Green and Efficient Future of Modern Dandruff Control

Introduction

The global personal care market for dandruff control is dominated by shampoo applications, but also encompasses other rinse-off formulations such as hair conditioners and even tonic-type uses. The market follows dynamics similar to the global hair care market.¹ Among the top 3 hair care brands worldwide, there is a specialized dandruff control brand: Procter & Gamble's Head & Shoulders, which became a classic example of the use of zinc pyrithione, the globally largest conventional anti-dandruff active ingredient. Two other commonly used conventional active ingredients are pyroctone olamine (Crinipan® PO) and climbazole (Crinipan® AD). These anti-dandruff active ingredients primarily aim to limit the intensive activity of Malassezia on the scalp, while salicylic acid is frequently used for keratolytic effects and supports the removal of dead skin flakes (dandruff).² Considering European legislation, "dandruff prevention" is a commonly used cosmetic claim and, beyond the general rules in the EU cosmetics regulation, is not subject to specific legislation. On the other hand, the US FDA permits only zinc pyrithione and salicylic acid from the compounds listed above to be used as anti-dandruff active ingredients.³ The anti-dandruff shampoo market is dominated by global brands, and the combination of multiple active ingredients has often been a common practice. Combining any of the three conventional anti-fungal compounds with the keratolytic effects of salicylic acid is one approach. For example, climbazole and salicylic acid were part of Henkel's Schwarzkopf Seborin shampoo.⁴ Other combinations have also been documented: Unilever's anti-dandruff shampoo CLEAR listed climbazole alongside zinc pyrithione.⁵ Beiersdorf applies pyroctone olamine in combination with climbazole in NIVEA shampoos,⁶ while Wella anti-dandruff shampoos contain pyroctone olamine alongside zinc pyrithione.⁷ Procter & Gamble's new European market shampoos use pyroctone olamine alongside the sodium salt of salicylic acid as part of the INCI list.⁸ Triggered by the reproductive toxicant classification of the substance, the ban on zinc pyrithione in cosmetic applications in Europe in 2022 forced manufacturers to move away from this technology.⁹ This limits the amount of anti-dandruff actives available to formula developers. In 2020, Symrise launched a completely new green technology for dandruff control that, like conventional actives, targets Malassezia but does so with a new and innovative mode of action.¹⁰ Propanediol caprylate (Crinipan® PMC green) significantly reduces dandruff compared to placebo in a 30-day shampoo study and equally compared to positive control (climbazole).¹¹ Subsequent studies demonstrated that the product supports a healthier scalp microbiome and also provides numerous additional benefits such as ease of use, effects on skin, hair, and sebum reduction.¹²

Experiments & Results

Efficacy of Propanediol Caprylate Against Pyroctone Olamine

In light of the ban on zinc pyrithione in cosmetic products in Europe, only two major conventional technologies remain for anti-dandruff shampoo manufacturers: Pyroctone olamine and climbazole. Since we have previously demonstrated the efficacy of our new green technology (propanediol caprylate) compared to climbazole as positive control,¹¹ we aimed to conduct a second comparative study with pyroctone olamine. The commonly known and effective use rate for anti-dandruff actives in shampoo is 0.5%. This use rate also reflects the previous maximum rate of climbazole permitted in cosmetics under European Cosmetics Regulation until 2019. Concurrent with implementation, a regulatory change in 2019 established new restrictions. As a result, climbazole today can be used at up to 2% in rinse-off anti-dandruff shampoo (Annex III/310), but has lower use rates in other applications (Annex V/32).¹³ To comparatively examine propanediol caprylate with pyroctone olamine, each of the ingredients was added at 0.5% use rate to two separate but identical clear and fragrance-free sodium laureth sulfate shampoo bases (Table 1). Pre-selected 21 volunteers with dandruff-prone and oily scalp underwent a 14-day pre-care procedure, instructed to wash their hair only with a standard neutral market shampoo free of active ingredients previously supplied by the institute. Following the conditioning phase, 12 subjects received test shampoo containing propanediol caprylate (randomized, blinded study) and 9 subjects received shampoo containing pyroctone olamine as positive control. Test shampoos were applied three times weekly with a 3-minute contact time before rinsing. Visual dandruff score was evaluated by a dermatologist immediately before first product application, at the end of the conditioning phase (D0), at the end of the test period, and after 28 days (D28). Dandruff was graded separately for flakes adhering to and not adhering to the scalp on a visual scale from 0 to 5. The sum of the two separate scores provided a total dandruff score on a scale from 0 to 10 (Figure 1). In both groups, at the end of the application phase (D28), a statistically significant reduction in adherent dandruff score was observed compared to baseline (D0) (propanediol caprylate p=0.0004; pyroctone olamine p=0.0056). Similarly, the reduction in non-adherent dandruff score at D28 compared to D0 was statistically significant for both shampoos tested (propanediol caprylate p=0.0050; pyroctone olamine p=0.0028). While no significant difference was detected between the two groups, total dandruff score decreased from 5.33 to 3.71 (p=0.0002) in the propanediol caprylate group and from 5.64 to 3.64 (p=0.0032) in the pyroctone olamine group. [caption id="attachment_158331" align="aligncenter"] Table 1: pH 5.5 simplified and fragrance-free shampoo formulations used in the in vivo comparative study between propanediol caprylate and pyroctone olamine[/caption] [caption id="attachment_158332" align="aligncenter"] Figure 1: Shampoo study; Mean visual dandruff values for adhering/non-adhering dandruff on a scale from 0 to 5 and overall on a scale from 0 to 10 in 21 subjects, as determined by professional evaluators in Poland.[/caption]

Efficacy of Propanediol Caprylate in Combination with Pyroctone Olamine

The cosmetic industry's general objective for superior efficacy of anti-dandruff applications can be understood from the 2% climbazole limit in rinse-off shampoos. This regulatory restriction is the ultimate result of shampoo manufacturers' demand for higher use rates. The SCCS European safety assessment process initially concluded that raising the shampoo use rate to 2% while maintaining the generic use rate at 0.5% would not work in the total exposure scenario; thus, while prioritizing a 2% limit for anti-dandruff shampoos, even lower use rates were established for other applications. In a recently published article by Clariant, an increased use level of 0.75% pyroctone olamine was reported to be particularly effective.¹⁴ As previously explained, the combination of different ingredients represents an attempt to achieve better efficacy. Considering all these factors, we aimed to conduct another randomized, blinded study comparing a simplified standard shampoo using 0.75% pyroctone olamine as positive control with a shampoo containing 0.5% propanediol caprylate combined with 0.25% pyroctone olamine. The respective use rates of pyroctone olamine or propanediol caprylate with pyroctone olamine combination were added to two separate but identical clear and fragrance-free sodium laureth sulfate shampoo bases (Table 2). Pre-selected 40 volunteers, half with oily and half with dry scalp and different dandruff problems, underwent a 14-day pre-care procedure, permitted to wash their hair only with an active-free, standard neutral market shampoo previously supplied by the institute. Following the conditioning phase, 20 subjects (10 with oily scalp, 10 with dry scalp) applied pyroctone olamine (positive control) shampoo, and the remaining 20 subjects (same split of oily/dry scalp) applied test shampoo with propanediol caprylate/pyroctone olamine combination. Test shampoos were applied at least three times weekly. Visual dandruff score was evaluated at the test institute before first application (D0), 14 (D14), 28 (D28), and 42 days (D42) following application. After a total of 63 days (D63), following the end of a subsequent 3-week washout period, an additional evaluation was performed and subjects returned to neutral shampoo use. Dandruff was graded on a visual scale from 0 to 10 (Figure 2). In both treatments, an anti-dandruff effect was observed reflecting a reduction in dandruff compared to D0. Although the pyroctone olamine positive control shampoo reduced scaling on the scalp somewhat faster, no significant difference was observed between the two treatments. Overall, both shampoos reduced dandruff. Looking at mean values, the group using the active ingredient combination interestingly showed a prolonged effect. Here, the mean dandruff score continued its downward trend even during the washout phase (D63 versus D42), while for the positive control shampoo, an increase in mean dandruff score was observed from D42 to D63 in line with baseline values. [caption id="attachment_158333" align="aligncenter"] Table 2: pH 5.5 simplified and fragrance-free shampoo formulations used in the in vivo comparative study of pyroctone olamine with a two-component combination (propanediol caprylate + pyroctone olamine).[/caption] [caption id="attachment_158334" align="aligncenter"] Figure 2: Shampoo study; Mean visual dandruff values on a scale from 0 to 10 in 40 subjects as determined by experts in Germany: Pyroctone olamine and propanediol caprylate + pyroctone olamine combination.[/caption]

Discussion

This additional in vivo study between propanediol caprylate and positive control pyroctone olamine underscores that the efficacy of the new technology is equivalent to conventional systems, as previously demonstrated against climbazole and placebo.¹⁰ The new, bio-based anti-dandruff active propanediol caprylate particularly significantly reduces flaking in oily scalp known as dandruff caused by Malassezia. The second study examines a new combination of conventional (pyroctone olamine) and next-generation (propanediol caprylate) ingredients. Comparison of the combination with the conventional during shampoo application initially revealed no significant difference between the two treatments, with both shampoos having the ability to reduce dandruff similarly when applied regularly. However, the presence of a continuing downward trend in dandruff flakes even during the washout phase with the active ingredient combination is particularly indicative of a prolonged effect. The use of propanediol caprylate appears to support long-term normalization toward a healthy balance on the scalp; this may be linked to the previously reported beneficial effects on the natural scalp microbiome.¹²

Conclusion

Propanediol caprylate (Crinipan® PMC green) is an important technology for a greener future of dandruff control, equally efficacious as conventional active ingredients and with apparent additional advantages. This liquid and easy-to-use cosmetic ingredient supports a healthy scalp microbiome and significantly reduces dandruff. Combination with low rates of conventional ingredients such as pyroctone olamine (Crinipan® PO) or with salicylic acid may be of interest: in addition to having a well-known active ingredient as part of the ingredient list, it offers sustainable, long-lasting, and cost-effective benefits.

Acknowledgments

We thank BU Micro Protection's global application laboratory, and particularly Jasmin Salmen for her expertise in the preparation of test shampoos.   References * First published in English in Personal Care Magazine: October 2022 issue. 1 Symrise AG, Market Review Dandruff Control, July 2021, https://www.symselect.com/dandruff-control_review 2 CosIng, the European Commission database for information on cosmetic substances and ingredients. Accessed 28.02.2022 via https://ec.europa.eu/growth/toolsdatabases/cosing/index.cfm?fuseaction=search.details_v2&id=37595 3 US Food&Drug Administration (FDA) (2021); https:// www.fda.gov/drugs/status-otc-rulemakings/rulemakinghistory-otc-dandruff-seborrheic-dermatitis-andpsoriasis-drug-products 4 Mintel GNPD database: Record ID 1562280, Henkel´s Schwarzkopf Seborin Dual Effect Shampoo Anticaspa (Anti-Dandruff Shampoo), published May 2011 in Chile 5 Mintel GNPD database: Record ID 2261277, Unilever´s CLEAR Men Antiforfora Shampoo Purificante (Anti-Dandruff Purifying Shampoo), published Dec 2013 in Italy 6 Mintel GNPD database: Record ID 1403922, Beiersdorf´s NIVEA for Men Anti-Schuppen Pure Shampoo (Anti-Dandruff Pure Shampoo), published October 2010 in Germany 7 Mintel GNPD database: Record ID 5854667, Wella Professionals Invigo Balance Shampoo, published July 2018 in the UK 8 Mintel GNPD database: Record ID 9397368, Procter & Gamble´s Head & Shoulders Sensitive Duschgel & Shampoo (Shower Gel & Shampoo), published February 2022 in Germany 9 COMMISSION REGULATION (EU) 2021/1902 of 29 October 2021 amending Annexes II, III and V to Regulation (EC) No 1223/2009 of the European Parliament and of the Council as regards the use in cosmetic products of certain substances classified as carcinogenic, mutagenic or toxic for reproduction: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32021R1902&qid=1635933838171 10 Genrich, F., Koch, C., Lange, S., Bugdahn, N., Schmaus, G. (Dec. 2020). Next Generation Dandruff Control; SOFWJournal 146 8-13 11 Genrich, F., Nordzieke, S. (April 2021) Shaping the Future with Green Dandruff Control; Euro Cosmetics 29, 16-18 12 Genrich, F., Koch, C., Massironi, M., Thomaz, F. (June 2021) Propanediol Caprylate: Shifting the Microbiome, Sebum Levels and Classic Approach to Dandruff; Cosmetics & Toiletries Vol 136; No. 6, 44-51 13 COMMISSION REGULATION (EU) 2019/698 of 30 April 2019 amending Annexes III and V to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32019R0698&qid=1646062668262 14 Kita, K., Caravieri, F., Birkel, S. (June 2021). Piroctone Olamine – Advancing Anti-dandruff Care & More, Efficient and safe scalp care for new formats & applications; SOFWJournal 147 26-31 15 Meunier, L., Genrich, F., Fontán Yanes, M.T. (August 2023) Advancing Salicylic Acid-based Dandruff Control; Euro Cosmetics; https://www.eurocosmetics-mag.com/advancing- salicylic-acid-baseddandruff-control/   Translator and Compiler Tuğba Bayazıt Technical Application Specialist Africa, Middle East, Turkey Laboratory Manager Symrise AG   Authors Dr. Florian Genrich¹, Laura Meunier¹ Dr. Steffen Nordzieke² 1 Symrise AG, Holzminden, Germany, Cosmetic Ingredients Division, Category Skin Protection 2 Symrise AG, Holzminden, Germany, Global Innovation Cosmetic Ingredients, Microbiology Research