganisms in the samples removed in this way. The preserving properties are adequate if, under the conditions of the test, a clear reduction or, where appropriate, no increase in the germ count results in the inoculated formulations after the prescribed times at the prescribed temperatures. Experimental details of the test procedure are described in the European Pharmacopoeia (ISBN 3-7692-2768-9; Supplement 2001 to the 3rd Edition, page 421-422, chapter 5.1.3).

(17) The initial germ count (CFU/g; 0 value) was in the range of from 230,000 to 400,000 in the various test series.

(18) The following two antimicrobial active products were compared in view of their activity and efficacy with respect the above mentioned test germs:

(19) Test Germs:

(20) Preservation test for Escherichia coli using strain Escherichia coli ATCC 8739

(21) TABLE-US-00005 days A2 (Phenonip) C2 (SPT) 0 400,000 400,000 2 167,000 74,000 7 26,000 38,000 14 2,100 0 21 0 0
Preservation test for Pseudomonas aeruginosa using strain Pseudomonas aeruginosa ATCC 9027

(22) TABLE-US-00006 days A2 (Phenonip) C2 (SPT) 0 230,000 230,000 2 100 0 7 0 0 14 0 0
Preservation test for Staphylococcus aureus using strain Staphylococcus aureus ATCC 6538

(23) TABLE-US-00007 days A2 (Phenonip) C2 (SPT) 0 300,000 300,000 2 32,000 600 7 900 0 14 100 0 21 0 0
Preservation test for Candida albicans using strain Candida albicans ATCC 10231

(24) TABLE-US-00008 days A2 (Phenonip) C2 (SPT) 0 400,000 400,000 2 194,000 167,000 7 157,000 93,000 14 157,000 100 21 83,000 0
Preservation test for Aspergillus niger using strain Aspergillus niger ATCC 16404

(25) TABLE-US-00009 days A2 (Phenonip) C2 (SPT) 0 230,000 230,000 2 189,000 113,000 7 93,000 700 14 93,000 0 21 20,000 0

(26) Formulation examples F1-F16: Cosmetic formulations comprising mixtures of 2-phenoxyethanol and tropolone

(27) Some efficiently preserved cosmetic formulations comprising mixtures of 2-phenoxyethanol and tropolone according to the invention are given in the following formulations of Formula 1 to Formula 16.

(28) Formulation F1: Anti-Wrinkle Cream

(29) TABLE-US-00010 Raw Material % weight Phase 1 Glyceryl Stearate Citrate 1.00 Glyceryl Laurate 1.00 Cetearyl Alcohol 2.00 Myristyl Myristate 1.00 Cetearyl Ethylhexanoate 4.00 Mineral oil 4.00 Cyclopentasiloxane, Cyclohexasiloxane 0.50 Acrylates/C1030 Alkyl Acrylate Crosspolymer 0.20 Phase 2 Water 83.14 Xanthan Gum 0.10 1,2-Hexanediol 1.00 Phase 3 Sodium Hydroxide 10% solution 0.10 Phase 4 Narcissus Tazetta Bulb Extract 1.00 Phase 5 Phenoxyethanol 0.80 Tropolone 0.16
Formulation F2: Anti-Inflammatory Lotion

(30) TABLE-US-00011 Raw Material % weight Phase 1 Cetearyl Alcohol and Ceteareth-20 3.50 Cetearyl Alcohol 0.50 Stearyl Heptanoate, Stearyl Caprylate 0.50 Glyceryl Stearate 1.00 Cetearyl Ethylhexanoate 4.00 Mineral oil 3.00 Hydrogenated Coco-Glycerides 1.00 Phase 2 Water 80.49 Disodium EDTA 0.10 Xanthan Gum 0.10 Glycerin 4.00 Phase 3 Water, Glycerin, Avena Sativa (Oat) Kernel Extract 1.00 Butylene Glycol, Pentylene Glycol, Dihydroavenanthramide D 0.10 Phase 4 Phenoxyethanol 0.70 Tropolone 0.01
Formulation F3: Sunscreen Lotion

(31) TABLE-US-00012 Raw Material % weight Phase 1 Potassium Cetyl Phosphate, Hydrogenated Palm Glycerides 1.00 Bisabolol 0.10 Cetearyl Alcohol 1.50 Myristyl Myristate 1.00 Cetearyl Ethylhexanoate 4.00 Stearyl Heptanoate, Stearyl Caprylate 1.00 Cyclopentasiloxane, Cyclohexasiloxane 0.50 Butyl Methoxydibenzoylmethane 1.50 4-Methylbenzylidene Camphor 1.50 Ethylhexyl Methoxycinnamate 7.00 VP/Hexadecene Copolymer 1.00 Acrylates/C1030 Alkyl Acrylate Crosspolymer 0.10 Phase 2 Water 75.495 Butylene Glycol 3.00 Phase 3 Sodium Hydroxide, 10% solution 0.50 Phase 4 Fragrance 0.20 Phase 5 Phenoxyethanol 0.60 Tropolone 0.005
Formulation F4: Anti-Itch Ointment

(32) TABLE-US-00013 Raw Material % weight Phase 1 Petrolatum 60.999 Mineral oil 30.00 Microcrystalline Wax 3.00 Beeswax 5.00 Phase 2 Zinc acetate 0.10 Phase 3 Hydrocortisone butyrate 0.10 Dihydroavenanthramide E 0.10 Phase 4 1,2-Hexanediol, 1,2-Octanediol (Caprylyl Glycol) 0.50 Phase 5 Phenoxyethanol 0.20 Tropolone 0.001
Formulation F5: Healing Spray

(33) TABLE-US-00014 Raw Material % weight Phase 1 Water 51.69 Ethanol SD40 40.00 Disodium EDTA 0.10 Pentylene Glycol 4.00 Phase 2 Polysorbate 20 2.00 Phase 3 Phenoxyethanol 0.20 Tropolone 0.01 Phase 4 Water, Glycerin, Beta-Glucan 2.00
Formulation F6: Soothing Powder

(34) TABLE-US-00015 Raw Material % weight Phase 1 Talc 98.24 Phase 2 Eucalyptus Oil 0.05 Phase 3 Zinc oxide 1.00 Menthol 0.10 Menthyl Lactate 0.10 Phase 4 Lavender oil 0.109 Phase 5 Phenoxyethanol 0.40 Tropolone 0.001
Formulation F7: Moisturising Gel

(35) TABLE-US-00016 Raw Material % weight Phase 1 Water 89.895 Carbomer 0.60 Phase 2 PEG-40 Hydrogenated Castor Oil, Trideceth-9 3.00 Pentylene Glycol 3.00 Water, Pentylene Glycol, Glycerin, Sodium Lactate, 2.00 Lactic Acid, Serine, Urea, Sorbitol, Sodium Chloride, Allantoin Phase 3 Aminomethyl Propanol 0.50 Phase 4 Phenoxyethanol 1.00 Tropolone 0.005
Formulation F8: Silicone Emulsion

(36) TABLE-US-00017 Raw Material % weight Phase 1 Potassium Cetyl Phosphate, Hydrogenated 1.00 Palm Glycerides Cyclohexasiloxane 4.00 Cetearyl Alcohol 1.50 Phenyl Trimethicone 3.00 Stearyl Heptanoate, Stearyl Caprylate 3.00 Dimethicone 1.00 Xanthan Gum 0.20 Isoamyl p-Methoxycinnamate 5.00 Phase 2 Water 77.19 Propylene Glycol 3.00 Phase 3 Farnesol 0.10 Menthyl Lactate 0.50 Phase 4 Phenoxyethanol 0.50 Tropolone 0.005 Phase 5 Rosemary oil 0.005
Formulation F9: Hair Conditioner

(37) TABLE-US-00018 Raw Material % weight Phase 1 Water 90.595 Polyquaternium-7 1.00 Cetearyl Alcohol, Glyceryl Stearate, 4.50 Stearalkonium Chloride Citric Acid 0.20 Phase 2 Caprylyl Glycol 1.00 Polysorbate 20 2.00 Phase 3 Phenoxyethanol 0.50 Tropolone 0.005 Phase 4 Fragrance 0.20
Formulation F10: Shampoo

(38) TABLE-US-00019 Raw Material % weight Phase 1 Water 62.40 Acrylates/C1030 Alkyl Acrylate Crosspolymer 0.60 Sodium Hydroxide 15% solution 0.10 Phase 2 Disodium EDTA 0.10 Decylene Glycoll 1.00 Phase 4 Glycol Distearate, Laureth-4, Cocamidopropyl Betaine 3.00 Phase 4 Sodium Laureth Sulfate (2 mole, 53%) 10.00 Cocoamphoacetate 5.00 Ammonium Cocoyl Isethionate 12.00 Acetamide MEA 1.00 Palmitamide MEA 0.50 Phase 5 Phenoxyethanol 1.00 Tropolone 0.01
Formulation F11: Anti-Perspirant Stick

(39) TABLE-US-00020 Raw Material % weight Phase 1 Stearyl Alcohol 22.499 Isopropyl Palmitate 20.00 Hydrogenated Castor Oil 10.00 Farnesol 0.30 Phase 2 Aluminum Zirconium Tetrachlorohydrex Glycine 20.00 Phase 3 Talc 2.00 Phase 4 Cyclpentasiloxane 20.00 Dimethiconol Beeswax 5.00 Phase 5 Phenoxyethanol 0.20 Tropolone 0.001
Formulation F12: Lotion Base for Wet Wipes (Emulsion)

(40) TABLE-US-00021 Raw Material % weight Phase 1 Cetearyl Isononanoate, Ceteareth-20, 3.00 Stearyl Alcohol, Glyceryl Stearate, Glycerin, Ceteareth-12, Cetyl Palmitate Mineral Oil 3.00 Phase 2 Water 84.99 Glycerin 0.50 Propyleneglycol 1.00 Hydrolite-5 3.00 Allantoin 0.10 Phase 3 Phenoxyethanol 1.00 Tropolone 0.01 Phase 4 Fragrance 0.40
Formulation F13: Base for Wet Wipes (Solution)

(41) TABLE-US-00022 Raw Material % weight Phase 1 Water 88.79 Propyleneglycol 8.00 Citric Acid 10% 0.10 Phase 2 Solubilizer (PEG-40 Hydrogenated 2.00 Castor Oil, Trideceth-9, Propylene Glycol Water) Fragrance 0.10 Phenoxyethanol 1.00 Tropolone 0.01
Formulation F14: Sunscreen Lotion

(42) TABLE-US-00023 Raw Material % weight Phase 1 Potassium Cetyl Phosphate, 1.00 Hydrogenated Palm Glycerides alpha-Bisabolol 0.10 Cetearyl Alcohol 1.50 Myristyl Myristate 1.00 Cetearyl Ethylhexanoate 4.00 Stearyl Heptanoate, Stearyl Caprylate 1.00 Cyclopentasiloxane, Cyclohexasiloxane 0.50 Butyl Methoxydibenzoylmethane (avobenzone) 1.50 4-Methylbenzylidene Camphor 1.50 Ethylhexyl Methoxycinnamate (Neo 8.00 HeliopanAV) VP/Hexadecene Copolymer 1.00 Acrylates/C1030 Alkyl Acrylate Crosspolymer 0.10 Phase 2 Water Ad 100 Phase 3 Sodium Hydroxide, 10% solution 0.50 Phase 4 Fragrance 0.20 Phase 5 Phenoxyethanol 1.00 Tropolone 0.012
Formulation F15: Silicone Emulsion with High SPF

(43) TABLE-US-00024 Raw Material % weight Phase 1 Potassium Cetyl Phosphate, 1.00 Hydrogenated Palm Glycerides Cyclohexasiloxane 4.00 Cetearyl Alcohol 1.50 Phenyl Trimethicone 3.00 Stearyl Heptanoate, Stearyl Caprylate 3.00 Dimethicone 1.00 Xanthan Gum 0.20 Isoamyl p-Methoxycinnamate 5.00 p-Methoxycinnamic acid-2-ethylhexyl 5.00 ester (Neo HeliopanAV) Butyl Methoxydibenzoylmethane (avobenzone) 0.50 Phase 2 Water Ad 100 Pentylene Glycol (1,2-Pentanediol) 1.50 Phase 3 Phenoxyethanol 0.60 Tropolone 0.01
Formulation F16: W/O Sunscreen Lotion with High SPF

(44) TABLE-US-00025 Raw Material % weight Phase 1 Polyglyceryl-2 Dipolyhydroxystearate 3.00 Glyceryl Oleate 1.00 Beeswax 1.20 Ethylhexyl Isononanoate 2.00 Caprylic/Capric Triglyceride 3.00 C 1215 Alkyl Benzoate 3.00 Benzophenone-3 6.00 Homosalate 10.00 Ethylhexyl Salicylate 5.00 Butyl Methoxydibenzoylmethane (avobenzone) 3.00 Ethylhexyl Methoxycinnamate 7.50 Phase 2 Water Ad 100 1,2-Hexanediol 0.25 1,2-Octanediol (Caprylyl Glycol) 0.25 Phase 3 Magnesium Sulfate 0.70 Phase 4 Sodium Chloride 0.50 Phase 5 Phenoxyethanol 0.50 Tropolone 0.01