UV Protection by Ciba Ciba Specialty Chemicals Holding Inc.; All rights reserved. The information given in the documentation is based on the present state of our knowledge. It shows without liability on our part the uses to which our products can be put. 1
UV Absorbers overview UV-A Test Methods (in vivo / in vitro) UV Protection by Ciba TINOSORB M TINOSORB S Registration status Market Products with Ciba UV Absorber 2
Protection at the beach around 1900 3
Objective: Tanning without Sunburn, 1930 First transparent sun protection creams From Tavenrath Simone, 2000 4
Skin cancer as headline, Germany 1993 Dangerous sun: How to save our skin From Tavenrath Simone, 2000 Warnings from: Sun Allergy Photodermatosis Sunburn Skin-aging Skin cancer 5
UV exposure of the skin Spectrum of the Sun Stratosphere Ozone layer Surface of the earth UV-C UV-B UV-A Visible light Infrared UV-B: 70% reflected by Stratum Corneum UV-A: 30% penetrates into Dermis Horny layer of the skin Epidermis Dermis Hypodermis Wavelength nm 200 290 320 400 800 6
Penetration of Sun Light Wavelength [nm] 280 300 350 400 600 Penetration Depth [µm] 1,5 6 60 90 550 Penetration Depth / µm 0 10 20 30 40 50 60 70 UVB UVA SC 800 1200 1200 2200 80 90 100 250 300 350 400 450 Wavelength / nm 7
Effects of UV Radiation on Human Skin Main risk of UVB 290-320 nm Sunburn Main risk of UVA 320-400 nm Accelerated photoageing Skin cancer Damage of blood vessels and connective tissues Contribution to sunburn Contribution to skin cancer 8
Requirements of UV Absorbers Efficacy Molecules have to provide an efficient absorption of UV radiation (UVB and/or UVA) Ease of Formulating Molecules have to be compatible with most ingredients used in formulations Safety Molecules have to be safe, i.e. avoid of adverse effects 9
Most frequently used cosmetic UV Absorbers 10
UV-Filter consumption in Western Europe TiO2 ZnO ZnO EHMC Other BP4 OT PSA 14% 3% 41% EHMC TiO2 Other 20% 4% 18% 13% OCT BP3 BP4 14% EHS MBC BMBM 9% 11% OCT OT PSA BP3 MBC EHS BMBM Volume: Total 4840 t Value: Total 97.3mio Kline 2002 11
Two most frequently used absorbers for UV-B and UV-A O O O O O UV-B: EthylHexyl MethoxyCinnamate (EHMC) OCH 3 UV-A: Butyl MethoxyDibenzoylMethane (BMBM) Molar Extiction Molar Extiction Wavelength (nm) The ideal combination? Wavelength (nm) 12
Photostability of BMBM and EHMC UVA/UVB-Ratio 1,00 0,80 0,60 0,40 0,20 0 1 2 3 4 % BMBM BMBM + 5% OCR + 5% OCR and 5% EHMC dashed lines: irradiation with 10 MED BMBM/EHMC combinations are not photostable 13
New UVA- and Broad-Spectrum UV Filters, 2003 # INCI Tradename UVB UVA Approved (Europe) Freely available S 71 S 73 S 79 S 80 S 81 TDSA DTS MBBT DPDT BEMT MEXORYL SX MEXORYL XL TINOSORB M NEOHELIOPAN AP TINOSORB S X X X X X X X X no no 14
UV Absorbers overview UV-A Test Methods (in vivo / in vitro) UV Protection by Ciba TINOSORB M TINOSORB S Registration status Market Products with Ciba UV Absorber 15
UV-A Test Methods (in-vivo / in-vitro) 16
In vivo: UVA-PF (PPD) Persistant Pigment Darkening = PPD Principle: Measurement of UVA-induced pigmentation 2 hours after irradiation when the pigmentation has stabilized. Conditions: UVA-dose about 15 J/cm² 10 volunteers of skin types 2,3 and 4 The Minimal Pigmenting Dose (MPD) corresponds to the minimal UVA dose producing the first perceptible pigmentation 2 hours after exposure to 6 increasing doses of UVA. Protected area is then compared with unprotected area. UVA PF = MDPp / MPD np 17
In vitro: Australian Standard Principle: 100 Measurement of the UVA-transmission of the formulation at d=0.0008cm between 320 and 360nm Definition: Transmission < 10% at any wavelength in this range 80 Transmission (%) 60 40 20 Australian Standard 0 290 310 330 350 370 390 400 λ (nm) 18
In vitro: UVA/UVB-ratio Principle: Ratio of the average of extinction E in the UVA- and the UVBrange, spectrum measured on special substrates 700 600 500 UV-B UV-A E (1%,1cm 400 300 200 100 0 290 310 330 350 370 390 Wavelength / nm UVA-UVB ratio of around 1 = broad band filter system UVA-UVB ratio of < 0.5 = UVB absorber UVA-UVB ratio of > 1 = UVA absorber 19
Star-rating UV-A / UV-B ratio 0.2 0.4 = 0.4 0.6 = 0.6 0.8 = > 0.8 = 20
In vitro: Critical Wavelength Principle: l c is the upper limit of the spectrum from 290nm on, within which 90% of the area under the extinction curve of the whole range between 290 and 400nm is covered 700 600 500 λ c E (1%,1cm 400 300 200 100 0 290 310 330 350 370 390 Wavelength / nm The higher the l c = The better the UVA protection 21
Photostable UVA Protection Traditional combination of BMBM (Parsol 1789) and EHMC are effective, but not photostable. Stabilization with OCR is effective for BMBM alone, but not in combination with EHMC TINOSORB M and TINOSORB S are the only broad spectrum and photostable UV Absorbers available on the market 22
UV Absorbers overview UV-A Test Methods (in vivo / in vitro) UV Protection by Ciba TINOSORB M o Properties o Performances o Formulating with TINOSORB M TINOSORB S Registration status Market Products with Ciba UV Absorber 23
TINOSORB M Organic Micropigment with Broad-Spectrum UVA/UVB Performance and High Inherent Photostability 24
Chemical Properties Active Ingredient of TINOSORB M: INCI name: Methylene Bis-Benzotriazolyl Tetramethylbutylphenol (abbr.: MBBT) N OH OH N Melting point: 195 C Solubility in H 2 O: < 10-8 g/l Molecular mass: 658.86 g/mol N N N N UV absorbance E1%,1cm 25
Physical Properties The micronization is performed with a ball milling process ending up with an aqueous dispersion of microfine MBBT particles (d 0.5 <200nm): Atomic Force Microscopic Image of TINOSORB M (Particle Size Range: 70 nm - 400 nm = 0,07µm - 0,40µm) 26
Composition of TINOSORB M MBBT particles 50.0% Surfactant (Decyl Glucoside) 7.5% Thickener (Xanthan gum) 0.2% Propylene glycol 0.4% Water ad 100% ph 10.5 11.5 No preservation necessary because of alkaline ph 27
Importance of small particle sizes The smaller the particle size, the higher the molar extinction of TINOSORB M Particles 40000 Molar Extinction / l/(mol cm 30000 20000 10000 d(0.5) = 0.16 µm d(0.5) = 0.21 µm d(0.5) = 0.34 µm d(0.5) = 0.78 µm d(0.5) = 4.37 µm 0 280 300 320 340 360 380 400 420 Wavelength / nm 28
Importance of small particle sizes Qualitative Explanation of the Increase of in vitro SPF with Smaller Particles The UV-attenuating coverage by the sunscreen film is more efficient with smaller particles. Average thickness of film: 20 µm; 10% particles =20% TINOSORB M Assumption: two layers of particles for an efficient coverage particle size d (µm) 10 5 2,5 1,25 Max. coverage 10% 20% 40% 80% 29
ph Stability of TINOSORB M TINOSORB M dispersion in water 2,5 3 6 8 11 13 ph value Stable formulations in a broad ph range possible 30
Concentration / SPF correlation SPF calc. 16 14 12 10 8 6 4 2 0 5 10 20 % TINOSORB M 6,6% TINOSORB M are required to fulfill Australian standard TINOSORB M is recommended up to 20% in cosmetic formulations 31
Synergistic effect of TINOSORB M and EHMC 40 35 SPF in-vivo 30 25 20 15 10 5 0 8% TINOSORB M 5% EHMC 5% EHMC + 8% TINOSORB M 5% EHMC + 20%TINOSORB M 32
TINOSORB M and TiO 2 3.5% TiO2 8% TINOSORB M 1,2000 1,2000 1,0000 1,0000 Extinction 0,8000 0,6000 0,4000 Extinction 0,8000 0,6000 0,4000 0,2000 0,2000 0,0000 0,0000 290 310 330 350 370 390 290 310 330 350 370 390 Wavelength / nm Wavelength / nm Combination 1,2000 SPF calc. = 12 Crit. Wavelength = 385 UVA/UVB ratio: 0.8 Australian Standard Fulfilled Star Rating: Extinction 1,0000 0,8000 0,6000 0,4000 0,2000 0,0000 290 310 330 350 370 390 Wavelength / nm 33
Comparison of UVA Performance UV-Absorber Australian Standard UVA/UVB Ratio Critical Wavelength (nm) TINOSORB M 6.6% 0.98 388 ZnO (Nanox) 8% 0.81 376 BMBM (Parsol 1789) 3% 1.22 383 TiO2 9% 0.29 348 Benzophenone-3 > 10% 0.5 364 Ethylhexyl Triazone >20% 0.08 324 Ethylhexyl Methoxycinnamate >10% 0.21 337 Octocrylene >10% 0,29 348 34
Synergistic effect of TINOSORB M with EHMC 12 10 ZnO TINOSORB M ZnO & 5% EHMC TINOSORB M & 5% EHMC UVA-PF 8 6 4 2 0 4 8 16 % UVA Filter (ZnO or TINOSORB M) 35
Photostability in vitro TINOSORB M EHMC BMBM MBC % recovery of UV-Filters 100 80 60 40 20 0 0 5 10 20 UV-Dose in MED Minimal Erythemal Dose Max MED in Central Europe 36
Stabilization of EHMC by TINOSORB M Recovery of EHMC in% 100 80 60 40 20 0 EHMC alone 2.4% EHMC & TINOSORB M 10% 0 10 UV-Dose in MED 37
Formulation Guideline with TINOSORB M Optimized way of incorporation After emulsification, during the cooling phase (~60 C), pour TINOSORB M into the emulsion under gentle stirring. Additional homogenization should be avoided. Alternative way of incorporation Incorporation of TINOSORB M into the water phase under continuous stirring prior to the emulsification at 75/80 C Incorporation into the oil phase has to be avoided Exposition time at high temperatures should be as short as possible 38
UV Absorbers overview UV-A Test Methods (in vivo / in vitro) UV Protection by Ciba TINOSORB M TINOSORB S o Properties o Performances o Formulating with TINOSORB S Registration status Market Products with Ciba UV Absorber 39
TINOSORB S The most efficient Broad-Spectrum UV-Absorber 40
Chemical Properties INCI name: Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine (abbr.: BEMT) OCH 3 Melting point: 80 C Solubility: Oil soluble Molecular mass: 627,8 g/mol Solubility in H 2 O: 10-7 g/l O HO N N N OH O 800 UV-spectrum of TINOSORB S 700 600 E (1%, 1cm 500 400 300 200 100 0 290 300 310 320 330 340 350 360 370 380 390 400 Wavelength / nm 41
Inherent Photostability by Photo-Tautomerism R 1 R 4 N N O H R 2 N R 5 R 3 h n R 1 R 4 N N O H R 2 N R 5 R 3 42
UV-A Protection with TINOSORB S Placebo TINOSORB S plus 5% EHMC PFA (PPD method) 18 16 14 12 10 8 6 4 2 0 Placebo 1% 2% 4% % TINOSORB S PFA (Japan) PA +++ PA ++ PA + 43
Comparison of UVA Performance UV-Absorber Australian Standard UVA/UVB Ratio Critical Wavelength (nm) TINOSORB S 2% 0.73 370 TINOSORB M 6.6% 0.98 388 ZnO (Nanox) 8% 0.81 376 BMBM (Parsol 1789) 3% 1.22 383 TiO2 9% 0.29 348 Benzophenone-3 > 10% 0.5 364 Ethylhexyl Triazone >20% 0.08 324 Ethylhexyl Methoxycinnamate >20% 0.21 337 Octocrylene >20% 0,29 348 44
Synergistic effect of TINOSORB S with EHMC UVA-PF 17 15 13 11 9 7 5 3 1 BMBM BMBM & 5% EHMC & 5% OCR TINOSORB S TINOSORB S & 5% EHMC 1 2 3 % UVA Filter (BMBM or TINOSORB S) 45
TINOSORB S and Ethylhexyl Triazone Extinction 1,6000 1,4000 SPF calc. 7 4% EHT 1,2000 1,0000 0,8000 0,6000 0,4000 0,2000 0,0000-0,2000290 310 330 350 370 390 Wavelength / nm Extinction 3% TINOSORB S 1,6000 1,4000 1,2000 1,0000 0,8000 0,6000 0,4000 0,2000 0,0000 290 310 330 350 370 390 Wavelength / nm SPF calc. 6 Combination SPF calc. = 20 Crit. Wavelength = 371 UVA/UVB ratio: 0.48 Australian Standard Fulfilled Star Rating: Extinction 1,6000 1,4000 1,2000 SPFcalc. 20 1,0000 0,8000 0,6000 0,4000 0,2000 0,0000 290 310 330 350 370 390 Wavelength / nm 46
Photostability in vitro TINOSORB S EHMC BMBM MBC % recovery of UV-Filters 100 80 60 40 20 0 0 5 10 20 UV-Dose in MED Minimal Erythemal Dose Max MED in Central Europe 47
Stabilization of BMBM by TINOSORB S 100 Recovery of BMBM in % 80 60 40 20 BMBM alone BMBM & 3%TINOSORB S 0 10 UV-Dose in MED 48
Formulation Guideline with TINOSORB S Solubilize TINOSORB S by adding it directly to the oil phase and heat up to 80 C. For cold process : solubilize TINOSORB S in the most polar oil Emulsification at room temperature O/W Emulsions Need of sufficient polar oils for solubilization Reasonable limit of use in O/W : < 5% W/O Emulsions Need of sufficient polar oils for solubilization Use of minimal quantity of non-polar oils for W/O s stability Reasonable limit of use in W/O : < 3% 49
Solubility of TINOSORB S Very good solubility (15-20%) UV Absorbers, Pyrrolidones Good solubility (8-15%) Fatty Acids Esters, Benzoic Acid Esters Low solubility (2-5%) Triacylglycerides, vegetables oils Very Low solubility (<1%) Alcohol, silicones and hydrocarbon derivates 50
Solubility of TINOSORB S Fatty Acid Esters Isodecyl Salicylate (Dermol IDSA) 18% Diethylhexyl Succinate (Crodamol OSU) 10% Dicaprylyl Carbonate ( Cetiol CC) 9% Propylene Glycol Dicaprylate/Dicaprate (Crodamol PC) 7% Isopropyl Myristate ( Tegosoft M) 6% Benzoic Acid Esters C12-C15 Alkyl Benzoate (Tegosoft TN) 13% Isostearyl Benzoate (Finsol SB) 8% Triacylglycerides Caprylic/Capric Triglyceride (Miglyol 812) 5% Pyrrolidones Caprylyl Pyrrolidone (Sulfadone LP100) 20% UV Absorbers Ethylhexyl Methoxycinnamate (TINOSORB OMC) 17% Ethylhexyl Salicylate (Eusolex OS) 20% 51
TINOSORB M & TINOSORB S the ideal couple 52
Characteristics of TINOSORB M & TINOSORB S TINOSORB M TINOSORB S Physical state Particles dispersion Powder Emulsion Phase Broad-spectrum Performance Critical Wavelength Water Covers long UVA 388nm Oil Higher absorbance 373nm UV-A/UV-B ratio 1.0 0.73 53
Synergy between TINOSORB M & TINOSORB S TINOSORB M conc. 0% 5% 10% 15% 18 16 14 12 10 8 6 4 2 0 TINOSORB S 0% TINOSORB S 2% 54
Summary TINOSORB M unique micronized organic particles broad band absorption wide coverage of UVA range Excellent photostability Synergy with most UV-B absorber TINOSORB S the first cosmetic UV-filter based on innovative HPT technology superior full spectrum protection oil solubility = formulation flexibility high efficacy at low concentrations = ideal for day care Photostable Synergy with most UV-B absorber 55
UV Absorbers overview UV-A Test Methods (in vivo / in vitro) UV Protection by Ciba TINOSORB M TINOSORB S Registration status Market Products with Ciba UV Absorber 56
Registration Status 57
TINOSORB M & TINOSORB S Registration Approved as UV filter in: Europe in a concentration of use up to 10% active (=20% TINOSORB M) (European cosmetics directive 76/768/EEC) Switzerland Brazil Paraguay Argentina Bolivia Uruguay French Guyana South Africa China Australia (only TINOSORB M) Taiwan 58
TINOSORB M & TINOSORB S Registration No registration of the raw material required. Sunscreen products have to be registered by Ministry of Health. Colombia Chile Ecuador Peru Korea Ongoing registration work: USA Japan Mexico Canada Sunscreen products are free to be placed on the market as long as no therapeutic claims are made: Honkong Singapore 59
UV Absorbers overview UV-A Test Methods (in vivo / in vitro) UV Protection by Ciba TINOSORB M TINOSORB S Registration status Market Products with Ciba UV Absorber 60
French Market All Pharmacy Brands (except L Oréal Brands) use TINOSORB M All Pharmacy Brands use Ciba Technology About 20 Brands on Market incorporate TINOSORB M and/or TINOSORB S 61
German Market BDF is most important purchaser of TINOSORB S (e.g. Nivea) Premium Brand Marbert incorporates TINOSORB First Private Label products on market with TINOSORB M 62
Swiss Market Highest per capita spendings on sunscreen Three out of the top four Sun Care Brands use TINOSORB (Nivea Sun, Daylong, Ambre Solaire, Sunlook) All PizBuin products contain TINOSORB M and TINOSORB S Private Label sunscreen with TINOSORB M launched 2003 63
Other Markets ESP No 1 Brand Nivea uses TINOSORB S Pharmacy brands ISDIN (A. Puig) and E.Carreras (Novartis) incorporate TINOSORB M GBR Two strong Mass Market brands use TINOSORB (Nivea, PizBuin) Incorporation of TINOSORB M in some Private Label products (Superdrugs s Solait, M&S, Tesco) ITA Market Leader Nivea incorporates TINOSORB S Local Brands (Collistar, Bottega Verde, Biovitamin C, Bio Nike) use TINOSORB M in some of their formulations 64
Ingredient Branding (official) RoC Minesol, Europe Co-Branding Daylong, Switzerland No more suntan, India 65
Ingredient Branding (inofficial) Bergasol, France Lutsine, France Ella Baché, France Polysianes, France Shandiz, Iran 66
Ciba Sunscreen Simulator 67
Ciba Sunscreen Simulator 68