The Chemistry and Use of 1,2-Alkanediols and Anti-oxidants for Product Protection Ravi Pillai PAGE 1 1,2-ALKANEDIOLS CHEMISTRY Straight chain with two vicinal hydroxy groups CH 2 - CH - (CH 2 ) n - CH 3 OH OH Colorless and odourless to-low odor (depending on the chain length) 1,2-Pentanediol (INCI: Pentylene Glycol, colorless liquid) 1,2-Hexanediol (colorless liquid) 1,2-Octanediol (INCI: Caprylyl Glycol, liquid to waxy solid) 1,2-Decanediol (INCI: Decylene Glycol, waxy solid) PAGE 2 1
1,2-ALKANEDIOLS CHEMISTRY Chemically inert, compatible with most cosmetic ingredients Multi-functional ingredients: moisturiser, solubilizer (if liquid), preservative booster Different from other typical glycols like propylene and butylene glycols vs. 1,2-Hexanediol Amphiphilic Molecule 2-Methyl-2,4-pentanediol INCI: Hexylene Glycol PAGE 3 1,2-ALKANEDIOLS ANTI-MICROBIAL ACTIVITY MIC values (ppm) Microorganism 1,2-Pentanediol (Pentylene Glycol) 1,2-Hexanediol 1,2-Octanediol (Caprylyl Glycol) 1,2-Decanediol (Decylene Glycol) Staphylococcus epidermidis 25000 25000 1800 225 Corynebacterium xerosis 25000 12500 3600 225 Brevibacterium epidermidis NA NA 3600 450 Propionibacterium acnes 50000 25000 1800 225 Malassezia furfur 25000 12500 225 28 Trichophyton mentagrophytes 25000 6300 900 112 Candida albicans 25000 12500 900 112 Aspergillus brasiliensis 25000 6300 225 56 Escherichia coli 25000 12500 1800 900 Pseudomonas aeruginosa 25000 6300 3600 450 decreasing MIC values (increasing anti-mic activity) Anti-microbial activity increases with increasing chain length; what about preservative efficacy? PAGE 4 2
1,2-ALKANEDIOLS WATER SOLUBILITY Partition coefficient, log P o/w (calculated), of 1,2-alkanediols: 1,2-Alkanediol log P o/w 1,2-Propanediol -0.8 1,2-Butanediol -0.3 1,2-Pentanediol (Pentylene Glycol) 0.2 1,2-Hexanediol 0.7 1,2-Octanediol (Caprylyl Glycol) 1.7 1,2-Decanediol (Decylene Glycol) 2.7 increasing log P o/w (decreasing water solubility) Water solubility decreases with increasing chain length The insolubility of 1,2-Decanediol in water may explain its poor preservative efficacy PAGE 5 1,2-ALKANEDIOLS PRODUCT PROTECTION The MIC of 1,2-alkanediols show broad spectrum activity but the preservative efficacy shows weakness against mold, especially A. brasiliensis. Higher doses are necessary to protect against fungus. The most cost effective way to use alkanediols is to combine it with low doses of preservatives to make up for the weakness against mold. The mode of anti-microbial action of alkanediols is shown to be membrane disruption 1, 2. 1,2-Alkanediols can boost the activity of preservatives and other antimicrobials, providing a synergistic effect. 1 Use of 1,2-Alkanediols in Personal Care Formulations - Closer Look at Antimicrobial Activity, S. Schnittger, et al., Paper presented at SCC Annual Scientific Meeting, New York (2006) 2 Antimicrobial Activity of Aliphatic Diols and Their Esters, M. Akedo, J. Food Science Vol 42 No. 3 (1977) PAGE 6 3
PROTECTION WITH 1,2-ALKANEDIOLS SOME POSSIBLE OPTIONS Organic acids Caprylyl Glycol + Sodium Benzoate 1,2-Hexanediol + Dehydroacetic Acid Pentylene Glycol + Potassium Sorbate Caprylyl Glycol + 1,2-Hexanediol + Anisic Acid ph needs to be <5.5 Phenoxyethanol Caprylyl Glycol + Phenoxyethanol Decylene Glycol + 1,2-Hexanediol + Phenoxyethanol Works at a wider ph range Iodopropynyl Butylcarbamate (IPBC) Caprylyl Glycol + IPBC Caprylyl Glycol + 1,2-Hexanediol + IPBC PAGE 7 PROTECTION WITH 1,2-ALKANEDIOLS SOME POSSIBLE OPTIONS 0.5% Phenoxyethanol + 0.5% Caprylyl Glycol in Anionic Emulsion 1% phenoxyethanol kills bacteria in 2 days 1 log reduction of yeast & mold in 7 days kills all microbes in 14 days All challenge tests conducted as per Ph. Eur. guidelines PAGE 8 4
initial 2 days 7 days 14 days 28 days cfu/g PROTECTION WITH 1,2-ALKANEDIOLS SOME POSSIBLE OPTIONS 0.7% Phenoxyethanol + 0.2% Dec Glycol + 0.1% Hexanediol in Anionic Emulsion 1,200,000 1,000,000 800,000 600,000 400,000 200,000 0 E. coli P. aeruginosa B. cepacia S. aureus C. albicans A. brasiliensis 1% phenoxyethanol kills bacteria & yeast in 2 days 1 log reduction of mold in 2 days kills all microbes in 7 days PAGE 9 PROTECTION WITH 1,2-ALKANEDIOLS SOME POSSIBLE OPTIONS 1.5% 1,2-Hexanediol + 0.2% Potassium Sorbate in Anionic Emulsion* kills bacteria in 2 days 1 log reduction of yeast & mold in 7 days kills all microbes in 14 days * ph - 5.5 PAGE 10 5
PROTECTION WITH 1,2-ALKANEDIOLS SOME POSSIBLE OPTIONS 0.4% 1,2-Hexanediol + 0.4% Cap Glycol + 0.4% Benzoate in Non-ionic Emulsion* kills all microbes in 2 days * ph - 5 PAGE 11 PROTECTION WITH 1,2-ALKANEDIOLS SOME FORMULATION TIPS Solubility varies: Pentylene Glycol is miscible in both water and cosmetic esters. Decylene Glycol is only soluble in cosmetic esters. When making emulsions, it is preferable to add the diols directly to water phase or at post emulsification 1,2-Alkanediols, especially the longer chain, can act as surfactants. Caprylyl Glycol Decylene Glycol Due to this, some emulsions tend to lose their viscosity or even break when these alkandiols are introduced. In such cases: addition of a viscosity modifier/stabilizer like carbomer may help increasing the emulsifier(s) is another option PAGE 12 6
cfu/g PROTECTION WITH 1,2-ALKANEDIOLS SOME FORMULATION TIPS 1,2-Alkanediols may form micelles in formulations with high surfactant content, losing part of their efficacy. They tend to lose some efficacy in SPF formulations due to migration to the lipophilic phase. Addition of solvents like butylene glycol or 1,3- propanediol helps to keep them in the water phase. As always, chelating agents are recommended to help boost the preservative efficacy. 1,2-Alkanediols are heat stable and works at a wide range of temperature (3-12) 1,2-Alkanediols comply with most global cosmetic regulations: 1,2-Pentanediol, 1,2-Hexanediol and 1,2-Octanediol appear in the Chinese FDA list 1,2-Decanediol appears in the 2004 PCPC/CTFA list PAGE 13 ANTI-OXIDANTS TROPOLONE INCI: Tropolone white to yellow powder nature identical compound Addition of 0.005-0.01% of Tropolone to Phenoxyethanol or 1,2-Alkanediols helps to make up their weakness against mold. O OH Challenge Test against Aspergillus brasiliens in Anionic Emulsion 300000 200000 100000 0 0' count 2d 7d 14d 28d 0.25% C6 + 0.25% C8 + 0.005% T 280000 300 0 0 0 0.25% C6 + 0.25% C8 280000 80000 68000 40000 30000 days PAGE 14 7
PROTECTION WITH ANTI-OXIDANTS PHENOXYETHANOL + TROPOLONE 1% (Phenoxyethanol + Parabens) vs. 1% (Phenoxyethanol + Tropolone) SPF 30 Sunscreen Formulation Phenoxyethanol + Parabens vs. Phenoxyethanol + Tropolone weak against yeast & mold kills all microbes in 14 days Tropolone helps provide faster kill PAGE 15 PROTECTION WITH ANTI-OXIDANTS 1,2-ALKANEDIOLS + TROPOLONE 0.25% 1,2-Hexanediol + 0.25% Cap Glycol + 0.005% Tropolone in Aqueous Gel kills bacteria and yeast in 2 days 1 log reduction of mold in 2 days kills all microbes in 7 days PAGE 16 8
PROTECTION WITH TROPOLONE SOME FORMULATION TIPS Tropolone is a very active anti-oxidant that it could discolor many formulations/packaging materials. Stability tests on formulation and packaging is necessary. Presence of free metal ions also increase the chance of discoloration Stable at ph 3-8 Use level is very low: 0.005-0.01%, if combined with a preservative like Phenoxyethanol When making emulsions, it is preferable to add Tropolone during the cooling phase, below 50 o C. Complies with the cosmetic regulations of USA, Europe and Japan. PAGE 17 ANTI-OXIDANTS HYDROXYACETOPHENONE INCI: Hydroxyacetophenone white to off-white powder with very light odor nature identical compound found in Rubus chamaemorus (cloudberry, found in Alpine region) FEMA/GRAS listed multi-functional ingredient: anti-oxidant, anti-irritant, preservative booster PAGE 18 9
PROTECTION WITH ANTI-OXIDANTS PHENOXY + HYDROXYACETOPHENONE (HAP) 0.5% Phenoxyethanol + 0.5% Hydroxyacetophenone in Wet Wipes Lotion Base kills bacteria in 2 days kills all microbes in 7 days, even with re-inoculation PAGE 19 PROTECTION WITH ANTI-OXIDANTS CAP GLYCOL + HAP 0.25% Cap Glycol + 0.25% Phenylpropanol + 0.5% Hydroxyacetoph in Shampoo kills bacteria and yeast in 2 days kills all microbes in 7 days PAGE 20 10
PROTECTION WITH ANTI-OXIDANTS 1,2-ALKANEDIOLS + HAP 0.25% Cap Glycol + 0.25% Hexanediol + 0.5% Hydroxyacetoph in Aqueous Toner kills bacteria in 2 days kills all microbes in 7 days PAGE 21 PROTECTION WITH ANTI-OXIDANTS PHENOXY + 1,2-ALKANEDIOLS + HAP 0.2% Phenoxyethanol + 0.3% 1,2-Alkanediols + 0.5% HAP in SPF 64 Emulsion kills bacteria in 2 days kills all microbes in 7 days PAGE 22 11
PROTECTION WITH HYDROXYACETOPHENONE SOME FORMULATION TIPS Hydroxyacetophenone is soluble in water up to 1%, with stirring and heating to 60 o C. Recommended dose: up to 1% Excellent solubility in glycols and Glycerin Stable at ph 3-9 and up to 100 o C Not compatible with certain proteins When making emulsions, it is preferable to add Hydroxyacetophenone directly to the water phase. Advisable to have a good solvent like a glycol to help keep Hydroxyacetophenone in the water phase when using in formulations with high lipophilic content including SPF formulations Complies with the cosmetic regulations of USA, Europe and Japan. PAGE 23 1,2-ALKANEDIOLS AND ANTI-OXIDANTS SUMMARY 1,2-Alkanediols like Caprylyl Glycol and 1,2-Hexanediol are multifunctional ingredients that can protect cosmetic formulations Combination of 1,2-alkanediols with preservatives like organic acids, phenoxyethanol and IPBC helps to preserve many cosmetic formulations 1,2-Alkanediols comply with the cosmetic regulations of most countries; suitable for global formulations Anti-oxidants like Tropolone and Hydroxyacetophenone help boost the efficacy of common preservatives and other anti-microbial ingredients. Use of water soluble solvents like glycols increase the efficacy of alkanediols and anti-oxidants by helping to keep the anti-microbials in the water phase of emulsions PAGE 24 12
Acknowledgements: Dr. Manuel Pesaro and his group, Symrise Life Essentials R&D, Germany contact: Ravi Pillai +1 201 462 2959 ravi.pillai@symrise.com THANK YOU! DISCLAIMER Symrise makes no warranties, either express or implied, as to the accuracy or completeness of the information set forth herein. Symrise expressly disclaims any implied warranty of merchantability and fitness for a particular purpose. Prospective users are requested to determine for themselves the suitability of Symrise materials and suggestions for any use prior to their utilization. Any necessary approvals from regulatory authorities for finished products must be obtained by the prospective user. Suggestions for applications involving our products or the reference to, or incorporation of, descriptive materials from patents and the citation of specific patents in this document may not be understood as recommendation for the use of Symrise products in violation of any patent or as a permission or licence to use any patent of Symrise or a third party. PAGE 25 13