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CONTENTS • Current Antimicrobials and their limitations • Galguard Trident: The Composition • Galguard Trident: Preservation Efficacy • Summary Challenges in Preservation • Significant amount of water in all formulation types • Manufacturing processes • Multi-use nature of products • All work-horse antimicrobials are under cloud: Toxicity issues and bad press Types of Preservatives • Parabens • Formaldehyde releasers • Isothiazolinones • Halogenated synthetic molecules • Quaternary ammonium • Miscellaneous (alcohols, ether alcohols, organic acids) Phenolic Antimicrobials Trichlosan Parabens Chlorxylenol Formaldehyde Releasers Imidazolidinyl urea DMDM Hydantoin Diazolidinyl urea Isothiazolinones Methyl isothiazolinone Chloromethyl isothiazolinone Halogenated Antimicrobials Iodopropynyl butyl carbamate Chlorphenesin Chlorhexidine Bronopol Organic Acids Sorbic acid Benzoic acid Dehydroacetic acid Quaternary Ammonium Salts Benzethonium chloride Benzalkonium chloride Cetyl pyridinium chloride Quaternium 15 Miscellaneous Phenoxy ethanol Benzyl alcohol Ethyl hexyl glycerol Phenethyl alcohol Work-horse preservatives for personal care • Parabens • DMDM Hydantoin and Urea derivatives • Methyl and chloromethyl isothiazolinones • IPBC • Trichlosan • Phenoxy ethanol Parabens & Formaldehyde Releasers • Parabens are implicated in disrupting endocrine system, ultimately linked to breast cancer [(Pharmacology & Toxicology (Vol. 86(3), pp 110-13, March 2000, Toxicology and Applied Pharmacology (Vol. 153(1), pp. 12-19 (Nov. 1998), Journal of Veterinary Medical Science (Vol. 64(3), pp227-35 (March 2002, Journal of Applied Toxicology, 24 (3): 167-176, (2004)] • DMDM Hydantoin and other formaldehyde releasers: Formaldehyde is classified as Category 3 CMR (carcinogenic, mutagenic and reproductive toxic) and hence all formaldehyde releasers are being phase out. DMDM Hydantoin is an allergen too. IPBC & Isothiazolinones • Iodopropynyl butyl carbamate: Contact allergen, presence iodine gets it implicated in Goiter and malfunctioning thyroid gland (American Journal of Contact Dermatitis 13(2),77-79 (2002) • Isothiazolinones: Found to be neurotoxic in animals. Skin sensitizer and irritant. All major manufacturers of personal care products are dropping it from ‘leave-on’ formulations. (Journal of Neuroscience 22 (17): 7408–7416. The Lancet, Volume 333, Issue 8633, Pages 314-316 (1989) Trichlosan • Trichlosan is reported to be an endocrine disruptor (thyroid function) and is reported to impair cardiac and skeletal muscles. There seems to be a special concern for children who are at higher risk of allergies and the immune systems (Toxicological Sciences, 2009, 107 (1): 56-64, Reproductive Toxicology, Apr 2009, 27(2):177-185) • Trichlosan is a phenolic and halogenated molecule and has been implicated in ecotoxicity (algae, dolphins) The Goal • To develop broad spectrum composition from safe antimicrobials that are not implicated in any controversy over toxicity to humans or the ecosystem. • To create a „stable‟ and „easy-to-use‟ composition of personal care ingredients that coincidentally exhibit antimicrobial activity. • To develop an „energy-efficient‟ and „eco-friendly‟ manufacturing process of creating the above composition. Galguard Trident • A „three-component‟ system is free from parabens, isothiazolinones, formaldehyde releasers including Hydantoin derivatives, Urea derivatives and Quaternium-15 • It is free from halogenated or phenolic molecules • The preservation technology is based on phenoxy ethanol and lipidated glycines, namely, N-capryloyl glycine and N-undecylenoyl glycine Galguard Trident: The constituents 2-Phenoxy ethanol • Occurs in nature (Green Tea) • Used as antiseptic in olden time CAS No 122-99-6 2-phenoxy ethanol • Preferred antimicrobial for preserving vaccines • Broad spectrum activity, more active against Gram -ve bacteria • Non-controversial, most widely used (produced), safe, popular with leave-on Cosmetic and Drug Preservation, Principles and Practice, Vol I, Ed Jon Kabara, Marcel Dekker N-octanoyl glycine • Non-preservative substances to inhibit microbial growth in cosmetics, C & T,17(3), 11-13, 16-19, (1996) CAS No 14246-53-8 N-Capryloyl glycine • Derma-protector; restores the skin's “acid layer” • Active against the normal resident skin flora • Reduces scalp irritation and inhibits 5 α-reductase action and hence the sebum production • Limits proliferation of the germs responsible for dandruff • Protective agent for cosmetic formulas; reduces the quantity of preservative, ideal for sensitive skin N-undecylenoyl glycine • Undecylenoyl amino acids for the treatment of skin disorders JP 49093521 (1974) • Cosmetic compositions comprising N-undecylenoyl glycine and N- capryloyl glycine. WO 9927902 (1992) • Compositions containing undecylenoyl glycine and capryloyl glycine for preserving personal care products US 20040096528 (2004) CAS No 54301-26-7 N-Undecylenoyl glycine Products containing lipidated glycines LJH 5-Alpha Control Cleansing Gel Melvita Roll-on Deodorant Products containing lipidated glycines John Master Organics-Morroccan Clay Purifying Mask Les Soin Bio Plante – Softness Deodorant Products containing lipidated glycines ATACHE Scientific Cosmetic Balancing cream Undecylenoyl glycine & Capryloyl glycine in Baby Care Neways Baby & Child Care Dr Luigi Rigano, Cosmetics & Toiletries, 128, 458-461(2013) Undecylenoyl glycine & Capryloyl glycine in Baby Care California Baby Super Sensitive Galguard Trident: Microemulsion Galguard Trident: Microemulsion Galguard Trident: Microemulsion • Microemulsion of water, phenoxy ethanol and lipo-glycines • Optically isotropic , W/O type microemulsion • Thermodynamically stable • It is 65 % active and the ratio of lipo-glycines to phenoxy ethanol is 1 : 4 Particle Sizing by Dynamic Light Scattering Zetasizer Ver 6.01 Malvern Instruments Ltd Dz =Z average = 10 nm Chemical Incompatibility pka 3.28 Benzoic acid pka 4.2, Acetic acid pKa 4.76 Sorbic acid pka 4.76 Galguard Trident: The Microemulsion • Thermodynamically stable • Chemical instability addressed • Delivery of other antimicrobials into microbes body • Microemulsion : nano-structure and easy fusion with the lipids of cell membrane and delivering the surfactants to disrupt the membrane • Peptide type surfactants (lipidated glycines) are good at breaching the cell membrane James Baker and team , Microbiol. Res. 2001, 156, 1 (Univ of Michigan) Kyle Vanderelick, Langmuir, 2003, 19, 591(Princeton Univ) HPLC analysis of Galguard Trident N-Undecylenoyl glycine: NMR Antimicrobial Efficacy of Galguard Trident Galguard Trident MICs Escherichia coli 4000 ppm Pseudomonas aeruginosa 4000 ppm Candida albicans 5000 ppm Staphylococcus aureus 6000 ppm Aspergillus niger 6000 ppm Propionibacterium acnes 7000 ppm Malassezia furfur 6000 ppm Galguard Trident: Germ Count Reduction Test ( 1%) Efficacy in Body Wash: 1.0 % Galguard Trident Efficacy in Cream: 1.0 % Galguard Trident Galguard Trident: Summary • Benefits: Preservation without any controversy • Preservation with well-accepted ingredients • Broad spectrum antimicrobial activity • Colorless, odorless, easy-to-use • Compatible with other ingredients • Applications: Skin-care, hair-care, baby-care, sun-care formulations • Nail-care, wet wipes • Both leave-on and rinse-off formulations • Recommended use level: 0.5 to 1.2 % on active basis • Best Efficacy: pH range of the formulation, 4 to 7.0 Galguard Trident Preservation without any controversy • Paraben -free and Formaldehyde-donors-free • Isothiazolinones-free (Methyl and chloromethyl analogs) • No halogen (bromo, chloro, iodo) containing antimicrobials • Free from phenolic molecules and quaternary ammonium compounds THANK YOU