Technical Information Irgacare MP March 2011 04_101002e-00/Page 1 of 8 = Registered trademark of BASF group Medical grade for oral care applications Personal Care
04_101002e-00 March 2011 Page 2 of 8 Irgacare MP Characterization Irgacare MP is a highly efficient broad-spectrum antimicrobial based on Triclosan. The product shows activity against gram-negative and gram-positive bacteria as well as yeast and fungi. Triclosan is widely used in personal care and human hygiene applications. Irgacare MP is a medical grade especially designed for incorporation into oral care applications. Chemical Name The active ingredient of Irgacare MP is 2,4,4 -trichloro-2 -hydroxy-diphenyl-ether Structural formula Cl OH O Cl Cl PRD-No.* 30480531 * BASF s commercial product numbers. INCI Name Triclosan Applications Oral Care, e.g. tooth paste, mouth rinses. Features / benefits Irgacare MP is effective at low concentrations against a broad spectrum of unwanted and pathogenic microorganisms being involved in plaque formation and malodor. Irgacare MP shows good substantivity to the dental enamel and mucosa leading to a long-lasting effect. In addition Irgacare MP provides an anti-inflammatory benefit. Guidelines for use Application Typical Use Level of Irgacare MP Tooth paste up to 0.3% Mouth rinse 0.03 0.1%
04_101002e-00 March 2011 Page 3 of 8 Irgacare MP Benefits There are both production and formulation benefits associated with Irgacare MP. A number of these benefits are highlighted below: Products Benefit Broad-Spectrum Activity Long-lasting activity on, teeth and mucosa Anti-inflammatory effect Compatibility Purity Solubility Impact to Application Broad-spectrum antibacterial activity claims can be made as the antimicrobial active works against aerobic and anaerobic gram-positive and gram-negative bacteria, and yeasts. Tests have shown effective long-lasting antibacterial activity in oral care applications. The anti-inflammatory activity of Irgacare on skin and mucosa membranes is well documented. This property of the active results in reduction of gingivitis and skin inflammation. Use of IrgacareMP can help reduce the irritation of other raw materials in a formulation (e.g. Sodium Lauryl Sulphate). Highly compatible with other personal care ingredients Toxicology Favorable toxicological profile Stability Triclosan displays a high thermal and chemical stability as well as photostability. Irgacare MP is produced under GMP and has a superior quality meeting the specification of the U.S. Pharmacopoeia The product is soluble in many solvents used in personal care formulations, but is only sparingly soluble in water. Irgacare MP shows bacteriostatic and bactericidal activity depending on the concentrations applied. The active has various modes of action with the main site of action being the cytoplasmatic membrane and the cytoplasm. Physical Properties Form Powder Color White Odor Trace aromatic Identity Conform to Standard Spectrum Melting Point: 56 58 C
04_101002e-00 March 2011 Page 4 of 8 Irgacare MP Minimum Inhibitory Concentration (MIC) of Irgacare MP Irgacare MP against oral microorganisms. Bacteria MIC * (ppm) Gram-positive species Actinomyces naeslundii 20 Actinomyces viscosus 20 Actinomyces odontolyticus 20 Actinomyces israelii 10 Peptococcus asaccharolyticus 10 Peptococcus saccharolyticus 10 Peptococcus magnus 50 Peptostreptococcus anaerobius 50 Streptococcus mutans 10 Streptococcus sanguis 10 Gram-negative species Actinobacillus actinomycetemcomitans 5 Bacteroides melaninogenicus 10 Bacteroides intermedius 10 Bacteroides endodontalis 50 Bacteroides oralis 10 Bacteroides distasonis 50 Fusobacterium nucleatum 50 Leptotrichia buccalis 20 Porphyromonas (Bacteroides) gingivalis 50 Veillonella parvula 20 Yeasts Candida albicans 10 *ref: Journal of Clinical Periodontology Vol. 18 No. 16 July 1991
04_101002e-00 March 2011 Page 5 of 8 Irgacare MP Activity in toothpaste biocidal activity With its excellent bactericidal activity Irgacare MP prevents the colonization of dental surfaces and the formation of plaque. To demonstrate this efficacy a test was designed which uses hydroxyapatite discs (HAP) as a dental model. Bactericidal activity of Irgacare MP on HAP disc 1 000 000 000 100 000 000 cell count [cfu/ml] 10 000 000 1 000 000 100 000 10 000 1 000 100 10 0 6 12 18 24 time [h] Control Toothpaste + 0.3% Irgacare MP The HAP discs were incubated in artificial saliva for 4 hrs (under stirring), rinsed with 10 ml NaCl, dried over night, and finally incubated in 10 ml of a toothpaste solution containing 500 ppm Irgacare MP for 30 min. Afterwards, all treated discs were put in 12 well Nunclon surface titre plates (one disc per well), and 4 ml Caso Broth inoculated with A. viscosus ATCC 43146 (ca.105 cfu / ml) were added. The titre plates were incubated at 37 C, samples were taken after 6 and 24 hrs and the colony count was determined. Irgacare MP also reduces already existing plaque caused by bacteria on the dental surface due to its good substantivity to the dental enamel. Reduction of dental plaque bacteria in a biofilm model on HAP disc 1 000 000 000 100 000 000 99.9% microorganism reduction 10 000 000 1 000 000 100 000 10 000 1000 100 Control 0.1% Irgacare MP 0.3% Irgacare MP Biofilm formation Hydroxyapatite (HAP) discs are pretreated with human saliva (pellicle formation) and exposed to a mixed culture of different oral bacteria containing early and late colonizers (Streptococcus sobrinus OMZ 918, Veilonella dispar OMZ 493, Fusobacterium nucleatum OMZ 598, Streptococcus oralis OMZ 607, Acinomyces naeslundii OMZ 745, Candida albicans OMZ 110). Treatment Discs are dipped 6 times during 2 days into 30% dentifrice suspension for 60 sec. Afterwards the discs were incubated anaerobically for 24 h at 37 C. The biofilms are harvested and the number of bacteria on the HAP discs is determined.
04_101002e-00 March 2011 Page 6 of 8 Irgacare MP Anti-inflammatory effect Irgacare MP was proven to be a potent inhibitor of cyclo-oxygenases and lipoxygenases, which are key enzymes of the arachidonic acid metabolism, resulting in a reduced formation of pro-inflammatory metabolites such as prostaglandine E2 and leukotriene B4 (A. Gaffar et al.: Journal of Clin. Periodontol. 480-484, 1995). Proposed mechanism of the anti-inflammatory activity of Irgacare MP. Arachidonic acid TCS Lipoxygenase TCS Cyclo-oxygenase (= component of Prostaglandin Synthetase) Leukotriene A Endoperoxides Leukotriene B-E Thromboxans Prostaglandins Findings that the active ingredient is capable of reducing cytotoxic effects of sodium lauryl sulphate on human gingival fibroplasts (E.J. Coleman at al: J. Dent. Res. 72 IADR abstracts, abstract no 1837, 1993) and on the oral mucosa (S.M. Waaler et al.: Scandinavian Journal of Dental Research 101, 192-195, 1993; A.B. Skaare et al.: J. Clin. Periodontol. 23, 1010-1013, 1996) further substantiate the anti-irritant and anti-inflammatory effects of Irgacare MP. Health & Safety Irgacare MP is safe for humans and the environment as multiple studies and 35 years of application without adverse effects demonstrate. Irgacare MP is not accumulated in humans and the environment but readily degraded in wastewater treatment plants and surface waters. A recent assessment (December 2010) by the expert panel of the US Cosmetics Ingredients Review (CIR) has reconfirmed that Triclosan is safe as used. In manufacturing, processing, or repackaging of pure product skin and eye irritation have to be prevented. Contact with eyes, skin and clothing should be avoided and containers kept closed. The products are for industrial use only.
04_101002e-00 March 2011 Page 7 of 8 Irgacare MP Registration Detailed information on product safety and the registration status is available on request. Cosmetic / Drug Registration Status of Irgacare MP Country Europe USA Status / Restrictions Approved for use in all cosmetics according to European Cosmetic Directive 76/768/EEC, Annex VI, Part 1. As preservative maximum allowed concentration in cosmetic end products: 0.3%. Topical antimicrobial drug products for over-the-counter (OTC) human use; Tentative final monograph for first aid antiseptic drug products max.1.0%. Topical antimicrobial drug products for over-the-counter (OTC) human use; Tentative final monograph for antimicrobial antiseptic hand wash products: max. 1.0%. Japan South Korea China Australia Philippines Canada Switzerland India Israel Drug Master File (DMF) and over-the-counter (OTC) public docket data supporting NDA s and IND s (Investigational New Drug Application) for oral and dermal uses. Japanese Cosmetic deregulation included in Japanese positive list for cosmetic ingredients as preservative in all cosmetic end-products ( max 0.1%) Japanese Quasi-Drug Regulation : following precedent uses for Triclosan as a QD active: 1. Medicated soaps, deo-soaps (solid) max. 0.5% 2. Liquid hand soaps max. 0.3% 3. Deodorants max. 0.2% 4. Toothpastes / mouth rinses max. 0.1% Approved as antiseptic / preservative up to 1% for use in all cosmetics. Chinese Cosmetic Regulation, max 2% for skin applications, 0.35% for mucous membrane applications. Triclosan listed in the Chinese Standard of Toothpaste with max. of 0.3%. No limit on Triclosan concentrations for therapeutics or for cosmetics as long as the safety aspects are controlled and the concentration is justified by product efficacy. Antimicrobial agent: Deodorants Maximum concentration in the finished product: 2%. As preservative in other cosmetic products: max 0.3% in finished product. Dentifrice Concentration not to exceed 0.3%. Labelling must be submitted along with analytical methods and data on PCDD/PCDF impurities. Mouthwash. Concentration not to exceed 0.03%. Labelling must be submitted along with analytical methods and data on PCDD/PCDF impurities. Approved for use in all cosmetics. Maximum allowed concentration in cosmetic end products: 0.3%. Approved as preservative with a maximum allowed concentration in cosmetic end products: 0.3%. Approved for use in all cosmetics. According to Goods and Services Ordinance, as preservative maximum allowed concentration in all cosmetic end products: 0.3%.
04_101002e-00 March 2011 Page 8 of 8 Irgacare MP Taiwan Law for the control of cosmetic hygiene: Medicated Cosmetics (antibacterial agent), Used in soap, shampoo, shave cream, facial cream, emulsions, and tonic waters as anti-bacterial agent. 0.3% (max 0.3% of Triclosan as preservatives in general cosmetics = no claim). Malaysia Approved for use in all cosmetics. According to Control of Drugs and Cosmetics, as preservative maximum allowed concentration in all cosmetics: 0.3%. South Africa Antimicrobial agent: Oral hygiene Products : max 0.2% 0.35% m/m (label: Contains Triclosan ). Preservative in cosmetic products: max 0.3%. Argentina Approved for use in all cosmetics. As preservative maximum allowed concentration in all types of products: 0.3%. Brazil Approved for use in all cosmetics. As preservative maximum allowed concentration in all types of products: 0.3%. Chile As antimicrobial agent: Liquid and solid deodorant soap; 0.50 g 2.00 g. %. As antimicrobial agent : Underarm deodorants; 0.10 g 0.20 g %. Mexico Approved for use in all cosmetics. As preservative maximum 0.3% in all types of products. Other uses up to 0.5% in all types of products. Norway Preservatives in cosmetic products max 0.3% Soaps and products which are rinsed off after use 0.5%; other products: max. 0.3%. Turkey Approved for use in all cosmetics. As preservative maximum allowed concentration in all types of products: 0.3%. Iceland Approved for use in all cosmetics. As preservative maximum allowed concentration in cosmetics: 0.3%. Note This document, or any answers or information provided herein by BASF, does not constitute a legally binding obligation of BASF. While the descriptions, designs, data and information contained herein are presented in good faith and believed to be accurate, it is provided for your guidance only. Because many factors may affect processing or application/use, we recommend that you make tests to determine the suitability of a product for your particular purpose prior to use. It does not relieve our customers from the obligation to perform a full inspection of the products upon delivery or any other obligation. NO WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, ARE MADE REGARDING PRODUCTS DESCRIBED OR DESIGNS, DATA OR INFORMATION SET FORTH, OR THAT THE PRODUCTS, DESIGNS, DATA OR INFORMATION MAY BE USED WITHOUT INFRINGING THE INTELLECTUAL PROPERTY RIGHTS OF OTHERS. IN NO CASE SHALL THE DESCRIPTIONS, INFORMATION, DATA OR DESIGNS PROVIDED BE CONSIDERED A PART OF OUR TERMS AND CONDITIONS OF SALE. March 2011 BASF SE - Care Chemicals Division - Personal Care - 67056 Ludwigshafen - www.personal-care.basf.com