SEBO- REGULATING. Tea tree oil.

SEBO- REGULATING Tea tree oil www.provitalgroup.com

Tea tree oil A novel natural antiseptic and bactericide for the cosmetic industry The history of Australia as a completely isolated continent resulted in the evolution of a unique flora. More than 1,000 indigenous species of the Myrtaceae family have been identified, including 200 Melaleuca species, although only Melaleuca alternifolia has the medicinal properties that have rendered its oil renowned. Australian aborigine tribes living in the north coast of New South Wales have long known the important germicide properties of Tea Tree leaves. They used to treat wounds, skin burns, insect bites and other skin complaints with a mixture prepared with these leaves and mud. However, the earliest articles about the antiseptic and bactericide properties of Tea Tree Oil were published no sooner than 1930. Later on, further articles about these properties appeared in The Australian Journal of Dentistry, The British Medical Journal and The Australian Journal of Pharmacy. In 1949, the health authorities officially acknowledged this plant and a monograph was included in the British Pharmaceutical Codex and in the 12 th edition of the Martindale Extra Pharmacopoeia (at present, a monograph on Tea Tree Oil is included in the 30 th edition of Martindale). V 03-03/17 12070-1

Below is a chronological list of researchers, who made outstanding contributions to study the properties of Tea Tree Oil (TTO): 1921-1926: Penfold He studied the anti-microbial activity of different essential oils and compared them with those of TTO (The Rideal Walker Coefficient: TTO = 11-13). 1930: Humphrey He prepared TTO solutions that were used in preparations to cleanse and cure wounds, in vaginal douches, deodorants and antiseptic soap for hands. 1933-1936: Penfold y col. Standardization of TTO (Oil Ti-Triol and Melasol). Results observed with this product were published in several scientific journals. 1939: Goldsborough Study about different applications of TTO (toothpaste, soap and shampoo), within a concentrations range of 3-10%. 1949 Inclusion of the monograph about Tea Tree Oil, in the British Pharmaceutical Codex and the 12 th edition of the Martindale Extra Pharmacopoeia. 1960: Feinblatt Clinical studies on TTO efficacy against Candida and Trichomonas. 1972: Walker Efficacy of TTO applications to treat feet infections. 1972-1979 V 03-03/17 12070-2

Determination of the MIC for TTO against different microorganisms. 1980-1990 Challenge Tests (USP method). Continuing clinical studies of TTO activity on different infectious pathologies and publication of the results in scientific journals, which illustrate the efficacy of TTO. During the last decade, a number of toxicological studies with TTO demonstrated lack of toxicity for topical applications of this product. Tea Tree Oil is the essential oil produced by steam extraction of the leaves and terminal branches of Melaleuca alternifolia Chell. (Myrtaceae) also called Australian Tea Tree. This ingredient is included in the 5th edition of the CTFA International Cosmetic Ingredient Dictionary, under the name Tea Tree Oil. Other accepted names are: - Australian Tea Tree Oil - Oil of Melaleuca alternifolia - Oil of Melaleuca terpinene-4-ol type - Melaleuca Oil TGA 92 (accepted in Australia for pharmaceutical products) - Melaleuca Oil (exclusively for external use products) - Tea Tree Oil (INCI name, recommended for cosmetic products) Its chemical composition mainly consists of mono- and sesquiterpenes. V 03-03/17 12070-3

TEA TREE OIL COMPONENTS CONCENTRATIONS ACCORDING TO THE AS-2782-1985 STANDARD TEA TREE OIL 4-Terpineol a-terpinene g-terpinene p-cymene 1,8-Cineol a-terpineol a-pinene Terpinolene Limonene Min. 30.0% 5.0-13.0% 10.0-28.0% 0.5-12.0% Max. 15.0% 1.5-8.0% 1.0-6.0% 1.5-5.0% 0.5-4.0% Min. 39% 7.5 10.5 % 16.0 24.0 % 0.5 3.5 % Max. 5.0% 1.0 8.0 % 1.0 6.0 % 1.5 5.0 % 0.5 2.0 % The most abundant antiseptic active principle of Tea Tree Oil is 4-Terpineol, which acts synergistically with the rest of components. According to the Australian standard, the minimum concentration of 4-Terpineol should be 30%. Another remarkable component is 1,8-Cineol, a mild irritant. According to the Australian standard its concentration must be lower than 15%. Present-day cosmetic industry focuses on the search of natural plant ingredients, from renewable sources, from organic cultivation when possible, which are really effective on the skin and safe to the users. Thus, products that can be easily incorporated into cosmetic formulations, highly stable and with a minimum of incompatibilities are demanded. TEA TREE OIL is natural oil that fulfils all of these requirements. Applications of this product are based on its bactericide and antiseptic properties, together with its mild local anesthetic effects. The following table shows the results of efficacy studies carried out with Tea Tree Oil on different microorganisms, expressed as Minimum Inhibitory Concentration (MIC). V 03-03/17 12070-4

MICROORGANISMS MIC (%) GRAM POSITIVE BACTERIA Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Streptococcus faecalis Streptococcus pyogenes Streptococcus agalactiae Propionibacterium acnes Beta haemolytic streptococcus 0.5-1.0 0.5-1.0 0.25 1.0 1.0 1.25 0.75 0.50 GRAM NEGATIVE BACTERIA Escherichia coli Klebsiella pneaumoniae Citrobacter sp Shigella sonnei Proteus mirabilis Legionella sp Pseudomonas aeruginosa FUNGI Trichophyton mentagrophytes Trichophyton rubrum Aspergillus niger Aspergillus flavus Candida albicans Microsporum canis Microporum gypseum Thermoacatinomycetes vulgaris 0.5 1.0-2.0 0.5-1.0 0.5 0.5-1.0 0.75-1.0 2.0 0.75 0.5 1.0 0.25 0.5 1.0 1.0 1.25 The table shows that the MIC of Tea Tree Oil on these microorganisms ranges approximately between 0.5-1.0%. V 03-03/17 12070-5

TEA TREE OIL CHARACTERISTICS BACTERICIDE ANTISEPTIC MILD LOCAL ANESTHETIC WOUND HEALING MORE THAN 60 YEARS OF USE-EFFECTIVENESS-SAFETY ORGANIC PRODUCT RENEWABLE SOURCES ENVIRONMENTALLY SAFE PLEASANT AROMA NON CORROSIVE NON STAINING NATURAL PRESERVATIVE APPLICATION: INDUSTRY-COSMETIC-PHARMACEUTICAL-VETERINARY CAUTIONS ON COSMETIC FORMULATIONS CONTAINING TEA TREE OIL 1 Compatibility with other ingredients in the formulation Since this is an essential oil, it is advisable in some cases, to include an antioxidant agent and chelating substances in the formulation. V 03-03/17 12070-6

2 - Compatibility with the packaging material Avoid LDPE packaging 3 Incorporation into the formulation It must be incorporated at temperatures below 40ºC TEA TREE OIL APPLICATIONS IN THE COSMETIC INDUSTRY AS A NATURAL PRESERVATIVE Every kind of cosmetics PERSONAL HYGIENE Liquid soap Bath gel Deodorant MOUTH HYGIENE Tooth paste Mouthwash SKIN CARE Facial products Body products After-sun products HAIR CARE Anti-dandruff shampoos and lotions V 03-03/17 12070-7

Shampoos and lotions for oily hair SHAVING PRODUCTS Shaving creams, lotions and foams After-shave lotions NAIL CARE Specific products for the nails 1) NATURAL PRESERVATIVE It is known that cosmetic preparations are good substrates for the growth and development of microorganisms with the consequent biological and physicochemical degradation. Tea Tree Oil is able to prevent such microbial contamination and is therefore used as a natural preservative. Tea Tree Oil acts as an effective preservative on the basis of its wide spectrum antibacterial and antifungal actions and its ph stability. Challenge Tests (in accordance with BP 1993-Appendix XVI and USP XXII) have been performed in order to evaluate the Tea Tree Oil concentration that has to be added to a cosmetic product for an effective natural preservative action. V 03-03/17 12070-8

0.5% Tea Tree Oil concentrations yielded the expected effects, even in formulations that contained high-risk biological products, such as the example moisturizing cream below: MOISTURIZING CREAM Octyl Palmitate 5,00% 5,00% Olive Oil 1,00 1,00 Jojoba Oil 4,00 4,00 Macadamia Nut Oil 1,00 1,00 Cetearyl Glucoside 4,00 4,00 Cetyl Alcohol 1,00 1,00 Vitamin A Palmitate 0,075 0,075 Butylene Glycol 2,00 2,00 Propylene Glycol 5,00 5,00 Hydrolyzed Collagen 1,00 1,00 Herbal Blend 1,00 1,00 Aloe Vera Gel 10,00 10,00 Disodium Edetate 0,10 0,10 Purified Water qs 100,0% qs 100,0% TEA TREE OIL PG - 0,50 Perfume 0,35 0,35 Challenge test-bp 1993 Does not meet criterion Meets criterion 2) BATH GEL During the last few years, consumers have been demanding products which, besides cleansing the skin, also protect it by including bactericide agents. Tea Tree Oil can be used in this kind of formulations, where it will play three simultaneous roles: skinprotector, preservative and fragrance for the final product. Below is a bath gel formula prepared following a green-organic concept. It is a liquid, colorless soap, free of preservatives and dyes, with a powerful antiseptic action without synthetic bactericides. V 03-03/17 12070-9

BATH GEL Sodium laureth sulphate 30% 30,00% Cocamidopropyl betaine 30% 15,00 Coco diethanolamide 1,50 Dimethicone copolyol 3,00 TEA TREE OIL PG 0,50 Water qs 100,0% 3) DEODORANTS Deodorants are cosmetic products that reduce or eliminate perspiration, prevent sweat degradation and may modify already produced smell. Ingredients directly influencing sweat degradation include bactericide agents, such as Tea Tree Oil, which acts as an active compound against sweat degradation-producing microorganisms according to the MIC table above. DEODORANT STICK 4) ANTI-ACNE Stearic acid 8,50% Propylene glycol 68,70 Sodium hydroxide 1,33 Water qs 100,00% TEA TREE OIL PG 1,00 Polysorbate 20 4,00 Arnica Extract 0,50 Gentian Extract 0,50 Perfume qs More than 80% teenagers suffer from acne. It is a common, inflammatory, recurrent disorder of skin pilosebaceous follicles, which gives rise to blackheads and pimples that eventually become nodules or cysts. Four factors are involved in this process: 1.- Pilosebaceous duct obstruction V 03-03/17 12070-10

2.- Increased sebum production 3.- Biochemical changes in the lipid composition of skin surface 4.- Bacterial colonization of the sebaceous follicle To treat this disorder, it is necessary to follow general hygiene and care recommendations and to use specific anti-acne products. Because of its antibacterial and antifungal actions, Tea Tree Oil can be used to formulate this kind of products in substitution of benzoil peroxide, which has some side effects. Clinical studies comparing the efficacy of an aqueous gel with 5% Tea Tree Oil and an aqueous lotion with 5% benzoil peroxide demonstrated that the former is a good substitute for the later. The efficacy of Tea Tree Oil can be improved by adding keratolytic products (AHA, salicylic acid, etc). FLUID EMULSION Teginacid H 2,00% Emulgator E-2155 3,00 Stearyl alcohol 4,00 Dimethicone 0,50 Caprylic/capric triglyceride 5,00 Avocado oil 3,00 Glycerin 2,00 Deionized water qs 100,0% TEA TREE OIL PG 5,00 Polysorbate 20 20,00 Pronalen Fruit Acids AHA-50 4,00 NaOH qs 5) MOUTH CARE PRODUCTS The goal of these products is to cleanse, protect and keep healthy the mouth cavity. V 03-03/17 12070-11

Tea Tree Oil can be added to their formulations as a natural preservative, and because of its anti-bacterial effects on microorganisms affecting this area. Studies have demonstrated that Tea Tree Oil efficiently protects against microorganisms that cause tooth pathologies by inhibiting their growth. TOOTHPASTE Glycerin 21,00% Hydroxyethylcellulose 1,50 Distilled water qs 100,00% PEG-12 3,00 Calcium glycerophosphate 1,00 Sodium saccharin 0,20 Sodium benzoate 0,25 Sodium monofluorophosphate 0,76 Sodium pyrophosphate 0,5 Di-calcium phosphate 45,00 TEA TREE OIL PG 0,50 Sodium lauryl sulfate 1,50 6) SHAVING PRODUCTS TTO can be added to every kind of shaving products because of its action as a natural preservative. However, it is especially recommendable for after-shave products due to its bactericide, disinfectant and wound healing actions. V 03-03/17 12070-12

AFTERSHAVE BALM Ceteareth-20 0,50% Ceteareth-12 0,50 Glyceryl stearate 3,00 Coco-capryl/caprate 5,00 Allantoin 0,20 Glycerin 3,00 Water qs 100,0% Ethyl alcohol 20,00 TEA TREE OIL PG 1,00 Carbomer 934 0,40 Sodium hydroxide qs CONCLUSION Tea Tree Oil is an active principle with a long history of use and demonstrated efficacy, useful for cosmetic applications, that PROVITAL GROUP now introduces as a novel concept for the development of products adjusted to the demands of modern consumers: namely effective, safe, natural and environment-friendly. BIBLIOGRAPHY Altman, P.M. "Australian Tea Tree Oil - an update" Cosmetics, Aerosols & Toiletries in Australia, 1991, vol. 5, nº 4 April/May 1991. Australian Journal of Dentistry, 1930, Various articles, p. 284-285. Basset et al. "A comparative study of Tea Tree Oil versus Benzoyl Peroxide in the treatment of Acne" Medical Journal of Australian, 1990, vol. 153, october 15, 1990. Belaiche, P. " L'huile essentielle de Melaleuca alternifolia Cheel. dans les infections vaginales a Candida albicans". Phytotherapie, 1985, vol. 15, 13-14. V 03-03/17 12070-13

Brophy, J.J. et al "Gas chromatographic quality control for Oil of Melaleuca Terpinene-4-ol type (Australian Tea Tree)" Journal of Agriculture and Food Chemistry, 1989, vol. 37, p. 1330.1335. Carson, C.F. & Riley, T.V. "A review - Antimicrobial activity of the essential oil of Melaleuca alternifolia" Letters in Applied Microbiology, 1993, vol. 16, p. 49-55. Directiva 93/35/CEE del Consejo del 14 de junio de 1993 (por la que se modifica por sexta vez la Directiva 76/768/CEE relativa a la aproximación de las legislaciones de los Estados miembros en materia de productos cosméticos). Feinblatt, H.M. "Cajeput type oil for the treatment of Furunculosis". Journal of the National Medical Association of the USA, january 1960, vol. 52, p. 32-34. Humphrey, E.M. "A new australian germicide". Medical Journal of Australia, 1930, pp. 417-418. Martindale Extra Pharmacopoeia 30th edition published by The Pharmaceutical Press, London, p. 1385. "Oleum Melaleuca" British Pharmaceutical Codex, 1949, p. 597-598. Penfold, A.R.; Morrison, E.R. " Some notes on the essential oil of Melaleuca alternifolia". Australian Journal of Pharmacy, 1937, p.274-275. Pena, E.F. "Melaleuca alternifolia oil-its use for Trichomonal vaginitis and other vaginal infections" Obstetrics and Gynecology, 1962, vol. 19, p. 793-795. "Preparaties and Applicantes". British Medical Journal, 1933. Priest, D. "Preserving naturally with Tea Tree Oil" IN-COSMETICS, Paris, April 1995 (Conference proceedings). Shemesh, A.; Mayo, W.L. "Australian Tea Tree Oil: a natural antiseptic and antifungal agent". Australian Journal of Pharmacy, september 1991, vol. 72. Walsh, L.J.; Longstaff, J. "The antimicrobial effects of an essential oil on selected oral pathogens" Periodontology, 1987, vol. 8, p. 11-15 Walker, M. "Clinical investigation of Australian Melaleuca alternifolia oil for a variety of Foot problems " Current Podiatry, 1972. V 03-03/17 12070-14

PROVITAL. S.A. Pol. Ind. Can Salvatella Gorgs Lladó, 200 08210 Barberà del Vallès Barcelona (España) Tel. (+34) 93 719 23 50 info@provitalgroup.com www.provitalgroup.com V06-02/15 12300,12310,12340,12350,12710,14540-0