Product Information Anti-Dandruff Agent Pyrion - Disulfide 3rd Issue: 15. Nov. 1999/Th
TABLE OF CONTENTS 1. Characteristics... 2 Structural formula... 2 2. Physical data... 3 Melting range... 3 Solubility... 3 Stability... 3 Compatibility... 3 Density... 3 3. Toxicology... 4 Oral Toxicity... 4 Dermal Toxicity... 4 Eye Irritation... 4 4. Effectiveness... 5 5. Form of delivery... 7 6. Recipes... 8 8. Storage... 9 9. Precautions... 10 10. Literature... 10 1
1 CHARACTERISTICS Name: Pyrion -Disulfide, Pyriondisulfide INCI-name: CTFA-name: Chemical names: Bispyrithione Bispyrithione 2,2 -Dithiopyridin-1,1 -dioxide 2,2 -Dithio-bis(pyridyl-N-oxide) Bis-2-pyridyl-1-oxide-disulfide Bis-(1-Oxy-pyridyl-2-disulfide) CAS-Nr.: 3696-28-4 EINECS-Nr.: 2230245 Total formula: C 10 H 8 N 2 O 2 S 2 Molecular weight: 252,3 g/mol Structural formula: O N S S N O Description: light grey to brownish aqueous suspension Assay of active: 40-41 % Odor: Application: weak, characteristic Anti-dandruff agent Recommended concentration in shampoos: 0,5-1 % based on active 2
2 PHYSICAL DATA 2.1 Melting range The pure and solid Pyrion-Disulfide will melt at about 212-214 C (413-417 F) with decomposition. 2.2 Solubility Pyrion-Disulfide is soluble in water. The solubility is 0,8-0,9 % of the pure compound or 2,0-2,3 % of the suspension at 20 C (68 F). This solubility is enough to formulate clear and transparent shampoos. The solubility of Pyrion-Disulfide in organic solvents is shown in the following table 1 : Ethanol 0,3 % Chloroform 3,8 % Dimethylformamide 0,8 % 2.3 Stability The aqueous suspension can be stored for a minimum of three years if the ph is between 4 and 8 and the temperature is between 10 and 25 C (50-77 F). Do not freeze. Pyrion-Disulfide is attacked by UV-light. We suggest to store Pyrion-Disulfide formulations in light-proof containers. If translucent containers are used a stability test should be done, especially when cationic or amphoteric surfactants are present (see also compatibility). 2.4 Compatibility Pyrion-Disulfide is compatible with most raw materials used in cosmetics. Merely if cationic or amphoteric surfactants are used an insoluble precipitate can be formed. Because this phenomenon also depends on the ph-value (acidic ph is preferred) and other ingredients (cationic conditioners) a stability test is highly recommended. Pyrion-Disulfide is compatible with many preservatives (eg. DMDM-Hydantoin, Parabenes, Isothiazolinones) and can be used together with them. 2.5 Density Density of the 40% suspension: approx. 1,12 g/cm³ 3
3 TOXICOLOGY Pyrion-Disulfide containing shampoos and hair lotions 2 are used worldwide. The safety as shown by studies is confirmed by the long history of its use. 3.1 Oral Toxicity Studies done by RÜ TGERS Organics GmbH showed, that the LD 50 of the acute oral toxicity of the pure dry Pyrion-Disulfide is 2000 mg/kg for rat. 3.2 Dermal Toxicity The dermal toxicity has been tested with six rabbits. According to the "Classification System for primary irritation" pure Pyrion-Disulfide is mildly irritating (Method: Code of Federal Regulation, Title 16, Section 1500.41). The LD 50 of the acute dermal toxicity of Pyrion-Disulfide has not been detected. There is no evidence that skin irritation occurs in the use of shampoos containing up to one percent pure Pyrion-Disulfide. 3.3 Eye Irritation The eye irritation has also been tested with rabbits. According to the "Classification System for primary irritation" a 0,8% Pyrion-Disulfide solution is non irritant (Method: Code of Federal Regulation, Title 16, Section 1500.42). 4
4 EFFECTIVENESS Pyrion-Disulfide is active against many gram positive and gram negative bacteria as well as against many fungi and yeast's. The detailed mechanism of its activity is still unknown. It is suspected that Pyrion-Disulfide is effective in many ways, because its field of activity is extremely large. In view of the above mentioned context it is obvious that the effectiveness of Pyrion-Disulfide as an anti-dandruff agent is due to its antimicrobial activity. Tests have shown that Pyrion-Disulfide is more effective than Piroctone Olamin and shows reduced greasiness on the scalp 3. The following tables of the minimal inhibition concentrations give an overview over the broad activity of Pyrion-Disulfide as a 40 % suspension: 4.1 Antibacterial Spectrum of Pyrion-Disulfide (40%) Method: Series dilution of suspensions, Calculation: Maximum likelihood method (MIC = minimal inhibition concentration) MIC in mg/l (ppm) A KLEBSIELLA PNEUMONIAE 30,9 B ENTEROBACTER CLOACAE 27,8 C ESCHERICHIA COLI 24,8 D BACILLUS STEAROTHERMOPHILUS 12,3 E BACILLUS SUBTILIS 11,0 F STREPTOCOCCUS PYROGENES 10,9 G MICROCOCCUS EPIDERMIDIS 9,7 H MICROCOCCUS AUREUS 9,6 I SHIGELLA SONNEI 9,3 J SALMONELLA TYPHIMURIUM 8,4 5
35 30 25 30,9 27,8 24,8 20 15 10 12,3 11 10,9 9,7 9,6 9,3 8,4 5 0 A B C D E F G H I J Abb. 1: ANTIBACTERIAL SPECTRUM OF PYRION-DISULFIDE (40%) 4.2 Antifungal Spectrum of Pyrion Disulfide (40%) Method: Series dilution of suspensions, Calculation: Maximum likelihood method (MIC = minimal inhibition concentration) MIC in mg/l (ppm) K ASPERGILLUS FUMIGATUS 10,9 L ASPERGILLUS NIGER 9,3 M PENICILLIUM SP. 6,3 N MICROSPORUM CANIS 6,3 O TRICHOPHYTON MENTAGROPHYTES 6,2 P CRYPTOCOCCUS NEOFORMANS 4,7 Q SACCHAROMYCES CEREVISIAE 3,1 R CANDILA ALBICANS 3,1 6
12 10,9 10 9,3 8 6 6,3 6,3 6,2 4,7 4 3,1 3,1 2 0 K L M N O P Q R Abb. 2: ANTIFUNGAL SPECTRUM OF PYRION-DISULFIDE (40%) 5 FORM OF DELIVERY 5.1 Pyrion-Disulfide 40% Aqueous Suspension Pyrion-Disulfide for immediate blending into shampoos to obtain a clear solution and nice appearance. Light grey to brownish aqueous suspension containing additionly a dispersant and a viscosity control agent. Typical product data Particle size 80 % < 5 µm (Fritsch Analysette 22 and Fraunhofer-calculation) Assay of active 40-41 % ph-value 4,0-6.0 Packaging open top plastic drums 25 kg net Special container volumes on request. For further information see our current Material-Safety-Data-Sheet. 7
6 RECIPES The following shampoos have been tested in our laboratory. They are intended for use by persons having technical skill and at their own discretion and risk. Nothing contained herein is to be considered as permission to practice any patent invention without permission of the patent owner. 6.1 Anti-Dandruff Shampoo 1 Ingredient Function Weight,% Sodium Laureth Sulfate (28%) Surfactant 30,0 Cool grass* Fragrance 0,5 Water Diluent 55,0 Pyrion-Disulfide (40%) Anti-Dandruff Agent 1,5 TEGO Betain L7** Foam Enhancer 12,0 NaCl Thickener 1,0 Preservative, Color, Citric Acid q.s. * Bell Flavors and Fragrances, USA **Th. Goldschmidt AG, Essen, D Preparation: Add ingredients in order and mix until homogenius. The mixture will be turbid in the beginning but becomes clear after some mixing. The viscosity can be adjusted with sodium chloride in a wide range. Adjust the ph to 5,5-7 with citric acid. Properties: medium to high viscous clear shampoo ph: 5,5-7 Aktives: approx.12 % 8
6.2 Anti-Dandruff Shampoo 2 Ingredient Function Weight,% Sodium Laureth Sulfate (approx. 30 %) Surfactant 20,0 Sodium Lauryl Sulfate (approx. 30 %) Surfactant 20,0 Cocoamidopropyl Betaine Foam Enhancer 6,0 Water Diluent 50,0 Pyrion-Disulfide (40%) Anti-Dandruff Agent 1,5 FD&C Blue #1 (0,1 %) Color 1,0 Fragrance Fragrance q.s. Preservative Preservative q.s. Citric Acid Neutralizer q.s. Thickener Thickener q.s. Procedure: Add ingredients in order and mix slowly until mixture is homogenius. When a clear solution has formed adjust the ph to 6. Remark: The viscosity can be adjusted with NaCl, Hydroxypropylcellulose, Xanthan or any other thickener on the market. If pearlescent pigments with high density are used, we suggest to use the ETD 2020 from BF Goodrich or Structure Plus from National Starch as thickeners. Properties: light blue and clear shampoo with various viscosity ph: 5,5-6,5 Aktives: approx. 15% 7 STORAGE Always store in well closed containers protected from light at between 10 C (50 F) and 30 C (86 F) Do not freeze Before any handling and sampling, homogenize well. Keep away from metals, metalsalts and strong oxidizers. Do not contaminate water, waste water, food or feed with the material. 9
8 PRECAUTIONS Pyrion-Disulfide should be handled with the precautions used in handling industrial chemicals. Keep Container closed when not in use. Do not take internally. May be fatal if swallowed. Avoid contact of the pure ingredient with skin or eyes. In case of contact flush with plenty of water. 10 LITERATURE 1 Lexikon der Rohstoffe, Bd. 2 (L-Z) 4. Aufl., 1996 [ISBN 3-87193-173-X] 2 Seifen-Ö le-fette-wachse 110 (1984) 160 3 Seifen-Ö le-fette-wachse 112 (1986) 667-671 10